464

reduction in the total dose of quinine would have much impact on the parasitological response seen with the ear- lier higher dose regimen. We cannot accept Nick’s asser- tion that our revised quinine regimen for-young children with severe malaria in Africa (15 mdkn load and 10 mgikg maintenance every 12 h) car& a five-fold in- creased risk of failing to enter the therapeutic range within the first 12 h of treatment.

As Nick points out, the larger fraction of quinine bound to plasma proteins in severe malaria ‘protects’ against toxicity even when total drug concentrations ex- ceed 20 me/L. However. such ‘nrotection’ is finite and. even in malaria, toxicity can be expected at high enough unbound concentration. Blindness, rather than cardiac toxicity, is the major feature of qumme overdose: this is rare when quinine is used for treatment of malaria, but it does occur (Yasapaiboon et al., 1984: JapaneseJournal of Ophthalmology, 28, 409; Rheeder & Sieling, 1991: South African Medical Journal, 79, 563; Hatch&Soussi et al., 1993: Archives Francazses de Pediatric, 50, 485). Al- though the ‘standard regimen’ probably achieves satisfac- tory unbound quinine concentrations in Thai adults, our data suggest that unbound levels may be unnecessarily high for Kenyan parasites, and that they approach the threshold of toxicity in young Kenyan children whose (weight-corrected) volume of distribution is smaller than that of adults.

We agree with Dr White that establishing the relative merits of any particular quinine regimen byclinical trial is extremelv difficult. Indeed. this is not how knowledge in this field has progressed.; rather it has moved from un- critical acceptance of empiric regimens to a strong basis in pharmacokinetics (to which Nick White’s contribution has been central) and rationally designed regimens. It is a logical extension of this approach to place more emphasis on unbound quinine levels and to try to establish the therapeutic range. We look forward to discussions with Dr White on how this annroach can be refined.

P. A. Winstanley Department of Pharmacolocy and Therapeutics University ofliverpool, P.O. Box 147 Liverpool, L69 8BX, UK

G. Pasvol Department of Infectious Diseases Northwick Park Hosnital Harrow, Middlesex, &HA 13 U3, UK

K. Marsh Kenya Medical Research Institute Kilifi Unit. P.O. Box 428 Kilt& Kenya and Nuffield Department of Clanical Medicine, The University, Oxford, UK 23 Februa y 1995

Did Joseph Conrad have loiasis? In 1890 Joseph Conrad commanded a Congo river

steamer for a 1300 miles (2000 km) voyage to Stanley Falls, where he had an attack of dysentery. He was bed- ridden for 7 months in 1891 at the age of 33 years, with painful swellings of the hands and legs which were diag- nosed as rheumatism of the left arm and neuralgia of the right arm. Later, a unifying fashionable diagnosis of gout was suggested. The hand swellings interfered with the writing of his first book, ‘Almayer’s Folly’. As he spent most of his time on deck during the Congo river trip, loiasis is a more likely diagnosis. His slow boat averaged only 35 miles (56 km) a day, and tabanid bites must have been a nuisance.

This symptomatology after Conrad’s single African ex- perience must not be confused with the repeated hand arthritis of a rheumatoid type which complicated his later years. He is recorded as supporting his right hand with his left as he wrote in 1909. Although loiasis can, rarely, be complicated by arthritis, a diagnosis of Reiter’s syn- drome is more feasible to explain his later arthritis.

Nucleo de Medicina Tropical e Nutricao Universidade de Brasilia CP 10 23 82 CEP 70 849 Brasilia, DF, Brazil

Philip Davis Marsden

9 March 1995

Absence of Lyme borreliosis from Gauteng, South Africa

We read with interest the report by Mason et al. (1994: Transactions, 88, 412) on the apparent absence of Lyme disease from Zimbabwe, and wish to draw vour readers’ attention to a limited survey we performed-in South Af- rica in 1988 and 1989 (Frean & Isaacson, 1992: Southern African Journal of Epidemiology and Infection, 7, 46-47). We studied 3 groups of subjects: 85 patients with signs and symptoms compatible with a diagnosis of Lyme dis- ease from Johannesburg teaching hospitals; 233 patients with a variety of neurological, cardiological and rheuma- tological conditions in whom Lyme disease was not pri- marily suspected; and 109 normal subjects (blood do- nors). Sera were screened at a dilution of 1:64, using a North American strain of Borrelia burgdorferi as antigen in an indirect immunofluorescence assay. Reactive spe- cimens were tested for evidence of syphilis (by rapid plasma reagin, fluorescent treponemal antibody absorp- tion, and Treponema pallidum haemagglutination tests), and autoimmune disease (rheumatoid and antinuclear factors). If these were negative, the titre of anti-borrelial antibodies was determined; a titre al:256 was con- sidered indicative of Lyme disease, and Western blotting was done. Twenty-nine of 427 sera (6.8%) were positive at 1:64; only one had a titre >1:256 in the absence of sy- philis and auto-antibodies, but the Western blot was ne- gative. Syphilis and auto-antibodies accounted for most (19129) positive reactions on screening. We concluded that there was no evidence of Lyme borreliosis in hu- mans on the Witwatersrand (now part of the Gauteng re- gion), and warned clinicians of the potential dangers of indiscriminate serological testing for Lyme disease in clinical practice in a non-endemic area. This practice may lead to inappropriate or even potentially harmful treat- ment if appropriate criteria, exclusion of cross reactions, and confirmatory tests are not applied. There is a small but steady demand for serological tests for Lyme disease (between 30 and 50 specimens per year are submitted to our laboratory), and it is evident that these caveats still apply.

J. A. Frean Margaretha IsaPcson

Department of Tropical Diseases School of Pathology South African Institute for Medical Research University of the Witwatersrand P. 0. Box 1038 Johannesburg 2000 South Africa 28 March 199.5