Post-mortem investigation of deaths due to pneumonia in children aged 1-59 months in sub-Saharan Africa and South Asia from 2016 to 2022: an observational study.

BACKGROUND: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network programme undertakes post-mortem minimally invasive tissue sampling (MITS), together with collection of ante-mortem clinical information, to investigate causes of childhood deaths across multiple countries. We aimed to evaluate the overall contribution of pneumonia in the causal pathway to death and the causative pathogens of fatal pneumonia in children aged 1-59 months enrolled in the CHAMPS Network. METHODS: In this observational study we analysed deaths occurring between Dec 16, 2016, and Dec 31, 2022, in the CHAMPS Network across six countries in sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and one in South Asia (Bangladesh). A standardised approach of MITS was undertaken on decedents within 24-72 h of death. Diagnostic tests included blood culture, multi-organism targeted nucleic acid amplifications tests (NAATs) of blood and lung tissue, and histopathology examination of various organ tissue samples. An interdisciplinary expert panel at each site reviewed case data to attribute the cause of death and pathogenesis thereof on the basis of WHO-recommended reporting standards. FINDINGS: Pneumonia was attributed in the causal pathway of death in 455 (40·6%) of 1120 decedents, with a median age at death of 9 (IQR 4-19) months. Causative pathogens were identified in 377 (82·9%) of 455 pneumonia deaths, and multiple pathogens were implicated in 218 (57·8%) of 377 deaths. 306 (67·3%) of 455 deaths occurred in the community or within 72 h of hospital admission (presumed to be community-acquired pneumonia), with the leading bacterial pathogens being Streptococcus pneumoniae (108 [35·3%]), Klebsiella pneumoniae (78 [25·5%]), and non-typeable Haemophilus influenzae (37 [12·1%]). 149 (32·7%) deaths occurred 72 h or more after hospital admission (presumed to be hospital-acquired pneumonia), with the most common pathogens being K pneumoniae (64 [43·0%]), Acinetobacter baumannii (19 [12·8%]), S pneumoniae (15 [10·1%]), and Pseudomonas aeruginosa (15 [10·1%]). Overall, viruses were implicated in 145 (31·9%) of 455 pneumonia-related deaths, including 54 (11·9%) of 455 attributed to cytomegalovirus and 29 (6·4%) of 455 attributed to respiratory syncytial virus. INTERPRETATION: Pneumonia contributed to 40·6% of all childhood deaths in this analysis. The use of post-mortem MITS enabled biological ascertainment of the cause of death in the majority (82·9%) of childhood deaths attributed to pneumonia, with more than one pathogen being commonly implicated in the same case. The prominent role of K pneumoniae, non-typable H influenzae, and S pneumoniae highlight the need to review empirical management guidelines for management of very severe pneumonia in low-income and middle-income settings, and the need for research into new or improved vaccines against these pathogens. FUNDING: Bill & Melinda Gates Foundation.

Prevalence and Missed Cases of Respiratory Distress Syndrome Disease Amongst Neonatal Deaths Enrolled in the Kenya Child Health and Mortality Prevention Surveillance Network (CHAMPS) Program Between 2017 and 2021.

Objectives. To describe RDS in neonatal deaths at the CHAMPS-Kenya site between 2017 and 2021. Methods. We included 165 neonatal deaths whose their Causes of death (COD) were determined by a panel of experts using data from post-mortem conducted through minimally invasive tissue specimen testing, clinical records, and verbal autopsy. Results. Twenty-six percent (43/165) of neonatal deaths were attributable to RDS. Most cases occurred in low birthweight and preterm neonates. From these cases, less than half of the hospitalizations were diagnosed with RDS before death, and essential diagnostic tests were not performed in most cases. Most cases received suboptimal levels of supplemental oxygen, and critical interventions like surfactant replacement therapy and mechanical ventilation were not adequately utilized when available. Conclusion. The study highlights the urgent need for improved diagnosis and management of RDS, emphasizing the importance of increasing clinical suspicion and enhancing training in its clinical management to reduce mortality rates.

Pattern and trends of Helicobacter pylori genotypes in gastric cancer: A Kenyan 8-year study.

Background: Notable geographic and temporal variations in the prevalence and genotypes of Helicobacter pylori, in relation to gastric pathologies, have been observed; however, their significance and trends in African populations is scarcely described. The aim of this study, was to investigate the association of H. pylori and its respective CagA and vacuolating cytotoxin A (VacA) genotypes with gastric adenocarcinoma, and to describe the trends of H. pylori genotypes over an 8-year period (2012-2019). Materials and methods: A total of 286 samples of gastric cancer cases and benign controls (one-to-one matching), from three main cities in Kenya, between 2012 and 2019 were included. Histologic evaluation, and CagA and VacA genotyping using PCR, was performed. Distribution of H. pylori genotypes was presented in proportions. To determine association, a univariate analysis was conducted using a Wilcoxon rank sum test for continuous variables, and a Chi-squared test or Fisher's exact test for categorical data. Results: The VacA s1m1 genotype was associated with gastric adenocarcinoma, {odds ratio (OR) = 2.68 [confidence interval (CI) of 95%: 0.83-8.65]; p = 0.108}, whilst VacA s2m2 was associated with a reduced probability of gastric adenocarcinoma [OR = 0.23 (CI 95%: 0.07-0.78); p = 0.031]. No association between cytotoxin associated gene A (CagA) and gastric adenocarcinoma was observed. Conclusion: Over the study period, an increase in all genotypes of H. pylori was seen, and although no predominant genotype was noted, there was significant year-to-year variation, with VacA s1 and VacA s2 showing the greatest variation. VacA s1m1 and VacA s2m2 were associated with increased, and reduced risk of gastric cancer, respectively. Intestinal metaplasia and atrophic gastritis did not appear to be significant in this population.

Epidemiology and antimicrobial resistance of staphylococci other than Staphylococcus aureus from domestic animals and livestock in Africa: a systematic review.

Introduction: Staphylococci other than Staphylococcus aureus (SOSA) in animals are becoming more pathogenic and antibiotic resistant and can potentially disseminate to humans. However, there is little synthesized information regarding SOSA from animals in Africa. This systematic review provides a comprehensive overview of the epidemiology and antimicrobial resistance of SOSA in companion animals (pets) and livestock in Africa. Method: This systematic review (PROSPERO-CRD42021252303) was conducted according to the PRISMA guidelines, and 75 eligible studies from 13 countries were identified until August 2022. Three electronic databases (Pubmed, Scopus and Web of Science) were employed. Results: The frequently isolated SOSA were S. epidermidis, S. intermedius, S. pseudintermedius, S. xylosus, S. chromogenes, S. hyicus, M. sciuri, S. hominis, and S. haemolyticus. Thirty (40%) studies performed antibiotic susceptibility testing (AST). Penicillin (58%) and tetracycline (28%) resistance were most common across all SOSA with high rates of resistance to aminoglycosides, fluoroquinolones, and macrolides in some species. Resistance to last-resort antibiotics such as linezolid and fusidic acid were also reported. Limited data on strain typing and molecular resistance mechanisms precluded analysis of the clonal diversity of SOSA on the continent. Conclusion: The findings of this review indicate that research on livestock-associated SOSA in Africa is lacking in some regions such as Central and Western Africa, furthermore, research on companion animals and more advanced methods for identification and strain typing of SOSA need to be encouraged. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021252303.

Genomic characterization of two community-acquired methicillin-resistant Staphylococcus aureus with novel sequence types in Kenya.

Staphylococcus aureus is a clinically important bacteria with high antimicrobial resistance (AMR) challenge globally. The emergence of methicillin-resistant Staphylococcus aureus (MRSA) clones with unique sequence types have been identified in the community showing evidence that the epidemiology of MRSA globally is changing and requires continual surveillance. We utilized whole genome sequencing to characterize two community acquired-MRSA (CA-MRSA) strains isolated from wound swabs from community-onset infections in two health facilities in Kenya. The two strains belonged to multilocus sequence type (MLST) sequence type (ST) 7460, and ST 7635. The resistance genes detected showed that the novel STs are carriers of clinically relevant resistance genes. Linezolid and mupirocin resistance was observed, yet mupirocin is not commonly used in the country. Mutations within resistance genes were also detected and the pathogenicity toward the human host matched various pathogenic global S. aureus families, e.g., S. aureus subsp. aureus USA300. Multidrug efflux transporters, important in antimicrobial resistance including restriction enzymes type I and type IV were detected. Plasmids identified showed similarities with the plasmids in other clinically significant non-staphylococcal species, such as Pseudomonas aeruginosa, Escherichia coli, Morganella morganii, and Enterococcus faecium. Both STs belong to clonal complex 8 (CC8) which is the most successful MRSA clone in Kenya. Spa type t30 to which ST 7635 belongs has not been reported in the country. The results of this study further highlight the need for epidemiological studies to reveal circulating strains and antimicrobial resistance spread between hospitals and the community. The genomic research highlights resistance to anti-staphylococcal broad-spectrum antimicrobials not used frequently in the country, jeopardizing successful MRSA treatment since most health facilities do not perform genotypic resistance tests for routine patient management. Preliminary insights into unidentified STs of CA-MRSA in Kenya show the need for molecular epidemiological surveillance studies to further understand the diversity of S. aureus in Africa.

Molecular Epidemiology of Mycobacterium tuberculosis Complex Strains in Urban and Slum Settings of Nairobi, Kenya.

Kenya is a country with a high tuberculosis (TB) burden. However, knowledge on the genetic diversity of Mycobacterium tuberculosis complex (MTBC) strains and their transmission dynamics is sparsely available. Hence, we used whole-genome sequencing (WGS) to depict the genetic diversity, molecular markers of drug resistance, and possible transmission clusters among MTBC strains in urban and slum settings of Nairobi. We analyzed 385 clinical MTBC isolates collected between 2010 and 2015 in combination with patients' demographics. We showed that the MTBC population mainly comprises strains of four lineages (L1-L4). The two dominating lineages were L4 with 55.8% (n = 215) and L3 with 25.7% (n = 99) of all strains, respectively. Genome-based cluster analysis showed that 30.4% (117/385) of the strains were clustered using a ≤5 single-nucleotide polymorphism (SNP) threshold as a surrogate marker for direct patient-to-patient MTBC transmission. Moreover, 5.2% (20/385) of the strains were multidrug-resistant (MDR), and 50.0% (n = 10) were part of a genome-based cluster (i.e., direct MDR MTBC transmission). Notably, 30.0% (6/20) of the MDR strains were resistant to all first-line drugs and are part of one molecular cluster. Moreover, TB patients in urban living setting had 3.8 times the odds of being infected with a drug-resistant strain as compared to patients from slums (p-value = 0.002). Our results show that L4 strains are the main causative agent of TB in Nairobi and MDR strain transmission is an emerging concern in urban settings. This emphasizes the need for more focused infection control measures and contact tracing of patients with MDR TB to break the transmission chains.

Secondary Infections in Patients with COVID-19 Pneumonia Treated with Tocilizumab Compared to Those Not Treated with Tocilizumab: A Retrospective Study at a Tertiary Hospital in Kenya.

Introduction: From the first case of SARS-Co-2 in Wuhan, China, to the virus being declared as a pandemic in March 2020, the world has witnessed morbidity and mortality on a global scale. Scientists have worked at a record pace to deliver a vaccine for the prevention of this deadly disease. Tocilizumab, an interleukin-6 (IL-6) blocker, received an emergency use authorization (EUA) by the Federal Drug Agency (FDA) in June 2021. Methods: This retrospective observational cohort study was conducted at the Aga Khan University Hospital, Nairobi, from March 8, 2020, to December 31, 2020. All patients with PCR confirmed COVID-19 pneumonia were included. Data were obtained from the medical records, and the admission registry was used to identify the patients, and both their electronic and paper-based files were retrieved from the medical records. Patient demographic data, medical history, baseline comorbidities, clinical characteristics, and outcome data were collected to study the infectious complications of Tocilizumab in patients affected by COVID-19 pneumonia. Results: A total of 913 patients who were diagnosed with COVID-19 were included. The overall superinfection infection rate among the COVID-19 patients was 6%. Superinfection in patients who received the Tocilizumab was 17.2% and in the non-Tocilizumab group was 4.8%. The superinfection rate among severe and critically ill patients was even higher at 41.8% and 69.9% (Tocilizumab group) and 2.1% and 11.8% (non-Tocilizumab group), respectively (p < 0.001). There was no difference in mortality observed between the groups (p = 0.846). Infection among HIV co-infection was very low at 2.3%. Conclusion: Contrary to some studies, a higher rate of infection was observed among the Tocilizumab group, and no difference in mortality was observed between Tocilizumab and the non-Tocilizumab group. Infection among patients with HIV remains low in this susceptible population.

Farming Practice Influences Antimicrobial Resistance Burden of Non-Aureus Staphylococci in Pig Husbandries.

Non-aureus staphylococci (NAS) are ubiquitous bacteria in livestock-associated environments where they may act as reservoirs of antimicrobial resistance (AMR) genes for pathogens such as Staphylococcus aureus. Here, we tested whether housing conditions in pig farms could influence the overall AMR-NAS burden. Two hundred and forty porcine commensal and environmental NAS isolates from three different farm types (conventional, alternative, and organic) were tested for phenotypic antimicrobial susceptibility and subjected to whole genome sequencing. Genomic data were analysed regarding species identity and AMR gene carriage. Seventeen different NAS species were identified across all farm types. In contrast to conventional farms, no AMR genes were detectable towards methicillin, aminoglycosides, and phenicols in organic farms. Additionally, AMR genes to macrolides and tetracycline were rare among NAS in organic farms, while such genes were common in conventional husbandries. No differences in AMR detection existed between farm types regarding fosfomycin, lincosamides, fusidic acid, and heavy metal resistance gene presence. The combined data show that husbandry conditions influence the occurrence of resistant and multidrug-resistant bacteria in livestock, suggesting that changing husbandry practices may be an appropriate means of limiting the spread of AMR bacteria on farms.

Assessment of independent comorbidities and comorbidity measures in predicting healthcare facility-onset Clostridioides difficile infection in Kenya.

INTRODUCTION: Clostridioides difficile is primarily associated with hospital-acquired diarrhoea. The disease burden is aggravated in patients with comorbidities due to increased likelihood of polypharmacy, extended hospital stays and compromised immunity. The study aimed to investigate comorbidity predictors of healthcare facility-onset C. difficile infection (HO-CDI) in hospitalized patients. METHODOLOGY: We performed a cross sectional study of 333 patients who developed diarrhoea during hospitalization. The patients were tested for CDI. Data on demographics, admission information, medication exposure and comorbidities were collected. The comorbidities were also categorised according to Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI). Comorbidity predictors of HO-CDI were identified using multiple logistic regression analysis. RESULTS: Overall, 230/333 (69%) patients had comorbidities, with the highest proportion being in patients aged over 60 years. Among the patients diagnosed with HO-CDI, 63/71(88.7%) reported comorbidities. Pairwise comparison between HO-CDI patients and comparison group revealed significant differences in hypertension, anemia, tuberculosis, diabetes, chronic kidney disease and chronic obstructive pulmonary disease. In the multiple logistic regression model significant predictors were chronic obstructive pulmonary disease (odds ratio [OR], 9.51; 95% confidence interval [CI], 1.8-50.1), diabetes (OR, 3.56; 95% CI, 1.11-11.38), chronic kidney disease (OR, 3.88; 95% CI, 1.57-9.62), anemia (OR, 3.67; 95% CI, 1.61-8.34) and hypertension (OR, 2.47; 95% CI, 1.-6.07). Among the comorbidity scores, CCI score of 2 (OR 6.67; 95% CI, 2.07-21.48), and ECI scores of 1 (OR, 4.07; 95% CI, 1.72-9.65), 2 (OR 2.86; 95% CI, 1.03-7.89), and ≥ 3 (OR, 4.87; 95% CI, 1.40-16.92) were significantly associated with higher odds of developing HO-CDI. CONCLUSION: Chronic obstructive pulmonary disease, chronic kidney disease, anemia, diabetes, and hypertension were associated with an increased risk of developing HO-CDI. Besides, ECI proved to be a better predictor for HO-CDI. Therefore, it is imperative that hospitals should capitalize on targeted preventive approaches in patients with these underlying conditions to reduce the risk of developing HO-CDI and limit potential exposure to other patients.

Systemic and Mucosal Concentrations of Nine Cytokines Among Individuals with Neisseria gonorrhoeae infection in Nairobi Kenya.

Introduction: The human-restricted sexually transmitted Neisseria gonorrhoeae (NG) has been shown to modulate the immune response against it and consequently the cytokines produced. The levels of cytokines in NG infection in the African population have not been well described. We aimed to quantify the systemic and mucosal cytokines in NG infection. Methods: This was a comparative cross-sectional study. Levels of nine cytokines (IL-1ß, IL-2, IL-4, 1L-6, 1L-10, 1L-12p70, IL-17A, TNF-α and INF-γ) were measured from plasma and genital samples (urethral swabs in men and cervicovaginal lavage in women) from 61 Neisseria gonorrhoeae infected individuals seeking treatment for sexually transmitted infections (STIs) at Casino Health Centre in Nairobi, Kenya. A comparative group of 61 NG-uninfected individuals, seeking treatment at the same facility but with laboratory-confirmed negative Neisseria gonorrhoeae, Chlamydia trachomatis (CT), Mycoplasma genitalium (MG) and Trichomonas vaginalis(TV) was also included. The Mann-Whitney U test was used to compare the cytokine levels between NG-infected and uninfected individuals. Data was analyzed using STATA ver. 15.1. Results: Overall, systemic IL-6, TNF-α and IL-10 were elevated while genital IL-10 and TNF-α were lower in NG positive participants. On subgroup analysis by sex, the levels of genital IL-1ß and IL-6 and systemic IL-6 were elevated in NG-infected men. None of the genital cytokines were elevated in NG-infected women, while all systemic cytokines, except INF-γ, were elevated in NG-infected women. Conclusions: Neisseria gonorrhoeae induced the production of different cytokines in men and women, with men having a pro-inflammatory genital response. These differences should be taken into consideration during development of various interventions e.g. vaccine development.

Diagnostic accuracy of the syndromic management of four STIs among individuals seeking treatment at a health centre in Nairobi, Kenya: a cross-sectional study.

INTRODUCTION: the syndromic approach to the management of sexually transmitted diseases (STIs) is recommended in areas without adequate laboratory support. We assessed the diagnostic accuracy of this approach in diagnosing Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG) among 18 to 49 year-old individuals seeking treatment for STIs in a health centre in Nairobi, Kenya. METHODS: participants were recruited between April and June 2019. After providing written informed consent, an interviewer-administered questionnaire was completed. Endocervical swabs from women and urethral swabs from men were collected for STI testing using polymerase chain reaction (PCR). Diagnostic accuracy of reported symptoms was calculated using PCR as the gold standard. RESULTS: a total of 297 individuals (148 men and 149 women) were recruited. Majority of the participants had at least one reported symptom (130/148; 87.8% men and 145/148; 97.3% women). The most commonly diagnosed STI was NG (85/297; 28.6% 95%CI 23.5%-34.1%). Vaginal discharge syndrome had moderate (44.4%) to high (92.9%) sensitivity, low specificity, low positive predictive value (PPV) (2.4 % to 31.5%) and high negative predictive value (NPV) (68.2% to 95.2%). The lower abdominal pain syndrome had moderate to high sensitivity (40% to 71.4%), low specificity (30.9% to 35.6%), low PPV (9.9% to 15.8%) and high NPV (79.2% to 93.8%). The urethral discharge syndrome had high sensitivity (71.4% to 84.8%); moderate specificity (37.6% to 51.7%); low to moderate PPV (5.4% to 53.8%) and high NPV (83.6% to 96.4%). The kappa scores for the three syndromes were generally poor. CONCLUSION: these findings support the need for the review of the syndromic management of STIs.

Whole-genome sequence-informed MALDI-TOF MS diagnostics reveal importance of Klebsiella oxytoca group in invasive infections: a retrospective clinical study.

BACKGROUND: Klebsiella spp. are opportunistic pathogens which can cause severe infections, are often multi-drug resistant and are a common cause of hospital-acquired infections. Multiple new Klebsiella species have recently been described, yet their clinical impact and antibiotic resistance profiles are largely unknown. We aimed to explore Klebsiella group- and species-specific clinical impact, antimicrobial resistance (AMR) and virulence. METHODS: We analysed whole-genome sequence data of a diverse selection of Klebsiella spp. isolates and identified resistance and virulence factors. Using the genomes of 3594 Klebsiella isolates, we predicted the masses of 56 ribosomal subunit proteins and identified species-specific marker masses. We then re-analysed over 22,000 Matrix-Assisted Laser Desorption Ionization - Time Of Flight (MALDI-TOF) mass spectra routinely acquired at eight healthcare institutions in four countries looking for these species-specific markers. Analyses of clinical and microbiological endpoints from a subset of 957 patients with infections from Klebsiella species were performed using generalized linear mixed-effects models. RESULTS: Our comparative genomic analysis shows group- and species-specific trends in accessory genome composition. With the identified species-specific marker masses, eight Klebsiella species can be distinguished using MALDI-TOF MS. We identified K. pneumoniae (71.2%; n = 12,523), K. quasipneumoniae (3.3%; n = 575), K. variicola (9.8%; n = 1717), "K. quasivariicola" (0.3%; n = 52), K. oxytoca (8.2%; n = 1445), K. michiganensis (4.8%; n = 836), K. grimontii (2.4%; n = 425) and K. huaxensis (0.1%; n = 12). Isolates belonging to the K. oxytoca group, which includes the species K. oxytoca, K. michiganensis and K. grimontii, were less often resistant to 4th-generation cephalosporins than isolates of the K. pneumoniae group, which includes the species K. pneumoniae, K. quasipneumoniae, K. variicola and "K. quasivariicola" (odds ratio = 0.17, p < 0.001, 95% confidence interval [0.09,0.28]). Within the K. pneumoniae group, isolates identified as K. pneumoniae were more often resistant to 4th-generation cephalosporins than K. variicola isolates (odds ratio = 2.61, p = 0.003, 95% confidence interval [1.38,5.06]). K. oxytoca group isolates were found to be more likely associated with invasive infection to primary sterile sites than K. pneumoniae group isolates (odds ratio = 2.39, p = 0.0044, 95% confidence interval [1.05,5.53]). CONCLUSIONS: Currently misdiagnosed Klebsiella spp. can be distinguished using a ribosomal marker-based approach for MALDI-TOF MS. Klebsiella groups and species differed in AMR profiles, and in their association with invasive infection, highlighting the importance for species identification to enable effective treatment options.

Deaths Attributed to Respiratory Syncytial Virus in Young Children in High-Mortality Rate Settings: Report from Child Health and Mortality Prevention Surveillance (CHAMPS).

BACKGROUND: Lower respiratory tract infections are a leading cause of death in young children, but few studies have collected the specimens needed to define the role of specific causes. The Child Health and Mortality Prevention Surveillance (CHAMPS) platform aims to investigate causes of death in children aged <5 years in high-mortality rate settings, using postmortem minimally invasive tissue sampling and other advanced diagnostic techniques. We examined findings for deaths identified in CHAMPS sites in 7 countries in sub-Saharan Africa and south Asia to evaluate the role of respiratory syncytial virus (RSV). METHODS: We included deaths that occurred between December 2016 and December 2019. Panels determined causes of deaths by reviewing all available data including pathological results from minimally invasive tissue sampling, polymerase chain reaction screening for multiple infectious pathogens in lung tissue, nasopharyngeal swab, blood, and cerebrospinal fluid samples, clinical information from medical records, and verbal autopsies. RESULTS: We evaluated 1213 deaths, including 695 in neonates (aged <28 days), 283 in infants (28 days to <12 months), and 235 in children (12-59 months). RSV was detected in postmortem specimens in 67 of 1213 deaths (5.5%); in 24 deaths (2.0% of total), RSV was determined to be a cause of death, and it contributed to 5 other deaths. Younger infants (28 days to <6 months of age) accounted for half of all deaths attributed to RSV; 6.5% of all deaths in younger infants were attributed to RSV. RSV was the underlying and only cause in 4 deaths; the remainder (n = 20) had a median of 2 (range, 1-5) other conditions in the causal chain. Birth defects (n = 8) and infections with other pathogens (n = 17) were common comorbid conditions. CONCLUSIONS: RSV is an important cause of child deaths, particularly in young infants. These findings add to the substantial body of literature calling for better treatment and prevention options for RSV in high-mortality rate settings.

Whole Genome Sequencing Reveals Virulence Potentials of Helicobacter pylori Strain KE21 Isolated from a Kenyan Patient with Gastric Signet Ring Cell Carcinoma.

Helicobacter pylori (H.pylori) infection is etiologically associated with severe diseases including gastric cancer; but its pathogenicity is deeply shaped by the exceptional genomic diversification and geographic variation of the species. The clinical relevance of strains colonizing Africa is still debated. This study aimed to explore genomic features and virulence potentials of H. pylori KE21, a typical African strain isolated from a native Kenyan patient diagnosed with a gastric cancer. A high-quality circular genome assembly of 1,648,327 bp (1590 genes) obtained as a hybrid of Illumina Miseq short reads and Oxford Nanopore MinION long reads, clustered within hpAfrica1 population. This genome revealed a virulome and a mobilome encoding more than hundred features potentiating a successful colonization, persistent infection, and enhanced disease pathogenesis. Furthermore, through an experimental infection of gastric epithelial cell lines, strain KE21 showed the ability to promote interleukin-8 production and to induce cellular alterations resulting from the injection of a functional CagA oncogene protein into the cells. This study shows that strain KE21 is potentially virulent and can trigger oncogenic pathways in gastric epithelial cells. Expended genomic and clinical explorations are required to evaluate the epidemiological importance of H. pylori infection and its putative complications in the study population.

Implementation of surgical site infection surveillance in low- and middle-income countries: A position statement for the International Society for Infectious Diseases.

Surgical site infection (SSI) rates in low- and middle-income countries (LMICs) range from 8 to 30% of procedures, making them the most frequent healthcare-acquired infection (HAI) with substantial morbidity, mortality, and economic impacts. Presented here is an approach to surgical site infection prevention based on surveillance and focused on five critical areas identified by international experts. These five areas include 1. Collecting valid, high-quality data; 2. Linking HAIs to economic incapacity, underscoring the need to prioritize infection prevention activities; 3. Implementing SSI surveillance within infection prevention and control (IPC) programs to enact structural changes, develop procedural skills, and alter healthcare worker behaviors; 4. Prioritizing IPC training for healthcare workers in LMICs to conduct broad-based surveillance and to develop and implement locally applicable IPC programs; and 5. Developing a highly accurate and objective international system for defining SSIs, which can be translated globally in a straightforward manner. Finally, we present a clear, unambiguous framework for successful SSI guideline implementation that supports developing sustainable IPC programs in LMICs. This entails 1. Identifying index operations for targeted surveillance; 2. Identifying IPC "champions" and empowering healthcare workers; 3. Using multimodal improvement measures; 4. Positioning hand hygiene programs as the basis for IPC initiatives; 5. Use of telecommunication devices for surveillance and healthcare outcome follow-ups. Additionally, special considerations for pediatric SSIs, antimicrobial resistance development, and antibiotic stewardship programs are addressed.

High Prevalence of Multidrug-Resistant Clostridioides difficile Following Extensive Use of Antimicrobials in Hospitalized Patients in Kenya.

Introduction: Clostridioides difficile is a neglected pathogen in many African countries as it is generally not regarded as one of the major contributors toward the diarrheal disease burden in the continent. However, several studies have suggested that C. difficile infection (CDI) may be underreported in many African settings. The aim of this study was to determine the prevalence of CDI in hospitalized patients, evaluate antimicrobial exposure, and detect toxin and antimicrobial resistance profiles of the isolated C. difficile strains. Methods: In this cross-sectional study, 333 hospitalized patients with hospital-onset diarrhoea were selected. The stool samples were collected and cultured on cycloserine-cefoxitin egg yolk agar (CCEY). Isolates were presumptively identified by phenotypic characteristics and Gram stain and confirmed by singleplex real-time PCR (qPCR) assays detecting the species-specific tpi gene, toxin A (tcdA) gene, toxin B (tcdB) gene, and the binary toxin (cdtA/cdtB) genes. Confirmed C. difficile isolates were tested against a panel of eight antimicrobials (vancomycin, metronidazole, rifampicin, ciprofloxacin, tetracycline, clindamycin, erythromycin, and ceftriaxone) using E-test strips. Results: C. difficile was detected in 57 (25%) of diarrheal patients over the age of two, 56 (98.2%) of whom received antimicrobials before the diarrheal episode. Amongst the 71 confirmed isolates, 69 (97.1%) harbored at least one toxin gene. More than half of the toxigenic isolates harbored a truncated tcdA gene. All isolates were sensitive to vancomycin, while three isolates (2.1%) were resistant to metronidazole (MIC >32 mg/L). High levels of resistance were observed to rifampicin (65/71, 91.5%), erythromycin (63/71, 88.7%), ciprofloxacin (59/71, 83.1%), clindamycin (57/71, 80.3%), and ceftriaxone (36/71, 50.7.8%). Among the resistant isolates, 61 (85.9%) were multidrug-resistant. Conclusion: Multidrug-resistant C. difficile strains were a significant cause of healthcare facility-onset C. difficile infections in patients with prior antimicrobial exposure in this Kenyan hospital.

Analysis of Candida auris fungemia at a single facility in Kenya.

OBJECTIVES: Candida auris emerged as a human pathogen in 2009 and has subsequently been identified around the world as a cause of invasive candidiasis. We did an analysis from a single institution in order to analyze risk factors and outcomes for C. auris candidemia. METHODS: Patients with candidemia were identified by the electronic medical record and reviewed for risk factors and outcome. Candida isolates were identified by Vitek2 as Candida haemulonii, but species determinations for 21 of the isolates using published molecular and proteomic methods identified all as C. auris. FINDINGS: From September 2010 to December 2016, C. auris accounted for 38% of 201 patients with candidemia, while C. albicans contributed 25%. C. auris patients had been hospitalized longer (mean 32 days vs. 13 days; p<0.001), were more likely to have central lines preceding candidemia than C. albicans patients (84% vs. 54%; p=<0.001) and had more commonly been treated with carbapenems (83% vs 61% for C. albicans [p=0.01]). The crude mortality was 29%, compared to 36% for C. albicans. CONCLUSIONS: These findings suggest an opportunistic pathogen that may be less virulent, but difficult to eradicate and that control efforts should focus on antimicrobial usage.

Seroprevalence data at a private teaching hospital in Kenya: An examination of Toxoplasma gondii, cytomegalovirus, rubella, hepatitis A, and Entamoeba histolytica.

BACKGROUND: Relevant seroprevalence data for endemic pathogens in a given region provide insight not only into a population's susceptibility to acute infection or risk for reactivation disease but also into the potential need for policy initiatives aimed at reducing these risks. Data from sub-Saharan Africa are sparse and since Aga Khan University Hospital Nairobi is an internationally accredited hospital equipped with a laboratory electronic medical record system, analysis of pertinent local seroprevalence data has been made possible. METHODS: We have analyzed serology data from laboratory electronic records at a 300 bed tertiary private teaching hospital in Kenya for the dates, 2008 to 2017 for Toxoplasma gondii, cytomegalovirus, and rubella, which were used primarily for antenatal screening. We also analyzed the data from hepatitis A and amebiasis serologies, which were used primarily for diagnostic purposes. RESULTS: For T. gondii, cytomegalovirus, and rubella, we used IgG serology to determine seroprevalence, finding rates of 32%, 86%, and 89%, respectively. There was no significant age-related difference in the 20 to 49 year old age range for any of these three pathogens. Of the Hepatitis A IgM tests that were ordered, 33% were positive with a peak positive rate of 70% in the five to nine year old age range. The seroprevalence of amebiasis was 4% and all cases of seropositivity were accompanied by compatible clinical illness (hepatic abscess). CONCLUSIONS: These data provide insight into seroprevalence rates of selected pathogens that can be used to guide screening and diagnostic laboratory testing as well as private and public immunization practices.