BACKGROUND: Several health institutions developed strategies to improve health content on Wikimedia platforms given their unparalleled reach. The objective of this study was to compare an online volunteer-based Wikimedia outreach campaign with university course Wikipedia assignments (both focused on improving hearing health content in Wikimedia's public digital knowledge archives), in terms of the reach of the contributions and the extent of the participants' input. A secondary objective was to examine the feasibility and the implementation of the different strategies. METHODS: The research team partnered for the (1) coordination of improvements in hearing and healthcare content through educational programs using Wikimedia platforms, (2) participation in the global campaign Wiki4WorldHearingDay2023 and (3) evaluation of the proposed strategies. Metrics used in the comparison of the two strategies included the number of articles edited, number of views of the edited articles (as reach) and the extent of edits, captured as the number of words. The feasibility evaluation included assessing recruitment success and the implementation of the proposed plan among faculty, students from various university programs, and volunteers representing different constituencies. RESULTS: The effort increased the availability of quality plain language information on hearing conditions and hearing care. Both strategies demonstrated to be feasible by their success in recruiting participants who contributed to the effort and by measurable outputs as edits. The contribution of content to Wikimedia platforms as part of education activities provided a more robust result. Wiki4WorldHearingDay2023 145 participants (78 from educational programs) contributed 167,000 words, 258 + references and 140 images to 322 Wikipedia articles (283 existing and 39 new ones), which were viewed 16.5 million times. Contributions occurred in six languages. Edits in Portuguese, mainly by those involved in educational programs, led the number of articles (226 or 70.2%) that were expanded or created during the 5-month tracking period. CONCLUSIONS: The elements that contributed to the success of the studied strategies include an impact topic, coordination with educational programs, international multidisciplinary collaborations, the dissemination of the initiative in several platforms, connection with a robust local Wikimedia affiliate, and the use of a technical infrastructure that provides metrics and coordination mechanisms.

BACKGROUND: Zoonotic sporotrichosis is a neglected fungal disease, whereby outbreaks are primarily driven by Sporothrix brasiliensis and linked to cat-to-human transmission. To understand the emergence and spread of sporotrichosis in Brazil, the epicentre of the current epidemic in South America, we aimed to conduct whole-genome sequencing (WGS) to describe the genomic epidemiology. METHODS: In this genomic epidemiology study, we included Sporothrix spp isolates from sporotrichosis cases from Brazil, Colombia, and the USA. We conducted WGS using Illumina NovaSeq on isolates collected by three laboratories in Brazil from humans and cats with sporotrichosis between 2013 and 2022. All isolates that were confirmed to be Sporothrix genus by internal transcribed spacer or beta-tubulin PCR sequencing were included in this study. We downloaded eight Sporothrix genome sequences from the National Center for Biotechnology Information (six from Brazil, two from Colombia). Three Sporothrix spp genome sequences from the USA were generated by the US Centers for Disease Control and Prevention as part of this study. We did phylogenetic analyses and correlated geographical and temporal case distribution with genotypic features of Sporothrix spp isolates. FINDINGS: 72 Sporothrix spp isolates from 55 human and 17 animal sporotrichosis cases were included: 67 (93%) were from Brazil, two (3%) from Colombia, and three (4%) from the USA. Cases spanned from 1999 to 2022. Most (61 [85%]) isolates were S brasiliensis, and all were reported from Brazil. Ten (14%) were Sporothrix schenckii and were reported from Brazil, USA, and Colombia. For S schenckii isolates, two distinct clades were observed wherein isolates clustered by geography. For S brasiliensis isolates, five clades separated by more than 100 000 single-nucleotide polymorphisms were observed. Among the five S brasiliensis clades, clades A and C contained isolates from both human and cat cases, and clade A contained isolates from six different states in Brazil. Compared with S brasiliensis isolates, larger genetic diversity was observed among S schenckii isolates from animal and human cases within a clade. INTERPRETATION: Our results suggest that the ongoing epidemic driven by S brasiliensis in Brazil represents several, independent emergence events followed by animal-to-animal and animal-to human transmission within and between Brazilian states. These results describe how S brasiliensis can emerge and spread within a country. FUNDING: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil; the São Paulo Research Foundation; Productivity in Research fellowships by the National Council for Scientific and Technological Development, and Ministry of Science and Technology of Brazil.

Introduction. Combining genomic and geospatial data can be useful for understanding Mycobacterium tuberculosis (Mtb) transmission in high tuberculosis burden settings. Methods. We performed whole genome sequencing (WGS) on Mtb DNA extracted from sputum cultures from a population-based tuberculosis study conducted in 2012-2016 in Gaborone, Botswana. We used kernel density estimation, spatial K-functions, and created spatial distributions of phylogenetic trees. WGS-based clusters of isolates <5 single nucleotide polymorphisms were considered recent transmission, and large WGS-based clusters (>10 members) were considered outbreaks. Results. We analyzed data from 1449 participants with culture-confirmed TB. Among these, 946 (65%) participants had both molecular and geospatial data. A total of 62 belonged to five large outbreaks (10-19 participants each). Geospatial clustering was detected in two of the five large outbreaks, suggesting heterogeneous spatial patterns within the community. Conclusions. Integration of genomic and geospatial data identified distinct patterns of tuberculosis transmission in a high-tuberculosis burden setting. Targeted interventions in these smaller geographies may interrupt on-going transmission. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Combining genomic and geospatial data can be useful for understanding Mycobacterium tuberculosis transmission in high-burden tuberculosis (TB) settings. We performed whole-genome sequencing on M. tuberculosis DNA extracted from sputum cultures from a population-based TB study conducted in Gaborone, Botswana, during 2012-2016. We determined spatial distribution of cases on the basis of shared genotypes among isolates. We considered clusters of isolates with ≤5 single-nucleotide polymorphisms identified by whole-genome sequencing to indicate recent transmission and clusters of ≥10 persons to be outbreaks. We obtained both molecular and geospatial data for 946/1,449 (65%) participants with culture-confirmed TB; 62 persons belonged to 5 outbreaks of 10-19 persons each. We detected geospatial clustering in just 2 of those 5 outbreaks, suggesting heterogeneous spatial patterns. Our findings indicate that targeted interventions applied in smaller geographic areas of high-burden TB identified using integrated genomic and geospatial data might help interrupt TB transmission during outbreaks.

The Republic of Guatemala's reported COVID-19 vaccination coverage is among the lowest in the Americas and there are limited studies describing the disparities in vaccine uptake within the country. We performed a cross-sectional ecological analysis using multi-level modeling to identify sociodemographic characteristics that were associated with low COVID-19 vaccination coverage among Guatemalan municipalities as of 30 November 2022. Municipalities with a higher proportion of people experiencing poverty (β = -0.25, 95% CI: -0.43--0.07) had lower vaccination coverage. Municipalities with a higher proportion of people who had received at least a primary education (β = 0.74, 95% CI: 0.38-1.08), children (β = 1.07, 95% CI: 0.36-1.77), people aged 60 years and older (β = 2.94, 95% CI: 1.70-4.12), and testing for SARS-CoV-2 infection (β = 0.25, 95% CI: 0.14-0.36) had higher vaccination coverage. In the simplified multivariable model, these factors explained 59.4% of the variation in COVID-19 vaccination coverage. Poverty remained significantly associated with low COVID-19 vaccination coverage in two subanalyses restricting the data to the time period of the highest national COVID-19-related death rate and to COVID-19 vaccination coverage only among those aged 60 years or older. Poverty is a key factor associated with low COVID-19 vaccination and focusing public health interventions in municipalities most affected by poverty may help address COVID-19 vaccination and health disparities in Guatemala.

Mayaro virus (MAYV, Togaviridae) and Oropouche orthobunyavirus (OROV, Peribunyaviridae) are emerging enzootic arboviruses in Latin America. Outbreaks of febrile illness associated with MAYV and OROV have been reported among humans mainly in the northern region of Brazil since the 1980s, and recent data suggest these viruses have circulated also in more populated areas of western Brazil. MAYV shares mosquito vectors with yellow fever virus and it has been historically detected during yellow fever epidemics. Aiming to investigate the transmission of OROV and MAYV at the human-animal interface during a yellow fever, chikungunya and Zika outbreaks in Brazil, we conducted a retrospective molecular investigation in 810 wild and domestic animals, 106 febrile patients, and 22.931 vectors collected from 2016 to 2018 in Cuiaba and Campo Grande metropolitan regions, western Brazil. All samples tested negative for OROV and MAYV RNA by RT-qPCR. Findings presented here suggest no active circulation of MAYV and OROV in the sampled hosts. Active surveillance and retrospective investigations are instrumental approaches for the detection of cryptic and subclinical activity of enzootic arboviruses and together serve as a warning system to implement appropriate actions to prevent outbreaks.

The Centers for Disease Control and Prevention launched the Laboratory Leadership Service (LLS) Fellowship Program in July 2015 to develop public health laboratory (PHL) leaders who will improve PHL quality and safety. This article describes a retrospective, summative evaluation to determine the extent to which LLS has met its short-term goals for PHL workforce development. The evaluation relied on existing data from routine LLS data collection and reporting, supplemented with a new alumni survey. The purpose of the design was threefold: 1) to reduce data collection burden on program staff and participants, 2) to assess the value and limits of routine fellowship data for comprehensive public health workforce development program evaluation, and 3) to identify ways to improve LLS's routine data collections for program evaluation. We used descriptive statistics, qualitative analysis, and participatory methods (i.e., a data party) to analyze and interpret data. Results show LLS short-term outcome achievement and highlight opportunities for program improvement, particularly related to the design of certain training requirements and for future evaluations. Overall, the evaluation contributes to lessons learned for PHL workforce development efforts, including how routine data collections can contribute to comprehensive public health workforce development evaluations.

BACKGROUND: The Americas are home to biologically and clinically diverse endemic fungi, including Blastomyces, Coccidioides, Emergomyces, Histoplasma, Paracoccidioides and Sporothrix. In endemic areas with high risk of infection, these fungal pathogens represent an important public health problem. OBJECTIVES: This report aims to summarise the main findings of the regional analysis carried out on the status of the endemic mycoses of the Americas, done at the first International Meeting on Endemic Mycoses of the Americas (IMEMA). METHODS: A regional analysis for the Americas was done, the 27 territories were grouped into nine regions. A SWOT analysis was done. RESULTS: All territories reported availability of microscopy. Seventy percent of territories reported antibody testing, 67% of territories reported availability of Histoplasma antigen testing. None of the territories reported the use of (1-3)--d-glucan. Fifty two percent of territories reported the availability of PCR testing in reference centres (mostly for histoplasmosis). Most of the territories reported access to medications such as trimethoprim-sulfamethoxazole, itraconazole, voriconazole and amphotericin B (AMB) deoxycholate. Many countries had limited access to liposomal formulation of AMB and newer azoles, such as posaconazole and isavuconazole. Surveillance of these fungal diseases was minimal. CONCLUSIONS: A consensus emerged among meeting participants, this group concluded that endemic mycoses are neglected diseases, and due to their severity and lack of resources, the improvement of diagnosis, treatment and surveillance is needed.

On July 15, 2021, the Secretary of Health of Honduras (SHH) was notified of an unexpected number of mucormycosis cases among COVID-19 patients. SHH partnered with the Honduras Field Epidemiology Training Program, the Executive Secretariat of the Council of Ministers of Health of Central America and the Dominican Republic (SE-COMISCA), Pan American Health Organization (PAHO), and CDC to investigate mucormycosis cases at four geographically distinct hospitals in Honduras. | | Mucormycosis is a severe, often fatal disease caused by infection with angioinvasive molds belonging to the order Mucorales. Risk factors for mucormycosis include certain underlying medical conditions (e.g., hematologic malignancy, stem cell or solid organ transplantation, or uncontrolled diabetes) and the use of certain immunosuppressive medications (1). COVID-19 might increase mucormycosis risk because of COVID-19–induced immune dysregulation or associated medical treatments, such as systemic corticosteroids and other immunomodulatory drugs (e.g., tocilizumab), which impair the immune response against mold infections (2). In India, an apparent increase in mucormycosis cases (which was referred to by the misnomer “black fungus”) was attributed to COVID-19 (3).

BACKGROUND: Between 2014 and 2016, Brazil experienced a severe shortage in penicillin supply, resulting in a lack of treatment among some pregnant women and newborns with syphilis and the use of non-evidence-based regimens. This study evaluated all live births in Fortaleza reported with CS in 2015 in order to identify the different therapeutic regimens used in newborns during this period of penicillin shortage. METHODS: A retrospective cross-sectional study design was conducted using manually extracted data from medical chart review of maternal and infant cases delivered in 2015 from all public maternity hospitals in the city of Fortaleza. Data collection occurred from June 2017 to July 2018. RESULTS: A total of 575 congenital syphilis cases were reported to the municipality of Fortaleza during 2015 and 469 (81.5%) were analyzed. Of these, only 210 (44.8%) were treated with a nationally-recommended treatment. As alternative therapeutic options, ceftriaxone was used in 65 (13.8%), Cefazolin in 15 (3.2%) and the combination of more than one drug in 179 (38.2%). Newborns with serum VDRL titers ≥1:16 (p = 0.021), who had some clinical manifestation at birth (p = 0.003), who were born premature (p <  0.001), with low birth weight (p = 0.010), with jaundice indicative of the need for phototherapy (p = 0.019) and with hepatomegaly (p = 0.045) were more likely to be treated with penicillin according to national treatment guidelines compared to newborns treated with other regimens. CONCLUSION: During the period of shortage of penicillin in Fortaleza, less than half of the infants reported with CS were treated with a nationally-recommended regimen, the remaining received treatment with medications available in the hospital of birth including drugs that are not part of nationally or internationally-recommended treatment recommendations.

Yellow fever virus (YFV) live attenuated vaccine can, in rare cases, cause life-threatening disease, typically in patients with no previous history of severe viral illness. Autosomal recessive (AR) complete IFNAR1 deficiency was reported in one 12-yr-old patient. Here, we studied seven other previously healthy patients aged 13 to 80 yr with unexplained life-threatening YFV vaccine-associated disease. One 13-yr-old patient had AR complete IFNAR2 deficiency. Three other patients vaccinated at the ages of 47, 57, and 64 yr had high titers of circulating auto-Abs against at least 14 of the 17 individual type I IFNs. These antibodies were recently shown to underlie at least 10% of cases of life-threatening COVID-19 pneumonia. The auto-Abs were neutralizing in vitro, blocking the protective effect of IFN-α2 against YFV vaccine strains. AR IFNAR1 or IFNAR2 deficiency and neutralizing auto-Abs against type I IFNs thus accounted for more than half the cases of life-threatening YFV vaccine-associated disease studied here. Previously healthy subjects could be tested for both predispositions before anti-YFV vaccination.

Measuring the impact of public health science or research is important especially when it comes to health outcomes. Achieving the desired health outcomes take time and may be influenced by several contributors, making attribution of credit to any one entity or effort problematic. Here we offer a science impact framework (SIF) for tracing and linking public health science to events and/or actions with recognized impact beyond journal metrics. The SIF was modeled on the Institute of Medicine's (IOM) Degrees of Impact Thermometer, but differs in that SIF is not incremental, not chronological, and has expanded scope. The SIF recognizes five domains of influence: disseminating science, creating awareness, catalyzing action, effecting change and shaping the future (scope differs from IOM). For public health, the goal is to achieve one or more specific health outcomes. What is unique about this framework is that the focus is not just on the projected impact or outcome but rather the effects that are occurring in real time with the recognition that the measurement field is complex, and it takes time for the ultimate outcome to occur. The SIF is flexible and can be tailored to measure the impact of any scientific effort: from complex initiatives to individual publications. The SIF may be used to measure impact prospectively of an ongoing or new body of work (e.g., research, guidelines and recommendations, or technology) and retrospectively of completed and disseminated work, through linking of events using indicators that are known and have been used for measuring impact. Additionally, linking events offers an approach to both tell our story and also acknowledge other players in the chain of events. The value added by science can easily be relayed to the scientific community, policy makers and the public.

BACKGROUND: Despite the well-known role of parents as caregivers, few studies have addressed their health outcomes related to the Zika virus epidemic. METHODS: A cross-sectional study was carried out with 146 primary caregivers of children 15-26 months of age, with laboratory and/or clinical evidence of Zika infection between August and October 2017 in three Brazilian municipalities: João Pessoa and Campina Grande in the state of Paraíba and Fortaleza in the state of Ceará. Caregivers reported on their child's life and health, family circumstances and underwent screening for stress using the Parenting Stress Index-Short Form. Children were evaluated for developmental delays and clinical outcomes. Differences in the prevalence of risk factors between caregivers with high or clinically relevant stress and those with normal stress were evaluated. RESULTS: Of the 146 participants, 13% (n = 19) were classified as having high or clinically relevant stress, all of them mothers. The two risk factors significantly and independently associated with high levels of stress, compared with individuals with normal stress levels, were "reporting difficulty in covering basic expenses" (adjusted OR 3.6 (95% CI 1.1-11.8; p = 0.034)) and "having a child with sleep problems" (adjusted OR 10.4 (95% CI 1.3-81.7; p = 0.026)). CONCLUSIONS: Some factors seem to contribute significantly more than others to the level of stress experienced by caregivers of children with evidence of Zika virus congenital infection. Interventions and preventive strategies should also target caregivers, who in turn will be able to respond to the unique characteristics of their child.

In this study, the prevalence rate, associated risk factors and genetic diversity of hepatitis C virus (HCV) infection were determined among people who use crack from an international drug trafficking route in Central-West, Brazil. Blood samples were collected from 700 users of crack from Campo Grande and two border cities of Mato Grosso do Sul State and tested for HCV infection using serological and molecular testing methodologies. Anti-HCV was detected in 31/700 (4.5%, 95% CI: 2.9-6.0%) and HCV RNA in 26/31 (83.9%) of anti-HCV positive samples. Phylogenetic analysis of three HCV sub-genomic regions (5'UTR, NS5B and HVR-1) revealed the circulation of 1a (73.9%), 1b (8.7%) and 3a (17.4%) genotypes. Next-generation sequencing and phylogenetic analysis of intra-host viral populations of HCV HVR-1 showed a significant variation in intra-host genetic diversity among infected individuals, with 58.8% composed of more than one sub-population. Bayesian analysis estimated that the most recent common HCV ancestor for strains identified here was introduced to this region after 1975 following expansion of intravenous drug use in Brazil. Multivariate analyses showed that only 'ever having injected drugs' was independently associated with HCV infection. These results indicate an increasing spread of multiple HCV strains requiring public health intervention, such as harm reduction, testing services and treatment among crack users in this important border region of Central Brazil.

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.

Individuals infected with Strongyloides stercoralis have been reported to produce different immunoglobulins isotypes, yet few studies have evaluated their use in strongyloidiasis diagnosis. The aim of this work was to evaluate the immunoreactivity of different classes and subclasses of anti-S. stercoralis circulating antibodies in alcoholic patients by ELISA and to perform immunoblotting in samples with discordant results between parasitological and immunological methods. 345 male patients with a clinical diagnosis of alcoholism hospitalized at a reference center for alcoholics in Salvador, Bahia, Brazil, were included in this study. The fecal samples were examined by three different parasitological methods (spontaneous sedimentation, Baermann-Moraes and Agar Plate Culture methods). The ELISA was performed for the detection of IgG, IgG1, IgG4, IgE and IgA1 anti-S. stercoralis. Immunoblotting, for the detection of specific IgA1, was used to elucidate discordant results between parasitological and immunological methods. S. stercoralis infection frequency in alcoholic patients by parasitological methods was 21.4% (74/345). Although IgE-ELISA demonstrated a high sensitivity and specificity in non-alcoholic patients, about 30% (22/74) of alcoholics with larvae in feces were negative. IgG1-ELISA detected the lowest frequency of antibodies in alcoholic patients with larvae in feces, only 57% (42/74). IgG4-ELISA was the best assay for S. stercoralis infection immunodiagnosis. Immunoreactivity in the immunoblotting for IgA1 at 90, 75, 26 and/or 17kDa bands was observed in 92% (33/36) of alcoholics with larvae excretion and negative ELISA for one or more antibody isotypes. In conclusion, IgG4-ELISA showed the highest sensitivity and specificity, thus demonstrating its superiority for strongyloidiasis immunodiagnosis in alcoholic and non-alcoholic individuals. Both, IgE and IgG1-ELISA presented high sensitivities and specificities for S. stercoralis infection diagnosis in non-alcoholics, however there was low reactivity in alcoholic individuals. This can be associated with an increased susceptibility to severe strongyloidiasis in these patients. IgA1-immunoblotting can be used to confirm S. stercoralis infection when there are discordant results between parasitological methods and ELISA.

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.

The cell block (CB) technique has allowed easy obtainment of samples such as cellular and culture suspensions, to perform specific molecular tests such as immunohistochemistry and in situ hybridization. It has been improved along time, accuracy, and quality of the diagnoses, however, the cost of a commercial gel matrix for the preparation of CB is high and not suitable depending on the situation. The objective of this study is to test agarose as an alternative to the commercial gel matrix in the preparation of Aspergillus fumigatus' CB.

INTRODUCTION: Vaccination against varicella-zoster virus (VZV) has been effective and safe in countries that routinely administer the vaccine. Brazil began universal VZV vaccination in 2013. This study aimed to identify VZV genotypes present in Manaus, Brazil prior to widespread immunization. METHODS: Vesicular lesions or cerebral-spinal-fluid samples were collected from patients diagnosed with VZV, herpes zoster, or meningitis/encephalitis. DNA was extracted, amplified, and sequenced. RESULTS: Half the isolates were clade-5 viruses and the remaining were divided between the European clades 1 and 3. CONCLUSIONS: This study provides insights into the circulating VZV genotypes in Manaus prior to widespread vaccination.

In the US Federal government, an analysis of alternatives (AoA) is required for a significant investment of resources. The AoA yields the recommended alternative from a set of viable alternatives for the investment decision. This paper presents an integrated AoA and project management framework for analyzing new or emerging alternatives (e.g., Cloud computing), as may be driven by an information system strategy that incorporates a methodology for analyzing the costs, benefits, and risks of each viable alternative. The case study in this paper, about a business improvement project to provide public health and safety services to citizens in a US Federal agency, is a practical application of this integrated framework and reveals the benefits of this integrated approach for an investment decision. The decision making process in the framework-as an integrated, organized, and adaptable set of management and control practices-offers a defensible recommendation and provides accountability to stakeholders.

Background: The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction. Methods: We performed quantitative polymerase chain reaction for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14643 episodes captured by surveillance of children <5 years of age during 2013-2014 from 16 countries. We used previously developed models of the association between pathogen quantity and diarrhea to calculate pathogen-specific weighted attributable fractions (AFs). Results: Rotavirus remained the leading etiology (overall weighted AF, 40.3% [95% confidence interval {CI}, 37.6%-44.3%]), though the AF was substantially lower in the Americas (AF, 12.2 [95% CI, 8.9-15.6]), based on samples from a country with universal rotavirus vaccination. Norovirus GII (AF, 6.2 [95% CI, 2.8-9.2]), Cryptosporidium (AF, 5.8 [95% CI, 4.0-7.6]), Shigella (AF, 4.7 [95% CI, 2.8-6.9]), heat-stable enterotoxin-producing Escherichia coli (ST-ETEC) (AF, 4.2 [95% CI, 2.0-6.1]), and adenovirus 40/41 (AF, 4.2 [95% CI, 2.9-5.5]) were also important. In the Africa Region, the rotavirus AF declined from 54.8% (95% CI, 48.3%-61.5%) in rotavirus vaccine age-ineligible children to 20.0% (95% CI, 12.4%-30.4%) in age-eligible children. Conclusions: Rotavirus remained the leading etiology of acute watery diarrhea despite a clear impact of rotavirus vaccine introduction. Norovirus GII, Cryptosporidium, Shigella, ST-ETEC, and adenovirus 40/41 were also important. Prospective surveillance can help identify priorities for further reducing the burden of diarrhea.

Bats are reservoir hosts for many paramyxoviruses, some of which cause human and zoonotic diseases of public health importance. We developed a Nipah virus nucleoprotein enzyme-linked immunosorbent assay to detect cross-reactive antibodies in serum samples from several bat species in Brazil. Our results warrant further investigation of henipa-like virus reservoirs in the Western hemisphere.

BACKGROUND: Childhood pneumonia is a major cause of childhood illness and the second leading cause of child death globally. Understanding the costs associated with the management of childhood pneumonia is essential for resource allocation and priority setting for child health. METHODS: We conducted a systematic review to identify studies reporting data on the cost of management of pneumonia in children younger than 5 years old. We collected unpublished cost data on non-severe, severe and very severe pneumonia through collaboration with an international working group. We extracted data on cost per episode, duration of hospital stay and unit cost of interventions for the management of pneumonia. The mean (95% confidence interval, CI) and median (interquartile range, IQR) treatment costs were estimated and reported where appropriate. RESULTS: We identified 24 published studies eligible for inclusion and supplemented these with data from 10 unpublished studies. The 34 studies included in the cost analysis contained data on more than 95 000 children with pneumonia from both low- and-middle income countries (LMIC) and high-income countries (HIC) covering all 6 WHO regions. The total cost (per episode) for management of severe pneumonia was US$ 4.3 (95% CI 1.5-8.7), US$ 51.7 (95% CI 17.4-91.0) and US$ 242.7 (95% CI 153.6-341.4)-559.4 (95% CI 268.9-886.3) in community, out-patient facilities and different levels of hospital in-patient settings in LMIC. Direct medical cost for severe pneumonia in hospital inpatient settings was estimated to be 26.6%-115.8% of patients' monthly household income in LMIC. The mean direct non-medical cost and indirect cost for severe pneumonia management accounted for 0.5-31% of weekly household income. The mean length of stay (LOS) in hospital for children with severe pneumonia was 5.8 (IQR 5.3-6.4) and 7.7 (IQR 5.5-9.9) days in LMIC and HIC respectively for these children. CONCLUSION: This is the most comprehensive review to date of cost data from studies on the management of childhood pneumonia and these data should be helpful for health services planning and priority setting by national programmes and international agencies.

Rhodnius prolixus not only has served as a model organism for the study of insect physiology, but also is a major vector of Chagas disease, an illness that affects approximately seven million people worldwide. We sequenced the genome of R. prolixus, generated assembled sequences covering 95% of the genome ( approximately 702 Mb), including 15,456 putative protein-coding genes, and completed comprehensive genomic analyses of this obligate blood-feeding insect. Although immune-deficiency (IMD)-mediated immune responses were observed, R. prolixus putatively lacks key components of the IMD pathway, suggesting a reorganization of the canonical immune signaling network. Although both Toll and IMD effectors controlled intestinal microbiota, neither affected Trypanosoma cruzi, the causal agent of Chagas disease, implying the existence of evasion or tolerance mechanisms. R. prolixus has experienced an extensive loss of selenoprotein genes, with its repertoire reduced to only two proteins, one of which is a selenocysteine-based glutathione peroxidase, the first found in insects. The genome contained actively transcribed, horizontally transferred genes from Wolbachia sp., which showed evidence of codon use evolution toward the insect use pattern. Comparative protein analyses revealed many lineage-specific expansions and putative gene absences in R. prolixus, including tandem expansions of genes related to chemoreception, feeding, and digestion that possibly contributed to the evolution of a blood-feeding lifestyle. The genome assembly and these associated analyses provide critical information on the physiology and evolution of this important vector species and should be instrumental for the development of innovative disease control methods.

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on Influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta-analysis of individual participant data (IPD) from 20,634 hospitalised patients with laboratory confirmed A(H1N1)pdm09 (n=20,021) or clinically diagnosed (n=613) 'pandemic influenza'. The primary outcome was radiologically confirmed influenza-related pneumonia (IRP). Odds ratios (OR) were estimated using generalized linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Among 20,634 included participants, 5,978 (29.0%) had IRP; conversely, 3,349 (16.2%) had confirmed absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0.83 (95%CI 0.64 - 1.06; p=0.136)]. Among the 5,978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR=0.72 (0.44-1.17; p=0.180)] or likelihood of requiring ventilatory support [adj. OR=1.17 (0.71-1.92; p=0.537)]; but early treatment versus later significantly reduced mortality [adj. OR=0.70 (0.55-0.88; p=0.003)] and likelihood of requiring ventilatory support [adj. OR=0.68 (0.54-0.85; p=0.001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support.

Disability is an emerging field within public health; people with significant disabilities account for more than 12% of the US population. Disparity status for this group would allow federal and state governments to actively work to reduce inequities. We summarize the evidence and recommend that observed differences are sufficient to meet the criteria for health disparities: population-level differences in health outcomes that are related to a history of wide-ranging disadvantages, which are avoidable and not primarily caused by the underlying disability. We recommend future research and policy directions to address health inequities for individuals with disabilities; these include improved access to health care and human services, increased data to support decision-making, strengthened health and human services workforce capacity, explicit inclusion of disability in public health programs, and increased emergency preparedness.

We analyzed a process for the annual selection of a Federal agency's best peer-reviewed, scientific papers with the goal to develop a relatively simple method that would use publicly available data to assess the presence of factors, other than scientific excellence and merit, in an award-making process that is to recognize scientific excellence and merit. Our specific goals were (a) to determine if journal, disease category, or major paper topics affected the scientific-review outcome by (b) developing design and analytic approaches to detect potential bias in the scientific review process. While indeed journal, disease category, and major paper topics were unrelated to winning, our methodology was sensitive enough to detect differences between the ranks of journals for winners and non-winners.

In order to estimate influenza-associated excess mortality in southern Brazil, we applied Serfling regression models to monthly mortality data from 1980 to 2008 for pneumonia/influenza- and respiratory/circulatory-coded deaths for all ages and for those aged >=60 years. According to viral data, 735% of influenza viruses were detected between April and August in southern Brazil. There was no clear influenza season for northern Brazil. In southern Brazil, influenza-associated excess mortality was 14/100 000 for all ages and 92/100 000 person-years for persons aged >=60 years using underlying pneumonia/influenza-coded deaths and 100/100 000 for all ages and 866/100 000 person-years for persons aged >=60 years using underlying respiratory/circulatory-coded deaths. Influenza-associated excess mortality rates for southern Brazil are similar to those published for other countries. Our data support the need for continued influenza surveillance to guide vaccination campaigns to age groups most affected by this virus in Brazil. Cambridge University Press 2012.

INTRODUCTION: During Brazil's national measles, mumps, and rubella (MMR) vaccination campaign in August 2004, an unexpectedly high rate of hypersensitivity-type adverse events (HAEs) was reported. MATERIALS AND METHODS: We reviewed information about children with suspected HAEs reported by clinicians to Brazil's national passive surveillance system for adverse events following immunization (AEFI), compared attack rate of HAE by manufacturer of MMR vaccine used in the campaign, and conducted a case-control study to determine possible risk factors for HAEs. RESULTS: During the 2004 national campaign, the rate of HAEs following MMR vaccination was one log higher for manufacturer A (15.2/100,000 doses administered) compared to the other two manufacturers (1.2 and 0.6/100,000 doses; p<0.0001); a similar pattern was observed retrospectively in analysis of the 2000-2003 AEFI surveillance (0.95 vs. 0.07 per 100,000 doses administered; p<0.0001). In the case-control study, among the 49 case-patients with HAEs identified, reported symptoms included conjunctival injection (60%), urticaria (55%), fever (54%), and facial edema (53%); no deaths occurred. The median time interval between vaccination and symptom onset was 42min (range: 5min-24h). We did not identify any differences in the proportion of case-patients and control children with a history of known allergy to food (including egg, egg-containing products or gelatin), drugs, or environmental antigens. DISCUSSION: Our study highlights the importance of a well-functioning routine AEFI surveillance system linked with mass vaccination campaigns. Such a system in Brazil permitted timely detection of HAEs and validation of a safety signal associated with one vaccine manufacturer. Unlike earlier publications, this outbreak linked to a single manufacturer of MMR showed no association with a prior allergic history to eggs or other foods, including gelatin; subsequent studies implicate the dextran stabilizer in MMR from manufacturer A as the likely cause of HAEs.

The diagnosis of recent HCV infection remains challenging due to the absence of serological markers specific to the early phase of infection. Clinical follow-up and seroconversion to anti-HCV immunoglobulin (Ig)G, detection of viral RNA and changes in levels of blood biomarkers associated with liver pathology provide circumstantial evidence of recent HCV infection. Studies based on anti-HCV IgG avidity, antigen-specific antibody profiling, HCV viral load fluctuations and signature changes in the HCV genome show potential to discriminate recent from persistent HCV infection. These markers require further evaluation and would necessitate use of samples from infected people originating from broad clinical and epidemiological contexts.