ABSTRACT
This paper investigates linkage to care following community-based screening for hepatitis B virus (HBV) in rural Senegal. HBV-positive participants who completed a biological and clinical examination to assess liver disease and treatment eligibility were referred to a regional hospital (if eligible for treatment), invited to join the Sen-B research cohort study (adults with detectable viral load) or referred to their local health centre (all others). Logistic regressions were conducted to investigate factors associated with (i) uptake of the scheduled post-screening examination, and (ii) HBV management initiation. Obstacles to HBV management were identified using thematic analysis of in-depth patient interviews. Of the 206 HBV-positive participants, 163 (79.1%) underwent the examination; 47 of the 163 (28.8%) initiated HBV management. Women, people not migrating for >6 months/year, individuals living in households with more agricultural and monetary resources, with other HBV-positive participants, and beneficiaries of the national cash transfer program, were all more likely to undergo the examination. The likelihood of joining the Sen-B cohort increased with household monetary resources, but decreased with agricultural resources. Initiation of HBV management in local health centre was higher among participants with a non-agricultural economic activity. Individuals reported wariness and confusion about HBV management content and rationale at various stages of the care continuum, in particular with respect to venous blood sampling and management without treatment. In conclusion, HBV community-based test-and-treat strategies are feasible, but early loss to follow-up must be addressed through simplified, affordable management and community support and sensitization.
Subject(s)
Hepatitis B , Mass Screening , Rural Population , Humans , Senegal/epidemiology , Female , Male , Adult , Middle Aged , Hepatitis B/diagnosis , Hepatitis B/epidemiology , Mass Screening/methods , Young Adult , Aged , Adolescent , Cohort Studies , Hepatitis B virus/genetics , Hepatitis B virus/isolation & purificationABSTRACT
BACKGROUND: Although mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is prevalent in West Africa, epidemiological data on HBV infection in women remain scarce. We studied i) hepatitis B surface antigen (HBsAg) prevalence and its correlates, ii) HBV screening history and serological status awareness, iii) MTCT risk and treatment needs in Senegalese women. METHODS: A cross-sectional population-based serosurvey for HBsAg positivity was conducted in 2018-2019 in the rural area of Niakhar (Fatick region, Senegal). Participants were offered home-based HBV screening and answered face-to-face questionnaires. HBsAg-positive participants underwent clinical and biological assessments. Data were weighted and calibrated to be representative of the area's population. Logistic regression models helped identify factors associated with HBsAg-positivity in adult women (> 15 years old). RESULTS: HBsAg prevalence in adult women was 9.2% [95% confidence interval: 7.0-11.4]. Factors associated with HBsAg-positivity were being 15-49 years old (ref: ≥ 50), living in a household with > 2 other HBsAg-positive members, and knowing someone with liver disease. Only 1.6% of women had already been tested for HBV; no one who tested HBsAg positive was already aware of their serological status. In women 15-49 years old, 5% risked MTCT and none were eligible for long-term antiviral treatment. CONCLUSIONS: Adult women have a high HBsAg prevalence but a low MTCT risk. Low rates of HBV screening and serological status awareness argue for the adoption of systematic screening during pregnancy using free and rapid diagnostic tests. Additionally, screening household members of HBsAg-positive women may greatly improve the cascade of care in rural Senegal. TRIAL REGISTRATION: ClinicalTrials.gov identifier (NCT number): NCT03215732.
Subject(s)
Hepatitis B , Pregnancy Complications, Infectious , Adult , Pregnancy , Female , Humans , Adolescent , Young Adult , Middle Aged , Hepatitis B Surface Antigens , Pregnancy Complications, Infectious/epidemiology , Hepatitis B e Antigens , Senegal/epidemiology , Cross-Sectional Studies , Infectious Disease Transmission, Vertical/prevention & control , Hepatitis B virus , Hepatitis B/diagnosis , Hepatitis B/epidemiology , Hepatitis B/prevention & control , Surveys and QuestionnairesABSTRACT
Using the culturomics approach, the previously unknown strain Marseille-P8953T, was isolated and classified within the Weizmannia genus. Strain Marseille-P8953T was isolated from the faeces of a healthy subject and consisted of Gram-stain positive, spore-forming, motile rod-shaped cells. A 99.2% similarity was observed between the 16S rRNA gene of strain Marseille-P8953T (accession number LR735539) and that of Weizmannia coagulans strain NBRC 12583T (accession number KX261624), its closest phylogenetic relative, while the genome of strain Marseille-P8953T (3.5 Mpb long, 46.5% GC content) shared the average nucleotide identity by Orthology and digital DNA-DNA Hybridisation values of 95 and 60.4%, respectively. Given the phylogenetic classification and phenotypic characteristics of strain Marseille-P8953T, we propose the creation of a new species within the Weizmannia genus named Weizmannia faecalis (= CSUR P8953T = CECT 9904 T).
Subject(s)
Bacillaceae , Bacillaceae/genetics , Base Composition , DNA, Bacterial/genetics , Humans , Phylogeny , RNA, Ribosomal, 16S/geneticsABSTRACT
Two strains, designated as Marseille-P2918T and Marseille-P3646T, were isolated from a 14-week-old Senegalese girl using culturomics: Urmitella timonensis strain Marseille-P2918T (= CSUR P2918, = DSM 103634) and Marasmitruncus massiliensis strain Marseille-P3646T (= CSUR P3646, = CCUG72353). Both strains were rod-shaped, anaerobic, spore forming motile bacteria. The 16S rRNA gene sequences of strains Marseille-P2918T (LT598554) and Marseille-P3646T (LT725660) shared 93.25% and 94.34% identity with Tissierella praeacuta ATCC 25539T and Anaerotruncus colihominis CIP 107754T, their respective phylogenetically closest species with standing in nomenclature. Therefore, strain Marseille-P2918T is classified within the family Tissierellaceae and order Tissierellales whereas strain Marseille-P3646T is classified within the family Oscillospiraceae and order Eubacteriales. The genome of strain Marseille-P2918T had a size of 2.13 Mb with a GC content of 50.52% and includes six scaffolds and six contigs, and that of strain Marseille-P3646T was 3.76 Mbp long consisting of five contigs with a 50.04% GC content. The genomes of both strains presented a high percentage of genes encoding enzymes involved in genetic information and processing, suggesting a high growth rate and adaptability. These new taxa are extensively described and characterised in this paper, using the concept of taxono-genomic description.
Subject(s)
RNA, Ribosomal, 16S , Humans , Child , Female , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , PhylogenyABSTRACT
BACKGROUND: We report results of years 2 and 3 of consecutive cluster-randomized controlled trials of trivalent inactivated influenza vaccine (IIV3) in Senegal. METHODS: We cluster-randomized (1:1) 20 villages to annual vaccination with IIV3 or inactivated poliovirus vaccine (IPV) of age-eligible residents (6 months-10 years). The primary outcome was total vaccine effectiveness against laboratory-confirmed influenza illness (LCI) among age-eligible children (modified intention-to-treat population [mITT]). Secondary outcomes were indirect (herd protection) and population (overall community) vaccine effectiveness. RESULTS: We vaccinated 74% of 12 408 age-eligible children in year 2 (June 2010-April 11) and 74% of 11 988 age-eligible children in year 3 (April 2011-December 2011) with study vaccines. Annual cumulative incidence of LCI was 4.7 (year 2) and 4.2 (year 3) per 100 mITT child vaccinees of IPV villages. In year 2, IIV3 matched circulating influenza strains. The total effectiveness was 52.8% (95% confidence interval [CI], 32.3-67.0), and the population effectiveness was 36.0% (95% CI, 10.2-54.4) against LCI caused by any influenza strain. The indirect effectiveness against LCI by A/H3N2 was 56.4% (95% CI, 39.0-68.9). In year 3, 74% of influenza detections were vaccine-mismatched to circulating B/Yamagata and 24% were vaccine-matched to circulating A/H3N2. The year 3 total effectiveness against LCI was -14.5% (95% CI, -81.2-27.6). Vaccine effectiveness varied by type/subtype of influenza in both years. CONCLUSIONS: IIV3 was variably effective against influenza illness in Senegalese children, with total and indirect vaccine effectiveness present during the year when all circulating strains matched the IIV3 formulation. CLINICAL TRIALS REGISTRATION: NCT00893906.
Subject(s)
Influenza Vaccines , Influenza, Human , Child , Humans , Influenza A Virus, H3N2 Subtype , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Senegal/epidemiology , Vaccines, InactivatedABSTRACT
Sub-Saharan Africa's hepatitis B virus (HBV) burden is primarily due to infection in infancy. However, data on chronic HBV infection prevalence and associated risk factors in children born post-HBV vaccination introduction are scarce. We estimated hepatitis B surface antigen (HBsAg) prevalence and risk factors in Senegalese children born during the HBV vaccination era. In 2018-2019, a community-based cross-sectional survey was conducted in Senegal among children born between 2004 and 2015 (ie after the three-dose HBV vaccine series was introduced (2004) but before the birth dose's introduction (2016)). HBsAg-positive children were identified using dried blood spots. A standardized questionnaire collected socioeconomic information. Data were age-sex weighted and calibrated to be representative of children living in the study area. Risk factors associated with HBsAg positivity were identified using negative binomial regression. Among 1,327 children, 17 were HBsAg-positive (prevalence = 1.23% (95% confidence interval [CI] 0.61-1.85)). Older age (adjusted incidence-rate ratio [aIRR] 1.31 per one-year increase, 95% CI 1.10-1.57), home vs healthcare facility delivery (aIRR 3.55, 95% CI 1.39-9.02), stitches (lifetime) (aIRR 4.79; 95% CI 1.84-12.39), tattoos (aIRR 8.97, 95% CI 1.01-79.11) and having an HBsAg-positive sibling with the same mother (aIRR 3.05, 95% CI 1.09-8.57) were all independently associated with HBsAg positivity. The low HBsAg prevalence highlights the success of the Senegalese HBV vaccination program. To further reduce HBV acquisition in children, high-risk groups, including pregnant women and siblings of HBsAg-positive individuals, must be screened. Vital HBV infection prevention measures include promoting delivery in healthcare facilities, and increasing awareness of prevention and control procedures.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Home Childbirth , Tattooing , Aged , Child , Cross-Sectional Studies , Female , Hepatitis B Surface Antigens , Hepatitis B Vaccines , Hepatitis B virus , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/prevention & control , Humans , Infectious Disease Transmission, Vertical , Pregnancy , Prevalence , Risk Factors , SiblingsABSTRACT
BACKGROUND: The population effects of influenza vaccination in children have not been extensively studied, especially in tropical, developing countries. In rural Senegal, we assessed the total (primary objective) and indirect effectiveness of a trivalent inactivated influenza vaccine (IIV3). METHODS: In this double-blind, cluster-randomized trial, villages were randomly allocated (1:1) for the high-coverage vaccination of children aged 6 months through 10 years with either the 2008-09 northern hemisphere IIV3 or an inactivated polio vaccine (IPV). Vaccinees were monitored for serious adverse events. All village residents, vaccinated and unvaccinated, were monitored for signs and symptoms of influenza illness using weekly home visits and surveillance in designated clinics. The primary outcome was all laboratory-confirmed symptomatic influenza. RESULTS: Between 23 May and 11 July 2009, 20 villages were randomized, and 66.5% of age-eligible children were enrolled (3918 in IIV3 villages and 3848 in IPV villages). Follow-up continued until 28 May 2010. There were 4 unrelated serious adverse events identified. Among vaccinees, the total effectiveness against illness caused by the seasonal influenza virus (presumed to all be drifted A/H3N2, based on antigenic characterization data) circulating at high rates among children was 43.6% (95% confidence interval [CI] 18.6-60.9%). The indirect effectiveness against seasonal A/H3N2 was 15.4% (95% CI -22.0 to 41.3%). The total effectiveness against illness caused by the pandemic influenza virus (A/H1N1pdm09) was -52.1% (95% CI -177.2 to 16.6%). CONCLUSIONS: IIV3 provided statistically significant, moderate protection to children in Senegal against circulating, pre-2010 seasonal influenza strains, but not against A/H1N1pdm09, which was not included in the vaccine. No indirect effects were measured. Further study in low-resource populations is warranted. CLINICAL TRIALS REGISTRATION: NCT00893906.
Subject(s)
Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Vaccination/statistics & numerical data , Vaccine Potency , Adolescent , Adult , Aged , Child , Child, Preschool , Double-Blind Method , Female , Humans , Infant , Influenza A virus/genetics , Influenza Vaccines/immunology , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Male , Middle Aged , Rural Population , Senegal/epidemiology , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology , Young AdultABSTRACT
OBJECTIVE: To investigate potential risk factors for acquisition in seven countries of the meningitis belt. METHODS: Households were followed up every 2 weeks for 2 months, then monthly for a further 4 months. Pharyngeal swabs were collected from all available household members at each visit and questionnaires completed. Risks of acquisition over the whole study period and for each visit were analysed by a series of logistic regressions. RESULTS: Over the course of the study, acquisition was higher in: (i) 5-to 14-year olds, as compared with those 30 years or older (OR 3.6, 95% CI 1.4-9.9); (ii) smokers (OR 3.6, 95% CI 0.98-13); and (iii) those exposed to wood smoke at home (OR 2.6 95% CI 1.3-5.6). The risk of acquisition from one visit to the next was higher in those reporting a sore throat during the dry season (OR 3.7, 95% CI 2.0-6.7) and lower in those reporting antibiotic use (OR 0.17, 95% CI 0.03-0.56). CONCLUSIONS: Acquisition of meningococcal carriage peaked in school age children. Recent symptoms of sore throat during the dry season, but not during the rainy season, were associated with a higher risk of acquisition. Upper respiratory tract infections may be an important driver of epidemics in the meningitis belt.
OBJECTIF: Investiguer les facteurs de risque potentiels d'acquisition dans sept pays de la ceinture de la méningite. MÉTHODES: Des ménages ont été suivis toutes les deux semaines pendant deux mois, puis tous les mois pendant quatre mois. Des prélèvements pharyngés sur écouvillons ont été collectés auprès de tous les membres disponibles du ménage à chaque visite et des questionnaires ont été remplis. Les risques d'acquisition sur l'ensemble de la période d'étude et pour chaque visite ont été analysés par une série de régressions logistiques. RÉSULTATS: Au cours de l'étude, l'acquisition a été plus élevée chez: (i) les 5-14 ans, par rapport à ceux âgés de 30 ans ou plus (OR = 3,6; IC95%: 1,4-9,9); (ii) les fumeurs (OR = 3,6; IC95%: 0,98-13); et (iii) les personnes exposées à la fumée de bois à la maison (OR = 2,6; IC95%: 1,3-5,6). Le risque d'acquisition d'une visite à l'autre était plus élevé chez les personnes signalant un mal de gorge pendant la saison sèche (OR = 3,7; IC95%: 2,0-6,7) et plus faible chez celles signalant une utilisation d'antibiotique (OR = 0,17; IC95%: 0,03-0,56). CONCLUSIONS: L'acquisition du portage du méningocoque a culminé chez les enfants d'âge scolaire. Les symptômes récents de maux de gorge pendant la saison sèche, mais pas pendant la saison des pluies, étaient associés à un risque d'acquisition plus élevé. Les infections des voies respiratoires supérieures pourraient être un facteur important d'épidémies dans la ceinture de la méningite.
Subject(s)
Carrier State/microbiology , Meningitis, Meningococcal/etiology , Respiratory Tract Infections/complications , Seasons , Adolescent , Adult , Africa South of the Sahara/epidemiology , Aged , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Logistic Models , Male , Meningitis, Meningococcal/microbiology , Middle Aged , Neisseria meningitidis, Serogroup A/growth & development , Pharyngitis , Risk Factors , Smoke/adverse effects , Smoking/adverse effects , Young AdultABSTRACT
BACKGROUND: In countries where hepatitis B virus (HBV) is endemic, including Senegal, the World Health Organization recommends systematic HBV screening of pregnant women and vaccination at birth to prevent mother-to-child transmission (MTCT). This study investigated healthcare workers' (HCW) knowledge and practices regarding HBV prevention and care in the rural region of Fatick in Senegal, as well as challenges they faced in implementing prevention activities related to HBV MTCT. METHODS: A mixed-methods survey was conducted between May-July 2017 among 112 HCW working in 15 healthcare facilities in two districts of the Fatick region using face-to-face questionnaires and semi-structured interviews. Descriptive statistics and chi-square/Mann-Whitney tests were used to analyze quantitative data, while qualitative data were analyzed thematically. RESULTS: The study population included 87 HCW in the quantitative component (83% women, median age [interquartile range, IQR] = 35 [31-40] years) and 11 in the qualitative component. A knowledge gap was observed in key areas of HBV infection: only 24, 51 and 38%, respectively, correctly reported that early HBV acquisition is associated with a high risk of developing chronic infection, that perinatal transmission is one of the main modes of HBV transmission in Senegal, and that three to four doses of HBV vaccine are required to ensure immunization in children. Despite good acceptability of systematic screening of pregnant women and vaccination at birth, only 48% of HCW mainly involved in prenatal care and 71% of those involved exclusively in vaccination routinely performed these two key interventions. HCW reported several structural barriers that may hinder their implementation: a lack of training in HBV and in counseling, poor availability of rapid diagnostic tests (RDT), high costs of both screening and treatment, a lack of adequate information on treatment options and missed opportunities for vaccination at birth. CONCLUSIONS: HCW working in the Fatick region may be insufficiently trained and supported to effectively implement HBV prevention strategies. Our findings suggest an urgent need to strengthen MTCT prevention in this region, by improving HCW knowledge in key areas of HBV infection, providing RDT and antiviral treatment at low cost, and enhancing community-based interventions for the timely vaccination of newborns.
Subject(s)
Health Personnel/psychology , Hepatitis B Vaccines/administration & dosage , Hepatitis B/prevention & control , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/prevention & control , Adult , Attitude of Health Personnel , Female , Hepatitis B/drug therapy , Humans , Infant, Newborn , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Rural Population , Senegal/epidemiology , Vaccination/statistics & numerical dataABSTRACT
Malnutrition is the leading cause of death worldwide in children under the age of five, and is the focus of the first World Health Organization (WHO) Millennium Development Goal. Breastfeeding, food and water security are major protective factors against malnutrition and critical factors in the maturation of healthy gut microbiota, characterized by a transient bifidobacterial bloom before a global rise in anaerobes. Early depletion in gut Bifidobacterium longum, a typical maternal probiotic, known to inhibit pathogens, represents the first step in gut microbiota alteration associated with severe acute malnutrition (SAM). Later, the absence of the Healthy Mature Anaerobic Gut Microbiota (HMAGM) leads to deficient energy harvest, vitamin biosynthesis and immune protection, and is associated with diarrhea, malabsorption and systemic invasion by microbial pathogens. A therapeutic diet and infection treatment may be unable to restore bifidobacteria and HMAGM. Besides refeeding and antibiotics, future trials including non-toxic missing microbes and nutrients necessary to restore bifidobacteria and HMAGM, including prebiotics and antioxidants, are warranted in children with severe or refractory disease.
Subject(s)
Gastrointestinal Microbiome , Gastrointestinal Tract/microbiology , Malnutrition/microbiology , Animals , Anti-Bacterial Agents , Antioxidants , Bacteria/classification , Bacteria/growth & development , Bacteria/pathogenicity , Bacteria, Aerobic/growth & development , Bacteria, Anaerobic/growth & development , Bifidobacterium/growth & development , Biodiversity , Child, Preschool , Diarrhea , Diet , Gastrointestinal Microbiome/immunology , Gastrointestinal Tract/metabolism , Humans , Immunoglobulin A , Infections , Kwashiorkor , Malabsorption Syndromes , Malnutrition/drug therapy , Malnutrition/metabolism , Parasites/classification , Parasites/growth & development , Phylogeny , Probiotics/therapeutic use , Risk Factors , Sepsis , Severe Acute Malnutrition , Viruses/classification , Viruses/growth & developmentABSTRACT
Background: Girls tend to have a lower risk of stunting than boys do in low-income countries.Objective: We evaluated differences in height status and complementary food (CF) intake between sexes from ages 2 to 39 mo in Senegal.Methods: Length and weight measurements were taken at ages 2-3, 4-5, 6-8, and 9-10 mo (n = 7319). Qualitative 24-h and 7-d food recalls were conducted in a subgroup (n = 2512). A smaller subsample was followed up to age 39 mo (n = 512). Height was measured, and intake of CF was noted. Boys and girls were compared in terms of height-for-age z score (HAZ) of WHO standards and National Center for Health Statistics growth reference, height-for-age difference, stunting, and consumption of CF by using chi-square tests, general linear models, and mixed-effects linear models (MLMs).Results: By using WHO standards, the mean HAZ was lower for boys than for girls in infancy, i.e., at 2-3 mo of age (-0.65 compared with -0.57; P = 0.002) and beyond, i.e., at 24-29 mo of age (-2.01 compared with -1.65; P < 0.001). Overall risk of stunting was 24.5% and 19.4% for boys and girls, respectively, during infancy (P < 0.001) compared with 59.2% and 47.9%, respectively, at 12-39 mo (P = 0.010). In MLMs from ages 2 to 39 mo, boys had a lower mean HAZ than girls had at age 2 mo (ß0 = -0.19; P = 0.035), and sex differences increased with increasing age (ß1 = -0.007 z scores/mo; P < 0.001). At 2-3 mo of age, boys were more likely to have been fed CF every day during the past week (15.8% compared with 11.2% for girls; P = 0.005) and to have eaten ≥2 meals in the past 24 h (13.4% compared with 8.2% for girls; P < 0.001).Conclusions: In Senegalese infants, CF intake differed by sex, with boys more likely to consume CF. Boys had lower HAZs than girls had during infancy, and sex differences increased up to age 39 mo. The importance of sex in complementary feeding and growth warrants further attention in low-income countries.
Subject(s)
Breast Feeding , Growth Disorders/epidemiology , Infant Nutritional Physiological Phenomena , Nutritional Status , Rural Population , Female , Humans , Infant , Male , Meals , Senegal/epidemiology , Sex FactorsABSTRACT
BACKGROUND: Malariometric information is needed to decide how to introduce malaria vaccines and evaluate their impact in sub-Saharan African countries. METHODS: This cross-sectional study (NCT01954264) was conducted between October and November, 2013, corresponding to the high malaria transmission season, in four sites with Health and Demographic Surveillance Systems (DSS) [two sites with moderate-to-high malaria endemicity in Burkina Faso (Nouna and Saponé) and two sites with low malaria endemicity in Senegal (Keur Socé and Niakhar)]. Children (N = 2421) were randomly selected from the DSS lists of the study sites and were stratified into two age groups (6 months-4 years and 5-9 years). A blood sample was collected from each child to evaluate parasite prevalence of Plasmodium falciparum and other Plasmodium species and gametocyte density by microscopy, and rapid diagnosis test in the event of fever within 24 h. Case report forms were used to evaluate malaria control measures and other factors. RESULTS: Plasmodium falciparum was identified in 707 (29.2%) children, with a higher prevalence in Burkina Faso than Senegal (57.5 vs 0.9% of children). In Burkina Faso, prevalence was 57.7% in Nouna and 41.9% in Saponé in the 6 months-4 years age group, and 75.4% in Nouna and 70.1% in Saponé in the 5-9 years age group. Infections with other Plasmodium species were rare and only detected in Burkina Faso. While mosquito nets were used by 88.6-97.0 and 64.7-80.2% of children in Burkina Faso and Senegal, other malaria control measures evaluated at individual level were uncommon. In Burkina Faso, exploratory analyses suggested that use of malaria treatment or any other medication within 14 days, and use of insecticide spray within 7 days decreased the prevalence of malaria infection; older age, rural residence, natural floor, grass/palm roof, and unavailability of electricity in the house were factors associated with increased malaria occurrence. CONCLUSIONS: Plasmodium falciparum infection prevalence in children younger than 10 years was 57.5% in Burkina Faso and 0.9% in Senegal, and variability was observed, among others, by age, study site and malaria control measures.
Subject(s)
Communicable Disease Control/methods , Disease Transmission, Infectious/prevention & control , Malaria, Falciparum/epidemiology , Malaria, Falciparum/prevention & control , Animals , Burkina Faso/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Epidemiologic Studies , Female , Humans , Infant , Male , Plasmodium/classification , Plasmodium/isolation & purification , Prevalence , Senegal/epidemiologyABSTRACT
A novel strain, Mt12T (=CSUR P1907 = DSM 100590), was isolated from the fecal sample of a 7-month-old girl from Senegal afflicted with severe acute malnutrition. This bacterium is a strictly anaerobic, spore-forming Gram-stain positive bacillus. The major cellular fatty acid was identified as tetradecanoic acid. Its 16S rRNA gene sequence exhibited 94.9% similarity with that of Crassaminicella profunda strain Ra1766HT, currently the closest species with a validly published name. The draft genome of strain Mt12T is 3,497,275-bp long with a 30.45% of G+C content. 3397 genes were predicted, including 3268 protein-coding genes and 129 RNAs, including eight 16S rRNAs. Genomic comparison with closely related species with an available genome showed a lower quantitative genomic content. The phylogenetic analysis alongside the dDDH values under 30% and phenotypic characteristics suggest that strain Mt12T represents a new genus within the family Clostridiaceae, for which the name Inediibacterium massiliense gen. nov., sp. nov. is proposed.
Subject(s)
Clostridiaceae/isolation & purification , Gastrointestinal Microbiome , Malnutrition , RNA, Ribosomal, 16S , Bacterial Typing Techniques , Base Composition , Clostridiaceae/genetics , DNA, Bacterial , Fatty Acids , Humans , Infant , Phylogeny , Sequence Analysis, DNAABSTRACT
Anaerococcus rubiinfantis sp. nov. strain mt16(T) is a new species within the genus Anaerococcus, which was isolated by the culturomics approach from the gut microbiota of an infant suffering from kwashiorkor. A phenotypic, biochemical and proteomic description of this strain is hereby presented alongside a complete annotation of its genome. This strictly anaerobic species forms Gram-positive non-sporeforming cocci. The major fatty acid was hexadecanoic acid. The phylogenetic analysis of strain mt16(T) showed a 97.9% similarity level with Anaerococcus vaginalis, the closest validly published species. Its genome is 1,929,161 bp long with 29.5% G + C content and contains 1808 protein-coding genes and 56 RNA genes, among which are six rRNA genes. Genomic analysis identified 41/1864 coding genes as ORFans (2.2%) and at least 620/1808 (34.9%) orthologous proteins which are not shared with the closest phylogenetic species. We believe that the extension of the human anaerobic gut compendium by culturomics is one of the first steps that will improve the understanding of the links between the microbiome and health or disease.
Subject(s)
Firmicutes/genetics , Genes, Bacterial , Genome, Bacterial , Gram-Positive Bacteria/genetics , Phylogeny , Anaerobiosis , Base Composition , Firmicutes/classification , Firmicutes/isolation & purification , Gastrointestinal Microbiome/genetics , Gene Ontology , Genome Size , Gram-Positive Bacteria/classification , Gram-Positive Bacteria/isolation & purification , Humans , Infant , Kwashiorkor/microbiology , Kwashiorkor/pathology , Molecular Sequence Annotation , Open Reading Frames , Palmitic Acid/isolation & purification , Palmitic Acid/metabolismABSTRACT
BACKGROUND: The Meningitis Vaccine Project (MVP) was established to address epidemic meningitis as a public health problem in sub-Saharan Africa and, to that end, worked to develop a group A meningococcal conjugate vaccine, PsA-TT. METHODS: Experiences in 4 clinical trial sites are described. Culturally sensitive collaborative strategies were adopted to manage acceptable communication methods, peculiarities with the consent process, participant medical issues, community care, and death. RESULTS: The clinical trials were completed successfully through community acceptance and active community collaboration. The trials also strengthened the capacities in the participating communities, and actively worked to resolve community problems. CONCLUSIONS: The understanding and integration of sociocultural realities of communities were major assets in the conduct and acceptance of these trials. MVP succeeded in these sites and provided a sound example for future clinical studies in Africa. CLINICAL TRIALS REGISTRATION: ISRTCN78147026 (PsA-TT 002); ISRCTN87739946 (PsA-TT 003); ISRCTN82484612 (PsA-TT 004); PACTR ATMR2010030001913177 (PsA-TT 006); and PACTR201110000328305 (PsA-TT 007).
Subject(s)
Disease Transmission, Infectious/prevention & control , Meningitis, Meningococcal/prevention & control , Meningococcal Vaccines/adverse effects , Meningococcal Vaccines/immunology , Africa South of the Sahara/epidemiology , Clinical Trials as Topic , Cultural Diversity , Humans , Meningitis, Meningococcal/epidemiology , Meningococcal Vaccines/administration & dosage , Patient Acceptance of Health CareABSTRACT
BACKGROUND: PsA-TT (MenAfriVac) is a conjugated polysaccharide vaccine developed to eliminate group A meningococcal disease in Africa. Vaccination of African study participants with 1 dose of PsA-TT led to the production of anti-A polysaccharide antibodies and increased serum bactericidal activity measured using rabbit complement (rSBA). Bactericidal responses measured with human complement (hSBA) are presented here. METHODS: Sera collected before and at 28 days and 1 year after vaccination with either PsA-TT or quadrivalent polysaccharide vaccine (PsACWY) from a random, age-distributed 360-subject subset of the Meningitis Vaccine Project study of PsA-TT in Africans aged 2-29 years were tested for hSBA. Geometric mean titer, fold-rise, and threshold analyses were compared between vaccine groups and age groups. hSBA, rSBA, and immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) results were compared and assay correlation and agreement determined. RESULTS: hSBA responses to PsA-TT were substantially higher than those to PsACWY at 28 days and 1 year following immunization, similar to previously reported rSBA and IgG results. The hSBA and IgG ELISA results identified differences between age groups that were not evident by rSBA. The rSBA data indicated sustained high titers 1 year after immunization, whereas hSBA GMTs at 1 year approached 4 in young children. CONCLUSIONS: The high level of protection following PsA-TT immunization campaigns is consistent with the strong hSBA immune responses observed here. Future implementation decisions will likely depend on immunologic data and their long-term correlation with disease and carriage prevention. Expanded immunologic and epidemiologic surveillance may improve the interpretation of differences between these immunoassays.
Subject(s)
Antibodies, Bacterial/blood , Blood Bactericidal Activity , Complement System Proteins , Immunoassay/methods , Meningococcal Vaccines/immunology , Neisseria meningitidis, Serogroup A/immunology , Adolescent , Adult , Africa , Animals , Child , Child, Preschool , Humans , Immunoglobulin G/blood , Meningococcal Vaccines/administration & dosage , Rabbits , Young AdultABSTRACT
BACKGROUND: The group A meningococcal vaccine (PsA-TT) clinical development plan included clinical trials in India and in the West African region between 2005 and 2013. During this period, the Meningitis Vaccine Project (MVP) accumulated substantial experience in the ethical conduct of research to the highest standards. METHODS: Because of the public-private nature of the sponsorship of these trials and the extensive international collaboration with partners from a diverse setting of countries, the ethical review process was complex and required strategic, timely, and attentive communication to ensure the smooth review and approval for the clinical studies. Investigators and their site teams fostered strong community relationships prior to, during, and after the studies to ensure the involvement and the ownership of the research by the participating populations. As the clinical work proceeded, investigators and sponsors responded to specific questions of informed consent, pregnancy testing, healthcare, disease prevention, and posttrial access. RESULTS: Key factors that led to success included (1) constant dialogue between partners to explore and answer all ethical questions; (2) alertness and preparedness for emerging ethical questions during the research and in the context of evolving international ethics standards; and (3) care to assure that approaches were acceptable in the diverse community contexts. CONCLUSIONS: Many of the ethical issues encountered during the PsA-TT clinical development are familiar to groups conducting field trials in different cultural settings. The successful approaches used by the MVP clinical team offer useful examples of how these problems were resolved. CLINICAL TRIALS REGISTRATION: ISRCTN17662153 (PsA-TT-001); ISRTCN78147026 (PsA-TT-002); ISRCTN87739946 (PsA-TT-003); ISRCTN46335400 (PsA-TT-003a); ISRCTN82484612 (PsA-TT-004); CTRI/2009/091/000368 (PsA-TT-005); PACTR ATMR2010030001913177 (PsA-TT-006); PACTR201110000328305 (PsA-TT-007).
Subject(s)
Clinical Trials as Topic/ethics , Meningococcal Vaccines/administration & dosage , Meningococcal Vaccines/immunology , Vaccination/ethics , Africa, Western , Humans , India , International Cooperation , Public-Private Sector PartnershipsABSTRACT
BACKGROUND: Mass vaccination campaigns of the population aged 1-29 years with 1 dose of group A meningococcal (MenA) conjugate vaccine (PsA-TT, MenAfriVac) in African meningitis belt countries has resulted in the near-disappearance of MenA. The vaccine was tested in clinical trials in Africa and in India and found to be safe and highly immunogenic compared with the group A component of the licensed quadrivalent polysaccharide vaccine (PsACWY). Antibody persistence in Africa and in India was investigated. METHODS: A total of 900 subjects aged 2-29 years were followed up for 4 years in Senegal, Mali, and The Gambia (study A). A total of 340 subjects aged 2-10 years were followed up for 1 year in India (study B). In study A, subjects were randomized in a 2:1 ratio, and in study B a 1:1 ratio to receive either PsA-TT or PsACWY. Immunogenicity was evaluated by measuring MenA serum bactericidal antibody (SBA) with rabbit complement and by a group A-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay. RESULTS: In both studies, substantial SBA decay was observed at 6 months postvaccination in both vaccine groups, although more marked in the PsACWY group. At 1 year and 4 years (only for study A) postvaccination, SBA titers were relatively sustained in the PsA-TT group, whereas a slight increasing trend, more pronounced among the youngest, was observed in the participants aged <18 years in the PsACWY groups. The SBA titers were significantly higher in the PsA-TT group than in the PsACWY group at any time point, and the majority of subjects in the PsA-TT group had SBA titers ≥128 and group A-specific IgG concentrations ≥2 µg/mL at any point in time in both the African and Indian study populations. CONCLUSIONS: Four years after vaccination with a single dose of PsA-TT vaccine in Africa, most subjects are considered protected from MenA disease. CLINICAL TRIALS REGISTRATION: PsA-TT-003 (ISRCTN87739946); PsA-TT-003a (ISRCTN46335400).
Subject(s)
Antibodies, Bacterial/blood , Blood Bactericidal Activity , Meningococcal Vaccines/administration & dosage , Meningococcal Vaccines/immunology , Adolescent , Adult , Africa , Animals , Child , Child, Preschool , Complement System Proteins , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Healthy Volunteers , Humans , India , Male , Rabbits , Time Factors , Young AdultABSTRACT
BACKGROUND: Group A meningococci are the source of major epidemics of meningitis in Africa. An affordable, highly immunogenic meningococcal A conjugate vaccine is needed. METHODS: We conducted two studies in Africa to evaluate a new MenA conjugate vaccine (PsA-TT). In study A, 601 children, 12 to 23 months of age, were randomly assigned to receive PsA-TT, a quadrivalent polysaccharide reference vaccine (PsACWY), or a control vaccine (Haemophilus influenzae type b conjugate vaccine [Hib-TT]). Ten months later, these children underwent another round of randomization within each group to receive a full dose of PsA-TT, a one-fifth dose of PsACWY, or a full dose of Hib-TT, with 589 of the original participants receiving a booster dose. In study B, 900 subjects between 2 and 29 years of age were randomly assigned to receive PsA-TT or PsACWY. Safety and reactogenicity were evaluated, and immunogenicity was assessed by measuring the activity of group A serum bactericidal antibody (SBA) with rabbit complement and performing an IgG group A-specific enzyme-linked immunosorbent assay. RESULTS: In study A, 96.0% of the subjects in the PsA-TT group and 63.7% of those in the PsACWY group had SBA titers that were at least four times as high as those at baseline; in study B, 78.2% of the subjects in the PsA-TT group and 46.2% of those in the PsACWY group had SBA titers that were at least four times as high as those at baseline. The geometric mean SBA titers in the PsA-TT groups in studies A and B were greater by factors of 16 and 3, respectively, than they were in the PsACWY groups (P<0.001). In study A, the PsA-TT group had higher antibody titers at week 40 than the PsACWY group and had obvious immunologic memory after receiving a polysaccharide booster vaccine. Safety profiles were similar across vaccine groups, although PsA-TT recipients were more likely than PsACWY recipients to have tenderness and induration at the vaccination site. Adverse events were consistent with age-specific morbidity in the study areas; no serious vaccine-related adverse events were reported. CONCLUSIONS: The PsA-TT vaccine elicited a stronger response to group A antibody than the PsACWY vaccine. (Funded by the Meningitis Vaccine Project through a grant from the Bill and Melinda Gates Foundation; Controlled-Trials.com numbers, ISRCTN78147026 and ISRCTN87739946.).
Subject(s)
Antibodies, Bacterial/blood , Meningococcal Vaccines/immunology , Neisseria meningitidis/immunology , Africa , Double-Blind Method , Female , Haemophilus Vaccines , Humans , Immunologic Memory , Infant , Male , Meningococcal Vaccines/adverse effects , Polysaccharides, Bacterial , Tetanus Toxoid , Vaccines, Conjugate/adverse effects , Vaccines, Conjugate/immunologyABSTRACT
BACKGROUND: The Demographic Surveillance System established in 1962 in Niakhar, Senegal, is the oldest in Africa. Here, we analyze trends in overall child mortality, malaria, and other causes of death in Niakhar from the beginning of data collection to 2010. METHODS: After an initial census, demographic data were updated yearly from 1963 through 2010. From 1984, causes of death were determined by the verbal autopsy technique. RESULTS: During 1963-2010, infant and under-5 mortality rates decreased from 223 to 18 and from 485 to 41, respectively. The decrease was progressive during the entire observation period, except during 1990-2000, when a plateau and then an increase was observed. Malaria-attributable mortality in under-5 children decreased from 13.5 deaths per 1000 children per year during 1992-1999 to 2.2 deaths per 1000 children per year in 2010. During this period, all-cause mortality among children aged <5 years decreased by 80%. CONCLUSIONS: Inadequate treatment for chloroquine-resistant malaria and an epidemic of meningitis during the 1990s were the 2 factors that interrupted a continuous decrease in child mortality. Direct and indirect effects of new malaria-control policies, introduced in 2003 and completed during 2006-2008, are likely to have been the key cause of the recent dramatic decrease in child mortality.