Saffiatou Darboe

Background: Neonatal sepsis is a major contributor to adverse neonatal outcomes in West Africa. High quality data on risk factors for sepsis in this region is limited, yet important for surveillance, prevention and management of newborns at greatest risk. This study aimed to describe the clinical epidemiology of sepsis for health-facility born neonates in an urban West African setting. Methods: This study comprised secondary data analyses from the Gambian cohort of the PregnAnZI-2 randomised clinical trial. Relatively healthy pregnant women and their offspring who delivered at two urban health facilities were included, with a combination of active and passive surveillance until 28 days. Neonatal sepsis was defined as suspected if clinical and laboratory (abnormal FBC or CRP) criteria were met, and confirmed if blood-culture was positive. A novel conceptual framework informed logistic regression models to identify 1) factors associated with neonatal sepsis and 2) contribution of sepsis towards neonatal mortality. Results: A total of 6515 neonates were included. The health-facility based incidence of neonatal sepsis was 20.2 cases/1000 live births (N=131 cases), predominantly early-onset (Burkholderia cepacia and Staphylococcus aureus the most prevalent bacteria in 24% (7/29) of confirmed sepsis each. Risk factors for sepsis included low 1-minute Apgar score (aOR 13.2, 95% CI 8.40-20.73), pre-labour maternal fever (aOR 5.0, 95% CI 1.15-21.69), easily recognisable congenital malformation (aOR 3.39, 95% CI 1.55-7.38) and low-birth weight (aOR 2.85, 95% CI 1.75-4.65). 40.7% of all neonatal deaths in the cohort occurred in neonates with sepsis, with 40-fold increase in mortality compared to neonates without sepsis (OR: 39.98, 95% CI 22.5 – 71.1). Conclusion: Sepsis, especially early onset, is a major morbidity for health facility born neonates delivered following relatively healthy pregnancy in urban Gambia, with high associated mortality. We identify neonatal phenotypes (low birth weight, newborns with low 1-minute apgar scores, or those with easily recognisable congenital malformations) who may benefit from enhanced postnatal surveillance or antibiotics to prevent or treat neonatal sepsis and reduce neonatal mortality. Trial Registration: NCT03199547: Clinicaltrials.gov . Registered on 23 ^rd June 2017

Background/Objectives: Urinary tract infections (UTIs) can predispose women to preeclampsia and prematurity, which are common causes of maternal and neonatal morbidity and mortality. In low-middle-income countries (LMICs), the capacity for screening and treating UTIs is limited. In sub-Saharan Africa, AMR surveillance data are scarce, especially in vulnerable populations such as pregnant women. The aim of this study was to determine the prevalence and antimicrobial resistance patterns of community-acquired urinary tract infections among pregnant women attending the antenatal clinics of three hospitals in Gambia. Methods: This was a hospital-based, cross-sectional, multicenter study conducted between November 2022 and January 2023. Patient information was obtained via a pre-tested questionnaire. The urine samples were analyzed via Gram staining and biochemical tests to determine the causative organisms. We also used antibiotic sensitivity testing to identify resistance patterns. The data collected were analyzed via SPSS version 20 and tested for associations at a significance level of p ≤ 0.05. Results: The prevalence of significant bacteriuria was 5% (n=100). Escherichia coli (40%) and Staphylococcus aureus (40%) were the most common uropathogens. The prevalence of resistance was found for trimethoprim/sulfamethoxazole and ampicillin, and multi-drug resistance was detected in only one isolate (Citrobacter freundii). Conclusion: This study revealed bacterial isolates with prevalent resistance to commonly prescribed drugs for community-acquired UTIs in pregnant women and suggested alternatives such as ceftriaxone, nitrofurantoin, erythromycin, and nalidixic acid as empirical treatment options. We recommend consistent health to combat drug resistance caused by inappropriate antibiotic use.

Streptococcus pyogenes–related skin infections are increasingly implicated in the development of rheumatic heart disease (RHD) in lower-resource settings, where they are often associated with scabies. The true prevalence of S pyogenes–related pyoderma may be underestimated by bacterial culture. A multiplex quantitative polymerase chain reaction (qPCR) assay for S pyogenes, Staphylococcus aureus, and Sarcoptes scabiei was applied to 250 pyoderma swabs from a cross-sectional study of children aged emm-typing was used to supplement previous whole genome sequencing (WGS) of cultured isolates. Pyoderma lesions with S pyogenes increased from 51% (127/250) using culture to 80% (199/250) with qPCR. Compared to qPCR, the sensitivity of culture was 95.4% for S pyogenes (95% confidence interval {CI}, 77.2%–99.9%) in samples with S pyogenes alone (22/250 [9%]), but 59.9% (95% CI, 52.3%–67.2%) for samples with S aureus coinfection (177/250 [71%]). Direct PCR-based emm-typing was successful in 50% (46/92) of cases, identifying 27 emm-types, including 6 not identified by WGS (total 52 emm-types). Bacterial culture significantly underestimates the burden of S pyogenes in pyoderma, particularly with S aureus coinfection. Molecular methods should be used to enhance the detection of S pyogenes in surveillance studies and clinical trials of preventive measures in RHD-endemic settings.

Streptococcus agalactiae (group B Streptococcus , GBS) has recently emerged as an important pathogen among adults. However, it is overlooked in this population, with all global efforts being directed towards its containment among pregnant women and neonates. This systematic review assessed the molecular epidemiology and compared how the lineages circulating among non-pregnant populations relate to those of pregnant and neonatal populations worldwide. A systematic search was performed across nine databases from 1 January 2000 up to and including 20 September 2021, with no language restrictions. The Joanna Briggs Institute (JBI) Prevalence Critical Appraisal Tool (PCAT) was used to assess the quality of included studies. The global population structure of GBS from the non-pregnant population was analysed using in silico typing and phylogenetic reconstruction tools. Twenty-four articles out of 13 509 retrieved across 9 databases were eligible. Most studies were conducted in the World Health Organization European region (12/24, 50 %), followed by the Western Pacific region (6/24, 25 %) and the Americas region (6/24, 25 %). Serotype V (23%, 2310/10240) and clonal complex (CC) 1 (29 %, 2157/7470) were the most frequent serotype and CC, respectively. The pilus island PI1 : PI2A combination (29 %, 3931/13751) was the most prevalent surface protein gene, while the tetracycline resistance tetM (55 %, 5892/10624) was the leading antibiotic resistance gene. This study highlights that, given the common serotype distribution identified among non-pregnant populations (V, III, Ia, Ib, II and IV), vaccines including these six serotypes will provide broad coverage. The study indicates advanced molecular epidemiology studies, especially in resource-constrained settings for evidence-based decisions. Finally, the study shows that considering all at-risk populations in an inclusive approach is essential to ensure the sustainable containment of GBS.

Background: Antimicrobial resistance poses a public health threat for the treatment of community-acquired urinary tract infections. This study determined the susceptibility patterns of uropathogens and associated risk factors among outpatients diagnosed with urinary tract infections at the Kanifing General Hospital in the Gambia. Methods: A cross-sectional analytic study was conducted among patients with suspected urinary tract infections at Kanifing General Hospital from March to May 2021. Data on socio-demographic and other risk factors were collected from the study participants using a structured pre-tested questionnaire. Mid-stream urine samples were collected, and bacteria identification and antimicrobial susceptibility testing done using standard microbiological methods. Descriptive and inferential statistical analysis were done to determine factors associated with urinary tract infection at 95% confidence level and a p -value < 0.05. Results: A total of 422 patients were enrolled with 82.5% (348/422) being females. The prevalence of community acquired urinary tract infection was 12.8% (54/422). Escherichia coli was the most prevalent isolate (74.1%, 40/54), followed by Klebsiella spp (8.5%, 10/54). Antimicrobial resistance was highest for Ampicillin (87.0%, 47/54), Trimethoprim/Sulfamethoxazole (77.8%, 42/54) and Tetracycline (75.9%, 41/54). Uropathogens sensitivity was 77.8% (42/54) for Nitrofurantoin and 75.9% (41/54) for Ceftazidime. Being female (aOR 5.90 95% CI = 1.48–23.67), previous history of urinary tract infection (aOR 2.34, 95% CI = 1.06–5.14), use of unprescribed antibiotics (aOR 2.0, 95% CI = 1.05–3.62) and having no formal education (aOR 8.02, 95% CI = 1.04–62.0) were significant factors associated for having uropathogenic bacterial infection. Conclusion: E. coli was the most prevalent uropathogen isolated. Ciprofloxacin, Nitrofurantoin and Ceftazidime were the most sensitive antibiotics. Routine surveillance of susceptibility of uropathogenic bacteria would be helpful to update clinicians on the choice of antibiotics.

Background: This detailed genomic study characterised multi-drug resistant-Gram negative bacilli (MDR-GNB) carriage in neonates < 2 kg and paired mothers at a low-resource African hospital. Methods: This cross-sectional cohort study was conducted at the neonatal referral unit in The Gambia with weekly neonatal skin and peri-anal sampling and paired maternal recto-vaginal swabs. Prospective bacteriological culture used MacConkey agar with species identification by API20E and API20NE. All GNB isolates underwent whole genome sequencing on Illumina Miseq platform. Multi-Locus Sequence Typing and SNP-distance analysis identified strain type and relatedness. Results: 135 swabs from 34 neonates and 21 paired mothers, yielded 137 GNB isolates, of which 112 are high quality de novo assemblies. Neonatal MDR-GNB carriage prevalence is 41% (14/34) at admission with 85% (11/13) new acquisition by 7d. Multiple MDR and ESBL-GNB species are carried at different timepoints, most frequently K. pneumoniae and E. coli, with heterogeneous strain diversity and no evidence of clonality. 111 distinct antibiotic resistance genes are mostly beta lactamases (Bla-AMPH, Bla-PBP, CTX-M-15, Bla-TEM-105). 76% (16/21) and 62% (13/21) of mothers have recto-vaginal carriage of ≥1 MDR-GNB and ESBL-GNB respectively, mostly MDR-E. coli (76%, 16/21) and MDR-K. pneumoniae (24%, 5/21). Of 21 newborn-mother dyads, only one have genetically identical isolates (E. coli ST131 and K. pneumoniae ST3476). Conclusions: Gambian hospitalised neonates exhibit high MDR and ESBL-GNB carriage prevalence with acquisition between birth and 7d with limited evidence supporting mother to neonate transmission. Genomic studies in similar settings are required to further understand transmission and inform targeted surveillance and infection prevention policies.

Antimicrobial resistance is a global health threat and efforts to mitigate it is warranted, thus the need for local antibiograms to improve stewardship. This study highlights the process that was used to develop an antibiogram to monitor resistance at a secondary-level health facility to aid empirical clinical decision making in a sub-Saharan African county. This retrospective cross-sectional descriptive study used 3 years of cumulative data from January 2016 to December 2018. Phenotypic data was manually imputed into WHONET and the cumulative antibiogram constructed using standardized methodologies according to CLSI M39-A4 guidelines. Pathogens were identified by standard manual microbiological methods and antimicrobial susceptibility testing was performed using Kirby-Bauer disc diffusion method according to CLSI M100 guidelines. A total of 14,776 non-duplicate samples were processed of which 1163 (7.9%) were positive for clinically significant pathogens. Among the 1163 pathogens, E. coli (n = 315) S. aureus (n = 232), and K. pneumoniae (n = 96) were the leading cause of disease. Overall, the susceptibility for E. coli and K. pneumoniae from all samples were: trimethoprim-sulfamethoxazole (17% and 28%), tetracycline (26% and 33%), gentamicin (72% and 46%), chloramphenicol (76 and 60%), and ciprofloxacin (69% and 59%), and amoxicillin/clavulanic (77% and 54%) respectively. Extended spectrum beta-lactamase (ESBL) resistance was present in 23% (71/315) vs. 35% (34/96) respectively. S. aureus susceptibility for methicillin was 99%. This antibiogram has shown that improvement in combination therapy is warranted in The Gambia.

The global burden of rheumatic heart disease (RHD) has triggered a World Health Organization response to drive forward development of a vaccine against the causative human pathogen Streptococcus pyogenes . This burden stems primarily from low- and middle-income settings where there are high levels of S. pyogenes skin and soft tissue infections, which can lead to RHD.

Aim: This detailed genomic study aimed to characterise multi-drug resistant-gram negative bacilli (MDR-GNB) intestinal and skin carriage in small vulnerable newborns and their paired mothers at a low-resource African hospital. Methods: This cross-sectional cohort study was conducted at the only neonatal referral unit in The Gambia with genomic analysis at MRC Unit The Gambia at LSHTM. Neonates K. pneumoniae and E. coli , with heterogeneous strain diversity, no evidence of clonality and 111 distinct antibiotic resistance genes, mostly Beta-Lactams ( Bla -AMPH, Bla- PBP, CTX-M-15, Bla- TEM-105). 76% (16/21) and 62% (13/21) of mothers had recto-vaginal carriage of at least 1 MDR-GNB and ESBL-GNB respectively, most commonly MDR- E. coli ( 76%, 16/21) and MDR- K. pneumoniae (24%, 5/21). Of 21 neonate-mother dyads only one had genetically identical isolates ( E. coli ST131 and K. pneumoniae ST3476). Conclusion: Gambian hospitalised small vulnerable neonates exhibit high MDR and ESBL-GNB carriage prevalence with acquisition between birth and 7 days. The heterogeneous strain diversity and lack of matching isolates between mothers and newborns suggests multiple environmental sources may be important in transmission. Larger genomic studies to confirm these findings in similar resource limited settings is foundational to inform targeted surveillance and infection prevention control policies. What is known: - MDR-GNB, especially Klebsiella pneumoniae and Escherichia coli , are important causes of neonatal invasive infections and mortality in Africa, classified by WHO as pathogens of high priority for research - Neonatal MDR-GNB carriage is a pre-curser for invasive infection, with preterm, low-birth weight neonates (“Small Vulnerable Newborns”) at greatest risk - Maternal MDR-GNB carriage is a risk factor for neonatal pathogen acquisition in Europe and other well-resourced settings, but a priority evidence gap exists for transmission pathways for small vulnerable African newborns What this study adds: - Hospitalised Gambian small vulnerable neonates have high carriage prevalence of MDR- and ESBL-GNB with acquisition occurring between birth and 7 days - Heterogeneous diversity of K. pneumoniae and E. coli strains suggests multiple environmental sources with no evidence of clonal outbreak - Beta-lactamase genes were most commonly identified with high rates of ESBL- and AMP-C gene production - Despite high maternal MDR-GNB carriage prevalence there is no genomic evidence indicating widespread transmission from mother to newborn