The Benefits of research partnerships to the community at KEMRI/Walter Reed Project

9TH Annual ethics conference. Theme : Bioethics medical, legal, environmental and cultural aspects in healthcare ethics at STRATHMORE UNIVERSITY, 25-26 OCTOBER 2012.Ethical Principles on Human Subject Protection in Clinical Research revolves around Autonomy, Beneficence and Justice. Beneficence requires that the benefits to research participants are maximized as you minimize the risk There’s need to enhance health, healthcare and general well being of communities participating in research Background well being of communities participating in research. Many local communities in developing countries have limited access to basic healthcare making them vulnerable and open to undue influence. Without collaborative partnership, strong interest and investment by government, research results may not influence policy making decisions and allocation of scarce healthcare resources. The KEMRI/Walter Reed Project a collaborative research program has conducted clinical trials for over 20 years in Kenya. During this period its objectives have included working with partners to maximize research benefits in the community in which it works by effectively utilizing the available resources to address local health needs

Care-seeking dynamics among patients with diabetes mellitus and hypertension in selected rural settings in Kenya

Diabetes mellitus and hypertension are two common non-communicable diseases (NCDs) that often coexist in patients. However, health-seeking behaviour in patients with diabetes mellitus or hypertension has not been extensively studied especially in low- and middle-income countries. This study aimed to examine care-seeking dynamics among participants diagnosed with diabetes and/or hypertension across nine counties in rural Kenya. We conducted a cross-sectional study among adults diagnosed with diabetes and/or hypertension through face-to-face interviews. Of the 1100 participants, 69.9% had hypertension, 15.5% diabetes while 14.7% had both. The mean age of the respondents was 64 years. The majority of the respondents (86%) were on allopathic treatment. Hospital admission, having a good self-rated health status and having social support for illness, were positively associated with appropriate health-seeking behaviour while use of alcohol and pharmacy or chemist as source of treatment were negatively associated with appropriate health-seeking behaviour. Our study found a high prevalence of appropriate health-seeking behaviour among respondents with the majority obtaining care from government facilities. The results are evidence that improving public health care services can promote appropriate health-seeking behaviour for non-communicable diseases and thus improve health outcomes

Performance of Quantitative Buffy Coat, QBC Fluorescence and Staining Technologies™ Test, and SD Bioline™ Malaria Rapid Test in Malaria Diagnosis in Western Kenya

Malaria remains the most important parasitic disease in sub-Saharan Africa as a cause of morbidity and mortality.  Effective management of malaria relies on prompt and accurate diagnosis to guide treatment.  The World Health Organization (WHO) recommends that all suspected malaria cases be tested before initiation of treatment, thus diagnosis of malaria requires parasitological confirmation of malaria parasites in the blood of suspected patients.  This cross-sectional study conducted at the Ahero County Hospital, Kisumu, Kenya, evaluated the performance of quantitative buffy coat (QBC) (QBC Fluorescence and Staining Technologies™(QBC F.A.S.T.™)-improved QBC system and SD Bioline™ malaria rapid tests) against 'gold standard' (Giemsa blood stained slides microscopy) for the detection of Plasmodium species in children<five years old (n=385)in a malaria holo-endemic area of western Kenya.  Real-time PCR was performed on discrepant samples across the tests and the gold standard (microscopy).Sensitivity of QBC, QBC F.A.S.T.™ and SD Bioline™ malaria rapid tests were 90% (95% CI: 85-94), 77% (95% CI: 71-83) and 91% (95% CI: 86-94), respectively, while specificity was 30% (95% CI: 24-37), 83% (95% CI: 77-88) and 67% (95% CI: 60-73), respectively.  The positive predictive values (PPV) were 58% (95% CI: 52-63), 83% (95% CI: 77-88) and 74% (95% CI: 63-80), respectively, while the negative predictive values (NPV) were 74% (95% CI: 63-84), 78% (95% CI: 71-83) and 87% (95% CI: 81-92), respectively.Although the standard QBC malaria test and the SD Bioline™ malaria rapid diagnostic test (RDT) showed better sensitivity relative to the improved QBC F.A.S.T.™ test, the latter had a better specificity.  The performance of these tests remains modest against microscopy. Keywords: Malaria, Quantitative buffy coat, QBC F.A.S.T.™, SD Bioline

Impact of Plasmodium falciparum infection on haematological parameters in children living in Western Kenya

<p>Abstract</p> <p>Background</p> <p>Malaria is the commonest cause of childhood morbidity in Western Kenya with varied heamatological consequences. The t study sought to elucidate the haemotological changes in children infected with malaria and their impact on improved diagnosis and therapy of childhood malaria.</p> <p>Methods</p> <p>Haematological parameters in 961 children, including 523 malaria-infected and 438 non-malaria infected, living in Kisumu West District, an area of malaria holoendemic transmission in Western Kenya were evaluated.</p> <p>Results</p> <p>The following parameters were significantly lower in malaria-infected children; platelets, lymphocytes, eosinophils, red blood cell count and haemoglobin (Hb), while absolute monocyte and neutrophil counts, and mean platelet volume (MPV) were higher in comparison to non-malaria infected children. Children with platelet counts of <150,000/uL were 13.8 times (odds ratio) more likely to have malaria. Thrombocytopaenia was present in 49% of malaria-infected children and was associated with high parasitaemia levels, lower age, low Hb levels, increased MPV and platelet aggregate flag. Platelet aggregates were more frequent in malaria-infected children (25% vs. 4%, p<0.0001) and associated with thrombocytopaenia rather than malaria status.</p> <p>Conclusion</p> <p>Children infected with <it>Plasmodium falciparum</it> malaria exhibited important changes in some haematological parameters with low platelet count and haemoglobin concentration being the two most important predictors of malaria infection in children in our study area. When used in combination with other clinical and microscopy, these parameters could improve malaria diagnosis in sub-patent cases.</p

Treatment of asymptomatic carriers with artemether-lumefantrine: an opportunity to reduce the burden of malaria?

Background: Increased investment and commitment to malaria prevention and treatment strategies across Africa has produced impressive reductions in the incidence of this disease. Nevertheless, it is clear that further interventions will be necessary to meet the international target of a reversal in the incidence of malaria by 2015. This article discusses the prospective role of an innovative malaria control strategy - the community-based treatment of asymptomatic carriers of Plasmodium falciparum, with artemisinin-based combination therapy (ACT). The potential of this intervention was considered by key scientists in the field at an Advisory Board meeting held in Basel, in April 2009. This article summarizes the discussions that took place among the participants. Presentation of the hypothesis: Asymptomatic carriers do not seek treatment for their infection and, therefore, constitute a reservoir of parasites and thus a real public-health risk. The systematic identification and treatment of individuals with asymptomatic P. falciparum as part of a surveillance intervention strategy should reduce the parasite reservoir, and if this pool is greatly reduced, it will impact disease transmission. Testing the hypothesis: This article considers the populations that could benefit from such a strategy and examines the ethical issues associated with the treatment of apparently healthy individuals, who represent a neglected public health risk. The potential for the treatment of asymptomatic carriers to impair the development of protective immunity, resulting in a \u27rebound\u27 and age escalation of malaria incidence, is also discussed. For policymakers to consider the treatment of asymptomatic carriers with ACT as a new tool in their malaria control programmes, it will be important to demonstrate that such a strategy can produce significant benefits, without having a negative impact on the efficacy of ACT and the health of the target population. Implications of the hypothesis: The treatment of asymptomatic carriers with ACT is an innovative and essential tool for breaking the cycle of infection in some transmission settings. Safe and effective medicines can save the lives of children, but the reprieve is only temporary so long as the mosquitoes can become re-infected from the asymptomatic carriers. With improvements in rapid diagnostic tests that allow easier identification of asymptomatic carriers, the elimination of the pool of parasites is within reach. © 2010 Ogutu et al; licensee BioMed Central Ltd

RTS,S malaria vaccine pilot studies : addressing the human realities in large-scale clinical trials

A malaria vaccine as part of the integrated malaria control and elimination efforts will have a major impact on public health in sub-Sahara Africa. The first malaria vaccine, RTS,S, now enters pilot implementation in three African countries. These pilot implementation studies are being initiated in Kenya, Malawi, and Ghana to inform the broader roll-out recommendation. Based on the malaria vaccine clinical trial experiences, key ethical practices for effective clinical trial research in low-resource settings are described. For successful vaccine integration into malaria intervention programs, the relational dynamics between researchers and trial communities must be made explicit. Incorporating community values and returning to research practices that serve the intended benefactors are key strategies that address the human realities in large-scale clinical trials and pilot implementation, leading to positive public health outcomes

Decorticate, decerebrate and opisthotonic posturing and seizures in Kenyan children with cerebral malaria

BACKGROUND: Abnormal motor posturing is often observed in children with cerebral malaria, but the aetiology and pathogenesis is poorly understood. This study examined the risk factors and outcome of posturing in Kenyan children with cerebral malaria. METHODS: Records of children admitted to Kilifi district hospital with cerebral malaria from January, 1999 through December, 2001 were reviewed for posturing occurring on or after admission. The clinical characteristics, features of raised intracranial pressure, number of seizures and biochemical changes in patients that developed posturing was compared to patients who did not. RESULTS: Of the 417 children with complete records, 163 (39.1%) had posturing: 85 on admission and 78 after admission to hospital. Decorticate posturing occurred in 80, decerebrate in 61 and opisthotonic posturing in 22 patients. Posturing was associated with age ≥ 3 years (48.1 vs 35.8%, p = 0.01) and features of raised intracranial pressure on funduscopy (adjusted OR 2.1 95%CI 1.2–3.7, p = 0.009) but not other markers of severity of disease. Unlike decorticate posturing, decerebrate (adjusted OR 1.9 95%CI 1.0–3.5) and opisthotonic posturing (adjusted OR 2.9 95%CI 1.0–8.1) were, in addition, independently associated with recurrence of seizures after admission. Opisthotonus was also associated with severe metabolic acidosis (OR 4.2 95%CI 3.2–5.6, p < 0.001). Thirty one patients with posturing died. Of these, 19 (61.3%) had features suggestive of transtentorial herniation. Mortality and neurological deficits on discharge were greatest in those developing posturing after admission. CONCLUSION: Abnormal motor posturing is a common feature of cerebral malaria in children. It is associated with features of raised intracranial pressure and recurrence of seizures, although intracranial hypertension may be the primary cause

Sample-ready multiplex qPCR assay for detection of malaria

BACKGROUND: Microscopy and antigen detecting rapid diagnostic tests are the diagnostic tests of choice in management of clinical malaria. However, due to their limitations, the need to utilize more sensitive methods such as real-time PCR (qPCR) is evident as more studies are now utilizing molecular methods in detection of malaria. Some of the challenges that continue to limit the widespread utilization of qPCR include lack of assay standardization, assay variability, risk of contamination, and the need for cold-chain. Lyophilization of molecular assays can overcome some of these limitations and potentially enable widespread qPCR utilization. METHODS: A recently published multiplex malaria qPCR assay was lyophilized by freezing drying into Sample-Ready™ format (MMSR). MMSR assay contained all the required reagents for qPCR including primers and probes, requiring only the addition of water and sample to perform qPCR. The performance of the MMSR assay was compared to the non-freeze dried, “wet” assay. Stability studies were done by maintaining the MMSR assays at four different ambient temperatures of 4°C, room temperature (RT), 37°C and 42°C over a period of 42 days, tested at seven-day intervals. Plasmodium falciparum and Plasmodium vivax DNAs were used for analysis of the MMSR assay either as single or mixed parasites, at two different concentrations. The C(T) values and the standard deviations (SD) were used in the analysis of the assay performance. RESULTS: The limit of detection for the MMSR assay was 0.244 parasites/μL for Plasmodium spp. (PLU) and P. falciparum (FAL) assay targets compared to “wet” assay which was 0.39 and 3.13 parasites/μL for PLU and FAL assay targets, respectively. The MMSR assay performed with high efficiencies similar to those of the “wet” assay and was stable at 37°C for 42 days, with estimated shelf-life of 5 months. When used to analyse field clinical samples, MMSR assay performed with 100% sensitivity and specificity compared to the “wet” assay. CONCLUSION: The MMSR assay has the same robust performance characteristics as the “wet” assay and is highly stable. Availability of MMSR assay allows flexibility and provides an option in choosing assay for malaria diagnostics depending on the application, needs and budget

Misclassification of Plasmodium infections by conventional microscopy and the impact of remedial training on the proficiency of laboratory technicians in species identification.

BACKGROUND: Malaria diagnosis is largely dependent on the demonstration of parasites in stained blood films by conventional microscopy. Accurate identification of the infecting Plasmodium species relies on detailed examination of parasite morphological characteristics, such as size, shape, pigment granules, besides the size and shape of the parasitized red blood cells and presence of cell inclusions. This work explores misclassifications of four Plasmodium species by conventional microscopy relative to the proficiency of microscopists and morphological characteristics of the parasites on Giemsa-stained blood films. CASE DESCRIPTION: Ten-day malaria microscopy remedial courses on parasite detection, species identification and parasite counting were conducted for public health and research laboratory personnel. Proficiency in species identification was assessed at the start (pre) and the end (post) of each course using known blood films of Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale and Plasmodium vivax infections with densities ranging from 1,000 to 30,000 parasites/μL. Outcomes were categorized as false negative, positive without speciation, P. falciparum, P. malariae, P. ovale, P. vivax and mixed infections. DISCUSSION AND EVALUATION: Reported findings are based on 1,878 P. falciparum, 483 P. malariae, 581 P. ovale and 438 P. vivax cumulative results collated from 2008 to 2010 remedial courses. Pre-training false negative and positive misclassifications without speciation were significantly lower on P. falciparum infections compared to non-falciparum infections (p < 0.0001). Post-training misclassifications decreased significantly compared to pre- training misclassifications which in turn led to significant improvements in the identification of the four species. However, P. falciparum infections were highly misclassified as mixed infections, P. ovale misclassified as P. vivax and P. vivax similarly misclassified as P. ovale (p < 0.05). CONCLUSION: These findings suggest that the misclassification of malaria species could be a common occurrence especially where non-falciparum infections are involved due to lack of requisite skills in microscopic diagnosis and variations in morphological characteristics within and between Plasmodium species. Remedial training might improve reliability of conventional light microscopy with respect to differentiation of Plasmodium infections