Impact of intermittent preventive treatment with sulphadoxine-pyrimethamine targeting the transmission season on the incidence of clinical malaria in children in Mali

<p>Abstract</p> <p>Background</p> <p>Recent studies have shown that intermittent preventive malaria treatment (IPT) in infants in areas of stable malaria transmission reduces malaria and severe anaemia incidence. However in most areas malaria morbidity and mortality remain high in older children.</p> <p>Methods</p> <p>To evaluate the effect of seasonal IPT with sulphadoxine pyrimethamine (SP) on incidence of malaria disease in area of seasonal transmission, 262 children 6 months-10 years in Kambila, Mali were randomized to receive either IPT with SP twice at eight weeks interval or no IPT during the transmission season of 2002 and were followed up for 12 months. Subjects were also followed during the subsequent transmission season in 2003 to assess possible rebound effect. Clinical malaria cases were treated with SP and followed to assess the <it>in vivo </it>response during both periods.</p> <p>Results</p> <p>The incidence rate of malaria disease per 1,000 person-months during the first 12 months was 3.2 episodes in the treatment group vs. 5.8 episodes in the control group with age-adjusted Protective Efficacy (PE) of 42.5%; [95% CI 28.6%–53.8%]. When the first 16 weeks of follow up is considered age-adjusted PE was 67.5% [95% CI 55.3% – 76.6%]. During the subsequent transmission season, the incidence of clinical malaria per 1000 persons-days was similar between the two groups (23.0 vs 21.5 episodes, age-adjusted IRR = 1.07 [95% CI, 0.90–1.27]). No significant difference was detected in <it>in vivo </it>response between the groups during both periods.</p> <p>Conclusion</p> <p>Two malaria intermittent treatments targeting the peak transmission season reduced the annual incidence rate of clinical malaria by 42.5% in an area with intense seasonal transmission. This simple strategy is likely to be one of the most effectives in reducing malaria burden in such areas.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov NCT00623155</p

A Randomized Open-Label Trial of Artesunate- Sulfadoxine-Pyrimethamine with or without Primaquine for Elimination of Sub-Microscopic P. falciparum Parasitaemia and Gametocyte Carriage in Eastern Sudan

In areas of seasonal malaria transmission, treatment of asymptomatic carriers of malaria parasites, whose parasitaemia persists at low densities throughout the dry season, could be a useful strategy for malaria control. We carried out a randomized trial to compare two drug regimens for clearance of parasitaemia in order to identify the optimum regimen for use in mass drug administration in the dry season.A two-arm open-label randomized controlled trial was conducted during the dry season in an area of distinct seasonal malaria in two villages in Gedarif State in eastern Sudan. Participants were asymptomatic adults and children aged over 6 months, with low-density P. falciparum infection detected by PCR. Participants were randomized to receive artesunate/sulfadoxine-pyrimethamine (AS+SP) combination for three days with or without a dose of primaquine (PQ) on the fourth day. Parasitaemia detected by PCR on days 3, 7 and 14 after the start of treatment and gametocytes detected by RT-PCR on days 7 and 14 were then recorded. 104 individuals who had low density parasitaemia at screening were randomized and treated during the dry season. On day 7, 8.3% were positive by PCR in the AS+SP+PQ group and 6.5% in the AS+SP group (risk difference 1.8%, 95%CI -10.3% to +13.8%). At enrolment, 12% (12/100) were carrying gametocytes. This was reduced to 6.4% and 4.4% by day 14 (Risk difference 1.9% (95%CI -9.3% to +13.2%) in AS+SP+PQ and AS+SP groups, respectively.Addition of primaquine to artemisinin combination treatment did not improve elimination of parasitaemia and prevention of gametocyte carriage in carriers with low-density parasitaemia in the dry season.ClinicalTrials.gov NCT00330902

Epidemiology of malaria in the forest-savanna transitional zone of Ghana.

BACKGROUND: Information on the epidemiology of malaria is essential for designing and interpreting results of clinical trials of drugs, vaccines and other interventions. As a background to the establishment of a site for anti-malarial drugs and vaccine trials, the epidemiology of malaria in a rural site in central Ghana was investigated. METHODS: Active surveillance of clinical malaria was carried out in a cohort of children below five years of age (n = 335) and the prevalence of malaria was estimated in a cohort of subjects of all ages (n = 1484) over a 12-month period. Participants were sampled from clusters drawn around sixteen index houses randomly selected from a total of about 22,000 houses within the study area. The child cohort was visited thrice weekly to screen for any illness and a blood slide was taken if a child had a history of fever or a temperature greater than or equal to 37.5 degree Celsius. The all-age cohort was screened for malaria once every eight weeks over a 12-month period. Estimation of Entomological Inoculation Rate (EIR) and characterization of Anopheline malaria vectors in the study area were also carried out. RESULTS: The average parasite prevalence in the all age cohort was 58% (95% CI: 56.9, 59.4). In children below five years of age, the average prevalence was 64% (95% CI: 61.9, 66.0). Geometric mean parasite densities decreased significantly with increasing age. More than 50% of all children less than 10 years of age were anaemic. Children less than 5 years of age had as many as seven malaria attacks per child per year. The attack rates decreased significantly with increasing cut-offs of parasite density. The average Multiplicity of Infection (MOI) was of 6.1. All three pyrimethamine resistance mutant alleles of the Plasmodium falciparum dhfr gene were prevalent in this population and 25% of infections had a fourth mutant of pfdhps-A437G. The main vectors were Anopheles funestus and Anopheles gambiae and the EIR was 269 infective bites per person per year. CONCLUSION: The transmission of malaria in the forest-savanna region of central Ghana is high and perennial and this is an appropriate site for conducting clinical trials of anti-malarial drugs and vaccines

Performance of physician-certified verbal autopsies: Multisite validation study using clinical diagnostic gold standards

Background: Physician review of a verbal autopsy (VA) and completion of a death certificate remains the most widely used approach for VA analysis. This study provides new evidence about the performance of physician-certified verbal autopsy (PCVA) using defined clinical diagnostic criteria as a gold standard for a multisite sample of 12,542 VAs. The study was also designed to analyze issues related to PCVA, such as the impact of a second physician reader on the cause of death assigned, the variation in performance with and without household recall of health care experience (HCE), and the importance of local information for physicians reading VAs.Methods: The certification was performed by 24 physicians. The assignment of VA was random and blinded. Each VA was certified by one physician. Half of the VAs were reviewed by a different physician with household recall of health care experience included. The completed death certificate was processed for automated ICD-10 coding of the underlying cause of death. PCVA was compared to gold standard cause of death assignment based on strictly defined clinical diagnostic criteria that are part of the Population Health Metrics Research Consortium (PHMRC) gold standard verbal autopsy study.Results: For individual cause assignment, the overall chance-corrected concordance for PCVA against the gold standard cause of death is less than 50%, with substantial variability by cause and physician. Physicians assign the correct cause around 30% of the time without HCE, and addition of HCE improves performance in adults to 45% and slightly higher in children to 48%. Physicians estimate cause-specific mortality fractions (CSMFs) with considerable error for adults, children, and neonates. Only for neonates for a cause list of six causes with HCE is accuracy above 0.7. In all three age groups, CSMF accuracy improves when household recall of health care experience is available.Conclusions: Results show that physician coding for cause of death assignment may not be as robust as previously thought. The time and cost required to initially collect the verbal autopsies must be considered in addition to the analysis, as well as the impact of diverting physicians from servicing immediate health needs in a population to review VAs. All of these considerations highlight the importance and urgency of developing better methods to more reliably analyze past and future verbal autopsies to obtain the highest quality mortality data from populations without reliable death certification