Eosinophils of patients with localized and diffuse cutaneous leishmaniasis: Differential response to Leishmania mexicana, with insights into mechanisms of damage inflicted upon the parasites by eosinophils.

Eosinophils are mainly associated with parasitic infections and allergic manifestations. They produce many biologically active substances that contribute to the destruction of pathogens through the degranulation of microbicidal components and inflammatory tissue effects. In leishmaniasis, eosinophils have been found within inflammatory infiltrate with protective immunity against the parasite. We analyzed the responses of eosinophils from patients with localized (LCL) and diffuse (DCL) cutaneous leishmaniasis, as well as from healthy subjects, when exposed to Leishmania mexicana. All DCL patients exhibited blood eosinophilia, along with elevated eosinophil counts in non-ulcerated nodules. In contrast, only LCL patients with prolonged disease progression showed eosinophils in their blood and cutaneous ulcers. Eosinophils from DCL patients secreted significantly higher levels of IL-6, IL-8, and IL-13, compared to eosinophils from LCL patients. Additionally, DCL patients displayed higher serum levels of anti-Leishmania IgG antibodies. We also demonstrated that eosinophils from both LCL and DCL patients responded to L. mexicana promastigotes with a robust oxidative burst, which was equally intense in both patient groups and significantly higher than in healthy subjects. Coincubation of eosinophils (from donors with eosinophilia) with L. mexicana promastigotes in vitro revealed various mechanisms of parasite damage associated with different patterns of granule exocytosis: 1) localized degranulation on the parasite surface, 2) the release of cytoplasmic membrane-bound "degranulation sacs" containing granules, 3) release of eosinophil extracellular traps containing DNA and granules with major basic protein. In conclusion, eosinophils damage L. mexicana parasites through the release of granules via diverse mechanisms. However, despite DCL patients having abundant eosinophils in their blood and tissues, their apparent inability to provide protection may be linked to the release of cytokines and chemokines that promote a Th2 immune response and disease progression in these patients.

Vacuna BCG e indicadores de mortalidad y morbilidad por COVID-19 en países con curva epidémica consolidada / TB vaccine and indicators of mortality and morbidity from COVID-19 in countries with a consolidated epidemic curve / Vacina BCG e indicadores de mortalidade e morbidade por COVID-19 em países com curva epidêmica consolidada / Vaccin BCG et indicateurs de mortalité et de morbidité dus au COVID-19 dans les pays à courbe épidémique consolidée

Resumen Objetivo: Señalar posible influencia de coberturas de vacunación con bacilos Calmette-Guérin (BCG) en indicadores de mortalidad y morbilidad por COVID-19, en países con curva epidémica consolidada. Materiales y Métodos: Se trata de un estudio ecológico mixto, del total de países que integran la Organización Mundial de la Salud (OMS).Se eligieron aquellos con curva epidémica consolidada por COVID-19, actualizada al 1 de junio 2020 e información tomada de base de datos de vacunación 1980-2018 Estimates of National Immunization Coverage, ambas fuentes de OMS, contrastando las coberturas y políticas de vacunación universal e ingreso per cápita con letalidad, mortalidad e incidencia en 45 países que cumplieron con los criterios, aplicando medidas de asociación e impacto potencial: riesgo relativo(RR) reducción de riesgo(RDR), muertes prevenibles en vacunados(MEV%), casos prevenibles en vacunados(CEV%) con intervalo de confianza para tasas con 99% de significancia. Resultados: Países con coberturas mayor de 60% y política actual de vacunación universal, en contraste con países con cero% coberturas, con reducción de indicadores de mortalidad y morbilidad: Letalidad 5.8-9.7%, mortalidad 883.8-937 por 106 (p<0.01) habitantes, incidencia 4,260-4,351.6 por 105 (p<0.01) habitantes; incremento de: MEV% 94.1-99.8%(p<0.01) y CEV% 96.9-99.6%(p<0.01). El mayor contraste de indicadores fue para países con ingreso medio bajo e ingreso medio alto. Países con coberturas menor de 60% contra cero % coberturas (ambos grupos con altos ingresos) con reducción (excepto Letalidad): Letalidad-1.861 a -4.703 %(p>0.01), mortalidad 774.3- 827.8 por 106 (p<0.01) habitantes, incidencia 4,193.13- 4,212.93 por 105 (p<0.01) habitantes, incremento de: MEV% 82.5-88.2%(p<0.01), CEV% 96.0-96.5%(p<0.01). También mayor diferencia de indicadores para países con coberturas cercanas al 60%, con política de vacunación universal actual. Conclusiones: Los países con coberturas de vacunación con BCG superior a 60% con mantenimiento de políticas de vacunación universal, tienen mayor reducción de indicadores de mortalidad, morbilidad por COVID-19 e incremento significativo de casos y muertes evitadas sugiriendo posible influencia por vacunación entre otros factores.

Abstract Objective: Indicate the possible influence of vaccination coverage with Calmette-Guérin bacilli (BCG) on indicators of mortality andmorbidity from COVID-19 in countries with a consolidated epidemic curve. of association and potential impact: relative risk (RR) Materials and methods: This is a mixed ecological study of all the countries that make up the World Health Organization (WHO). Those with an epidemic curve consolidated by COVID-19 updated to June 1, 2020 and information taken from the vaccination database 1980-2018 Estimates of National Immunization Coverage, both sources of WHO, were chosen, contrasting the coverage and policies of universal vaccination and income per capita with lethality, mortality and incidence in 45 countries that met the criteria applying measures of association and potential impact: relative risk (RR), risk reduction (RDR), preventable deaths in vaccinated (MEV%), preventable cases in vaccinated (CEV%) with confidence interval for rates with 99% significance. Results: Countries with coverage greater than 60% and current universal vaccination policy in contrast to countries with zero% coverage, with reduction in mortality and morbidity indicators: Mortality 5.8-9.7%, mortality 883.8-937 per 106 (p <0.01) inhabitants, incidence 4,260-4,351.6 per 105 (p <0.01) inhabitants; Increase of: MEV% 94.1-99.8% (p <0.01) and CEV% 96.9-99.6% (p <0.01). The greatest contrast of indicators were for countries with lower middle income and upper middle income. Countries with coverage less than 60% versus zero% coverage (both groups with high incomes) with reduction (except case fatality): case fatality-1.861 to -4.703% (p> 0.01), mortality774.3-827.8 per 106 (p <0.01) inhabitants, incidence 4,193.13- 4,212.93 per 105 (p <0.01) inhabitants, increase of: MEV% 82.5- 88.2% (p <0.01), CEV% 96.0-96.5 (p <0.01) .Also greater difference of indicators for countries with coverage close to 60% with current universal vaccination policy. Conclusions: Countries with BCG vaccination coverage greater than 60% with maintenance of universal vaccination policies, have a greater reduction in mortality indicators, morbidity from COVID-19 and a significant increase in cases and deaths, suggesting possible influence by vaccination among other factors.

Resumo Objetivo: Indique a possível influência da cobertura vacinal com bacilos de Calmette-Guérin (BCG) nos indicadores de mortalidade e morbidade do COVID-19 em países com uma curva epidêmica consolidada. Materiais e métodos: É um estudo ecológico misto do número total de países que compõem a Organização Mundial da Saúde (OMS). Aqueles com uma curva epidêmica consolidada pelo COVID-19 atualizada para 1º de junho de 2020 e informações retiradas do banco de dados de vacinação 1980-2018, foram escolhidas as Estimativas de Cobertura Nacional de Imunizações, ambas as fontes da OMS, contrastando a cobertura e as políticas de vacinação universal e renda. per capita com letalidade, mortalidade e incidência em 45 países que atenderam aos critérios de aplicação de possíveis medidas de associação e impacto: risco relativo(RR),redução de risco (RDR), mortes evitáveis em vacinados (MEV%), casos evitáveis em vacinados (CEV%) com intervalo de confiança para taxas com significância de 99%. Resultados: Países com cobertura superior a 60% e política atual de vacinação universal em contraste com países com cobertura zero, com redução nos indicadores de mortalidade e morbidade: Mortalidade 5,8-9,7%, mortalidade 883.8-937 por 106 (p <0,01) habitantes, incidência 4,260-4,351.6 por 105 (p <0,01) habitantes; Aumento de: MEV% 94.1-99.8% (p <0,01) e CEV% 96.9-99.6% (p <0,01). O maior contraste de indicadores ocorreu nos países com renda média baixa e renda média alta. Países com cobertura inferior a 60% versus zero% (ambos os grupos com renda alta) com redução (exceto casos fatais): casos fatalidade -1.861 a -4.703 % (p> 0,01), mortalidade 774.3-827.8 por 106 habitantes (p <0,01), incidência 4,193.13- 4,212.93 por 105 (p <0,01) habitantes, aumento de: MEV% 82.5-88.2 % (p<0,01), CEV% 96.0-96.5% (p <0,01). Também maior diferença de indicadores para países com cobertura perto de 60% com a atual política universal de vacinação. Conclusões: Os países com cobertura vacinal para BCG superior a 60% com manutenção de políticas universais de vacinação apresentam maior redução nos indicadores de mortalidade, morbidade por COVID-19 e um aumento significativo de casos e mortes evitaram sugerir uma possível influência através da vacinação, entre outros fatores.

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