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Background: We explore the spatial distribution of comorbidity with trachoma and potentially visual-impairing non-communicable diseases (NCDs) and their risk factors among Kenyan pastoralists., Methods: Using a cross-sectional study design, we recruited and clinically examined 262 study participants for NCDs (hypertension or diabetes) and trachoma using the World Health Organization grading system. Network models estimated interactions and risks linked with trachoma and NCDs while the Poisson point process determined their spatial distribution., Results: Of the 262 participants, 140 (53%) had trachoma, with >71% of these cases identified among females and those >60 y of age. A total of 36 trachoma cases co-occurred with hypertension (26%) and diabetes (0.01%). NCDs were frequent among those with recurring trachoma (21%) and trachomatous trichiasis (14.3%). Trachoma and NCDs clustered together in <1 km distances (R=0.18, p=0.02). In network analysis, age was strongly associated with trachoma and NCDs. Trachoma was linked with geographic location while diabetes was linked with water source distances. Education level became the central risk factor., Conclusions: We demonstrate a twin trachoma-NCD burden that is higher among elderly pastoralists in southern Kenya. Attenuating adverse population-level visual impairment, including integrating the trachoma SAFE strategy with NCD comprehensive care, amplifies the benefits from economies of scale, accelerating realization of Sustainable Development Goal 3 and universal health coverage in hard-to-reach areas., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Non-typhoidal Salmonella (NTS) is a common cause of gastroenteritis in young children, with limited data on NTS serovars and antimicrobial resistance in Africa., Methods: We determined the prevalence of Salmonella spp. and frequency of antimicrobial resistance among serovars identified in stools of 0-59 month-old children with moderate-to-severe diarrhea (MSD) and controls enrolled in the Vaccine Impact on Diarrhea in Africa (VIDA) Study in The Gambia, Mali, and Kenya in 2015-2018, and compared with data from the Global Enteric Multicenter Study (GEMS; 2007-2010) and the GEMS-1A study (2011). Salmonella spp. was detected by quantitative real-time PCR (qPCR) and culture-based methods. Identification of serovars was determined by microbiological methods., Results: By qPCR, the prevalence of Salmonella spp. among MSD cases was 4.0%, 1.6%, and 1.9% and among controls was 4.6%, 2.4%, and 1.6% in The Gambia, Mali, and Kenya, respectively, during VIDA. We observed year-to-year variation in serovar distribution and variation between sites. In Kenya, Salmonella enterica serovar Typhimurium decreased (78.1% to 23.1%; P < .001) among cases and controls from 2007 to 2018, whereas serogroup O:8 increased (8.7% to 38.5%; P = .04). In The Gambia, serogroup O:7 decreased from 2007 to 2018 (36.3% to 0%; P = .001) but S. enterica serovar Enteritidis increased during VIDA (2015 to 2018; 5.9% to 50%; P = .002). Only 4 Salmonella spp. were isolated in Mali during all 3 studies. Multidrug resistance was 33.9% in Kenya and 0.8% in The Gambia across all 3 studies. Ceftriaxone resistance was only observed in Kenya (2.3%); NTS isolates were susceptible to ciprofloxacin at all sites., Conclusions: Understanding variability in serovar distribution will be important for the future deployment of vaccines against salmonellosis in Africa., Competing Interests: Potential conflicts of interest. M. A. W. reports receiving funding from the Centers for Disease Control and Prevention (CDC) and Institute of Tropical Medicine. S. M. T. reports multiple grants paid to her institution from the National Institutes of Health (NIH), the Bill & Melindat Gates Foudation (BMGF), Wellcome Trust, Affinivax, Lumen Biosciences, PATH, and Medical Research Council. She also reports payments as royalties related to intellectual property for Salmonella vaccines and Klebsiella/Pseudomonas vaccines and consulting fees and travel support from the University of Washington for a grant proposal. She also reports holding multiple planned, issued, and pending patents on Salmonella, Klebsiella, and Pseudomonas vaccines and hold multiple unpaid committee roles with the American Society of Tropical Medicine and Hygiene. E. R. Houpt reports funding from the Bill and Melinda Gates Foundation (OPP1129479). K. L. K. reports consultation fees and travel support from PATH and the University of Washington related to diarrheal diseases and grant support to her institution from the National Institutes of Health, Institut Pasteur, and the Bill & Melinda Gates Foundation. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10 -3 versus 1.4x10 -3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors - synonymous rates: 4.6x10 -3 vs. 2.3x10 -3 ; and nonsynonymous rates: 6.9x10 -4 vs. 2.7x10 -4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P =0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target., (© The Author(s) 2022. Published by Oxford University Press.)

Integrating nutrition communication in agricultural intervention programs aimed at increased food availability and accessibility in resource-poor areas is crucial. To enhance the sustainability and scalability of nutrition communication, the present study piloted the approach of 'nutrition integrated agricultural extension' and tested nutrition-related outcomes with two types of nutrition messages (specific vs. sensitive) and two delivery channels (public sector vs. private sector). The study intervention comprised (i) vegetable seed kit distribution, (ii) ongoing agricultural extension activities by public or private sectors and (iii) nutrition communication with two different messages. The intervention was tested with three treatment arms and reached 454 farmers (>65% female) in rural Kakamega County, Western Kenya. Pre-/post-surveys measured outcome variables focused on farmers' nutrition-related knowledge, attitudes and practices in vegetable production and consumption, and household dietary diversity score. Results showed that all treatments increased nutrition knowledge (p < 0.05). Nutrition-specific communication was more effective than nutrition-sensitive communication. Nutrition communication through either the public or the private agricultural sector was both effective. Before the study intervention, many participants believed that vegetable consumption was beneficial and wanted to increase intake. After the intervention, the number of participants who felt eating more vegetables was challenging decreased slightly. Nutrition communication was found to be especially important in conveying recommended food amounts and promoting increased vegetable consumption. Seasonality affected on-farm crop diversity and vegetable consumption results in this study., (© The Author(s) 2021. Published by Oxford University Press.)

Background: Minimally invasive tissue sampling (MITS) is an alternative to complete autopsy for determining causes of death. Multiplex molecular testing performed on MITS specimens poses challenges of interpretation, due to high sensitivity and indiscriminate detection of pathogenic, commensal, or contaminating microorganisms., Methods: MITS was performed on 20 deceased children with respiratory illness, at 10 timepoints up to 88 hours postmortem. Samples were evaluated by multiplex molecular testing on fresh tissues by TaqMan® Array Card (TAC) and by histopathology, special stains, immunohistochemistry (IHC), and molecular testing (PCR) on formalin-fixed, paraffin-embedded (FFPE) tissues. Results were correlated to determine overall pathologic and etiologic diagnoses and to guide interpretation of TAC results., Results: MITS specimens collected up to 3 days postmortem were adequate for histopathologic evaluation and testing. Seven different etiologic agents were detected by TAC in 10 cases. Three cases had etiologic agents detected by FFPE or other methods and not TAC; 2 were agents not present on TAC, and 2 were streptococci that may have been species other than those present on TAC. Result agreement was 43% for TAC and IHC or PCR, and 69% for IHC and PCR. Extraneous TAC results were common, especially when aspiration was present., Conclusions: TAC can be performed on MITS up to 3 days after death with refrigeration and provides a sensitive method for detection of pathogens but requires careful interpretation in the context of clinicoepidemiologic and histopathologic findings. Interpretation of all diagnostic tests in aggregate to establish overall case diagnoses maximizes the utility of TAC in MITS., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: We used postmortem minimally invasive tissue sampling (MITS) to assess the effect of time since death on molecular detection of pathogens among respiratory illness-associated deaths., Methods: Samples were collected from 20 deceased children (aged 1-59 months) hospitalized with respiratory illness from May 2018 through February 2019. Serial lung and/or liver and blood samples were collected using MITS starting soon after death and every 6 hours thereafter for up to 72 hours. Bodies were stored in the mortuary refrigerator for the duration of the study. All specimens were analyzed using customized multipathogen TaqMan® array cards (TACs)., Results: We identified a median of 3 pathogens in each child's lung tissue (range, 1-8; n = 20), 3 pathogens in each child's liver tissue (range, 1-4; n = 5), and 2 pathogens in each child's blood specimen (range, 0-4; n = 5). Pathogens were not consistently detected across all collection time points; there was no association between postmortem interval and the number of pathogens detected (P = .43) and no change in TAC cycle threshold value over time for pathogens detected in lung tissue. Human ribonucleoprotein values indicated that specimens collected were suitable for testing throughout the study period., Conclusions: Results suggest that lung, liver, and blood specimens can be collected using MITS procedures up to 4 days after death in adequately preserved bodies. However, inconsistent pathogen detection in samples needs careful consideration before drawing definitive conclusions on the etiologic causes of death., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

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., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials., Methods: We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, quantitative polymerase chain reaction (qPCR)-attributable Shigella (defined by an ipaH gene cycle threshold <27.9). Among Shigella MSD cases, we determined risk factors for death and derived a clinical severity score., Results: Compared to culture-positive Shigella MSD cases (n = 745), culture-negative/qPCR-attributable Shigella cases (n = 852) were more likely to be under 12 months, stunted, have a longer duration of diarrhea, and less likely to have high stool frequency or a fever. There was no difference in dehydration, hospitalization, or severe classification from a modified Vesikari score. Twenty-two (1.8%) Shigella MSD cases died within the 14-days after presentation to health facilities, and 59.1% of these deaths were in culture-negative cases. Age <12 months, diarrhea duration prior to presentation, vomiting, stunting, wasting, and hospitalization were associated with mortality. A model-derived score assigned points for dehydration, hospital admission, and longer diarrhea duration but was not significantly better at predicting 14-day mortality than a modified Vesikari score., Conclusions: A composite severity score consistent with severe disease or dysentery may be a pragmatic clinical endpoint for severe shigellosis in vaccine trials. Reliance on culture for microbiologic confirmation may miss a substantial number of Shigella cases but is currently required to measure serotype specific immunity., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Monovalent rotavirus vaccine, Rotarix (GlaxoSmithKline), was introduced in Kenya in July 2014 and is recommended to infants as oral doses at ages 6 and 10 weeks. A multisite study was established in 2 population-based surveillance sites to evaluate vaccine impact on the incidence of rotavirus-associated hospitalizations (RVHs)., Methods: Hospital-based surveillance was conducted from January 2010 to June 2017 for acute diarrhea hospitalizations among children aged <5 years in 2 health facilities in Kenya. A controlled interrupted time-series analysis was undertaken to compare RVH pre- and post-vaccine introduction using rotavirus-negative cases as a control series. The change in incidence post-vaccine introduction was estimated from a negative binomial model that adjusted for secular trend, seasonality, and multiple health worker industrial actions (strikes)., Results: Between January 2010 and June 2017 there were 1513 and 1652 diarrhea hospitalizations in Kilifi and Siaya; among those tested for rotavirus, 28% (315/1142) and 23% (197/877) were positive, respectively. There was a 57% (95% confidence interval [CI], 8-80%) reduction in RVHs observed in the first year post-vaccine introduction in Kilifi and a 59% (95% CI, 20-79%) reduction in Siaya. In the second year, RVHs decreased further at both sites, 80% (95% CI, 46-93%) reduction in Kilifi and 82% reduction in Siaya (95% CI. 61-92%); this reduction was sustained at both sites into the third year., Conclusions: A substantial reduction in RVHs and all-cause diarrhea was observed in 2 demographic surveillance sites in Kenya within 3 years of vaccine introduction., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Rotavirus remains a leading cause of pediatric diarrheal illness and death worldwide. Data on rotavirus vaccine effectiveness in sub-Saharan Africa are limited. Kenya introduced monovalent rotavirus vaccine (RV1) in July 2014. We assessed RV1 effectiveness against rotavirus-associated hospitalization in Kenyan children., Methods: Between July 2014 and December 2017, we conducted surveillance for acute gastroenteritis (AGE) in 3 Kenyan hospitals. From children age-eligible for ≥1 RV1 dose, with stool tested for rotavirus and confirmed vaccination history we compared RV1 coverage among rotavirus positive (cases) vs rotavirus negative (controls) using multivariable logistic regression and calculated effectiveness based on adjusted odds ratio., Results: Among 677 eligible children, 110 (16%) were rotavirus positive. Vaccination data were available for 91 (83%) cases; 51 (56%) had 2 RV1 doses and 33 (36%) 0 doses. Among 567 controls, 418 (74%) had vaccination data; 308 (74%) had 2 doses and 69 (16%) 0 doses. Overall 2-dose effectiveness was 64% (95% confidence interval [CI], 35%-80%); effectiveness was 67% (95% CI, 30%-84%) for children aged <12 months and 72% (95% CI, 10%-91%) for children aged ≥12 months. Significant effectiveness was seen in children with normal weight for age, length/height for age and weight for length/height; however, no protection was found among underweight, stunted, or wasted children., Conclusions: RV1 in the Kenyan immunization program provides significant protection against rotavirus-associated hospitalization which persisted beyond infancy. Malnutrition appears to diminish vaccine effectiveness. Efforts to improve rotavirus uptake and nutritional status are important to maximize vaccine benefit., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Kenya introduced 10-valent pneumococcal conjugate vaccine (PCV10) among children <1 year in 2011 with catch-up vaccination among children 1-4 years in some areas. We assessed changes in pneumococcal carriage and antibiotic susceptibility patterns in children <5 years and adults., Methods: During 2009-2013, we performed annual cross-sectional pneumococcal carriage surveys in 2 sites: Kibera (children <5 years) and Lwak (children <5 years, adults). Only Lwak had catch-up vaccination. Nasopharyngeal and oropharyngeal (adults only) swabs underwent culture for pneumococci; isolates were serotyped. Antibiotic susceptibility testing was performed on isolates from 2009 and 2013; penicillin nonsusceptible pneumococci (PNSP) was defined as penicillin-intermediate or -resistant. Changes in pneumococcal carriage by age (<1 year, 1-4 years, adults), site, and human immunodeficiency virus (HIV) status (adults only) were calculated using modified Poisson regression, with 2009-2010 as baseline., Results: We enrolled 2962 children (2073 in Kibera, 889 in Lwak) and 2590 adults (2028 HIV+, 562 HIV-). In 2013, PCV10-type carriage was 10.3% (Lwak) to 14.6% (Kibera) in children <1 year and 13.8% (Lwak) to 18.7% (Kibera) in children 1-4 years. This represents reductions of 60% and 63% among children <1 year and 52% and 60% among children 1-4 years in Kibera and Lwak, respectively. In adults, PCV10-type carriage decreased from 12.9% to 2.8% (HIV+) and from 11.8% to 0.7% (HIV-). Approximately 80% of isolates were PNSP, both in 2009 and 2013., Conclusions: PCV10-type carriage declined in children <5 years and adults post-PCV10 introduction. However, PCV10-type and PNSP carriage persisted in children regardless of catch-up vaccination., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Data on pneumococcal conjugate vaccine (PCV) indirect effects in low-income countries with high human immunodeficiency virus (HIV) burden are limited. We examined adult pneumococcal pneumonia incidence before and after PCV introduction in Kenya in 2011., Methods: From 1 January 2008 to 31 December 2016, we conducted surveillance for acute respiratory infection (ARI) among ~12 000 adults (≥18 years) in western Kenya, where HIV prevalence is ~17%. ARI cases (cough or difficulty breathing or chest pain, plus temperature ≥38.0°C or oxygen saturation <90%) presenting to a clinic underwent blood culture and pneumococcal urine antigen testing (UAT). We calculated ARI incidence and adjusted for healthcare seeking. The proportion of ARI cases with pneumococcus detected among those with complete testing (blood culture and UAT) was multiplied by adjusted ARI incidence to estimate pneumococcal pneumonia incidence., Results: Pre-PCV (2008-2010) crude and adjusted ARI incidences were 3.14 and 5.30/100 person-years-observation (pyo), respectively. Among ARI cases, 39.0% (340/872) had both blood culture and UAT; 21.2% (72/340) had pneumococcus detected, yielding a baseline pneumococcal pneumonia incidence of 1.12/100 pyo (95% confidence interval [CI]: 1.0-1.3). In each post-PCV year (2012-2016), the incidence was significantly lower than baseline; with incidence rate ratios (IRRs) of 0.53 (95% CI: 0.31-0.61) in 2012 and 0.13 (95% CI: 0.09-0.17) in 2016. Similar declines were observed in HIV-infected (IRR: 0.13; 95% CI: 0.08-0.22) and HIV-uninfected (IRR: 0.10; 95% CI: 0.05-0.20) adults., Conclusions: Adult pneumococcal pneumonia declined in western Kenya following PCV introduction, likely reflecting vaccine indirect effects. Evidence of herd protection is critical for guiding PCV policy decisions in resource-constrained areas., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)