Characteristics, risk factors, and outcomes related to Zika virus infection during pregnancy in Northeastern Thailand: A prospective pregnancy cohort study, 2018-2020.

BACKGROUND: In response to the 2015-2016 Zika virus (ZIKV) outbreak and the causal relationship established between maternal ZIKV infection and adverse infant outcomes, we conducted a cohort study to estimate the incidence of ZIKV infection in pregnancy and assess its impacts in women and infants. METHODOLOGY/PRINCIPAL FINDINGS: From May 2018-January 2020, we prospectively followed pregnant women recruited from 134 participating hospitals in two non-adjacent provinces in northeastern Thailand. We collected demographic, clinical, and epidemiologic data and blood and urine at routine antenatal care visits until delivery. ZIKV infections were confirmed by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Specimens with confirmed ZIKV underwent whole genome sequencing. Among 3,312 women enrolled, 12 (0.36%) had ZIKV infections, of which two (17%) were detected at enrollment. Ten (83%, 3 in 2nd and 7 in 3rd trimester) ZIKV infections were detected during study follow-up, resulting in an infection rate of 0.15 per 1,000 person-weeks (95% CI: 0.07-0.28). The majority (11/12, 91.7%) of infections occurred in one province. Persistent ZIKV viremia (42 days) was found in only one woman. Six women with confirmed ZIKV infections were asymptomatic until delivery. Sequencing of 8 ZIKV isolates revealed all were of Asian lineage. All 12 ZIKV infected women gave birth to live, full-term infants; the only observed adverse birth outcome was low birth weight in one (8%) infant. Pregnancies in 3,300 ZIKV-rRT-PCR-negative women were complicated by 101 (3%) fetal deaths, of which 67 (66%) had miscarriages and 34 (34%) had stillbirths. There were no differences between adverse fetal or birth outcomes of live infants born to ZIKV-rRT-PCR-positive mothers compared to live infants born to ZIKV-rRT-PCR-negative mothers. CONCLUSIONS/SIGNIFICANCE: Confirmed ZIKV infections occurred infrequently in this large pregnancy cohort and observed adverse maternal and birth outcomes did not differ between mothers with and without confirmed infections.

Safety and immunogenicity of locally produced trivalent inactivated influenza vaccine (Tri Fluvac) in healthy Thai adults aged 18-64 years in Nakhon Phanom: A Phase III double blinded, three-arm, randomized, controlled trial.

BACKGROUND: Domestic influenza vaccine production facilitates a sustainable supply for mitigating seasonal influenza and improves national health security by providing infrastructure and experience for pandemic vaccine production, if needed. METHODS: A Phase III, double blind, randomized controlled trial was conducted from Sep 2019-Oct 2020 in healthy adults 18-64 years in Nakhon Phanom, Thailand. Randomization (3:3:1) compared study vaccine (Tri Fluvac), saline placebo, and an active comparator (licensed vaccine). Primary outcomes were superior efficacy compared to placebo based on RT-PCR-confirmed influenza virus infection within 12 months and non-inferiority compared to active comparator based on immunogenicity (HAI assay) at 28 days. Safety was also assessed. RESULTS: The trial enrolled 4,284 participants (Tri Fluvac = 1,836; placebo = 1,836; active comparator = 612). There were 29 RT-PCR positive influenza infections (10 Tri Fluvac, 5.5/1,000 PY; 19 placebo, 10.4/1,000PY; 0 comparator) for an absolute protective efficacy of 46.4 (95 % CI = -22.0-76.5) compared with placebo, but the power was 43.7 %. Seroconversion difference rates between Tri Fluvac and comparator at Day 28 were 1.74 (95 % CI: -2.77, 6.25), 2.22 (-2.40, 6.84), and -0.57 (-5.41, 4.27) for A(H1N1), A(H3N2), and B strains, respectively. Adverse and severe adverse events occurred in 175 (9.5 %) Tri Fluvac, 177 (10.8 %) placebo, and 66 (10.8 %) comparator arms (p-value = 0.437, Tri Fluvac vs. comparator) CONCLUSIONS: Tri Fluvac was well tolerated, and immunogenicity was non-inferior to the active comparator, meeting U.S. Food and Drug Administration (FDA) criteria for adult vaccine licensure. Few acute respiratory infections were reported during intense COVID-19 pandemic restrictions, resulting in insufficient power to evaluate clinical efficacy.

Genetic basis of sudden death after COVID-19 vaccination in Thailand.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 vaccination reduces morbidity and mortality associated with coronavirus disease 2019 (COVID-19); unfortunately, it is associated with serious adverse events, including sudden unexplained death (SUD). OBJECTIVE: We aimed to study the genetic basis of SUD after COVID-19 vaccination in Thailand. METHODS: From April to December 2021, cases with natural but unexplained death within 7 days of COVID-19 vaccination were enrolled for whole exome sequencing. RESULTS: Thirteen were recruited, aged between 23 and 72 years; 10 (77%) were men, 12 were Thai; and 1 was Australian. Eight (61%) died after receiving the first dose of vaccine, and 7 (54%) died after receiving ChAdOx1 nCoV-19; however, there were no significant correlations between SUD and either the number or the type of vaccine. Fever was self-reported in 3 cases. Ten (77%) and 11 (85%) died within 24 hours and 3 days of vaccination, respectively. Whole exome sequencing analysis revealed that 5 cases harbored SCN5A variants that had previously been identified in patients with Brugada syndrome, giving an SCN5A variant frequency of 38% (5 of 13). This is a significantly higher rate than that observed in Thai SUD cases occurring 8-30 days after COVID-19 vaccination during the same period (10% [1 of 10]), in a Thai SUD cohort studied before the COVID-19 pandemic (12% [3 of 25]), and in our in-house exome database (12% [386 of 3231]). CONCLUSION: These findings suggest that SCN5A variants may be associated with SUD within 7 days of COVID-19 vaccination, regardless of vaccine type, number of vaccine dose, and presence of underlying diseases or postvaccine fever.

Trends in Incidence of Two Major Subtypes of Liver and Bile Duct Cancer: Hepatocellular Carcinoma and Cholangiocarcinoma in Songkhla, Southern Thailand, 1989-2030.

BACKGROUND: The incidence of liver and bile duct cancer continues to rise, especially in Thailand. We aimed to project the trends in incidence of this rare but lethal cancer in southern Thailand in order to determine its future disease burden. METHODS: Gender-specific trends in age-standardized incidence rates per 100,000 person-years for hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) cases in Songkhla province of southern Thailand diagnosed between 1989 and 2013 were estimated and projected up to year 2030 using three different modeling techniques: a joinpoint model, an age-period-cohort model, and a modified age-period-cohort model. RESULTS: Of 2,676 liver and bile duct (LBD) cancer cases identified, 73% were males, 51% were aged between 50 and 69 years, and HCC (44.4%) was slightly more common than CCA (38.1%). The models all predicted an increase in the incidence rate of CCA up to 2025 for both sexes whereas the incidence of HCC is expected to decrease among males and stabilize among females. The incidence rates of HCC and CCA among males in 2030 could reach 6.7 and 9.4 per 100,000 person-years, respectively, whereas the expected rates of HCC and CCA among females are expected to be around 1.5 and 3.9 per 100,000 person-years, respectively. CONCLUSIONS: The incidence of cholangiocarcinoma is expected to increase in Songkhla and will contribute a larger proportion of LBD cancers in the future. Future public health efforts and research studies should focus on this increasing trend.

Imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection from Oman to Thailand, June 2015.

Thailand reported the first Middle East respiratory syndrome (MERS) case on 18 June 2015 (day 4) in an Omani patient with heart condition who was diagnosed with pneumonia on hospital admission on 15 June 2015 (day 1). Two false negative RT-PCR on upper respiratory tract samples on days 2 and 3 led to a 48-hour diagnosis delay and a decision to transfer the patient out of the negative pressure unit (NPU). Subsequent examination of sputum later on day 3 confirmed MERS coronavirus (MERS-CoV) infection. The patient was immediately moved back into the NPU and then transferred to Bamrasnaradura Infectious Disease Institute. Over 170 contacts were traced; 48 were quarantined and 122 self-monitored for symptoms. High-risk close contacts exhibiting no symptoms, and whose laboratory testing on the 12th day after exposure was negative, were released on the 14th day. The Omani Ministry of Health (MOH) was immediately notified using the International Health Regulation (IHR) mechanism. Outbreak investigation was conducted in Oman, and was both published on the World Health Organization (WHO) intranet and shared with Thailand's IHR focal point. The key to successful infection control, with no secondary transmission, were the collaborative efforts among hospitals, laboratories and MOHs of both countries.

Two consecutive outbreaks of food-borne cholera associated with consumption of chicken rice in northwestern Thailand.

Hainanese chicken rice (cooked rice mixed with chicken fat and served with sliced chicken and cucumber) is a well-known Chinese dish in Southeast Asian countries. We report two consecutive outbreaks of cholera associated with consumption of chicken rice among attendants of two meetings in northwestern Thailand in April 2010. Active case finding was carried out among persons who attended the meetings and in the community. Environmental investigation was conducted at the implicated food shop and in the affected areas. The first outbreak involved 17 cholera cases (35.4%) among 48 attendants and 16 cases in the community. The onset of symptoms was between April 19 and 23, 2010. People who ate the chicken rice had a higher attack rate of infection than those who did not. All 12 food handlers at the implicated food shop were screened for cholera infection by rectal swab culture; 3 were culture-positive. Although the food shop was closed temporarily following the outbreak, some chicken rice was produced and served at the second meeting and caused 11 more cases (23.4%) among 47 meeting attendants. All cholera isolates obtained from patients and food handlers were V. cholerae O1, biotype El Tor, serotype Ogawa, and had similar antibiograms and genetic patterns by pulsed-field gel electrophoresis. The chicken rice which was possibly contaminated by an infected food handler served as the vehicle of transmission. A repeat cholera outbreak caused by the same vehicle can occur when control measures are not adequately followed.

Serological response to the 2009 pandemic influenza A (H1N1) virus for disease diagnosis and estimating the infection rate in Thai population.

BACKGROUND: Individuals infected with the 2009 pandemic virus A(H1N1) developed serological response which can be measured by hemagglutination-inhibition (HI) and microneutralization (microNT) assays. METHODOLOGY/PRINCIPAL FINDINGS: MicroNT and HI assays for specific antibody to the 2009 pandemic virus were conducted in serum samples collected at the end of the first epidemic wave from various groups of Thai people: laboratory confirmed cases, blood donors and health care workers (HCW) in Bangkok and neighboring province, general population in the North and the South, as well as archival sera collected at pre- and post-vaccination from vaccinees who received influenza vaccine of the 2006 season. This study demonstrated that goose erythrocytes yielded comparable HI antibody titer as compared to turkey erythrocytes. In contrast to the standard protocol, our investigation found out the necessity to eliminate nonspecific inhibitor present in the test sera by receptor destroying enzyme (RDE) prior to performing microNT assay. The investigation in pre-pandemic serum samples showed that HI antibody was more specific to the 2009 pandemic virus than NT antibody. Based on data from pre-pandemic sera together with those from the laboratory confirmed cases, HI antibody titers ≥ 40 for adults and ≥ 20 for children could be used as the cut-off level to differentiate between the individuals with or without past infection by the 2009 pandemic virus. CONCLUSIONS/SIGNIFICANCE: Based on the cut-off criteria, the infection rates of 7 and 12.8% were estimated in blood donors and HCW, respectively after the first wave of the 2009 influenza pandemic. Among general population, the infection rate of 58.6% was found in children versus 3.1% in adults.

A food borne outbreak of gastroenteritis due to shigella and possibly salmonella in a school.

On August 5, 2005, a private hospital reported a large number of students with gastrointestinal illness from the same school in Bangkok, Thailand. The Bureau of Epidemiology along with the Bangkok Metropolitan Administration investigated this outbreak, to determine risk factors, identify the source of infection and possible causative organism, and recommend prevention and control strategies. A case was defined as a person who was studying or working at School A and who developed abdominal pain, diarrhea, nausea or vomiting during the five-day period of August 4 to 8, 2005. A descriptive study was carried out for active case-finding, medical records review, and case interviews. We conducted the retrospective cohort study among third and fourth grade students. Stool samples were collected and tested at the Thai National Institute of Health and at private hospital laboratories. The overall attack rate was 37%. Main symptoms were diarrhea, fever, headache, abdominal pain, vomiting, and nausea. The highest attack rate (63%) was among fourth-grade students. Based on food-history data collected from ill and well students, a multiple logistic regression analysis showed that a mixed chicken and rice dish served for lunch on August 4 was associated with illness (OR 3.28, 95% CI 1.46-7.36). Among stools samples from 103 cases, Shigella group D was found in 18 cases, Salmonella group C in 5 cases, and Salmonella group E in 2 cases. This food borne outbreak of gastroenteritis was most likely caused by Shigella spp although the possibility of mixed contamination with Shigella and Salmonella spp cannot be ruled out. Food borne outbreaks such as this can be prevented through simple and effective hygienic measures.

An avian influenza H5N1 virus that binds to a human-type receptor.

Avian influenza viruses preferentially recognize sialosugar chains terminating in sialic acid-alpha2,3-galactose (SAalpha2,3Gal), whereas human influenza viruses preferentially recognize SAalpha2,6Gal. A conversion to SAalpha2,6Gal specificity is believed to be one of the changes required for the introduction of new hemagglutinin (HA) subtypes to the human population, which can lead to pandemics. Avian influenza H5N1 virus is a major threat for the emergence of a pandemic virus. As of 12 June 2007, the virus has been reported in 45 countries, and 312 human cases with 190 deaths have been confirmed. We describe here substitutions at position 129 and 134 identified in a virus isolated from a fatal human case that could change the receptor-binding preference of HA of H5N1 virus from SAalpha2,3Gal to both SAalpha2,3Gal and SAalpha2,6Gal. Molecular modeling demonstrated that the mutation may stabilize SAalpha2,6Gal in its optimal cis conformation in the binding pocket. The mutation was found in approximately half of the viral sequences directly amplified from a respiratory specimen of the patient. Our data confirm the presence of H5N1 virus with the ability to bind to a human-type receptor in this patient and suggest the selection and expansion of the mutant with human-type receptor specificity in the human host environment.

Probable person-to-person transmission of avian influenza A (H5N1).

BACKGROUND: During 2004, a highly pathogenic avian influenza A (H5N1) virus caused poultry disease in eight Asian countries and infected at least 44 persons, killing 32; most of these persons had had close contact with poultry. No evidence of efficient person-to-person transmission has yet been reported. We investigated possible person-to-person transmission in a family cluster of the disease in Thailand. METHODS: For each of the three involved patients, we reviewed the circumstances and timing of exposures to poultry and to other ill persons. Field teams isolated and treated the surviving patient, instituted active surveillance for disease and prophylaxis among exposed contacts, and culled the remaining poultry surrounding the affected village. Specimens from family members were tested by viral culture, microneutralization serologic analysis, immunohistochemical assay, reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis, and genetic sequencing. RESULTS: The index patient became ill three to four days after her last exposure to dying household chickens. Her mother came from a distant city to care for her in the hospital, had no recognized exposure to poultry, and died from pneumonia after providing 16 to 18 hours of unprotected nursing care. The aunt also provided unprotected nursing care; she had fever five days after the mother first had fever, followed by pneumonia seven days later. Autopsy tissue from the mother and nasopharyngeal and throat swabs from the aunt were positive for influenza A (H5N1) by RT-PCR. No additional chains of transmission were identified, and sequencing of the viral genes identified no change in the receptor-binding site of hemagglutinin or other key features of the virus. The sequences of all eight viral gene segments clustered closely with other H5N1 sequences from recent avian isolates in Thailand. CONCLUSIONS: Disease in the mother and aunt probably resulted from person-to-person transmission of this lethal avian influenzavirus during unprotected exposure to the critically ill index patient.