Efficacy of halofantrine in the treatment of uncomplicated falciparum malaria.

In the last decade, Plasmodium falciparum resistance to a number of commonly used anti-malarials especially chloroquine, has increased considerably. Newer anti-malarial drugs are therefore being aggressively evaluated as alternatives. A randomized double-blind controlled trial was therefore undertaken, to compare the efficacy of halofantrine to that of metakelfin, in the treatment of moderately severe infections of Plasmodium falciparum in an endemic malaria area in Kenya. Three hundred and thirty five subjects with laboratory confirmed malaria were recruited and randomized to receive treatment with either halofantrine (171 subjects) or metakelfin (164 subjects). Two thirds (66%) of the study subjects were under the age of five years, and were therefore considered to have minimal immunity. All study subjects were initially admitted to hospital for three days and then followed up as out-patients on days 7, 14, 21, and 28. The level of parasitaemia, the presence of fever and the occurrence of adverse effects were evaluated. Halofantrine was found to be comparable to metakelfin in terms of resolution of fever (mean time 45 and 51 hours respectively). No major adverse side effects were observed. Halofantrine is a viable drug in the treatment of uncomplicated P. falciparum malaria.

Treatment of symptomatic trichomoniasis among adult women using oral nitroimidazoles.

Successful treatment of infections with Trichomonas vaginalis (TV) is difficult because of many confounding factors such as poor abstinence from sex during chemotherapy, lack of standardised chemotherapy, difficulties in understanding transmission patterns and low detection rates among infected individuals. The purpose of this study was to establish the present efficacy of the available drugs at their recommended single or double dosages for Kenya. Adult symptomatic females (age 17-39 years) with positive High Vaginal Swabs but without pregnancy were recruited into the study; and asked to swallow one of the following medicine: nimorazole 2G (Naxogin Farmitalia Carlo Erba, Italy), nimorazole 4G in two equally divided doses 24 hours apart (2GBD), nimorazole 3G, tinidazole 2G (Fasigyn, Pfizer Ltd) and ornidazole 1.5G (Tiberal, Roche, Switzerland). All patients were reviewed 48 hours after the drugs administration and 24 hours after the last dose for the group which received nimorazole 2GBD. 153 patients were recruited into the study. 121 came for follow up out of which 49 were dropped from the study for involvement in sexual intercourse leaving only 72 for the final analysis. Clinical cure was 100% for the group receiving nimorazole 2GBD and nimorazole 3G. Parasitological cure was highest for the group on nimorazole 2GBD (100%) and lowest for the group on tinidazole (50%). Instruction to avoid sex during treatment were withheld from patients. This made it easier during the follow up to pick out and drop from the study those who had had sexual contact.

Immune responses after treatment for Schistosoma mansoni infections.

The changes in the immune responses of patients before and at 3 weeks after treatment with anti-schistosomal drugs were investigated. Lymphocyte responses to Concanavalin A and to worm antigens were inhibited after treatment, whereas responses to cercarial and egg antigens remained unchanged. Eosinophil levels were significantly elevated after treatment and were positively correlated with the increase in anti-worm antibodies (r = 0.587), and negatively associated with anti-egg antibodies (r = -0.727). Although the eosinophil-dependent cytotoxicity to schistosomula was not significantly enhanced after treatment, some increased killing was evident of half the patients (7/15). On the other hand, the ability of adherent mononuclear cells to stimulate eosinophil functions was markedly enhanced by treatment (P less than 0.001). These studies suggest that treatment may enhance some of the potentially protective host's immune mechanisms.

Post kala-azar dermal leishmaniasis: the Kenyan experience.

Post kala-azar dermal leishmaniasis (PKDL) occurs occasionally after successful cure of visceral leishmaniasis. Twelve patients with diagnosis consistent with PKDL were seen at Clinical Research Centre from 1981 to 1985. Clinical presentation ranged from macular hypopigmented lesion to generalized nodular lesions. All lesions cleared either by self-cure or by treatment with sodium stibogluconate.

Eosinophilia and eosinophil helminthotoxicity in patients treated for Schistosoma mansoni infections.

The changes in eosinophil levels and in eosinophil-mediated antibody-dependent schistosomular cytotoxicity, following treatment for Schistosoma mansoni infections, have been investigated in 2 similar groups of patients aged 15-50 years. Patients in group 1 were treated with either hycanthone or oxamniquine, and those in group 2 with hycanthone or praziquantel. Eosinophil levels were significantly increased in both groups. In group 1 peripheral blood eosinophil counts rose from a mean of 175/microliters before treatment to 745/microliters 3 weeks after treatment, and in group 2 from 181/microliters to 1066/microliters. The increase in eosinophil levels was positively correlated with a rise in circulating anti-adult worm antibodies (r = -0.587, P less than 0.05), whereas a negative correlation was recorded with anti-egg antibodies (r = -0.727). Despite some enhanced eosinophil helminthotoxicity following treatment in some of the individuals in group 1 (7/15), the change overall was not significant. In group 2, in which a different standard anti-schistosomular antibody was used, the eosinophil killing capacity recorded at 3 weeks was lower than that before commencement of treatment (t = 2.89, P less than 0.01). The eosinophil stimulating activity, detected in cultured mononuclear cell supernatants (MCS) from individual patients, correlated with eosinophil levels (r = 0.582, P less than 0.02) but there was no association with eosinophil killing. MCS activity did not appear to be boosted by treatment. These studies showed that peripheral blood eosinophil counts were increased following treatment, but their ability to kill schistosome larvae is variable and may depend on the immune serum used as the source of anti-schistosomular antibody.

Comparison of human immune responses to purified Vero cell and human diploid cell rabies vaccines by using two different antibody titration methods.

Antibody responses to a conventional rabies preexposure regimen of a new purified Vero cell rabies vaccine (PVRV) and a human diploid cell vaccine (HDCV) were compared in 80 healthy Kenyan veterinary students. Forty-three of the students received the PVRV and 37 received the HDCV on days 0, 7, and 28. Antibody responses were monitored by using the rapid fluorescent-focus inhibition test (RFFIT) and an inhibition enzyme immunoassay (INH EIA) on days 0, 7, 28, and 49. Both vaccines elicited a rapid antibody response. A good correlation between the RFFIT titers and the INH EIA titers was obtained (r = 0.90). Our results also showed that the INH EIA was more reproducible and might therefore be a suitable substitute for the more expensive and less reproducible RFFIT. The geometric mean titers determined by both tests in the two groups of students were statistically similar during the test period. The RFFIT and the INH EIA gave comparable geometric mean titers, which differed significantly only on day 28 in the PVRV group. The effect of the new PVRV is comparable to that of the more expensive HDCV, as determined by the present test systems. The PVRV could therefore be the vaccine of choice, especially in tropical rabies-endemic areas, where the high cost of the HDCV has confined its use to a privileged few.

Treatment of visceral leishmaniasis in Kenya by aminosidine alone or combined with sodium stibogluconate.

The treatment of leishmaniasis, as currently conducted in Kenya with sodium stibogluconate, is unsatisfactory as it is expensive, resistance and relapses may occur, and major adverse effects have been reported. Recently, aminosidine (paromomycin) sulphate has shown good antileishmanial activity on its own as well as synergism with pentavalent antimony, administered concurrently. The present study was designed to assess the effectiveness of parenteral aminosidine, alone or combined with sodium stibogluconate, in visceral leishmaniasis, compared to treatment by stibogluconate alone. 53 patients were allocated to the 3 therapeutic regimes. The presenting signs and symptoms of leishmaniasis were those commonly seen in the visceral form of the disease, particularly in Kenya. At termination, clinical cures were achieved in all 53 patients with no difference between treatment groups. Spleen aspirates revealed the best parasitological results in patients receiving the combined treatment, with only 13% failures (partial cures + relapses), as opposed to 21% failures with aminosidine alone and 45% with stibogluconate alone. Treatment with aminosidine alone was the cheapest and safest regime.

Comparative study of aminosidine, etophamide and nimorazole, alone or in combination, in the treatment of intestinal amoebiasis in Kenya.

417 patients suffering from intestinal amoebiasis were randomly allocated to 6 different treatment groups in a controlled study in 3 District Hospitals in Kenya. The patients received either aminosidine (A), etophamide (E), nimorazole (N), or the combinations NA, NE, EA. Treatment in all cases was given twice daily for 5 days. Before and after treatment, rectosigmoidoscopy was done in each patient, and stool examination with characterization of invasive (IF) and non invasive (NIF) forms of amoeba was done daily throughout treatment, and on Days 15, 30 and 60 of follow-up. Clinical cure was good after all the treatments, varying from 90 to 100%; parasitological cure at the end of treatment was 100% in the NA and EA treatments groups, and 98% in A group. The incidence of relapses was nil in the EA group, followed by 3% in NA and 6% in A groups. Anatomical cure (healing of ulcers) was 97.8% in the NA group, 95.5% in the N group and 88.5% in the A group. Drug tolerance was excellent or good after all the treatments, except that the EA combination produced diarrhoea in 76.5% of patients. Overall analysis of the findings, including tolerance of the various treatments, showed that aminosidine either alone or in combination with nimorazole gave the best results. Ulcers seen on rectosigmoidoscopy were more common in patients excreting invasive forms of amoebae in their stools.

Comparison of four nitroimidazole compounds for treatment of symptomatic amoebiasis in Kenya.

Four antiamoebic drugs currently used in many Kenyan hospitals and health centres were compared for their efficacy on symptomatic luminal amoebiasis in Kiambu, Kilifi, and Machakos hospitals during this study. The drugs were; the brand metronidazole (Flagyl, May & Baker, Kenya Ltd.), the generic metronidazole (Metrozol, Cosmos Ltd., Nairobi, Kenya), the brand tinidazole (Fasigyn, Pfizer Laboratories Ltd.) and the generic tinidazole (Tynazole Laboratory and Allied Equipments, Kenya Ltd). Clinical cure was achieved in all individuals receiving any of the four drugs. Parasitological cure was better for those receiving either Flagyl or Fasigyn, than those receiving the generic counterparts. Both parasitological and clinical cures were achieved in about 50% of all those who received either Flagyl or Fasigyn. It appears that Flagyl and Fasigyn are not as efficacious as previously reported but are still much better than their generic counterparts for the treatment of symptomatic Entamoeba histolytica infections.

A rapid staining technique for Leishmania parasites in splenic aspirate smears.

A quick and suitable method for staining Leishmania donovani and other blood protozoa is described. The method, which could have wide applications, is a modification of Field's staining technique as used for malaria parasites. It uses the same stains in a different order. The method has been tried on smears containing malaria and trypanosomes, and the results were good. It is very cheap and requires no special apparatus or training.

A study of the efficacy and safety of albendazole (Zentel) in the treatment of intestinal helmenthiasis in Kenyan children less than 2 years of age.

One hundred children comprising of 57 males and 43 females aged between 8 and 24 months entered the study. 46 children had single and 54 children had multiple helminth infections. All children received albendazole 200 mg (10 ml) suspension as a single dose. Albendazole proved very effective and safe in the treatment of single and multiple helminth infections in children under 2 years of age, achieving cure rates of 100% in both Ascaris lumbricoides and Necator americanus respectively, 83% in Trichuris trichiura and 66% in Hymenolepis nana. Treatment of polyparasitism appears to be of benefit in improving nutritional status using haemoglobin concentrations as an index.

The suitability of East African primates as animal models of visceral leishmaniasis.

The susceptibility of four East African primate species to experimental infection with Leishmania donovani was investigated. Vervet monkeys (Cercopithecus aethiops), Sykes monkeys (C. mitis) and baboons (Papio cynocephalus) all supported low grade infections for periods ranging between four and eight months and subsequently showed evidence of self-cure. Greater bushbabies (Galago crassicaudatus) remained completely refractory throughout the course of the experiment. The significance of hepatic histiocytic nodules in the infected primates, similar to those observed in asymptomatic human visceral leishmaniasis, and the susceptibility of Old World primates to experimental infection are discussed.

Electron microscopy of Leishmania donovani in splenic aspirates from patients with visceral leishmaniasis during treatment with sodium stibogluconate.

Studies were made of the ultrastructure of amastigotes of Leishmania donovani before and during treatment of patients with sodium stibogluconate. The most consistent effects of treatment on the amastigotes were a reduction in average size, greater irregularity of the cell outline, and a moderate increase in the electron density of the cytoplasm associated with a greater concentration of ribosomes. It is suggested that the drug affects active transport functions or permeability of the plasma membrane.