A randomized, controlled Phase 1b trial of the Sm-TSP-2 Vaccine for intestinal schistosomiasis in healthy Brazilian adults living in an endemic area.

BACKGROUND: Recombinant Schistosoma mansoni Tetraspanin-2 formulated on Alhydrogel (Sm-TSP-2/Alhydrogel) is being developed to prevent intestinal and hepatic disease caused by S. mansoni. The tegumentary Sm-TSP-2 antigen was selected based on its unique recognition by cytophilic antibodies in putatively immune individuals living in areas of ongoing S. mansoni transmission in Brazil, and preclinical studies in which vaccination with Sm-TSP-2 protected mice following infection challenge. METHODS: A randomized, observer-blind, controlled, Phase 1b clinical trial was conducted in 60 healthy adults living in a region of Brazil with ongoing S. mansoni transmission. In each cohort of 20 participants, 16 were randomized to receive one of two formulations of Sm-TSP-2 vaccine (adjuvanted with Alhydrogel only, or with Alhydrogel plus the Toll-like receptor-4 agonist, AP 10-701), and 4 to receive Euvax B hepatitis B vaccine. Successively higher doses of antigen (10 µg, 30 µg, and 100 µg) were administered in a dose-escalation fashion, with progression to the next dose cohort being dependent upon evaluation of 7-day safety data after all participants in the preceding cohort had received their first dose of vaccine. Each participant received 3 intramuscular injections of study product at intervals of 2 months and was followed for 12 months after the third vaccination. IgG and IgG subclass antibody responses to Sm-TSP-2 were measured by qualified indirect ELISAs at pre- and post-vaccination time points through the final study visit. RESULTS: Sm-TSP-2/Alhydrogel administered with or without AP 10-701 was well-tolerated in this population. The most common solicited adverse events were mild injection site tenderness and pain, and mild headache. No vaccine-related serious adverse events or adverse events of special interest were observed. Groups administered Sm-TSP-2/Alhydrogel with AP 10-701 had higher post-vaccination levels of antigen-specific IgG antibody. A significant dose-response relationship was seen in those administered Sm-TSP-2/Alhydrogel with AP 10-701. Peak anti-Sm-TSP-2 IgG levels were observed approximately 2 weeks following the third dose, regardless of Sm-TSP-2 formulation. IgG levels fell to low levels by Day 478 in all groups except the 100 µg with AP 10-701 group, in which 57% of subjects (4 of 7) still had IgG levels that were ≥4-fold higher than baseline. IgG subclass levels mirrored those of total IgG, with IgG1 being the predominant subclass response. CONCLUSIONS: Vaccination of adults with Sm-TSP-2/Alhydrogel in an area of ongoing S. mansoni transmission was safe, minimally reactogenic, and elicited significant IgG and IgG subclass responses against the vaccine antigen. These promising results have led to initiation of a Phase 2 clinical trial of this vaccine in an endemic region of Uganda. TRIAL REGISTRATION: NCT03110757.

A Two-stage Approach for Rapid Assessment of the Proportion Achieving Viral Suppression Using Routine Clinical Data.

BACKGROUND: Improving viral suppression among people with HIV reduces morbidity, mortality, and transmission. Accordingly, monitoring the proportion of patients with a suppressed viral load is important to optimizing HIV care and treatment programs. But viral load data are often incomplete in clinical records. We illustrate a two-stage approach to estimate the proportion of treated people with HIV who have a suppressed viral load in the Dominican Republic. METHODS: Routinely collected data on viral load and patient characteristics were recorded in a national database, but 74% of patients on treatment at the time of the study did not have a recent viral load measurement. We recruited a subset of these patients for a rapid assessment that obtained additional viral load measurements. We combined results from the rapid assessment and main database using a two-stage weighting approach and compared results to estimates obtained using standard approaches to account for missing data. RESULTS: Of patients with recent routinely collected viral load data, 60% had a suppressed viral load. Results were similar after applying standard approaches to account for missing data. Using the two-stage approach, we estimated that 77% (95% confidence interval [CI] = 74, 80) of those on treatment had a suppressed viral load. CONCLUSIONS: When assessing the proportion of people on treatment with a suppressed viral load using routinely collected data, applying standard approaches to handle missing data may be inadequate. In these settings, augmenting routinely collected data with data collected through sampling-based approaches could allow more accurate and efficient monitoring of HIV treatment program effectiveness.

EVITA Dengue: a cluster-randomized controlled trial to EValuate the efficacy of Wolbachia-InfecTed Aedes aegypti mosquitoes in reducing the incidence of Arboviral infection in Brazil.

BACKGROUND: Arboviruses transmitted by Aedes aegypti including dengue, Zika, and chikungunya are a major global health problem, with over 2.5 billion at risk for dengue alone. There are no licensed antivirals for these infections, and safe and effective vaccines are not yet widely available. Thus, prevention of arbovirus transmission by vector modification is a novel approach being pursued by multiple researchers. However, the field needs high-quality evidence derived from randomized, controlled trials upon which to base the implementation and maintenance of vector control programs. Here, we report the EVITA Dengue trial design (DMID 17-0111), which assesses the efficacy in decreasing arbovirus transmission of an innovative approach developed by the World Mosquito Program for vector modification of Aedes mosquitoes by Wolbachia pipientis. METHODS: DMID 17-0111 is a cluster-randomized trial in Belo Horizonte, Brazil, with clusters defined by primary school catchment areas. Clusters (n = 58) will be randomized 1:1 to intervention (release of Wolbachia-infected Aedes aegypti mosquitoes) vs. control (no release). Standard vector control activities (i.e., insecticides and education campaigns for reduction of mosquito breeding sites) will continue as per current practice in the municipality. Participants (n = 3480, 60 per cluster) are children aged 6-11 years enrolled in the cluster-defining school and living within the cluster boundaries who will undergo annual serologic surveillance for arboviral infection. The primary objective is to compare sero-incidence of arboviral infection between arms. DISCUSSION: DMID 17-0111 aims to determine the efficacy of Wolbachia-infected mosquito releases in reducing human infections by arboviruses transmitted by Aedes aegypti and will complement the mounting evidence for this method from large-scale field releases and ongoing trials. The trial also represents a critical step towards robustness and rigor for how vector control methods are assessed, including the simultaneous measurement and correlation of entomologic and epidemiologic outcomes. Data from this trial will inform further the development of novel vector control methods. TRIAL REGISTRATION: ClinicalTrials.gov NCT04514107 . Registered on 17 August 2020 Primary sponsor: National Institute of Health, National Institute of Allergy and Infectious Diseases.

Acceptability and perceptions of HIV oral self-testing across settings: A comparative qualitative study among Dominican and Tanzanian female sex workers.

Rapid oral HIV self-tests (HIVST) have potential to increase the proportion of people who know their HIV status, especially among stigmatised populations. This study was embedded in two cohorts of female sex workers (FSW) in the Dominican Republic (DR) and Tanzania. Qualitative interviews with 40 FSW were conducted to explore perceived acceptability of HIVST. Interviews were analysed using inductive and deductive thematic coding. Emergent themes were organised by socio-ecological framework levels. FSW in both settings responded positively to the ease of use of HIVST but questioned test accuracy due to the use of saliva rather than blood. FSW in the DR had a more cautious response, while women in Tanzania had favourable perceptions expressing eagerness to use it. At the individual level, themes shaping participants' interest included autonomy, HIV risk perception, and emotional well-being for those with reactive test results, and self-efficacy. At the interpersonal level, privacy, confidentiality, sex work and HIV stigma and social support were salient. Structural level themes focused on health systems including linkages to HIV treatment, provider roles, and access (cost, travel, distribution). Understanding FSW's perceptions and acceptability of HIVST is essential to its integration into health systems and programmes using a community-driven approach.

The Effects of the Affordable Care Act on Health Care Access and Utilization Among Asian American Subgroups.

OBJECTIVES: We examined changes in health care access and utilization associated with the Patient Protection and Affordable Care Act (ACA) for different Asian American subgroups relative to non-Latino whites (whites). RESEARCH DESIGN: Using 2003-2017 California Health Interview Survey data, we examined changes in 4 health care access measures and 2 utilization measures among whites and 7 Asian American subgroups. We estimated the unadjusted and adjusted percentage point changes on the absolute scale from the pre-ACA to post-ACA periods. Adjusted estimates were obtained from multivariable logistic regression models that controlled for predisposing, enabling, and need factors. We also estimated the pre-ACA to post-ACA changes between whites and Asian American subgroups using a difference-in-difference approach. RESULTS: After the ACA was implemented, uninsurance decreased among all Asian American subgroups, but improvements in disparities relative to whites in these measures were limited. In particular, Koreans had the largest absolute reduction in uninsurance (-16.8 percentage points) and were the only subgroup with a significant reduction in terms of disparities relative to whites (-10.1 percentage points). However, little or no improvement was observed in the other 3 access measures (having a usual source of care, delayed medical care in past year, or delayed prescription drug use in past year) and 2 utilization measures (having a physician visit or emergency department visit in past year). CONCLUSIONS: Despite coverage gains among Asian American subgroups, especially Koreans, disparities in access and utilization persisted across all Asian American subgroups.

Estimating Hidden Population Sizes with Venue-based Sampling: Extensions of the Generalized Network Scale-up Estimator.

BACKGROUND: Researchers use a variety of population size estimation methods to determine the sizes of key populations at elevated risk of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), an important step in quantifying epidemic impact, advocating for high-risk groups, and planning, implementing, and monitoring prevention, care, and treatment programs. Conventional procedures often use information about sample respondents' social network contacts to estimate the sizes of key populations of interest. A recent study proposes a generalized network scale-up method that combines two samples-a traditional sample of the general population and a link-tracing sample of the hidden population-and produces more accurate results with fewer assumptions than conventional approaches. METHODS: We extended the generalized network scale-up method from link-tracing samples to samples collected with venue-based sampling designs popular in sampling key populations at risk of HIV. Our method obviates the need for a traditional sample of the general population, as long as the size of the venue-attending population is approximately known. We tested the venue-based generalized network scale-up method in a comprehensive simulation evaluation framework. RESULTS: The venue-based generalized network scale-up method provided accurate and efficient estimates of key population sizes, even when few members of the key population were sampled, yielding average biases below ±6% except when false-positive reporting error is high. It relies on limited assumptions and, in our tests, was robust to numerous threats to inference. CONCLUSIONS: Key population size estimation is vital to the successful implementation of efforts to combat HIV/AIDS. Venue-based network scale-up approaches offer another tool that researchers and policymakers can apply to these problems.

The burden of HIV among female sex workers, men who have sex with men and transgender women in Haiti: results from the 2016 Priorities for Local AIDS Control Efforts (PLACE) study.

INTRODUCTION: Despite the higher risk of HIV among female sex workers (FSWs), men who have sex with men (MSM) and transgender women (TGW), these populations are under-represented in the literature on HIV in Haiti. Here, we present the first nationally representative estimates of HIV prevalence and the first care and treatment cascade for FSWs, MSM and TGW in Haiti. We also examine the social determinants of HIV prevalence in these groups and estimate FSW and MSM population size in Haiti. METHODS: Data were collected between April 2016 and February 2017 throughout the 10 geographical departments of Haiti. The Priorities for Local AIDS Control Efforts (PLACE) method was used to: (1) recruit participants for a behavioural survey; (2) provide rapid testing, counselling and linkage to care for syphilis and HIV; and (3) measure viral load using dried blood spots for participants testing HIV positive. RESULTS: Study participants included 990 FSWs, 520 MSM and 109 TGW. HIV prevalence was estimated at 7.7% (95% CI 6.2%, 9.6%) among FSWs, 2.2% (0.9%, 5.3%) among MSM and 27.6% (5.0%, 73.5%) among TGW. Of participants who tested positive for syphilis, 17% of FSWs, 19% of MSM and 74% of TGW were co-infected with HIV. Economic instability and intimate partner violence (IPV) were significantly associated with HIV among MSM; food insecurity, economic instability and history of rape were significantly associated with HIV among TGW. Fewer than one-third of participants living with HIV knew their status, and more than a quarter of those who knew their status were not on treatment. While approximately four in five FSW and MSM participants on treatment for HIV were virally suppressed, viral suppression was less common among TGW participants at only 46%. CONCLUSIONS: This study demonstrates a need for targeted interventions to prevent and treat HIV among key populations in Haiti. Potential high-impact interventions may include venue-based, peer navigator-led outreach and testing for HIV and syphilis and improving screening and case management for structural violence and IPV. TGW are in urgent need of such interventions due to our observations of alarmingly high HIV prevalence and low frequency of HIV viral suppression among TGW.

Estimating Sizes of Key Populations at the National Level: Considerations for Study Design and Analysis.

BACKGROUND: National estimates of the sizes of key populations, including female sex workers, men who have sex with men, and transgender women are critical to inform national and international responses to the HIV pandemic. However, epidemiologic studies typically provide size estimates for only limited high priority geographic areas. This article illustrates a two-stage approach to obtain a national key population size estimate in the Dominican Republic using available estimates and publicly available contextual information. METHODS: Available estimates of key population size in priority areas were augmented with targeted additional data collection in other areas. To combine information from data collected at each stage, we used statistical methods for handling missing data, including inverse probability weights, multiple imputation, and augmented inverse probability weights. RESULTS: Using the augmented inverse probability weighting approach, which provides some protection against parametric model misspecification, we estimated that 3.7% (95% CI = 2.9, 4.7) of the total population of women in the Dominican Republic between the ages of 15 and 49 years were engaged in sex work, 1.2% (95% CI = 1.1, 1.3) of men aged 15-49 had sex with other men, and 0.19% (95% CI = 0.17, 0.21) of people assigned the male sex at birth were transgender. CONCLUSIONS: Viewing the size estimation of key populations as a missing data problem provides a framework for articulating and evaluating the assumptions necessary to obtain a national size estimate. In addition, this paradigm allows use of methods for missing data familiar to epidemiologists.

New Boletaceae taxa from Guyana: Binderoboletus segoi gen. and sp. nov., Guyanaporus albipodus gen. and sp. nov., Singerocomus rubriflavus gen. and sp. nov., and a new combination for Xerocomus inundabilis.

Binderoboletus segoi gen. and sp. nov., Guyanaporus albipodus gen. and sp. nov. and Singerocomus rubriflavus gen. and sp. nov. (Boletaceae, Boletales, Basidiomycota) are described from the Pakaraima Mountains and adjacent lowlands of Guyana. Xerocomus inundabilis, originally described from the central Brazilian Amazon and based solely on the type collection, is redescribed from numerous collections from Guyana and transferred into Singerocomus. These boletes occur in Neotropical forests dominated by ectomycorrhizal trees in the genera Dicymbe (Fabaceae subfam. Caesalpinioideae), Aldina (Fabaceae subfam. Papilionoideae) and Pakaraimaea (Dipterocarpaceae). Three of the species were repeatedly found in a multiyear sporocarp survey in Dicymbe corymbosa-monodominant forest. Macromorphological, micromorphological, habitat and multilocus DNA sequence data are provided for each species. A molecular phylogenetic analysis based on a large taxon set across the Boletaceae justifies erection of the new genera.

Understanding the high prevalence of HIV and other sexually transmitted infections among socio-economically vulnerable men who have sex with men in Jamaica.

OBJECTIVES: This study estimates HIV prevalence among men who have sex with men (MSM) in Jamaica and explores social determinants of HIV infection among MSM. DESIGN: An island-wide cross-sectional survey of MSM recruited by peer referral and outreach was conducted in 2011. A structured questionnaire was administered and HIV/STI tests done. We compared three groups: MSM who accepted cash for sex within the past 3 months (MSM SW), MSM who did not accept cash for sex (MSM non-SW), and MSM with adverse life events (ever raped, jailed, homeless, victim of violence or low literacy). RESULTS: HIV prevalence among 449 MSM was 31.4%, MSM SW 41.1%, MSM with adverse life events 38.5%, 17 transgender MSM (52.9%), and MSM non-SW without adverse events 21.0%. HIV prevalence increased with age and number of adverse life events (test for trend P < 0.001), as did STI prevalence (P = 0.03). HIV incidence was 6.7 cases/100 person-years (95% CI: 3.74, 12.19). HIV prevalence was highest among MSM reporting high-risk sex; MSM SW who had been raped (65.0%), had a STI (61.2%) and who self identified as female (55.6%). Significant risk factors for HIV infection common to all 3 subgroups were participation in both receptive and insertive anal intercourse, high-risk sex, and history of a STI. Perception of no or little risk, always using a condom, and being bisexual were protective. CONCLUSION: HIV prevalence was high among MSM SW and MSM with adverse life events. Given the characteristics of the sample, HIV prevalence among MSM in Jamaica is probably in the range of 20%. The study illustrates the importance of social vulnerability in driving the HIV epidemic. Programs to empower young MSM, reduce social vulnerability and other structural barriers including stigma and discrimination against MSM are critical to reduce HIV transmission.

Sarcodon in the Neotropics I: new species from Guyana, Puerto Rico and Belize.

Four species of the ectomycorrhizal (ECM) genus Sarcodon (Bankeraceae, Thelephorales, Basidiomycota) are described as new to science. Sarcodon pakaraimensis sp. nov. is described from forests dominated by the ECM trees Pakaraimaea dipterocarpacea (Dipterocarpaceae) and Dicymbe jenmanii (Fabaceae subfam. Caesalpinioideae) in the Pakaraima Mountains of Guyana. Sarcodon portoricensis sp. nov. is described from lower montane wet forest within the El Yunque National Forest of Puerto Rico. Sarcodon quercophilus sp. nov. and Sarcodon umbilicatus sp. nov. are described from Quercus (Fagaceae) cloud forests within the Maya Mountains of Belize. The discovery of these species is significant given that the majority of the approximately 87 described Sarcodon species are north temperate or boreal in distribution and frequently associate with coniferous host plants; these constitute the most recent records for Sarcodon from the greater Neotropics. Each of the new species is morphologically consistent with accepted diagnostic characters for Sarcodon: pileate-stipitate stature, a dentate hymenophore, determinate basidiomatal development, fleshy, non-zonate context and brown, tuberculate basidiospores. DNA (ITS) sequence analysis corroborated the generic placement of S. pakaraimensis, S. portoricensis, S. quercophilus and S. umbilicatus and, along with morphological differences, supported their recognition as distinct species. Macromorphological, micromorphological, habitat and DNA sequence data from the nuc rDNA internal transcribed spacer region (ITS) are provided for each of the new species. A key to Neotropical Sarcodon species and similar extralimital taxa is provided.

Cantharellaceae of Guyana II: new species of Craterellus, new South American distribution records for Cantharellus guyanensis and Craterellus excelsus, and a key to the Neotropical taxa.

Craterellus olivaceoluteus sp. nov. and Craterellus cinereofimbriatus sp. nov. are described as new to science. These fungi were collected from Guyana in association with ectomycorrhizal host trees in the genera Dicymbe (Fabaceae subfam. Caesalpinioideae) and Pakaraimaea (Dipterocarpaceae). Cantharellus guyanensis Mont., originally described from French Guiana, is redescribed from recent collections from Guyana, with additional range extensions for the species provided based on material examined from French Guiana, Venezuela, and north central, northeastern and southern Brazil, circumscribing nearly the entire Guiana Shield region and beyond. A new distribution record from French Guiana is provided for Craterellus excelsus T.W. Henkel & Aime. Macromorphological, micromorphological and habitat data are provided for the new species and C. guyanensis as well as DNA sequence data from the nuclear ribosomal regions of the internal transcribed spacer (ITS) and 28S large subunit (LSU); additional sequence data is provided for C. guyanensis and C. excelsus specimens collected outside Guyana. The relationships of these taxa within the Cantharellaceae were evaluated with phylogenetic analyses of ITS and LSU sequence data. This work brings the total number of Cantharellaceae species known from Guyana to eight. A key to the Cantharellus and Craterellus species known from the lowland Neotropics and extralimital montane Central and South America is provided.

The ectomycorrhizal fungal community in a neotropical forest dominated by the endemic dipterocarp Pakaraimaea dipterocarpacea.

Ectomycorrhizal (ECM) plants and fungi can be diverse and abundant in certain tropical ecosystems. For example, the primarily paleotropical ECM plant family Dipterocarpaceae is one of the most speciose and ecologically important tree families in Southeast Asia. Pakaraimaea dipterocarpacea is one of two species of dipterocarp known from the Neotropics, and is also the only known member of the monotypic Dipterocarpaceae subfamily Pakaraimoideae. This Guiana Shield endemic is only known from the sandstone highlands of Guyana and Venezuela. Despite its unique phylogenetic position and unusual geographical distribution, the ECM fungal associations of P. dipterocarpacea are understudied throughout the tree's range. In December 2010 we sampled ECM fungi on roots of P. dipterocarpacea and the co-occurring ECM tree Dicymbe jenmanii (Fabaceae subfamily Caesalpinioideae) in the Upper Mazaruni River Basin of Guyana. Based on ITS rDNA sequencing we documented 52 ECM species from 11 independent fungal lineages. Due to the phylogenetic distance between the two host tree species, we hypothesized that P. dipterocarpacea would harbor unique ECM fungi not found on the roots of D. jenmanii. Although statistical tests suggested that several ECM fungal species did exhibit host preferences for either P. dipterocarpacea or D. jenmanii, most of the ECM fungi were multi-host generalists. We also detected several ECM fungi that have never been found in long-term studies of nearby rainforests dominated by other Dicymbe species. One particular mushroom-forming fungus appears to be unique and may represent a new ECM lineage of Agaricales that is endemic to the Neotropics.

New species and distribution records for Clavulina (Cantharellales, Basidiomycota) from the Guiana Shield, with a key to the lowland neotropical taxa.

Three new and one previously described species of Clavulina (Clavulinaceae, Cantharellales, Basidiomycota) are reported from the central Guiana Shield region from tropical rainforests dominated by ectomycorrhizal trees of the leguminous genus Dicymbe (Fabaceae subfam. Caesalpinioideae). We provide morphological, DNA sequence, habitat, and fruiting occurrence data for each species. The new species conform to a generic concept of Clavulina that includes coralloid, branched basidiomata with amphigenous hymenia, basidia with two or 2-4 incurved sterigmata and postpartal septa present or absent, and smooth, hyaline, guttulate basidiospores. Placements of the new species in Clavulina were corroborated with DNA sequence data from the internal transcribed spacer and large subunit of the nuclear ribosomal repeat, and their infrageneric relationships were examined with phylogenetic analyses based on DNA from the region coding for the second largest subunit of DNA-dependent RNA polymerase II (rpb2). To facilitate future studies of the genus in the neotropics, a key is provided for all Clavulina species described from the lowland neotropics.

New species of Clavulina (Cantharellales, Basidiomycota) with resupinate and effused basidiomata from the Guiana Shield.

Three new species of Clavulina (Cantharellales, Basidiomycota) are described from rainforests dominated by ectomycorrhizal trees of the leguminous genus Dicymbe (Fabaceae subfam. Caesalpinioideae) from the central Guiana Shield. Species of Clavulina typically form branched, coralloid basidiomata with amphigenous hymenia. However, the three species described here form resupinate or effuso-coralloid basidiomata, macromorphological forms previously unknown in Clavulina. Macromorphological, micromorphological, habitat and DNA sequence data are provided for each new species. Micromorphological features and DNA sequence data from the second largest subunit of DNA-dependant RNA polymerase II (rpb2) and internal transcribed spacer (ITS) and large subunit (28S) of the ribosomal repeat justify placement of these new species in Clavulina. Comparisons with described Clavulina species and other resupinate taxa within the Cantharellales are provided.

New species and distribution records of Clavulina (Cantharellales, Basidiomycota) from the Guiana Shield.

Two new species of Clavulina Schroet. (Clavulinaceae, Cantharellales, Basidiomycota) and new distribution records for Clavulina amazonensis Corner and Clavulina sprucei (Berk.) Corner are described from the Pakaraima Mountains of Guyana, in the central Guiana Shield region. These fungi occur in rainforests dominated by ectomycorrhizal (ECM) trees of the leguminous genus Dicymbe (Fabaceae subfam. Caesalpinioideae). Macromorphological, micromorphological and habitat data are provided for each species. Nuclear ribosomal DNA sequences of the internal transcribed spacer region and 28S subunit were obtained for new species and from representative collections of C. amazonensis and C. sprucei. The two new species, Clavulina kunmudlutsa sp. nov. and Clavulina tepurumenga sp. nov., constitute important edible fungi for the Patamona Amerindians. Our specimens of C. sprucei represent the first reports of the species since 1853 as well as a range extension of nearly 1500 km, while sequence data from basidiomata as well as ECM roots suggest that this taxon consists of a cryptic species complex.