A primary series of Sinovac COVID-19 vaccine (CoronaVac) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine successfully increased anti-spike antibodies, neutralizing antibodies, and T-lymphocytes, as was also observed following booster doses of Oxford-AstraZeneca or BNT162b2 (Pfizer-BioNTech) vaccine. However, information regarding the dynamics of specific B- and T-lymphocytes induced by additional vaccinations remains limited. We examined the dynamics of specific B- and T-lymphocyte subsets induced by primary series vaccinations and booster doses over a two-year period of COVID-19 vaccination among healthcare personnel (HCP) enrolled in a prospective cohort study in Thailand. HCP, recruited between January and March 2021, had blood specimens collected at enrollment and at three-month intervals for cellular immune response testing. COVID-19 vaccinated participants (verified against documentation) were grouped by vaccination schedules: (A) CoronaVac with Oxford-AstraZeneca vaccine as the first booster dose (n = 46), (B) CoronaVac with Pfizer-BioNTech vaccine as the first booster dose (n = 53), and (C) Oxford-AstraZeneca vaccine (n = 29). All three groups had up to four subsequent booster doses of either the same or different platforms. Following the B-lymphocyte enzyme-linked immunospot and the T-lymphocyte intracellular cytokine staining assays, SARS-CoV-2 spike 1 (S1)- and receptor-binding domain (RBD)-specific antibody-secreting B-lymphocytes, and Interferon Gamma (IFN-Ƴ)- and/or Tumor Necrosis Factor Alpha (TNF-α)-producing T-lymphocytes for all blood collection time points were counted. Among participants without evidence of infection (i.e.,  those who tested negative for SARS-CoV-2 antibodies prior to vaccination and those who tested negative by SARS-CoV-2 real-time reverse transcription polymerase chain reaction during the study), levels of cellular immune response during weeks 1-12 since the last vaccine dose were compared between vaccine doses using the Kruskal-Wallis test. In all three groups, compared to the primary series, the first booster dose induced significant SARS-CoV-2 antigen-specific antibody-secreting B-lymphocyte counts (range 4.2-9.0-fold increase) but non-significant S1-specific cytokine-producing T-lymphocyte counts (range 0.5-1.3-fold). There were no notable differences in both antigen-specific antibody-secreting B-lymphocyte and specific cytokine-producing T-lymphocyte counts following the second, third, and fourth booster doses in all three groups compared to the first booster dose. Initial COVID-19 booster doses were essential for overall increases in the peak counts of antigen-specific B-lymphocytes, prior to minimal contraction phases occurred following additional boosters, while antigen-specific T-lymphocyte counts maintained a consistently high levels of immune response. The second, third, and fourth booster doses restored the levels of both B- and T-lymphocytes after the immune responses waned in a time-dependent manner.

INTRODUCTION: By the end of 2021, U.S. spike (S) antibody seroprevalence from COVID-19 vaccination, infection, or both (hybrid immunity) reached over 90%. With high seroprevalence, quantitative antibody concentrations are needed to characterize population immunity. We measured quantitative S antibody concentrations in a national blood donor cohort and evaluated their correlation with protection against infection. METHODS: One blood specimen per quarter in 2022 was tested for quantitative S IgG and infection-induced (nucleocapsid [N]) total Ig antibodies from a national blood donor sub-cohort of 106,969 people. Median S antibody concentrations were calculated by quarter and by history of vaccination and infection. Among vaccinated donors without N antibodies, protection (measured as 1 minus hazard ratios compared with unvaccinated donors) against N antibody seroconversion was estimated by S antibody concentration. Median S antibody levels were compared using the Kruskal-Wallis tests. RESULTS: Median S antibody concentrations increase from 1380 binding antibody units (BAU)/mL in quarter (Q) 1 2022 to 1720 BAU/mL in Q4 2022. In Q4, S antibody levels were lowest in the infection-only group (median: 75 BAU/mL) and higher in the vaccine-only (median: 1950 BAU/mL) and hybrid immunity group (median: 2550 BAU/mL). Protection against first-time infection increased with higher antibody concentrations; 5010 BAU/mL (95% CI 4120-6550) was associated with 50% protection. DISCUSSION: During 2022, this nationwide study showed mildly increased S IgG concentrations over time among blood donors. Vaccination and hybrid immunity resulted in higher antibody concentrations than infection alone. Higher antibody concentrations were associated with increased protection from infection.

The Centers for Disease Control and Prevention (CDC) funds tuberculosis (TB) Centers of Excellence (COEs) that support TB control and prevention efforts in the United States. In 2018, the TB COEs conducted a multiphased assessment among U.S. staff involved in TB service delivery to identify needs related to TB training, resources, and medical consultation. Representatives from each TB COE and CDC's Division of TB Elimination formed a workgroup to guide the design of the needs assessment. The group used an online survey for data collection. Participants were staff working in some capacity on TB within the United States, Puerto Rico, and the U.S. Virgin Islands. Staff could be in non-public health (e.g., community health center, hospital, laboratory, private practice) or public health (state or local health department staff responsible for TB) settings and did not have to be a clinical health care provider (N = 1,482). We identified four priority areas for future TB training and education efforts. These areas include (1) focus on key topics; (2) tailor training and products to different professions, settings, and skill levels; (3) keep learners updated on the latest resources and best practices; and (4) use a mix of training methods and formats. The findings highlighted future priorities for TB training and education and were shared with health department TB programs throughout the United States.

Trichomonas vaginalis (TV) and bacterial vaginosis (BV) are highly prevalent vaginal infections. Both are associated with pelvic inflammatory disease and HIV acquisition and transmission, though the underlying mechanisms are incompletely understood. We characterized the effect of TV and BV infection on inflammatory markers in the vagina among reproductive-aged women in Atlanta, Georgia. Cervicovaginal lavage specimens were collected from HIV seronegative women at a baseline visit and again three months later. Eighteen individual cytokines, 17 T cell subsets, BV, and TV were measured at both timepoints. After natural log transformation, the median cytokine concentration and number of T cells were compared by infection status statistically using the Kruskal-Wallis test. A cytokine inflammation score and a T cell score were created using principal components analysis. The scores were then used as outcomes in separate linear mixed regression models with a random intercept. Sixty women had baseline data and 43 were seen for follow-up. The median age was 30 years, 78% self-reported Black race. TV and BV prevalence at the baseline visit was 15% and 37%, respectively. The concentration of 16 out of 18 cytokines differed by infection status. In multivariable modeling, neither TV nor BV were associated with cytokine score. Most CD4+ T cell subsets (7 out of 9) differed by infection status. In a multivariable model, TV infection was associated with a higher T cell score (1.54; 95%CI 0.00, 3.08). BV was not associated with a higher T cell score. Increased concentration of vaginal mucosal T cells may explain the observed association between TV infection and HIV risk.

BACKGROUND: Tuberculosis (TB) Building and Strengthening Infection Control Strategies (TB BASICS) aimed to achieve improvements in TB infection prevention and control (IPC) through structured training and mentorship. METHODS: TB BASICS was implemented in six Chinese provinces from 2017-2019. Standardized, facility-based risk assessments tailored to inpatient, laboratory, and outpatient departments were conducted quarterly for 18 months. Knowledge, attitudes, and practices surveys were administered to healthcare workers (HCW) at nine participating facilities during the first and last assessments. Kruskal-Wallis rank sum test assessed score differences between departments (alpha = 0.05). RESULTS: Fifty-seven departments received risk assessments. IPC policies and practices improved substantially during follow up. Facility-based assessment scores were significantly lower in outpatient departments than other departments (p <0.05). All indicators achieved at least partial implementation by the final assessment. Low scores persisted for implementing isolation protocols, while personal protective equipment use among staff was consistent among all departments. Overall, we observed minimal change in IPC knowledge among HCW. In general, HCW had favorable views of their own IPC capabilities, but reported limited agency to improve institutional IPC. CONCLUSIONS: TB BASICS demonstrated improvements in TB IPC implementation. Structured training and mentorship engaged HCW to maintain confidence and competency for TB prevention.

PURPOSE: Renal ultrasounds are performed in patients with myelomeningocele to screen for markers of kidney health, including hydronephrosis. We evaluated the diagnostic accuracy of hydronephrosis to screen for low kidney function defined by estimated glomerular filtration rate (eGFR). MATERIALS AND METHODS: We performed a retrospective cross-sectional study using data from 2 cohorts of children and youth with myelomeningocele. The first cohort is the Urological Management to Preserve Initial Renal Function Protocol for Young Children With Spina Bifida (UMPIRE; 2016-2022) and the second from the National Spina Bifida Patient Registry (NSBPR; 2009-2021). We identified patients aged 1 to 18 years with available eGFR data within 6 months of an ultrasound. We excluded NSBPR patients younger than 6 years to address potential duplication across cohorts. The primary outcome was eGFR < 90 mL/min/1.73 m(2), calculated using the bedside Schwartz formula. Hydronephrosis was dichotomized into any/none. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of any hydronephrosis using eGFR as the reference standard. RESULTS: In UMPIRE, 221 patients were included with median age 2.4 years (IQR, 1.9-3.8) and 24% having eGFR < 90. Any hydronephrosis vs none conferred a sensitivity/specificity/PPV/NPV of 25%/75%/24%/77%, respectively. In NSBPR, 2269 patients were included with median age 13 years (IQR, 9.6-16.3) and 17% having eGFR < 90. Any hydronephrosis vs none conferred a sensitivity/specificity/PPV/NPV of 24%/87%/26%/85%, respectively. CONCLUSIONS: In 2 cohorts of children and youth with myelomeningocele, hydronephrosis conferred a sensitivity of ∼25% for a creatinine-based eGFR < 90 mL/min/1.73 m(2). This low sensitivity suggests that hydronephrosis alone is a poor screening marker of kidney health.

BACKGROUND: Data regarding ocular tuberculosis (OTB) in the United States have not been previously reported. We evaluated trends of OTB compared with other extrapulmonary TB (EPTB). METHODS: We estimated the proportion of all EPTB cases (with or without concurrent pulmonary involvement) with OTB reported to the National Tuberculosis Surveillance System during 1993-2019. We compared demographics and clinical characteristics of people with OTB and other EPTB during 2010-2019. P values were calculated by chi-square test for categorical variables and Kruskal-Wallis for continuous variables. RESULTS: During 1993-2019, 1766 OTB cases were reported, representing 1.6% of 109 834 all EPTB cases: 200 (0.5% of 37 167) during 1993-1999, 395 (1.0% of 41 715) during 2000-2009, and 1171 (3.8% of 30 952) during 2010-2019. In contrast to persons with other EPTB, persons with OTB were older (median, 48 vs 44 years; P < .01), more likely to be US-born (35% vs 28%; P < .01), more likely to have diabetes (17% vs 13%; P < .01), and less likely to have HIV (1% vs 8%; P < .01). OTB was less likely to be laboratory confirmed (5% vs 75%; P < .01), but patients were more likely to be tested by interferon gamma release assay (IGRA; 84% vs 56%; P < .01) and to be IGRA positive (96% vs 80%; P < .01). CONCLUSIONS: Reported OTB increased during 1993-2019 despite decreasing TB, including EPTB; the largest increase occurred during 2010-2019. OTB was rarely laboratory confirmed and was primarily diagnosed in conjunction with IGRA results. More research is needed to understand the epidemiology of OTB to inform clinical and diagnostic practices.

Blood-based diagnostic biomarkers for amyotrophic lateral sclerosis will improve patient outcomes and positively impact novel drug development. Critical to the development of such biomarkers is robust method validation, optimization and replication with adequate sample sizes and neurological disease comparative blood samples. We sought to test an amyotrophic lateral sclerosis biomarker derived from diverse samples to determine if it is disease specific. Extracellular vesicles were extracted from blood plasma obtained from individuals diagnosed with amyotrophic lateral sclerosis, primary lateral sclerosis, Parkinson's disease and healthy controls. Immunoaffinity purification was used to create a neural-enriched extracellular vesicle fraction. MicroRNAs were measured across sample cohorts using real-time polymerase chain reaction. A Kruskal-Wallis test was used to assess differences in plasma microRNAs followed by post hoc Mann-Whitney tests to compare disease groups. Diagnostic accuracy was determined using a machine learning algorithm and a logistic regression model. We identified an eight-microRNA diagnostic signature for blood samples from amyotrophic lateral sclerosis patients with high sensitivity and specificity and an area under the curve calculation of 98% with clear statistical separation from neurological controls. The eight identified microRNAs represent disease-related biological processes consistent with amyotrophic lateral sclerosis. The direction and magnitude of gene fold regulation are consistent across four separate patient cohorts with real-time polymerase chain reaction analyses conducted in two laboratories from diverse samples and sample collection procedures. We propose that this diagnostic signature could be an aid to neurologists to supplement current clinical metrics used to diagnose amyotrophic lateral sclerosis.

Rationale & Objective: The 2021 CKD-EPI removes Black race as a factor in calculating the estimated glomerular filtration rate (eGFR). We assessed its effect on CKD prevalence in the demographically-diverse US Military Health System. Study Design: A retrospective calculation of the eGFR from serum creatinine measured over 2016-2019 using both the 2009 and 2021 CKD-EPI equations. Setting & Population: Multicenter health care network with data from 1,502,607 adults in the complete case analysis and from 1,970,433 adults in an imputed race analysis. Predictors: Serum creatinine, age, sex, and race. Outcome: CKD stages 3-5, defined as the last eGFR persistently < 60 mL/min/1.73m2 for ≥90 days. Analytical Approach: The t test and Kruskal-Wallis test were used for continuous variables and Χ2 for categorical data. Results: The population in the complete case analysis had a median age of 40 years and was 18.8% Black race and 35.4% female. With the 2021 equation, the number of Black adults with CKD stages 3-5 increased by 58.1% from 4,147 to 6,556, a change in the crude prevalence from 1.47% to 2.32%. The number of non-Black adults with CKD stages 3-5 decreased by 30.4% from 27,596 to 19,213, a crude prevalence change from 2.26% to 1.58%. Similar results were seen with race imputation. Cumulatively, among adults with CKD stages 3-5 by at least one equation, 45.8% of Black adults were reclassified to more advanced stages of CKD and 44.0% of non-Black adults were reclassified to less severe stages across eGFR thresholds that could change clinical management. Limitations: Potential underestimation of CKD in individuals with only 1 measurement. Conclusions: Adoption of the 2021 CKD-EPI equation in the Military Health System reclassifies many Black adults into new CKD stages 3-5 or into more advanced CKD stages, with the opposite effect on non-Black adults. This may have an effect on CKD treatment and outcomes in ways that are yet unknown. Plain-Language Summary: Until recently, kidney function level was calculated from equations that adjusted the result if the individual was of Black race. Because this may contribute to racial disparities in kidney disease care, a new equation was developed in 2021 that excludes race as a factor. We assessed the possible effects of this equation using data from adults in the US Military Health System from 2016 to 2019. With the new equation, the number of Black adults classified with kidney disease increased while that of non-Black adults decreased. There were similar trends seen in the more severe levels of kidney disease, which could affect decisions in clinical care. These results emphasize the potential positive and negative outcomes to be monitored with the new equation. © 2024 The Authors

OBJECTIVE: The effects of sanitation and hygiene interventions on the gut microbiome and enteric pathogen burden are not well understood. We measured the association between free chlorine residue (FCR) levels in drinking water, microbiome composition, and stool enteric pathogens in infants and young children in Haiti. METHODS: FCR levels were measured in household drinking water and enteric pathogen burden was evaluated using multiplex RT-PCR of stool among 131 children from one month to five years of age living in Mirebalais, Haiti. Microbiome profiling was performed using metagenomic sequencing. RESULTS: Most individuals lived in households with undetectable FCR measured in the drinking water (112/131, 86%). Detection of enteric pathogen DNA in stool was common and did not correlate with household water FCR. The infant microbiome in households with detectable FCR demonstrated reduced richness (fewer total number of species, P=0.04 Kruskall-Wallis test) and less diversity by Inverse Simpson measures (P=0.05) than households with undetectable FCR. Infants in households with a detectable FCR were more likely to have abundant Bifidobacterium. Using in vitro susceptibility testing, we found that some Bifidobacterium species were resistant to chlorine. CONCLUSIONS: FCR in household drinking water did not correlate with enteric pathogen burden in our study.

BACKGROUND: Hand hygiene (HH) is an important practice that prevents transmission of infectious diseases, such as COVID-19. However, in resource-limited areas, where water and soap are not always available, it can be difficult to practice HH correctly and at appropriate moments. The purpose of this study was to assess HH knowledge and behaviors among students from six elementary schools in Quetzaltenango, Guatemala to identify gaps that could later inform interventions to improve HH. METHODS: We conducted knowledge, attitude, and practices (KAP) surveys among primary school students during the COVID-19 pandemic in July 2022. We also observed students' HH practices at three different moments during the day, making note of the use of the HH station and materials, duration of handwashing, presence of a HH assistant, and the students' sex. We also used the Quantitative Personal Hygiene Assessment Tool (qPHAT), to measure hand dirtiness before eating, after restroom use, and upon arriving to school. RESULTS: We surveyed 109 students across six schools. Mean scores were 4 out of 5 for knowledge, 8 out of 8 for attitudes, and 6 out of 7 for HH practices. Most students identified "before eating" as a critical moment for HH (68.8%), fewer identified "after restroom use" (31.2%), and no students mentioned HH being necessary "after coughing or sneezing". We observed 326 HH opportunities of which 51.2% performed correct HH (used water and soap for at least 20 s or used alcohol-based hand rub, where materials were available). We collected 82 qPHAT hand swabs. A Kruskal Wallis test revealed a significant difference in hand dirtiness between entering the school and after restroom use (p = 0.017), but no significant difference before eating and after entering the school (p = 0.6988). CONCLUSIONS: The results from the KAP survey show high scores, however correct identification of key moments for HH was relatively uncommon, especially after restroom use and after coughing or sneezing. Additionally, half of HH opportunities observed had correct HH practices and on average, hands were dirtiest when arriving at school. These findings will inform interventions to improve HH practices and behaviors, which will be evaluated with follow-up data collection.

BACKGROUND: Historically, malaria has been the predominant cause of acute febrile illness (AFI) in sub-Saharan Africa. However, during the last two decades, malaria incidence has declined due to concerted public health control efforts, including the widespread use of rapid diagnostic tests leading to increased recognition of non-malarial AFI etiologies. Our understanding of non-malarial AFI is limited due to lack of laboratory diagnostic capacity. We aimed to determine the etiology of AFI in three distinct regions of Uganda. METHODS: A prospective clinic-based study that enrolled participants from April 2011 to January 2013 using standard diagnostic tests. Participant recruitment was from St. Paul's Health Centre (HC) IV, Ndejje HC IV, and Adumi HC IV in the western, central and northern regions, which differ by climate, environment, and population density. A Pearson's chi-square test was used to evaluate categorical variables, while a two-sample t-test and Krukalis-Wallis test were used for continuous variables. RESULTS: Of the 1281 participants, 450 (35.1%), 382 (29.8%), and 449 (35.1%) were recruited from the western, central, and northern regions, respectively. The median age (range) was 18 (2-93) years; 717 (56%) of the participants were female. At least one AFI pathogen was identified in 1054 (82.3%) participants; one or more non-malarial AFI pathogens were identified in 894 (69.8%) participants. The non-malarial AFI pathogens identified were chikungunya virus, 716 (55.9%); Spotted Fever Group rickettsia (SFGR), 336 (26.2%) and Typhus Group rickettsia (TGR), 97 (7.6%); typhoid fever (TF), 74 (5.8%); West Nile virus, 7 (0.5%); dengue virus, 10 (0.8%) and leptospirosis, 2 (0.2%) cases. No cases of brucellosis were identified. Malaria was diagnosed either concurrently or alone in 404 (31.5%) and 160 (12.5%) participants, respectively. In 227 (17.7%) participants, no cause of infection was identified. There were statistically significant differences in the occurrence and distribution of TF, TGR and SFGR, with TF and TGR observed more frequently in the western region (p = 0.001; p < 0.001) while SFGR in the northern region (p < 0.001). CONCLUSION: Malaria, arboviral infections, and rickettsioses are major causes of AFI in Uganda. Development of a Multiplexed Point-of-Care test would help identify the etiology of non-malarial AFI in regions with high AFI rates.

BACKGROUND: South Africa is disproportionately impacted by non-communicable diseases (NCDs) and HIV/AIDS. We investigated the prevalence of known/unknown NCD risk factors, HIV, and NCD risk factor-HIV comorbidity; and treatment status on known diseases to determine the prevalence of controlled/uncontrolled disease. METHODS: This cross-sectional study (June 2018-March 2019) within an integrated testing centre in Soweto, South Africa, screened adults (aged ≥18 years) for body mass index (BMI), hypertension (HT), rapid glucose and cholesterol, and HIV. Results were stratified by age group, sex, HIV-status, and self-reported ART use. Analysis included Fisher's exact, chi-squared, Kruskal Wallis, and Student's T-tests. FINDINGS: Of 780 enrolled participants, 19.2% were HIV-positive, 37.5% were overweight/obese, 18.0% hypertensive, 10.8% hyperglycaemic, and 8.1% had hypercholesterolaemia. Significantly more women had overweight/obese BMI than men (46.8% vs 19.7%; p<0.0001), and women aged 25-34 years had significantly more hypercholesterolaemia than same-aged men (18.2% vs 5.6%; p = 0.02). HIV-positive participants had significantly more hyperglycaemia than HIV-negative participants (16.1% vs 9.6%; p = 0.02), and those on ART (63.9%) had significantly more hypercholesterolaemia than those not on ART (21.7% vs. 4.9%; p = 0.002). Of participants with HT, hyperglycaemia, and hypercholesterolaemia; 72.4%, 96.1%, and 93.3% were newly diagnosed. All participants with previously diagnosed NCDs remained with uncontrolled disease. INTERPRETATION: There is a high burden of HIV, NCD risk factors, and comorbidity in Soweto, and amongst young adults (18-34 years), especially women. Lowering age requirements for glucose/cholesterol screening to 18+ years, regardless of BMI, HIV-status, or ART use, may yield timely NCD diagnosis/management.

BACKGROUND: In yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration. METHODS: We conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR(1)YF(1)), MMR followed by YF vaccine four weeks later (MMR(1)YF(2)), or YF followed by MMR vaccine four weeks later (YF(1)MMR(2)). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests. RESULTS: Of 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR(1)YF(1) group versus 96.3% in the MMR(1)YF(2) group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR(1)YF(1) versus 94.7% MMR(1)YF(2), a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR(1)YF(1) versus 97.9% MMR(1)YF(2), a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR(1)YF(1) versus 97.5% YF(1)MMR(2), a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted. CONCLUSION: Effective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration. TRIAL REGISTRATION: The study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017.

INTRODUCTION: We developed a standardized method, "Possible poor treatment response" (PPTR), to help ascertain efficacy endpoints in Study S31/A5349 (NCT02410772), an open-label trial comparing two 4-month rifapentine-based regimens with a standard 6-month regimen for the treatment of pulmonary TB. We describe the use of the PPTR process and evaluate whether the goals of minimizing bias in efficacy endpoint assessment and attainment of relevant data to determine outcome for all participants were achieved. METHODS/DESIGN: A PPTR event was defined as the occurrence of one or more pre-specified triggers. Each PPTR required initiation of a standardized evaluation process that included obtaining multiple sputum samples for microbiology. RESULTS: Among 2,343 participants with culture-confirmed drug-susceptible TB, 454 individuals (19.4%) had a total of 534 individual PPTR events, of which 76.6% were microbiological (positive smear or culture at or after 17 weeks). At least one PPTR event was experienced by 92.4% (133 of 144) of participants with TB-related unfavorable outcome, and between 13.8 and 14.7% of participants with favorable and not assessable outcomes. 75% of participants with TB-related unfavorable outcomes had microbiological confirmation of failure to achieve disease-free cure. DISCUSSION: Standardized methodologies, such as our PPTR approach, could facilitate unbiased efficacy outcome determinations, improve discrimination between outcomes that are related and unrelated to regimen efficacy, and enhance the ability to conduct pooled analyses of contemporary trials. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT02410772.

BACKGROUND: The use of synthetic insecticides against mosquitoes may lead to resistance development and potential health hazards in humans and the environment. Consequently, a paradigm needs to shift towards the alternative use of botanical insecticides that could strengthen an insecticide resistance management programme. This study aimed to assess the insecticidal effects aqueous, hexane, and methanol crude leaf extracts of Calpurnia aurea, Momordica foetida, and Zehneria scabra on an insectary colony of Anopheles stephensi larvae and adults. METHODS: Fresh leaves of C. aurea, M. foetida and Z. scabra were collected and dried, then separately ground to powder. Powdered leaves of test plants were extracted using sonication with aqueous, hexane, and methanol solvents. The extracts were concentrated, and a stock solution was prepared. For comparison, Temephos (Abate®) and control solutions (a mixture of water and emulsifier) were used as the positive and negative controls, respectively. Different test concentrations for the larvae and the adults were prepared and tested according to WHO (2005) and CDC (2010) guidelines to determine lethal concentration (LC) values. Mortality was observed after 24 h exposure. The statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) software (Kruskal-Wallis test) and R software (a generalized linear model was used to determine LC(50) and LC(90) values of the extracts). RESULTS: The lowest LC(50) values were observed in aqueous extracts of M. foetida followed by Z. scabra extract and C. aurea leaves at 34.61, 35.85, and 38.69 ppm, respectively, against the larvae. Larval mortality was not observed from the hexane extracts and negative control, while the standard larvicide (temephos) achieved 100% mortality. Further, the adulticidal efficacy was greatest for aqueous extract of Z. scabra with LC(50) = 176.20 ppm followed by aqueous extract of C. aurea (LC(50) = 297.75 ppm). CONCLUSION: The results suggest that the leaf extracts of the three test plants have the potential of being used for the control of vector An. stephensi larvae and adult instead of synthetic mosquitocides. Further studies need to be conducted to identify the active ingredients and their mode of action.

OBJECTIVES: Acute gastroenteritis (AGE) outbreaks commonly occur in congregate settings, including schools and childcare facilities. These outbreaks disrupt institutions, causing absences and temporary facility closures. This study analyzed the epidemiology of school and childcare AGE outbreaks in the United States. METHODS: We analyzed AGE outbreaks occurring in kindergarten to grade 12 schools and childcare facilities reported via the National Outbreak Reporting System in the United States from 2009 to 2019 and compared this information to 2020 data. Outbreak and case characteristics were compared using the Kruskal-Wallis rank sum test, 2 goodness-of-fit test, and Fisher exact test. RESULTS: From 2009 to 2019, there were 2623 school, 1972 childcare, and 38 school and childcare outbreaks. School outbreaks were larger (median, 29 cases) than childcare outbreaks (median, 10 cases). Childcare outbreaks were longer (median, 15 days) than school outbreaks (median, 9 days). Norovirus (2383 outbreaks; 110190 illnesses) and Shigella spp. (756 outbreaks; 9123 illnesses) were the most reported etiologies. Norovirus was the leading etiology in schools; norovirus and Shigella spp. were dominant etiologies in childcare centers. Most (85.7%) outbreaks were spread via person-to-person contact. In 2020, 123 outbreaks were reported, 85% in the first quarter. CONCLUSIONS: Schools and childcare centers are common AGE outbreak settings in the United States. Most outbreaks were caused by norovirus and Shigella spp. and spread via person-to-person transmission. Fewer outbreaks were reported in 2020 from the COVID-19 pandemic. Prevention and control efforts should focus on interrupting transmission, including environmental disinfection, proper handwashing, safe diapering, and exclusion of ill persons.

BACKGROUND: Host-pathogen dynamics associated with HIV infection are quite distinct in children versus adults. We interrogated the functional fitness of the lymphocyte responses in two cohorts of perinatally infected HIV+ pediatric subjects with early anti-retroviral therapy (ART) initiation but divergent patterns of virologic control. We hypothesized that sub-optimal viral control would compromise immune functional fitness. METHODS: The immune responses in the two HIV+ cohorts (n = 6 in each cohort) were benchmarked against the responses measured in age-range matched, uninfected healthy control subjects (n = 11) by utilizing tests for normality, and comparison [the Kruskal-Wallis test, and the two-tailed Mann-Whitney U test (where appropriate)]. Lymphocyte responses were examined by intra-cellular cytokine secretion, degranulation assays as well as phosflow. A subset of these data were further queried by an automated clustering algorithm. Finally, we evaluated the humoral immune responses to four childhood vaccines in all three cohorts. RESULTS: We demonstrate that contrary to expectations pediatric HIV+ patients with sub-optimal viral control display no significant deficits in immune functional fitness. In fact, the patients that display better virologic control lack functional Gag-specific T cell responses and compared to healthy controls they display signaling deficits and an enrichment of mitogen-stimulated CD3 negative and positive lymphocyte clusters with suppressed cytokine production. CONCLUSIONS: These results highlight the immune resilience in HIV+ children on ART with sub-optimal viral control. With respect to HIV+ children on ART with better viral control, our data suggest that this cohort might potentially benefit from targeted interventions that might mitigate cell-mediated immune functional quiescence.

INTRODUCTION: Limited evidence exists on the comparative effectiveness of local treatments for prostate cancer (PCa) due to the lack of generalizability. Using granular national data, we sought to examine the association between radical prostatectomy (RP) and intensity-modulated radiation therapy (IMRT) treatment and survival. METHODS: Records were abstracted for localized PCa cases diagnosed in 2004 across seven state registries to identify patients undergoing RP (n=3019) or IMRT (n=667). Comorbidity was assessed by the Adult Comorbidity Evaluation-27 (ACE-27). Propensity score matching (PSM) was used to balance covariates between treatment groups. All-cause and PCa-specific mortality were primary endpoints. A subgroup analysis of patients with high-risk PCa (RP, n=89; IMRT, n=95) was conducted. RESULTS: Following PSM, matched patients (n=502 pairs) treated with either RP or IMRT were well-balanced with respect to covariates. With a median followup of 10.5 years (interquartile range [IQR] 9.9-11.0), the 11-year overall survival (OS) was 71.2% (95% confidence interval [CI] 66.9-75.8) for RP and 62.3% (95% CI 57.4-67.6) for IMRT. IMRT was associated with a 41% increased risk of all-cause mortality (hazard ratio [HR] 1.41, 95% CI 1.13-1.76) but not PCa-specific mortality (HR 1.75, 95% CI 0.84-3.64), as compared to RP. In patients with high-risk PCa, IMRT, as compared to RP, was not associated with statistically significant difference in all-cause (HR 1.53, 95% CI 0.97-2.42) or PCa-specific mortality (HR 1.92, 95% CI 0.69-5.36). CONCLUSIONS: Despite a low mortality rate at 10 years and possible residual confounding, we found a significantly increased risk of all-cause mortality, but no PCa-specific mortality associated with IMRT as compared to RP in this population-based study.

BACKGROUND: We examined SARS-CoV-2 anti-spike 1 IgG antibody levels following COVID-19 vaccination (AstraZeneca [AZ], Sinovac [SV], Pfizer-BioNTech [PZ]) among Thai healthcare providers. METHODS: Blood specimens were tested using enzyme-linked immunosorbent assay. We analyzed seven vaccination regimens: (1) one dose of AZ or SV, (2) two doses of homologous (2AZ, 2SV) or heterologous (1AZ+1PZ) vaccines, and (3) three doses of heterologous vaccines (2SV+1AZ, 2SV+1PZ). Differences in antibody levels were assessed using Kruskal-Wallis statistic, Mann-Whitney test, or Wilcoxon matched-pairs signed-rank test. Antibody kinetics were predicted using fractional polynomial regression. RESULTS: The 563 participants had median age of 39years; 92% were female; 74% reported no underlying medical condition. Antibody levels peaked at 22-23days in both 1AZ and 2SV vaccinees and dropped below assay's cutoff for positive (35.2 binding antibody units/ml [BAU/ml]) in 55days among 1AZ vaccinees compared with 117days among 2SV vaccinees. 1AZ+1PZ vaccination regimen was highly immunogenic (median 2279 BAU/ml) 1-4weeks post vaccination. 2SV+1PZ vaccinees had significantly higher antibody levels than 2SV+1AZ vaccinees 4weeks post vaccination (3423 vs. 2105 BAU/ml; p-value<0.01), and during weeks 5-8 (3656 vs. 1072 BAU/ml; p-value<0.01). Antibodies peaked at 12-15days in both 2SV+1PZ and 2SV+1AZ vaccinees, but those of 2SV+1AZ declined more rapidly and dropped below assay's cutoff in 228days while those of 2SV+1PZ remained detectable. CONCLUSIONS: 1AZ+1PZ, 2SV+1AZ, and 2SV+1PZ vaccinees had substantial IgG levels, suggesting that these individuals likely mounted sufficient anti-S1 IgG antibodies for possible protection against SARS-CoV-2 infection.

As newborn screening programs transition from paper-based data exchange toward automated, electronic methods, significant data exchange challenges must be overcome. This article outlines a data model that maps newborn screening data elements associated with patient demographic information, birthing facilities, laboratories, result reporting, and follow-up care to the LOINC, SNOMED CT, ICD-10-CM, and HL7 healthcare standards. The described framework lays the foundation for the implementation of standardized electronic data exchange across newborn screening programs, leading to greater data interoperability. The use of this model can accelerate the implementation of electronic data exchange between healthcare providers and newborn screening programs, which would ultimately improve health outcomes for all newborns and standardize data exchange across programs. Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

INTRODUCTION: Studies documented significant reductions in emergency department visits and hospitalizations for acute stroke during the COVID-19 pandemic. A limited number of studies assessed the adherence to stroke performance measures during the pandemic. We examined rates of stroke hospitalization and adherence to stroke quality-of-care measures before and during the early phase of pandemic. METHODS: We identified hospitalizations with a clinical diagnosis of acute stroke or transient ischemic attack among 406 hospitals who contributed data to the Paul Coverdell National Acute Stroke Program. We used 10 performance measures to examine the effect of the pandemic on stroke quality of care. We compared data from 2 periods: pre-COVID-19 (week 11-24 in 2019) and COVID-19 (week 11-24 in 2020). We used χ(2) tests for differences in categorical variables and the Wilcoxon-Mann-Whitney rank test or Kruskal-Wallis test for continuous variables. RESULTS: We identified 64,461 hospitalizations. We observed a 20.2% reduction in stroke hospitalizations (from 35,851 to 28,610) from the pre-COVID-19 period to the COVID-19 period. Hospitalizations among patients aged 85 or older, women, and non-Hispanic White patients declined the most. A greater percentage of patients aged 18 to 64 were hospitalized with ischemic stroke during COVID-19 than during pre-COVID-19 (34.4% vs 32.5%, P < .001). Stroke severity was higher during COVID-19 than during pre-COVID-19 for both hemorrhagic stroke and ischemic stroke, and in-hospital death among patients with ischemic stroke increased from 4.3% to 5.0% (P = .003) during the study period. We found no differences in rates of receiving care across stroke type during the study period. CONCLUSION: Despite a significant reduction in stroke hospitalizations, more severe stroke among hospitalized patients, and an increase in in-hospital death during the pandemic period, we found no differences in adherence to quality of stroke care measures.

INTRODUCTION: Infants with myelomeningocele are at risk for chronic kidney disease caused by neurogenic bladder dysfunction. Urodynamic evaluation plays a key role to risk stratify individuals for renal deterioration. OBJECTIVE: To present baseline urodynamic findings from the Urologic Management to Preserve Initial Renal function for young children with spina bifida (UMPIRE) protocol, to present the process that showed inadequacies of our original classification scheme, and to propose a refined definition of bladder hostility and categorization. STUDY DESIGN: The UMPIRE protocol follows a cohort of newborns with myelomeningocele at nine children's hospitals in the United States. Infants are started on clean intermittent catheterization shortly after birth. If residual volumes are low and there is no or mild hydronephrosis, catheterization is discontinued. Baseline urodynamics are obtained at or before 3 months of age to determine further management. Based on protocol-specific definitions, urodynamic studies were reviewed by the clinical site in addition to a central review team; and if necessary, by all site urologists to achieve 100% concurrence. RESULTS: We reviewed 157 newborn urodynamic studies performed between May 2015 and September 2017. Of these 157 infants, 54.8% were boys (86/157). Myelomeningocele closure was performed in-utero in 18.4% (29/157) and postnatally in 81.5% (128/157) of newborns. After primary review, reviewers agreed on overall bladder categorization in 50% (79/157) of studies. Concurrence ultimately reached 100% with further standardization of interpretation. We found that it was not possible to reliably differentiate a bladder contraction due to detrusor overactivity from a volitional voiding contraction in an infant. We revised our categorization system to group the "normal" and "safe" categories together as "low risk". Additionally, diagnosis of detrusor sphincter dyssynergia (DSD) with surface patch electrodes could not be supported by other elements of the urodynamics study. We excluded DSD from our revised high risk category. The final categorizations were high risk in 15% (23/157); intermediate risk in 61% (96/157); and low risk in 24% (38/157). CONCLUSION: We found pitfalls with our original categorization for bladder hostility. Notably, DSD could not be reliably measured with surface patch of electrodes. The effect of this change on future renal outcomes remains to be defined.

Background: The UNAIDS 90-90-90 Fast-Track targets provide a framework for assessing coverage of HIV testing services (HTS) and awareness of HIV status - the "first 90." In Kenya, the bulk of HIV testing targets are aligned to the five highest HIV-burden counties. However, we do not know if most of the new HIV diagnoses are in these five highest-burden counties or elsewhere. Methods: We analyzed facility-level HTS data in Kenya from 1 October 2015 to 30 September 2016 to assess the spatial distribution of newly diagnosed HIV-positives. We used the Moran's Index (Moran's I) to assess global and local spatial auto-correlation of newly diagnosed HIV-positive tests and Kulldorff spatial scan statistics to detect hotspots of newly diagnosed HIV-positive tests. For aggregated data, we used Kruskal-Wallis equality-of-populations non-parametric rank test to compare absolute numbers across classes. Results: Out of 4,021 HTS sites, 3,969 (98.7%) had geocodes available. Most facilities (3,034, 76.4%), were not spatially autocorrelated for the number of newly diagnosed HIV-positives. For the rest, clustering occurred as follows; 438 (11.0%) were HH, 66 (1.7%) HL, 275 (6.9%) LH, and 156 (3.9%) LL. Of the HH sites, 301 (68.7%) were in high HIV-burden counties. Over half of 123 clusters with a significantly high number of newly diagnosed HIV-infected persons, 73(59.3%) were not in the five highest HIV-burden counties. Clusters with a high number of newly diagnosed persons had twice the number of positives per 1,000,000 tests than clusters with lower numbers (29,856 vs. 14,172). Conclusions: Although high HIV-burden counties contain clusters of sites with a high number of newly diagnosed HIV-infected persons, we detected many such clusters in low-burden counties as well. To expand HTS where most needed and reach the "first 90" targets, geospatial analyses and mapping make it easier to identify and describe localized epidemic patterns in a spatially dispersed epidemic like Kenya's, and consequently, reorient and prioritize HTS strategies.

PURPOSE: Urinary tract infections (UTI) commonly occur in patients with spina bifida (SB) and pose a risk for renal scarring. Routine antibiotic prophylaxis has been utilized in newborns with SB to prevent UTI. We hypothesized that prophylaxis can safely be withheld in newborns with SB until clinical assessment allows for risk stratification. MATERIALS AND METHODS: Newborns with myelomeningocele at nine institutions were prospectively enrolled in the UMPIRE study and managed by a standardized protocol with a strict definition for UTI. Patient data were collected regarding details of reported UTI, baseline renal ultrasound findings, vesicoureteral reflux, use of clean intermittent catheterization (CIC), and circumcision status in boys. Risk Ratios (RRs) and corresponding 95% confidence intervals (CIs) were calculated using log-binomial models. RESULTS: From 2/2015 through 8/2019, data were available on 299 newborns (50.5% male). During the first four months of life, 48 (16.1%) newborns were treated for UTI with 23 (7.7%) having positive cultures; however, only 12 (4.0%) met the strict UTI definition. Infants with grade 3-4 hydronephrosis had an increased risk of UTI compared to infants with no hydronephrosis (RR=10.1; 95%CI=2.8, 36.3). Infants on CIC also had an increased risk of UTI (RR=3.3; 95%CI=1.0, 10.5). CONCLUSIONS: The incidence of a culture-positive, symptomatic UTI among newborns with SB in the first 4 months of life was low. Patients with high grades of hydronephrosis or those on CIC had a significantly greater incidence of UTI. Our findings suggest that routine antibiotic prophylaxis may not be necessary for most newborns with SB.

BACKGROUND: In the era of evidence-based medicine, haematological reference intervals are essential for the interpretation of data for clinical decision-making, monitoring of treatment and research. It is not uncommon that reference intervals used in most African countries have been obtained from published scientific literature, textbooks, reagent/instrument manuals. OBJECTIVE: The aim of this study was to determine haematological reference intervals of healthy adults in Bamenda, Cameroon. METHODS: This was a cross-sectional study conducted between June and November 2015. Participants were voluntary blood donors at the Blood Bank Service of the Regional Hospital Bamenda aged between 18 and 65 years. The mean, median and standard deviation of the mean were calculated for each haematological parameter. The 95th percentile reference intervals were determined using the 2.5th and 97.5th percentile. The differences between gender for all the parameters were evaluated using the Kruskal-Wallis test. Significance was determined at the 95% confidence level. RESULTS: Out of a total of 340 participants, 202 (59.4%) were men and 138 (40.6%) were women. The median red blood cell, haemoglobin, haematocrit and mean cell haemoglobin concentration were significantly higher in men than women (p < 0.001). The median white blood cell, absolute lymphocytes count, absolute granulocytes and platelet counts for men were significantly lower than those for women (p < 0.011). CONCLUSION: We propose that the present established haematological reference intervals in this study should be used for clinical management of patients and interpretation of laboratory data for research in Bamenda.

BACKGROUND: Increased Attalea butyracea palm propagation, notable for its role as key habitat for the primary Chagas disease vector in Panama, has been linked to landscape disturbance in single-palm observations in this region. Close proximity of these palms to human dwellings is proposed to increase risk of Chagas disease transmission from sylvatic transmission cycles to domestic transmission involving human populations. This study examines the relationship between landscape disturbance and mature A. butyracea spatial distribution, density, and proximity to human populations and vector and reservoir species' movement corridors at a regional scale in a 300 km(2) heterogeneous tropical landscape in central Panama. METHODS: We remotely identified the locations of over 50,000 mature A. butyracea palms using high-resolution WorldView2 satellite imagery. A local Getis-Ord Gi* spatial analysis identified significant clusters of aggregated palms. Associations between palm and cluster abundance and a landscape disturbance gradient, derived from official Panama land cover data, were tested using Chi-square tests for Homogeneity and Z-test for proportions. Kruskall-Wallis non-parametric analysis of variance tests were run to assess whether palm cluster area varied by disturbance level, or whether disturbance was associated with proximity of palms and palm clusters to susceptible populations or vector movement corridors. RESULTS: Our findings indicate a regional relationship between landscape disturbance and A. butyracea occurrence. We observe a significant increase in both individual and clustered A. butyracea in secondary forest, but a reduction of palms in agricultural settings. We do not detect evidence of any reduction in abundance of palms in residential settings. The majority of residential and commercial buildings in our study area are within vector flight distance of potential vector habitat in palm crowns. CONCLUSIONS: We observe probable anthropogenic elimination of A. butyracea palms in agricultural, but not residential, settings. Even in heavily deforested regions, significant concentrations of mature palms remain in close proximity to human establishments.

INTRODUCTION: South Africa is the HIV epidemic epicentre; however, non-communicable diseases (NCDs) will be the most common cause of death by 2030. To improve identification and initiation of care for HIV and NCDs, we assessed proportion of clients referred and linked to care (LTC) for abnormal/positive screening results and time to LTC and treatment initiation from a HIV Testing Services (HTS) Centre before and after integrated testing for NCDs with optional peer-navigated linkage to care. MATERIALS AND METHODS: This two-phase prospective study was conducted at an adult HTS Centre in Soweto, South Africa. Phase 1 (February-June 2018) utilised standard of care (SOC) HTS services (blood pressure [BP], HIV rapid diagnostic testing (RDT), sexually transmitted infections [STI]/Tuberculosis [TB] symptom screening) with passive referral for abnormal/positive results. Phase 2 (June 2018-March 2019) further integrated blood glucose/cholesterol/chlamydia RDT, with optional peer-navigated referral. Enrolled referred clients completed telephonic follow-up surveys confirming LTC/treatment initiation ≤3 months post-screening. Socio-demographics, screening results, time to LTC/treatment initiation, peer-navigated referral uptake were reported. Analysis included Fisher's exact, chi-squared, Kruskal Wallis, and Student's T-tests. Thematic analysis was conducted for open-ended survey responses. RESULTS: Of all 320 referrals, 40.0% were HIV-infections, 11.9% STIs, 6.6% TB, and 28.8% high/low BP. Of Phase 2-only referrals, 29.4% were for glucose and 23.5% cholesterol. Integrated NCD-HTS had significantly more clients LTC for HIV (76.7%[n = 66/86] vs 52.4%[n = 22/42], p = 0.0052) and within a shorter average time (6-8 days [Interquartile range (IQR):1-18.5] vs 8-13 days [IQR:2-32]) as compared to SOC HTS. Integrated NCD-HTS clients initiated HIV/STIs/BP treatment on average more quickly as compared to SOC HTS (5 days for STIs [IQR:1-21], 8 days for HIV/BP [IQR:5-17 and 2-13, respectively] vs 10 days for STIs [IQR: 4-32], 19.5 days for HIV [IQR:6.5-26.5], 8 days for BP [IQR:2-29)]. Participants chose passive over active referral (89.1% vs 10.9%; p<0.0001). Participants rejecting peer-navigated referral preferred to go alone (55.7% [n = 39/70]). Non-LTC was due to being busy (41.1% [n = 39/95]) and not being ready/refusing treatment (31.6% [n = 30/95]). Normalised results assessed at referral clinic (49.7% [n = 98/196]), prescribed lifestyle modification/monitoring (30.9% [n = 61/196]), and poor clinic flow/congestion and/or further testing required (10.7% [n = 21/196]) were associated with non-treatment initiation. CONCLUSION: Same-day treatment initiation is not achieved across diseases, despite peer-navigated referral. There are psychosocial and health systems barriers at entry to care/treatment initiation. Additional research may identify best strategies for rapid treatment initiation.

BACKGROUND: While HIV Testing Services (HTS) have increased, many South Africans have not been tested. Non-communicable diseases (NCDs) are the top cause of death worldwide. Integrated NCD-HTS could be a strategy to control both epidemics. Healthcare service strategies depends partially on positive user experience. We investigated client satisfaction of services and clinic flow time of an integrated NCD-HTS clinic. METHODS: This prospective, cross-sectional study evaluated HTS client satisfaction with an HTS clinic at two phases. Phase 1 (February-June 2018) utilised standard HTS services: counsellor-led height/weight/blood pressure measurements, HIV rapid testing, and symptoms screening for sexually transmitted infections/Tuberculosis. Phase 2 (June 2018-March 2019) further integrated counsellor-led obesity screening (body mass index/abdominal circumference measurements), rapid cholesterol/glucose testing; and nurse-led Chlamydia and human papilloma virus (HPV)/cervical cancer screening. Socio-demographics, proportion of repeat clients, clinic flow time, and client survey data (open/closed-ended questions using five-point Likert scale) are reported. Fisher's exact test, chi-square analysis, and Kruskal Wallis test conducted comparisons. Multiple linear regression determined predictors associated with clinic time. Content thematic analysis was conducted for free response data. RESULTS: Two hundred eighty-four and three hundred thirty-three participants were from Phase 1 and 2, respectively (N = 617). Phase 1 participants were significantly older (median age 36.5 (28.0-43.0) years vs. 31.0 (25.0-40.0) years; p = 0.0003), divorced/widowed (6.7%, [n = 19/282] vs. 2.4%, [n = 8/332]; p = 0.0091); had tertiary education (27.9%, [n = 79/283] vs. 20.1%, [n = 67/333]; p = 0.0234); and less female (53.9%, [n = 153/284] vs 67.6%, [n = 225/333]; p = 0.0005), compared to Phase 2. Phase 2 had 10.2% repeat clients (n = 34/333), and 97.9% (n = 320/327) were 'very satisfied' with integrated NCD-HTS, despite standard HTS having significantly shorter median time for counsellor-led HTS (36.5, interquartile range [IQR]: 31.0-45.0 vs. 41.5, IQR: 35.0-51.0; p < 0.0001). Phase 2 associations with longer clinic time were clients living together/married (est = 6.548; p = 0.0467), more tests conducted (est = 3.922; p < 0.0001), higher overall satisfaction score (est = 1.210; p = 0.0201). Those who matriculated experienced less clinic time (est = - 7.250; p = 0.0253). CONCLUSIONS: It is possible to integrate counsellor-led NCD rapid testing into standard HTS within historical HTS timeframes, yielding client satisfaction. Rapid cholesterol/glucose testing should be integrated into standard HTS. Research is required on the impact of cervical cancer/HPV screenings to HTS clinic flow to determine if it could be scaled up within the public sector.

PURPOSE: The lifetime risk of renal damage in children with spina bifida is high but only limited baseline imaging data are available for this population. We evaluated a large prospective cohort of infants with spina bifida to define their baseline imaging characteristics. MATERIALS AND METHODS: The UMPIRE Protocol for Young Children with Spina Bifida is an iterative quality improvement protocol that follows a cohort of newborns at 9 United States centers. Using descriptive statistics, we report the initial baseline imaging characteristics, specifically regarding renal bladder ultrasound, cystogram and dimercaptosuccinic acid nuclear medicine scan. RESULTS: Data on 193 infants from 2015 to 2018 were analyzed. Renal-bladder ultrasound was normal in 55.9% of infants, while 40.4% had Society for Fetal Urology grade 1 to 2 hydronephrosis in at least 1 kidney, 3.7% had grade 3 to 4 hydronephrosis in either kidney and 21.8% had grade 1 or higher bilateral hydronephrosis. There was no vesicoureteral reflux in 84.6% of infants. A third of enrolled infants underwent dimercaptosuccinic acid nuclear medicine renal scan, of whom 92.4% had no renal defects and 93.9% had a difference in differential function of less than 15%. CONCLUSIONS: The majority of infants born with spina bifida have normal baseline imaging characteristics and normal urinary tract anatomy at birth. This proactive protocol offers careful scheduled surveillance of the urinary tract with the goal of lifelong maintenance of normal renal function and healthy genitourinary development.