EAST AFRICA HIGH COMMISSION

FILARIASIS RESEARCHANNUAL REPO T

1952

.: . ~ , '. 1953PRINTED BY THE HIGH COMM:lSSION PRINTER, NAIROBI

FILARIASIS RESEARCH UNIT ANNUAL REPORT

No.4, 1952SECTION I-GENERAL

lntrodnctor:y NoteDue to the long waiting period before publication of articles in medical

and scientific journals, the earlier Annual Reports of this Department have beendetailed in presentation. As a result, such Reports could only be made availableto a small proportion of interested workers. Accordingly in this publication areturn is made to the more usual method of presentation, a summary beinggiven of work done, with detailed sectional reports submitted for publicationin scientific journals.

AimsPrior to World War II it was thought that, with the exception of the South

Pacific area, the filarial infections of the torrid zones were of secoudary import­ance, and that no effective remedies were available.

The experience of the Allies at war was such, however,' that by 1947 thependulum of medical thought had swung to the other extrem~, to the view thatthe filarial infections are of primary importance. Also, as the result of muchresearch, there had become available preparations claimed to be effective againstthe filarial infections.

This change of view was responsible for tbe establishment of the FilariasisResearch Unit, created in 1949 as a High Commission Service to investigate theproblems of filariasis in East Africa. There are three such iufections found inthis area, namely, filariasis bancrofti, onchocerciasis and .acanthocheilonemiasis;we have not studied this last-named infection in any detail, as this work hadbeen undertaken by the Liverpool School of Tropical Medicine.

Work was planned from three aspects-

first: to establish the relative importance of the filarial infections bydetermining the incidence and by establishing the effect on the infectedindividual;

second; to investigate methods of control, aimed at the vector, or atthe reservoir., or at both;

third: to investigate methods of treatment.

Accommodation

The Research project has its headquarters at Mwanza on Lake Victoria.The European housing is complete and the laboratory is now almost ready foroccupation.

StaffDirector: Lt.-Col. W. Laurie, DB.O., M.D., T.D.D., LM.S. (Retd,).

Physicians: P. Jordan, M.B., B.S., D.T.M. & H.One vacancy.

Helminthologist: One yacancy.

Entomologist: A. Smitll, B.Se., Ph.D.

Lahoratory Technicians: R. Rhodes-Jones, W. Edwards, R. C. Young.

Photographer: Vacant.

Librarian: Vacant.

2

SECTION 1-BANCROFTIAN FILARIASIS IN EAST AFRICA

Introductory

The two important late manifestations of bancroftian filariasis are hydro­coele and elephantiasis. The incidence of such late manifestations varies con­siderably from area to area, e.g. elephantiasis is common in the South Pac.ific,whereas hydrocoele is uncommon. Another complication, hitherto recognized onlyin the South Pacific area, is "mumu", defiued as "an acute recurrent conditionassociated with lymphangitis of an extremity, with funiculitis and epididymo­orchitis or both". This is a sensitisation phenomenon and is establi~hed withiua few weeks in the majority of individuals exp'Osed to infection. It was thiscondition which produced 25 per ceut casualties in the American South PacificForce in World War 11.

Any disease which is capable of affectiug large nnmbers of the populationand which early produces attacks of crippling fever, etc. must be regarded as aserious medical and economic problem. This general consideration is reinforcedin the case of bancroftian filariasis by the fact tbat elephantiasis is a commonlate manifestation.

If this were the picture 01' East African filariasis bancrCF/ti there could beno two opinions as to its seriousness. But as has been pointed out in ewierreports, we consider tlla t tbe South Pacific disease is quite different fromthat found in East Africa. Here mumu is very rare, if it occurs at all; and hydro­coele is a much COITunoner late complication than is elephantiasis.

Field SurveysThe first essential in investigating the importance of filariasis is to establish

accurately the inCIdence of such infections through the whole of East Africa;the methods of work have been describ::d in detail in our 1951 Report. Here itneed only be said ithat the work is difficult and that progress is slow, largely dueto the cutting down of the field staff and to bad communications, which allowof work being carried out only for about eight months per annum. The Tanga­nyika Survey is almost complete, and survey work has begun in' Kenya.

In the 1951 Report the results of surveys of the following TanganyikaProvinces were given in detail:-

Lake Province,

Eastern Province.

Tanga Province.

Northern Province.

This 1952 Report gives details of findings in the Southern and Southern HighlandsProvinces. Other results are not yet ready for pnblication. The work throughouthas been the responsibility of Dr. P. Jordan of this Department.

It is hoped later to publish fuller details showing the close association ofbancroftian filariasis with high temperatures and high humidity.

(1) Southern Highlands ProIn this Pro'vince particular

cerciasis being present as wenpreviously been reported as aProvince. In this search tbe specadministration was utilized as ou

(a) Location and geography

The Province is bounded t<by the Central and Western ]boundary) and in the soutb itLake Nyasa.

The Provinc;e is roughly tlangle bein~ formed by the nortHighlands extending from Iringarea at the northern tip of Lakand finally the low-lying areaThe central part of the triangleof tsetse-infested bushland to thRiver in the east.

(b) Climate

The climatic conditions e)graphical features outlined abca year and in parts receive asnorth of Lake Nyasa has the gthis gradually decreases towards40 inches. The central area reothis towards the east.

Temperatures again rougrtemperature of less than 50·P.in most places of 75°F. to 80temperatures. The are<r at the rperature of between 65°F. to '75°P. to 80°F. over most ofranges in some places. The lo\\of the central area have a maxi

The population of the PnHighlands supporting a modeLake Nyasa is one of the mmentioned above, mOISt of the c

The vegetation consists mai

(c) ResultsBancroftian filariasis.-Th

the clinical findings are shown

~.

!.'.

,SIS IN EAST AFRICA

lancroftian filariasis are hydro'­late manifestations varies con­common in the South Pacific,

ication, hitherto recognized only, "an acute reCllrrent conditionvith funiculitis and epididymo­~enon and is establi~hed withinDoSed to infection. It was thisin the American South Pacific

rge numbers of the populationrer, etc. must be regarded as alera] consideration is reinforcedthat elephantiasis is a common

ltiasis bancrofti there could belas been pointed out in earlierisease is quite different frome, if it occurs at all; and hydro­,n is elephantiasis.

:ance of filariasis is to establishIgh the whole of East Africa;IiI in our 1951 Report. Here itJat progress is slow, largely duei communications, which allownonths per annum, The Tanga­'k has begun in' Kenya.

of the following Tanganyika

outhern and Southern Highlands,blication. The work throughoutthis Department.

howiug the close association ofd high humidity,

..

3

(1) Southern Highlands ProvinceIn this Pro'vince particular attention was paid to the possibility of oncho­

cerciasis being present as wen as other filarial infections; onchocercias,is hadpreviously been reported as a rare occurrence in two isolated areas in thisProvince. In this search the specific reaction of onchocerciasis patients to hetrazanadmin.istration was utilized as one diagnostic method.

(a) Location and geography

The Province is bounded to the east by the Southern Province, to the northby the Central and Western Provinces (the latter also forming the westernboundary) and in the south it borders on Northern Rhodesia, Nyasaland andLake Nyasa.

The Province is roughly triangular in shape, the southern apex of the tri­aUgle being, formed by the northern end of Lake Nyasa, the eastern side by theHighlands extending from Iringa to the lake and the west side by the low-lyingarea at the northern tip of Lake Nyasa, the Poroto Mountains south of Mbeya,and finally the low-lying area round Lake Rukwa together with the lake itself.The central part of the triangle is mainly undeveloped, consi~ting of large areasof tsetse-infested bushland to the west and the low-lying valley of the great RuahaRiver in the east.

(b) Climate

The climatic conditions experienced in the area are governed by the geo­graphical features outlined above. The Highlands average 50 to 60 in, of raina year and in parts receive as much as 80 in. or more. The area immediatelynorth of Lake Nyasa has the greatest rainfall in the Territory, with over 100 in.,this..gradually decreases towards the Lake Rukwa area, which averages only 30 to40 inches. The central area receives 30 to 40 in. in the west but rather less thanthis towards the east. '

Temperatures again roughly foHow the contours, there being a mJnlmumtemperature of less than 50°F. round most of the high ground, with a maximumin most places of 75°F. to 80 OF., though the higher areas have still lowertemperatures.. The area', at the northern end of Lake Nyasa has a minimum tem­perature of between 65°F. to 70°F. The maximum temperature ranges are from75 oF. to 80°F. over most of the high ground, with slightly lower temperatureranges in some places, The lower areas round Lake Nyasa and Rnkwa and mostof the central area have a maximum temperature of over 80°F.

The population of the Province varies with the geographical features-theHighlands supporting a moderately dense population, while the area north ofLake Nyasa is one of the most densely populated areas in the Territory, Asmentioned above, most of the central area is uninhabited.

The vegetation consists mainly of varying combinations of grass and woodland.

(c) Results

Bancroftian filariasis.-The results of the blood examinations together withthe clinical findings are shown in Table No. 1.

4

Three hundred and thirty!hetrazan per kg, body weight,their skin 2 to 8 hours after thepruritus associated by Laurie (patients.

(d) Discussion

Bancroftian filariasis-.-Itfilariasis does not occllr in th!the area in which it has beenwas known previously, beingby Trant (1949). The p."esentHawking (1940) reported an inwhereas our findings show thaand Tukuyu, filariasis does noKwira 16 miles north of Tukbeing encountered. It is consi!to a radius of about 16 milesMountains are encountered Jshore, the population were un,for the detennination of incid

Onchocerciasis.-Five hunpresence of nodules on theirfast flowing streams provided awere found.

Peters (personal communsnips on six blind persons, J

result in each case.

This area of filarial infectround the head of Lake Nyaiby either wide-spread hetrazancombination of both.

The se'cond endemic focusreview of filariasis in Tanganyadult males at Kimande in Iriin the valley of the great Ruah40 miles north-north-west of ]present but will be investigat,a filarial incidence of 4 ~r I

extremity of the great Ruabathat the infection extends dowr

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5

On.cnocerciasis.-Five hundred and eighty-six males were examined for thepresence of nodules on their trunk, chest, neck and arms in the areas wherefast flowing streams provided a potential place for Simulium breeding. No noduleswere found.

Three hundred and thirty of the above were also given approximately 3 mgms.hetra.zan per kg. body weight, but although some complained of irritation oftheir skin 2 to 8 hours after the drug, none experienced the immediate and intensepruritus associated by Laurie (1951) with the giving of hetrazan to onchocerciasispatients.

Peters (personal communication) working at Njombe has performed. skinsnips on six blind persons, none of whom showed nodules, with a negativeresult in each case.

(d) Discussion.

Bancro/tian filariasis. -It WIll be seen that WIth two exceptions bancroftianfilariasis does not occur in the Southern Highlands Province of Tanganyika. Ofthe area in which it has been found, that at the northern end of Lake Nyasawas known previously, being reported by Hawking (1940) and fully describedby Trant (1949). The present survey, however, has helped to' localize it, sinceHawking (194D) reported an incidence of (?) 10 per cent as far north as Tukuyu,whereas our findings show that at Masoko, about half way between the lakeand Tukuyu, filariasis does not exist, and the finding of two blood infections atK~ira 16 'miles north of Tukuyu is probably due to non-indigenous infectionsbeing encountered. It is considered likely that the Lake ;Nyasa focus is limitedto a radius of about 16 miles from the lake, where the foothills of the PorotoMountains are encountered It was unfortunate that at Lusungo, on the lakeshore, the population were unco-operative and no random sample was obtainedfor the determination of incidence of clinical conditions.

Thi:;:, area of filarial infection localized, as it is likely to be, to a small arearound the head of Lake Nyasa is suitably situated for attempts at eradicationby either wide-spread hetrazan administration, extensive use of insecticides or acombination of both.

The second endemic focus appears not to have been described in Hawking'sreview of filariasis in Tanganyika (1940). It will be seen that the 1llarial rate inadult males at Kimande in Iringa district is 24 per cent. This village is situatedin the valley of the great Ruaha River, near an extensive swamp area and about40 miles north-north-west of Iringa. The extent of this focus is not known atpresent but will be investigated in further surveys. At Rujewa (Mbeya district)a filarial incidence of 4 per cent was found. This village is at the south-westextremity of the great Ruaha Valley, and the finding of filariasis here suggeststhat the infection extends down the valley from Kimande,

6

The high hydrocoele and elephantiasis rates found at Lugarawa in Njombedistrict c.re somewhat o-f a surprise. Although the persons were questioned as toprevious residence elsewhere, they maintained that they had only lived inLugarawa. This may indicate a focns of some other infection causing hydrocoele.In this respect it is of interest to note also that a case of elephantiasis was seen1S well.

The finding of two cases of infection with A. perstans at Kibau probablyrepresents infection in non-indigenous Africans who may have come from theheavily infected A. persIans area in the neighbouring Province.

In any case this low incidence is unlikely to be of any importance.

(e) Onchocerciasis

Although some hundreds of persons were examined, no evidence of noduleformation was found.

Pup<e of Simulium species were obtained at Njombe and Lugarawa in Njombedistrict. Those from the latter location have been identified by McMahon asS. damno.l'um and S. r.nedusteformis. In the streams of the Poroto Mountains inRungwe district lai'v<e' and pupre were found attached to rocks in fast floWingstreams.

The apparent very low incidence of onchocerciasis in an area where S. naveiand S. damnosllm have been found (Hawking, 1940) may be accounted for bythe altitude of Njombe. At 5,600 ft. it is above the altitude limit originallysuggested by McMahon for the occurrence of onchocerciasis. The temperature ataltitudes above this presumably prevents the cycle of development of the larvalforms in the fly.

The numerous' fast flowing mountain streams accessible only with difficultyalmost certainly harbour Simuliurl'!; since they have been found at Njornbe itselfand now at Lugarawa, it is not unlikely that S. ntevei and S. damnosum have awider distribution tllan is known at present. It is possible, therefore, that smallisolated foci of onchocercal infection will eventually be found in the hills roundthis part of the Province.

The possibility that such isolated foci do exist 1S supported by the work ofLebied who has shown that the presence of the "sausage" forms of Mf. volvulusin S. damnosum depresses the efficiency of the indirect flight muscles and thusrestricts. the flight range of the infected fiies. From this it is suggested that thedisease will be less widespread than the normal range of the vector.

The incidence of blindness seems to be low throughout the Province, and itcan safely be said that although the disease has been found it is of no verygreat importa.nce. The nuisance value of the biting Simulium is probably moreimportant, particularly to the Europeans.

(2) Filariasis in the SoutheliThe survey described he;

July, and was completed in No,

METHODS

The Province is dividedof these was visited, and a vilhvillages were selected at rand·was impossible to select a viImunity of about 1,000 person:very few and far between innumbers of bloods obtained in

The administrative authorivisit and to help to allay thlstrange European, "out for blobackward community. When pthe people to come at night, ablood specimens were taken toThe necessity for taking the bgetting the same co-operatiogiven us if we had btype of work is naturally undonly volunteers could be examdesired statistically, but undeunless considerable time was toin mind that the presence ofdangers to those travelling at nvillages did not make the task

When our visit was beingmade of hydrocoeles. The pea]gated and that this disease isworm into the skin and that la'story was told in the simplest teobjects of our work were descritnature, it is unlikely that the rwho told his people we wenmOre people than would have'

Bloods were taken from (from two persons were takenapproximate age of all persons'and scrota for evidence of filarmade of the scrota.l inspectiorlaughter), it is considered thatnon-random £ample. Hydrocoeby the people.

The bloods were dried ove:the next few days and examinerin the laboratory by traineddirect supervision of the write!

independently and the two reSIslide was examined by the w[negatives. The number of micr

;

~

found at Lugarawa in Njombe. persons were questioned as tothat ~hey had only lived in

er infection causing hydrocoele.t case of elephantiasis was seen

A. perstans at Kibau probablywho may have come from thering Province.

be of any importance.

~amined, no evidence of nodule

'ornbe and Lugarawa in Njombe'en identified by McMahon asns of the Poroto Mountains inached to rocks in fast flowing

:iasis in an area where S. ntevei940) may be accounted for by'e the altitude limit originallyhocerciasis. The temperature at~ of development of the larval

accessible only with difficulty'e been found at Njornbe itselfevei and S. damnosum. have apossible, therefore, that small

ly be found in the hills rou.nd

is supported by the work oflusage" forms of Mj. volvulusdirect flight muscles and thusu this it is suggested that therange o{ the vector.

lroughout the Province, and itbeen found lit is of no veryg Simulium is probably more

7

(2) Filariasis in the Southern Province of Tanganyika TerritoryThe survey described here was started during the months of June and

July, and was completed in November, 1952.

METHODS

The Province is divided administratively into a number of districts. Eachof these was visited, and a village in each geographical region was surveyed. Thevillages were selected at random by the local authorities, but in some cases itwas impossible to select a village having sufficient numbers of people. A com­munity of about 1,000 persons is considered ideal, but viHages of this size arevery few and far between in this sparsely popuLated province-hence the lownumbers of bloods obtained in some places.

The administrative authorities were asked to assist with propaganda for ourvisit and to help to allay the fears and snspicions that the appearance of astrange European, "out for blood", at night, inevitably produces amongst such abackward community. When possible, a film show was put on in order to enticethe people to come at night, a drop of blood being the price of admission. Nightblood specimens were taken to determine the incidence of W. ban.emjti infection.The necessity for taking the bloods during the hours of darkness prevented ourgetting the same co-operation from the Africans as ;would have beengiven us if we had been able to work by day, since oUrtype of work is naturally under suspicion of being some fprm of witchcraft,only volunteers could be examined and bled. Such a method, leaves much to bedesired statistically, but under the circumstances little more could be doneunless considerable time was to be devoted to each village. It must also be bornein mind that the prese.nce of lion and other wild beasts presented very realdangers to those travelling at night, and the very scattered arrangement of manyvinages did not make the task of attracting people easier.

When our visit was being publicized by the administration, no mention wasmacie of hydrocoeles. The people were told that eJephanti.asis was being investi­gated and that this disease is spread by a mosquito wlUch introduces a smallworm into the skin and that later the person may develop the disease. A suitablestory was told in the simplest terms of the nature of the disease, and the aims andobjects of our work were described, nevertheless, in spite of much hard work of thisnature, it is unlikely that the people understood what was happening. The chiefwho told his people we were inoculating them against the disease prodncedmore people than would have come with hours of persuasion!

Bloods were taken from as many people as possible after 8 p'.m. Bloods{rom two persons were taken on each numbered slide, the number, sex andapproximate age of all persons being noted. Legs were examined for elephantiasis,and scrota for evidence of filarial disease. Since no mention had previously beenmade of the scrotal inspection (which is usnally carried aLIt amid uproariouslaughter), it is considered that the results are not unduly biased in spite of thenon-random sample. HydrocoeJes are not generally associated with elephantiasisby the people.

The bloods were dried overnight, stained with hrematoxylin and eosin withinthe next few days and examined for microfilarire of W. banaojti and A. perstansin the laboratory by trained African laboratory assistants working under thedirect supervision of the writer. Each slide was examined by twO' such Africans

independently and the two results compared. If the results differed greatly, theslide was examined by the writer, who also examined 10 per cent of all thenegativecS. The number of microfilarire Were counted.

8

Since the sample of population varied in the' villages-in some cases adultmales only; in other males and females, but no children; in yet others manychiLdren-and since it is recognized that the micro·filarial rate varies with sexand age, the microfilarial rate of a village is defined as the incidence of micro­filarire of W. bancrofti found in the blood of adult males (over the age of 16).Since only one blood specimen was taken from each individual at a time severalhours before the microfilarial peak, it is considered that many cases of micro­filarremia were missed. The microfilarial rates as given in the table are there­fore almost certain to be below the true rates of the villages concerned.

The number of microfilarire counted in the blood sample gives some ideaof the microfilarial density per thick drop of blood (approximately 30 cmm.).Since the bloods are taken over a period of time when the microfilarial countsare rising, such a method is considered to give a reasonably accurate indicationof the density of microfilarire.

LOCATION

The Southern Province borders on Portuguese East Africa to the south; tothe east it is bounded by the Indian Ocean, and to the west by Lake Nyasa. Tothe north-west lies the Central Province of the Territory.

Topographically the area consists of a coastal plain with a rising hinterlandintersected by a number of rivers. Heights vary from sea level in the east to9,000 ft. in the west.'

CLIMATE

The Indian Ocean, with the north-east and south-west monsoons on the onehand, and the mountains in the west on the other hand, determine the climaticcondition~ in the Province. The r.astern half of the area has an average of 30 to40 in. of rain a year, the western half a little more than this, with the extremewest averaging b.etween 50 and 60 inches. Throughout the Province, the rainfalls mainly bet~een November and March. The maximum temperature in theeastern half of the area is over 85 e F., whereas in the west it is slightly lower thanthis (SO°P, to S5°F.) apart from the mountainous region where the temperatureis lower still. '

In the cool s'eason, the narrow coastal belts have an average of over 70°F.,while over the rest of the eastern half of the Province the temperature is between65°P. and 70°F. In the west the temperature is lower, except for the shore ofLake Nyasa (65 e F. to 70 e p.) and the mountains (55°F. to 60° F.).

The isopleths run north-south. At the coast the mean annual vapour pressureis in the region of 26 millibars and it diminishes steadily further inland to abollt18 rnillibars half way across the Province. This is the recording for the rest ofthe Province, willi some slight reduction in the high ground.

VEGETATION

A coco-nut belt on the coast gives way to woodlands and wooded grasslandsfurther inland. The area on the whole is dry and waterless except during therains, as drainage is facilitated by porous soils.

POPULATION

This Province is one of the least populated in the territory, principallyowing to large tracts of waterless country and the tsetse fly. The coastal belt andthe Rumuva River area in the south are well populated.

;..

:~l

';'

The inhabitants of this Precently they travelled little.groundnuts, and the addition~

to travel much more than was I

RESULTS

The accompanying tablemicrofilarial incidence of W. ,and adult females are given,microfilarial rates are calcuh:filariasis-the clinical rates arfor A. perstans infection.

The "filarial raie" JepreS I

microfilarremia or clinical fila!

Climatic data are also giv'

DISCUSSION

Hawking (1940) producelof filariasis in the territory.other investigators, and in allof bancroftial filariasis wasslides-thus no accurate estirn:be made. The area with a cs.:both for W. bancrofti and A.the great variation of incidenthat a high incidence is founddecreases, except in the rive(Kilamarondo). Generally Spl

mean vapour pressure, a low(

The highest incidence wa:(in adult males) of over 70 pthat in a highly endemic filarlation are infected. In this vilJcorrect when it is rememberedbefore the generally acceptedwould almost certainly be fOlinfection was found to be Vel

High rates were also reeldence was found. Although t2,000 ft. escarpment, where cof the district.

Mikindani district coversthe River Ruvuma. The highcoast, 54 per cent a shOlt dis

ln Newala and Nasasi diat the' coast. These districts 1peratures than places nearer tlower.

In Tunduru district it is ~

reached. No bancroftial diseaand very little at Npelembe, 50

,..

ae villages-in some cases adult10 children; in yet others manyllcrofilarial rate varies with sexfined as the incidence of micro­dult males (over the age of 16).each individual at a time severalered that many cases ':If micro­IS given in the table are there­. the villages concerned.

, blood sample gives some ideaload (approximately 30 cmm.).

Je when the microfilarial countsa reasonably accurate indication

:se East Africa to the south; toto the west by Lake Nyasa. To

Territory.

11 plain with a rising hinterlandfrom sea level in the east to

outh-west monsoons on the oneer hand, determine the climaticle area has an average of 30 toare than this, with the extreme)ughout the Province, the rain~ maximum temperature in thethe west it is slightly lower thanIS region where the temperature

have an average of over 70 o P.,'ince the temperature is betweenlower, except for the shore of(55°P. to 60 oP.).

Ie mean annual vapDur pressuresteadily further inland to aboutis the recording for the rest ofhigh ground.

10dlands and wooded grasslandsod waterless except during the

:d in the territory, principallytsetse fly. The coastal belt and

tted.

"

9

The inhabitants of this Province belong to many different tribes, and untilrecently they travelled little. The development of the area, particularly forgroundnuts, and the additional transport facilities available, enable the Africansto travel much more than was possible previously.

RESULTS

The accompanying table summarizes the results of the village surveys. Themicrofilarial incidence of W. bancrofti and A. perslans for children, adult malesand adult females are given, together with the clinical rates. The bancroftialmicrofilarial rates are calcUlated for the number of persons free of clinicatfilariasis-the clinical rates are determined for adults examined as are the ratesfor A. perstans infection.

The "filarial rate" represents the number of adults-male or female-withmicrofilanemia or clinical filariasis in the population examined.

Climatic data are also given for each village.

DISCUSSION

Hawking (1940) produced a map of Tanganyika showing the distributionof filariasis in the territory. His paper was based principally on the work ofother investigators, and in all reports from the Southern Province the occurrenceof bancroftial filariasis was demonstrated by the examination of day bloodslides-thus no accurate estimate of the incidence of the bancroftial disease couldbe made. The area with a calculated incidence of 5 per cent' or more is shownboth for W. bancrofti and A. perstans infection. The present tepDrt demonstratesthe great variation of incidence throughout the endemic filarial area. It is seenthat a high incidence is found at the coast and for some way inland but graduallydecreases, except in the river valleys where a high incidence is still found(Kilamarondo). Generally speaking, the fall in incidence follows the fall inmean vapour pressure, a lower mean annual vapour pressure occurring inland.

• The highest incidence was observed in the Kilwa district, where filarial rates(in adult males) of over 70 per cent were found. O'Connor (1932) consideredthat in a highly endemic filarial area probably 100 per cent of the adult popu­lation are infected. In this village it is easy to imagine that this hypothesis iscorrect when it is remembered that the bloods were taken at 8 p.m.-four hoursbefore the generally accepted peak period, at which time more positive caseswould almost certainly be found. In thi;> area also the incidence of A. persl(111Sinfection was found to be very high.

High rates were also recorded in Lindi district, but at Rondo a lower inci­dence was found. Although this. place is near the coast it is on the top of a2,000 ft. escarpment, where colder conditions are experienced than in the resta f the district.

Mikindani district covers a smail coastal area and includes the estuary ofthe River Ruvuma. The high rates found in this district-63 per cent on thecoast, 54 per cent a short distance up the river-are what one would expect.

In Newala and Nasasi districts the rates are shown to be lower than thoseat the coast. These districts have much higher ground and slightly lower tem­peratures than places nearer the sea; the mean vapour pressure also tends to be[ower.

In Tunduru district it is seen that the edge of the bancroftial area has beenreached. No bancroftial disease was found at Mbesa, near the Ruvuma River,and very little at Npelembe, 50 miles north-west of Tunduru.

Iv

It will be observed that infection with A. perstans appears to affect infantsmore frequently than does W. bancrofti infection.

Songea district appears to be almost free of bancroftial disease-this is notsurprising, since much of the area is On high ground. At Lituhi on Lake Nyasa arate of only 3 per cent was found. It was expected that in this area a higherrate would be found, and it is interesting to note here that at the northern endof tbe lake very high rates have been recorded (Hawking (1940), Jordan (1953)).The two places are on the lake and thus at the same altitude, and temperaturerecordings' are very similar, but at Lusungu the rainfall amounts to over 100 in.per year, whereas at Lituhi about half this figure is recorded. It is thought thatthis difference is probably sufficient to account to a large extent for the differentfilarial rates noted, since the high rainfall at Lllsung,o will result in a muchincreased seasonal mosquito population, and the seasonal vapor pressure willbe high, thus facilitating transmission of the disease. Other places in Songeawere free of the disease.

The results from Ruponda district are not as complete as elsewhere sincethe investigating research o·fticer was unable to carry out clinical examinationsowing to, illness. Bloods were, however, taken by the African laboratory assistants,and the results of these are shown in the table. It will be seen that in thisdistrict high microfilarial rates were found.

The results obtained during this survey are consistent with our view that ahigh incidence is found when a high temperature is combined with a high relativehumidity.

The endemic area of A. persIans infection is very much smaller than theW. bancrofli area" bjjt very high rates were found in some villages-villages alsohaving high bancroftial rates-viz. Nanjirinji, Likiwage in Kilwa districr, andRuponda, Liwale and Kilamarondo in Rupondo district. It must, however, benoted that the disease does occur in other areas free of bancroftial infection.

A number of infection were found in infants. The ages of Africans areinvariably unknown to the indi\;iduals themselves, and all ages have, therefore,to be estimated. In adults fairly large errors may be made, but in infants it isconsidered that one can, estimate age to within a few months. When ages of theinfants below wete noted, the tendency was always to increase the age slightly.Bearing this in mind, t.he following are the youngest infants found infected,together with their village of origin:-

..._--- ---- -. ~--------,---'-~-~

40 % and higher ! 632

130

Totaladult malexamine.

Villageswith

mf. rates

0-19%

As mentioned above, J

elephantiasis when considerin;the table that in this part ofportance, and hydrocoeles arthat in some places over 30to be affected. This differenclfestations is interesting, sincemuch higher elephantiasis raconfirms Brygoo's (1951) vie~

t'estations varies locally, in Sj

further demonstrated wheninvestigated. In all, seven ca:Likiwage in Kilwa district.

A rough estimate is malbancroftian filariasis througbcof people are infected and if,a cause of much ill health, it .filariasis must be regarded as

When the villages are grmales and the clinical rates dis a very much bigher incidethe highest rates:--

It will be shown in a fufilarial rates the microfilarialthat the incidence of clinic~i

the microfilarial density in I

Departmental Report for 195C

The youngest patient ocwho had bilateral disease of 1elephantiasis occurring in chichildren was seen.

20--39% .. I 1,136

An analysis of the sex l

that only eight occurred in mwhereas the remaining 11 we)

The survey describedA. perSians is more widesprea,indicated.

A. perSians.

A. perstans; W. bancrojti.

A. perstans.

I Infection ----

I1-----·-I A. persIans.

, A. perSians.

i A. persians; W. bancrojii.

I A. persIans.iI

I A. persIans; W. bancrojii.

8 months (approx.)

9 months (approx.) ..

Age

9 months (approx.)

12 months (approx.) ..

12 months (approx.)

18 months (approx.) ..

18 months (approx.) ..

\8 months (approx.) ..

Village

Likiwage

Nanjirinji

Kilamarondo

Namasakata

'"'.

bancroftial disease-this is notmd. At Lituhi on Lake Nyasa a~cted that in this area a highere here that at the northem endHawking (1940), Jordan (1953)).same altitude, and temperature

:ainfall amounts to over 100 in.e is recorded. It is thought thatI a large extent for the different~usllngo will result in a muche seasonal vapor pressure willisease. Other places in Songea

as complete as elsewhere sincecarry out clinical examinationshe African laboratory assistants,.e. It will be seen that in this

;onsistent with our view that a:s combined with a high relative

is very much smaller than theI in some villages-villages alsojkiwage in Kilwa district, andI district. It must, however, be;ee of bancroftial infection.

nts. The ages of Africans areI, and all ages have, therefore,I be made, but in iufants it isfew months. When ages of the.ys to increase the age slightly.ungest infants found infected,

I Infection

-..-1 A. persians. ----­

A. persians.

A. persians; W. banerO/li.

A. persians.

A. persians; W. banera/ti.

A. perstans; W. bancrojii.

A. perstans.

A. persians.

r.l'tans appears to affect infants

."

11

The survey described indicates that infection with W. banerafli andA. persians is more widespread in the Southern Province than previous reports hadindicated.

As mentioned above, most workers tend to stress the importance ofelephantiasis when considering the effects of the disease, but it will be seen fromthe table that in this part of Africa elephantiasis is not of any very great im­portance, and hydrocoeLes are likely to be much more troublesome-it is seenthat in some places over 30 per cent of the adult male population were foundto be affected. This difference between the incidence of these two clinical mani­festations is interesting, since with similar microfilarial rates in the Pacific verymuch higher elephantiasis rates have been found (Buxton, J928), but it furtherconfinns Brygoo's (1951) view that the occurrence of the different clinical mani­festations varies locally, in sp~te of similar microfilarial incidences. This fact isfurther demonstrated when the incidence of elephantiasis of the scrotum isinvestigated. In all, seven cases were seen, and six were in the same village­Likiwage in Kilwa district.

An analysis of the sex distrihution of the 19 cases of elephantiasis showsthat only eight occurred in males, of whom 1,790 were, examined, (0.4 per cent),whereas the remaining 1l were found in 1,359 females (0.8 per cent).

When the villages are grouped according to the microfilarial rates of adultmales and the clinical rates determined for each group, it is ~pparent that mereis a very much higher incidence of clinical manifestations in the group havingthe highest rates;-

Villages Total No. Per Cent No.with adult males of cases of incidence of of cases of

mf. rates examined hydrocoele hydrocoele elephantiasis

,---I0-19% 130 9 7

20-39% 1,136 106 9

40% and higher 632 204 32 6

It will be shown in a further paper that in the villages with higher micro­filarial rates the microfilarial densities are also high. It thus seems not unlikelythat the incidence of clinical manifestations is dependent, in part at least, onthe microfilarial density in the area, as was put forward by Laurie in theDepartmental Report for 1950.

The youngest patient observed with elephantiasis was a boy of 14 yearswho had bilateral disease of his legs. Jordan (1952) reported four other cases ofelephantiasis occurring in children below this age. No case of hydrocoele inchildren was seen.

A rough estimate is made below of the number of adults infected withbancroftian filariasis throughout the Province. It shows that very large numbersof people are infected and if, as some beheve, the late effects of filariasis area cause of much ill health, it is obvious that in parts of this province bancroftianfilariasis must be regarded as a disease of major importance.

TABLE n.-FILARIASIS IN THE SOUTHERN PROVINCe, TANGANYIKA TERRITORY.

N

PJ _. p.1 ~ 0 a '?'~. 8 Z~::s~g~~gs(p .;-'- ::r::r ......... ~ (1) _ ~O~o::r::r ... zo:::: 0 s:::: CD (Jl 0 _. 0o $, '& ~ q" ,..." 0 P ~ ;:; c~o r-+p:lp;!~P'O"~ q....... ~ (J) fA ~. ~ ....... ';:::t ~< 0::r ~ .... n 9::r~ 00,<: ~o .., g.::r"" ~ 0 goo -e:~~ _. CD ~ 0 ~ O·~ ~c:: 0 '" C> "'"'0 l" d e;

OQ a-~ ~~~ 8"=:rc/).~o' ..... go~..,~ 'lj::J~S- .... ~g.e:.,"'~s:- 0 (l> e:., 0;' QQ E! f, 0 ~(l>Sfcr~ ,....~(Jlt"""B1>'<:!Q.~~9~d~e;~(b _ (I'l 9~~ l-'i)_... -.

~ g-~~>~~ -0(1)<=,'0::::;'-"" '-'(rJ("D~~~~~ r:nc: o.~''''''''' d '< '<0 ...] II';'3 v;.;j. _ ~ ~ v) ; S'S l" ........ ' ....·01>''O'<;;l <: ~ 3;> >-3;:l,o ........ (1) ?>,...,t1>N' ~ 0 '" 3 0''< ;J: ~8. ~ ~~ ~ ft" ~ ~ :q" po. ~ (JQ 5";>< 0.. d ::::.~ <1 ~. ~ 0. a _. <n' ~o<:~ ... "' ...... Sl~ (\) ~ 0. -'.-;0. (") ;!;. >­--::rd d::rS;::,;l':l1

1>' .... 5'-00 ..... -0;< riQ" lij" tr f:IJ _. O'Q-... g 0.. 5' d d ~_. fJ) a (\) c. 0... ~ CIJ':;l __ ._,..,

ot1

-- ~.::J ~- '"'" ~:::

Zi·

0>-o d", ....?> -.

OQ (JQ ......~ g \0_. (I'l t...J,

0. ~ a

'"(1)0.

~UJ(IJ i=t'" ...~ d:=tOQ'" ....::r

f-r1,?_.~ ..-

~WX~ >Cl '"[~. ~

;:;n §.'" '"....... ;to~ (;;'u-.

~o>I>' 0 d....... U) ......

'" ?> tiQ..... {JOo~;;:;. 0 ::J \0....... _. rJ) v-.

, ......o. CGO(1)

0..

Ii

... iOo> t1x UJ ....

g~n ::;.... 0

~ ~... .;'::l 0

o'd 0o p.Q :..;rt! c:

~;4l~ @c: ::J

f;f os.

Alti­tudefeet

.......... ~::r ::r ~, 'D00 ...... LI\

"'::r N;'; (I> ~;:o() ~§;o t<1o .l---'-S:::: (JJ (f)S ~ .......... C

"'0 0". o' 0 ~I>' 0 CJ ....., .....::J P '" ..... C/)

'<: '" ;::r_. 0 ("D

d>--j"""(JQ::r ~t:l'>(I> ~ 0

~~~oo*.., (1) 0(tl -:I) 0-'v.o ~ Od. 5f-.- S-~~G

Village

·Cases of elepbantiasis of the legs with hydrocoele,tHydrocoele cases include all cases of genital filarial disease, i,e" hydrocoele and elephantiasis of scrolllm,

SOUTHERN PROVINCE RESULTS:-W. bitncrofri: rates are for persons not showing elephaut.iasis or hydrocoele,Clinieal rates: represent incidence of hydrocoele or elephantiasis (percentage for e(ephantiasis nol given since it would be so small in most cases),Filarial rates: represent total rate of filariasis-mierofilaraemia, hydwcoele and eLephanliasis.A. persIans rates: based on total numbers examined, i.e" clinical and non-clinical cases,All figures to the nearest whole number.No cases of onchocerciasis seen but in t.he mountains there are streams in certain of which there is breeding of Simuliidae.

3 I>' ::tJ '0_. ~ p;- 0p ...,::\.it ::i' Pi I>' . 1

("D en 0 ,....,

,~(1) ~.~ ~~ ~ v:;. ()

o l" 0f!l.3 g 8.. ~p ..... ..,(JQ ... 0....... -O~-(I>.go ..... OQ.-+ ::r :::::3 I-f

~g.~]~0.. ~ ('D ::::t _.to-, _.0...-+ ~

o '"~d 0 c' c:: a.-nl-l;e.;?,---

District

Ruponda

Masasi

Tunduru

Mikindani

Newala .,

Lindi

Songea "

\

Non-clinieal Cases Clinical Rates 'II Ban· [Non-clinical BloodsTemperature '. -'1--- croftian I .positive

, , ~ Incid~nce M/ Males Femat6s' Filafial: MJ. perstansRalQ- i ~ bancroftl 1n blood' --.-------- Rates I

fall i__,'__ ~ 1-------- I Ele- I Ele- --------ins. r ~ ,8 .: Adults Hydrocoelet p~a':l- I phan- -----', Adults

M M' I'" "" Chll- 1------· . hasls , tmsls I ~ I CM- ----of'l ;F' 5. ~ dren 'I Males IFemalesj--,-o-----r--o-- 11 • -';x I dren Males Females

\. I~ I :5' ----1---, Nos., % Nos.! % "'~, S ---------

__ 1 . .--I--~~-~.%+vel %+ve! %+~,!~en seen_l-.!een .~! ~ I~_+ve %+ve %+ve

Kilwa I Nanjidnj; '500 30--40 I >85 65-70 24 100 9 I' 55.1 40 t- 46 37 2 (1)* 0 73! 40 I 12 41 'I 32Likiwage 750 30-40 >85 65-70 24 2,000 9 63 40 I 77 38 0 1 77' 41 24 44 39Kilwa 0 30-40 >85 >70 26 3.000 I 18 73 none Inot random sample 73 0 6

scenMcllinga 0 30--40 > 85 > 75 26 3,000 I 19 45 25 23 21 1 3 54 26 0 0 0Rondo 2,000' 40-50 >85 65-70 26 500 0 18 0'1 1 3 0 0, 21 0 0 0 0Mtama 400' 30--40 > 85 65-70' 25 2,OlJO 15 46 25 18 20 3 (2)* 1 '58 26 0 I 0 0Ndumbwe 0 30-40 >85 >75 27 1,400 31 44 42 18 35 0 2 63 144 0 0 0Kilayo ,100 30--40 >85 65-70 27 1,000 19 40 35 13 22 0 5 54 38 0 0 0Namikuda . , 750 30--40 >85' 65-70 25 1,200 small 22 111 72 13 0 1 35 1{ 0 0 0

Nos.Newala 2,000 30--40 >85 65-70 25 2,000 0 15 3 6 4 0 0 I 18 3 0 0 0Kitanga:ri 1,750 30-40 >85 65-70 25 1,500 6 26 20 II 7 I 0 O· 31 20 0 0 0Chydia 2,000 30-40 >85 65-70 24 1,000 9 13 \10 3 I 9 I I 0 24 10 0 0 0Lulindi . , [,500 30-40 > 85 65-70 24 1,000 I 22 10 5 6' 1 0 28 10 0 3 3Namasakata 2,000 40-50 80-85 60-65 18 400 I 0 18 0 3 8 I 0 0 24 0 6 33 23Mbesa .. 1,500 40-50 80-85 65-70. 18 1,000 0 0 0 0, 0 0 0 0 0 0 3 [4Nampungu,. 2,500 40-50 80-85 60-65 18 700 small 17: sma,1l 2 I 9 I 0 0 23 I 10 6 19 10

Nos. '1 No" I IMpelembe .. 3,500 40-50 80-85 60-65 18 300 0 0 0 I 5, 0 0 5 I 0 4 20 4Lusewa .. 2,500 40-50 80-85 60-65 18 500 0, 0 I 0 0 0: 0 0 0 I 0 6 37 15Myangayanga 4,200 40-50 75-80 55-60 16 700 O! 0 0, 0 I 0 0 0 0 i 0 0 0 0Lituhi 1,500 50-60 80-85 65·-70 17 1,200 0 0] 0 i 2 'I 3 '0 0 3 I 0 0 0 0Ruponda 1,200 30-·40 >85 65-70 24 1,000 'small 22 small 112 8 I () - 1 28 - 33 44

I, Nos, Nos. J

Liwale 2,000 30--40 >85 65-70 20 2,000 5 35 13 not reported 35 13 21 50 20Kilamarondo, 1,200 30--40 >85 65-70120 11,000 I 10 49 38 I not reported 49 38 Hi 62 I 51

s­~(1) ~

'" (1)::r no (1)

~ ~

&'~§,~n.., 0g,d~Er.., (I>I1l38­p;' ~'

,.

",

!-'''',

l

Symptoms and Signs

(1) Skin Tests with An.tigens

The African is still in a primitive state and the taking of night bIo04s insurveys may be difficult and even dangerous; further, such a method gives afalsely-low index of the incidence of bancroftian filariasis in any community.Alternative methods include serological and skin reactions to antigens. Fairley(1931) first suggested this method; in his report he did admit, however, thatsensitivity to filarial antigens may persist long after all other signs of infectionhave disappeared. We have investigated this problem since r949; previous resultsare summarized below:-

INTRODUCTORY

Ninety years ago Demarquay found Mf. bancrofti in flu~d from a hydl'o­colele and 80 years ago Lewis found these forms in human blood. From thattime on attention has been focused on these larval forms; little or nothing isknown of the natural history of the infection and little or nothing is knownof the factors operating to produce elephantiasis and hydrocoele. This negleetof the basic pathology is shown most markedly in the testing of new dnu~~'; insuch tests the effect always recorded is microfilaricidal activity of th.e ··d.rugalthough such is at the best only an indirect measure of efficacy. In this, a.sin previous reports, we have recorded such effects, but only as an index of theaction of the drug on the adult worm or at least on the adult female worm.

1952 RESULTS

Most of the work In the literature recommends dosages of 0.01 or 0.02 ccs.with dilutions of 1: 8,000, 12,000 or 16,000. Accordingly it was decided to trythese dilutions. The results have been very disappointing as will be seen fromthe accompanyIng figures.

The control group in all these experiments is considered to be of great im­portance, and at present unsatisfactory. In an endemIc area of bancroftianfilariasis Is not considered justifiable to put into the control groups persons whoare free from elephantiasis or hydrocoele and have no blood infection as deter­mIned by a single thick drop preparation.

Recent work on the clinical examination of so-called "control groups" andthose showIng microfilar<emia shows that one or both spermatic cords are enlarged

-

Control

Cocassolution

Salineextract

O. volvulus

diagnostic value.

0·1 mis.L. cariniiD. medinensis

0·1 mls.Control0·1 mJs.

(Normal saline with. 0'5 %phenol.)

0'1 % saline extract with 0'5 % phenol preservative.False-positive reactions almost as com.mon. as reactions in

infected individuals.

0·1 mls.D. immitis

D. immitis D. medinensis L. carinii

at first 0·25 mis., later 0'1 mls.Saline lipoid-free lipoid-freeextract extract extract

I /l ,000 dilution antigen in all cases.even poorer than in 1950, i.e., of no

1951Antigens usedDosage i.d.MateriaL

1950

AntIgens usedDosage i.d.

StrengthResults

StrengthResults

00 I 0_C'l '()

-_. __._--- .-:.v-

00<t 0C'l '"v-<t ""'''' '"u

~

v-0

oc~. -co ~<'. N-.Sc;

00 i M'X> S-C"") ! '"0'" ~

O':""!OO ,,",G- " ]N ":'"")'"::;- .0

-------- '0'3 ~0

00 I ~ ti'j~ '0

E " on~

u

"0 '" c:,000

.iii :0t> c: ~'0'"0 '" u '-'___ ~B

'""' > -0

co 0 ';;)''"

0("')00 cc .:3 "0 '""''' if>'= ;..

.... " .~ '"----00 '" ~C 'n '"c:c: '" ",.~

]ONN ~ .~ '"0- - '" ." a'~ ~ .c

------- 0:; ~C:f/J ~

r:>.'"'" <....- . "0 Q)..c: v 0

oo-;;o~ooc: _c_

'" "'''''' C§Z-M .£

~ a3.~ .~

'"~..2"'O.5

0 ~~§y '"<.> <.>

OON ""'0- ::' o~~ g .SN <:'"l<t "0 2~:gc:: '"--.._-- .£ ~~o"'C 8

.~ ~~ ~ '"oo:a ~~V")o oJ "L.,,--,,>,_ b~z - o,~...c:: ~ '"0.> (Il oZl " ..... :£- .__.-

'" '~'~'§~ '"000 00 '"-~ ''=::: {) :£000 00 ,... ~ Q.) ....t"-<"iq, 00

~~~v.,

C'l'....:: "0 -=0.<d -a ",$'''; u,

,o .... <t 00 ".~ "*~~~~ c:-'-'.~-~N C'lN "''" on 0 .~.5~~ C

000 00 0_ .s~ E E 0"' ........ ........ .... '" ~ 8·~ ~0

lit I I "O~

~..,..,..,""'''"' :>"~

"''0'" '0\0 ...o~ ~o~----- .con rn ..... ·C i2 . ~0""',,", ""'''"'

~<.......,.lR~tUlt-:~

00""00 """" ';i ° °..c::<i:.Dllc~£/\ 11/\ '" ~'O'o §c;"'''on", c: c::::lO-._-_._- "", 082_°.0000 00 -(j ~c:roC'i:iVt:

~~d'<t<t

$~ &~~§] ~. I00

q-l()('r. ('r.(""'.: Q,) .I. <5 'g ~ d ~ :a "'C tr.I.~._ ...... o ..... ·~

88-8 00 V].=! ~ tUC.,\j ~.~00 '<Ii (J;:::J _ (a) c: Q):-o ll>C'l,,",N ON~~-"~" (....f--... .~.E lZ cd rJ'J ~ ~ ~ 4>

t::!1I":~~~.oc:g

'"cd .-I- ~A" 4.)'-

on '0 ..c:::~~e~~£..cuc: '"0 S ~ ~.~ ~~ ~ ~ ~ §'" <:::>. '" 0

~-g6~~~~:;~'" "0 ....tp...... c ,,'"

c;g Ou~"-:'-l\..;~I3,)v.J".<:1 0

1;J'l 8~ .~~Cd ~ ~~'";:Ie~.::1~ .~~ 0"'C Z ~ t,) ..... "'-: c:1

,.J~ ~ >la:~'S a- ~t.C l)

'";';~~~o;i;~~z

;:,'0 0'= '"0

"";:l

"'-<

14

in 30 out of 53 (56 per cent) of the microfilarial cases, compared with 14 outof 46 (31 per cent) of the so-called control group. Although it is realized thereare different causes of thickening of the cords, it is considered that the majorityof cases in a filarial endemic area will be due to filariasis and that the figure of31 per cent obtained for the control group indicates that a large proportion ofso~cal1ed "apparently filaria-free" cases are probably filarial. (Further supportfor this was obtained during the Southern Province work.) This is in keeping withO'Connor's view that practically 100 per cent of persons in an endemic area areinfected and that the general method of examining for elephantiasis, hydrocodeand microfilanemia is not an adequate indication of filarial incidence in acommunity.

In view of this, it is suggested that little serious attention be given tothose in the present control groups, as they are likely to confuse the issue.

. The following results have been obtained using the original criteria, i.e. bloodnegative, and absence of hydrocoele and elephantiasis for the "apparently filaria­fr~e group".

Control cases with a history of adenitis or evidence of thickening of thespermatic cord (but from the above criteria in the "apparently filarial-free"group) were investigated separately and considered as filarial cases; the results ofthis are shown below..RESULTS OF SKIN TESTING

Criteria for positive reactions were:or 30-minute reading.

.any increase in size of bleb at 10-minute

(b) Filarial case~:

1/8,000. Twenty·tl1/12,000 Two po,1/16,000. One pas

Cases exclude.1/12,000. Fa'll1/16,000. Thr,

(3) L. carini!.(n) Filaria-free cases:

1/12,000. Seven pc1/16,000. Five PO!

Cases excludec1/12,000. Two1/16,000. Two

(b) Filarial cases:

1/12,000. One posi

1/16,000. Three pc

Cases excluded

1/12,000. Thn:

1/16,000. Thre

(1) D. immitis-quantity 0.01 ccs.(a) Filaria-free:

1/8,000. Fourteen positive out of twenty-three.1/12,0'00. Six positive out of twelve.1/16,000. Six positive out of twenty-two.

By eliminating cases in which there was a control reaction, or thosein which there was a history of filariasis or adenitis or evidence ofthickening of the spermatic cord, the following results are obtained:-

1/12,000. One positive out of five.1/16,000. Two positive out of twelve.

(b) Filarial cases:1/8,000. Fourteen positive out of twenty-nine.1/12,000. One positive out of two.1/16,000. Five positive out of seventeen.

Cases excluded from the filaria-free group above­1/12,000. Three positive out of five.1/16,000. Two positive out of six.

(2) D. medinensis

(a) Filaria·-free :1/8,000. Eighteen out of twenty-three react.1/12,000. Seven out of twelve react.1/16,000. Six out of twenty-two react.

Excluding persons as in 1 (a) above-­1/12,000. One out of five reacts.1/16,000. Two out of twelve react,

D. immitis ..D. medinensisL. carinii

D. immitis ..(Cases excluded from filari,

group) ..D. medinensis

(Cases excluded from filari,group) ..

L. carinii(Cases excluded from filaria

group) ..

From the above limited1/12,000 dilution, but much

~.

t .....'.

",

15

al cases, compared with 14 outlp. Although it is realized there, is considered that the majority) filariasis and that the figure ofcates that a large proportion ofbably filariaL (Further sup,port~e work.) This is in ket'ping withpersons in an endemic area are

ing Ear elephantiasis, hydrocoeletion of filarial incidence in a

serious attention be given tolikely to confuse the issue.

19 the original criteria, i.e. bloodtiasis for the "apparently filaria-

(b) Filarial cases:1/8,000. Twenty-three positive out of twenty-nine.1/12,000. Two positive out of two.1/16,000. One positive out of seventeen.

Cases excluded from 2 (a) as in 1 (a).1/12,000. Four positive out of five.1/ 16,000. Three positive out of five.

(3) L. carinli.(a) Filaria-free cases;

1/12,000. Seven positive out of twelve.1/16,000. Five positive out of twenty-two.

Cases excluded as in 1 (a).

1/12,000. Two positive out of five.I /16,000. Two positive out of twelve.

t' evidence of thickening oE thein the "apparently filarial-free"~d as filarial cases; the results of

'ease in size of bleb at 10-minute

(b) Filarial cases:

1/12,000. One positive out of two.

1/16,000. Three positive out of seventeen.

Cases excluded as in 1 (a).

1/12,000. Three positive out of five.

1/16,000. Three positive out of five.

TABULATED RESULTS

Filaria Free

12-2 positive12-2 positive12-2 positive

5-1 positive5-1 positive5-2 positive

1/8,000 I.......,_1_/1_2_?_00__1__1_/1_6_,0_00__

23-14 positive \I 23-18 positive II

I -

D. immitisD. medinensisL. carinii

was a control reaction, or those!isis or adenitis or evidence oflHowi ng results are obtained;-

I-three.

J.

e. Filarial Cases

1/8,000.y-nine. I1/12,000 1/16,000

1-------------------

1.

:roup above-

eact.

D. immitis .. . . . . 29-14 2-1 17- 5(Cases excluded from filaria free

group) .. 5-3 6-2D. medinensis 29-23 2-2 17-1

(Cases excluded from filaria freegroup) .. 5-4 5-3

L. carinii 2-1 17-3(Cases excluded from filaria free

group) .. 5-3 5-3

Filarial cases

From the above limited numbers, D. medinensis antigen appears the best in1/12,000 dilution, but much larger numbers are required.

16

(2) Elephantiasis

In the text above and In the earlier reports attention is drawn to the lack ofknowledge of the disease processes in the filarial infections. This is particularlytrue of elephantiasis. The list of possible causative agents suggested by previousworkers include:-

The worm itself living or dead.

The microfilarire.

Accumulation of ova.

Hypertrophy of the reticulo-endothelial system.

in East Afriea hydrocoele i1tiasis, the incidence of the f(higher than the incidence ofthe importance of bancroftAs an example, figures are gi

INCIDENCE OF LATE

Investigations are at prattempt to differentiate filarsignificant difference foundfluids.

(4) Filarial Lymphlldenopatll

Although much has beeliittle is known on this subjlstudied by Jordan of this de

The present investigaticpronounced in this area asinto four groups:-

(i) A control group sh(and elephantiasis.

(ii) Persons with micFOf

(iii) Persons with microf

(iv) Persons with hydroc

In any patient with 1)'could be found has, for the Ifilarial in origin. Bilateral arno allowance has been madbe pathological have been n

The results are analysedgroups there is little increasetrol series apart from a hiinguinal glands in patients,incidence is higher in themicrofilari~ in their blood.

It is the writer's opinion that in the beginning the process is a sensitizationphenomenon, a local reaction to the presence of the, adult worm. Later the localchanges reach a non-specific phase. This view is supported by recent satisfactorypathological investigations, e.g., Rifkin and Thompson (1945) suggest three stagesof tissue change, namely, an early acute allergic stage followed by a sub-acutestage of gra11ulation tissue overgrowth in the areas round the adult parasite, andfinally a stage of chronic non-specific tissue overgrowth.

A paragraph from the 1951 Report may be repeated here:-

"This consideration of elephantiasis is important for two reasons:firstly, if the view be correct that elephantiasis is due to an irreversible localtissue change " then the affected individual can expect little help fromdrugs and secondly, if the view be correct that the cause of the tissue <ohang,esis the death of the adult worm theu drug treatment may actually be harm­ful. "

Also in this problem of elephantiasis our findings differ from those of theSouth Pacific workeTS. In East' Africa elephantiasis is not a common complica­tion of bancro.ftian filariasis. Even in Kye1a, probably the most heavily affectedarea in East Africa, the incidence of elephantiasis in the whole population doesnot rise above 4 per cent. The explanation is that elephantiasis is found as alate manifestation anI? in areas where infections are intense, i.e. where not onlyis there a highl incidence of microfilarremia in the population but also whereindividuals so affected show very high microfilaria counts: the microfilarremiaof East Africa' never rises to the levels reported from the South Pacific wherethe vector is a day-biter. Other points of difference are: in East Africaelephantiasis is limited practically either to the legs or the male genitalia (80 percent to 25 per cent) with elephantiasis arms representing not more than 1 percent of the total affected; further, the age of onset in East Africa is much earlierthan in the Pacific, e.g. Trant (1950 Annual Report) and Jordan (1951 AnnualReport) both record established elephantiasis in cbildren under eight years of age.One possible explanation is that in this area infection becomes established veryearly; for example Jordan (1951) reports microfilarremia in two children a fewmonths old.

(3) Genital Filariasis

In this term we inclUde elephantiasis of scrotum, lymph scrotum, and un­complicated hydrocoele. The two first-named complications always begin assimple hydrocoele, a fact of much importance in the consideration of prevention.

It is in this complication that East African bancroftiasis shows itselfstrikingly different as compared with wuchereriasis malayi and wuchereriasispacifica; in the Malayan infections hydrocoele is not found and in the pacificainfections it is a much less important complication than elephantiasis, whereas

AGE GROUP INYEARS

0-910-1920-2930--3940-4950-5960 and over

TOTAL

Iv--No.

212

128

1510-50

"'.' '.

. .;,,~

"

;

"

17

tttention is drawn to the lack of11 infections. This is particularlyive agents suggested by previous

in East Africa hydrocoele is much commoner and more crippling than elephan­tiasis, the incidence of the former being ten times that of the latter and 250 timeshigher than the incidence of non-specific hydrocoele in Britain. We consider thatthe importance of bancroftian hydrocoele has been seriously under-estimated.As an example, figures are given below from a survey On Ukara Island.

INCIDENCE OF LATE MANlFESTATJONS OF BAlliCROFTIAN FILARIASIS_. --,

PHYSICAL DEFECTS-

Elephantiasis Legs HydrocoeleROUP IN ,

EARS Male Female

I~--- No. %

No. % No. %I

,2 - 1·. · . ~ -- -

· . · . I - 2 1 12 2· . · . 2 1 14 4 27 13· . · . 12 5 14 5 36 15

8 5 24 10,

29 I 17· . · .· . · . 15 11 12 9 18 I 13

over · . 10 8 6 10 28 I 241---

OTAL · . 50 3 72' 4 151 I 8=~;::;:=:=:;;;::;=~=~;;;;:;;;;;;:;;==~

AGE Gy

T

0-910-1920-2930-3940-4950-5960 and

system.

~ repeated here;-

is important for two reasons;sis is due to an irreversible locallUal can expect little help fromit the cause of the tissue changesreatment may actually be harm-

ing the process is a sensitizationthe adult worm. Later the localsupported by recent satisfactory

npson (1945) suggest three stages: stage followed by a sub-acuteas round the aduJt parasite, andergrowth.

indings differ from those of thelsis is not a common complica­obably the most heavily affected:is in the whole population doesthat elephantiasis is found as a; are intense, i.e. where not only

the population but also whereria counts: the microfilanemiad from the South Pacific wherelifference are; in East Africa~gs or the male genitalia (80 per:presenting not more than 1 perlet in East Africa is much earlier'Port) and Jordan (1951 Annual:hildren under eight years of age.lfection becomes established very·filanemia in two cbildren a few

rotum, lymph scrotum, and un­complications always begin asthe consideration of prevention.

rican bancroftiasis shows itself:riasis malayi and wuchereriasisis not found and in the pacificaltion than elephantiasis, whereas

Investigations are at present being carried out on hydrocoele fluids in anattempt to differentiate filarial and non-filarial hydrocoeles. To date the onlysignificant difference found is that of microfilarire in certain of the hydrocoelefluids.

(4)· FUarial Lymphadenopathy

Although much has been written on filarial lymphadenopathy in the Pacific,little is known on this subject in East Africa. This problem has recently beenstudied by Jordan of this department.

The present investigation indicates that. lymphatic enlargement is not aspronounced in this area as in the Far East. The cases seen have been dividedinto fom groups:-

(i) A control group showing no microfilarremia and absence of hydrocoeleand elephantiasis.

(ii) Persons with microfilarremia, but no hydrocoe1e or elephantiasis.

(iii) Persons with microfilara:mia and hydrocoe1e or elephantiasis.

(iv) Persons with hydrocoele and elephantiasis but no microfilarremia.

In any patient with lymphatic enlargement for which no obvious causecould be found has, for the purposes of the present investigation, been regarded asfilarial in origin. Bita teral and unilateral cases have not been differentiated, andno allowance has been made for size--all glands considered by the observer tobe pathological have been recorded.

The results are analysed in the following table, which shows that in the infectedgroups there is little increase in the incidence of lymphadenopathy over the con­trol series apart from a higher incidence of enlargement of the femoral andinguinal glands in patients with established hydrocoele or elephantiasis; thisincidence is higher in the group with negative bloods than in those showingmicrofilaria:: in their blood.

18DISTRIBlITION OF WORKING

---_.•---------

Total PALPABLE GLANDSNo. --- ---------Seen Femoral rng. Epitro. Axill. Neck

I--~--

Negative blood no evidence of Ifilarial disease-control · . 58 20 15 25 2 I

Microfilaraemia only . . . . 60 20 15 14 2 , 2Microfilaraemia with hydrocoele .

or elephantiasis .. · . 36 18 9 17 1 1Negative blood with hydrocoele or

elephantiasis .. . . · . 83 49 32 23 0 2

Days Lost per Year

0- 30 ..31- 60 ..61- 90 ..91-120 ..

121 onwards

21I

E

KEy: Ing.= Ingninal. Epitro. = Epitrochlear. Axill.= Axillary.As regards the relia.biJity of the control series it has to be remembered

that in an endemic area it is likely that many more people are infected inthe population than is indicated by the microfilarial rate and the hydrocoele.elephantiasis rate. O'Connor (1932) considers that probably 100 per cent ofpersons in a hyperendemic area are likely to be infected. If tnis is true, then itmeans that it is virtually impossible to get a true control series in an endemicarea. (In the observer's opinion the same objections apply to the use of controlsfor skin testing select~d from an endemic filarial area.)

This criticism of tne control group may account for the similarity of fintlingsbetween this group a.nd the micro-filarremia gronp. The greater increase inlymphadenopathy in the next two groups is comistent with the view generallyheld that these later manifestations are due to ohstruction caused by the adultfilaria; enlarged inguinal lymph glands are considered by Manson-Bahr (1951) tobe one of tne signs of the tertiary stage of filarial infection. But it is also ofinterest to note 1}ere the low incidence of epitrochlear glandular enlargementeven in the late s'tages of the disease; Manson-Bahr (1951) also lists enlargedepitrochlear glands as a sign of the tertiary stage of the disease. Buxton (I928)showed a positive correlation between epitrochlear glandular enlargement andelephantiasis.

It would appear therefore that this sign at any rate is not common infilarial disease in those parts of Tanganyika which have been surveyed to date.

(5) The Economic Aspects of BlmcroHian Filarias~s

The importance of filariasis paCifica lies in the "mumu" of the early stagesof infection and the elephantiasis found commonly as a late complication. Thereis nO mumu seen in East Africa: the economic importance of the disease liesin the crippling effects of genital filariasis and of elephantiasis. This problem wasdiscussed in the 1951 Report, "rom which tvlO tables are given below.

&'1ALYSIS OF WORlONG DAYS LOST

Annua1-1--------No. of I No. or Average I Annual

No. case:s I cases ~~ cases days lost AverageDISEASE of missing doing, missing by those days lost

cases some I no work I work missing by totalwcr k I work. cases seen

Hydrocoele I 168 661 I 39 63 25Elephantiasis 102 63 II 1 , ,63 i 63 38Mixed cases 34 19 2 I 56 I 97 , 55

I I I_____·r_.· ~~~

From the above tables itcompletely crippled a high IHistories taken from severalthat in the recurrent cripplinlpains in the legs and pains inof classification, details arehistories.

CLASSmCATION 0

Degree of Pain-

NilPain originally but no recurreiSlight recurrent pain, not criptPain when present affects work

(Similar investigations Ci)

give a figure of about 70 pc

The attacks of pain admiably, from one to two days cprevent work at any time. Thwork in the year (compared vanalysis was made to investi€With microfilarremia but no Sl1

The above findings are a,

(1) IntroductionSince individuals showin

venienced by the parasite, thlhave any effect either on the Icoele or on the recurrent cr:important cause of loss of \\evidence of efficiency in pretiasis, a possibility which hasof recent years. In this com"Whereas in most protozo.

,.'. t"

.; "

, .~

",

19

DISTRJBUTION OF WORKING DAYS LOST BY PERSONS WITH CLINICAL FILARIASISCONDITIONS

PALPABLE GLANDS-'-~~I----------JIng. IEpitN. IA,m. Nock

15 I 25 2 I15 I 14 2 2

9 17

32 23 o 2

Days Lost per Year Hydrocoele Elephantiasis I Mixed- I% % I %

0- 30 · . · . · . 29 44 23 37·1 5I

26,331- 60 · . · . · . 14 21'2 15 24·2 5 26·361- 90 · . · . · . 10 15 ·1 13 21·0 3 15-891-120 · . · . · . 6 9'1 6 8·0 2 10·6

121 onwards , . · . 7 10·6 6 9·7 4 21·0

66 100 63 100 19 100,

---------------------_.,---------'----

CLASSmCATION OF RECURRENT ATTACKS OF FEVER, ETC.

,(Similar investigations carried out with patients suffering from elephantiasis

give a figure of about 70 per cent showing interference with working capacity.)

From the above tables it is seen that although relatively few individuals arecompletely crippled a high proportion of individuals lose much working time.Histories taken from several hundred patients (hydrocoele or elephantiasis) showthat in the recurrent crippling attacks the patient suffers from fever, groin pain,pains in the legs and pains in the scrotum. Using the degree of pain as a methodof classification, details are given below of a few of such hydrocoele casehistories.

%36171136

Hydrocoele

No.21106

21

Degree of Pain-Scrotum or Groin

NilPain originally but no recurrenceSlight recurrent pain, not cripplingPain when present affects working capacity

lear. Axill. = Axillary.~ries it has to be rememberedi more people are infected inlaria! rate and the hydrocoele­l1at probably 100 per cent ofinfected. If this is tme, then itIe control series in an endemiclUS apply to the use of controlsI area.)

mt for the similarity of findingsroup. The greateT increase in.sistent with the view generallybstruction caused by the adultered by Manson-BahT (1951) to':ial infection. But it is also of'ochlear glandular enlargementahr (1951) also lists enlarged; of the disease. Buxton (1928)ear glaudular enlargement and

t any rate is not common in~h have been surveyed to date.

,is

he "mumu" of the early stages[y as a late complication. Thereimportauce of the disease lies

elephantiasis. This problem was)les are given below.

The attacks of pain admitted by the 21 patients in group I V varied consider­ably, from one to two days off work per month to a degree of pain sufficient toprevent work at any time. The average time lost per person amounted to 47 dayswork in the year (compared with 63 days as reported in last year's summary). Ananalysis was made to investigate whether the occurrence of pain was associatedWith microfilanemia but no such relationship could be established.

The above findings are again considered below in regard to treatment.

Treatment,YS LOST

'~ casesnissingwork

39.6356

AnnualAveragedays lostby thosemissingwork

636397

AnnualAveragedays lostby total

cases seen

253855

(1) IntroductionSince individuals showing only microfilara:mia appear not to be incon­

venienced by the parasite, the only problem in treatment is whether drugs usedhave anyeffed either on the physical changes present in elephantiasis and hydro­coele or on the recurr~nt cTippling attaeks of pain, etc., which are the mostimportant cause of loss of \vorking time. Drugs should also be considered forevidence of efficiency in preventing the onset of hydrocoele and of elephan­tiasis, a possibility which has received little mention in the voluminous literatureof recent years. In this connexion we again quote Temkin (1945), who sayS-,"Whereas in most protozoan and helminthic infections the object of the

-----~_._-------

20

MICROFILARlJE LEVELS IN BI

AF"

Tot'. Total ! Total Mic

Dose Drug IPatients --.(mgms. per kg.)

Before---,. ------

HETRAZAN AND EUPHANTIAS]

In the last tlu'ee yearspatients with elephantiasis ofseven females with elephanliawere adulti. More than 100

Tlle results quoted in thworkers elsewhere. One poiU'count obtained immediately,again even many months aft(so treated may be in a hyper­depression of the microfilarifemale worm has been killed

1,2343,5234,783

*Excll

18­2963

Under 5051-70mgms...Over 70 mgms.

HETRAZAN MiD PUBLIC HEAL

In the absence of any Iindication of the chemotherremarkable effect of hetrazanprove of value as one methodifficult completely to rendelthe microfilarremia be of a hifilarial count in any patient <:

over a period of time. One icertainty what is the level of

. infective to the iusect vector.at one time the "safe" levelHewitt (1949) stated that the10 mfs. per 60 mm'. This isthan it has received. Work onhalted because of technical dshow that in blood meals t,unit volume of blood may bewhom the mosquito had fed.is that the microfilaria: are rbut exist il1 clumps. Anotherinsect's proboscis may strikefrom a pool formed throughfirst-mentioned type of feedimlcrofilarire. With this in mileradication 0:£ filariasis basedthe affected individuals' micr(

therepeutic attack is well defined, this is not the case in filariasis ... it is notcertain that a drug which will kill the filarire will also cure the disease ... deadparasites may in themselves be responsible for some of the manifestations offilariasis". The only other workers who have kept this in mind are Culbertsonet at. (1946) and Oliver-Gonzales et al. (1949). '

In all discussions on drugs for the treatment of bancroftian filariasis thequestions to be considered are:-

1. Is the drug microfilaricidal? This is only of importance as a measure ofassessing the effect of the drug on the adult worm, at least on the adultfemale worm.

2. Has the drug any effect on the physical changes of elephantiasis and ofhydrocoele?

3. Has the drug any effect on the disabling recurrent fever, etc., associatedwith the latc manifestations?

4. Has the drug any effect iu preventing the onset of elephantiasis or ofhydrocoele in individuals harbouring W. bancrofti, i.e. any effect onsymptom-free bancroHiasis?

(2) Hetrazan

This substance 1-diethyl carbamyl 4-methyl piperazine is marketed as thedihydrogen citrate salt. Harned et al. (1948) give details of the pharmacology.This preparation is replarkably safe and is a strikingly effective microfilaricidalagent even in the smallest of doses. It is an expensive drug and little is knoyvn ofits action on the bancroftian parasite. Previous departmental reports discusscertain results in detail, and the l11aterial which follows is an extension of suc~

reports.

EFFECTS ON SYMPTOM-FREE BANCROFTIASIS

In the present state of ignorance the only way of assessing the value ofa drug in preventip.g elephantiasis and hydrocoele is to administer the drug tolarge numbers of patients with symptom-free bancroftiasis and to follow thehistories of such patients over a period of years. This has been done in two of theworst areas in Tanganyika, namely Kyela and Ukara. In both experiments wechose symptom-free individuals with heavy microfilanemia and aimed at adminis­tering a total does' of salt of not less than 70 mgms. per kg. body weight.

Kyela Campaig;;,--Dne hundred and twenty-five individuals were treatedduring August, 1950. (Both sexes, all adults with the exception of eight children.)To date (January, 1953), no individual has developed hydrocoele or elephantiasis.

Ukara Campaign.--Dne hundred and thirty-one individuals were treatedduring October, 1951. (Both sexes, all adults with the exception of 12 children.)To date (January, 1953), no individual has developed hydrocoele or elephantiasis.

Over the years a random untreated group of 256 sympton-free individnals ofboth sexes should show an incidence of about 20 cases of elephantiasis andabout 20 cases of hydrocoele. It is still too early to see whether we have succeededin preventing the onset of hydrocoele or elephantiasis in the individuals treatedby us.

EFFECT ON MICROFILAR..EMIA

Reports from aU affected parts of the world are unanimous in their agree­ment that hetrazan is strikingly and immediately microfilaricidal When adminis­tered to individuals showing bancroftian mkrofilara:mia. This has also beenour experience: a typical table ill given below.

;.'

,;~.

.,

21

----------,------,---------------------

MICROFILARIIE LEVELS IN BLOOD OF INDIVIDUALS ON UKARA FIFTEEN MONTHS

AFIER HETRAZAN TREATMENT

----~--I----I---·--1----1----1

2511

9

IMf. Counts p. 60 mm3 in Pal.

not made Mf.-free

Under I Over10 mf. 10-30 30-100 100

111853

No. ofPat.

madeMe

Neg.

%9799·499

Reduc­tion

Total ofMicrofil

1,234 403,523 204,783 45

Before After

18"2963

TotalPatients

. TotalDose Drug

(mgrns. per kg.)

Under 50 ..51-70mgms...Over 70 mgms.

se in filariasis • . . it is not10 cure the disease ... deadne of the manifestations ofthis in mind are Culbertson

importance as a measure of. worm, at least on the adult

of bancroftian filariasis the

1ges of elephantiasis and of ------'------------·Excluding one exceptionally high value.

:urrent fever, etc., associated

onset of elephantiasis or ofbancrojli, i.e. any effect on

The results quoted in the above table are in keeping with those quoted byworkers elsewhere. One point worthy o·f note is that the low or zero, microfilariacount obtained immediately after administration of hetrazan is not found to riseagain even many months after treatment has been given, although the individualso treated may be in a hyper-endemic area of filariasis. This seemingly permanentdepression of the microfilarial count indicates that at the very least the adultfemale worm has been killed or sterilized. .

erazine is marketed as theretails of the phannacology.~gly effective microfilaricidale drug and little is kno~n of:lepartmental reports discuss)WS is an extension of sucjJ.

of assessing the value ofs to administer the drug to:roftiasis and to follow thehas been done in two of thera. In both experiments wea~mia and aimed at adrninis-per kg. body weight.

ve individuals were treatedexception of eight children.)hydrocoele or elephantiasis.

oe indivitiuals were treatede exception of 12 children.)hydrocoele or elephantiasis.

, sympton-free individuals ofcases of elephantiasis and

~ whether we have succeededis in the individuals treated

HETRAZAN AND PUBLIC HEALTH

In the absence of any proof that microfilaricidal activity may serve as anindication of the chemotherapeutic value of a drug, the ir11portance of thisremarkable effect of hetrazan on microfilarremia lies in the possibility that it mayProve of value. as one method of eradicating filariasis. Although it is sometimesdifficult completely to render an infected person microfilaria-free, especially iftme microfilarremia be of a high degree, it is easy markedly· to depress the micro­filarial count in any patient even with doses as low as one to two tablets weeklyover a period of time. One important drawback is that no one knows with anycertainty what is the level of microfilanemia below which the human host is non­infective to the insect vector. Work on this subject has been vr::ry unsatisfactory:at one time the "safe" level suggested was 30 mfs. per 60 mm" but recentlyHewitt (1949) stated that the "safe" level is much below this, probably below10 mfs. per 60 mm". This is a basic experiment requiring much more attentionthan it has received. Work on the subject in this department has been temporarilyhalted because of technical difficulties, but already our results (see 1951 Report)show that in blood meals taken up by mosquitoes the microfilaria count perunit volume of blood may be mnch higher than the level found in the host uponwhom the mosquito had fed. One suggestion put forward to explain our resultsis that the microfilarire are not distributed evenly through the peripheral bloodbut exist in, clumps. Another possibility is that chance may play a part, e.g., theinsect's proboscis may strike' a venule, it may enter a capillary, or it may suckfrom a pool fanned through leakage from vessels damaged in passing. Only thefirst-mentioned type of feeding is likely to permit of the ready taking-up ofmicrofilarire. With this in mind it is inadvisable at present to plan campaigns oferadication of filariasis based on the assumption that it is necessary only to lowerthe affected individuals' microfilarial blood levels below 10 per 60 mm".

~ unanimous in their agree­icrofilaricidal when adrninis­rremia. This has also been

HETRAZAN AND ELEPHANTlASIS

In the last three years we have been able to treat adequately over 200patients with elephantiasis of the legs; one patient with elephantiasis arms; andseven females with elephantiasis breasts. The sexes were almost equal; almost allwere adult!:. More than 100 patients have been followed-up for over two years

22

and nearly 50. for over one year. Measurements show that there has been nosignificant change in the sizes of the affected limbs. This does not mean thathetrazan is of no value in the treatment of elephantiasis. In the text above it hasbeen shown that the real disabling factor in elephantiasis is not the physicalchange alone but the recurrent attacks of fever and pains in the Xegsand groins. In our 1951 Annual Report we mentioned that elephantiasispatients treated with hetrazan had volnnteered the information that since treat­ment they had not suffered from such recunent disabling attacks. The importanceof this was not stressed at that time, as we wished for fuller proof. Our latestsurvey of results of treatment shows without doubt that this is a true claim, inthat at least half of the paients treated have been relieved of all symptoms. Thepatients themselves speak enthusiastically of the results of treatment in spiteof the unchanged condition of the elephantid legs. It is therefore our opinion thathetrazan I'S of value when a.dministered to individuals suffering from bancroftianelephantiasis.

Note.-Since writing the above a patient has reported to us with what seemsto be a cured elephantiasis o:f one leg. The individual, an African male aged 30,was admitted on 18th November, 1950, with a complaint of elephantiasis leftleg of four years' duration this being associated with recunent attacks of painand fever. Examination showed the left lo,wer limb to be larger than the right,the enlargement being limited mainly to the foot and ankle, an early degreeof elephantiasis with no skin changes, typically the kind of patient we suggested(1951 Report, p. 39) m,~ght bet;lefit from hetrazan administration. The patient wasgiven a total of 90 tablets each 50 mgms. of banocide in three days, a total do~age

of 75 mgms. per kg. body weight.

On 20th February, 1953, the patient returned claiming he had been cured;measurement showed 110 difference between the right and the left leg, and thepatient was wearing shoes of nonrial size. He also stated that all attacks of painand fever had ceased after the treatment. Our record shows that this "cure"had been reported iin a f~llow-up observation (1951) by one of the medical staff,who had decided to give a longer period of observation before making publicthe findings.

HETRAZAN AND GE!,!ITAL FILARIASIS

By reason of its bulk alone genital filariasis even of moderate degree isusually much more crippling than is even moderately advanced elephantiasis ofthe legs: also, as shown above, genital filariasis is more common than elephan­tiasis. In areas where bancroftian filariasis is hyper-endemic genital filariais maybe found in one of every four male adults over middle age. Altho,ugh the treat­ment of genital filariasis is a pressing problem, remarkably little attention hasbeen paid to such conditions. Hydrocoeles, lymph scrotum, and elephantiasisscrotum do not only cripple the patient because of the tissue changes. As withelephantiasis, the really crippling factor is that of recurrent attacks of fever andpains: such attacks correspond exactly to those seen in elephantiasis. In thestudy of the value of any drug therefore two questions have to be answered:firstly, does the drug in any way affect the physical changes present, and secondly,does the drug in any way affect the recurrent attacks of fever, etc. In our 1951Report we claimed to have cured two simple hydrocoeles (total seven patients)by the administration of hetrazan. This was an important advance, the signifi­cance of which is not likely to be appreciated except in areas where bancIoftianhydrocoele i& a senoul> problem.

Later results are:-

(a) Hetrazan and filarial.simple increase in scrotal sizin whom, before treatment, thad been satisfactorily treatethan 70 mgms. hetrazan per

Results of 17 observed­

Cured

Worse

Reduction in size 01

No change

Note.-In more than(Every cure occurred insized hydrocoeles.) FouranCe of the crippling aUae

As a striking example ofreport received from an Afrwhom we sent hetrazan for

"1 beg to report on IT

I took the first medafter one hour I vomitelI felt like vomiting till latlday 1 took the second pahour and felt the sametake the medicine at bedtilike vomiting every nowwith the exception of one

After six days treatlTand the ~.crotum has rettarea of one square inchmedicine and finished it altreatment but the said a

(b) Genital {ilariasis.-Thiago. Physical findings followi

Improved or cured

Worse

No change

Note.-As with elephskin changes have developsion of such skin changtreported disappearance of

It is considered that in eprove of value in the controlcure a significant proportion

,. ", "

."

23

(b) Genital {ilariasis.-Thirteen such patients were treated over 12 monthsago. Physical findings following treatment are:-

It is considered that in elephantiasis and in genital filariasis hetrazan mayprove of value in the control of secondary disabling features. Further, it maycure a significant proportiou of individuals suffering from simple hydrocoele.

No change 13

Note.-As with elephantiasis limbs, it would seem that once well-markedskin changes have developed, the giving of hetrazan does not lead to regres­sion of such skin changes, but here also at least one half of the patientsreported disappearance of the disabling attacks of pain and fever.

8

7

Nil

Nil

Reduction in size of hydrocoe1e

No change

Worse

Improved or cured

Worse

Results of 17 observed­

Cured

Note.-In more than 50 per cent of patients complete cure was recorded.(Every cure occurred in individuals originally showing small Qr moderatelysized hydrocoeles.) Four of the remaining nine patients reported disappear­ance of the crippling attacks of pain and fever.

As a striking example of the efficacy of hetrazan we give in full below areport received from an African patient so.me 800 miles away from here, towhom we sent hetrazan for the treatment of his condition:-

"I beg to report on my illness as follows:-

I took the first medicine with water as directed before breakfast, butafter one hour I vomited and felt weak, sleepy and had a headache, andI felt like vomiting till late evening, when I regained.my usual strength. Nextday I took the second package after breakfact but vomited again after onehour and felt the same sym.ptoms as outlined above. Then I decided totake the medicine at bedtime, which I did, but with great difficulty. as I feltlike vomiting every now and then, but otherwise' it was quite' aU rightwith the exception of one night only, when I vomited after three hours.

After six days treatment I found that all the swelling has disappearedand the scrotum has returned to its usual size with the exception of anarea of one square inch where the fat still exists. I continued with themedicine and finished it all. It is now about 15 days since I have finished thetreatment but the said area of one square inch is still there."

Later results are:-

(a) Hetrazan and filarial hydrocoele (where there are no changes other thapsimple increase in scrotal size).-It has been possible to trace 54 such patientsin whom, before treatment, the skin changes were slight or absent, 17 of whomhad been satisfactorily treated at least one year previously (treatment not lessthan 70 mgms. hetrazan per kg. body weight).

reported to us with what seemsdual, an African male aged 30,complaint of elephantiasis leftwith recurrent attacks of painnb to be larger than the right,ot and ankle, an early degreeIe kind of patient we suggestedldministration. The patient waside in three days, a total dosage

'> even of moderate degree isltely advanced elephantiasis ofi more common than elephan­'r-endemic genital filariais mayliddle age. Although the treat­'emarkably little attention has)h scrotum, and elephantiasis)f the tissue changes. As withrecurrent attacks of fever andseen in elephantiasis. In the

testions have to be answered:changes present, and secondly,cks of fever, etc. In our 1951:lrocoeles (total seven patients)mportant advance, the signifi­:pt in areas where bancroftian

claiming he had been cured;'ight and the left leg, and theI stated that all attacks of painrecord shows that this "cure"1) by one of the medical staff,ervation before making public

; show that there has been nolbs. This does not mean thatmtiasis. In the text above it haslephantiasis is not the physicalfever and pains in the leas

mentioned that elephanti~sisle information that since treat­sabling attacks. The importanceled for fuller proof. Our latesttht that this is a true claim, in1 relieved of all symptoms. The) results of treatment in spiteIt is therefore our opinion that

'uals suffering from bancroflian

24

(3) Protostib

INTRODUCTORY

This is the trade name (May & Baker) of N-methyl glucamine antimoniatein which pentavelent Sb forms 27 per cent of the total. The substance ismarketed in ampoules of 30 per cent strength for use intravenously or intra­mnscularly. Excretion is via the kidneys and is rapid.

It is generally presumed that the effectiveness of heavy metal preparationsis due to the heavy metal, in this case antimony, and reports on such substaru:esusually express the dose in terms of the metal itself, as is done below.

This is not the whole answer: the factor which determines the safety of thepreparation and the total amount requiIed is the salt itself, not the heavy metalcontent alone, e.g. in the treatment of kala azar it may be necessary to give toadults tctal doses as high as 72 grm. of the salt, i.e. 20 grm. of antimony, a dosagegreatly in excess of what is tolerated or what would be necessary with certainother SbY preparations.

In previous reports we have pointed out the disadvantages of protostib:heavy doses are required of this expensive preparation: it is not without danger,e.g. we quoted four patients of 164 developing exfoliative dermatitis: the sub­stance must be given by injection; patients agree that the injections are painful:and here also we do not know enough about the disease to know whether it isa good thing to kill the adult worm, which protostib undoubtedly seems to do ina proportion of patieots receiving sufficient treatment.

Because of the above disadvantages we do not recommend this drug for fieldwork, although, as will be seen below, it has proved beneficial in certain of ourpatients.

EFFECT ON SYMPTOM-f'REE BANCROFTIASIS

Our large-scale field experiment was carried out with the same objects inview as the experiments with hetrazan, i.e. to establish whether or oot adminis­tration of protostib to symptom-free individuals showing micr01ilarrernia willaffect the incidence of late complications. Of the 130 patients treated 18 monthsago we have traced 110. So far no single individual has developed late compli­cations either hydrocoele or elephantiasis. Observation contioues.

EFFECT ON MICROFlLARA::MIA

We have already stated in previous reports that the effect of protostib on themicrofilarial level in no way resembles that of hetrazan: there is no directmicrofilaricidal effect; the fall in the microfilarial blood level is slow andundoubtedly related to the effect of the heavy metal on the adult female wornl.Given sufficient time, however, protostib does by this effect produce a markedand sustained fall in the microfilarial blood levels. This is shown below.

M1CROFILARlAL LEVELS IN BLOOD OF PATIENTS EIGHTEEN MONTHS AFTER

TREATMENT WITH PROTOSTlB

---~:~-:~--- I Total I No. of I MI'. counts' per 60-:l~Dose D~ug Tota~ microtilariae Reduc- I patients patients not made mr. freemgms. "b. patten,s 1---

1-- tlOn I made ---1---1 1---

per kg. I mr. under I OverBefore I After free lOmfs. 10--30 31-100 100~-i--I % ~------i--

Under 200 'I Q Imgms. Sb 15 1,107 232 79 II 4 6 2 3

200-240 mgms. I I ISb. .. 68 5,421 I 448 92 I 29 25 9 5Over 240 rngrns. I I

Sb. 47 3,925 i 387 91 I 23 15 5 3

-----

The tabulated data showstoxic level there was no guall

or sterilized. In fact the hea~

body weight, only lowered ttwhereas much lower total dc[n one individual, not includ(2,200 per 60 mm:! fell after tre

PROTOSTIB AND ELEPHANTIASI

Of the 56 elephantiasis Imonths ago it has been possiltotal amounts of the drug.

ResultsNo change in size of afj

. complete abolitionpains, etc.

No change in size ofrecurrent attacks of

N a change in size of aimproved or worse

It will be seen that proaffected patients; but such I

by the use of hetrazan.

PROTOSTIB AND GENITAL FlU

(a) Sirnple hydrocoele.-:mcnths ago.

ResultsCured, i.e. clisappearanc

symptoms and sigm

Improved, i.e. reductionin number of attack

No change ..

The individuals showinloriginally had been large, oj

NOle.-Protostib, /il<.small or moderately sizedrug hetrazan is to be p,

('b) Lymph scrotum or elobserved for more than 12the condition of the skin orstated most positively that lof the recurrent pain,

~

,..

'l'-methyl glucamine antimoniateDf the total. The substance isfor use intravenously or intra­

rapid.

:ss of heavy metal preparationsand reports on such substaru::es

elf, as is done below.

ich determines the safety of thesalt itself, not the heavy metalit may be necessary to give to

~. 20 grm. of antimony, a dosagevould be necessary with certain

he disadvantages of protostib:'ation: it is not without danger,exfoliative delmatitis: the su b-that the injections are painful:

e disease to know whether it is;tib undoubtedly seems to do innent.

,t recommend this drug for fieldved beneficial in certain of our

out with the same objects inablish whether or not adminis­s showing microfilarremia wi!!130 patients treated 18 monthslual has developed late compti­,ation continues.

1t the effect of protostib on the. hetrazan: there is no directrial blood level is slow and~tal on the adult female worm .. this effect produce a marked,Is, This is shown below.

; EIGHTEEN MONrHS AFTERlsnB

II

f i Mf. counts per 60 lllmJ in1.8 i patients not made mf. free

_I it~K \10-30 ,I 31-100 [ ~o8r! I i

6 I 2 3 i

25 I 9 5 I'l5 5 3

25

The tabulated data shows that even with total doses dangerously near to thetoxic level there was no guarantee that the adult female wom1 would be killedor sterilized. In fact the heaviest total dosage given. of 274 mgrns. SbY per kg.body weight, only lowered the initial microfilanemia to 50 per cent of its value,whereas much lower total doses often rendered the individuals microfilaria-free.rn one individual, not included above, the initial high microfilari blood level of2,200 per 60 mm3 fell after treatment only to 350 microfi[arire per 60 mm3 blood.

PROTOSTIB AND ELEPHANTIASIS

Of the 56 elephantiasis patients treated by us with protostib more than 12months ago it has been possible to trace 40 of whom 39 had received satisfactorytotal amounts< of the drug.

Results

No change in size of affected limbs: much improvement or. complete abolition of recmrent attacks of fever, leg

pains, etc. 28

No change in size of affected limbs: some lessening ofrecurrent attacks of fever, leg pains, etc. .. 6

No change in size of affected limbs: recurrent attacks notimproved or worse 5

It will be seen that protostib in sufficient dosage does bring relief to theaffected patients: but such relief can be o'btained more safely and more easilyby the use of betrazan.

PROTOSTIB AND GENITAL FILARIASIS

(a).Simple hydrocoele.-Seventeen patients, treated with Protostib over 12months ago.

Results

Cured, i.e. disappearance of hydrocoele and of all relatedsymptoms and signs 9

Improved, i.e. reduction in size of hydrocoele with reductionin number of attacks of recurrent fever 2

No change .. 6

The individuals s.howing no change were those in whom the hydrocoelesoriginally had been large, of a diameter of 30 em. or more.

Note.-PrO'to'Stib, like hetrazan, can cure a certain proportion of simplesmall or moderately sized filarial hydrocoeles but here again the ,~impler saferdrug hetrazan is to be preferred.

(b) Lymph scrotum or elephantiasis scrotum.-Five treated patients have beenobserved for more than 12 months: in no case was there any improvement inthe condition of the skin or the size of the tumour, but two of the five patientsstated most positively that they felt greatly improved, with no crippling attacksof the recurrent pain.

EFFECT OF SOLU

No conclusions can be 1

30-60 mgms.Sb.5

Oyer 60 mgms.

26

(4) Neostibosan and SoIustibosan

These preparations are produced by Messrs Bayer & Co., who have kindlykept us supplied with material free of charge.

N £OSTIBOSAN

The makers state that neostibosan is diethylamine p-aminophenylstibonatewith the antimony pentavalent and representing 42 per cent of the total. Thecompound is sold as powder in ampoules. It may be injected intramuscularly orintravenously. The solution is prepared with distilled water: it must be freshLyprepared and must not be heated. The makers recommend that treatment beginwith small doses and state that using kala azar treatment as a basis the totaldosage for an adult (of about 100 lb.) is 3.0 g. of the salt, i.e. 1.26 grm. ofantimony. This total dosage can be given as an intensive course daily overeight days, or intermittently every two to three days up to the required total.Contraindications include ascites, nepluitis, pneumonia and jaundice.

A point already made in the text above is that, although the dosages areexpressed in terms of SbY , the compound containing the Sb Y is of importanceand not merely the dose of the heavy metal itself, e.g. the total dosage ofneostibosan recommended by the makers as sufficient for the treatment of kalaazar is only 3 g. (J .26 g. of SbV ), whereas the corresponding total dosage ofprotostib is 72 grm. of salt (20 g. of SbV

). Excretion is mainly via the kidneys atfirst rapid, then slow. This slowing-up of excretion and the firm linkage of Sbv

in the compound may account for the activity of the substance.

A mass therapy campaign with neostibosan was begun on Ukara Island buthad to be temporarily, abandoned, As a result, very few patients have beenobserved for a sufficiently long period to allow of our reporting on the use of thisdrug in bancroftian filariasis.

SOLUSTIBOSAN

Solustibosan is'the diethYl-amino-ethanol salt of sodium antimony gluconate:here also, the Sb is pentavalent; with the newer preparation (solustibosan con­centrated) antimony forms 37 per cent of the total. The drug is marketed as asterile aqueous solution of which .1 m!. contains approximately 370 mgms. of salt,JOO mgms. Sb Y • The drug may be given intravenously or intramuscularly. It israpidly excreted via the kidneys, 80 per cent being excreted on the first day.Although this compound is said to be very similar in its chemical structure toprotostib, the total doses of soIustibosan recommended as necessary for the cureof kala azar, when measured by the total antimony administered, are only one­sixth of the dose recommended for protostib, i.e. the makers recoounend totaldoses of solustibosan up to 13.3 grm. (not 5 grm. as reported in our 1950Filariasis Report p. 44). Probably due to its rapid excretion, the substance isrelatively safe and daily doses as high as 110 mgms. of substance per kg. (not 90mgms. as stated in our 1950 Report) are well tolerated by rabbits.

The doses recoounended by the makers for the treatment of kala azar:Average daily dose for adults=O.l mls. per kg. body weight for ten consecutivedays. For a 50 kg. adult this \vould represent a total of 50 mls. of substance.

Another preparation is solustibosan oleosum, in which 1 ml. of the sub­.stance contains 200 mgms. of solustibosan and 54 mgms. Sb5 • So far we have notused this preparation.

Treatment of patients has begun with solnstibosan but only a few individualshave been observed for a sufficiently long post-treatment period. Brief detailsare given below,

~'

I TolTotal Dose I Total I micTOfimgms. Sb5 patients

per kg ---

IBefore

undeT~Omgms.II--->---Sb5 .. 2 I 217

I

4 I 2953 1 263

EFFEcr OF SOLUSTlBOSAN ON

Satisfactory data for a 10available only from 14 patilmeasurement of the leg enhSUbjective improvement withpatients reported that such at

On the question of the (are insufficient to permit of a

(5) Arsenamide

INTRODUCTORY

Introduced first by Otto,formula:-

AS (S.CHCOOH

The drug must be givenby the bowel and the kidneyscent trivalent arsenic in amJdosage recommended is 0.2 1

fifteen days. Latterly one ofhalf the time, in seven days.

The material used by usMessrs. Lilly and Messrs Atpreparations in certain respe.microfilaria;, and reports ocCertain workers consider th:trivalent and pentavalent anbility to a satisfactory propcwho> have much experience cFrom our animal expcrimcnbe used in the field, and, ashospitalized during the full cnumbers treated. Recentty OI

developed jaundice a few da~

been due to infective hepati·likely cause.

27

'ayer & CO., who have kindly

lmine p-aminophenylstibonate2 per cent of the total. Thebe injected intramuscularly or.ed water: it must be freshlyomrnend that treatment beginreatment as a basis the totalf the salt, i.e. 1.26 grm. of

intensive course daily overays up to the required total.'nia and jaundice.

.1, although the dosages arelng the SbY is of importanceOf, e.g. the total dosage ofent for the treatment of kalaorresponding total dosage of1 is mainly via the kidneys atand the firm linkage of Sb Y

he substance.

begun on Ukara Island but;ery few patients have beenJr reporting on the use of this

. sodium antimony g1uconate:)reparation (solustibosan con­I. The drug is marketed as a-roximately 370 mgms. of salt,usly or intramuscularly. It is19 excreted on the first day.r in its chemical structure toded as necessary for tbe cure1 administered, are only one­the makers recommend totalm. as reported in our 1950d excretion, the substance is. of substance per kg. (not 90ited by rabbits.

the treatment of kala azar:iy weight for ten consecutiveotal of 50 mls. of substance.

in which 1 m!. of the sub­.gms. Sb5

• So far we have not

;an but only a few indtviduals'eatment period. Brief details

EFFECT OF SOLUSTIBOSAN "conc." ON MICROFILARiEMIA~'A· __•___•• ------

I I 'Total No of Mr. counts p. 60 mm3 in patientsTotal Dose I Total Il1Icrofilanae RedUC-

1

patients not made mf.-freemgms. Sbs patients Hon made --- ---

per kg.

I

-1- mf Under 10-30 31-100 OverBefore After I neg. 10 ruC 100--,-----1

I % IUnd<;;r30mgms. I I Q

Sb' . 2 217 201 Nos.I insig-I nificant

30-60 mglrls. ISb.s 4 295 II

I96 2 2

Over 60 mgms. 3 263 7 98 2 1

No conclusions can be reached on the small numbers shown above.

EFFECT OF SQLUSTIBOSAN ON ELEPHANTIASIS

Satisfactory data for a long enough post-treatment period of observation areavailable only from 14 patients: no patient showed any improvement in themeasurement of the leg enlargement but 6 of the 14 patients reported muchsubjective improvement with no recurrence of periodic attacks of pain and fourpatients reported that such attacks were much less frequent and severe.

On the question of the effect of solustibosan on filarial hydrocoele the dataare insufficient to permit of analysis. This work continues.

(5) Arsenamide

INTRODUCTORYIntroduced first by Otto and Maren, this organic arseFlical preparation has the

formula :-

AS (S.CHCOOH)2 /--> CH.NH2

. II",-_ a

The drug must be given intravenously and is excreted fairly rapidly equallyby the bowel and the kidneys. It is. marketed as the sodium salt containing 18 percent trivalent arsenic in ampoules of 1 or 2 per cent buffered solution. Thedosage recommended is 0.2 mgms. of arsenic daily per kg. of body weight forfifteen days. Latterly one of our workers has given the same total dosage inhalf the time, in seven days, by giving injections twice daily.

The material used by us in our tests was kindly supplied free of charge bylvlessrs. Lilly and Messrs Abbott. This heavy metal differs from the antimonialpreparations in certain respects: the As is trivalent; reports state it acts on themicrofilarire, and reports on the question of its toxicity are very conflicting.Certain workers consider that in filariasis it is practcally impossible both withtrivalent and pentavalent arsenical preparations to reconcile effect and tolera­bility to a satisfactory proportion: on the other hand Otto and his co-workers,who have much experience of arsenamide, consider it to be relatively non-toxic.From our animal experiments we are not satisfied that arsenamide may safelybe used in the field, and, as a result, all patients treated by us have had to behospitalized during the full course: this has imposed a serious limitation on thenumbers treated. Recently one patient treated with a full course of arsenamidedeveloped jaundice a few days after the course finished. Although this may havebeen due to infective hepatitis, arsenical posioning cannot be excluded as thelikely cause.

28

______. p";",, No, [ L~-I 3 I 4 1__5_1 6

Before treatment I' 210 mfs. p. 60 mm31 25 I 10 'I' 28 I[ 38 1 ISO

After treatment ('; II I I 8 . 1 '! I I

In two years it has been possible to treat satisfactorily only 36 patients.Of the 36 patients, 13 have been under observation over a period of time suffi­ciently long to permit of conclusions being drawn. Brief details are given below.

EFFECT ON MrCROFILARtEMIA

In the six patients for whom records exist the drug did appear to have adirect effect on the level of: microfilaria; in the blood. This effect was not nearlyso marked as is found with hetrazan: by the end of a fifteen-day course thefindings in the six patients were~

Total microfilaria; levels before treatrnent=461 per 60 mm3.

Total microfilaria; levels at end of course = 46.

This effect is also shown on Mr. perstans: one of the six patients had adouble infection i.e. W. bancrofti and D. perstans and the Mf. persIans level fellas fast as the Mf, bancrofti level.

Twelve months after treatment the findings in detail were--

Numberdissected

-_._---,~

Species

Most adult mosquitoes tthe north coast, and Nyamanlcent and at Nyamanga 24.8 pefilariasis. Individuals of IIfollowing is a summary for

Dissection Results

One of the aims laid doeliminating filariasis from arimethods of control present tlor to remove the vector. Insterilizing or so lowering thehim non-infective to the vecto]As yet the factor preventingknows what is the microfilabecome infected to any signiJmore fully in the future.

The year's work consist.Island.

Biting Incidences

Catches, made seasonaUJthat A.. gambia! and A. [linesnight, with very smail numbewell. Catches made concurreiC. annulioris and C. antennfrom 7 p.m. to 3 a.m. and are'

A. gambiae 3,187A. junestus 1,128A. pharoensis 93T. ajricanus 1,106T. ud/armis 1,080C. antermatus 34

The other method of canpossible by tbe introduction 0

ing of such a method is notcontrol must be maintainedexperiment, we have maintaiu,function of which is to obtmethods of vector control. lflight range of vectors, and, j

should be little risk of re-inv

Transrnissioll

'.

;-

,.j:

In patient No.5, a female who had the double infection, no Mf. perstanswere found in the blood.

EFFECr ON ELEPHA.."ITIASIS

Two of the elephantiasis patients treated have been observed for over a year.In neither patient has there been any lessening of the size of the elephantoidlegs, and neither patient reports any of the subjective improvement which hasbeen so' marJced' with certain of the other preparations discussed above.

EFFECT ON GENITAL FILARIASIS

Five such patients have been observed [or periods longer than one year. Infour of the five (patients the cOildition was advanced, with elephantoid changesof the scrotal skin. The remaining patient showed a smali hydrocoele only. Oneof the four elephantoid scrota showed also lymph scrotum with Mf. baneroftiin tbe escaping fluid. Immediately after treatment the Mf. bancrofti disappearedfrom tbe lymph scrotum fluid. Results of treatment have been:-

(i) Patient with the early bydrocoele considers himself cured: there is now noevidence of hydrocoele and no recurrent attacks of pain and fever.

(ii) Of the four patients with advanced genital filariasis one is very pleased:he feels much better and claims that his scrotal swelling has decreasedin size. (This is supported by measurements before and after treatment.)The other three report no change and complain that the treatment hashad no e'ffect on tbe recurrent attacks of fever and of pain: onepatient reported that these attacks had become worse and more frequent,the last one causing him to be confined to bed for two weeks.

Until we are satisfied that arsenamide is of value and safe for use in thefield it wil1 not be possible to carry out extended field trials such as reportedabove for other d,rngs.

Summary.-The number of patients treated is as yet too small to express anydefinite views, but it would seem that arsenamide is not capable of doing anythingwhich cannot be done more easily and more safely by other drugs.

6

150

satisfactorily only 36 patients.on over a period of time suffi­

Brief details are given below.

rre drug did appear to' have alad. This effect was not nearlyld of a fifteen-day course the

I per 60 mm·.

6.

one of the six patients had aand the Mf. perstans level fell

in detail were----

3 I 4 I 5 I-----I---i---10 28 II 388 1

ble infection, no Mf. perstans

been observed for over a year.)f the size of the elephantoidective improvement which hasI'ations discussed above.

riods longer tban one year. InIced, with elephantoid cbang,esa small hydrocoele only. One

h scrotum with Mj. bancrojtithe Mf. bancrofti disappearednt have been:-

himself cured: there is now noittacks of pain and fever.

filariasis one is very pleased:scrotal swelling has decreased

lts before and after treatment.)rnplain that the treatment hasof fever and of pain: one

orne worse and more frequent,o bed for two weeks.

value and safe for use in the:l field trials such as reported

as yet too small to express anynot capable of doing anything

{ by other drugs.

29

Transmission

One of the aims laid down is tbat we study methods of controlling oreliminatiag filariasis from areas where this is thought necessary. Two obviousmethods of control present themselves, namely to render the host non-infectiveor to remove the vector. In the text above we have discussed the question ofsterilizing or so lowering the microfilaria: count in the host's blood as to makehim non-infective to the vector. Retrazan has been suggested as the drug of choice.As yet the factor preventing large-scale control on such Jines is that no oneknows what is the microfilaria: blood level below which the vector does notbecome infected to any significant degree. It is hoped to investigate this mattermore fully in the futme.

The other method of control, that of eUminating the vector, has been madepossible by the introduction of the newer insecticides. The planning and the cost­ing of such a method is not easy particularly when it is remembered that vector

control must be maintained for about ten years. As a preliminary to such anexperiment, we have maintained on Ukara Island a field entomological team, thefunction of which is to obtain the basic data necessary in the planning ofmethods of vector contra!' Ukara Island has been chosen because it is ont offlight range of vectors, and, in the event of vector control being attempted, thereshould be little risk of re-invasion by mosquitoes.

The year's work consisted largely of field studies on m?squitoes of UkaraIsland.

Dissection Results

Most adult mosquitoes have been collected from two vilJages-Bubanja onthe north coast, and Nyamanga near the centre of the island. At Bubania 25.9 percent and at Nyamanga 24.8 per cent of the inhabitants are infected with bancroftialfilariasis. Individuals of 11 species of mosquitoes have been dissected. Thefollowing is a summary for species found with filarial "worms:-

Number % with Number %withNumber with develop- with infective

Species dissected develop- mental infective formsmenta! forms formsforms

------ ------ --------- ------

A. gambiae 3,187 52 1·7 15 004A.lunes{us 1,128 35 3'1 11 1·0A. pharoensis 93 12 12·9 0 0T. a.fi"icanus 1,106 8 0·7 0 0T. uni;formis 1,080 6 0·6 0 0C. antennatus 34 1 3·0 0 0

---_.

Biting Incidences

Catches, made seasonally, of mosquitoes biting a man in a cone but showthat A. gambhe and A. funestus are the most numerous species biting indoors atnight, with very small numbers of T. atri'canus. T. uniformis and C. annulioris aswell. Catches made concurrently outdoors show that T. ajricanus, T. uniformh.C. annulioris and C. antennatus are largely outdoor biters. Collections extendfrom 7 p.m. to 3 a.m. and are made on alteruate nights until three such collections

30

are made in each village. The average number of mosquitoes collected indoors pernight between 7 p.m. and 3 a.m. is interpreted as a rough estimate of the numberwhich bite a sleeping person at night. At Bubanja, A. gambia? bites are of theorder of 200 per night at the end of the long rains (March-May) and three pernight at the end of the long dry season (June-September). A. funestus bites atthe rate of 30 per night at the end of the long rains, 50 per night in July, andone per night at the end of the long dry season. The incidence of biting ofA. gambia: and A. funestus is lower at NY'amanga than Bubanja.

An occasional T. airicanus, T. uniformis, and C. antennarus is taken incollections at Nyamanga but at Bubanja the biting incidences of these speciesare high. Local abundance of these species can be accounted for by their exten­sive breeding in a bay in the coast nearby.

The T{eniorhynchus species do not show extreme peaks of biting, although atthe end of the long rains T. uniformis bites at the rate of 65 per nigbt outdoors,compared with 10 per night at the end of the dry season, T. african us appearsto be more even in its seasonal biting incidence, and bites at the rate of 20 pernight at the end of the long dry season. As these Ta:niorhynchus species are mainlyoutdoor biters, their habits have been investigated to find the times when, andthe places Where, they come into contact with man and animals. The Wakarasit outside theil' huts, often grouped round a small fire, before they have theirevening meal indoors at about 9 p.m. At this time they are exposed to t4e bitesof T a:niorhynchus species and C. antennarus. People are also brought into con­tact with Ta:niorhYl1chus, and are bitten, when they visit latrines. The latrinesare often situate-d amongst rocks and closely pruned trees which occur together.In some villages, such as Bubanja, and Busangu, trees are pollarded 6 in. to3 ft. off the ground and a Clump of pollards forms a latrine. At Bubanja,T. africanus, T. uniformis and C. antenna/us rest in crevices in rocks, amongthe leaves of plants near rocks, and among the leaves of pollarded trees. In theshade of the pOllards and the rocks people are bitten day and night, although thelatrines are used mainly at night.

Host preferences.

Mr. Weitz of the Lister Institute of Preventative Medicine in England verykmdly undertook the analysis of a large number of blood smears. Precipitin testson mosquitoes resting on the walls of huts show that 91 per cent of A. gambia:,85 per cent of A. funestus, 36.8 per cent of T a?niorhynchus airicanus, 26.1 percent of Ta?niorhynchus uniformis and 13.9 per cent C. annulioris had fe-d onman. Whereas Culicines resting in 'huts had fe~ largely on domestic or wild animalsA. gambia? and A. funestus collected from the walls of huts had fed mainly onman. The precipitin test results confirm dissection findings that on Ukara islandCulicines can be excluded as vectors of bancroftian filariasis, and strongly supportsthat infective forms of fiJari~ in A. gambia? and A. funestus, taken resting in huts,are derived from man. It is also concluded that, although a low percentage ofA. gambia: and A. funes/us are infective there is a very high probability that theinfective forms will be transmitted to people and not to domestic or wild animals.A. phwa:nsis is normally scarce on the island, but follOWing failure of the shortrains in November, there was a slight increase in numbers at Bubanja, althoughnone were found at Nyamanga. A. phara:nsis has been recorded as highly anthro­pophilic by other workers, so there is a possibility that this species may be aminor vector on Ukara. It occurs in such small numbers, however, that even j'finfective forms do exist, this species is of little importance (lS a vector on Ukara.

,.~

The distribution of mosq~

Collections of mosqu

1. Mosquitoes rest afound higher thaI11 huts at BusanC. annulioris weTthe aid of alaibeyond the reactfumes from thethe top of the hut

2. A. gambia: and A.dark half of a j

cattle half. In afemale A. gambifJcattle sections c(collected simultantions, 337 A. gamsections comparedsections.

3. There is an indicati,for resting in mantions the ratio ofis 13 per cent COlA. gambia? restin!of collections inA. gambia! was f,cent in man's sec

Factors affecting biting ael

1. A hut fire. It is tIlfire is always smasticks are kept buat 7 p.m. The finsmoulder for twobait" in a hut wilhuts, fires and beanalysis, Which shactivities of A. gao

2. Attractiveness of cshowed that a bo~

as a man of 38 yelbution of childrelsix and sixteen hithe bites of A. gao

Outdoor resting places

T. africanus, T. unifo.doors, can be collected eaJhave been made of blood

.-"

' .."

toes collected indoors perh estimate of the numbergambice bites are of the

-arch-May) and three perler). A. funeSlus bites atjO per night in July, ande incidence of biting ofBubanja.

antenna/us is taken incidences of these speciesunted for hy their exten-

aks of biting, although atof 65 per night outdoors,,on, T. ajricanus appearsites at the rate of 20 perynchus species are mainlyfind the times when, andnd animals. The Wakara~, before they have their. are exposed to the bitesre also brought into con­iisit latrines. The latrinesees which occur together.s are pollarded 6 in. to; a latrine. At Bub·anja,revices in rocks, amongof pollarded trees. In they and night, although the

!fedicine in England very)0. smears. Precipitin tests1 per cent of A. gambia:,nclms africanus, 26.1 per7. annulior'is had fed ondomestic or wild animals

, huts had fed mainly onngs that on Ukara islandisis, and strongly supportsI'tus, taken resting in huts,lugh a low percentage of

high probability that thedomestic or wild animals.)wing failure of the shortbers at Bubanja, although'ecorded as highly anthro­,at this species may be aers, however, that even iflee as a vector on Ukara.

31

The distribution of mosquitoes resting in huts

Collections of mosquitoes resting on the walls of huts show:-

1. Mosquitoes rest at the base of the. wans of a cone hut and are rarelyfound higher than 7 ft. above the ground. Collections were made from11 huts at Busangu on the. east coast. Ninety-three A. gambia: and sixC. annulioris were taken by coHectors standing on the floor, and withthe aid of a ladder simultaneous searching revealed no- mosquitoesbeyond the reach of a collector on the floor. It is thought that thefumes from the fires, or their sticky resinous deposit on the walls atthe top of the hut, repel the mosquitoes.

2. A. gambia: and A. funestus are found resting in greater numbers in thedark half of a hut which comprises man's section than the lightercattle half. In a series of collections from 20 huts at Nyamanga 276female A. gambia: and 46 A. funestus were collected from the walls ofcattle sections compared with 433 A. gambia! and 91 A. fUl1'estuscoHected simultaneously in man's section. In another series of collec­tions, 337 A. gambia! and 90 A. funestus were collected resting in cattlesections compared with 777 A. gambia! and 256 A. funest·us from man'ssections.

3. There is an indication that female A. funestus shows a stronger preferencefor resting in man's half than female A. gambia:. In one s:eries of collec­tions the ratio of A. funestus to A. gambia: resting in the cattle sectionis 13 per cent compared with 21 per cent ratio of A. funestus toA. gambir:e resting in man's half. This is supported by another seriesof collections in which a ratio of 25 per ~nt female A. funestus toA. gambir:e was found resting in cattle sections compared with 35 percent in man's sections.

Factor~ affecting biting activities in a hut

1. A hut fire. It is the custom of the Wakara to cook in their huts. Thefire is always small, because firewood is scarce, and only three or foursticks are kept burning. Fires are lit at noon and for an evening mealat 7 p.m. The fire may be built up before the people go to bed andsmoulder for two or thrce hours. Mosquitoes were collected off "humanbait" in a hut with a fire and a hut without one. All combinations ofhuts, fires and hoys were employed to give data for proper statisticalanalysis, which showed that fires had no significant effect on the bitingactivities of A. gambia! and A. funestus.

2. Attractiveness of child and adutt. An experiment at the end of Mayshowed that a boy aged teu years was equally attractive to A. gam.bia!as a man of 38 years. Observations on type of bed covering and on distri­bution of children in beds showed that children between the ages ofsix and sixteen have tittle bed clothing and are thus most exposed tothe bites of A. gambia: and A. funestus.

Outdoor resting places

T. africanus, T. uniformis and C. antennafus, which largely bite man out­doors, can be collected easily from their natural outdoor resting places. Smearshave been made of blood fed individuals of these species resting outdoors and

-

32

analysis will give ns some indication of their host preference. C. univittatus andC. annulioris are commonly fonnd resting in crevices in river banks and alongthe sides of gullies madc by erosion at the centre of the island. Nearly everyspecimen in these places is nnfed but occasional individuals of C. univittatustaken from a hand-made pit at Nyamanga are freshly gorged. Collections fromthe pit in July indicated that Anopheles ru[ipes and Anopheles longipalpis arecommon outdoors in July although they are rarely found indoors. A. gambire.A. funestus and A. rhodesien.sis have been taken from the hand made pit andfrom caves towards the centre of the island. Collections made at intervals ofan hour over 24 hours from the walls of a cave show that A. gambia, A. funeslusand other species leave the cave afteT dusk and that individuals of the sam13species enter the cave at dawn and that a small number of them are gorged withblood.

Breeding placey

It is mentioned in the 1951 Report that little breeding occurs in coastalwaters, and that there is a high seasonal peak after the long rains. A larval surveyin May and June shows that extensive cultivation of rice in river valleys isthe main factor in producing the high seasonal incidence of A. gambire andA. funestus. Rice is planted principally in the river basins in March and by meansof a well-regulated system of irrigation the Wakara flood wide' areas of land.The livers rise in the high centre of the island and spread over wide beds inthe coastal region. The bulk;. of the rice is grown on the west side of theisland. A coarse grass called rubimbili is widely grown as cattle fodder.. Thisg,rass is planted in the sandy beds of rivers, in small fields and pits dug in thesandy beaches. The pits and fields contain water and in some areas such as thenorth-west coast they are the main breeding places of A. funestus in the locality.The breeding places of other mosquitoes have been noted and these and otherdetails will be published in due course.

Snails have been collected 'from various parts of the island to find the hostor hosts of Schistosoma species.

SECTION 3-0JIntroductory

Our aims and intentionsintroduction to this report,onchocerciasis, to investigate

Field SurveysThe first stage is to carr

fashion as that used to establito date is:-

Tangankiya.-Isolated Ci

suffering from onchocerciasis,to certain parts of the Sourrreported above, it was not pcthe Southern Highlands Prois possible that two to threeso limited in extent, and tilunlikely that onchocerciasis vin Tangany'ika; in any eventthe methOds now in use in K

Kenya.-We have begunshall require to do little mOT<tion available shows that thewith five foci all found inVictoria. One of the areas is (the number of people at risKenya, the disease is a seriOIare now almost completed,

Ueanda,-As we havc TIl

latest information (already r'the east there is a large focusin the centre of the country,the White Nile, there is a lasize, extending along practica,and forming a line related to

Throughout thc affectedbreeding habits of which rene

Symptoms and Signs

(1) Introductory

Economically and clinicalproblem than is bancroftiasis,late manifestations suffer anindividual infected is a sickmay mean practically the whcimportance, but. the skin chanand even in the early stages tiness a common eud-result in

The essential difference ;lies in the agent responsible flthe elephantiasis and genital fiadult worm (living or dead wechanges are all due to the I

~

....

.~

'"

preference. C. univittattts andices in river banks and along'e of the island. Nearly everyI individuals of C. univittatuseshly gorged. Collections fromI1d Anopheles longipalpis are:ly found indoors, A. gambite,from the hand made pit and

llections made at intervals ofJW that A. gambi~, A. funestus

that individuals of the samellllber of them are gorged with

tie breeding occurs in coastalthe long rains. A larval survey

ou of rice in river valleys isiucidence of A. gambite andbasius in March and by means

.ara flood wide areas of land.and spread over wide beds inlin on the west side of the

grown as cattle fodder. ThismaH fields and pits dug in theand in some areas such as theI of A. funestus in the locality.:en noted and these and other

of the island to find the host

,"

33

SECTION 3-0NCHOCERCIASIS IN EAST AFRICAIntroductory

Our aims and intentions in regard to onchocerciasis are as quoted in theintroduction to this report, i.e. to establish how common and how serious isonchocerciasis, to investigate methods of control, and to investigate treatment.

Field SurveysThe first stage is to carry out a survey of the three territories in the same

fashion as that used to establish the picture of W. bdncrofli iufection. Informationto date is:--

Tangankiya.-lsolated cases have been reported in the past of individualssuffering from onchocerciasis. Such cases are very few in number and are limitedto certain parts of the Southern Highlands Province: in a survey of that areareported above, it was not possible to demonstrate any case of .onchocerciasis inthe Southern llighlands Province, although suitable vectors were identified. Itis possible that two to three isolated foci of infection do exist, but they must beso limited in extent, and the number of individuals at risk so few, that it isunlikely that onchocerciasis will ever be anythiug other than a minor problemin Tanganyika; in any event it will be easily possible to control the vector bythe methods now in use in Kenya.

Kenya.-We have begun survey work in Kenya but iLis expected that weshall require to do little more than confirm the exact work of others. Informa­tion available shows that the disease is limited to the Nyanza Province of Kenya,with five foci all found in an area bounding the north-<;ast corner of LakeVictoria. One of the areas is continuous with affected areas in Uganda. Althoughthe number of people at risk is a relatively small proportion of the total inKenya, the disease is a serious problem: fortunately adequate control measuresare now almost completed.

Uganda.-As we have not yet started work in Uganda, we give below thelatest information (already reported. 1951) contributed by Bamley (1952). Inth~ east there is a large focus extending from the Mount Elgon area in Kenya:in the centre of the country, extendiug from Jinja a coufiiderable distance alongthe White Nile, there is a large focus: there are many scattered foci, small insize, extending along practically the whole of the western boundary of Ugandaand forming a line related to the Great Lakes, Lake Albert and Lake Edward.

Throughout the affected areas in Uga.nda the vector is 5'. damnosum, thebreeding habits of which render it more easily controlled than S. neavei.

Symptoms and Signs

(1) IntroductoryEconomically and clinically onchoceriasis is proportionately a more serious

problem than is bancroftiasis. In the latter infection only the relatively few withlate manifestations snffer any inconvenience, whereas in onchocerciasis everyindividual infected is a sick person requiring treatment. In certain areas thismay mean practically the whole population of the area. The nodules are of noimportance, but the skin changes are crippling (leading to suicide in rare cases)and even in the early stages the eye lesions interfere with efficiency, with blind­ness a wmmon end-result in the late stages.

The essential difference between .onchocerciasis and bancroftian infectionlies in the agent responsible for the production of the changes: in bancroftiasisthe elephantiasis and genital filariasis are caused in one way or another by theadult worm (living or dead we do not know), hut in onchocerciasis the importantchanges are all due to the microfilaria:, the positive phototropism of which

34

accounts for its presence in C()untless numbers in the skin and in the eyes: theskin becomes sensitized to dead microfilari~ and the presence of the larval formsin the eyes leads to the local tissue reactions which produce interference withfunction. Undoubtedly the nodules found in the skin are caused by presence ofthe adult worm but these are of no clinical importance. Other changes reportedinclude onchocercal elephantiasis and hydrocoele, but we have never seen suchlesions, which must be ra re in East Africa.

The more important diagnostic aids are dealt with in detail below: theseinclude skin biopsy, reactions to antigens, nodule biopsy, skin changes and eyechanges.

(2) Skill BiopsyThis method is laborious and time-consuming and only positive results are

of value: due to the irregular scatter of the microfilaria; over the body, evenobviously infected individuals may show negative skin snips. In spite of this weUSe skin snipping as one method of diagnosis. The snips are always taken fromthe right shoulder to aJlow of standardization of results.

(3) Reactions to AntigensSo far this has proved as unsatisfactory in onchocerciasis as in bancroftiasis:

skin tests and serological tests with antigens are not as yet of any practical value.

(4) N (}du~es

If nodule'S be exCised, it is easy to demonstrate in them the presence of theadult worms, but such is not a practicable procedure in field work and ~ notessential. The site and character of the nodules are almost diagnostic in them­selves and can be tak;en as valuable confirmatory evidence in doubtful cases.

(5) Skin ChangesIn well-established cases, when taken in conjuncti{)n with the history of

intense generalized itching day and night, the skin changes should suggest thediagnosis. The \Vhole affected skin area is thickened, dry, rough, shiny andinflamed and shows linear scratch marks. The pruritis precedes the skin changes,some of which may be due to the trauma of continuous scratching.

That the skili reactions are a sensitization phenomenon related to the deathin situ {)f micro-filaria; is well shown by the administration of hetrazan. As inbancroftiasis this drug is markedly microfilaricidal and the administration of evenone tablet to a patient wilh onchocerciasis results in an almost immediate markedexacerbation of the pruritis with the whole of the skin inflamed and with theface showing peau d' orange. This is a valuable diagnostic aid.

(6) E)'e Le~iolIs

Microfilarite volvulus are commonly found in the eyes of patients withonchocerciasis, this being one indication of the positive phototropism of the larvalforms, which in turn is a result of the day-biting habits of the vector. Photophobiais the earliest symptom, with blindness the end-result. The incidence of eye lesionsvaries from area to area: Bowie (1950) talking of the Belgian Congo mentions"caravans" of hlind men and women. In Kenya the incidence of eye C()mpIica­tions is probably less than was suggested by the original surveys, which probablyincluded blindness due to other causes. The exciting agent in the production oteye changes is the presence of dead microfilarire. In this work on onchocerciasiswe have been fortunate in being allowed to co-opt Dr. Roy McKelvie by kindpermission of the Director of Medical Services, Kenya. Dr. McKelvie is aoophthalmologist with much experience of the eye changes in onchocerciasis. Forour 1951 Report he contributed an authoritative summary of the problem.

(1) !ntroductoryThe fact that elimination

not relieve the clinician of hi!do more harm than good: tlmay be very trying for thenothing will make good any chas made progress so slow: ethe control of an ophthalmolproduce drug schedules safethe investigation of every drugparticularly the skiu lesions afilaria;? What effect has the

(2) HetraZ!lD

EFFECT ON SKIN CHANGBS

The harmful agent is th<unlike bancroftiasis, the miefactor, and it is only to beskin changes and pruritis unThis means that for the firstlow to prevent damage to theThereafter, when almost all 0

to increase the dosage, in thethe adult worms. For the Ii;along, the liues used in theto it (reactions may be conhistaminics). In our original (day, our doses being in sorr(1949). This was done delibeonly permissible because the ISuch C()urses should never beone mgm. per kg. body weilskin reaction becomes minilmdrug per kg. body weight thndrug per kg. body weight. Thione week.

Hetrazan is remarkably nkills or sterilizes the femalethat it does not do so and twithin a year. Even if this Ivalue: the importance of tl:courses or of giving routineweekly, as a suppressant.

The Kisii area of Kenyaor not hetrazan in adequateto do with W. bancroft!: thework designed to eradicate S.fore now be given without iexplain certain of the failuredetails were given of the rcsuseries of hospital patients. A,before the eradication experirto follow them up'. A much h

- ,<:'';~'.

~

I skin and in the eyes: the)resence of the larval fonns

produce interference withare caused by presence of

Ice. Other changes reportedt we have never seen such

lith in detail below: these)psy, skin changes and eye

1d only posItIve results are'lalire over the body, eveni1 snips. In spite of this we:lips are always taken fromIts.

erciasis as in bancroftiasis:; yet of any practical value.

n them the presence of thee in field work and is notalmost diagnostic in them­dence in doubtful cases.

LCtion with the history 01:hange-s should suggest the;d, dry, rough, shiny andprecedes the skin changes,

uous scratching.

menan related to the death;tration of hetrazan. As iu

the administration of evenI almost immediate marked.kin inflamed and with the)stic aid.

the eyes of patients with: phototropism of the larvalof the vector. Photophobia

'he incidence of eye lesionse Belgian Congo mentionsincidence of eye complica­Lal surveys, which probably:rg,ent in the production ofhis work on onchocerciasis)r. Roy McKelvie by kind:nya. Dr. McKelvie is annges in onchocerciasis. ForLmary of the problem,

...

35

Treatment(1) Introdudory

The fact that elimination of the vector of onchocerciasis is practicable doesnot relieve the clinician of his legacy of sick people. But careless treatment maydo more harm than good: the intense skin reaction to over-enthusiastic dosagemay be very trying for the patient, although it does finally settle down; butnothing will make good any damage done to the eyes. It is tbis possibility whichhas made progress so slow: each patient must be hospitalized and must be underthe control of an ophthalmologist: only by such measures will it be possible toproduce drug schedules safe for field use. Problems which must be answered inthe investigation of every drug are; has the drug any effect on the changes present,particularly the skin lesions and eye lesions? What effect has the drug on micro­filarire? What effect has the drug on the adult worm?

(2) lHetrazan

EFFECT ON SKIN CHANGES

The harmful agent is the dead microfilaria: consequently in onchocerciasis,unlike bancroftiasis, the microfilaricidal activity of a drug is the importantfactor, and it is only to be expected that an effective drug will exacerbate theskin changes and pruritis until the great mass of microfilarire has been killed.This means that for the first two to three days of treatment dosage must below to prevent damage to the eyes or even death of the patient (Rodhain, 1949).Thereafter, when aJmOSI all of the microfilarire havc been killed, ~t is safe greatlyto increase the dosage, in the hope of completing the cure by killing or sterilizingthe adult worms. For the first few days the pattern of treatmeut shOUld bealong the lines used in the administcrIng at scrum to au iudIvidual sensitiveto it (reactions may be controlled to some extent by administration of anti­histaminics). In our original experiments we used heavy doses even on the firstday, our doses being in some cases 50 time higher thau those used by Burch(949). This was doue deliberately, to investigate certain eye' changes, and wasonly pelmissible becausc the patients were under the care of ·an ophthalmologist.Such courses should never be used m field work. The type of course suggested isone m~m: per kg. body. ~eight of hetrazan citrate ~hree times daily until theskm reactIon becomes mlTIlmal, then an lllcrease of th{s dosage to about 5 mgm.drug per kg. body weight three times daily, with a total dose' of about 70 mgm.drug per kg. body weight. This means that the course of treatment will last aboutone week.

Hetrazan is remarkably microfilaricidal, but what is not known is whether itkills or sterilizes the female adult worm. Much of the published work suggeststhat it does not do so and that the skin becomes reinfested with microfilarirewithin a year. Even if this be tIlle it does not mean that hetrazan is of novalue: the importance of the condition fully justifies the giving of repeatedcourses or of giving routine prophylactic treatment, even as low as two tabletsweekly, as a suppressant.

The Kisii area of Kenya provides a suitable testing ground to settle whetheror not hetrazan in adequate dosage can sterilize the female worm as it seemsto do with W. banero-iti: the Kenya medical authorities have almost completedwork designed to eradicate S. neavei. Treatment of infected individuals can there­fore now be given without the complicating factor of re-infection which mayexplain certain of the failures reported in the literature. In our 1951 Reportdetails were given of the results obtained by the administration of hetrazan to aseries of hospital patients, As these patients were later re-exposed to infectionbefore the eradication experiments began it has not beeu thought worth whileto foHow them. up. A much larger series of patients is now being treated.

36

EFFECT ON EYE CHANGES

Hetrazan may harm the eyes of patients given this drug for the treatment ofonchocerciasis. On the other hand it may do good, e.g. Boase (1952), an EastAfrican ophthalmologist, reports that a patient admitted blind to hospital withsevere bilateral optic neuritis recovered normal sight after treatment with hetrazan.With McKelvie we gave in our 1951 Report our findings in 16 patients treatedwith hetrazan: in no case did the hetrazan cause other than temporary upset;a re-examination of the patients several weeks after treatment showed that thedrug had done no obviolls harm to the eyes and had at least temporarily clearedthe skin of microfilaria;. These patients have not been observed further to date.

(3) Protostib

INTRODUCTORY

Details of this drug have been given in section II of this Report.

The three immediate problems presenting themselves are: what effect hasprotostib on the eye and skin changes, on the microfilaria;, and on the adultworm? Further, if the drug is of benefit, what is a safe schedule of treatment?So far we have been able to treat only 22 patients (17 males and 5 females), alladults except three chIidren under eleven years of age. With two exceptions allpatients showed microfilaria; in the skin clippings and seven showed nodules:in view of the fact ~,hat we were testing a new drng all patients chosen fortreatment had no physical changes in the eyes except three individuals ~ith

minimal nummular corneal opacities. Eight others showed photophobia only,and seven repO'l'ted "things moving in the eyes".

The total dosage we aimed to give was that found effective in certain ban.croftian lesions, Le. a total of over 240 mgms. Sbv per kg. body weight, thistotal being sp'read over ten days, with first amounts small because of dange1of reactions.

EFFECT ON SKIN CHANGES

The time that, has elapsed since the treating of the patients is too short to'Jllow of our assessing what eftect treatment has had on the skin thickening, etc.This note refers to the skin changes during treatment to cut reactions to aminimum. Doses given in the first two to three days were low. The numberstreated (22 in all) are too small to permit of a detailed analysis by groups but

our reports give some indication that a certain pattern of reaction was commonto almost all the patients.

Important points are-

(a) even with initial doses as high as 12 mgms. Sbv per kg. body weight, theskin did not react in the violent fashion so typical of that followinghetrazan administration: the itching, if it appeared, was not intense,and (Edema and inflammation of the skin were absent or minimal:

(b) when itching did appear as the result of treatment, this itching was foundto be present for several days during treatment;

(c) three of the 22 patients showed no reaction throughout treatment.

The picture shown suggests that there is no mass death of microfilaria; suchas occurs with hetrazan treatment, i.e. it suggests that the protostib is not activelymicrofilaricidal. Tbe effect of treatment on the adult worm will only be ascer·tained by a long post-treatment observation period.

EFFEcr ON EYE CHANGES

The preliminary report abis not strongly microfilaricidal :ment with protostib. In the eyes.reaction such as seen with hetrthe photophobia and "crawlingrelieved by the time the seriesthat their sight had improved,namely blurring of vision aspresent at the end of the cour

The value or otherwise ofdepend on its effect on the aduthan the lack of marked mic]will be an advantage. The efte·~tudied by excision of nodules,

(4) Solustibosao

fNTRODUCTORY

The .preparation used as :section 2. The problems to be !

effect has the drug on the phadult worm? This study has be19 received suflicient quantitiesthe patients were adults, eight nshowed microfilaria; in the skininitial eye lesions are described t

EFFECT ON SKIN CHANGES

In this study we describe 0

giving of the drug. Only generatoo small to permit of detailed

With this drug, as with protas those following hetrazan. OnImation of the skin was absentsecond day and continued for Inot so severe as with hetrazan,ment. Every patient showed itcthat every patient complained 0

the course of treatment.

From the results with thlsuggests that solustibosan is mOlhetrazan. Reactions did not beftinued practically throughout thFrom the point of view of ttpatient's view-point it is a disadan individual as the African I

get steadily worse with treatmerrefuse to finish the treatment.

It is not possible as yet tcon the adult worm.

~.

t.'.

,~~

37

-., .,

lis drug for the treatment of, e.g. Boase (1952), an Eastlitted blind to hospital withfter treatment with hetrazan.ldings in 16 patients treated)ther than temporary 11pset;

treatment showed that tbeI at least temporarily cleareden observed further to date.

of this Report.

selves are; what effect has:rofilari~, and on the adultsafe schedule of treatment?17 males and 5 females), all1ge. With two exceptions alllnd seven showed nodules:rug aU patients chosen forcept three individuals withshowed photophobia only,

md effective in certain ban.per kg. body weight, thi!

's small because of danger

the patients is too short toon the skin thickening, etc.Jent to cut reactions to a{s were low. The numbersiled analysis by groups butJ of reaction was commOn

IV per kg. body weight, the) typical of that followingappeared, was not intense,. absent or minimal;

nent, this itching was found:nt;

afoughout treatment.

death of microfilari<e suchtbe protostib is not activelyt worm will only be ascer-

EFFECT ON EVE CHANGES

The preliminary report above on the skin changes suggests that protostibis not strongly microfilaricidal; this is supported by the eye 'changes during treat­ment with protostib. In the eyes, as in the skin, there was no immediate wild localreaction such as seen with hetrazan treatment. Of the 22 patients five stated thatthe photophobia and "crawling in the eyes" present before treatment had beenrelieved by the time the series of injections had finished: two patients reportedthat their sight had improved, and only one patient showed an adverse reaction,namely blurring of vision as though "looking through smoke": this was stillpresent at the end of the course of treatment.

The value or ·otherwise of peotostib for the treatment of onchocerciasis willdepend on its effect on the adult worms. If the drug proves to be an adulticidethan the lack of marked microfilaricidal effect will not be a disadvantage: itwill be an advantage. The effect of protostib on the adults can only be directlystudied by excision of nodules, work which we have not begun as yet.

(4) SoIustibosan

INTRODUCTORYI

The preparation used as solustibosan "conc." is described in the text insection 2. The problems to be studied here have already been outlined, i.e. whateffect has the drug on the physical changes, on the microfilar,l<e, and on theadult worm? This study has begun; of the first group of patierits treated, only19 received sufficient quantities of drug to allow of preliminary assessment. Allthe patients were adults, eight males and eleven females: all with two exceptionsshowed microfilari<e in the skin clippings, and ten showed typical nodules. Theinitial eye lesions are described below.

EFFECT ON SKIN CHANGES

In ·this study we describe only the skin reactions immedi~tely related to thegiving of the drug. Only general indications are given below, as the numbers aretoo small to permit of detailed analysis.

With tbis drug, as with protostib, the skin reactions were in no way as violentas those following hetrazan. Only one patient showed redema of the skin: inflam­matioo of the skin was absent or minimal; itching usually began about thesecond day and continued for four to five injections; the degree of itching wasnot so severe as with hetrazan, but was more marked than with protostib treat­ment. EvelY patient shOWed itching of some degree. One interesting reaction isthat every patient complained of headache and fever for at least two days duringthe course of treatment.

From the resuJts with the small nnmber of patients treated the picturesuggests that solustibosan is more microfilaricidal than protostib, but less so thanhetrazan. Reactions did not begin until the second or third day. Then they con­tinued practically throughout the course, stopping short about the ninth injection.From the point of view of the physician this is an advantage, but from thepatient's view-point it is a disadvantage, especially when dealing with so primitivean individual as tbe African native, as he cannot understand why he shouldget steadily worse with treatment. The result is that a high proportion of patientsrefuse to finish the treatment.

It is not possible as yet to say whether or not solustibosan has any effecton the adult worm.

I39

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It is that theat activity of)ef of micro­nt of damagetibosan to be

::it were moreblind in one

ophobia withmaining nine,ugh all had

. or counting~r the first in­ied, with one>atients com~

So eyes, whileObservation

nistration ofowed photo­e had photo­I small num­ents showing"crawling"},eye lesions.

increasing ininjection andsensation of

JUt treatmenttion ("smoke

iscussion on'01. We have'eli advancedJlern for the

",