Introduction: Despite sharing common psychosocial and developmental experiences, adolescents living with perinatally and behaviourally acquired HIV‐1 infection are different in terms of timing of HIV ...infection and developmental stage at infection. Therefore, it is of interest to identify similarities and differences between these two groups of adolescents living with HIV in their experiences, facilitators and barriers during the transition process.
Methods: A detailed literature search of peer‐reviewed published papers was conducted on PubMed to identify relevant original research or viewpoints published up to September 2016. Conference s and other unpublished data sources were not included.
Results: Existing published literature, mainly using qualitative methods, explores the transition from paediatric to adult healthcare provision, as experienced by these two groups of young people. Reports highlight the variation and similarities in their experiences and challenges of transition. Findings from the USA and Europe predominate, while experience from Africa and Asia is lacking, despite the importance of these regions in the global epidemic.
Conclusions: Published transition data remain limited, and there are few studies focusing on behaviourally infected adolescents and key population groups (e.g. adolescents who use drugs, lesbian/gay/transgender individuals). Robust definitions of the transition process and standardized outcome measures are required to facilitate cross‐study and geographic comparisons.
Background. Dengue is the most common arboviral infection of humans. There are currently no specific treatments for dengue. Balapiravir is a prodrug of a nucleoside analogue (called R1479) and an ...inhibitor of hepatitis C virus replication in vivo. Methods. We conducted in vitro experiments to determine the potency of balapiravir against dengue viruses and then an exploratory, dose-escalating, randomized placebo-controlled trial in adult male patients with dengue with <48 hours of fever. Results. The clinical and laboratory adverse event profile in patients receiving balapiravir at doses of 1500 mg (n = 10) or 3000 mg (n = 22) orally for 5 days was similar to that of patients receiving placebo (n = 32), indicating balapiravir was well tolerated. However, twice daily assessment of viremia and daily assessment of NS1 antigenemia indicated balapiravir did not measurably alter the kinetics of these virological markers, nor did it reduce the fever clearance time. The kinetics of plasma cytokine concentrations and the whole blood transcriptional profile were also not attenuated by balapiravir treatment. Conclusions. Although this trial, the first of its kind in dengue, does not support balapiravir as a candidate drug, it does establish a framework for antiviral treatment trials in dengue and provides the field with a clinically evaluated benchmark molecule. Clinical Trials Registration. NCT01096576.
Water pollution within and nearby different livestock farm types was assessed comprehensively for the first time in Vietnam. The samples of wastewater, ground water, and surface water were collected ...from 130 pig farms, 80 poultry farms, and 40 cow farms. Water quality was first assessed by individual parameter evaluation method in which measured values of water quality parameters were compared with the permissible limits in the national technical regulations on livestock’s effluent (QCVN 62), surface water quality, and ground water quality. Subsequently, the overall quality of surface and ground water samples was evaluated by mean of water quality index (WQI). The results showed the large variations in effluent’s quality, implying the considerable differences in wastewater treatment efficiency within and among farm types. Effluent from livestock farms was highly polluted by organic matters (expressed as BOD
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and COD) and especially by microorganisms (expressed as total coliform—CF). Almost all wastewater samples contained higher number of CF than QCVN 62 (3900 MPN/100ml), with mean concentration of CF in effluent from cow farms, pig farms, and poultry farms were 1.2e+07 ± 5.0e+07 MPN/100ml, 8.8e+04 ± 7.1e+04 MPN/100ml, 1.5e+06 ± 4.2e+06 MPN/100ml, respectively. Improperly treated livestock’s waste was likely to have impacts on quality of ground water and receiving surface water bodies. High CF contamination in effluent leads to 70% of the ground water samples in cow farms and poultry farms classified as unsuitable for drinking water supply by WQI values. Although effluent from poultry farms had smaller quantity and better quality, their receiving surface water bodies exhibited the worst quality, with average WQI of 37.5 ± 16.2 compared to 49.9 ± 12 of pig farms and 50.3 ± 20.8 of cow farms. This result suggests that livestock’s effluent was not only pollution source of surface water bodies nearby livestock farms.
Abstract
Background
One of the generally accepted constructs of dengue pathogenesis is that clinical disease severity is at least partially dependent upon plasma viremia, yet data on plasma viremia ...in primary versus secondary infections and in relation to clinically relevant endpoints remain limited and contradictory.
Methods
Using a large database comprising detailed clinical and laboratory characterization of Vietnamese participants enrolled in a series of research studies executed over a 15-year period, we explored relationships between plasma viremia measured by reverse transcription–polymerase chain reaction and 3 clinically relevant endpoints—severe dengue, plasma leakage, and hospitalization—in the dengue-confirmed cases. All 4 dengue serotypes and both primary and secondary infections were well represented. In our logistic regression models we allowed for a nonlinear effect of viremia and for associations between viremia and outcome to differ by age, serotype, host immune status, and illness day at study enrollment.
Results
Among 5642 dengue-confirmed cases we identified 259 (4.6%) severe dengue cases, 701 (12.4%) patients with plasma leakage, and 1441 of 4008 (40.0%) patients recruited in outpatient settings who were subsequently hospitalized. From the early febrile phase onwards, higher viremia increased the risk of developing all 3 endpoints, but effect sizes were modest (ORs ranging from 1.12–1.27 per 1-log increase) compared with the effects of a secondary immune response (ORs, 1.67–7.76). The associations were consistent across age, serotype, and immune status groups, and in the various sensitivity and subgroup analyses we undertook.
Conclusions
Higher plasma viremia is associated with increased dengue severity, regardless of serotype or immune status.
From the early febrile phase onwards, higher plasma viremia increases the risk of subsequent progression to adverse dengue outcomes, with little evidence for effect modification by potential confounders. However, the effect sizes are modest compared with a secondary immune response.
Dengue infection can cause a wide spectrum of clinical outcomes. The severe clinical manifestations occur sufficiently late in the disease course, during day 4-6 of illness, to allow a window of ...opportunity for risk stratification. Markers of inflammation may be useful biomarkers. We investigated the value of C-reactive protein (CRP) measured early on illness days 1-3 to predict dengue disease outcome and the difference in CRP levels between dengue and other febrile illnesses (OFI).
We performed a nested case-control study using the clinical data and samples collected from the IDAMS-consortium multi-country study. This was a prospective multi-center observational study that enrolled almost 8000 participants presenting with a dengue-like illness to outpatient facilities in 8 countries across Asia and Latin America. Predefined severity definitions of severe and intermediate dengue were used as the primary outcomes. A total of 281 cases with severe/intermediate dengue were compared to 836 uncomplicated dengue patients as controls (ratio 1:3), and also 394 patients with OFI.
In patients with confirmed dengue, median (interquartile range) of CRP level within the first 3 days was 30.2 mg/L (12.4-61.2 mg/L) (uncomplicated dengue, 28.6 (10.5-58.9); severe or intermediate dengue, 34.0 (17.4-71.8)). Higher CRP levels in the first 3 days of illness were associated with a higher risk of severe or intermediate outcome (OR 1.17, 95% CI 1.07-1.29), especially in children. Higher CRP levels, exceeding 30 mg/L, also associated with hospitalization (OR 1.37, 95% CI 1.14-1.64) and longer fever clearance time (HR 0.84, 95% CI 0.76-0.93), especially in adults. CRP levels in patients with dengue were higher than patients with potential viral infection but lower than patients with potential bacterial infection, resulting in a quadratic association between dengue diagnosis and CRP, with levels of approximately 30 mg/L associated with the highest risk of having dengue. CRP had a positive correlation with total white cell count and neutrophils and negative correlation with lymphocytes, but did not correlate with liver transaminases, albumin, or platelet nadir.
In summary, CRP measured in the first 3 days of illness could be a useful biomarker for early dengue risk prediction and may assist differentiating dengue from other febrile illnesses.
Background. Dengue shock syndrome (DSS) is a severe manifestation of dengue virus infection that particularly affects children and young adults. Despite its increasing global importance, there are no ...prospective studies describing the clinical characteristics, management, or outcomes of DSS. Methods. We describe the findings at onset of shock and the clinical evolution until discharge or death, from a comprehensive prospective dataset of 1719 Vietnamese children with laboratory-confirmed DSS managed on a single intensive care unit between 1999 and 2009. Results. The median age of patients was 10 years. Most cases had secondary immune responses, with only 6 clear primary infections, and all 4 dengue virus serotypes were represented during the 10-year study. Shock occurred commonly between days 4 and 6 of illness. Clinical signs and symptoms were generally consistent with empirical descriptions of DSS, although at presentation 153 (9%) were still febrile and almost one-third had no bleeding. Overall, 31 (2%) patients developed severe bleeding, primarily from the gastrointestinal tract, 26 of whom required blood transfusion. Only 8 patients died, although 123 of 1719 (7%) patients had unrecordable blood pressure at presentation and 417 of the remaining 1596 (26%) were hypotensive for age. The majority recovered well with standard crystalloid resuscitation or following a single colloid infusion. All cases were classified as severe dengue, while only 70% eventually fulfilled all 4 criteria for the 1997 World Health Organization classification of dengue hemorrhagic fever. Conclusions. With prompt intervention and assiduous clinical care by experienced staff, the outcome of this potentially fatal condition can be excellent.
We assessed predominantly pediatric patients in Vietnam with dengue and other febrile illness 3 months after acute illness. Among dengue patients, 47% reported >1 postacute symptom. Most resolved by ...3 months, but alopecia and vision problems often persisted. Our findings provide additional evidence on postacute dengue burden and confirm children are affected.
Background: Viremia is a critical factor in understanding the pathogenesis of dengue infection, but limited data exist on viremia kinetics. This study aimed to investigate the kinetics of viremia and ...its effects on subsequent platelet count, severe dengue, and plasma leakage. Methods: We pooled data from three studies conducted in Vietnam between 2000 and 2016, involving 2340 dengue patients with daily viremia measurements and platelet counts after symptom onset. Viremia kinetics were assessed using a random effects model that accounted for left-censored data. The effects of viremia on subsequent platelet count and clinical outcomes were examined using a landmark approach with a random effects model and logistic regression model with generalized estimating equations, respectively. The rate of viremia decline was derived from the model of viremia kinetics. Its effect on the clinical outcomes was assessed by logistic regression models. Results: Viremia levels rapidly decreased following symptom onset, with variations observed depending on the infecting serotype. DENV-1 exhibited the highest mean viremia levels during the first 5–6 days, while DENV-4 demonstrated the shortest clearance time. Higher viremia levels were associated with decreased subsequent platelet counts from day 6 onwards. Elevated viremia levels on each illness day increased the risk of developing severe dengue and plasma leakage. However, the effect size decreased with later illness days. A more rapid decline in viremia is associated with a reduced risk of the clinical outcomes. Conclusions: This study provides comprehensive insights into viremia kinetics and its effect on subsequent platelet count and clinical outcomes in dengue patients. Our findings underscore the importance of measuring viremia levels during the early febrile phase for dengue studies and support the use of viremia kinetics as outcome for phase-2 dengue therapeutic trials. Funding: Wellcome Trust and European Union Seventh Framework Programme.
Dengue is the most important mosquito-borne viral infection to affect humans. Although it usually manifests as a self-limited febrile illness, complications may occur as the fever subsides. A ...systemic vascular leak syndrome that sometimes progresses to life-threatening hypovolaemic shock is the most serious complication seen in children, typically accompanied by haemoconcentration and thrombocytopenia. Robust evidence on risk factors, especially features present early in the illness course, for progression to dengue shock syndrome (DSS) is lacking. Moreover, the potential value of incorporating serial haematocrit and platelet measurements in prediction models has never been assessed.
We analyzed data from a prospective observational study of Vietnamese children aged 5-15 years admitted with clinically suspected dengue to the Hospital for Tropical Diseases in Ho Chi Minh City between 2001 and 2009. The analysis population comprised all children with laboratory-confirmed dengue enrolled between days 1-4 of illness. Logistic regression was the main statistical model for all univariate and multivariable analyses. The prognostic value of daily haematocrit levels and platelet counts were assessed using graphs and separate regression models fitted on each day of illness. Among the 2301 children included in the analysis, 143 (6%) progressed to DSS. Significant baseline risk factors for DSS included a history of vomiting, higher temperature, a palpable liver, and a lower platelet count. Prediction models that included serial daily platelet counts demonstrated better ability to discriminate patients who developed DSS from others, than models based on enrolment information only. However inclusion of daily haematocrit values did not improve prediction of DSS.
Daily monitoring of platelet counts is important to help identify patients at high risk of DSS. Development of dynamic prediction models that incorporate signs, symptoms, and daily laboratory measurements, could improve DSS prediction and thereby reduce the burden on health services in endemic areas.
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