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Background Invasive bacterial diseases (IBD) cause significant mortality in young infants. There are limited population-based data on IBD in young infants in Sub-Saharan Africa. Methods We conducted population-based surveillance for IBD among infants aged 0-90 days in a demographic surveillance area in rural Gambia between 1 March 2011 and 31 December 2017. Infants admitted to health facilities within the study area had standardised clinical evaluation plus conventional microbiological investigation. We defined IBD as isolation of pathogenic bacteria from blood, cerebrospinal fluid, lung, or pleural aspirate. We determined incidence, aetiology and case-fatality of IBD. Results A total of 3794 infants were admitted and 3605 (95%) had at least one sample collected for culture. We detected 254 (8.0%) episodes of IBD (bacteraemia 241; meningitis 14; pneumonia seven). The incidence of IBD in infants aged 0-90 days was 25 episodes/1000 person-years (95% confidence interval (CI) = 22-28), the incidence in neonates was 50 episodes/1000 person-years (95% CI = 43-58) and the incidence in infants aged 29-90 days was 12 episodes/1000 person-years (95% CI = 9-15). The most common pathogens causing IBD were Staphylococcus aureus (n = 102, 40%), Escherichia coli (n = 37, 15%), Streptococcus pneumoniae (n = 24, 9%) and Klebsiella pneumoniae (n = 12, 5%). Case-fatality was 29% (95% CI = 23-37) in neonates and 19% (95% CI = 11-29) in infants aged 29-90 days. A minimum of 7.3% of all young infant deaths in the population were caused by IBD. Conclusions IBD are common in young infants in rural Gambia and have a high case-fatality. Strategies are needed to prevent IBD in young infants. Overcoming barriers to widespread implementation of existing vaccines and developing new vaccines against the most common pathogens causing IBD should be among top priorities for reducing the high mortality rate in young infants. [ABSTRACT FROM AUTHOR]

Background: The introduction in many countries of conjugate vaccines against Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis has led to significant reductions in acute bacterial meningitis (ABM) in children. However, recent population-based data on ABM in sub-Saharan Africa are limited. Methods: Population-based surveillance for meningitis was carried out in a rural area of The Gambia under demographic surveillance from 2008 to 2017, using standardised criteria for referral, diagnosis and investigation. We calculated incidence using population denominators. Results: We diagnosed 1,666 patients with suspected meningitis and collected cerebrospinal fluid (n = 1,121) and/or blood (n = 1,070) from 1,427 (88%) of cases. We identified 169 cases of ABM, 209 cases of suspected non-bacterial meningitis (SNBM) and 1,049 cases of clinically suspected meningitis (CSM). The estimated average annual incidence of ABM was high at 145 per 100,000 population in the <2-month age group, 56 per 100,000 in the 2–23-month age group, but lower at 5 per 100,000 in the 5–14-year age group. The most common causes of ABM were Streptococcus pneumoniae (n = 44), Neisseria meningitidis (n = 42), and Gram-negative coliform bacteria (n = 26). Eighteen of 22 cases caused by pneumococcal serotypes included in PCV13 occurred prior to vaccine introduction and four afterwards. The overall case fatality ratio for ABM was 29% (49/169) and was highest in the <2-month age group 37% (10/27). The case fatality ratio was 8.6% (18/209) for suspected non-bacterial meningitis and 12.8% (134/1049) for clinically suspected meningitis cases. Conclusions: Gambian children continue to experience substantial morbidity and mortality associated with suspected meningitis, especially acute bacterial meningitis. Such severely ill children in sub-Saharan Africa require improved diagnostics and clinical care. [ABSTRACT FROM AUTHOR]

Background: Cryptosporidium is a major pathogen associated with diarrheal disease in young children. We studied Cryptosporidium diarrhea in children enrolled in the Global Enteric Multicenter Study (GEMS) in rural Gambia. Methods: We recruited children <5 years of age with moderate-to-severe diarrhea (MSD) for 3 years (2008–2010), and children with either MSD or less severe diarrhea (LSD) for one year (November 2011-November 2012) at sentinel health centers. One or more randomly selected controls were matched to each case. Stool samples were tested to identify Cryptosporidium by immunoassay. A subset of randomly selected case-controls pairs were tested for Cryptosporidium species. We investigated the epidemiology of, and evaluated possible risk factors for, Cryptosporidium-positive diarrhea. Results: We enrolled 1938 cases (1381 MSD, 557 LSD) and 2969 matched controls; 231/1929 (12.0%) of diarrhea cases and 141/2962 (4.8%) of controls were positive for Cryptosporidium. Most Cryptosporidium diarrhea cases (85.7%, 198/231) were aged 6–23 months, and most (81.4%, 188/231) occurred during the rainy season. Cryptosporidium hominis (C. hominis) was the predominant (82.6%) species. We found associations between increased risk of Cryptosporidium-positive MSD or LSD, or both, with consumption of stored drinking water and certain animals living in the compound—cow, cat (MSD only) and rodents (LSD only). Larger households, fowl living in the compound, and the presence of Giardia infection were associated with decreased risk of Cryptosporidium MSD and LSD. Conclusion: Cryptosporidium-positive diarrhea is prevalent in this setting, especially at 6–23 months of age. The preponderance of Cryptosporidium infection in the rainy season and increased risk of Cryptosporidium-positive diarrhea with consumption of stored drinking water suggest water-borne transmission. Further investigation is needed to clarify the role of animals and contamination of stored drinking water in Cryptosporidium transmission. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus bacteremia is a substantial cause of childhood disease and death, but few studies have described its epidemiology in developing countries. Using a population-based surveillance system for pneumonia, sepsis, and meningitis, we estimated S. aureus bacteremia incidence and the case-fatality ratio in children <5 years of age in 2 regions in the eastern part of The Gambia during 2008-2015. Among 33,060 children with suspected pneumonia, sepsis, or meningitis, we performed blood culture for 27,851; of 1,130 patients with bacteremia, 198 (17.5%) were positive for S. aureus. S. aureus bacteremia incidence was 78 (95% CI 67-91) cases/100,000 person-years in children <5 years of age and 2,080 (95% CI 1,621-2,627) cases/100,000 person-years in neonates. Incidence did not change after introduction of the pneumococcal conjugate vaccine. The case-fatality ratio was 14.1% (95% CI 9.6%-19.8%). Interventions are needed to reduce the S. aureus bacteremia burden in The Gambia, particularly among neonates. [ABSTRACT FROM AUTHOR]

The gastric pathogen Helicobacter pylori is one of the most genetically diverse of bacterial species. Much of its diversity stems from frequent mutation and recombination, preferential transmission within families and local communities, and selection during persistent gastric mucosal infection. MLST of seven housekeeping genes had identified multiple distinct H. pylori populations, including three from Africa: hpNEAfrica, hpAfrica1 and hpAfrica2, which consists of three subpopulations (hspWAfrica, hspCAfrica and hspSAfrica). Most detailed H. pylori population analyses have used strains from non-African countries, despite Africa's high importance in the emergence and evolution of humans and their pathogens. Our concatenated sequences from seven H. pylori housekeeping genes from 44 Gambian patients (MLST) identified 42 distinct sequence types (or haplotypes), and no clustering with age or disease. STRUCTURE analysis of the sequence data indicated that Gambian H. pylori strains belong to the hspWAfrica subpopulation of hpAfrica1, in accord with Gambia's West African location. Despite Gambia's history of invasion and colonisation by Europeans and North Africans during the last millennium, no traces of Ancestral Europe1 (AE1) population carried by those people were found. Instead, admixture of 17% from Ancestral Europe2 (AE2) was detected in Gambian strains; this population predominates in Nilo-Saharan speakers of North-East Africa, and might have been derived from admixture of hpNEAfrica strains these people carried when they migrated across the Sahara during the Holocene humid period 6,000–9,000 years ago. Alternatively, shared AE2 ancestry might have resulted from shared ancestral polymorphisms already present in the common ancestor of sister populations hpAfrica1 and hpNEAfrica. [ABSTRACT FROM AUTHOR]

Fourteen years after the first introduction of conjugate Haemophilus influenzae type b vaccine in The Gambia, effective disease control was maintained, with associated low carriage and high seroprotection. Continued surveillance must determine if protection wanes and a booster dose is needed.Background. The Gambia was the first country in Africa to introduce conjugate Haemophilus influenzae type b (Hib) vaccine, which, as in other developing countries but unlike industrialized countries, is delivered as a 3-dose primary series with no booster. This study assessed its effectiveness 14 years after introduction.Methods. Using methods standardized during >20 years in the study site, clinical and microbiological surveillance for invasive Hib disease (primarily meningitis) in the Western Region of The Gambia from 2007 to 2010 was complemented with studies of Hib carriage in children aged 1 to <2 years, Hib antibody levels in children aged <5 years, and Hib vaccine coverage and timing in children aged 1 to <2 years.Results. The incidence of Hib meningitis remained low (averaging 1.3 per 100 000 children aged <5 years annually), as did the Hib oropharyngeal carriage rate (0.9%). Hib antibody levels were protective in >99% of those surveyed, albeit with lower titers in older children; and coverage of conjugate Hib vaccination was high (91% having 3 doses at 1–2 years of age) using a schedule that was delivered at median ages of 2.6 months, 4.3 months, and 6 months for the first, second, and third doses, respectively.Conclusions. Conjugate Hib vaccine was delivered on time in a 3-dose primary series without booster to a high proportion of eligible children and this was associated with effective disease control up to 14 years after introduction. It is important that surveillance continues in this first African country to introduce the vaccine to determine if effective control persists or if a booster dose becomes necessary as has been the case in industrialized countries. [ABSTRACT FROM AUTHOR]

Background: A village-randomized trial of a seven-valent pneumococcal-conjugate-vaccine (PCV-7) conducted in rural Gambia showed a decrease of vaccine-type (VT) and a non-significant increase in non-vaccine-type (NVT) nasopharyngeal carriage of pneumococci two years after vaccination. Here, we report findings four years after vaccination. Methods: PCV-7 was given to all children below 30 months of age enrolled in the trial and to those born during its course in all study villages. Villages were randomized (older children and adults) to receive PCV-7 (wholly vaccinated villages) or serogroup-C-meningococcal-conjugate-vaccine (partly vaccinated villages). Cross-sectional surveys (CSS) to collect nasopharyngeal swabs were conducted before and at various intervals after vaccination. Sixteen of these randomized villages (8 wholly vaccinated and 8 partly vaccinated) participated in a CSS conducted four years after vaccination started. Results: Four years after vaccination, the prevalence of VT pneumococcal carriage was slightly higher in partly than in wholly vaccinated villages [6.4% versus 3.9% (p = 0.120)] compared to 24.4% in the pre-vaccination CSS (p<0.001). Prevalence of NVT four years after vaccination was similar between study groups [32.7% versus 29.8% (p = 0.392), respectively] compared to 51.1% in the pre-vaccination CSS (p<0.001). Four years after vaccination started, lower prevalence of serotype 6A was detected in wholly vaccinated than in partly vaccinated villages (1.6% versus 3.5%, p = 0.093) whilst the prevalence of serotype 19A was similar between groups (2.9% versus 2.5%, p = 0.779). The most prevalent serotype 19A clone was ST 847. The most prevalent serotype 6A clone before vaccination was ST3324 whilst after vaccination ST913 and ST1737 predominated. Fourteen out of 26 STs detected among the serotype 6A isolates were new while no new 19A serotype ST was found. Conclusions: The decline in prevalence of VT pneumococci seen shortly after PCV-7 vaccination was sustained four years later with only a small difference between study arms. No significant serotype replacement was detected. Trial Registration: ClinicalTrials.gov ISRCTN51695599 [ABSTRACT FROM AUTHOR]

Background: Little is known about the population biology of Streptococcus pneumoniae in developing countries, although the majority of pneumococcal infections occur in this setting. The aim of the study was to apply MLST to investigate the population biology of S. pneumoniae in West Africa. Methods: Seventy three invasive and carriage S. pneumoniae isolates from three West African countries including The Gambia, Nigeria and Ghana were investigated. The isolates covered seven serotypes (1, 3, 5, 6A, 11, 14, 23F) and were subjected to multilocus sequence typing and antibiotic susceptibility testing. Results: Overall, 50 different sequence types (STs) were identified, of which 38% (29) were novel. The most common ST was a novel clone-ST 4012 (6.5%), and some clones including STs 913, 925, 1737, 2160 and 3310 appeared to be specific to the study region. Two STs including ST 63 and ST 4012 were associated with multiple serotypes indicating a history of serotype switching. ST 63 was associated with serotypes 3 and 23F, while ST 4012 was associated with serotypes 6A and 23. eBURST analyses using the stringent 6/7 identical loci definition grouped the 50 STs into 5 clonal complexes and 65 singletons, expressing a high level of genetic diversity among the isolates. Compared to the other serotypes, serotypes 1 and 5 isolates appeared to be more clonal. Internationally recognized antibiotic resistant clones of S. pneumoniae were generally absent in the population investigated and the only multidrug resistant isolate identified (1/66) belong to the Pneumocococcal Epidemiology Network clone ST 63. Conclusions: The pneumococcal population in West Africa is quite divergent, and serotypes that are common in invasive disease (such as serotypes 1 and 5) are more likely to be clonal than serotypes that are common in carriage. [ABSTRACT FROM AUTHOR]

Dizygotic (DZ) twinning has a genetic component and is common among sub-Saharan Africans; in The Gambia its frequency is up to 3% of live births. Variation in PTX3, encoding Pentraxin 3, a soluble pattern recognition receptor that plays an important role both in innate immunity and in female fertility, has been associated with resistance to Mycobacterium tuberculosis pulmonary disease and to Pseudomonas aeruginosa infection in cystic fibrosis patients. We tested whether PTX3 variants in Gambian women associate with DZ twinning, by genotyping five PTX3 single nucleotide polymorphisms (SNPs) in 130 sister pairs (96 full sibs and 34 half sibs) who had DZ twins. Two, three and five SNP haplotypes differed in frequency between twinning mothers and those without a history of twinning (from P= 0.006 to 3.03e-06 for two SNP and three SNP haplotypes, respectively). Twinning mothers and West African tuberculosis-controls from a previous study shared several frequent haplotypes. Most importantly, our data are consistent with an independently reported association of PTX3 and female fertility in a sample from Ghana. Taken together, these results indicate that selective pressure on PTX3 variants that affect the innate immune response to infectious agents, could also produce the observed high incidence of DZ twinning in Gambians. [ABSTRACT FROM AUTHOR]

Background: A recent trial with PCV-7 in a rural Gambian community showed reduced vaccine-type pneumococcal carriage in fully vaccinated compared with control communities. We measured pneumococcal polysaccharide antibody concentrations in this trial to understand further the mechanisms underlying the observed changes. Methods: A single-blind, cluster-randomized (by village) trial was conducted in 21 Gambian villages. In 11 villages, all residents received PCV-7 (Vaccine group); in 10 control villages only children ,30 months old or those born during the study received PCV-7. Subjects over the age of 30 months resident in vaccine villages received a single dose of PCV-7 whilst those in control villages received a single dose of a serogroup C meningococcal conjugate vaccine. Serum antibody concentrations against specific pneumococcal polysaccharides were measured in approximately 200 age-stratified subjects before, 4-6, 12 and 24 months following vaccination. Results: Baseline pneumococcal antibody concentrations were generally high and increased with age up to 10 years. One dose of PCV-7 increased geometric mean antibody concentrations (GMC) in vaccinated versus control villages for vaccine serotypes 6B and 18C, and 4 and 18C, in the young (under 5 years) and older age groups (5+ years) respectively. There were significantly higher proportions of subjects in the vaccinated than in the control communities with an antibody concentration believed to protect against carriage (.5.0 µg/mL) for all but serotype 9V of the PCV-7 serotypes in the older group, but not in the younger age group. Conclusion: Higher antibodies in vaccinated communities provide an explanation for the lower pneumococcal carriage rates in fully vaccinated compared to control communities. [ABSTRACT FROM AUTHOR]

Smoke from biomass fuels is a risk factor for pneumonia, the leading cause of child death worldwide. Although particulate matter (PM) is the metric of choice for studying the health effects of biomass smoke, measuring children's PM exposure is difficult. Carbon monoxide (CO), which is easier to measure, can be used as a proxy for PM exposure. We measured the exposure of children ≤5 years of age in The Gambia to CO using small, passive, color stain diffusion tubes. We conducted multiple CO measurements on a subset of children to measure day-to-day exposure variability. Usual CO exposure was modeled using a mixed effects model, which also included individual and household level exposure predictors. Mean measured CO exposure for 1181 children (n=2263 measurements) was 1.04±1.46 p.p.m., indicating that the Gambian children in this study on average have a relatively low CO exposure. However, 25% of children had exposures of 1.3 p.p.m. or higher. CO exposure was higher during the rainy months (1.33±1.62 p.p.m.). Burning insect coils, using charcoal, and measurement done in the rainy season were associated with higher exposure. A parsimonious model with fuel, season, and other PM sources as covariates explained 39% of between-child variation in exposure and helped remove within-child variability. [ABSTRACT FROM AUTHOR]

Background: Introduction of pneumococcal conjugate vaccines (PCVs) of limited valency is justified in Africa by the high burden of pneumococcal disease. Long-term beneficial effects of PCVs may be countered by serotype replacement. We aimed to determine the impact of PCV-7 vaccination on pneumococcal carriage in rural Gambia. Methods and Findings: A cluster-randomized (by village) trial of the impact of PCV-7 on pneumococcal nasopharyngeal carriage was conducted in 21 Gambian villages between December 2003 to June 2008 (5,441 inhabitants in 2006). Analysis was complemented with data obtained before vaccination. Because efficacy of PCV-9 in young Gambian children had been shown, it was considered unethical not to give PCV-7 to young children in all of the study villages. PCV-7 was given to children below 30 mo of age and to those born during the trial in all study villages. Villages were randomized (older children and adults) to receive one dose of PCV-7 (11 vaccinated villages) or meningococcal serogroup C conjugate vaccine (10 control villages). Cross-sectional surveys (CSSs) to collect nasopharyngeal swabs were conducted before vaccination (2,094 samples in the baseline CSS), and 4-6, 12, and 22 mo after vaccination (1,168, 1,210, and 446 samples in CSS-1, -2, and -3, respectively). A time trend analysis showed a marked fall in the prevalence of vaccine-type pneumococcal carriage in all age groups following vaccination (from 23.7% and 26.8% in the baseline CSS to 7.1% and 8.5% in CSS-1, in vaccinated and control villages, respectively). The prevalence of vaccine-type pneumococcal carriage was lower in vaccinated than in control villages among older children (5 y to ,15 y of age) and adults (≥15 y of age) at CSS-2 (odds ratio [OR] = 0.15 [95% CI 0.04-0.57] and OR = 0.32 [95% CI 0.10-0.98], respectively) and at CSS-3 (OR = 0.37 [95% CI 0.15-0.90] for older children, and 0% versus 7.6% for adults in vaccinated and control villages, respectively). Differences in the prevalence of non-vaccine-type pneumococcal carriage between vaccinated and control villages were small. Conclusions: Vaccination of Gambian children reduced vaccine-type pneumococcal carriage across all age groups, indicating a "herd effect" in non-vaccinated older children and adults. No significant serotype replacement was detected. [ABSTRACT FROM AUTHOR]

Background: Non-Typhoidal Salmonella (NTS) is an important cause of invasive bacterial disease and associated with mortality in Africa. However, little is known about the environmental reservoirs and predominant modes of transmission. Our study aimed to study the role of domestic animals in the transmission of NTS to humans in rural area of The Gambia. Methodology: Human NTS isolates were obtained through an active population-based case-control surveillance study designated to determine the aetiology and epidemiology of enteric infections covering 27,567 Gambian children less than five years of age in the surveillance area. Fourteen children infected with NTS were traced back to their family compounds and anal swabs collected from 210 domestic animals present in their households. Identified NTSs were serotyped and genotyped by multi-locus sequencing typing. Principal Findings: NTS was identified from 21/210 animal sources in the households of the 14 infected children. Chickens carried NTS more frequently than sheep and goats; 66.6%, 28.6% and 4.8% respectively. The most common NTS serovars were S. Colindale in humans (21.42%) and S. Poona in animals (14.28%). MLST on the 35 NTS revealed four new alleles and 24 sequence types (ST) of which 18 (75%) STs were novel. There was no overlap in serovars or genotypes of NTS recovered from humans or animal sources in the same household. Conclusion: Our results do not support the hypothesis that humans and animals in close contact in the same household carry genotypically similar Salmonella serovars. These findings form an important baseline for future studies of transmission of NTS in humans and animals in Africa. Author Summary: Salmonellosis is a neglected tropical disease causing serious dysentery and septicaemia particularly in young infants, elderly and immunocompromised individuals such as HIV patients and associated with substantial mortality in developing countries. Salmonellosis also constitutes a major public health problem as it is considered the most widespread bacterial zoonosis of food origin throughout the world. Many epidemiological data exist from developed countries concerning transmission of Non-Typhoidal Salmonella (NTS) but few are available from developing countries. In addition few studies in sub-Saharan Africa have considered the interface between humans and their environment in relation to animals present in the household and food hygiene. This study describes the prevalence of NTS among fourteen Gambian children and 210 domestic animals living in close proximity (household) to the children in a rural setting in The Gambia. We found that the domestic animals living in the same household as patients carried different NTS serovar and genotypes; indicating that zoonotic transmission does not occur in our setting. This study provides baseline data for future studies of transmission of NTS in rural Africa. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori is an important agent of gastroduodenal disease in Africa and throughout the world. We sought to determine an optimum method for genotyping H. pylori strains from children and adults in The Gambia, West Africa. Results: Virulence genes were amplified in 127 of 190 cases tested (121 adults and 6 children); each of 60 bacterial cultures, and 116 from DNA extracted directly from biopsies. The proportion of biopsies that were cagA+, the ratio of vacAs1/s2, and vacAm1/m2, and the proportion of mixed strain populations in individual subjects changed with age. Strains lacking virulence cagA and vacA genes and with apparently homogeneous (one predominant strain) infections were more common among infants than adults. Conclusions: In order to detect the range of bacterial genotypes harbored by individual patients, direct PCR proved slightly superior to isolation of H. pylori by biopsy culture, but the techniques were complementary, and the combination of both culture and direct PCR produced the most complete picture. The seemingly higher virulence of strains from adult than infant infections in The Gambia merits further analysis. [ABSTRACT FROM AUTHOR]

Background: Malaria is a risk factor for invasive non-typhoidal Salmonella (NTS) infection in children. In the last 10 years, indices of malaria infection in The Gambia have fallen substantially. Methods: We compared temporal trends of childhood malaria and NTS infection in two Gambian locations. In Fajara, on the coast, the incidence of NTS infection at three time points between 1979 and 2005 was compared to the percentage of malaria positive outpatient thick blood films and the percentage of admissions associated with malaria over time. In Basse, in the eastern part of the country, the incidence of NTS infection at three time points between 1989 and 2008 was compared to the prevalence of malaria parasitaemia at four time points between 1992 and 2008. Results: The estimated incidence of NTS infection in Fajara fell from 60 (1979-1984) to 10 (2003-05) cases per 100,000 person years. The proportion of outpatients in Fajara with suspected malaria who were parasitaemic fell from 33% (1999) to 6% (2007) while the proportion of admissions associated with malaria fell from 14.5% (1999) to 5% (2007). In Basse, the estimated incidence of NTS infection fell from 105 (1989-1991) to 29 (2008) cases per 100,000 person years while the prevalence of malaria parasitaemia fell from 45% (1992) to 10% (2008). The incidence of pneumococcal bacteraemia in Fajara and Basse did not fall over the study period. Conclusions: These data support an association between malaria and NTS infection. Reductions in malaria infection may be associated with reduced rates of invasive childhood NTS infection. [ABSTRACT FROM AUTHOR]

Mycobacterium africanum (MAF) is a common cause of human pulmonary tuberculosis in West Africa. We previously described phenotypic differences between MAF and Mycobacterium tuberculosis (MTB) among 290 patients. In the present analysis, we compared 692 tuberculosis patients infected with the two most common lineages within the (MTB) complex found in the Gambia, namely MAF West African type 2 (39% prevalence) and Euro-American MTB (55% prevalence). We identified additional phenotypic differences between infections with these two organisms. MAF patients were more likely to be older and HIV infected. In addition, they had worse disease on chest X-ray, despite complaining of cough for an equal duration, and were more likely severely malnourished. In this cohort, the prevalence of MAF did not change significantly over a 7-year period. [ABSTRACT FROM AUTHOR]

Background: Currently available tools cannot be used to distinguish between sub-species of the M. tuberculosis complex causing latent tuberculosis (TB) infection. M. africanum causes up to half of TB in West- Africa and its relatively lower progression to disease suggests the presence of a large reservoir of latent infection relative to M. tuberculosis. Methods: We assessed the immunogenicity of the TbD1 region, present in M. africanum and absent from "modern" M. tuberculosis, in an ELISPOT assay using cells from confirmed M. africanum or M. tuberculosis infected TB patients without HIV infection in the Gambia. Results: Antigens from the TbD1 region induced IFNγ responses in only 35% patients and did not discriminate between patients infected with M. africanum vs. M. tuberculosis, while PPD induced universally high responses. Conclusions: Further studies will need to assess other antigens unique to M. africanum that may induce discriminatory immune responses. [ABSTRACT FROM AUTHOR]

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Background. There is considerable variability in the outcome of Mycobacterium tuberculosis infection. We hypothesized that Mycobacterium africanum was less likely than M. tuberculosis to transmit and progress to tuberculosis disease. Methods. In a cohort study of patients with tuberculosis and their household contacts in The Gambia, we categorized 1808 HIV-negative tuberculosis contacts according to exposure to M. tuberculosis or M. africanum. Positive skin test results indicated transmission, and development of tuberculosis during 2 years of follow-up indicated progression to disease. Results. Transmission rates were similar, but rates of progression to disease were significantly lower in contacts exposed to M. africanum than in those exposed to M. tuberculosis (1.0% vs. 2.9%; hazard ratio [HR], 3.1 [95% confidence interval {CI}, 1.1- 8.7]). Within M. tuberculosis sensu stricto, contacts exposed to a Beijing family strain were most likely to progress to disease (5.6%; HR relative to M. africanum, 6.7 [95% CI, 2.0 -22]). Conclusions. M. africanum and M. tuberculosis transmit equally well to household contacts, but contacts exposed to M. africanum are less likely to progress to tuberculosis disease than those exposed to M. tuberculosis. The variable rate of progression by lineage suggests that tuberculosis variability matters in clinical settings and should be accounted for in studies evaluating tuberculosis vaccines and treatment regimens for latent tuberculosis infection. [ABSTRACT FROM AUTHOR]

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background. To prepare for national introduction of a pneumococcal conjugate vaccine of restricted valency, we studied nasopharyngeal carriage of Streptococcus pneumoniae in Gambian infants. Methods. We studied 236 infants in 21 villages. We collected nasopharyngeal swab samples at birth, twice per month for 6 months, and every second month until 1 year of age. We studied time to acquisition and duration of pneumococcal carriage according to serotype. Results. All infants carried S. pneumoniae at some point. Sixty-five serotypes were found, and the 5 most common serotypes (6B, 19F, 6A, 14, and 23F) accounted for 51% of isolates. The mean age at first acquisition of carriage was 33 days (95% confidence interval, 29-36 days). There were no significant differences in acquisition rates between the 6 most common serotypes (P = .067) or between vaccine serotypes, vaccine-related serotypes, or nonvaccine serotypes (P = .317). However, the duration of carriage differed significantly between the 6 most common serotypes (P = .004). The rate of reacquisition of carriage and the duration of carriage did not differ significantly between the 6 most common serotypes (P = .229 and P = .699 respectively). However, nonvaccine types were acquired faster (P = .004) and were carried for a shorter duration (P< .001) than were vaccine serotypes. A previous episode of serotype 14 carriage was associated with delayed reacquisition of this serotype (P = .005) and longer duration of carriage (P = .017). Conclusions. The data provided in this study regarding time to acquisition and duration of pneumococcal carriage in Gambian infants provide an important baseline for evaluating the impact of the introduction of a pneumococcal conjugate vaccine in The Gambia and elsewhere in Africa. [ABSTRACT FROM AUTHOR]

The introduction of molecular diagnostic methods is crucial for improved understanding of the aetiology and epidemiology of bacterial infections in communities in resource poor settings. A blood sample from a 7 month old patient diagnosed with malaria in 2001 in a Gambian outpatient clinic was reported as culture negative after it was subjected to traditional bacterial culture protocols. We re-addressed the analysis of the blood sample from this case more recently (after 6.5 years in archival storage) in pilot work establishing 16S rRNA PCR in our molecular laboratory. Initial 16S rRNA PCR results confirmed the presence of bacterial DNA in the sample. 16S rRNA sequence analysis identified the organism as Campylobacter spp. In light of the molecular evidence we successfully grew the organism using appropriate culture conditions and subsequently biochemically confirmed that the isolate was Campylobacter jejuni. PCR and DNA sequencing of a set of seven C. jejuni housekeeping genes and in silico Multilocus Sequence Typing (MLST) analysis revealed that the isolate exhibits a novel sequence type (ST) of C. jejuni (ST 2928) and belongs to ST-443 clonal complex. This study demonstrates the potential for molecular tools to enhance the diagnosis of bacterial infections, which remain a major killer globally, not least in children in the developing world. Improvements in diagnostics are needed, and will be important not only for sick individuals but also for populations, where better measures of disease burden will contribute significantly to the improvement of public health policy. [ABSTRACT FROM AUTHOR]

Background: The study describes the molecular epidemiology of Streptococcus pneumoniae causing invasive disease in Gambian children Methods: One hundred and thirty-two S. pneumoniae isolates were recovered from children aged 2-29 months during the course of a pneumococcal conjugate vaccine trial conducted in The Gambia of which 131 were characterized by serotyping, antibiotic susceptibility, BOX-PCR and MLST. Results: Twenty-nine different serotypes were identified; serotypes 14, 19A, 12F, 5, 23F, and 1 were common and accounted for 58.3% of all serotypes overall. MLST analysis showed 72 sequence types (STs) of which 46 are novel. eBURST analysis using the stringent 6/7 identical loci definition, grouped the isolates into 17 clonal complexes and 32 singletons. The population structure of the 8 serotype 1 isolates obtained from 4 vaccinated and 2 unvaccinated children were the same (ST 618) except that one (ST3336) of the isolates from an unvaccinated child had a novel ST which is a single locus variant of ST 618. Conclusion: We provide the first background data on the genetic structure of S. pneumoniae causing IPD prior to PC7V use in The Gambia. This data will be important for assessing the impact of PC7V in post-vaccine surveillance from The Gambia. [ABSTRACT FROM AUTHOR]

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Background: IFN-γ Release Assays (IGRAs) have been licensed for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). Their performance may depend on assay format and may vary across populations and settings. We compared the diagnostic performance of an in-house T -cell and commercial whole blood-based IGRAs for the diagnosis of LTBI and TB disease in The Gambia. Methods: Newly diagnosed sputum smear positive cases and their household contacts were recruited. Cases and contacts were bled for IGRA and contacts had a Mantoux skin test. We assessed agreement and discordance between the tests and categorized a contact's level of M. tuberculosis exposure according to where s/he slept relative to a case: the same room, same house or a different house. We assessed the relationship between exposure and test results by multiple logistic regression. Results: In 80 newly diagnosed TB cases, the sensitivity of ELISPOT was 78.7% and for QFT-GIT was 64.0% (p = 0.047). Of 194 household contacts 57.1% and 58.8% were positive for ELISPOT and QFT-GIT respectively. The overall agreement between both IGRAs for LTBI in contacts was 71.4% and there was no significant discordance (p = 0.29). There was significant discordance between the IGRAs and TST. Neither IGRA nor TST had evidence of false positive results because of Bacille Calmette Gu&erin;rin (BCG) vaccination. However, agreement between QFT-GIT and TST as well as discordance between both IGRAs and TST were associated with BCG vaccination. Both IGRAs responded to the M. tuberculosis exposure gradient and were positively associated with increasing TST induration (p = 0.003 for ELISPOT and p = 0.001 for QFT-GIT). Conclusion: The ELISPOT test is more sensitive than the QFT-GIT for diagnosing TB disease. The two tests perform similarly in the diagnosis of LTBI in TB contacts. Significant discordance between the two IGRAs and between each and the TST remain largely unexplained. [ABSTRACT FROM AUTHOR]

Background: Few studies on bacteraemia in Africa have been published. We aimed to prospectively identify the causative organisms of bacteraemia in The Gambia and their relation to clinical diagnoses, outcome and antimicrobial susceptibility. Methods: Between November 2003 and February 2005 we studied those admitted to the Medical Research Council hospital who were suspected of having bacteraemia. We documented clinical features, outcome, pathogens identified and their susceptibility patterns, and searched for factors associated with bacteraemia. Results: 871 patients were admitted and had a blood culture taken. The median age was 2 years (range 2 months to 80 years) and 36 of 119 tested were HIV positive; 54.5% were male. 297 (34%) had a positive result and 93 (10.7% overall) were considered a genuine pathogen. Those with bacteraemia were more likely to die in hospital (OR 2.79; 1.17-6.65, p = 0.017) and to have a high white cell count (WCC; OR 1.81;95% CI 1.09-3.02; p = 0.022). Three organisms accounted for 73% of bacteraemias: Streptococcus pneumoniae (45.2%), Staphylococcus aureus (18.3%) and Escherichia coli (9.7%) while non-typhoidal salmonellae (NTS) accounted for 8.6%. Antimicrobial susceptibility of S. pneumoniae was very high to penicillin (97.5%); high resistance was found to cotrimoxazole. S. aureus was generally highly susceptible to cloxacillin, gentamicin and chloramphenicol. E. coli and NTS were all susceptible to ciprofloxacin and mostly susceptible to gentamicin. Thirteen (33%) S. pneumoniae isolates were of serotypes contained in a 7-valent pneumococcal conjugate vaccine and 20 (51.3%) were of the same serogroup. Conclusion: In The Gambia, those with bacteraemia are more likely than those without to die in hospital and to have a raised peripheral blood WCC. S. pneumoniae is the most common organism isolated. Introduction of a pneumococcal conjugate vaccine can be expected to lead to a reduction in disease incidence. [ABSTRACT FROM AUTHOR]

Background. To prepare for the introduction of a pneumococcal conjugate vaccine of restricted valency, we studied the nasopharyngeal carriage of Streptococcus pneumoniae in Gambian villagers. Methods. A cross-sectional survey was conducted in 21 villages after a census. We recorded demographic characteristics, information on medical history, and data on possible risk factors for carriage from subjects. We collected a nasopharyngeal swab specimen from each subject for isolation and serotyping of S. pneumoniae and for antibiotic susceptibility testing. Results. The prevalence of S. pneumoniae carriage among 2872 villagers was 72%. It was highest among infants (i.e., children aged <1 year; 97%); the rate was 93% among babies aged <1 month and decreased with increasing age (P < .001). Prevalence of carriage was linked to proximity to another village. Sixty-three percent of isolates recovered from children aged <5 years were covered by the 7-valent vaccine or were of a vaccine-related serotype, compared with 43% of isolates overall. Forty-three isolates (14.3%) tested were initially penicillin resistant; none had high-level resistance, and 4 had intermediate resistance. The rates of resistance to other antibiotics were as follows: trimethoprim-sulfamethoxazole, 39%; tetracycline, 32.3%; chloramphenicol, 6.3%; cefotaxime, 0.3%; and erythromycin, 0%. The rates were highest for isolates of vaccine serotypes. Conclusions. Pneumococcal carriage rates among Gambian villagers are very high. A pneumococcal conjugate vaccine of restricted valency should reduce the pool of antibiotic-resistant pneumococci. The large reservoir of pneumococci of nonvaccine serotypes will require close monitoring when the vaccine is introduced. [ABSTRACT FROM AUTHOR]

Objectives To describe the characteristics of pneumococcal isolates obtained from patients with invasive pneumococcal disease in The Gambia. Methods Pneumococcal isolates were obtained from children aged ≤6 years with invasive pneumococcal disease during a Haemophilus influenzae vaccine effectiveness study (1997-2002) and from patients with invasive pneumococcal disease admitted to the MRC hospital, Fajara, for routine care (1996-2003). Isolates were identified, serotyped and tested for antibiotic susceptibility. Results Five hundred and thirty one pneumococcal isolates were obtained from 518 patients; 55 (10.6%) patients died; 415 isolates (79%) were from blood culture, 84 (16%) from CSF, and 42 (8%) from lung aspirates. Forty serogroups and serotypes were identified; six accounted for 64% and 16 for 86% of all episodes; 33.7% were of serotypes 1 and 5. 23.5% were of a 7-valent vaccine serotype, 57.1% were of a 9-valent vaccine serotype; 56% were of a 7-valent serogroup and 78% were of a 9-valent serogroup. There was a significant increase in the proportion of isolates of non-vaccine serogroup with increasing age ( P < 0.0001). Antibiotic resistance had not significantly increased over time; but intermediate non-susceptibility to penicillin had risen and resistance to chloramphenicol had fallen in isolates of vaccine serotype compared with those of non-vaccine serotype. Conclusions The majority of invasive pneumococcal disease in The Gambia is caused by pneumococci of relatively few serogroups. A conjugate vaccine would be expected to reduce the pneumococcal disease burden substantially and to have a beneficial effect on pneumococcal antibiotic resistance to penicillins. [ABSTRACT FROM AUTHOR]

Background: New tools are required to improve tuberculosis (TB) diagnosis and treatment, including enhanced ability to compare new treatment strategies. The ELISPOT assay uses Mycobacterium tuberculosis-specific antigens to produce a precise quantitative readout of the immune response to pathogen. We hypothesized that TB patients in The Gambia would have reduced ELISPOT counts after successful treatment. Methods: We recruited Gambian adults with sputum smear and culture positive tuberculosis for ELISPOT assay and HIV test, and followed them up one year later to repeat testing and document treatment outcome. We used ESAT-6, CFP-10 and Purified Protein Derivative (PPD) as stimulatory antigens. We confirmed the reliability of our assay in 23 volunteers through 2 tests one week apart, comparing within and between subject variation. Results: We performed an ELISPOT test at diagnosis and 12 months later in 89 patients. At recruitment, 70/85 HIV-negative patients (82%) were ESAT-6 or CFP-10 (EC) ELISPOT positive, 77 (90%) were PPD ELISPOT positive. Eighty-two cases (96%) successfully completed treatment: 44 (55%; p < 0.001) were EC ELISPOT negative at 12 months, 17 (21%; p = 0.051) were PPD ELISPOT negative. Sixty (73%) cured cases had a CFP-10 ELISPOT count decrease, 64 (78%) had an ESAT-6 ELISPOT count decrease, 58 (70%) had a PPD ELISPOT count decrease. There was a mean decline of 25, 44 and 47 SFU/2 × 105 cells for CFP-10, ESAT-6 and PPD respectively (p < 0.001 for all). Three of 4 HIV positive patients were cured, all 3 underwent ELISPOT reversion; all 4 not cured subjects (3 HIV-negative, 1 HIV positive) were ESAT-6, CFP-10 and PPD ELISPOT positive at 12 months. Conclusion: Successful tuberculosis treatment is accompanied by a significant reduction in the M. tuberculosis-specific antigen ELISPOT count. The ELISPOT has potential as a proxy measure of TB treatment outcome. Further investigation into the decay kinetics of T-cells with treatment is warranted. [ABSTRACT FROM AUTHOR]

Background : The tuberculosis (TB) epidemic in Africa is on the rise, even in low-HIV prevalence settings. Few studies have attempted to identify possible reasons for this. We aimed to identify risk factors for pulmonary tuberculosis in those attending a general outpatients clinic in The Gambia, a sub-Saharan African country with relatively low HIV prevalence in the community and in TB patients. Methods: We conducted a case control study at the Medical Research Council Outpatients' clinic in The Gambia. Pulmonary TB cases were at least 15 years old, controls were age and sex matched clinic attendees. Participants were interviewed using a structured questionnaire. Results: 100 sputum smear positive TB cases and 200 clinic controls were recruited. HIV prevalence was 6.1% in cases and 3.3% in controls. Multivariable assessment of host factors showed that risk of TB was increased among the Jola ethnic group and smokers, and decreased in those in a professional occupation. Assessment of environmental factors showed an increased risk with household crowding, history of household exposure to a known TB case, and absence of a ceiling in the house. In a combined multivariable host-environment model, the risk of TB increased with crowding, exposure to a known TB case, as well as amongst the Jola ethnic group. Conclusion: In The Gambia, household crowding and past household exposure to a known TB case are the standout risk factors for TB disease. Further research is needed to identify why risk of TB seems to differ according to ethnicity. [ABSTRACT FROM AUTHOR]

Background: Studies in Africa investigating health-seeking behaviour by interviewing tuberculosis patients have revealed patient knowledge issues and significant delays to diagnosis. We aimed to study health-seeking behaviour and experience of those with cough in The Gambia and to identify whether they had tuberculosis. Methods: During a round of a population under 3-monthly demographic surveillance, we identified people >10 years old who had been coughing ≥ 3 weeks. A questionnaire was administered concerning demographic data, cough, knowledge, health seeking, and experience at health facilities. Case finding utilised sputum smear and chest X-ray. Results: 122/29,871 coughing individuals were identified. Of 115 interviewed, 93 (81%) had sought treatment; 76 (81.7%) from the health system. Those that visited an alternative health provider first were significantly older than those who visited the health system first (p = 0.03). The median time to seek treatment was 2 weeks (range 0 - 106). 54 (58.1%) made their choice of provider because they believed it was right. Of those who left the health system to an alternative provider (n = 13): 7 believed it was the best place, 3 cited cost and 2 failure to improve. 3 cases were identified by sputum analysis, 11 more by X-ray; all had visited the health system first. Total 'excess' cough time was 1079 person weeks. Conclusion: The majority of people with cough in this population seek appropriate help early. Improved case detection might be achieved through the use of chest X-ray in addition to sputum smear. [ABSTRACT FROM AUTHOR]

The purified protein derivative (PPD) skin test for Mycobacterium tuberculosis infection lacks specificity. We assessed 2 more specific M. tuberculosis antigens (ESAT-6 and CFP-10) by enzyme-linked immunospot assay (ELISPOT) compared with PPD by ELISPOT and skin test in The Gambia. Of 735 household contacts of 130 sputum smear–positive tuberculosis cases, 476 (65%) tested positive by PPD ELISPOT, 300 (41%) tested positive by PPD skin test, and 218 (30%) tested positive by ESAT-6/CFP-10 ELISPOT. Only 15 (2%) had positive ESAT- 6/CFP-10 results and negative PPD results by ELISPOT. With increasing M. tuberculosis exposure, the percentage of subjects who were PPD skin test positive/ESAT-6/CFP-10 ELISPOT negative increased (P < .001) whereas the percentage of subjects who were PPD skin test negative/PPD ELISPOT positive decreased (Pp ). Eighteen (31%) SAT-6/CFP-10 ELISPOT–positive subjects in the lowest exposure category had negative .011 PPD skin test results. ESAT-6/CFP-10 ELISPOT probably offers increased specificity in the diagnosis of M. tuberculosis infection in this tropical setting of endemicity, at the cost of some sensitivity. [ABSTRACT FROM AUTHOR]

Background: Bacterial meningitis is an important cause of childhood morbidity and mortality world-wide. In the developing world, where the burden of acute meningitis and its long-term sequelae are especially high, staff with limited training at primary health care facilities must be able to recognize the symptoms and signs of meningitis, so that suspected cases can be referred urgently to hospitals.Methods: Children who presented with possible invasive bacterial infection to health facilities in The Gambia, West Africa, between 1993 and 1995 were investigated in a standardized manner and clinical findings were documented. Bacterial meningitis was defined as the growth of bacteria from the cerebrospinal fluid. Clinical findings were compared between cases of meningitis and other children.Results: Of 2097 children between 2 months and 3 years of age investigated, 51 had a confirmed diagnosis of bacterial meningitis. In multivariate analysis using a model adjusting for age but not including respiratory signs, the variables associated independently with meningitis were appearance of being very sick (odds ratio for meningitis vs. no meningitis or no lumbar puncture performed (OR) 4.1, 95% CI 1.5-11.1), being lethargic or unconscious (OR 5.2, 95% CI 2.1-13), a stiff neck (OR 29.3, 95% CI 12.2-70.3), a bulging fontanel (OR 3.2, 95% CI 1.2-8.5) and reduced feeding as a prompted complaint (OR 2.9, 95% CI 1.3-6.7). A combination model of a history of convulsions, or being lethargic or unconscious, or having a stiff neck, as used in the WHO-Integrated Management of Childhood Illness (IMCI) guidelines, had a sensitivity of 98% and a specificity of 72% to predict meningitis.Conclusions: A combination of a limited number of signs is sufficient to predict meningitis with high sensitivity, without a large number of children who do not have meningitis being unnecessarily referred. [ABSTRACT FROM AUTHOR]

In developing countries, endemic childhood meningitis is a severe disease caused most commonly by Streptococcus pneumoniae or Haemophilus influenzae type b (Hib). Although many studies have shown that fatality rates associated with meningitis caused by these organisms are high in developing countries, little is known about the long-term outcome of survivors. The purpose of this study was to assess the importance of disabilities following pneumococcal and Hib meningitis in The Gambia. 257 children aged 0–12 years hospitalized between 1990 and 1995 with culture-proven S. pneumoniae (n = 134) or Hib (n = 123) meningitis were included retrospectivcly in the study. 48% of children with pneumococcal meningitis and 27% of children with Hib meningitis died whilst in hospital. Of the 160 survivors, 89 (55%) were followed up between September 1996 and October 1997. Of the children with pneumococcal meningitis that were traced, 58% had clinical sequelae; half of them had major disabilities preventing normal adaptation to social life. 38% of survivors of Hib meningitis had clinical sequelae, a quarter of whom had major disabilities. Major handicaps found were hearing loss, mental retardation, motor abnormalities and seizures. These data show that despite treatment with effective antibiotics, pneumococcal and Hib meningitis kill many Gambian children and leave many survivors with severe sequelae. Hib vaccination is now given routinely in The Gambia; an effective pneumococcal vaccine is needed. [ABSTRACT FROM AUTHOR]

Particulate matter (PM) is an important metric for studying the health effects of household air pollution. There are limited data on PM exposure for children in homes that use biomass fuels, and no previous study has used direct measurement of personal exposure in children younger than 5 years of age. We estimated PM2.5 exposure for 1266 children in The Gambia by applying the cookhouse PM2.5-CO relationship to the child's CO exposure. Using this indirect method, mean PM2.5 exposure for all subjects was 135 ± 38 μg/m³; 25% of children had exposures of 151 μg/m³ or higher. Indirectly estimated exposure was highest among children who lived in homes that used firewood (collected or purchased) as their main fuel (144 μg/m³) compared to those who used charcoal (85 μg/m³). To validate the indirect method, we also directly measured PM2.5 exposure on 31 children. Mean exposure for this validation data set was 65 ± 41 μg/m³ using actual measurement and 125 ± 54 μg/m³ using the indirect method based on simultaneously-measured CO exposure. The correlation coefficient between direct measurements and indirect estimates was 0.01. Children in The Gambia have relatively high PM2.5 exposure. There is a need for simple methods that can directly measure PM2.5 exposure in field studies. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of virulence genes in non-typhoidal Salmonella (NTS) and its association with commonly used antibiotics in West Africa is unknown. Methodology: We tested 185 NTS isolates from children, animals, and food products for the presence of twelve virulence genes by PCR. Ten of the virulence genes tested belonged to the five Salmonella pathogenicity islands implicated in its pathogenesis. Results: Ten of twelve virulence genes except sopE and pefA were present in at least 70% of the isolates tested; sopE and pefA were observed in 33% and 44% of the isolates, respectively. The most prevalent gene was invA (99.5%), which is an invasion gene conserved within the Salmonella enterica. pipD and sopB genes, which were associated with serovar Enteritidis, were detected in 92.4% and 94.1% of isolates respectively. S. Istanbul and S. Javiana, which were isolated from chicken-serving restaurants, carried all the virulence genes of the five pathogenicity islands. There was significant association between sopB, sitC, orfLC, pipD and pefA virulence genes and resistance to commonly used antibiotics in Senegal and The Gambia, namely amoxicillin, ticarcillin, trimethoprim plus sulfamethoxazole, tetracycline, trimethoprim, spectinomycin, streptomycin, sulfonamides and nitrofurantoin. Conclusions: This study shows that virulence genes are present in NTS strains isolated from various sources. The significant association between some virulence genes and antibiotic resistance may have important implications with regard to the spread and persistence of resistance and virulence genes in Salmonella and to the prudent use of antimicrobial agents in humans and animals in West Africa. [ABSTRACT FROM AUTHOR]

Objective To compare oxygen supply options for health facilities in the Gambia and develop a decision-making algorithm for choosing oxygen delivery systems in Africa and the rest of the developing world. Methods Oxygen cylinders and concentrators were compared in terms of functionality and cost. Interviews with key informants using locally developed and adapted WHO instruments, operational assessments, cost-modelling and cost measurements were undertaken to determine whether oxygen cylinders or concentrators were the better choice. An algorithm and a software tool to guide the choice of oxygen delivery system were constructed. Findings In the Gambia, oxygen concentrators have significant advantages compared to cylinders where power is reliable; in other settings, cylinders are preferable as long as transporting them is feasible. Cylinder costs are greatly influenced by leakage, which is common, whereas concentrator costs are affected by the cost of power far more than by capital costs. Only two of 12 facilities in the Gambia were found suitable for concentrators; at the remaining 10 facilities, cylinders were the better option. Conclusion Neither concentrators nor cylinders are well suited to every situation, but a simple options assessment can determine which is better in each setting. Nationally this would result in improved supply and lower costs by comparison with conventional cylinders alone, although ensuring a reliable supply would remain a challenge. The decision algorithm and software tool designed for the Gambia could be applied in other developing countries. [ABSTRACT FROM AUTHOR]

Objective To assess whether traditional measures of access to health care (distance and travel time to a facility) and non-traditional measures (social and financial support indicators) are associated with mortality among children under 5 years of age in the Gambia. Methods We conducted a case--control study in a population under demographic surveillance. Cases (n = 140) were children under 5 years of age who died between 31 December 2003 and 30 April 2006. Each case was matched in age and sex to five controls (n = 700). Information was gathered by interviewing primary caregivers. The data were analysed using conditional logistic regression. Findings Of traditional measures of access, only rural versus urban/periurban residence was important: children from rural areas were more likely to die (OR: 4.9; 95% confidence interval, CI: 1.2--20.2). For non-traditional measures, children were more likely to die if their primary caregivers lacked help with meal preparation (OR: 2.3; 95% CI: 1.2--4.1), had no one to relax with (OR: 1.8; 95% CI: 1.1--2.9), had no one who could offer good advice (OR: 23.1; 95% CI: 4.3--123.4), had little say over how earned money was spent (OR: 12.7; 95% CI: 1.3--127.6), were unable to cut spending for health care (OR: 2.5; 95% CI: 1.5--4.2) or had to carry out odd jobs to pay for the care (OR: 3.4; 95% CI: 2.1--5.5). A protective effect was observed when the caregiver had other children to care for (OR: 0.2; 95% CI: 0.1--0.5). Conclusion Improving access to health-care for children in the Gambia and similar settings is not simply a matter of reducing travel time and distance to a health facility, but requires improvements in caregivers' support networks and their access to the financial resources they need. [ABSTRACT FROM AUTHOR]

Abstract: Invasive Hib disease, which remains a major cause of childhood mortality and morbidity in most of the developing world, was eliminated in The Gambia by 2002 following the introduction of conjugate Hib vaccine in 1997. Formal disease surveillance was stopped in 2002 but five cases (including three of meningitis) were detected non-systematically between July 2005 and April 2006. This equates to an incidence of 3 per 100,000 annually for meningitis, a likely underestimate. The age distribution of cases (median 15 months, range 0–36 months) was older than previously seen and there were examples of apparent vaccine failure, but the cause for this re-emergence is not clear. No evidence was found of the emergence of a hypervirulent strain. The re-establishment of continuing surveillance is required to answer the questions raised by this report, and is particularly important in settings like The Gambia, where a booster dose is not given, to determine long-term effects of national immunisation with Hib vaccine. [Copyright &y& Elsevier]

The article presents the results of a study examining the effects of a high-dose vitamin A regimen on maternal and infant plasma vitamin A levels, its role in reducing infant Helicobacter pylori infection, nasopharyngeal pneumococcal carriage, and improving infant gut epithelial integrity. The double-blind, randomized trial enrolled 200 mother and infant pairs from a moderately vitamin A deficient area in rural Gambia. The results did not support the increase in vitamin A dosage and suggest that possible adverse side effects and negative interactions may result with high vitamin A doses. The article recommends that the World Health Organization does not implement the higher doses, as previously suggested.

OBJECTIVE. To compare the enzyme-linked immunospot (ELISPOT) assay with the tuberculin skin test (TST) in children for the diagnosis of Mycobacterium tuberculosis infection in the Gambia. METHODS. We divided child contacts of sputum smear-positive tuberculosis cases into 3 age categories (<5, 5-9, and 10-14 years) and assessed agreement between the 2 tests plus their relationship to prior Bacille Calmette-Guerin (BCG) vaccination. We categorized a child's level of M tuberculosis exposure according to where he/she slept relative to a case: the same room, same house, or a different house. The relationship between exposure and test result was assessed by multiple logistic regression. RESULTS. In child contacts of 287 cases, 225 (32.5%) of 693 were positive by TST and 232 (32.3%) of 718 by ELISPOT. The overall agreement between tests was 83% and the discordance was not significant. Both tests responded to the M tuberculosis exposure gradient in each age category. The percentage of those who were TST positive/ELISPOT negative increased with increasing exposure. At the lowest exposure level, the percentage of ELISPOT-positive children who were TST negative was increased compared with the highest exposure level. Neither test had evidence of false positive results because of BCG. CONCLUSIONS. In Gambian children, the ELISPOT is slightly less sensitive than the TST in the diagnosis of M tuberculosis infection from recent exposure, and neither test is confounded by prior BCG vaccination. Evidence of reduced TST sensitivity in subjects with the lowest known recent M tuberculosis exposure suggests that, when maximal sensitivity is important, the 2 tests may lie best used together. [ABSTRACT FROM AUTHOR]

The article reports on the global health risk presented by pneumococcal disease. 1.6 million people, of whom 1 million are children, die of pneumococcal pneumonia, meningitis, and sepsis each year. People with HIV infection have a risk increased by 20-40%. Antibiotic resistance can make the diseases difficult to treat. Clinical trials show that pneumococcal conjugate vaccines improve child survival. A trial in Gambia showed treatment to reduce mortality from all causes by 16% and to provide from 65-83% protection from infection, depending on HIV status. The article calls for affordable vaccines to be made available to developing countries, where their administration can be worked into the preexisting vaccine system.

Background: The continuing impact of pneumococcal conjugate vaccines (PCVs) in regions with high pneumococcal transmission is threatened by the persistence of vaccine serotypes (VTs) and the emergence of nonvaccine serotypes (NVTs)., Methods: In 2016, we conducted a cross-sectional carriage survey (CSS5) in a community where PCV7 was first introduced in 2006 during a cluster-randomized trial conducted before nationwide introduction of PCV7 (2009) and PCV13 (2011). We estimated prevalence of PCV13 VT and NVT by age and compared these with earlier surveys before (CSS0), during (CSS1-3), and after the trial but before PCV13 (CSS4). Genomic analysis was conducted for the nontypeable pneumococci., Results: Prevalence of PCV13 VT carriage decreased during the 10 years between CSS0 and CSS5 across all age groups (67.6% to 13.5%, P < .001; 59.8% to 14.4%, P < .001; 43.1% to 17.9%, P < .001; and 24.0% to 5.1%, P < .001, in <2, 2-4, 5-14, and ≥15 years, respectively). However, there was no difference between CSS4 and CSS5 in children ≥2 years and adults (children <2 years, no data). The prevalence of PCV13 NVT increased between CSS0 and CSS5 for children <2 years but decreased in older children and adults. In CSS5, serotypes 3, 6A, and 19F were the most common VT and nontypeable isolates were the most common NVT. Among nontypeable isolates, 73.0% lost the ability to express a capsule. Of these, 70.8% were from a VT background., Conclusions: The decrease in PCV13 VT that has occurred since the introduction of PCV13 appears to have plateaued. Significant carriage of these serotypes remains in all age groups., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV7) in August 2009, followed by PCV13 in May, 2011, using a schedule of three primary doses without a booster dose or catch-up immunisation. We aimed to assess the long-term impact of PCV on disease incidence., Methods: We did 10 years of population-based surveillance for invasive pneumococcal disease (IPD) and WHO defined radiological pneumonia with consolidation in rural Gambia. The surveillance population included all Basse Health and Demographic Surveillance System residents aged 2 months or older. Nurses screened all outpatients and inpatients at all health facilities using standardised criteria for referral. Clinicians then applied criteria for patient investigation. We defined IPD as a compatible illness with isolation of Streptococcus pneumoniae from a normally sterile site (cerebrospinal fluid, blood, or pleural fluid). We compared disease incidence between baseline (May 12, 2008-May 11, 2010) and post-vaccine years (2016-2017), in children aged 2 months to 14 years, adjusting for changes in case ascertainment over time., Findings: We identified 22 728 patients for investigation and detected 342 cases of IPD and 2623 cases of radiological pneumonia. Among children aged 2-59 months, IPD incidence declined from 184 cases per 100 000 person-years to 38 cases per 100 000 person-years, an 80% reduction (95% CI 69-87). Non-pneumococcal bacteraemia incidence did not change significantly over time (incidence rate ratio 0·88; 95% CI, 0·64-1·21). We detected zero cases of vaccine-type IPD in the 2-11 month age group in 2016-17. Incidence of radiological pneumonia decreased by 33% (95% CI 24-40), from 10·5 to 7·0 per 1000 person-years in the 2-59 month age group, while pneumonia hospitalisations declined by 27% (95% CI 22-31). In the 5-14 year age group, IPD incidence declined by 69% (95% CI -28 to 91) and radiological pneumonia by 27% (95% CI -5 to 49)., Interpretation: Routine introduction of PCV13 substantially reduced the incidence of childhood IPD and pneumonia in rural Gambia, including elimination of vaccine-type IPD in infants. Other low-income countries can expect substantial impact from the introduction of PCV13 using a schedule of three primary doses., Funding: Gavi, The Vaccine Alliance; Bill & Melinda Gates Foundation; UK Medical Research Council; Pfizer Ltd., Competing Interests: Declaration of interests RA was employed by GlaxoSmithKline Vaccines and received grant awards from WHO, Gavi, and the Bill & Melinda Gates Foundation whilst employed at MRC Gambia. MK, SH, and BG received grants from the Bill & Melinda Gates Foundation. MK received grants from Gavi, Merck, and Pfizer, and personal fees from Pfizer. All other authors declare no competing interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Enteroaggregative Escherichia coli (EAEC) cause acute and persistent diarrhea, mostly in children worldwide. Outbreaks of diarrhea caused by EAEC have been described, including a large outbreak caused by a Shiga toxin expressing strain. This study investigated the association of EAEC virulence factors with diarrhea in children less than 5 years. We characterized 428 EAEC strains isolated from stool samples obtained from moderate-to-severe diarrhea cases (157) and healthy controls (217) children aged 0-59 months recruited over 3 years as part of the Global Enteric Multicenter Study (GEMS) in The Gambia. Four sets of multiplex polymerase chain reaction were applied to detect 21 EAEC-virulence genes from confirmed EAEC strains that target pCVD432 (aatA) and AAIC (aaiC). In addition, Kirby-Bauer disc diffusion antimicrobial susceptibility testing was performed on 88 EAEC strains following Clinical Laboratory Standard Institute guidelines. We observed that the plasmid-encoded enterotoxin [odds ratio (OR): 6.9, 95% confidence interval (CI): 2.06-29.20, P < 0.001], aggregative adherence fimbriae/I fimbriae (aggA) [OR: 2.2, 95% CI: 1.16-4.29, P = 0.008], and hexosyltransferase (capU) [OR: 1.9, 95% CI 1.02-3.51, P = 0.028] were associated with moderate-to-severe diarrhea among children < 12 months old but not in the older age strata (> 12 months). Our data suggest that some EAEC-virulent factors have age-specific associations with moderate-to-severe diarrhea in infants. Furthermore, our study showed that 85% and 72% of EAEC strains tested were resistant to sulphamethoxazole-trimethoprim and ampicillin, respectively. Sulphamethoxazole-trimethoprim and ampicillin are among the first-line antibiotics used for the treatment of diarrhea in The Gambia.

Molecular analyses of lung aspirates from Gambian children with severe pneumonia detected pathogens more frequently than did culture and showed a predominance of bacteria, principally Streptococcus pneumoniae, >75% being of serotypes covered by current pneumococcal conjugate vaccines. Multiple pathogens were detected frequently, notably Haemophilus influenzae (mostly nontypeable) together with S. pneumoniae., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Objective: Haemophilus influenzae type b (Hib) conjugate vaccine was first introduced in Africa in The Gambia in 1997 as a primary 3-dose course in infancy with no booster, and was followed by the disappearance of invasive Hib disease by 2002. A cluster of cases detected non-systematically in post-infant children in 2005-2006 raised the question of the need for a booster dose. The objective of this study was to determine the incidence of invasive Hib disease in Gambian children 14 years after the introduction of Hib conjugate vaccine., Study Design: This hospital-based clinical and microbiological Hib disease surveillance in 3 hospitals in the western region of The Gambia was undertaken between October 2007 and December 2010 applying the same methods used in a previous Hib vaccine effectiveness study in 1997-2002., Results: The annual incidences of Hib meningitis and all invasive Hib disease in children aged <5 years remained below 5 cases per 100,000 children during 2008-2010. The median age of patients with any invasive Hib disease was 5 months., Conclusion: Hib conjugate vaccination as a primary 3-dose course in The Gambia remains highly effective in controlling invasive Hib disease, and current data do not support the introduction of a booster dose., (Copyright © 2013. Published by Mosby, Inc.)

Helicobacter pylori is a globally important and genetically diverse gastric pathogen that infects most people in developing countries. Eradication efforts are complicated by antibiotic resistance, which varies in frequency geographically. There are very few data on resistance in African strains. Sixty-four Gambian H. pylori strains were tested for antibiotic susceptibility. The role of rdxA in metronidazole (Mtz) susceptibility was tested by DNA transformation and sequencing; RdxA protein variants were interpreted in terms of RdxA structure. Forty-four strains (69%) were resistant to at least 8 μg of Mtz/ml. All six strains from infants, but only 24% of strains from adults, were sensitive (P = 0.0031). Representative Mtz-resistant (Mtz(r)) strains were rendered Mtz susceptible (Mtz(s)) by transformation with a functional rdxA gene; conversely, Mtz(s) strains were rendered Mtz(r) by rdxA inactivation. Many mutations were found by Gambian H. pylori rdxA sequencing; mutations that probably inactivated rdxA in Mtz(r) strains were identified and explained using RdxA protein's structure. All of the strains were sensitive to clarithromycin and erythromycin. Amoxicillin and tetracycline resistance was rare. Sequence analysis indicated that most tetracycline resistance, when found, was not due to 16S rRNA gene mutations. These data suggest caution in the use of Mtz-based therapies in The Gambia. The increasing use of macrolides against respiratory infections in The Gambia calls for continued antibiotic susceptibility monitoring. The rich variety of rdxA mutations that we found will be useful in further structure-function studies of RdxA, the enzyme responsible for Mtz susceptibility in this important pathogen.

Rationale: Biomarkers that can be used to evaluate new interventions against latent tuberculosis infection (LTBI) and predict reactivation TB disease are urgently required., Objectives: To evaluate ESAT-6 and CFP-10 (EC) IFN-γ ELISPOT as a biomarker for treatment efficacy in LTBI., Methods: This was a randomized, blinded, and placebo-controlled trial of INH in EC ELISPOT and Mantoux test positive participants., Measurements and Main Results: Participants received a 6-month course of 900 mg INH twice weekly or a matching placebo. INH acetylator genotypes were determined and urine tested for INH metabolites to confirm adherence. The proportion of positive responders for CFP-10 and ESAT-6 between treatment arms was compared using mixed effects logistic regression models. A Tweedie (compound Poisson) model was fitted to allow for zero inflation and overdispersion of quantitative response. The proportions of EC ELISPOT-positive subjects reduced over time (P < 0.001) but did not differ by study arm (P = 0.36). Median spot-forming units for ESAT-6 and CFP-10 also declined significantly with time (P < 0.001) but did not differ by study arm (P = 0.74 and 0.71, respectively). There was no evidence of an interaction between acetylator status and INH treatment with respect to ELISPOT results over time., Conclusions: In contacts with LTBI, INH therapy plays no role in observed decreases in Mycobacterium tuberculosis antigen-specific T-cell responses over time. IFN-γ ELISPOT is probably not a useful biomarker of treatment efficacy in LTBI. Clinical trial registered with www.clinicaltrials.gov (NCT 00130325).

Background: Gambian infants frequently acquire Streptococcus pneumoniae soon after birth. We investigated the indirect effect of 7-valent pneumococcal conjugate vaccine (PCV-7) on pneumococcal acquisition in newborn Gambian babies., Methods: Twenty-one villages were randomised to receive PCV-7 to all subjects (11 vaccinated villages) or to infants aged 2-30 months (10 control villages). Other control villagers received Meningococcal C conjugate vaccine. From 328 babies born during the trial, nasopharyngeal swabs were collected after birth, then weekly until 8 weeks of age when they received their first dose of PCV-7. Pneumococcal carriage and acquisition rates were compared between the study arms and with a baseline study., Results: 57.4% of 2245 swabs were positive for S. pneumoniae. Overall carriage was similar in both arms. In vaccinated villages fewer infants carried pneumococci of vaccine serotypes (VT) (16.9% [31/184] vs. 37.5% [54/144], p<0.001) and more carried pneumococci of non-vaccine serotypes (NVT) (80.9% [149/184] vs. 75.7% [109/144], p = 0.246). Infants from vaccinated villages had a significantly lower acquisition rate of VT (HR 0.39 [0.26-0.58], p<0.001) and increased acquisition of NVT (HR 1.16 [0.87-1.56], p = 0.312). VT carriage (51.6% vs. 37.5%, p = 031 in control and 46.1% vs. 16.8%, p<0.001 in vaccinated villages) and acquisition rates (HR 0.68 [0.50-0.92], p = 0.013 in control villages and HR 0.31 [0.19-0.50], p<.001 in vaccinated villages) were significantly lower in both study arms than in the baseline study. NVT carriage (63.2% vs. 75.7%, p = 0.037 in control and 67.2% vs. 75.3%, p = 0.005 in vaccinated villages) and acquisition rates (HR 1.48 [1.06-2.06], p = 0.022) and (HR 1.52 [1.11-2.10], p = 0.010 respectively) were significantly higher., Conclusion: PCV-7 significantly reduced carriage of VT pneumococci in unvaccinated infants. This indirect effect likely originated from both the child and adult vaccinated populations. Increased carriage of NVT pneumococci needs ongoing monitoring., Trial Registration: ISRCTN Register 51695599.