Desempeño de la definición de caso sospechoso de influenza antes y durante la pandemia por COVID-19 / Performance of the case definition of suspected influenza before and during the COVID-19 pandemic

Objetivos Este estudio tuvo como objetivo evaluar el desempeño, antes y durante la pandemia de la COVID-19, de la definición de caso de sospecha de influenza en la vigilancia comunitaria en México. Métodos Se llevó a cabo un análisis transversal de un estudio de cohorte y, con el fin de confirmar o descartar la infección por virus influenza, se analizaron los casos que cumplían con los criterios de caso sospechoso (n = 20.511) y con evidencia concluyente de laboratorio (reacción cuantitativa en cadena de la polimerasa en tiempo real). Resultados Se documentaron una alta sensibilidad y una discreta especificidad, que posteriormente disminuyó, así como su precisión diagnóstica, durante el brote de la COVID-19. Sin embargo, no se observaron diferencias en el área bajo la curva de características operativas del receptor entre los períodos analizados. Conclusión La definición de caso evaluada sigue siendo una alternativa rentable para identificar a los pacientes que pueden beneficiarse de los medicamentos antivirales específicos contra la influenza, incluso durante el brote mundial de COVID-19 (AU)

Objective This study aimed to evaluate the performance, before and during the COVID-19 pandemic, of the case definition of suspected influenza used in community surveillance in Mexico. Methods A cross-sectional analysis of a cohort study was perfomed and cases that met the suspected case criteria (n = 20,511) and that had laboratory-conclusive evidence (quantitative real-time polymerase chain reaction) to confirm or discard influenza virus infection, were analysed. Results A high sensitivity and modest specificity were documented, which later decreased during the COVID-19 outbreak, as well as its diagnostic accuracy. However, no significant differences were observed in the area under the receiver operating characteristics curve among the analysed periods. Conclusion The evaluated case definition remains to be a cost-effective alternative for identifying patients who may benefit from influenza-specific antiviral drugs, even during the global COVID-19 outbreak (AU)

Performance of the case definition of suspected influenza before and during the COVID-19 pandemic.

OBJECTIVE: This study aimed to evaluate the performance, before and during the COVID-19 pandemic, of the case definition of suspected influenza used in community surveillance in Mexico. METHODS: A cross-sectional analysis of a cohort study was performed and cases that met the suspected case criteria (n = 20,511) and that had laboratory-conclusive evidence (quantitative real-time polymerase chain reaction) to confirm or discard influenza virus infection were analysed. RESULTS: A high sensitivity and modest specificity were documented, which later decreased during the COVID-19 outbreak, as well as its diagnostic accuracy. However, no significant differences were observed in the area under the receiver operating characteristics curve among the analysed periods. CONCLUSIONS: The evaluated case definition remains to be a cost-effective alternative for identifying patients who may benefit from influenza-specific antiviral drugs, even during the global COVID-19 outbreak.

Survival in adult pneumonia inpatients fulfilling suspected COVID-19 criteria and baseline negative RT-qPCR.

OBJECTIVES: The objective of this study was to evaluate the survival experience of suspicion COVID-19 hospitalized patients with pneumonia and negative baseline reverse-transcription quantitative polymerase chain reaction (RT-qPCR) test results. STUDY DESIGN: We conducted a nationwide retrospective cohort study in Mexico. METHODS: Adult pneumonia inpatients fulfilling suspected COVID-19 criteria, and hospital entry from March to August 2020, were enrolled. The Kaplan-Meier method was to use to compare survival estimates among patients with negative RT-qPCR nasopharyngeal or oropharyngeal swabs and those with a baseline positive test. RESULTS: Data from 64,624 individuals fulfilling suspected COVID-19 criteria were analyzed and 1.6% of them had negative RT-qPCR tests. The overall mortality rate was higher among laboratory-positive patients (48.5% vs. 34.2%, P < 0.001) and, at any given threshold, the survival estimates were higher among RT-qPCR-negative pneumonia inpatients. CONCLUSIONS: The pathogenic mechanism of COVID-19 remains poorly understood and suspected cases with pneumonia and negative laboratory results represent a major challenge for healthcare systems. Our findings suggest that RT-qPCR-negative inpatients may have an improved disease prognosis, but the in-hospital mortality was still high among them. However, further research is needed to clarify the clinical and epidemiological implications of our results.

Predictors of severe symptomatic laboratory-confirmed SARS-CoV-2 reinfection.

OBJECTIVE: The aim of the study was to evaluate factors predicting severe symptomatic laboratory-confirmed (via Reverse transcription polymerase chain reaction, RT-PCR polymerase chain reaction) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. STUDY DESIGN: This is a nationwide retrospective cohort study that was conducted in Mexico. METHODS: Data from 258 reinfection cases (at least 28 days between both episodes onset) were analyzed. We used risk ratios (RRs) and 95% confidence intervals (CIs) to evaluate predictors of severe (dyspnea requiring hospital admission) secondary SARS-CoV-2 infection. RESULTS: The risk of severe disease was 14.7%, and the observed overall fatality rate was 4.3%. Patients with more serious primary disease were more likely to develop severe symptoms (39.5% vs. 5.5%, P < 0.001) during reinfection. In multiple analysis, factors associated with an increased risk of severe symptomatic SARS-CoV-2 reinfection were increasing age (RRper year = 1.007, 95% CI = 1.003-1.010), comorbidities (namely, obesity [RR = 1.12, 95% CI = 1.01-1.24], asthma [RR = 1.26, 95% CI = 1.06-1.50], type 2 diabetes mellitus [RR = 1.22, 95% CI = 1.07-1.38]), and previous severe laboratory-confirmed coronavirus disease 2019 (RR = 1.20, 95% CI = 1.03-1.39). CONCLUSIONS: To the best of our knowledge, this is the first study evaluating disease outcomes in a large set of laboratory-positive cases of symptomatic SARS-CoV-2 reinfection, and factors associated with illness severity were characterized. Our results may contribute to the current knowledge of SARS-CoV-2 pathogenicity and to identify populations at increased risk of a poorer outcome after reinfection.

Survival in adult inpatients with COVID-19.

BACKGROUND: The mortality of the coronavirus disease 2019 (COVID-19) pandemic is high, and data regarding its prognosis are scarce. We aimed to assess the survival experience and determining factors in adult inpatients with laboratory-confirmed COVID-19. METHODS: We conducted a nationwide and retrospective cohort study. Data from 66,123 individuals were analyzed using the Kaplan-Meier method, and a multivariate Cox proportional hazard regression model was fitted. RESULTS: The 7-day survival was 72.2% and went to 47.6%, 35.0%, and 23.9% on days 15, 21, and 30 of hospital stay, respectively. In the multiple analysis, factors associated with an increased risk of dying were male gender, age, pneumonia at hospital admission, immunosuppression, and personal history of chronic non-communicable diseases. Reduced risk of a fatal outcome was observed among patients with asthma history. CONCLUSIONS: To the best of our knowledge, this is the largest study analyzing the survival probability in a large subset of Latin-American adults with COVID-19, in whom the disease burden has been high. Our results contribute to achieving a better understanding of disease evolution.

[Performance of the case definition of suspected influenza before and during the COVID-19 pandemic]. / Desempeño de la definición de caso sospechoso de influenza antes y durante la pandemia por COVID-19.

OBJECTIVE: This study aimed to evaluate the performance, before and during the COVID-19 pandemic, of the case definition of suspected influenza used in community surveillance in Mexico. METHODS: A cross-sectional analysis of a cohort study was perfomed and cases that met the suspected case criteria (n = 20,511) and that had laboratory-conclusive evidence (quantitative real-time polymerase chain reaction) to confirm or discard influenza virus infection, were analysed. RESULTS: A high sensitivity and modest specificity were documented, which later decreased during the COVID-19 outbreak, as well as its diagnostic accuracy. However, no significant differences were observed in the area under the receiver operating characteristics curve among the analysed periods. CONCLUSION: The evaluated case definition remains to be a cost-effective alternative for identifying patients who may benefit from influenza-specific antiviral drugs, even during the global COVID-19 outbreak.

Predictors of laboratory-positive COVID-19 in children and teenagers.

OBJECTIVE: The aim of the study was to identify factors predicting laboratory-positive coronavirus disease 2019 (COVID-19) in pediatric patients with acute respiratory symptoms. STUDY DESIGN: We conducted a cross-sectional analysis of a prospective cohort study. METHODS: Data from 1849 individuals were analyzed. COVID-19 was confirmed (reverse transcription-quantitative polymerase chain reaction) in 15.9% of patients, and factors predicting a positive test result were evaluated through prevalence odds ratios and 95% confidence intervals. RESULTS: Increasing age, personal history of obesity, and household contact with a case were found to be associated, in the multiple regression model, with increased odds of a positive test result. Young patients residing in areas with higher population sizes, as well as those with severe respiratory symptoms, were less likely to be laboratory confirmed. CONCLUSIONS: Early identification and isolation of children and teenagers with suggestive symptoms of COVID-19 is important to limit viral spread. We identified several factors predicting the laboratory test result. Our findings are relevant from a public health policy perspective, particularly after the restart of in-person academic activities.

Desempeño de la definición de caso sospechoso de influenza antes y durante la pandemia por COVID-19 / Performance of the case definition of suspected influenza before and during the COVID-19 pandemic

OBJETIVOS: Este estudio tuvo como objetivo evaluar el desempeño, antes y durante la pandemia de la COVID-19, de la definición de caso de sospecha de influenza en la vigilancia comunitaria en México. MÉTODOS: Se llevó a cabo un análisis transversal de un estudio de cohorte y, con el fin de confirmar o descartar la infección por virus influenza, se analizaron los casos que cumplían con los criterios de caso sospechoso (n = 20.511) y con evidencia concluyente de laboratorio (reacción cuantitativa en cadena de la polimerasa en tiempo real). RESULTADOS: Se documentaron una alta sensibilidad y una discreta especificidad, que posteriormente disminuyó, así como su precisión diagnóstica, durante el brote de la COVID-19. Sin embargo, no se observaron diferencias en el área bajo la curva de características operativas del receptor entre los períodos analizados. CONCLUSIÓN: La definición de caso evaluada sigue siendo una alternativa rentable para identificar a los pacientes que pueden beneficiarse de los medicamentos antivirales específicos contra la influenza, incluso durante el brote mundial de COVID-19

OBJECTIVE: This study aimed to evaluate the performance, before and during the COVID-19 pandemic, of the case definition of suspected influenza used in community surveillance in Mexico. METHODS: A cross-sectional analysis of a cohort study took place and cases fulfilling the suspected case criteria (n = 20,511), and with laboratory-conclusive evidence (quantitative real-time polymerase chain reaction) to confirm or discard influenza virus infection, were analyzed. RESULTS: A high sensitivity and modest specificity were documented, and this later decreased during the COVID-19 outbreak, as well as its diagnostic accuracy. However, no significant differences were observed in the area under the receiver operating characteristics among the analyzed periods. CONCLUSION: The evaluated case definition remains to be a cost-effective alternative to identify patients who may benefit from influenza-specific antiviral drugs, even during the COVID-19 global outbreak

Measuring HIV vaccine efficacy.

Some HIV vaccine candidates have a potential VE I (vaccine efficacy for infectiousness) type effect, which tends to reduce the viral load and may reduce infectiousness of an infected individual. In general, the efficacy of this kind of vaccine is very difficult to assess because it requires information on contacts of vaccinated infected individuals, and current methods to estimate VE I rely on the time elapsed between infections of an individual and his/her sexual partner, thus making infection of the sexual partner necessary to assess the efficacy. To avoid behavioural changes that may affect the estimates, HIV status is kept undisclosed to participants, which raises many ethical questions. Here we present a method that allows immediate notification of HIV status to both members of a couple, reducing the risk of infection when one of them has not been infected and allowing immediate medical treatment. The method allows for estimation of any VE I and VE S (vaccine efficacy for susceptibility) effect, and it is robust to the most common situations found in these type of studies, namely: differential risk of participants, staggered enrollment and small sample sizes.

Educational campaign versus malathion spraying for the control of Aedes aegypti in Colima, Mexico.

OBJECTIVE: To evaluate the effect of an educational campaign for reducing the breeding places of Aedes aegypti, the principal vector of dengue; and to compare its effects with the ones obtained by spraying of malathion at ultralow volume. DESIGN: Randomised community trial. SETTING: Colima city, in the State of Colima, Mexico. PARTICIPANTS: Householders of 187 houses, randomly selected from the west sector of the city. DATA: In each house, an entomological survey was done, as well as one for knowledge, attitude and practices (KAP), before the intervention and six months after. The intervention consisted of educational campaign alone (47 houses); malathion spraying at ultra low volume alone (46 houses); both treatments simultaneously (49 houses) and no intervention, or control group (45 houses). MAIN RESULTS: The global average of the positive containers by house (C+/C) was reduced from 0.97 to 0.77. A two way analysis of variance showed that this reduction was more apparent in the houses that received educational campaign (F=8.4, p<0.005) with relation to the ones that received malathion spraying (F=0.38, p>0.5), while the combination of both treatments demonstrated a discrete negative interaction (F=6.52, p<0.05). These effects were independent of climatic changes and level of knowledge about dengue, as the KAP indicator did not show any significant changes in any group (F=1.14, p>0.1). CONCLUSION: The results indicated that the educational campaign reduced the A aegypti breeding places more effectively than the use of chemicals spraying, and that the combination of both treatments can reduce its efficiency, possibly because of the false expectancy of protection that spraying creates. The KAP surveys seemed to have very limited value in evaluating quantitatively the programmes of eradication of the dengue vector.

[Factors that modify the larval indices of Aedes aegypti in Colima, Mexico]. / Factores que modifican los índices larvarios de Aedes aegypti en Colima, México.

OBJECTIVE: In order to investigate the variables that could have the greatest impact on larval indices of Aedes aegypti, the main vector of dengue, a descriptive, longitudinal study was carried out in the city of Colima, which is located in the Mexican Pacific coastal state of the same name. METHODS: A total of 187 dwellings were inspected to determine the house index (HI) and the number of positive containers per house (C+/H), during the rainy season and the dry season. The following were recorded as independent variables: the air temperature, the season, the use of ultra low volume (ULV) spraying of malathion, the Premise Condition Index (PCI), and the score on a survey of knowledge, attitudes, and practices (KAP). RESULTS: Both the multivariate logistic regression and the multivariate lineal regression showed a reduction of HI and C+/H due to the effect of the dry season. Paradoxically, the temperature seemed to have a negative correlation with the larval indices, and this effect was more pronounced during the dry season. The PCI showed the most significant correlation with HI and C+/H, independently of the other variables. The ULV sprayings showed a small negative effect on the indices, while the KAP score did not indicate any association at all. CONCLUSIONS: Some conclusions that can be drawn from this study are as follows: higher temperatures can reduce the larval indices during the dry season, the PCI can be an adequate estimator of the Ae. aegypti infestation rate, ULV spraying reduces the number of larval breeding sites, and the KAP score has little association with the larval indices.

A note on the distribution of the number of vaccinated infected under non-random mixing conditions.

A common situation in vaccine efficacy (VE) estimation is dealing with non-randomly mixing populations, which may subject vaccinated and unvaccinated individuals to a different infection pressure. These conditions may lead to a bias in VE estimates. The derivation of the statistical distribution of the number of vaccinated and infected out of a sample of n infections in a VE trial is essential to develop estimates and their properties. For randomly mixing populations, it has been shown recently that this follows a hypergeometric distribution for 'all/nothing' vaccines, whereas it is a non-central hypergeometric distribution for 'leaky' ones. Here it is shown that these distributions still hold under non-random mixing conditions, provided that mixing preferences and contact rates are independent of vaccination status. These conditions are met when vaccine and placebo are randomized.

Urn models and vaccine efficacy estimation.

We derive the distribution of the number of infections among unvaccinated and vaccinated individuals for model 1 (leaky) and model 2 (all/nothing) vaccines, assuming random mixing of a homogeneous population. For all/nothing vaccines, we show that the distribution of the number of infected vaccinated individuals conditioning on n observed infections follows a hypergeometric distribution, and the vaccine efficacy estimate (VE) can be derived from the usual estimate of the total population size in a capture-recapture sampling program. For leaky vaccines, we show that the number of vaccinated infected follows a distribution that was first derived by Wallenius. We found that the current point estimates of VE for each model perform very well, but the urn model construction presented here provides a strong framework for estimation and hypothesis testing on the parameters, and can be applied when the available data are a sample of the population. Since the method does not require an underlying transmission model, it can be applied to estimate the VE for non-contagious diseases.

A basic result on the integral for birth-death Markov processes.

In this paper a regenerative argument is used to derive an expression for the expectation of the integral under the stochastic path of a birth-death Markov process up to extinction time as well as for the expected time to extinction. Some applications to classical-birth-death processes are given.

Threshold parameters and metapopulation persistence.

A method is presented to estimate the minimum viable metapopulation size based on the basic reproductive number R(0) and the expected time to extinction tau(E) for epidemiological models. We exemplify our approach with two simple deterministic metapopulation models of the patch occupancy type and then proceed to stochastic versions that permit the estimation of the minimum viable metapopulation size.