Incidence Of Human Disease Research Articles

Detection of Arboviruses and Other Micro-Organisms in Experimentally Infected Mosquitoes Using Massively Parallel Sequencing

Human disease incidence attributed to arbovirus infection is increasing throughout the world, with effective control interventions limited by issues of sustainability, insecticide resistance and the lack of effective vaccines. Several promising control strategies are currently under development, such as the release of mosquitoes trans-infected with virus-blocking Wolbachia bacteria. Implementation of any control program is dependent on effective virus surveillance and a thorough understanding of virus-vector interactions. Massively parallel sequencing has enormous potential for providing comprehensive genomic information that can be used to assess many aspects of arbovirus ecology, as well as to evaluate novel control strategies. To demonstrate proof-of-principle, we analyzed Aedes aegypti or Aedes albopictus experimentally infected with dengue, yellow fever or chikungunya viruses. Random amplification was used to prepare sufficient template for sequencing on the Personal Genome Machine. Viral sequences were present in all infected mosquitoes. In addition, in most cases, we were also able to identify the mosquito species and mosquito micro-organisms, including the bacterial endosymbiont Wolbachia. Importantly, naturally occurring Wolbachia strains could be differentiated from strains that had been trans-infected into the mosquito. The method allowed us to assemble near full-length viral genomes and detect other micro-organisms without prior sequence knowledge, in a single reaction. This is a step toward the application of massively parallel sequencing as an arbovirus surveillance tool. It has the potential to provide insight into virus transmission dynamics, and has applicability to the post-release monitoring of Wolbachia in mosquito populations.

Induction and regulation of pathogenic Th17 cell responses in schistosomiasis

Schistosomiasis is a major tropical disease caused by trematode helminths in which the host mounts a pathogenic immune response against tissue-trapped parasite eggs. The immunopathology consists of egg antigen-specific CD4 T cell-mediated granulomatous inflammation that varies greatly in magnitude in humans and among mouse strains in an experimental model. New evidence, covered in this review, intimately ties the development of severe pathology to IL-17-producing CD4 T helper (Th17) cells, a finding that adds a new dimension to the traditional CD4 Th1 vs. Th2 cell paradigm. Most examined mouse strains, in fact, develop severe immunopathology with substantial Th17 as well as Th1 and Th2 cell responses; a solely Th2-polarized response is an exception that is only observed in low-pathology strains such as the C57BL/6. The ability to mount pathogenic Th17 cell responses is genetically determined and depends on the production of IL-23 and IL-1β by antigen presenting cells following recognition of egg antigens; analyses of several F2 progenies of (high × low)-pathology strain crosses demonstrated that quantitative trait loci governing IL-17 levels and disease severity vary substantially from cross to cross. Low pathology is dominant, which may explain the low incidence of severe disease in humans; however, coinfection with intestinal nematodes can also dampen pathogenic Th17 cell responses by promoting regulatory mechanisms such as those afforded by alternatively activated macrophages and T regulatory cells. A better understanding of the pathways conducive to severe forms of schistosomiasis and their regulation should lead to interventions similar to those presently used to manage other immune-mediated diseases.

MiR-122 acts as a tumor suppressor in hepatocarcinogenesis in vivo

miR-122, an abundant liver-specific microRNA (miRNA), regulates cholesterol metabolism and promotes hepatitis C virus (HCV) replication. Reduced miR-122 expression in hepatocel- lular carcinoma (HCC) correlates with metastasis and poor progno- sis. Nevertheless, the consequences of sustained loss of function of miR-122 in vivo have not been determined. Here, we demonstrate that deletion of mouse Mir122 resulted in hepatosteatosis, hepatitis, and the development of tumors resembling HCC. These pathologic manifestations were associated with hyperactivity of oncogenic pathways and hepatic infiltration of inflammatory cells that produce pro-tumorigenic cytokines, including IL-6 and TNF. Moreover, deliv- ery of miR-122 to a MYC-driven mouse model of HCC strongly inhib- ited tumorigenesis, further supporting the tumor suppressor activity of this miRNA. These findings reveal critical functions for miR-122 in the maintenance of liver homeostasis and have important therapeu- tic implications, including the potential utility of miR-122 delivery for selected patients with HCC and the need for careful monitoring of patients receiving miR-122 inhibition therapy for HCV. http://www.ncbi.nlm.nih.gov/pubmed/22820290 Abstract: MicroRNA-122 (miR-122), which accounts for 70% of the liver's total miRNAs, plays a pivotal role in the liver. However, its intrinsic physiological roles remain largely undetermined. We dem- onstrated that mice lacking the gene encoding miR-122a (Mir122a) are viable but develop temporally controlled steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC). These mice exhibited a striking disparity in HCC incidence based on sex, with a male-to-female ratio of 3.9:1, which recapitulates the disease incidence in humans. Impaired expression of microsomal triglyceride transfer protein (MTTP) contributed to steatosis, which was reversed by in vivo resto- ration of Mttp expression. We found that hepatic fibrosis onset can be partially attributed to the action of a miR-122a target, the Klf6 tran- script. In addition, Mir122a � /� livers exhibited disruptions in a range of pathways, many of which closely resemble the disruptions found in human HCC. Importantly, the reexpression of miR-122a reduced dis- ease manifestation and tumor incidence in Mir122a � /� mice. This study demonstrates that mice with a targeted deletion of the Mir122a gene possess several key phenotypes of human liver diseases, which provides a rationale for the development of a unique therapy for the treatment of chronic liver disease and HCC.

What can systems pharmacology contribute to drug development? Disease modelling as a predictive tool

has not progressed as quickly (and development costs represent at least 70% of the billion dollar cost of taking a new chemical entity from conception to market). The reasons are clear: with the possible exception of antiinfectives, drugs for most therapeutic indications involve perturbations of complex interactive systems, our preclinical models all involve sweeping simplifications, and clinical trials usually involve heterogeneous groups of patients. Systems pharmacology approaches present one approach to addressing this complexity. Genetically engineered animal models offer useful approximations to human disease, but an animal model supplemented by a computational disease model greatly increases the range of questions that can be asked. Atherosclerosis presents a case in point: its aetiology is complex, it is affected by environmental and behavioural factors, including diet and smoking, and it may take several decades for the condition to progress to clinical disease. The Apoe-/- mouse reflects many of the features of human atherosclerosis, but there are important differences: in humans the dominant circulating atherogenic particles consist of LDL, while in the Apoe-/- mouse VLDL and IDL predominate. How do these differences affect the ability of the mouse model to predict the outcome of drug treatment or lifestyle changes in humans? Another limitation of the mouse model is that, despite its biological similarities with human atherosclerosis, it does not lead to the same clinical outcomes of angina and heart attack. Why is that? Given these limitations of the mouse model, can it still guide the development of prevention and treatment regimens to reduce the incidence of human heart disease? Chan et al have presented a computational model of atherosclerotic progression that has the potential to improve the predictive power of animal models of the disease, and (when the model is extended from mice to humans) to enable

Geographical and environmental factors driving the increase in the Lyme disease vector Ixodes scapularis.

The population densities of many organisms have changed dramatically in recent history. Increases in the population density of medically relevant organisms are of particular importance to public health as they are often correlated with the emergence of infectious diseases in human populations. Our aim is to delineate increases in density of a common disease vector in North America, the blacklegged tick, and to identify the environmental factors correlated with these population dynamics. Empirical data that capture the growth of a population are often necessary to identify environmental factors associated with these dynamics. We analyzed temporally- and spatially-structured field collected data in a geographical information systems framework to describe the population growth of blacklegged ticks (Ixodes scapularis) and to identify environmental and climatic factors correlated with these dynamics. The density of the ticks increased throughout the study's temporal and spatial ranges. Tick density increases were positively correlated with mild temperatures, low precipitation, low forest cover, and high urbanization. Importantly, models that accounted for these environmental factors accurately forecast future tick densities across the region. Tick density increased annually along the south-to-north gradient. These trends parallel the increases in human incidences of diseases commonly vectored by I. scapularis. For example, I. scapularis densities are correlated with human Lyme disease incidence, albeit in a non-linear manner that disappears at low tick densities, potentially indicating that a threshold tick density is needed to support epidemiologically-relevant levels of the Lyme disease bacterium. Our results demonstrate a connection between the biogeography of this species and public health.

Dual signaling by innate and adaptive immune receptors is required for TLR7-induced B-cell–mediated autoimmunity

Toll-like receptor 7 (Tlr7) has been linked to systemic lupus disease incidence in humans and mice, but how TLR7 potentiates autoimmunity is unclear. We used a Tlr7 transgenic (tg) mouse model to investigate the cellular and molecular events required to induce spontaneous autoimmunity through increased TLR7 activity. We determined that Tlr7 exerts B-cell-intrinsic effects in promoting spontaneous germinal center (GC) and plasmablast B-cell development, and that these B-cell subsets are dependent on T-cell-derived signals through CD40L and SLAM-associated protein (SAP), but not IL-17. Antigen specificity also factored into TLR7-induced disease, as both a restricted T cell receptor (TCR) specificity and MHC haplotype H2(k/k) protected Tlr7tg mice from spontaneous lymphocyte activation and autoantibody production. Inflammatory myeloid cell expansion and autoimmunity did not develop in Tlr7tgIgH(-/-) mice, suggesting either that spontaneous TLR7 activation does not occur in dendritic cells, or, if it does occur, cannot drive these events in the absence of B-cell aid. These data indicate that autoimmune disease in Tlr7tg mice is contingent upon B cells receiving stimulation both through innate pathways and T-cell-derived signals and suggest a codependent relationship between B cells and T cells in the development of autoimmunity.

Environmental factors associated with American cutaneous leishmaniasis in a new Andean focus in Colombia

To evaluate the environmental and ecological factors associated with Leishmania transmission and vector abundance in Chaparral, Tolima-Colombia. First, we compared the ecological characteristics, abundance of phlebotomies and potential reservoir hosts in the peridomestic environment (100 m radius) of randomly selected houses, between two townships with high and low cutaneous leishmaniasis incidence. Second, we examined peridomestic correlates of phlebotomine abundance in all 43 houses in the higher risk township. The high transmission township had higher coverage of forest (23%vs. 8.4%) and shade coffee (30.7%vs. 11%), and less coffee monoculture (16.8%vs. 26.2%) and pasture (6.3%vs. 12.3%), compared to the low transmission township. Lutzomyia were more abundant in the high transmission township 2.5 vs. 0.2/trap/night. Lutzomyia longiflocosa was the most common species in both townships: 1021/1450 (70%) and 39/80 (49%). Numbers of potential wild mammal reservoirs were small, although four species were found to be infected with Leishmania (Viannia) spp. In the high transmission township, the overall peridomiciliary capture rate of L. longiflocosa was 1.5/trap/night, and the abundance was higher in houses located nearer to forest (ρ = -0.30, P = 0.05). The findings are consistent with a domestic transmission cycle with the phlebotomies dependent on dense vegetation near the house.

MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis

MicroRNA-122 (miR-122), which accounts for 70% of the liver's total miRNAs, plays a pivotal role in the liver. However, its intrinsic physiological roles remain largely undetermined. We demonstrated that mice lacking the gene encoding miR-122a (Mir122a) are viable but develop temporally controlled steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC). These mice exhibited a striking disparity in HCC incidence based on sex, with a male-to-female ratio of 3.9:1, which recapitulates the disease incidence in humans. Impaired expression of microsomal triglyceride transfer protein (MTTP) contributed to steatosis, which was reversed by in vivo restoration of Mttp expression. We found that hepatic fibrosis onset can be partially attributed to the action of a miR-122a target, the Klf6 transcript. In addition, Mir122a(-/-) livers exhibited disruptions in a range of pathways, many of which closely resemble the disruptions found in human HCC. Importantly, the reexpression of miR-122a reduced disease manifestation and tumor incidence in Mir122a(-/-) mice. This study demonstrates that mice with a targeted deletion of the Mir122a gene possess several key phenotypes of human liver diseases, which provides a rationale for the development of a unique therapy for the treatment of chronic liver disease and HCC.

Geographic Variation in the Relationship between Human Lyme Disease Incidence and Density of Infected Host-Seeking Ixodes scapularis Nymphs in the Eastern United States

Prevention and control of Lyme disease is difficult because of the complex biology of the pathogen's (Borrelia burgdorferi) vector (Ixodes scapularis) and multiple reservoir hosts with varying degrees of competence. Cost-effective implementation of tick- and host-targeted control methods requires an understanding of the relationship between pathogen prevalence in nymphs, nymph abundance, and incidence of human cases of Lyme disease. We quantified the relationship between estimated acarological risk and human incidence using county-level human case data and nymphal prevalence data from field-derived estimates in 36 eastern states. The estimated density of infected nymphs (mDIN) was significantly correlated with human incidence (r = 0.69). The relationship was strongest in high-prevalence areas, but it varied by region and state, partly because of the distribution of B. burgdorferi genotypes. More information is needed in several high-prevalence states before DIN can be used for cost-effectiveness analyses.

Reducing hazards for humans from animals: emerging and re-emerging zoonoses

Pathogens that are capable of infecting more than one host, more than one taxonomic order and wild hosts, all present a higher relative risk of (re-)emergence. A long environmental persistence gives pathogens a more selective advantage. In case of an emerging or re-emerging zoonosis, the prevalence of infection in animals and the exposure determine the incidence in humans. Human exposure to zoonotic agents depends on lifestyle and occupation (e.g., veterinarians and farmers are more at risk for zoonoses related to livestock). Efforts to increase awareness, provide information on prevention, and apply biosecurity are essential. Moreover, a substantial decline in the incidence of human disease implies the prevention, the control or the elimination of zoonoses in the animal compartments. The only way to prevent health hazards is to adapt the existing systems of health governance at global, regional, national and local levels in a harmonised and coordinated manner. To achieve such a goal, the One Health strategy was recently developed to expand interdisciplinary collaborations and communications on all aspects of health care for humans and animals, veterinary, human medical, public health professionals and stakeholders....

Remotely sensed vegetation moisture as explanatory variable of Lyme borreliosis incidence

The strong correlation between environmental conditions and abundance and spatial spread of the tick Ixodes ricinus is widely documented. I. ricinus is in Europe the main vector of the bacterium Borrelia burgdorferi, the pathogen causing Lyme borreliosis (LB). Humidity in vegetated systems is a major factor in tick ecology and its effects might translate into disease incidence in humans. Time series of two remotely sensed indices with sensitivity to vegetation greenness and moisture were tested as explanatory variables of LB incidence. Wavelet-based multiresolution analysis allowed the examination of these signals at different temporal scales in study sites in Belgium, where increases in LB incidence were reported in recent years. The analysis showed the potential of the tested indices for disease monitoring, the usefulness of analyzing the signal in different time frames and the importance of local characteristics of the study area for the selection of the vegetation index.

Synchronous phenology of juvenile Ixodes scapularis, vertebrate host relationships, and associated patterns of Borrelia burgdorferi ribotypes in the midwestern United States

To elucidate features of enzootic maintenance of the Lyme disease bacterium that affect human risk of infection, we conducted a longitudinal study of the phenology of the vector tick, Ixodes scapularis, at a newly invaded site in the north-central United States. Surveys for questing ticks and ticks parasitizing white-footed mice and eastern chipmunks revealed that I. scapularis nymphal and larval activity peaked synchronously in June and exhibited an atypical, unimodal seasonality. Adult seasonal activity was bimodal and distributed evenly in spring and fall. We discuss implications of these phenology data for the duration of the I. scapularis life cycle. Densities of Borrelia burgdorferi-infected, questing nymphs were comparable to those found in endemic areas elsewhere in the midwestern and northeastern U.S. Molecular genetic diversity of B. burgdorferi infecting these ticks and rodents was assessed by analysis of the ribosomal spacer types (RSTs). RST 1, a clade that includes strains with highly pathogenic properties, was relatively uncommon (3.4%) in contrast to the northeastern U.S., whereas less pathogenic ribotypes of the RST 2 and 3 clades were more common. These features of the ecology of this midwestern Lyme disease system likely contribute to the lower incidence of Lyme disease in humans in the Upper Midwest compared with that of the Northeast owing to reduced exposure to pathogenic strains of B. burgdorferi.

Vaccines for canine leishmaniasis.

Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with immunosuppressive diseases, and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL) in the Americas, the Middle East, Central Asia, China, and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases, and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost–effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine VL. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans and dogs against VL.

Low doses of ethanol decrease the activity of the angiotensin-converting enzyme in the aorta of aging rats and rats treated with a nitric oxide synthase inhibitor and dexamethasone

In the present study, the activity of ACE (angiotensin-converting enzyme) in the aorta of senescent rats and rats treated with the NOS (NO synthase) inhibitor L-NAME (NG-nitro-L-arginine methyl ester) or dexamethasone and the effect of low doses of ethanol (0.2-1.2g/kg of body weight, daily for 8-12days) on this activity were studied. We found that ACE activity increased with age and in response to L-NAME and dexamethasone treatment. Ethanol at a dose of 0.4g/kg of body weight per day decreased ACE activity in the aorta of aged rats and of rats treated with L-NAME or dexamethasone to the level of activity in young control rats. The optimal ethanol dose (the dose inducing a maximum decrease in ACE activity) increased with increasing doses of dexamethasone: 0.4g/kg of body weight per day at 30μg of dexamethasone/kg of body weight and 0.8g/kg of body weight per day at 100μg of dexamethasone/kg of body weight. It was also found that optimal doses of ethanol increased the number of cells in the thymus of rats treated with dexamethasone. The optimal dose of ethanol of 0.4g/kg of body weight per day, which induced a maximum decrease in ACE activity in rat aorta, corresponded to a dose of 30g of ethanol/day, which, according to epidemiological data, produces a maximum decrease in the incidence of cardiovascular disease in humans. In conclusion, the decrease in ACE activity in vessels may be one of the main mechanisms of the beneficial effects of low doses of ethanol on human health.

Identification of 2 Loci Associated with Development of Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniels

Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs. It is characterized by chronic progressive degenerative lesions of the mitral valve. The valve leaflets become thickened and prolapse into the left atrium resulting in mitral regurgitation (MR). MMVD is most prevalent in small to medium sized dog breeds, Cavalier King Charles Spaniels (CKCS) in particular. The onset of MMVD is highly age dependent, and at the age of 10 years, nearly all CKCS are affected. The incidence of a similar disease in humans-mitral valve prolapse-is 1-5%. By defining CKCSs with an early onset of MMVD as cases and old dogs with no or mild signs of MMVD as controls, we conducted a genome-wide association study (GWAS) to identify loci associated with development of MMVD. We have identified a 1.58 Mb region on CFA13 (P(genome) = 4.0 × 10(-5)) and a 1.68 Mb region on CFA14 (P(genome) = 7.9 × 10(-4)) associated with development of MMVD. This confirms the power of using the dog as a model to uncover potential candidate regions involved in the molecular mechanisms behind complex traits.

Cytokine and Phenotypic Cell Profiles ofLeishmania infantumInfection in the Dog

Leishmaniasis has reemerged in recent years showing a wider geographic distribution and increased global incidence of human and canine disease than previously known. Dogs are the main domestic/peridomestic reservoir hosts of zoonotic visceral leishmaniasis caused by Leishmania infantum. Since the evolution of leishmaniasis and clinical appearance is a consequence of complex interactions between the parasite and host immune response, a profound knowledge about the immune profile developed in dog's infection is crucial for vaccine and immunomodulatory therapy design. The main goal of this paper is to compile the recent advances made on cytokine and phenotypic cell profiles in different tissues and organs of dogs infected with L. infantum. This paper also stressed that the knowledge of the immune responses developed, namely, in liver, lymph node, and spleen is very limited. All data emphasizes that more research on canine leishmaniasis is necessary for the development of new and efficacious tools to control zoonotic leishmaniasis.

Tick‐borne encephalitis in Latvia 1973–2009: epidemiology, clinical features and sequelae

To report a 37-year observational experience in Latvia relating the incidence of human tick-borne encephalitis (TBE) and its clinical manifestations, to the field abundance of ticks. Tick abundance was measured by standard flagging techniques. Incidence of human tick-borne disease was derived from Public Health reporting data. Clinical and follow-up data were determined from hospital cohorts from 1973 to 2009. Two TBE incidence peaks in the mid-1970s and the 1990s correlated with increased field abundance of ticks. Increased human TBE in the 1970s was associated with higher field abundance of both Ixodes ricinis and I. Persulcatus. The 1990s peak was particularly associated with I. ricinus, the species predominating in western/central Latvia, and with other factors, including changed agricultural land usage. Proportions of patients with meningitic or focal forms of TBE were similar in the two outbreaks and the intervening periods. Meningeal irritation occurred in 90%, altered consciousness in 19%, ataxia in 34%, seizures in 9%, bulbar features in 2-3% and limb weakness in 15% with shoulder amyotrophy predominating in 5%. Annual mortality varied from 0 to 1.3% and was not related to the overall incidence of TBE. Follow-up for 1-13 years of a cohort of 100 patients revealed long-term sequelae in over 50%, more commonly in those suffering focal forms of acute TBE. Clinical features and mortality of the 1970s and 1990s TBE outbreaks were similar and did not point to a change in virulence.

Multi-source analysis reveals latitudinal and altitudinal shifts in range of Ixodes ricinus at its northern distribution limit

BackgroundThere is increasing evidence for a latitudinal and altitudinal shift in the distribution range of Ixodes ricinus. The reported incidence of tick-borne disease in humans is on the rise in many European countries and has raised political concern and attracted media attention. It is disputed which factors are responsible for these trends, though many ascribe shifts in distribution range to climate changes. Any possible climate effect would be most easily noticeable close to the tick's geographical distribution limits. In Norway- being the northern limit of this species in Europe- no documentation of changes in range has been published. The objectives of this study were to describe the distribution of I. ricinus in Norway and to evaluate if any range shifts have occurred relative to historical descriptions.MethodsMultiple data sources - such as tick-sighting reports from veterinarians, hunters, and the general public - and surveillance of human and animal tick-borne diseases were compared to describe the present distribution of I. ricinus in Norway. Correlation between data sources and visual comparison of maps revealed spatial consistency. In order to identify the main spatial pattern of tick abundance, a principal component analysis (PCA) was used to obtain a weighted mean of four data sources. The weighted mean explained 67% of the variation of the data sources covering Norway's 430 municipalities and was used to depict the present distribution of I. ricinus. To evaluate if any geographical range shift has occurred in recent decades, the present distribution was compared to historical data from 1943 and 1983.ResultsTick-borne disease and/or observations of I. ricinus was reported in municipalities up to an altitude of 583 metres above sea level (MASL) and is now present in coastal municipalities north to approximately 69°N.ConclusionI. ricinus is currently found further north and at higher altitudes than described in historical records. The approach used in this study, a multi-source analysis, proved useful to assess alterations in tick distribution.

Regional Differences in the Association Between Land Cover and West Nile Virus Disease Incidence in Humans in the United States

West Nile virus (WNV) is generally considered to be an urban pathogen in the United States, but studies associating land cover and disease incidence, seroprevalence, or infection rate in humans, birds, domesticated and wild mammals, and mosquitoes report varying and sometimes contradictory results at an array of spatial extents. Human infection can provide insight about basic transmission activity; therefore, we analyzed data on the incidence of WNV disease in humans to obtain a comprehensive picture of how human disease and land cover type are associated across the United States. Human WNV disease incidence in Northeastern regions was positively associated with urban land covers, whereas incidence in the Western United States was positively associated with agricultural land covers. We suggest that these regional associations are explained by the geographic distributions of prominent WNV vectors: Culex pipiens complex (including Cx. pipiens and Cx. quinquefasciatus) in the Northeast and Cx. tarsalis in the Western United States.

Forty years of visceral leishmaniasis in the State of Piaui: a review

Visceral leishmaniasis (VL) has been known to occur in the state of Piauí since 1934. The typically rural disease began to appear in urban areas over time, being concentrated mainly in Teresina, the capital of Piauí. Teresina was also affected by the first urban epidemic of VL in Brazil. Over 1,000 cases of the disease were reported during urbanization (1981-1986). Human population growth and migration led to land occupation on the outskirts of Teresina. These factors have contributed to vector proliferation, increasing the incidence of VL. At present, the incidence of human and canine disease is quite high and uncontrolled in Piauí. It seems that some measures, such as the elimination of seropositive dogs, failed to significantly reduce the number of new VL cases in Teresina. Despite previously conducted studies, little is known about VL epidemiology in urban areas. The aim of this review is to reveal the situation of VL in Teresina during the last 40 years, focusing on the major factors that may contribute to the high incidence and persistence of VL infection.