High Anti-Interferon-Alpha Autoantibody Levels in Severe/Critical COVID-19 Patients from Peru.

Innate immune responses through the production of type I interferon-α (anti-IFN-α) play an essential role in the defense against viruses. The autoantibodies (auto-Abs) anti-IFN-α are implicated in COVID-19 pathogenesis with higher levels among patients with worse prognoses. The study aimed to assess the levels of anti-IFN-α auto-Abs in Peruvian patients with severe/critical hospitalized COVID-19 compared to asymptomatic/mild COVID-19 outpatients and healthy controls. We analyzed 101 serum samples, including 56 (55.5%) severe/critical, 13 (12.3%) asymptomatic/mild COVID-19 patients, and 32 (32.2%) healthy controls, which we tested using a commercial ELISA anti-IFN-α-auto-Abs kit. We observed seropositivity of 48.2% (26/54) to anti-IFN-α auto-Abs among the severe/critical COVID-19 group, but 0% (0/13) and 3.1% (1/32) among the asymptomatic/mild COVID-19 and healthy groups (P = 0.021), respectively. Furthermore, we observed a significant association between the log10 of anti-IFN-α auto-Abs and the COVID-19 status, with the log10 of anti-IFN-α auto-Abs levels being significantly higher among the severe/critical COVID-19 group compared to the healthy controls (ß = 1.20; confidence interval [95% CI]: 0.72-1.67; P < 0.001). Such association remains significant either when adjusted by age and gender (adjusted ß = 1.16; 95% CI: 0.62-1.70; P < 0.001) and when adjusted by the subjects' age, gender, and obesity (adjusted ß = 1.16; 95% CI: 0.62-1.70; P < 0.001). Despite not measuring neutralizing activity, this study highlights the high frequency of these auto-Abs in the Peruvian population with a worse prognosis of COVID-19.

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.

Monkeypox in Latin America and the Caribbean: assessment of the first 100 days of the 2022 outbreak.

During the 2022 monkeypox (mpox) epidemic's first 100 days, 99 non-endemic countries, including 25 Latin American and Caribbean (LAC) countries, reported >64,000 cases. We aim to assess the cases' introduction, epidemiological profile, initial response, transmission dynamics, and main challenges ahead among LAC countries during the first 100 days of the mpox 2022 epidemic. We used mixed methods, including desktop research and open data analysis. The 2022 mpox epidemic has progressed consistently through LAC, with Brazil and Peru combining for over 80% of the confirmed LAC cases. Although Brazil reports the highest mpox case counts (n = 4472), Peru reports the highest incidence (41 confirmed cases per 1 million inhabitants). Initially, LAC missed the opportunity to focus on the high-risk population, including the people living with HIV (PLHIV) and gay, bisexual, and men who have sex with men (GBMSM). Moreover, the main challenges ahead include stigmatization, vaccine inequity, barriers to accessing diagnostics, and complete isolation. Furthermore, we estimated that Colombia, Brazil, the United States, and Peru are the world frontrunners in mpox duplication time (estimated between 6.4 and 8.8) and effective reproductive number (estimated between 2.7 and 3.8). In addition, Brazil reported its first case of inverse zoonosis in a dog and Peru its first autochthonous MPXV lineage, B.1.6. LAC has become the epicenter of the 2022 mpox epidemic, with Brazil and Peru emerging as the new mpox hot zones. Therefore, LAC countries must join efforts to control this epidemic and overcome the challenges of vaccine inequity and stigmatization.

Femicides and Victim's age-Associated Factors in Peru.

Background. Femicides are an increasing social problem worldwide. In this study, we aim to describe the trend of femicides in the prepandemic decade and characterize the femicide victims and their perpetrators. Methods. We assessed the trend of femicides in Peru during 2010-2019 and performed a cross-sectional study to analyze the femicides reported in 2019 using open data. Results. We analyzed 166 femicides reported in 24/25 regions of Peru in 2019 and calculated a yearly incidence of 1.01 femicides per 100,000 women. This incidence level represents an increase of 38% compared to the mean annual incidence from 2010 to 2018 (0.74 femicides per 100,000 women). Most femicides occurred in urban areas (64%), through strangling/asphyxiation (25.9%), stabbing (23%), and shooting (16%). Most victims were mothers (61%) 30 years old or over (51%). Most perpetrators have had a partner history with their victims (69%), 30 years old or over (62%), employed (57%), and consumed enablers (51%). Our regression analysis observed that the victim's age was associated with the perpetrator's age and partner history. Conclusions. Femicides are endemic in Peru, and the main characteristics of the victims and their perpetrators offer opportunities for tackling this social problem in Peru and similar low- to middle-income countries.

Effects of hydrometeorological and other factors on SARS-CoV-2 reproduction number in three contiguous countries of tropical Andean South America: a spatiotemporally disaggregated time series analysis.

Background: The COVID-19 pandemic has caused societal disruption globally, and South America has been hit harder than other lower-income regions. This study modeled the effects of six weather variables on district-level SARS-CoV-2 reproduction numbers (Rt ) in three contiguous countries of tropical Andean South America (Colombia, Ecuador, and Peru), adjusting for environmental, policy, healthcare infrastructural and other factors. Methods: Daily time-series data on SARS-CoV-2 infections were sourced from the health authorities of the three countries at the smallest available administrative level. Rt values were calculated and merged by date and unit ID with variables from a unified COVID-19 dataset and other publicly available sources for May-December, 2020. Generalized additive models were fitted. Findings: Relative humidity and solar radiation were inversely associated with SARS-CoV-2 Rt . Days with radiation above 1000 kJ/m2 saw a 1.3% reduction in Rt , and those with humidity above 50% recorded a 0.9% reduction in Rt . Transmission was highest in densely populated districts, and lowest in districts with poor healthcare access and on days with lowest population mobility. Wind speed, temperature, region, aggregate government policy response, and population age structure had little impact. The fully adjusted model explained 4.3% of Rt variance. Interpretation: Dry atmospheric conditions of low humidity increase district-level SARS-CoV-2 reproduction numbers, while higher levels of solar radiation decrease district-level SARS-CoV-2 reproduction numbers - effects that are comparable in magnitude to population factors like lockdown compliance. Weather monitoring could be incorporated into disease surveillance and early warning systems in conjunction with more established risk indicators and surveillance measures. Funding: NASA's Group on Earth Observations Work Programme (16-GEO16-0047).

Características espacio temporales de la trasmisión de la malaria en la región Loreto entre los años 2000 y 2019

Introducción: La eliminación de la malaria es la solución definitiva para evitar que la creciente resistencia a los medicamentos e insecticidas amenace los avances alcanzados en la lucha contra la malaria desde comienzos del siglo XXI. Objetivo: Analizar las características espacio temporales de la trasmisión de la malaria en Loreto. Método: Se realizó un estudio de tipo series de tiempo y se analizó la incidencia semanal de malaria en Loreto en los últimos 20 años (2000-2019) utilizando los datos del Sistema de Vigilancia Epidemiológica del Ministerio de Salud. Con esta información se modeló la incidencia semanal de malaria reportada por las unidades de vigilancia epidemiológica de Loreto y se determinaron sus características espacio temporales a nivel macro y microregional. Adicionalmente se caracterizaron las zonas "calientes" así como su estabilidad en el tiempo. Resultados: Durante los últimos 20 años observamos que Loreto tuvo un patrón de trasmisión estacional de la malaria, de intensidad moderada y zonas de trasmisión difusa, Adicionalmente, se observó que las tres redes de salud más "calientes" consistentemente fueron Maynas Ciudad, Loreto y Datem del Marañón, y que cada de estas redes exhibieron diferentes zonas calientes micro regionales de alta estabilidad temporal durante los altibajos estacionales de la malaria. Conclusiones: Loreto es una región receptiva para malaria cuya trasmisión se caracteriza por un patrón estacional, de intensidad moderada, con zonas de trasmisión difusa y presencia de focos activos de elevada trasmisión (zonas calientes macro y micro regionales) de alta estabilidad temporal.

Introduction: The elimination of malaria is the definitive solution to prevent the growing resistance to drugs and insecticides from threatening the progress made since the beginning of the 21st century. Objective: To analyze the spatio-temporal characteristics of malaria transmission in the Loreto region. Methods: We carried out a time series study, and the weekly incidence of malaria in Loreto in the last 20 years (2000-2019) was analyzed using data from the Epidemiological Surveillance System of the Ministry of Health. With this information, we modeled the weekly incidence of malaria across the Loreto surveillance reporting units and determine its spatio-temporal characteristics at the macro and micro-regional levels. Additionally, we characterized the "hot zones" and their stability over time. Results: During the last 20 years, we observed that Loreto has a seasonal malaria transmission, of moderate intensity, with different areas of diffuse transmission, Additionally, we observed that the three "hottest" health networks were, consistently, Maynas Ciudad, Loreto, and Datem del Marañón, with each of them also exhibiting different microregional hot zones of high temporal stability during its seasonal ups and downs. Conclusions: Loreto is a receptive region for malaria whose transmission is characterized by a seasonal pattern, of moderate intensity, with areas of diffuse transmission and the presence of active foci of high transmission (macro and micro-regional hot zones) with high temporal stability.

Regional clustering and waves patterns due to COVID-19 by the index virus and the lambda/gamma, and delta/omicron SARS-CoV-2 variants in Peru.

Background: Coronavirus disease 2019 (COVID-19) impact varies substantially due to various factors, so it is critical to characterize its main differences to inform decision-makers about where to focus their interventions and differentiate mitigation strategies. Up to this date, little is known about the patterns and regional clustering of COVID-19 waves worldwide. Methods: We assessed the patterns and regional clustering of COVID-19 waves in Peru by using the weekly mortality rates for each of the 25 regions as an outcome of interest. We obtained the death counts from the National Informatics System of Deaths and population estimates from the National Registry of Identification and Civil Status. In addition, we characterized each wave according to its duration, peak, and mortality rates by age group and gender. Additionally, we used polynomial regression models to compare them graphically and performed a cluster analysis to identify regional patterns. Results: We estimated the average mortality rate at the first, second, and third waves at 13.01, 14.12, and 9.82 per 100,000 inhabitants, respectively, with higher mortality rates among elders and men. The patterns of each wave varied substantially in terms of duration, peak, impact, and wave shapes. Based on our clustering analysis, during the first wave caused by the index virus, the 25 regions of Peru presented six different wave patterns. However, the regions were clustered in two different wave patterns during the second and third, caused by alpha/lambda/delta and omicron. Conclusions: The propagation of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) variants behaved in Peru with varying wave patterns and regional clustering. During the COVID-19 pandemic, the weekly mortality rates followed different spatiotemporal patterns with solid clustering, which might help project the impact of future waves of COVID-19.

Recurrence of Urinary Tract Infections due to Escherichia coli and Its Association with Antimicrobial Resistance.

We analyzed the association between antibiotic resistance and recurrent urinary tract infection (rUTI) by Escherichia coli. Susceptibility levels to 14 antimicrobial agents and the presence of extended-spectrum ß-lactamases (ESBL) were established using MicroScan. Incidences of multidrug resistant (MDR), extensively drug resistant (XDR), and ESBL-producer isolates as well as rUTIs were estimated. The time to recurrence was established adjusted for number of antibiotic-resistant families and MDR as predictors of interest, respectively. Overall, 8,553 urinary tract infection (UTI) cases related to E. coli, including 963 rITU, were analyzed with levels of resistance >30% in all cases, except for amikacin, nitrofurantoin, and carbapenems. The incidence of rUTI was of 11.3%, being 46.5%, 24.3%, and 42.5% for MDR, XDR, and ESBLs, respectively. Bivariate analysis showed that rUTI was associated with age, gender, resistance to specific antimicrobials, MDR, and XDR. The number of antibiotic families tested as resistant, MDR, XDR, gender, and age were associated with time to recurrence when adjusted for number of antibiotic families, and MDR, gender, and age were related when adjusted for MDR. High rates of antibiotic resistance to the usual antibiotics was observed in E. coli causing UTI, with female sex, age, and antibiotic resistance being risk factors for the development of rUTI.

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.

Serie de Redacción Científica: Revisiones Sistemáticas / Scientific Writing Series: Systematic Review

Introducción:La revisión sistemática es la evaluación comprehensiva, reproducible, crítica y explícita de la mejor evidencia disponible en respuesta a una pregunta de investigación específica. Para conseguir ello las revisiones sistemáticas deben cubrir como mínimo los siguientes siete pasos: i) una pregunta de investigación específica y estructurada usando la técnica PICO; ii) criterios de elegibilidad de las evidencias; iii) una estrategia de búsqueda clara y reproducible; iv) selección de las evidencias y extracción de datos; v) análisis de sesgos; vi) síntesis de resultados; y, vii) publicación. Si los datos son suficientes y homogéneos es factible incluir en las síntesis de resultados el metanálisis de los mismos. De esta manera las revisiones sistemáticas y metanálisis pueden generar conocimiento nuevo y fundamental para la toma de decisiones en el área clínica y en otras áreas

Introduction:The systematic review is the comprehensive, reproducible, critical, and detailed evaluation of the best available evidence in response to a specific research question. To achieve this, systematic reviews should cover at least the following seven steps: i) a detailed and structured research question using the PICO technique; ii) evidence eligibility criteria; iii) a precise and reproducible search strategy; iv) selection of evidence and data extraction; v) analysis of biases; vi) synthesis of results; and vii) publication. If the data are sufficient and homogeneous, it is feasible to include their meta-analysis to synthesize results. In this way, systematic reviews and meta-analyzes can generate new and fundamental knowledge for decision-making in the clinical and other areas

Tolerance to disinfectants (chlorhexidine and isopropanol) and its association with antibiotic resistance in clinically-related Klebsiella pneumoniae isolates.

Disinfectants play an essential role in controlling the dissemination of bacteria in health care settings, but it may also contribute to the selection of antibiotic resistance bacteria. This study looked at Klebsiella pneumoniae isolates collected from three hospitals in Lima, Peru, in order to evaluate: their susceptibility to chlorhexidine [CHG] and isopropanol [ISP]), and their association with antimicrobial susceptibility. We analyzed 59 K. pneumoniae isolates and assessed their CHG and ISP susceptibility by minimum inhibitory concentrations (MICs). Additionally, we performed a regression analysis to assess the association between disinfectant tolerance and antibiotic resistance (measured by the disc diffusion method), colistin resistance (by microdilution), carbapenemases presence (by polymerase chain reaction [PCR]), and clonal relationships (by pulsed-field gel electrophoresis [PFGE]). Eleven K. pneumoniae strains were isolated from fomites, and 48 strains from clinical samples. The MIC range of these isolates was 8-128 µg/ml for CHG and 16-256 mg/ml for ISP. We found that resistance to trimethoprim/sulfamethoxazole (TMP/SMX) was the main factor associated with CHG log2 MIC (ß = 0.65; 95%CI: 0.03, 1.27; R2 = 0.07). In the case of ISP, the log2(MIC) was associated with the institution of origin, showing lower ISP log2(MIC) in fomites compared to clinical samples(ß = -0.77; 95%CI: -1.54, -0.01; R2 = 0.08). Resistance to CHG and ISP among K. pneumoniae isolates found in Peruvian hospitals seems to be elevated and highly variable. Further studies are needed to confirm our results and implement actionable interventions if necessary.

Serie de Redacción Científica: Revisiones Sistemáticas / Scientific Writing Series: Systematic Review

RESUMEN Introducción: La revisión sistemática es la evaluación comprehensiva, reproducible, crítica y explícita de la mejor evidencia disponible en respuesta a una pregunta de investigación específica. Para conseguir ello las revisiones sistemáticas deben cubrir como mínimo los siguientes siete pasos: i) una pregunta de investigación específica y estructurada usando la técnica PICO; ii) criterios de elegibilidad de las evidencias; iii) una estrategia de búsqueda clara y reproducible; iv) selección de las evidencias y extracción de datos; v) análisis de sesgos; vi) síntesis de resultados; y, vii) publicación. Si los datos son suficientes y homogéneos es factible incluir en las síntesis de resultados el metanálisis de los mismos. De esta manera las revisiones sistemáticas y metanálisis pueden generar conocimiento nuevo y fundamental para la toma de decisiones en el área clínica y en otras áreas

ABSTRACT Introduction: The systematic review is the comprehensive, reproducible, critical, and detailed evaluation of the best available evidence in response to a specific research question. To achieve this, systematic reviews should cover at least the following seven steps: i) a detailed and structured research question using the PICO technique; ii) evidence eligibility criteria; iii) a precise and reproducible search strategy; iv) selection of evidence and data extraction; v) analysis of biases; vi) synthesis of results; and vii) publication. If the data are sufficient and homogeneous, it is feasible to include their meta-analysis to synthesize results. In this way, systematic reviews and meta-analyzes can generate new and fundamental knowledge for decision-making in the clinical and other areas.

Multidrug resistance bacteremia in neonates and its association with late-onset sepsis and Coagulase-negative Staphylococci.

INTRODUCTION: This study aimed to assess the association between multidrug resistance (MDR) and late-onset sepsis (LOS) among newborns with bloodstream infection (BSI). METHODOLOGY: In this cross-sectional study, we routinely tested every newborn with a presumptive diagnosis of sepsis admitted to the largest reference maternity hospital in Lima, Peru for BSI over an 18-month period. We tested every isolate for MDR by using the disk-diffusion method and assessed its associated factors by using a robust Poisson regression analysis with a particular focus on its association with LOS (vs. early-onset sepsis, EOS). RESULTS: We analyzed a total of 489 subjects, including 340 (69%) newborns with LOS, and estimated an MDR rate of 80% (95% confidence interval, CI: 76%-83%), which was significantly higher (p-value < 0.001) among LOS (85%; 95% CI: 81%-89%) than EOS cases (67%; 95% CI: 59%-75%). The primary isolate was coagulase-negative Staphylococci (CoNS) (60%), which exhibited a limited subset of antibiotic MDR patterns, most of which were characterized by their resistance to cefoxitin, gentamicin, and clindamycin and levofloxacin. Overall, the prevalence of MDR was higher among LOS compared to EOS cases (adjusted prevalence ratio [aPR] = 1.28; 95% CI: 1.14-1.45), and among BSI due to CoNS compared to other bacteria (Apr = 1.10; 95% CI: 1.01-1.20). CONCLUSIONS: MDR among newborns with sepsis is exceptionally high, being even higher among those with LOS than newborns with EOS, and among those infected with CoNS compared to other bacteria. Furthermore, CoNS exhibited a limited subset of MDR patterns, which could be used to guide therapeutic decisions.

Multidrug resistance and its association with Enterobacteriales and age among pregnant Peruvian women with- bacteremia.

INTRODUCTION: This study aimed to assess the prevalence of multidrug resistance (MDR) and its associated factors among pregnant Peruvian women with bacteremia. METHODOLOGY: In an 18-month cross-sectional study, all pregnant women were routinely tested with a presumptive diagnosis of sepsis admitted to the largest reference maternity hospital (Instituto Nacional Materno Perinatal) in Lima, Peru for bacteremia. Every isolate was tested for antimicrobial susceptibility as defined by the Institute of Clinical and Laboratory Standards (CLSI). Additionally, associated factors were assessed with MDR and the number of resistant antimicrobial categories using robust Poisson regression models with link log, especially focused on its association with age and bacterial families or species. RESULTS: A total of 236 blood cultures of pregnant women (33.4 ± 11.4 years old) was analyzed. The prevalence of MDR was 70% (95% confidence interval [CI]: 64%-76%). The main etiological agent was Escherichia coli (65%), showing an MDR rate of 74% (68%-81%). Overall, we observed that the MDR rate was associated with Enterobacteriales (adjusted prevalence rate, (aPR) = 1.29; 95% CI: 1.03-1.61) and age 35 or older (PR = 1.18; 95% CI: 1.01-1.39). However, the number of resistant antimicrobial categories was associated with Enterobacteriales (aPR = 1.44; 95% CI: 1.25-1.67) and hospital-acquired infections (PR = 0.81; 95% CI: 1.01-1.39). CONCLUSIONS: The prevalence of MDR among pregnant women with sepsis was alarmingly high, being even higher among women age 35 or older and among those with hospital-acquired infections.

Publication and associated factors of clinical trials registered in Peru.

OBJECTIVE: We aim to determine the percentage of publication and its associated factors of clinical trials (CTs) registered in Peru. METHODS: Using a cross-sectional study design, we assessed CTs registered at the CT's Peruvian Registry (REPEC) during the 2011-2016 period, and evaluated its percentage of publication and associated factors. We used a bibliographic search algorithm to determine if the CTs were published and assessed the associated factors by using a Cox regression to estimate the adjusted hazard ratios (aHR) as the magnitude of association of interest. RESULTS: We analyzed 228 CTs, of which 63% were published. The regression analysis identified the year of registration (aHR 2012 = 1.15 [0.58-2.27]; aHR 2013 = 0.45 [0.21-0.95]; aHR 2014 = 0.89 [0.43-1.82]; aHR 2015-2016 = 0.16 [0.05-0.58]), total number of participants (aHR = 1.12; 1.05-1.18), and phase III-IV (aHR = 2.15; 0.1.16-4.03) as factors associated with the publication of the CTs. CONCLUSIONS: The percentage of publication of CTs executed in Peru is insufficient, and it increases the older the year of its registration in the REPEC, mayor of the number of participating countries, and if it is a phase III or IV study.

Serie de Redacción Científica: Estudio de Casos y Controles / Scientific Writing Series: Case-Control studies

Introducción: Un estudio de casos y controles es un estudio en el que se compara individuos que tuvieron un desenlace de interés o outcome (casos) versus individuos que no tuvieron dicho resultado (controles) con respecto a la exposición de interés, potencialmente un "factor de riesgo" o "factor de protección". El objetivo de un estudio de casos y controles es primariamente determinar si existe asociación entre una exposición (o varias) y un desenlace de interés. Esta asociación debe ser cuantificada y reportada como un odds ratio o razón de momios teniendo en cuenta sus fortalezas y limitaciones. En general, este tipo de estudios ofrece como ventajas su relativo bajo costo y rapidez con la que es posible realizarlos. Sin embargo, no son idóneos si lo que se quiere investigar son desenlaces de interés frecuente o con periodos de latencia largos. En el presente artículo se han revisado las principales consideraciones metodológicas del diseño de los estudios de casos y controles esperando con ello contribuir objeto de promover su correcta utilización e interpretación.

Introduction: A case-control study is a study comparing individuals who had an outcome of interest (cases) versus individuals who had no such outcome (controls) with respect to the exposure of interest, potentially a "risk factor "or" protection factor." The objective of a case-control study is primarily to determine if there is an association between one exposure (or several) and an outcome of interest. This association must be quantified and reported as an odds ratio or odds ratio taking into account its strengths and limitations. In general, this type of study offers as advantages its relatively low cost and speed with which it is possible to carry them out. However, they are not ideal if what you want to investigate are frequent outcomes or with long latency periods. In this article, the primary methodological considerations of the design of case-control studies have been reviewed, hoping thereby to contribute to promoting their correct use and interpretation.

Metodologías Cuantitativas 2: Sesgo de confusión y cómo controlar un confusor / Quantitative Methodologies 2: Confusion bias and how to control a confounding factor

Identificar el sesgo de confusión y cómo controlarlo es uno de los desafíos metodológicos más importantes en el diseño de estudios que buscan identificar la causalidad. Este sesgo está presente en cualquier análisis de la asociación entre una exposición y un resultado de interés, una asociación que puede estar sesgada o no por una tercera variable llamada confusor. Podemos diagnosticar un confusor en todos los casos en los que este crea una asociación espuria entre una variable de exposición o variable independiente y la variable de resultado o variable dependiente. Para controlar el sesgo de confusión, podemos usar diferentes métodos. Estos incluyen aquellas técnicas aplicadas en el diseño del estudio, tales como restricción, aleatorización y coincidencia, y aquellas técnicas empleadas en el análisis de datos, como la estratificación, el análisis multivariado, la estandarización, los puntajes de propensión, el análisis de sensibilidad y el inverso ponderación de probabilidad. En esta revisión, analizamos cómo identificar una variable de confusión y las principales técnicas para controlar el sesgo de confusión.

Addressing confounding bias is one of the challenges when conducting causality studies. This occurs when we report a causal association between an exposure and an outcome, when in fact it could be result of the effect of a third factor called confounding variable. That is, when a confounder variable creates a spurious relationship between the exposure or independent variable and the outcome of interest or dependent variable. By knowing the confounding variables and their association with the exposure of interest, the confounding bias could be controlled. To control for confounding bias, we can use different methods. These include techniques applied in study design, such as restriction, randomization, and coincidence, and techniques used in data analysis, such as stratification, multivariate analysis, standardization, propensity scores, analysis sensitivity and the inverse probability weighting. In this review, we discuss how to identify a confounding variable and the main techniques for controlling for confounding bias.

Association between the proportion of Plasmodium falciparum and Plasmodium vivax infections detected by passive surveillance and the magnitude of the asymptomatic reservoir in the community: a pooled analysis of paired health facility and community data.

BACKGROUND: Passively collected malaria case data are the foundation for public health decision making. However, because of population-level immunity, infections might not always be sufficiently symptomatic to prompt individuals to seek care. Understanding the proportion of all Plasmodium spp infections expected to be detected by the health system becomes particularly paramount in elimination settings. The aim of this study was to determine the association between the proportion of infections detected and transmission intensity for Plasmodium falciparum and Plasmodium vivax in several global endemic settings. METHODS: The proportion of infections detected in routine malaria data, P(Detect), was derived from paired household cross-sectional survey and routinely collected malaria data within health facilities. P(Detect) was estimated using a Bayesian model in 431 clusters spanning the Americas, Africa, and Asia. The association between P(Detect) and malaria prevalence was assessed using log-linear regression models. Changes in P(Detect) over time were evaluated using data from 13 timepoints over 2 years from The Gambia. FINDINGS: The median estimated P(Detect) across all clusters was 12·5% (IQR 5·3-25·0) for P falciparum and 10·1% (5·0-18·3) for P vivax and decreased as the estimated log-PCR community prevalence increased (adjusted odds ratio [OR] for P falciparum 0·63, 95% CI 0·57-0·69; adjusted OR for P vivax 0·52, 0·47-0·57). Factors associated with increasing P(Detect) included smaller catchment population size, high transmission season, improved care-seeking behaviour by infected individuals, and recent increases (within the previous year) in transmission intensity. INTERPRETATION: The proportion of all infections detected within health systems increases once transmission intensity is sufficiently low. The likely explanation for P falciparum is that reduced exposure to infection leads to lower levels of protective immunity in the population, increasing the likelihood that infected individuals will become symptomatic and seek care. These factors might also be true for P vivax but a better understanding of the transmission biology is needed to attribute likely reasons for the observed trend. In low transmission and pre-elimination settings, enhancing access to care and improvements in care-seeking behaviour of infected individuals will lead to an increased proportion of infections detected in the community and might contribute to accelerating the interruption of transmission. FUNDING: Wellcome Trust.

Serie de Redacción Científica: Estudios Trasversales / Scientific Writing Series: Cross-Sectional studies

Los estudios transversales se caracterizan por la medición simultánea de la exposición y el outcome de interés. Son el diseño idóneo para estimar prevalencias, analizar la precisión diagnóstica de una prueba y validar instrumentos, para lo cual es esencial controlar los sesgos de información, selección y confusión ya sea por diseño o por análisis. Asimismo, es crucial escoger la medida de asociación idónea para cada outcome de interés, llámese el odds ratio para eventos raros y la razón de prevalencias para los eventos frecuentes. Finalmente, para su redacción y publicación se recomienda revisar las guías STROBE y STARD

Cross-sectional studies are characterized by the simultaneous measurement of exposure and the outcome of interest. They are the ideal design to estimate prevalence, analyze the diagnostic accuracy of a test and validate instruments, for which it is essential to control information bias, selection, and confusion either by design or by analysis. It is also crucial to choose the appropriate association measure for each outcome of interest, call the odds ratio for rare events, and the prevalence ratio for frequent events. Finally, for its writing and publication, it is recommended to review the STROBE and STARD guidelines

Metodologías cuantitativas: Cálculo del tamaño de muestra con STATA y R / Quantitative methods: Sample size calculation with STATA and R

El cálculo de tamaño de muestra es un aspecto esencial del diseño de estudios cuantitativos. Un adecuado tamaño de muestra nos permite determinar cuál es la mínima cantidad de participantes necesarios para probar nuestra hipótesis de interés. De esta manera, podemos reducir costos, maximizar el uso de nuestros recursos de investigación y garantizar la factibilidad del estudio. Contradictoriamente, a pesar de su relevancia muy pocos investigadores dominan esta habilidad. Esta revisión tiene por objeto revisar los conceptos básicos para realizar un cálculo de tamaño de muestra y compartir códigos de Stata y R específicamente diseñados para facilitar estos cálculos.

The calculation of sample size is an essential aspect of the design of quantitative studies. An adequate sample size allows us to determine the minimum number of participants necessary to test our hypothesis of interest. Hence, we can reduce costs, maximize the use of our research resources and guarantee the feasibility of the study. Contradictorily, despite its relevance, very few researchers dominate this skill. This review aims to review the basics of sample size calculation and share Stata and R codes specifically designed to facilitate these calculations.