Predictors of Severity of Influenza-Related Hospitalizations: Results From the Global Influenza Hospital Surveillance Network (GIHSN).

BACKGROUND: The Global Influenza Hospital Surveillance Network (GIHSN) has since 2012 provided patient-level data on severe influenza-like-illnesses from >100 participating clinical sites worldwide based on a core protocol and consistent case definitions. METHODS: We used multivariable logistic regression to assess the risk of intensive care unit admission, mechanical ventilation, and in-hospital death among hospitalized patients with influenza and explored the role of patient-level covariates and country income level. RESULTS: The data set included 73 121 patients hospitalized with respiratory illness in 22 countries, including 15 660 with laboratory-confirmed influenza. After adjusting for patient-level covariates we found a 7-fold increase in the risk of influenza-related intensive care unit admission in lower middle-income countries (LMICs), compared with high-income countries (P = .01). The risk of mechanical ventilation and in-hospital death also increased by 4-fold in LMICs, though these differences were not statistically significant. We also find that influenza mortality increased significantly with older age and number of comorbid conditions. Across all severity outcomes studied and after controlling for patient characteristics, infection with influenza A/H1N1pdm09 was more severe than with A/H3N2. CONCLUSIONS: Our study provides new information on influenza severity in underresourced populations, particularly those in LMICs.

Age Differences in Comorbidities, Presenting Symptoms, and Outcomes of Influenza Illness Requiring Hospitalization: A Worldwide Perspective From the Global Influenza Hospital Surveillance Network.

Background: The Global Influenza Hospital Surveillance Network (GIHSN) was established in 2012 to conduct coordinated worldwide influenza surveillance. In this study, we describe underlying comorbidities, symptoms, and outcomes in patients hospitalized with influenza. Methods: Between November 2018 and October 2019, GIHSN included 19 sites in 18 countries using a standardized surveillance protocol. Influenza infection was laboratory-confirmed with reverse-transcription polymerase chain reaction. A multivariate logistic regression model was utilized to analyze the extent to which various risk factors predict severe outcomes. Results: Of 16 022 enrolled patients, 21.9% had laboratory-confirmed influenza; 49.2% of influenza cases were A/H1N1pdm09. Fever and cough were the most common symptoms, although they decreased with age (P < .001). Shortness of breath was uncommon among those <50 years but increased with age (P < .001). Middle and older age and history of underlying diabetes or chronic obstructive pulmonary disease were associated with increased odds of death and intensive care unit (ICU) admission, and male sex and influenza vaccination were associated with lower odds. The ICU admissions and mortality occurred across the age spectrum. Conclusions: Both virus and host factors contributed to influenza burden. We identified age differences in comorbidities, presenting symptoms, and adverse clinical outcomes among those hospitalized with influenza and benefit from influenza vaccination in protecting against adverse clinical outcomes. The GIHSN provides an ongoing platform for global understanding of hospitalized influenza illness.

[Surveillance, prevention, and control of influenza virus in Peru]. / Vigilancia, prevención y control del virus de la influenza en Perú.

The importance of surveilling the circulation of the influenza virus and timely vaccination of different populations in Peru was analyzed in three sessions by a group of clinical experts from different specialties. The Peruvian national influenza surveillance system has many selected establishments that have become currently ineffective in terms of a timely report. Most of the samples come from Lima. The viral distribution is inadequately analyzed. The northern and jungle areas of the country have weather and season conditions different to those in Lima and on the southern highlands. This lack of coordination is accentuated by the opportunity of arrival of the influenza vaccine in the country. The Ministry of Health uses a trivalent vaccine but the possibility of a tetravalent vaccine with the two type-B lineages must be analyzed from a cost-benefit standpoint. The appropriateness of vaccinating two times a year, regionally, should be assessed.

La importancia de la vigilancia de la circulación del virus de influenza y la vacunación oportuna a las diferentes poblaciones del Perú, fue analizada en tres sesiones por un grupo de clínicos expertos de diferentes especialidades. En Perú, en los últimos años, el sistema nacional de vigilancia de influenza tiene muchos establecimientos seleccionados que son ineficaces en la notificación oportuna. La mayoría de las muestras provienen de Lima. La distribución viral es inadecuadamente analizada. El norte y la selva tienen estaciones climáticas diferentes a Lima y la sierra sur. Esta descoordinación se acentúa con la oportunidad de la llegada de la vacuna de influenza al país. El Ministerio de Salud utiliza una vacuna trivalente pero la posibilidad de una vacuna tetravalente con los dos linajes de tipo B, debe ser analizada desde el punto de vista de costo-beneficio. Se debería evaluar la pertinencia de vacunar en dos momentos anuales, regionalmente.

Vigilancia, prevención y control del virus de la influenza en Perú / Surveillance, prevention, and control of influenza virus in Peru

RESUMEN La importancia de la vigilancia de la circulación del virus de influenza y la vacunación oportuna a las diferentes poblaciones del Perú, fue analizada en tres sesiones por un grupo de clínicos expertos de diferentes especialidades. En Perú, en los últimos años, el sistema nacional de vigilancia de influenza tiene muchos establecimientos seleccionados que son ineficaces en la notificación oportuna. La mayoría de las muestras provienen de Lima. La distribución viral es inadecuadamente analizada. El norte y la selva tienen estaciones climáticas diferentes a Lima y la sierra sur. Esta descoordinación se acentúa con la oportunidad de la llegada de la vacuna de influenza al país. El Ministerio de Salud utiliza una vacuna trivalente pero la posibilidad de una vacuna tetravalente con los dos linajes de tipo B, debe ser analizada desde el punto de vista de costo-beneficio. Se debería evaluar la pertinencia de vacunar en dos momentos anuales, regionalmente.

ABSTRACT The importance of surveilling the circulation of the influenza virus and timely vaccination of different populations in Peru was analyzed in three sessions by a group of clinical experts from different specialties. The Peruvian national influenza surveillance system has many selected establishments that have become currently ineffective in terms of a timely report. Most of the samples come from Lima. The viral distribution is inadequately analyzed. The northern and jungle areas of the country have weather and season conditions different to those in Lima and on the southern highlands. This lack of coordination is accentuated by the opportunity of arrival of the influenza vaccine in the country. The Ministry of Health uses a trivalent vaccine but the possibility of a tetravalent vaccine with the two type-B lineages must be analyzed from a cost-benefit standpoint. The appropriateness of vaccinating two times a year, regionally, should be assessed.

Spatial and temporal characteristics of the 2009 A/H1N1 influenza pandemic in Peru.

BACKGROUND: Highly refined surveillance data on the 2009 A/H1N1 influenza pandemic are crucial to quantify the spatial and temporal characteristics of the pandemic. There is little information about the spatial-temporal dynamics of pandemic influenza in South America. Here we provide a quantitative description of the age-specific morbidity pandemic patterns across administrative areas of Peru. METHODS: We used daily cases of influenza-like-illness, tests for A/H1N1 influenza virus infections, and laboratory-confirmed A/H1N1 influenza cases reported to the epidemiological surveillance system of Peru's Ministry of Health from May 1 to December 31, 2009. We analyzed the geographic spread of the pandemic waves and their association with the winter school vacation period, demographic factors, and absolute humidity. We also estimated the reproduction number and quantified the association between the winter school vacation period and the age distribution of cases. RESULTS: The national pandemic curve revealed a bimodal winter pandemic wave, with the first peak limited to school age children in the Lima metropolitan area, and the second peak more geographically widespread. The reproduction number was estimated at 1.6-2.2 for the Lima metropolitan area and 1.3-1.5 in the rest of Peru. We found a significant association between the timing of the school vacation period and changes in the age distribution of cases, while earlier pandemic onset was correlated with large population size. By contrast there was no association between pandemic dynamics and absolute humidity. CONCLUSIONS: Our results indicate substantial spatial variation in pandemic patterns across Peru, with two pandemic waves of varying timing and impact by age and region. Moreover, the Peru data suggest a hierarchical transmission pattern of pandemic influenza A/H1N1 driven by large population centers. The higher reproduction number of the first pandemic wave could be explained by high contact rates among school-age children, the age group most affected during this early wave.

Capacity-building efforts by the AFHSC-GEIS program.

Capacity-building initiatives related to public health are defined as developing laboratory infrastructure, strengthening host-country disease surveillance initiatives, transferring technical expertise and training personnel. These initiatives represented a major piece of the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) contributions to worldwide emerging infectious disease (EID) surveillance and response. Capacity-building initiatives were undertaken with over 80 local and regional Ministries of Health, Agriculture and Defense, as well as other government entities and institutions worldwide. The efforts supported at least 52 national influenza centers and other country-specific influenza, regional and U.S.-based EID reference laboratories (44 civilian, eight military) in 46 countries worldwide. Equally important, reference testing, laboratory infrastructure and equipment support was provided to over 500 field sites in 74 countries worldwide from October 2008 to September 2009. These activities allowed countries to better meet the milestones of implementation of the 2005 International Health Regulations and complemented many initiatives undertaken by other U.S. government agencies, such as the U.S. Department of Health and Human Services, the U.S. Agency for International Development and the U.S. Department of State.

Influenza and other respiratory viruses in three Central American countries.

BACKGROUND: Despite the disease burden imposed by respiratory diseases on children in Central America, there is a paucity of data describing the etiologic agents of the disease. AIMS: To analyze viral etiologic agents associated with influenza-like illness (ILI) in participants reporting to one outpatient health center, one pediatric hospital, and three general hospitals in El Salvador, Honduras, and Nicaragua Material & METHODS: Between August 2006 and April 2009, pharyngeal swabs were collected from outpatients and inpatients. Patient specimens were inoculated onto cultured cell monolayers, and viral antigens were detected by indirect and direct immunofluorescence staining. RESULTS: A total of 1,756 patients were enrolled, of whom 1,195 (68.3%) were under the age of 5; and 183 (10.4%) required hospitalization. One or more viral agents were identified in 434 (24.7%) cases, of which 17 (3.9%) were dual infections. The most common viruses isolated were influenza A virus (130; 7.4% of cases), respiratory syncytial virus (122; 6.9%), adenoviruses (63; 3.6%), parainfluenza viruses (57; 3.2%), influenza B virus (47; 2.7% of cases), and herpes simplex virus 1 (22; 1.3%). In addition, human metapneumovirus and enteroviruses (coxsackie and echovirus) were isolated from patient specimens. DISCUSSION: When compared to the rest of the population, viruses were isolated from a significantly higher percentage of patients age 5 or younger. The prevalence of influenza A virus or influenza B virus infections was similar between the younger and older age groups. RSV was the most commonly detected pathogen in infants age 5 and younger and was significantly associated with pneumonia (p < 0.0001) and hospitalization (p < 0.0001). CONCLUSION: Genetic analysis of influenza isolates identified A (H3N2), A (H1N1), and B viruses. It also showed that the mutation H274Y conferring resistance to oseltamivir was first detected in Honduran influenza A/H1N1 strains at the beginning of 2008. These data demonstrate that a diverse range of respiratory pathogens are associated with ILI in Honduras, El Salvador, and Nicaragua. RSV infection in particular appears to be associated with severe disease in infants in the region.

Epidemiology of influenza-like illness in the Amazon Basin of Peru, 2008-2009.

BACKGROUND: Data addressing the incidence and epidemiology of influenza and influenza-like illness (ILI) in tropical regions of the world is scarce, particularly for the neotropics of South America. METHODS: We conducted active, population-based surveillance for ILI across 45 city blocks within the Amazon Basin city of Iquitos, Peru. Demographic data and household characteristics were collected for all participants, and participating households were visited three times weekly to inquire about ILI (fever plus cough or sore throat) among household residents. Nasal and oropharyngeal swabs were collected from participants with ILI and tested for influenza virus infection. RESULTS: Between May 1, 2008 and July 8, 2009, we monitored 10,341 participants for ILI for a total of 11,569.5 person-years. We detected 459 ILI episodes, with 252 (54.9%) of the participants providing specimens. Age-adjusted incidence of ILI was estimated to be 46.7 episodes/1000 person-years. Influenza A and B viruses were detected in 25 (9.9%) and 62 (24.6%) specimens of ILI patients, respectively, for an estimated age-adjusted incidence rate of 16.5 symptomatic influenza virus infections/1000 person-years. Risk factors for ILI included age, household crowding, and use of wood as cooking fuel. For influenza virus infection specifically, age and use of wood as a cooking fuel were also identified as risk factors, but no effect of household crowding was observed. CONCLUSIONS: Our results represent the initial population-based description of the epidemiology of ILI in the Amazon region of Peru, which will be useful for developing region-specific strategies for reducing the burden of respiratory disease.

Changes in the viral distribution pattern after the appearance of the novel influenza A H1N1 (pH1N1) virus in influenza-like illness patients in Peru.

BACKGROUND: We describe the temporal variation in viral agents detected in influenza like illness (ILI) patients before and after the appearance of the ongoing pandemic influenza A (H1N1) (pH1N1) in Peru between 4-January and 13-July 2009. METHODS: At the health centers, one oropharyngeal swab was obtained for viral isolation. From epidemiological week (EW) 1 to 18, at the US Naval Medical Research Center Detachment (NMRCD) in Lima, the specimens were inoculated into four cell lines for virus isolation. In addition, from EW 19 to 28, the specimens were also analyzed by real time-polymerase-chain-reaction (rRT-PCR). RESULTS: We enrolled 2,872 patients: 1,422 cases before the appearance of the pH1N1 virus, and 1,450 during the pandemic. Non-pH1N1 influenza A virus was the predominant viral strain circulating in Peru through (EW) 18, representing 57.8% of the confirmed cases; however, this predominance shifted to pH1N1 (51.5%) from EW 19-28. During this study period, most of pH1N1 cases were diagnosed in the capital city (Lima) followed by other cities including Cusco and Trujillo. In contrast, novel influenza cases were essentially absent in the tropical rain forest (jungle) cities during our study period. The city of Iquitos (Jungle) had the highest number of influenza B cases and only one pH1N1 case. CONCLUSIONS: The viral distribution in Peru changed upon the introduction of the pH1N1 virus compared to previous months. Although influenza A viruses continue to be the predominant viral pathogen, the pH1N1 virus predominated over the other influenza A viruses.

Molecular characterization of adenovirus circulating in Central and South America during the 2006-2008 period.

BACKGROUND: Human Adenoviruses are recognized pathogens, causing a broad spectrum of diseases. Serotype identification is critical for epidemiological surveillance, detection of new strains and understanding of HAdvs pathogenesis. Little data is available about HAdvs subtypes in Latin America. METHODS: In this study, we have molecularly characterized 213 adenoviruses collected from ILI presenting patients, during 2006-08, in Central and South America. RESULTS: Our results indicate that 161(76%) adenoviruses belong to subgroup C, 45 (21%) to subgroup B and 7 (3%) to subtype E4.

Epidemiological and molecular characteristics of HIV-1 infection among female commercial sex workers, men who have sex with men and people living with AIDS in Paraguay.

An HIV seroprevalence and molecular study was conducted among 935 subjects: 723 female commercial sex workers, 92 men who have sex with men and 120 HIV-positive volunteers. The reported injection drug use rates were 0.7% in female commercial sex workers and 3% in men who have sex with men. Sexually transmitted infections were reported in 265 (37%) of the female commercial sex workers and 38 (41%) of the men who have sex with men. A total of 20 (2.8%) female commercial sex workers and 12 (13%) men who have sex with men became HIV infected during the study period. A history of sexually transmitted infection increased the risk of subsequent HIV infection twofold (adjusted odds ratio of 2.5) among the female commercial sex workers, while cocaine use had an adjusted odds ratios of 6.61 among men who have sex with men. From 130 samples, and based on heteroduplex mobility assaying for the env gene, with sequencing of part of pol and/or full genomes, subtype B was the predominant subtype identified (66%); followed by subtype F (22%) and subtype C (4%). Recombinant CRF12-BF strains were identified in 6% and CRF17_BF was identified in 2%.

Epidemiological and molecular characteristics of HIV-1 infection among female commercial sex workers, men who have sex with men and people living with AIDS in Paraguay / Características epidemiológicas e moleculares da infecção por HIV-1 entre as mulheres que trabalham no comércio do sexo, entre homens que mantém relações sexuais com homens e nas pessoas convivendo com AIDS no Paraguai

An HIV seroprevalence and molecular study was conducted among 935 subjects: 723 female commercial sex workers, 92 men who have sex with men and 120 HIV-positive volunteers. The reported injection drug use rates were 0.7 percent in female commercial sex workers and 3 percent in men who have sex with men. Sexually transmitted infections were reported in 265 (37 percent) of the female commercial sex workers and 38 (41 percent) of the men who have sex with men. A total of 20 (2.8 percent) female commercial sex workers and 12 (13 percent) men who have sex with men became HIV infected during the study period. A history of sexually transmitted infection increased the risk of subsequent HIV infection twofold (adjusted odds ratio of 2.5) among the female commercial sex workers, while cocaine use had an adjusted odds ratios of 6.61 among men who have sex with men. From 130 samples, and based on heteroduplex mobility assaying for the env gene, with sequencing of part of pol and/or full genomes, subtype B was the predominant subtype identified (66 percent); followed by subtype F (22 percent) and subtype C (4 percent). Recombinant CRF12-BF strains were identified in 6 percent and CRF17_BF was identified in 2 percent.

Um estudo de soroprevalência e de avaliação molecular do HIV foi realizado com 935 indivíduos: 723 mulheres que trabalhavam no comércio do sexo, 92 homens que mantinham relações sexuais com outros homens e com 120 voluntários HIV-positivos. O relato de uso de drogas injetáveis foi de 0,7 por cento nas mulheres que trabalhavam no comércio do sexo e de 3 por cento nos homens que mantinham relações sexuais com outros homens. Infecções sexualmente transmitidas foram relatadas por 265 (37 por cento) das mulheres que trabalhavam no comércio do sexo e em 38 (41 por cento) dos homens que mantinham relações sexuais com homens. Um total de 20 (2,8 por cento) mulheres que trabalhavam no comércio do sexo e 12 (13 por cento) homens que mantinham relações sexuais com homens se infectou com HIV durante o período do estudo. História prévia de infecção sexualmente transmitida aumentou em duas vezes o risco de infecção subseqüente por HIV (odds ratio ajustado de 2,5) entre as mulheres que trabalhavam no comércio do sexo, enquanto cocaína apresentou odds ratio ajustado de 6,61 entre os homens que mantinham relações sexuais com outros homens. De 130 amostras, com base no ensaio da mobilidade heteroduplex para o gene env, com sequenciamento de parte do pol e/ou genomas completos, o subtipo B foi o subtipo mais identificado (66 por cento); seguido pelo subtipo F (22 por cento) e subtipo C (4 por cento). Cepas recombinantes CRF12-BF foram identificadas em 6 por cento e CRF17_BF foi identificada em 2 por cento.

Immigration status and HIV-risk related behaviors among female sex workers in South America.

This study compares immigrant (i.e., foreigner) with non-immigrant (i.e., local/native) HIV-related risk behaviors among female sex workers (FSW) in South America. A total of 1,845 FSW were enrolled in Argentina, Bolivia, Ecuador, and Uruguay. According to their nationality, 10.1% of participants were immigrant FSW. Immigrant FSW were more likely to be younger in Argentina; to work in a disco/bar in Bolivia; to be single and use illegal drugs in Ecuador; and to work in a brothel, consume alcohol, and have sex with foreign clients in Uruguay. HIV-related sexual and drug use behaviors were more common among immigrant FSW in Bolivia, Ecuador, and Uruguay. Country-specific HIV/STI prevention and control programs should be developed for immigrant FSW populations in South America.

Association of herpes simplex virus type 2 infection and syphilis with human immunodeficiency virus infection among men who have sex with men in Peru.

BACKGROUND: We evaluated associations between human immunodeficiency virus (HIV) infection, herpes simplex virus type 2 (HSV-2) infection, and syphilis among men who have sex with men (MSM) in Peru. METHODS: A surveillance survey of 3280 MSM was conducted; sexual behavior was assessed with a structured computer-assisted self-interview, and serum antibody testing was performed for HIV, HSV-2, and Treponema pallidum. RESULTS: HIV, HSV-2, and syphilis seroprevalences of 13.9%, 46.3%, and 13.4% were detected, respectively. HSV-2 seroprevalence was twice as high in HIV-infected subjects (80.5%) than it was in HIV-uninfected subjects (40.8%) (P < .01), and HSV-2 seropositivity (adjusted odds ratio [AOR], 5.66) was found to be strongly associated with HIV infection. In addition, homosexual self-definition (AOR, 3.12), exchange of sex for money (AOR, 1.61), unprotected sex (no condom) (AOR, 2.81), history of sex work (AOR, 1.89), oral receptive sex (AOR, 1.43), and cocaine use before/during sex (AOR, 2.53) within the preceding 6 months, as well as such sexually transmitted infections (STIs) and STI syndromes as proctitis (AOR, 2.80), genital ulcer disease (GUD) (AOR, 2.06), prior syphilis (AOR, 2.64), genital warts (AOR, 1.70), and self-reported STIs within the preceding 6 months (AOR, 1.61), were also found to be significant predictors of HIV infection. CONCLUSIONS: We found a strong association between HSV-2 seropositivity and HIV infection. Intervention measures against GUD due to HSV-2 infection and syphilis, such as routine testing, early detection, HSV-2 suppressive treatment, and condom distribution, need to be enhanced as part of STI prevention strategies at a national level to effectively reduce HIV infection among MSM in Peru.

Randomized, double-blind, phase III, pivotal field trial of the comparative immunogenicity, safety, and tolerability of two yellow fever 17D vaccines (Arilvax and YF-VAX) in healthy infants and children in Peru.

We conducted a randomized, double-blind, phase III yellow fever (YF) vaccine trial among 1,107 healthy children in Sullana in northern Peru. The safety and efficacy (by measurement of geometric mean neutralizing antibody titer responses) were determined for two YF vaccines, ARILVAX (n = 738) and YF-VAX(R) (n = 369). Serocon-version rates were higher (94.9%) in ARILVAX than in YF-VAX (90.6%) recipients. The two-sided 95% confidence interval (YF-VAX-ARILVAX) was (-12.8% to -2.5%), indicating that the higher seroconversion rate for Arilvax was significant. Post-vaccination (30-day) mean log(10) neutralization indices were found to be similar for both products: 1.32 for ARILVAX and 1.26 for YF-VAX (P = 0.1404, by analysis of variance). A similar number of subjects in each group reported at least one adverse event (AE); 441 (59.8%) for ARILVAX versus 211 (59.9%) for YF-VAX. Most (591; 96.7%) of these were of a mild nature and resolved without treatment. There were no treatment-related serious AEs. This is the first randomized, double-blind comparison of two YF vaccines in a pediatric population; both vaccines were shown to be highly immunogenic and well-tolerated.

Manifestaciones clínicas, epidemiológicas y serotipos en un brote de dengue clásico en el departamento de Lambayeque. Enero-junio 2001 / Clinical, epidemiological manifestations and serotipos in an outbreak of classic dengue in Lambayeque's department. January - June, 2001

Objetivo: Describir las manifestaciones clínicas, epidemiológicas y serotipos del dengue en un brote en el departamento de Lambayeque entre enero y junio del 2001. Materiales y métodos: Se realizó un estudio descriptivo transversal de reporte de casos. Los datos se obtuvieron de la ficha epidemiológica de investigación de Dengue de la Dirección de Salud Lambayeque en los casos de dengue confirmado. Resultados: Se confirmó dengue en 68 pacientes con igual distribución por sexo. Las manifestaciones clínicas más frecuentes fueron: fiebre (97,1 por ciento), cefalea (91.2 por ciento), dolor óseo (80,9 por ciento) y dolor retroobitario (80,9 por ciento). La manifestación hemorrágica más frecuente fue petequias. La prueba de lazo sólo se presentó en 2 casos (4,4 por ciento). El distrito más afectado fue Olmos con 28 casos (41.2 por ciento). 22 (32,4 por ciento) casos fueron considerados como probables importados, de los cuales el destino de viaje con mayor frecuencia fue Bagua (18,2 por ciento); y 46 como probables casos autóctonos (67.6 por ciento). Se aisló el virus en 6 casos, en 4 de ellos se identificó el serotipo DEN 1, y en 2 el DEN 2. Conclusiones: Las manifestaciones clínicas son compatibles con otras epidemias reportadas en las Américas. Los virus circulantes fueron identificados como DEN 1 y DEN 2. Se demostró por primera vez la presencia de casos autóctonos en el departamento de Lambayeque. El distrito más afectado fue Olmos ubicándose en el escenario epidemiológico III-A. La circulación simultánea de dos serotipos de dengue aumenta el riesgo de dengue hemorrágico.