Allergies and Diabetes as Risk Factors for Dengue Hemorrhagic Fever: Results of a Case Control Study

Background

The physiopathology of dengue hemorrhagic fever (DHF), a severe form of Dengue Fever, is poorly understood. We are unable to identify patients likely to progress to DHF for closer monitoring and early intervention during epidemics, so most cases are sent home. This study explored whether patients with selected co-morbidities are at higher risk of developing DHF.

Methods

A matched case-control study was conducted in a dengue sero-positive population in two Brazilian cities. For each case of DHF, 7 sero-positive controls were selected. Cases and controls were interviewed and information collected on demographic and socio-economic status, reported co-morbidities (diabetes, hypertension, allergy) and use of medication. Conditional logistic regression was used to calculate the strength of the association between the co-morbidities and occurrence of DHF.

Results

170 cases of DHF and 1,175 controls were included. Significant associations were found between DHF and white ethnicity (OR = 4.70; 2.17–10.20), high income (OR = 6.84; 4.09–11.43), high education (OR = 4.67; 2.35–9.27), reported diabetes (OR = 2.75; 1.12–6.73) and reported allergy treated with steroids (OR = 2.94; 1.01–8.54). Black individuals who reported being treated for hypertension had 13 times higher risk of DHF then black individuals reporting no hypertension.

Conclusions

This is the first study to find an association between DHF and diabetes, allergy and hypertension. Given the high case fatality rate of DHF (1–5%), we believe that the evidence produced in this study, when confirmed in other studies, suggests that screening criteria might be used to identify adult patients at a greater risk of developing DHF with a recommendation that they remain under observation and monitoring in hospital.     

Risk of adult street vendor exposure to traffic-related air pollution in Bangkok,Thailand

Traffic-related air pollution (TRAP), including particulate matter (PM) in respirable coarse and fine size fractions (PM10 and PM2.5), is known to have exposure effects on human health and environment. Real-time PM10 and PM2.5 concentrations were collected from the study locations in Bangkok, Thailand, using TSI AM510 particle counters. Temperature and % relative humidity (%RH) were also collected. Data were compared to data from the closest station of the Pollution Control Department (PCD), Thailand. Real-time mean concentration varied from 86 to 1107 µg/m³ (PM10) and varied from 25 to 664 µg/m³ (PM2.5). In addition, real-time mean PM10 (223.1 µg/m³) was nearly four times greater than that measured by the PCD station, 60 µg/m³. Temperature and %RH from real-time air monitoring and PCD station were comparable. In each study location (five locations, two in morning and afternoon/evening), there were significant positive correlations between PM10 and PM2.5 concentrations and significant negative correlations between temperature and RH%. Results suggested that outdoor TRAP via measured real-time PM concentrations were more realistic exposure concentration estimates among street vendors as related to respiratory and other symptoms than data obtained from PCD station. Nevertheless, PM10 as measured by the PCD station might be a reasonable surrogate for estimated outdoor PM2.5 exposure.     

A Prospective Nested Case-Control Study of Dengue in Infants: Rethinking and Refining the Antibody-Dependent Enhancement Dengue Hemorrhagic Fever Model

Background

Dengue hemorrhagic fever (DHF) is the severe and life-threatening syndrome that can develop after infection with any one of the four dengue virus (DENV) serotypes. DHF occurs almost exclusively in individuals with secondary heterologous DENV infections and infants with primary DENV infections born to dengue immune mothers. The widely accepted explanation for the pathogenesis of DHF in these settings, particularly during infancy, is antibody-dependent enhancement (ADE) of DENV infection.

Methods and Findings

We conducted a prospective nested case-control study of DENV infections during infancy. Clinical data and blood samples were collected from 4,441 mothers and infants in up to two pre-illness study visits, and surveillance was performed for symptomatic and inapparent DENV infections. Pre-illness plasma samples were used to measure the associations between maternally derived anti-DENV3 antibody-neutralizing and -enhancing capacities at the time of DENV3 infection and development of infant DHF.The study captured 60 infants with DENV infections across a wide spectrum of disease severity. DENV3 was the predominant serotype among the infants with symptomatic (35/40) and inapparent (15/20) DENV infections, and 59/60 infants had a primary DENV infection. The estimated in vitro anti-DENV3 neutralizing capacity at birth positively correlated with the age of symptomatic primary DENV3 illness in infants. At the time of symptomatic DENV3 infection, essentially all infants had low anti-DENV3 neutralizing activity (50% plaque reduction neutralizing titers [PRNT₅₀] ≤50) and measurable DENV3 ADE activity. The infants who developed DHF did not have significantly higher frequencies or levels of DENV3 ADE activity compared to symptomatic infants without DHF. A higher weight-for-age in the first 3 mo of life and at illness presentation was associated with a greater risk for DHF from a primary DENV infection during infancy.

Conclusions

This prospective nested case-control study of primarily DENV3 infections during infancy has shown that infants exhibit a full range of disease severity after primary DENV infections. The results support an initial in vivo protective role for maternally derived antibody, and suggest that a DENV3 PRNT₅₀ >50 is associated with protection from symptomatic DENV3 illness. We did not find a significant association between DENV3 ADE activity at illness onset and the development of DHF compared with less severe symptomatic illness. The results of this study should encourage rethinking or refinement of the current ADE pathogenesis model for infant DHF and stimulate new directions of research into mechanisms responsible for the development of DHF during infancy.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00377754","term_id":"NCT00377754"}}NCT00377754 Please see later in the article for the Editors'' Summary     

Challenges in Dengue Fever in the Elderly: Atypical Presentation and Risk of Severe Dengue and Hospita-Acquired Infection

Background/methods

To better understand dengue fever in the elderly, we compared clinical features, World Health Organization (WHO) dengue classification and outcomes between adult (<60) and elderly (≥60) dengue patients. We explored the impact of co-morbidity and hospital-acquired infection (HAI) on clinical outcomes in the elderly. All patients managed at the Communicable Disease Centre, Singapore, between 2005 and 2008 with positive dengue polymerase chain reaction (PCR) or who fulfilled WHO 1997 or 2009 probable dengue criteria with positive dengue IgM were included.

Results

Of the 6989 cases, 295 (4.4%) were elderly. PCR was positive in 29%. The elderly suffered more severe disease with more dengue haemorrhagic fever (DHF) (29.2% vs. 21.4%) and severe dengue (SD) (20.3% vs. 14.6%) (p<0.05). Classic dengue symptoms were more common in the adult group. The elderly were less likely to fulfill WHO 1997 (93.6% vs. 96.4%) (p = 0.014), but not WHO 2009 probable dengue (75.3% vs. 71.5%). Time to dengue diagnosis was similar. There was no significant difference in the frequency of warning signs between the two groups, but the elderly were more likely to have hepatomegaly (p = 0.006) and malaise/lethargy (p = 0.033) while the adults had significantly more mucosal bleeding (p<0.001). Intensive care admission occurred in 15 and death in three, with no age difference. Notably, the elderly stayed in hospital longer (median 5 vs. 4 days), and suffered more pneumonia (3.8% vs. 0.7%) and urinary infection (1.9% vs. 0.3%) (p = 0.003). Predictors of excess length of stay were age (adjusted odds ratio [aOR] 2.01, 95% confidence interval [CI] 1.37–2.88), critical illness (aOR 5.13, 95%CI 2.59–9.75), HAI (aOR 12.06, 95%CI 7.39–19.9), Charlson score (aOR 6.9, 95%CI 2.02–22.56) and severe dengue (DHF/dengue shock syndrome/SD) (aOR 2.24, 95%CI 1.83–2.74).

Conclusion

Elderly dengue patients present atypically and are at higher risk of DHF, SD and HAI. Aside from dengue severity, age, co-morbidity and HAI were associated with longer hospital stay.     

Health Risk Assessment of Petrol Station Workers in the Inner City of Bangkok,Thailand, to the Exposure to BTEX and Carbonyl Compounds by Inhalation

The occupational health risk of petrol station workers from exposure to BTEX and carbonyl compounds via inhalation was estimated in the inner city of Bangkok. Personal sampling was performed within the workers’ breathing zone using 2,4 dinitrophenylhydrazine cartridges and charcoal glass tubes connected to a personal air pump during eight working hours at six petrol stations. BTEX and carbonyl compounds were quantitatively analyzed by GC/FID and HPLC/UV, respectively. Of all detectable BTEX and carbonyl compounds, the levels of the four most prevalent compounds (benzene, ethylbenzene, formaldehyde, and acetaldehyde) were used to assess the lifetime cancer risk and 95% confidence interval of the risk levels were found to be totally higher than acceptable criteria for benzene (1.82 × 10^–4–2.50 × 10^–4), formaldehyde (7.81 × 10^–6–1.04 × 10^–5), ethylbenzene (4.11 × 10^–6–5.52 × 10^–6), and acetaldehyde (1.39 × 10^–6–2.45 × 10^–6). Thus, petrol station workers in the inner city of Bangkok have a potentially high cancer risk through inhalation exposure. With respect to the noncarcinogenic agents, toluene, m,p-xylene, o-xylene, and propionaldehyde, all non-cancer health risk were within hazard quotients of 1 and of acceptable risk.     

Origin of the Dengue Fever Mosquito,Aedes aegypti,in California

Dengue fever is among the most widespread vector-borne infectious diseases. The primary vector of dengue is the Aedes aegypti mosquito. Ae. aegypti is prevalent in the tropics and sub-tropics and is closely associated with human habitats outside its native range of Africa. While long established in the southeastern United States of America where dengue is re-emerging, breeding populations have never been reported from California until the summer of 2013. Using 12 highly variable microsatellite loci and a database of reference populations, we have determined that the likely source of the California introduction is the southeastern United States, ruling out introductions from abroad, from the geographically closer Arizona or northern Mexico populations, or an accidental release from a research laboratory. The power to identify the origin of new introductions of invasive vectors of human disease relies heavily on the availability of a panel of reference populations. Our work demonstrates the importance of generating extensive reference databases of genetically fingerprinted human-disease vector populations to aid public health efforts to prevent the introduction and spread of vector-borne diseases.     

Phylodynamics of HIV-1 from a phase III AIDS vaccine trial in Bangkok, Thailand

Background

In 2003, a phase III placebo-controlled trial (VAX003) was completed in Bangkok, Thailand. Of the 2,546 individuals enrolled in the trial based on high risk for infection through injection drug use (IDU), we obtained clinical samples and HIV-1 sequence data (envelope glycoprotein gene gp120) from 215 individuals who became infected during the trial. Here, we used these data in combination with other publicly available gp120 sequences to perform a molecular surveillance and phylodynamic analysis of HIV-1 in Thailand.

Methodology and Findings

Phylogenetic and population genetic estimators were used to assess HIV-1 gp120 diversity as a function of vaccination treatment, viral load (VL) and CD4⁺ counts, to indentify transmission clusters and to investigate the timescale and demographics of HIV-1 in Thailand. Three HIV-1 subtypes were identified: CRF01_AE (85% of the infections), subtype B (13%) and CRF15_AE (2%). The Bangkok IDU cohort showed more gp120 diversity than other Asian IDU cohorts and similar diversity to that observed in sexually infected individuals. Moreover, significant differences (P<0.02) in genetic diversity were observed in CRF01_AE IDU with different VL and CD4⁺ counts. No phylogenetic structure was detected regarding any of the epidemiological and clinical factors tested, although high proportions (35% to 50%) of early infections fell into clusters, which suggests that transmission chains associated with acute infection play a key role on HIV-1 spread among IDU. CRF01_AE was estimated to have emerged in Thailand in 1984.5 (1983–1986), 3–6 years before the first recognition of symptomatic patients (1989). The relative genetic diversity of the HIV-1 population has remained high despite decreasing prevalence rates since the mid 1990s.

Conclusions

Our study and recent epidemiological reports indicate that HIV-1 is still a major threat in Thailand and suggest that HIV awareness and prevention needs to be strengthened to avoid AIDS resurgence.     

The Impact of the Demographic Transition on Dengue in Thailand: Insights from a Statistical Analysis and Mathematical Modeling

Background

An increase in the average age of dengue hemorrhagic fever (DHF) cases has been reported in Thailand. The cause of this increase is not known. Possible explanations include a reduction in transmission due to declining mosquito populations, declining contact between human and mosquito, and changes in reporting. We propose that a demographic shift toward lower birth and death rates has reduced dengue transmission and lengthened the interval between large epidemics.

Methods and Findings

Using data from each of the 72 provinces of Thailand, we looked for associations between force of infection (a measure of hazard, defined as the rate per capita at which susceptible individuals become infected) and demographic and climactic variables. We estimated the force of infection from the age distribution of cases from 1985 to 2005. We find that the force of infection has declined by 2% each year since a peak in the late 1970s and early 1980s. Contrary to recent findings suggesting that the incidence of DHF has increased in Thailand, we find a small but statistically significant decline in DHF incidence since 1985 in a majority of provinces. The strongest predictor of the change in force of infection and the mean force of infection is the median age of the population. Using mathematical simulations of dengue transmission we show that a reduced birth rate and a shift in the population''s age structure can explain the shift in the age distribution of cases, reduction of the force of infection, and increase in the periodicity of multiannual oscillations of DHF incidence in the absence of other changes.

Conclusions

Lower birth and death rates decrease the flow of susceptible individuals into the population and increase the longevity of immune individuals. The increase in the proportion of the population that is immune increases the likelihood that an infectious mosquito will feed on an immune individual, reducing the force of infection. Though the force of infection has decreased by half, we find that the critical vaccination fraction has not changed significantly, declining from an average of 85% to 80%. Clinical guidelines should consider the impact of continued increases in the age of dengue cases in Thailand. Countries in the region lagging behind Thailand in the demographic transition may experience the same increase as their population ages. The impact of demographic changes on the force of infection has been hypothesized for other diseases, but, to our knowledge, this is the first observation of this phenomenon. Please see later in the article for the Editors'' Summary     

Health risk assessment from dermal exposure to pesticide residues on vegetables among greengrocers in fresh market,Bangkok, Thailand

Pesticide residues (PRs) in market vegetables have been reported regularly. Greengrocers may be exposed to several sorts of PRs on vegetables through hand contact. Health risk assessment from occupational exposure to PRs on vegetables is particularly concerning. This study was conducted among 91 vegetable vendors at a large fresh market in Bangkok. Hand wipe samples were collected in the dry season to extract and analyze PRs including organophosphates (OPs), pyrethroids (PYs), and carbamates (CAs) by gas chromatography (GC-FPD/GC-μECD) and liquid chromatography (LC–MS). The results showed that all wipe samples contained OPs, PYs, and CAs, mainly chlorpyrifos (0.01–0.14 µg/hands) and cypermethrin (0.42–11.64 µg/hands). The frequently detected PRs were aldicarb (87.2%), carbofuran (69.2%), permethrin (63.7%), and profenofos (60.0%). At 99th percentile values of PR exposure, average daily dose was 2.42 × 10^?5 mg/kg/d and hazard index did not exceed the acceptable level (0.287). Glove wearing, hand washing, and work-related factors were significantly associated with PRs on hands after adjusted for gender (p-value < 0.05). Greengrocers may therefore not be at risk from PRs on vegetables and exposure via hands during their work. However, these findings suggest that proper personal hygiene practices among greengrocers should be considered to prevent them from PR exposure and potential health risks.     

Multi-locus Sequence Typing and Whole Genome Sequence Analysis of Cryptococcus neoformans Isolated from Clinical Specimens in Vajira Hospital,Bangkok, Thailand

Mycopathologia - The basidiomycete yeast Cryptococcus neoformans causes disease in immunocompromized patients. Whole genome sequencing (WGS) technology provides insights into the molecular...     

2006年广州登革热病原体的分离鉴定及其生物学性质的观察

目的：对2006年广州流行登革热病原进行分离鉴定及生物学性质研究。方法：采用传代蚊细胞微量培养方法对2006年广州登革热病原进行分离,并通过脑内途径观察其对乳鼠的致病性;经间接免疫荧光和RT-PCR技术,对患者血清标本中的病毒特异抗体及新分离的病原体进行检测和鉴定;将此次分离的病原体与1980年分离的同型毒株进行生物学性质比较。结果：从57份患者血清标本中分离出10株病毒,在传代蚊细胞中可产生稳定的细胞病变并对乳鼠致病;其基因组为登革1型病毒特异的RNA分子,经鉴定为登革1型病毒;此次分离的登革1型病毒与1980年分离的同型毒株在致细胞产生病变的时间和严重程度,蚀斑的大小、形态以及致乳鼠发病的时间等生物学性质上有所不同。结论：2006年广州流行登革热病原为登革1型病毒,且与1980年分离的同型毒株在生物学性质方面存在明显差异。     

Environmental Determinants of Campylobacteriosis Risk in Philadelphia from 1994 to 2007

Campylobacter species infections are a common cause of acute gastroenteritis, and may uncommonly be complicated by renal, neurological, and rheumatologic sequelae. Although excess summertime campylobacteriosis has been observed, environmental mechanisms driving disease seasonality are poorly understood. We sought to evaluate the relationship between environmental factors and campylobacteriosis risk in a major North American metropolitan area. We evaluated 1532 cases of campylobacteriosis reported in Philadelphia between 1994 and 2007. We constructed Poisson regression models with oscillatory smoothers, and also used case-crossover design, to evaluate the associations between environmental exposures and disease risk on weekly and daily time scales. Both methods control for confounding by seasonally oscillating environmental factors. Incidence was greatest in June and July, with annual periodicity. Weekly incidence was associated with increasing relative humidity, (incidence rate ratio (IRR) per % 1.017, 95% CI 1.008–1.025), temperature (IRR per °C 1.041, 95% CI 1.011–1.072), and decreasing Delaware River temperature during the same week (IRR per °C 0.922, 95% CI 0.883–0.962), and at 4-week lags (IRR per °C 0.953, 95% CI 0.919–0.990). No acute associations were identified in case-crossover analyses. Our findings affirm the summertime seasonality of campylobacteriosis in Philadelphia, and the link between warm, humid weather and disease risk. However, the link between low river temperatures and enhanced campylobacteriosis risk in humans described here is novel, consistent with known links between watershed temperature and Campylobacter survival, and implicates local watersheds as epidemiologically important reservoirs for foodborne pathogens.