Adverse Drug Reactions and Changes in Haematological and Clinical Chemistry to Two ACTs among Nigerian Children with Acute Uncomplicated Malaria.

BACKGROUND: Adverse drug reaction (ADR) is a global and frequently occurring medical emergency with increased cases of mortality annually. ADRs can occur with the use of all drugs including artemisinin-based combination therapy (ACTs) which are currently the treatment of choice for acute uncomplicated malaria globally. Numerous doses of ACTs are administered daily in malaria endemic areas. AIMS: This study determined the incidence, pattern of presentation and factors associated with ADRs to two ACTs- artemisinin piperaquine (AP) and artemether-lumefantrine (AL) among children with confirmed acute uncomplicated malaria in Ibadan, Nigeria. METHODS: Children aged 2-10 years enrolled into a larger study evaluating the safety and efficacy of artemisinin /piperaquine (AP) and artemether /lumefantrine (AL) using the WHO 28-day protocol were studied. Monitoring for ADR was based on history from the parent and /or child (for occurrences of treatment emergent signs and symptoms), physical examinations and abnormalities in laboratory investigations- full blood count, blood chemistry and liver function tests. Causality assessment for the ADR was by the Naranjo algorithm scale. RESULT: 108 of 114 (94.7%) children completed the study. Over half [61(56.5%] were males. The mean age of enrollees was 65.1±30.0 months. Day 28 adequate clinical and parasitological response (ACPR) for AP was 96.1% and 90.4% for AL. Observed ADRs were cough, diarrhea, loss of appetite, abdominal pain, rash, irritability, insomnia and headache. The prevalence was similar in the two treatment groups (AL=14%, AP= 11%; ρ=1.000). The incidence of ADR to both ACTs was 12/1000 patients per day. All ADRs were mild and resolved spontaneously. No notable associated factor to ADR was detected in this study. CONCLUSION: Artemether-lumefantrine and Artemisinin piperaquine were found to be safe in the study population.

CONTEXTE: La réaction indésirable aux médicaments (ADR) est une urgence médicale mondiale fréquente avec une augmentation des cas de mortalité chaque année. Les ADR peuvent survenir avec l'utilisation de tous les médicaments, y compris les thérapies à base d'artémisinine (ACT), qui sont actuellement le traitement de choix pour le paludisme aigu non compliqué dans le monde entier. De nombreuses doses d'ACT sont administrées quotidiennement dans les zones d'endémie palustre. OBJECTIFS: Cette étude a déterminé l'incidence, le modèle de présentation et les facteurs associés aux ADR à deux ACT - l'artémisinine-pipéraquine (AP) et l'artéméther-luméfantrine (AL) chez les enfants atteints de paludisme aigu non compliqué confirmé à Ibadan, au Nigeria. MÉTHODES: Des enfants âgés de 2 à 10 ans, inscrits dans une étude plus vaste évaluant l'innocuité et l'efficacité de l'artémisinine/pipéraquine (AP) ou de l'artéméther/luméfantrine (AL) selon le protocole de l'OMS sur 28 jours, ont été étudiés. La surveillance des ADR était basée sur l'anamnèse des parents et/ou de l'enfant (pour les signes et symptômes émergents liés au traitement), les examens physiques et les anomalies des investigations de laboratoire - numération globulaire complète, chimie sanguine et tests de la fonction hépatique. L'évaluation de la causalité pour l'ADR a été effectuée selon l'échelle algorithmique de Naranjo. RÉSULTATS: 108 enfants sur 114 (94,7%) ont terminé l'étude. Plus de la moitié [61 (56,5%)] étaient des garçons. L'âge moyen des participants était de 65,1±30,0 mois. Le taux de RCAP jour 28 pour AP était de 96,1% et de 90,4% pour AL. Les ADR observées étaient la toux, la diarrhée, la perte d'appétit, les douleurs abdominales, l'éruption cutanée, l'irritabilité, l'insomnie et les maux de tête. La prévalence était similaire dans les deux groupes de traitement (AL=14%, AP=11% ; ρ=1,000). L'incidence des ADR aux deux ACT était de 12/1000 patients par jour. Tous les ADR étaient légers et se sont résolus spontanément. Aucun facteur associé notable aux ADR n'a été détecté dans cette étude. CONCLUSION: AL et AP se sont révélés sûrs dans la population étudiée. MOTS-CLÉS: Réactions indésirables aux médicaments, ACT, Paludisme, Nigeria.

Comparative evaluation of three histidine-rich Protein-2 based rapid diagnostic tests, microscopy and PCR for guiding malaria treatment in Ibadan, Southwest Nigeria.

BACKGROUND: Malaria rapid diagnostic tests (mRDTs) are the preferred option for programmatic deployment. AIMS: There are numerous mRDTs on the Nigerian market and there is a need to guide practitioners on the relative performance of the commonly used brands of mRDT in Nigeria. SUBJECTS AND METHODS: The performance of three commonly used Histidine-Rich-Protein-2-based mRDTs (SD-Bioline™, Carestart™ and Paracheck-Pf™) against microscopy of Giemsa stained blood and polymerase chain reaction (PCR) was evaluated among 190 febrile under-5 children in Ibadan, Nigeria. We calculated the sensitivity, specificity, predictive values, accuracy, and agreements. RESULTS: There were 53.2% males. The prevalence of malaria parasite by microscopy was 46.8% and 57.9% by PCR. Malaria parasite detection by SD-Bioline™ was 60.5%, Carestart™: 60.0% and Paracheck-Pf™ 60.0%. Using microscopy as the gold standard, the sensitivities of SD-Bioline™, Carestart™ and Paracheck-Pf™ mRDT were 97.8%, 96.7% and 97.8% respectively while the specificities were 73.0%, 72.0% and 74.0% respectively. Using PCR as the gold standard, the sensitivity for both SD-Bioline™ and Paracheck-Pf™ was 85.5% and for CareStart was 84.6% while the specificity of SD-Bioline™, Carestart™, and Paracheck-Pf™ was 73.8%, 72.4%, and 75.0% respectively. The test accuracy was 81.0% for both SD-Bioline™ and Paracheck-Pf™ and 80.0% for Caresatrt™. The kappa coefficient of agreement between PCR and each of SD-Bioline™, Carestart, ParaCheck™ and microscopy was 0.597, 0.578, 0.609 and 0.739 respectively. CONCLUSION: The performance of the three mRDTs is a proof that any of the three is suitable for use in the diagnosis of malaria in the southwest of Nigeria.

Evaluation of the comparative efficacy and safety of artemether-lumefantrine, artesunate-amodiaquine and artesunate-amodiaquine-chlorpheniramine (Artemoclo™) for the treatment of acute uncomplicated malaria in Nigerian children.

OBJECTIVE: To evaluate the comparative efficacy and safety of artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ) and artesunate-amodiaquine-chlorpheniramine (AQC) for the treatment of acute uncomplicated malaria among Southwest Nigerian children. SUBJECTS AND METHODS: One hundred and sixty children aged 6 months to 14 years with acute uncomplicated malaria were randomized to AL (n = 53), ASAQ (n = 53), or AQC (n = 54). Enrollees were seen daily on days 0-3 and then on days 7, 14, 21, 28 and 42 for clinical and parasitological evaluations. Paired samples of genomic DNA at enrolment and at the time of recurrent parasitaemia were genotyped using nested PCR to distinguish between reinfection and recrudescence. Detailed haematological and biochemical evaluations were carried out in a subset of enrollees on days 0, 7 and 28 as part of a safety evaluation. RESULTS: Of the 160 children, 144 (90%) completed the study. The mean fever clearance times and parasite clearance times for AL, ASAQ and AQC were comparable (p = 0.94 and p = 0.122, respectively). On day 14, the adequate clinical and parasitological response (ACPR) for AL and AQC was 100% and for ASAQ it was 90% (p = 0.39). The PCR-uncorrected results on days 28 and 42 and the ACPR-corrected results on day 42 were similar for all drugs (p = 0.62 and p = 0.56, respectively). AQC resulted in the best parasite clearance and haematological recovery on day 2 (p = 0.022 and p = 0.018, respectively). Biochemical parameters were not adversely affected by the three artemisinin-based combination therapies (ACTs) and these were well tolerated. CONCLUSION: The three ACTs were efficacious and safe, but AQC resulted in a better haematological recovery on day 2 and higher cure rates throughout the study period.

PERSISTENCE OF PLASMODIUM FALCIPARUM HRP2 ANTIGEN AFTER EFFECTIVE ANTIMALARIAL THERAPY.

Introduction: Histidine Rich Protein 2 based (HRP2-based) malaria rapid diagnostic tests (mRDTs) have been shown to perform as well as routine light microscopy, however, they are limited by some factors including persistence of HRP2 antigenemia. In this paper we report the evaluation of an HRP2-based mRDT in a prospective study that enrolled children and followed them up for 28 days. Methods: Children aged below five years, with acute episode of fever/pyrexia, were enrolled. The enrolled participants had expert malaria microscopy and RDT done at enrolment (Day 0), and on days 1, 2, 3, 7, 14, 21, and 28. The malaria RDT test was considered positive when the antigen and control lines were visible in their respective windows, negative when only the control band was visible and invalid when the control band was not visible. Faint test lines were considered positive. The RDT results were compared to those of expert microscopy. Results: Two hundred and twenty-six children aged 29.2 ± 15.5 months were enrolled. The proportion of children positive by expert malaria microscopy and RDT was 100% and 95.6% respectively. During the 28 day follow up of the children the proportions positive by microscopy and RDT on days 3, 7, 14, and 28 were 1% and 94.6%, 0% and 93.5%, 0% and 91%, and 16.5% and 80.6% respectively. Gender and age dependent analysis of proportion of positive children were similar. Proportion of children with persistence of HRP2 antigen appeared to be lower in those with parasite density below 200/µL, however, this observation requires further evaluation in larger studies. Conclusion: the study revealed a high proportion of persistence of HRP2 antigen in the children 28 days after effective antimalarial therapy. Histidine rich protein 2 based malaria rapid diagnostic tests are not recommended for monitoring of antimalarial therapies.

PARASITE-BASED DIAGNOSIS OF MALARIA IN PREGNANT WOMEN IN A TERTIARY HOSPITAL IN SOUTHWEST NIGERIA.

Background: Malaria in pregnancy has significant adverse consequences for the mother, foetus and baby. Presumptive diagnosis continues despite recommendation for parasite-based diagnosis. We performed Paracheck-PfTM, an HRP-II based malaria Rapid diagnostic test (Paracheck-Pf RDT) and microscopy among pregnant women in a prospective, cross sectional study, at the University College Hospital in Ibadan, Nigeria. Methods: The study was conducted between 2009-2011. Consecutive pregnant women presumptively diagnosed as having malaria >18 years were enrolled after obtaining written informed consent. Demographic information, symptoms and clinical measurements were obtained. Capillary blood was obtained by finger prick for thick blood smear and RDT evaluation. Summary statistics included mean (standard deviation) for quantitative variables and percentages for categorical variables. Chi-square, analysis of variance (ANOVA), the odds ratio (OR) and 95% confidence intervals (CI) were computed with p-value less than 0.05 considered statistically significant. Results: Of the 746 pregnant women aged 30.9 ± 4.6 years enrolled, 243 (32.7%) were primigravida. The mean gestational age was 23.3 ± 9.2 weeks with about 81% in the second and third trimester. The prevalence of malaria parasitaemia by microscopy and Paracheck-PfTM were 22.8% and 24.5% respectively. The geometric mean parasite density was 2,091/µL (range 40-156,975/µL). HIV positivity rate was 8.1 % and 16.1% of patients were anaemic (PCV <30%). Women with axillary temperature >37.4°C were significantly more likely to have malaria parasitaemia [p<0.0001] by microscopy. Sensitivity and specificity of Paracheck overall were 69.9% and 88.2% respectively while those at of parasite densities ≥200/µL were 84.8% and 88.7% respectively. Positive and negative predictive values were 66.9% and over 90% respectively. Conclusion: RDTs are a reasonable alternative in view of the need for parasite-based diagnosis of malaria.

PERSPECTIVE: SUSTAINING EFFECTIVE MALARIA CONTROL DURING THE COVID-19 PANDEMIC.

The COVID-19 pandemic has spread to many malaria endemic countries in sub Saharan Africa. There is little or no experience on how the impact of policies put in place to curtail further spread of the pandemic will affect the epidemiology of malaria during the malaria season. The objective of this write-up is to put in perspective, the need to ensure effective malaria control in the midst of the COVID-19 crises. Proper integration of the COVID-19 safety and treatment guidelines with malaria control policies and effective diagnosis in malaria endemic countries in sub Saharan Africa are important in mitigating morbidity and mortality rates which may rise if malaria cases are neglected due to the current burden of the COVID-19 pandemic.

Blood banking in a malaria-endemic area: evaluating the problem posed by malarial parasitaemias.

The emergence and wide dissemination of drug-resistant malarial parasites underscore the need to prevent post-transfusion malaria. In Nigeria, as in most of sub-Saharan Africa, however, blood donors are not routinely screened for malarial infection. Recently, 391 consecutive potential blood donors in a malaria-endemic area of south-western Nigeria were each checked for malarial parasitaemia using three methods: microscopy (all samples), OptiMAL (315 samples) and/or the Clinotech Malaria Cassette (142 samples). OptiMAL detects parasite-specific lactate dehydrogenase whereas the Clinotech test detects the surface proteins of merozoites and sporozoites. Microscopy revealed parasitaemias in 79 (20.2%) of the potential donors, the levels of parasitaemia varying from 34 to 6289 asexual parasites/microl (mean=445/microl). The prevalence of malarial parasitaemia, as detected by microscopy, was significantly higher during the rainy season than in the dry season (27.3% v. 5.5%; P<0.0001). There was no significant association between patent parasitaemia and fever (i.e. an axillary temperature > or =37.5 degrees C), blood group, gender or anaemia. The corresponding prevalences of malarial parasitaemia detected using the rapid diagnostic tests were 3.8% (12/315) for OptiMAL and 57.8% (82/142) for the Clinotech. With the results of the microscopy used as the 'gold standard', OptiMAL gave a sensitivity of only 16.0% but a specificity of 98.5%. The corresponding values for the Clinotech tests were 69.2% and 50.0%, respectively. It would clearly be beneficial to include screening for malaria parasitaemia in the routine investigation of potential blood donors in Nigeria, especially during the rainy season, when the risk of transfusion-transmitted malaria appears relatively high.

High efficacy of two artemisinin-based combinations (artemether-lumefantrine and artesunate plus amodiaquine) for acute uncomplicated malaria in Ibadan, Nigeria.

OBJECTIVE: To test the hypothesis that artesunate plus amodiaquine (ASAQ) is as effective as artemether-lumefantrine (AL) in the treatment of acute uncomplicated malaria in Nigerian children. METHODS: In an open label, randomized controlled clinical trial, children aged 6 months to 10 years were randomized to receive artesunate (4 mg/kg daily) plus amodiaquine (10 mg/kg daily) or AL (5-14 kg, one tablet; 15-24 kg, two tablets and 25-34 kg, three tablets twice daily). Both drug regimens were given for 3 days and follow-up was for 28 days. RESULTS: A total of 132 children (66 in each group) were randomized to receive either ASAQ or AL. Day 28 cure rates in the per protocol (PP) population were 93% for ASAQ and 95% for AL (OR = 0.71, 95% CI = 0.12-3.99, rho = 0.66). Using Kaplan-Meier product-limit estimates of failure, the median survival time for ASAQ was 21 days and for AL 28 days (P = 0.294). PCR corrected day 28 cure rate for PP populations were 98.4% for ASAQ and 100% for AL. Both drugs were well-tolerated. CONCLUSION: ASAQ is as effective as AL and both combinations were efficacious and safe.

Malaria prevention practices among mothers delivering in an urban hospital in southwest Nigeria.

BACKGROUND & OBJECTIVES: The pregnant woman is more prone to malaria than her non-pregnant counterpart with grave consequences for both mother and baby. This study aims at determining the malaria prevention practices among pregnant women in an area hyper-endemic for malaria. METHODS: For the study 983 parturient mothers were enrolled in Ibadan, southwest Nigeria. Information was collected on sociodemographic characteristics, use of malaria chemoprophylaxis, use of anti-vector measures, and malaria parasitaemia. RESULTS: Most mothers [956/972 (98.4%)] reported the use of anti-vector measures for malaria prevention. These include, window screens (78.9%), insecticides spray (69.9%), mosquito coils (25.3%), untreated bednets (2.5%), and insecticide-treated nets (1.1%). Most mothers used anti-vector measures either singly or in combination. About 86% (840/972) of the mothers used drugs for chemoprophylaxis. Thirteen (1.3%) mothers used chemoprophylaxis alone (CP), 135 (13.9%) used anti-vector measures alone (AV) while 820 (84.4%) used chemoprophylaxis plus anti-vector (CPAV). Weekly dose of pyrimethamine [214 (25%)] and intermittent preventive treatment with sulphadoxine-pyrimethamine [598 (71.2%)] were the widely used chemoprophylactic drugs. The prevalence of patent parasitaemia at delivery was 7.7% (1/13), 12.1% (99/820) and 16.3% (22/135) among CP, CPAV and AV groups respectively. Geometric mean parasite densities among the respective groups were 7840/microl, 1228/microl and 8936/microl. CONCLUSION: Window screens and insecticide sprays were widely used for malaria prevention while the use of ITN was very low among enrolled mothers. There is a need to pay concerted efforts to improve ITN usage rate in Nigeria.

Prevalence of malaria at booking among antenatal clients in a secondary health care facility in Ibadan, Nigeria.

The prevalence of malaria parasitemia at booking was studied in 1,848 pregnant women in a secondary hospital in Ibadan, Nigeria. Main outcome variables were patent parasitemia and fever. 8.4% hadpatent malaria parasitaemia. Most clients (89%) with parasitemia were asymptomatic. Febrile subjects booked at an earlier gestational age [22.7 versus 24.2 weeks] than afebrile patients (p = 0.0052). Anemia was more prevalent among patients with patent parasitemia than those without (58.1% versus 22.6%, p < 0.0001). Malaria parasitaemia was higher among nulliparous women than other parity groups (p < 0.0001). Symptomatic malaria was associated with early booking for antenatal care and malaria parasitemia was a significant determinant of anemia. The prevalence of malaria parasitaemia in this study is much lower than in previous reports.

Enhanced efficacy of amodiaquine and chlorpheniramine combination over amodiaquine alone in the treatment of acute uncomplicated Plasmodium falciparum malaria in children.

OBJECTIVE: To evaluate the comparative efficacy of amodiaquine (AMQ) alone and the combination of AMQ and chlorpheniramine (CP) in the treatment of acute uncomplicated malaria in children. SUBJECTS: Of the 110 children enrolled in the study, 103 with acute uncomplicated malaria, aged 6 months to 12 years, were evaluated using the 14-day modification of the WHO field test. The patients were randomized to 2 groups. Group 1 received supervised treatment with AMQ alone (10 mg AMQ base/kg daily for 3 days), while group 2 received supervised treatment with AMQ (same dose as group 1) plus CP (AMQCP) for 7 days. RESULTS: Both treatment regimens were well tolerated and no patient was withdrawn as a result of recurrent vomiting or drug-related adverse events. There was no significant difference in mean fever and parasite clearance times. The cure rates at day 7 were 90.2 versus 100% (rho = 0.027) for AMQ versus AMQCP, while the day 14 cure rates were 85.9 versus 98.1% for AMQ versus AMQCP, respectively (rho = 0.016). CONCLUSION: The combination of AMQ plus CP proved significantly more effective than AMQ alone in the treatment of acute uncomplicated falciparum malaria, most probably due to the enhancement of the antimalarial effect of AMQ by CP. The combination of AMQCP could be a better alternative to AMQ alone as a companion drug in artemisinin-based combination therapies.

Pre-hospital treatment of febrile illness in children attending the General Outpatients Clinic, University College Hospital, Ibadan, Nigeria.

Many childhood febrile illnesses are treated at home prior to presentation. This study gathered information on treatment practices of caregivers for febrile illnesses in an urban area. A Cross sectional survey of consenting guardians of 535 consecutive febrile children under 10 years presenting at General Outpatients' (GOP) Clinic. University College Hospital. Ibadan was carried out. Thick blood smears were examined for malaria parasite. The mean (SD) age of the febrile children was 3.2 (2.8) years. Nineteen (17.5%) children were brought within 24 hours of noticing fever. Malaria was presumed to be the diagnosis by 217 (40.6%) respondents: 247 (46.2%) did not know the cause of fever. Most. 469 (87.7%) respondents gave drugs bought from chemists/pharmacy shops before presentation at the GOP. Paracetamol 1380 (81.0%)] and chloroquine [171 (36.5%)] were the most commonly used drugs. Twenty-six (15.2%) respondents used chloroquine correctly. One hundred and ninety-nine of 476 children (41.8%) were smear positive and 88 of 191 (46.1%) children whose guardians presumed malaria had parasites. This study reiterates the fact that majority of childhood febrile illnesses are first treated at home. It underscores the need to empower caregivers by appropriate education on knowledge, attitude and practice of the management including home management of malaria.

How well equipped are healthcare facilities to manage childhood malaria? The situation in selected local government areas in South Western Nigeria.

Using a structured questionnaire, surveys were conducted in 55 of 123 primary and secondary healthcare facilities in 4 selected local government areas in Southwestern Nigeria. Heads of healthcare facilities (HCFs) surveyed include nurses (41.8%), medical officers (21.8%) and community extension workers (21.8%). Twenty five (45.5%) HCFs run special clinics for children. About one fifth (20.3%) of staff had received continuing education on management of malaria. Forty seven (85%) HCFs possessed and used national guidelines for management of malaria. Although 48.9% of HCFs had microscopes, fewer had microscope slides, lancets and Giemsa stain which are also required items for definitive diagnosis of malaria. Healthcare workers were not well informed on some aspects in the management of malaria. Selected healthcare workers from various categories attended a workshop where they were trained to correct inadequate knowledge, attitude and practice in the management of malaria. These workers were to train their colleagues on their return to their respective HCFs.

ADVERSE EVENTS TO FIRST LINE ANTI-TUBERCULOSIS DRUGS IN PATIENTS CO-INFECTED WITH HIV AND TUBERCULOSIS.

BACKGROUND: The combination and use of multiple drugs in the treatment of tuberculosis (TB) predispose to adverse drug events and reactions. This study evaluated the incidence, frequency, and severity of adverse events to first line anti-tuberculosis (anti-TB) drugs in patients with TB and co-infections with Human Immunodeficiency Virus (HIV). OBJECTIVE: The objective of this study was to determine the effects of HIV status on the risk of developing adverse events to first line anti-TB therapy. METHOD: The study was carried out between 2006 and 2007 when TB therapy was administered without concomitant anti-retroviral therapy. Patients with TB presenting at the chest clinic of a tertiary hospital were sequentially enrolled. Those with TB alone were allocated to the first group while those with TB-HIV infection were allocated to a second group. A checklist of adverse events to the drugs was used to screen for adverse drug events and reactions during the period of anti-TB therapy. Adverse drug events were graded as serious and others (mild-moderate). RESULTS: One hundred and three patients completed the study. Thirty one (30.1%) of the patients had TB-HIV co-infection. Majority (70.4%) of the events were detected during the first week of therapy, 92% of these events were mild-moderate. Eight (25.5%) of those with TB-HIV co-infection had serious adverse events. All the serious events occurred in the TB-HIV group. Independent factors for occurrence of ADEs include HIV status, increasing age, and female gender. CONCLUSION: The rate of adverse drug events among patients on first line antituberculosis treatment was higher in HIV co-infected patients.

Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: double-blind randomised controlled trial.

BACKGROUND: Increasing resistance to sulfadoxine-pyrimethamine is leading to a decline in its effectiveness. We aimed to assess the safety profile of chlorproguanil-dapsone (CD), and to compare the safety and efficacy of this drug with that of sulfadoxine-pyrimethamine (SP) as treatment for uncomplicated falciparum malaria. METHODS: We undertook a double-blind, randomised trial in 1850 consecutively recruited children with uncomplicated falciparum malaria, pooling data from five African countries. Analyses were based on all randomised patients with available data. FINDINGS: CD was significantly more efficacious than SP (odds ratio 3.1 [95% CI 2.0-4.8]); 1313 patients (96%) given CD and 306 (89%) given SP achieved acceptable clinical and parasitological response by day 14. Adverse events were reported in 46% and 50% of patients randomised to CD and SP, respectively (treatment difference -4.4%, [95% CI -10.1 to 1.3]). Haemoglobin in the CD group was significantly lower than in the SP group at day 7, a difference of -4 g/L (95% CI -6 to -2). Mean day 14 haemoglobin (measured only for the small number of patients whose day 7 data caused concern) was 94 g/L (92-96) and 97 g/L (92-102) after CD and SP, respectively. Glucose-6-phosphate dehydrogenase deficient patients on CD had greater odds than those on SP of having a fall of 20 g/dL or more in haemoglobin when baseline temperature was high. Methaemoglobinaemia was seen in the CD group (n=320, mean 0.4% [95% CI 0.4-0.4]) before treatment, 4.2% (95% CI 3.8-4.6) (n=301) at day 3, and 0.6% (0.6-0.7) (n=300) at day 7). INTERPRETATION: CD had greater efficacy than SP in Africa and was well tolerated. Haematological adverse effects were more common with CD than with SP and were reversible. CD is a useful alternative where SP is failing due to resistance.

Prevalence of multiple intestinal helminths among children in a rural community.

Impairment of physical and mental development has been identified as deleterious effects of helminthic infection. As a result, there have been concerted efforts to control this group of diseases especially among children who are most vulnerable. However, knowing the prevalence of multiple infections will strengthen or otherwise justify the use of broad spectrum antihelminthics in the prophylaxis and treatment of intestinal helminthes among children. This study was carried out in a farming community with no tarred access road, electricity or pipe-borne water. The diagnosis of intestinal helminthes was by Kato-Katz thick smear examination technique. One hundred and seventy stool samples from 88 male and 82 female children were examined. The mean age of the children was 8 +/- 1.6years. One hundred and sixteen of 170 (68.2%) of the study volunteers had one intestinal helminthic infection or the other. Co-infection by more than one helminth was not uncommon and this occurred in 49.1% of the infected population while 35.4%, 11.2% and 2.6% had double, triple and quadruple infections respectively. Ascaris lumbricoides and hookworm were the most common combinations observed in the study 52.6%, followed by the combination of A. lumbricoides and T. trichiura 17.5%. The triad of A. lumbricoides, hookworm and T. trichiura accounted for 12.3% among the multiply infected population. However, quadruple infection with A. lumbricoides, hookworm, T. trichliura and E. vernlicularis had 2.6% prevalence rate among the study population. Ascaris lumbricoides is the most prevalent among all the children, with a prevalence of 81.6%, 63.3% and 52.4% among children aged 12 -17years, 6-11 years and 0-5 years respectively. In conclusion, the presence of multiple infections especially of Ascaris lumbricoides and hookworm in almost 26% of the study population and multiple infections in 49.1% of the infected population justified the use of broadspectrum antihelminthics in the management of helminthiasis among school children of the rural community. Thus treatment and mass chemotherapy directed at school children will be a step in the right direction.

Molecular analysis of Plasmodium falciparum recrudescent malaria infections in children treated with chloroquine in Nigeria.

Parasite genotyping by a polymerase chain reaction was used to distinguish recrudescent from newly acquired Plasmodium falciparum infections in 50 of 160 Nigerian children taking part in a chloroquine efficacy study in Ibadan, Nigeria. A finger prick blood sample was taken from each child before and after treatment to identify recrudescent parasites. By investigating allelic variation in three polymorphic antigen loci, merozoite surface protein-1 (MSP-1), MSP-2, and glutamate-rich protein (GLURP), we determined parasite diversity in the population and in the infected host. DNA from pretreatment and post-treatment samples from 47 of the 50 patients who failed therapy was successfully amplified by the PCR. The MSP-1, MSP-2, and GLURP genotypes in all samples showed extensive diversity, indicating polyclonal infections. The average number of clones per infection in pre-treatment sample was 2.5 with MSP-1, 4.9 with MSP-2, and 2 with GLURP. The extent of multiplicity decreased significantly (P = 0.016) in posttreatment samples. Multiplicity of infection and initial parasite density were not age dependent. Comparison of the variant alleles in pretreatment and post-treatment samples of each patient indicates that 26 of the 47 children had genuinely recrudescent disease. Conversely, post-treatment samples from five children showed completely new genotypes, indicating either a previously sequestered population of parasites or a newly acquired infection. Overall, this study has shown the diversity and complexity of P. falciparum population in Ibadan, Nigeria. The study has also shown the dynamics of P. falciparum infections in this population before and after chloroquine treatment in an area of high malaria transmission.

Comparative efficacy of halofantrine, chloroquine and sulfadoxine-pyrimethamine for treatment of acute uncomplicated falciparum malaria in Nigerian children.

One hundred and ten children aged 6 months to 11 years were randomly treated with halofantrine (HF), sulfadoxine-pyrimethamine (S-P) or chloroquine (CQ) for acute uncomplicated Plasmodium falciparum malaria in an endemic area of south-western Nigeria. The response of infection to treatment in each child was monitored for 14 d. The mean fever clearance times were 1.9 d (n = 36), 1.6 d (n = 27), and 1-7 d (n = 28) for children treated with HF, S-P and CQ, respectively. The parasite clearance times were 3.4 d (n = 39), 4.4 d (n = 24) and 4.1 d (n = 15) in the 3 groups of children. The cure rate at day 7 was 92.3% (36/39) in children treated with HF, 72.7% (24/33) in those treated with S-P, and 39.5% (15/38) in those treated with CQ. By day 14, 4 of 36 (11.1%) parasitologically cured patients treated with HF had experienced recrudescences. The corresponding figures among children treated with S-P or CQ were 8.3% and 13.3%, respectively. The 3 drugs were well tolerated. The results of the study showed a further decline in the sensitivity of P. falciparum infections to CQ, while HF and S-P remained relatively effective in the treatment of malaria in south-west Nigeria.

Cardiac effects of halofantrine in children suffering from acute uncomplicated falciparum malaria.

The cardiac effects of halofantrine were assessed in 42 children with acute symptomatic uncomplicated Plasmodium falciparum malaria by electrocardiographic (ECG) and clinical monitoring over a period of 14 d. The children were treated with oral halofantrine 8 mg/kg body weight every 6 h for 3 doses. There was significant prolongation of the P-R interval (compared with the pre-treatment value) only at 8 h after drug administration. However, first degree auriculoventricular (AV) block occurred in 2 children at 8 h or 8 and 48 h, and second degree AV block in another child at 48 h. There was significant prolongation of the Q-Tc interval at 8, 16, 24, 48 and 72 h after treatment; the proportions of children with Q-Tc interval > 0.44 s were also significantly higher at all these times except 72 h. Rhythm disturbance was rare. There was no significant ECG change at 168 or 336 h. Despite the ECG abnormalities, there was no clinical symptom. These findings indicate that, in children, the currently recommended dose of halofantrine for the treatment of falciparum malaria may produce serious cardiac side effects.

Enhanced efficacy of chloroquine-chlorpheniramine combination in acute uncomplicated falciparum malaria in children.

Chlorpheniramine, a histamine H1 receptor antagonist, reverse chloroquine resistance in Plasmodium falciparum in vitro. However, the clinical significance of this remains unclear. We have evaluated the efficacy of chloroquine and a chloroquine-chlorpheniramine combination in 112 consecutive children with acute symptomatic uncomplicated falciparum malaria. There was no significant difference in the parasite and fever clearance times in the 2 treatment groups. However, the proportion of patients in whom parasitaemia increased 24 h after commencement of treatment was significantly higher in the chloroquine group than in the chloroquine-chlorpheniramine group (28.5% vs. 8.3%, chi 2 = 6.61, P < 0.01). There was also a higher proportion of children with RII and RIII responses to treatment in the chloroquine than in the chloroquine-chlorpheniramine group but the difference was not statistically significant. The cure rate on day 14 was higher in the chloroquine-chlorpheniramine group than in the chloroquine group. Chloroquine and its combination with chlorpheniramine were well tolerated, the only prominent adverse effect being pruritus, with equal incidence in both groups. Chlorpheniramine reversed chloroquine resistance in vitro in a similar manner to verapamil in isolates of P. falciparum obtained from the patients. Failure of a response in vivo to chloroquine correlated with resistance in vitro in patients treated with this drug. In contrast, all but one patient with isolates which were chloroquine resistant in vitro were successfully treated with chloroquine-chlorpheniramine combination. These data suggest the enhanced efficacy of chloroquine-chlorpheniramine combination in treating acute uncomplicated P. falciparum infection in children from an endemic area of Nigeria.