Choclo virus (CHOV) recovered from deep metatranscriptomics of archived frozen tissues in natural history biorepositories.

BACKGROUND: Hantaviruses are negative-stranded RNA viruses that can sometimes cause severe disease in humans; however, they are maintained in mammalian host populations without causing harm. In Panama, sigmodontine rodents serve as hosts to transmissible hantaviruses. Due to natural and anthropogenic forces, these rodent populations are having increased contact with humans. METHODS: We extracted RNA and performed Illumina deep metatranscriptomic sequencing on Orthohantavirus seropositive museum tissues from rodents. We acquired sequence reads mapping to Choclo virus (CHOV, Orthohantavirus chocloense) from heart and kidney tissue of a two-decade old frozen museum sample from a Costa Rican pygmy rice rat (Oligoryzomys costaricensis) collected in Panama. Reads mapped to the CHOV reference were assembled and then validated by visualization of the mapped reads against the assembly. RESULTS: We recovered a 91% complete consensus sequence from a reference-guided assembly to CHOV with an average of 16X coverage. The S and M segments used in our phylogenetic analyses were nearly complete (98% and 99%, respectively). There were 1,199 ambiguous base calls of which 93% were present in the L segment. Our assembled genome varied 1.1% from the CHOV reference sequence resulting in eight nonsynonymous mutations. Further analysis of all publicly available partial S segment sequences support a clear relationship between CHOV clinical cases and O. costaricensis acquired strains. CONCLUSIONS: Viruses occurring at extremely low abundances can be recovered from deep metatranscriptomics of archival tissues housed in research natural history museum biorepositories. Our efforts resulted in the second CHOV genome publicly available. This genomic data is important for future surveillance and diagnostic tools as well as understanding the evolution and pathogenicity of CHOV.

Two Decades of Wildlife Pathogen Surveillance: Case Study of Choclo orthohantavirus and Its Wild Reservoir Oligoryzomys costaricensis.

The Costa Rican pygmy rice rat (Oligoryzomys costaricensis) is the primary reservoir of Choclo orthohantavirus (CHOV), the causal agent of hantavirus disease, pulmonary syndrome, and fever in humans in Panama. Since the emergence of CHOV in early 2000, we have systematically sampled and archived rodents from >150 sites across Panama to establish a baseline understanding of the host and virus, producing a permanent archive of holistic specimens that we are now probing in greater detail. We summarize these collections and explore preliminary habitat/virus associations to guide future wildlife surveillance and public health efforts related to CHOV and other zoonotic pathogens. Host sequences of the mitochondrial cytochrome b gene form a single monophyletic clade in Panama, despite wide distribution across Panama. Seropositive samples were concentrated in the central region of western Panama, consistent with the ecology of this agricultural commensal and the higher incidence of CHOV in humans in that region. Hantavirus seroprevalence in the pygmy rice rat was >15% overall, with the highest prevalence in agricultural areas (21%) and the lowest prevalence in shrublands (11%). Host-pathogen distribution, transmission dynamics, genomic evolution, and habitat affinities can be derived from the preserved samples, which include frozen tissues, and now provide a foundation for expanded investigations of orthohantaviruses in Panama.

Hantavirus in Panama: Twenty Years of Epidemiological Surveillance Experience.

Twenty years have passed since the emergence of hantavirus zoonosis in Panama at the beginning of this millennium. We provide an overview of epidemiological surveillance of hantavirus disease (hantavirus pulmonary syndrome and hantavirus fever) during the period 1999-2019 by including all reported and confirmed cases according to the case definition established by the health authority. Our findings reveal that hantavirus disease is a low-frequency disease, affecting primarily young people, with a relatively low case-fatality rate compared to other hantaviruses in the Americas (e.g., ANDV and SNV). It presents an annual variation with peaks every 4-5 years and an interannual variation influenced by agricultural activities. Hantavirus disease is endemic in about 27% of Panama, which corresponds to agroecological conditions that favor the population dynamics of the rodent host, Oligoryzomys costaricensis and the virus (Choclo orthohantavirus) responsible for hantavirus disease. However, this does not rule out the existence of other endemic areas to be characterized. Undoubtedly, decentralization of the laboratory test and dissemination of evidence-based surveillance guidelines and regulations have standardized and improved diagnosis, notification at the level of the primary care system, and management in intensive care units nationwide.

The bibliometric landscape of infectious disease research in Panama (1990-2019).

Background: This work aims to analyze the landscape of scientific publications on subjects related to One Health and infectious diseases in Panama. The research questions are: How does the One Health research landscape look like in Panama? Are historical research efforts aligned with the One Health concept? What infectious diseases have received more attention from the local scientific community since 1990? Methods: Boolean searches on the Web of Science, SCOPUS and PubMed were undertaken to evaluate the main trends of publications related to One Health and infectious disease research in the country of Panama, between 1990 and 2019. Results: 4546 publications were identified since 1990, including 3564 peer-reviewed articles interconnected with One Health related descriptors, and 211 articles focused particularly on infectious diseases. A pattern of exponential growth in the number of publications with various contributions from Panamanian institutions was observed. The rate of multidisciplinary research was moderate, whereas those of interinstitutional and intersectoral research ranged from low to very low. Research efforts have centered largely on protozoan, neglected and arthropod-borne diseases with a strong emphasis on malaria, Chagas and leishmaniasis. Conclusion: Panama has scientific capabilities on One Health to tackle future infectious disease threats, but the official collaboration schemes and strategic investment to develop further competencies need to be conciliated with modern times, aka the pandemics era. The main proposition here, addressed to the government of Panama, is to launch a One Health regional center to promote multidisciplinary, interinstitutional and intersectoral research activities in Panama and beyond.

Leptospirosis: Epidemiological and Clinical Characteristics at the National Reference Hospital in Panama.

Leptospirosis represents a public health problem in Panama, with an incidence rate of 1 in 100,000 inhabitants in 2014. Despite active surveillance and reports of outbreaks in the news, publications about human leptospirosis in Panama are scarce. The objective of this study was to describe the epidemiological and clinical features of leptospirosis in a cohort of patients admitted to the national reference hospital from January 2013 to December 2018. A total of 188 patients with suspected leptospirosis were identified, but only 56.9% (107 of 188) of the medical records could be retrieved. Microagglutination assays were completed in 45% (48 of 107) of the patients, confirming leptospirosis in 29.2% (14 of 48) of the patients. The most prevalent serogroup identified was Leptospira interrogans icterohemorrhagiae (4 of 14, 28.6%). The majority of patients with confirmed disease were middle-aged (36.4 ± 15.7 years), male (11 of 14, 78.6%), and symptomatic for 6.8 ± 0.7 days before admission. The predominant clinical presentation was fever (13 of 14, 92.9%), abdominal pain (7 of 14, 50%), and jaundice (8 of 14, 57.1%). Respiratory failure (8 of 14, 57.1%), elevated creatinine levels on admission (8 of 14, 57.1%), transfusion of blood-derived products (6 of 14, 42.9%), and required use of vasopressors (4 of 14, 28.6%) were common complications. Mortality was 28.6% (4 of 14). Empiric antibiotic therapy was initiated in almost all patients (10 of 12, 83.3%), and was appropriate in 90% (9 of 10) of them. Our study highlights the high prevalence of severe disease and reveals the diagnostic challenges concealing the true burden of leptospirosis in Panama. However, the small number of confirmed patients limits the generalization of these findings.

Neuromyelitis Optica Spectrum Disorder in Central America and the Caribbean: A Multinational Clinical Characterization Study.

Here, a study of NMOSD in Central America and the Caribbean with a multinational collaborative, multicentric and descriptive approach involving 25 institutions from 9 countries is presented. Demographics, clinical manifestations, expanded disability scale status (EDSS), brain and spinal cord MRI, serological anti-AQP4-IgG and anti-MOG-IgG antibodies, and cerebrospinal fluid (CSF) oligoclonal bands were included. A central serological repository utilized the cell-based assay. The specimens outside of this network employed diverse methodologies. Data were collected at the Gorgas Commemorative Institute of Health Studies (ICGES), Panama, and included 186 subjects, of which 84% were females (sex ratio of 5.6:1). Mestizos constituted 72% of the study group. The median age was 42.5 years (IQR: 32.0-52.0). Associated autoimmune diseases (8.1%) were myasthenia gravis, Sjögren's syndrome and systemic lupus erythematosus. The most common manifestation was optic neuritis-transverse myelitis (42.5%). A relapsing course was described in 72.3% of cases. EDSS scores of 0-3.5 were reported in 57.2% of cases and higher than 7.0 in 14.5%. Positive anti-AQP4-IgG antibody occurred in 59.8% and anti-MOG-IgG antibody in 11.5% of individuals. Antibody testing was lacking for 13.4% of patients. The estimated crude prevalence of NMOSD from Panama and the Dominican Republic was 1.62/100,000 (incidence of 0.08-0.41) and 0.73/100,000 (incidence 0.02-0.14), respectively. This multinational study contributes additional insights and data on the understanding of NMOSD in this Latin American region.

Case Report: First Confirmed Case of Coinfection of SARS-CoV-2 With Choclo orthohantavirus.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a major international public health concern. The World Health Organization (WHO) declared the pandemic of coronavirus disease 2019 (COVID-19) on March 11, 2020. In Panama, the first SARS-CoV-2 infection was confirmed on March 9, 2020, and the first fatal case associated to COVID-19 was reported on March 10. This report presents the case of a 44-year-old female who arrived at the hospital with a respiratory failure, five days after the first fatal COVID-19 case, and who was living in a region where hantavirus pulmonary syndrome cases caused by Choclo orthohantavirus (CHOV), are prevalent. Thus, the clinical personnel set a differential diagnosis to determine a respiratory disease caused by the endemic CHOV or the new pandemic SARS-CoV-2. This case investigation describes the first coinfection by SARS-CoV-2 and CHOV worldwide. PCR detected both viruses during early stages of the disease and the genomic sequences were obtained. The presence of antibodies was determined during the patient's hospitalization. After 23 days at the intensive care unit, the patient survived with no sequelae, and antibodies against CHOV and SARS-CoV-2 were still detectable 12 months after the disease. The detection of the coinfection in this patient highlights the importance, during a pandemic, of complementing the testing and diagnosis of the emergent agent, SARS-CoV-2, with other common endemic respiratory pathogens and other zoonotic pathogens, like CHOV, in regions where they are of public health concern.

Cytokine Profiles and Antibody Response Associated to Choclo Orthohantavirus Infection.

Background: New World Hantaviruses (NWHs) are the etiological agent underlying hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with high mortality rates in humans. In Panama, infections with Choclo Orthohantavirus (CHOV) cause a much milder illness characterized by higher seroprevalence and lower mortality rates. To date, the cytokine profiles and antibody responses associated with this milder form of HCPS have not been defined. Therefore, in this study, we examined immune serological profiles associated with CHOV infections. Methods: For this retrospective study, sera from fifteen individuals with acute CHOV-induced HCPS, were analyzed alongside sera from fifteen convalescent phase individuals and thirty-three asymptomatic, CHOV-seropositive individuals. Cytokine profiles were analyzed by multiplex immunoassay. Antibody subclasses, binding, and neutralization against CHOV-glycoprotein (CHOV-GP) were evaluated by ELISA, and flow cytometry. Results: High titers of IFNγ, IL-4, IL-8, and IL-10 serum cytokines were found in the acute individuals. Elevated IL-4 serum levels were found in convalescent and asymptomatic seropositive individuals. High titers of IgG1 subclass were observed across the three cohorts analyzed. Neutralizing antibody response against CHOV-GP was detectable in few acute individuals but was strong in both convalescent and asymptomatic seropositive individuals. Conclusion: A Th1/Th2 cytokine signature is characteristic during acute mild HCPS caused by CHOV infection. High expression of Th2 and IL-8 cytokines are correlated with clinical parameters in acute mild HCPS. In addition, a strong IL-4 signature is associated with different cohorts, including asymptomatic individuals. Furthermore, asymptomatic individuals presented high titers of neutralizing antibodies.

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.

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.

Sociocultural determinants of adoption of preventive practices for hantavirus: A knowledge, attitudes, and practices survey in Tonosí, Panama.

INTRODUCTION: Hantaviruses are a group of single-stranded RNA viruses carried by small rodent reservoirs, transmitted to humans through inhalation of aerosolized particles of rodent feces, urine, or saliva. In Panama, the Choclo orthohantavirus has been associated with Hantavirus Pulmonary Syndrome (n = 54) and Hantavirus Fever (n = 53). In 2018, there were 107 cases of hantavirus diseases, the majority in the Tonosí district, and 4 deaths. As there is no vaccine or treatment for hantavirus, proper prevention measures by community members is key to stopping outbreaks. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated hantavirus knowledge, attitudes, and practices in one corregimiento of Tonosí, Panama to determine what factors influence uptake of prevention practices and high level of knowledge. We conducted a cross-sectional survey with 124 residents covering hantavirus knowledge, attitudes based in the Health Belief Model (perceived severity, perceived susceptibility, perceived obstacles, perceived benefits, and cues to action) and prevention practices. There was an overall high level of knowledge (median score: 4/6), though 20% did not know the route of transmission. The mean number of reported practices performed per person was 8.4 (range: 4-12). Most people had heard of hantavirus through other community members. In linear regression, lower perceived obstacles predicted higher preventive practice score. Reported obstacles to preventive practices included physical restrictions, such as age and health state. In ordinal logistic regression, higher education level and knowing more people who had previously been sick with hantavirus contributed to higher knowledge score. CONCLUSIONS: Future interventions should focus on removing barriers to performing preventive practices. As most people learned of hantavirus through community members, interventions should be community-based and involve those who have experienced the disease. Any future education materials should address confusions about route of transmission and be targeted at those with a lower education level.

Implementation of bamboo and monkey-pot traps for the sampling cavity-breeding mosquitoes in Darién, Panama.

Despite the importance of Aedes, Haemagogus and Sabethes in the transmission of yellow fever virus (YFV) and the public health impacts of recent YFV epidemics in the Americas, relatively little has been reported on the biology and ecology of these vectors. Many Aedes, Haemagogus and Sabethes spp. in the American tropics inhabit and develop in the forest canopy and are difficult to sample with conventional entomological surveillance methods. We tested the utility of two previously developed phytotelmata-style oviposition traps (bamboo Guadua angustifolia) and (monkey-pot Lecythis minor), for collecting immature forms of these mosquitoes in a forest near the community of Aruza Abajo, Darién Province, Panama. Our results showed distribution of mosquito species emerging from the two types of traps was found to be significantly different (X2 = 210.23; df = 14; P < 0.001), with significantly greater numbers of Sabethes (Peytonulus) aurescens (Lutz) and Sabethes (Peytonulus) undosus (Coquillett) emerging from the bamboo traps. More females of Sabethes (Sabethes) cyaneus (Fabricius) were captured in the monkey-pot traps, although the difference was not significant. No differences were observed in the average time to emergence for the two traps. These results suggest that various phytotelmata-style traps, including monkey-pot and bamboo, could be used to improve entomological surveillance of YFV vectors in the American tropic.

Dengue with Hemorrhagic Manifestations and Acute Pancreatitis: Case Report and Review.

Dengue fever is an acute viral disease transmitted by arthropods, which has become a major public health problem, especially in tropical and subtropical areas. We found 17 reported cases of dengue complicated with pancreatitis in the world literature, 13 cases were found in Asia, one in Europe, and two in Latin America. This is the first and an unusual case of dengue with hemorrhagic manifestations complicated with acute pancreatitis in Panama. A 37-year-old woman with an unknown past medical history presented to Santo Tomas Hospital (Panama City, Panama) with sudden abdominal pain in the epigastrium and left hypochondrium, described as a burning-like pain radiating towards the back. Five days before the admission, the patient had fever, chills, headache, retro-orbital pain, dizziness, arthralgia, loss of appetite, and fatigue. In the emergency room, a diagnosis of acute pancreatitis was made and the patient was hospitalized. Physical examination showed bleeding gums, and laboratory tests show leukopenia and thrombocytopenia, which suggested an infection caused by the dengue virus. The dengue infection was confirmed using quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). The patient received supportive treatment and the symptoms resolved. She was discharged on the ninth day of hospitalization without any sequela. The final diagnosis was hemorrhagic dengue complicated by acute pancreatitis.

Molecular Epidemiology of Dengue in Panama: 25 Years of Circulation.

Dengue virus (DENV) is the most prevalent arbovirus in terms of human public health importance globally. In addition to DENV epidemiological surveillance, genomic surveillance may help investigators understand the epidemiological dynamics, geographic distribution, and temporal patterns of DENV circulation. Herein, we aimed to reconstruct the molecular epidemiology and phylogeny of DENV in Panama to connect the epidemiological history of DENV dispersal and circulation in Latin America. We retrospectively analyzed the epidemiological data obtained during 25 years of DENV surveillance in Panama. DENV was reintroduced in Panama in 1993 after a 35 year absence of autochthonous transmission. The increase in the number of total dengue cases has been accompanied by an increase in severe and fatal cases, with the highest case fatality rate recorded in 2011. All four serotypes were detected in Panama, which is characterized by serotype replacement and/or co-circulation of multiple serotypes. Phylogenetic analysis of datasets collected from envelope (E) gene sequences obtained from viruses isolated from human sera demonstrated that circulating viruses were highly diverse and clustered in distinct clades, with co-circulation of clades from the same genotype. Our analyses also suggest that Panamanian strains were related to viruses from different regions of the Americas, suggesting a continuous exchange of viruses within the Americas.

Building an integrated infrastructure for exploring biodiversity: field collections and archives of mammals and parasites.

Museum specimens play an increasingly important role in predicting the outcomes and revealing the consequences of anthropogenically driven disruption of the biosphere. As ecological communities respond to ongoing environmental change, host-parasite interactions are also altered. This shifting landscape of host-parasite associations creates opportunities for colonization of different hosts and emergence of new pathogens, with implications for wildlife conservation and management, public health, and other societal concerns. Integrated archives that document and preserve mammal specimens along with their communities of associated parasites and ancillary data provide a powerful resource for investigating, anticipating, and mitigating the epidemiological, ecological, and evolutionary impacts of environmental perturbation. Mammalogists who collect and archive mammal specimens have a unique opportunity to expand the scope and impact of their field work by collecting the parasites that are associated with their study organisms. We encourage mammalogists to embrace an integrated and holistic sampling paradigm and advocate for this to become standard practice for museum-based collecting. To this end, we provide a detailed, field-tested protocol to give mammalogists the tools to collect and preserve host and parasite materials that are of high quality and suitable for a range of potential downstream analyses (e.g., genetic, morphological). Finally, we also encourage increased global cooperation across taxonomic disciplines to build an integrated series of baselines and snapshots of the changing biosphere. Los especímenes de museo desempeñan un papel cada vez más importante tanto en la descripción de los resultados de la alteración antropogénica de la biosfera como en la predicción de sus consecuencias. Dado que las comunidades ecológicas responden al cambio ambiental, también se alteran las interacciones hospedador-parásito. Este panorama cambiante de asociaciones hospedador-parásito crea oportunidades para la colonización de diferentes hospedadores y para la aparición de nuevos patógenos, con implicancias en la conservación y manejo de la vida silvestre, la salud pública y otras preocupaciones de importancia para la sociedad. Archivos integrados que documentan y preservan especímenes de mamíferos junto con sus comunidades de parásitos y datos asociados, proporcionan un fuerte recurso para investigar, anticipar y mitigar los impactos epidemiológicos, ecológicos y evolutivos de las perturbaciones ambientales. Los mastozoólogos que recolectan y archivan muestras de mamíferos, tienen una oportunidad única de ampliar el alcance e impacto de su trabajo de campo mediante la recolección de los parásitos que están asociados con los organismos que estudian. Alentamos a los mastozoólogos a adoptar un paradigma de muestreo integrado y holístico y abogamos para que esto se convierta en una práctica estándarizada de la obtención de muestras para museos. Con este objetivo, proporcionamos un protocolo detallado y probado en el campo para brindar a los mastozoólogos las herramientas para recolectar y preservar materiales de parásitos y hospedadores de alta calidad y adecuados para una gran variedad de análisis subsecuentes (e.g., genéticos, morfológicos, etc.). Finalmente, también abogamos por una mayor cooperación global entre las diversas disciplinas taxonómicas para construir una serie integrada de líneas de base y registros actuales de nuestra cambiante biosfera.

Costs of multiple sclerosis in Panama from societal, patient perspectives and health-related quality of life.

The purpose of this work is to estimate the costs associated with managing patients with MS in Panama and evaluating the impact of the disease on their health-related quality of life (HRQoL). Multicentric observational, retrospective, cross-sectional study. The costs were estimated from societal and patient perspectives and expressed in USD, 2015. The focus of the study is based on prevalence and on a "bottom-up" approach. To estimate the total cost per patient, annual reported use for each resource was multiplied by its unit cost. To evaluate HRQoL, patients completed the EQ-5D-3L questionnaire. 108 patients took part in the study. 82.41% were women with 44.78 (SD: 12.27) years. 61.11% presented mild (EDSS = 0-3.5), 25.93% moderate (EDSS = 3.5-6) and 12.96%, severe disability (EDSS≥6.5). The mean annual cost from the patient's perspective was estimated at 777.99 USD (SD: 1,741.45) per patient. The mean cost from a societal perspective was estimated at 23,803.21 USD (SD: 13,331.83) per patient. Disease-modifying therapies (DMT) accounted for the main component of the cost. A deterioration in HRQoL was observed as the disease advances and as disability increases, with mobility and usual activities being the areas most affected by its progression. From both perspective, the cost per MS patient in Panama is high. In addition to the high economic impact, MS also exerts a negative impact on patient HRQoL, which increases as the disease advances.

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.

The reintroduction of DENV-2 in 2011 in Panama and subsequent outbreak characteristic.

The circulation of the South-east Asian/American (AS/AM) dengue 2 virus (DENV-2) genotype in the Americas has been associated with a high rate of severe disease. From 1993, the year DENV was reintroduced in Panama, until 2011 there were 29 dengue-associated deaths, 17 of which occurred in 2011, the most severe outbreak with a case fatality rate (CFR) of 44% (17 deaths out of 38 severe dengue cases). During this outbreak DENV-2 was reintroduced into the country, whereas over the prior five years DENV-1 and -3 were predominant. Herein, we describe the 2011 Panama outbreak and genetically characterize the Panamanian DENV-2 strains, which were associated with severe dengue disease in Panama. Our results suggest that the DENV-2 isolates from this outbreak belonged to the AS/AM genotype sub-clade 2BI and were genetically close to viruses described in the outbreaks in Nicaragua, Honduras, Guatemala and Mexico from 2006-2011. Sub-clade 2BI has previously been associated with severe disease in Nicaragua during outbreaks from 2005-2007.

Unusual pattern of chikungunya virus epidemic in the Americas, the Panamanian experience.

BACKGROUND: Chikungunya virus (CHIKV) typically causes explosive epidemics of fever, rash and polyarthralgia after its introduction into naïve populations. Since its introduction in Panama in May of 2014, few autochthonous cases have been reported; most of them were found within limited outbreaks in Panama City in 2014 and Puerto Obaldia town, near the Caribbean border with Colombia in 2015. In order to confirm that Panama had few CHIKV cases compared with neighboring countries, we perform an epidemiological analysis of chikungunya cases reported from May 2014 to July 2015. Moreover, to understand this paucity of confirmed CHIKV cases, a vectorial analysis in the counties where these cases were reported was performed. METHODS: Chikungunya cases were identified at medical centers and notified to health authorities. Sera samples were analyzed at Gorgas Memorial Institute for viral RNA and CHIKV-specific antibody detection. RESULTS: A total of 413 suspected cases of CHIKV infections were reported, with incidence rates of 0.5 and 0.7 per 100,000 inhabitants in 2014 and 2015, respectively. During this period, 38.6% of CHIKV cases were autochthonous with rash and polyarthralgia as predominant symptoms. CHIKV and DENV incidence ratios were 1:306 and 1:34, respectively. A phylogenetic analysis of E1/E2 genomic segment indicates that the outbreak strains belong to the Asian genotype and cluster together with CHIKV isolates from other American countries during the same period. Statistical analysis of the National Vector Control program at the district level shows low and medium vector infestation level for most of the counties with CHIKV cases. This index was lower than for neighboring countries. CONCLUSIONS: Previous training of clinical, laboratory and vector workers allowed a good caption and detection of the chikungunya cases and fast intervention. It is possible that low/medium vector infestation level could explain in part the paucity of chikungunya infections in Panama.