RESUMO
The World Health Organization (WHO) aims to reduce new leprosy cases by 70% by 2030, necessitating advancements in leprosy diagnostics. Here we discuss the development of two WHO's target product profiles for such diagnostics. These profiles define criteria for product use, design, performance, configuration and distribution, with a focus on accessibility and affordability. The first target product profile outlines requirements for tests to confirm diagnosis of leprosy in individuals with clinical signs and symptoms, to guide multidrug treatment initiation. The second target product profile outlines requirements for tests to detect Mycobacterium leprae or M. lepromatosis infection among asymptomatic contacts of leprosy patients, aiding prophylactic interventions and prevention. Statistical modelling was used to assess sensitivity and specificity requirements for these diagnostic tests. The paper highlights challenges in achieving high specificity, given the varying endemicity of M. leprae, and identifying target analytes with robust performance across leprosy phenotypes. We conclude that diagnostics with appropriate product design and performance characteristics are crucial for early detection and preventive intervention, advocating for the transition from leprosy management to prevention.
L'Organisation mondiale de la Santé (OMS) vise à réduire le nombre de nouveaux cas de lèpre de 70% d'ici 2030, ce qui nécessite un meilleur diagnostic de la maladie. Dans le présent document, nous évoquons le développement de deux profils de produit cible établis par l'OMS à cette fin. Ces profils définissent des critères en matière d'utilisation, de conception, de performances, de configuration et de distribution du produit, en accordant une attention particulière à l'accessibilité et à l'abordabilité. Le premier profil de produit cible décrit les exigences pour les tests servant à confirmer le diagnostic de la lèpre chez les individus qui présentent des signes cliniques et des symptômes, afin d'orienter l'instauration d'un traitement à base de plusieurs médicaments. Le second profil de produit cible décrit les exigences pour les tests servant à détecter une infection à Mycobacterium leprae ou M. lepromatosis parmi les contacts asymptomatiques de patients lépreux, ce qui contribue à l'adoption de mesures prophylactiques et à la prévention. Nous avons eu recours à une modélisation statistique pour évaluer les exigences de sensibilité et de spécificité de ces tests diagnostiques. Cet article met en évidence les obstacles à l'atteinte d'un niveau élevé de spécificité en raison de l'endémicité variable de M. leprae, et à l'identification d'analytes cibles offrant de bons résultats chez les phénotypes lépreux. Nous concluons qu'un diagnostic reposant sur des caractéristiques de performance et de conception appropriées est essentiel pour détecter rapidement la maladie et intervenir en amont, et nous plaidons pour une prévention plutôt qu'une gestion de la lèpre.
La Organización Mundial de la Salud (OMS) pretende reducir los nuevos casos de lepra en un 70% para 2030, lo que requiere avances en el diagnóstico de la lepra. Aquí se analiza el desarrollo de dos perfiles de productos objetivo de la OMS para este tipo de diagnósticos. Estos perfiles definen los criterios de uso, diseño, rendimiento, configuración y distribución de los productos, centrándose en su accesibilidad y asequibilidad. El primer perfil de producto objetivo describe los requisitos de las pruebas para confirmar el diagnóstico de la lepra en personas con signos y síntomas clínicos, con el fin de orientar el inicio del tratamiento con múltiples fármacos. El segundo perfil de producto objetivo describe los requisitos de las pruebas para detectar la infección por Mycobacterium leprae o M. lepromatosis entre los contactos asintomáticos de los pacientes con lepra, para facilitar las intervenciones profilácticas y la prevención. Se utilizaron modelos estadísticos para evaluar los requisitos de sensibilidad y especificidad de estas pruebas diagnósticas. El artículo destaca las dificultades para lograr una alta especificidad, dada la diferente endemicidad de M. leprae, y para identificar analitos diana con un rendimiento sólido en todos los fenotipos de lepra. Concluimos que los diagnósticos con un diseño de producto y unas características de rendimiento adecuados son fundamentales para la detección precoz y la intervención preventiva, lo que favorece la transición del manejo de la lepra a la prevención.
Assuntos
Hanseníase , Humanos , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Mycobacterium leprae/genética , Sensibilidade e Especificidade , Modelos Estatísticos , Diagnóstico PrecoceRESUMO
INTRODUCTION: Diverticulitis is a prevalent gastrointestinal disease that may require surgical intervention. The aim of the study was to investigate the involvement of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) as biomarkers of severity in complicated diverticular disease (CDD) in Mexican patients and their correlation with the need for surgical intervention, the length of hospital stay, and mortality. MATERIAL AND METHODS: An observational, longitudinal, and retrospective study performed from 2017 to 2021 was considered in patients over 18 years of age, with a diagnosis of CDD by using computed tomography and with a hemogram taken in the first 24 hours upon admission to the emergency department to describe the sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) of NLR and PLR in the CDD. Results: A total of 102 Mexican patients suffering from CDD, 54% women and 46% men with a mean of 59 years, were analyzed. According to Hinchey's classification, 79 (77.5%) patients showed type I, 12 (12.8%) type II, 5 (4.9%) type III, and 6 (5.9%) type IV. The mean hospital stay was 8.8 days, with a mortality rate of 3.9%. The cut-off value was established at 5.1 for NLR according to the results of the receiver operating characteristic (ROC) curve with an area under the curve (AUC) of 0.633, a sensitivity of 90%, a specificity of 43%, PPV of 21.8%, and NPV of 96% for the prediction of CDD. A cut-off value for PLR at 72 was established according to the results of the ROC curve with an AUC of 0.482, a sensitivity of 78%, a specificity of 40%, PPV of 96%, and NPV of 9% for the prediction of CDD. CONCLUSION: The NLR and PLR are easily calculable and accessible biomarkers that can be part of the decision-making for the diagnosis and treatment of CDD in Mexican people as has been observed in other populations. However, more prospective, multicenter comparative studies are needed to assess the efficacy and safety of these biomarkers in relation to those already described.
RESUMO
La importancia del análisis cefalométrico dentro del diagnóstico en ortodoncia ha ido incrementando a través de los años, por ello, el interés de comparar la confiabilidad de los sistemas digitales con el trazado manual convencional. Objetivo: Definir el grado de concordancia entre los resultados de trazado cefalométrico manual y con Nemoceph. Material y métodos: Se utilizaron ocho medidas lineales y angulares del análisis cefalométrico de Steiner. Se realizó un estudio transversal, correlacional, en el cual se analizaron 70 radiografías laterales de cráneo digitales. Los resultados se dividieron en dos grupos, trazado manual y trazado cefalométrico con Nemoceph, los cuales fueron evaluados con un índice de correlación intraclase. Conclusión: Se reportó un grado de correlación intraclase mayor a 0.75, estableciendo que el sistema digital exhibe la misma precisión del manual, con algunas ventajas convenientes a la época (AU)
The importance taken by the cephalometric analysis within the orthodontic diagnosis has been increasing over the years, for that reason the interest of comparing the reliability of the digital systems with the conventional manual tracing. Objective: To define the degree of concordance between the results of manual cephalometric tracing and with Nemoceph. Material and methods: Eight linear and angular measurements of Steiner's cephalometric analysis were used. A crosssectional, correlational study was conducted in which 70 digital skull lateral radiographs were analyzed. The results were divided into two groups; manual tracing and cephalometric tracing with Nemoceph, which were evaluated with an intraclass correlation index. Conclusion: a correlation degree greater than 0.75 was reported. Establishing that the digital system exhibits the same precision of the manual, with some advantages suited to the age (AU)
Assuntos
Humanos , Cefalometria/métodos , Radiografia Dentária Digital , Má Oclusão/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Estudos Transversais , MéxicoRESUMO
BACKGROUND The transmission routes for American cutaneous leishmaniasis (ACL) are in flux, so studies examining its transmission in humans, mammalian hosts, and sand fly vectors are urgently needed. OBJECTIVES The aim of this work was understand the epidemiological cycles of Leishmania spp., which causes ACL in the Andean Region of Venezuela, by identifying the Leishmania and the sand fly species involved in human and dog infections. METHODS Thirty-one biopsies from patients in Mérida and Táchira states with suspected ACL were studied by both parasitological tests (cultures and hamster inoculation) and a molecular test [Internal transcribed spacer 1 (ITS1) nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)]. We also conducted a survey to detect Leishmania infection in dogs (Immunifluorescence antibody test and ITS1 nested PCR-RFLP) and sand flies (ITS1 nested PCR-RFLP) from El Carrizal, a highly endemic focus of ACL in Venezuela. FINDINGS Three different Leishmania species were identified in the clinical samples from humans (Leishmania braziliensis, L. guyanensis, and L. mexicana) and dogs (L. guyanensis and L. mexicana). The predominant sand fly species found were those from the Verrucarum group (infected with L. mexicana) and Lutzomyia migonei (infected with L. guyanensis and L. mexicana). MAIN CONCLUSIONS We show that Lu. migonei may be the putative vector in two ACL epidemiological cycles, involving L. guyanensis and L. mexicana. We also report for the first time the presence of L. guyanensis in domestic animals.
Assuntos
Humanos , Leishmania , Leishmania/parasitologia , Polimorfismo de Fragmento de Restrição , Reação em Cadeia da PolimeraseRESUMO
The aim of this work was to establish a modified pre-diagnostic polymerase chain reaction (PCR) protocol using a single primer set that enables successful amplification of a highly conserved mammalian sequence in order to determine overall sample DNA quality for multiple mammalian species that inhabit areas endemic for leishmaniasis. The gene encoding interphotoreceptor retinoid-binding protein (IRBP), but not other conserved genes, was efficiently amplified in DNA samples from tail skin, ear skin, bone marrow, liver and spleen from all of the species tested. In tissue samples that were PCR-positive for Leishmania, we found that DNA from 100 percent, 55 percent and 22 percent of the samples tested resulted in a positive PCR reaction for the IRBP, beta-actin and beta-globin genes, respectively. Nucleotide sequencing of an IRBP amplicon resolved any questions regarding the taxonomical classification of a rodent, which was previously based simply on the morphological features of the animal. Therefore, PCR amplification and analysis of the IRBP amplicon are suitable for pre-diagnostically assessing DNA quality and identifying mammalian species living in areas endemic to leishmaniasis and other diseases.
Assuntos
Animais , Cães , Actinas , DNA de Protozoário , Proteínas do Olho , Leishmaniose/veterinária , Reação em Cadeia da Polimerase/veterinária , Proteínas de Ligação ao Retinol , Globinas beta , Actinas , Primers do DNA , Doenças Endêmicas , Proteínas do Olho , Leishmaniose , Marsupiais , Reação em Cadeia da Polimerase/métodos , Roedores , Proteínas de Ligação ao Retinol , Globinas betaRESUMO
En 1999, en el Hospital del Niño se registró un nuevo caso de Leishmaniasis visceral sobre un niño de dos años proveniente del cantón de Taipiplaya (Provincia Caranavi). Por este motivo se realiza en este cantón una evaluación transversal de la leishmaniasis visceral mediante pruebas serológicas y moleculares involucrando a 122 inpiduos clínicamente sanos y un individuo con infección positiva a Leishmania cutánea, Se demostró la circulación de Leishmania sp. en 32,3 por ciento de sujetos estudiados. El 14,4 por ciento de la población examinada presentó anticuerpos anti-rk39, demostrándose la circulación de Leishmania chagasi responsable de la leishmaniasis visceral. No podemos descartar la posibilidad de la existencia de coinfecciones mixtas inter-especie de Leishmania como también de coinfecciones mixtas por Leishmania sp y Trypanosoma cruzi, responsable de la enfermedad de Chagas.
Assuntos
Humanos , Doença de Chagas/etiologia , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Infecções por Protozoários , Testes Sorológicos , Bolívia/epidemiologia , Leishmania infantum/patogenicidadeRESUMO
En 1999, en el Hospital del Niño se registró un nuevo caso de Leishmaniasis visceral sobre un niño de dos años proveniente del cantón de Taipiplaya (Provincia Caranavi). Por este motivo se realiza en este cantón una evaluación transversal de la leishmaniasis visceral mediante pruebas serológicas y moleculares involucrando a 122 individuos clínicamente sanos y un individuo con infección positiva a Leishmania cutánea, Se demostró la circulación de Leishmania sp. en 32,3% de sujetos estudiados. El 14.4% de la población examinada presentó anticuerpos anti-rk39, demostrándose la circulación de Leishmania chagasi responsable de la leishmaniasis visceral. No podemos descartar la posibilidad de la existencia de coinfecciones mixtas inter-especie de Leishmania como también de coinfecciones mixtas por Leishmania sp. y Trypanosoma cruzi, responsable de la enfermedad de Chagas.
In 1999, in the "Hospital del Niño". a new case of visceral leishmaniasis was identified in a 2 years old child from Taipiplaya in the Caranavi district. For this reason, a visceral leishmaniasis evaluation using serological and molecular tests was realized on 122 healthy people and also on one leishmania cutanea infected person. Leishmania spp was present in 32,3 % of the studied people and 14,4 % had an anti-rk39 antibody, attesting the existence of Leishmania chagasi responsible for visceral leishmaniasis. The possibility of mixed infections with other Leishmania species as well as mixed infections Leishmania spp and Trypanosama cruzi, responsible for chagas disease should not be discarded.