Incidence of severe Plasmodium falciparum malaria as a primary endpoint for vaccine efficacy trials in Bandiagara, Mali

Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF 480, Baltimore, MD, USA.
Vaccine (Impact Factor: 3.62). 08/2004; 22(23-24):3169-74. DOI: 10.1016/j.vaccine.2004.01.054
Source: PubMed


Potential endpoints for blood stage malaria vaccine efficacy trials include uncomplicated malaria disease, which is hard to differentiate from other febrile illnesses, and mortality, which requires prohibitively large sample sizes. Strictly defined severe malaria predicts malaria-associated mortality where case fatality rates are known. To assess the suitability of severe malaria as a trial endpoint, we conducted a census in 1999 and measured the incidence of severe malaria from 1999 to 2001 in Bandiagara, Mali. The annual incidence of severe malaria in children <6 years of age was 2.3% (n = 2,284) yielding an estimated sample size of 4,580 for a vaccine trial designed to detect 50% efficacy with 80% power at P = 0.05 with 5% loss to follow-up. A trial using severe malaria as an endpoint in this setting would thus require expanding the study population or the length of the trial. This approach may be useful in assessing the suitability of potential sites for malaria vaccine trials.

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Available from: Yacouba Cissoko, Sep 29, 2014
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    • "Malaria transmission is highly seasonal, with minimal transmission during the dry season in March with essentially no detectable infective mosquito bites. Transmission occurs during the rainy season from July to November with a peak of up to 60 infective mosquito bites per person per month in August or September [12, 13]. Plasmodium falciparum represents 97% of malaria infections, with the remaining 3% due mostly to Plasmodium malariae and rare Plasmodium ovale infections. "
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    ABSTRACT: Background The recent decline in malaria incidence in many African countries has been attributed to the provision of prompt and effective anti-malarial treatment using artemisinin-based combination therapy (ACT) and to the widespread distribution of long-lasting, insecticide-treated bed nets (LLINs). At a malaria vaccine-testing site in Bandiagara, Mali, ACT was introduced in 2004, and LLINs have been distributed free of charge since 2007 to infants after they complete the Expanded Programme of Immunization (EPI) schedule and to pregnant women receiving antenatal care. These strategies may have an impact on malaria incidence. Methods To document malaria incidence, a cohort of 400 children aged 0 to 14 years was followed for three to four years up to July 2013. Monthly cross-sectional surveys were done to measure the prevalence of malaria infection and anaemia. Clinical disease was measured both actively and passively through continuous availability of primary medical care. Measured outcomes included asymptomatic Plasmodium infection, anaemia and clinical malaria episodes. Results The incidence rate of clinical malaria varied significantly from June 2009 to July 2013 without a clear downward trend. A sharp seasonality in malaria illness incidence was observed with higher clinical malaria incidence rates during the rainy season. Parasite and anaemia point prevalence also showed seasonal variation with much higher prevalence rates during rainy seasons compared to dry seasons. Conclusions Despite the scaling up of malaria prevention and treatment, including the widespread use of bed nets, better diagnosis and wider availability of ACT, malaria incidence did not decrease in Bandiagara during the study period.
    Full-text · Article · Sep 2014 · Malaria Journal
    • "The hospital admissions may be a small proportion of cases in comparison to incidence in the community. Incidence of severe malaria can be a good indicator to assess the effectiveness of malaria control activities or success of a vaccine.[2021] At present, mortality impact is the most important public health measure, but it represents a smaller proportion of the disease burden and will, thus, require large sample size for any meaningful conclusion.[22] "
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    ABSTRACT: Background and Objectives: Infection with Plasmodium falciparum, caused 627,000 deaths in 2012 in the world. P. falciparum infection causes myriads of clinical manifestations. Exact clinical manifestation resulting in poor prognosis in hyper-endemic epidemiological settings need to be ascertained to save human lives. A hospital-based study was conducted to elucidate the different severe clinical presentations of falciparum malaria and to examine the critical clinical and laboratory parameters on the prognosis of these severe manifestations in a stable hyper-endemic falciparum area in the state of Odisha, India. Materials and Methods: Consecutive patients admitted in a tertiary care hospital with severe manifestations of malaria as per WHO criteria and confirmed by parasitological examination were included in the study. A detailed clinical and biochemical parameters were examined. Clinical data were reviewed before being double entered into a computer and analyzed. Statistical analyses were carried out using Epi Info 6.04. Continuous and normal distributed data were compared by two-tailed Student's t-test and proportions compared with χ2 tests with Yates’ correction or Fisher's exact test. Results and Discussion: A total of 1320 patients with clinical malaria, diagnosed at outpatients’ department were admitted in the hospital during the 1 year study period of which, 292 (22.1%) were children under 14 years of age. The major clinical categories on admission were hyperpyrexia (70.7%), cerebral malaria (9.4%), malarial anemia (7.7%), algid malaria (1.5%), and malaria associated categories were respiratory infection (2.2%), hepatitis (2.0%), urinary tract infection (1.8%), enteric fever (3.3%), and sickle cell disease (1.2%). The overall case fatality rate (CFR) was 4.3 (57/1320). The CFR in children 12.3 (36/292) was significantly higher when compared to adults, that is, 2.0 (21/1028). The major causes of death were cerebral malaria (45.6%), malaria along with a respiratory infection (19.3%) and anemia (10.5%). Malarial anemia along sickle cell disease accounted for 19.3% of all malaria related deaths. Proportion of mortality due to acute renal failure was higher in adults. Biochemical parameters suggest involvement of multiple organs. The findings suggest that the area can be effectively managed by sustained and continuous preventive and curative efforts.
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    • "With less than one infecting bite per person per month at the height of the dry season in March, the transmission season starts in June, peaks at up to 60 infected mosquito bites per person per month in August or September, and ends in December Following transmission fluctuations, malaria incidence is seasonal too, with an intense peak in September to October. In 1999, the clinical malaria incidence was 1.7 episodes per transmission season in children less than 10 years [33,34]. Plasmodium falciparum represents 97% of malaria infections, Plasmodium malariae 3%, and rare infections are due to Plasmodium ovale. "
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    ABSTRACT: Background: Heterogeneous patterns of malaria transmission are thought to be driven by factors including host genetics, distance to mosquito breeding sites, housing construction, and socio-behavioural characteristics. Evaluation of local transmission epidemiology to characterize malaria risk is essential for planning malaria control and elimination programmes. The use of geographical information systems (GIS) techniques has been a major asset to this approach. To assess time and space distribution of malaria disease in Bandiagara, Mali, within a transmission season, data were used from an ongoing malaria incidence study that enrolled 300 participants aged under six years old". Methods: Children's households were georeferenced using a handheld global position system. Clinical malaria was defined as a positive blood slide for Plasmodium falciparum asexual stages associated with at least one of the following signs: headache, body aches, fever, chills and weakness. Daily rainfall was measured at the local weather station.Landscape features of Bandiagara were obtained from satellite images and field survey. QGIS™ software was used to map malaria cases, affected and non-affected children, and the number of malaria episodes per child in each block of Bandiagara. Clusters of high or low risk were identified under SaTScan(®) software according to a Bernoulli model. Results: From June 2009 to May 2010, 296 clinical malaria cases were recorded. Though clearly temporally related to the rains, Plasmodium falciparum occurrence persisted late in the dry season. Two "hot spots" of malaria transmission also found, notably along the Yamé River, characterized by higher than expected numbers of malaria cases, and high numbers of clinical episodes per child. Conversely, the north-eastern sector of the town had fewer cases despite its proximity to a large body of standing water which was mosquito habitat. Conclusion: These results confirm the existence of a marked spatial heterogeneity of malaria transmission in Bandiagara, providing support for implementation of targeted interventions.
    Full-text · Article · Mar 2013 · Malaria Journal
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