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Staphylococcus aureus is a major cause of neonatal infections in various anatomical sites, resulting in high morbidity and mortality in The Gambia. These clinical infections are often preceded by nasal carriage of S. aureus , a known risk factor. To determine whether potential sources of newborn S. aureus infections were from carriage, and to characterize S. aureus present in different anatomical sites (blood, ear, eye, umbilical cord, skin, pus, oropharynx, breast milk and vagina), we performed whole-genome sequencing of 172 isolates from clinical sites as well as from healthy and unhealthy carriage. A random selection of mothers ( n  = 90) and newborns ( n  = 42) participating in a clinical trial and testing positive for S. aureus were considered for this study. Sequence data were analyzed to determine S. aureus multilocus sequence types and selected antimicrobial and virulence gene profiles. Our findings revealed that in The Gambia, ST15 is the dominant sequence type associated with both carriage and clinical infection. In addition, S. aureus isolates causing clinical infection among neonates were genetically similar to those colonizing their oropharynx, and the different anatomical sites were not found to be uniquely colonized by S. aureus of a single genomic profile. Furthermore, while S. aureus associated with clinical infection had similar antimicrobial resistance gene profiles to carriage isolates, only hemolysin and adhesive factor virulence genes were significantly higher among clinical isolates. In conclusion, this study confirmed S. aureus oropharyngeal colonization among neonates as a potential source of clinical infection in The Gambia. Hence, interventions aiming to reduce neonatal clinical infections in The Gambia should consider decreasing oropharyngeal S. aureus carriage. Trial registration The trial was registered at ClinicalTrials.gov NCT03199547.

•Pneumococcal protein antigens could provide serotype-independent protection.•Two PHiD-CV/dPly/PhtD vaccine formulations were assessed in healthy infants.•Both protein-based vaccines elicited immune responses to pneumococcal proteins.•The vaccines had no impact on pneumococcal nasopharyngeal carriage prevalence.•Future evaluations will assess their impact against pneumococcal disease endpoints. Conserved pneumococcal proteins are potential candidates for inclusion in vaccines against pneumococcal diseases. In the first part of a two-part study, an investigational vaccine (PHiD-CV/dPly/PhtD-30) containing 10 pneumococcal serotype-specific polysaccharide conjugates (10VT) combined with pneumolysin toxoid and pneumococcal histidine triad protein D (30μg each) was well tolerated by Gambian children. Part two, presented here, assessed the efficacy of two PHiD-CV/dPly/PhtD formulations against pneumococcal nasopharyngeal carriage (NPC) prevalence in infants. In this phase 2, randomized, controlled, observer-blind trial, healthy infants aged 8–10weeks, recruited from a peri-urban health center, were randomized (1:1:1:1:1:1) into six groups. Four groups received PHiD-CV/dPly/PhtD (10 or 30μg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine at ages 2–3–4months (3+0 infant schedule) and two groups PHiD-CV/dPly/PhtD-30 or PHiD-CV at 2–4–9months (2+1 infant schedule). The primary objective was impact on non-10VT NPC at ages 5–9–12months. Secondary objectives included confirmatory analysis of protein dose superiority and safety/reactogenicity. Impact on pneumococcal NPC acquisition, bacterial load, and ply and phtD gene sequencing were explored. 1200 infants were enrolled between June 2011 and May 2012. Prevalences of pneumococcal (60–67%) and non-10VT (55–61%) NPC were high at baseline. Across all post-vaccination time points, efficacy of PHiD-CV/dPly/PhtD-10 and PHiD-CV/dPly/PhtD-30 against non-10VT NPC (3+0 schedule) was 1.1% (95% CI −21.5, 19.5) and 2.1% (−20.3, 20.3), respectively; efficacy of PHiD-CV/dPly/PhtD-30 (2+1 schedule) was 0.5% (−22.1, 18.9) versus PHiD-CV. No differences were observed in pneumococcal NPC acquisition, clearance, or bacterial load. Both protein-based vaccines elicited immune responses to pneumococcal proteins. In this high carriage prevalence setting, inclusion of pneumococcal proteins in the PHiD-CV/dPly/PhtD investigational vaccine had no impact on pneumococcal NPC in infants, regardless of protein dose or schedule. Future evaluations will assess its impact against pneumococcal disease endpoints. Funding: PATH, GlaxoSmithKline Biologicals SA. ClinicalTrials.gov identifier NCT01262872.

The SARS-CoV-2 disease, first detected in Wuhan, China, in December 2019 has become a global pandemic and is causing an unprecedented burden on health care systems and the economy globally. While the travel history of index cases may suggest the origin of infection, phylogenetic analysis of isolated strains from these cases and contacts will increase the understanding and link between local transmission and other global populations. The objective of this analysis was to provide genomic data on the first six cases of SARS-CoV-2 in The Gambia and to determine the source of infection. This ultimately provide baseline data for subsequent local transmission and contribute genomic diversity information towards local and global data. Our analysis has shown that the SARS-CoV-2 virus identified in The Gambia are of European and Asian origin and sequenced data matched patients’ travel history. In addition, we were able to show that two COVID-19 positive cases travelling in the same flight had different strains of SARS-CoV-2. Although whole genome sequencing (WGS) data is still limited in sub-Saharan Africa, this approach has proven to be a highly sensitive, specific and confirmatory tool for SARS-CoV-2 detection.

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. 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. 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. Please see later in the article for the Editors' Summary.

Climate variability has had major health consequences for both humans and animals. A cross-sectional study was conducted in six administrative regions of The Gambia to respond to three questions: (i) what are the livestock farmers' perceived occurrences and causes of climate variability? (ii) what are the perceived impacts of climate variability on livestock farming? (iii) what factors influence livestock farmers' knowledge and perception of the causes and impact of climate variability? A total of 440 livestock farmers comprising 351 (80%) males and 89 (20%) females were interviewed and 6 Focus Group Discussions were held. The data were analysed using descriptive statistics, Pearson's chi-squares test and Binary logistic regression. Livestock farmers are aware of the causes and effects of climate variability on their productivity. Climate variability caused cattle farmers to have production issues, and as a result, this investigation also reveals the impact on their productivity. Finally, the result also shows that the explanatory variables (age and region of residence) were the main factors significantly influencing livestock farmers' perception of climate variability. There is need for the government of The Gambia to address the challenges faced by livestock farmers due to climate variability.

Background Group A Streptococcus (GAS) is a major human pathogen and an important cause of maternal and neonatal sepsis. Asymptomatic bacterial colonization is considered a necessary step towards sepsis. Intra-partum azithromycin may reduce GAS carriage. Methods A posthoc analysis of a double-blind, placebo-controlled randomized-trial was performed to determine the impact of 2 g oral dose of intra-partum azithromycin on maternal and neonatal GAS carriage and antibiotic resistance. Following screening, 829 mothers were randomized who delivered 843 babies. GAS was determined by obtaining samples from the maternal and newborn nasopharynx, maternal vaginal tract and breastmilk. Whole Genome Sequencing (WGS) of GAS isolates was performed using the Illumina Miseq platform. Results GAS carriage was lower in the nasopharynx of both mothers and babies and breast milk among participants in the azithromycin arm. No differences in GAS carriage were found between groups in the vaginal tract. The occurrence of azithromycin-resistant GAS was similar in both arms, except for a higher prevalence in the vaginal tract among women in the azithromycin arm. WGS revealed all macrolide-resistant vaginal tract isolates from the azithromycin arm were Streptococcus dysgalactiae subspecies equisimilis expressing Lancefield group A carbohydrate (SDSE(A)) harbouring macrolide resistant genes msr(D) and mef(A) . Ten of the 45 GAS isolates (22.2%) were SDSE(A). Conclusions Oral intra-partum azithromycin reduced GAS carriage among Gambian mothers and neonates however carriage in the maternal vaginal tract was not affected by the intervention due to azithromycin resistant SDSE(A). SDSE(A) resistance must be closely monitored to fully assess the public health impact of intrapartum azithromycin on GAS. Trial registration ClinicalTrials.gov Identifier NCT01800942

Introduction of pneumococcal vaccines in Nigeria is a priority as part of the Accelerated Vaccine Introduction Initiative (AVI) of the Global Alliance for Vaccines and Immunisation (GAVI). However, country data on the burden of pneumococcal disease (IPD) is limited and coverage by available conjugate vaccines is unknown. This study was carried out to describe the pre vaccination epidemiology and population biology of pneumococcal carriage in Nigeria. This was a cross sectional survey. Nasopharyngeal swabs (NPS) were obtained from a population sample in 14 contiguous peri-urban Nigerian communities. Data on demographic characteristics and risk factor for carriage were obtained from all study participants. Pneumococci isolated from NPS were characterised by serotyping, antimicrobial susceptibility and Multi Locus Sequencing Typing (MLST). The prevalence of pneumococcal carriage was 52.5%. Carriage was higher in children compared to adults (67.4% vs. 26%), highest (≈90%) in infants aged <9 months and reduced significantly with increasing age (P<0.001). Serotypes 19F (18.6%) and 6A (14.4%) were most predominant. Potential vaccine coverage was 43.8%, 45.0% and 62% for PCV-7, PCV-10 and PCV-13 respectively. There were 16 novel alleles, 72 different sequence types (STs) from the isolates and 3 Sequence Types (280, 310 and 5543) were associated with isolates of more than one serotype indicative of serotype switching. Antimicrobial resistance was high for cotrimoxazole (93%) and tetracycline (84%), a third of isolates had intermediate resistance to penicillin. Young age was the only risk factor significantly associated with carriage. Pneumococcal carriage and serotype diversity is highly prevalent in Nigeria especially in infants. Based on the coverage of serotypes in this study, PCV-13 is the obvious choice to reduce disease burden and prevalence of drug resistant pneumococci. However, its use will require careful monitoring. Our findings provide sound baseline data for impact assessment following vaccine introduction in Nigeria.

We conducted an ancillary study among individuals who had participated in a PCV-7 trial in rural Gambia, to determine the influence of season on the prevalence of pneumococcal carriage. 636 individuals above 30 months of age were followed from 4 to 20 months after vaccination with PCV-7 or meningococcal-conjugate-vaccine. Nasopharyngeal swabs were collected periodically between November 2006 and June 2008. Overall, 4,495 NPS were collected. Prevalence of pneumococcal nasopharyngeal carriage in the study subjects (median age 11 years) was 55.0%; this prevalence decreased linearly with increasing age (p = 0.001). Prevalence of carriage was significantly higher during the dry than the rainy season for any pneumococcal carriage [57.6% versus 47.8% (p<0.001)], pneumococcal vaccine serotype carriage [10.3% versus 6.5% (p< 0.001)] and non-vaccine serotype carriage [49.7% versus 42.7% (p<0.001)]. Differences remained significant in the adjusted analysis. In areas of Africa with marked variation in rainfall, seasonality of pneumococcal carriage needs to be considered when interpreting carriage data.

Background Vertical transmission can result in neonatal infection and disease. Reducing the transmission of bacterial pathogens from mother to infant may be an effective means of preventing neonatal infection, including bacterial conjunctivitis. Methods In a double-blind, randomized trial, we assessed the effect of administering a single dose of oral azithromycin to women in labour on bacterial colonization of the neonate. A reduction in purulent neonatal conjunctivitis was a secondary objective of the trial. Ocular samples were collected from the lower fornix of infants presenting with clinical signs of purulent conjunctivitis during the first eight weeks of life. Incidence of purulent conjunctivitis was compared between trial arms. Bacterial infection was assessed using PCR and incidence of purulent conjunctivitis due to bacteria was also compared between arms. Results Forty of 843 infants (4.7%) presented clinical signs of purulent conjunctivitis. No significant difference in incidence of purulent conjunctivitis was seen between azithromycin and placebo arms [4.3% (18/419) versus 5.2% (22/424), OR = 0.82, 95% CI (0.44,1.54), p  = 0.628]. S. aureus was the most commonly identified pathogen, detected in 38% of cases. Incidence of purulent-conjunctivitis due to bacterial infection was lower in the azithromycin arm [1.2% (5/419) versus 3.8% (16/424), OR = 0.31, 95% CI (0.12–0.82), p  = 0.025)]. The incidence of gram-positive bacteria was also lower in the azithromycin arm [1.0% (4/419) versus 3.3% (14/424), OR = 0.28, 95%CI (0.10–0.82), p  = 0.029]. Conclusions Oral azithromycin given to women during labour may have the potential to reduce the incidence of bacterial neonatal conjunctivitis. Trial registration ClinicalTrials.gov, identifier NCT01800942 , registration date 26 Feb 2013.

CRM- based pneumococcal conjugate vaccines generally have little impact on the overall prevalence of pneumococcal carriage because of serotype replacement. In contrast, protein vaccines could substantially reduce the overall prevalence of pneumococcal carriage with potential microbiological and clinical consequences. Therefore, trials of pneumococcal protein vaccines need to evaluate their impact on carriage of other potentially pathogenic bacteria in addition to the pneumococcus. As a prelude to a trial of an investigational pneumococcal vaccine containing pneumococcal polysaccharide conjugates and pneumococcal proteins, the prevalence of carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella species and Staphylococcus aureus in the nasopharynx of 1030 Gambian infants (median age 35 weeks) was determined. An oropharyngeal swab was obtained at the same time from the first 371 infants enrolled. Standard microbiological techniques were used to evaluate the bacterial flora of the pharynx and to compare that found in the oropharynx and in the nasopharynx. The overall pneumococcal carriage rate was high. Isolation rates of S. pneumoniae and Moraxella species were significantly higher using nasopharyngeal rather than oropharyngeal swabs (76.1% [95% CI 73.4%,78.7%] vs. 21.3% [95% CI 17.2%,25.8%] and 48.9% [95% CI 45.8%, 52.0%] vs. 20.5% % [95% CI 16.5%,25.0%] respectively). In contrast, S. aureus and H. influenzae were isolated more frequently from oropharyngeal than from nasopharyngeal swabs (65.0% [95% CI 59.9%, 69.8%] vs. 33.6% [95% CI 30.7%, 36.5%] and 31.8% [95% CI 16.5%, 25.0%] vs. 22.4% [95% CI 19.9%, 25.1%] respectively). No group A β haemolytic streptococci were isolated. Collection of an oropharyngeal swab in addition to a nasopharyngeal swab will provide little additional information on the impact of a novel pneumococcal vaccine on pneumococcal carriage but it might provide additional, valuable information on the impact of the vaccine on the overall microbiota of the pharynx.