Cost-effectiveness of district-wide seasonal malaria chemoprevention when implemented through routine malaria control programme in Kita, Mali using fixed point distribution

Background Seasonal malaria chemoprevention (SMC) is a strategy for malaria control recommended by the World Health Organization (WHO) since 2012 for Sahelian countries. The Mali National Malaria Control Programme adopted a plan for pilot implementation and nationwide scale-up by 2016. Given that SMC is a relatively new approach, there is an urgent need to assess the costs and cost effectiveness of SMC when implemented through the routine health system to inform decisions on resource allocation. Methods Cost data were collected from pilot implementation of SMC in Kita district, which targeted 77,497 children aged 3–59 months. Starting in August 2014, SMC was delivered by fixed point distribution in villages with the first dose observed each month. Treatment consisted of sulfadoxine-pyrimethamine and amodiaquine once a month for four consecutive months, or rounds. Economic and financial costs were collected from the provider perspective using an ingredients approach. Effectiveness estimates were based upon a published mathematical transmission model calibrated to local epidemiology, rainfall patterns and scale-up of interventions. Incremental cost effectiveness ratios were calculated for the cost per malaria episode averted, cost per disability adjusted life years (DALYs) averted, and cost per death averted. Results The total economic cost of the intervention in the district of Kita was US $357,494. Drug costs and personnel costs accounted for 34$0.73 and US $0.86, respectively; total annual financial and economic costs per child receiving SMC were US$2.92 and US $3.43, respectively. Accounting for coverage, the economic cost per child fully adherent (receiving all four rounds) was US$6.38 and US $4.69, if weighted highly adherent, (receiving 3 or 4 rounds of SMC). When costs were combined with modelled effects, the economic cost per malaria episode averted in children was US$4.26 (uncertainty bound 2.83–7.17), US $144 (135–153) per DALY averted and US$ 14,503 (13,604–15,402) per death averted. Conclusions When implemented at fixed point distribution through the routine health system in Mali, SMC was highly cost-effective. As in previous SMC implementation studies, financial incentives were a large cost component

Long-term cellular immunity of vaccines for Zaire Ebola Virus Diseases

Recent Ebola outbreaks underscore the importance of continuous prevention and disease control efforts. Authorized vaccines include Merck’s Ervebo (rVSV-ZEBOV) and Johnson & Johnson’s two-dose combination (Ad26.ZEBOV/MVA-BN-Filo). Here, in a five-year follow-up of the PREVAC randomized trial (NCT02876328), we report the results of the immunology ancillary study of the trial. The primary endpoint is to evaluate long-term memory T-cell responses induced by three vaccine regimens: Ad26–MVA, rVSV, and rVSV–booster. Polyfunctional EBOV-specific CD4+ T-cell responses increase after Ad26 priming and are further boosted by MVA, whereas minimal responses are observed in the rVSV groups, declining after one year. In-vitro expansion for eight days show sustained EBOV-specific T-cell responses for up to 60 months post-prime vaccination with both Ad26-MVA and rVSV, with no decline. Cytokine production analysis identify shared biomarkers between the Ad26-MVA and rVSV groups. In secondary endpoint, we observed an elevation of pro-inflammatory cytokines at Day 7 in the rVSV group. Finally, we establish a correlation between EBOV-specific T-cell responses and anti-EBOV IgG responses. Our findings can guide booster vaccination recommendations and help identify populations likely to benefit from revaccination

Measuring the impact of seasonal malaria chemoprevention as part of routine malaria control in Kita, Mali

Abstract Background Seasonal malaria chemoprevention (SMC) is a new strategy recommended by WHO in areas of highly seasonal transmission in March 2012. Although randomized controlled trials (RCTs) have shown SMC to be highly effective, evidence and experience from routine implementation of SMC are limited. Methods A non-randomized pragmatic trial with pre-post design was used, with one intervention district (Kita), where four rounds of SMC with sulfadoxine + amodiaquine (SP + AQ) took place in August–November 2014, and one comparison district (Bafoulabe). The primary aims were to evaluate SMC coverage and reductions in prevalence of malaria and anaemia when SMC is delivered through routine programmes using existing community health workers. Children aged 3–59 months from 15 selected localities per district, sampled with probability proportional to size, were surveyed and blood samples collected for malaria blood smears, haemoglobin (Hb) measurement, and molecular markers of drug resistance in two cross-sectional surveys, one before SMC (July 2014) and one after SMC (December 2014). Difference-in-differences regression models were used to assess and compare changes in malaria and anaemia in the intervention and comparison districts. Adherence and tolerability of SMC were assessed by cross-sectional surveys 4–7 days after each SMC round. Coverage of SMC was assessed in the post-SMC survey. Results During round 1, 84% of targeted children received at least the first SMC dose, but coverage declined to 67% by round 4. Across the four treatment rounds, 54% of children received four complete SMC courses. Prevalence of parasitaemia was similar in intervention and comparison districts prior to SMC (23.4 vs 29.5%, p = 0.34) as was the prevalence of malaria illness (2.4 vs 1.9%, p = 0.75). After SMC, parasitaemia prevalence fell to 18% in the intervention district and increased to 46% in the comparison district [difference-in-differences (DD) OR = 0.35; 95% CI 0.20–0.60]. Prevalence of malaria illness fell to a greater degree in the intervention district versus the comparison district (DD OR = 0.20; 95% CI 0.04–0.94) and the same for moderate anaemia (Hb < 8 g/dL) (DD OR = 0.26, 95% CI 0.11–0.65). The frequency of the quintuple mutation (dhfr N51I, C59R and S108N + dhps A437G and K540E) remained low (5%) before and after intervention in both districts. Conclusions Routine implementation of SMC in Mali substantially reduced malaria and anaemia, with reductions of similar magnitude to those seen in previous RCTs. Improving coverage could further strengthen SMC impact. Trial registration clinical trial registration number NCT0289429

Impact of different levels of supervision on the recovery of severely malnourished children treated by community health workers in mali

(1) Background: The Ministry of Health in Mali included the treatment of severe acute malnutrition (SAM) into the package of activities of the integrated community case management (iCCM). This paper evaluates the most effective model of supervision for treating SAM using community health workers (CHWs). Methods (2): This study was a prospective non-randomized community intervention trial with two intervention groups and one control group with different levels of supervision. It was conducted in three districts in rural areas of the Kayes Region. In the high supervision group, CHWs received supportive supervision for the iCCM package and nutrition-specific supervision. In the light supervision group, CHWs received supportive supervision based on the iCCM package. The control group had no specific supervision. (3) Results: A total of 6112 children aged 6-59 months with SAM without medical complications were included in the study. The proportion of cured children was 81.4% in those treated by CHWs in the high supervision group, 86.2% in the light supervision group, and 66.9% in the control group. Children treated by the CHWs who received some supervision had better outcomes than those treated by unsupervised CHWs (p < 0.001). There was no difference between areas with light and high supervision, although those with high supervision performed better in most of the tasks analyzed. (4) Conclusions: Public policies in low-income countries should be adapted, and their model of supervision of CHWs for SAM treatment in the community should be evaluated.publishedVersionPeer reviewe

Inactive hepatitis B carriers: outcomes of patients followed at hôpital principal de Dakar, Senegal

The evolutive profile of inactive HBV carriers is variable. Patients can remain inactive, or may evolve into chronic active hepatitis or hepatocellular carcinoma. Aim: to describe the long-term outcome of chronic hepatitis B inactive carriers followed at Hôpital Principal de Dakar. This is a retrospective study including all inactive HBV carriers, followed since 2001, and with regular monitoring of at least 5 years. Transaminases, viral load and screening for hepatocellular carcinoma were performed every 6 to 12 months. We included 52 patients. The mean follow-up was 76.2 months (60-162), the mean age 36 years (13-62 years) and the sex ratio 0.93 (25 men, 27 women). Four patients (7.7%) had an ALT above the normal. Eleven patients (21.1%) had persistently elevated viral load greater than 2000 IU/ml, while in three cases (5.8%), this increase was transient. Twenty-six patients (50%) had a detectable viral load, but still below 2000 IU/ml. Twelve patients (23.1%) had an undetectable viral load for the duration of monitoring. Eleven patients (21.2%) underwent liver biopsy. The activity or fibrosis were minimal in all cases (A or F = 1) or absent (A or F = 0). Only four patients (7.7%), had HBs seroconversion after a follow-up of six, seven and ten years. There was no focal lesion or cirrhosis detected during the follow-up. After a follow-up of at least 5 years, inactive HBV carriers remain inactive in 92.3% of cases. Their evolutive profile is characterized by an absence of elevated liver enzymes but with fluctuations of the viral load. HBs seroconversion rate is low and the risk of progression to hepatocellular carcinoma almost nil

<it>Ex vivo </it>susceptibility of <it>Plasmodium falciparum </it>isolates from Dakar, Senegal, to seven standard anti-malarial drugs

Abstract Background As a result of widespread chloroquine and sulphadoxine-pyrimethamine resistance, artemisinin-based combination therapy (ACT) (which includes artemether-lumefantrine and artesunate-amodiaquine) has been recommended as a first-line anti-malarial regimen in Senegal since 2006. Since then, there have been very few reports on the ex vivo susceptibility of Plasmodium falciparum to anti-malarial drugs. To examine whether parasite susceptibility has been affected by the widespread use of ACT, the ex vivo susceptibility of local isolates was assessed at the military hospital of Dakar. Methods The ex vivo susceptibility of 93 P. falciparum isolates from Dakar was successfully determined using the Plasmodium lactate dehydrogenase (pLDH) ELISA for the following drugs: chloroquine (CQ), quinine (QN), mefloquine (MQ), monodesethylamodiaquine (MDAQ), lumefantrine (LMF), dihydroartemisinin (DHA) and doxycycline (DOX). Results After transformation of the isolate IC50 in ratio of IC50 according to the susceptibility of the 3D7 reference strain (isolate IC50/3D7 IC50), the prevalence of the in vitro resistant isolates with reduced susceptibility was 50% for MQ, 22% for CQ, 12% for DOX, 6% for both QN and MDAQ and 1% for the drugs LMF and DHA. The highest significant positive correlations were shown between responses to CQ and MDAQ (r = 0.569; P r = 0.511; P r = 0.428; P = 0.0001), LMF and MQ (r = 0.413; P = 0.0002), QN and DHA (r = 0.402; P = 0.0003) and QN and MQ (r = 0.421; P = 0.0001). Conclusions The introduction of ACT in 2002 has not induced a decrease in P. falciparum susceptibility to the drugs DHA, MDAQ and LMF, which are common ACT components. However, the prevalence of P. falciparum isolates with reduced susceptibility has increased for both MQ and DOX. Taken together, these data suggest that intensive surveillance of the P. falciparum in vitro susceptibility to anti-malarial drugs in Senegal is required.</p

Scaling severe acute malnutrition treatment with community health workers: a geospatial coverage analysis in rural Mali

Background: In 2015, the Ministry of Health in Mali included the treatment of severe acute malnutrition (SAM) into the package of activities of the integrated Community Case Management (iCCM). This paper aims to analyze the impact of including community health workers (CHWs) as treatment providers outside the Health Facilities (HFs) on the coverage of SAM treatment when scaling up the intervention in the three largest districts of the Kayes Region in Mali. Methods: A baseline coverage assessment was conducted in August 2017 in the three districts before the CHWs started treating SAM. The end-line assessment was conducted one year later, in August 2018. Coverage was assessed by the standardized methodology called Semi-Quantitative Evaluation of Access and Coverage (SQUEAC). The primary outcome was treatment coverage and other variables evaluated were the geographical distribution of the HFs, CHW’s sites and overlapping between both health providers, the estimation of children with geographical access to health care and the estimation of children screened for acute malnutrition in their communities. Results: Treatment coverage increased in Kayes (28.7–57.1%) and Bafoulabé (20.4–61.1%) but did not in Kita (28.4–28.5%). The decentralization of treatment has not had the same impact on coverage in all districts, with significant differences. The geospatial analyses showed that Kita had a high proportion of overlap between HFs and/or CHWs 48.7% (39.2–58.2), a high proportion of children without geographical access to health care 70.4% (70.1–70.6), and a high proportion of children not screened for SAM in their communities 52.2% (51.9–52.5). Conclusions: Working with CHWs in SAM increases treatment coverage, but other critical aspects need to be considered by policymakers if this intervention model is intended to be scaled up at the country level. To improve families’ access to nutritional health care, before establishing decentralized treatment in a whole region it must be considered the geographical location of CHWs. This previous assessment will avoid overlap among health providers and ensure the coverage of all unserved areas according to their population densities need.The Innocent FoundationThe European Civil Protection and Humanitarian Aid Operation (ECHO)Post Code Lottery FoundationDepto. de Biodiversidad, Ecología y EvoluciónFac. de Ciencias BiológicasTRUEpu

Prevalence of molecular markers of <it>Plasmodium falciparum</it> drug resistance in Dakar, Senegal

<p>Abstract</p> <p>Background</p> <p>As a result of the widespread resistance to chloroquine and sulphadoxine-pyrimethamine, artemisinin-based combination therapy (ACT) (including artemether-lumefantrine and artesunate-amodiaquine) has been recommended as a first-line anti-malarial regimen in Senegal since 2006. Intermittent preventive treatments with anti-malarial drugs based on sulphadoxine-pyrimethamine are also given to children or pregnant women once per month during the transmission season. Since 2006, there have been very few reports on the susceptibility of <it>Plasmodium falciparum</it> to anti-malarial drugs. To estimate the prevalence of resistance to several anti-malarial drugs since the introduction of the widespread use of ACT, the presence of molecular markers associated with resistance to chloroquine and sulphadoxine-pyrimethamine was assessed in local isolates at the military hospital of Dakar.</p> <p>Methods</p> <p>The prevalence of genetic polymorphisms in genes associated with anti-malarial drug resistance, i.e., <it>Pfcrt</it>, <it>Pfdhfr</it>, <it>Pfdhps</it> and <it>Pfmdr1</it>, and the copy number of <it>Pfmdr1</it> were evaluated for a panel of 174 isolates collected from patients recruited at the military hospital of Dakar from 14 October 2009 to 19 January 2010.</p> <p>Results</p> <p>The <it>Pfcrt</it> 76T mutation was identified in 37.2% of the samples. The <it>Pfmdr1</it> 86Y and 184F mutations were found in 16.6% and 67.6% of the tested samples, respectively. Twenty-eight of the 29 isolates with the 86Y mutation were also mutated at codon 184. Only one isolate (0.6%) had two copies of <it>Pfmdr1</it>. The <it>Pfdhfr</it> 108N/T, 51I and 59R mutations were identified in 82.4%, 83.5% and 74.1% of the samples, respectively. The double mutant (108N and 51I) was detected in 83.5% of the isolates, and the triple mutant (108N, 51I and 59R) was detected in 75.3%. The <it>Pfdhps</it> 437G, 436F/A and 613S mutations were found in 40.2%, 35.1% and 1.8% of the samples, respectively. There was no double mutant (437G and 540E) or no quintuple mutant (<it>Pfdhfr</it> 108N, 51I and 59R and <it>Pfdhps</it> 437G and 540E). The prevalence of the quadruple mutant (<it>Pfdhfr</it> 108N, 51I and 59R and <it>Pfdhps</it> 437G) was 36.5%.</p> <p>Conclusions</p> <p>Since 2004, the prevalence of chloroquine resistance had decreased. The prevalence of isolates with high-level pyrimethamine resistance is 83.5%. The prevalence of isolates resistant to sulphadoxine is 40.2%. However, no quintuple mutant (<it>Pfdhfr</it> 108N, 51I and 59R and <it>Pfdhps</it> 437G and 540E), which is associated with a high level of sulphadoxine-pyrimethamine resistance, has been identified to date. The resistance to amodiaquine remains moderate.</p