Khadime Sylla

Efficacy and tolerability of artesunate-amodiaquine (Camoquin plus®) versus artemether-lumefantrine (Coartem®) against uncomplicated Plasmodium falciparum malaria: multisite trial in Senegal and Ivory Coast.

Objective  To compare, in a phase IV trial, the efficacy and tolerability of artesunate‐amodiaquine (Camoquin plus®) dosed at 300 and 600 mg of amodiaquine per tablet to artemether‐lumefantrine (Coartem®) for the treatment of Plasmodium falciparum uncomplicated malaria in Ivory Cost and Senegal.

The association between malaria parasitaemia, erythrocyte polymorphisms, malnutrition and anaemia in children less than 10 years in Senegal: a case control study

BackgroundMalaria and anaemia (Haemoglobin <11 g/dl) remain frequent in tropical regions and are closely associated. Although anaemia aetiologies are known to be multi-factorial, most studies in malaria endemic areas have been confined to analysis of possible associations between anaemia and individual factors such as malaria. A case control study involving children aged from 1 to 10 years was conducted to assess some assumed contributors to anaemia in the area of Bonconto Health post in Senegal.MethodsStudy participants were randomly selected from a list of children who participated in a survey in December 2010. Children aged from 1 to 10 years with haemoglobin level below 11 g/dl represented cases (anaemic children). Control participants were eligible if of same age group and their haemoglobin level was >= 11 g/dl. For each participant, a physical examination was done and anthropometric data collected prior to a biological assessment which included: malaria parasitaemia infection, intestinal worm carriage, G6PD deficiency, sickle cell disorders, and alpha-talassaemia.ResultsThree hundred and fifty two children < 10 years of age were enrolled (176 case and 176 controls). In a logistic regression analysis, anaemia was significantly associated with malaria parasitaemia (aOR=5.23, 95%CI[1.1-28.48]), sickle cell disorders (aOR=2.89, 95%CI[1,32-6.34]), alpha-thalassemia (aOR=1.82, 95%CI[1.2-3.35]), stunting (aOR=3.37, 95%CI[1.93-5.88], age ranged from 2 to 4 years (aOR=0.13, 95%CI[0.05-0.31]) and age > 5 years (aOR=0.03, 95%CI[0.01-0.08]). Stratified by age group, anaemia was significantly associated with stunting in children less than 5 years (aOR=3.1 95%CI[1.4 – 6.8]), with, sickle cell disorders (aOR=3.5 95%CI [1.4 – 9.0]), alpha-thalassemia (or=2.4 95%CI[1.1–5.3]) and stunting (aOR=3.6 95%CI [1.6–8.2]) for children above 5 years. No association was found between G6PD deficiency, intestinal worm carriage and children’s gender.ConclusionMalaria parasitaemia, stunting and haemoglobin genetic disorders represented the major causes of anaemia among study participants. Anaemia control in this area could be achieved by developing integrated interventions targeting both malaria and malnutrition.

Monitoring the efficacy and safety of three artemisinin based-combinations therapies in Senegal: results from two years surveillance

BackgroundMalaria remains a major public health problem in developing countries. Then in these countries prompt access to effective antimalarial treatment such as Artemisinin based-Combination Therapies (ACT) proves to be an essential tool for controlling the disease. In Senegal, since 2006 a nationwide scaling up program of ACT is being implemented. In this context it has become relevant to monitor ACT efficacy and provide recommendations for the Senegalese national malaria control program.MethodsAn open randomized trial was conducted during two malaria transmission seasons (2011 and 2012) to assess the efficacy and safety of three combinations: dihydro-artemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ). The primary end point of the study was represented by a PCR adjusted adequate clinical and parasitological response (ACPR) at day 28. Secondary end points included: (i) a ACPR at days 35 and 42, (ii) a parasite and fever clearance time, (iii) ACTs safety and tolerability. The 2003 WHO’s protocol for antimalarial drug evaluation was used to assess each outcome.ResultsOverall, 534 patients were randomized selected to receive, either ASAQ (n = 180), AL (n = 178) or DHAPQ (n = 176). The PCR adjusted ACPR at day 28 was 99.41% for the group ASAQ, while that was 100% in the AL and DHAPQ groups (p = 0.37). The therapeutic efficacy was evaluated at 99.37% in the ASAQ arm versus 100% in AL and DHAPQ arm at day 35 (p = 0.37). At day 42, the ACPR was 99.27% in the ASAQ group versus 100% for both AL and DHAPQ groups, (p = 0.36). No serious adverse event was noted during the study period. Also a similar safety profile was noted in the 3 study groups.ConclusionIn the context of scaling up of ACTs in Senegal, ASAQ, AL and DHAPQ are highly effective and safe antimalarial drugs. However, it’s remains important to continue to monitor their efficacy.Trial registrationPACTR 201305000552290.

Feasibility, safety and effectiveness of combining home based malaria management and seasonal malaria chemoprevention in children less than 10 years in Senegal: a cluster-randomised trial.

BACKGROUND Home-based management of malaria (HMM) may improve access to diagnostic testing and treatment with artemisinin combination therapy (ACT). In the Sahel region, seasonal malaria chemoprevention (SMC) is now recommended for the prevention of malaria in children. It is likely that combinations of antimalarial interventions can reduce the malaria burden. This study assessed the feasibility, effectiveness and safety of combining SMC and HMM delivered by community health workers (CHWs). METHODS A cluster-randomised trial was carried out during two transmission seasons in eight villages located in the south-eastern part of Senegal. Intervention communities received HMM+SMC while control communities received HMM. Primary end point was the incidence of malaria attacks during the follow up period. Secondary end points included: malaria diagnostic accuracy; access to ACT treatment; SMC coverage; safety and drug tolerability. RESULTS The adjusted rate ratio for incidence of malaria attacks in intervention and control communities was 0.15, indicating a protective effect of HMM+SMC of 85% (95% CI: 39.9-96.3%, p=0.01). Access to ACT treatment was 96.4% while SMC coverage represented 97.3% (95% CI: 91.3-100%) in 2010, and 88.8% (95% CI: 84.2-93.6%) in 2011. No serious adverse events were recorded. CONCLUSION It seems feasible and safe to combine SMC with HMM intervention, while achieving high coverage and effectiveness of both SMC and HMM. TRIAL REGISTRATION (www.pactr.org) PACTR201305000551876.

Efficacy and tolerability of a new formulation of artesunate-mefloquine for the treatment of uncomplicated malaria in adult in Senegal: open randomized trial

BackgroundPrompt treatment of malaria attacks with arteminisin-based combination therapy (ACT) is an essential tool for malaria control. A new co-blister tablet of artesunate-mefloquine (AM) with 25 mg/kg mefloquine has been developed for the management of uncomplicated malaria attacks. This non-inferiority randomized trial, was conducted to evaluate the efficacy and safety of the new formulation of AM in comparison to artemether-lumefantrine (AL) for the treatment of acute uncomplicated Plasmodium falciparum malaria in adults in Senegal.MethodsThe study was carried out from September to December 2010 in two health centres in Senegal. The study end points included (i) PCR corrected adequate clinical and parasitological response (ACPR) at day 28, (ii) ACPR at days 42 and 63, (iii) parasites and fever clearance time, (iv) incidence of adverse events and patients biological profile at day 7 using the WHO 2003 protocol for anti-malarial drug evaluation.ResultsOverall, 310 patients were randomized to receive either AM (n = 157) or AL (n = 153). PCR corrected ACPR at day 28 was at 95.5% in the AM arm while that in the AL arm was at 96.7% (p = 0.83). Therapeutic efficacy was at 98.5% in the AM arm versus 98.2% in the AL group at day 42 (p = 1). At day 63, ACPR in the AM and AL arms was at 98.2% and 97.7%, respectively (p = 0.32). The two treatments were well tolerated with similar biological profile at day 7. However, dizziness was more frequent in the AM arm.ConclusionArtesunate-mefloquine (25 mg/Kg mefloquine) is efficacious and well-tolerated for the treatment of uncomplicated P. falciparum malaria in adult patients.

Multicentre study evaluating the non-inferiority of the new paediatric formulation of artesunate/amodiaquine versus artemether/lumefantrine for the management of uncomplicated Plasmodium falciparum malaria in children in Cameroon, Ivory Coast and Senegal

BackgroundThis multicentre study was carried out in Cameroon, Ivory Coast and Senegal to evaluate the non-inferiority of the new paediatric formulation of artesunate/amodiaquine (AS+AQ)(Camoquin-Plus Paediatric®) in suspension form versus artemether/lumefantrine (AL)(Coartem®) in the management of African children with uncomplicated falciparum malaria.MethodsIt was an open randomized trial including children aged between 7 months and 7 years. The endpoints were Adequate Clinical and Parasitological Response (ACPR) at day 28, the clinical and biological tolerability. Statistical analyses were done in Intention To Treat (ITT) and in Per protocol (PP).ResultsAt the end of the study 481 patients were enrolled in the three countries (249 in the AS+AQ arm and 232 in the AL arm). ACRP in ITT after PCR correction did not show any statistical difference between the two groups with 97.6% for AS+AQ versus 94.8% for AL. In the PP analysis, the corrected ACRP were respectively 98.7% and 96.9% for the two regimens. The clinical tolerance was good without significant difference. Anaemia was significantly higher at D7 in the two groups compared to D0.ConclusionThis study demonstrates the non-inferiority of AS+AQ versus AL, its efficacy and tolerance in the management of uncomplicated Plasmodium falciparum malaria in African children.

Acceptability by community health workers in Senegal of combining community case management of malaria and seasonal malaria chemoprevention

BackgroundCommunity case management of malaria (CCMm) and seasonal malaria chemoprevention (SMC) are anti-malarial interventions that can lead to substantial reduction in malaria burden acting in synergy. However, little is known about the social acceptability of these interventions. A study was undertaken to assess whether combining the interventions would be an acceptable approach to malaria control for community health workers (CHWs).MethodsSixty-one interviews and six focus group discussions were conducted nested in a cluster-randomized trial assessing the impact of combining CCMm and SMC in a rural area of Senegal. Participants consisted of: (i) members of village associations, (ii) members of families who had access to the interventions as well as members of families who did not access the interventions, (iii) CHWs, and (iv) community leaders, e g, religious guides and village chiefs.ResultsThe interventions were acceptable to the local population and perceived as good strategy to make health care services available to community members and thus, to reduce the delays in access to anti-malarial treatment as well as expenses related to patients’ transfer to the health post. The use of malaria rapid diagnostic test (RDT) contributed to improving CHWs diagnostic capacity as well as malaria treatment practices. Study participants notified RDT and drugs stock-out as the major risk for sustainability of the intervention at community level.ConclusionCombining CCMm and SMC is a well accepted, community-based approach that can contribute to control malaria in areas where malaria transmission is seasonal.

Parasitic Infections among Children under Five Years in Senegal: Prevalence and Effect on Anaemia and Nutritional Status

Although malaria is declining in many countries in Africa, malaria and anaemia remain frequent in children. This study was conducted to assess the relationship between malaria parasitaemia, intestinal worms, and anaemia, in children <5 years living in low transmission area in Senegal. A survey was carried out in 30 villages in the central part of Senegal. A two-level random cluster sampling technique was used to select study participant. Children <5 years were enrolled after informed consent. For each child, blood thick and smear tests were performed, haemoglobin concentration was measured with HemoCue, and stool samples were collected and examined using the Ritchie technique. A total of 736 children were recruited. Malaria parasite prevalence was 1.5% (0.7–2.6); anaemia was found in 53.4% (48.2–58.9), while intestinal parasites and stunting represented 26.2% (22.6–30.2) and 22% (18.6–25.5), respectively. In a logistic regression analysis, anaemia was significantly associated with malaria parasitaemia (aOR= 6.3 (1.5–53.5)) and stunting (aOR = 2 (1.2–3.1)); no association was found between intestinal parasites and anaemia. Malaria and anaemia remain closely associated even when malaria is declining. Scaling up antimalarial interventions may contribute to eliminate malaria and reduce the occurrence of anaemia among children.

Selection of Antimalarial Drug Resistance after Intermittent Preventive Treatment of Infants and Children (IPTi/c) in Senegal

Our study investigated the possible impact of SP-IPT given to infants and children on the prevalence of SP-resistant haplotypes in the Plasmodium falciparum genes Pfdhfr and Pfdhps, comparing sites with and without IPTi/c. P. falciparum positive samples (N = 352) collected from children < 5 years were analyzed to determine the prevalence of SP resistance-related haplotypes by nested PCR followed by sequence-specific oligonucleotide probe-enzyme-linked immunosorbent assay. The prevalence of the Pfdhfr triple mutant haplotype (CIRN) increased in both groups, but only significantly in the IPTi/c group from 41% to 65% in 2011 (P = 0.005). Conversely, the Pfdhps 437G mutation decreased in both groups from 44.6% to 28.6% (P = 0.07) and from 66.7% to 47.5% (P = 0.02) between 2010 and 2011 in the control and the IPTi/c groups, respectively. A weak trend for decreasing prevalence of quadruple mutants (triple Pfdhfr + Pfdhps 437G) was noted in both groups (P = 0.15 and P = 0.34). During the two cross-sectional surveys some significant changes were observed in the SP resistance-related genes.

Safety and Efficacy of Adding a Single Low Dose of Primaquine to the Treatment of Adult Patients With Plasmodium falciparum Malaria in Senegal, to Reduce Gametocyte Carriage: A Randomized Controlled Trial.

Summary Adding low-dose primaquine to malaria treatment reduced gametocyte carriage by 73%. Patients who received primaquine had more frequent hemoglobinuria and there was a greater reduction in haemoglobin concentration in G6PD-deficient patients. One patient who received primaquine developed moderately severe anemia.