Clinical and epidemiological characteristics of Madariaga and Venezuelan equine encephalitis virus infections.

Madariaga virus (MADV) and Venezuelan equine encephalitis virus (VEEV) are emerging arboviruses affecting rural and remote areas of Latin America. However, there are limited clinical and epidemiological reports available, and outbreaks are occurring at an increasing frequency. We addressed this gap by analyzing all the available clinical and epidemiological data of MADV and VEEV infections recorded since 1961 in Panama. A total of 168 of human alphavirus encephalitis cases were detected in Panama from 1961 to 2023. Here we describe the clinical signs and symptoms and epidemiological characteristics of these cases, and also explored signs and symptoms as potential predictors of encephalitic alphavirus infection when compared to those of other arbovirus infections occurring in the region. Our results highlight the challenges clinical diagnosis of alphavirus disease in endemic regions with overlapping circulation of multiple arboviruses.

Everglades virus: an underrecognized disease-causing subtype of Venezuelan equine encephalitis virus endemic to Florida, USA.

Everglades virus (EVEV) is subtype II of the Venezuelan equine encephalitis virus (VEEV) complex (Togaviridae: Alphavirus), endemic to Florida, USA. EVEV belongs to a clade that includes both enzootic and epizootic/epidemic VEEV subtypes. Like other enzootic VEEV subtypes, muroid rodents are important vertebrate hosts for EVEV and certain mosquitoes are important vectors. The hispid cotton rat Sigmodon hispidus and cotton mouse Peromyscus gossypinus are important EVEV hosts, based on natural infection (virus isolation and high seropositivity), host competence (experimental infections), and frequency of contact with the vector. The mosquito Culex (Melanoconion) cecedei is the only confirmed vector of EVEV based upon high natural infection rates, efficient vector competence, and frequent feeding upon muroid rodents. Human disease attributed to EVEV is considered rare. However, cases of meningitis and encephalitis are recorded from multiple sites, separated by 250 km or more. Phylogenetic analyses indicate that EVEV is evolving, possibly due to changes in the mammal community. Mutations in the EVEV genome are of concern, given that epidemic strains of VEEV (subtypes IAB and IC) are derived from enzootic subtype ID, the closest genetic relative of EVEV. Should epizootic mutations arise in EVEV, the abundance of Aedes taeniorhynchus and other epizootic VEEV vectors in southern Florida provides a conducive environment for widespread transmission. Other factors that will likely influence the distribution and frequency of EVEV transmission include the establishment of Culex panocossa in Florida, Everglades restoration, mammal community decline due to the Burmese python, land use alteration by humans, and climate change.

Madariaga and Venezuelan equine encephalitis virus seroprevalence in rodent enzootic hosts in Eastern and Western Panama.

While rodents are primary reservoirs of Venezuelan equine encephalitis virus (VEEV), their role in Madariaga virus (MADV) transmission remains uncertain, particularly given their overlapping geographic distribution. This study explores the interplay of alphavirus prevalence, rodent diversity, and land use within Darien and Western Panama provinces. A total of three locations were selected for rodent sampling in Darien province: Los Pavitos, El Real de Santa Maria and Santa Librada. Two sites were selected in Western Panama province: El Cacao and Cirí Grande. We used plaque reduction neutralization tests to assess MADV and VEEV seroprevalences in 599 rodents of 16 species across five study sites. MADV seroprevalence was observed at higher rates in Los Pavitos (Darien province), 9.0%, 95% CI: 3.6-17.6, while VEEV seroprevalence was elevated in El Cacao (Western Panama province), 27.3%, 95% CI: 16.1-40.9, and El Real de Santa María (Darien province), 20.4%, 95% CI: 12.6-29.7. Species like Oryzomys coesi, 23.1%, 95% CI: 5.0-53.8, and Transandinomys bolivaris, 20.0%, 95% CI: 0.5-71.6 displayed higher MADV seroprevalences than other species, whereas Transandinomys bolivaris, 80.0%, 95% CI: 28.3-99.4, and Proechimys semispinosus, 27.3%, 95% CI: 17.0-39.6, exhibited higher VEEV seroprevalences. Our findings provide support to the notion that rodents are vertebrate reservoirs of MADV and reveal spatial variations in alphavirus seropositivity among rodent species, with different provinces exhibiting distinct rates for MADV and VEEV. Moreover, specific rodent species are linked to unique seroprevalence patterns for these viruses, suggesting that rodent diversity and environmental conditions might play a significant role in shaping alphavirus distribution.

Infectivity of three Mayaro Virus geographic isolates in human cell lines.

Mayaro virus (MAYV) is an emergent arthropod-borne virus that causes an acute febrile illness accompanied by arthralgia, similar to chikungunya virus. Increasing urbanization of MAYV outbreaks in the Americas has led to concerns for geographic expansion and spillover. Given the potential importance of this pathogen, we sought to fill critical gaps in knowledge regarding MAYV infectivity and geographic variation. This study describes the cytopathogenicity of MAYV in human dermal fibroblasts, human skeletal muscle satellite cells, human embryonic kidney cells (HEK), peripherally derived human macrophages, and Vero cells. We found that regional differences between these viruses do not affect replication kinetics, with high titers peaking at 37 h post infection. MAYV-U, did however, cause the most cytopathic effect in a time-dependent manner. Compared to the other two prototypic isolates, MAYV-U harbors unique mutations in the E2 protein, D60G and S205F, that are likely to interact with the host cell receptor and could affect infectivity. We further demonstrate that pre-treatment of cells with interferon-ß inhibited viral replication in a dose-dependent manner. Together, these findings advance our understanding of MAYV infection of human target cells and provide initial data regarding variation according to geography.

Everglades virus evolution: Genome sequence analysis of the envelope 1 protein reveals recent mutation and divergence in South Florida wetlands.

Everglades virus (EVEV) is a subtype (II) of Venezuelan equine encephalitis virus (VEEV), endemic in southern Florida, USA. EVEV has caused clinical encephalitis in humans, and antibodies have been found in a variety of wild and domesticated mammals. Over 29,000 Culex cedecei females, the main vector of EVEV, were collected in 2017 from Big Cypress and Fakahatchee Strand Preserves in Florida and pool-screened for the presence of EVEV using reverse transcription real-time polymerase chain reaction. The entire 1 E1 protein gene was successfully sequenced from fifteen positive pools. Phylogenetic analysis showed that isolates clustered, based on the location of sampling, into two monophyletic clades that diverged in 2009. Structural analyses revealed two mutations of interest, A116V and H441R, which were shared among all isolates obtained after its first isolation of EVEV in 1963, possibly reflecting adaptation to a new host. Alterations of the Everglades ecosystem may have contributed to the evolution of EVEV and its geographic compartmentalization. This is the first report that shows in detail the evolution of EVEV in South Florida. This zoonotic pathogen warrants inclusion into routine surveillance given the high natural infection rate in the vectors. Invasive species, increasing urbanization, the Everglades restoration, and modifications to the ecosystem due to climate change and habitat fragmentation in South Florida may increase rates of EVEV spillover to the human population.

Lobomycosis Epidemiology and Management: The Quest for a Cure for the Most Neglected of Neglected Tropical Diseases.

Lobomycosis is a chronic disease caused by Lacazia loboi, which is endemic to the Amazon rainforest, where it affects forest dwellers in Brazil. There is no disease control program and no official therapeutic protocol. This situation contributes to an unknown disease prevalence and unmet needs of people disabled by this disease who seek access to treatment. This review provides an update on the subject with an emphasis on therapeutic advances in humans. All relevant studies that addressed epidemiology, diagnosis, or therapeutics of lobomycosis were considered. Seventy-one articles published between 1931 and 2021 were included for a narrative literature review on the epidemiology and quest for a cure. An effective therapy for lobomycosis has been found following decades of research led by the State Dermatology Program of Acre in the Amazon rainforest, where the largest number of cases occur. This discovery opened new avenues for future studies. The main recommendations here, addressed to the Brazilian Ministry of Health, are for lobomycosis to become a reportable disease to ensure that disease prevalence is measured, and that it be prioritized such that affected individuals may access treatment free-of-charge.

Evaluating sampling strategies for enzootic Venezuelan equine encephalitis virus vectors in Florida and Panama.

Determining effective sampling methods for mosquitoes are among the first objectives in elucidating transmission cycles of vector-borne zoonotic disease, as the effectiveness of sampling methods can differ based on species, location, and physiological state. The Spissipes section of the subgenus Melanoconion of Culex represents an understudied group of mosquitoes which transmit Venezuelan equine encephalitis viruses (VEEV) in the Western Hemisphere. The objective of this study was to determine effective collection methods that target both blood-engorged and non-engorged females of the Spissipes section of Culex subgenus Melanoconion to test the hypothesis that favorable trapping methods differ between species and by physiological status within a species. Mosquitoes were collected using two commercially available traps, (CDC-light trap and BG-Sentinel trap), two novel passive traps (a novel mosquito drift fence and pop-up resting shelters), and two novel aspirators, (a small-diameter aspirator and a large-diameter aspirator) in Darién, Panama, and Florida, USA. The total number of female mosquitoes collected for each species was compared using rarefaction curves and diversity metrics. We also compared the utility of each trap for collecting total females and blood-engorged females of four Spissipes section mosquito species in Florida and Darién. In Darién, it was found that both blood-engorged and unfed females of Cx. pedroi were most effectively collected using the mosquito drift fence at 57.6% and 61.7% respectively. In contrast, the most unfed Cx. spissipes were collected using the mosquito drift fence (40.7%) while blood-engorged females were collected effectively by pop-up resting shelters (42.3%). In Florida, the best sampling technique for the collection of blood-engorged Cx. panocossa was the large diameter aspirator at 41.9%, while the best trap for collecting Cx. cedecei was the pop-up resting shelter at 45.9%. For unfed female Spissipes section mosquitoes in Florida, the CDC light trap with CO2 collected 84.5% and 98.3% of Cx. cedecei and Cx. panocossa respectively in Florida. Rarefaction analysis, and both the Shannon and Simpsons diversity indices all demonstrated that the mosquito drift fence was capable of collecting the greatest diversity of mosquito species regardless of location. The finding that the proportions of unfed and blood-engorged mosquitoes collected by traps differed both among and between species has implications for how studies of VEEV vectors will be carried out in future investigations. In Florida a combination of pop-up resting shelters and use of a large-diameter aspirator would be optimal for the collection of both VEEV vectors for host-use studies. Results demonstrate that traps can be constructed from common materials to collect mosquitoes for VEEV vector studies and could be assessed for their utilization in vectors of other systems as well. Unfortunately, no single method was effective for capturing all species and physiological states, highlighting a particular need for assessing trap utility for target species of a study.

Comparison of SARS-CoV-2 Receptors Expression in Primary Endothelial Cells and Retinoic Acid-Differentiated Human Neuronal Cells.

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is primarily responsible for coronavirus disease (COVID-19) and it is characterized by respiratory illness with fever and dyspnea. Severe vascular problems and several other manifestations, including neurological ones, have also been frequently reported, particularly in the great majority of "long hauler" patients. SARS-CoV-2 infects and replicates in lung epithelial cells, while dysfunction of endothelial and neuronal brain cells has been observed in the absence of productive infection. It has been shown that the Spike protein can interact with specific cellular receptors, supporting both viral entry and cellular dysfunction. It is thus clear that understanding how and when these receptors are regulated, as well as how much they are expressed would help in unveiling the multifaceted aspects of this disease. Here, we show that SH-SY5Y neuroblastoma cells express three important cellular surface molecules that interact with the Spike protein, namely ACE2, TMPRSS2, and NRP1. Their levels increase when cells are treated with retinoic acid (RA), a commonly used agent known to promote differentiation. This increase matched the higher levels of receptors observed on HUVEC (primary human umbilical vein endothelial cells). We also show by confocal imaging that replication-defective pseudoviruses carrying the SARS-CoV-2 Spike protein can infect differentiated and undifferentiated SH-SY5Y, and HUVEC cells, although with different efficiencies. Neuronal cells and endothelial cells are potential targets for SARS-CoV-2 infection and the interaction of the Spike viral protein with these cells may cause their dysregulation. Characterizing RNA and protein expression tempo, mode, and levels of different SARS-CoV-2 receptors on both cell subpopulations may have clinical relevance for the diagnosis and treatment of COVID-19-infected subjects, including long hauler patients with neurological manifestations.

The COVID-19 crisis and Amazonia's indigenous people: Implications for conservation and global health.

Ecosystem health and zoonotic diseases are closely interwoven. Even as we grapple with the SARS-Coronavirus-2 pandemic, which may have its origins in wildlife, weakening environmental policies in the Brazilian Amazon are elevating the risk of additional zoonotic spillover events. We examine the links between deforestation and disease emergence in the Amazon, as illustrated by outbreaks of yellow fever virus, Venezuelan equine encephalitis virus, and Oropouche virus. It has been well established that in Brazil, indigenous territories exhibit lower rates of forest conversion and degradation than in areas designated for sustainable use. In this way, Amazonia's indigenous tribes promote public health while sustaining ecosystem services. However, indigenous land rights are under attack due to current policies enabling illegal land grabbing, mining and logging. Further adding to the existential struggle of indigenous tribes, malaria and SARS-Coronavirus-2 are wreaking havoc on these vulnerable populations. There is a critical need for protection of indigenous people's rights and health, as well as a sustained effort to support the study of mechanisms underlying anthropogenic land use change and zoonotic disease risk.

Blood Biomarkers for Detection of Brain Injury in COVID-19 Patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus attacks multiple organs of coronavirus disease 2019 (COVID-19) patients, including the brain. There are worldwide descriptions of neurological deficits in COVID-19 patients. Central nervous system (CNS) symptoms can be present early in the course of the disease. As many as 55% of hospitalized COVID-19 patients have been reported to have neurological disturbances three months after infection by SARS-CoV-2. The mutability of the SARS-COV-2 virus and its potential to directly affect the CNS highlight the urgency of developing technology to diagnose, manage, and treat brain injury in COVID-19 patients. The pathobiology of CNS infection by SARS-CoV-2 and the associated neurological sequelae of this infection remain poorly understood. In this review, we outline the rationale for the use of blood biomarkers (BBs) for diagnosis of brain injury in COVID-19 patients, the research needed to incorporate their use into clinical practice, and the improvements in patient management and outcomes that can result. BBs of brain injury could potentially provide tools for detection of brain injury in COVID-19 patients. Elevations of BBs have been reported in cerebrospinal fluid (CSF) and blood of COVID-19 patients. BB proteins have been analyzed in CSF to detect CNS involvement in patients with infectious diseases, including human immunodeficiency virus and tuberculous meningitis. BBs are approved by the U.S. Food and Drug Administration for diagnosis of mild versus moderate traumatic brain injury and have identified brain injury after stroke, cardiac arrest, hypoxia, and epilepsy. BBs, integrated with other diagnostic tools, could enhance understanding of viral mechanisms of brain injury, predict severity of neurological deficits, guide triage of patients and assignment to appropriate medical pathways, and assess efficacy of therapeutic interventions in COVID-19 patients.

Multidrug therapy for leprosy can cure patients with lobomycosis in Acre State, Brazil: a proof of therapy study

Lobomycosis, also referred to as lacaziosis, is an endemic cutaneous and subcutaneous fungal disease that mainly affects Amazonian forest dwellers in Brazil. There is no disease control program in place in Brazil, and antifungal therapy failures are common, and the therapy is inaccessible to most patients. We performed a randomized, unblinded clinical trial testing the cure rate of multiple drug therapy (MDT) for leprosy with surgical excision, with or without itraconazole. A control arm consisted of patients who did not adhere to either therapeutic regimens but continued to be followed up. Multiple drug therapy consisted of monthly supervised doses of 600 mg rifampicin, 300 mg clofazimine, and 100 mg dapsone, in addition to daily doses of 50 mg clofazimine and 100 mg dapsone. The patients in the MDT plus itraconazole arm also received itraconazole 100 mg twice daily. We followed up 54 patients from the MDT group and 26 patients from the MDT plus itraconazole group for an average of 4 years and 9 months. The 23 controls were followed up for 6 months on average. The following endpoints were observed: 1) unchanged (no apparent improvement), 2) improved (reduction in lesion size and/or pruritus), and 3) cured (complete remission of the lesions, no viable fungi, and no relapse for 2 years after the end of the drug treatment). The results indicated a significantly greater likelihood of cure associated with the use of multidrug therapy for leprosy with or without itraconazole when compared with the control group. The addition of itraconazole to MDT was not associated with improved outcomes, suggesting that MDT alone is effective(AU).

Multidrug Therapy for Leprosy Can Cure Patients with Lobomycosis in Acre State, Brazil: A Proof of Therapy Study.

Lobomycosis, also referred to as lacaziosis, is an endemic cutaneous and subcutaneous fungal disease that mainly affects Amazonian forest dwellers in Brazil. There is no disease control program in place in Brazil, and antifungal therapy failures are common, and the therapy is inaccessible to most patients. We performed a randomized, unblinded clinical trial testing the cure rate of multiple drug therapy (MDT) for leprosy with surgical excision, with or without itraconazole. A control arm consisted of patients who did not adhere to either therapeutic regimens but continued to be followed up. Multiple drug therapy consisted of monthly supervised doses of 600 mg rifampicin, 300 mg clofazimine, and 100 mg dapsone, in addition to daily doses of 50 mg clofazimine and 100 mg dapsone. The patients in the MDT plus itraconazole arm also received itraconazole 100 mg twice daily. We followed up 54 patients from the MDT group and 26 patients from the MDT plus itraconazole group for an average of 4 years and 9 months. The 23 controls were followed up for 6 months on average. The following endpoints were observed: 1) unchanged (no apparent improvement), 2) improved (reduction in lesion size and/or pruritus), and 3) cured (complete remission of the lesions, no viable fungi, and no relapse for 2 years after the end of the drug treatment). The results indicated a significantly greater likelihood of cure associated with the use of multidrug therapy for leprosy with or without itraconazole when compared with the control group. The addition of itraconazole to MDT was not associated with improved outcomes, suggesting that MDT alone is effective.

Clinical and Serological Findings of Madariaga and Venezuelan Equine Encephalitis Viral Infections: A Follow-up Study 5 Years After an Outbreak in Panama.

BACKGROUND: Human cases of Madariaga virus (MADV) infection were first detected during an outbreak in 2010 in eastern Panama, where Venezuelan equine encephalitis virus (VEEV) also circulates. Little is known about the long-term consequences of either alphavirus infection. METHODS: A follow-up study of the 2010 outbreak was undertaken in 2015. An additional survey was carried out 2 weeks after a separate 2017 alphavirus outbreak in a neighboring population in eastern Panama. Serological studies and statistical analyses were undertaken in both populations. RESULTS: Among the originally alphavirus-seronegative participants (n = 35 of 65), seroconversion was observed at a rate of 14.3% (95% CI, 4.8%-30.3%) for MADV and 8.6% (95% CI, 1.8%-23.1%) for VEEV over 5 years. Among the originally MADV-seropositive participants (n = 14 of 65), VEEV seroconversion occurred in 35.7% (95% CI, 12.8%-64.9%). In the VEEV-seropositive participants (n = 16 of 65), MADV seroconversion occurred in 6.3% (95% CI, 0.2%-30.2%). MADV seroreversion was observed in 14.3% (95% CI, 1.8%-42.8%) of those who were originally seropositive in 2010. VEEV seroconversion in the baseline MADV-seropositive participants was significantly higher than in alphavirus-negative participants. In the population sampled in 2017, MADV and VEEV seroprevalence was 13.2% and 16.8%, respectively. Memory loss, insomnia, irritability, and seizures were reported significantly more frequently in alphavirus-seropositive participants than in seronegative participants. CONCLUSIONS: High rates of seroconversion to MADV and VEEV over 5 years suggest frequent circulation of both viruses in Panama. Enhanced susceptibility to VEEV infection may be conferred by MADV infection. We provide evidence of persistent neurologic symptoms up to 5 years following MADV and VEEV exposure.

Endemic and Epidemic Human Alphavirus Infections in Eastern Panama: An Analysis of Population-Based Cross-Sectional Surveys.

Madariaga virus (MADV) has recently been associated with severe human disease in Panama, where the closely related Venezuelan equine encephalitis virus (VEEV) also circulates. In June 2017, a fatal MADV infection was confirmed in a community of Darien Province. We conducted a cross-sectional outbreak investigation with human and mosquito collections in July 2017, where sera were tested for alphavirus antibodies and viral RNA. In addition, by applying a catalytic, force-of-infection (FOI) statistical model to two serosurveys from Darien Province in 2012 and 2017, we investigated whether endemic or epidemic alphavirus transmission occurred historically. In 2017, MADV and VEEV IgM seroprevalences were 1.6% and 4.4%, respectively; IgG antibody prevalences were MADV: 13.2%, VEEV: 16.8%, Una virus (UNAV): 16.0%, and Mayaro virus: 1.1%. Active viral circulation was not detected. Evidence of MADV and UNAV infection was found near households, raising questions about its vectors and enzootic transmission cycles. Insomnia was associated with MADV and VEEV infections, depression symptoms were associated with MADV, and dizziness with VEEV and UNAV. Force-of-infection analyses suggest endemic alphavirus transmission historically, with recent increased human exposure to MADV and VEEV in Aruza and Mercadeo, respectively. The lack of additional neurological cases suggests that severe MADV and VEEV infections occur only rarely. Our results indicate that over the past five decades, alphavirus infections have occurred at low levels in eastern Panama, but that MADV and VEEV infections have recently increased-potentially during the past decade. Endemic infections and outbreaks of MADV and VEEV appear to differ spatially in some locations of eastern Panama.

West Nile Virus-Induced Neurologic Sequelae-Relationship to Neurodegenerative Cascades and Dementias.

PURPOSE OF REVIEW: West Nile virus (WNV) emerged from Central Africa in the 1990s and is now endemic throughout much of the world. Twenty years after its introduction in the USA, it is becoming apparent that neurological impairments can persist for years following infection. Here, we review the epidemiological data in support of such long-term deficits and discuss possible mechanisms that drive these persistent manifestations. RECENT FINDINGS: Focusing on the recently discovered antimicrobial roles of amyloid and alpha-synuclein, we connect WNV late pathology to overlapping features encountered in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. We also summarize new research on microglial activation and engulfment of neural synapses seen in recovered WNV as well as in neurodegenerative diseases, and discuss how loss of integrity of the blood-brain barrier (BBB) may exacerbate this process. SUMMARY: Neuroinvasive viral infections such as WNV may be linked epidemiologically and mechanistically to neurodegeneration. This may open doors to therapeutic options for hitherto untreatable infectious sequelae; additionally, it may also shed light on the possible infectious etiologies of age-progressive neurodegenerative dementias.

Islands as Hotspots for Emerging Mosquito-Borne Viruses: A One-Health Perspective.

During the past ten years, an increasing number of arbovirus outbreaks have affected tropical islands worldwide. We examined the available literature in peer-reviewed journals, from the second half of the 20th century until 2018, with the aim of gathering an overall picture of the emergence of arboviruses in these islands. In addition, we included information on environmental and social drivers specific to island setting that can facilitate the emergence of outbreaks. Within the context of the One Health approach, our review highlights how the emergence of arboviruses in tropical islands is linked to the complex interplay between their unique ecological settings and to the recent changes in local and global sociodemographic patterns. We also advocate for greater coordination between stakeholders in developing novel prevention and mitigation approaches for an intractable problem.

Human and Equine Infection with Alphaviruses and Flaviviruses in Panamá during 2010: A Cross-Sectional Study of Household Contacts during an Encephalitis Outbreak.

Members of the genera Alphavirus (family Togaviridae) and Flavivirus (family Flaviridae) are important zoonotic human and equine etiologic agents of neurologic diseases in the New World. In 2010, an outbreak of Madariaga virus (MADV; formerly eastern equine encephalitis virus) and Venezuelan equine encephalitis virus (VEEV) infections was reported in eastern Panamá. We further characterized the epidemiology of the outbreak by studying household contacts of confirmed human cases and of equine cases with neurological disease signs. Serum samples were screened using a hemagglutination inhibition test, and human results were confirmed using plaque reduction neutralization tests. A generalized linear model was used to evaluate the human MADV and VEEV seroprevalence ratios by age (in tercile) and gender. Overall, antibody prevalence for human MADV infection was 19.4%, VEEV 33.3%, and Mayaro virus 1.4%. In comparison with individuals aged 2-20 years, people from older age groups (21-41 and > 41 years) were five times more likely to have antibodies against VEEV, whereas the MADV prevalence ratio was independent of age. The overall seroprevalence of MADV in equids was 26.3%, VEEV 29.4%, West Nile virus (WNV) 2.6%, and St. Louis encephalitis virus (SLEV) was 63.0%. Taken together, our results suggest that multiple arboviruses are circulating in human and equine populations in Panamá. Our findings of a lack of increase in the seroprevalence ratio with age support the hypothesis of recent MADV exposure to people living in the affected region.

Deforestation and vector-borne disease: Forest conversion favors important mosquito vectors of human pathogens.

The global burden of vector-borne diseases accounts for more than 17% of infectious diseases in humans. Rapid global expansion of previously obscure pathogens, such as Zika and chikungunya viruses in recent years highlights the importance of understanding how anthropogenic changes influence emergence and spillover of vector-borne diseases. Deforestation has been identified as one anthropogenic change that influences vector-borne disease prevalence, although contrasting pictures of the effects of deforestation on vector-borne disease transmission have been reported. These conflicting findings are likely attributable to the inherent complexity of vector-borne disease systems, which involve diverse groups of vectors, hosts and pathogens, depending on geography. The current study represents a quantitative exploration of the link between deforestation and mosquitoes, the most important common constituents of vector-borne disease systems. Analysis of data compiled from published field studies for 87 mosquito species from 12 countries revealed that about half of the species (52.9%) were associated with deforested habitats. Of these species that are favored by deforestation, a much larger percentage (56.5%) are confirmed vectors of human pathogens, compared to those negatively impacted by deforestation (27.5%). Moreover, species that serve as vectors of multiple human pathogens were all favored by deforestation, including Anopheles bancroftii, Anopheles darlingi, Anopheles farauti, Anopheles funestus s.l., Anopheles gambiae s.l., Anopheles subpictus, Aedes aegypti, Aedes vigilax, Culex annulirostris, and Culex quinquefasciatus. Our quantitative analysis of vector and non-vector species, demonstrates that the net effect of deforestation favors mosquitoes that serve as vectors of human disease, while the obverse holds true for non-vectors species. These results begin to unify our understanding of the relationship between deforestation and vector mosquitoes, an important step in quantifying how land use change, specifically deforestation, affects human risk of vector-borne disease.

Epidemiology of Emergent Madariaga Encephalitis in a Region with Endemic Venezuelan Equine Encephalitis: Initial Host Studies and Human Cross-Sectional Study in Darien, Panama.

BACKGROUND: Neurotropic arboviral infections are an important cause of encephalitis. A zoonotic, vector-borne alphavirus, Madariaga virus (MADV; formerly known as South American eastern equine encephalitis virus), caused its first documented human outbreak in 2010 in Darien, Panama, where the genetically similar Venezuelan equine encephalitis virus (VEEV) is endemic. We report the results of a seroprevalence survey of animals and humans, illustrating contrasting features of MADV and VEEV ecology and epidemiology. METHODS: Small mammals were trapped in 42 sites in Darien, Panama, using Sherman traps, Tomahawk traps, and mist nets for bats. Blood was tested for the presence of neutralizing antibodies to MADV and VEEV. In addition, bird sera collected in 2007 in Chagres, Panama, were tested for MADV and VEEV neutralizing antibodies. Viremia was ascertained by RT-PCR. Human exposure to these two viruses was determined by IgG ELISA, followed by plaque reduction neutralization tests. To identify relevant risk factors for MADV or VEEV exposure, logistic regression analysis was performed, and the most parsimonious model was selected based on the Akaike information criterion. RESULTS: The animal survey yielded 32 bats (16 species), 556 rodents (12 species), and 20 opossums (4 species). The short-tailed cane mouse (Zygodontomys brevicauda) found abundantly in pasture and farms, had the highest MADV seroprevalence (8.3%). For VEEV, the shrub and forest-dwelling long-whiskered rice rat (Transandinomys bolivaris) had the highest seroprevalence (19.0%). Viremia was detected in one animal (Z. brevicauda). Of the 159 bird sera (50 species) tested, none were positive for either virus. In humans (n = 770), neutralizing antibodies to MADV and VEEV were present in 4.8% and 31.5%, respectively. MADV seropositivity was positively associated with cattle ranching, farming, and fishing. Having VEEV antibodies and shrubs near the house diminished risk. Age, forest work, farming and fishing were risk factors for VEEV, while having MADV antibodies, glazed windows, waste pick-up and piped water were protective. CONCLUSION: Our findings suggest that the short-tailed cane mouse and the long-whiskered rice rat serve as hosts for MADV and VEEV, respectively. The preferred habitat of these rodent species coincides with areas associated with human infection risk. Our findings also indicate that MADV emerged recently in humans, and that the transmission cycles of these two sympatric alphaviruses differ spatially and in host utilization.