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

BACKGROUND: Prompt 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. METHODS: The 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. RESULTS: Overall, 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. CONCLUSION: Artesunate-mefloquine (25 mg/Kg mefloquine) is efficacious and well-tolerated for the treatment of uncomplicated P. falciparum malaria in adult patients

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

BACKGROUND: Malaria 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. METHODS: Study 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. RESULTS: Three 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. CONCLUSION: Malaria 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

Haemoglobin changes and risk of anaemia following treatment for uncomplicated falciparum malaria in sub-Saharan Africa.

BACKGROUND: Anaemia is common in malaria. It is important to quantitate the risk of anaemia and to distinguish factors related to the natural history of disease from potential drug toxicity. METHODS: Individual-patient data analysis based on nine randomized controlled trials of treatments of uncomplicated falciparum malaria from 13 sub-Saharan African countries. Risk factors for reduced haemoglobin (Hb) concentrations and anaemia on presentation and after treatment were analysed using mixed effect models. RESULTS: Eight thousand eight hundred ninety-seven patients (77.0% <5 years-old) followed-up through 28 days treated with artemisinin combination therapy (ACT, 90%, n = 7968) or non-ACT. At baseline, under 5's had the highest risk of anaemia (77.6% vs. 32.8%) and higher parasitaemia (43,938 μl) than older subjects (2784 μl). Baseline anaemia increased the risk of parasitological recurrence. Hb began to fall after treatment start. In under 5's the estimated nadir was ~35 h (range 29-48), with a drop of -12.8% from baseline (from 9.8 g/dl to 8.7 g/dl, p = 0.001); in under 15's, the mean Hb decline between day 0-3 was -4.7% (from 9.4 to 9.0 g/dl, p = 0.001). The degree of Hb loss was greater in patients with high pre-treatment Hb and parasitaemia and with slower parasite reduction rates, and was unrelated to age. Subsequently, Hb increased linearly (+0.6%/day) until day 28, to reach +13.8% compared to baseline. Severe anaemia (<5 g/dl, 2 per 1000 patients) was transient and all patients recovered after day 14, except one case of very severe anaemia associated with parasite recurrence at day 28. There was no systematic difference in Hb concentrations between treatments and no case of delayed anaemia. CONCLUSION: On presentation with acute malaria young children with high parasitaemia have the highest risk of anaemia. The majority of patients experience a drop in Hb while on treatment as early as day 1-2, followed by a linear increase through follow-up. The degree of the early Hb dip is determined by pre-treatment parasitaemia and parasite clearance rates. Hb trends and rick of anaemia are independent of treatment

West Africa International Centers of Excellence for Malaria Research: Drug Resistance Patterns to Artemether-Lumefantrine in Senegal, Mali, and The Gambia.

In 2006, artemether-lumefantrine (AL) became the first-line treatment of uncomplicated malaria in Senegal, Mali, and the Gambia. To monitor its efficacy, between August 2011 and November 2014, children with uncomplicated Plasmodium falciparum malaria were treated with AL and followed up for 42 days. A total of 463 subjects were enrolled in three sites (246 in Senegal, 97 in Mali, and 120 in Gambia). No early treatment failure was observed and malaria infection cleared in all patients by day 3. Polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) was 100% in Mali, and the Gambia, and 98.8% in Senegal. However, without PCR adjustment, ACPR was 89.4% overall; 91.5% in Mali, 98.8% in Senegal, and 64.3% in the Gambia (the lower value in the Gambia attributed to poor compliance of the full antimalarial course). However, pfmdr1 mutations were prevalent in Senegal and a decrease in parasite sensitivity to artesunate and lumefantrine (as measured by ex vivo drug assay) was observed at all sites. Recrudescent parasites did not show Kelch 13 (K13) mutations and AL remains highly efficacious in these west African sites

Molecular Epidemiology of Human Immunodeficiency Virus Type 1 Sub-Subtype A3 in Senegal from 1988 to 2001

The global human immunodeficiency virus (HIV)epidemic is characterized by significant genetic diversity in circulating viruses. We have recently characterized a group of viruses that form a distinct sub-subtype within the subtype A radiation, which we have designated HIV type 1 (HIV-1) sub-subtype A, circulating in West Africa. A prospective study of a cohort of female sex workers (FSW) in Dakar, Senegal over an 18-year period indicated that an A3-specific sequence in the C2-V3 region of the env gene was found in 46 HIV-1-infected women. HIV-1 sub-subtype A3 appeared in the FSW population as early as 1988 and continued to be transmitted as of 2001. We also found that HIV-1 A3 is not confined to the FSW cohort in Senegal but is also circulating in the general population in Dakar. Furthermore, analyses of viral sequences from a few other West and Central African countries also demonstrated evidence of HIV-1 A3 sequence in isolates from HIV-1-infected people in Ivory Coast, Nigeria, Niger, Guinea Bissau, Benin, and Equatorial Guinea. Overall, because of the evidence of sub-subtype A3 in the general population in Senegal, as well as in a few neighboring West and Central African countries, along with the increasing incidence of infection with A3-containing viruses in the Dakar high-risk FSW population, we feel that HIV-1 sub-subtype A3 viruses are important to distinguish and monitor

Global stability of enzymatic chain of full reversible Michaelis-Menten reactions

International audienceWe consider a chain of metabolic reactions catalyzed by enzymes, of reversible Michaelis-Menten type with full dynamics, i.e. not reduced with any quasi- steady state approximations. We study the corresponding dynamical system and show its global stability if the equilibrium exists. If the system is open, the equilibrium may not exist. The main tool is monotone systems theory. Finally we study the implications of these results for the study of coupled genetic-metabolic systems

Evolution of malaria mortality and morbidity after the emergence of chloroquine resistance in Niakhar, Senegal

Background: Recently, it has been assumed that resistance of Plasmodium to chloroquine increased malaria mortality. The study aimed to assess the impact of chemoresistance on mortality attributable to malaria in a rural area of Senegal, since the emergence of resistance in 1992, whilst chloroquine was used as first-line treatment of malaria, until the change in national anti-malarial policy in 2003. Methods: The retrospective study took place in the demographic surveillance site (DSS) of Niakhar. Data about malaria morbidity were obtained from health records of three health care facilities, where diagnosis of malaria was based on clinical signs. Source of data concerning malaria mortality were verbal autopsies performed by trained fieldworkers and examined by physicians who identified the probable cause of death. Results: From 1992 to 2004, clinical malaria morbidity represented 39% of total morbidity in health centres. Mean malaria mortality was 2.4 parts per thousand and 10.4 parts per thousand among total population and children younger than five years, respectively, and was highest in the 1992-1995 period. It tended to decline from 1992 to 2003 (Trend test, total population p = 0.03, children 0-4 years p = 0.12 - children 1-4 years p = 0.04 - children 5-9 years p = 0.01). Conclusion: Contrary to what has been observed until 1995, mortality attributable to malaria did not continue to increase dramatically in spite of the growing resistance to chloroquine and its use as first-line treatment until 2003. Malaria morbidity and mortality followed parallel trends and rather fluctuated accordingly to rainfall

Pregnancy Recruitment for Population Research: the National Children's Study Vanguard Experience in W ayne C ounty, M ichigan

Background To obtain a probability sample of pregnancies, the N ational C hildren's S tudy conducted door‐to‐door recruitment in randomly selected neighbourhoods in randomly selected counties in 2009–10. In 2011, an experiment was conducted in 10 US counties, in which the two‐stage geographic sample was maintained, but participants were recruited in prenatal care provider offices. We describe our experience recruiting pregnant women this way in W ayne C ounty, M ichigan, a county where geographically eligible women attended 147 prenatal care settings, and comprised just 2% of total county pregnancies. Methods After screening for address eligibility in prenatal care offices, we used a three‐part recruitment process: (1) providers obtained permission for us to contact eligible patients, (2) clinical research staff described the study to women in clinical settings, and (3) survey research staff visited the home to consent and interview eligible women. Results We screened 34 065 addresses in 67 provider settings to find 215 eligible women. Providers obtained permission for research contact from 81.4% of eligible women, of whom 92.5% agreed to a home visit. All home‐visited women consented, giving a net enrolment of 75%. From birth certificates, we estimate that 30% of eligible county pregnancies were enrolled, reaching 40–50% in the final recruitment months. Conclusions We recruited a high fraction of pregnancies identified in a broad cross‐section of provider offices. Nonetheless, because of time and resource constraints, we could enrol only a fraction of geographically eligible pregnancies. Our experience suggests that the probability sampling of pregnancies for research could be more efficiently achieved through sampling of providers rather than households.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97525/1/ppe12047.pd