Impact of intra-partum azithromycin on carriage of group A streptococcus in the Gambia: a posthoc analysis of a double-blind randomized placebo-controlled trial.

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.

Stillbirths, Neonatal Morbidity, and Mortality in Health-Facility Deliveries in Urban Gambia.

The Gambia Demographic and Health Survey 2013 data showed that up to 63% of deliveries in the country occur in health facilities. Despite such a high rate, there are few facility-based studies on delivery outcomes in the country. This analysis ancillary to a randomized control trial describes occurrence of poor pregnancy outcomes in a cohort of women and their infants delivering in a government health facility in urban Gambia.

Declines in Pediatric Bacterial Meningitis in the Republic of Benin Following Introduction of Pneumococcal Conjugate Vaccine: Epidemiological and Etiological Findings, 2011-2016.

Background: Pediatric bacterial meningitis (PBM) remains an important cause of disease in children in Africa. We describe findings from sentinel site bacterial meningitis surveillance in children <5 years of age in the Republic of Benin, 2011-2016.

Methods: Cerebrospinal fluid (CSF) was collected from children admitted to Parakou, Natitingou, and Tanguieta sentinel hospitals with suspected meningitis.

Long-lasting effect of oral azithromycin taken by women during labour on infant nutrition: Follow-up cohort of a randomized clinical trial in western Gambia.

Objective: To assess the effect of administering an oral dose of 2g of azithromycin in Gambian women during labour on infant growth.

Methods: Children whose mothers had been randomized to receive either an oral dose of 2g of azithromycin or placebo during labour were visited at home at the end of infancy by trained study nurses blind to the treatment allocation. The follow-up visit of these cohorts (exposed and non-exposed to azithromycin), which was not part of the original trial design, was conducted between November 2014 and May 2015 when the infants were 11 to 13 months of age.

Zinc as an adjunct therapy in the management of severe pneumonia among Gambian children: randomized controlled trial.

Background: The benefit of zinc as an adjunct therapy for severe pneumonia is not established. We assessed the benefit of adjunct zinc therapy for severe pneumonia in children and determined whether the study children were zinc deficient.

Methods: This was a randomized, parallel group, double-blind, placebo-controlled trial with an allocation ratio of 1:1 conducted in children with severe pneumonia to evaluate the efficacy of daily zinc as an adjunct treatment in preventing 'treatment failure' (presence of any sign of severe pneumonia) on day-5 and day-10 and in reducing the time to resolution of signs of severe pneumonia.

Long-term Impact of Oral Azithromycin Taken by Gambian Women During Labor on Prevalence and Antibiotic Susceptibility of Streptococcus pneumoniae and Staphylococcus aureus in Their Infants: Follow-up of a Randomized Clinical Trial.

Background: Oral azithromycin given to women in labor decreases maternal and neonatal bacterial carriage but increases azithromycin-resistant bacteria during at least 4 weeks following the intervention. We assessed the prevalence of bacterial carriage and azithromycin resistance 12 months after treatment among study infants.

Methods: Nasopharyngeal swabs (NPSs) were collected between November 2014 and May 2015 from children aged 11-13 months whose mothers had received azithromycin or placebo during labor.

Does azithromycin given to women in labour decrease ocular bacterial infection in neonates? A double-blind, randomized trial.

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.

Maternal pneumococcal nasopharyngeal carriage and risk factors for neonatal carriage after the introduction of pneumococcal conjugate vaccines in The Gambia.

Objectives: Pneumococcal nasopharyngeal carriage occurs early in life. However, the role of vertical transmission is not well understood. The aims of this study were to describe carriage among mothers and their newborns, and to assess for risk factors for neonatal carriage.

Standardized Interpretation of Chest Radiographs in Cases of Pediatric Pneumonia From the PERCH Study.

Background.: Chest radiographs (CXRs) are a valuable diagnostic tool in epidemiologic studies of pneumonia. The World Health Organization (WHO) methodology for the interpretation of pediatric CXRs has not been evaluated beyond its intended application as an endpoint measure for bacterial vaccine trials.

Maternal colonization with Staphylococcus aureus and Group B streptococcus is associated with colonization in newborns.

Objectives: Although Staphylococcus aureus and Group B streptococcus (GBS) are major causes of neonatal sepsis in sub-Saharan Africa, it is unclear how these bacteria are transmitted to the neonate.

Methods: In a cohort of 377 Gambian women and their newborns, nasopharyngeal swabs were collected at delivery (day 0), and 3, 6, 14 and 28 days later. Breast milk samples and vaginal swabs were collected from the mother.

Azithromycin in Labor Lowers Clinical Infections in Mothers and Newborns: A Double-Blind Trial.

Background And Objectives: We have recently completed a proof-of-concept trial showing that bacterial colonization decreased in women and newborns after the administration of azithromycin during labor. Here, we aim to assess the effect of the intervention on maternal and neonatal clinical infections.

Methods: This was a double-blind, placebo-controlled randomized trial.

Childhood pneumonia and crowding, bed-sharing and nutrition: a case-control study from The Gambia.

Setting: Greater Banjul and Upper River Regions, The Gambia.

Objective: To investigate tractable social, environmental and nutritional risk factors for childhood pneumonia.

Design: A case-control study examining the association of crowding, household air pollution (HAP) and nutritional factors with pneumonia was undertaken in children aged 2-59 months: 458 children with severe pneumonia, defined according to the modified WHO criteria, were compared with 322 children with non-severe pneumonia, and these groups were compared to 801 neighbourhood controls.

Oral azithromycin given during labour decreases bacterial carriage in the mothers and their offspring: a double-blind randomized trial.

Bacterial sepsis remains a leading cause of death among neonates with Staphylococcus aureus, group B streptococcus (GBS) and Streptococcus pneumoniae identified as the most common causative pathogens in Africa. Asymptomatic bacterial colonization is an intermediate step towards sepsis. We conducted a phase III, double-blind, placebo-controlled randomized trial to determine the impact of giving one oral dose of azithromycin to Gambian women in labour on the nasopharyngeal carriage of S.

Pharmacokinetics of Transfer of Azithromycin into the Breast Milk of African Mothers.

Azithromycin (AZI) is used for its antibiotic and antimalarial properties in pregnancy. Reported estimates of AZI breast milk transfer, based on concentrations in mostly single samples from small numbers of women, have suggested that infant intake is safe. To better characterize infant intake and the associated potential benefits and risks, AZI was measured by liquid chromatography-mass spectrometry in four breast milk samples taken over 28 days postpartum from each of 20 Gambian women given 2 g AZI during labor.

Prevention of bacterial infections in the newborn by pre-delivery administration of azithromycin: Study protocol of a randomized efficacy trial.

Background: Neonatal deaths, estimated at approximately 4 million annually, now account for almost 40% of global mortality in children aged under-five. Bacterial sepsis is a leading cause of neonatal mortality. Assuming the mother is the main source for bacterial transmission to newborns, the primary objective of the trial is to determine the impact of one oral dose of azithromycin, given to women in labour, on the newborn's bacterial carriage in the nasopharynx.

Etiology of severe childhood pneumonia in the Gambia, West Africa, determined by conventional and molecular microbiological analyses of lung and pleural aspirate samples.

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.

Discovery and validation of biomarkers to guide clinical management of pneumonia in African children.

Background: Pneumonia is the leading cause of death in children globally. Clinical algorithms remain suboptimal for distinguishing severe pneumonia from other causes of respiratory distress such as malaria or distinguishing bacterial pneumonia and pneumonia from others causes, such as viruses. Molecular tools could improve diagnosis and management.

The effectiveness of conjugate Haemophilus influenzae type B vaccine in The Gambia 14 years after introduction.

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.

Incidence of Haemophilus influenzae type b disease in The Gambia 14 years after introduction of routine Haemophilus influenzae type b conjugate vaccine immunization.

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.

The exposure of infants and children to carbon monoxide from biomass fuels in The Gambia: a measurement and modeling study.

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.

Effects of community-wide vaccination with PCV-7 on pneumococcal nasopharyngeal carriage in the Gambia: a cluster-randomized trial.

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.

Antibody and T-cell responses during acute and convalescent stages of invasive pneumococcal disease.

Objective: To understand the pattern of immune responses to pneumococcal proteins during invasive disease as a guide to their development as vaccine candidates.

Methods: The antibody concentration and avidity, as well as frequency of interferon-gamma (IFN-γ)-, interleukin-10 (IL-10)-, and tumor necrosis factor-alpha (TNF-α)-containing CD4+ T-lymphocytes in response to pneumolysin, pneumococcal surface protein A (PspA), and choline-binding protein A (CbpA), during and after invasive pneumococcal disease (IPD) in 20 children were compared to those of 20 healthy matched controls.

Results: During the acute phase of IPD, the concentrations of antibodies against these three pneumococcal proteins were lower, whereas the frequencies of IL-10- and TNF-α-producing CD4+ T-cells were higher, compared to values obtained during convalescence and in healthy controls (p < 0.

Exogenous re-infection by a novel Streptococcus pneumoniae serotype 14 as a cause of recurrent meningitis in a child from The Gambia.

We report a case of an infant who experienced exogenous re-infection of Streptococcus pneumoniae serotype 14 as a cause of recurrent meningitis after apparently successful antibiotic treatment with ceftriaxone. eBURST analysis revealed that isolates from the two episodes of meningitis belonged to hypervirulent ST63 and ST3321 clonal complexes respectively.

Molecular epidemiology of pneumococci obtained from Gambian children aged 2-29 months with invasive pneumococcal disease during a trial of a 9-valent pneumococcal conjugate vaccine.

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.

Immunogenicity and serotype-specific efficacy of a 9-valent pneumococcal conjugate vaccine (PCV-9) determined during an efficacy trial in The Gambia.

This study aimed to determine the immunogenicity of a 9-valent pneumococcal conjugate vaccine (PCV-9) in a subgroup of Gambian children enrolled in a large vaccine efficacy trial. To place the antibody results in context, in this paper we also report previously unpublished data on serotype-specific clinical vaccine efficacy from the main trial. In the sub-study, a single 2-4 ml venous blood specimen was collected from 212 Gambian children 4-6 weeks after the administration of a third dose of PCV-9 or placebo.