Emmanuel Ezedinachi

Chlorproguanil−Dapsone−Artesunate versus Artemether−Lumefantrine: A Randomized, Double-Blind Phase III Trial in African Children and Adolescents with Uncomplicated Plasmodium falciparum Malaria

Background Chlorproguanil−dapsone−artesunate (CDA) was developed as an affordable, simple, fixed-dose artemisinin-based combination therapy for use in Africa. This trial was a randomized parallel-group, double-blind, double-dummy study to compare CDA and artemether−lumefantrine (AL) efficacy in uncomplicated Plasmodium falciparum malaria and further define the CDA safety profile, particularly its hematological safety in glucose-6-phosphate dehydrogenase (G6PD) -deficient patients. Methods and Findings The trial was conducted at medical centers at 11 sites in five African countries between June 2006 and August 2007. 1372 patients (≥1 to <15 years old, median age 3 years) with acute uncomplicated P. falciparum malaria were randomized (2∶1) to receive CDA 2/2.5/4 mg/kg once daily for three days (N = 914) or six-doses of AL over three days (N = 458). Non-inferiority of CDA versus AL for efficacy was evaluated in the Day 28 per-protocol (PP) population using parasitological cure (polymerase chain reaction [PCR]-corrected). Cure rates were 94.1% (703/747) for CDA and 97.4% (369/379) for AL (treatment difference –3.3%, 95%CI –5.6, −0.9). CDA was non-inferior to AL, but there was simultaneous superiority of AL (upper 95%CI limit <0). Adequate clinical and parasitological response at Day 28 (uncorrected for reinfection) was 79% (604/765) with CDA and 83% (315/381) with AL. In patients with a G6PD-deficient genotype (94/603 [16%] hemizygous males, 22/598 [4%] homozygous females), CDA had the propensity to cause severe and clinically concerning hemoglobin decreases: the mean hemoglobin nadir was 75 g/L (95%CI 71, 79) at Day 7 versus 97 g/L (95%CI 91, 102) for AL. There were three deaths, unrelated to study medication (two with CDA, one with AL). Conclusions Although parasitologically effective at Day 28, the hemolytic potential of CDA in G6PD-deficient patients makes it unsuitable for use in a public health setting in Africa. Trial Registration ClinicalTrials.gov NCT00344006

Artemether-lumefantrine versus artesunate plus amodiaquine for treating uncomplicated childhood malaria in Nigeria: randomized controlled trial.

BackgroundThe therapeutic efficacy of artesunate plus amodiaquine and artemether/lumefantrine were assessed in an area of Nigeria with high levels of Plasmodium falciparum resistance to chloroquine and sulphadoxine-pyrimethamine.ParticipantsChildren aged 6 to 59 months with uncomplicated P. falciparum infection and parasite density 1,000 to 200,000 parasites/μL enrolled following informed consent by parents.MethodsEligible children were randomly assigned to receive either a 3-day course of artesunate (4 mg/kg) plus amodiaquine (10 mg/kg) or 6-dose course of artemether/lumefantrine (20/120 mg tablets) over three days. Patients were followed up with clinical and laboratory assessments until day 14 using standard WHO in-vivo antimalarial drug test protocol.ResultsA total 119 eligible children were enrolled but 111 completed the study. Adequate clinical and parasitological response (ACPR) was 47 (87.0%) and 47 (82.5%) for artemether-lumefantrine (AL) and artesunate+amodiaquine (AAMQ) respectively (OR 0.7, 95% confidence interval 0.22 to 2.22). Early treatment failure (ETF) occurred in one participant (1.8%) treated with AAQ but in none of those with AL. Two (3.7%) patients in the AL group and none in the AAQ group had late clinical failure. Late parasitological failure was observed in 9 (15.8) and 5 (9.3%) of patients treated with AAQ and AL respectively. None of participants had a serious adverse event.ConclusionArtemether-lumenfantrine and artesunate plus amodiaquine have high and comparable cure rates and tolerability among under-five children in Calabar, Nigeria.

Malaria and its treatment in rural villages of Aboh Mbaise, Imo State, Nigeria.

We examined the malaria situation among 489 children under 5 years of age in the rural villages of Aboh Mbaise, Nigeria, using a combination of a standard questionnaire technique and laboratory diagnosis to confirm clinical observations. The results show a high prevalence rate of 52.8% for Plasmodium falciparum in this area. The geometric mean parasite density (GMPD) was 19,361.4/mm3. The proportion of children with fever and/or parasitaemia was not related to age, although the numbers in the febrile group appeared to increase with age. Using 37.5 degrees C as the threshold for fever, 48.7% of the heavily infected group (more than 1000/mm3) were afebrile while 51.3% were febrile. High grade temperatures above 38 degrees C were associated with high parasitaemia above 10,000 parasites/mm3. Of the 911 children who died in the area within the last five years, 22.4% died of fever of unknown origin, 39.7% from malaria, 22.5% from convulsion, 10.5% from diarrhoea and 4.6% from cough. Chloroquine is the drug of choice for the treatment of malaria and there were many cases of drug abuse, and use of sub-curative doses prescribed by non-medically qualified staff.

Correlation between in vivo and in vitro response of chloroquine-resistant Plasmodium falciparum in Calabar, South-Eastern Nigeria

Since chloroquine-resistant Plasmodium falciparum (CRPF) has emerged in Nigeria, we monitored the susceptibility of the parasite strain to a standard chloroquine (C25) dose in our Childrens Emergency Unit. Chloroquine (CQ) is the drug of choice for malaria chemotherapy in Nigeria. The WHO 7-day in vivo evaluation and Rieckmanns microtitre technique (in vitro test) were used. 33 children of mean age 4.9 years were enrolled in the study. 27 (81.8%) of the in vitro cultures were successful. 16 (59.3%) of the successful isolates still showed schizogony at CQ concentration of 5.7 pmol/well and above. 28 (84.8%) of the children completed the in vivo study. 15 (53.6%) were parasitaemic on day 7 and/or day 14 and were regarded as parasitologic failures. The isolates from 14 of these children showed corresponding in vitro resistance of CQ concentrations equal to or above 5.7 pmol/well. The proportion of RIII (= 13.3%) appears to have increased as compared to 5.9% recorded in 1987. We conclude that there appears to be a good correlation between in vivo evaluation of parasitologic failures (53.6%) and in vitro resistance (59.3%). It thus appears that CRPF is definitely increasing in South-Eastern Nigeria. This can be expected not only to complicate malaria chemotherapy in the Childrens Emergency Unit of the University of Calabar Teaching Hospital, but will contribute immensely to the deterioration of malaria therapy and control in Nigeria.

Assessment of ability of Nigerian mothers to recognize anaemia in children with malaria.

time the child was seen, the tumour reached across the midline and down into the pelvis in all children. Ultrasound demonstrated a tumour arising from the kidney, part of which was still recognizable and often hydronephrotic. The contralateral kidney was normal and the liver was free of metastases in all children. The chest X-ray did not reveal pulmonary metastases. Intravenous urogram was not performed, as the diagnosis could be made with confidence on the ultrasound.

Malaria in Women and Children

Learning Objectives After reading this chapter and answering the discussion questions that follow, you should be able to Explain the global burden of malaria, discuss its clinical manifestations, and appraise its health impact on women and children. Analyze the mechanisms and consequences of malaria and HIV co-infection and discuss current treatment, control and prevention strategies. Describe the challenges posed by vector resistance to insecticides, parasite resistance to antimalarials, climate change, wars/conflicts, and HIV/AIDS to malaria control and prevention efforts. Evaluate social, cultural, and economic limitations of community-based programs for malaria control and prevention.

Treatment delay attitude of caregivers in management of childhood malaria in rural communities in Nigeria.

Aims: The aim of this paper was to assess the promptness of caregivers action at the onset of malaria symptoms to giving recommended effective anti -malaria drugs from