Progress Toward Rubella and Congenital Rubella Syndrome Control - South-East Asia Region, 2000-2016.

In 2013, the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR)* adopted the goal of elimination of measles and control† of rubella and congenital rubella syndrome (CRS) by 2020 (1). Rubella is the leading vaccine-preventable cause of birth defects. Although rubella typically causes a mild fever and rash in children and adults, rubella virus infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, or a constellation of congenital malformations known as CRS, commonly including visual, auditory, and/or cardiac defects, and developmental delay (2). Rubella and CRS control capitalizes on the momentum created by pursuing measles elimination because the efforts are programmatically linked. Rubella-containing vaccine (RCV) is administered as a combined measles and rubella vaccine, and rubella cases are detected through case-based surveillance for measles or fever and rash illness (3). This report summarizes progress toward rubella and CRS control in SEAR during 2000-2016. Estimated coverage with a first RCV dose (RCV1) increased from 3% of the birth cohort in 2000 to 15% in 2016 because of RCV introduction in six countries. RCV1 coverage is expected to increase rapidly with the phased introduction of RCV in India and Indonesia beginning in 2017; these countries are home to 83% of the SEAR birth cohort. During 2000-2016, approximately 83 million persons were vaccinated through 13 supplemental immunization activities (SIAs) conducted in eight countries. During 2010-2016, reported rubella incidence decreased by 37%, from 8.6 to 5.4 cases per 1 million population, and four countries (Bangladesh, Maldives, Sri Lanka, and Thailand) reported a decrease in incidence of ≥95% since 2010. To achieve rubella and CRS control in SEAR, sustained investment to increase routine RCV coverage, periodic high-quality SIAs to close immunity gaps, and strengthened rubella and CRS surveillance are needed.

Virologic Monitoring of Poliovirus Type 2 after Oral Poliovirus Vaccine Type 2 Withdrawal in April 2016 - Worldwide, 2016-2017.

The Global Polio Eradication Initiative (GPEI) has made substantial progress since its launch in 1988; only 37 wild poliovirus type 1 (WPV1) cases were detected in 2016, the lowest annual count ever. Wild poliovirus type 3 has not been detected since November 2012, and wild poliovirus type 2 was officially declared eradicated in September 2015. This success is attributable to the wide use of live oral poliovirus vaccines (OPVs). Since 2001, numerous outbreaks were caused by the emergence of genetically divergent vaccine-derived polioviruses (VDPVs) whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (1). In 2015, circulating VDPV type 2 (cVDPV2) outbreaks were detected in five countries worldwide (Nigeria, Pakistan, Guinea, Burma, and South Sudan), and VDPV2 single events were reported in 22 countries. These events prompted the GPEI to withdraw the type 2 component (Sabin2) of trivalent OPV (tOPV) in a globally coordinated, synchronized manner in April 2016 (2,3), at which time all OPV-using countries switched to using bivalent OPV (bOPV), containing Sabin types 1 and 3. This report details for the first time the virologic tracking of elimination of a live vaccine that has been withdrawn from routine and mass immunization systems worldwide (3). To secure elimination, further monitoring is warranted to detect any use of tOPV or monovalent OPV type 2 (mOPV2).

Japanese Encephalitis Surveillance and Immunization - Asia and Western Pacific Regions, 2016.

Japanese encephalitis (JE) virus is the most important vaccine-preventable cause of encephalitis in the Asia-Pacific region. The World Health Organization (WHO) recommends integration of JE vaccination into national immunization schedules in all areas where the disease is a public health priority (1). This report updates a previous summary of JE surveillance and immunization programs in Asia and the Western Pacific in 2012 (2). Since 2012, funding for JE immunization has become available through the GAVI Alliance, three JE vaccines have been WHO-prequalified,* and an updated WHO JE vaccine position paper providing guidance on JE vaccines and vaccination strategies has been published (1). Data for this report were obtained from a survey of JE surveillance and immunization practices administered to health officials in countries with JE virus transmission risk, the 2015 WHO/United Nations Children's Fund Joint Reporting Form on Immunization, notes and reports from JE meetings held during 2014-2016, published literature, and websites. In 2016, 22 (92%) of 24 countries with JE virus transmission risk conducted JE surveillance, an increase from 18 (75%) countries in 2012, and 12 (50%) countries had a JE immunization program, compared with 11 (46%) countries in 2012. Strengthened JE surveillance, continued commitment, and adequate resources for JE vaccination should help maintain progress toward prevention and control of JE.

Global Measles and Rubella Laboratory Network Support for Elimination Goals, 2010-2015.

In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan (GVAP)* with the objective to eliminate measles and rubella in five World Health Organization (WHO) regions by 2020. In September 2013, countries in all six WHO regions had established measles elimination goals, and additional goals for elimination of rubella and congenital rubella syndrome were established in three regions (1). Capacity for surveillance, including laboratory confirmation, is fundamental to monitoring and verifying elimination. The 2012-2020 Global Measles and Rubella Strategic Plan of the Measles and Rubella Initiative(†) calls for effective case-based surveillance with laboratory testing for case confirmation (2). In 2000, the WHO Global Measles and Rubella Laboratory Network (GMRLN) was established to provide high quality laboratory support for surveillance (3). The GMRLN is the largest globally coordinated laboratory network, with 703 laboratories supporting surveillance in 191 countries. During 2010-2015, 742,187 serum specimens were tested, and 27,832 viral sequences were reported globally. Expansion of the capacity of the GMRLN will support measles and rubella elimination efforts as well as surveillance for other vaccine-preventable diseases (VPDs), including rotavirus, and for emerging pathogens of public health concern.

Influenza seasonality and vaccination timing in tropical and subtropical areas of southern and south-eastern Asia.

OBJECTIVE: To characterize influenza seasonality and identify the best time of the year for vaccination against influenza in tropical and subtropical countries of southern and south-eastern Asia that lie north of the equator. METHODS: Weekly influenza surveillance data for 2006 to 2011 were obtained from Bangladesh, Cambodia, India, Indonesia, the Lao People's Democratic Republic, Malaysia, the Philippines, Singapore, Thailand and Viet Nam. Weekly rates of influenza activity were based on the percentage of all nasopharyngeal samples collected during the year that tested positive for influenza virus or viral nucleic acid on any given week. Monthly positivity rates were then calculated to define annual peaks of influenza activity in each country and across countries. FINDINGS: Influenza activity peaked between June/July and October in seven countries, three of which showed a second peak in December to February. Countries closer to the equator had year-round circulation without discrete peaks. Viral types and subtypes varied from year to year but not across countries in a given year. The cumulative proportion of specimens that tested positive from June to November was > 60% in Bangladesh, Cambodia, India, the Lao People's Democratic Republic, the Philippines, Thailand and Viet Nam. Thus, these tropical and subtropical countries exhibited earlier influenza activity peaks than temperate climate countries north of the equator. CONCLUSION: Most southern and south-eastern Asian countries lying north of the equator should consider vaccinating against influenza from April to June; countries near the equator without a distinct peak in influenza activity can base vaccination timing on local factors.

Vaccine-related mumps infections in Thailand and the identification of a novel mutation in the mumps fusion protein.

An outbreak of nine cases of mumps was reported from a total of 97 vaccinated nursing students at two medical colleges in Thailand in 2010, 16-26 days after administration of MMR vaccine containing the L-Zagreb mumps strain. Symptoms ranged in severity from fever and parotid swelling to orchitis. Clinical samples were obtained from seven patients and three were suitable for further study. Sequencing confirmed that the SH gene of the mumps virus in the unpassaged clinical specimens was identical to the L-Zagreb SH gene in the vaccine. Further analysis of the viral genome identified nucleotide position 5170 as a novel mutation which corresponds to an amino acid change in the fusion protein. This study provides another virologically confirmed example of mumps resulting from the L-Zagreb vaccine strain.

Genetic characterization of measles viruses that circulated in Thailand from 1998 to 2008.

During the period between 1998 and 2008, 48 representative measles viruses (MeVs) circulating in Thailand were subjected to genetic characterization. Three genotypes, G2, D5, and D9 were detected. The results suggested that measles genotype D5, which has been circulating since at least 1998, is the endemic genotype in Thailand. Genotype G2 was detected between 1998 and 2001. In addition, almost all of the MeVs detected throughout the country in 2008 were genotype D9. This is the first report of genotype D9 in Thailand. This report provides important baseline data about measles genotypes in Thailand and this information will be needed to help verify measles elimination in Thailand.

Developing rubella vaccination policy in Nepal--results from rubella surveillance and seroprevalence and congenital rubella syndrome studies.

BACKGROUND: The Government of Nepal is interested in preventing congenital rubella syndrome (CRS). Surveillance data were analyzed and studies conducted to assess the burden of rubella and CRS and aid in developing a rubella vaccination strategy. METHODS: (1) Analysis of rubella cases reported through measles surveillance, 2004-2009; (2) in 2008, rubella seroprevalence among women 15 to 39 years of age was evaluated; and (3) in 2009, children attending a school for the deaf were examined for ocular defects associated with CRS. RESULTS: From 2004-2009, there were 3,710 confirmed rubella cases and more than 95% of these cases were less than 15 years of age. Of 2,224 women of childbearing age (WCBA) tested for anti-rubella IgG, 2,020 (90.8%) were seropositive. Using a catalytic infection model, approximately 1,426 infants were born with CRS (192/100,000 live births) in 2008. Among 243 students attending a school for the deaf, 18 (7.4%) met the clinical criteria for CRS. CONCLUSIONS: Rubella and CRS were documented as significant public health problems in Nepal. A comprehensive approach is necessary, including introducing rubella vaccine in the routine program, assuring immunity among WCBA, strengthening routine immunization, integrating rubella surveillance with measles case-based surveillance, and establishing CRS surveillance.

Global distribution of measles genotypes and measles molecular epidemiology.

A critical component of laboratory surveillance for measles is the genetic characterization of circulating wild-type viruses. The World Health Organization (WHO) Measles and Rubella Laboratory Network (LabNet), provides for standardized testing in 183 countries and supports genetic characterization of currently circulating strains of measles viruses. The goal of this report is to describe the lessons learned from nearly 20 years of virologic surveillance for measles, to describe the global databases for measles sequences, and to provide regional updates about measles genotypes detected by recent surveillance activities. Virologic surveillance for measles is now well established in all of the WHO regions, and most countries have conducted at least some baseline surveillance. The WHO Global Genotype Database contains >7000 genotype reports, and the Measles Nucleotide Surveillance (MeaNS) contains >4000 entries. This sequence information has proven to be extremely useful for tracking global transmission patterns and for documenting the interruption of transmission in some countries. The future challenges will be to develop quality control programs for molecular methods and to continue to expand virologic surveillance activities in all regions.

Status of global virologic surveillance for rubella viruses.

The suspected measles case definition captures rubella cases. Therefore, measles surveillance will be improved in the course of the control and eventual elimination of rubella transmission. One aspect of rubella control, virologic surveillance, is reviewed here. A systematic nomenclature for rubella viruses (RVs) based on 13 genotypes has been established and is updated when warranted by increases in information about RVs. From 2005 through 2010, the genotypes of RVs most frequently reported were 1E, 1G, and 2B, and genotypes 1a, 1B, 1C, 1h, 1j, and 2C were less frequently reported. Virologic surveillance can support rubella control and elimination. Synopses of rubella virologic surveillance in various countries, regions, and globally are given, including characterization of viruses from imported cases in a country that has eliminated rubella and studies of endemic viruses circulating in countries without rubella control objectives. Current challenges are discussed.

Evidence for subclinical avian influenza virus infections among rural Thai villagers.

BACKGROUND: Regions of Thailand reported sporadic outbreaks of A/H5N1 highly pathogenic avian influenza (HPAI) among poultry between 2004 and 2008. Kamphaeng Phet Province, in north-central Thailand had over 50 HPAI poultry outbreaks in 2004 alone, and 1 confirmed and 2 likely other human HPAI infections between 2004 and 2006. METHODS: In 2008, we enrolled a cohort of 800 rural Thai adults living in 8 sites within Kamphaeng Phet Province in a prospective study of zoonotic influenza transmission. We studied participants' sera with serologic assays against 16 avian, 2 swine, and 8 human influenza viruses. RESULTS: Among participants (mean age 49.6 years and 58% female) 65% reported lifetime poultry exposure of at least 30 consecutive minutes. Enrollees had elevated antibodies by microneutralization assay against 3 avian viruses: A/Hong Kong/1073/1999(H9N2), A/Thailand/676/2005(H5N1), and A/Thailand/384/2006(H5N1). Bivariate risk factor modeling demonstrated that male gender, lack of an indoor water source, and tobacco use were associated with elevated titers against avian H9N2 virus. Multivariate modeling suggested that increasing age, lack of an indoor water source, and chronic breathing problems were associated with infection with 1 or both HPAI H5N1 strains. Poultry exposure was not associated with positive serologic findings. CONCLUSIONS: These data suggest that people in rural central Thailand may have experienced subclinical avian influenza infections as a result of yet unidentified environmental exposures. Lack of an indoor water source may play a role in transmission.

A comparison study of measles antibody between two doses vaccination at 9, 18 months and single dose at 9 months in children 4-6 years old.

BACKGROUND: The authors have added the second dose of measles vaccine to children aged 18 months since 1997 because of the measles outbreaks in Nan province in 1993-1994. OBJECTIVE: To compare measles antibody level between two doses vaccination at 9, 18 months and single dose at 9 months in children at the age of 4 to 6 years old. MATERIAL AND METHOD: A cross sectional serological study in children 4 to 6 years old was performed between August 2008 and August 2009 at three hospitals in Nan and Phrae provinces. The subjects were divided into two groups, 1) 100 children in Nan provincial hospital received two doses of measles vaccination at the age of 9 and 18 months and 2) 91 children received single dose measles vaccination at the age of 9 months, 41 from Phrae provincial hospital and 50 from Weingsa district hospital. Blood samples were drawn for measles antibody measurement by ELISA assays at Virus Research Institute, National Institute of Health, Thailand. RESULTS: The mean measles antibody level in children 4 to 6 years old in both groups was a satisfactory high level, 1,887.67 and 1,621.02 mIU/ml in single and two doses vaccination respectively, which were not statistically significant (p = 0.431). The higher level in single dose group could be explained by the average age being younger than the two doses group by one year (4 years 2 months vs. 5 years 4 months). Therefore, the waning immunity in younger age group is suspected to be less than the older age group. The rate of protective measles antibody level (> or = 255 mIU/ml) was significantly higher in the two doses group than the single dose, 87% compared to 76% (p = 0.046), which represented primary vaccine failure at the age 4 to 6 years of 13% and 24%, respectively. CONCLUSION: The authors suggest that a second dose of measles vaccine at the age of 18 months be administered to decrease the number of primary vaccine failure from 24% to 13%. Further studies in the same age group and in different areas are required to confirm these findings.

Successes and challenges of expansion of environmental poliovirus surveillance in the WHO South-East Asia Region.

The last decade has witnessed an exponential expansion of environmental surveillance (ES) of poliovirus in sewage samples in the World Health Organization (WHO) South-East Asia Region. This has grown from only three sites in Mumbai, India in 2001 to 56 sites in 2017 in Bangladesh, India, Indonesia, Myanmar, Nepal and Thailand. ES is critical to the region in providing evidence of silent transmission of vaccine-derived poliovirus and Sabin-like poliovirus type 2 - especially since the global "switch" to cease use of oral polio vaccine type 2 - and for monitoring the effectiveness of containment activities. This targeted expansion of ES to supplement surveillance for acute flaccid paralysis (AFP) required quality assurance in ES procedures, improvements in the sensitivity of the laboratory-based surveillance system, and establishment of real-time data analysis for evidence-based programmes. ES in the region has provided documentary evidence for the absence of indigenous wild poliovirus in circulation and no importations via international travellers. Post-switch, while no vaccine-derived poliovirus was detected from AFP cases, ES identified five ambiguous vaccine-derived polioviruses in 2016 and early 2017, with no evidence of circulation. Future challenges include monitoring for vaccine-derived poliovirus strains shed for a prolonged time by immunodeficient individuals, and expanding ES to areas lacking sewage networks. To maintain the polio-free status of the WHO South-East Asia Region and achieve a world free of poliomyelitis, critical evaluation of immunization coverage, continued performance of surveillance for acute flaccid paralysis, and enhanced analysis of sewage samples to detect any breach in containment are essential.

Measles antibody in mothers and infants 0-2 years and response to measles vaccine at the age of 9 and 18 months.

BACKGROUND: Despite the declining trends in measles cases corresponding to an increase in routine measles immunization coverage, measles outbreaks occur in some isolated areas in Nan province, northern Thailand. The primary reason for these outbreaks is inadequate vaccine coverage. Another reason is primary vaccine failure. OBJECTIVES: To study maternal and cord blood measles antibody, the kenetic change of infant measles antibody from 0-9 months and the response to measles vaccine at the age of 9 and 18 months. MATERIAL AND METHOD: A prospective cohort study for measles antibody of 1,010 mothers and infants 0-2 years was done between April 1999 and March 2001 at three hospitals in Nan province. Consecutive blood samples were drawn for measles antibody measurement by ELISA assays at Virus Research Institute, National Institute of Health, Thailand. The demographic data of mothers and infants were recorded at each visit. RESULTS: Maternal and cord blood measles antibody were high and the authors found a higher level in cord blood than in maternal level. Measles antibody level in infants declined significantly from the age of 4 months (246.4 +/- 364.2 mlU/L) to their lowest level at the age of 9 months (17.7 +/- 197.1 mlU/L). CONCLUSION: After the first dose of 9-month measles vaccination, the authors found the seroconversion rate of 82.2 percent. The seroconversion rate was significantly higher to 99.6 percent after the second dose at 18 months old.

Geographical distribution of hantaviruses in Thailand and potential human health significance of Thailand virus.

Phylogenetic investigations, sequence comparisons, and antigenic cross-reactivity studies confirmed the classification of Thailand virus (THAIV) as a distinct hantavirus species. The examination of sera from 402 rodents trapped in 19 provinces of Thailand revealed that five greater bandicoot rats (Bandicota indica) and one lesser bandicoot rat (B. savilei) from four provinces were focus reduction neutralization test (FRNT) antibody-positive for THAIV. One of 260 patients from Surin province in Thailand (initially suspected of having contracted leptospirosis, but found to be negative) showed symptoms compatible with hemorrhagic fever with renal syndrome (HFRS). The serum of this patient showed high titers of hantavirus-reactive IgM and IgG. FRNT investigations confirmed virus-neutralizing antibodies against THAIV. These observations suggest that THAIV or THAI-like viruses occur throughout Indochina and may represent an additional causative agent of HFRS.

Antibody response after measles immunization.

RATIONALE: Measles is still an important public health problem in Thailand despite measles vaccination being practiced since 1984. Vaccine failure is one of the suspected reasons for the high incidence of measles. OBJECTIVE: To study the seroconversion rate of 9-month-old infants and to study the antibody level in 18 month-old and 4 year-old children who had measles vaccination at 9 months of age. MATERIAL AND METHOD: Enrolled infants and children who attended the child health clinic for routine immunization at the Queen Sirikit National Institute of Child Health from March 1, 1994 to May 31, 1995. They were divided into 3 groups. Group A, 9 month-old infants who came for measles vaccination. Blood samples were drawn twice from these infants, before measles vaccination and 3 months later for measles antibody level. Group B and C were 18 month-old and 4-year-old children who came for their first and second DTP (Diphtheria, Tetanus, Pertussis vaccine) booster. One blood sample for measles antibody was drawn from the latter group of children. Measles antibody was determined by micro-neutralization technic at the National Institute of Health (NIH). The geometric mean antibody titer before and after measles vaccination was compared by using the paired t-test. RESULTS: There were 30, 31 and 34 infants/children in group A, B and C respectively. No significant measles antibody (NT antibody was less than 1:4) was detected in 93.5 per cent of 9-month-old infants. The seroconversion rate at 3 months after vaccination in group A children was 68.75 per cent while in group B, 9 months after vaccination it was 53.3 per cent. Ninety seven per cent of children in group C had NT antibody above 1:4. The geometric mean titer (GMT) of measles antibody in 9-month (before vaccination), 12-month, 18-month infants and 4 year old children was 1:2.5; 1:14.8, 1:8.2 and 1:73.8, respectively (p < 0.05). CONCLUSION: Almost 70 per cent of vaccinees at 9 months of age had seroconversion to measles vaccine with GMT of 1:14.8 while fifty three per cent of 18 month old children had an average GMT of 1:8.2. The GMT of the two groups was significantly different (p < 0.05). At 4 years of age almost all the children had NT antibody to measles with a GMT of 1:73.8 (p < 0.05) Vaccine failure is likely to be one factor responsible for the high incidence of measles after the introduction of measles vaccine into the Expanded Program of Immunization (EPI). The authors suggest giving a booster dose of measles at 15 months of age to boost the antibody level before waning of measles antibody at 18 months old, in order to protect this group of children from contracting measles.

Prospective study of avian influenza virus infections among rural Thai villagers.

BACKGROUND: In 2008, 800 rural Thai adults living within Kamphaeng Phet Province were enrolled in a prospective cohort study of zoonotic influenza transmission. Serological analyses of enrollment sera suggested this cohort had experienced subclinical avian influenza virus (AIV) infections with H9N2 and H5N1 viruses. METHODS: After enrollment, participants were contacted weekly for 24 mos for acute influenza-like illnesses (ILI). Cohort members confirmed to have influenza A infections were enrolled with their household contacts in a family transmission study involving paired sera and respiratory swab collections. Cohort members also provided sera at 12 and 24 months after enrollment. Serologic and real-time RT-PCR assays were performed against avian, swine, and human influenza viruses. RESULTS: Over the 2 yrs of follow-up, 81 ILI investigations in the cohort were conducted; 31 (38%) were identified as influenza A infections by qRT-PCR. Eighty-three household contacts were enrolled; 12 (14%) reported ILIs, and 11 (92%) of those were identified as influenza infections. A number of subjects were found to have slightly elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2) virus: 21 subjects (2.7%) at 12-months and 40 subjects (5.1%) at 24-months. Among these, two largely asymptomatic acute infections with H9N2 virus were detected by >4-fold increases in annual serologic titers (final titers 1:80). While controlling for age and influenza vaccine receipt, moderate poultry exposure was significantly associated with elevated H9N2 titers (adjusted OR = 2.3; 95% CI, 1.04-5.2) at the 24-month encounter. One subject had an elevated titer (1:20) against H5N1 during follow-up. CONCLUSIONS: From 2008-10, evidence for AIV infections was sparse among this rural population. Subclinical H9N2 AIV infections likely occurred, but serological results were confounded by antibody cross-reactions. There is a critical need for improved serological diagnostics to more accurately detect subclinical AIV infections in humans.

Antibody response to an eight-site intradermal rabies vaccination in patients infected with Human Immunodeficiency Virus.

OBJECTIVE: To investigate the rabies virus neutralizing antibody response in HIV-1-infected patients with CD4+ cell count 200 cells/microL after post-exposure prophylaxis using an eight-site intradermal rabies vaccination regimen. METHODS: In a prospective cohort study, 27 HIV-1 infected patients were recruited, none of which had a history of rabies vaccination. All patients provided informed consent and were separated into two groups according to their CD4+ cell count (patients with CD4+ counts of 200 cells/microL). All patients received Purified Chick Embryo Cell rabies Vaccine (PCECV) using a modified eight-site regimen in which 0.1 mL of vaccine was injected intradermally on each of days 0, 3, 7, 14, and 30 (8-8-8-8-8). CD4+ cell counts, HIV-1 viral load and rabies virus neutralizing antibody (RVNAb) concentrations as determined by the Rapid Fluorescent Focus Inhibition Test (RFFIT) were evaluated on blood samples taken on days 0, 3, 7, 14, 30, 90, 180 and 365 after vaccination. RESULTS: Of the 27 patients included in the study, 18 patients (67%) had CD4+ cell counts of >200 cells/microL and 9 patients (33%) had CD4+ counts of or=0.5 IU/mL). There was no statistically significant difference in RVNAb concentrations between the two groups on days 3, 7, 14, 30, 90, 180 and 365 after vaccination. CONCLUSION: PCECV is immunogenic in HIV-1-infected patients with CD4+ cell counts below 200 cells/microL when administered in a modified eight-site intradermal PEP regimen.

Development of serological assays for Thottapalayam virus, an insectivore-borne Hantavirus.

Thottapalayam virus (TPMV), a member of the genus Hantavirus in the family Bunyaviridae, was isolated from an insectivore, Suncus murinus (musk shrew), captured in southern India in 1964. While the isolation of TPMV predates the discovery of the prototype Hantaan virus, little is known about its genetics and biology. To date, preliminary evidence suggests that TPMV differs significantly, both antigenically and genetically, from all known rodent-borne hantaviruses. However, since detailed epizootiological studies have not been conducted, it is unclear if TPMV is naturally harbored by an insectivore host or if TPMV represents a "spillover" from its natural rodent reservoir host. Moreover, to what extent TPMV causes infection and/or disease in humans is not known. To address these issues, we first studied the antigenic profile of TPMV using monoclonal antibodies against Hantaan and Seoul viruses and polyclonal immune sera against Puumala virus and TPMV. Armed with this newfound information, we developed an enzyme-linked immunosorbent assay system for the diagnosis of TPMV infections in shrews and humans, using a recombinant TPMV N antigen manipulated to have an E5/G6 epitope to be captured by monoclonal antibody clone E5/G6. Using this assay, we found anti-TPMV antibodies in sera from a patient with high fever of unknown etiology in Thailand and from two shrews captured in Indonesia. Seropositivity was verified by the indirect immunofluorescence antibody test, Western blotting analysis, and focus reduction neutralization test. Collectively, our data indicate that TPMV is harbored by Suncus murinus as its host in nature and is capable of infecting humans.