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Nwakanma D.C.,Medical Research Council Laboratories | Neafsey D.E.,Cambridge Broad Institute | Jawara M.,Medical Research Council Laboratories | Adiamoh M.,Medical Research Council Laboratories | And 12 more authors.
Genetics | Year: 2013

Understanding genetic causes and effects of speciation in sympatric populations of sexually reproducing eukaryotes ischallenging, controversial, and of practical importance for controlling rapidly evolving pests and pathogens. The major African malariavector mosquito Anopheles gambiae sensu stricto (s.s.) is considered to contain two incipient species with strong reproductiveisolation, hybrids between the M and S molecular forms being very rare. Following recent observations of higher proportions of hybridforms at a few sites in West Africa, we conducted new surveys of 12 sites in four contiguous countries (The Gambia, Senegal, Guinea-Bissau, and Republic of Guinea). Identification and genotyping of 3499 A. gambiae s.s. revealed high frequencies of M/S hybrid formsat each site, ranging from 5 to 42%, and a large spectrum of inbreeding coefficient values from 0.11 to 0.76, spanning most of therange expected between the alternative extremes of panmixia and assortative mating. Year-round sampling over 2 years at one of thesites in The Gambia showed that M/S hybrid forms had similar relative frequencies throughout periods of marked seasonal variation inmosquito breeding and abundance. Genome-wide scans with an Affymetrix high-density single-nucleotide polymorphism (SNP) microarrayenabled replicate comparisons of pools of different molecular forms, in three separate populations. These showed strongdifferentiation between M and S forms only in the pericentromeric region of the X chromosome that contains the molecular formspecificmarker locus, with only a few other loci showing minor differences. In the X chromosome, the M/S hybrid forms were moredifferentiated from M than from S forms, supporting a hypothesis of asymmetric introgression and backcrossing. © 2013 by the Genetics Society of America.

PubMed | University of Otago, University of Witwatersrand, Korean International Vaccine Institute, Institute Pasteur Of Dakar and 15 more.
Type: | Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America | Year: 2016

Assessing healthcare utilization is important to identify weaknesses of healthcare systems, to outline action points for preventive measures and interventions, and to more accurately estimate the disease burden in a population.A healthcare utilization survey was developed for the Typhoid Fever Surveillance in Africa Program (TSAP) to adjust incidences of salmonellosis determined through passive, healthcare facility-based surveillance. This cross-sectional survey was conducted at 11 sites in 9 sub-Saharan African countries. Demographic data and healthcare-seeking behavior were assessed at selected households. Overall and age-stratified percentages of each study population that sought healthcare at a TSAP healthcare facility and elsewhere were determined.Overall, 88% (1007/1145) and 81% (1811/2238) of the population in Polesgo and Nioko 2, Burkina Faso, respectively, and 63% (1636/2590) in Butajira, Ethiopia, sought healthcare for fever at any TSAP healthcare facility. A far smaller proportion-namely, 20%-45% of the population in Bissau, Guinea-Bissau (1743/3885), Pikine, Senegal (1473/4659), Wad-Medani, Sudan (861/3169), and Pietermaritzburg, South Africa (667/2819); 18% (483/2622) and 9% (197/2293) in Imerintsiatosika and Isotry, Madagascar, respectively; and 4% (127/3089) in Moshi, Tanzania-sought healthcare at a TSAP healthcare facility. Patients with fever preferred to visit pharmacies in Imerintsiatosika and Isotry, and favored self-management of fever in Moshi. Age-dependent differences in healthcare utilization were also observed within and across sites.Healthcare utilization for fever varied greatly across sites, and revealed that not all studied populations were under optimal surveillance. This demonstrates the importance of assessing healthcare utilization. Survey data were pivotal for the adjustment of the programs estimates of salmonellosis and other conditions associated with fever.

PubMed | University of Otago, Centers for Disease Control and Prevention, Korean International Vaccine Institute, University of Antananarivo and 13 more.
Type: | Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America | Year: 2016

New immunization programs are dependent on data from surveillance networks and disease burden estimates to prioritize target areas and risk groups. Data regarding invasive Salmonella disease in sub-Saharan Africa are currently limited, thus hindering the implementation of preventive measures. The Typhoid Fever Surveillance in Africa Program (TSAP) was established by the International Vaccine Institute to obtain comparable incidence data on typhoid fever and invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa through standardized surveillance in multiple countries.Standardized procedures were developed and deployed across sites for study site selection, patient enrolment, laboratory procedures, quality control and quality assurance, assessment of healthcare utilization and incidence calculations.Passive surveillance for bloodstream infections among febrile patients was initiated at thirteen sentinel sites in ten countries (Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania). Each TSAP site conducted case detection using these standardized methods to isolate and identify aerobic bacteria from the bloodstream of febrile patients. Healthcare utilization surveys were conducted to adjust population denominators in incidence calculations for differing healthcare utilization patterns and improve comparability of incidence rates across sites.By providing standardized data on the incidence of typhoid fever and iNTS disease in sub-Saharan Africa, TSAP will provide vital input for targeted typhoid fever prevention programs.

Wejse C.,University of Aarhus | Wejse C.,Aarhus University Hospital | Wejse C.,Bandim Health Project
International Journal of Infectious Diseases | Year: 2015

The Millennium Development Goal for tuberculosis (TB) is to stop the increase in incidence and halve the mortality of TB between 1990 and 2015. This goal has now been reached on a global scale, although not in the most affected region of Africa. The new target is TB elimination, defined as one case of active TB per one million population per year, which is to be reached before 2050. This review will discuss the main tools in play, namely case-finding and new diagnostics, increased access and effectiveness of anti-TB therapy (directly observed therapy, short course (DOTS)), preventive therapy for latent infection, and vaccination. Each approach is discussed and a way forward in research and management is suggested. © 2014 The Author.

Nielsen J.,Bandim Health Project | Prudhon C.,Health and Nutrition Tracking Service | de Radigues X.,Health and Nutrition Tracking Service
International Journal of Epidemiology | Year: 2011

Background: The humanitarian response to the crisis in Darfur is the largest humanitarian operation in the world. To investigate the evolution of the conditions of the affected population, we analysed trends in malnutrition and mortality, the most widely accepted indicators for assessing the degree of severity of a crisis. Methods: We did a meta-analysis of 164 publicly available surveys taking into account changes in the contextual situation and humanitarian aid; type of population [residents and internally displaced persons (IDPs)]; and seasonal variations. Data on global acute malnutrition (GAM), severe acute malnutrition (SAM), crude death rate (CDR) and under-five death rate (U5DR) were analysed using a random effect model. Results: GAM and SAM decreased by 16% and 28%, respectively, in 2004- 05, whereas CDR dropped by 44-75% per year depending on state and type of population and U5DR decreased by an overall 50% yearly. Both security and the humanitarian contexts became increasingly complex after 2005, but levels of malnutrition stabilized in North and South Darfur. In West Darfur, GAM remained stable but SAM tended to increase for IDPs, although mortality rates remained constant. Mortality increased slightly for residents in South Darfur after 2005, even though nutritional status was stable. GAM, SAM, CDR and U5DR fluctuated markedly with seasons. Conclusion: A meta-analysis of myriads of surveys permitted us to draw an overall picture of the situation in Darfur and to identify some of its influencing factors. The large humanitarian operation, which gained momentum through 2004-05, was able to contain the crisis despite huge difficulties, but did not compensate for seasonal variations. The situation has remained fragile with some negative patterns tending to emerge. It is crucial that the humanitarian situation continues to be closely monitored. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2011; all rights reserved.

PubMed | Aarhus University Hospital, University of Southern Denmark, Statens Serum Institute and Bandim Health Project
Type: Journal Article | Journal: Transactions of the Royal Society of Tropical Medicine and Hygiene | Year: 2015

Data regarding the association between diabetes mellitus (DM) and tuberculosis (TB) in Africa are scare. We did a DM screening survey among TB patients and non-TB controls in Guinea-Bissau.The study was conducted at the Bandim Health Project (BHP) in the capital Bissau. From July 2010 to July 2011, newly diagnosed TB cases were identified through a TB notification system. Concurrently, non-TB controls were selected randomly from the BHPs demographic surveillance database and visited at home. Participants were tested using fasting blood glucose (FBG) measurements. DM was diagnosed as FBG 7 mmol/l. Our survey was linked to the patient database at the only existing Diabetes Clinic in Bissau.TB patients (n=110) were older than the controls (n=572) (35 vs 31 years; p=0.02), more often male (55% vs 37%; p<0.001) and had a lower body mass index (18.7 vs 24.2 kg/m(2); p<0.001). The prevalence of DM was 2.8% (3/107) for TB patients and 2.1% (11/531) for controls (p=0.64). Excluding two controls already receiving anti-diabetic treatment, the prevalence of DM was 2.8% (3/107) vs 1.7% (9/529) (p=0.44).The prevalence of DM was low, also among TB patients. No association between DM and TB was found.

Rudolf F.,Aarhus University Hospital | Haraldsdottir T.L.,Aarhus University Hospital | Ostergaard L.,Aarhus University Hospital | Eugen-Olsen J.,Copenhagen University | Wejse C.,Bandim Health Project
International Journal of Tuberculosis and Lung Disease | Year: 2014

SETTING: The Bandim Health Project study area in Bissau, Guinea-Bissau. OBJECTIVE: To assess the potential usefulness of predictors (elsewhere applied) and clinical scores (TBscore and TBscore II) based on signs and symptoms typical of tuberculosis (TB) in case finding. DESIGN: Observational prospective cohort study of patients with signs and symptoms suggestive of pulmonary TB (PTB) from 2010 to 2012. RESULTS: We included 1089 PTB suspects with a mean age of 34 years (95%CI 33-35); human immunodeficiency virus (HIV) prevalence was 15.1%. PTB was diagnosed in 107 suspects (76.4% sputum smear-positive, 25.2% HIV-infected). Cough > 2 weeks had the highest diagnostic ability (area under the receiver operating characteristic curve [AUC] 0.66, 95%CI 0.62-0.71), while TBscore < 3 best excluded PTB (negative likelihood ratio [LR-] 0.3) when HIV status was not known. TBscore II ≥ 3 had the highest diagnostic ability in HIVi nfected PTB suspects (AUC 0.62, 95%CI 0.53-0.72), while the absence of self-reported weight loss best excluded PTB (LR- 0.2). Cough > 2 weeks as a trigger for smear microscopy missed 32.1% of smear-positive PTB cases. CONCLUSION: Case finding could be improved by screening symptomatic adults for cough and/or weight loss using TBscore II as the trigger for smear microscopy. To suspect PTB only in patients with cough > 2 weeks (non-HIV-infected) or with current cough, fever, weight loss or night sweats (HIV-infected) was not effective in patients whose HIV status was unknown at first visit. © 2014 The Union.

Aage S.,Statens Serum Institute | Kiraly N.,Murdoch Childrens Research Institute | Da Costa K.,Bandim Health Project | Byberg S.,Statens Serum Institute | And 6 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2015

Background Neonatal vitamin A supplementation (NVAS) is currently being considered as policy in countries at risk of deficiency. A previous study suggested that NVAS may be associated with increased atopy. We examined the effect of NVAS on atopy by conducting long-term follow-up of a previous randomized controlled trial in Guinea-Bissau. Methods In 2002-2004, we randomized 4345 normal birthweight neonates to NVAS (50 000 IU retinyl palmitate) or placebo together with their Bacillus Calmette-Guérin vaccination. In 2013, we visited the 1692 (39%) children now aged 8-10 years who were still living in the study area, and 1478 (87%) were found at home. Provided consent, a skin prick test was performed, and history of allergic symptoms was recorded. Associations of NVAS and atopy (defined as skin prick test reaction of ≥3 mm) were analysed using binomial regression. Results Of the 1430 children with a valid skin prick test, 228 (16%) were positive (more boys (20%) than girls (12%), P-value < 0.0001). NVAS did not increase the overall risk of atopy (RR 1.10 [95% CI 0.87-1.40]). However, NVAS was associated with significantly increased risk among females (RR 1.78 [1.17-2.72]) but not among males (0.86 [0.64-1.15], P-value for interaction between NVAS and gender = 0.005). Furthermore, NVAS was associated with increased risk of wheezing among females (RR 1.80 [1.03-3.17], but not among males, P-value for interaction = 0.05). Conclusion The study corroborated previous observations; NVAS was associated with increased risk of atopy and wheezing, in this study only among females. Further studies on NVAS and atopy are warranted. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Aaby P.,Statens Serum Institute | Ravn H.,Statens Serum Institute | Roth A.,Statens Serum Institute | Roth A.,Lund University | And 9 more authors.
Archives of Disease in Childhood | Year: 2012

Background: Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants. Methods: 2320 LBW newborns were visited at 2, 6 and 12 months of age to assess nutritional and vaccination status. The authors examined survival until the 6-month visit for children who were DTP vaccinated and DTP unvaccinated at the 2-month visit. Results: Two-thirds of the children had received DTP at 2 months and 50 deaths occurred between the 2-month and 6-month visits. DTP vaccinated children had a better anthropometric status for all indices than DTP unvaccinated children. Small mid-upper arm circumference (MUAC) was the strongest predictor of mortality. The death rate ratio (DRR) for DTP vaccinated versus DTP unvaccinated children differed significantly for girls (DRR 2.45; 95% CI 0.93 to 6.45) and boys (DRR 0.53; 95% CI 0.23 to 1.20) (p=0.018, homogeneity test). Adjusting for MUAC, the overall effect for DTP vaccinated children was 2.62 (95% CI 1.34 to 5.09); DRR was 5.68 (95% CI 1.83 to 17.7) for girls and 1.29 (95% CI 0.56 to 2.97) for boys (p=0.023, homogeneity test). While anthropometric indices were a strong predictor of mortality among boys, there was little or no association for girls. Conclusion: Surprisingly, even though the children with the best nutritional status were vaccinated early, early DTP vaccination was associated with increased mortality for girls.

Isendahl J.,Karolinska Institutet | Manjuba C.,Hospital Nacional Simao Mendes | Rodrigues A.,Bandim Health Project | Xu W.,Karolinska Institutet | And 6 more authors.
BMC Infectious Diseases | Year: 2014

Background: The burden of bloodstream infections is insufficiently studied in children in Africa and many healthcare facilities lack the capacity to identify invasive disease. Often studies have been limited to febrile patients or patients admitted to hospital. Methods: Blood cultures and malaria diagnostics was performed on 372 consecutive children presenting with tachycardia and/or fever to a referral paediatric emergency department in Bissau, Guinea-Bissau. Bacterial species detection, antimicrobial susceptibility testing and molecular typing were performed. The capacity of clinical parameters to identify bacteraemia was evaluated. Results: The prevalence of bloodstream infection was 12% (46/372) and in 46% (21/46) of the infections the child was non-febrile at presentation to the hospital. The predictive value for bacteraemia was poor for all assessed clinical parameters. Staphylococcus aureus accounted for 54% (26/48) of the isolates followed by non-typhoidal Salmonella, 10% (5/48), Streptococcus pneumoniae, 8% (4/48), and Salmonella Typhi, 6% (3/48). Among S. aureus there was a large diversity of spa types and 38% produced Pantone-Valentine leukocidin. Antibiotic resistance was low, however two out of three Klebsiella pneumoniae isolates produced extended-spectrum beta-lactamases. Malaria was laboratory confirmed in only 5% of the children but 64% (237/372) received a clinical malaria diagnosis. Conclusions: Bacteraemia was common irrespective of the presence of fever among children presenting to the hospital. The high prevalence of Staphylococcus aureus may be due to contamination. There is an imminent need to improve microbiological diagnostic facilities and to identify algorithms that can identify children at risk of bloodstream infections in Africa. © 2014 Isendahl et al.; licensee BioMed Central.

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