Spatial and Temporal Patterns of Phlebotominae Sand Flies (Diptera: Psychodidae) in a Cutaneous Leishmaniaisis Focus in Northern Argentina

Phlebotomine sand ßies (Diptera: Psychodidae) were captured in an area of Argentina endemic for American cutaneous leishmaniasis (ACL). A total of 44,944 ßies were collected during a 130-wk interepidemic period from 1990 through 1993. These sand ßies included Lutzomyia neivai (Pinto) (97.8%), Lutzomyia migonei (Franc¸a) (1.2%), Lutzomyia cortelezzii (Bre`thes) (0.8%), Lutzomyia shannoni (Dyar) (0.1%), and Lutzomyia punctigeniculata (Floch and Abonnenc) (0.1%). Lutzomyia neivai was more abundant in secondary forests and peridomestic environments associated with human cases than in primary forest or xeric thorn scrub areas. Time series analyses of species densities suggested a bimodal or trimodal annual pattern related to rainfall peaks, a 5-wk reproductive cycle, and peridomestic local populations that were located adjacent to secondary forests. In general, sand ßy abundance was correlated with the rainfall of the previous year. Lutzomyia neivai spatial distributions were consistent with ACL incidence patterns during the study and in the recent outbreaks in Argentina. However, Lu. migonei also may be involved in peridomestic transmission. Our results suggest that there is a need for improved, long-term surveillance of sand ßies and ACL cases, as well as development of effective intervention strategies.Fil: Salomón, Oscar Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Wilson, M. l.. University of Michigan; Estados UnidosFil: Munstermann, L. E.. University of Yale; Estados UnidosFil: Travi, B. l.. Centro Internacional de Investigaciones Medicas; Colombi

¿Oncocercosis en Colombia? Una revaluación del foco de López de Micay

Human onchocerciasis was first described as existing in Colombia in 1965 in a small focus in Lopez de Micay on the Pacific Coast. Subsequent follow-up of the focus 12 years later showed that infection-prevalence had fallen from 15 to 7.5%. Since no patients were reported thereafter, the focus was considered to have been extinguished until 1989, when a child with occular keratitis was referred to the University Hospital in Cali. Onchocerciasis was confirmed by skin,snip examination. In July 1989 a multidisciplinaty team conducted a new survey in the area. Skin biopsies were obtained from 170 individuals. Infection-prevalence detected by skin-snip examination was 4.1% (71170). Ten percent of the surveyed males and 0.9% of the females had detectable microfilariae (mf) in skin. Microfilariae density in skin varied between 0.5 mf per milligram of skin to 47 mflmg and was directly related to the patients' age. Neither palpable subcutaneous nodules nor dermal alterations attributable to the parasite were detected in any of the patients. Occular pathology was found in two patients, consisting of bilateral keratitis and retinal degeneration, respectively. Simuliid activity at the time of the survey was very low and collection was not attempted. We hypothesise that active transmission may be taking place further upstream, where vector activity is greater. An increase in non-immune human settlement in the area is expected, due to the future construction of hydroelectrical plants and related connecting highways. Questions are therefore raised concerning the impact of immigration of naive population to this hypoendemic focus.En 1965 se describió el primer foco de oncocercosis humana en Colombia en López de Micay, en la costa pacífica. Doce años después, una visita de seguimiento mostró que la prevalencia de infección había disminuido del 15 al 7,5%. Ya que no se volvieron a reportar pacientes, se consideró extinguido el foco hasta 1989, cuando un niño con queratitis ocular fue remitido al Hospital Universitario de Cali. Se confirmó el diagnóstico de oncocercosis con una biopsia de piel. En julio de 1989 se hizo una nueva visita al área y se tomaron muestras a 170 personas. La prevalencia de infección detectada por biopsia de piel fue de 4,1% (71170). Se detectaron microfilarias (mf) en piel en 10% de los hombres muestreados y 0,9% de las mujeres. La microfilarodermia varió entre 0,5 mf por miligramo de piel y 47mflmg y estaba directamente relacionada con la edad. No se encontraron nódulos subcutáneos palpables ni alteraciones dérmicas atribuibles al parásito en ningún paciente. Dos pacientes presentaron cambios oculares: queratitis bilateral y degeneración de la retina, respectivamente. Durante la visita, la actividad de los simúlidos fue muy baja y no se intentaron capturas. Es probable que la transmisión ocurra en sitios río arriba, donde la actividad de los vectores es mayor. Con la construcción de vías de acceso y una planta hidroeléctrica se espera un aumento de la población no inmune en el área. Cabe preguntar, cúal será el impacto de esta población susceptible sobre este foco hipoendémico

Inflammatory stimuli alter bone marrow composition and compromise bone health in the malnourished host

Inflammation has a role in the pathogenesis of childhood malnutrition. We investigated the effect of malnutrition and inflammatory challenge on bone marrow composition and bone health. We studied an established murine model of moderate acute malnutrition at baseline and after acute inflammatory challenge with bacterial lipopolysaccharide (LPS), a surrogate of Gram-negative bacterial sepsis, or Leishmania donovani, the cause of visceral leishmaniasis. Both of these infections cause significant morbidity and mortality in malnourished children. Of the 2 stimuli, LPS caused more pronounced bone marrow changes that were amplified in malnourished mice. LPS challenge led to increased inflammatory cytokine expression (Il1b, Il6, and Tnf), inflammasome activation, and inflammatory monocyte accumulation in the bone marrow of malnourished mice. Depletion of inflammatory monocytes in Csfr1-LysMcre-DT malnourished mice significantly reduced the inflammasome activation and IL1-ß production after LPS challenge. The inflammatory challenge also led to increased expansion of mesenchymal stem cells (MSCs), bone marrow adiposity, and expression of genes (Pparg, Adipoq, and Srbp1) associated with adipogenesis in malnourished mice. This suggests that inflammatory challenge promotes differentiation of BM MSCs toward the adipocyte lineage rather than toward bone-forming osteoblasts in the malnourished host. Concurrent with this reduced osteoblastic potential there was an increase in bone-resorbing osteoclasts, enhanced osteoclast activity, upregulation of inflammatory genes, and IL-1B involved in osteoclast differentiation and activation. The resulting weakened bone formation and increased bone resorption would contribute to the bone fragility associated with malnutrition. Lastly, we evaluated the effect of replacing lipid rich in omega-6 fatty acids (corn oil) with lipid-rich in omega-3 fatty acids (fish oil) in the nutrient-deficient diet. LPS-challenged malnourished mice that received dietary fish oil showed decreased expression of inflammatory cytokines and Rankl and reduced osteoclast differentiation and activation in the bone marrow. This work demonstrates that the negative effect of inflammatory challenge on bone marrow is amplified in the malnourished host. Increasing dietary intake of omega-3 fatty acids may be a means to reduce inflammation and improve bone health in malnourished children

Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

Comparative Microsatellite Typing of New World Leishmania infantum Reveals Low Heterogeneity among Populations and Its Recent Old World Origin

Leishmania infantum (syn. L. chagasi) is the causative agent of visceral leishmaniasis (VL) in the New World (NW) with endemic regions extending from southern USA to northern Argentina. The two hypotheses about the origin of VL in the NW suggest (1) recent importation of L. infantum from the Old World (OW), or (2) an indigenous origin and a distinct taxonomic rank for the NW parasite. Multilocus microsatellite typing was applied in a survey of 98 L. infantum isolates from different NW foci. The microsatellite profiles obtained were compared to those of 308 L. infantum and 20 L. donovani strains from OW countries previously assigned to well-defined populations. Two main populations were identified for both NW and OW L. infantum. Most of the NW strains belonged to population 1, which corresponded to the OW MON-1 population. However, the NW population was much more homogeneous. A second, more heterogeneous, population comprised most Caribbean strains and corresponded to the OW non-MON-1 population. All Brazilian L. infantum strains belonged to population 1, although they represented 61% of the sample and originated from 9 states. Population analysis including the OW L. infantum populations indicated that the NW strains were more similar to MON-1 and non-MON-1 sub-populations of L. infantum from southwest Europe, than to any other OW sub-population. Moreover, similarity between NW and Southwest European L. infantum was higher than between OW L. infantum from distinct parts of the Mediterranean region, Middle East and Central Asia. No correlation was found between NW L. infantum genotypes and clinical picture or host background. This study represents the first continent-wide analysis of NW L. infantum population structure. It confirmed that the agent of VL in the NW is L. infantum and that the parasite has been recently imported multiple times to the NW from southwest Europe

Current and Future Niche of North and Central American Sand Flies (Diptera: Psychodidae) in Climate Change Scenarios

Ecological niche models are useful tools to infer potential spatial and temporal distributions in vector species and to measure epidemiological risk for infectious diseases such as the Leishmaniases. The ecological niche of 28 North and Central American sand fly species, including those with epidemiological relevance, can be used to analyze the vector’s ecology and its association with transmission risk, and plan integrated regional vector surveillance and control programs. In this study, we model the environmental requirements of the principal North and Central American phlebotomine species and analyze three niche characteristics over future climate change scenarios: i) potential change in niche breadth, ii) direction and magnitude of niche centroid shifts, iii) shifts in elevation range. Niche identity between confirmed or incriminated Leishmania vector sand flies in Mexico, and human cases were analyzed. Niche models were constructed using sand fly occurrence datapoints from Canada, USA, Mexico, Guatemala and Belize. Nine non-correlated bioclimatic and four topographic data layers were used as niche components using GARP in OpenModeller. Both B2 and A2 climate change scenarios were used with two general circulation models for each scenario (CSIRO and HadCM3), for 2020, 2050 and 2080. There was an increase in niche breadth to 2080 in both scenarios for all species with the exception of Lutzomyia vexator. The principal direction of niche centroid displacement was to the northwest (64%), while the elevation range decreased greatest for tropical, and least for broad-range species. Lutzomyia cruciata is the only epidemiologically important species with high niche identity with that of Leishmania spp. in Mexico. Continued landscape modification in future climate change will provide an increased opportunity for the geographic expansion of NCA sand flys’ ENM and human exposure to vectors of Leishmaniases