Introduction to, and evaluation of, immunoassays in a malaria research institute in Tanzania.

Various immunoassays have been introduced into, and evaluated at, the Amani Medical Centre in north-east Tanzania. These include immunoblotting to identify mosquito bloodmeals, immunoradiometric and immunoenzymatic assays to assess the presence of circumsporozoite protein in mosquitoes, and enzyme-linked immunosorbent assays to measure antibodies to circumsporozoite antibody in people. The assays were shown to be reliable and practicable for use in the study of malaria epidemiology.

The effects of house spraying with DDT or lambda-cyhalothrin against Anopheles arabiensis on measures of malarial morbidity in children in Tanzania.

The effects of house spraying of DDT and lambda-cyhalothrin against populations of Anopheles arabiensis were assessed in children aged between 1 and 10 years with regard to fever episodes and parasite prevalences. DDT and lambda-cyhalothrin treatment did not reduce the prevalence of malaria episodes as defined by fever (temperatures > or = 37.4 degrees C and/or fever reported) combined with high parasitaemia (> or = 100 parasites/200 leucocytes). However, the prevalence of malaria parasitaemia, of the episodes of fever with any level of malaria parasitaemia and of high parasitaemia alone were significantly reduced. Furthermore, the reduction in mean parasite densities was greater in children of the 1-2 years age group for both insecticides and also for children of 3-5 years age group with lambda-cyhalothrin. Measured and/or reported fever and high parasitaemia were correlated and the data indicated that most of the fevers in these children could be attributed to malaria. Using this criterion it is concluded that the population of An. arabiensis responded to both DDT and lambda-cyhalothrin house spraying which in turn also reduced malaria-related morbidity.

Falciparum malaria fully cleared by amodiaquine, pyrimethamine-sulfadoxine and pyrimethamine-sulfalene in areas of chloroquine resistance in Dodoma, Tanzania.

The in vivo response of Plasmodium falciparum to chloroquine, amodiaquine, pyrimethamine-sulfalene (MetakelfinR) and pyrimethamine-sulfadoxine (FansidarR) was assessed in Dodoma in 1988. Asymptomatic schoolchildren with pure P. falciparum infection were given full curative doses of one of the above antimalarials. Daily parasitological follow-ups were made for seven days. Overall successful follow-up cases were 101, 108, 95 and 97 on chloroquine, amodiaquine, MetakelfinR and FansidarR respectively. The overall resistance rate in the area was 28%. Most of the resistant cases were RII type. There was only one case of MetakelfinR resistance. Amodiaquine and FansidarR were fully effective in eliminating asexual parasitaemia from the blood in all the cases during the seven days of follow-up. The results indicate that chloroquine, a commonly used antimalarial in Tanzania, is not as effective as amodiaquine, a less used drug. Although the 'antifols' are still highly effective in Tanzania, their potency could change with continued use. These drugs should, therefore, be protected and used judiciously.

The chemotherapy of rodent malaria, XXXVIII. Studies on the activity of three new antimalarials (WR 194,965, WR 228,258 and WR 225,448) against rodent and human malaria parasites (Plasmodium berghei and P. falciparum).

In addition to their blood schizontocidal action on Plasmodium berghei in vivo, two Mannich bases WR 194,965 and 228,258 are also active against chloroquine-sensitive and chloroquine-resistant lines of P. falciparum in vitro. The response of the lines to each drug differs but shows no correlation in either case with response to chloroquine. The 8-aminoquinoline WR 225,448 is also active against P. falciparum in vitro but at much higher concentrations than the Mannich bases. Application of the 'chloroquine-induced pigment clumping (CIPC) test' and the study of ultrastructural changes induced in P. berghei in drug-treated mice indicate that WR 194,965 has a mode of action somewhat resembling that of quinine. WR 228,258 in vitro shows a chloroquine-like effect, but not in vivo, suggesting that its mode of action in vivo is different from that of chloroquine. WR 225,448 has no action in the CIPC in vitro and affects primarily mitochondria of the parasites in vivo. It probably acts through a metabolite. Both pre-erythrocytic and erythrocytic stages of rodent malaria parasites are affected by WR 225,448.

Efficacy of chloroquine on Plasmodium falciparum transmitted at Amani, eastern Usambara Mountains, north-east Tanzania: an area where malaria has recently become endemic.

In order to assess the response of newly endemic falciparum malaria to currently used antimalarials, a field study was conducted in Amani, Tanzania. The efficacy of chloroquine (CQ) on Plasmodium falciparum was assessed by in-vivo and in-vitro methods. Fifty-four patients with pure falciparum malaria were treated with CQ and followed daily for 3 days and weekly for one month. Eighty-three per cent of infections exhibited some degree of in-vivo resistance to CQ (46% RI, 28% RII and 9% RIII). Pretreatment blood samples were obtained from all 54 patients for in-vitro sensitivity testing for CQ, amodiaquine (AQ), quinine (QN), and mefloquine (MQ). In-vitro data correlated well with in-vivo data; 80% of successful isolates were resistant to CQ. Forty-five per cent of successful isolates were resistant to AQ, 2% to QN, and none to MQ. The antimalarial levels yielding 99% inhibition (EC99) for CQ, AQ, QN, and MQ were 12.86, 3.24, 24.09 and 0.81 microM respectively. Urine HPTLC revealed CQ metabolites in 15% of study patients who denied recent CQ ingestion and had a negative Dill-Glazko test. This implies the high rate of CQ resistance observed in this study could be due in part to the widespread use of CQ for self-medication. Although the day 3 mean CQ plasma level was higher for sensitive and RI infections than for RII and RIII infections, the difference did not reach statistical significance. Our study results confirm that P. falciparum transmitted at Amani is highly resistant to CQ.