Malaria and ELISA HTLV-III antibody reactivity

De Jonckheere, J. (1977). ‘The use of an axenic medium for differentiation. between oathoeenic and nonaathonenic Maegleria fowbri isolates. Applied and Ekironmental Mtcrobiology,

33, 751-757.

De lonckheere, 1. F. & Dierickx, I’. J. (1982). Derermina&on of acid -phosphatase and le&ine aminopeptidase activity as an identification method for pathogenic Naeglena fowleri. Troprcal Medicine

Kilvington,

S.,

ferentiation lovanienns

Transactions and Hygiene,

of the Royal Society of 76, 773-775. Mann, P. & Warhurst, D. (1984). Difbetween Naegleria fowleri and Naeglena

using isoenzyme elec
Accepted

for

publication

16th

Chloroquine-resistantR~a~~aarum

September,

African population is low and that they were nonimmune persons. This report reinforces the idea that it is necessary to carrv on euidemiological studies in Rwanda, in order to clarify ;he extensiin of malaria, the imm&e status of different communities and the existence of P. falciparum strains resistant to chloroquine. J. GASCON’ I.

PLUYMAEKAERS’

i.

L. BADA’

‘HBpital Nemba, Ruiengeri, Rwanda. ‘Debartamento Microbioloeia, Fakltad de Medicinn, Universidad Autbnoma, Barcelona, Spain.

Gascon, J.,

References Pluymaekaers, J. & Bada, J. L.

1984). Changing pattern of malaria in Nyarutovu (Rwanda). Transactions of the Royal Socie@ of Tropzal Medtcine and Hygiene, 78, 421-422. WHO (1984). Malaria risk in international travel. Week& Epidemrological Record, 59, 22 I-227.

1985

malaria

from

Plasmodium falciparum Chloroquine-resistant malaria has been documented in most East African countries and in some Central African countries, including Burundi and eastern Zaire, but Rwanda has not vet been included (WHO. 1984). R&entlv. we have seen three adul; Africans with chloroquine-resistant I’. falciparum malaria in the Nemba Hosoital. situated in the commune of Nvarutovu in Rwanda. Two of the patients were treated with a total dose of 1500 mg of chloroquine base given orally over four days; this regimen was repeated after one week. The third patient was treated with a total dose of 1200 mg of chloroquine base over four days given by intramuscular injections, because he did not tolerate medication by mouth. In none of the three patients was complete parasite clearance achieved, and after an initial drop in parasite density during the first three or four days, the mean parasite density started to increase again on day five. They were completely cured by -Fansidar. These cases fulfil the WHO criteria for RI1 resistance of P. falciparum to chloroquine and show that in Rwanda it exists and is, perhaps, widespread. It is certain that we have done neither in vitro tests for chloroquine sensitivity, nor have we determined bioavailability of chloroquine in the patients. Nevertheless, we repeated a second course of chloroquine by mouth in two of the patients, and the third was treated by i.m. injections. At the same time, the therapeutic response to Fansidar was good. Most of the reports about chloroquine resistance in I’. falczparum make reference to non-immune populations. These three patients we report here were from Nyarutovu, a part of Rwanda where malaria transmission is absent or extremely low (GASCON et al., 1984), and all had travelled to malarious areas a few davs earher. It is probable that immunity to malaria in this

Accepted

for

publication

27th

September,

1985

Malaria and ELBA HTLV-III antibody reactivity Considerable interest has recently been focussed on the association between seropositivity for HTLV retroviral antibodies and Planodium falciparum malaria. BIGGAR et al. (1985) showed that the prevalence of antibodies against HTLV-I, II and III in healthy Africans from Zaire correlated strongly with a high antibodv titre to P. falcioarum. In 17 children aged between 8 and 14 years the prevalence of antibodies against HTLV-III was 35%. In another study 66% of clinically healthy Ugandan children (serum samples collected in 197211973) were positive for antibodies to HTLV-III (SAXINGER er al., 1985). We recently screened sera for antibodies to HTLVIII from 92 Gambian children under the age of 10 (samples collected in 197611977), 38 with acute P. falciparum malaria and the remainder with low grade chronic malaria or partially protected from malaria (FACER, 1980). The children were residents of areas hyperendemic for malaria, the Kombo St. Mary and Foni Brefet districts of The Gambia. The oarasitaemia of children with acute malaria ranged Ifrom O-5 to 40% and all had a high titre of antibodies to P. fhlciparum in a micro-ELISA (mean titre 1.1, range 0.5 to 2.8)*. Sera were screened for antibodies recognizing HTLV-III with the Abbot or Wellcome HTLV-III EIA. All children were seronegative for HTLV-III antibodies. In addition five adult Caucasians with acute falciparum malaria and high (ELISA) titres of anti-malaria antibodies ranging from 0.9 to 4.1 (mean 2.1)* were also seronegative for HTLV-III rerrovirus antibody reactivity. Although a negative *anti-I’.

falciparum ELISA ELISA

ELISA value = value for parasitized red cells minus value for non-parasitized red cells.

352

T~~~sacno~s OF THE ROYAL SOCIETYOF TROPICALMEDICINEAND HYGIENE(1986) 80. CORRESPONDENCE

test doesnot exclude the possibilityof exposureto or infection with HTLV-III, recent evidencehasshown that >80% of virus posmveindividualsare antibody positive (WONG-STAAL & GALLO, 1985). Our results,althoughpreliminary, suggestthat the spreadof HTLV-III from its origin in Central and East Africa (SAXINGERet al., 1985)had not reached The Gambiato any large extent during the period of sampling(1976-77).Obviously additionalsamplingis required to substantiatethis since there is often regional variation in the incidence of HTLV-III seropositivity as shown in the Kenyan study by BIGGARet al. (1985). The results also suggest that the lymphocyte abnormalitiesobservedduring acutemalariamay not relateto infection with HTLV-III. Gambianchildren with acutemalariawere found to have a transientT4 lymphopeniagiving a low T4/T8 ratio (WHITTLE et al., 1984).The authorsof this report speculatedthat a latent T4 cytopathic retrovirus, after activation by malaria,might accountfor the depressed numbersof T4 cells.However, the lack of evidencefor HTLV-III infections in this population suggeststhat this may not be the casein this instancealthoughit is possible that the virus hasspreadsince1977to this region of West Africa. Caucasianswith acute malaria also presentwith a T4 lymphopenia(TROYE-BLOMBERG et al.. 1984;Facer. unnublishedobservations)although we’find their se&negative for HTLV-III antibodi&. This suggeststhat the T4 lymphopeniamight be a reaction to the malaria infection rather than to a manifestationof an underlying HTLV-III infection, asindicatedby the rapid recovery of the T4 population following anti-malarialchemotherapy(WHITTLE et al., 1984).An alternative explanationfor the T4 lymphopeniaof malariais that recirculating T-cells are selectively sequesteredin lymph nodes as observedin Ugandanpatientswith advancedtuberculosis(ROOK,1976)or in the spleenor liver (PLAYFAIR et al., 1979).It hasbeensuggestedthat suchtrapping mechanisms may affect the T4 cellsto a greaterextent than the T8 cells (SWANSON BECK et al., 1985). The correlation between high malaria antibody titres and high antibody titres to retroviruses(BIGGAR et al., 1984)still needsexplanation. Clearly further epidemiologicaland virologic studiesare required, in particular on the current incidenceof HTLV-III in The Gambia and its associationwith malaria.

We thank ProfessorL. H. Collier for helpful commentsand discussion. CHRISTINE A. FACER

Departyqts

A. BENTLEY M. WITHERS P. K. KATAAHA

of Haematology

TheandLondon ViroloP ospztal Medical London El 2AD

College,

References Biggar,R. J., Gigase,P. L., Melby, E. M., Kestens,L., Sarin,P.S.,Bodner,A. J., Demedts, P., Stevens, W. J.,

Paluku, L., Delacollette, C. & Blattner, W. A. (1985). ELISA HTLV retrovirus antibody reactivity associated with malaria and immune complexes in healthy Africans. Lancet, ii, 520-523. Facer, C. A. (1980). Direct Coombs antiglobulin reactions in Gambian children with P. falciparum malaria. II. Specificitv of ervthrocvte-bound IeG. Clinical and Expetimkal

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39, 279-288.

Playfair, J. H. L., de Souza, J. B., Dockrell, H. M., Agomo, P. U. & Taverne, J. (1979). Cell mediated immunity in the liver of rmce vaccinated with malaria. Nature,

282,

731-734.

Rook. G. A. W. (1976). Immune reswnses to mvcobacteria in’ mice and men.’ Proceedings if the Royai Society of Medicine. 69. 442. Saxinger, E. C., Levine, P. H., Dean, A. G., The, G. de, Lange-Wantzin, G., Moghissi, J., Laurent, F., Hoh, M., Sarngadharan, M. G. & Gallo, R. C. (1985). Evidence for exposure to HTLV-III in Uganda before 1973. Science, 227, 1036-1038. Swanson Beck, J., Potts, R. C., Kardjito, T. & Grange, J. M. (1985). T4 lymphopenia in patients with active pulmonary tuberculosis. Clinical and Experimental Immunology, 60, 49-54. Troye-Blomberg, M., Romero, P., Patarraya, M. E., Bjorkman, A. & Perlmann, P. (1984). Regulation of the immune response in P. falciparum malaria III. Proliferative response to antigen in vitro and subset composition of T cells from patients with acute infection or from immune adults. Clinical and Experimental Immunology, 58, 380-387. Whittle, H. C., Brown, J., March, K., Greenwood, B., Seidelin, P., Tighe, H. & Wedderburn, L. (1984). T-cell control of Epstein-Barr virus-infected B-cells is lost during P. falciparum malaria. Nature, 312, 449-450. Wong-Staal, F. & Gallo, R. C. (1985). Human T-lymphocytotropic retroviruses. Nature, 317, 395-403. Accepted for publication

9th January,

1985.