Fever In Thailand Research Articles

Genome sequence of dengue virus serotype 1 isolated from a pediatric patient enrolled in an Ivermectin trial in Thailand.

We sequenced the genome of dengue virus serotype 1 (DENV1) strain 4101301, isolated from a child with dengue fever in Thailand and cultured in C6/36 mosquito cells. These data are crucial for studying DENV1's genetic diversity, evolution, and epidemiology and advancing the knowledge for developing antiviral drugs and vaccines targeting DENV.

877. Diagnostic Values of Viral Target Enriched and Metagenomic NGS among Patients with Acute Undifferentiated Fever in Thailand

Abstract Background Despite extensive lab testing, infectious agents were not detected in ∼50% of patients hospitalized for acute undifferentiated febrile illness (AUFI) at Siriraj Hospital, Bangkok, Thailand. Unbiased metagenomic Next Generation Sequencing (mNGS) enables detection of many microbes present in patient samples. Target enrichment for viruses in these libraries represents a highly sensitive and cost-effective approach for overcoming host background present in clinical specimens. Plasma collected from 440 patients with AUFI between 2014-2021 were analyzed by both viral target enrichment and mNGS to determine their diagnostic values for the identification of human pathogens. Methods Benzonase-treated plasma was extracted on an Abbott m2000 instrument. mNGS libraries were prepared from ds-cDNA and hybridized to CVRP probes (Twist Biosciences) covering > 15,000 strains of vertebrate viruses. Target enriched libraries were run on a MiSeq; mNGS libraries were sequenced on a NextSeq. Reads were processed by the SURPI or DiVir pipelines and viral reads were mapped in the CLC Bio Genomics Workbench. Results We identified viruses in 23% of our AUFI population using CVRP. mNGS increased viral detection to 26.8% and overall pathogen detection to 41.8%. Both methods identified relatively prevalent viruses such as Dengue, HIV-1, HBV, HAV and CHIKV, less common viruses such as Measles, HHV-6B, CMV, and PARV and emerging viruses such as SFTS virus with a high degree of correlation between NGS and clinical data. Bacterial pathogens identified by mNGS included Rickettsia typhi, R. felis and Capnocytophaga canimorsus. Identification of parasites P. falciparum and P. vivax was consistent with clinical presentations. mNGS failed to detect blood-culture positive patients with Klebsiella pneumoniae, Pseudomonas aeruginosa, and Streptococcus gallolyticus septicemia. Conclusion CVRP and mNGS demonstrated that viral and rickettsial infections were important etiologies for AUFI in Thailand. This data supports the current recommendation of empirical therapy with ceftriaxone and doxycycline or azithromycin in severe or hospitalized AUFI. Implications for proper management of AUFI include lower rates of unnecessary testing and antimicrobial use. Disclosures Julie Yamaguchi, BS, Abbott Labs: Patents|Abbott Labs: Employee|Abbott Labs: Stocks/Bonds Michael G. Berg, PhD, Abbott Laboratories: employee|Abbott Laboratories: Stocks/Bonds Sonja Weiss, BS, Abbott Laboratories: Employee|Abbott Laboratories: Stocks/Bonds Pakpoom Phoompoung, MD, Abbott Labs: Grant/Research Support|Abbott Labs: Mahidol University is a partner in the Abbott Pandemic Defense Coalition Gavin Cloherty, PhD, Abbott Labs: Patents|Abbott Labs: Employee|Abbott Labs: Stocks/Bonds Yupin Suputtamongkol, MD, Abbott Labs: Grant/Research Support|Abbott Labs: Mahidol University is partner in the Abbott Pandemic Defense Coalition

548. Target Enriched NGS Reveals Wide Breadth of Viruses Causing Acute Undifferentiated Fever in Thailand

Abstract Background Despite extensive laboratory testing, infectious agents were not detected in approximately 50% of patients hospitalized for acute undifferentiated febrile illnesses (AUFI) at Siriraj Hospital, Bangkok, Thailand. Unbiased Metagenomic Next Generation Sequencing (mNGS) enables detection of any microbe present in patient samples. Target enrichment for viruses represents a highly sensitive and cost-effective approach for overcoming host background in clinical specimens. Plasma collected from 800 patients with undiagnosed AUFI between 2013-2020 were analyzed by mNGS coupled to target enrichment to identify known and novel viruses. Methods Plasma was pre-treated with benzonase before extraction on an Abbott m2000 instrument. mNGS libraries were prepared from double-stranded cDNA with Illumina Nextera XT reagents on an epMotion then combined in pools of 24 and hybridized to Comprehensive Viral Research Panel (CVRP; Twist Biosciences) probes covering >15,000 strains of vertebrate viruses. Captured viral sequences were amplified, quantified, and sequenced together on a MiSeq. Reads were taxonomically classified by the SURPI pipeline and aligned in CLC Bio Genomics Workbench software. Results CVRP method optimization enabled sequencing of 24-48 libraries per MiSeq run, for which >50% genome coverage was obtained with model viruses spiked into clinical specimens at 1000 cp/ml. This approach revealed an array of >24 different viruses found in 26% of samples. Dengue was the most prevalent at 7.4%, with all four genotypes detected. Other common causes of AUFI such as Chikungunya, HIV-1, HAV, HBV, HCV, and CMV were present in 1.5-2.5% of cases. Less prevalent (< 1%) infections included HEV, HSV-2, EBV, HHV-6, Enterovirus B&D and Parvovirus B19. We also encountered sporadic cases of Measles, Cardiovirus, West Nile, Rotavirus, Picobirnavirus, Polyomavirus 4&5, Kubovirus, and Rabies lyssavirus. Conclusion Target capture successfully demonstrated that viruses were important etiologies for unresolved cases of AUFI in Thailand. This data has led to a better understanding of the epidemiology of this clinical syndrome and has implications for proper management of AUFI, including lower rates of unnecessary testing and antimicrobial use. Disclosures Julie Yamaguchi, BS, Abbott Labs: Employee Michael G. Berg, PhD, Abbott Labs: Employee Pakpoom Phoompoung, MD, Abbott Labs: Grant/Research Support|Abbott Labs: Employee Jenna Malinauskas, MS, Abbott Labs: Employee Gavin Cloherty, PhD, Abbott: Employee|Abbott: Stocks/Bonds|Abbott Labs: Employee Yupin Suputtamongkol, MD, Abbott Labs: Grant/Research Support.

Influence of climate variables on dengue fever occurrence in the southern region of Thailand.

The 3-5year epidemic cycle of dengue fever in Thailand makes it a major re-emerging public health problem resulting in being a burden in endemic areas. Although the Thai Ministry of Public Health adopted the WHO dengue control strategy, all dengue virus serotypes continue to circulate. Health officers and village health volunteers implement some intervention options but there is a need to ascertain most appropriate (or a combination of) interventions regarding the environment and contextual factors that may undermine the effectiveness of such interventions. This study aims to understand the dengue-climate relationship patterns at the district level in the southern region of Thailand from 2002 to 2018 by examining the statistical association between dengue incidence rate and eight environmental patterns, testing the hypothesis of equal incidence of these. Data on environmental variables and dengue reported cases in Nakhon Si Thammarat province situated in the south of Thailand from 2002 to 2018 were analysed to (1) detect the environmental factors that affect the risk of dengue infectious disease; to (2) determine if disease risk is increasing or decreasing over time; and to (3) identify the high-risk district areas for dengue cases that need to be targeted for interventions. To identify the predictors that have a high and significant impact on reported dengue infection, three steps of analysis were used. First, we used Partial Least Squares (PLS) Regression and Poisson Regression, a variant of the Generalized Linear Model (GLM). Negative co-efficient in correspondence with the PLS components suggests that sea-level pressure, wind speed, and pan evaporation are associated with dengue occurrence rate, while other variables were positively associated. Using the Akaike information criterion in the stepwise GLM, the filtered predictors were temperature, precipitation, cloudiness, and sea level pressure with the standardized coefficients showing that the most influential variable is cloud cover (three times more than temperature and precipitation). Also, dengue occurrence showed a constant negative response to the average increase in sea-level pressure values. In southern Thailand, the predictors that have been locally determined to drive dengue occurrence are temperature, rainfall, cloud cover, and sea-level pressure. These explanatory variables should have important future implications for epidemiological studies of mosquito-borne diseases, particularly at the district level. Predictive indicators guide effective and dynamic risk assessments, targeting pre-emptive interventions.

Incorporating human mobility data improves forecasts of Dengue fever in Thailand

Over 390 million people worldwide are infected with dengue fever each year. In the absence of an effective vaccine for general use, national control programs must rely on hospital readiness and targeted vector control to prepare for epidemics, so accurate forecasting remains an important goal. Many dengue forecasting approaches have used environmental data linked to mosquito ecology to predict when epidemics will occur, but these have had mixed results. Conversely, human mobility, an important driver in the spatial spread of infection, is often ignored. Here we compare time-series forecasts of dengue fever in Thailand, integrating epidemiological data with mobility models generated from mobile phone data. We show that geographically-distant provinces strongly connected by human travel have more highly correlated dengue incidence than weakly connected provinces of the same distance, and that incorporating mobility data improves traditional time-series forecasting approaches. Notably, no single model or class of model always outperformed others. We propose an adaptive, mosaic forecasting approach for early warning systems.

Spatiotemporal patterns and climatic drivers of severe dengue in Thailand

ObjectivesThe burden of dengue fever in Thailand is considerable, yet there are few large-scale studies exploring the drivers of transmission. This study aimed to investigate the spatiotemporal patterns and climatic drivers of severe dengue in Thailand. MethodsGeographic Information System (GIS) techniques and spatial cluster analysis were used to visualize the spatial distribution and detect high-risk clusters of severe dengue in 76 provinces of Thailand from January 1999 to December 2014. The seasonal patterns of severe dengue cases in different provinces were identified. A two-stage modelling approach combining a generalized linear model with a distributed lag non-linear model was used to quantify the effects of monthly mean temperature and relative humidity on the occurrence of severe dengue cases in 51 provinces of Thailand. ResultsSignificant severe dengue clustering was detected, especially during epidemic years, and the location of these clusters showed substantial inter-annual variation. Severe dengue cases in Northern and Northeastern Thailand peaked in June to August and this pattern was stable across the study period, whereas the seasonality of severe dengue cases in other regions (especially Central Thailand) was less predictable. The risk of the occurrence of severe dengue cases increased with an increase in mean temperature in Northeastern Thailand, Central Thailand, and Southern Thailand, with peaks occurring between 24 °C to 30 °C in Northeastern Thailand and 27 °C to 29 °C in Southern Thailand West Coast, respectively. Relative humidity significantly affected the occurrence of severe dengue cases in Northeastern and Central Thailand, with optimal ranges observed for each region. ConclusionsOur findings substantiate the potential for developing climate-based dengue early warning systems for Thailand, and have implications for informing pre-emptive vector control.

Cross-sectional study of brucellosis and Q fever in Thailand among livestock in two districts at the Thai-Cambodian border, Sa Kaeo province

Brucellosis and Q fever impart high morbidity in humans and economic losses among livestock worldwide. However their prevalence is still not fully known in Thailand. We conducted a sero-survey of brucellosis and Q fever in beef, dairy cattle, goat, and sheep herds from Thai communities at the border with Cambodia, a cross-border trading center. Serum samples were tested for brucellosis and Q fever by antibody-based tests at the National Institute of Animal Health, Thailand. We surveyed a total of 520 individuals from 143 herds. Brucellosis herd-level seroprevalence for beef cattle and small ruminants (goats and sheep) was 2.6% (3/117) and 13.3% (2/15) respectively. Q fever herd-level seroprevalence for beef cattle, dairy cattle, and small ruminants was 4.3% (5/117), 27.3% (3/11) and 33.3% (5/15) respectively. This study identified a significant burden of brucellosis and Q fever among small ruminants and dairy cattle at the Thai-Cambodian border.

Seroprevalence of Coxiella burnetii Antibodies Among Ruminants and Occupationally Exposed People in Thailand, 2012-2013.

AbstractLittle is known about the burden of Q fever in Thailand. We conducted a serological study to describe the prevalence of anti-Coxiella burnetii antibodies among ruminants and occupationally exposed persons in response to the report of the first two Q fever endocarditis patients in Thailand in 2012. We randomly selected ruminant sera from brucellosis surveillance and examined sera of 661 occupationally exposed subjects from two provinces of Thailand: Chiangmai and Nakornratchasima. Animal and human sera were tested using commercial enzyme-linked immunosorbent assay (ELISA). Environmental samples, vaginal swab, and milk from cows in Chiangmai farms with detectable anti-C. burnetii serum antibodies were tested using polymerase chain reaction (PCR). Among the 1,632 animal sera tested, 64 (3.9%) were seropositive. The prevalence was highest in dairy cattle (4.6%, 45/988), followed by goats (3.5%, 18/516) and sheep (2.1%, 1/48). The prevalence of anti-C. burnetii antibodies in each species varied significantly by province: the prevalence in cattle was higher in Chiangmai (5.5% versus 0%), however, the prevalence in sheep and goats was higher in Nakornratchasima (5.9% versus 1.0%). Four out of 60 milk samples were positive by PCR (6.7%). No environmental samples were positive. Among 661 human samples, 83 (12.6%) were ELISA positive. Seroprevalence was statistically higher in Chiangmai compare with Nakornratchasima (42.8% versus 3.0%). Coxiella burnetii infection exists in Thailand, but the prevalence varies by geographic distribution and animal reservoirs. Further studies focusing on the burden and risk factors of C. burnetii infection among high-risk groups should be conducted.

Vertical transmission of Indian Ocean Lineage of chikungunya virus in Aedes aegypti and Aedes albopictus mosquitoes.

BackgroundThe re-emergence of chikungunya (CHIK) fever in Thailand has been caused by a novel lineage of chikungunya virus (CHIKV) termed the Indian Ocean Lineage (IOL). The Aedes albopictus mosquito is thought to be a primary vector of CHIK fever in Thailand, whereas Ae. aegypti acts as a secondary vector of the virus. The vertical transmission is believed to be a primary means to maintain CHIKV in nature and may be associated with an increased risk of outbreak. Therefore, the goal of this study was to analyze the potential of these two Thai mosquito species to transmit the virus vertically and to determine the number of successive mosquito generations for the virus transmission.MethodsTwo-hundred-and-fifty female Ae. aegypti and Ae. albopictus mosquitoes were artificially fed a mixture of human blood and CHIKV IOL. Mosquito larvae and adults were sampled and screened for CHIKV by one-step qRT-PCR. LLC-MK2 cell line was used to isolate CHIKV in the mosquitoes each generation. The virus isolate was identified by immunocytochemical staining and was confirmed by sequencing. Both mosquito species fed on human blood without CHIKV and uninfected LLC-MK2 cells were used as controls.ResultsAedes aegypti and Ae. albopictus mosquitoes were able to transmit CHIKV vertically to F5 and F6 progenies, respectively. The virus isolated from the two mosquito species caused cytopathic effect in LLC-MK2 cells by 2 days post-infection and immunocytochemical staining showed the reaction between CHIKV IOL antigen and specific monoclonal antibody in the infected cells. DNA sequence confirmed the virus transmitted vertically as CHIKV IOL with E1-A226V mutation. No CHIKV infection was observed in both mosquito species and LLC-MK2 cells from control groups.ConclusionsThe study demonstrated that Ae. aegypti and Ae. albopictus mosquitoes from Thailand are capable of transmitting CHIKV IOL vertically in the laboratory. Our results showed that Ae. albopictus is more susceptible and has a greater ability to transmit the virus vertically than Ae. aegypti. This knowledge would be useful for risk assessments of the maintenance of CHIKV in nature, which is crucial for disease surveillance, vector control and the prevention of potential CHIKV epidemics.

50 Years Ago in TheJournal ofPediatrics: Shock Associated with Dengue Infection: I. Clinical and Physiological Manifestations of Dengue Hemorrhagic Fever in Thailand, 1964

50 Years Ago in TheJournal ofPediatrics: Shock Associated with Dengue Infection: I. Clinical and Physiological Manifestations of Dengue Hemorrhagic Fever in Thailand, 1964

Immunological evidence of Zika virus transmission in Thailand.

To identify immunological evidence of Zika virus transmission in Thailand. To undertake a preliminary serosurvey of possible exposure to Zika virus, 21 serum samples from cohort of acute undifferentiated fever patients were examined for immunoreactivity to Zika, Dengue, Japanese encephalitis and Chikungunya envelope antigens by Western blot analysis. Twenty of the 21 serum samples showed immunoreactivity to at least one of the antigens, with seven samples showing immunoreactivity to all antigens. Of particular note, two serum samples showed immunoreactivity only to Zika envelope antigen, with no immunoreactivity to other envelope antigens. This study presents the first evidence of Zika virus transmission in Thailand, although as yet the relationship between transmission and possible cases of Zika fever in Thailand requires further investigation.

Real-time Forecasting of the 2014 Dengue Fever Season in Thailand

Real-time surveillance of an infectious disease in a third world country poses many problems that are not conventionally confronted by statistical researchers. As the first ones - to our knowledge - to attempt real-time forecasts of dengue fever in Thailand, we have faced these problems head-on in our quest to build a model that accurately predicts case counts in the presence of erratic reporting, shifting population dynamics, and potential climate change.

Chikungunya virus was isolated in Thailand, 2010.

Chikungunya fever (CHIKF) is an acute febrile illness caused by a mosquito-borne alphavirus, chikungunya virus (CHIKV). This disease re-emerged in Kenya in 2004, and spread to the countries in and around the Indian Ocean. The re-emerging epidemics rapidly spread to regions like India and Southeast Asia, and it was subsequently identified in Europe in 2007, probably as a result of importation of chikungunya cases. On the one hand, chikungunya is one of the neglected diseases and has only attracted strong attention during large outbreaks. In 2008–2009, there was a major outbreak of chikungunya fever in Thailand, resulting in the highest number of infections in any country in the region. However, no update of CHIKV circulating in Thailand has been published since 2009. In this study, we examined the viral growth kinetics and sequences of the structural genes derived from CHIKV clinical isolates obtained from the serum specimens of CHIKF-suspected patients in Central Thailand in 2010. We identified the CHIKV harboring two mutations E1-A226V and E2-I211T, indicating that the East, Central, and South African lineage of CHIKV was continuously circulating as an indigenous population in Thailand.Electronic supplementary materialThe online version of this article (doi:10.1007/s11262-014-1105-5) contains supplementary material, which is available to authorized users.

Impact of combined vector-control and vaccination strategies on transmission dynamics of dengue fever: a model-based analysis

Dengue fever is a vector-borne disease prevalent in tropical and subtropical regions. It is an important public health problem with a considerable and often under-valued disease burden in terms of frequency, cost and quality-of-life. Recent literature reviews have documented the development of mathematical models of dengue fever both to identify important characteristics for future model development as well as to assess the impact of dengue control interventions. Such reviews highlight the importance of short-term cross-protection; antibody-dependent enhancement; and seasonality (in terms of both favourable and unfavourable conditions for mosquitoes). The compartmental model extends work by Bartley (2002) and combines the following factors: seasonality, age-structure, consecutive infection by all four serotypes, cross-protection and immune enhancement, as well as combined vector-host transmission. The model is used to represent dengue transmission dynamics using parameters appropriate for Thailand and to assess the potential impact of combined vector-control and vaccination strategies including routine and catch-up vaccination strategies on disease dynamics. When seasonality and temporary cross-protection between serotypes are included, the model is able to approximate the observed incidence of dengue fever in Thailand. We find vaccination to be the most effective single intervention, albeit with imperfect efficacy (30.2 %) and limited duration of protection. However, in combination, control interventions and vaccination exhibit a marked impact on dengue fever transmission. This study shows that an imperfect vaccine can be a useful weapon in reducing disease spread within the community, although it will be most effective when promoted as one of several strategies for combating dengue fever transmission.

The First Reported Case of Bartonella Endocarditis in Thailand

Bartonella species have been shown to cause acute, undifferentiated fever in Thailand. A study to identify causes of endocarditis that were blood culture-negative using routine methods led to the first reported case in Thailand of Bartonella endocarditis A 57 year-old male with underlying rheumatic heart disease presented with severe congestive heart failure and suspected infective endocarditis. The patient underwent aortic and mitral valve replacement. Routine hospital blood cultures were negative but B. henselae was identified by serology, PCR, immunohistochemistry and specific culture techniques.

Prospective field study of transovarial dengue-virus transmission by two different forms of Aedes aegypti in an urban area of Bangkok, Thailand

A prospective field study was conducted to determine transovarial dengue-virus transmission in two forms of Aedes aegypti mosquitoes in an urban district of Bangkok, Thailand. Immature Aedes mosquitoes were collected monthly for one year and reared continuously until adulthood in the laboratory. Mosquitoes assayed for dengue virus were processed in pools and their dengue virus infection status was determined by one-step RT-PCR and nested-PCR methods. Of a total 15,457 newly emerged adult Ae. aegypti, 98.2% were dark and 1.8% of the pale form. The results showed that the minimum infection rate (MIR) by transovarial transmission (TOT) of dengue virus during the one-year study ranged between 0 to 24.4/1,000 mosquitoes. Dengue virus TOT increased gradually during the hot summer months, reaching a peak in April-June, while dengue cases peaked in September, a rainy month near the end of the rainy season. Therefore, mosquito infections due to TOT were prevalent four months before a high incidence of human infections. TOT dengue virus infections occurred in both forms of Ae. aegypti. All four dengue serotypes were detected, with DEN-4 predominant, followed by DEN-3, DEN-1, and DEN-2, respectively.

The first reported case of Bartonella endocarditis in Thailand

Bartonella species have been shown to cause acute, undifferentiated fever in Thailand. A study to identify causes of endocarditis that were blood culture-negative using routine methods led to the first reported case in Thailand of Bartonella endocarditis A 57 year-old male with underlying rheumatic heart disease presented with severe congestive heart failure and suspected infective endocarditis. The patient underwent aortic and mitral valve replacement. Routine hospital blood cultures were negative but B. henselae was identified by serology, PCR, immunohistochemistry and specific culture techniques.

Spotted Fever GroupRickettsiasp. Closely Related toR. japonica,Thailand

To the Editor: In response to a recent report that suggested human infection with Rickettsia japonica in northeastern Thailand (1), we phylogenetically reexamined spotted fever group rickettsiae (SFGR) from Thailand. The organism had been isolated from a male Haemaphysalis hystricis tick found on Mt. Doi Suthep, Chiang Mai, northern Thailand, in December 2001. The strain was designated TCM1 and was not distinguishable from R. japonica by indirect immunoperoxidase stain using monoclonal antibody (2). After propagating strain TCM1 in L-929 cell culture, we extracted DNA by using a Wizard Genomic DNA Purification Kit (Promega, Madison, WI, USA). We subjected the DNA to sequencing that targeted a 491-bp fragment of rickettsial outer membrane protein A (ompA), a 394-bp fragment of the rickettsial genus–specific 17-kDa antigen gene, and a 1,250-bp fragment of citrate synthase gene (gltA). Direct sequencing of amplicons was performed as previously described (3). Phylogenetic analyses based on ompA indicated that strain TCM1 was closely related to and clustered within the same clade as R. japonica strain YH (98.4% identity) (Figure, panel A). Also, a 17-kDa antigen gene obtained from strain TCM1 showed 99.5% identity to the corresponding gene of R. japonica (Figure, panel B). Our phylogenetic analysis with ompA and 17-kDa antigen gene showed that strain TCM1 was closely related to R. japonica but distinguished from Rickettsia sp. PMK94 (which was closely related to R. heilongjiangensis from northeastern China) (3); another SFGR agent, R. honei from Ixodes granulatus ticks in Thailand (4), was apparently different from strain TCM1 (Figure). Phylogenetic analyses based on gltA (99.4%–99.6% identity) showed that strain TCM1 is also closely related to R. japonica and Rickettsia sp. strain PMK94 (data not shown). Thus, we describe the R. japonica group in Thailand. DNA sequences of strain TCM1 were determined and deposited in GenBank/EMBL/DDBJ under the following accession nos.: ompA, {type:entrez-nucleotide,attrs:{text:AB359459,term_id:169219351,term_text:AB359459}}AB359459; 17-kDa antigen, {type:entrez-nucleotide,attrs:{text:AB359457,term_id:169219347,term_text:AB359457}}AB359457; gltA, {type:entrez-nucleotide,attrs:{text:AB359458,term_id:169219349,term_text:AB359458}}AB359458. Figure Phylogenetic analysis based on ompA gene (A) and rickettsial genus–specific 17-kDa antigen gene (B). Sequences were aligned by using the ClustalW software package (http://clustalw.ddbj.nig.ac.jp/top-j.html), and neighbor-joining phylogenetic tree ... R. japonica is the specific pathogen of Japanese spotted fever, which has been found mainly in southwestern Japan (5). The present strain, closely related to R. japonica, is likely to have been isolated from H. hystricis in Thailand because R. japonica frequently has been isolated, or detected by PCR, from the same tick species in Japan (6). Such tick species–specificity of SFGR should be considered when speculating on any geopathologic relationships of rickettsioses among different SFGR-endemic areas. Previous reports on spotted fever–positive results of human serosurveys (7,8) and on a clinical case (9) in northern Thailand may provide epidemiologic background. In Asia, multiple species of rickettsiea (e.g., R. japonica, R. heilongjiangensis, R. honei) are the causative agents of spotted fever rickettsioses, so the agent closely related to R. japonica could cause spotted fever in Thailand. Additionally, R. japonica has been found in Korea (10), and our current study indicates that R. japonica and its genetic variants are widely distributed in Far Eastern countries, including Japan (Grant-in-Aid for International Cooperative Research, unpub. data). Therefore, the epidemiology and genetic variation of SFGR throughout Asia should be examined by molecular studies.

Relationship between Transmission Intensity and Incidence of Dengue Hemorrhagic Fever in Thailand

BackgroundDengue is the most prevalent mosquito-borne virus, and potentially fatal dengue hemorrhagic fever (DHF) occurs mainly in secondary infections. It recently was hypothesized that, due to the presence of cross-immunity, the relationship between the incidence of DHF and transmission intensity may be negative at areas of intense transmission. We tested this hypothesis empirically, using vector abundance as a surrogate of transmission intensity.Methodology/Principal FindingsHouse Index (HI), which is defined as the percentage of households infested with vector larvae/pupae, was obtained from surveys conducted on one million houses in Thailand, between 2002 and 2004. First, the utility of HI as a surrogate of transmission intensity was confirmed because HI was correlated negatively with mean age of DHF in the population. Next, the relationship between DHF incidence and HI was investigated. DHF incidence increased only up to an HI of about 30, but declined thereafter. Reduction of HI from the currently maximal level to 30 would increase the incidence by more than 40%. Simulations, which implemented a recently proposed model for cross-immunity, generated results that resembled actual epidemiological data. It was predicted that cross-immunity generates a wide variation in incidence, thereby obscuring the relationship between incidence and transmission intensity. The relationship would become obvious only if data collected over a long duration (e.g., >10 years) was averaged.ConclusionThe negative relationship between DHF incidence and dengue transmission intensity implies that in regions of intense transmission, insufficient reduction of vector abundance may increase long-term DHF incidence. Further studies of a duration much longer than the present study, are warranted.

Serological and virological features of dengue fever and dengue haemorrhagic fever in Thailand from 1999 to 2002

Serological and virological features of dengue fever (DF) and dengue haemorrhagic fever (DHF) in Thailand were analysed in 2715 patients from 1999 to 2002. The illness was caused by DEN-1 in 45%, DEN-2 in 32%, DEN-3 in 18% and DEN-4 in 5% of patients. Almost all of the DHF cases caused by DEN-2 and DEN-4 were in secondary infection, while approximately 20% of the DHF cases caused by DEN-1 and DEN-3 were in primary infection. Male:female ratio and age distribution were not different among four serotypes in primary and secondary infections. These results indicate that DEN-1 and DEN-3 induce DHF in both primary and secondary infections, and suggest that DEN-2 and DEN-4 in Thailand are less likely to cause DHF in primary infections.