Higher gametocyte production and mosquito infectivity in chronic compared to incident Plasmodium falciparum infections.

Plasmodium falciparum gametocyte kinetics and infectivity may differ between chronic and incident infections. In the current study, we assess parasite kinetics and infectivity to mosquitoes among children (aged 5-10 years) from Burkina Faso with (a) incident infections following parasite clearance (n = 48) and (b) chronic asymptomatic infections (n = 60). In the incident infection cohort, 92% (44/48) of children develop symptoms within 35 days, compared to 23% (14/60) in the chronic cohort. All individuals with chronic infection carried gametocytes or developed them during follow-up, whereas only 35% (17/48) in the incident cohort produce gametocytes before becoming symptomatic and receiving treatment. Parasite multiplication rate (PMR) and the relative abundance of ap2-g and gexp-5 transcripts are positively associated with gametocyte production. Antibody responses are higher and PMR lower in chronic infections. The presence of symptoms and sexual stage immune responses are associated with reductions in gametocyte infectivity to mosquitoes. We observe that most incident infections require treatment before the density of mature gametocytes is sufficient to infect mosquitoes. In contrast, chronic, asymptomatic infections represent a significant source of mosquito infections. Our observations support the notion that malaria transmission reduction may be expedited by enhanced case management, involving both symptom-screening and infection detection

Malaria Incidence in Children in South-West Burkina Faso: Comparison of Active and Passive Case Detection Methods

<div><p>Background</p><p>The aim of this study was to determine the incidence and seasonal pattern of malaria in children in South-West Burkina Faso, and to compare, in a randomized trial, characteristics of cases detected by active and passive surveillance. This study also enabled the planning of a malaria vaccine trial.</p><p>Methods</p><p>Households with young children, located within 5 kilometers of a health facility, were randomized to one of two malaria surveillance methods. In the first group, children were monitored actively. Each child was visited twice weekly; tympanic temperature was measured, and if the child had a fever or history of fever, a malaria rapid diagnostic test was performed and a blood smear collected. In the second group, children were monitored passively. The child’s parent or caregiver was asked to bring the child to the nearest clinic if he was unwell. Follow up lasted 13 months from September 2009.</p><p>Results</p><p>Incidence of malaria (Fever with parasitaemia ≥5,000/µL) was 1.18 episodes/child/year in the active cohort and 0.89 in the passive cohort (rate ratio 1.32, 95% CI 1.13–1.54). Malaria cases in the passive cohort were more likely to have high grade fever; but parasite densities were similar in the two groups. Incidence was highly seasonal; when a specific case definition was used, about 60% of cases occurred within the 4 months June-September.</p><p>Conclusion</p><p>Passive case detection required at least a 30%–40% increase in the sample size for vaccine trials, compared to active detection, to achieve the same power. However we did not find any evidence that parasite densities were higher with passive than with active detection. The incidence of malaria is highly seasonal and meets the WHO criteria for Seasonal Malaria Chemoprevention (SMC). At least half of the malaria cases in these children could potentially be prevented if SMC was effectively deployed.</p></div

Number and proportion of the annual^* malaria cases falling in the four months June to September 2010.

*<p>The year studied was from 1^st October 2009 to 30^th September 2010.</p

Specificity of RDT in relation to malaria cases (>0 parasites/µL) by calendar month.

<p>Specificity of RDT in relation to malaria cases (>0 parasites/µL) by calendar month.</p

Arithmetic mean parasite density among parasite positive malaria cases by calendar month.

<p>Arithmetic mean parasite density among parasite positive malaria cases by calendar month.</p

Map of the study area, Banfora district, Burkina Faso Households of study participants are identified as “white circle” when assigned to active case detection and “gray circle” when assigned to passive case detection.

<p>Map of the study area, Banfora district, Burkina Faso Households of study participants are identified as “white circle” when assigned to active case detection and “gray circle” when assigned to passive case detection.</p

Characteristics of the study population, number and (percentage).

*<p>3 children in the PCD and 1 child in the ACD cohorts had missing data for bednet use.</p>**<p>5 children in the PCD and 5 children in the ACD cohorts had missing data for LLIN use.</p>***<p>5 children in PCD and 1 child in ACD had missing Haemoglobin.</p

Study profile.

<p>Study profile.</p

Malaria case definition using objective fever (Temperature≥38.0): Sensitivity and specificity of alternatives parasite threshold.

<p>Malaria case definition using objective fever (Temperature≥38.0): Sensitivity and specificity of alternatives parasite threshold.</p

Nelson-Aalen cumulative hazard, mean number of children with a measured fever or history of fever in the last 24 hours and a positive RDT, by surveillance method.

<p>Nelson-Aalen cumulative hazard, mean number of children with a measured fever or history of fever in the last 24 hours and a positive RDT, by surveillance method.</p