Novel genes and sex differences in COVID-19 severity.

Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

Excess tuberculosis risk during and following incarceration in Paraguay: a retrospective cohort study.

Background: The increased risk of tuberculosis (TB) among people deprived of liberty (PDL) is due to individual and institution-level factors. We followed a cohort of PDL from 5 prisons in Paraguay to describe the risk of TB during incarceration and after they were released. Methods: We linked a 2013 national census of prisons with TB records from the TB Program from 2010 to 2021 to identify TB notifications among incarcerated and formerly incarcerated individuals. We used multivariable Cox regression models to quantify the risk of TB during and following incarceration and to identify risk factors associated with TB. Findings: Among 2996 individuals incarcerated, 451 (15.1%) were diagnosed with TB. Of these, 262 (58.1%) cases occurred during incarceration and 189 (41.9%) occurred in the community after release. In prison, the hazard ratio of developing TB was 1.97 (95% CI: 1.52-2.61) after six months of incarceration and increased to 2.78 (95% CI: 1.82-4.24) after 36 months compared with the first six months. The overall TB notification rate was 2940 per 100,000 person-years. This rate increased with the duration of incarceration from 1335 per 100,000 person-years in the first year to 8455 per 100,000 person-years after 8 years. Among former prisoners, the rate of TB decreased from 1717 in the first year after release to 593 per 100 000 person-years after 8 years of follow up. Interpretation: Our study shows the alarming risk of TB associated with prison environments in Paraguay, and how this risk persists for years following incarceration. Effective TB control measures to protect the health of people during and following incarceration are urgently needed. Funding: Paraguay National Commission of Science and Technology grant CONACYT PIN 15-705 (GS, GES, SA).

The concentration of tuberculosis within Paraguay's incarcerated and Indigenous populations, 2018-2022.

While incidence of tuberculosis (TB) has decreased globally, in Paraguay, considered a medium-incidence country by the WHO, TB incidence has increased slightly from 42 per 100,000 in 2010 to 46 per 100,000 in 2022. We conducted a retrospective study of TB cases notified to the Paraguay National Program for Tuberculosis Control (NPTC) from 2018 to 2022 and quantified trends in specific populations identified as vulnerable. Of the 13,725 TB cases notified in Paraguay from 2018 to 2022, 2,331 (17%) occurred among incarcerated individuals and 1,743 (12.7%) occurred among self-identified Indigenous individuals. In 2022, the relative risk of TB was 87 and 6.4 among the incarcerated and Indigenous populations, compared with the non-incarcerated and non-Indigenous populations respectively. We found significant heterogeneity in TB incidence across Paraguay's 17 departments. Our findings highlight the urgency of expanding access to TB diagnosis, treatment, and prevention in populations at heightened risk of TB in Paraguay.

Genomic epidemiology reveals the impact of national and international restrictions measures on the SARS-CoV-2 epidemic in Brazil.

Brazil has experienced some of the highest numbers of COVID-19 cases and deaths globally and from May 2021 made Latin America a pandemic epicenter. Although SARS-CoV-2 established sustained transmission in Brazil early in the pandemic, important gaps remain in our understanding of virus transmission dynamics at the national scale. Here, we describe the genomic epidemiology of SARS-CoV-2 using near-full genomes sampled from 27 Brazilian states and a bordering country - Paraguay. We show that the early stage of the pandemic in Brazil was characterised by the co-circulation of multiple viral lineages, linked to multiple importations predominantly from Europe, and subsequently characterized by large local transmission clusters. As the epidemic progressed under an absence of effective restriction measures, there was a local emergence and onward international spread of Variants of Concern (VOC) and Variants Under Monitoring (VUM), including Gamma (P.1) and Zeta (P.2). In addition, we provide a preliminary genomic overview of the epidemic in Paraguay, showing evidence of importation from Brazil. These data reinforce the usefulness and need for the implementation of widespread genomic surveillance in South America as a toolkit for pandemic monitoring that provides a means to follow the real-time spread of emerging SARS-CoV-2 variants with possible implications for public health and immunization strategies.

Manifestaciones clínicas de la fiebre por Chikunguña en población adulta: un breve estudio descriptivo realizado en Caaguazú, Paraguay / Clinical manifestations of Chikungunya fever in adult population: a brief descriptive study conducted in Caaguazú, Paraguay

Introducción. La infección por el virus del Chikunguña (CHIKV) se presenta típicamente como una enfermedad febril aguda que es autolimitada y se caracteriza predominantemente por poliartralgia y mialgias graves. Objetivo. el propósito de este estudio fue describir las características clínicas de la infección aguda por el virus del Chikunguña en una población adulta. Materiales y Método. Este fue un estudio observacional, descriptivo y transversal. La población de estudio incluyó adultos de una región específica de Paraguay durante la epidemia de CHIKV en 2022-2023. Los criterios de inclusión abarcaron a todos los pacientes que se presentaron el Hospital Regional dentro de los cinco días posteriores al desarrollo de síntomas típicos de CHIKV, confirmados por RT-PCR, y tras excluir dengue y Zika. Resultados. Se incluyeron un total de 803 adultos, con una edad media de 45,13 ± 18.63 años y una proporción de género masculino/femenino de 1:1.79. En las semanas epidemiológicas 8, 10 y 11 se documentaron 78, 120 y 132 casos, respectivamente. Las manifestaciones clínicas más comunes fueron fiebre en el 97% de los casos (n=583), artralgia y artritis en el 86,03% (n=653), mialgias en el 77,08% (n=585) y cefalea en el 73,91% (n=561). Hubo 6 muertes (0,75% del total de casos). Conclusión. La presentación clínica de CHIKV durante la epidemia 2023 en Paraguay es consistente con descripciones previas en otras regiones. La enfermedad generó un número significativo de consultas médicas y llevó a la saturación del sistema de salud pública, siendo fatal en un pequeño porcentaje de casos. Palabras clave: fiebre chikunguña; epidemias; sintomatología; adulto

Introduction. Chikungunya virus (CHIKV) infection typically presents as an acute febrile illness that is self-limiting and predominantly characterized by severe polyarthralgia and myalgia. Objective.The purpose of this study was to describe the clinical characteristics of acute chikungunya virus infection in an adult population. Materials and Methods.This was a descriptive, cross-sectional, observational study. The study population included adults from a specific region of Paraguay during the CHIKV epidemic in 2022-2023. Inclusion criteria encompassed all patients who presented to the hospital within five days after developing typical symptoms of acute CHIKV infection, confirmed by RT-PCR, and after excluding the presence of dengue and Zika. Results. A total of 803 adults were included, with an average age of 45.13 ± 18.63 years and a male/female ratio of 1:1.79. At epidemiological weeks 8, 10, 11, 78, 120, and 132 cases were documented, respectively. The most common clinical manifestations were fever in 97% of the cases (n=583), arthralgia and arthritis in 86.03% (n=653), myalgias in 77.08% (n=585), and headache in 73.91% (n=561). There were 6 deaths (0.75% of the total cases). Conclusion. The clinical presentation of CHIKV during the 2023 epidemic in Paraguay is consistent with previous descriptions in other regions. The disease generated a significant number of medical consultations and led to saturation of the public health system, which was fatal in a small percentage of cases. Key words: chikungunya fever; epidemic;symptomatology;adult

Characteristics of acute chikungunya virus infection in children: an epidemiological study in the Department of Caaguazú, Paraguay

Introduction: The rapid transmission and severe symptoms associated with acute chikungunya virus (CHIKV) infection in children make it a highly concerning health issue. Objective: This study aimed to describe the characteristics of acute chikungunya virus infection in children from the Department of Caaguazú, Paraguay. Material and Methods: A retrospective observational study was conducted in the Department of Caaguazú, Paraguay, in 2023, with all patients who came to the Regional Hospital within 5 days of developing characteristic symptoms of acute CHIKV infection and tested positive for the virus by RT-PCR. Patients with Dengue or Zika infections were excluded. We collected data on clinical characteristics using a standardized case record form and created an electronic dataset for analysis. Results: A total of 461 children were included in the study. 51.6% were women. Cases were divided into groups based on pediatric age: infants (0-23 months, n=88, 19.1%), preschoolers (2-5 years, n=115, 24.9%), schoolchildren (6-11 years, n=163, 35.4%), and adolescents (12-17 years and 11 months, n=95, 20.6%). Schoolchildren and adolescents experienced a higher prevalence of myalgia (64.6%) and arthralgia (63.7%). Vomiting (89%), headache (89.4%), and retro-orbital pain (95%) were more common in preschoolers, schoolchildren, and adolescents, while rash (39.5%) and petechiae (18.5%) were more prevalent in infants. Four children died during the study period. Conclusion: The 2023 CHIKV virus epidemic in Paraguay had different clinical presentations depending on the age of the affected children, with fatal outcomes occurring in a small percentage of cases.

Introducción: La rápida transmisión y los síntomas graves asociados con la infección aguda por el virus de la chikungunya (CHIKV) en niños lo convierten en un problema de salud altamente preocupante. Objetivo: Este estudio tuvo como objetivo describir las características de la infección aguda por el virus de la chikungunya en niños del Departamento de Caaguazú, Paraguay. Materiales y métodos: Un estudio retrospectivo fue realizado en el Departamento de Caaguazú, Paraguay, en 2023, con todos los pacientes que acudieron al Hospital Regional dentro de los 5 días posteriores al desarrollo de síntomas característicos de la infección aguda por CHIKV y que dieron positivo para el virus mediante RT-PCR. Pacientes con infecciones por Dengue o Zika fueron excluidos. Se recogieron datos sobre las características clínicas mediante un formulario normalizado de registro de casos y se creó un conjunto de datos electrónicos para su análisis. Resultados: Se incluyeron en el estudio un total de 461 niños. 51,6% eran mujeres. Los casos se dividieron en grupos según la edad pediátrica: lactantes (0-23 meses, n=88, 19,1 %), preescolares (2-5 años, n=115, 24,9%), escolares (6-11 años, n=163, 35.4%), and adolescentes (12-17 años and 11 meses, n=95, 20.6 %). La mialgia (64,6%) y la artralgia (63.7%) fueron más prevalentes en escolares y adolescentes. El vómito (89%), la cefalea (89,4%) y el dolor retroorbitario (95%) fueron más comunes en preescolares, escolares y adolescentes, mientras que la erupción cutánea (39,5%) y las petequias (18,5%) fueron más prevalentes en lactantes. Cuatro niños fallecieron durante el período de estudio. Conclusión: La epidemia de virus de la CHIKV de 2023 en Paraguay tuvo diferentes presentaciones clínicas dependiendo de la edad de los niños afectados, con resultados fatales ocurriendo en un pequeño porcentaje de casos.

Calidad microbiológica del agua procedente de tanques y pozos artesianos de establecimientos sanitarios

Introducción: Las aguas procedentes de establecimientos de salud, son comúnmente utilizadas por funcionarios y pacientes. Para que sean aceptables para uso humano, las aguas de los establecimientos deben cumplir con criterios microbiológicos establecidos en normas nacionales. Objetivo: Determinar la calidad microbiológica de muestras de agua de establecimientos sanitarios del departamento de Caaguazú. Métodos: Estudio descriptivo observacional, de corte transversal. Se analizaron 104 muestras de agua potable y tratada de hospitales, unidades de salud familiar y puestos de salud, de los 22 distritos de Caaguazú. Para evaluar la calidad microbiológica del agua se analizaron heterotróficos totales, coliformes totales, coliformes termotolerantes, Escherichia coli y Pseudomonas aeruginosa. Las muestras se procesaron mediante filtración de membrana, placas rehidratables, medios convencionales y sistemas miniaturizados consistentes en una interfaz de programación de aplicaciones. Las muestras se catalogaron como aceptables o inaceptables acorde la norma NP Nº 24-001-80. Resultados: De las 104 muestras, 58 (56 %) fueron aceptables y 46 (44 %) fueron inaceptables. Las causas de esta última condición fueron presencia de coliformes totales (42 %), alto recuento de heterótrofas (13 %), presencia de coliformes termotolerantes (11,5 %), presencia de Escherichia coli (9,6 %) y presencia de Pseudomonas aeruginosa (2 %). Conclusiones: La mayoría de las muestras de agua fueron de calidad microbiológica aceptable; pero como se detectó un porcentaje considerable de muestras inaceptables y la presencia de especies como Escherichia coli y Pseudomonas aeruginosa, es recomendable corregir las técnicas de tratamiento de agua y enfatizar en los controles de calidad microbiológica, en los centros sanitarios estudiados.

Introduction: The waters from health establishments are commonly used by officials and patients. To be acceptable for human use, water from establishments must meet microbiological criteria established in national standards. Objective: To determine the microbiological quality of water samples from sanitary establishments in the department of Caaguazú. Methods: A descriptive, observational, cross-sectional study was conducted in 104 samples of drinking and treated water from hospitals, family health units and health posts from the 22 districts of Caaguazú. These samples were studied to evaluate the microbiological quality of the water, total heterotrophs, total coliforms, thermotolerant coliforms, Escherichia coli and Pseudomonas aeruginosa were analyzed. Samples were processed by membrane filtration, rehydratable plates, conventional media, and miniaturized systems consisting of an application programming interface. They were classified as acceptable or unacceptable according to standard NP Nº 24-001-80. Results: Fifty eight (56%) samples, out of the 104, were acceptable and 46 (44%) were unacceptable. The causes of this last condition were the presence of total coliforms (42%), high count of heterotrophs (13%), presence of thermotolerant coliforms (11.5%), presence of Escherichia coli (9.6%) and presence of Pseudomonas aeruginosa (2%). Conclusions: Most of the water samples were assessed to be acceptable in microbiological quality; however, since a considerable percentage of unacceptable samples and the presence of species such as Escherichia coli and Pseudomonas aeruginosa were detected, it is recommended to correct the water treatment techniques emphasizing microbiological quality controls in the health centers studied.

Perfil de resistencia antimicrobiana de los aislamientos de Klebsiella pneumoniae en una Unidad de Cuidados Intensivos de Paraguay / Antimicrobial resistance profile of samples with Klebsiella pneumoniae from an Intensive Care Unit in Paraguay

Resumen Introducción: Klebsiella pneumoniae produce enzimas como Betalactamasas de Espectro Extendido (BLEE) y Carbapenemasas. Estas enzimas tienen implicancia en las Unidades de Cuidados Intensivos (UCI), porque posibilitan la supervivencia de especies bacterianas a condiciones desfavorables y por ende, facilitan su permanencia en ambiente intrahospitalario. Existe evidencia de presencia de Klebsiella pneumoniae en UCI, en muestras procedentes de: pacientes, personal de salud, habitación, lavamanos y fórmulas nutricionales. Objetivo: Evaluar el perfil de resistencia de los aislamientos de Klebsiella pneumoniae en una UCI de Paraguay. Material y métodos: Estudio descriptivo observacional, transversal. Se recolectaron 200 muestras (124 fórmulas enterales, 40 ambiente y 36 pacientes). Variables analizadas: origen de muestra, presencia del germen, producción de enzimas y perfil de resistencia. Resultados: Se aisló Klebsiella pneumoniae en 14% de las muestras. Se identificó al germen en: 25% pacientes, 12,9% fórmulas enterales y 7,5% ambiente. Se observó producción de BLEE en 85,7% de las cepas, con perfiles de resistencia idénticos, y producción de carbapenemasas en 14,3% de las cepas, con perfiles de resistencia diferentes. Conclusión: la presencia y los perfiles de resistencia de Klebsiella pneumoniae en las tres clases de muestras estudiadas, sugieren transferencia de genes de resistencia y diseminación del germen en UCI.

Abstract Introduction: Klebsiella pneumoniae produces enzymes such as Extended Spectrum Betalactamases (ESBL) and Carbapenemases. These enzymes have implica tions in Intensive Care Units (ICU), because they enable the survival of bacterial species under unfavorable conditions and, therefore, facilitate their permanence in the hospital environment. There is evidence of the presence of Klebsiella pneumoniae in the ICU, in samples from: patients, health staff, room, sink, and nutri tional formulas. Objective: To evaluate the resistance profile of Klebsiella pneumoniae isolates in an ICU in Paraguay. Material and methods: descriptive, observational, cross-sectional study. 200 samples were collected (124 enteral formulas, 40 ambient and 36 patients). Variables analyzed: sample origin, presence of the germ, enzyme production and resistance profile. Results: Klebsiella pneumoniae was isolated in 14% of the samples. The germ was identified in: 25% patients, 12.9% enteral formulas and 7.5% environment. Pro duction of ESBL was observed in 85.7% of the strains, with identical resistance profiles, and production of carbapenemases in 14.3% of the strains, with different resistance profiles. Conclusion: the presence and resistance profiles of Klebsiella pneumoniae in the three classes of samples studied, suggest transfer of resistance genes and disse mination of the germ in ICU.

Actitudes hacia la vacuna contra la COVID-19 en la población general paraguaya / Attitudes towards the COVID-19 vaccine in the general paraguayan population

Introducción: La pandemia de COVID-19 ha provocado cambios que afectan los sistemas de salud y el abordaje de las enfermedades infecciosas a nivel mundial. La esperanza de recuperar un cierto nivel de "normalidad" se basa en el desarrollo de vacunas. Objetivos: El objetivo de este estudio fue describir las actitudes hacia la vacuna COVID-19 en la población paraguaya, explorando factores que podrían ser abordados para apoyar la campaña de vacunación contra el SARS-CoV-2. Materiales y métodos: Estudio transversal y descriptivo. Los participantes fueron reclutados a través de una encuesta basada en Internet, difundida a través de las redes sociales, durante el mes de marzo de 2021. Todos los participantes recibieron información completa sobre el objetivo del estudio, la privacidad y el procesamiento de datos. Resultados: De los 2297 participantes, el 67,9% (n=1559) eran mujeres, el 49,9% (n=1147) estaban empleados, el 89,1% (n=2046) reportaron educación universitaria y el 96,6% (n=2218) eran de áreas urbanas. En general, el 81,8 % (n=1879) de los participantes afirmó que estarían dispuestos a vacunarse contra el COVID-19 si hubiera una vacuna disponible. Se ha encontrado una relación significativa entre haber solicitado la vacuna antigripal y la intención de vacunarse frente al COVID-19 (p<0,0001), con un OR: 3,09 (IC 95% 2,1-4,5). Conclusión: El porcentaje de participantes inclinados a vacunarse contra el COVID-19 es similar al de aquellos que esperan una inmunización adecuada de la vacuna. Las agencias gubernamentales y de salud deben hacer un esfuerzo para brindar información precisa que responda a las inquietudes de las personas sobre la vacunación, en cualquier nivel de la sociedad.

Introduction: Insufficient physical activity is one of the main public health problems globally. Teen behavior patterns and lifestyle may affect their physical and mental health. Objectives: The objective of this study was to know the patterns of physical activity and sedentary behaviors in the adolescent population nationwide. Materials and methods: A quantitative, observational, descriptive cross-sectional study, the questionnaire of the Global School Health Survey was applied in school adolescents of the eighth and ninth grades of the 3rd cycle of Basic School Education and the 1st, 2nd and 3rd year of Secondary Education in 49 schools and colleges in the country. 1,803 students aged 13 to 15 years were included in this study. Results. 27% of adolescents between the ages of 13 and 15 in Paraguay are active, being significantly higher in men than in women (p-value 0.000) and 22% are inactive more frequently in women than in men (p-value 0.000). It was observed that 33.5% of the adolescents had sedentary behavior, 43.4% of the adolescents did not use active displacement to attend school. Adolescents who did not participate in physical education classes at school accounted for 15.6%. Conclusion: Although 27% of adolescents between the ages of 13 and 15 are active, the large percentage of inactive adolescents with sedentary behavior is worrying.