Background: Intermittent preventive treatment with sulphadoxine-pyrimethamine (IPT-SP) is currently the recommended regimen for prevention of malaria in pregnancy in endemic areas. This study sets out to evaluate the effectiveness of IPT-SP in the prevention of maternal and placental malaria in parturient mothers in Ibadan, Nigeria, where the risk of malaria is present all year round.

The seeking of healthcare for childhood illnesses was studied in three rural Nigerian communities of approximately 10,000 population each. The aim was to provide a baseline understanding of illness behaviour on which to build a programme for the promotion of prepackaged chloroquine and cotrimoxazole for early and appropriate treatment of childhood fevers at the community level. A total of 3117 parents of children who had been ill during the 2 weeks prior to interview responded to questions about the nature of the illness and the actions taken. Local illness terms were elicited, and the most prevalent recent illness and the actions taken. Local illness terms were elicited, and the most prevalent recent illnesses were 'hot body' (43.9 per cent), malaria, known as iba (17.7 per cent), and cough (7.4 per cent). The most common form of first-line treatment was drugs from a patent medicine vendor or drug hawker (49.6 per cent). Only 3.6 per cent did nothing. Most who sought care (77.5 per cent) were satisfied with their first line of action, and did not seek further treatment. The average cost of an illness episode was less than US$2.00 with a median of US$1.00. Specifically, chloroquine tablets cost an average of US 29 cents per course. Analysis found a configuration of signs and symptoms associated with chloroquine use, to include perception of the child having malaria, high temperature and loss of appetite. The configuration positively associated with antibiotic use consisted of cough and difficult breathing. The ability of the child's care-givers, both parental and professional, to make these distinctions in medication use will provide the foundation for health education in the promotion of appropriate early treatment of childhood fevers in the three study sites.

BackgroundIn West Africa, envenoming by saw-scaled or carpet vipers (Echis ocellatus) causes great morbidity and mortality, but there is a crisis in supply of effective and affordable antivenom (ISRCTN01257358).MethodsIn a randomised, double-blind, controlled, non-inferiority trial, “EchiTAb Plus-ICP” (ET-Plus) equine antivenom made by Instituto Clodomiro Picado was compared to “EchiTAb G” (ET-G) ovine antivenom made by MicroPharm, which is the standard of care in Nigeria and was developed from the original EchiTAb-Fab introduced in 1998. Both are caprylic acid purified whole IgG antivenoms. ET-G is monospecific for Echis ocellatus antivenom (initial dose 1 vial) and ET-Plus is polyspecific for E. ocellatus, Naja nigricollis and Bitis arietans (initial dose 3 vials). Both had been screened by pre-clinical and preliminary clinical dose-finding and safety studies. Patients who presented with incoagulable blood, indicative of systemic envenoming by E. ocellatus, were recruited in Kaltungo, north-eastern Nigeria. Those eligible and consenting were randomly allocated with equal probability to receive ET-Plus or ET-G. The primary outcome was permanent restoration of blood coagulability 6 hours after the start of treatment, assessed by a simple whole blood clotting test repeated 6, 12, 18, 24 and 48 hr after treatment. Secondary (safety) outcomes were the incidences of anaphylactic, pyrogenic and late serum sickness-type antivenom reactions.FindingsInitial doses permanently restored blood coagulability at 6 hours in 161/194 (83.0%) of ET-Plus and 156/206 (75.7%) of ET-G treated patients (Relative Risk [RR] 1.10 one-sided 95% CI lower limit 1.01; P = 0.05). ET-Plus caused early reactions on more occasions than did ET-G [50/194 (25.8%) and 39/206 (18.9%) respectively RR (1.36 one-sided 95% CI 1.86 upper limit; P = 0.06). These reactions were classified as severe in 21 (10.8%) and 11 (5.3%) of patients, respectively.ConclusionAt these doses, ET-Plus was slightly more effective but ET-G was slightly safer. Both are recommended for treating E. ocellatus envenoming in Nigeria.Trial RegistrationCurrent Controlled Trials ISRCTN01257358

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The effect of combining promethazine with chloroquine was examined against Plasmodium falciparum in vitro in the Aotus-P. falciparum model and in bioassays from volunteers given promethazine. The combination of chloroquine plus promethazine (1 ϫ 10 Ϫ6 M) reversed chloroquine resistance in standard P. falciparum clones and patient parasite isolates from Nigeria. The combination reduced the 50% inhibitory concentrations (IC 50 s) for chloroquine against resistant parasites by 32-92%. Coadministration of promethazine with chloroquine also demonstrated a dose-dependent effect in Aotus monkeys infected with chloroquine-resistant P. falciparum. Monkeys were given a chloroquine dose (20 mg/kg of body weight for seven days), which normally has no effect on parasitemia, plus 10, 20, 40, or 80 mg of promethazine/kg of body weight. In one monkey, parasitemia was suppressed at the lowest promethazine dose, but re-treatment with 20 mg/kg resulted in clearance of parasitemia. Initial treatment with chloroquine and 20 or 40 mg/kg of promethazine cleared parasitemia in some animals followed by recrudescence. Retreatment at higher doses cured one monkey and resulted in initial clearance and delayed recrudescence 28 or 63 days after treatment in two monkeys. Recrudescent parasitemia in the two monkeys was low (10 parasites/l of blood) and subsequently cleared without re-treatment. An in vitro bioassay model was developed to examine the effects of clinically achievable doses of promethazine on parasites susceptibilities in vitro. Plasma samples taken at hourly intervals from patients given a single oral dose of 25 mg of promethazine decreased the IC 50 values for chloroquine by 20-58% with the most significant reductions occurring in plasma obtained from volunteers 3-4 hr after ingestion. Plasma obtained from two volunteers 6 hr after ingestion of the drug demonstrated no effect on chloroquine susceptibility, suggesting that study of the pharmacokinetic disposition and potential interaction is warranted to optimize the dose regimen in patients for antimalarial efficacy. Historic use of this drug combination for treatment or prevention of chloroquine-associated pruritus or as an antiemetic suggest that the combination is safe and effective when used at standard dosages. The results from this study demonstrate that promethazine is a potent modulator of chloroquine resistance. Clinical evaluation of therapeutic regimens is required to validate clinical efficacy of this promising combination for treatment of uncomplicated chloroquine-resistant malaria.

1 Oral amodiaquine (AQ) has been used to treat patients with symptomatic malaria in Zambia (n = 14) and Nigeria (n = 5). Clinical cure was obtained in all patients and no serious adverse drug reactions were seen. 2 As in healthy subjects, AQ achieved low plasma concentrations. Plasma concentration vs time profiles of desethylamodiaquine (AQm) from the present study did not differ from those obtained from healthy subjects. 3 In contrast to previous results from healthy subjects, the mean ratio of red cell (RBC) plasma AQm concentration in the present study was 0.80 : 1 at the start of the study and rose in a linear manner (r = 0.873; P < 0.01) to 3.04: 1 by the end (n = 10; P < 0.01). The final mean value was similar to that seen in healthy subjects. 4 These data show that there are differences in the disposition of orally administered AQ between healthy subjects and patients with clinical malaria. The relevance of this observation to the frequency of adverse reactions to AQ in these two groups is not established.

BackgroundHypertension is a major challenge to public health as it is frequently associated with sudden death due to the silent nature of the condition. By the time of diagnosis, some patients would have developed target-organ damage (TOD) and associated clinical conditions (ACC) due to low levels of detection, treatment and control. TOD and ACC are easy to evaluate in a primary healthcare (PHC) setting and offer valuable information for stratifying cardiovascular risks in the patient. The aim of this study was to evaluate the prevalence and correlates of TOD and established cardiovascular disease (CVD) in hypertensive Nigerian adults.MethodsA cross-sectional study was conducted on 2 000 healthy Yoruba adults between 18 and 64 years who lived in a rural community in south-western Nigeria. Participants diagnosed to have hypertension were examined for TOD and ACC by the presence of electrocardiographically determined left ventricular hypertrophy (LVH), microalbuminuria or proteinuria, retinopathy, or history of myocardial infarction and stroke.ResultsA total of 415 hypertensive participants were examined and of these, 179 (43.1%) had evidence of TOD and 45 (10.8%) had established CVD. TOD was associated with significantly higher systolic (SBP) and diastolic blood pressure (DBP). The prevalence of LVH was 27.9%, atrial fibrillation 16.4%, microalbuminuria 12.3%, proteinuria 15.2%, hypertensive retinopathy 2.2%, stroke 6.3%, congestive heart failure (CHF) 4.6%, ischaemic heart disease 1.7%, and peripheral vascular disease 3.6%. Compared with those with normal blood pressure (BP), the multivariate adjusted odds ratios (95% confidence interval) of developing TOD was 3.61 (0.59–8.73) for those with newly diagnosed hypertension; 4.76 (1.30–13.06) for those with BP ≥ 180/110 mmHg; and 1.85 (0.74–8.59) for those with diabetes mellitus.ConclusionsThis study provides new data on TOD and its correlates in a nationally representative sample of hypertensive adults in Nigeria. In this low-resource setting, attempts should be made to detect hypertensive patients early within the community and manage them appropriately before irreversible organ damage and complications set in. The methods used in this study are simple and adaptable at the primary healthcare level for planning prevention and intervention programmes.