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

Allergy sensitization and asthma among 13-14 year old school children in Nigeria

Background: The prevalence of asthma and role of atopy in asthma among children has not been clearly defined in Nigeria.Objective: To determine the prevalence of asthma and investigate risk factors related to allergy sensitization among urban and rural school children in southwest Nigeria.Methods: Validated ISAAC questionnaire was administered to 1736 high school children in randomly selected schools in rural and urban communities. Identified asthma cases were matched to controls. Allergy skin tests, blood eosinophil count, serum IgE and stool examination for parasites were performed. Dust samples from homes were also collected and analyzed for allergens.Results: The prevalence of asthma was 7.5% (95% CI 6.0 to 9.2%) and 8% (95% CI 6.0-10.4%) in the rural and urban communities respectively . Risk factors for asthma included cigarette-smoking, cats in the home and family size. Eosinophil count (109/L) was elevated in asthmatics [0.70 (95% CI 0.48-1.11) vs. 0.32 (95% CI 0.19-0.69); p<0.01], but IgE levels were similar between the two groups (298±229 IU/mL vs. 288±257; p=0.97). Positive skin tests to cat hair, cockroach, mango blossom and mouse epithelium were more frequent in asthmatics than in healthy controls, especially in the rural communities. There was no correlation between allergens in dust collected from homes and skin test reactivity.Conclusion: Asthma prevalence is similar in rural and urban children in Southwest Nigeria and atopy with elevated IgE was not observed to be a major factor for asthma in our cohort of children in both communities.Key words: Asthma, risk factors, prevalence, atopy, sensitization, childre

A qualitative study of the feasibility and community perception on the effectiveness of artemether-lumefantrine use in the context of home management of malaria in south-west Nigeria

<p>Abstract</p> <p>Background</p> <p>In Nigeria ACT use at the community level has not been evaluated and the use of antimalarial drugs (commonly chloroquine (CQ)) at home has been shown to be largely incorrect. The treatment regimen of ACT is however more complicated than that of CQ. There is thus a need to determine the feasibility of using ACT at the home level and determine community perception on its use.</p> <p>Methods</p> <p>A before and after qualitative study using key informant interviews (KII) and focus group discussions (FGDs) was conducted in selected villages in Ona-Ara local government area. At baseline, 14 FGDs and 14 KIIs were conducted. Thereafter, community medicine distributors (CMDs) were trained in each village to dispense artemeter-lumenfantrine (AL) to febrile children aged 6–59 months presumed to have uncomplicated malaria. After one year of drug distribution, nine KIIs and 10 FGDs were conducted. Participants and key informants were mothers and fathers with children under five years, traditional heads of communities, opinion leaders and health workers.</p> <p>Results</p> <p>None of the participants have heard of AL prior to study. Participants were favourably disposed to introduction of AL into the community. Mothers/caregivers were said to have used AL in place of the orthodox drugs and herbs reported commonly used prior to study after commencement of AL distribution. The use of CMDs for drug distribution was acceptable to the participants and they were judged to be efficient as they were readily available, distributed correct dose of AL and mobilised the community effectively. AL was perceived to be very effective and no significant adverse event was reported. Major concerns to the sustainability of the program were the negative attitudes of health workers towards discharge of their duties, support to the CMDs and the need to provide CMDs incentives. In addition regular supply of drugs and adequate supervision of CMDs were advised.</p> <p>Conclusion</p> <p>Our findings showed that the use of AL at home and community level is feasible with adequate training of community medicine distributors and caregivers. Community members perceived AL to be effective thus fostering acceptability. The negative attitudes of the health workers and issue of incentives to CMDs need to be addressed for successful scaling-up of ACT use at community level.</p

Intermittent preventive treatment with sulphadoxine-pyrimethamine is effective in preventing maternal and placental malaria in Ibadan, south-western Nigeria

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Method</p> <p>During a larger study evaluating the epidemiology of congenital malaria, the effect of malaria prophylaxis was examined in 983 parturient mothers. Five hundred and ninety eight mothers (60.8%) received IPT-SP, 214 (21.8%) received pyrimethamine (PYR) and 171 (17.4%) did not take any chemoprophylactic agent (NC).</p> <p>Results</p> <p>The prevalence of maternal parasitaemia in the IPT-SP, PYR and NC groups was 10.4%, 15.9% and 17% respectively (p = 0.021). The prevalence of placental parasitaemia was 10.5% in the IPT-SP, 16.8% PYR and 17% NC groups, respectively (p = 0.015). The prevalence of maternal anaemia (haematocrit <30%) was 5.7% vs. 8.9% vs. 13.4% among the IPT-SP, PYR and NC groups respectively (p < 0.0001) while that of pre-term delivery (GA <37 weeks) was 10.5%, 19.2% and 25.3% among IPT-SP, PYR and NC groups respectively (p < 0.0001). Babies born to mothers in the IPT-SP, PYR and NC groups had mean birth weights of 3204 ± 487.16, 3075 ± 513.24 and 3074 ± 505.92 respectively (ρ < 0.0001). There was a trend towards a lower proportion of low birth weight babies in the IPT-SP group (p = 0.095).</p> <p>Conclusion</p> <p>IPT-SP is effective in preventing maternal and placental malaria as well as improving pregnancy outcomes among parturient women in Ibadan, Nigeria. The implementation of the recently adopted IPT-SP strategy should be pursued with vigour as it holds great promise for reducing the burden of malaria in pregnancy in Nigeria.</p

Assessment of a treatment guideline to improve home management of malaria in children in rural south-west Nigeria

<p>Abstract</p> <p>Background</p> <p>Many Nigerian children with malaria are treated at home. Treatments are mostly incorrect, due to caregivers' poor knowledge of appropriate and correct dose of drugs. A comparative study was carried out in two rural health districts in southwest Nigeria to determine the effectiveness of a guideline targeted at caregivers, in the treatment of febrile children using chloroquine.</p> <p>Methods</p> <p>Baseline and post intervention knowledge, attitude and practice household surveys were conducted. The intervention strategy consisted of training a core group of mothers ("mother trainers") in selected communities on the correct treatment of malaria and distributing a newly developed treatment guideline to each household. "Mother trainers" disseminated the educational messages about malaria and the use of the guideline to their communities.</p> <p>Results</p> <p>Knowledge of cause, prevention and treatment of malaria increased with the one-year intervention. Many, (70.4%) of the respondents stated that they used the guideline each time a child was treated for malaria. There was a significant increase in the correct use of chloroquine from 2.6% at baseline to 52.3% after intervention among those who treated children at home in the intervention arm compared with 4.2% to 12.7% in the control arm. The correctness of use was significantly associated with use of the guideline. The timeliness of commencing treatment was significantly earlier in those who treated febrile children at home using chloroquine than those who took their children to the chemist or health facility (p < 0.005). Mothers considered the guideline to be explicit and useful. Mother trainers were also considered to be effective and acceptable.</p> <p>Conclusion</p> <p>The use of the guideline with adequate training significantly improved correctness of malaria treatment with chloroquine at home. Adoption of this mode of intervention is recommended to improve compliance with drug use at home. The applicability for deploying artemisinin-based combination therapy at the community level needs to be investigated.</p

Knowledge and utilization of intermittent preventive treatment for malaria among pregnant women attending antenatal clinics in primary health care centers in rural southwest, Nigeria: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Intermittent preventive treatment for prevention of malaria in pregnancy (IPTp) is a key component of malaria control strategy in Nigeria and sulfadoxine-pyrimethamine (SP) is the drug of choice. Despite the evidence of the effectiveness of IPTp strategy using SP in reducing the adverse effects of malaria during pregnancy the uptake and coverage in Nigeria is low. This study set out to assess the use of IPTp among pregnant women attending primary health centres in the rural area and determine factors that influence the uptake.</p> <p>Methods</p> <p>A cross-sectional study was carried out between July and August 2007 among 209 pregnant women selected by systematic random sampling from antenatal care attendees at primary health care in a rural Local Government Area of Ekiti State, Nigeria. Information on knowledge of IPT, delivery, adherence and acceptability was obtained using an interviewer administered questionnaire. Descriptive statistics such as means, range, proportions were used. Chi-square test was used to examine association between categorical variables. All analyses were performed at 5% level of significance.</p> <p>Results</p> <p>One hundred and nine of 209 (52.2%) respondents have heard about IPTp but only 26 (23.9%) were able to define it. Fifty seven (27.3%) reported to have received at least one dose of IPTp during the index pregnancy and all were among those who have heard of IPTp (52.3%). Twenty one of the 57 (36.8%) took the SP in the clinic. Only three of the twenty-one (14.3%) were supervised by a health worker. Twenty two of the 36 women (61.1%) who did not take their drugs in the clinic would have liked to do so if allowed to bring their own drinking cups. Almost half (43.9%) of those who had used IPTp during the index pregnancy expressed concern about possible adverse effect of SP on their pregnancies. Periodic shortages of SP in the clinics were also reported.</p> <p>Conclusion</p> <p>In this study, IPTp use among pregnant women was very low and there was poor adherence to the Directly Observed Therapy (DOT) scheme. Concerted effort should be made to increase awareness of IPTp among the public especially women of child bearing age. Health workers should also be trained and monitored to ensure adherence.</p

Plasmodium falciparum clearance with artemisinin-based combination therapy (ACT) in patients with glucose-6-phosphate dehydrogenase deficiency in Mali

URL : http://www.malariajournal.com/content/9/1/332Background: Artemisinin-based combination therapy (ACT) is currently the most effective medicine for the treatment of uncomplicated malaria. Artemisinin has previously been shown to increase the clearance of Plasmodium falciparum in malaria patients with haemoglobin E trait, but it did not increase parasite inhibition in an in vitro study using haemoglobin AS erythrocytes. The current study describes the efficacy of artemisinin derivatives on P. falciparum clearance in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), a haemoglobin enzyme deficiency, not yet studied in the same context, but nonetheless is a common in malaria endemic areas, associated with host protection against uncomplicated and severe malaria. The impact of G6PD deficiency on parasite clearance with ACT treatment was compared between G6PD-deficient patients and G6PD-normal group. Methods: Blood samples from children and adults participants (1 to 70 years old) with uncomplicated P. falciparum malaria residing in Kambila, Mali were analysed. Study participants were randomly assigned to receive either artemether-lumefantrine (Coartem®) or artesunate plus mefloquine (Artequin™). A restriction-fragment length polymorphism analysis of PCR-amplified DNA samples was used to identify the (A-) allele of the gene mutation responsible for G6PD deficiency (G6PD*A-). 470 blood samples were thus analysed and of these, DNA was extracted from 315 samples using the QIAamp kit for PCR to identify the G6PD*A- gene. Results

Safety profile of Coartem®: the evidence base

This article reviews the comprehensive data on the safety and tolerability from over 6,300 patients who have taken artemether/lumefantrine (Coartem®) as part of Novartis-sponsored or independently-sponsored clinical trials. The majority of the reported adverse events seen in these studies are mild or moderate in severity and tend to affect the gastrointestinal or nervous systems. These adverse events, which are common in both adults and children, are also typical of symptoms of malaria or concomitant infections present in these patients. The wealth of safety data on artemether/lumefantrine has not identified any neurological, cardiac or haematological safety concerns. In addition, repeated administration is not associated with an increased risk of adverse drug reactions including neurological adverse events. This finding is especially relevant for children from regions with high malaria transmission rates who often receive many courses of anti-malarial medications during their lifetime. Data are also available to show that there were no clinically relevant differences in pregnancy outcomes in women exposed to artemether/lumefantrine compared with sulphadoxine-pyrimethamine during pregnancy. The six-dose regimen of artemether/lumefantrine is therefore well tolerated in a wide range of patient populations. In addition, post-marketing experience, based on the delivery of 250 million treatments as of July 2009, has not identified any new safety concerns for artemether/lumefantrine apart from hypersensitivity and allergies, known class effects of artemisinin derivatives

The clinical efficacy of artemether/lumefantrine (Coartem®)

Current World Health Organization (WHO) guidelines for the treatment of uncomplicated falciparum malaria recommend the use of artemisinin-based combination therapy (ACT). Artemether/lumefantrine is an ACT prequalified by the WHO for efficacy, safety and quality, approved by Swissmedic in December 2008 and recently approved by the USA FDA. Coartem® is a fixed-dose combination of artemether and lumefantrine. Its two components have different modes of action that provide synergistic anti-malarial activity. It is indicated for the treatment of infants, children and adults with acute, uncomplicated infection due to Plasmodium falciparum or mixed infections including P. falciparum. A formulation with improved palatability has been developed especially for children (Coartem® Dispersible), which rapidly disperses in a small amount of water for ease of administration

Low coverage of intermittent preventive treatment for malaria in pregnancy in Nigeria: demand-side influences

BACKGROUND: Nigeria instituted intermittent preventive treatment for malaria (IPTp) using sulphadoxine-pyrimethamine (SP) for pregnant women in 2001, but coverage remains low. This study examined the influence of demand side factors on IPTp coverage. METHODS: Data were collected using a household survey from 1307 women who were delivered of a live baby within the one-year period preceding the study and through an exit poll from 146 women attending antenatal clinics (ANC). Data analysis examined coverage based on the national and WHO guidelines for IPTp delivery which differ with regards to use of IPTp in the last month of pregnancy. Focus group discussions (FGDs) were undertaken to further explain demand side constraints to coverage. RESULTS: From the household survey, 96.1% of respondents attended ANC, with most having five or more visits. Overall IPTp coverage for the first and second doses was 13.7% and 7.3% respectively. The coverage was higher in the urban areas compared to rural areas (p < 0.01). Amongst women who could have received IPTp based on the timing of their attendance, only 14.1% and 14.3% were offered the first dose based on national and WHO guidelines, while 7.7% and 7.5% were offered the second dose respectively giving significant missed opportunities. Amongst ANC attendees offered first and second doses, 98.9% and 96.9% respectively took the medicine. Only 13.6% and 21.5% of these clients reported taking the drug under direct observation. The low level of coverage was confirmed by exit survey data, which found coverage of 11.6% and 3.0% for the first and second doses. The FGDs revealed that women do not have many concerns about side effects, but they take drugs providers give them because they believe such drugs must be safe. CONCLUSION: This study found low coverage of IPTp and high levels of missed opportunities supporting findings that high ANC attendance does not guarantee high IPTp coverage. Demand side factors such as ANC attendance, appropriate timing of attendance, and perceptions about side effects were not constraining factors to increased coverage, raising the need to examine supply side factors