Etiology of Acute Febrile Illness in the Peruvian Amazon as determined by modular formatted quantitative PCR: A Protocol for RIVERA, a Health Facility-Based Case-Control Study.

Background: The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI. Methods: A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21-28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI. Discussion: The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 hours and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific, prevalent pathogens as a cause of acute illness. Study Registration: Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.

Dengue and COVID-19 Co-Circulation in the Peruvian Amazon: A Population-Based Study.

The COVID-19 pandemic affected the main Amazon cities dramatically, with Iquitos City reporting the highest seroprevalence of anti-SARS-CoV-2 antibodies during the first COVID-19 wave worldwide. This phenomenon raised many questions about the possibility of a co-circulation of dengue and COVID-19 and its consequences. We carried out a population-based cohort study in Iquitos, Peru. We obtained a venous blood sample from a subset of 326 adults from the Iquitos COVID-19 cohort (August 13-18, 2020) to estimate the seroprevalence of anti-dengue virus (DENV) and anti-SARS-CoV-2 antibodies. We tested each serum sample for anti-DENV IgG (serotypes 1, 2, 3, and 4) and SARS-CoV-2 antibodies anti-spike IgG and IgM by ELISA. We estimated an anti-SARS-CoV-2 seroprevalence of 78.0% (95% CI, 73.0-82.0) and an anti-DENV seroprevalence of 88.0% (95% CI, 84.0-91.6), signifying a high seroprevalence of both diseases during the first wave of COVID-19 transmission in the city. The San Juan District had a lower anti-DENV antibody seroprevalence than the Belen District (prevalence ratio, 0.90; 95% CI, 0.82-0.98). However, we did not observe these differences in anti-SARS-CoV-2 antibody seroprevalence. Iquitos City presented one of the highest seroprevalence rates of anti-DENV and anti-SARS-CoV-2 antibodies worldwide, but with no correlation between their antibody levels.

Etiology of acute febrile illness in the peruvian amazon as determined by modular formatted quantitative PCR: a protocol for RIVERA, a health facility-based case-control study.

BACKGROUND: The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI. METHODS: A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21-28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI. DISCUSSION: The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 h and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific prevalent pathogens as a cause of acute illness. STUDY REGISTRATION: Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.

Seroprevalence of anti-SARS-CoV-2 antibodies in Iquitos, Peru in July and August, 2020: a population-based study.

BACKGROUND: Detection of anti-SARS-CoV-2 antibodies among people at risk of infection is crucial for understanding both the past transmission of COVID-19 and vulnerability of the population to continuing transmission and, when done serially, the intensity of ongoing transmission over an interval in a community. We aimed to estimate the seroprevalence of COVID-19 in a representative population-based cohort in Iquitos, one of the regions with the highest mortality rates from COVID-19 in Peru, where a devastating number of cases occurred in March, 2020. METHODS: We did a population-based study of SARS-CoV-2 transmission in Iquitos at two timepoints: July 13-18, 2020 (baseline), and Aug 13-18, 2020 (1-month follow-up). We obtained a geographically stratified representative sample of the city population using the 2017 census data, which was updated on Jan 20, 2020. We included people who were inhabitants of Iquitos since COVID-19 was identified in Peru (March 6, 2020) or earlier. We excluded people living in institutions, people receiving any pharmacological treatment for COVID-19, people with any contraindication for phlebotomy, and health workers or individuals living with an active health worker. We tested each participant for IgG and IgM anti-SARS-CoV-2 antibodies using the COVID-19 IgG/IgM Rapid Test (Zhejiang Orient Gene Biotech, China). We used survey analysis methods to estimate seroprevalence accounting for the sampling design effect and test performance characteristics. FINDINGS: We identified 726 eligible individuals and enrolled a total of 716 participants (99%), distributed across 40 strata (four districts, two sexes, and five age groups). We excluded ten individuals who: did not have consent from a parent or legal representative (n=3), had moved to Iquitos after March 6, 2020 (n=3), were in transit (n=2), or had respiratory symptoms (n=1). After adjusting for the study sampling effects and sensitivity and specificity of the test, we estimated a seroprevalence of 70% (95% CI 67-73) at baseline and 66% (95% CI 62-70) at 1 month of follow-up, with a test-retest positivity of 65% (95% CI 61-68), and an incidence of new exposures of 2% (95% CI 1-3). We observed significant differences in the seroprevalence between age groups, with participants aged 18-29 years having lower seroprevalence than those aged younger than 12 years (prevalence ratio 0·85 [95% CI 0·73-0·98]; p=0·029). INTERPRETATION: After the first epidemic peak, Iquitos had one of the highest rates of seroprevalence of anti-SARS-CoV-2 antibodies worldwide. Nevertheless, the city experienced a second wave starting in January, 2021, probably due to the emergence of the SARS-CoV-2 P1 variant, which has shown higher transmissibility and reinfection rates. FUNDING: Dirección Regional de Salud de Loreto (DIRESA), Loreto, Peru. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Incomplete Protection against Dengue Virus Type 2 Re-infection in Peru.

BACKGROUND: Nearly half of the world's population is at risk for dengue, yet no licensed vaccine or anti-viral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide life-long protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010-2011, 15 years after the first outbreak of DENV-2 in the region. METHODOLOGY/PRINCIPAL FINDINGS: We estimated the age-dependent prevalence of serotype-specific DENV antibodies from longitudinal cohort studies conducted between 1993 and 2010. During the 2010-2011 epidemic, active dengue cases were identified through active community- and clinic-based febrile surveillance studies, and acute inapparent DENV infections were identified through contact tracing studies. Based on the age-specific prevalence of DENV-2 neutralizing antibodies, the age distribution of DENV-2 cases was markedly older than expected. Homologous protection was estimated at 35.1% (95% confidence interval: 0%-65.2%). At the individual level, pre-existing DENV-2 antibodies were associated with an incomplete reduction in the frequency of symptoms. Among dengue cases, 43% (26/66) exhibited elevated DENV-2 neutralizing antibody titers for years prior to infection, compared with 76% (13/17) of inapparent infections (age-adjusted odds ratio: 4.2; 95% confidence interval: 1.1-17.7). CONCLUSIONS/SIGNIFICANCE: Our data indicate that protection from homologous DENV re-infection may be incomplete in some circumstances, which provides context for the limited vaccine efficacy against DENV-2 in recent trials. Further studies are warranted to confirm this phenomenon and to evaluate the potential role of incomplete homologous protection in DENV transmission dynamics.

The impact of indoor residual spraying of deltamethrin on dengue vector populations in the Peruvian Amazon.

Dengue is an important public health problem in the Amazon area of Peru, resulting in significant morbidity each year. As in other areas of the world, ultra-low volume (ULV) application of insecticides is the main strategy to reduce adult populations of the dengue vector Aedes aegypti, despite growing evidence of its limitations as a single control method. This study investigated the efficacy of deltamethrin S.C. applied through indoor residual spraying (IRS) of dwellings in reducing A. aegypti populations. The residual effect of the insecticide was tested by monthly bioassays on the three most common indoor surfaces found in the Amazon area: painted wood, unpainted wood and brick. The results showed that in an area with moderate levels of A. aegypti infestation, IRS dramatically reduced all immature indices the first week after deltamethrin IRS application and the adult index from 18.5 to 3.1, four weeks after intervention (p<0.05). Even though housing conditions facilitated reinfestation with A. aegypti (100% of the houses have open roof eaves, 31.5% lack sewage systems, and 60.4% collected rain in open containers), indices remained low compared to baseline 16 weeks after insecticide application. Bioassays showed that deltamethrin S.C. caused mortalities >80% 8 weeks after application on all types of surfaces. The residual effect of the insecticide was greater on brick than on wooden walls (p<0.05). Our results demonstrate that IRS can have both an immediate and sustained effect on reducing adult and immature A. aegypti populations and should be considered as an adult mosquito control strategy by dengue vector control programs.

[Lessons learned in the control of Aedes aegypti to address dengue and the emergency of chikungunya in Iquitos, Peru]. / Lecciones aprendidas en el control de Aedes aegypti para afrontar el dengue y la emergencia de chikungunya en Iquitos, Perú.

Dengue has affected Iquitos since 1990 causing outbreaks of major impact on public health and for this reason great efforts have been made for its temporal control. Currently, with the expansion of the chikungunya virus in the Americas and the threat of the emergence of the virus in Iquitos, we reflect on lessons learned by way of the activities undertaken in the area of vector control; epidemiological surveillance, diagnosis and clinical management during periods of outbreaks of dengue, in a way that will allow us to better face the threat of an outbreak of chikungunya virus in the largest city in the Peruvian Amazon.

Itaya virus, a Novel Orthobunyavirus Associated with Human Febrile Illness, Peru.

Our genetic analyses of uncharacterized bunyaviruses isolated in Peru identified a possible reassortant virus containing small and large gene segment sequences closely related to the Caraparu virus and a medium gene segment sequence potentially derived from an unidentified group C orthobunyavirus. Neutralization tests confirmed serologic distinction among the newly identified virus and the prototype and Caraparu strains. This virus, named Itaya, was isolated in 1999 and 2006 from febrile patients in the cities of Iquitos and Yurimaguas in Peru. The geographic distance between the 2 cases suggests that the Itaya virus could be widely distributed throughout the Amazon basin in northeastern Peru. Identification of a new Orthobunyavirus species that causes febrile disease in humans reinforces the need to expand viral disease surveillance in tropical regions of South America.

Lecciones aprendidas en el control de Aedes aegypti para afrontar el dengue y la emergencia de chikungunya en Iquitos, Perú / Lessons learned in the control of Aedes aegypti to address dengue and the emergency of chikungunya in Iquitos, Peru

El dengue ha afectado a Iquitos desde 1990 causando varios brotes de gran impacto en la salud pública y por el que se desplegaron grandes esfuerzos para su control temporal. Actualmente, ante la expansión del virus chikungunya en las Américas y la amenaza de la emergencia del virus en Iquitos, reflexionamos a modo de lecciones aprendidas las actividades emprendidas en el área del control vectorial; la vigilancia epidemiológica; el diagnóstico y el manejo clínico durante los periodos de brotes de dengue, de modo que nos permita enfrentar mejor la amenaza de un brote del virus chikunguña en la ciudad más grande de la Amazonía peruana.

Dengue has affected Iquitos since 1990 causing outbreaks of major impact on public health and for this reason great efforts have been made for its temporal control. Currently, with the expansion of the chikungunya virus in the Americas and the threat of the emergence of the virus in Iquitos, we reflect on lessons learned by way of the activities undertaken in the area of vector control; epidemiological surveillance, diagnosis and clinical management during periods of outbreaks of dengue, in a way that will allow us to better face the threat of an outbreak of chikungunya virus in the largest city in the Peruvian Amazon.

Publicaciones científicas de investigadores del Instituto de Investigaciones en Ciencias de la Salud (IICS) de la Universidad Nacional de Asunción periodo junio 1999 – junio 2011 / Scientific publications of researchers of the Institute of Health Sciences Research from the National University of Asuncion period June 1999 – June 2011

La publicación de los trabajos de investigación, es el último eslabón que cierra el círculo de la Investigación, pero que no siempre ocurre. Desde su creación, el IICS ha estado publicando sus trabajos en forma continua. En este trabajo se presenta un listado de publicaciones realizadas por investigadores del IICS como autor principal o coautor en un periodo de 12 años (Junio 1999 - Junio 2011) en revistas indexadas y ordenadas por apellido de autores. Se divide en tres partes: 1) Publicaciones internacionales que comprende 115 artículos científicos; 2) Publicaciones Nacionales con 141 artículos, preferentemente en la revista Memorias del IICS, que es la revista oficial de la institución, indexada por la base de datos LILACS e incluida en el catálogo del Sistema LATINDEX, HINARI y en el sitio SciELO 3) Índice de autores con identificación de publicaciones internacionales (I) y nacionales (N). No están incluidas las publicaciones que fueron realizadas en revistas no indexadas ó boletines informativos, así como la publicación de los resúmenes de comunicaciones a Congresos Nacionales o Internacionales. Con esta contribución, queremos ofrecer a la comunidad científica en el área de la salud, la posibilidad de acceder a la bibliografía científica de investigadores del IICS, que junto con los libros previamente publicados como "Publicaciones 1989" y "Bibliografía Mayo 1989-Mayo 1999", engloba la producción científica del IICS desde sus inicios hasta el presente.

The publication of the research works is the last step that closes the circle of research but it does not always occur. Since its creation, the IICS has been publishing its works continuously. This work presents a list of publications made by researchers of the IICS as principal investigator or co-author in a period of 12 years (June 1999 - June 2011) in indexed journals and ordered by the last name of the authors. It is divided in three parts: 1) International publications that comprises 115 scientific articles; 2) National publication that includes 141 articles mainly in the journal Memorias del IICS which is the official journal of the institution, indexed in LILACS database and included in the catalog of the LATINDEX System, HINARI and in the SciELO site 3) Index of authors with identification of international (I) and nationals (N) publications. Publications that were made in non-indexed journals or informative bulletins were not included as well as the publication of summaries of the communication to national and international congresses. With this contribution, we would like to offer to the scientific health community the possibility of access to the scientific production of the researchers of the IICS, that together with the previously published books “Publicaciones 1989“ and “Bibliografía Mayo 1989-Mayo 1999“ embraces the scientific production of the IICS since its beginnings up to now.

Crescimento e estado nutricional de pré-escolares residentes na regiäo Amazônica do Peru / Growth and nutritional status of preschool children living in the how Peruvian Amazon Bazin

Estuda o estado nutricional de 1684 pré-escolares menores de 5 anos (862 meninos e 822 meninas), residentes na Regiäo Amazônica do Peru. Os dados foram obtidos da Pesquisa Nacional de Nutriçäo e Saúde (ENNSA), realizada no Peru, em 1984. O crescimento e estado nutricional foi avaliado através dos seguintes indicadores: peso para idade, altura para idade, peso para altura e perímetro braquial. Os resultados mostram uma elevada prevalência de baixa estatura (porcentagem de adequaçäo à mediana menor que 95 por cento para o índice altura para idade) e baixa prevalência de inadequaçäo de peso (porcentagem de adequaçäo à mediana menor que 80 por cento para o índice peso para altura). De acordo com o índice peso para idade, 38 por cento das crianças estiveram adequadamente nutridas e apenas 0,8 por cento apresentaram desnutriçäo grave

Crescimento e estado nutricional de pre-escolares resistentes na regiao amazonica do peru

Foi estudado o estado nutricional de 1684 pre-escolares menores de 5 anos (862 meninos 2 822 meninas), residentes na Regiao Amazonica do Peru. Os dados foram obtidos da Pesquisa Nacional de Nutricao e Saude (ENNSSA), realizada no Peru, em 1984. O crecismento e estado nutricional foi avaliado atraves dos seguintes indicadores: peso para idade, altura para idade, peso para altura e perimetro braquial. Os resultados mostram uma levada prevalencia de baixa estatura (porcentagem de adequacao a mediana menor que 95 por cento para indice altura para idade) e baixa prevalencia de inadequacao de peso (porcentagem de adequacao a mediana menor que 80 por cento para o indice peso para altura). De acordo com o indice peso para idade, 38 por cento das criancas estiveram adequadamente nutridas e apenas 0,8 por cento apresentaram desnutricao grave.

Prevalencia del déficit de peso y estatura en niños pre-escolares residentes en la selva baja Peruana / Prevalence of weight and hight deficiency in children living at the Peruvian Amazon jungle

Se midió el peso y estatura de 1699 niños menores de 6 años residentes en la selva amazónica del Perú, los datos fueron obtenidos en la Encuesta Nacional de Nutrición y Salud realizada en Perú en el año de 1984. Para evaluar la prevalencia de problemas de crecimiento en estos niños. El peso y la talla fueron presentadas en relación a las curvas de crecimiento de la NCHS-USA/OMS (Centro Nacional de estadística en Salud de los Estados Unidos y la Organización Mundial de Salud). Los resultados muestran una elevada prevalencia de déficit de estatura sobre todo en los niños mayores de un año. Se encontró que la prevalencia de déficit de peso y sobrepeso es baja