Tropical Medicine Update

Tropical Medicine Update

CPFI Annual Meeting, Myrtle Beach, SC June 11, 2016

Ron Herman, Ph.D.

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Learning ObjectivesLearning Objectives On completion of this session, the participants will be

able to: Review CDC and WHO recommendations for the drugs

used to treat the most common parasitic infections (including intestinal helminths, filariasis, schistosomiasis, intestinal protozoa, leishmaniasis, and Guinea worm).

Identify the current WHO recommendations for both the prevention and treatment of the most deadly tropical disease, malaria.

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Learning ObjectivesLearning Objectives On completion of this session, the participants will

be able to: Recognize what is new with some of the most

neglected tropical diseases; including; onchocerciasis, leishmaniasis, Guinea worm disease and trachoma.

Identify the resources where information can be obtained for emerging viruses of international concern, including Chikungunya, Zika and Ebola.

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IntroductionIntroduction Soil-transmitted helminths are among the most common

causes of infection in the developing world. The WHO estimates that 270 million pre-school children and

600 million school-age children are in need of treatment. Approximately half of the world's population is at risk of

malaria, particularly those living in lower-income countries. A child dies of malaria every 30 seconds. There were 214 million cases of malaria in 2015, causing nearly

438,000 deaths, mostly among African children (90%). The good news, however, is that malaria is preventable and

curable. This death rate is 40% lower than 15 years earlier.WHO – Key Facts 4

Neglected Tropical DiseasesNeglected Tropical Diseases Neglected Tropical Diseases have been

identified by the:CDC in Atlanta http://www.cdc.gov/globalhealth/ntd/diseases/ind

ex.htmlWHO in Genevahttp://www.who.int/neglected_diseases/resources

/en/

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Neglected Tropical DiseasesNeglected Tropical Diseases Additional useful resource:Molyneux and Malecela; Neglected Tropical

Diseases and the Millennium Development Goals - why the “other diseases” matter: reality versus rhetoric. Parasites & Vectors2011; 4:234

http://www.parasitesandvectors.com/content/4/1/234

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Neglected Tropical DiseasesNeglected Tropical DiseasesWhich diseases are considered Neglected Tropical Diseases (NTD’s)?Buruli ulcer Fascioliasis RabiesChagas disease Trypanosomiasis (African

Sleeping Sickness)Schistosomiasis*

Cysticercosis Leishmaniasis Soil-transmitted Helminths *Dengue fever Leprosy (Hansen's disease) Trachoma*Dracunculiasis (Guinea Worm Disease)*

Lymphatic filariasis* Yaws

Echinococcosis Onchocerciasis** Disease is controllable by mass drug administration (MDA) or effective intervention

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Neglected Tropical DiseasesNeglected Tropical Diseases

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Prevalence of Parasitic InfectionsPrevalence of Parasitic InfectionsDisease Millions of Infections per yearAscariasis Helminth (Roundworm) 800Hookworm Helminth (Hookworm) 700Trichuriasis Helminth (Whipworm) 500Filariasis Helminth (Fluke) 250Onchocerciasis Helminth (Fluke) 30Schistosomiasis Trematode Helminth (Fluke) 200Amebiasis Amebae 400Giardiasis Amebae 200Trypanosomiasis Protozoa 13Malaria Protozoa 800

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Soil Transmitted HelminthsSoil Transmitted Helminths They are among the most common infections

worldwide and affect the poorest and most deprived communities.

The main species that infect people are Roundworm (Ascaris lumbricoides)Pinworm (Enterobius vermicularis)Whipworm (Trichuris trichiura) Hookworms (Necator americanus and

Ancylostoma duodenale).10

Soil Transmitted HelminthsSoil Transmitted Helminths Transmission can happen in several ways: Eggs that are attached to vegetables are

ingested by a new host when the vegetables are not carefully cooked, washed or peeled;

Eggs are ingested from contaminated water sources;

Eggs are ingested by children who play in the contaminated soil and then put their hands in their mouths without washing them.

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Soil Transmitted HelminthsSoil Transmitted Helminths Ingested eggs then turn grow in the

newly infected host. The worms feed on host tissues, including

blood, which leads to a loss of iron and protein.

The worms increase malabsorption of nutrients.

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Soil Transmitted HelminthsSoil Transmitted Helminths Morbidity is related to the number of worms

harbored within a person. People with light infections usually have no

symptoms. Heavier infections can cause a range of symptoms

including intestinal manifestations (diarrhea and abdominal pain), general malaise and weakness, and impaired cognitive and physical development.

Hookworms cause chronic intestinal blood loss that can result in anemia.

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WHO Recommended TreatmentWHO Recommended Treatment Albendazole (Valbazen®)Dose (For adults and children > 25 Kg)Ascaris, hookworm, whipworm, pinworm, and

trichostrongyliasis: single 400 mg doseStrongyloides 400 mg QD x 3 daysCapillariasis 400 mg QD x 10 days

Dose for younger children 15-25 Kg give 200 mgFor 6 months – 15 Kg give 100 mg

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WHO Alternative TreatmentWHO Alternative TreatmentMebendazoleDose (For adults and children > 25 Kg)Ascaris, hookworm, whipworm, pinworm, and

trichostrongyliasis: single 500 mg doseStrongyloides 200 mg BID x 3 daysCapillariasis 200 mg BID x 10 days

Dose for younger children 15-25 Kg give 200 mgFor 6 months – 15 Kg give 100 mg

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Filarial Helminth (Fluke)Filarial Helminth (Fluke) Onchocerciasis (River Blindness) It is a parasitic disease transmitted by

repeated bites of infected blackflies (Simulium spp.).

These blackflies breed in fast-flowing rivers and streams, mostly in remote villages located near fertile land where people rely on agriculture.

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Filarial Helminth (Fluke)Filarial Helminth (Fluke) Onchocerciasis (River Blindness) In the human body, the adult worms produce

embryonic larvae (microfilariae) that migrate to the skin, eyes and other organs.

When a female blackfly bites an infected person during a blood meal, it also ingests microfilariae which develop further in the blackfly and are then transmitted to the next human host during subsequent bites.

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Filarial Helminth (Fluke)Filarial Helminth (Fluke)Onchocerciasis TreatmentIvermectin150 mcg/kg (usually 2 tablets in adults) as a

single dose, with water on an empty stomach. Repeat every 6-12 months.

Diethylcarbamazine25 mg daily for 3 days, then 50 mg daily for

3 days, then 100-150 mg daily for 10 days.

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Filarial Helminth (Fluke)Filarial Helminth (Fluke)Onchocerciasis Elimination ProgramAggressive nationwide treatment

programs, with over 40 million people treated has resulted in the WHO recognizing elimination of the disease in many countries and an over 85% reduction in infections in many others.

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Filarial Helminth (Fluke)Filarial Helminth (Fluke) Lymphatic Filariais (Elephantiasis) Infection occurs when filarial parasites are

transmitted to humans through mosquitoes. Infection is usually acquired in childhood

causing hidden damage to the lymphatic system. The painful and profoundly disfiguring visible

manifestations of the disease, is due to lymphedema.

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Filarial Helminth (Fluke)

Filarial Helminth (Fluke)

Lymphatic Filariais(Elephantiasis)

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Filarial Helminth (Fluke)Filarial Helminth (Fluke) Lymphatic Filariais (Elephantiasis) Treatment Ivermectin 200-400 mcg/kg as a single dose, with water on an

empty stomach. It can be given with or without a single dose of albendazole 400 mg.

Diethylcarbamazine 5-6 mg/kg daily in divided doses for 2-3 weeks.

Begin at a low dose and increase over 3-5 days.

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Trematode Helminth (Fluke)Trematode Helminth (Fluke) SchistosomiasisTransmission occurs when people suffering

from schistosomiasis contaminate freshwater sources with their excreta containing parasite eggs which hatch in water.

People become infected when larval forms of the parasite – released by freshwater snails –penetrate the skin during contact with infested water.

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Trematode Helminth (Fluke)Trematode Helminth (Fluke)Schistosomiasis TreatmentPraziquantel (Biltricide®)Dose 40-60 mg/kg/day in 2-3 doses,

for just 1 day

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Intestinal ProtozoaIntestinal Protozoa Amebiasis Transmission occurs via the fecal–oral route, either

directly by person-to-person contact or indirectly by eating or drinking fecally contaminated food or water.

The clinical spectrum ranges from asymptomatic infection, diarrhea and dysentery to fulminant colitis and peritonitis.

Treatment - Metronidazole (Flagyl®) Dose: 750 mg TID x 10days or (30 mg/kg/day)

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Intestinal ProtozoaIntestinal Protozoa Giardiasis Infection occurs through ingestion of G. intestinalis cysts

in water (including both unfiltered drinking-water and recreational waters) or food contaminated by the feces of infected humans or animals.

Intestinal symptoms include chronic diarrhea, abdominal cramps, bloating, fatigue and weight loss however, many infections are asymptomatic.

Treatment - Metronidazole (Flagyl®) Dose: 2 g once daily for 3 days (or 5 mg/kg TID x 5-10

days).26

Intestinal ProtozoaIntestinal Protozoa Giardiasis - Precautions There is a significant risk for travelers in contact with

recreational waters used by wildlife, with unfiltered water in swimming pools or with contaminated municipal water supplies.

Avoid eating uncooked food (especially raw fruit and vegetables) or ingesting any potentially contaminated (i.e. unfiltered) drinking-water or recreational water. Water can be purified by boiling for at least 5 min, or by filtration or chlorination, or by chemical treatment with hypochlorite or iodine (less reliable).

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Cutaneous ProtozoaCutaneous Protozoa Leishmaniasis It is caused by the protozoan parasite,

Leishmania, which is transmitted by the bite of infected female sandflies.

There are 3 main forms of leishmaniasis –cutaneous (the most common), and mucocutaneous and visceral (the most serious form of the disease).

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Cutaneous ProtozoaCutaneous Protozoa Leishmaniasis – Treatment A pentavalent antimonial is the first line agent

given at a dose of 20 mg/kg of Sb5+ either as:Melgumine Antimoniate (85 mg/ml)Sodium Stibogluconate (100 mg/ml)

The medication is given IV or IM for 20-28 days.

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Cutaneous ProtozoaCutaneous Protozoa Leishmaniasis – Treatment Alternatives include:Pentamidine – 4 mg/kg daily or every other day for

a total of 15 dosesMiltefosine – 100 mg PO daily for 4 weeks

(Children 2.5 mg/kg)Ketoconazole 600 mg daily for 28 daysParomycin sulfate – Topically for cutaneous lesions

– BID for 10-20 days30

Dracunculiasis (Guinea-worm)Dracunculiasis (Guinea-worm) Dracunculiasis is a crippling parasitic disease on

the verge of eradication, only 22 human cases were reported in 2015.

The disease is usually transmitted when people who have little or no access to improved drinking water sources swallow stagnant water contaminated with parasite-infected water-fleas (Cyclops) that carry infective guinea-worm larvae.

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Dracunculiasis (Guinea-worm)Dracunculiasis (Guinea-worm) Of the 20 countries that were endemic for the

disease in the mid-1980s, only 4 countries reported cases in 2015 (Chad (9), Mali (5), South Sudan (5) and Ethiopia (3)).

From the time infection occurs, it takes between 10–14 months for the transmission cycle to complete until a mature worm emerges from the body.

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Dracunculiasis (Guinea-worm)Dracunculiasis (Guinea-worm)Treatment/PreventionThere is no vaccine to prevent, nor is

there any medication to treat the disease. Prevention is possible however and it is

through preventive strategies that the disease is on the verge of eradication.

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Dracunculiasis (Guinea-worm)Dracunculiasis (Guinea-worm)Prevention strategies include:heightening surveillance to detect every case within

24 hours of worm emergence;preventing transmission from each worm by

treatment, cleaning and bandaging regularly the affected skin-area until the worm is completely expelled from the body;

preventing drinking water contamination and ensuring wider access to improved drinking-water;

promoting health education and behavior change.

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TrachomaTrachoma Trachoma is the leading infectious cause of

blindness in the world. It is caused by an obligate intracellular bacterium called Chlamydia trachomatis.

The infection is transmitted through contact with eye and nose discharge of infected people, particularly young children who are the principal reservoir of infection. It is also spread by flies which have been in contact with the eyes and noses of infected people.

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TrachomaTrachomaControl Programs:Surgery to treat the blinding stage of the

disease (trachomatous trichiasis),Antibiotics to treat infection,Facial cleanliness, andEnvironmental improvement, particularly

improving access to water and sanitation.36

TrachomaTrachomaTreatment:Tetracycline 1% Eye Ointment,

apply QID for 6 weeks.Azithromycin 1g PO single dose,

(Children < 10 yr, 10 mg/kg)

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Parasitic Diseases - ProtozoaParasitic Diseases - ProtozoaMalaria – it is caused by a protozoa

parasite from the Plasmodium species.Plasmodium falciparumPlasmodium vivaxPlasmodium malariaePlasmodium ovarium

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Vector: Anopheles mosquitoVector: Anopheles mosquito

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Who is at risk?Who is at risk?Most cases and deaths are in sub-

Saharan Africa. However, Asia, Latin America, the Middle East and parts of Europe are also affected. Malaria is present in over 100 countries and territories.

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Malaria Affected AreasMalaria Affected Areas

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SymptomsSymptoms First symptoms are minor – similar to other viral

infections: Fever, headache, chills and vomiting. Usually appear 10 to 15 days after a person is

infected. If not treated promptly with effective medicines,

malaria can cause severe illness and is often fatal.Metabolic acidosis, severe anemia and hypoglycemia. Coma and acute renal failure.

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Treatment GoalTreatment Goal Uncomplicated MalariaEarly treatment of malaria will shorten its

duration, prevent complications and avoid a majority of deaths.

Treatment aims to cure patients of the disease rather than to diminish the number of parasites carried by an infected person.

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Diagnosis of MalariaDiagnosis of Malaria WHO Guidelines for the Treatment of Malaria –

3rd Edition, 2015: All cases of suspected malaria should have a

parasitological test (microscopy or Rapid diagnostic test (RDT)) to confirm diagnosis.

However, it is often based on clinical criteria (clinical diagnosis). Clinical diagnosis alone has very low specificity.

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Diagnosis of MalariaDiagnosis of Malaria Areas where parasitological diagnosis is not

currently available: The decision to provide antimalarial treatment

must be based on the prior probability of the illness being malaria.

Carefully weigh the risk of withholding antimalarial treatment from the patient with the risk associated with antimalarial treatment.

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Clinical DiagnosisClinical Diagnosis In settings where the risk of malaria is low:

Clinical diagnosis of uncomplicated malaria should be based on the degree of exposure to malaria and a history of fever in the previous 3 days with no features of other severe diseases.

In settings where the risk of malaria is high: Clinical diagnosis should be based on a history of fever in

the previous 24 h and/or the presence of anemia, for which pallor of the palms appears to be the most reliable sign in young children.

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WHO Treatment Recommendations

WHO Treatment Recommendations

Strong recommendation, high quality evidence, treat uncomplicated P falciparum malaria. Treat children and adults, except pregnant

women in their first trimester, with one of the following recommended artemsinin-based combination therapies (ACT):

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WHO Treatment Recommendations - Revised

WHO Treatment Recommendations - Revised

Strong recommendation, high quality evidence, based on pharmacokinetic modelling: Children <25 Kg should be treated with

dihydroartemisinin + piperaquine at a minimum of 2.5 mg/kg bw of dihydroartemisinin and 20 mg/kg bw of piperaquine daily for 3 days.

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WHO Treatment Recommendations

WHO Treatment Recommendations

Artemether + lumefantrineArtesunate + amodiaquineArtesunate + mefloquineDihydroartemisinin + piperaquineArtesunate + sulfadoxine-pyrimethamine (SP)

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WHO Treatment Recommendations - Duration

WHO Treatment Recommendations - DurationStrong recommendation, high quality

evidence: ACT regimens should provide 3 days

of treatment with an artemisininderivative.

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WHO General Treatment Recommendations

WHO General Treatment Recommendations

Prompt treatment for all episodes of disease (within 24 hours of the onset of symptoms if possible);

Use of insecticide-treated nets for night-time prevention of mosquito bites;

For pregnant women in highly endemic areas, preventive doses of sulfadoxine–pyrimethamine (IPT/SP) to periodically clear the placenta of parasites;

Indoor residual spraying to kill mosquitoes that rest on the walls and roofs of houses. WHO 2015

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ChemoprophylaxisChemoprophylaxis Travelers and their doctors should be aware

that NO ANTIMALARIAL PROPHYLACTIC REGIMEN GIVES COMPLETE PROTECTION, but good chemoprophylaxis (adherence to the recommended drug regimen) does reduce the risk of fatal disease.

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ChemoprophylaxisChemoprophylaxis The following should also be taken into account:

Dosing schedules for children should be based on body weight. Antimalarials that have to be taken daily should be started the

day before arrival in the risk area. Weekly chloroquine should be started 1 week before arrival. Weekly mefloquine should preferably be started 2–3 weeks

before departure, to achieve higher pre-travel blood levels and to allow side-effects to be detected before travel so that possible alternatives can be considered.

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Possible RegimensPossible Regimens Atovaquone-Proguanil Combination

(Malarone™) Chloroquine plus Proguanil Chloroquine aloneMefloquine (Lariam™) Doxycycline Proguanil (Paludrine™) alone

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Which one do you use?Which one do you use? There is not an easy answer. Resistance to these

agents has become a problem, so the answer to which one depends on where you are going.

It is essential that you check with the CDC for the specific area that you are traveling to make sure that the agent you choose is effective in that region of the world.

https://www.cdc.gov/malaria/travelers/country_table/a.html

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Malaria VaccineMalaria Vaccine RTS,S/AS01 is a malaria vaccine against Plasmodium

falciparum, the most deadly malaria parasite globally, and the most prevalent in Africa. It has been developed through a partnership between

GlaxoSmithKline Biologicals (GSK) and the PATH Malaria Vaccine Initiative (MVI), with support from the Bill & Melinda Gates Foundation.

It offers no protection against P. vivax malaria, which predominates in many countries outside of Africa.

The vaccine is being considered as a complementary malaria control tool in Africa.

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Malaria VaccineMalaria Vaccine It is the first malaria vaccine to have completed pivotal

Phase 3 testing and obtained a positive scientific opinion by a stringent medicines regulatory authority.

The Phase 3 trial of RTS,S enrolled over 15,000 infants and young children in seven sub-Saharan African countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, and the United Republic of Tanzania).

The RTS,S vaccine requires the administration of 4 doses—the first 3 doses at monthly intervals and a fourth dose 18 months later.

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Malaria VaccineMalaria Vaccine Results were released in January. Among children aged 5-17 months who received four

doses on a 0, 1, 2, 20 month schedule, vaccine efficacy against clinical malaria was 39% over the full duration of the trial.

With a four-dose schedule, the overall efficacy against severe malaria among children in this age group was 31.5%, with reductions in severe anaemia, malaria hospitalizations and all-cause hospitalizations also seen.

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PreventionPrevention Personal prevention focuses on reducing the transmission of the

disease by controlling the malaria-bearing mosquito. Use of mosquito nets treated with long-lasting insecticide, a very cost-

effective method; There are now insect impregnated tents and tarpaulins, There insecticide treated blankets and top sheets Indoor residual spraying of insecticides. Insect repellant sprays and creams like DEET.

Environmental prevention: Reducing standing water habitats where insects breed.

http://apps.who.int/malaria/docs/WHO-TRS-936s.pdf

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Insecticide ResistanceInsecticide Resistance This has become a concern in Africa where

there is increasing mosquito resistance to key insecticides DDT and pyrethroids.There are no alternative, effective

insecticides.Vector control has resulted in a change in

habitat for the insects.http://apps.who.int/malaria/docs/WHO-TRS-936s.pdf

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Emerging InfectionsEmerging Infections Where do you go to learn about new and emerging

health concerns? Chikungunya Fever

http://www.who.int/mediacentre/factsheets/fs327/en/ http://www.cdc.gov/chikungunya/

Zika Virus http://www.who.int/mediacentre/factsheets/zika/en/ http://www.cdc.gov/zika/index.html

Ebola Virus Disease http://www.who.int/mediacentre/factsheets/fs103/en/ http://www.cdc.gov/vhf/ebola/

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ConclusionConclusion Short term medical trips have an amazing

opportunity to be involved in helping to impact some of these neglected tropical diseases.

New treatments are continually being developed.Hopefully, your understanding of these

treatments has been improved;And your ability to access these new

developments has been enhanced.62