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La tuberculosis sigue siendo una epidemia mundial y en Chile no ha mostrado una tendencia descendente en los últimos años, con un aumento en los casos infantiles. En los niños, el diagnóstico es un reto debido a la baja carga bacilar y las características de las lesiones, que suelen ser cerradas. Métodos tradicionales como los cultivos, considerados anteriormente como el gold standard, con frecuencia arrojan resultados negativos. Sin embargo, los avances en pruebas moleculares han permitido un progreso significativo en la confirmación bacteriológica. Otras herramientas diagnósticas, como la prueba de tuberculina (PPD) y los ensayos de liberación de interferón gamma (IGRAs), tienen sensibilidades y especificidades variables, siendo útiles como pruebas complementarias. Las imágenes juegan un papel clave en la evaluación diagnóstica de tuberculosis pulmonar y extrapulmonar en pacientes pediátricos. Esta revisión aborda la epidemiología y el proceso diagnóstico de la tuberculosis infantil.

Tuberculosis remains a global epidemic, and in Chile, it has not shown a downward trend in recent years, with an increase in pediatric cases. Diagnosing tuberculosis in children presents challenges due to the low bacillary load and the closed nature of the lesions. Traditional methods like cultures, once considered the gold standard, often yield negative results. However, advances in molecular testing have significantly improved bacteriological confirmation. Other diagnostic tools, such as the tuberculin skin test (PPD) and interferon-gamma release assays (IGRAs), offer variable sensitivities and specificities and are useful as complementary tests. Imaging plays a critical role in the diagnostic evaluation of pulmonary and extrapulmonary tuberculosis in pediatric patients. This review addresses the epidemiology and diagnostic process of pediatric tuberculosis.

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Combination COVID-19/influenza rapid tests provide a way to quickly and accurately differentiate between the two infections. The goal of this economic evaluation was to assess the cost and health benefits of a combination COVID-19/influenza Rapid Diagnostic Test (RDT) vs. current standard-of-care in the Brazilian private healthcare setting. A dual decision tree model was developed to estimate the impact of rapid differentiation of COVID-19 and influenza in a hypothetical cohort of 1,000 adults with influenza-like illness in an ambulatory healthcare setting. The model compared the use of a combination COVID-19/influenza RDT to Brazil standard diagnostic practice of a COVID-19 RDT and presumptive influenza diagnosis. Different levels of influenza prevalence were modeled with co-infection estimated as a function of the COVID-19 prevalence. Outcomes included accuracy of diagnosis, antiviral prescriptions and healthcare resource use (hospital bed days and ICU occupancy). Depending on influenza prevalence, considering 1,000 patients with influenza-like illness, a combination RDT compared to standard practice was estimated to result in between 88 and 149 fewer missed diagnoses of influenza (including co-infection), 161 to 185 fewer cases of over-diagnosis of influenza; a 24 to 34% reduction in hospital bed days and a 16 to 26% reduction in ICU days. In the base case scenario (20% influenza, 5% COVID-19), the combination RDT was estimated to result in cohort cost savings of $99. Based upon a de novo economic model, this analysis indicates that use of a combination RDT could positively impact influenza antiviral prescriptions and lower healthcare resource use.

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Abstract Combination COVID-19/influenza rapid tests provide a way to quickly and accurately differentiate between the two infections. The goal of this economic evaluation was to assess the cost and health benefits of a combination COVID-19/influenza Rapid Diagnostic Test (RDT) vs. current standard-of-care in the Brazilian private healthcare setting. A dual decision tree model was developed to estimate the impact of rapid differentiation of COVID-19 and influenza in a hypothetical cohort of 1,000 adults with influenza-like illness in an ambulatory healthcare setting. The model compared the use of a combination COVID-19/influenza RDT to Brazil standard diagnostic practice of a COVID-19 RDT and presumptive influenza diagnosis. Different levels of influenza prevalence were modeled with co-infection estimated as a function of the COVID-19 prevalence. Outcomes included accuracy of diagnosis, antiviral prescriptions and healthcare resource use (hospital bed days and ICU occupancy). Depending on influenza prevalence, considering 1,000 patients with influenza-like illness, a combination RDT compared to standard practice was estimated to result in between 88 and 149 fewer missed diagnoses of influenza (including co-infection), 161 to 185 fewer cases of over-diagnosis of influenza; a 24 to 34% reduction in hospital bed days and a 16 to 26% reduction in ICU days. In the base case scenario (20% influenza, 5% COVID-19), the combination RDT was estimated to result in cohort cost savings of $99. Based upon a de novo economic model, this analysis indicates that use of a combination RDT could positively impact influenza antiviral prescriptions and lower healthcare resource use.

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BACKGROUND: Most anaemia studies focus on children and women of childbearing age. We assessed the frequency and main aetiologies of anaemia according to sociodemographic characteristics at the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a cohort of middle-aged adults. METHODS: The primary analyses included 15,051 participants aged 35-74 years with a valid blood cell count. We built logistic models to analyse the association between socioeconomic characteristics and anaemia diagnosis. We also described the main aetiologies in a subset (n = 209) of participants with anaemia. RESULTS: Anaemia was present in 3.0% (95% confidence interval [95%CI]: 2.6-3.4%) of men and 7.4% (95%CI: 6.9-8.0%) of women. The frequency of anaemia diagnosis was higher in women in all subgroups except for the oldest age stratum (65-74 years). The frequency of anaemia was particularly high in Blacks (6.0% and 15.5% in men and women, respectively). The most common causes of anaemia were iron deficiency (in women), chronic kidney disease, and chronic inflammation (in men). The frequency of unexplained anaemia was respectively 33.3% and 34.2% for men and women, and this condition was more frequent among participants of Black or Mixed races. CONCLUSIONS: Anaemia was associated with age, female sex, Black race, and low socioeconomic status. Unexplained anaemia was common and more frequent in individuals of Black and Mixed races. ELSA-Brasil follow-up data may provide further insight into the relevance of unexplained anaemia in this setting.

This study aims to assess the frequency, associated factors, and (in a subsample) the leading causes of anaemia in a large epidemiological study in 6 Brazilian state capitals. Our primary analyses included 15,051 participants aged 35­74 years. Anaemia was present in 3.0% of men and 7.4% of women. The frequency of anaemia diagnosis was higher in women in all subgroups except for the oldest age stratum (65­74 years). The frequency of anaemia was particularly high in Blacks (6.0% and 15.5% in men and women, respectively). The most common causes of anaemia were iron deficiency (in women), chronic kidney disease, and chronic inflammation (in men). Despite an extensive workout to determine the causes of anaemia, this condition remained unexplained in approximately one-third of cases. Unexplained anaemia was more frequent among participants of Black or Mixed races. Besides providing a clear epidemiological description of anaemia in this setting, our work also provides insight into the interpretation of current cutoffs for anaemia diagnosis.

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Human adenoviruses (HAdV) are one of the most important pathogens detected in acute respiratory diseases in pediatrics and immunocompromised patients. In 1953, Wallace Rowe described it for the first time in oropharyngeal lymphatic tissue. To date, more than 110 types of HAdV have been described, with different cellular tropisms. They can cause respiratory and gastrointestinal symptoms, even urinary tract inflammation, although most infections are asymptomatic. However, there is a population at risk that can develop serious and even lethal conditions. These viruses have a double-stranded DNA genome, 25-48 kbp, 90 nm in diameter, without a mantle, are stable in the environment, and resistant to fat-soluble detergents. Currently the diagnosis is made with lateral flow immunochromatography or molecular biology through a polymerase chain reaction. This review aimed to highlight the HAdV variability and the pandemic potential that a HAdV3 and 7 recombinant could have considering the aggressive outbreaks produced in health facilities. Herein, we described the characteristics of HAdV, from the infection to treatment, vaccine development, and the evaluation of the social determinants of health associated with HAdV, suggesting the necessary measures for future sanitary control to prevent disasters such as the SARS-CoV-2 pandemic, with an emphasis on the use of recombinant AdV vaccines to control other potential pandemics.

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Abstract Objective: To analyze the performance of the cystic fibrosis (CF) newborn screening (NBS) program over its first five years in a Brazilian northeastern state. Methods: A population-based study using a screening algorithm based on immunoreactive trypsinogen (IRT)/IRT. Data were retrieved from the state referral screening center registry. The program performance was evaluated using descriptive indicators such as the results of an active search, coverage, newborn's age at the time of blood sampling, the time between sample collection and its arrival at the laboratory, and the child's age at diagnosis of disease. Results: The public CF screening program covered 82.6% of the 1,017,576 births that occurred, with an accumulated five-year incidence of 1:20,767 live births. The median (25th-75th) age at diagnosis was 3.5 (2.3-7.3) months. The sampling before 7 days of life for the first IRT (IRT1) increased between 2013 and 2017 from 42.2 to 48.3%. Around 5% of IRT1 samples and 30% of the second samples were collected after 30 days of life. In the first and second stages of screening, 23.6% and 19.9% of the infants, respectively, were lost to follow-up. In both stages of screening, the samples were retained at the health units for a median (25th-75th) of 9.0 (7.0-13.0) days. Conclusions: The coverage by the CF-NBS program was satisfactory as compared to other Brazilian state rates and the percentage of IRT1 samples collected within the first week of life increased progressively. However, time of samples retention at the health units, inappropriate sampling, inherent methodological problems, and loss of follow-up need to improve.

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OBJECTIVE: To analyze the performance of the cystic fibrosis (CF) newborn screening (NBS) program over its first five years in a Brazilian northeastern state. METHOD: A population-based study using a screening algorithm based on immunoreactive trypsinogen (IRT)/IRT. Data were retrieved from the state referral screening center registry. The program performance was evaluated using descriptive indicators such as the results of an active search, coverage, newborn's age at the time of blood sampling, the time between sample collection and its arrival at the laboratory, and the child's age at diagnosis of disease. RESULTS: The public CF screening program covered 82.6% of the 1,017,576 births that occurred, with an accumulated five-year incidence of 1:20,767 live births. The median (25th-75th) age at diagnosis was 3.5 (2.3-7.3) months. The sampling before 7 days of life for the first IRT (IRT1) increased between 2013 and 2017 from 42.2 to 48.3%. Around 5% of IRT1 samples and 30% of the second samples were collected after 30 days of life. In the first and second stages of screening, 23.6% and 19.9% of the infants, respectively, were lost to follow-up. In both stages of screening, the samples were retained at the health units for a median (25th-75th) of 9.0 (7.0-13.0) days. CONCLUSIONS: The coverage by the CF-NBS program was satisfactory as compared to other Brazilian state rates and the percentage of IRT1 samples collected within the first week of life increased progressively. However, time of samples retention at the health units, inappropriate sampling, inherent methodological problems, and loss of follow-up need to improve.

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BACKGROUND: Lot Quality Assurance Sampling (LQAS), a tool used for monitoring health indicators in low resource settings resulting in "high" or "low" classifications, assumes that determination of the trait of interest is perfect. This is often not true for diagnostic tests, with imperfect sensitivity and specificity. Here, we develop Lot Quality Assurance Sampling for Imperfect Tests (LQAS-IMP) to address this issue and apply it to a COVID-19 serosurveillance study design in Haiti. METHODS: We first derive a modified procedure, LQAS-IMP, that accounts for the sensitivity and specificity of a diagnostic test to yield correct classification errors. We then apply the novel LQAS-IMP to design an LQAS system to classify prevalence of SARS-CoV-2 antibodies among healthcare workers at eleven Zanmia Lasante health facilities in Haiti. Finally, we show the performance of the LQAS-IMP procedure in a simulation study. RESULTS: We found that when an imperfect diagnostic test is used, the classification errors in the standard LQAS procedure are larger than specified. In the modified LQAS-IMP procedure, classification errors are consistent with the specified maximum classification error. We then utilized the LQAS-IMP procedure to define valid systems for sampling at eleven hospitals in Haiti. CONCLUSION: The LQAS-IMP procedure accounts for imperfect sensitivity and specificity in system design; if the accuracy of a test is known, the use of LQAS-IMP extends LQAS to applications for indicators that are based on laboratory tests, such as SARS-CoV-2 antibodies.

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Purpose of Review: Review international efforts to build a global public health initiative focused on toxoplasmosis with spillover benefits to save lives, sight, cognition and motor function benefiting maternal and child health. Recent Findings: Multiple countries' efforts to eliminate toxoplasmosis demonstrate progress and context for this review and new work. Summary: Problems with potential solutions proposed include accessibility of accurate, inexpensive diagnostic testing, pre-natal screening and facilitating tools, missed and delayed neonatal diagnosis, restricted access, high costs, delays in obtaining medicines emergently, delayed insurance pre-approvals and high medicare copays taking considerable physician time and effort, harmful shortcuts being taken in methods to prepare medicines in settings where access is restricted, reluctance to perform ventriculoperitoneal shunts promptly when needed without recognition of potential benefit, access to resources for care, especially for marginalized populations, and limited use of recent advances in management of neurologic and retinal disease which can lead to good outcomes. Supplementary Information: The online version contains supplementary material available at 10.1007/s40124-022-00268-x.

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Serological tests detect antibodies generated by infection or vaccination, and are indispensable tools along different phases of a pandemic, from early monitoring of pathogen spread up to seroepidemiological studies supporting immunization policies. This work discusses the development of an accurate and affordable COVID-19 antibody test, from production of a recombinant protein antigen up to test validation and economic analysis. We first developed a cost-effective, scalable technology to produce SARS-COV-2 spike protein and then used this antigen to develop an enzyme-linked immunosorbent assay (ELISA). A receiver operator characteristic (ROC) analysis allowed optimizing the cut-off and confirmed the high accuracy of the test: 98.6% specificity and 95% sensitivity for 11+ days after symptoms onset. We further showed that dried blood spots collected by finger pricking on simple test strips could replace conventional plasma/serum samples. A cost estimate was performed and revealed a final retail price in the range of one US dollar, reflecting the low cost of the ELISA test platform and the elimination of the need for venous blood sampling and refrigerated sample handling in clinical laboratories. The presented workflow can be completed in 4 months from first antigen expression to final test validation. It can be applied to other pathogens and in future pandemics, facilitating reliable and affordable seroepidemiological surveillance also in remote areas and in low-income countries.

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ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Saliva in the Diagnosis of COVID-19: A Review and New Research Directions. Fernandes LL, Pacheco VB, Borges L et al. Journal of Dental Research. 2020. https://doi.org/10.1177/0022034520960070. SOURCE OF FUNDING: Hospital Israelita Albert Einstein and Universidade Cruzeiro do Sul, São Paulo, Brazil. The authors have no actual or potential conflicts of interest. TYPE OF STUDY/DESIGN: Systematic review.

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ABSTRACT COVID-19 pandemic is a rapidly spreading virus that is changing the World and the way doctors are practicing medicine. The huge number of patients searching for medical care and needing intensive care beds led the health care system to a burnout status especially in places where the care system was already overloaded. In this setting, and also due to the absence of a specific treatment for the disease, health authorities had to opt for recommending or imposing social distancing to relieve the health system and reduce deaths. All other medical specialties nondirectly related to the treatment of COVID-19 had to interrupt or strongly reduce their activities in order to give room to seriously ill patients, since no one knows so far the real extent of the virus damage on human body and the consequences of doing non deferrable procedures in this pandemic era. Despite not been a urological disease, the urologist needs to be updated on how to deal with these patients and how to take care of himself and of the medical team he works with. The aim of this article is to review briefly some practical aspects of COVID-19 and its implications in the urological practice in our country.

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Background: SARS-CoV-2 virus changed society's behaviour. Population was advised to reduce unnecessary heath care use to accommodate urgent cases and daily increase of COVID-19 patients. Health care facilities faced huge challenges, having to readjust their response to preserve good quality of care. In Portugal, a significant reduction in the number of admissions to the Emergency Department (ED) was reported all over the country, however the impact on the dynamics of undeferrable surgery remains to be reported. This study compares the volume and characteristics of urgent/emergency surgery during the 2020 COVID-19 pandemic with the homologous period in 2019, chronologically illustrating the national evolution of new COVID-19 cases and the social and hospital containment response. Methods: A retrospective observational study was conducted in a tertiary hospital center located in the most affected region by COVID-19 in Portugal. Medical records of patients who underwent urgent/emergency surgery between March 1st and May 2nd of both 2020 and 2019 were examined and the volume of surgeries were compared. Also, daily national updates from Portuguese Directorate-General for Health were analysed. Results: During the COVID-19 pandemic approximately 30% less patients underwent urgent/emergency surgery (99%CI = 0.18-0.61, p < 0.001). Waiting time for surgery showed no difference between both years (p = 0.068), but patients who did surgery during the 2020 pandemic had higher mortality rates than the ones who did it in 2019 (11.4% in 2020 and 5.9% in 2019, p = 0.001). Reduction in surgery volume was correlated with the increasing number of infected cases nationally. Conclusion: This study demonstrates decreasing numbers of urgent/emergency procedures during the COVID-19 pandemic that may be justified by the national growth number of infected cases. Preoperative mass screening strategy was implemented without compromising the efficiency of surgical service, but patients' mortality was higher. The importance of visiting the ED during COVID-19 pandemic for serious cases that cannot be managed in other settings should be highlighted.

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COVID-19 pandemic is a rapidly spreading virus that is changing the World and the way doctors are practicing medicine. The huge number of patients searching for medical care and needing intensive care beds led the health care system to a burnout status especially in places where the care system was already overloaded. In this setting, and also due to the absence of a specific treatment for the disease, health authorities had to opt for recommending or imposing social distancing to relieve the health system and reduce deaths. All other medical specialties non-directly related to the treatment of COVID-19 had to interrupt or strongly reduce their activities in order to give room to seriously ill patients, since no one knows so far the real extent of the virus damage on human body and the consequences of doing non deferrable procedures in this pandemic era. Despite not been a urological disease, the urologist needs to be updated on how to deal with these patients and how to take care of himself and of the medical team he works with. The aim of this article is to review briefly some practical aspects of COVID-19 and its implications in the urological practice in our country.

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In the past four months SARS-CoV-2 has reached most countries in the world. Public health strategies based on widespread testing and proper isolation of positive cases have shown to be helpful to reduce local transmission of SARS-CoV-2. Confirmatory tests, that identify viral RNA, and screening serological tests that identify viral antigens or host antibodies against viral proteins are part of the tools that nations can use to fight infectious disease epidemics. Understanding how each test works can provide insights about their test characteristics and how they can be used for different clinical and public health goals. Testing is a key strategy to reduce viral transmission, not only for this epidemic, but also for others to come.

En los últimos cuatro meses, el virus SARS-CoV-2 ha llegado a la mayoría de países en el mundo. Las estrategias de salud pública basadas en la realización masiva de pruebas diagnósticas y el aislamiento focalizado de casos positivos han demostrado ser útiles para la reducción de la transmisión de SARS-CoV-2. Las pruebas confirmatorias, que identifican el ARN viral, y las pruebas serológicas que identifican antígenos virales o anticuerpos contra las proteínas virales del huésped son herramientas que las naciones pueden usar para combatir las epidemias producidas por agentes infecciosos. El comprender cómo funcionan estas pruebas puede ayudar a entender sus características y cómo pueden ser usadas para diferentes objetivos clínicos y de salud pública. Las pruebas diagnósticas son herramientas clave para reducir la transmisión viral, no solo en esta epidemia, sino para otras por venir.

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This review presents literature that highlights saliva's utility as a biofluid in the diagnosis and monitoring of COVID-19. A systematic search was performed in 5 electronic databases (PubMed, Embase, LILACS, Scopus, and Web of Science). Studies were eligible for inclusion if they assessed the potential diagnostic value and/or other discriminatory properties of biological markers in the saliva of patients with COVID-19. As of July 22, 2020, a total of 28 studies have investigated the presence of SARS-CoV-2 RNA in saliva. Several of those studies confirmed reliable detection of SARS-CoV-2 in the saliva of patients with COVID-19. Saliva offered sensitivity and specificity for SARS-CoV-2 detection comparable to that of the current standard of nasopharyngeal and throat swabs. However, the utility of saliva in diagnosing COVID-19 infection remains understudied. Clinical studies with larger patient populations that measure recordings at different stages during the disease are still necessary to confirm the accuracy of COVID-19 diagnosis with saliva. Nevertheless, the utility of saliva as a diagnostic tool opens the possibility of using rapid and less invasive diagnostic strategies by targeting bioanalytes rather than the pathogen.

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