Mosquito-transmitted viruses such as dengue are a global and growing public health challenge. Without widely available vaccines, mosquito control is the primary tool for fighting the spread of these viruses. New mosquito control technologies are needed to complement existing methods, given current challenges with scalability, acceptability, and effectiveness. A field trial was conducted in collaboration with the Communities Organized to Prevent Arboviruses project in Ponce, Puerto Rico, to measure entomological and epidemiological effects of reducing Aedes aegypti populations using Wolbachia incompatible insect technique. We packed and shipped Wolbachia-males from California and released them into 19 treatment clusters from September 2020 to December 2020. Preliminary evaluation revealed sub-optimal Wolbachia-male densities and impact on the wild-type population. In 2021, we shifted to a phased release strategy starting in four clusters, reducing the mosquito population by 49% (CI 29-63%). We describe the investigation into male quality and other factors that may have limited the impact of Wolbachia-male releases. Laboratory assays showed a small but significant impact of packing and shipping on male fitness. However, mark-release-recapture assessments suggest that male daily survival rates in the field may have been significantly impacted. We compared induced-sterility levels and suppression of the wild population and found patterns consistent with mosquito population compensation in response to our intervention. Analysis of epidemiological impact was not possible due to very low viral transmission rates during the intervention period. Our entomological impact data provide evidence that Wolbachia incompatible-male releases reduced Ae. aegypti populations, although efficacy will be maximized when releases are part of an integrated control program. With improvement of shipping vessels and shipped male fitness, packing and shipping male mosquitoes could provide a key solution for expanding access to this technology. Our project underscores the challenges involved in large and complex field effectiveness assessments of novel vector control methods.

Neisseria gonorrhoeae infection (gonorrhoea) is a global public health challenge, causing substantial sexual and reproductive health consequences, such as infertility, pregnancy complications and increased acquisition or transmission of HIV. There is an urgency to controlling gonorrhoea because of increasing antimicrobial resistance to ceftriaxone, the last remaining treatment option, and the potential for gonorrhoea to become untreatable. No licensed gonococcal vaccine is available. Mounting observational evidence suggests that N. meningitidis serogroup B outer membrane vesicle-based vaccines may induce cross-protection against N. gonorrhoeae (estimated 30%-40% effectiveness using the 4CMenB vaccine). Clinical trials to determine the efficacy of the 4CMenB vaccine against N. gonorrhoeae are underway, as are Phase 1/2 studies of a new gonococcal-specific vaccine candidate. Ultimately, a gonococcal vaccine must be accessible, affordable and equitably dispensed, given that those most affected by gonorrhoea are also those who may be most disadvantaged in our societies, and most cases are in less-resourced settings. This vaccine value profile (VVP) provides a high level, holistic assessment of the current data to inform the potential public health, economic and societal value of pipeline vaccines. This was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations. All contributors have extensive expertise on various elements of the N. gonorrhoeae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using published data obtained from peer-reviewed journals or reports.

The genotypes referred to in this article were stated incorrectly. The genotype number 49 should have been stated as 48 and the number 27 should have been stated as 26. These errors occurred in the 'Abstract' section on page 1, in the ‘Discussion’ section on page 11, and within Fig. 5 on page 12. | | The sentence in the 'Abstract' should have read: | | ‘Using previously described 2× standard deviation (sd) criteria to group sequences into separate clusters, we expanded the number of genogroups to 10 (GI-GX) and the number of genotypes to 48 (9 GI, 26 GII, 3 GIII, 2 GIV, 2 GV, 2 GVI and 1 genotype each for GVII, GVIII, GIX [formerly GII.15] and GX).’ | | The sentence in the 'Discussion' section on page 11 should have read: | | ‘Viruses in these ten genogroups can be further divided into 48 confirmed capsid genotypes based on amino acids of the complete VP1 and 60 confirmed P-types based on partial nucleotide sequences of RdRp regions.’ | | Fig. 5 on page 12 erroneously stated ‘27+2T’. This should have been stated as ‘26+2T’.

This study characterizes community perceptions on a large-scale project seeking to reduce the population of Aedes aegypti mosquitoes and prevent arboviral disease transmission in Ponce, Puerto Rico; and to leverage on these perceptions to make modifications to ensure effective project implementation. In 2017-2018 the team conducted informal interviews, focus groups, and in-depth interviews with leaders and residents of the communities, focusing on challenges and potential solutions to the project implementation. Possible challenges to the project implementation included the lack of geographic consistency between clusters defined by researchers and the participants' description of the communities' geographic boundaries. Few children living in the communities could affect the ability of the project to adequately measure arboviral disease incidence. Also, population attrition due to out-migration, and lack of community leaders and communication channels after Hurricane Maria could affect participation in project activities. Lack of trust on strangers was an important challenge due to criminal activity involving violence and drug use in some community areas. Solutions to the identified challenges included identifying emerging leaders and implementing community meetings to promote project activities. The information that community members provided helped us to understand the natural disasters' impact on population attrition in these communities with a disproportionate impact in younger groups, resulting in an aging population. We identified lack of community organization and leadership and increasing number of abandoned houses that could turn into Aedes aegypti breeding sites. The formative work helped to better define the geographic areas that the study would cover, evaluate the acceptability of innovative vector control methods, and identify communication methods used by residents. With this information, challenges and potential solutions in recruiting participants were anticipated, and the community engagement and communications plans were developed. We recommend selecting clusters before research, because opinions towards mosquito control technologies could vary in added clusters.

Plastics are a group of useful chemicals that have increased in usage since the 1950s (Miranda, Silva et al. 2019). Plastics are stable regarding both temperature resistance and chemical interactivity. Because of these properties, plastics are utilized in a variety of health products such as toothbrushes, break-resistant beverage containers, and intravenous tubing. Although plastics are extremely useful, they also break down in the environment and present a source of exposure to humans in the form of microplastics. A microplastic is commonly defined as a plastic with any dimension less than 5 millimeters (Guven, Gokdag et al., 2017; Stapleton 2019). Researchers have defined a smaller group of plastics as nanoplastics, as smaller than 1000 nanometers (Gigault et al., 2018). Here we will retain the term microplastics to include all plastic particles smaller than 5 millimeters. | | To address the emerging public health concerns for exposure to microplastics, an interdisciplinary working group was formed, combining staff from the National Center of Environmental Health (NCEH) and the Agency for Toxic Substances and Disease Registry (ATSDR). NCEH has taken the lead on investigating microplastics in drinking water. This is consistent with its other efforts to provide safe water support to local and state health departments to address risks to human health. ATSDR has evaluated whether exposures to microplastics in the environment are hazardous, in alignment with its mandate to evaluate potential health effects of hazardous substances in the environment.

Arboviral diseases transmitted by Aedes species mosquitoes pose an increasing public health challenge in tropical regions. Wolbachia-mediated population suppression (Wolbachia suppression) is a vector control method used to reduce Aedes mosquito populations by introducing male mosquitoes infected with Wolbachia, a naturally occurring endosymbiotic bacterium. When Wolbachia-infected male mosquitoes mate with female wild mosquitoes, the resulting eggs will not hatch. Public support is vital to the successful implementation and sustainability of vector control interventions. Communities Organized to Prevent Arboviruses (COPA) is a cohort study to determine the incidence of arboviral disease in Ponce, Puerto Rico and evaluate vector control methods. Focus groups were conducted with residents of COPA communities to gather their opinion on vector control methods; during 2018-2019, adult COPA participants were interviewed regarding their views on Wolbachia suppression; and a follow-up questionnaire was conducted among a subset of participants and non-participants residing in COPA communities. We analyzed factors associated with support for this method. Among 1,528 participants in the baseline survey, median age was 37 years and 63% were female. A total of 1,032 (68%) respondents supported Wolbachia suppression. Respondents with an income of $40,000 or more were 1.34 times as likely [95% CI: 1.03, 1.37] to support Wolbachia suppression than those who earned less than $40,000 annually. Respondents who reported repellant use were 1.19 times as likely to support Wolbachia suppression [95% CI: 1.03, 1.37]. A follow-up survey in 2020 showed that most COPA participants (86%) and non-participants living in COPA communities (84%) supported Wolbachia suppression during and after an educational campaign. The most frequent questions regarding this method were related to its impact on human and animal health, and the environment. Continuous community engagement and education efforts before and during the implementation of novel vector control interventions are necessary to increase and maintain community support.

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, while ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid-organ transplant recipients in particular are at increased risk of infections from multi-drug resistant organisms, due to host and donor factors and immunosuppressive therapy - there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in-situ, may modify the risk of infection. As such, it is not feasible to have a 'one-size-fits-all' style of stewardship for this patient population. The objective of this whitepaper is to identify opportunities, risk factors and ASP strategies that should be assessed with SOT recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance, and identification of research opportunities.

Cronobacter spp. are emerging infectious foodborne bacteria that can cause acute meningitis and necrotizing enterocolitis in neonates and immunocompromised individuals. Although, little is known about its reservoirs or transmission routes, it has been linked to powdered infant formula worldwide. Three Cronobacter spp. (C. sakazakii, C. malonaticus, and C. turicensis) have been described as more virulent, and isolated frequently from infant meningitis cases. The estimated mortality rates are as high as 80% in infants. Thus, surveillance and typing of Cronobacter spp. isolated from food and environmental samples is essential to prevent contamination and spread of this pathogen. In this study, we have characterized 83 Cronobacter isolates recovered from various environmental samples by conventional microbiologic protocols. Species identification was accomplished by VITEK 2 system and real-time PCR analysis. Subsequently, these isolates were analyzed using VITEK MS system. Single locus sequence typing (SLST) was achieved by characterizing the regions of 16S rRNA and rpoB genes. Multilocus sequence typing (MLST) was performed by sequence characterization of seven housekeeping genes (atpD, fusA, glnS, gltB, gyrB, infB, and pps) using ABI 3500XL Genetic Analyzer. VITEK MS system identified, the majority of isolates as Cronobacter sakazakii with a high confidence value (99.9%). MLST analysis ascertained 12 distinct clonal complexes (CC1, CC4, CC8, CC13, CC17, CC21, CC31, CC40, CC52, CC64, CC73, and CC83) for the recovered C. sakazakii isolates. The results suggest that the MALDI-TOF MS is a reliable diagnostic tool for rapid species identification whereas 7-loci MLST is a powerful technique to discriminate and differentiate Cronobacter spp. isolates.

This evaluation describes an increase in reported drug-related risk behaviors (DRRBs) among females who are diagnosed with early syphilis over a 5-year span in New York State, excluding New York City. Integrating sexually transmitted infection prevention efforts with harm reduction services may help decrease syphilis rates in areas where DRRBs rates are high.

BACKGROUND: Real-time reverse transcription polymerase chain reaction (rRT-PCR) and antigen tests are important diagnostics for SARS-CoV-2. Sensitivity of antigen tests has been shown to be lower than that of rRT-PCR; however, data to evaluate epidemiologic characteristics that affect test performance are limited. METHODS: Paired mid-turbinate nasal swabs were collected from university students and staff and tested for SARS-CoV-2 using both Quidel Sofia SARS Antigen Fluorescent Immunoassay (FIA) and rRT-PCR assay. Specimens positive by either rRT-PCR or antigen FIA were placed in viral culture and tested for subgenomic RNA (sgRNA). Logistic regression models were used to evaluate characteristics associated with antigen results, rRT-PCR cycle threshold (Ct) values, sgRNA, and viral culture. RESULTS: Antigen FIA sensitivity was 78.9% and 43.8% among symptomatic and asymptomatic participants respectively. Among rRT-PCR positive participants, negative antigen results were more likely among asymptomatic participants (OR 4.6, CI:1.3-15.4) and less likely among participants reporting nasal congestion (OR 0.1, CI:0.03-0.8). rRT-PCR-positive specimens with higher Ct values (OR 0.5, CI:0.4-0.8) were less likely, and specimens positive for sgRNA (OR 10.2, CI:1.6-65.0) more likely, to yield positive virus isolation. Antigen testing was >90% positive in specimens with Ct values <29. Positive predictive value of antigen test for positive viral culture (57.7%) was similar to that of rRT-PCR (59.3%). CONCLUSIONS: SARS-CoV-2 antigen test advantages include low cost, wide availability and rapid turnaround time, making them important screening tests. The performance of antigen tests may vary with patient characteristics, so performance characteristics should be accounted for when designing testing strategies and interpreting results.

Reinfection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is believed to be rare (1). Some level of immunity after SARS-CoV-2 infection is expected; however, the evidence regarding duration and level of protection is still emerging (2). The Kentucky Department for Public Health (KDPH) and a local health department conducted an investigation at a skilled nursing facility (SNF) that experienced a second COVID-19 outbreak in October 2020, 3 months after a first outbreak in July. Five residents received positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results during both outbreaks. During the first outbreak, three of the five patients were asymptomatic and two had mild symptoms that resolved before the second outbreak. Disease severity in the five residents during the second outbreak was worse than that during the first outbreak and included one death. Because test samples were not retained, phylogenetic strain comparison was not possible. However, interim period symptom resolution in the two symptomatic patients, at least four consecutive negative RT-PCR tests for all five patients before receiving a positive test result during the second outbreak, and the 3-month interval between the first and the second outbreaks, suggest the possibility that reinfection occurred. Maintaining physical distance, wearing face coverings or masks, and frequent hand hygiene are critical mitigation strategies necessary to prevent transmission of SARS-CoV-2 to SNF residents, a particularly vulnerable population at risk for poor COVID-19-associated outcomes.* Testing, containment strategies (isolation and quarantine), and vaccination of residents and health care personnel (HCP) are also essential components to protecting vulnerable residents. The findings of this study highlight the importance of maintaining public health mitigation and protection strategies that reduce transmission risk, even among persons with a history of COVID-19 infection.

BACKGROUND: With a shortage of effective options for control of Aedes aegypti in Puerto Rico due to widespread resistance to conventional mosquito adulticides, an alternative approach was investigated to reduce vector populations. In two areas (totaling 144 ha) of the municipality of Bayamón, Puerto Rico, Bacillus thuringiensis israelensis (Bti) AM65-52 WDG was applied at a rate of 500 g/ha using vehicle-mounted aqueous wide-area larvicide spray applications weekly for 4 weeks and then every other week for a further 16 weeks. Bioassay jars were placed in the field to monitor for deposition of Bti droplets in open spaces, and under vegetation and building coverage. Autocidal gravid ovitraps were placed throughout the field site to monitor the population of adult female Ae. aegypti in both treatment and control sites. RESULTS: Larvicide spray was successfully deposited into jars in an array of open and covered locations, as confirmed by larval bioassays. After the fourth weekly spraying, differences in autocidal gravid ovitrap densities were observed between treatment and control sites resulting in 62% (P = 0.0001) and 28% (P < 0.0001) reductions in adult female Ae. aegypti numbers. CONCLUSION: Repeated wide-area larvicide spray application of Bti AM65-52 WDG to residential areas in Puerto Rico effectively suppressed dengue vector populations. The success of this trial has led to expansion of the WALS® program to a larger area of Bayamón and other municipalities in Puerto Rico.

Antigen-based tests for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), are inexpensive and can return results within 15 minutes (1). Antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in asymptomatic and symptomatic persons within the first 5-12 days after symptom onset (2). These tests have been used at U.S. colleges and universities and other congregate settings (e.g., nursing homes and correctional and detention facilities), where serial testing of asymptomatic persons might facilitate early case identification (3-5). However, test performance data from symptomatic and asymptomatic persons are limited. This investigation evaluated performance of the Sofia SARS Antigen Fluorescent Immunoassay (FIA) (Quidel Corporation) compared with real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection among asymptomatic and symptomatic persons at two universities in Wisconsin. During September 28-October 9, a total of 1,098 paired nasal swabs were tested using the Sofia SARS Antigen FIA and real-time RT-PCR. Virus culture was attempted on all antigen-positive or real-time RT-PCR-positive specimens. Among 871 (79%) paired swabs from asymptomatic participants, the antigen test sensitivity was 41.2%, specificity was 98.4%, and in this population the estimated positive predictive value (PPV) was 33.3%, and negative predictive value (NPV) was 98.8%. Antigen test performance was improved among 227 (21%) paired swabs from participants who reported one or more symptoms at specimen collection (sensitivity = 80.0%; specificity = 98.9%; PPV = 94.1%; NPV = 95.9%). Virus was isolated from 34 (46.6%) of 73 antigen-positive or real-time RT-PCR-positive nasal swab specimens, including two of 18 that were antigen-negative and real-time RT-PCR-positive (false-negatives). The advantages of antigen tests such as low cost and rapid turnaround might allow for rapid identification of infectious persons. However, these advantages need to be balanced against lower sensitivity and lower PPV, especially among asymptomatic persons. Confirmatory testing with an FDA-authorized nucleic acid amplification test (NAAT), such as RT-PCR, should be considered after negative antigen test results in symptomatic persons, and after positive antigen test results in asymptomatic persons (1).

Pregnant women might be at increased risk for severe coronavirus disease 2019 (COVID-19) (1,2). The COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) (3) collects data on hospitalized pregnant women with laboratory-confirmed SARS-CoV-2, the virus that causes COVID-19; to date, such data have been limited. During March 1-August 22, 2020, approximately one in four hospitalized women aged 15-49 years with COVID-19 was pregnant. Among 598 hospitalized pregnant women with COVID-19, 54.5% were asymptomatic at admission. Among 272 pregnant women with COVID-19 who were symptomatic at hospital admission, 16.2% were admitted to an intensive care unit (ICU), and 8.5% required invasive mechanical ventilation. During COVID-19-associated hospitalizations, 448 of 458 (97.8%) completed pregnancies resulted in a live birth and 10 (2.2%) resulted in a pregnancy loss. Testing policies based on the presence of symptoms might miss COVID-19 infections during pregnancy. Surveillance of pregnant women with COVID-19, including those with asymptomatic infections, is important to understand the short- and long-term consequences of COVID-19 for mothers and newborns. Identifying COVID-19 in women during birth hospitalizations is important to guide preventive measures to protect pregnant women, parents, newborns, other patients, and hospital personnel. Pregnant women and health care providers should be made aware of the potential risks for severe COVID-19 illness, adverse pregnancy outcomes, and ways to prevent infection.

BACKGROUND: Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis. METHODS: This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer >/=1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response. DISCUSSION: Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis. TRIAL REGISTRATION: Trial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.

Relocation from one's birthplace may affect human immunodeficiency virus (HIV) outcomes, but national estimates of HIV outcomes among Hispanics/Latinos by place of birth are limited. We analyzed Medical Monitoring Project data collected in 2015-2018 from 2564 HIV-positive Hispanic/Latino adults and compared clinical outcomes between mainland US-born (referent group), Puerto Rican (PR-born), and those born outside the United States (non-US-born). We reported weighted percentages of characteristics and used logistic regression with predicted marginal means to examine differences between groups (p < 0.05). PR-born Hispanics/Latinos were more likely to be prescribed antiretroviral therapy (ART) (94%) and retained in care (94%) than mainland-US-born (79% and 77%, respectively) and non-US-born (91% and 87%, respectively) Hispanics/Latinos. PR-born Hispanics/Latinos were more likely to have sustained viral suppression (75%) than mainland-US-born Hispanics/Latinos (57%). Non-US-born Hispanics/Latinos were more likely to be prescribed ART (91% vs. 79%), retained in care (87% vs. 77%), and have sustained viral suppression (74% vs. 57%) than mainland-US-born Hispanics/Latinos. Greater Ryan White HIV/AIDS-funded facility usage among PR-born, better mental health among non-US-born, and less drug use among PR-born and non-US-born Hispanics/Latinos may have contributed to better HIV outcomes. Expanding programs with comprehensive HIV/AIDS services, including for mental health and substance use, may reduce HIV outcome disparities among Hispanics/Latinos.

Zika virus (ZIKV) was first discovered in 1947 in Uganda but was not considered a public health threat until 2007 when it found to be the source of epidemic activity in Asia. Epidemic activity spread to Brazil in 2014 and continued to spread throughout the tropical and subtropical regions of the Americas. Despite ZIKV being zoonotic in origin, information about transmission, or even exposure of non-human vertebrates and mosquitoes to ZIKV in the Americas, is lacking. Accordingly, from February 2017 to March 2018, we sought evidence of sylvatic ZIKV transmission by sampling whole blood from approximately 2000 domestic and wild vertebrates of over 100 species in West-Central Brazil within the active human ZIKV transmission area. In addition, we collected over 24,300 mosquitoes of at least 17 genera and 62 species. We screened whole blood samples and mosquito pools for ZIKV RNA using pan-flavivirus primers in a real-time reverse-transcription polymerase chain reaction (RT-PCR) in a SYBR Green platform. Positives were confirmed using ZIKV-specific envelope gene real-time RT-PCR and nucleotide sequencing. Of the 2068 vertebrates tested, none were ZIKV positive. Of the 23,315 non-engorged mosquitoes consolidated into 1503 pools tested, 22 (1.5%) with full data available showed some degree of homology to insect-specific flaviviruses. To identify previous exposure to ZIKV, 1498 plasma samples representing 62 species of domestic and sylvatic vertebrates were tested for ZIKV-neutralizing antibodies by plaque reduction neutralization test (PRNT90). From these, 23 (1.5%) of seven species were seropositive for ZIKV and negative for dengue virus serotype 2, yellow fever virus, and West Nile virus, suggesting potential monotypic reaction for ZIKV. Results presented here suggest no active transmission of ZIKV in non-human vertebrate populations or in alternative vector candidates, but suggest that vertebrates around human populations have indeed been exposed to ZIKV in West-Central Brazil.

We found Rickettsia parkeri in Amblyomma ovale ticks collected in Veracruz, Mexico, in 2018. We sequenced gene segments of gltA, htrA, sca0, and sca5; phylogenetic reconstruction revealed near-complete identity with R. parkeri strain Atlantic Rainforest. Enhanced surveillance is needed in Mexico to determine the public health relevance of this bacterium.

In response to the 2016 Zika outbreak, Aedes aegypti mosquitoes from 38 locations across Puerto Rico were screened using Centers for Disease Control and Prevention bottle bioassays for sensitivity to insecticides used for mosquito control. All populations were resistant to pyrethroids. Naled, an organophosphate, was the most effective insecticide, killing all mosquitoes tested.

BACKGROUND: Approximately 30% of people living with HIV worldwide are estimated to be unaware of their infection. HIV self-testing (HIVST) is a strategy recommended by the World Health Organization to increase access to and uptake of testing among key populations who are at high risk for HIV infection. OBJECTIVE: This study aimed to describe the development and feasibility of a free, anonymous, internet-based HIVST strategy designed for men who have sex with men in Curitiba, Brazil (electronic testing [e-testing]). METHODS: The project was developed under the scope of the "A Hora e Agora" (The Time is Now) program. Individuals aiming to request an HIVST package (two tests each) answered an anonymous 5-minute questionnaire regarding inclusion criteria and sexual risk behavior. Eligible individuals could receive one package every 6 months for free. Website analytics, response to online questionnaires, package distribution, and return of test results were monitored via a platform-integrated system. RESULTS: Between February 2015 and January 2016, the website documented 17,786 unique visitors and 3218 completed online questionnaires. Most individuals self-reported being white (77.0%), young (median age: 25 years, interquartile range: 22-31 years), educated (87.3% completed secondary education or more), and previously tested for HIV (62.5%). Overall, 2526 HIVST packages were delivered; of those, 542 (21.4%) reported a result online or by mail (23 reactive and 11 invalid). During the study period, 37 individuals who reported using e-testing visited the prespecified health facility for confirmatory testing (30 positive, 7 negative). CONCLUSIONS: E-testing proved highly feasible and acceptable in this study, thus supporting scale-up to additional centers for men who have sex with men in Brazil.

Noroviruses are genetically diverse RNA viruses associated with acute gastroenteritis in mammalian hosts. Phylogenetically, they can be segregated into different genogroups as well as P (polymerase)-groups and further into genotypes and P-types based on amino acid diversity of the complete VP1 gene and nucleotide diversity of the RNA-dependent RNA polymerase (RdRp) region of ORF1, respectively. In recent years, several new noroviruses have been reported that warrant an update of the existing classification scheme. Using previously described 2x standard deviation (sd) criteria to group sequences into separate clusters, we expanded the number of genogroups to 10 (GI-GX) and the number of genotypes to 49 (9 GI, 27 GII, 3 GIII, 2 GIV, 2 GV, 2 GVI and 1 genotype each for GVII, GVIII, GIX [formerly GII.15] and GX). Viruses for which currently only one sequence is available in public databases were classified into tentative new genogroups (GNA1 and GNA2) and genotypes (GII.NA1, GII.NA2 and GIV.NA1) with their definitive assignment awaiting additional related sequences. Based on nucleotide diversity in the RdRp region, noroviruses can be divided into 60 P-types (14 GI, 37 GII, 2 GIII, 1 GIV, 2 GV, 2 GVI, 1 GVII and 1 GX), 2 tentative P-groups and 14 tentative P-types. Future classification and nomenclature updates will be based on complete genome sequences and will be coordinated and disseminated by the international norovirus classification-working group.

In February 2019, following the annual taxon ratification vote, the order Bunyavirales was amended by creation of two new families, four new subfamilies, 11 new genera and 77 new species, merging of two species, and deletion of one species. This article presents the updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV).

Accurate and precise estimates of local-level epidemiologic measures are critical to informing policy and program decisions, but they often require advanced statistical knowledge, programming/coding skills, and extensive computing power. In response, we developed the Rate Stabilizing Tool (RST), an ArcGIS-based tool that enables users to input their own record-level data to generate more reliable age-standardized measures of chronic disease (eg, prevalence rates, mortality rates) or other population health outcomes at the county or census tract levels. The RST uses 2 forms of empirical Bayesian modeling (nonspatial and spatial) to estimate age-standardized rates and 95% credible intervals for user-specified geographic units. The RST also provides indicators of the reliability of point estimates. In addition to reviewing the RST's statistical techniques, we present results from a simulation study that illustrates the key benefit of smoothing. We demonstrate the dramatic reduction in root mean-squared error (rMSE), indicating a better compromise between accuracy and stability for both smoothing approaches relative to the unsmoothed estimates. Finally, we provide an example of the RST's use. This example uses heart disease mortality data for North Carolina census tracts to map the RST output, including reliability of estimates, and demonstrates a subsequent statistical test.

Chemotherapy is limited in the treatment of leishmaniasis due to the toxic effects of drugs, low efficacy of alternative treatments, and resistance of the parasite. This work assesses the in vitro activity of flavopereirine on promastigote cultures of Leishmania amazonensis. In addition, an in silico evaluation of the physicochemical characteristics of this alkaloid is performed. The extract and fractions were characterized by thin-layer chromatography and HPLC-DAD, yielding an alkaloid identified by NMR. The antileishmanial activity and cytotoxicity were assayed by cell viability test (MTT). The theoretical molecular properties were calculated on the Molinspiration website. The fractionation made it possible to isolate a beta-carboline alkaloid (flavopereirine) in the alkaloid fraction. Moreover, it led to obtaining a fraction with greater antileishmanial activity, since flavopereirine is very active. Regarding the exposure time, a greater inhibitory effect of flavopereirine was observed at 24 h and 72 h (IC50 of 0.23 and 0.15 mug/mL, respectively). The extract, fractions, and flavopereirine presented low toxicity, with high selectivity for the alkaloid. Furthermore, flavopereirine showed no violation of Lipinski's rule of five, showing even better results than the known inhibitor of oligopeptidase B, antipain, with three violations. Flavopereirine also interacted with residue Tyr-499 of oligopeptidase B during the molecular dynamics simulations, giving a few insights of a possible favorable mechanism of interaction and a possible inhibitory pathway. Flavopereirine proved to be a promising molecule for its antileishmanial activity.

This investigation was initiated to control Aedes aegypti and Zika virus transmission in Caguas City, Puerto Rico, during the 2016 epidemic using Integrated Vector Management (IVM), which included community awareness and education, source reduction, larviciding, and mass-trapping with autocidal gravid ovitraps (AGO). The epidemic peaked in August to October 2016 and waned after April 2017. There was a preintervention period in October/November 2016 and IVM lasted until August 2017. The area under treatment (23.1 km2) had 61,511 inhabitants and 25,363 buildings. The city was divided into eight even clusters and treated following a cluster randomized stepped-wedge design. We analyzed pools of female Ae. aegypti adults for RNA detection of dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV) viruses using 360 surveillance AGO traps every week. Rainfall, temperature, and relative humidity were monitored in each cluster. Mosquito density significantly changed (generalized linear mixed model; F8, 14,588 = 296; P < 0.001) from 8.0 +/- 0.1 females per trap per week before the intervention to 2.1 +/- 0.04 after the percentage of buildings treated with traps was 60% and to 1.4 +/- 0.04 when coverage was above 80%. Out of a total 12,081 mosquito pools, there were 1 DENV-, 7 CHIKV-, and 49 ZIKV-positive pools from October 2016 to March 2017. Afterward, we found only one positive pool of DENV in July 2017. This investigation demonstrated that it was possible to scale up effective Ae. aegypti control to a medium-size city through IVM that included mass trapping of gravid Ae. aegypti females.

We piloted a health navigation strategy to promote timely linkage to care among men who have sex with men (MSM) and transgender women (TW) recently diagnosed with HIV in Guatemala City. We used a mixed-methods approach, integrating quantitative data collected during clinic visits and qualitative data from in-depth interviews, to characterize acceptability of navigation and time to linkage, defined as having the first clinical care visit. Out of 54 participants who enrolled in the pilot (n = 52 MSM; n = 2 TW), 50 (92.6%) accepted navigation and all were linked to care. Median time to linkage was 3 days (Interquartile Range 2-5 days). In qualitative interviews, participants expressed feeling scared and alone following their diagnosis and appreciated the support of a navigator, especially when they did not feel they could access their existing support networks. Future research and evaluation should continue to assess how to best use health navigation to support key populations recently diagnosed with HIV.

In 2018, the family Arenaviridae was expanded by inclusion of 1 new genus and 5 novel species. At the same time, the recently established order Bunyavirales was expanded by 3 species. This article presents the updated taxonomy of the family Arenaviridae and the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.

Neuraminidase inhibitors (NAIs) are the main class of antivirals currently used for the treatment of influenza infections. As influenza viruses are constantly evolving, drug-resistance can emerge resulting in reduced effectiveness of treatment. This study evaluated the presence of molecular markers associated with NAI susceptibility in 724 influenza A(H1N1)pdm09 positive samples from Brazilian surveillance system from the 2014-2016 seasons, including 76 isolates tested for oseltamivir (OST) susceptibility and 23 isolates also tested for zanamivir, peramivir and laninamivir susceptibility. We identified the H275Y (n=3) and I223K (n=1) NA substitutions, associated with reduced inhibition (RI) by the NAIs. Noteworthy, no epidemiological links were identified among the patients infected with the mutant viruses. Phylogenetic analysis from NA and hemagglutinin genes showed that mutant viruses were not clustered. All mutant virus strains carried the permissive substitutions V241I and N369K, in addition to the N386K, which has been shown to destabilize the NA structure. Functional NA analysis of one virus containing the H275Y mutation confirmed its highly RI profile to OST and peramivir and demonstrated that it had decreased viral replication and NA thermostability compared to the wild type virus. The remaining tested isolates presented normal inhibition profile to the NAIs tested. In conclusion, the overall frequency of influenza A(H1N1)pdm09 viruses bearing mutations associated with NAI RI was 0.6%, similar to what has been observed in recent global studies.

Men who have sex with men (MSM) are disproportionately affected by HIV in Guatemala and may benefit from health navigation programs designed to support timely linkage to HIV care. We conducted qualitative in-depth interviews with MSM (n = 19) linked to care within days of their diagnosis with the support of a health navigator. We used narrative analysis and systematic coding to identify themes related to HIV diagnosis and experiences with navigators. Participants experienced strong feelings of fear upon receiving a positive HIV test result. This fear led to social isolation and limited reliance on family and friend networks for support. Health navigators developed strong relationships with participants by providing the emotional support they were lacking and supporting them to overcome their fear and other structural barriers to HIV care, including stigma. Findings support the important role of navigation for MSM in Guatemala and could be transferable to other settings in Latin America.

In 2015, a community-wide intervention was launched in the city of Curitiba to evaluate the uptake of multiple HIV testing. A three-stage cluster sampling of 4800 men aged 15-64 years was selected in Curitiba. Logistic regression models were used to establish driving factors of HIV testing over the past 12 months. In the total sample, 49.5% have tested for HIV once in lifetime and 18.7% in the last 12 months. Among MSM, the proportions were much higher: 75.9% and 47.8% respectively. In the multivariate analysis, a significantly higher likelihood of HIV testing was found for young men (15-24 years), men with better educational level, those with more than 6 casual partners, and MSM compared to heterosexual men. The results indicate that the intervention to increase HIV diagnosis has substantially expanded MSM access to HIV testing.