Azithromycin for Bacterial Watery Diarrhea: A Reanalysis of the AntiBiotics for Children With Severe Diarrhea (ABCD) Trial Incorporating Molecular Diagnostics.

BACKGROUND: Bacterial pathogens cause substantial diarrhea morbidity and mortality among children living in endemic settings, yet antimicrobial treatment is only recommended for dysentery or suspected cholera. METHODS: AntiBiotics for Children with severe Diarrhea was a 7-country, placebo-controlled, double-blind efficacy trial of azithromycin in children 2-23 months of age with watery diarrhea accompanied by dehydration or malnutrition. We tested fecal samples for enteric pathogens utilizing quantitative polymerase chain reaction to identify likely and possible bacterial etiologies and employed pathogen-specific cutoffs based on genomic target quantity in previous case-control diarrhea etiology studies to identify likely and possible bacterial etiologies. RESULTS: Among 6692 children, the leading likely etiologies were rotavirus (21.1%), enterotoxigenic Escherichia coli encoding heat-stable toxin (13.3%), Shigella (12.6%), and Cryptosporidium (9.6%). More than one-quarter (1894 [28.3%]) had a likely and 1153 (17.3%) a possible bacterial etiology. Day 3 diarrhea was less common in those randomized to azithromycin versus placebo among children with a likely bacterial etiology (risk difference [RD]likely, -11.6 [95% confidence interval {CI}, -15.6 to -7.6]) and possible bacterial etiology (RDpossible, -8.7 [95% CI, -13.0 to -4.4]) but not in other children (RDunlikely, -0.3% [95% CI, -2.9% to 2.3%]). A similar association was observed for 90-day hospitalization or death (RDlikely, -3.1 [95% CI, -5.3 to -1.0]; RDpossible, -2.3 [95% CI, -4.5 to -.01]; RDunlikely, -0.6 [95% CI, -1.9 to .6]). The magnitude of risk differences was similar among specific likely bacterial etiologies, including Shigella. CONCLUSIONS: Acute watery diarrhea confirmed or presumed to be of bacterial etiology may benefit from azithromycin treatment. CLINICAL TRIALS REGISTRATION: NCT03130114.

Phenotypic and molecular characterization of ß-lactamase-producing Klebsiella species among children discharged from hospital in Western Kenya.

BACKGROUND: The emergence and spread of ß-lactamase-producing Klebsiella spp. has been associated with a substantial healthcare burden resulting in therapeutic failures. We sought to describe the proportion of phenotypic resistance to commonly used antibiotics, characterize ß-lactamase genes among isolates with antimicrobial resistance (AMR), and assess the correlates of phenotypic AMR in Klebsiella spp. isolated from stool or rectal swab samples collected from children being discharged from hospital. METHODS: We conducted a cross-sectional study involving 245 children aged 1-59 months who were being discharged from hospitals in western Kenya between June 2016 and November 2019. Whole stool or rectal swab samples were collected and Klebsiella spp. isolated by standard microbiological culture. ß-lactamase genes were detected by PCR whilst phenotypic antimicrobial susceptibility was determined using the disc diffusion technique following standard microbiology protocols. Descriptive analyses were used to characterize phenotypic AMR and carriage of ß-lactamase-producing genes. The modified Poisson regression models were used to assess correlates of phenotypic beta-lactam resistance. RESULTS: The prevalence of ß-lactamase carriage among Klebsiella spp. isolates at hospital discharge was 62.9% (154/245). Antibiotic use during hospitalization (adjusted prevalence ratio [aPR] = 4.51; 95%CI: 1.79-11.4, p < 0.001), longer duration of hospitalization (aPR = 1.42; 95%CI: 1.14-1.77, p < 0.002), and access to treated water (aPR = 1.38; 95%CI: 1.12-1.71, p < 0.003), were significant predictors of phenotypically determined ß-lactamase. All the 154 ß-lactamase-producing Klebsiella spp. isolates had at least one genetic marker of ß-lactam/third-generation cephalosporin resistance. The most prevalent genes were blaCTX-M 142/154 (92.2%,) and blaSHV 142/154 (92.2%,) followed by blaTEM 88/154 (57.1%,) and blaOXA 48/154 (31.2%,) respectively. CONCLUSION: Carriage of ß-lactamase producing Klebsiella spp. in stool is common among children discharged from hospital in western Kenya and is associated with longer duration of hospitalization, antibiotic use, and access to treated water. The findings emphasize the need for continued monitoring of antimicrobial susceptibility patterns to inform the development and implementation of appropriate treatment guidelines. In addition, we recommend measures beyond antimicrobial stewardship and infection control within hospitals, improved sanitation, and access to safe drinking water to mitigate the spread of ß-lactamase-producing Klebsiella pathogens in these and similar settings.

Plasmid-mediated quinolone resistance genes detected in Ciprofloxacin non-susceptible Escherichia coli and Klebsiella isolated from children under five years at hospital discharge, Kenya.

BACKGROUND: The increasing spread of fluoroquinolone resistant enteric bacteria is a global public health concern. Children recently discharged from the hospital are at high risk of carriage of antimicrobial resistance (AMR) due to frequent exposure to antimicrobials during inpatient stays. This study aimed to determine the prevalence, correlates of ciprofloxacin (CIP) non-susceptibility, and distribution of plasmid-mediated quinolone resistance (PMQR) genes in Escherichia coli (E. coli) and Klebsiella spp isolated from children under five years being discharged from two Kenyan Hospitals. METHODS: E. coli and Klebsiella spp were isolated from fecal samples from children discharged from hospital and subjected to antimicrobial susceptibility testing (AST) by disc diffusion and E-test. CIP non-susceptible isolates were screened for seven PMQR genes using multiplex polymerase chain reaction (PCR). Poisson regression was used to determine the association between the carriage of CIP non-susceptible isolates and patient characteristics. RESULTS: Of the 280 CIP non-susceptible isolates: 188 E. coli and 92 Klebsiella spp isolates identified among 266 discharged children, 195 (68%) were CIP-non-susceptible with minimum inhibitory concentrations (MICs) of ≥ 1 µg/mL. Among these 195 isolates, 130 (67%) had high-level CIP MIC = ≥ 32 µg/mL). Over 80% of the isolates had at least one PMQR gene identified: aac(6')lb-cr (60%), qnrB (24%), oqxAB (22%), qnrS (16%), and qepA (6%), however, qnrA was not identified in any isolates tested. Co-carriage of qnrB with acc(6')-lb-cr was the most predominant accounting for 20% of all the isolates. Ceftriaxone use during hospital admission and the presence of extended spectrum beta-lactamase (ESBL) production were significantly associated with the carriage of CIP non-susceptible E. coli and Klebsiella spp. CONCLUSION: CIP non-susceptibility is common among E. coli and Klebsiella spp isolated from hospital discharged children in Kenya. Carriage and co-carriage of PMQR, including the newly identified qepA gene, were frequently observed. These findings suggest that children leaving the hospital may serve as an important reservoir for transmission of resistant E. coli and Klebsiella spp to the community. Enhanced surveillance for AMR determinants is critical to inform interventions to control antimicrobial-resistant bacteria.

Cytomegalovirus Viremia Predicts Postdischarge Mortality in Kenyan HIV-Exposed Uninfected Children.

BACKGROUND: Cytomegalovirus (CMV) viremia is associated with mortality in severely ill immunocompetent adults and hospitalized children with HIV (CWH). We measured CMV viremia in HIV-exposed and -unexposed Kenyan children aged 1-59 months discharged from hospital and determined its relationship with postdischarge mortality. METHODS: CMV DNA levels were measured in plasma from 1024 children (97 of which were HIV exposed uninfected [HEU], and 15 CWH). Poisson and Cox proportional hazards regression models were used to identify correlates of CMV viremia ≥ 1000 IU/mL and estimate associations with 6-month mortality, respectively. RESULTS: CMV viremia was detected in 31% of children, with levels ≥ 1000 IU/mL in 5.8%. HIV infection, age < 2 years, breastfeeding, and midupper arm circumference < 12.5 cm were associated with CMV viremia ≥ 1000 IU/mL. Among HEU children, CMV ≥ 1000 IU/mL (hazard ratio [HR] = 32.0; 95% confidence interval [CI], 2.9-354.0; P = .005) and each 1-log increase in CMV viral load (HR = 5.04; 95% CI, 1.7-14.6; P = .003) were associated with increased risk of mortality. CMV viremia was not significantly associated with mortality in HIV-unexposed children. CONCLUSIONS: CMV levels at hospital postdischarge predict increased risk of 6-month mortality in Kenyan HEU children. CMV suppression may be a novel target to reduce mortality in HEU children. CLINICAL TRIAL REGISTRATION: NCT02414399.

Enteric Permeability, Systemic Inflammation, and Post-Discharge Growth Among a Cohort of Hospitalized Children in Kenya and Pakistan.

OBJECTIVES: To determine whether gut permeability is associated with post-discharge growth and systemic inflammation among hospitalized children in low- and middle-income countries. METHODS: Children aged 2-23 months being discharged from Civil Hospital Karachi (Pakistan) and Migori County Referral Hospital (Kenya) underwent lactulose-rhamnose ratio (LRR) permeability testing and were compared to age-matched children from their home communities. Linear mixed effect models estimated the associations between LRR among discharged children with change in length-for-age (LAZ) and weight-for-age z score (WAZ) at 45, 90, and 180 days after discharge. Linear regression tested if relationships between LRR, systemic inflammation [C-reative protein (CRP), Cluster of Differentiation 14 (CD14), Tumour Necrosis Factor Alpha (TNFα), Interleukin-6 (IL-6)], and enterocyte damage [Intestinal Fatty-Acid Binding protein (I-FABP)] differed between the hospitalized and community groups. RESULTS: One hundred thirty-seven hospitalized and 84 community participants were included. The hospitalized group had higher log-LRR [0.43, 95% confidence interval (CI): 0.15-0.71, P = 0.003] than the community children. Adjustment for weight-for-length z score at discharge attenuated this association (0.31, 95% CI: 0.00-0.62, P = 0.049). LRR was not associated with changes in WAZ or LAZ in the post-discharge period. Associations between LRR and CRP (interaction P = 0.036), TNFα ( P = 0.017), CD14 ( P = 0.078), and IL-6 ( P = 0.243) differed between community and hospitalized groups. LRR was associated with TNFα ( P = 0.004) and approached significance with CD14 ( P = 0.078) and IL-6 ( P = 0.062) in community children, but there was no evidence of these associations among hospitalized children. CONCLUSIONS: Although increased enteric permeability is more prevalent among children being discharged from hospital compared to children in the community, it does not appear to be an important determinant of systemic inflammation or post-discharge growth among hospitalized children.

'They can stigmatize you': a qualitative assessment of the influence of school factors on engagement in care and medication adherence among adolescents with HIV in Western Kenya.

School-related factors may influence retention in care and adherence to antiretroviral therapy (ART) among adolescents with human immunodeficiency virus (HIV). We analyzed data from in-depth interviews with 40 adolescents with HIV (aged 14 -19 years), 40 caregivers of adolescents with HIV, and 4 focus group discussions with healthcare workers to evaluate contextual factors affecting adherence to ART and clinic attendance among adolescents, with a focus on the school environment. Informed by Anderson's Model of Health Services Utilization, transcripts were systematically coded and synthesized to identify school-related themes. All groups identified the school environment as a critical barrier to engagement in HIV care and medication adherence for adolescents with HIV. Adolescent participants reported inflexible school schedules and disclosure to school staff as the biggest challenges adhering to clinic appointments and ART. Adolescents described experiencing stigma and discrimination by peers and school staff and would adjust when, where and how often they took ART to avoid inadvertent disclosure. Boarding school students faced challenges because they had limited private space or time. Caregivers were often instrumental in navigating school permissions, including identifying a treatment supporter among school staff. Additional research engaging school staff may guide interventions for schools to reduce stigma and improve adherence and retention.

Exclusive breastfeeding among working mothers in Kenya: Perspectives from women, families and employers.

Exclusive breastfeeding (EBF) for the first 6 months of life improves survival, growth and development. In Kenya, recent legislation and policies advocate for maternity leave and workplace support for breastfeeding and breast milk expression. We conducted a qualitative study to describe factors influencing EBF for 6 months among mothers employed in commercial agriculture and tourism. We interviewed employed mothers (n = 42), alternate caregivers and employed mothers' husbands (n = 20), healthcare providers (n = 21), daycare directors (n = 22) and commercial flower farm and hotel managers (n = 16) in Naivasha, Kenya. Despite recognizing the recommended duration for EBF, employed mothers describe the early cessation of EBF in preparation for their return to work. Managers reported supporting mothers through flexible work hours and duties. Yet, few workplaces have lactation spaces, and most considered adjusting schedules more feasible than breastfeeding during work. Managers and healthcare providers believed milk expression could prolong EBF but thought mothers lack experience with pumping. The most frequently suggested interventions for improving EBF duration were to expand schedule flexibility (100% of groups), provide on-site daycare (80% of groups) and workplace lactation rooms (60% of groups), improve milk expression education and increase maternity leave length (60% of groups). Returning to work corresponds with numerous challenges including lack of proximate or on-site childcare and low support for and experience with milk expression. These factors currently make EBF for 6 months unattainable for most mothers in these industries. Interventions and supports to improve breastfeeding upon return to work are recommended to strengthen employed mothers' opportunity for EBF.

Male partner antenatal clinic attendance is associated with increased uptake of maternal health services and infant BCG immunization: a national survey in Kenya.

BACKGROUND: Male partner antenatal clinic (ANC) attendance may improve maternal uptake of maternal child health (MCH) services. METHODS: We conducted a cross-sectional survey of mother-infant pairs attending week-6 or month-9 infant immunizations at 120 high-volume MCH clinics throughout Kenya. Clinics were selected using probability proportionate to size sampling. Women were interviewed using structured questionnaires and clinical data was verified using MCH booklets. Among married women, survey-weighted logistic regression models accounting for clinic-level clustering were used to compare outcomes by male ANC attendance and to identify its correlates. RESULTS: Among 2521 women attending MCH clinics and had information on male partner ANC attendance, 2141 (90%) were married of whom 806 (35%) had male partners that attended ANC. Among married women, male partner ANC attendance was more frequent among women with higher education, women who requested their partners to attend ANC, had male partners with higher education, did not report partner violence, and had disclosed their HIV status (p < 0·001 for each). Additionally, male ANC attendance was associated with higher uptake of ANC visits [adjusted Odds Ratio (AOR) = 1·67, 95% confidence interval (CI) 1·36-2·05,], skilled delivery (AOR = 2·00, 95% CI 1·51-2·64), exclusive breastfeeding (AOR = 1·70, 95% CI 1·00-2·91), infant Bacille Calmette Guerin (BCG) immunization (AOR = 3·59, 95% CI 1·00-12·88), and among HIV-infected women, antiretroviral drugs (aOR = 6·16, 95% CI 1·26-30·41). CONCLUSION: Involving male partners in MCH activities amplifies benefits of MCH services by engaging partner support for maternal uptake of services.

Preexposure Prophylaxis for Human Immunodeficiency Virus (HIV) Prevention Among HIV-uninfected Pregnant Women: Estimated Coverage Using Risk-based Versus Regional Prevalence Approaches.

Antenatal register data from 62 clinics in 5 regions of Kenya were used to estimate women with human immunodeficiency virus (HIV) risk (partner HIV status, syphilis). With individual risk-guided preexposure prophylaxis (PrEP) offer in all regions, 39% of pregnant women would be offered PrEP nationally. Offering PrEP to all women in high-prevalence regions reached 26% of the pregnant women.

Non-disclosure to male partners and incomplete PMTCT regimens associated with higher risk of mother-to-child HIV transmission: a national survey in Kenya.

Health worker experience and community support may be higher in high HIV prevalence regions than low prevalence regions, leading to improved prevention of mother-to-child HIV transmission (PMTCT) programs. We evaluated 6-week and 9-month infant HIV transmission risk (TR) in a high prevalence region and nationally. Population-proportionate-to-size sampling was used to select 141 clinics in Kenya, and mobile teams surveyed mother-infant pairs attending 6-week and 9-month immunizations. HIV DNA testing was performed on HIV-exposed infants. Among 2521 mother-infant pairs surveyed nationally, 2423 (94.7%) reported HIV testing in pregnancy or prior diagnosis, of whom 200 (7.4%) were HIV-infected and 188 infants underwent HIV testing. TR was 8.8% (4.0%-18.3%) in 6-week and 8.9% (3.2%-22.2%) in 9-month cohorts including mothers with HIV diagnosed postpartum, of which 53% of infant infections were due to previously undiagnosed mothers. Of 276 HIV-exposed infants in the Nyanza survey, TR was 1.4% (0.4%-5.3%) at 6-week and 5.1% (2.5%-9.9%) at 9-months. Overall TR was lower in Nyanza, high HIV region, than nationally (3.3% vs. 7.2%, P = 0.02). HIV non-disclosure to male partners and incomplete ARVs were associated with TR in both surveys [aOR = 12.8 (3.0-54.3); aOR = 5.6 (1.2-27.4); aOR = 4.5 (1.0-20.0), aOR = 2.5, (0.8-8.4), respectively]. TR was lower in a high HIV prevalence region which had better ARV completion and partner HIV disclosure, possibly due to programmatic efficiencies or community/peer/partner support. Most 9-month infections were among infants of mothers without prior HIV diagnosis. Strategies to detect incident or undiagnosed maternal infections will be important to achieve PMTCT.

Prevalence and correlates of non-disclosure of maternal HIV status to male partners: a national survey in Kenya.

BACKGROUND: Prevention of mother-to-child HIV transmission (PMTCT) programs usually test pregnant women for HIV without involving their partners. Non-disclosure of maternal HIV status to male partners may deter utilization of PMTCT interventions since partners play a pivotal role in decision-making within the home including access to and utilization of health services. METHODS: Mothers attending routine 6-week and 9-month infant immunizations were enrolled at 141 maternal and child health (MCH) clinics across Kenya from June-December 2013. The current analysis was restricted to mothers with known HIV status who had a current partner. Multivariate logistic regression models adjusted for marital status, relationship length and partner attendance at antenatal care (ANC) were used to determine correlates of HIV non-disclosure among HIV-uninfected and HIV-infected mothers, separately, and to evaluate the relationship of non-disclosure with uptake of PMTCT interventions. All analyses accounted for facility-level clustering, RESULTS: Overall, 2522 mothers (86% of total study population) met inclusion criteria, 420 (17%) were HIV-infected. Non-disclosure of HIV results to partners was higher among HIV-infected than HIV-uninfected women (13% versus 3% respectively, p < 0.001). HIV-uninfected mothers were more likely to not disclose their HIV status to male partners if they were unmarried (adjusted odds ratio [aOR] = 3.79, 95% CI: 1.56-9.19, p = 0.004), had low (≤KSH 5000) income (aOR = 1.85, 95% CI: 1.00-3.14, p = 0.050), experienced intimate partner violence (aOR = 3.65, 95% CI: 1.84-7.21, p < 0.001) and if their partner did not attend ANC (aOR = 4.12, 95% CI: 1.89-8.95, p < 0.001). Among HIV-infected women, non-disclosure to male partners was less likely if women had salaried employment (aOR = 0.42, 95%CI: 0.18-0.96, p = 0.039) and each increasing year of relationship length was associated with decreased likelihood of non-disclosure (aOR = 0.90, 95% CI: 0.82-0.98, p = 0.015 for each year increase). HIV-infected women who did not disclose their HIV status to partners were less likely to uptake CD4 testing (aOR = 0.32, 95% CI: 0.15-0.69, p = 0.004), to use antiretrovirals (ARVs) during labor (OR = 0.38, 95% CI 0.15-0.97, p = 0.042), or give their infants ARVs (OR = 0.08, 95% CI 0.02-0.31, p < 0.001). CONCLUSION: HIV-infected women were less likely to disclose their status to partners than HIV-uninfected women. Non-disclosure was associated with lower use of PMTCT services. Facilitating maternal disclosure to male partners may enhance PMTCT uptake.

Malaria Parasitemia and Parasite Density in Antiretroviral-Treated HIV-Infected Adults Following Discontinuation of Cotrimoxazole Prophylaxis.

BACKGROUND: Cotrimoxazole (CTX) discontinuation increases malaria incidence in human immunodeficiency virus (HIV)-infected individuals. Rates, quantity, and timing of parasitemia rebound following CTX remain undefined. METHODS: Serial specimens from a trial of HIV-infected individuals receiving antiretroviral treatment (ART) randomized to continue (the CTX arm) or discontinue (the STOP-CTX arm) were examined for malaria parasites by quantitative reverse transcription polymerase chain reaction (PCR). Specimens obtained at enrollment and then quarterly for 12 months and at sick visits were assessed; multiplicity of infection was evaluated by PCR that targeted the polymorphic msp-1/msp-2 alleles. RESULTS: Among 500 HIV-infected adults receiving ART (median ART duration, 4.5 years), 5% had detectable parasitemia at baseline. After randomization, parasite prevalence increased over time in the STOP-CTX arm, compared with the CTX arm, with values of 4% and <1%, respectively, at month 3, 8% and 2% at month 6, 14% and 2% at month 9, and 22% and 4% at month 12 (P = .0034). The combined mean parasite density at the various time points was higher in the STOP-CTX arm (4.42 vs 3.13 log10 parasites/mL; P < .001). The parasitemia incidence was 42.0 cases per 100 person-years in the STOP-CTX arm and 9.9 cases per 100 person-years in the CTX arm, with an incidence rate ratio of 4.3 (95% confidence interval, 2.7-7.1; P < .001). After enrollment, mixed infections (multiplicity of infection, >1) were only present in the STOP-CTX arm. CONCLUSION: Discontinuation of CTX by HIV-infected adults receiving ART resulted in progressive increases in malaria parasitemia prevalence and burden. CLINICAL TRIALS REGISTRATION: NCT01425073.

Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya: A Randomized Non-inferiority Trial.

BACKGROUND: Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organization (WHO) for HIV-1-infected individuals in settings with high infectious disease prevalence. The WHO 2006 guidelines were developed prior to the scale-up of antiretroviral therapy (ART). The threshold for CTX discontinuation following ART is undefined in resource-limited settings. METHODS AND FINDINGS: Between 1 February 2012 and 30 September 2013, we conducted an unblinded non-inferiority randomized controlled trial of CTX prophylaxis cessation versus continuation among HIV-1-infected adults on ART for ≥ 18 mo with CD4 count > 350 cells/mm3 in a malaria-endemic region in Kenya. Participants were randomized and followed up at 3-mo intervals for 12 mo. The primary endpoint was a composite of morbidity (malaria, pneumonia, and diarrhea) and mortality. Incidence rate ratios (IRRs) were estimated using Poisson regression. Among 538 ART-treated adults screened, 500 were enrolled and randomized, 250 per arm. Median age was 40 y, 361 (72%) were women, and 442 (88%) reported insecticide-treated bednet use. Combined morbidity/mortality was significantly higher in the CTX discontinuation arm (IRR = 2.27, 95% CI 1.52-3.38; p < 0.001), driven by malaria morbidity. There were 34 cases of malaria, with 33 in the CTX discontinuation arm (IRR = 33.02, 95% CI 4.52-241.02; p = 0.001). Diarrhea and pneumonia rates did not differ significantly between arms (IRR = 1.36, 95% CI 0.82-2.27, and IRR = 1.43, 95% CI 0.54-3.75, respectively). Study limitations include a lack of placebo and a lower incidence of morbidity events than expected. CONCLUSIONS: CTX discontinuation among ART-treated, immune-reconstituted adults in a malaria-endemic region resulted in increased incidence of malaria but not pneumonia or diarrhea. Malaria endemicity may be the most relevant factor to consider in the decision to stop CTX after ART-induced immune reconstitution in regions with high infectious disease prevalence. These data support the 2014 WHO CTX guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT01425073.

Frequency and correlates of malaria over-treatment in areas of differing malaria transmission: a cross-sectional study in rural Western Kenya.

BACKGROUND: In 2010, the World Health Organization shifted its malaria guidelines from recommending the empiric treatment of all febrile children to treating only those with laboratory-confirmed malaria. This study evaluated the frequency and predictors of malaria over-treatment among febrile malaria-negative children in Kenya. METHODS: Between 2012 and 2013, 1,362 children presenting consecutively with temperature ≥37.5°C to Kisii and Homa Bay hospitals were enrolled in a cross-sectional study evaluating causes of fever. Children were screened for malaria using smear microscopy and rapid diagnostic tests and managed according to standard of care at the hospitals. The frequency of anti-malarial prescriptions among children with laboratory-confirmed malaria negative children (malaria over-treatment) was determined; and clinical and demographic correlates of overtreatment evaluated using logistic regression. Because of differences in malaria endemicity, analyses were stratified and compared by site. RESULTS: Among 1,362 children enrolled, 46 (7%) of 685 children in Kisii, and 310 (45.8%) of 677 in Homa Bay had laboratory-confirmed malaria; p < 0.001. Among malaria-negative children; 210 (57.2%) in Homa Bay and 45 (7.0%) in Kisii received anti-malarials; p < 0.001. Predictors of over-treatment in Homa Bay included ≥ one integrated management of childhood illness (IMCI) danger sign (aOR = 8.47; 95% CI: 4.81-14.89), fever lasting ≥ seven days (aOR = 4.94; 95% CI: 1.90-12.86), and fever ≥39°C (aOR = 3.07; 95% CI: 1.58-5.96). In Kisii, only fever ≥39°C predicted over-treatment (aOR = 2.13; 95% CI: 1.02-4.45). CONCLUSIONS: Malaria over-treatment was common, particularly in Homa Bay, where the prevalence of malaria was extremely high. Severe illness and high or prolonged fever were associated with overtreatment. Overtreatment may result in failure to treat other serious causes of fever, drug resistance, and unnecessarily treatment costs.

Maternal Tenofovir Disoproxil Fumarate Use in Pregnancy and Growth Outcomes among HIV-Exposed Uninfected Infants in Kenya.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is commonly used in antiretroviral treatment (ART) and preexposure prophylaxis regimens. We evaluated the relationship of prenatal TDF use and growth outcomes among Kenyan HIV-exposed uninfected (HEU) infants. MATERIALS AND METHODS: We included PCR-confirmed HEU infants enrolled in a cross-sectional survey of mother-infant pairs conducted between July and December 2013 in Kenya. Maternal ART regimen during pregnancy was determined by self-report and clinic records. Six-week and 9-month z-scores for weight-for-age (WAZ), weight-for-length (WLZ), length-for-age (LAZ), and head circumference-for-age (HCAZ) were compared among HEU infants with and without TDF exposure using t-tests and multivariate linear regression models. RESULTS: Among 277 mothers who received ART during pregnancy, 63% initiated ART before pregnancy, of which 89 (32%) used TDF. No differences in birth weight (3.0 kg versus 3.1 kg, p = 0.21) or gestational age (38 weeks versus 38 weeks, p = 0.16) were detected between TDF-exposed and TDF-unexposed infants. At 6 weeks, unadjusted mean WAZ was lower among TDF-exposed infants (-0.8 versus -0.4, p = 0.03), with a trend towards association in adjusted analyses (p = 0.06). There were no associations between prenatal TDF use and WLZ, LAZ, and HCAZ in 6-week or 9-month infant cohorts. CONCLUSION: Maternal TDF use did not adversely affect infant growth compared to other regimens.

Factors associated with exclusive breastfeeding by maternal HIV status: a population-based survey in Kenya.

BACKGROUND: Exclusive breastfeeding (EBF) in the first six months remains low globally, despite known benefits of lower morbidity and mortality among breastfed infants. It is important to understand factors associated with breastfeeding to support optimal breastfeeding practices, particularly in settings with a high burden of HIV. METHODS: We analyzed data from a population-level survey of mother-infant pairs attending 6-week or 9-month immunizations at 141 clinics across Kenya. Primary outcomes included maternal report of (1) EBF at 6-week visit, defined as currently feeding the infant breast milk only, (2) EBF for the first 6-months of life, defined as breastfeeding or feeding the infant breast milk only with no introduction of other liquids or solid foods until 6 months, and (3) continued breastfeeding with complementary feeding at 9-months. Correlates of breastfeeding practices were assessed using generalized Poisson regression models accounting for facility-level clustering. RESULTS: Among 1662 mothers at 6-weeks, nearly all self-reported breastfeeding of whom 93% were EBF. Among 1180 mothers at 9-months, 99% had ever breastfed, 94% were currently breastfeeding and 73% reported 6-month EBF. At 6-weeks, younger age (< 25 years) (adjusted Prevalence Ratio (aPR) 0.96; 95% CI 0.93, 0.99), lower education (aPR 0.96; 95% CI 0.93, 0.99) and recent infant illness (aPR 0.97; 95% CI 0.94, 1.00) were associated with lower EBF prevalence while women living with HIV (WLWH) had higher EBF prevalence (aPR 1.06; 95% CI 1.02, 1.10) than women without HIV. 6-month EBF prevalence was 26% higher in WLWH (aPR 1.26; 95% CI 1.15, 1.35) than women without HIV, 14% lower in women reporting mild or above depressive symptoms (aPR 0.86; 95% CI 0.76, 0.99) than those with none or minimal depressive symptoms, and 15% lower in women with versus without history of intimate partner violence (aPR 0.85; 95% CI 0.74, 0.98). At 9-months, WLWH had a lower prevalence of continued breastfeeding with complementary feeding (aPR 0.73; 95% CI 0.64, 0.84) than women without HIV. CONCLUSION: WLWH had higher EBF prevalence in the first 6-months, but lower prevalence of continued breastfeeding at 9-months. Strategies to support EBF and continued breastfeeding beyond 6-months postpartum, particularly among WLWH, are needed.

ß-Lactamase and Macrolide Resistance Gene Carriage in Escherichia coli Isolates Among Children Discharged From Inpatient Care in Western Kenya: A Cross-sectional Study.

Background: Antimicrobial resistance (AMR) is a global threat to infectious disease control, particularly among recently hospitalized children. We sought to determine the prevalence and mitigating factors of resistance in enteric Escherichia coli among children discharged from health facilities in western Kenya. Methods: Between June 2016 and November 2019, children aged 1 to 59 months were enrolled at the point of discharge from the hospital. E coli was isolated by microbiological culture from rectal swabs at baseline. ß-Lactamases and macrolide resistance-conferring genes were detected by polymerase chain reaction. A modified Poisson regression model was used to assess the predictors mph(A) and CTX-M-type extended-spectrum ß-lactamase (ESBL). Results: Of the 238 children whose E coli isolates were tested, 91 (38.2%) and 109 (45.8%) had detectable CTX-M-type ESBL and mph(A) genes, respectively. Antibiotic treatment during hospitalization (adjusted prevalence ratio [aPR], 2.47; 95% CI, 1.12-5.43; P = .025), length of hospitalization (aPR, 1.42; 95% CI, 1.00-2.01; P = .052), and the practice of open defecation (aPR, 2.47; 95% CI, 1.40-4.36; P = .002) were independent predictors for CTX-M-type ESBL and mph(A) genes. Pneumococcal vaccination was associated with a 43% lower likelihood of CTX-M-type ESBL (aPR, 0.57; 95% CI, .38-.85; P = .005), while measles vaccination was associated with a 32% lower likelihood of mph(A) genes (aPR, 0.68; 95% CI, .49-.93; P = .017) in E coli isolates. Conclusions: Among children discharged from the hospital, history of vaccination, shorter hospital stay, lack of in-hospital antibiotic exposure, and improved sanitation were associated with a lower likelihood of AMR genes. To mitigate the continued spread of AMR, AMR control programs should consider strategies beyond antimicrobial stewardship, including improvements in sanitation, increased vaccine coverage, and the development of novel vaccines.

Prevalence and Correlates of Stunting among a High-Risk Population of Kenyan Children Recently Hospitalized for Acute Illnesses.

Stunting (length/height-for-age z-score < -2) is associated with significant morbidity and mortality among children under 5 years of age in sub-Saharan Africa. Children who are stunted and recently hospitalized for acute illness may be at particularly elevated risk for post-discharge mortality. In this cross-sectional analysis, we measured the prevalence of stunting at hospital discharge and identified host, caregiver, and environmental correlates of stunting among children aged 1-59 months in Western Kenya enrolled in the Toto Bora Trial. Child age- and site-adjusted prevalence ratios were estimated using Poisson regression. Of the 1,394 children included in this analysis, 23% were stunted at hospital discharge. Older children (12-23 months and 24-59 months versus 0-5 months) had a higher prevalence of stunting (adjusted prevalence ratio [aPR]: 1.58; 95% CI: 1.04-2.36 and aPR: 1.59; 95% CI: 1.08-2.34, respectively). HIV-exposed, uninfected children (aPR: 1.94; 95% CI: 1.39-2.70), children with HIV infection (aPR: 2.73; 95% CI: 1.45-5.15), and those who were never exclusively breastfed in early life (aPR 2.51; 95% CI: 1.35-4.67) were more likely to be stunted. Caregiver education (primary school or less) and unimproved sanitation (pit latrine without slab floor or open defecation) were associated with increased risk of stunting (aPR: 1.94; 95% CI: 1.54-2.44; aPR: 1.99; 95% CI: 1.20-3.31; aPR: 3.57; 95% CI: 1.77-7.21, respectively). Hospital discharge represents an important opportunity for both identifying and delivering targeted interventions for nutrition-associated poor outcomes among a high-risk population of children.

Clinical and nutritional correlates of bacterial diarrhoea aetiology in young children: a secondary cross-sectional analysis of the ABCD trial.

OBJECTIVE: The objective was to assess the association between nutritional and clinical characteristics and quantitative PCR (qPCR)-diagnosis of bacterial diarrhoea in a multicentre cohort of children under 2 years of age with moderate to severe diarrhoea (MSD). DESIGN: A secondary cross-sectional analysis of baseline data collected from the AntiBiotics for Children with Diarrhoea trial (NCT03130114). PATIENTS: Children with MSD (defined as >3 loose stools within 24 hours and presenting with at least one of the following: some/severe dehydration, moderate acute malnutrition (MAM) or severe stunting) enrolled in the ABCD trial and collected stool sample. STUDY PERIOD: June 2017-July 2019. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Likely bacterial aetiology of diarrhoea. Secondary outcomes included specific diarrhoea aetiology. RESULTS: A total of 6692 children with MSD had qPCR results available and 28% had likely bacterial diarrhoea aetiology. Compared with children with severe stunting, children with MAM (adjusted OR (aOR) (95% CI) 1.56 (1.18 to 2.08)), some/severe dehydration (aOR (95% CI) 1.66 (1.25 to 2.22)) or both (aOR (95% CI) 2.21 (1.61 to 3.06)), had higher odds of having likely bacterial diarrhoea aetiology. Similar trends were noted for stable toxin-enterotoxigenic Escherichia coli aetiology. Clinical correlates including fever and prolonged duration of diarrhoea were not associated with likely bacterial aetiology; children with more than six stools in the previous 24 hours had higher odds of likely bacterial diarrhoea (aOR (95% CI) 1.20 (1.05 to 1.36)) compared with those with fewer stools. CONCLUSION: The presence of MAM, dehydration or high stool frequency may be helpful in identifying children with MSD who might benefit from antibiotics.

Childhood growth during recovery from acute illness in Africa and South Asia: a secondary analysis of the childhood acute illness and nutrition (CHAIN) prospective cohort.

Background: Growth faltering is well-recognized during acute childhood illness and growth acceleration during convalescence, with or without nutritional therapy, may occur. However, there are limited recent data on growth after hospitalization in low- and middle-income countries. Methods: We evaluated growth following hospitalization among children aged 2-23 months in sub-Saharan Africa and South Asia. Between November 2016 and January 2019, children were recruited at hospital admission and classified as: not-wasted (NW), moderately-wasted (MW), severely-wasted (SW), or having nutritional oedema (NO). We describe earlier (discharge to 45-days) and later (45- to 180-days) changes in length-for-age [LAZ], weight-for-age [WAZ], mid-upper arm circumference [MUACZ], weight-for-length [WLZ] z-scores, and clinical, nutritional, and socioeconomic correlates. Findings: We included 2472 children who survived to 180-days post-discharge: NW, 960 (39%); MW, 572 (23%); SW, 682 (28%); and NO, 258 (10%). During 180-days, LAZ decreased in NW (-0.27 [-0.36, -0.19]) and MW (-0.23 [-0.34, -0.11]). However, all groups increased WAZ (NW, 0.21 [95% CI: 0.11, 0.32]; MW, 0.57 [0.44, 0.71]; SW, 1.0 [0.88, 1.1] and NO, 1.3 [1.1, 1.5]) with greatest gains in the first 45-days. Of children underweight (<-2 WAZ) at discharge, 66% remained underweight at 180-days. Lower WAZ post-discharge was associated with age-inappropriate nutrition, adverse caregiver characteristics, small size at birth, severe or moderate anaemia, and chronic conditions, while lower LAZ was additionally associated with household-level exposures but not with chronic medical conditions. Interpretation: Underweight and poor linear growth mostly persisted after an acute illness. Beyond short-term nutritional supplementation, improving linear growth post-discharge may require broader individual and family support. Funding: Bill & Melinda Gates FoundationOPP1131320; National Institute for Health ResearchNIHR201813.