J.B.O. Were

Visceral leishmaniasis unresponsive to antimonial drugs II. Response to high dosage sodium stibogluconate or prolonged treatment with pentamidine

Ten Kenyan patients with visceral leishmaniasis unresponsive to sodium stibogluconate, at a dose of 16 to 20 mg Sb/kg body-weight/day given for 30 to 98 days, were treated with 20 mg Sb/kg bw given every eight hours. This regimen was modified or abandoned in six patients because of suspected toxicity, although toxicity was difficult to assess because of intercurrent illness. Toxic effects included lethargy, anorexia, vomiting, electrocardiographic changes, fall in haemoglobin and rise in liver enzymes. One patient died, probably from a cardiac arrhythmia. Two patients were cured, four responded partially and four showed no response. Pentamidine, at a dose of 4 mg/kg body-weight given one to 3 times per week for 5 to 39 weeks, was given as initial treatment in one patient and after failure of sodium stibogluconate in seven. Toxic effects included nephritis, hepatitis, transient diabetes and subcutaneous abscesses. Two patients were cured, two responded partially, three showed no response and one, after apparent cure, relapsed and was unresponsive to additional pentamidine treatment. Low-frequency, long-duration pentamidine was often useful in maintaining any improvement made during treatment with the less well tolerated high-dose, high frequency sodium stibogluconate. We observed the step-wise development of resistance to both sodium stibogluconate and pentamidine. The problems of managing patients with visceral leishmaniasis which is unresponsive to conventional doses of pentavalent antimonials are discussed and some tentative suggestions put forward.

Visceral leishmaniasis unresponsive to antimonial drugs I. Clinical and immunological studies

Ten Kenyan patients with visceral leishmaniasis, unresponsive to sodium stibogluconate at a dose of 16 to 20 mg Sb/kg/day given for 30 to 98 days, have been studied clinically and immunologically and compared with 57 antimony-responsive patients. Pulmonary tuberculosis and previous treatment with antimonial drugs were the only factors which were more common in unresponsive patients. The degree of immunosuppression and rate of recovery of immunoreactivity did not differ between antimony-responsive and -unresponsive patients. Only one patient had never been treated before (primary unresponsiveness). In the other nine patients secondary unresponsiveness occurred after one or more treatment courses, suggesting that the parasite developed resistance to antimony. Antimony-unresponsiveness in visceral leishmaniasis is a serious problem numerically, clinically and economically. A plea is made that the initial treatment of visceral leishmaniasis should be adequate in dose and duration.

Anaemia, blood transfusion practices, HIV and mortality among women of reproductive age in western Kenya☆

Severe anaemia among women in sub-Saharan Africa is frequently treated with blood transfusions. The risk of transmission of human immunodeficiency virus (HIV) through blood products has led to a re-evaluation of the indications for transfusions. Prospective surveillance of women admitted to a district hospital in western Kenya was conducted from 1 December 1990 to 31 July 1991, for haemoglobin (Hb) transfusion status, and outcome. Of the 2986 enrolled women (mean Hb 10.4 g/dL, SD +/- 2.6, median age 24.4 years), 6% were severely anaemic (Hb < 6.0 g/dL). Severe anaemia was associated with a higher mortality rate (10.7% vs. 1.4%, odds ratio (OR) = 8.2, 95% confidence interval (CI) 2.6, 34.2) compared with women with Hb > or = 6.0 g/dL. Decreased mortality rates in hospital were observed with increasing Hb values (OR = 0.43, 95% CI 0.19, 0.98), but blood transfusions did not improve survival in hospital (OR = 1.56, 95% CI 0.22, 11.03). The attributable mortality due to HIV infection and severe anaemia was 75% and 31%, respectively. Maternal/child health care services must include prevention strategies for HIV transmission and the prevention, recognition, and treatment of severe anaemia.

Cutaneous leishmaniasis caused by Leishmania major in Baringo District, Kenya

Leishmania major was isolated from lesions of a patient suffering from cutaneous leishmaniasis in Baringo District of Kenya. Isoenzyme mobilities of this strain were compared with those of L. major, L. donovani, L. aethiopica and L. tropica reference strains and also L. major from a sand fly, Phlebotomus duboscqi, and a rodent, Arvicanthis niloticus, trapped in the same region. The patients isolate had similar banding patterns to the L. major reference strain and also the rodent and the sand fly strains with the 9 enzymes examined. This is the first report in Kenya of an indigenous case with naturally acquired zoonotic cutaneous leishmaniasis.

Acute phase protein concentrations predict parasite clearance rate during therapy for visceral leishmaniasis

Visceral leishmaniasis (VL) remains a major health problem in Kenya and other parts of Africa, Central America and Asia. Currently, splenic aspirate smear and culture are the standard methods of monitoring therapy and relapse. Acute phase reactant markers, C-reactive protein (CRP), serum amyloid A protein (SAA) and alpha 1-acid glycoprotein (AGP) were evaluated as less invasive techniques for monitoring therapy in 59 patients with VL before, during and after therapy. CRP, SAA and AGP were elevated in VL patients at admission and the concentrations decreased with effective therapy to reach normal levels by the end of therapy (SAA and AGP) or by 3 months follow-up (CRP). Two groups of patients were selected on the basis of rate of parasite clearance. The acute phase protein concentrations were significantly raised in those slower to clear parasites. Analysis of sensitivity and specificity of acute phase proteins as predictors of parasite clearance suggested that they might represent useful non-invasive markers for monitoring disease activity, response to therapy and relapse in VL.

Human cutaneous leishmaniasis caused by Leishmania donovani s.l. in Kenya

Our laboratory is characterizing Leishmania stabilates and isolates from active leishmaniasis cases. Smears and cultures from aspirates made on different dates from a single lesion on the bridge of the nose of an 18 years old Kenyan male from Nyandarua District contained Leishmania. The isolates, NLB-271 and NLB-271-IA, were characterized by cellulose acetate electrophoresis (CAE) using 20 enzyme systems and by Southern analysis using 2 deoxyribonucleic acid (DNA) probes (pDK10 and pDK20) from a Dakar strain of L. major (MHOM/SN/00/DK1) and a third probe, p7-059 from L. infantum strain ITMAP-263. Digestion of the two Leishmania DNAs with endonucleases HindIII and PstI, followed by hybridization with the 3 probes, revealed DNA fragment banding patterns indistinguishable from those of the L. donovani species complex. The CAE isoenzyme profiles of these 2 Kenyan isolates were indistinguishable from those of Kenyan L. donovani strains we designated as zymodeme Z6. Excluding post-kala-azar dermal leishmaniasis, this constitutes the first human case of cutaneous leishmaniasis caused by L. donovani s.l. in Kenya. Previously, cutaneous leishmaniasis cases in Kenya have been due to L. aethiopica, L. major and L. tropica only.

Safety and immunogenicity of a Plasmodium falciparum sporozoite vaccine: boosting of antibody response in a population with prior natural exposure to malaria

Recombinant sporozoite vaccine or placebo were administered once to 25 volunteers from an area endemic for malaria. Antibody to R32tet32 rose in 9 of 15 receiving vaccine and remained elevated in 6 for 6 months. Mean absorbance increase was 0.43 +/- 0.40 with vaccine, 0.01 +/- 0.23 with placebo, and 0.72 +/- 0.19 in responders. Six non-responders had significantly lower pre-immunization levels (0.07 +/- 0.05) than responders (0.39 +/- 0.25). There was an association between an increase in immunofluorescence (n = 4) and an increase in absorbance (n = 9) among vaccine recipients (n = 15). Vaccine-induced increase in antibody to natural circumsporozoite antigen was indicated by increases in immunofluorescence and by increases in circumsporozoite precipitation score in 2 of the 5 responders with highest antibody increase measured by enzyme-linked immunosorbent assay. Response to subunit sporozoite vaccine paralleled response to prior natural sporozoite exposure and was significant and prolonged in a population with prior natural exposure to malaria.

Field application of an ELISA using redefined Leishmania antigens for the detection of visceral leishmaniasis

Two soluble antigens from Leishmania donovani of 116 kDa and 70 kDa molecular mass, and a soluble mixture of crude antigens, were used in an enzyme-linked immunosorbent assay (ELISA) for the detection of visceral leishmaniasis (VL) in the field, and compared with the direct agglutination test (DAT). The tests were carried out on 8 VL patients, 34 normal individuals from an area endemic for the disease, and 68 former visceral leishmaniasis patients 1-5 years after treatment. The 70 kDa ELISA and the DAT had a sensitivity and specificity of 100% (95% confidence interval 63-100%), while the 116 kDa ELISA and the soluble crude antigen ELISA were 37.5% (9-76%) and 50% (16-84%) sensitive, respectively. When using ELISA (116 kDa or 70 kDa), 68-69% of sera tested 1-2 years, and 92-94% of sera tested 5 years, after treatment were negative. In contrast, when DAT or ELISA with crude antigen were used, the negativity rate was 31% 1-2 years, and 53% 5 years, after treatment. DAT was therefore not an accurate test for diagnosis in the field. The use of the 70 kDa antigen in ELISA was an accurate alternative to DAT in the detection of VL.

A new focus of kala-azar due to Leishmania donovani sensu lato in Kenya

Three Masai children from Kekonyokie South Location, Kajiado District were diagnosed with visceral leishmaniasis (kala-azar). Leishmanial isolates from the patients were characterized as Leishmania donovani sensu lato, by cellulose acetate electrophoresis. Case histories indicated that the disease was acquired locally. A survey of 409 children at 7 local primary schools and one nursery school revealed no additional case. Sandfly surveys using light traps and sticky paper traps recovered 10 species of sandfly, including 2 Phlebotomus species. P. martini was prevalent throughout the area. P. orientalis was only rarely encountered, but it was the first collection record of this species in the southern portion of the Rift Valley in Kenya. Although no Leishmania-infected sandfly was found, P. martini is probably the vector of kala-azar in the location, as it is elsewhere in Kenya.