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Childhood mortality remains a major public health challenge in low-income and middle-income countries, particularly in sub-Saharan Africa, despite major advances in universal sanitation and immunisations. Mass drug administration (MDA) of azithromycin, a broad-spectrum antibiotic, has shown promise in reducing under-5 mortality in high-risk regions, although its mechanism of protection remains largely unknown. In this Personal View, we analyse current evidence, potential effect of MDA on antimicrobial resistance, and relevant ethical principles, and propose priorities for future public health interventions. Our review of key randomised controlled trials revealed highly variable outcomes of azithromycin MDA differing by participants' age, geographical location, comorbidities, coinfections, and concurrent therapies. Intermittent use of azithromycin has been linked to rising macrolide resistance in several pathogens, spillover effects in untreated populations, and ecological disruptions. Ethical concerns, including informed consent and allocation of limited resources, require careful consideration. We propose a multifaceted approach including investments in water, sanitation, and hygiene infrastructure, vaccination programmes, and robust antimicrobial resistance surveillance. Policy makers and global health stakeholders must prioritise context-specific, evidence-based strategies that strengthen local capacity, improve community engagement, and implement robust monitoring systems to ensure that the potential benefits of MDA are sustained and do not imperil public health.

Infections caused by multi-drug resistant Enterobacterales (MDR-E) are difficult to treat and cause significant mortality, especially in developing countries. This study characterized the phenotypic and genotypic profiles of 49 randomly selected beta-lactam resistant MDR-E previously isolated from patients being managed in hospitals in Nigeria using whole genome sequencing. The study isolates exhibited 85.5% resistance to 3rd generation cephalosporins and 65.3% resistance to carbapenems. The bla TEM-1B (29, 59.2%) , bla CTX-M-15 (38, 77.6%) , and bla NDM-1 (17, 51.5%) were the most common penicillinase, ESBL, and carbapenem resistant genes across isolates, respectively. Seventeen (45%) of bla CTX-M-15 was carried on the insertion sequence ISEc9 while bla NDM-1 (11, 64.7%) were associated with ISEc33. None of the 21 plasmids detected were associated with β-lactamase genes. Higher resistance rates were found in E. coli ST-88 (n = 2) and the high-risk ST-692 (n = 2). For Klebsiella species, the high-risk clones ST-476 (n = 8) and ST-147 (n = 3) predominated and had higher phenotypic resistance rates and higher number of AMR genes. The mechanisms and pattern of antibiotic resistance differ from patterns previously described with isolates harbouring a wide range of AMRGs. The detection of several chromosomally mediated carbapenemases in our study also represents a significant finding that warrants further investigation to better understand its’ implications for clinical practice and public health. The selected MDR-Es were found to be pan-susceptible to tigecycline and had very low resistance to fosfomycin, suggesting a potential for these as empiric treatments. A surveillance approach incorporating both conventional laboratory techniques and modern molecular techniques is essential for the comprehensive characterization of the emergence and dissemination of antimicrobial resistance in Enterobacterales infections within Nigeria.

Group B Streptococcus (GBS) causes invasive infections in neonates and has been implicated as a cause of prelabour rupture of membranes, preterm delivery and stillbirths. The success of phase II trials of polyvalent polysaccharide GBS vaccines indicates that these infections are potentially preventable. Nigeria is the most populous country in Africa with one of the highest birth rates, one of the highest neonatal sepsis incidence rates and one of the highest mortality rates in the world. Therefore, before the possible introduction of preventive strategies such as intrapartum antibiotic prophylaxis or GBS vaccine into Nigeria, it is vital that there is accurate data on the aetiology of neonatal sepsis and on the incidence of GBS neonatal sepsis in particular. The objective of this study was to determine the incidence and aetiology of neonatal sepsis in Nigeria with a focus on GBS sepsis and also to assess the potential impact of a GBS vaccine. A literature search was conducted on the databases of African journals online, PubMed and Google Scholar for works conducted between 1987 to 2017. Case reports, reviews, and studies not stating specific culture methods or specific bacteria isolated were excluded. Data extracted included; incidence of neonatal sepsis, method of blood culture, blood volume, sample size, bacterial agents isolated and history of antibiotic use. PRISMA guidelines were followed and modified Down's and Black criteria used to evaluate the quality of studies. A total of 5,114 studies were reviewed for neonatal sepsis out of which 24 consisting of a total of 2,280 cases were selected for final review. Nine studies met criteria for assessment of hospital based incidence of neonatal sepsis representing 31,305 hospital births. The incidence of neonatal sepsis was 18.2/1000 livebirths with range from 7-55/1000 livebirths while the GBS incidence was 0.06/1000 livebirths with range from 0-2/1000 live births. We discovered various limitations such as identification techniques that could result in underestimation of the true incidence of GBS sepsis. Pathogens such as Klebsiella pneumoniae and Staphylococcus aureus were more commonly isolated than GBS. The hospital based incidence of neonatal sepsis was high at 18.2/1000 live births while that due to GBS was 0.06/1000 live births. The burden of neonatal sepsis, including that attributable to GBS is substantial and could be reduced by preventive strategies such as intrapartum antibiotic prophylaxis or GBS vaccine. There is however very sparse meaningful data currently. Well planned prospective studies with larger sample sizes, more advanced isolation and identification techniques and those following up invasive disease cases for possible short and long term sequelae are needed-not only prior to possible introduction of the vaccine to determine the baseline epidemiology, but also thereafter to monitor its impact on the population. Strategies need to be developed to also reduce the morbidity and mortality attributable to other bacteria that have an incidence even greater than that of GBS.

Invasive non-typhoidal Salmonella (iNTS) disease manifesting as bloodstream infection with high mortality is responsible for a huge public health burden in sub-Saharan Africa. Salmonella enterica serovar Typhimurium ( S . Typhimurium) is the main cause of iNTS disease in Africa. By analysing whole genome sequence data from 1303  S . Typhimurium isolates originating from 19 African countries and isolated between 1979 and 2017, here we show a thorough scaled appraisal of the population structure of iNTS disease caused by S . Typhimurium across many of Africa’s most impacted countries. At least six invasive S . Typhimurium clades have already emerged, with ST313 lineage 2 or ST313-L2 driving the current pandemic. ST313-L2 likely emerged in the Democratic Republic of Congo around 1980 and further spread in the mid 1990s. We observed plasmid-borne as well as chromosomally encoded fluoroquinolone resistance underlying emergences of extensive-drug and pan-drug resistance. Our work provides an overview of the evolution of invasive S . Typhimurium disease, and can be exploited to target control measures. Invasive Salmonella Typhimurium bloodstream infection causes a significant public health burden in sub-Saharan Africa. Here, the authors analyse whole genome sequences of 1,302 S. Typhimurium isolates from Africa and describe its evolution, geographic spread, and antimicrobial resistance characteristics.

[...]from a public health perspective, it will be necessary to immunise children if they are a major source of SARS-CoV-2 transmission and if the candidate vaccines block transmission. [...]from an ethical perspective, there is a balance between risk and benefit in offering a COVID-19 vaccine to children that will offer minimal or no direct benefit to the recipient, no benefit to the public, and as yet, unknown medium-term and long-term risks to the recipient. [...]because individuals are not equally susceptible and contagious, our current target to vaccinate 65–70% of the population to archive herd immunity might be an overestimate.10 If young children are excluded, there will be more vaccines available for the more epidemiologically susceptible subgroups.

There is paucity of data regarding the geographical distribution, incidence, and phylogenetics of multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction of whole genome sequenced 249 contemporaneous S . Typhi isolated between 2008-2015 in 11 sub-Saharan African countries, in context of the 2,057 global S . Typhi genomic framework. Despite the broad genetic diversity, the majority of organisms (225/249; 90%) belong to only three genotypes, 4.3.1 (H58) (99/249; 40%), 3.1.1 (97/249; 39%), and 2.3.2 (29/249; 12%). Genotypes 4.3.1 and 3.1.1 are confined within East and West Africa, respectively. MDR phenotype is found in over 50% of organisms restricted within these dominant genotypes. High incidences of MDR S . Typhi are calculated in locations with a high burden of typhoid, specifically in children aged <15 years. Antimicrobial stewardship, MDR surveillance, and the introduction of typhoid conjugate vaccines will be critical for the control of MDR typhoid in Africa. Typhoid fever is caused by the bacterium Salmonella Typhi. Here, Park et al. analyse the genomes of 249 S . Typhi isolates from 11 sub-Saharan African countries, identifying genes and plasmids associated with antibiotic resistance and showing that multi-drug resistance is highly pervasive in sub-Saharan Africa.

Background Cardiac complications contribute significantly to morbidity in children with sickle cell anaemia (SCA). Little is known about the geometry and contractile function of the left ventricle (LV) of affected children in sub-Saharan Africa, which has the greatest burden of this disease. Objective To compare the LV systolic function of children with SCA in the steady state with that of matched haemoglobin AA controls. Methods Clinical, laboratory and LV M-mode echocardiographic parameters of 120 steady-state SCA patients aged 3–14 years were compared with those of matched Hb AA controls. Univariate and multivariate analyses were performed using SPSS software, version 22 (IBM, Armonk, NY, USA). Results The median ejection fraction of 62.00 (IQR = 55.0–67.0) for the subjects was significantly less than that of 68.00 (IQR = 65.8–73.0) for the controls ( p  < 0.001) and correlated negatively with age (ρ=-0.25, p  = 0.006), BSA (ρ=-0.24, p  = 0.008), systolic BP (ρ=-0.23, p  = 0.022), and diastolic BP (ρ=-0.31, p  = 0.002). Left ventricular systolic dysfunction (LVSD) was present in 27% of the SCA patients but only in 1% of the controls (χ² = 26.5, p  < 0.001). The odds of having LVSD decreased by 0.9 for every 1% increase in HbF level (CI = 0.82–0.99, p  = 0.03). Abnormal LV geometry, detected in 52% of the subjects, was associated with the presence of LVSD (Fisher’s exact test, p  < 0.001). The odds of having abnormal LV geometry decreased by 0.5 for every 1 g increase in Hb level (CI = 0.27–0.87, p  = 0.02). Conclusions LVSD is more common in SCA patients than in controls and is less likely to occur in patients with higher HbF levels. Approximately one in every two children with SCA have abnormal LV geometry, which is less likely to occur at higher Hb levels.

Gordon Dougan and colleagues report whole-genome sequencing of a global collection of 179 Salmonella Typhimurium isolates, including 129 diverse sub-Saharan African isolates associated with invasive disease. They determine the phylogenetic structure of invasive Salmonella Typhimurium in sub-Saharan Africa and find that the majority are from two closely related highly conserved lineages, which emerged in the last 60 years in close temporal association with the current HIV epidemic. A highly invasive form of non-typhoidal Salmonella (iNTS) disease has recently been documented in many countries in sub-Saharan Africa. The most common Salmonella enterica serovar causing this disease is Typhimurium ( Salmonella Typhimurium). We applied whole-genome sequence–based phylogenetic methods to define the population structure of sub-Saharan African invasive Salmonella Typhimurium isolates and compared these to global Salmonella Typhimurium populations. Notably, the vast majority of sub-Saharan invasive Salmonella Typhimurium isolates fell within two closely related, highly clustered phylogenetic lineages that we estimate emerged independently ∼52 and ∼35 years ago in close temporal association with the current HIV pandemic. Clonal replacement of isolates from lineage I by those from lineage II was potentially influenced by the use of chloramphenicol for the treatment of iNTS disease. Our analysis suggests that iNTS disease is in part an epidemic in sub-Saharan Africa caused by highly related Salmonella Typhimurium lineages that may have occupied new niches associated with a compromised human population and antibiotic treatment.

Infections caused by multi-drug resistant Escherichia coli cause significant morbidity and mortality especially in developing countries. In this study, we describe the molecular characteristics of E. coli isolated from clinical specimens and the patients’ outcomes. Phenotypic methods were used in the identification and antimicrobial susceptibility testing of E. coli from clinical specimens from a tertiary hospital in Abuja, Nigeria. Whole genome sequencing was used to describe the antimicrobial resistance genes, serotypes, sequence types/clonal complexes, and mobile genetic elements. The mean age of the patients was 20.3 years with 70.1% females and majority of isolates 75% from urine, 21% from blood cultures, and 3% each from cerebrospinal fluid and endo-cervical swabs. Of the 107 non-duplicate E. coli isolates, 101 (94.3%) were resistant to ampicillin, 95 (88.8%) to trimethoprim/sulfamethoxazole, 86 (80.4%) to ceftriaxone, 60 (56.1%) to gentamicin, and eight (7.5%) to meropenem. There were 102 (95.3%) isolates that were multi-drug resistant (MDR). Expression of Extended Spectrum Beta Lactamase (ESBL) phenotype was detected in 54 (50%) and bla CTX-M-15 genes detected in 75 (70.1%) isolates. The carbapenemase genes bla NDM-1 and bla NDM-5 were detected in six (5.6%), while the AmpC gene- bla CMY-2 , was detected in seven (6.5%) isolates. Two (1.9%) isolates simultaneously harboured the bla OXA-1 , bla CMY-2 , bla CTX-M-15 , and bla NDM-5 genes. In total, 35 sequence types (STs) were found with the majority being ST131 (n = 23; 21.5%). The most common serotype was O25:H4 associated with all 23 strains of ST131, followed by O1:H6/ST648 (n = 6). The ST410, ST671, and ST101 strains displayed phenotypic resistance to wide array of antibiotic classes and harbored high numbers of antibiotic resistance genes via in-silico analysis. The ST410 strain in particular harbored a higher number of antibiotic resistance genes and was phenotypically resistant to a wider array of antibiotics. Four pairs of isolates were closely related with three isolates (ST131, ST38, ST652) having a pairwise SNP difference of zero. 71/72 75/76 52/14. The MDR E. coli lineages circulating in this setting pose a clinical and public health threat as they can hinder effective prevention and management of infections. The genetic diversity and MDR E. coli with the emergence of ST410 and ST101 clones is concerning because of the potential for rapid dissemination in hospitals and communities- further increasing the problems of antibiotic resistance. Continuous routine surveillance of E. coli infections for AMR in hospitals becomes imperative, aimed at development of effective antimicrobial stewardship programs, facilitating prudent use of antimicrobial agents, and limiting dissemination of resistant strains.