Premature deaths by visceral leishmaniasis in Brazil investigated through a cohort study: A challenging opportunity?

BACKGROUND: Visceral Leishmaniasis (VL) is the most severe form of leishmaniasis because it can lead to death. In the Americas, 96% of cases are in Brazil, and despite efforts, the fatality rate has increased in the past years. We analyzed deaths associated to VL in Brazil and investigated the factors that could influence on the timeliness of fatal outcome with emphasis on time (tStoD). METHODOLOGY: The registered deaths by VL were sourced from the Brazilian National Notification System from 2007-2014. Through a retrospective cohort study, univariate and multivariable Cox proportional hazards model analysis were performed and investigated the factors that could influence the time (tStoD). These factors were analyzed through survival models. RESULTS: Out of the 1,589 reported deaths, the median for onset of the symptoms and the case notification date (tStoN) is 25 days (10-61), and for date of case notification and death (tNotD) is 9 days (4-17). The time (tStoN) to event investigation for HIV non-infected individuals was 1.4 (1.16-1.68) greater than the HIV positive group. At the same time peri-urban and urban area were 0.83 (0.47-1.44) and 1.33 (1.16-1.52), respectively. The explorations revealed apparent differences between the time to event investigation (both for tStoN and tNotD) and the age at the onset of the symptoms. According to the tStoN the rate of notification is 1.73 times greater in patients under 5 years old at the onset of the clinical symptoms compared to older patients. CONCLUSION: VL patients under 5 years old were diagnosed earlier and had shorter survival. It could mean that in younger population, although properly diagnosed, the fatality pattern might be related to the severity of the disease. Main host characteristics were evaluated, and age and co-infections seem to have an impact in the disease progression.

Detección molecular de Leishmania (Viannia) lainsoni Silveira, Shaw, Braga & Ishikawa, 1987 (Kinetoplastida: Trypanosomatidae) en humanos de Paraguay

RESUMEN La leishmaniasis es una de las enfermedades tropicales más desatendidas, causada por el parásito Leishmania. En Paraguay, la especie responsable de la leishmaniasis cutánea es (LC) es L. (Viannia) braziliensis. Aquí se reporta un caso diagnosticado de Leishmaniasis, y análisis moleculares empleando reacción en cadena de la polimerasa - polimorfismos de restricción de fragmentos de restricción (PCR-RFLP) demostraron que el caso fue causado por L. (V.) lainsoni. Este es el primer registro de esta especie para Paraguay, con lo cual se extiende el rango de distribución conocido de la especie, unos 1.430 km al sur de localidades previamente conocidas. Se necesitan más estudios para conocer la incidencia real de esta especie en casos de LC en Paraguay, y para identificar reservorios naturales del parásito en la naturaleza.

ABSTRACT Leishmaniasis is one of the most neglected tropical diseases worldwide caused by the parasite Leishmania. In Paraguay the species responsible for cutaneous leishmaniasis (CL) is L. (Viannia) braziliensis. Here we report a case diagnosed with Leishmaniasis, and molecular analyses using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) demonstrate that the case was caused by L. (V.) lainsoni. This is the first record of this species for Paraguay, with which we extend the distribution range of the parasite 1,430 km southwards from the southernmost previous known locality. More studies are needed to know the actual incidence of this species in cases of CL in Paraguay, and to identify natural reservoirs in the wild.

Gene expression profile of cytokines produced in biopsies from patients with American cutaneous leishmaniasis.

American cutaneous leishmaniasis (ACL) causes a local inflammatory process, inducing expression of several cytokine genes. Particularly, IFN-γ can predict to disease susceptibility. Based in these data, this study was aimed to investigate the gene expression profile of IFN-γ, IL-10, IL-27, TNF-γ, TGF-ß and IL-6 produced in biopsies from ACL patients; and whether the gene expression profile of IFN-γ could determine the disease evolution. Gene expression of 6 cytokines was investigated in 40 formalin-fixed paraffin embedded (FFPE) biopsies from patients with cutaneous leishmaniosis (CL); and 10 FFPE biopsies from patients with mucosal leishmaniasis (ML) (control). All 50 patients were infected with Leishmania (Viannia) braziliensis. Gene expression was determined by qPCR; and a normal control group was used for calculations (5 normal biopsies). Values were expressed as Relative Quantification (RQ). The 40 CL patients were classified into 2 groups. CLlowIFN-γ, 35 patients with RQ for IFN-γ below 100; and CLhighIFN-γ, 5 (12.5%) patients with RQ above 100. Significant increase of mRNA levels of IFN-γ, IL-10 and IL-27 was shown in CLhighIFN-γ group when compared with CLlowIFN-γ and ML groups. TNF-α levels in CLlowIFN-γ group were higher than CLhighIFN-γ and ML groups. TGF-ß and IL-6 were similar in 3 groups. Comparison of cytokine expression/group showed that CLlowIFN-γ group had an equilibrium between the cytokines analyzed. In ML group, IFN-γ was over-expressed; but in CLhighIFN-γ group, besides IFN-γ, IL-27 was also over-expressed. The immune response to Leishmania induces to identification of some markers, which can be determined by analysis by gene expression of cytokines produced in biopsies.

Cutaneous and mucocutaneous leishmaniasis.

Tegumentary leishmaniases are caused by approximately 15 species of protozoa of the genus Leishmania. They prevail in tropical and subtropical areas of the Old and New World but human mobility also makes them a medical problem in nonendemic areas. Clinical manifestations may comprise cutaneous and mucocutaneous forms that may be localized, disseminated, or diffuse in distribution and may differ in Old and New World leishmaniases. Diagnosis and treatment vary according to the clinical manifestations, geographic area, and Leishmania species involved. This article highlights the diversity and complexity of tegumentary leishmaniases, which are worsened by human immunodeficiency virus/Leishmania coinfection.