Mass drug administration to reduce malaria incidence in a low-to-moderate endemic setting: short-term impact results from a cluster randomised controlled trial in Senegal.

Background: In Africa, the scale-up of malaria control interventions, including seasonal malaria chemoprevention (SMC), has dramatically reduced malaria burden, but progress toward malaria elimination has stalled. We evaluated mass drug administration (MDA) as a strategy to accelerate reductions in malaria incidence in Senegal. Methods: We conducted an open-label, cluster-randomised controlled trial in a low-to-moderate transmission setting of Tambacounda, Senegal. Eligible villages had a population size between 200-800. All villages received pyrethroid-piperonyl butoxide bednets and proactive community case management of malaria at baseline. Sixty villages were randomised 1:1 to either three cycles of MDA with dihydroartemisinin-piperaquine+single-low dose primaquine administered to individuals aged ≥3 months, six-weeks apart starting the third week of June (intervention), or standard-of-care, which included three monthly cycles of SMC with sulfadoxine-pyrimethamine+amodiaquine administered to children aged 3-120 months starting end of July (control). MDA and SMC were delivered door-to-door. The primary outcome was clinical malaria incidence in all ages assessed during the peak transmission season (July-December), the year after intervention. Here, we report safety, coverage, and impact outcomes during the intervention year. The trial is registered at ClinicalTrials.Gov (NCT04864444). Findings: Between June 21, 2021 and October 3, 2021, 6505, 7125, and 7250 participants were administered MDA and 3202, 3174, and 3146 participants were administered SMC across cycles. Coverage of ≥1 dose of MDA drugs was 79%, 82%, and 83% across cycles. During the transmission season of the intervention year, MDA was associated with a 55% [95% CI: 28%-72%] lower incidence of malaria compared to control (MDA: 93 cases/1000 population; control: 173 cases/1000 population). No serious adverse events were reported in either arm. Interpretation: In low-to-moderate malaria transmission settings with scaled-up malaria control interventions, MDA with dihydroartemisinin-piperaquine+single-low dose primaquine is effective and well-tolerated for reducing malaria incidence. Further analyses will focus on the sustainability of this reduction. Funding: United States President's Malaria Initiative.

Prevalence of Malaria Infection in Pregnant Women Attending Antenatal Clinics in Southern Senegal.

Despite marked progress in Senegal, three regions in the southeast part continue to have a high burden of malaria, but there have been no recent studies assessing the prevalence of malaria associated with pregnancy. This study aimed to determine the prevalence of malaria infection in pregnant women attending antenatal clinics in Senegal. During the malaria transmission season of 2019, pregnant women attending 11 health care facilities for a scheduled visit and those presenting unwell with signs of malaria were invited to participate in a malaria screening study. A finger prick blood sample was taken for malaria diagnosis by rapid diagnosis test (RDT) and polymerase chain reaction (PCR). A total of 877 pregnant women were enrolled, 787 for a scheduled antenatal consultation and 90 for an unscheduled consultation with signs of malaria. The prevalence of Plasmodium falciparum among the first group was 48% by PCR and 20% by RDT, and that among the second group was 86% by PCR and 83% by RDT. RDT sensitivity in capturing asymptomatic, PCR-positive infections was 9.2% but ranged from 83% to 94% among febrile women. The prevalence of infection by PCR in women who reported having received at least three doses of sulfadoxine pyrimethamine (SP) was 41.9% compared with 58.9% in women who reported they had not received any SP doses (prevalence ratio adjusted for gravidity and gestational age, 0.54; 95% CI, 0.41-0.73). The burden of P. falciparum infections remains high among pregnant women, the majority of which are not captured by RDT. More effective measures to prevent malaria infection in pregnancy are needed.

Feasibility and safety of integrating mass drug administration for helminth control with seasonal malaria chemoprevention among Senegalese children: a randomized controlled, observer-blind trial.

BACKGROUND: The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal. METHODS: Female and male children aged 1-14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1-3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1-3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1-3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed. RESULTS: From 9 to 22 June 2022, 627 children aged 1-14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13-5.00, p = 0.63). CONCLUSIONS: Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model. TRIAL REGISTRATION: The study is registered at Clinical Trial.gov NCT05354258.

Provider and User Acceptability of Integrated Treatment for the Control of Malaria and Helminths in Saraya, South-Eastern Senegal.

Integration of vertical programs for the control of malaria, schistosomiasis, and soil-transmitted helminthiasis has been recommended to achieve elimination of malaria and neglected tropical diseases (NTD) by 2030. This qualitative study was conducted within the context of a randomized controlled trial to explore the perceptions and views of parents/caregivers of at-risk children and healthcare providers to determine their acceptability of the integrated malaria-helminth treatment approach. Randomly selected parents/caregivers of children enrolled in the trial, healthcare providers, trial staff, malaria, and NTD program managers were interviewed using purpose-designed topic guides. Transcripts obtained from the interviews were coded and common themes identified using content analysis were triangulated. Fifty-seven study participants comprising 26 parents/caregivers, 10 study children aged ≥ 10 years, 15 trial staff, four healthcare providers, and two managers from the Senegal Ministry of Health were interviewed. Thirty-eight of the participants (66.7%) were males, and their ages ranged from 10 to 65 years. Overall, the integrated malaria-helminth treatment approach was considered acceptable, but the study participants expressed concerns about the taste, smell, and side effects associated with amodiaquine and praziquantel in the combination package. Reluctance to accept the medications was also observed among children aged 10 to 14 years due to peer influence and gender-sensitive cultural beliefs. Addressing concerns about the taste and smell of amodiaquine and praziquantel is needed to optimize the uptake of the integrated treatment program. Also, culturally appropriate strategies need to be put in place to cater for the inclusion of children aged 10 to 14 years in this approach.

Prevalence of malaria-helminth co-infections among children living in a setting of high coverage of standard interventions for malaria and helminths: Two population-based studies in Senegal.

Background: Concurrent infections of Plasmodium falciparum with Soil Transmitted Helminths (STH) and Schistosoma spp are still a major public health problem among children living in Sub-Saharan Africa. We conducted two prospective studies among children living in urban and rural settings of Senegal, where control programmes for malaria, STH and schistosomiasis have been sustained, to determine the prevalence of malaria-helminth co-infection. Methods: We enrolled 910 children aged 1-14 years from Saraya and Diourbel districts of Senegal in June and November 2021, respectively. We collected finger-prick blood samples from the children for malaria parasite detection using microscopy and PCR methods. Stool samples were also collected and Kato-Katz and PCR methods were used to detect STH and S. mansoni; and Merthiolate-iodine-formalin (MIF) test for other intestinal protozoans. Urine samples were analyzed using a filtration test, Point of Care Circulating Cathodic Antigens (POC-CCA) and PCR methods for detection of S. haematobium. Statistical analyses were performed to compare the continuous and categorical variables across the two study sites and age groups, as well as using the adjusted Odds ratios (aOR) to explore risk factors for malaria-helminth co-infections. Results: The overall prevalence of polyparasitism with P. falciparum, STH, S. haematobium and S. mansoni among children in the two study sites was 2.2% (20/910) while prevalence of P. falciparum-S. haematobium co-infection was 1.1% (10/910); P. falciparum-S. mansoni 0.7% (6/910) and P. falciparum with any intestinal protozoan 2.4% (22/910). Co-infection was slightly higher among 5-14 year old children (17/629, 2.7%; 95% CI: 1.43-3.97) than 1-4 years (3/281, 1.1%; 95% CI: -0.12-2.32) and, in boys (13/567, 2.3%; 95% CI: 1.27-3.96) than girls (7/343, 2.1%; 95% CI: 0.52-3.48). Children aged 5-14 years (aOR = 3.37; 95% CI: 0.82-13.77, p = 0.09), who were boys (aOR = 1.44; 95% CI: 0.48-4.36, p = 0.51) and lived in Saraya (aOR = 1.27; 95% CI: 0.24-6.69, p = 0.77) had a higher risk of malaria-helminth co-infection than other age group, in girls and those who lived in Diourbel. Living in houses with spaces between the walls and roofs as well as frequent contacts with water during swimming were statistically significant risk factors for malaria-helminth co-infection. Conclusions: The prevalence of malaria-helminth co-infection is low in two districts in Senegal, possibly due to sustained implementation of effective control measures for malaria and NTDs. These findings could help to develop and implement strategies that would lead to elimination of malaria and helminths in the study areas.

Field evaluation of the diagnostic performance of EasyScan GO: a digital malaria microscopy device based on machine-learning.

BACKGROUND: Microscopic examination of Giemsa-stained blood films remains the reference standard for malaria parasite detection and quantification, but is undermined by difficulties in ensuring high-quality manual reading and inter-reader reliability. Automated parasite detection and quantification may address this issue. METHODS: A multi-centre, observational study was conducted during 2018 and 2019 at 11 sites to assess the performance of the EasyScan Go, a microscopy device employing machine-learning-based image analysis. Sensitivity, specificity, accuracy of species detection and parasite density estimation were assessed with expert microscopy as the reference. Intra- and inter-device reliability of the device was also evaluated by comparing results from repeat reads on the same and two different devices. This study has been reported in accordance with the Standards for Reporting Diagnostic accuracy studies (STARD) checklist. RESULTS: In total, 2250 Giemsa-stained blood films were prepared and read independently by expert microscopists and the EasyScan Go device. The diagnostic sensitivity of EasyScan Go was 91.1% (95% CI 88.9-92.7), and specificity 75.6% (95% CI 73.1-78.0). With good quality slides sensitivity was similar (89.1%, 95%CI 86.2-91.5), but specificity increased to 85.1% (95%CI 82.6-87.4). Sensitivity increased with parasitaemia rising from 57% at < 200 parasite/µL, to ≥ 90% at > 200-200,000 parasite/µL. Species were identified accurately in 93% of Plasmodium falciparum samples (kappa = 0.76, 95% CI 0.69-0.83), and in 92% of Plasmodium vivax samples (kappa = 0.73, 95% CI 0.66-0.80). Parasite density estimates by the EasyScan Go were within ± 25% of the microscopic reference counts in 23% of slides. CONCLUSIONS: The performance of the EasyScan Go in parasite detection and species identification accuracy fulfil WHO-TDR Research Malaria Microscopy competence level 2 criteria. In terms of parasite quantification and false positive rate, it meets the level 4 WHO-TDR Research Malaria Microscopy criteria. All performance parameters were significantly affected by slide quality. Further software improvement is required to improve sensitivity at low parasitaemia and parasite density estimations. Trial registration ClinicalTrials.gov number NCT03512678.

Effectiveness of seasonal malaria chemoprevention administered in a mass campaign in the Kedougou region of Senegal in 2016: a case-control study.

Background: Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) is a malaria prevention strategy recommended since 2012 by the World Health Organization (WHO) for children under 5 years. In Senegal, the scaling up of SMC started in 2013 in the south-eastern regions of the country with an extension of the target to 10 years old children. The scaling up of SMC requires regular evaluation of the strategy as recommended by the WHO. This study was conducted to evaluate the effectiveness of SMC. Methods: A case-control study was conducted in some villages of the health districts of Saraya and Kedougou in the Kedougou region from July to December 2016. A case was a sick child, aged 3 months to 10 years, seen in consultation and with a positive malaria rapid diagnostic test (RDT). The control was a child of the same age group with a negative RDT and living in the same compound as the case or in a neighbouring compound. Each case was matched with two controls. Exposure to SMC was assessed by interviewing the mothers/caretakers and by checking the SMC administration card. Results: Overall, 492 children, including 164 cases and 328 controls, were recruited in our study. Their mean ages were 5.32 (+/- 2.15) and 4.44 (+/-2.25) years for cases and controls, respectively. The number of boys was higher in both cases (55.49%; CI 95%=47.54-63.24%) and controls (51,22%; CI 95%=45.83-56.58%). Net ownership was 85.80% among cases and 90.85% among controls (p=0,053). The proportion of controls who received SMC was higher than that of cases (98.17% vs 85.98% and p=1.10 -7). The protective effectiveness of SMC was 89% (OR= 0.12 (CI 95%=0.04-0.28)). Conclusions: SMC is an effective strategy in the control of malaria in children. Case-control studies are a good approach for monitoring the efficacy of drugs administered during SMC.

Malaria parasite carriage before and two years after the implementation of seasonal malaria chemoprevention: a case study of the Saraya health district, southern Senegal.

Background : Seasonal malaria chemoprevention (SMC) has been adopted and implemented in the southern regions of Senegal in children aged between three and 120 months since 2013. Scaling up this strategy requires its evaluation to assess the impact. This study was carried out to determine the dynamics of Plasmodium falciparum carriage before and after two years of SMC implementation. Methods : Four household surveys were conducted in villages in the health district of Saraya, which is a SMC implementation area in Senegal. These villages were selected using probability proportional to size sampling. Each selected village was divided into segments containing at least 50 children. In each segment, a household questionnaire was administered to the parents or legal representatives of children aged three to 120 months. Blood smears were collected to determine P. falciparum prevalence by microscopy one month before the first round of SMC, one month after the last round of the first SMC campaign and two years after the start of the implementation. Results : A total of 2008 children were included with a mean average age of 4.81 (+/-2.73) years. Of the study population, 50.33% were more than five years old and 50.3% were male. In 2013, mosquito net ownership was 99.4 % before the SMC campaign and 97.4% after. In 2015, it was 36.6% before and 45.8% after the campaign. In 2013, the prevalence of plasmodium carriage was 11.8% before and 6.1% after the SMC campaign. In 2015, the prevalence was 4.9% before the administration of SMC and this increased up to 15.3% after. Malaria prevalence was high among children over five years old and in boys. Conclusions : The decrease in Plasmodium falciparum parasite prevalence, which subsequently increased after two years of SMC implementation in this study, suggests adding an extra cycle of the SMC or adjusting the administration period.

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.

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.

Acceptability and Utilization of Three Nutritional Supplements during Pregnancy: Findings from a Longitudinal, Mixed-Methods Study in Niger.

Nutritional status in pregnancy is a key determinant of birth outcomes. In low-income countries, maternal diets are often limited, and daily nutrient supplements are recommended to fill nutrient gaps. As a result, it is important to understand the factors influencing acceptability and utilization of nutrient supplements in these settings. Qualitative data (individual interviews and focus group discussions with pregnant women, household members, and study staff) and quantitative data (unannounced household spot checks) were collected in 24 villages in the Maradi region of south-central Niger. Each village was randomly assigned to one of three study arms, with pregnant women receiving either iron and folic acid (IFA) supplements, multiple micronutrient (MMN) supplements, or medium-quantity lipid-based nutrient supplements (MQ-LNS) for daily consumption during pregnancy. Data were collected longitudinally to capture changes in perspective as women progressed through their pregnancy. Participants accepted all three supplement types, and perceived a wide range of health benefits attributed to supplement consumption. However, several important barriers to appropriate consumption were reported, and rumors about the supplements leading to childbirth complications also decreased utilization. The household spot checks suggested that IFA had the highest level of correct consumption. Overall, despite a stated high level of acceptance and enthusiasm for the supplements among participants and their household members, certain fears, side effects, and organoleptic factors led to decreased utilization. The effectiveness of future programs to improve maternal nutritional status through supplementation may be improved by understanding perceived barriers and facilitating factors among participants and tailoring communication efforts appropriately.