Hantavirus Outbreak Research Articles

Machine learning identifies straightforward early warning rules for human Puumala hantavirus outbreaks

Human Puumala virus (PUUV) infections in Germany fluctuate multi-annually, following fluctuations of the bank vole population size. We applied a transformation to the annual incidence values and established a heuristic method to develop a straightforward robust model for the binary human infection risk at the district level. The classification model was powered by a machine-learning algorithm and achieved 85% sensitivity and 71% precision, despite using only three weather parameters from the previous years as inputs, namely the soil temperature in April of two years before and in September of the previous year, and the sunshine duration in September of two years before. Moreover, we introduced the PUUV Outbreak Index that quantifies the spatial synchrony of local PUUV-outbreaks, and applied it to the seven reported outbreaks in the period 2006–2021. Finally, we used the classification model to estimate the PUUV Outbreak Index, achieving 20% maximum uncertainty.

Hantavirus outbreaks in the American Southwest: Propagation and retraction of rodent and virus diffusion waves from sky-island refugia

Hantavirus outbreaks in the American Southwest are hypothesized to be driven by episodic seasonal events of high precipitation, promoting rapid increases in virus-reservoir rodent species that then move across the landscape from high quality montane forested habitats (refugia), eventually over-running human residences and increasing disease risk. In this study, the velocities of rodents and virus diffusion wave propagation and retraction were documented and quantified in the sky-islands of northern New Mexico and related to rodent-virus relationships in refugia versus nonrefugia habitats. Deer mouse (Peromyscus maniculatus) refugia populations exhibited higher Sin Nombre Virus (SNV) infection prevalence than nonrefugia populations. The velocity of propagating diffusion waves of Peromyscus from montane to lower grassland habitats was measured at [Formula: see text] m/day (SE), with wave retraction velocities of [Formula: see text] m/day. SNV infection diffusion wave propagation velocity within a deer mouse population averaged [Formula: see text] m/day, with a faster retraction wave velocity of [Formula: see text] m/day. A spatio-temporal analysis of human Hantavirus Pulmonary Syndrome (HPS) cases during the initial 1993 epidemic revealed a positive linear relationship between the time during the epidemic and the distance of human cases from the nearest deer mouse refugium, with a landscape diffusion wave velocity of [Formula: see text] m/day ([Formula: see text]). These consistent diffusion propagation wave velocity results support the traveling wave component of the HPS outbreak theory and can provide information on space–time constraints for future outbreak forecasts.

Hantavirus Replication Cycle-An Updated Structural Virology Perspective.

Hantaviruses infect a wide range of hosts including insectivores and rodents and can also cause zoonotic infections in humans, which can lead to severe disease with possible fatal outcomes. Hantavirus outbreaks are usually linked to the population dynamics of the host animals and their habitats being in close proximity to humans, which is becoming increasingly important in a globalized world. Currently there is neither an approved vaccine nor a specific and effective antiviral treatment available for use in humans. Hantaviruses belong to the order Bunyavirales with a tri-segmented negative-sense RNA genome. They encode only five viral proteins and replicate and transcribe their genome in the cytoplasm of infected cells. However, many details of the viral amplification cycle are still unknown. In recent years, structural biology methods such as cryo-electron tomography, cryo-electron microscopy, and crystallography have contributed essentially to our understanding of virus entry by membrane fusion as well as genome encapsidation by the nucleoprotein. In this review, we provide an update on the hantavirus replication cycle with a special focus on structural virology aspects.

Multiplex PCR-Based Nanopore Sequencing and Epidemiological Surveillance of Hantaan orthohantavirus in Apodemus agrarius, Republic of Korea.

Whole-genome sequencing of infectious agents enables the identification and characterization of emerging viruses. The MinION device is a portable sequencer that allows real-time sequencing in fields or hospitals. Hantaan orthohantavirus (Hantaan virus, HTNV), harbored by Apodemus agrarius, causes hemorrhagic fever with renal syndrome (HFRS) and poses a critical public health threat worldwide. In this study, we aimed to evaluate the feasibility of using nanopore sequencing for whole-genome sequencing of HTNV from samples having different viral copy numbers. Amplicon-based next-generation sequencing was performed in A. agrarius lung tissues collected from the Republic of Korea. Genomic sequences of HTNV were analyzed based on the viral RNA copy numbers. Amplicon-based nanopore sequencing provided nearly full-length genomic sequences of HTNV and showed sufficient read depth for phylogenetic analysis after 8 h of sequencing. The average identity of the HTNV genome sequences for the nanopore sequencer compared to those of generated from Illumina MiSeq revealed 99.8% (L and M segments) and 99.7% (S segment) identities, respectively. This study highlights the potential of the portable nanopore sequencer for rapid generation of accurate genomic sequences of HTNV for quicker decision making in point-of-care testing of HFRS patients during a hantavirus outbreak.

Epidemiological Approach to the Hantavirus Outbreak and the Role of the Social Dimension of Health Care

In late 2018, in the town of Epuyén, Argentine Patagonia, the outbreak of Andes hantavirus begins. Evidence led to the interhuman transmission hypothesis. The comparative analysis carried out by the National Administration of Laboratories and Health Institutes (ANLIS, <i>Administración Nacional de Laboratorios e Institutos de Salud</i>) Malbrán of Argentina showed that the viral genotype was Andes Sur. The percentage of genetic identity reached 99.9% and confirmed, univocally, that the transmission mechanism was from person to person. This finding indicates a unique and extraordinary event that required a multidimensional approach, incorporating the collective health approach to transform biomedical therapeutics through an intersectoral, interinstitutional and intercultural work based on the dynamics of social determination and its impact on the health/disease/attention/care process. The chain of contagion had 4 clusters with 34 confirmed cases and 11 deaths. Overall mortality was 32.4%, women doubling the number of deaths compared to men. This article presents not only the hard data of the outbreak, but also the observation of the socio-cultural context in which it took place and the value of social determination in the health care process, criteria without which selective respiratory isolation (ARS, <i>aislamiento respiratorio selectivo</i>), the main tool for containing the outbreak, would not have been possible in the multiethnic and multicultural context of the Patagonian region. Incidentally, 8.7% of the population of Chubut province recognizes itself as indigenous and more than half of the 100 communities are distributed in the area where the outbreak occurred. The concept of indigenous health is linked to a holistic view of balance between the individual and the universe, confronting the hegemony of the bio-model. This confrontation challenged the health team to look more deeply into the social collective and to find there the agreements and synergies that allowed the successful continuation of the intervention until the resolution and conclusion of the outbreak.

Hantavirus pulmonary syndrome outbreaks associated with climate variability in Northwestern Argentina, 1997-2017.

BackgroundRodent-borne hantaviruses (genus Orthohantavirus) are the etiologic agents causing two human diseases: hemorrhagic fever with renal syndrome (HFRS) in Euroasia; and hantavirus pulmonary syndrome (HPS) in North and South America. In South America fatality rates of HPS can reach up to 35%–50%. The transmission of pathogenic hantaviruses to humans occurs mainly via inhalation of aerosolized excreta from infected rodents. Thus, the epidemiology of HPS is necessarily linked to the ecology of their rodent hosts and the contact with a human, which in turn may be influenced by climatic variability. Here we examined the relationship between climatic variables and hantavirus transmission aim to develop an early warning system of potential hantavirus outbreaks based on ecologically relevant climatic factors.Methodology and main findingsWe compiled reported HPS cases in northwestern Argentina during the 1997–2017 period and divided our data into biannual, quarterly, and bimestrial time periods to allow annual and shorter time delays to be observed. To evaluate the relationship of hantavirus transmission with mean temperature and precipitation we used dynamic regression analysis. We found a significant association between HPS incidence and lagged rainfall and temperature with a delay of 2 to 6 months. For the biannual and quarterly models, hantavirus transmission was positively associated with lagged rainfall and temperature; whereas the bimestrial models indicate a direct relationship with the rainfall but inverse for temperature in the second lagged period.Conclusions/SignificanceThis work demonstrates that climate variability plays a significant role in the transmission of hantavirus in northwestern Argentina. The model developed in this study provides a basis for the forecast of potential HPS outbreaks based on climatic parameters. Our findings are valuable for the development of public health policies and prevention strategies to mitigate possible outbreaks. Nonetheless, a surveillance program on rodent population dynamics would lead to a more accurate forecast of HPS outbreaks.

Spatial and Temporal Evolutionary Patterns in Puumala Orthohantavirus (PUUV) S Segment.

The S segment of bank vole (Clethrionomys glareolus)-associated Puumala orthohantavirus (PUUV) contains two overlapping open reading frames coding for the nucleocapsid (N) and a non-structural (NSs) protein. To identify the influence of bank vole population dynamics on PUUV S segment sequence evolution and test for spillover infections in sympatric rodent species, during 2010–2014, 883 bank voles, 357 yellow-necked mice (Apodemus flavicollis), 62 wood mice (A. sylvaticus), 149 common voles (Microtus arvalis) and 8 field voles (M. agrestis) were collected in Baden-Wuerttemberg and North Rhine-Westphalia, Germany. In total, 27.9% and 22.3% of bank voles were positive for PUUV-reactive antibodies and PUUV-specific RNA, respectively. One of eight field voles was PUUV RNA-positive, indicating a spillover infection, but none of the other species showed evidence of PUUV infection. Phylogenetic and isolation-by-distance analyses demonstrated a spatial clustering of PUUV S segment sequences. In the hantavirus outbreak years 2010 and 2012, PUUV RNA prevalence was higher in our study regions compared to non-outbreak years 2011, 2013 and 2014. NSs amino acid and nucleotide sequence types showed temporal and/or local variation, whereas the N protein was highly conserved in the NSs overlapping region and, to a lower rate, in the N alone coding part.

Immunocytochemical and Ultrastructural Evidence Supporting That Andes Hantavirus (ANDV) Is Transmitted Person-to-Person Through the Respiratory and/or Salivary Pathways.

In South America Andes hantavirus (ANDV) is hosted by the rodent Oligoryzomys longicaudatus (also known as pygmy rice rat). In humans, ANDV causes Hantavirus Pulmonary Syndrome (HPS), with a fatality rate of about 40%. Epidemiologic and molecular evidence has shown that ANDV can be transmitted from person to person. Sin Nombre hantavirus, occurring in North America, and ANDV are genetically related, and both cause HPS with similar clinical evolution and mortality rate. However, only ANDV is transmitted from person to person. A recent hantavirus outbreak in a small village in Southern Argentine, with 29 HPS cases and 11 deaths has brought to mind that person-to-person transmission continues to be a public health emergency. The present investigation was aimed to understand how does ANDV actually spread between persons. Tissue samples of lung and salivary glands from infected Oligoryzomys longicaudatus and lethal cases of human HPS were investigated by bright field immunocytochemistry, multichannel immunofluorescence, and transmission electron microscopy. The findings are consistent with ANDV infection and replication in the lung alveolar epithelium and macrophages, and in the secretory cells of the submandibular salivary glands. In the lung of infected Oligoryzomys longicaudatus and human cases HPS, the bulk of immunoreactive hantavirus antigens was localized in epithelial cells of the alveolar walls and macrophages. The ultrastructural study supports that in the lung of HPS patients the virus replicates in the alveolar epithelial cells with virus particles being discharged into the alveolar lumen. Virus-like particles were seen within vacuoles of the lung macrophages. Considering that these macrophages can reach the conductive segments of the airways, their expectoration becomes a deadly bullet for ANDV transmission. In the submandibular glands of infected rodents and HPS cases, ANDV antigens were in capillary endothelium, the secretory cells and filling the lumen of the excretory pathway. It is proposed that in patients with HPS caused by ANDV the alveolar epithelium and macrophages would be the gate for the airway spreading of the virus, while the salivary glands are a target for virus replication and an exit pathway through saliva.

Dynamics of Puumala hantavirus outbreak in Black Sea Region, Turkey.

Some of the hantavirus species in Euro-Asia cause haemorrhagic fever with renal syndrome (HFRS) in humans. The first documented human hantavirus infection in Turkey was diagnosed in 2009. This report describes the dynamics of the first hantavirus outbreak that emerged in humans in the Western Black Sea Region of Turkey. All the suspected cases of hantavirus infection were admitted to the Infectious Diseases and Clinical Microbiology Department at the Zonguldak Bülent Ecevit University Hospital in Zonguldak, Turkey. The patients were carefully interviewed, examined and evaluated using routine laboratory tests and hantavirus diagnostic tools. Hantavirus-reactive antibodies (IgM and IgG) in serum samples were detected via enzyme immune assay (EIA) and immunofluorescence assay (IFA) in the acute and convalescence stages of the disease. The presence of hantavirus ribonucleic acid (RNA) was analysed via reverse transcription polymerase chain reaction (RT-PCR) in serum and urine samples. A focus reduction neutralization test (FRNT) was performed to confirm specific hantavirus serotypes. In addition, a case-control study was conducted to identify possible risk factors for hantavirus transmission in the outbreak area. A control group was composed of asymptomatic individuals who were seronegative for hantavirus IgM and IgG and living in the outbreak area. A total of 55 suspected cases of hantavirus infection were admitted to the inpatient clinic between February and June of 2009. Twenty-four patients were diagnosed with acute HFRS via EIA or IFA. In 22 of the 24 infected patients, Puumala virus (PUUV) was identified as the causative hantavirus type by detecting IgM in the acute stage and an increase in the IgG level in follow-up serum samples. PUUV was also verified as the infecting agent by FRNT in two of the 24 cases. Among the 24 laboratory-confirmed HFRS cases, 21 (87.5%) were males and 3 (12.5%) were females, and the mean age was 45.92years (standard deviation±16.90years). Almost all these individuals were living in villages or rural areas. The 24 HFRS cases were matched with 26 healthy controls for statistical analyses and according to binary logistic regression analysis, and dealing with rodent control activities in gardens or in annexes of their homes (p=0.021 and Odds ratio [OR]=17.11) and being male (p=0.019 and OR=22.37) were detected as statistically significant risk factors for hantavirus infection. The most commonly observed clinical complaints were fatigue (95.8%), shivering (91.7%), fever (87.1%), headache (70.8%) and nausea (70.8%). Haemodialysis was required for four patients (16.7%). Except for the first case diagnosed with acute hantavirus infection, no patient died. The mean delay time to hospital admission from initiation of symptoms was 5.3days, the mean duration of febrile days was 2.6days, and the mean duration of hospital stay was 8.5days. Hantaviruses are circulating in Turkey and causing sporadic or epidemic infection in humans. Additional investigations are needed to better understand the dynamics of hantaviruses in this country.

Implication of Predator Interaction of the Spread of Hantavirus Infection

Hantaviruses are etiological agents of zoonotic diseases and certain other diseases, which pose a serious threat to human health. When rodent and predator populations share in an ecology, the competitive force of the populations can lead to a reduction or elimination of a hantavirus outbreak. The effect of the predator eliminating rodents and predator populations that tends to reduce or eliminate hantavirus infection is investigated. The existence of several equilibrium points of the model is identified and local and global stabilities of the model at these equilibrium points are analysed in detail. Numerical simulations are carried out to illustrate our model results.

In All Things There is a Law of Cycles; Pathogen-host Interactions in Hantavirus Infections.

Hantaviruses are carried by rodents, insectivores and bats. Some serotypes are able to cause disease in humans, i.e. hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia, and hantavirus cardio-pulmonary syndrome (HCPS) on the American continent. We examine the multiple factors that drive hantavirus outbreak occurrence in Europe like rodent population structure, habitat suitability and its changes, general climatic and local/temporal meteorological conditions, food availability in its various facets (hard, soft mast), predators, biodiversity and anthropogenic factors.

Natural infection of Neotropical bats with hantavirus in Brazil

Bats (Order: Chiroptera) harbor a high diversity of emerging pathogens presumably because their ability to fly and social behavior favor the maintenance, evolution, and dissemination of these pathogens. Until 2012, there was only one report of the presence of Hantavirus in bats. Historically, it was thought that these viruses were harbored primarily by rodent and insectivore small mammals. Recently, new species of hantaviruses have been identified in bats from Africa and Asia continents expanding the potential reservoirs and range of these viruses. To assess the potential of Neotropical bats as hosts for hantaviruses and its transmission dynamics in nature, we tested 53 bats for active hantaviral infection from specimens collected in Southeastern Brazil. Part of the hantaviral S segment was amplified from the frugivorous Carollia perspicillata and the common vampire bat Desmodus rotundus. DNA sequencing showed high similarity with the genome of Araraquara orthohantavirus (ARQV), which belongs to one of the more lethal hantavirus clades (Andesorthohantavirus). ARQV-like infection was detected in the blood, urine, and organs of D. rotundus. Therefore, we describe a systemic infection in Neotropical bats by a human pathogenic Hantavirus. We also propose here a schematic transmission dynamics of hantavirus in the study region. Our results give insights to new, under-appreciated questions that need to be addressed in future studies to clarify hantavirus transmission in nature and avoid hantavirus outbreaks.

Gastrointestinal Tract As Entry Route for Hantavirus Infection.

Background: Hantaviruses are zoonotic agents that cause hemorrhagic fevers and are thought to be transmitted to humans by exposure to aerosolized excreta of infected rodents. Puumala virus (PUUV) is the predominant endemic hantavirus in Europe. A large proportion of PUUV-infected patients suffer from gastrointestinal symptoms of unclear origin. In this study we demonstrate that PUUV infection can occur via the alimentary tract.Methods: We investigated susceptibility of the human small intestinal epithelium for PUUV infection and analyzed the resistance of virions to gastric juice. As model for intestinal virus translocation we performed infection experiments with human intestinal Caco-2 monolayers. In animal experiments we infected Syrian hamsters with PUUV via the intragastric route and tested seroconversion and protective immunity against subsequent Andes virus challenge.Results: PUUV retained infectivity in gastric juice at pH >3. The virus invaded Caco-2 monolayers in association with endosomal antigen EEA1, followed by virus replication and loss of epithelial barrier function with basolateral virus occurrence. Cellular disturbance and depletion of the tight junction protein ZO-1 appeared after prolonged infection, leading to paracellular leakage (leak flux diarrhea). Moreover, animal experiments led to dose-dependent seroconversion and protection against lethal Andes virus challenge.Conclusions: We provide evidence that hantavirus can infect the organism via the alimentary tract and suggest a novel aspect of hantavirus infection and pathogenesis.Significance: Hantaviruses are zoonotic pathogens causing severe hemorrhagic fevers worldwide. They are transmitted to humans by small mammals. To date, these viruses were thought to infect exclusively through the airborne route by inhalation of aerosols from infectious animal droppings or by rodent bites. In our work we could show that the alimentary tract is an alternative path of infection for hantaviruses, meaning a new association of virus and disease. These findings have impact on current textbook knowledge and bring many implications for hantavirus epidemiology and outbreak prevention measures.

Sequence-Independent, Single-Primer Amplification Next-Generation Sequencing of Hantaan Virus Cell Culture-Based Isolates.

Hantaan virus (HTNV), identified in the striped field mouse (Apodemus agrarius), belongs to the genus Hantavirus of the family Bunyaviridae and contains tripartite RNA genomes, small (S), medium (M), and large (L) segments. HTNV is a major causative for hemorrhagic fever with renal syndrome (HFRS) with fatality rates ranging from 1% to 15% in the Republic of Korea (ROK) and China. Defining of HTNV whole-genome sequences and isolation of the infectious particle play a critical role in the characterization and preventive and therapeutic strategies of hantavirus outbreaks. Next-generation sequencing (NGS) provides an advanced tool for massive genomic sequencing of viruses. However, the isolation of viral infectious particles is a huge obstacle to investigate and develop anti-virals for hantaviruses. Here, we report 12 HTNV isolates from lung tissues of the striped field mouse in the highly HFRS-endemic areas. Sequence-independent, single-primer amplification (SISPA) NGS was attempted to recover the genomic sequences of HTNV isolates. The nucleotide sequence of HTNV S, M, and L segments were covered up to 99.4-100%, 97.5-100%, and 95.6-99.8%, respectively, based on the full length of the prototype HTNV 76-118. The whole-genome sequencing of HTNV isolates was accomplished by additional reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification cDNA ends (RACE) PCR. In conclusion, this study will lead to the attempt and usage of SISPA NGS technologies to delineate the whole-genome sequence of hantaviruses, providing a new era of viral genomics for the surveillance, trace, and disease risk management of HFRS incidents.

Scientific Collaborations: How Do We Measure the Return on Relationships?

Emerging infectious diseases (EIDs), the majority of which are zoonotic, represent a tremendous challenge for public health and biosurveillance infrastructure across the globe. Due to the complexity of zoonotic pathogens, it is essential that research and response to EIDs be a transdisciplinary effort. And while crisis and circumstance may be the initial catalyst for responding to an outbreak, we provide examples of how transdisciplinary scientific collectives, which are organized and solidified in advance of crises, can transform the way the world responds to outbreaks and in some cases could even prevent one from occurring (1). Current methods for assessing whether a cooperative engagement between countries is producing measurable and sustainable value is based on the ideas of return on investment and do not consider the inherent importance of relationships. In this article, we apply the idea of return on relationships (ROR) and propose a method for measuring ROR, using a system dynamics modeling framework commonly used in epidemiology. Tracking the numerous and diverse scientific collaborations that emerged from a training workshop for biosurveillance of bats held in Singapore in 2014, we apply a methodology for visualizing and measuring the relationship networks and outcomes that result. Additionally, the collaborative, multidisciplinary network that coalesced in response to the Hantavirus outbreak in New Mexico is 1993 is discussed as an example of the long-term benefits of ROR.

Environmental conditions in favour of a hantavirus outbreak in 2015 in Germany?

Bank voles can harbour Puumala virus (PUUV) and vole populations usually peak in years after beech mast. A beech mast occurred in 2014 and a predictive model indicates high vole abundance in 2015. This pattern is similar to the years 2009/2011 when beech mast occurred, bank voles multiplied and human PUUV infections increased a year later. Given similar environmental conditions in 2014/2015, increased risk of human PUUV infections in 2015 is likely. Risk management measures are recommended.

Environmental fluctuations lead to predictability in Sin Nombre hantavirus outbreaks

Predicting outbreaks of zoonotic infections in reservoir hosts that live in highly fluctuating environments, such as Sin Nombre virus (SNV) in deer mice, is particularly challenging because host populations vary widely in response to environmental conditions and the relationship between field infection rates and abundance often appears to contradict conventional theory. Using a stage‐structured host‐pathogen model parameterized and cross‐validated from a unique 15‐year data set, we show how stochastic population fluctuations can lead to predictable dynamics of SNV in deer mice. Significant variation in host abundance and the basic reproductive number of the virus results in intermittent crossing of the critical host population density necessary for SNV endemicity and frequent local extinctions. When environmental conditions favor growth of the host population above the threshold, host–pathogen interactions lead to delayed density dependence in reservoir prevalence. The resultant ecological delay may provide a neglected opportunity for outbreak prediction in zoonoses.

Modeling to predict cases of hantavirus pulmonary syndrome in Chile.

BackgroundHantavirus pulmonary syndrome (HPS) is a life threatening disease transmitted by the rodent Oligoryzomys longicaudatus in Chile. Hantavirus outbreaks are typically small and geographically confined. Several studies have estimated risk based on spatial and temporal distribution of cases in relation to climate and environmental variables, but few have considered climatological modeling of HPS incidence for monitoring and forecasting purposes.MethodologyMonthly counts of confirmed HPS cases were obtained from the Chilean Ministry of Health for 2001–2012. There were an estimated 667 confirmed HPS cases. The data suggested a seasonal trend, which appeared to correlate with changes in climatological variables such as temperature, precipitation, and humidity. We considered several Auto Regressive Integrated Moving Average (ARIMA) time-series models and regression models with ARIMA errors with one or a combination of these climate variables as covariates. We adopted an information-theoretic approach to model ranking and selection. Data from 2001–2009 were used in fitting and data from January 2010 to December 2012 were used for one-step-ahead predictions.ResultsWe focused on six models. In a baseline model, future HPS cases were forecasted from previous incidence; the other models included climate variables as covariates. The baseline model had a Corrected Akaike Information Criterion (AICc) of 444.98, and the top ranked model, which included precipitation, had an AICc of 437.62. Although the AICc of the top ranked model only provided a 1.65% improvement to the baseline AICc, the empirical support was 39 times stronger relative to the baseline model.ConclusionsInstead of choosing a single model, we present a set of candidate models that can be used in modeling and forecasting confirmed HPS cases in Chile. The models can be improved by using data at the regional level and easily extended to other countries with seasonal incidence of HPS.

Impact of the Yosemite Hantavirus Outbreak on Hantavirus Antibody Testing at a National Reference Laboratory

In conjunction with the 2012 Yosemite hantavirus outbreak, the number of sera our facility tested for hantavirus antibodies increased. We tracked test results and used the data set to determine if a more efficient testing algorithm was possible. Sera were screened using laboratory-developed pan-hantavirus IgG and IgM enzyme immunoassays (EIAs), with an index of >1.10 defined as positive. Sera that were IgM positive by screening (screen IgM(+)) were tested for Sin Nombre virus (SNV)-specific IgM using a laboratory-developed EIA; screen IgM(+) IgG(+) sera were also tested for SNV IgG using a laboratory-developed immunoblot assay. SNV antibody-positive samples were sent to state public health laboratories (PHL) or the CDC for confirmation. Of 3,946 sera tested from July through December 2012, 205 were screen IgM(+) IgG negative (IgG(-)); 7/205 were SNV IgM(+), but only 1/5 sent to PHL/CDC was confirmed as SNV IgM(+). Of 61 screen IgM(+) IgG(+) sera, 16 were SNV antibody positive; 13/16 sera (from 11 patients) went to PHL/CDC, where SNV infection was confirmed for all patients. Of 12 confirmed patients, 7 had been exposed at Yosemite. A modified algorithm defining screen indices of ≥2.00 as positive identified 11/12 confirmed cases while reducing the number of sera requiring SNV-specific antibody testing by 65%; the patient missed was not tested until 3 months after the onset of symptoms. Hantavirus antibody testing at our facility identified 12 SNV-infected patients, including 7 exposed at Yosemite. Some screen IgM(+) IgG(-) SNV IgM(+) results were false positives, emphasizing the value of PHL/CDC confirmatory testing. We identified a modified algorithm requiring analysis of fewer specimens for SNV-specific antibodies without loss of sensitivity.

Global Trade Tradeoff: Rickettsial Disease in Taiwan

Global Trade Tradeoff: Rickettsial Disease in Taiwan