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Klebsiella pneumoniae causes community- and healthcare-associated infections in children and adults. Globally in 2019, an estimated 1.27 million (95% Uncertainty Interval [UI]: 0.91–1.71) and 4.95 million (95% UI: 3.62–6.57) deaths were attributed to and associated with bacterial antimicrobial resistance (AMR), respectively. K. pneumoniae was the second leading pathogen in deaths attributed to AMR resistant bacteria. Furthermore, the rise of antimicrobial resistance in both community- and hospital-acquired infections is a concern for neonates and infants who are at high risk for invasive bacterial disease. There is a limited antibiotic pipeline for new antibiotics to treat multidrug resistant infections, and vaccines targeted against K. pneumoniae are considered to be of priority by the World Health Organization. Vaccination of pregnant women against K. pneumoniae could reduce the risk of invasive K.pneumoniae disease in their young offspring. In addition, vulnerable children, adolescents and adult populations at risk of K. pneumoniae disease with underlying diseases such as immunosuppression from underlying hematologic malignancy, chemotherapy, patients undergoing abdominal and/or urinary surgical procedures, or prolonged intensive care management are also potential target groups for a K. pneumoniae vaccine. A ‘Vaccine Value Profile’ (VVP) for K.pneumoniae, which contemplates vaccination of pregnant women to protect their babies from birth through to at least three months of age and other high-risk populations, provides a high-level, holistic assessment of the available information to inform the potential public health, economic and societal value of a pipeline of K. pneumoniae vaccines and other preventatives and therapeutics. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public–private partnerships, and multi-lateral organizations, and in collaboration with stakeholders from the WHO. All contributors have extensive expertise on various elements of the K.pneumoniae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

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.

Background We aimed to identify interventions used to implement antimicrobial stewardship practices among hospitalized patients in least-developed countries. Methods The research team searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for studies of AMS interventions in the least developed and low-income countries, published between 2000 and 2023. Included studies had a population of hospitalized patients of all age groups in least-developed countries, implemented an AMS intervention, and reported its impact on prescription practices, clinical outcomes, or microbiological results. The risk of bias was assessed using the integrated quality criteria for review of multiple study designs. A total of 443 articles were identified, 386 articles were screened, 16 full-text papers were reviewed, and 10 studies were included in the analysis. Results The ten studies included three controlled before and after, two qualitative, one controlled interrupted time series, two non-controlled interrupted time series, one quasi-experimental study, and one randomized controlled trial. Three studies implemented either enabling, persuasive, or structural interventions respectively. The rest used bundled strategies, including a combination of persuasive, enabling, structural, and restrictive interventions. Bundled interventions using enabling and persuasive strategies were the most common. These involved creating a prescription guideline, training prescribers on updated methods, and subsequent review and feedback of patient files by members of an AMS team. Improved microbiological surveillance was important to most studies but, sustained improvement in appropriate prescriptions was dependent on enabling or persuasive efforts. Studies noted significant improvements in appropriate prescriptions and savings on the costs of antibiotics. None evaluated the impact of AMS on AMR. Conclusion AMS practices generally involve multiple strategies to improve prescription practices. In the setting of least-developed countries, enabling and persuasive interventions are popular AMS measures. However, measured outcomes are heterogeneous, and we suggest that further studies assessing the impact of AMS should report changes in AMR patterns (microbiological outcomes), patient length of stay and mortality (patient outcomes), and changes in prescription practices (prescription outcomes). Reporting on these as outcomes of AMS interventions could make it easier for policymakers to compare which interventions have desirable outcomes that can be generalized to similar settings.

Progress has been made in the reduction of morbidity and mortality from neonatal sepsis. However, diagnosis continues to rely primarily on conventional microbiologic techniques, which can be inaccurate. The objective of this review is to provide the clinician with an overview of the current information available on diagnosing this condition. We review currently available diagnostic approaches for documenting neonatal sepsis and also describe novel approaches for diagnosing infection in neonates who are under development and investigation. Substantial progress has been made with molecular approaches and further development of non-culture-based methods offer promise. The potential ability to incorporate antimicrobial resistance gene testing in addition to pathogen identification may provide a venue to incorporate a predominantly molecular platform into a larger program of neonatal care.

ObjectivesWe studied neonates with suspected early-onset sepsis (EOS, sepsis developing in the first 72 hours after delivery) in Malawi to (1) describe clinical characteristics and microbiological findings, (2) identify which patient characteristics may be associated with pathogen positivity on blood culture, and (3) describe mortality and its potential determinants.DesignProspective observational study (May 2018–June 2019).SettingNeonatal ward in Queen Elizabeth Central Hospital, the largest government hospital in Malawi.PatientsAll neonates with suspected EOS in whom a blood culture was obtained.ResultsOut of 4308 neonatal admissions, 1244 (28.9%) had suspected EOS. We included 1149 neonates, of which 109 blood cultures had significant growth (9.5%). The most commonly isolated pathogens were Staphylococcus aureus, Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli and Acinetobacter baumanii. Many of the Gram negatives were extended-spectrum beta lactamase-producing Enterobacteriaceae, and these were 40–100% resistant to first-line and second-line antimicrobials. Gestational age (GA) of <32 weeks was associated with pathogen-positive blood cultures (<28 weeks: adjusted OR (AOR) 2.72, 95% CI 1.04 to 7.13; 28–32 weeks: AOR 2.26, 95% CI 1.21 to 4.21; p=0.005). Mortality was 17.6% (202/1149) and associated with low birth weight (<1000 g: AOR 47.57, 95% CI 12.59 to 179.81; 1000–1500 g: AOR 11.31, 95% CI 6.97 to 18.36; 1500–2500 g: AOR 2.20, 95% CI 1.42 to 3.39; p<0.001), low Apgar scores at 5 min (0–3: AOR 18.60, 95% CI 8.81 to 39.27; 4–6: AOR 4.41, 95% CI 2.81 to 6.93; p<0.001), positive maternal venereal disease research laboratory status (AOR 2.53, 95% CI 1.25 to 5.12; p=0.001) and congenital anomalies (AOR 7.37, 95% CI 3.61 to 15.05; p<0.001). Prolonged rupture of membranes was inversely associated with mortality (AOR 0.43, 95% CI 0.19 to 0.98; p 0.007).ConclusionIn Malawi, EOS was suspected in nearly a third of neonatal admissions and had a high mortality. Ten per cent were culture-confirmed and predicted by low GA. To reduce the impact of suspected neonatal sepsis in least developed countries, improved maternal and antenatal care and development of rapid point of care methods to more accurately guide antimicrobial use could simultaneously improve outcome and reduce antimicrobial resistance.

•Incidence, serotype and antimicrobial susceptibility data for S. pneumoniae in children in Africa.•The pooled incidence of invasive pneumococcal disease (IPD) was 61.1 per 100,000 person-years.•The pooled prevalence of penicillin susceptibility to S. pneumoniae was 78.1%.•Cumulatively, PCV10 and PCV13 included 66.9% and 80.6% of IPD serotypes, respectively.•These data provide a reliable baseline from which to monitor the impact of broad PCV introduction. Determining the incidence, disease-associated serotypes and antimicrobial susceptibility of invasive pneumococcal disease (IPD) among children in Africa is essential in order to monitor the impact of these infections prior to widespread introduction of the pneumococcal conjugate vaccine (PCV). To provide updated estimates of the incidence, serotype distribution, and antimicrobial susceptibility profile of Streptococcus pneumoniae causing disease in Africa, we performed a systematic review of articles published from 2000 to 2015 using Ovid Medline and Embase. We included prospective and surveillance studies that applied predefined diagnostic criteria. Meta-analysis for all pooled analyses was based on random-effects models. We included 38 studies consisting of 386,880 participants in 21 countries over a total of 350,613 person-years. The pooled incidence of IPD was 62.6 (95% CI 16.9, 226.5) per 100,000 person-years, including meningitis which had a pooled incidence of 24.7 (95% CI 11.9, 51.6) per 100,000 person-years. The pooled prevalence of penicillin susceptibility was 78.1% (95% CI 61.9, 89.2). Cumulatively, PCV10 and PCV13 included 66.9% (95% CI 55.9, 76.7) and 80.6% (95% CI 66.3, 90.5) of IPD serotypes, respectively. Our study provides an integrated and robust summary of incidence data, serotype distribution and antimicrobial susceptibility for S. pneumoniae in children ≤5years of age in Africa prior to widespread introduction of PCV on the continent. The heterogeneity of studies and wide range of incidence rates across the continent indicate that surveillance efforts should be intensified in all regions of Africa to improve the integrity of epidemiologic data, vaccine impact and cost benefit. Although the incidence of IPD in young children in Africa is substantial, currently available conjugate vaccines are estimated to cover the majority of invasive disease-causing pneumococcal serotypes. These data provide a reliable baseline from which to monitor the impact of the broad introduction of PCV.

This study aimed at determining the intra- and inter-rater reliability in ultrasound body composition measurements and investigating the differences between malnourished and non-malnourished infants. Sonographic images for measurements of fat and muscle thickness were compared between 9 malnourished and 9 non-malnourished hospitalized infants. The mean of fat and muscle thickness sums were 12.44 ± 7.58 mm and 28.98 ± 7.18 mm, respectively. The intra- and inter-rater intraclass correlation coefficient were above 0.9 for both measurements, indicating high intra- and inter-rater reliability. Compared to non-malnourished infants, malnourished infants have 45% of fat thickness sum and 71% of muscle thickness sum. Ultrasound measurements of body composition in infants were different between hospitalized malnourished and non-malnourished infants. This approach has the potential to be utilized more broadly, from assessing the nutritional status of critically ill infants in intensive care units to screening for malnutrition in high-risk infant populations.

IntroductionAntimicrobial resistance (AMR) is increasing in low resource settings. It complicates the management of infectious diseases and is an increasing cause of death. This is due to, among other things, lack of health resources for appropriate diagnosis and unregulated access to antimicrobials in the public sphere. Developing context-specific interventions that enable judicious use of antimicrobials is important to curb this problem.MethodsWe will conduct a systematic review of antimicrobial stewardship (AMS) approaches in Development Assistance Committee in least developed and low-income countries. The inclusion criteria are antimicrobial stewardship interventions in hospitalised patients of all age groups and exclusion criteria are community-based trials and studies that solely focus on viral, fungal or parasite infections. Antimicrobial stewardship interventions will be classified as structural, enabling, persuasive, restrictive or combined. Outcomes of included studies will be classified as clinical, microbiological or behavioural outcomes. The studies to be included will be randomised controlled trials, controlled before–after studies, interrupted time series trials, cohort and qualitative studies. Data will be extracted using forms adapted from the Cochrane collaboration data collection form. This systematic review will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and risk of bias will be done according to the Integrated quality Criteria for Review of Multiple Study Designs.Ethics and disseminationOur findings will be presented to clinicians and policymakers, to support developing AMS protocols for low resource settings. We will publish our results in peer-reviewed journals.Trial registration numberCRD42020210634.

Background Respiratory cryptosporidiosis has been documented in children with diarrhea. We sought to describe the dynamics of respiratory involvement in children hospitalized with gastrointestinal (GI) diarrheal disease. Methods We conducted a prospective, observational longitudinal study of Malawian children 2-24 months hospitalized with diarrhea. Nasopharyngeal (NP) swabs, induced sputum and stool specimens were collected. Participants that were positive by Cryptosporidium PCR in any of the three compartments were followed up with fortnightly visits up to 8 weeks post-enrollment. Results Of the 162 children recruited, participants had mild-moderate malnutrition (mean HAZ -1.6 (SD 2.1)), 37 (21%) were PCR-positive for Cryptosporidium at enrollment (37 stool, 11 sputum, and 4 NP) and 27 completed the majority of follow-up visits (73%). Cryptosporidium was detected in all compartments over the 4 post-enrollment visits, most commonly in stool (100% at enrollment with mean cycle thresholds (Ct) of 28.8±4.3 to 44% at 8 weeks with Ct 29.9±4.1), followed by sputum (31% at enrollment with mean Ct 31.1±4.4 to 20% at 8 weeks with Ct 35.7±2.6), then NP (11% with mean Ct 33.5±1.0 to 8% with Ct 36.6±0.7). Participants with Cryptosporidium detection in both the respiratory and GI tract over the study period reported respiratory and GI symptoms in 81% and 62% of study visits, respectively, compared to 68% and 27%, respectively, for those with only GI detection, and had longer GI shedding (17.5±6.6 v. 15.9±2.9 days). Conclusion Cryptosporidium was detected in both respiratory and GI tracts throughout the 8 weeks post-enrollment. The development of therapeutics for Cryptosporidium in children should target the respiratory as well as GI tract.