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BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause very high morbidity and mortality throughout Latin American countries. However, few population-based seroprevalence surveys have been conducted to quantify attack rates and characterize drivers of transmission. METHODS: We conducted a population-based cross-sectional study to assess the seroprevalence of antibodies against SARS-CoV-2 in ten cities in Colombia between September and December 2020. The study involved multi-stage cluster sampling at each city. Participants provided a serum sample and answered a demographic and risk factor questionnaire. Prior infection by SARS-CoV-2 was ascertained using the "SARS-CoV-2 Total (COV2T) Advia Centaur - Siemens" chemiluminescence assay. FINDINGS: A total of 17863 participants from 7320 households participated in the study. Seroprevalence varied substantially between cities, ranging from 26% (95%CI 23-29 %) in Medellín to 68% (95%CI 62-74 %) in Guapi. There were no differences in seroprevalence by sex, but seropositivity was higher in certain ethnic groups. There was substantial heterogeneity in seroprevalence within cities, driven to a large extent by a strong association between socioeconomic stratum and seropositivity. INTERPRETATION: Colombia has been one of the Latin American countries most affected by the COVID-19 pandemic. This study documented very high attack rates in several Colombian cities by the end of 2020 and identified key drivers of heterogeneities including ethnicity and socioeconomic stratum. Few studies of seroprevalence of SARS-CoV-2 have been conducted in Latin America, and therefore this study contributes to the fundamental understanding of the pandemic in the region. FUNDING: The study was sponsored by, Ministerio de Ciencia y Tecnología e Innovación -CT361/2020, Ministerio de Salud y Protección Social, Fundación Universitaria del Norte, Imperial College of London, Universidad Nacional de Colombia (Sede Medellín), Universidad de Córdoba, California University, Unidad Nacional de Gestión del Riesgo, Centro de Atención y Diagnóstico de Enfermedades Infecciosas -CDI-, Centro Internacional de Entrenamiento e Investigaciones Médicas -CIDEIM-, Departamento Administrativo Nacional de Estadística - DANE, Fondo Nacional de Turismo -FONTUR-, Secretarías de Salud Departamentales, Distritales y Municipales and Instituto Nacional de Salud.
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BACKGROUND: Control of cutaneous leishmaniasis by public health systems in the Americas relies on case identification and treatment. Point-of-care diagnostics that can be performed by health workers within or near affected communities could effectively bring the health system to the resource-limited sites providing early diagnosis and treatment, reducing morbidity and the burden of disease. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study was undertaken to evaluate the diagnostic test performance of Isothermal Recombinase Polymerase Amplification (RPA) targeting Leishmania kinetoplast DNA, coupled with a lateral flow (LF) immunochromatographic strip, in a field setting and a laboratory reference center. Minimally invasive swab and FTA filter paper samples were obtained by community health workers and highly trained technicians from ulcerated lesions of > 2 weeks' evolution from 118 patients' ≥ 2 years of age in the municipality of Tumaco, Nariño. Extracted DNA was processed by RPA-LF at a reference center or in a primary health facility in the field. Evaluation was based on a composite "gold standard" that included microscopy, culture, biopsy and real-time polymerase chain reaction detection of Leishmania 18S rDNA. Standard of care routine diagnostic tests were explored as comparators. Sensitivity and specificity of RPA-LF in the reference lab scenario were 87% (95%CI 74-94) and 86% (95%CI 74-97), respectively. In the field scenario, the sensitivity was 75% (95%CI 65-84) and specificity 89% (95%CI 78-99). Positive likelihood ratios in both scenarios were higher than 6 while negative likelihood ratios ranged to 0.2-0.3 supporting the usefulness of RPA-LF to rule-in and potentially to rule-out infection. CONCLUSIONS/SIGNIFICANCE: The low complexity requirements of RPA-LF combined with non-invasive sampling support the feasibility of its utilization by community health workers with the goal of strengthening the diagnostic capacity for cutaneous leishmaniasis in Colombia. TRIAL REGISTRATION: ClinicalTrials.gov NCT04500873.
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Leishmania/genética , Leishmania/aislamiento & purificación , Leishmaniasis Cutánea/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Cromatografía de Afinidad , Colombia , Estudios Transversales , Cartilla de ADN/genética , ADN de Cinetoplasto/genética , ADN Protozoario/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Técnicas de Amplificación de Ácido Nucleico , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: Detection and management of neglected tropical diseases such as cutaneous leishmaniasis present unmet challenges stemming from their prevalence in remote, rural, resource constrained areas having limited access to health services. These challenges are frequently compounded by armed conflict or illicit extractive industries. The use of mobile health technologies has shown promise in such settings, yet data on outcomes in the field remain scarce. METHODS: We adapted a validated prediction rule for the presumptive diagnosis of CL to create a mobile application for use by community health volunteers. We used human-centered design practices and agile development for app iteration. We tested the application in three rural areas where cutaneous leishmaniasis is endemic and an urban setting where patients seek medical attention in the municipality of Tumaco, Colombia. The application was assessed for usability, sensitivity and inter-rater reliability (kappa) when used by community health volunteers (CHV), health workers and a general practitioner, study physician. RESULTS: The application was readily used and understood. Among 122 screened cases with cutaneous ulcers, sensitivity to detect parasitologically proven CL was >95%. The proportion of participants with parasitologically confirmed CL was high (88%), precluding evaluation of specificity, and driving a high level of crude agreement between the app and parasitological diagnosis. The chance-adjusted agreement (kappa) varied across the components of the risk score. Time to diagnosis was reduced significantly, from 8 to 4 weeks on average when CHV conducted active case detection using the application, compared to passive case detection by health facility-based personnel. CONCLUSIONS: Translating a validated prediction rule to a mHealth technology has shown the potential to improve the capacity of community health workers and healthcare personnel to provide opportune care, and access to health services for underserved populations. These findings support the use of mHealth tools for NTD research and healthcare.
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Diagnóstico Precoz , Leishmaniasis Cutánea/diagnóstico , Aplicaciones Móviles , Medicina Tropical/métodos , Adaptación Fisiológica , Adolescente , Adulto , Colombia/epidemiología , Agentes Comunitarios de Salud , Femenino , Humanos , Leishmaniasis Cutánea/epidemiología , Masculino , Tamizaje Masivo/métodos , Área sin Atención Médica , Reproducibilidad de los Resultados , Medicina Tropical/instrumentación , Adulto JovenRESUMEN
BACKGROUND: Control of cutaneous leishmaniasis (CL) relies on chemotherapy, yet gaps in our understanding of the determinants of therapeutic outcome impede optimization of antileishmanial drug regimens. Pharmacodynamic (PD) parameters of antimicrobials are based on the relationship between drug concentrations/exposure and microbial kill. However, viable Leishmania persist in a high proportion of individuals despite clinical resolution, indicating that determinants other than parasite clearance are involved in drug efficacy. METHODS: In this study, the profiles of expression of neutrophils, monocytes, Th1 and Th17 gene signatures were characterized in peripheral blood mononuclear cells (PBMCs) during treatment with meglumine antimoniate (MA) and clinical cure of human CL caused by Leishmania (Viannia). We explored relationships of immune gene expression with plasma and intracellular antimony (Sb) concentrations. RESULTS: Our findings show a rapid and orchestrated modulation of gene expression networks upon exposure to MA. We report nonlinear pharmacokinetic/pharmacodynamic (PK/PD) relationships of Sb and gene expression dynamics in PBMCs , concurring with a time lag in the detection of intracellular drug concentrations and with PK evidence of intracellular Sb accumulation. CONCLUSIONS: Our results quantitatively portray the immune dynamics of therapeutic healing, and provide the knowledge base for optimization of antimonial drug treatments, guiding the selection and/or design of targeted drug delivery systems and strategies for targeted immunomodulation.
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Antiprotozoarios , Leishmania , Leishmaniasis Cutánea , Antiprotozoarios/uso terapéutico , Humanos , Leishmaniasis Cutánea/tratamiento farmacológico , Leucocitos Mononucleares , Antimoniato de Meglumina/uso terapéuticoRESUMEN
[ABSTRACT]. Universal health coverage is a public health priority in the Americas. Social innovation in health offers novel solutions to unmet needs, by enabling health care delivery to be more inclusive, affordable, and effective. In 2017, an international collaborative consortium launched an open call for solutions that sought to identify social innovations in health in Central America and the Caribbean. The focus was set on how these solutions can strengthen health care delivery, with emphasis on reducing the impact of neglected transmissible diseases. A crowdsourcing strategy was implemented to identify social innovations in health. These were evaluated by an external panel of experts and practitioners and civil society representing the health and social innovation sectors, based on the appropriateness, innovativeness, and affordability of the solution. The three top-scoring solutions were analyzed through case studies including site visits by a team of investigators. Two key findings emerged from the response to the call: 1) innovative solutions were based on the knowledge and experience of individuals and communities facing adverse situations; 2) this knowledge was shared through health promotion and education, leading to empowerment of the communities. The principal challenges addressed by the solutions were the limited access to quality health care services and failed traditional strategies for vector control. The solutions identified demonstrated how social innovation can strengthen health systems by delivering novel solutions to health needs and articulating communities to enable them to work hand-in-hand with the health system toward universal health.
[RESUMEN]. La cobertura universal de salud es una prioridad de salud pública en la Región de las Américas. La innovación social en materia de salud ofrece soluciones novedosas a las necesidades insatisfechas, al permitir que la prestación de servicios de salud sea más inclusiva, asequible y eficaz. En 2017, un consorcio de colaboración internacional lanzó una convocatoria abierta de soluciones con el fin de identificar innovaciones sociales en materia de salud en América Central y el Caribe. Esta se centró en la forma en que esas soluciones pueden fortalecer la prestación de atención sanitaria, con énfasis en la reducción de los efectos de las enfermedades transmisibles desatendidas. Para identificar las innovaciones sociales en materia de salud se aplicó una estrategia de colaboración masiva (crowdsourcing). Las propuestas fueron evaluadas por un grupo externo conformado por expertos, profesionales y la sociedad civil que representaban a los sectores de la salud y la innovación social, sobre la base de la idoneidad, la capacidad de innovación y la asequibilidad de la solución. Se analizaron las tres soluciones mejor calificadas mediante estudios de casos que incluyeron visitas al lugar por parte de un equipo de investigadores. De la respuesta a la convocatoria surgieron dos conclusiones clave: 1) las soluciones innovadoras se basaron en el conocimiento y la experiencia de las personas y las comunidades que se enfrentaban a situaciones adversas, y 2) este conocimiento se compartió a través de actividades de promoción de la salud y educación, lo que condujo al empoderamiento de las comunidades. Los principales problemas que abordaron las soluciones fueron el acceso limitado a servicios de atención sanitaria de calidad y el fracaso de las estrategias tradicionales de control de vectores. Las soluciones identificadas demostraron cómo la innovación social puede fortalecer los sistemas de salud proporcionando soluciones novedosas a las necesidades de salud y apoyando a las comunidades para que puedan colaborar estrechamente con el sistema de salud hacia la salud universal.
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Enfermedades Desatendidas , Atención a la Salud , Participación Social , América Central , Región del Caribe , Enfermedades Desatendidas , Atención a la Salud , Participación Social , América Central , Región del CaribeRESUMEN
[EXTRACTO]. Actualmente se presta cada vez más atención a los determinantes políticos, económicos, ambientales y sociales de la salud. Esto ha generado una mayor demanda de investigación para la salud a nivel mundial que incluya a los países de ingresos bajos y medianos, con objeto de alcanzar los objetivos de desarrollo sostenible de las Naciones Unidas. Además del financiamiento, se necesitan suficientes recursos humanos e infraestructura para que estos países lleguen a ser asociados en un plano de igualdad con las instituciones de investigación internacionalmente reconocidas de los países de ingresos altos que establecen las agendas de investigación, y para garantizar que el programa de investigación mundial refleje sus necesidades. Las limitaciones en la capacidad de investigación y las grandes disparidades existentes entre los países de ingresos altos y los de ingresos bajos y medianos en cuanto a su capacidad de producir y usar la investigación para la salud han contribuido a producir una falta de evidencia que permita fundamentar la práctica clínica y orientar las políticas sanitarias regionales y mundiales. Esto ha perpetuado las desigualdades en la salud...
[EXTRACTO]. Existe atualmente um maior reconhecimento dos determinantes políticos, econômicos, ambientais e sociais da saúde. A consequência disso foi um aumento da demanda por pesquisa em saúde global, com participação dos países de baixa e média renda, para cumprir os objetivos de desenvolvimento sustentável das Nações Unidas. Além de financiamento, são necessários recursos humanos e infraestrutura suficientes para que esses países se tornem parceiros em igualdade de condições com instituições de pesquisa internacionalmente reconhecidas em países de alta renda que definem as agendas de pesquisa e cuidam para que o programa global de pesquisa em saúde reflita suas necessidades. A limitada capacidade de pesquisa e as grandes disparidades entre países de alta renda e países de baixa e média renda no tocante à capacidade de produzir e usar pesquisas para a saúde contribuíram para a falta de evidências para informar a prática e orientar as políticas de saúde regionais e globais, o que perpetuou as desigualdades em saúde...
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Investigación sobre Servicios de Salud , Determinantes Sociales de la Salud , Desarrollo Sostenible , Américas , Región del Caribe , Investigación sobre Servicios de Salud , Determinantes Sociales de la Salud , Desarrollo Sostenible , Región del CaribeRESUMEN
El concepto de intersectorialidad, aplicado al campo de la salud en la región de las Américas, tiene sus bases en la Declaración Salud para Todos de Alma-Ata de 1978 (1). En ese documento, se enfatizó sobre la estrategia de atención primaria y la búsqueda de equidad en salud, resaltando que la intersectorialidad «entraña la participación, además del sector sanitario, de todos los sectores y campos de actividad conexos del desarrollo nacional y comunitario [ ]¼ (2). De esa manera 39 años después, el reto de la intersectorialidad sigue vigente tal y como se expresa en la estrategia de investigación para la salud de la Organización Mundial de la Salud (OMS), en la que se destaca la necesidad de incorporar los hallazgos de la investigación científica en las políticas públicas, la promoción y en la atención médica (1, 3). Siguiendo esa línea, la falta de implementación de medidas e intervenciones, cuya eficacia y costo-efectividad han sido demostradas, genera un impacto negativo en la salud y por ende en la economía de los países tanto con altos como bajos ingresos (4, 5). En ese sentido, se reconoce que la limitada comunicación entre los actores de los diferentes sectores constituye la barrera más importante para la implementación de los resultados de las investigaciones y su incorporación en el diseño de las políticas públicas (6- 8). En efecto, la interacción promovida por la intersectorialidad beneficia la comunicación y la generación de políticas de salud pública (8, 9).
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Salud Pública , Organización Mundial de la SaludRESUMEN
Treatment failure and parasite drug susceptibility in dermal leishmaniasis caused by Leishmania (Viannia) species are poorly understood. Prospective evaluation of drug susceptibility of strains isolated from individual patients before drug exposure and at clinical failure allows intrinsic and acquired differences in susceptibility to be discerned and analyzed. To determine whether intrinsic susceptibility or loss of susceptibility to miltefosine contributed to treatment failure, we evaluated the miltefosine susceptibility of intracellular amastigotes and promastigotes of six Leishmania (Viannia) braziliensis and six Leishmania (Viannia) panamensis strains isolated sequentially, at diagnosis and treatment failure, from two children and four adults ≥55 years old with concurrent conditions. Four patients presented only cutaneous lesions, one had mucosal disease, and one had disseminated mucocutaneous disease. Expression of the Leishmania drug transporter genes abca2, abca3, abcc2, abcc3, abcg4, abcg6, and LbMT was evaluated by quantitative reverse transcription-PCR (qRT-PCR). Intracellular amastigotes (median 50% effective concentration [EC50], 10.7 µmol/liter) were more susceptible to miltefosine than promastigotes (median EC50, 55.3 µmol/liter) (P < 0.0001). Loss of susceptibility at failure, demonstrated by a miltefosine EC50 of >32 µmol/liter (the upper limit of intracellular amastigote assay), occurred in L. panamensis infection in a child and in L. braziliensis infection in an adult and was accompanied by decreased expression of the miltefosine transporter LbMT (LbMT/ß-tubulin, 0.42- to 0.26-fold [P = 0.039] and 0.70- to 0.57-fold [P = 0.009], respectively). LbMT gene polymorphisms were not associated with susceptibility phenotype. Leishmania ABCA3 transporter expression was inversely correlated with miltefosine susceptibility (r = -0.605; P = 0.037). Loss of susceptibility is one of multiple factors involved in failure of miltefosine treatment in dermal leishmaniasis.
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Leishmania/efectos de los fármacos , Leishmania/patogenicidad , Leishmaniasis Cutánea/tratamiento farmacológico , Fosforilcolina/análogos & derivados , Transportador de Casetes de Unión a ATP, Subfamilia G , Transportadoras de Casetes de Unión a ATP/metabolismo , Adolescente , Adulto , Niño , Resistencia a Medicamentos , Femenino , Humanos , Leishmaniasis Cutánea/metabolismo , Masculino , Persona de Mediana Edad , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Fosforilcolina/uso terapéutico , Estudios Prospectivos , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Children have a lower response rate to antimonial drugs and higher elimination rate of antimony (Sb) than adults. Oral miltefosine has not been evaluated for pediatric cutaneous leishmaniasis. METHODS: A randomized, noninferiority clinical trial with masked evaluation was conducted at 3 locations in Colombia where Leishmania panamensis and Leishmania guyanensis predominated. One hundred sixteen children aged 2-12 years with parasitologically confirmed cutaneous leishmaniasis were randomized to directly observed treatment with meglumine antimoniate (20 mg Sb/kg/d for 20 days; intramuscular) (n = 58) or miltefosine (1.8-2.5 mg/kg/d for 28 days; by mouth) (n = 58). Primary outcome was treatment failure at or before week 26 after initiation of treatment. Miltefosine was noninferior if the proportion of treatment failures was ≤15% higher than achieved with meglumine antimoniate (1-sided test, α = .05). RESULTS: Ninety-five percent of children (111/116) completed follow-up evaluation. By intention-to-treat analysis, failure rate was 17.2% (98% confidence interval [CI], 5.7%-28.7%) for miltefosine and 31% (98% CI, 16.9%-45.2%) for meglumine antimoniate. The difference between treatment groups was 13.8%, (98% CI, -4.5% to 32%) (P = .04). Adverse events were mild for both treatments. CONCLUSIONS: Miltefosine is noninferior to meglumine antimoniate for treatment of pediatric cutaneous leishmaniasis caused by Leishmania (Viannia) species. Advantages of oral administration and low toxicity favor use of miltefosine in children. CLINICAL TRIAL REGISTRATION: NCT00487253.
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Antiprotozoarios/administración & dosificación , Leishmania/aislamiento & purificación , Leishmaniasis Cutánea/tratamiento farmacológico , Meglumina/administración & dosificación , Compuestos Organometálicos/administración & dosificación , Fosforilcolina/análogos & derivados , Administración Oral , Antiprotozoarios/efectos adversos , Niño , Preescolar , Colombia , Femenino , Humanos , Masculino , Meglumina/efectos adversos , Antimoniato de Meglumina , Compuestos Organometálicos/efectos adversos , Fosforilcolina/administración & dosificación , Fosforilcolina/efectos adversos , Insuficiencia del TratamientoRESUMEN
BACKGROUND: The clinical and epidemiological significance of Leishmania DNA in extralesional sites is obscured by uncertainty of whether the DNA derives from viable parasites. To examine dissemination of Leishmania during active disease and the potential participation of human infection in transmission, Leishmania 7SLRNA was exploited to establish viability and estimate parasite burden in extralesional sites of dermal leishmaniasis patients. METHODS: The feasibility of discriminating parasite viability by PCR of Leishmania 7SLRNA was evaluated in relation with luciferase activity of luc transfected intracellular amastigotes in dose-response assays of Glucantime cytotoxicity. Monocytes, tonsil swabs, aspirates of normal skin and lesions of 28 cutaneous and 2 mucocutaneous leishmaniasis patients were screened by kDNA amplification/Southern blot. Positive samples were analyzed by quantitative PCR of Leishmania 7SLRNA genes and transcripts. RESULTS: 7SLRNA amplification coincided with luciferase activity, confirming discrimination of parasite viability. Of 22 patients presenting kDNA in extralesional samples, Leishmania 7SLRNA genes or transcripts were detected in one or more kDNA positive samples in 100% and 73% of patients, respectively. Gene and transcript copy number amplified from extralesional tissues were comparable to lesions. 7SLRNA transcripts were detected in 13/19 (68%) monocyte samples, 5/12 (42%) tonsil swabs, 4/11 (36%) normal skin aspirates, and 22/25 (88%) lesions; genes were quantifiable in 15/19 (79%) monocyte samples, 12/13 (92%) tonsil swabs, 8/11 (73%) normal skin aspirates. CONCLUSION: Viable parasites are present in extralesional sites, including blood monocytes, tonsils and normal skin of dermal leishmaniasis patients. Leishmania 7SLRNA is an informative target for clinical and epidemiologic investigations of human leishmaniasis.