Seasonal malaria chemoprevention combined with community case management of malaria in children under 10 years of age, over 5 months, in south-east Senegal: A cluster-randomised trial

Abstract

Background: Seasonal malaria chemoprevention (SMC) is recommended in the Sahel region of Africa for children under 5 years of age, for up to 4 months of the year. It may be appropriate to include older children, and to provide protection for more than 4 months. We evaluated the effectiveness of SMC using sulfadoxine-pyrimethamine plus amodiaquine given over 5 months to children under 10 years of age in Saraya district in south-east Senegal in 2011.

Methods and findings: Twenty-four villages, including 2,301 children aged 3-59 months and 2,245 aged 5-9 years, were randomised to receive SMC with community case management (CCM) (SMC villages) or CCM alone (control villages). In all villages, community health workers (CHWs) were trained to treat malaria cases with artemisinin combination therapy after testing with a rapid diagnostic test (RDT). In SMC villages, CHWs administered SMC to children aged 3 months to 9 years once a month for 5 months. The study was conducted from 27 July to 31 December 2011. The primary outcome was malaria (fever or history of fever with a positive RDT). The prevalence of anaemia and parasitaemia was measured in a survey at the end of the transmission season. Molecular markers associated with resistance to SMC drugs were analysed in samples from incident malaria cases and from children with parasitaemia in the survey. SMC was well tolerated with no serious adverse reactions. There were 1,472 RDT-confirmed malaria cases in the control villages and 270 in the SMC villages. Among children under 5 years of age, the rate difference was 110.8/1,000/month (95% CI 64.7, 156.8; p < 0.001) and among children 5-9 years of age, 101.3/1,000/month (95% CI 66.7, 136.0; p < 0.001). The mean haemoglobin concentration at the end of the transmission season was higher in SMC than control villages, by 6.5 g/l (95% CI 2.0, 11; p = 0.007) among children under 5 years of age, and by 5.2 g/l (95% CI 0.4, 9.9; p = 0.035) among children 5-9 years of age. The prevalence of parasitaemia was 18% in children under 5 years of age and 25% in children 5-9 years of age in the control villages, and 5.7% and 5.8%, respectively, in these 2 age groups in the SMC villages, with prevalence differences of 12.5% (95% CI 6.8%, 18.2%; p < 0.001) in children under 5 years of age and 19.3% (95% CI 8.3%, 30.2%; p < 0.001) in children 5-9 years of age. The pfdhps-540E mutation associated with clinical resistance to sulfadoxine-pyrimethamine was found in 0.8% of samples from malaria cases but not in the final survey. Twelve children died in the control group and 14 in the SMC group, a rate difference of 0.096/1,000 child-months (95% CI 0.99, 1.18; p = 0.895). Limitations of this study include that we were not able to obtain blood smears for microscopy for all suspected malaria cases, such that we had to rely on RDTs for confirmation, which may have included false positives.

Conclusions: In this study SMC for children under 10 years of age given over 5 months was feasible, well tolerated, and effective in preventing malaria episodes, and reduced the prevalence of parasitaemia and anaemia. SMC with CCM achieved high coverage and ensured children with malaria were promptly treated with artemether-lumefantrine.

Trial registration: www.clinicaltrials.gov NCT01449045.

Fig 1. The age distribution and seasonal pattern of patient admissions to Saraya Hospital with malaria in 2011.

The number of patients admitted to Saraya Hospital with severe malaria in 2011, by month of admission (A) and by age (B). Individual patient data (age, date of admission, and primary diagnosis) were extracted from the hospital registers for all patients admitted from 1 January to 31 December 2011. (A) also shows a line indicating monthly rainfall (on the right-hand axis). (C) shows the proportion of cases that could potentially have been prevented by seasonal malaria chemoprevention (SMC), if SMC had been provided for children up to the age of 5 years or up to the age of 10 years, for 4 consecutive months or for 5 consecutive months starting on the date indicated. The y-axis shows the cases in 2011 in the given age group that fell in a 4- or 5-month window starting from the given date, as a proportion of total cases. From January to December there were a total of 195 admissions with severe malaria, 147 of them under 10 years of age, and of those, 91/147 (62%) were under 5 years and 56 (38%) were 5–9 years of age. In all, 7/195 patients died, 1 aged 18 years and the other 6 aged under 5 years. Ten of the 195 patients had cerebral malaria; all these patients were under 10 years of age—7 of them under 5 years of age and 3 aged 5–9 years. In all, 165 (85%) of the 195 cases occurred in the 5 months from July to November (rainfall data from Climate-Data.org).

Fig 2. Map of the study area showing the location of the study villages.

SMC, seasonal malaria chemoprevention.

Fig 3. Trial profile.

SMC, seasonal malaria chemoprevention.

Fig 4. Timing of the 5 monthly cycles of seasonal malaria chemoprevention delivery in each village.

Fig 5. The timing of RDT-confirmed malaria episodes in each age group, in SMC and control villages, for 5 months from the SMC start date.

The y-axis shows the Nelson–Aalen cumulative hazard, equal to the mean number of episodes of malaria experienced per child from the start of the study up to the given time (in months since the date when cycle 1 started in SMC villages), in children in villages targeted with SMC and in the control villages. CCM, community case management; RDT, rapid diagnostic test; SMC, seasonal malaria chemoprevention.

Fig 6. The effect of SMC on the number of children who experienced multiple episodes of malaria during the transmission season.

The number of children who were treated for RDT-confirmed malaria 1, 2, 3, 4, or 5 times is shown for children in each age group, in villages targeted with SMC and in control villages. CCM, community case management; RDT, rapid diagnostic test; SMC, seasonal malaria chemoprevention.

Fig 7. The effect of SMC on the prevalence of parasitaemia.

The prevalence of P. falciparum infection at the end of the transmission season in each arm of the trial, by age group. CCM, community case management; SMC, seasonal malaria chemoprevention.

Fig 8. The effect of SMC on the prevalence of gametocyte carriage: The prevalence of gametocyte carriage at the end of the transmission season in each arm of the trial, by age group.

There were no carriers aged 8–9 years in the CCM group. CCM, community case management; SMC, seasonal malaria chemoprevention.

Fig 9. The effect of SMC on anaemia.

The distribution of haemoglobin concentrations measured at the end of the transmission season is shown, for each age group of children, in villages with SMC and in control villages, using a kernel density estimator to plot the smoothed distribution of concentrations in each group. The left-hand plot shows children aged less than 5 years, the middle plot children 5–9 years of age. In the right-hand plot the 2 age groups have been superimposed for comparison. CCM, community case management; SMC, seasonal malaria chemoprevention.