Genetic Diversity of CD14 Promoter Gene Polymorphism (rs2569190) is Associated With Regulation of Malaria Parasitemia and Susceptibility to Plasmodium falciparum Infection.

CD14 is a multifunctional receptor expressed on many cell types and has been shown to mediate immune response resulting in the activation of an inflammatory cascade, with polymorphism of its promoter (rs2569190) found to be associated with susceptibility to several diseases. In malaria infection, the CD14 gene demonstrated a pathogenic profile in regulating experimental cerebral malaria, with reports of elevated levels of soluble CD14 in serum of patients but no definitive conclusion. We present a detailed analysis of genetic diversity of CD14 promoter gene (snp −159 C/T; rs2519190) polymorphism between a malaria-infected group and uninfected controls and its association with clinical parameters of disease. Genomic DNA samples obtained from 106 Plasmodium falciparum malaria–infected patients and 277 uninfected controls were elucidated with a polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay. Our results show a significant diversity (P=3.32E−06) in the genotypic frequency (3.8% versus 22.4%) of the rs2569190 mutant variant between the malaria-infected group and controls, respectively. The mutant allele had the lowest frequency among the malaria-infected group demonstrating its necessity for infection. Mean parasitemia (parasites/μL of blood) was significantly regulated based on CD14 polymorphic profile (19 855 versus 37 041 versus 49 396 for homozygote mutants, heterozygotes, and homozygote wild type, respectively). Interestingly, we found no association between CD14 genetic variants with fever, age of patients, or anemia. How this affects disease severity between subregional and continental groups deserves further clarification, including extending these studies in a larger group and among severe and asymptomatic patients with malaria

Effectiveness of artemisinin-based combination therapy used in the context of home management of malaria: A report from three study sites in sub-Saharan Africa

BACKGROUND: The use of artemisinin-based combination therapy (ACT) at the community level has been advocated as a means to increase access to effective antimalarial medicines by high risk groups living in underserved areas, mainly in sub-Saharan Africa. This strategy has been shown to be feasible and acceptable to the community. However, the parasitological effectiveness of ACT when dispensed by community medicine distributors (CMDs) within the context of home management of malaria (HMM) and used unsupervised by caregivers at home has not been evaluated. METHODS: In a sub-set of villages participating in a large-scale study on feasibility and acceptability of ACT use in areas of high malaria transmission in Ghana, Nigeria and Uganda, thick blood smears and blood spotted filter paper were prepared from finger prick blood samples collected from febrile children between six and 59 months of age reporting to trained CMDs for microscopy and PCR analysis. Presumptive antimalarial treatment with ACT (artesunate-amodiaquine in Ghana, artemether-lumefantrine in Nigeria and Uganda) was then initiated. Repeat finger prick blood samples were obtained 28 days later for children who were parasitaemic at baseline. For children who were parasitaemic at follow-up, PCR analyses were undertaken to distinguish recrudescence from re-infection. The extent to which ACTs had been correctly administered was assessed through separate household interviews with caregivers having had a child with fever in the previous two weeks. RESULTS: Over a period of 12 months, a total of 1,740 children presenting with fever were enrolled across the study sites. Patent parasitaemia at baseline was present in 1,189 children (68.3%) and varied from 60.1% in Uganda to 71.1% in Ghana. A total of 606 children (51% of infected children) reported for a repeat test 28 days after treatment. The crude parasitological failure rate varied from 3.7% in Uganda (C.I. 1.2%-6.2%) to 41.8% in Nigeria (C.I. 35%-49%). The PCR adjusted parasitological cure rate was greater than 90% in all sites, varying from 90.9% in Nigeria (C.I. 86%-95%) to 97.2% in Uganda (C.I. 95%-99%). Reported adherence to correct treatment in terms of dose and duration varied from 81% in Uganda (C.I. 67%-95%) to 97% in Ghana (C.I. 95%-99%) with an average of 94% (C.I. 91%-97%). CONCLUSION: While follow-up rates were low, this study provides encouraging data on parasitological outcomes of children treated with ACT in the context of HMM and adds to the evidence base for HMM as a public health strategy as well as for scaling-up implementation of HMM with ACTs

Evaluation of the efficacy and safety of artemether-lumefantrine in the treatment of acute uncomplicated Plasmodium falciparum malaria in Nigerian infants and children

<p>Abstract</p> <p>Background</p> <p>The six-dose regimen of artemether-lumefantrine (AL) is now considered the gold standard for the treatment of uncomplicated <it>Plasmodium falciparum </it>malaria. There are few reports evaluating co-artemether in very young Nigerian infants and children. Results of the evaluation of the six-dose regimen in very young infants and children in Nigeria are presented in this report.</p> <p>Methods</p> <p>As part of a larger African study, this open label, non-comparative trial, assessed the efficacy and safety of six-dose regimen of AL tablets in 103 Nigerian infants and children weighing between five and 25 kg suffering from acute uncomplicated malaria. Treatment was administered under supervision over three days with children as in-patients. 12-lead ECG tracings were taken pre-treatment and at day 3.</p> <p>Results</p> <p>Ninety-three infants and children completed the study as stipulated by the protocol. Mean fever and parasite clearance times for the intent to treat population (ITT) were 24.9 h ± (1.28) and 26 h ± (4.14) and the corresponding figures for the per-protocol population (PP) were 19.24 h ± 13.9 and 25.62 h ± 11.25 respectively. Day 14 cure rates for the ITT and PP were 95.1% and 100% respectively while day 28 cure rates were 91.3% and 95.7% respectively. The overall PCR corrected day 28 cure rate was 95.1% for the ITT. The six-dose regimen of AL was well tolerated with no drug-related serious adverse events. Although six patients recorded a QTc prolongation of > 60 ms on D3 over D0 recording, no patient recorded a QTc interval > 500 ms.</p> <p>Conclusion</p> <p>The six-dose regimen of AL tablets is safe and effective for the treatment of acute uncomplicated malaria in Nigerian infants and children weighing between five and 25 kg.</p> <p>Trial registration</p> <p>NCT00709969</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

Contributions of malaria, helminths, HIV and iron deficiency to anaemia in pregnant women attending ante-natal clinic in SouthWest Nigeria

Background: Iron deficiency is a dominant source of anaemia in many settings. To evaluate the key cause of anaemia in the study area, the prevalence of anaemia due to major public health diseases was compared with anaemia due to iron deficiency. Methods: Pregnant women were recruited from ante-natal (n=490) and HIV clinics (n=217) with their personal data documented using a questionnaire. Microscopy of Giemsa-stained thick smears was used for detection of malaria parasites while helminths in stools were detected using direct smear method. Haematocrit values were determined by capillary method. Serum ferritin levels were determined using enzyme-linked immunosorbent assay. Data was analysed using SPSS version 22.0. Results: The mean age of the recruited women was 28.6\ub15.4 years old. There were 68.1% cases of anaemia of which 35.5% was due to infections only predominantly HIV and malaria, 14.9% from unknown sources while anaemia due to iron deficiency only was 7.1%. Conclusion: It can safely be inferred that malaria and HIV predispose to anaemia than iron deficiency in the study area. Although pregnant women are dewormed and given IPTp for helminths and malaria treatment respectively, there should be complementary routine malaria screening at ANC visits for those with HCT values &lt;33% and those infected with HIV

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

The content of African diets is adequate to achieve optimal efficacy with fixed-dose artemether-lumefantrine: a review of the evidence

A fixed-dose combination of artemether-lumefantrine (AL, Coartem®) has shown high efficacy, good tolerability and cost-effectiveness in adults and children with uncomplicated malaria caused by Plasmodium falciparum. Lumefantrine bioavailability is enhanced by food, particularly fat

Efficacy and Safety of Artemether-Lumefantrine in the Treatment of Acute, Uncomplicated Plasmodium falciparum Malaria: A Pooled Analysis

Randomized trials have confirmed the efficacy and safety of artemether-lumefantrine (AL) for treatment of uncomplicated Plasmodium falciparum malaria. Data from seven studies supported by Novartis (1996–2007), including 647 adults (> 16 years of age, 83.3% completed the study) and 1,332 children (≤ 16 years of age, 89.3% completed the study) with microscopically confirmed uncomplicated P. falciparum malaria and treated with the recommended regimen of AL, were pooled. The 28-day polymerase chain reaction–corrected parasitologic cure rate (primary efficacy endpoint) was 97.1% (495 of 510) in adults and 97.3% (792 of 814) in children (evaluable population). Gametocytemia prevalence after day was 4.2% (23 of 554) in adults and 0.9% (8 of 846) in children. No noteworthy safety signals were observed. Serious adverse events occurred in 1.4% of the adults and 1.3% of the children. This study is the largest data set to date assessing AL therapy for treatment of acute uncomplicated P. falciparum malaria. Artemether-lumefantrine showed high cure rates and rapid resolution of parasitemia, fever, and gametocytemia in adults and children, and showed an excellent safety and tolerability profile