Clinical and phylogenetic influenza dynamics for the 2019-20 season in the global influenza hospital surveillance network (GIHSN) - Pilot study.

BACKGROUND: The Global Influenza Hospital Surveillance Network (GIHSN) has operated with the aim of investigating epidemiological and clinical factors related to severe influenza-related hospitalisations. STUDY DESIGN: A common GIHSN core protocol for prospective patient enrolment was implemented. Hospital personnel completed a standardized questionnaire regarding the included patients' medical history, compiled a hospitalisation summary, collected an upper respiratory swab sample for laboratory diagnosis, and genome sequencing was performed for a subset of samples. Patient data were compared according to influenza subtype, lineage, and phylogenetic groups using the Fisher's exact test. RESULTS: From September 2019 to May 2020, 8791 patients aged ≥5 years were included. Among them, 3021 (34.4%) had a laboratory-confirmed influenza diagnosis. Influenza A(H1N1)pdm09 dominated the season among all age groups, while the B/Victoria-like lineage accounted for over half of the infections among younger age groups (5-49 years). Sequencing of the hemagglutinin segment was possible for 623 samples and revealed an influenza A and B clade frequency among severe influenza hospitalisations similar to other medically attended surveillance networks, such as the WHO GISRS. No phylogenetic clustering was observed among hemagglutinin substitutions depending on the administration of supplemental oxygen or vaccine failure. CONCLUSIONS: The GIHSN confirms its ability as an international hospital-based active surveillance network to provide valuable information on influenza infection dynamics in hospital settings. Increasing the number of participating sites and compiling more complete data, such as genome sequencing, will allow the exploration of associations between viral factors, vaccine protection, and disease severity.

Influenza in Latin America: A report from the Global Influenza Initiative (GII).

The Global Influenza Initiative (GII) is a global expert group that aims to raise acceptance and uptake of influenza vaccines globally and provides recommendations and strategies to address challenges at local, national, regional, and global levels. This article provides a consolidated estimation of disease burden in Latin America, currently lacking in published literature, and delivers the GII recommendations specific to Latin America that provide guidance to combat existing vaccination challenges. While many countries worldwide, especially in the tropics and subtropics, do not have a seasonal influenza policy, 90% of Latin American countries have a seasonal influenza policy in place. Local governments in the Latin American countries and The Pan American Health Organization's Technical Advisory Group on Vaccine-preventable Diseases play a major role in improving the vaccination coverage and reducing the overall disease burden. Influenza seasonality poses the biggest challenge in deciding on optimal timing for vaccination in Latin America, as in temperate climates seasonal influenza activity peaks during the winter months (November-February and May-October) in the northern and southern hemispheres, respectively, while in the tropics and subtropical regions it usually occurs throughout the year, but especially during the rainy season. Besides this, vaccine mismatch with circulating strains, misconception concerning influenza vaccine effectiveness, and poor disease and vaccine awareness among the public are also key challenges that need to be overcome. Standardization of clinical case definitions is important across all Latin American countries. Surveillance (mostly passive) has improved substantially in the Latin American countries over the past decade, but more is still required to better understand the disease burden and help inform policies.

First Report of Trypanosoma cruzi Infection in Salivary Gland of Bats from the Peruvian Amazon.

In the Americas, 8 million people are infected with Chagas disease, and an additional 90 million people are at risk for infection. Little is known about the role bats play in the sylvatic transmission cycle of Trypanosoma cruzi, the parasite causing Chagas disease. Here, we captured bats in the villages of Palmiche, Pachacutec, Nuevo San Martin, and Mayuriaga located in the Datem del Marañon Province in Loreto, Peru. Venous blood samples were collected by cardiac puncture or from the upper extremities, and trypanosomatids were identified by microscopy and molecularly. We collected blood samples from 121 bats on filter paper for molecular studies and 111 slides for microscopic examination of thin and thick blood smears from 16 different bat species. The prevalence of trypanosomatids in all bats species was 34.7% (42/121) and the prevalence of T. cruzi was 4.1% (5/121). In hematophagous bat species, the prevalence of trypanosomatids and T. cruzi was 36.9% (27/73) and 2.7% (2/73), respectively. In non-hematophagous bats, the prevalences of trypanosomatids and T. cruzi were 31.2% (15/48) and 6.2% (3/48), respectively. Also, we confirm the presence of T. cruzi in salivary glands of hematophagous bats Diaemus youngi. These results suggest a sylvatic cycle of trypanosomatid transmission in which bats may harbor infectious T. cruzi parasites that could be transmitted to humans via hematophagous bat bites or salivary contamination by non-hematophagous bats of vegetables consumed by humans.

Enterovirus-71 genotype C isolated in Peru between 2006 and 2009.

Enterovirus-71 (EV71) was first isolated in California, United States in 1969, belongs to the genus Enterovirus, family Picornaviridae. Although infection normally causes mild, often undiagnosed illness, it can cause central nervous system infections that could turn fatal. Based on VP1 gene analysis, EV71 has been classified into six separate genotypes. Although the molecular epidemiology of EV71 has been well described via studies originating from Asia and Europe, it is mostly unknown in South America. From our study, four EV71 isolates from Peru were characterized using phylogenetic methods to determine their relationship with known reference strains. These four Peruvian EV71 isolates from between 2006 and 2009 were analyzed by RT-PCR using primers capable of amplifying the entire VP1 gene. Reference strains representing all six known genotypes were used to determine any recognizable phylogenetic relationships. In fact, all of our isolates clustered together within the genotype C1 lineage- separate from Asian, European, North American, and Australian strains. We present evidence that EV71 genotype C1 exists in Peru, and this is the first such report documenting EV71 genotype C1 circulating in South America. Gathering additional isolates will help elucidate a more complete global epidemiological picture of EV71 infections.

Molecular epidemiology of coxsackievirus A16 strains from four sentinel surveillance sites in Peru.

OBJECTIVES: To determine the molecular epidemiology of seven coxsackievirus A16 (CVA16) strains previously reported by this research group. METHODS: Full-length VP1 and VP4 sequences were obtained and phylogenetic analyses were performed. RESULTS: Six strains were classified as genotype C. Moreover, one divergent strain not clustered in any of the three currently reported genotypes was found. CONCLUSION: This is the first report of CVA16 in Peru and provides valuable baseline data about its potential distribution in South America, as well as evidence of a potential divergent genotype that has never before been reported.

Weather Regulates Location, Timing, and Intensity of Dengue Virus Transmission between Humans and Mosquitoes.

BACKGROUND: Dengue is one of the most aggressively expanding mosquito-transmitted viruses. The human burden approaches 400 million infections annually. Complex transmission dynamics pose challenges for predicting location, timing, and magnitude of risk; thus, models are needed to guide prevention strategies and policy development locally and globally. Weather regulates transmission-potential via its effects on vector dynamics. An important gap in understanding risk and roadblock in model development is an empirical perspective clarifying how weather impacts transmission in diverse ecological settings. We sought to determine if location, timing, and potential-intensity of transmission are systematically defined by weather. METHODOLOGY/PRINCIPAL FINDINGS: We developed a high-resolution empirical profile of the local weather-disease connection across Peru, a country with considerable ecological diversity. Applying 2-dimensional weather-space that pairs temperature versus humidity, we mapped local transmission-potential in weather-space by week during 1994-2012. A binary classification-tree was developed to test whether weather data could classify 1828 Peruvian districts as positive/negative for transmission and into ranks of transmission-potential with respect to observed disease. We show that transmission-potential is regulated by temperature-humidity coupling, enabling epidemics in a limited area of weather-space. Duration within a specific temperature range defines transmission-potential that is amplified exponentially in higher humidity. Dengue-positive districts were identified by mean temperature >22°C for 7+ weeks and minimum temperature >14°C for 33+ weeks annually with 95% sensitivity and specificity. In elevated-risk locations, seasonal peak-incidence occurred when mean temperature was 26-29°C, coincident with humidity at its local maximum; highest incidence when humidity >80%. We profile transmission-potential in weather-space for temperature-humidity ranging 0-38°C and 5-100% at 1°C x 2% resolution. CONCLUSIONS/SIGNIFICANCE: Local duration in limited areas of temperature-humidity weather-space identifies potential locations, timing, and magnitude of transmission. The weather-space profile of transmission-potential provides needed data that define a systematic and highly-sensitive weather-disease connection, demonstrating separate but coupled roles of temperature and humidity. New insights regarding natural regulation of human-mosquito transmission across diverse ecological settings advance our understanding of risk locally and globally for dengue and other mosquito-borne diseases and support advances in public health policy/operations, providing an evidence-base for modeling, predicting risk, and surveillance-prevention planning.

A Controlled Study of Tuberculosis Diagnosis in HIV-Infected and Uninfected Children in Peru.

BACKGROUND: Diagnosing tuberculosis in children is challenging because specimens are difficult to obtain and contain low tuberculosis concentrations, especially with HIV-coinfection. Few studies included well-controls so test specificities are poorly defined. We studied tuberculosis diagnosis in 525 children with and without HIV-infection. METHODS AND FINDINGS: 'Cases' were children with suspected pulmonary tuberculosis (n = 209 HIV-negative; n = 81 HIV-positive) and asymptomatic 'well-control' children (n = 200 HIV-negative; n = 35 HIV-positive). Specimens (n = 2422) were gastric aspirates, nasopharyngeal aspirates and stools analyzed by a total of 9688 tests. All specimens were tested with an in-house hemi-nested IS6110 PCR that took <24 hours. False-positive PCR in well-controls were more frequent in HIV-infection (P≤0.01): 17% (6/35) HIV-positive well-controls versus 5.5% (11/200) HIV-negative well-controls; caused by 6.7% (7/104) versus 1.8% (11/599) of their specimens, respectively. 6.7% (116/1719) specimens from 25% (72/290) cases were PCR-positive, similar (P>0.2) for HIV-positive versus HIV-negative cases. All specimens were also tested with auramine acid-fast microscopy, microscopic-observation drug-susceptibility (MODS) liquid culture, and Lowenstein-Jensen solid culture that took ≤6 weeks and had 100% specificity (all 2112 tests on 704 specimens from 235 well-controls were negative). Microscopy-positivity was rare (0.21%, 5/2422 specimens) and all microscopy-positive specimens were culture-positive. Culture-positivity was less frequent (P≤0.01) in HIV-infection: 1.2% (1/81) HIV-positive cases versus 11% (22/209) HIV-negative cases; caused by 0.42% (2/481) versus 4.7% (58/1235) of their specimens, respectively. CONCLUSIONS: In HIV-positive children with suspected tuberculosis, diagnostic yield was so low that 1458 microscopy and culture tests were done per case confirmed and even in children with culture-proven tuberculosis most tests and specimens were false-negative; whereas PCR was so prone to false-positives that PCR-positivity was as likely in specimens from well-controls as suspected-tuberculosis cases. This demonstrates the importance of control participants in diagnostic test evaluation and that even extensive laboratory testing only rarely contributed to the care of children with suspected TB. TRIAL REGISTRATION: This study did not meet Peruvian and some other international criteria for a clinical trial but was registered with the ClinicalTrials.gov registry: ClinicalTrials.gov NCT00054769.

Non-rhinovirus enteroviruses associated with respiratory infections in Peru (2005-2010).

BACKGROUND: Enteroviruses (EVs) are a common cause of respiratory tract infections and are classified into seven species (EVA-D and rhinoviruses [RHVs] A-C) with more than 200 different serotypes. Little is known about the role of non-RHV EVs in respiratory infections in South America. The aim of this study was to describe the epidemiology of non-RHV EVs detected in patients with influenza-like illness enrolled in a passive surveillance network in Peru. METHODS: Throat swabs and epidemiological data were collected from participants after obtaining verbal consent. Viral isolation was performed in cell culture and identified by immunofluorescence assay. Serotype identification of EV isolates was performed using commercial monoclonal antibodies. Identification of non-serotypeable isolations was carried out by reverse transcriptase-PCR, followed by sequencing. RESULTS: Between 2005 and 2010, 24,239 samples were analyzed, and 9,973 (41.1%) possessed at least one respiratory virus. EVs were found in 175 samples (0.7%). Our results revealed a clear predominance of EVB species, 90.9% (159/175). No EVDs were isolated. The mean and median ages of EV-positive subjects were 9.1 and 4.0 years, respectively, much younger than the population sampled, 17.6 and 12.0 years. Sixteen serotypes were identified, four EVA, 11 EVB, and one EVC species. The most common serotypes were coxsackievirus B1, coxsackievirus B2, coxsackievirus B5, and coxsackievirus B3. CONCLUSION: This study provides data about the serotypes of EVs circulating in Peru and sets the need for further studies.

HIV infection and high-risk behaviours in a Paraguayan military population.

Between July 2005 and January 2006 we evaluated 1248 Paraguayan active duty military volunteers. Participants provided a blood sample for HIV testing and answered an anonymous survey. HIV seroprevalence was 0.4% (5 of 1248) among participants. The median age at first sexual intercourse was 16 years. Only 14.8% of participants reported condom use with every sexual encounter. Military students used condoms the most. Participants older than 45 years, compared with younger participants, had a fourfold (adjusted odds ratio 4.3) increased risk of not using condoms. Men were less likely to use a condom, more likely to practice anal intercourse, and had more sexual partners than women. Officers and non-commissioned officers were identified to have a twofold (as measured by adjusted odds ratio = 2.00 and 2.22, respectively) increased risk of having more than two sexual partners in the last month compared with students. Both officers and non-commissioned officers were twice as likely as students to practice anal intercourse. Despite the high-risk behaviours reported by those surveyed, HIV seroprevalence in active duty personnel was low. Future efforts should emphasize on the correct condom use keeping focus on the high-risk behaviours of groups at risk, and on routinely testing the military personnel for HIV.

Occurrence and correlates of symptom persistence following acute dengue fever in Peru.

Dengue virus (DENV) infection causes an acute febrile illness generally considered to result in either complete recovery or death. Some reviews describe persistent symptoms after the febrile phase, although empirical data supporting this phenomenon is scarce. We evaluated symptom persistence in acute febrile DENV-infected and DENV-negative (controls) individuals from Peru. Self-reported solicited symptoms were evaluated at an acute and a follow-up visit, occurring 10-60 days after symptom onset. Rate of persistence of at least one symptom was 7.7% and 10.5% for DENV infected and control subjects, respectively (P < 0.01). The DENV-infected individuals had lower rates of persistent respiratory symptoms, gastrointestinal symptoms, headache, and fatigue, but higher rates of persistent rash compared with controls. Older age and female gender were positively associated with symptom persistence. As dengue cases continue to increase annually, even a relatively low frequency of persistent symptoms may represent a considerable worldwide morbidity burden.

[Human metapneumovirus in children: first cases in Colombia]. / Metaneumovirus humano en niños: primeros casos en Colombia.

Human metapneumovirus is a newly discovered pathogen associated with respiratory disease and occurring mainly in children. It produces an acute viral respiratory disease picture that varies from mild disease to severe, and which can require strict surveillance in intensive care units. Currently, reverse transcriptase polymerase chain reaction and cell culture are the most common methods for its diagnosis. The first six cases of human metapneumovirus in Colombia are presented from Medellín.

Adenovirus respiratory tract infections in Peru.

BACKGROUND: Currently, there is a paucity of data regarding human adenovirus (HAdv) circulation in Andean regions of South America. To address this shortcoming, we report the clinical, phylogenetic, and epidemiologic characteristics of HAdv respiratory tract infection from a large sentinel surveillance study conducted among adults and children in Peru. METHODS/PRINCIPAL FINDINGS: Oropharyngeal swabs were collected from participants visiting any of 38 participating health centers, and viral pathogens were identified by immunofluorescence assay in cell culture. In addition, molecular characterization was performed on 226 randomly selected HAdv samples. Between 2000 and 2010, a total of 26,375 participants with influenza-like illness (ILI) or severe acute respiratory infection (SARI) were enrolled in the study. HAdv infection was identified in 2.5% of cases and represented 6.2% of all viral pathogens. Co-infection with a heterologous virus was found in 15.5% of HAdv cases. HAdv infection was largely confined to children under the age of 15, representing 88.6% of HAdv cases identified. No clinical characteristics were found to significantly distinguish HAdv infection from other respiratory viruses. Geographically, HAdv infections were more common in sites from the arid coastal regions than in the jungle or highland regions. Co-circulation of subgroups B and C was observed each year between 2006 and 2010, but no clear seasonal patterns of transmission were detected. CONCLUSIONS/SIGNIFICANCE: HAdv accounted for a significant fraction of those presenting with ILI and SARI in Peru and tended to affect the younger population disproportionately. Longitudinal studies will help better characterize the clinical course of patients with HAdv in Peru, as well as determine the role of co-infections in the evolution of illness.

Sentinel surveillance of influenza-like illness in two hospitals in Maracay, Venezuela: 2006-2010.

BACKGROUND: Limited information exists on the epidemiology of acute febrile respiratory illnesses in tropical South American countries such as Venezuela. The objective of the present study was to examine the epidemiology of influenza-like illness (ILI) in two hospitals in Maracay, Venezuela. METHODOLOGY/PRINCIPAL FINDINGS: We performed a prospective surveillance study of persons with ILI who presented for care at two hospitals in Maracay, Venezuela, from October 2006 to December 2010. A respiratory specimen and clinical information were obtained from each participant. Viral isolation and identification with immunofluorescent antibodies and molecular methods were employed to detect respiratory viruses such as adenovirus, influenza A and B, parainfluenza, and respiratory sincytial virus, among others. There were 916 participants in the study (median age: 17 years; range: 1 month--86 years). Viruses were identified in 143 (15.6%) subjects, and one participant was found to have a co-infection with more than one virus. Influenza viruses, including pandemic H1N1 2009, were the most frequently detected pathogens, accounting for 67.4% (97/144) of the viruses detected. Adenovirus (15/144), parainfluenza virus (13/144), and respiratory syncytial virus (11/144) were also important causes of ILI in this study. Pandemic H1N1 2009 virus became the most commonly isolated influenza virus during its initial appearance in 2009. Two waves of the pandemic were observed: the first which peaked in August 2009 and the second--higher than the preceding - that peaked in October 2009. In 2010, influenza A/H3N2 re-emerged as the most predominant respiratory virus detected. CONCLUSIONS/SIGNIFICANCE: Influenza viruses were the most commonly detected viral organisms among patients with acute febrile respiratory illnesses presenting at two hospitals in Maracay, Venezuela. Pandemic H1N1 2009 influenza virus did not completely replace other circulating influenza viruses during its initial appearance in 2009. Seasonal influenza A/H3N2 was the most common influenza virus in the post-pandemic phase.

Evidence of rabies virus exposure among humans in the Peruvian Amazon.

In May of 2010, two communities (Truenococha and Santa Marta) reported to be at risk of vampire bat depredation were surveyed in the Province Datem del Marañón in the Loreto Department of Perú. Risk factors for bat exposure included age less than or equal to 25 years and owning animals that had been bitten by bats. Rabies virus neutralizing antibodies (rVNAs) were detected in 11% (7 of 63) of human sera tested. Rabies virus ribonucleoprotein (RNP) immunoglobulin G (IgG) antibodies were detected in the sera of three individuals, two of whom were also seropositive for rVNA. Rabies virus RNP IgM antibodies were detected in one respondent with no evidence of rVNA or RNP IgG antibodies. Because one respondent with positive rVNA results reported prior vaccination and 86% (six of seven) of rVNA-positive respondents reported being bitten by bats, these data suggest nonfatal exposure of persons to rabies virus, which is likely associated with vampire bat depredation.

Metaneumovirus humano en niños: primeros casos en Colombia / Human metapneumovirus in children: first cases in Colombia

El metaneumovirus humano es un nuevo patógeno asociado a infecciones respiratorias, principalmente en niños, que produce cuadros clínicos que van desde leves hasta graves, los cuales pueden incluso requerir tratamiento en unidades de cuidados intensivos. Hasta el momento, la reacción en cadena de la polimerasa con transcripción inversa y el cultivo celular son los métodos más usados para su diagnóstico. Se presentan los seis primeros casos de metapneumovirus humano en niños de Medellín, Colombia.

Human metapneumovirus is a newly discovered pathogen associated with respiratory disease and occurring mainly in children. It produces an acute viral respiratory disease picture that varies from mild disease to severe, and which can require strict surveillance in intensive care units. Currently, reverse transcriptase polymerase chain reaction and cell culture are the most common methods for its diagnosis. The first six cases of human metapneumovirus in Colombia are presented from Medellín.

Correlation of serotype-specific dengue virus infection with clinical manifestations.

BACKGROUND: Disease caused by the dengue virus (DENV) is a significant cause of morbidity throughout the world. Although prior research has focused on the association of specific DENV serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) with the development of severe outcomes such as dengue hemorrhagic fever and dengue shock syndrome, relatively little work has correlated other clinical manifestations with a particular DENV serotype. The goal of this study was to estimate and compare the prevalence of non-hemorrhagic clinical manifestations of DENV infection by serotype. METHODOLOGY AND PRINCIPAL FINDINGS: Between the years 2005-2010, individuals with febrile disease from Peru, Bolivia, Ecuador, and Paraguay were enrolled in an outpatient passive surveillance study. Detailed information regarding clinical signs and symptoms, as well as demographic information, was collected. DENV infection was confirmed in patient sera with polyclonal antibodies in a culture-based immunofluorescence assay, and the infecting serotype was determined by serotype-specific monoclonal antibodies. Differences in the prevalence of individual and organ-system manifestations were compared across DENV serotypes. One thousand seven hundred and sixteen individuals were identified as being infected with DENV-1 (39.8%), DENV-2 (4.3%), DENV-3 (41.5%), or DENV-4 (14.4%). When all four DENV serotypes were compared with each other, individuals infected with DENV-3 had a higher prevalence of musculoskeletal and gastrointestinal manifestations, and individuals infected with DENV-4 had a higher prevalence of respiratory and cutaneous manifestations. CONCLUSIONS/SIGNIFICANCE: Specific clinical manifestations, as well as groups of clinical manifestations, are often overrepresented by an individual DENV serotype.

Novel strain of Andes virus associated with fatal human infection, central Bolivia.

To better describe the genetic diversity of hantaviruses associated with human illness in South America, we screened blood samples from febrile patients in Chapare Province in central Bolivia during 2008-2009 for recent hantavirus infection. Hantavirus RNA was detected in 3 patients, including 1 who died. Partial RNA sequences of small and medium segments from the 3 patients were most closely related to Andes virus lineages but distinct (<90% nt identity) from reported strains. A survey for IgG against hantaviruses among residents of Chapare Province indicated that 12.2% of the population had past exposure to >1 hantaviruses; the highest prevalence was among agricultural workers. Because of the high level of human exposure to hantavirus strains and the severity of resulting disease, additional studies are warranted to determine the reservoirs, ecologic range, and public health effect of this novel strain of hantavirus.

Human metapneumovirus strains circulating in Latin America.

The human metapneumovirus (HMPV) is responsible for acute respiratory tract infections in young children, elderly patients, and immunocompromised hosts. In this study, we genetically analyzed the circulating HMPV in Central and South America from July 2008 to June 2009 and characterized the strains present in this region. Samples were collected during an international collaborative influenza like illness surveillance study and then sequenced with specific primers for the HMPV G gene. Our results show that two distinct clusters of HMPV circulated in Central and South America, subtypes A2 and B2 being the predominant strains.