Samuel Blay Nguah

Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial.

Summary Background Severe malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa. Quinine is still the established treatment of choice, although evidence from Asia suggests that artesunate is associated with a lower mortality. We compared parenteral treatment with either artesunate or quinine in African children with severe malaria. Methods This open-label, randomised trial was undertaken in 11 centres in nine African countries. Children (<15 years) with severe falciparum malaria were randomly assigned to parenteral artesunate or parenteral quinine. Randomisation was in blocks of 20, with study numbers corresponding to treatment allocations kept inside opaque sealed paper envelopes. The trial was open label at each site, and none of the investigators or trialists, apart from for the trial statistician, had access to the summaries of treatment allocations. The primary outcome measure was in-hospital mortality, analysed by intention to treat. This trial is registered, number ISRCTN50258054. Findings 5425 children were enrolled; 2712 were assigned to artesunate and 2713 to quinine. All patients were analysed for the primary outcome. 230 (8·5%) patients assigned to artesunate treatment died compared with 297 (10·9%) assigned to quinine treatment (odds ratio [OR] stratified for study site 0·75, 95% CI 0·63–0·90; relative reduction 22·5%, 95% CI 8·1–36·9; p=0·0022). Incidence of neurological sequelae did not differ significantly between groups, but the development of coma (65/1832 [3·5%] with artesunate vs 91/1768 [5·1%] with quinine; OR 0·69 95% CI 0·49–0·95; p=0·0231), convulsions (224/2712 [8·3%] vs 273/2713 [10·1%]; OR 0·80, 0·66–0·97; p=0·0199), and deterioration of the coma score (166/2712 [6·1%] vs 208/2713 [7·7%]; OR 0·78, 0·64–0·97; p=0·0245) were all significantly less frequent in artesunate recipients than in quinine recipients. Post-treatment hypoglycaemia was also less frequent in patients assigned to artesunate than in those assigned to quinine (48/2712 [1·8%] vs 75/2713 [2·8%]; OR 0·63, 0·43–0·91; p=0·0134). Artesunate was well tolerated, with no serious drug-related adverse effects. Interpretation Artesunate substantially reduces mortality in African children with severe malaria. These data, together with a meta-analysis of all trials comparing artesunate and quinine, strongly suggest that parenteral artesunate should replace quinine as the treatment of choice for severe falciparum malaria worldwide. Funding The Wellcome Trust.

Effect of the Affordable Medicines Facility--malaria (AMFm) on the availability, price, and market share of quality-assured artemisinin-based combination therapies in seven countries: a before-and-after analysis of outlet survey data.

BACKGROUND Malaria is one of the greatest causes of mortality worldwide. Use of the most effective treatments for malaria remains inadequate for those in need, and there is concern over the emergence of resistance to these treatments. In 2010, the Global Fund launched the Affordable Medicines Facility--malaria (AMFm), a series of national-scale pilot programmes designed to increase the access and use of quality-assured artemisinin based combination therapies (QAACTs) and reduce that of artemisinin monotherapies for treatment of malaria. AMFm involves manufacturer price negotiations, subsidies on the manufacturer price of each treatment purchased, and supporting interventions such as communications campaigns. We present findings on the effect of AMFm on QAACT price, availability, and market share, 6-15 months after the delivery of subsidised ACTs in Ghana, Kenya, Madagascar, Niger, Nigeria, Uganda, and Tanzania (including Zanzibar). METHODS We did nationally representative baseline and endpoint surveys of public and private sector outlets that stock antimalarial treatments. QAACTs were identified on the basis of the Global Funds quality assurance policy. Changes in availability, price, and market share were assessed against specified success benchmarks for 1 year of AMFm implementation. Key informant interviews and document reviews recorded contextual factors and the implementation process. FINDINGS In all pilots except Niger and Madagascar, there were large increases in QAACT availability (25·8-51·9 percentage points), and market share (15·9-40·3 percentage points), driven mainly by changes in the private for-profit sector. Large falls in median price for QAACTs per adult equivalent dose were seen in the private for-profit sector in six pilots, ranging from US

Genome-wide association study indicates two novel resistance loci for severe malaria

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Predicting the Clinical Outcome of Severe Falciparum Malaria in African Children: Findings From a Large Randomized Trial

4·82. The market share of oral artemisinin monotherapies decreased in Nigeria and Zanzibar, the two pilots where it was more than 5% at baseline. INTERPRETATION Subsidies combined with supporting interventions can be effective in rapidly improving availability, price, and market share of QAACTs, particularly in the private for-profit sector. Decisions about the future of AMFm should also consider the effect on use in vulnerable populations, access to malaria diagnostics, and cost-effectiveness. FUNDING The Global Fund to Fight AIDS, Tuberculosis and Malaria, and the Bill & Melinda Gates Foundation.

Hemoglobin estimation by the HemoCue® portable hemoglobin photometer in a resource poor setting

Malaria causes approximately one million fatalities per year, mostly among African children. Although highlighted by the strong protective effect of the sickle-cell trait, the full impact of human genetics on resistance to the disease remains largely unexplored. Genome-wide association (GWA) studies are designed to unravel relevant genetic variants comprehensively; however, in malaria, as in other infectious diseases, these studies have been only partly successful. Here we identify two previously unknown loci associated with severe falciparum malaria in patients and controls from Ghana, West Africa. We applied the GWA approach to the diverse clinical syndromes of severe falciparum malaria, thereby targeting human genetic variants influencing any step in the complex pathogenesis of the disease. One of the loci was identified on chromosome 1q32 within the ATP2B4 gene, which encodes the main calcium pump of erythrocytes, the host cells of the pathogenic stage of malaria parasites. The second was indicated by an intergenic single nucleotide polymorphism on chromosome 16q22.2, possibly linked to a neighbouring gene encoding the tight-junction protein MARVELD3. The protein is expressed on endothelial cells and might therefore have a role in microvascular damage caused by endothelial adherence of parasitized erythrocytes. We also confirmed previous reports on protective effects of the sickle-cell trait and blood group O. Our findings underline the potential of the GWA approach to provide candidates for the development of control measures against infectious diseases in humans.

Respiratory viruses in children hospitalized for acute lower respiratory tract infection in Ghana

Four predictors were independently associated with an increased risk of death: acidosis, cerebral manifestations of malaria, elevated blood urea nitrogen, or signs of chronic illness. The standard base deficit was found to be the single most relevant predictor of death.

Giardia lamblia: a major parasitic cause of childhood diarrhoea in patients attending a district hospital in Ghana

BackgroundIn resource poor settings where automated hematology analyzers are not available, the Cyanmethemoglobin method is often used. This method though cheaper, takes more time. In blood donations, the semi-quantitative gravimetric copper sulfate method which is very easy and inexpensive may be used but does not provide an acceptable degree of accuracy. The HemoCue® hemoglobin photometer has been used for these purposes. This study was conducted to generate data to support or refute its use as a point-of-care device for hemoglobin estimation in mobile blood donations and critical care areas in health facilities.MethodEDTA blood was collected from study participants drawn from five groups: pre-school children, school children, pregnant women, non-pregnant women and men. Blood collected was immediately processed to estimate the hemoglobin concentration using three different methods (HemoCue®, Sysmex KX21N and Cyanmethemoglobin). Agreement between the test methods was assessed by the method of Bland and Altman. The Intraclass correlation coefficient (ICC) was used to determine the within subject variability of measured hemoglobin.ResultsOf 398 subjects, 42% were males with the overall mean age being 19.4 years. The overall mean hemoglobin as estimated by each method was 10.4 g/dl for HemoCue, 10.3 g/dl for Sysmex KX21N and 10.3 g/dl for Cyanmethemoglobin. Pairwise analysis revealed that the hemoglobin determined by the HemoCue method was higher than that measured by the KX21N and Cyanmethemoglobin. Comparing the hemoglobin determined by the HemoCue to Cyanmethemoglobin, the concordance correlation coefficient was 0.995 (95% CI: 0.994-0.996, p < 0.001). The Bland and Altmans limit of agreement was -0.389 - 0.644 g/dl with the mean difference being 0.127 (95% CI: 0.102-0.153) and a non-significant difference in variability between the two measurements (p = 0.843). After adjusting to assess the effect of other possible confounders such as sex, age and category of person, there was no significant difference in the hemoglobin determined by the HemoCue compared to Cyanmethemoglobin (coef = -0.127, 95% CI: -0.379 - 0.634).ConclusionHemoglobin determined by the HemoCue method is comparable to that determined by the other methods. The HemoCue photometer is therefore recommended for use as on-the-spot device for determining hemoglobin in resource poor setting.

Comparative evaluation of two rapid field tests for malaria diagnosis: Partec Rapid Malaria Test ® and Binax Now ® Malaria Rapid Diagnostic Test

BackgroundAcute respiratory tract infections are one of the major causes of morbidity and mortality among young children in developing countries. Information on the viral aetiology of acute respiratory infections in developing countries is very limited. The study was done to identify viruses associated with acute lower respiratory tract infection among children less than 5 years.MethodNasopharyngeal samples and blood cultures were collected from children less than 5 years who have been hospitalized for acute lower respiratory tract infection. Viruses and bacteria were identified using Reverse Transcriptase Real-Time Polymerase Chain Reaction and conventional biochemical techniques.ResultsOut of 128 patients recruited, 33(25.88%%, 95%CI: 18.5% to 34.2%) were positive for one or more viruses. Respiratory Syncytial Virus (RSV) was detected in 18(14.1%, 95%CI: 8.5% to 21.3%) patients followed by Adenoviruses (AdV) in 13(10.2%, 95%CI: 5.5% to 16.7%), Parainfluenza (PIV type: 1, 2, 3) in 4(3.1%, 95%CI: 0.9% to 7.8%) and influenza B viruses in 1(0.8%, 95%CI: 0.0 to 4.3). Concomitant viral and bacterial co-infection occurred in two patients. There were no detectable significant differences in the clinical signs, symptoms and severity for the various pathogens isolated. A total of 61.1% (22/36) of positive viruses were detected during the rainy season and Respiratory Syncytial Virus was the most predominant.ConclusionThe study has demonstrated an important burden of respiratory viruses as major causes of childhood acute respiratory infection in a tertiary health institution in Ghana. The data addresses a need for more studies on viral associated respiratory tract infection.

Aetiological agents of cerebrospinal meningitis: a retrospective study from a teaching hospital in Ghana

BackgroundAcute childhood diarrhoea remains one of the leading causes of childhood morbidity and mortality in developing countries. The WHO has accordingly underlined the need for epidemiological surveys of infantile diarrhoea in all geographical areas. This study was conducted to determine the incidence of intestinal parasites among stool samples from children examined at a secondary health care facility in a rural area of Ghana.MethodA retrospective study was conducted to investigate the incidence of intestinal parasites among children who had their stools examined at the Agogo Hospital laboratory. Stool microscopy results from January 2006 through May 2009 were obtained from archived records of the laboratory. Results for children less than 18 years were transcribed unto a standardized datasheet, entered into an electronic database designed using Microsoft® access 2007 and analyzed using Stata/ SE11.1 statistical software. The incidences of the parasites were determined and presented with their Poisson exact 95% confidence intervals for the various ages.ResultsThe median age of the 1080 children included in the study was 5 years (IQR: 2-12 years) with 51.9% being females. The overall incidence of all parasites was 114 per 1000 with Giardia lamblia being the most common (89.5%). Children aged less than a year had the lowest parasite incidence of 13 per 1000 with all being Giardia lamblia, while those aged 15-17 years had the highest of 169 per 1000. The incidence for Giardia lamblia only was lowest at 13 per 1000 for those under a year old, highest at 152 per 1000 for the 15-17 year group and 97 per 1000 for all ages combined. There was a significant rise in incidence of Giardia lamblia with age (Trend x2 = 18.6, p < 0.001). Five (4.3%) of the 118 positive stool samples had mixed parasites infection. Enterobius vermicularis, Taeniaspp and Trichuris trichiura were not seen in any of the stool samples.ConclusionGiardia lamblia is the most prevalent intestinal parasite in examined stool samples of children within the Ashanti Akim North Municipality and its prevalence significantly increases with age. Measures must be put in place to educate the community on proper personal hygiene to reduce giardiasis.

Comparison of the Novel Partec Rapid Malaria Test to the Conventional Giemsa Stain and the Gold Standard Real-Time PCR

BackgroundAbout 90% of all malaria deaths in sub-Saharan Africa occur in children under five years. Fast and reliable diagnosis of malaria requires confirmation of the presence of malaria parasites in the blood of patients with fever or history suggestive of malaria; hence a prompt and accurate diagnosis of malaria is the key to effective disease management. Confirmation of malaria infection requires the availability of a rapid, sensitive, and specific testing at an affordable cost. We compared two recent methods (the novel Partec Rapid Malaria Test® (PT) and the Binax Now® Malaria Rapid Diagnostic Test (BN RDT) with the conventional Giemsa stain microscopy (GM) for the diagnosis of malaria among children in a clinical laboratory of a hospital in a rural endemic area of Ghana.MethodsBlood samples were collected from 263 children admitted with fever or a history of fever to the pediatric clinic of the Agogo Presbyterian Hospital. The three different test methods PT, BN RDT and GM were performed independently by well trained and competent laboratory staff to assess the presence of malaria parasites. Results were analyzed and compared using GM as the reference standard.ResultsIn 107 (40.7%) of 263 study participants, Plasmodium sp. was detected by GM. PT and BN RDT showed positive results in 111 (42.2%) and 114 (43.4%), respectively. Compared to GM reference standard, the sensitivities of the PT and BN RDT were 100% (95% CI: 96.6-100) and 97.2% (95% CI: 92.0-99.4), respectively, specificities were 97.4% (95% CI: 93.6-99.3) and 93.6% (95% CI: 88.5-96.9), respectively. There was a strong agreement (kappa) between the applied test methods (GM vs PT: 0.97; p < 0.001 and GM vs BN RDT: 0.90; p < 0.001). The average turnaround time per tests was 17 minutes.ConclusionIn this study two rapid malaria tests, PT and BN RDT, demonstrated a good quality of their performance compared to conventional GM. Both methods require little training, have short turnaround times, are applicable as well as affordable and can therefore be considered as alternative diagnostic tools in malaria endemic areas. The species of Plasmodium cannot be identified.