Infectiousness of the human population to Anopheles arabiensis by direct skin feeding in an area hypoendemic for malaria in Senegal.

Direct skin feeding experiments are sensitive assays to determine human infectiousness to mosquitoes but are rarely used in malaria epidemiological surveys. We determined the infectiousness of inhabitants of a malaria hypoendemic area in Senegal. Gametocyte prevalence by microscopy was 13.5% (26 of 192). Of all individuals who were gametocyte positive, 44.4% (11 of 25) infected ≥ 1 Anopheles arabiensis mosquito and 10.8% (54 of 500) of mosquitoes became infected. Of all individuals who were gametocyte negative by microscopy, 4.3% (7 of 162) infected ≥ 1 mosquito and 0.4% (12 of 3240) of mosquitoes became infected. The 18.2% (12 of 66) of all mosquito infections was a result of submicroscopic gametocyte carriage and two individuals without asexual parasites or gametocytes by microscopy were infectious to mosquitoes. When infectivity and local demography was taken into account, children 5-14 years of age contributed 50.8% of the human infectious reservoir for malaria. Adults and submicroscopic gametocyte carriers may contribute considerably to onward malaria transmission in our setting

Study of variations in the broncho-arterial pedicles of the upper right lung lobe

Bronchial distribution and functional arterial vascularization of the upper lobe of the right lung are subject to many anatomical variations. The control of  these variations is essential for endoscopic and agiographic examinations. It also offers a better guarantee for safe and controlled surgery. In this  preliminary work, the exploitation of 15 heart-lung blocks treated by the injection corrosion method allowed us to study the general arrangement of the  broncho-arteries of the right upper lung lobe and their anatomical variations in the Senegalese population. Our results were as follows: the right upper  lobar bronchus was born on average at 1.25 cm from the tracheal bifurcation, with an average length of 1.13 cm. It ended with trifurcation into apical  (B1), dorsal (B2) and ventral (B3) segmental bronchi in 10 cases (66.66%); in 3 cases (20%), it ended with bifurcation into the dorsal segmental bronchus  and the apico-ventral trunk (B1+B3) (1 case), the apico-dorsal trunk (B1+B2) and the ventral segmental bronchus (B3), finally, in ventral and dorsal  segmentary bronchi giving each one an apical branch (1 case); in a last case, it ended by quadrifurcation, giving an external parabronche. The right upper  lobe was vascularized by 1 to 4 arteries, with eight modes of vascularization. It received more frequently two arteries. The anterior mediastinal  artery was the most common (100%). These results allowed us to discuss anatomical variations in the bronchial tree of the right upper lung lobe and the  pulmonary arterial distribution in that lobe. These variations must be taken into account during endoscopic examinations of imaging and surgery of  pulmonary excision, under penalty of accidents.&nbsp

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

Anti-malarial prescriptions in three health care facilities after the emergence of chloroquine resistance in Niakhar, Senegal (1992–2004)

<p>Abstract</p> <p>Background</p> <p>In the rural zone of Niakhar in Senegal, the first therapeutic failures for chloroquine (CQ) were observed in 1992. In 2003, the national policy regarding first-line treatment of uncomplicated malaria was modified, replacing CQ by a transitory bi-therapy amodiaquine/sulphadoxine-pyrimethamine (AQ/SP), before the implementation of artemisinin-based combination therapy (ACT) in 2006.</p> <p>The aims of the study were to assess the evolution of anti-malarial prescriptions in three health care facilities between 1992 and 2004, in parallel with increasing CQ resistance in the region.</p> <p>Methods</p> <p>The study was conducted in the area of Niakhar, a demographic surveillance site located in a sahelo-sudanese region of Senegal, with mesoendemic and seasonal malaria transmission. Health records of two public health centres and a private catholic dispensary were collected retrospectively to cover the period 1992–2004.</p> <p>Results</p> <p>Records included 110,093 consultations and 292,965 prescribed treatments. Twenty-five percent of treatments were anti-malarials, prescribed to 49% of patients. They were delivered all year long, but especially during the rainy season, and 20% of patients with no clinical malaria diagnosis received anti-malarials. Chloroquine and quinine represented respectively 55.7% and 34.6% of prescribed anti-malarials. Overall, chloroquine prescriptions rose from 1992 to 2000, in parallel with clinical malaria; then the CQ prescription rate decreased from 2000 and was concomitant with the rise of SP and the persistence of quinine use. AQ and SP were mainly used as bi-therapy after 2003, at the time of national treatment policy change.</p> <p>Conclusion</p> <p>The results show the overall level of anti-malarial prescription in the study area for a considerable number of patients over a large period of time. Even though resistance to CQ rapidly increased from 1992 to 2001, no change in CQ prescription was observed until the early 2000s, possibly due to the absence of an obvious decrease in CQ effectiveness, a lack of therapeutic options or a blind follow-up of national guidelines.</p

A Trial of the Efficacy, Safety and Impact on Drug Resistance of Four Drug Regimens for Seasonal Intermittent Preventive Treatment for Malaria in Senegalese Children

UNLABELLED: In the Sahel, most malaria deaths occur among children 1-4 years old during a short transmission season. A trial of seasonal intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) and a single dose of artesunate (AS) showed an 86% reduction in the incidence of malaria in Senegal but this may not be the optimum regimen. We compared this regimen with three alternatives. METHODS: 2102 children aged 6-59 months received either one dose of SP plus one dose of AS (SP+1AS) (the previous regimen), one dose of SP plus 3 daily doses of AS (SP+3AS), one dose of SP plus three daily doses of amodiaquine (AQ) (SP+3AQ) or 3 daily doses of AQ and AS (3AQ+3AS). Treatments were given once a month on three occasions during the malaria transmission season. The primary end point was incidence of clinical malaria. Secondary end-points were incidence of adverse events, mean haemoglobin concentration and prevalence of parasites carrying markers of resistance to SP. FINDINGS: The incidence of malaria, and the prevalence of parasitaemia at the end of the transmission season, were lowest in the group that received SP+3AQ: 10% of children in the group that received SP+1AS had malaria, compared to 9% in the SP+3AS group (hazard ratio HR 0.90, 95%CI 0.60, 1.36); 11% in the 3AQ+3AS group, HR 1.1 (0.76-1.7); and 5% in the SP+3AQ group, HR 0.50 (0.30-0.81). Mutations associated with resistance to SP were present in almost all parasites detected at the end of the transmission season, but the prevalence of Plasmodium falciparum was very low in the SP+3AQ group. CONCLUSIONS: Monthly treatment with SP+3AQ is a highly effective regimen for seasonal IPT. Choice of this regimen would minimise the spread of drug resistance and allow artemisinins to be reserved for the treatment of acute clinical malaria

Author Correction: Implementation, coverage and equity of large-scale door-to-door delivery of Seasonal Malaria Chemoprevention (SMC) to children under 10 in Senegal.

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Effectiveness of Seasonal Malaria Chemoprevention in Children under Ten Years of Age in Senegal: A Stepped-Wedge Cluster-Randomised Trial.

BACKGROUND: Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ), given each month during the transmission season, is recommended for children living in areas of the Sahel where malaria transmission is highly seasonal. The recommendation for SMC is currently limited to children under five years of age, but, in many areas of seasonal transmission, the burden in older children may justify extending this age limit. This study was done to determine the effectiveness of SMC in Senegalese children up to ten years of age. METHODS AND FINDINGS: SMC was introduced into three districts over three years in central Senegal using a stepped-wedge cluster-randomised design. A census of the population was undertaken and a surveillance system was established to record all deaths and to record all cases of malaria seen at health facilities. A pharmacovigilance system was put in place to detect adverse drug reactions. Fifty-four health posts were randomised. Nine started implementation of SMC in 2008, 18 in 2009, and a further 18 in 2010, with 9 remaining as controls. In the first year of implementation, SMC was delivered to children aged 3-59 months; the age range was then extended for the latter two years of the study to include children up to 10 years of age. Cluster sample surveys at the end of each transmission season were done to measure coverage of SMC and the prevalence of parasitaemia and anaemia, to monitor molecular markers of drug resistance, and to measure insecticide-treated net (ITN) use. Entomological monitoring and assessment of costs of delivery in each health post and of community attitudes to SMC were also undertaken. About 780,000 treatments were administered over three years. Coverage exceeded 80% each month. Mortality, the primary endpoint, was similar in SMC and control areas (4.6 and 4.5 per 1000 respectively in children under 5 years and 1.3 and 1.2 per 1000 in children 5-9 years of age; the overall mortality rate ratio [SMC: no SMC] was 0.90, 95% CI 0.68-1.2, p = 0.496). A reduction of 60% (95% CI 54%-64%, p < 0.001) in the incidence of malaria cases confirmed by a rapid diagnostic test (RDT) and a reduction of 69% (95% CI 65%-72%, p < 0.001) in the number of treatments for malaria (confirmed and unconfirmed) was observed in children. In areas where SMC was implemented, incidence of confirmed malaria in adults and in children too old to receive SMC was reduced by 26% (95% CI 18%-33%, p < 0.001) and the total number of treatments for malaria (confirmed and unconfirmed) in these older age groups was reduced by 29% (95% CI 21%-35%, p < 0.001). One hundred and twenty-three children were admitted to hospital with a diagnosis of severe malaria, with 64 in control areas and 59 in SMC areas, showing a reduction in the incidence rate of severe disease of 45% (95% CI 5%-68%, p = 0.031). Estimates of the reduction in the prevalence of parasitaemia at the end of the transmission season in SMC areas were 68% (95% CI 35%-85%) p = 0.002 in 2008, 84% (95% CI 58%-94%, p < 0.001) in 2009, and 30% (95% CI -130%-79%, p = 0.56) in 2010. SMC was well tolerated with no serious adverse reactions attributable to SMC drugs. Vomiting was the most commonly reported mild adverse event but was reported in less than 1% of treatments. The average cost of delivery was US$0.50 per child per month, but varied widely depending on the size of the health post. Limitations included the low rate of mortality, which limited our ability to detect an effect on this endpoint. CONCLUSIONS: SMC substantially reduced the incidence of outpatient cases of malaria and of severe malaria in children, but no difference in all-cause mortality was observed. Introduction of SMC was associated with an overall reduction in malaria incidence in untreated age groups. In many areas of Africa with seasonal malaria, there is a substantial burden in older children that could be prevented by SMC. SMC in older children is well tolerated and effective and can contribute to reducing malaria transmission. TRIAL REGISTRATION: ClinicalTrials.gov NCT00712374

Methods to collect Anopheles mosquitoes and evaluate malaria transmission: A comparative study in two villages in Senegal

<p>Abstract</p> <p>Background</p> <p>Various methods have been studied as replacement of human landing catches (HLC) for mosquito sampling in entomological studies on malaria transmission. Conflicting results have been obtained in comparing relative efficiency of alternative methods, according to the area, the species present and their density. The aim of this study was to compare the number and characteristics of mosquitoes sampled in two areas of Senegal by three different methods: HLC, light traps adjacent to an occupied bed net (LT/N), pyrethrum spray catches (PSC).</p> <p>Methods</p> <p>Collections were performed in two villages: Dielmo (Soudan savanna) and Bandafassi (Soudan Guinean savanna), two or three nights per month for a 4-5 months period during the maximal transmission season in 2001-2002. Species were identified and <it>Plasmodium </it>infection determined by ELISA. The specific composition, circumsporozoite protein rate and entomological inoculation rate were calculated.</p> <p>Results</p> <p>The diversity of mosquito species captured was maximal with LT/N, minimal with PSC. The mean number of anopheles captures each night was significantly different according to the method used and the species. PSC displayed a significantly lower anopheles density. HLC was the most efficient sampling method when <it>Anopheles gambiae </it>was the main vector (in Bandafassi); LT/N when it was <it>Anopheles funestus </it>(in Dielmo). A significant correlation was found between HLC and LT/M but correlation parameters were different according to the species. Circumsporozoite protein rates were not significantly different between methods or species. The entomological inoculation rate varied along with vector density and thus with methods and species.</p> <p>Conclusions</p> <p>The choice of sampling method influenced entomological data recorded. Therefore, the sampling technique has to be chosen according to the vector studied and the aim of the study. Only HLC must be considered as the reference method, but in some conditions LT/N can be used as an alternative method.</p

Impact of combining intermittent preventive treatment with home management of malaria in children less than 10 years in a rural area of Senegal: a cluster randomized trial

<p>Abstract</p> <p>Background</p> <p>Current malaria control strategies recommend (i) early case detection using rapid diagnostic tests (RDT) and treatment with artemisinin combination therapy (ACT), (ii) pre-referral rectal artesunate, (iii) intermittent preventive treatment and (iv) impregnated bed nets. However, these individual malaria control interventions provide only partial protection in most epidemiological situations. Therefore, there is a need to investigate the potential benefits of integrating several malaria interventions to reduce malaria prevalence and morbidity.</p> <p>Methods</p> <p>A randomized controlled trial was carried out to assess the impact of combining seasonal intermittent preventive treatment in children (IPTc) with home-based management of malaria (HMM) by community health workers (CHWs) in Senegal. Eight CHWs in eight villages covered by the Bonconto health post, (South Eastern part of Senegal) were trained to diagnose malaria using RDT, provide prompt treatment with artemether-lumefantrine for uncomplicated malaria cases and pre-referral rectal artesunate for complicated malaria occurring in children under 10 years. Four CHWs were randomized to also administer monthly IPTc as single dose of sulphadoxine-pyrimethamine (SP) plus three doses of amodiaquine (AQ) in the malaria transmission season, October and November 2010. Primary end point was incidence of single episode of malaria attacks over 8 weeks of follow up. Secondary end points included prevalence of malaria parasitaemia, and prevalence of anaemia at the end of the transmission season. Primary analysis was by intention to treat. The study protocol was approved by the Senegalese National Ethical Committee (approval 0027/MSP/DS/CNRS, 18/03/2010).</p> <p>Results</p> <p>A total of 1,000 children were enrolled. The incidence of malaria episodes was 7.1/100 child months at risk [95% CI (3.7-13.7)] in communities with IPTc + HMM compared to 35.6/100 child months at risk [95% CI (26.7-47.4)] in communities with only HMM (aOR = 0.20; 95% CI 0.09-0.41; <it>p </it>= 0.04). At the end of the transmission season, malaria parasitaemia prevalence was lower in communities with IPTc + HMM (2.05% versus 4.6% <it>p </it>= 0.03). Adjusted for age groups, sex, <it>Plasmodium falciparum </it>carriage and prevalence of malnutrition, IPTc + HMM showed a significant protective effect against anaemia (aOR = 0.59; 95% CI 0.42-0.82; <it>p </it>= 0.02).</p> <p>Conclusion</p> <p>Combining IPTc and HMM can provide significant additional benefit in preventing clinical episodes of malaria as well as anaemia among children in Senegal.</p

Resistance to DDT and Pyrethroids and Increased kdr Mutation Frequency in An. gambiae after the Implementation of Permethrin-Treated Nets in Senegal

Introduction: The aim of this study was to evaluate the susceptibility to insecticides of An. gambiae mosquitoes sampled in Dielmo (Senegal), in 2010, 2 years after the implementation of Long Lasting Insecticide-treated Nets (LLINs) and to report the evolution of kdr mutation frequency from 2006 to 2010. Methods: WHO bioassay susceptibility tests to 6 insecticides were performed on adults F0, issuing from immature stages of An. gambiae s.l., sampled in August 2010. Species and molecular forms as well as the presence of L1014F and L1014S kd