OBJECTIVE: To determine if the prevalence of schistosomiasis in children aged 9-12 years is associated with the prevalence in 5-8-year-olds and adults after preventive chemotherapy in schools or the community. METHODS: We combined data from four community-randomized, preventive chemotherapy trials in treatment-naïve populations in Côte d'Ivoire, Kenya and the United Republic of Tanzania during 2010-2016 according to the number of praziquantel treatments and the delivery method. Schistosoma mansoni infection was sought on two slides prepared from each participant's first stool using the Kato-Katz technique. We assessed associations between S. mansoni prevalence in 9-12-year-olds and 5-8-year-olds and adults in the community before and after treatment using Bayesian regression models. FINDINGS: Stool samples from 47 985 5-8-year-olds, 81 077 9-12-year-olds and 20 492 adults were analysed. We found associations between the prevalence in 9-12-year-olds and that in 5-8-year-olds and adults after preventive treatment, even when only school-age children were treated. When the prevalence in 9-12-year-olds was under 10%, the prevalence in 5-8-year-olds was consistently under 10%. When the prevalence in 9-12-year-olds was under 50%, the prevalence in adults after two or four rounds of preventive chemotherapy was 10%-15% lower than before chemotherapy. Post-chemotherapy age-group associations were consistent with pre-chemotherapy associations in this analysis and previous studies. CONCLUSION: The prevalence of S. mansoni infection in 9-12-year-olds was associated with the prevalence in other age groups and could be used to guide community treatment decisions.

Recent reports of hookworm infection in Alabama, USA, has prompted surveillance in Mississippi, given the states' similar environmental conditions. We collected stool specimens from 277 children in Rankin County, Mississippi. Kato-Katz microscopic smear, agar plate culture, and quantitative PCR indicated no soil-transmitted helminths. Nevertheless, further surveillance in other high-risk Mississippi counties is warranted.

Diagnostic limitations challenge management of clinically indistinguishable acute infectious illness globally. Gene expression classification models show great promise distinguishing causes of fever. We generated transcriptional data for a 294-participant (USA, Sri Lanka) discovery cohort with adjudicated viral or bacterial infections of diverse etiology or non-infectious disease mimics. We then derived and cross-validated gene expression classifiers including: 1) a single model to distinguish bacterial vs. viral (Global Fever-Bacterial/Viral [GF-B/V]) and 2) a two-model system to discriminate bacterial and viral in the context of noninfection (Global Fever-Bacterial/Viral/Non-infectious [GF-B/V/N]). We then translated to a multiplex RT-PCR assay and independent validation involved 101 participants (USA, Sri Lanka, Australia, Cambodia, Tanzania). The GF-B/V model discriminated bacterial from viral infection in the discovery cohort an area under the receiver operator curve (AUROC) of 0.93. Validation in an independent cohort demonstrated the GF-B/V model had an AUROC of 0.84 (95% CI 0.76-0.90) with overall accuracy of 81.6% (95% CI 72.7-88.5). Performance did not vary with age, demographics, or site. Host transcriptional response diagnostics distinguish bacterial and viral illness across global sites with diverse endemic pathogens.

Murine typhus is a febrile, fleaborne disease caused by infection with Rickettsia typhi bacteria. Cases can range from mild and nonspecific to fatal. We report 2 cases of murine typhus in Costa Rica, confirming the presence and circulation of R. typhi causing severe disease in the country.

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested an association between PFAS and prostate cancer, but evidence from population-based studies is limited. We investigated the association between pre-diagnostic serum PFAS concentrations and aggressive prostate cancer risk in a large prospective study. We measured pre-diagnostic serum concentrations of eight PFAS, including perfluorooctanoate (PFOA), for 750 aggressive prostate cancer cases and 750 individually matched controls within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We assessed the reproducibility of PFAS concentrations in serial samples collected up to six years apart among 60 controls using intraclass correlation coefficients (ICCs). Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with prostate cancer, adjusting for other PFAS and potential confounders. Concentrations of most PFAS were consistent (ICC>0.7) across the serial samples over time. We observed an inverse association between PFOA and aggressive prostate cancer (OR(continuous) = 0.79, 95% CI = 0.63, 0.99), but the association was limited to cases diagnosed ≤3 years after blood collection and became statistically non-significant for cases diagnosed with later follow-up (>3 years, OR(continuous) = 0.90, 95% CI = 0.79, 1.03). Other PFAS were not associated with aggressive prostate cancer risk. Although we cannot rule out an increased risk at higher levels, our findings from a population with PFAS serum concentrations comparable to the general population do not support an association with increased risk of aggressive prostate cancer.

The COVID-19 pandemic has created an unprecedented natural experiment in drug policy, treatment delivery, and harm reduction strategies by exposing wide variation in public health infrastructures and social safety nets around the world. Using qualitative data including ethnographic methods, questionnaires, and semi-structured interviews with people who use drugs (PWUD) and Delphi-method with experts from field sites spanning 13 different countries, this paper compares national responses to substance use during the first wave of the COVID-19 pandemic. Field data was collected by the Substance Use x COVID-19 (SU x COVID) Data Collaborative, an international network of social scientists, public health scientists, and community health practitioners convened to identify and contextualise health service delivery models and social protections that influence the health and wellbeing of PWUD during COVID-19. Findings suggest that countries with stronger social welfare systems pre-COVID introduced durable interventions targeting structural drivers of health. Countries with fragmented social service infrastructures implemented temporary initiatives for PWUD led by non-governmental organisations. The paper summarises the most successful early pandemic responses seen across countries and ends by calling for greater systemic investments in social protections for PWUD, diversion away from criminal-legal systems toward health interventions, and integrated harm reduction, treatment and recovery supports for PWUD.

Purpose: Sexual violence (SV) and adolescent relationship abuse (ARA) are common in the U. S. and have strong associations with negative health and wellbeing outcomes. Manhood 2.0 is the first U.S. program designed for community settings to build bystander skills while also challenging harmful gender norms. A cluster-randomized trial comparing Manhood 2.0 to Job Skills, a job readiness training control condition, demonstrated that it is a promising strategy to prevent sexual violence and adolescent relationship abuse. Such community-based interventions may be particularly relevant in lower resource urban settings, and the costs of such prevention programs have not been considered previously. Methods: The aim of the present study is to perform systematic and standardized cost calculations associated with implementing Manhood 2.0 among adolescent males. In addition, this study provides detailed cost information of the community-based intervention program, as well as costs associated with implementing the Job Skills control program. Program implementation data were recorded throughout the study period (20152019) by the Manhood 2.0 study team. Results: The cost of implementing Manhood 2.0 is $4,771 per complete round of program delivery and $451 per participant, which is approximately the same cost as the control Job Skills program ($4,432 and $453 per participant). The marginal cost per additional round of Manhood 2.0 program is $3,682. Conclusion: Implementation of a community-based program requires substantial resources and collaborations with community partners especially in economically disadvantaged neighborhoods. This study provides a snapshot of the cost information of a community-based intervention program from the implementing agencys perspective, which is essential in helping decision-makers understand the costs they will incur by implementing prevention programs and ensuring program feasibility and sustainability. 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

BACKGROUND: The disaccharide galactose-α-1,3-galactose (alpha-gal) is expressed in mammals other than humans, apes, and old-world monkeys. In humans, elevated immunoglobulin E (IgE) antibodies specific for alpha-gal can result in allergic hypersensitivity known as alpha-gal syndrome (AGS). Case reports and series suggest that tick bites can induce alpha-gal-specific IgE (sIgE) antibodies. OBJECTIVE: To evaluate tick exposure as a risk factor for AGS and elevated alpha-gal sIgE level. METHODS: We conducted a case-control study comparing patients with AGS from a North Carolina allergy clinic with controls who were patients at a nearby internal medicine clinic. Cases and controls were administered a questionnaire to obtain information about demographics, home environment, outdoor activities, and recollection of tick bite. Serum samples taken at the time of enrollment were tested for total IgE, alpha-gal sIgE, and antibodies to other tick-borne pathogens. RESULTS: The patients with AGS were more likely to recall finding a tick on themselves (odds ratio [OR], 11.20; 95% confidence interval [CI], 4.97-25.15), live near wooded forest (OR, 2.27; 95% CI, 0.92-5.55), and spend 17 or more hours per week outdoors in wooded areas (OR, 5.58; 95% CI, 2.56-12.19). The patients with AGS were also more likely to report 4 or more tick bites (OR, 33.05; 95% CI, 9.92-155.12) and reactions at the site of tick bites (OR, 7.93; 95% CI, 3.74-16.80). Furthermore, elevated alpha-gal sIgE level was observed in 33% of the controls and was associated with tick exposure in the controls (OR, 4.25; 95% CI, 2.21-8.18). CONCLUSION: The results define tick bite as a risk factor for AGS and elevated alpha-gal sIgE level.

BACKGROUND: Current isolation techniques for spotted fever group Rickettsia from clinical samples are laborious and are limited to tissue, blood and blood derivatives with volumes ideally greater than 1 mL. We validated the use of simplified methodologies for spotted fever group Rickettsia culture isolation that overcome sample volume limitations and provide utility in clinical diagnostics and research studies. METHODOLOGY/PRINCIPAL FINDINGS: A modified cell culture method is evaluated for the isolation of Rickettsia ssp. from human diagnostic samples. Culture sampling method, culture platform, and growth phase analysis were evaluated to determine best practices for optimal culture isolation conditions. Rickettsial isolates (R. conorii, R. rickettsii, and R. parkeri) were grown in Vero E6 cells over a course of 5 to 7 days at low inoculum treatments (~40 bacterial copies) to standardize the sampling strategy at a copy number reflective of the bacteremia in acute diagnostic samples. This methodology was verified using small volumes (50 μL) of 25 unprocessed clinical whole blood, plasma, and serum samples from acute samples of patients suspected of having Rocky Mountain Spotted Fever, of which 10 were previously confirmed positive via the PanR8 qPCR assay, 13 had no detectable Rickettsia DNA by the PanR8 qPCR assay, and 2 were not previously tested; these samples resulted in the cultivation of 7 new R. rickettsii isolates. CONCLUSIONS/SIGNIFICANCE: We observed that rickettsial isolate growth in culture is reproducibly identified by real-time PCR testing of culture media within 72 hours after inoculation. Additionally, specimen sedimentation prior to isolation to remove red blood cells was found to decrease the amount of total viable organism available in the inoculum. A small volume culture method was established focusing on comparative qPCR detection rather than bacterial visualization, taking significantly shorter time to detect, and requiring less manipulation compared to traditional clinical isolate culture methods.

Understanding the distribution of pathogens causing acute febrile illness (AFI) is important for clinical management of patients in resource-poor settings. We evaluated the proportion of AFI caused by specific pathogens among outpatients in Bangladesh. During May 2019-March 2020, physicians screened patients aged 2 years in outpatient departments of four tertiary level public hospitals. We randomly enrolled patients having measured fever (100.4F) during assessment with onset within the past 14 days. Blood and urine samples were tested at icddr,b through rapid diagnostic tests, bacterial culture, and polymerase chain reaction (PCR). Acute and convalescent samples were sent to the Centers for Disease Control and Prevention (USA) for Rickettsia and Orientia (R/O) and Leptospira tests. Among 690 patients, 69 (10%) had enteric fever (Salmonella enterica serotype Typhi orSalmonella enterica serotype Paratyphi), 51 (7.4%) Escherichia coli, and 28 (4.1%) dengue detected. Of the 441 patients tested for R/O, 39 (8.8%) had rickettsioses. We found 7 (2%) Leptospira cases among the 403 AFI patients tested. Nine patients (1%) were hospitalized, and none died. The highest proportion of enteric fever (15%, 36/231) and rickettsioses (14%, 25/182) was in Rajshahi. Dhaka had the most dengue cases (68%, 19/28). R/O affected older children and young adults (IQR 8-23 years) and was detected more frequently in the 21-25 years age-group (17%, 12/70). R/O was more likely to be found in patients in Rajshahi region than in Sylhet (aOR 2.49, 95% CI 0.85-7.32) between July and December (aOR 2.01, 1.01-5.23), and who had a history of recent animal entry inside their house than not (aOR 2.0, 0.93-4.3). Gram-negative Enterobacteriaceae were the most common bacterial infections, and dengue was the most common viral infection among AFI patients in Bangladeshi hospitals, though there was geographic variability. These results can help guide empiric outpatient AFI management.

Murine typhus, which is caused by Rickettsia typhi, has a wide range of clinical manifestations. It has a low mortality rate but may result in meningoencephalitis and interstitial pneumonia in severe cases. Comparisons of complete genome sequences of R. typhi isolates from North Carolina, USA (Wilmington), Myanmar (B9991PP), and Thailand (TH1527) identified only 26 single nucleotide polymorphism (SNP) and 7 insertion-deletion (INDEL) sites in these highly syntenic genomes. Assays were developed to further define the distribution of these variant sites among 15 additional isolates of R. typhi with different histories from Asia, the USA, and Africa. Mismatch amplification mutation assays (MAMA) were validated for 22 SNP sites, while the 7 INDEL sites were analyzed directly on agarose gels. Six SNP types, 9 INDEL types, 11 total types were identified among these 18 isolates. Replicate DNA samples as well as comparisons of isolates with different passage and source histories gave consistent genetic typing profiles. Comparison of the SNP and INDEL markers to R. typhi's nearest neighbor Rickettsia prowazekii demonstrated that the majority of the SNPs represent intra-species variation that arose post divergence of these two species while several INDEL sites also exhibited intraspecies variability among the R. prowazekii genomes that have been completely sequenced. The assays for the presence of these SNP and INDEL sites, particularly the latter, comprise a low technology gel method for consistently distinguishing R. typhi and R. prowazekii as well as for differentiating genetic types of R. typhi.

Clinical and laboratory diagnosis of rickettsial diseases is challenging because of the undifferentiated symptoms (commonly fever, headache, and malaise) and low bacteremia (< 100 genomic copies [gc]/mL) during the early acute stage of illness. Early treatment with doxycycline is critical for a positive outcome, especially in Rickettsia rickettsii (Rocky Mountain spotted fever) infections where cases may be fatal within 5 to 10 days from symptom onset, emphasizing the need for more sensitive diagnostics. A real-time reverse transcriptase polymerase chain reaction (PCR) assay, RCKr, was developed and validated for Rickettsia spp. nucleic acid detection in human clinical samples. The limit of detection for RCKr was determined to be 20 gc/mL, compared with our 2013 (Kato etal.) laboratory developed test, PanR8 at 1,800 to 2,000 gc/mL. Inclusivity, exclusivity, accuracy, and precision results correlated as expected. From an evaluation of 49 banked clinical samples, RCKr detected 35 previously positive samples, as well as two specimens that were PanR8 real-time PCR negative yet clinically diagnosed as possible rickettsiosis. Ct values from RCKr clinical sample testing show a 100-fold increase relative to PanR8. Additional testing is needed to understand the clinical sensitivity of RCKr; however, this study demonstrates RCKr to have high analytical specificity and sensitivity for Rickettsia detection.

The WHO guidelines for monitoring and evaluating Schistosoma mansoni control programs are based on the Kato-Katz (KK) fecal examination method; however, there are limitations to its use, particularly in low prevalence areas. The point-of-care urine circulating cathodic antigen (POC-CCA) assay has emerged as a useful tool for mapping schistosomiasis prevalence, but its use in monitoring and evaluating control programs has not been evaluated. Before POC-CCA can be used for these programs, it must be determined how previous guidance based on the KK method can be translated to the POC-CCA assay; furthermore, its performance in different endemicity settings must be evaluated. Urine and stool specimens were collected from students attending public primary schools in western Kenya before mass treatment with praziquantel at baseline (51 schools), year 1 (45 schools), year 2 (34 schools), and year 3 (20 schools). Prevalence and infection intensity were determined by the KK method and POC-CCA assay. Changes in prevalence and intensity were compared within the strata of schools grouped according to the baseline prevalence determined by the KK method (0-10%, > 10-20%, > 20%). The prevalence determined by the POC-CCA assay was higher than that determined by the KK method at all time points for all strata. The prevalence determined by the KK method decreased from baseline to 2 and 3 years, as did infection intensity (with one exception). A corresponding decrease was not always replicated by the POC-CCA assay results. The POC-CCA assay did not perform as expected, and the concordance of results of the two tests was poor. Furthermore, there are emerging concerns regarding the specificity of the POC-CCA assay. Therefore, it is impossible to translate historical data and programmatic guidelines based on the KK method results to the POC-CCA assay.

Ehrlichiosis, caused by Gram-negative bacteria of the genus Ehrlichia, is considered an emerging infectious disease due to the increasing number of reported cases. Symptoms are non-specific and occur within 1 to 2 weeks following the bite of an infected tick. Confirmatory laboratory diagnostic methods vary in sensitivity and specimen requirements, which can lead to delayed diagnosis. PCR testing serves as an efficient approach to Ehrlichia confirmation in the acute stage of illness. Published assays have been effectively used to detect human ehrlichiosis at limit of detections ranging from 10 to 50 genomic copies (GC) of Ehrlichia DNA. With the discovery of new species capable of human infection, we wanted to develop assays that are sensitive and encompass a wide range of Ehrlichia. Here we developed and validated two sensitive and specific real-time PCR assays (PanE1 and PanE2) for the detection of Ehrlichia species, as well as two real-time PCR assays (ECh2 and ECh4) for the detection of Ehrlichia chaffeensis, specifically. The limit of detection was determined to be 10 GC per reaction with 100% confidence, and as little as 1 GC with lower efficiencies. Accuracy was assessed at 100% correlation. Specificity from exclusivity testing demonstrated that neither the Ehrlichia species assays (n = 60), nor the E. chaffeensis specific assays (n = 64) had cross reactivity with near neighbors or environmental bacteria. A positive predictive value of 100% and a negative predictive value of ≥93% was determined by evaluating banked clinical specimens from 62 patients with the assays. These real-time PCR assays are effective tools to detect human Ehrlichia species during the acute stage of illness. Early detection of Ehrlichia infection by these real-time PCR assays can facilitate diagnosis and treatment.

IMPORTANCE: Engaging adolescent boys and young men in preventing violence against women is a potentially impactful public health strategy. OBJECTIVE: To evaluate the effectiveness of a community-based, gender-transformative program (ie, Manhood 2.0) on perpetration of gender-based violence by adolescent boys and young men. DESIGN, SETTING, AND PARTICIPANTS: In this unblinded cluster randomized clinical trial, neighborhoods were designated as the unit of clustering (1:1 allocation). Three-month (ie, time point 2 [T2]) and 9-month (ie, time point 3 [T3]) follow-ups were conducted. The trial took place in 20 Pittsburgh, Pennsylvania, neighborhoods and 1 centrally located site with concentrated disadvantage. Pittsburgh-based adolescent boys and young men (ages 13 to 19 years) were recruited between July 27, 2015, and June 5, 2017, through youth-serving organizations and community-based alternatives to residential placement for juvenile justice-involved youth. Intention-to-treat analysis was conducted from June 2018 to November 2019. INTERVENTIONS: Manhood 2.0, an international program adapted for adolescent boys and young men in US urban communities, encourages these individuals to challenge gender norms that foster violence against women and unhealthy sexual relationships. Individuals in the control population received job-readiness training. Each program was 18 hours. MAIN OUTCOMES AND MEASURES: The primary outcome was change in participant-level perpetration of sexual violence (SV) or adolescent relationship abuse (ARA) at T3. RESULTS: Among 866 participants, 465 individuals (54%) enrolled in 11 intervention clusters and 401 individuals (46%) enrolled in 10 control clusters. In the intervention group, 325 participants (70%) were analyzed at T2 and 334 participants (72%) were analyzed at T3; in the control group, 262 participants (65%) were analyzed at T2 and 301 participants (75%) were analyzed at T3. Mean (SD) age was 15.5 (1.6) years; 609 participants (70%) self-identified as non-Hispanic Black, and 178 (20%) self-identified as Hispanic, multiracial, or other race/ethnicity other than White. Among individuals in the intervention group, 296 participants (64%) reported any SV or ARA perpetration at baseline, and 173 participants (52%) reported any SV or ARA perpetration at T3. Among individuals in the control group, 213 participants (53%) reported any SV or ARA perpetration at baseline, and 124 participants (41%) reported any SV or ARA perpetration at T3). The difference in reduction between groups was not significant. There was no evidence of an intervention effect for the primary outcome (adjusted odds ratio [OR], 1.32; 95% CI, 0.86-2.01; P = .20). CONCLUSIONS AND RELEVANCE: The findings from this evaluation of a community-based gender-transformative program for adolescent boys and young men did not show a significant intervention effect in reducing SV or ARA perpetration between Manhood 2.0 and a job-readiness control program. Combining gender-transformative approaches with job-readiness programs may be relevant for violence prevention in low-resource urban settings. Attention to improving implementation and strategies to sustain such community-based efforts are needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02427061.

Efforts to control Schistosoma mansoni infection depend on the ability of programs to effectively detect and quantify infection levels and adjust programmatic approaches based on these levels and program goals. One of the three major objectives of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) has been to develop and/or evaluate tools that would assist Neglected Tropical Disease program managers in accomplishing this fundamental task. The advent of a widely available point-of-care (POC) assay to detect schistosome circulating cathodic antigen (CCA) in urine with a rapid diagnostic test (the POC-CCA) in 2008 led SCORE and others to conduct multiple evaluations of this assay, comparing it with the Kato-Katz (KK) stool microscopy assay-the standard used for more than 45 years. This article describes multiple SCORE-funded studies comparing the POC-CCA and KK assays, the pros and cons of these assays, the use of the POC-CCA assay for mapping of S. mansoni infections in areas across the spectrum of prevalence levels, and the validation and recognition that the POC-CCA, although not infallible, is a highly useful tool to detect low-intensity infections in low-to-moderate prevalence areas. Such an assay is critical, as control programs succeed in driving down prevalence and intensity and seek to either maintain control or move to elimination of transmission of S. mansoni.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was funded in 2008 to conduct research that would support country schistosomiasis control programs. As schistosomiasis prevalence decreases in many places and elimination is increasingly within reach, a sensitive and specific test to detect infection with Schistosoma mansoni and Schistosoma haematobium has become a pressing need. After obtaining broad input, SCORE supported Leiden University Medical Center (LUMC) to modify the serum-based antigen assay for use with urine, simplify the assay, and improve its sensitivity. The urine assay eventually contributed to several of the larger SCORE studies. For example, in Zanzibar, we demonstrated that urine filtration, the standard parasite egg detection diagnostic test for S. haematobium, greatly underestimated prevalence in low-prevalence settings. In Burundi and Rwanda, the circulating anodic antigen (CAA) assay provided critical information about the limitations of the stool-based Kato-Katz parasite egg-detection assay for S. mansoni in low-prevalence settings. Other SCORE-supported CAA work demonstrated that frozen, banked urine specimens yielded similar results to fresh ones; pooling of specimens may be a useful, cost-effective approach for surveillance in some settings; and the assay can be performed in local laboratories equipped with adequate centrifuge capacity. These improvements in the assay continue to be of use to researchers around the world. However, additional work will be needed if widespread dissemination of the CAA assay is to occur, for example, by building capacity in places besides LUMC and commercialization of the assay. Here, we review the evolution of the CAA assay format during the SCORE period with emphasis on urine-based applications.

BACKGROUND: Rickettsia felis has recently emerged worldwide as a cause of human illness. Typically causing mild, undifferentiated fever, it has been implicated in several cases of non-fatal neurological disease in Mexico and Sweden. Its distribution and pathogenicity in Southeast Asia is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We retroactively tested cerebrospinal fluid (CSF) or sera from 64 adult patients admitted to hospital in North Sulawesi, Indonesia with acute neurological disease. Rickettsia felis DNA was identified in the CSF of two fatal cases of meningoencephalitis using multi-locus sequence typing semi-nested PCR followed by Sanger sequencing. DNA from both cases had 100% sequence homologies to the R. felis reference strain URRWXCal2 for the 17-kDa and ompB genes, and 99.91% to gltA. CONCLUSION/SIGNIFICANCE: The identification of R. felis in the CSF of two fatal cases of meningoencephalitis in Indonesia suggests the distribution and pathogenicity of this emerging vector-borne bacteria might be greater than generally recognized. Typically Rickettsia are susceptible to the tetracyclines and greater knowledge of R. felis endemicity in Indonesia should lead to better management of some acute neurological cases.

INTRODUCTION: This study analyzed the associations among male adolescents' gender attitudes, intentions to intervene, witnessing peers' abusive behaviors, and multiple forms of adolescent violence perpetration. This community-based evaluation aims to inform future youth violence prevention efforts through the identification of potential predictors of interpersonal violence perpetration. METHODS: Cross-sectional data were from baseline surveys conducted with 866 male adolescents, aged 13-19 years, from community settings in 20 lower-resource neighborhoods in Pittsburgh, PA (August 2015 - June 2017), as part of a cluster RCT to evaluate a sexual violence prevention program. Participants completed in-person, anonymous electronic surveys about gender attitudes, bystander intentions, witnessing peers' abusive behaviors, violence perpetration, and demographics. The analysis was conducted between 2018 and 2019. RESULTS: The youth identified mostly as African American (70%) or Hispanic, multiracial, or other (21%). Most (88%) were born in the U.S., and 85% were in school. Youth with more equitable gender attitudes had lower odds of self-reported violence perpetration across multiple domains, including dating abuse (AOR=0.46, 95% CI=0.29, 0.72) and sexual harassment (AOR=0.50, 95% CI=0.37, 0.67). The relationship between intentions to intervene and violence perpetration was inconclusive. Witnessing peers engaged in abusive behaviors was associated with increased odds of multiple types of violence perpetration, such as dating abuse (witnessed 3 or more behaviors, AOR=2.41, 95% CI=1.31, 4.44). CONCLUSIONS: This is the first U.S.-based study to elicit information from male adolescents in community-based settings (rather than schools or clinics) about multiple types of interpersonal violence perpetration. Findings support violence prevention strategies that challenge harmful gender and social norms while simultaneously increasing youths' skills in interrupting peers' disrespectful and harmful behaviors.

Portions of northern Mexico are experiencing a re-emergence of Rocky Mountain spotted fever (RMSF), a tickborne disease caused by Rickettsia rickettsii, a member of the spotted fever group of rickettsiae (SFGR). Infection with R. rickettsii can result in serious and life-threatening illness in people and dogs. Canine seroprevalence has been used as a sentinel for human RMSF in previous studies. This study aims to quantify SFGR seroprevalence in canines in three northern Mexican states and identify risk factors associated with seropositivity. A total of 1,136 serum samples and 942 ticks were obtained from dogs participating in government sterilization campaigns and from animal control facilities in 14 Mexican cities in three states. SFGR antibodies were detected using indirect immunofluorescence antibody assays at titre values >/=1/64. Six per cent (69 dogs) showed antibodies to SFGR, with the highest seroprevalence reported in Baja California (12%), Coahuila (4%) and Sonora (4%). Dogs from Baja California had three times higher odds of having SFGR antibodies compared to dogs from Sonora (OR = 3.38, 95% CI, 1.81-6.37). Roughly one quarter (25%) of surveyed dogs were parasitized by ticks (Rhipicephalus sanguineus sensu lato) at the time of sample collection. A portion of collected ticks were tested for rickettsial DNA using polymerase chain reaction. Positive samples were then sequenced, showing evidence of SFGR including R. massiliae, R. parkeri and R. rickettsii. Dogs that spent the majority of time on the street, such as free-roaming or community-owned dogs, showed a greater risk of tick infestation, seropositivity, bearing seropositive ticks, and may play a pivotal role in the spread of SFGR among communities. Estimating the seroprevalence of SFGR in the canine population can help public health campaigns target high-risk communities for interventions to reduce human RMSF cases.

Perfluoroalkyl substances (PFAS) are chemicals used in the manufacture of consumer products. PFAS may act as endocrine disruptors, influencing metabolic pathways and weight-related outcomes. We analyzed associations of maternal serum pregnancy concentrations of PFAS with gestational weight gain (GWG). We used data from 905 women in a subsample of the Avon Longitudinal Study of Parents and Children. Women were routinely weighed in antenatal check-ups; absolute GWG was determined by subtracting the first weight measurement from the last. Linear regression was used to explore associations of maternal PFAS concentrations with absolute GWG, stratified by pre-pregnancy body mass index. Associations of maternal PFAS concentrations with absolute GWG were null. Ten percent higher perfluorooctane sulfonic acid (PFOS) was associated with GWG of -0.03kg (95% CI: -0.11, 0.06) and -0.12kg (95% CI: -0.30, 0.06) among under-/normal weight and overweight/obese mothers, respectively. Overall, findings suggest no association between maternal PFAS concentrations and GWG.

Concerns are heightened from detecting environmentally persistent man-made per- and polyfluoroalkyl substances (PFAS) in drinking water systems around the world. Many PFAS, including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), remain in the human body for years. Since 1999-2000, assessment of exposure to PFOS, PFOA, and other select PFAS in the U.S. general population has relied on measuring PFAS serum concentrations in participants of the National Health and Nutrition Examination Survey (NHANES). Manufacturers have replaced select chemistries ("legacy" PFAS) with PFAS with shorter biological half-lives (e.g., GenX, perfluorobutanoate [PFBA]) which may efficiently eliminate in urine. However, knowledge regarding exposure to these compounds is limited. We analyzed 2682 urine samples for 17 legacy and alternative PFAS in 2013-2014 NHANES participants >/=6years of age. Concentrations of some of these PFAS, measured previously in paired serum samples from the same NHANES participants, suggested universal exposure to PFOS and PFOA, and infrequent or no exposure to two short-chain PFAS, perfluorobutane sulfonate and perfluoroheptanoate. Yet, in urine, PFAS were seldom detected; the frequency of not having detectable concentrations of any of the 17 PFAS was 67.5%. Only two were detected in >1.5% of the population: PFBA (13.3%) and perfluorohexanoate (PFHxA, 22.6%); the 90th percentile urine concentrations were 0.1mug/L (PFBA), and 0.3mug/L (PFHxA). These results suggest that exposures to short-chain PFAS are infrequent or at levels below those that would result in detectable concentrations in urine. As such, these findings do not support biomonitoring of short-chain PFAS or fluorinated alternatives in the general population using urine, and highlight the importance of selecting the adequate biomonitoring matrix.

Chikungunya, a mosquito-borne viral, acute febrile illness (AFI) is associated with polyarthralgia and polyarthritis. Differentiation from other AFI is difficult due to the non-specific presentation and limited availability of diagnostics. This 3-year study identified independent clinical predictors by day post-illness onset (DPO) at presentation and age-group that distinguish chikungunya cases from two groups: other AFI and dengue. Specimens collected from participants with fever </=7 days were tested for chikungunya, dengue viruses 1-4, and 20 other pathogens. Of 8,996 participants, 18.2% had chikungunya, and 10.8% had dengue. Chikungunya cases were more likely than other groups to be older, report a chronic condition, and present <3 DPO. Regardless of timing of presentation, significant positive predictors for chikungunya versus other AFI were: joint pain, muscle, bone or back pain, skin rash, and red conjunctiva; with dengue as the comparator, red swollen joints (arthritis), joint pain, skin rash, any bleeding, and irritability were predictors. Chikungunya cases were less likely than AFI and dengue to present with thrombocytopenia, signs of poor circulation, diarrhea, headache, and cough. Among participants presenting <3 DPO, predictors for chikungunya versus other AFI included: joint pain, skin rash, and muscle, bone or back pain, and absence of thrombocytopenia, poor circulation and respiratory or gastrointestinal symptoms; when the comparator was dengue, joint pain and arthritis, and absence of thrombocytopenia, leukopenia, and nausea were early predictors. Among all groups presenting 3-5 DPO, pruritic skin became a predictor for chikungunya, joint, muscle, bone or back pain were no longer predictive, while arthritis became predictive in all age-groups. Absence of thrombocytopenia was a significant predictor regardless of DPO or comparison group. This study identified robust clinical indicators such as joint pain, skin rash and absence of thrombocytopenia that can allow early identification of and accurate differentiation between patients with chikungunya and other common causes of AFI.

BACKGROUND: Since 2000, the reported prevalence of tick-borne spotted fever group rickettsioses (SFGR) has increased considerably. We compared the level of antibody reactivity among healthy blood donors from two widely separated regions of the United States, and evaluated the impact of antibody prevalence on public health surveillance in one of these regions. METHODS: Donor serum samples were evaluated by indirect immunofluorescence antibody assay to identify immunoglobulin G antibodies reactive with Rickettsiarickettsii. The Georgia Department of Public Health (GDPH) analyzed characteristics of cases from 2016 surveillance data to evaluate the utility of laboratory surveillance for case assessment. RESULTS: Of the Georgia donors (N = 1,493), 11.1% demonstrated antibody titers reactive with R. rickettsii at titers >/= 64, whereas 6.3% of donors from Oregon and Washington (N =1,511) were seropositive. Most seropositive donors had a titer of 64; only 3.1% (N = 93) of all donors had titers >/= 128. During 2016, GDPH interviewed 243 seropositive case-patients; only 28% (N = 69) met criteria defined in the national SFGR case definition. CONCLUSIONS: These findings suggest that a single IgG antibody titer is an unreliable measure of diagnosis and could inaccurately affect surveillance estimates that define magnitude and clinical characteristics of SFGR.

Injection drug use and heterosexual transmission from male key populations to their female partners have been the dominant modes of HIV transmission in Vietnam. A demonstration project was conducted to offer immediate antiretroviral therapy (ART) (regardless of CD4 cell count) to HIV-seropositive partners in serodiscordant couples. During March-December 2013, couples HIV testing and counselling (HTC) and immediate ART were offered in two drug use-affected provinces. Of 256 couples receiving couples HTC, 146 (57%) were serodiscordant; 134 (92%) seropositive partners initiated ART irrespective of CD4 cell count. Of these, 86% were male; 57% reported ever using illicit drugs; median CD4 cell count before ART initiation was 374 cells/mm(3). Consistent condom use was reported by 58, 70 and 71% among HIV-positive partners at months 0, 3 and 12. At 12 months after ART initiation, 119 (89%) HIV-positive partners were retained in care; 96 (95% of those tested) achieved viral suppression (<1000 copies/ml). Uptake of immediate ART and viral suppression among those initiating ART were high, paving the way for ART regardless of CD4 cell count as national policy in Vietnam.

Extensive practice-based evidence from international settings, as well as in-depth evaluations of programs promoting gender equity, have demonstrated effectiveness in reducing perpetration of violence against women and girls. Such "gender-transfor-mative programs" encourage critical analysis of gender norms, challenge homophobia and gender-based harassment, build skills to question harmful masculine norms, interrupt harmful and disrespectful behaviors, and encourage more equitable behaviors. Here we describe the history of a gender-transformative program, "Program H," first developed in Brazil and Mexico, the rationale for and evaluation of this original program, and the processes of adaptation for the US urban community-based setting, and highlight the risks as well as opportunities on the work with young men and boys in the future.

National control programs for the preventive chemotherapy of neglected tropical diseases (NTDs) use mass drug administration (MDA) to reduce infection levels in communities and rely on diagnostic tests to monitor program progress and inform interventions. Control programs for Schistosoma mansoni have conventionally employed stool examinations using the Kato–Katz method for program monitoring. Limitations of the Kato–Katz technique include the substantial time and effort required to make and read slides, its poor sensitivity at low levels of infection, and the occasional unwillingness of participants to provide stool samples. Nevertheless, it is widely available and has been the most relied-on technique for evaluating the prevalence of intestinal schistosomiasis for decades. Therefore, it is the method recommended by the current WHO guidelines for S. mansoni control programs.

Per- and polyfluoroalkyl substances (PFAS) have been widely used in commercial and industrial manufacturing processes since the 1950s. Inverse associations between prenatal exposure to PFAS and birth size have been found in populations around the globe. This study examined the association of prenatal maternal serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) and birth size in British boys. The study included 457 mother-son dyads participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Birth weight (g), crown to heel length (cm), and head circumference (cm) were collected at delivery. PFAS were detected in all maternal serum samples during pregnancy (median: 30 weeks gestation (interquartile range: 12-33)). Median concentrations (interquartile range) were 13.8ng/mL (11.0, 17.7), 3.0ng/mL (2.3, 3.8), 1.9ng/mL (1.4, 2.5), and 0.4ng/mL (0.3, 0.5) for PFOS, PFOA, PFHxS, and PFNA, respectively. In multivariable linear regression models, inverse associations were detected between PFOS (continuous) and birth weight (beta=-8.50g, 95% CI=-15.93, -1.07g), crown to heel length (beta=-0.04cm, 95% CI=-0.08, -0.01cm), and head circumference (beta=-0.02cm, 95% CI=-0.04, -0.002cm). In conclusion, prenatal exposure to high levels of PFOS may be associated with reduced birth size in male infants.

Global health security depends on effective surveillance for infectious diseases. In Uganda, resources are inadequate to support collection and reporting of data necessary for an effective and responsive surveillance system. We used a cross-cutting approach to improve surveillance and laboratory capacity in Uganda by leveraging an existing pediatric inpatient malaria sentinel surveillance system to collect data on expanded causes of illness, facilitate development of real-time surveillance, and provide data on antimicrobial resistance. Capacity for blood culture collection was established, along with options for serologic testing for select zoonotic conditions, including arboviral infection, brucellosis, and leptospirosis. Detailed demographic, clinical, and laboratory data for all admissions were captured through a web-based system accessible at participating hospitals, laboratories, and the Uganda Public Health Emergency Operations Center. Between July 2016 and December 2017, the expanded system was activated in pediatric wards of 6 regional government hospitals. During that time, patient data were collected from 30,500 pediatric admissions, half of whom were febrile but lacked evidence of malaria. More than 5,000 blood cultures were performed; 4% yielded bacterial pathogens, and another 4% yielded likely contaminants. Several WHO antimicrobial resistance priority pathogens were identified, some with multidrug-resistant phenotypes, including Acinetobacter spp., Citrobacter spp., Escherichia coli, Staphylococcus aureus, and typhoidal and nontyphoidal Salmonella spp. Leptospirosis and arboviral infections (alphaviruses and flaviviruses) were documented. The lessons learned and early results from the development of this multisectoral surveillance system provide the knowledge, infrastructure, and workforce capacity to serve as a foundation to enhance the capacity to detect, report, and rapidly respond to wide-ranging public health concerns in Uganda.

The reference standard for the confirmation of a recent rickettsial infection is by the observation of a four-fold or greater rise in antibody titres when testing paired acute and convalescent (two to four weeks after illness resolution) sera by serological assays (Figure 1). At the acute stage of illness, diagnosis is performed by molecular detection methods most effectively on DNA extracted from tissue biopsies (eschars, skin rash, and organs) or eschar swabs. Less invasive and more convenient samples such as blood and serum may also be used for detection; however, the low number of circulating bacteria raises the possibility of false negative results. Optimal sampling practices and enhanced sensitivity must therefore be considered in order to provide a more accurate laboratory diagnosis.