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Diarrheal disease contributes substantially to illness and death in children in low-income countries (1,2). Recent investigations of enteric illness have shown many cases with >1 pathogen identified (3-5). The paradigm [...]

Meningococcal disease is endemic to the African 'meningitis belt'; outbreaks occur regularly (1,2). Neisseria meningitidis serogroup A causes most (80%) cases. However, during 2002-2003, serogroup W135 caused a major epidemic [...]

Introduction and Rationale The introduction of routine immunisation with pneumococcal conjugate vaccines (PCVs) in developing countries is expected to significantly reduce childhood deaths [1]. The 7-valent pneumococcal conjugate vaccine (PCV-7), [...]

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]

Background: Shigella is a major cause of diarrhea in young children worldwide. Multiple vaccines targeting Shigella are in development, and phase 3 clinical trials are imminent to determine efficacy against shigellosis., Methods: The Enterics for Global Health (EFGH) Shigella surveillance study is designed to determine the incidence of medically attended shigellosis in 6- to 35-month-old children in 7 resource-limited settings. Here, we describe the microbiological methods used to isolate and identify Shigella . We developed a standardized laboratory protocol for isolation and identification of Shigella by culture. This protocol was implemented across all 7 sites, ensuring consistency and comparability of results. Secondary objectives of the study are to determine the antibiotic resistance profiles of Shigella , compare isolation of Shigella from rectal swabs versus whole stool, and compare isolation of Shigella following transport of rectal swabs in Cary-Blair versus a modified buffered glycerol saline transport medium., Conclusions: Data generated from EFGH using culture methods described herein can potentially be used for microbiological endpoints in future phase 3 clinical trials to evaluate vaccines against shigellosis and for other clinical and public health studies focused on these organisms., Competing Interests: Potential conflicts of interest. All authors: No potential conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Enteropathogenic Escherichia coli (EPEC) and Shigella are etiologic agents of diarrhea in children <5 years old living in resource-poor countries. Repeated bouts of infection lead to lifelong morbidity and even death. The goal of this study was to characterize local mucosal immune responses in Shigella - and EPEC-infected children <5 years of age with moderate to severe diarrhea (MSD) enrolled in the Global Enteric Multicenter Study (GEMS). We hypothesized that infection with each of these pathogens would induce distinct gut mucosal immune profiles indicative of disease etiology and severity. To test this hypothesis, innate and adaptive immune markers were measured in stools from children with diarrhea due to EPEC, Shigella , or other organisms and in children who had no diarrhea. Shigella- positive diarrhea evoked robust proinflammatory and T H 1/T H 2 cytokine responses compared to diarrhea caused by EPEC or other organisms, with the exception of interleukin 5 (IL-5), which was associated with EPEC infection. The presence of IL-1β, IL-4, IL-16, and tumor necrosis factor beta (TNF-β) was associated with the absence of dysentery. EPEC-positive diarrhea evoked high levels of IL-1β, vascular endothelial growth factor (VEGF), and IL-10. Granulocyte-macrophage colony-stimulating factor (GM-CSF) had opposing roles in disease severity, being associated with absence of diarrhea in EPEC-infected children and with dysenteric Shigella infection. High levels of antigen-specific antibodies were detected in the controls and children with Shigella without dysentery, which suggests a protective role against severe disease. In summary, this study identified distinct local immune responses associated with two clinically relevant diarrheagenic pathogens, Shigella and EPEC, in children and identified protective immune phenotypes that can inform the development of preventive measures. IMPORTANCE Shigella and enteropathogenic Escherichia coli are primary agents of moderate to severe diarrhea in children <5 years of age living in resource-poor countries. Repeated bouts of illness lead to lifelong health impairment and even death. Aiming to understand the local host immunity to these pathogens in relation to disease prognosis and to identify prophylaxis and therapeutic targets, we investigated innate and adaptive immune profiles in stools from children infected with EPEC with and without diarrhea, Shigella with and without dysentery, and controls in well characterized clinical samples obtained during the Global Enteric Multicenter Study. For the first time, we report pathogen-specific mucosal immune profiles associated with severity or absence of disease in children <5 years of age that can inform prevention and treatment efforts.

Purpose: Trachoma is the leading infectious cause of blindness worldwide. Conjunctival scarring is initiated by recurrent Chlamydia trachomatis infection. However, disease progression to trichiasis occurs even in regions where chlamydial prevalence is currently low, which suggests that other factors, for example other bacterial infection, may also drive inflammation and scarring, particularly in the late stages of trachoma. This study was undertaken to investigate whether trachomatous trichiasis or conjunctival scarring are associated with increased prevalence of bacterial infection., Methods: Within a case-control study design, individuals with trichiasis or conjunctival scarring (without trichiasis) were compared with normal matched control subjects. Subjects were examined for signs of trachoma. Conjunctival swab samples were collected for bacteriologic culture and C. trachomatis PCR., Results: Recruited for the study were 121 trichiasis case-control pairs and 117 conjunctival scarring case-control pairs. Eyes with trichiasis were more frequently infected with bacteria (37%) than were normal control eyes (7%) (OR: 8.2; P < 0.001; 95% CI: 3.24-20.8). Bacterial infection was more common with increased trichiasis severity. In the conjunctival scarring case-control group, scarred eyes had slightly more bacterial infection (11%) than did normal control eyes (6%), although this was not significantly different (OR: 2.2; P = 0.144; 95% CI: 0.79-6.33)., Conclusions: Trichiasis is associated with increased risk of bacterial infection, and there may be a similar trend in eyes with conjunctival scarring. Bacterial infection of the conjunctiva is associated with inflammation, which may result in progressive scarring. Prospective studies are needed to determine the contribution of bacterial infection to disease progression. Bacterial infection probably also contributes to the development of corneal opacification.

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 co-trimoxazole. 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.

Purpose: Trachoma is the leading infectious cause of blindness. However, there are few data on the natural history of trachomatous trichiasis to guide program planning or that investigate its pathogenesis., Methods: A cohort of Gambians with trichiasis in one or both eyes who had declined surgery was observed. Clinical examinations were performed at baseline and 4 years later. Conjunctival swab samples were collected for Chlamydia trachomatis PCR and bacteriology., Results: One hundred fifty-four people were examined at baseline and 4 years later (241 nonsurgical eyes). At baseline 124 (52%) eyes had major trichiasis (5+ lashes), 75 (31%) minor trichiasis (1-4 lashes), and 42 (17%) no trichiasis. By 4 years, trichiasis had developed in 12 (29%) of 42 previously unaffected eyes. Minor trichiasis progressed to major in 28 (37%) of 75 eyes. New corneal opacification more commonly developed in eyes that had major (10%) compared to minor (5%) trichiasis at baseline. Bacterial infection was common (23%), becoming more frequent with increasing trichiasis. C. trachomatis infection was rare (1%). Conjunctival inflammation was common (29%) and was associated with progressive trichiasis and corneal opacification., Conclusions: Trichiasis progressed in the long-term in this environment, despite a low prevalence of C. trachomatis. Blinding corneal opacification develops infrequently, unless major trichiasis is present. Epilation and early surgery need to be formally compared for the management of minor trichiasis. The pathologic correlates and promoters of conjunctival inflammation need to be investigated.