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Resistance to chloroquine (CQ) in Plasmodium falciparum has reached unacceptably high levels in many endemic countries. The pre-treatment factors that identify the children who are at risk of treatment failure after being given CQ were evaluated in 385 children with acute, uncomplicated, Plasmodium falciparum malaria. These children each took part in one of six antimalarial drug trials conducted, between July 1996 and July 2004, in a hyper-endemic area of south-western Nigeria. Following treatment with CQ, 149 (39%) of the children failed treatment by day 7 or 14. In a multivariate analysis, an age ofor =7 years [giving an adjusted odds ratio (AOR) of 2.17, with a 95% confidence interval (CI) of 1.19-3.85; P = 0.01], an asexual parasitaemia ofor =100,000/microl (AOR = 2.17; CI = 1.08-4.35; P = 0.03), the presence of gametocytaemia (AOR = 2.08; CI = 1.14-3.85; P = 0.02) and enrolment4 years after commencement of the study (i.e. after 2000; AOR = 2.13; CI = 1.3-4.0; P = 0.003) were found to be independent predictors at presentation of the subsequent failure of treatment with CQ. Compared with the other children, those who failed to clear their parasitaemias within 3 days and those who still had fever 1-2 days after commencing treatment were more likely to be treatment failures. Together, these findings may have implications for malaria-control efforts in all areas of sub-Saharan Africa where treatment of malaria depends almost entirely on antimalarial monotherapy.

Resistance to chloroquine in Plasmodium falciparum can be reversed, both in vitro and in vivo, by chlorpheniramine, a histamine H(1) receptor antagonist. This reversal raises the possibility of using chlorpheniramine to prolong the clinical usefulness of chloroquine in resource-poor communities. The factors that identify children at risk of treatment failure after being given chloroquine plus chlorpheniramine have now been evaluated in 281 children with uncomplicated, P. falciparum malaria. The children, who had taken part in six trials of antimalarial drugs between February 1996 and September 1999, in a hyper-endemic area of south-western Nigeria, were enrolled prospectively for the present study. Following treatment with chloroquine plus chlorpheniramine, 13 (5%) of the children failed treatment by day 7 or 14. In a multivariate analysis, an age ofor =3 years (adjusted odds ratio = 11.1; 95% confidence interval = 2.2-55.3; P = 0.003) and a parasitaemia that took3 days to clear (adjusted odds ratio=7.9; 95% confidence interval = 1.3-49.4; P = 0.027) were found to be independent predictors of treatment failure. In addition, compared with the children who had a lower axillary temperature then, the children who had an axillary temperature ofor =38 degrees C 2 days after commencing treatment were significantly more likely to be treatment failures. In resource-poor communities using chloroquine plus chlorpheniramine, the easily identifiable predictors of treatment failure might be used to identify children requiring alternative antimalarial drugs.

Seven methanol extracts of seven plants from seven plant families were screened for antimalarial properties. The plants were identified and selected from Gboko and Kastina-Ala local government areas in the Tivland ethnobotany in the Middle Belt Zone of Nigeria. Methanol plant extracts were evaluated for in vitro. antimalarial properties using the lactate dehydrogenase technique, with a multiresistant strain of Plasmodium falciparum. K1. Quantification of activity was by estimation of the concentration of extracts that inhibited 50% growth of parasite (IC50) in µg/ml. Of the seven plants screened, Erythrina senegalensis. DC (Leguminosae), Pericopsis elata. Harms (Papilionaceae), and Bridelia micrantha. Benth (Fabaceae) had IC50 values of 99.7, 124.8, and 158.7 µg/ml, respectively. Nauclea latifolia. SM (Rubiaceae) extract exhibited the least activity in the assay with an IC50 value of 478.9 µg/ml.

The clinical characteristics and the kinetics of the disposition of the hepatomegaly associated with acute, uncomplicated Plasmodium falciparum malaria were investigated in 162 children in an endemic area of Nigeria. Hepatomegaly was significantly more common in the younger than in the older children. Complete resolution occurred in 48% following antimalarial chemotherapy. In the children in whom hepatomegaly did not resolve, a reduction in liver size of17% by the time parasitaemia was cleared (usually on day 3) was associated with non-resolution of hepatomegaly by days 7 or 14 of follow-up. An increase in liver size to at least 125% of the baseline value by day 4 or 5 was associated with a lack of therapeutic response, providing the child involved was aged5 years. In the children who had complete clearance of parasitaemia and resolution of hepatomegaly, there was no significant relationship between the parasitaemia-derived conventional indices of therapeutic response [i.e. time to clearance of 50% (PC50) or 90% (PC90) of the parasitaemia, and the parasite-clearance time (PCT)] and the corresponding parameters derived from measurement of liver size [i.e. time for resolution of 50% (HR50) or 90% (HR90) of the hepatomegaly and the hepatomegaly-resolution time (HRT)] in the same patients. However, as the HR50:PC50, HR90:PC90 and HRT:PCT ratios were similar (range = 1.6-2.1), the liver parameters may have therapeutic application. In the children with drug-sensitive P. falciparum infections and in whom hepatomegaly completely resolved, the area produced by plotting liver size against time (i.e. the area under the curve of hepatomegaly v. time, or AUChp) increased in proportion to the liver size below the costal margin (P = 0.02, from analysis of variance), but there was no significant difference in the half-lives of hepatomegaly (t1/2hp) or in the ratios of liver size to AUChp, indicating that the kinetics of the resolution of hepatomegaly were linear in the range examined. Comparison of the kinetic indices of hepatomegaly and parasitaemia showed that, although the half-lives of parasitaemia and hepatomegaly and the corresponding clearance values were similar, there was no correlation between these parameters among those in whom hepatomegaly completely resolved and parasitaemia completely cleared. These results indicate that routine clinical measurement of the liver size in children with hepatomegaly during acute, uncomplicated, P. falciparum malaria may have some use in evaluating and monitoring the therapeutic responses of infections. The resolution of hepatomegaly, a reflection of pathological changes, lags behind clearance of parasitaemia in children with P. falciparum malaria, and supports the use of the liver 'rate' as a malariometric index for assessing the intensity of transmission in endemic areas.

The efficacy of chloroquine plus chlorpheniramine, a histamine H receptor antagonist, which reverses chloroquine 1 insensitivity in Plasmodium falciparum in vitro and in vivo , was evaluated in 30 pregnant women with recrudescent chloroquine-resistant Plasmodium falciparum malaria. All patients had at least one or more treatment failures with one or more courses of chloroquine or pyrimethamine-sulphadoxine. There was a prompt response to treatment with parasitaemia and fever clearing in all patients within 48 and 96 hours respectively of commencement of therapy with the combination. The cure rate on day 14 was 77%. Parasitaemia recurred in seven patients after day 14 and was successfully treated with oral mefloquine. The combination was well tolerated; pruritus and drowsiness were the only noticeable adverse effects. The progress of pregnancy and its outcome were not adversely affected by treatment with the combination. When fully developed, the combination of chloroquine plus chlorpheniramine may be an alternative in the treatment of chloroquine-resistant malaria during pregnancy in Nigerian women.

SummaryA safe and efficient method for obtaining blood smears for the diagnosis of placental malaria infection is required in order to reduce the risks associated with direct blood contact. We describe a simple and safe method of needle aspiration of the placenta for the diagnosis of placental malaria infection. The method was compared with the conventional incision method in 60 consecutive placentae obtained at term. The quality of the blood smear prepared with the methods were similar. There was a significant correlation between parasite counts from samples prepared with both the incision and aspiration methods. Altman-Bland analysis of the counts revealed narrow limits of agreement with an insignificant bias. The method is useful for obtaining blood smears from the placenta for the diagnosis of placental malaria infection and reducing contact with potential pathogens in blood.

SummarySeventy-three placentae and 73 newborn babies were examined from 72 consecutive parturient Nigerian women at term. Ten of the placentae had ring forms of Plasmodium falciparum only, 17 placentae had ring forms and schizonts, and two placentae had only schizonts. Pigment granules alone was present in two placentae, and pigment granules in combination with ring forms and/or schizonts were seen in 10 placentae. There was seasonal variation in both maternal and placental parasite infection. There was also a positive correlation between peripheral and placental parasite density. First-born babies of primigravidae with infected placentae weighed less and had body lengths lower than those of first-born babies with non-infected placentae but the difference was not statistically significant. Their weights and lengths were also significantly less than those of babies of multigravidae with infected placentae. Peripheral parasitaemia was present in 16 of 73 (21 per cent) newborn babies. Parasite density in the...