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Objective: To describe an approach using principles of experience-based codesign (EBCD) and quality improvement (QI) to integrate family experience into the development of a pediatric weight management program. Methods: Clinic development occurred in 3 plan, do, study, act (PDSA) cycles that were driven by family experience data. During these cycles, families were engaged in feedback sessions that informed program development. Staff reflected on feedback and designed and tested changes that would improve service delivery. Results: The first PDSA cycle resulted in the fundamental program parameters and a formalized patient engagement strategy. The second cycle focused on pilot programming, and feedback was used to develop the structured group program. During the third cycle, feedback sessions were embedded into the structured group programs. Program changes included focusing on health rather than weight-based outcomes, adjusting the timing of program offerings, increasing experiential learning opportunities, and providing more opportunities for peer support. Conclusions: Both EBCD and QI methodologies informed the process of family engagement and program development. This pragmatic approach might be useful for the development of other family-centered pediatric programs.

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., Competing Interests: NV, NQ, NT, KD, HD, PL, DT, TV, CS, RG No competing interests declared, TJ reports receiving personal fees as members of the Roche Pharmaceuticals Advisory Board on Severe Dengue, outside the submitted work, SY reports receiving personal honorarium for attending the Novartis dengue drug ad board meeting and Takeda dengue education symposium, outside the submitted work, BW reports receiving personal fees (a) as a member of the Roche Advisory Board on Severe Dengue and (b) as a member of the Data Monitoring and Adjudication Committees for the Takeda dengue vaccine trials, both outside the remit of the submitted work, (© 2024, Vuong et al.)

Background: Improvements in the early diagnosis of dengue are urgently needed, especially in resource-limited settings where the distinction between dengue and other febrile illnesses is crucial for patient management., Methods: In this prospective, observational study (IDAMS), we included patients aged 5 years and older with undifferentiated fever at presentation from 26 outpatient facilities in eight countries (Bangladesh, Brazil, Cambodia, El Salvador, Indonesia, Malaysia, Venezuela, and Viet Nam). We used multivariable logistic regression to investigate the association between clinical symptoms and laboratory tests with dengue versus other febrile illnesses between day 2 and day 5 after onset of fever (ie, illness days). We built a set of candidate regression models including clinical and laboratory variables to reflect the need of a comprehensive versus parsimonious approach. We assessed performance of these models via standard measures of diagnostic values., Findings: Between Oct 18, 2011, and Aug 4, 2016, we recruited 7428 patients, of whom 2694 (36%) were diagnosed with laboratory-confirmed dengue and 2495 (34%) with (non-dengue) other febrile illnesses and met inclusion criteria, and were included in the analysis. 2703 (52%) of 5189 included patients were younger than 15 years, 2486 (48%) were aged 15 years or older, 2179 (42%) were female and 3010 (58%) were male. Platelet count, white blood cell count, and the change in these variables from the previous day of illness had a strong association with dengue. Cough and rhinitis had strong associations with other febrile illnesses, whereas bleeding, anorexia, and skin flush were generally associated with dengue. Model performance increased between day 2 and 5 of illness. The comprehensive model (18 clinical and laboratory predictors) had sensitivities of 0·80 to 0·87 and specificities of 0·80 to 0·91, whereas the parsimonious model (eight clinical and laboratory predictors) had sensitivities of 0·80 to 0·88 and specificities of 0·81 to 0·89. A model that includes laboratory markers that are easy to measure (eg, platelet count or white blood cell count) outperformed the models based on clinical variables only., Interpretation: Our results confirm the important role of platelet and white blood cell counts in diagnosing dengue, and the importance of serial measurements over subsequent days. We successfully quantified the performance of clinical and laboratory markers covering the early period of dengue. Resulting algorithms performed better than published schemes for distinction of dengue from other febrile illnesses, and take into account the dynamic changes over time. Our results provide crucial information needed for the update of guidelines, including the Integrated Management of Childhood Illness handbook., Funding: EU's Seventh Framework Programme., Translations: For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests TJ reports personal fees from the Roche Severe Dengue Advisory Board, Takeda Pharmaceutical Company, Merck Pharmaceuticals, and Emergent Biosolutions, as a member of advisory boards, outside the submitted work. BAW reports personal fees from Takeda Pharmaceutical Company and from the Roche Severe Dengue Advisory Board, outside the submitted work. SY reports personal fees from Roche, outside the submitted work. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Dengue shock syndrome (DSS) is one of the major clinical phenotypes of severe dengue. It is defined by significant plasma leak, leading to intravascular volume depletion and eventually cardiovascular collapse. The compensatory reserve Index (CRI) is a new physiological parameter, derived from feature analysis of the pulse arterial waveform that tracks real-time changes in central volume. We investigated the utility of CRI to predict recurrent shock in severe dengue patients admitted to the ICU., Methods: We performed a prospective observational study in the pediatric and adult intensive care units at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. Patients were monitored with hourly clinical parameters and vital signs, in addition to continuous recording of the arterial waveform using pulse oximetry. The waveform data was wirelessly transmitted to a laptop where it was synchronized with the patient's clinical data., Results: One hundred three patients with suspected severe dengue were recruited to this study. Sixty-three patients had the minimum required dataset for analysis. Median age was 11 years (IQR 8-14 years). CRI had a negative correlation with heart rate and moderate negative association with blood pressure. CRI was found to predict recurrent shock within 12 h of being measured (OR 2.24, 95% CI 1.54-3.26), P < 0.001). The median duration from CRI measurement to the first recurrent shock was 5.4 h (IQR 2.9-6.8). A CRI cutoff of 0.4 provided the best combination of sensitivity and specificity for predicting recurrent shock (0.66 [95% CI 0.47-0.85] and 0.86 [95% CI 0.80-0.92] respectively)., Conclusion: CRI is a useful non-invasive method for monitoring intravascular volume status in patients with severe dengue., (© 2022. The Author(s).)

Background: Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of 10 biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD)., Methods: We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included., Results: On days 1-3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults., Conclusions: Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients., Funding: This study was supported by the EU's Seventh Framework Programme (FP7-281803 IDAMS), the WHO, and the Bill and Melinda Gates Foundation., Competing Interests: NV, PL, HD, NN, DT, KD, NC, NC, EP, CS, KR, DB, NA, CH, PO No competing interests declared, DM reports receiving personal fees from the Wellcome Trust (grant number 215010/Z/18/Z), during the conduct of the study. LL reports receiving personal fees from ROCHE Advisory Board on Severe Dengue. TJ reports receiving personal fees as members of the ROCHE Advisory Board on Severe Dengue, outside the submitted work. BW reports personal fees as a member of the Data Monitoring and Adjudication Committees for the Takeda dengue vaccine trials and as a member of the ROCHE Advisory Board on Severe Dengue, outside the submitted work. RG reports receiving personal fees from the Wellcome Trust (grant number 106680/Z/14/Z), during the conduct of the study. SY reports receiving personal fees as a member of the ROCHE Advisory Board on Severe Dengue, for work on Janssen Pharmaceuticals Advisory Board for Dengue Antiviral Development, and from the Wellcome Trust (grant number 106680/Z/14/Z)., (© 2021, Vuong et al.)

Background: In recent years, researchers have had an increased focus on multiplex microarray assays, in which antibodies are measured against multiple related antigens, for use in seroepidemiological studies to infer past transmission., Methods: We assess the performance of a flavivirus microarray assay for determining past dengue virus (DENV) infection history in a dengue-endemic setting, Vietnam. We tested the microarray on samples from 1 and 6 months postinfection from DENV-infected patients (infecting serotype was determined using reverse-transcription polymerase chain reaction during acute, past primary, and secondary infection assessed using plaque reduction neutralization tests 6 months postinfection)., Results: Binomial models developed to discriminate past primary from secondary infection using the protein microarray (PMA) titers had high area under the curve (0.90-0.97) and accuracy (0.84-0.86). Multinomial models developed to identify most recent past infecting serotype using PMA titers performed well in those with past primary infection (average test set: κ = 0.85, accuracy of 0.92) but not those with past secondary infection (κ = 0.24, accuracy of 0.45)., Conclusions: Our results suggest that the microarray will be useful in seroepidemiological studies aimed at classifying the past infection history of individuals (past primary vs secondary and serotype of past primary infections) and thus inferring past transmission intensity of DENV in dengue-endemic settings. Future work to validate these models should be undertaken in different transmission settings and with samples later after infection., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

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., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

The ability to preserve microbial communities in faecal samples is essential as increasing numbers of studies seek to use the gut microbiome to identify biomarkers of disease. Here we use shotgun metagenomics to rigorously evaluate the technical and compositional reproducibility of five room temperature (RT) microbial stabilisation methods compared to the best practice of flash-freezing. These methods included RNALater, OMNIGene-GUT, a dry BBL swab, LifeGuard, and a novel method for preserving faecal samples, a Copan FLOQSwab in an active drying tube (FLOQSwab-ADT). Each method was assessed using six replicate faecal samples from five participants, totalling 180 samples. The FLOQSwab-ADT performed best for both technical and compositional reproducibility, followed by RNAlater and OMNIgene-GUT. LifeGuard and the BBL swab had unpredictable outgrowth of Escherichia species in at least one replicate from each participant. We further evaluated the FLOQSwab-ADT in an additional 239 samples across 10 individuals after storage at -20 °C, RT, and 50 °C for four weeks compared to fresh controls. The FLOQSwab-ADT maintained its performance across all temperatures, indicating this method is an excellent alternative to existing RT stabilisation methods., (© 2021. The Author(s).)

Dengue is the most common mosquito-borne viral infection in the world. The most feared complication is a poorly understood vasculopathy that occurs in only a small minority of symptomatic individuals, especially children and young adults, but can result in potentially fatal dengue shock syndrome (DSS). Based mainly on expert opinion, WHO management guidelines for DSS recommend prompt infusion of a crystalloid fluid bolus followed by a tapering crystalloid fluid regimen, supplemented if necessary by boluses of synthetic colloid solutions. However, following publication of a number of major trials undertaken in other, primarily adult, critical care scenarios, use of both synthetic colloid solutions and of fluid boluses for volume expansion have become controversial. Synthetic colloids tend to be used for severe DSS cases in order to boost intravascular oncotic pressure, based on the classic Starling hypothesis in which opposing hydrostatic and oncotic forces determine fluid flow across the microvascular barrier. However, the revised Starling model emphasizes the critical contribution of the endothelial glycocalyx layer (EGL), indicating that it is the effective oncotic pressure gradient across the EGL not endothelial cells per se that opposes filtration. Based on several novel concepts that are integral to the revised Starling model, we review the clinical features of DSS and discuss a number of implications that are relevant for fluid management. We also highlight the need for context-specific clinical trials that address crucially important questions around the management of DSS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Trung, Trieu and Wills.)

Background: Dengue viruses (DENV) can be transmitted from an adult female Aedes aegypti mosquito through the germ line to the progeny; however, there is uncertainty if this occurs at a frequency that is epidemiologically significant. We measured vertical transmission of DENV from field-reared Ae. aegypti to their F1 progeny after feeding upon blood from dengue patients. We also examined the transmission potential of F1 females., Methods: We examined the frequency of vertical transmission in field-reared mosquitoes, who fed upon blood from acutely viremic dengue patients, and the capacity for vertically infected females to subsequently transmit virus horizontally, in two sets of experiments: (i) compared vertical transmission frequency of field-reared Ae. aegypti and Ae. albopictus, in individual progeny; and (ii) in pooled progeny derived from field- and laboratory-reared Ae. aegypti., Results: Of 41 DENV-infected and isofemaled females who laid eggs, only a single female (2.43%) transmitted virus to one of the F1 progeny, but this F1 female did not have detectable virus in the saliva when 14 days-old. We complemented this initial study by testing for vertical transmission in another 460 field-reared females and > 900 laboratory-reared counterparts but failed to provide any further evidence of vertical virus transmission., Conclusions: In summary, these results using field-reared mosquitoes and viremic blood from dengue cases suggest that vertical transmission is uncommon. Field-based studies that build on these observations are needed to better define the contribution of vertical DENV transmission to dengue epidemiology.

Owing to the finding that Dengvaxia ® (the only licensed dengue vaccine to date) increases the risk of severe illness among seronegative recipients, the World Health Organization has recommended screening individuals for their serostatus prior to vaccination. To decide whether and how to carry out screening, it is necessary to estimate the transmission intensity of dengue and to understand the performance of the screening method. In this study, we inferred the annual force of infection (FOI; a measurement of transmission intensity) of dengue virus in three locations in Vietnam: An Giang (FOI = 0.04 for the below 10 years age group and FOI = 0.20 for the above 10 years age group), Ho Chi Minh City (FOI = 0.12) and Quang Ngai (FOI = 0.05). In addition, we show that using a quantitative approach to immunoglobulin G (IgG) levels (measured by indirect enzyme-linked immunosorbent assays) can help to distinguish individuals with primary exposures (primary seropositive) from those with secondary exposures (secondary seropositive). We found that primary-seropositive individuals-the main targets of the vaccine-tend to have a lower IgG level, and, thus, they have a higher chance of being misclassified as seronegative than secondary-seropositive cases. However, screening performance can be improved by incorporating patient age and transmission intensity into the interpretation of IgG levels.

Dengue has been estimated to cause a substantial health and economic burden in Vietnam. The most recent studies have estimated that it is responsible for 39884 disability-adjusted life years (DALYs) annually, representing an economic burden of US$94.87 million per year (in 2016 prices). However, there are alternative burden estimates that are notably lower. This variation is predominantly due to differences in how the number of symptomatic dengue cases is estimated. Understanding the methodology of these burden calculations is vital when interpreting health economic analyses of dengue. This review aims to provide an overview of the health and economic burden estimates of dengue in Vietnam. We also highlight important research gaps for future studies., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: After new analysis, Sanofi Pasteur now recommends their dengue vaccine (Dengvaxia) should only be given to individuals previously infected with dengue and the World Health Organization's recommendations regarding its use are currently being revised. As a result, the potential costs of performing large-scale individual dengue screening and/or dengue serosurveys have become an important consideration for decision making by policymakers in dengue-endemic areas., Methods: We used an ingredients-based approach to estimate the financial costs for conducting both a school-based dengue serosurvey and school-based individual dengue screening within a typical province in Vietnam, using an existing commercial indirect immunoglobulin G enzyme-linked immunosorbent assay kit. This costing is hypothetical and based on estimates regarding the resources that would be required to perform such activities., Results: We estimated that performing a school-based individual screening of 9-year-olds would cost US$9.25 per child tested or US$197,827 in total for a typical province. We also estimated that a school-based serosurvey would cost US$10,074, assuming one class from each of the grades that include 8- to 11-year-olds are sampled at each of the 12 selected schools across the province., Conclusions: The study indicates that using this vaccine safely on a large-scale will incur noteworthy operational costs. It is crucial that these be considered in future cost-effectiveness analyses informing how and where the vaccine is deployed.

Background: Patients with dengue can experience a variety of serious complications including hypovolemic shock, thrombocytopenia, and bleeding. These problems occur as plasma viremia is resolving and are thought to be immunologically mediated. Early corticosteroid therapy may prevent the development of such complications but could also prolong viral clearance., Methods: We performed a randomized, placebo-controlled, blinded trial of low-dose (0.5 mg/kg) or high-dose (2 mg/kg) oral prednisolone therapy for 3 days in Vietnamese patients aged 5-20 years admitted with dengue and fever for ≤72 hours, aiming to assess potential harms from steroid use during the viremic phase. Intention-to-treat analysis was performed using linear trend tests with a range of clinical and virological endpoints specified in advance. In addition to recognized complications of dengue, we focused on the are under the curve for serial plasma viremia measurements and the number of days after enrollment to negative viremia and dengue nonstructural protein 1 status., Results: Between August 2009 and January 2011, 225 participants were randomized to 1 of the 3 treatment arms. Baseline characteristics were similar across the groups. All patients recovered fully and adverse events were infrequent. Aside from a trend toward hyperglycemia in the steroid recipients, we found no association between treatment allocation and any of the predefined clinical, hematological, or virological endpoints., Conclusions: Use of oral prednisolone during the early acute phase of dengue infection was not associated with prolongation of viremia or other adverse effects. Although not powered to assess efficacy, we found no reduction in the development of shock or other recognized complications of dengue virus infection in this study.

Dengue is mosquito-borne virus infection that annually causes ~50 million clinically apparent cases worldwide. An internally controlled one-step real-time multiplex RT-PCR assay was developed for detection and quantitation of DENV RNA in plasma sample by using specific primers and fluorogenic TaqMan probes. All primers and probes targeted sequences near the 3' end of the NS5 gene. The method comprised two multiplex assays and was validated for sensitivity, specificity, linearity, reproducibility and precision. An internal control template was spiked into each clinical specimen to provide quality assurance for each experimental step. The assay allowed for detection of between 0.5 and 3 infectious particles per mL, is rapid and has been operationally characterized in 287 Vietnamese dengue patients from two therapeutic intervention trials at the Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We describe the magnitude and kinetics of plasma viremia and nonstructural protein 1 (sNS1) levels in sequential samples from 167 children with acute dengue, enrolled early in a community study in Vietnam. All children recovered fully, and only 5 required hospitalization. Among those with dengue virus type 1 (DENV-1), plasma viremia was significantly greater in primary (49) than secondary (44) infections and took longer to resolve. In primary DENV-2 and 3 infections, viremia was significantly lower than among primary DENV-1 infections. Concentrations of sNS1 were significantly higher for DENV-1 than for DENV-2 after adjusting for viremia, with marked differences in the kinetic profiles between primary and secondary infections. Secondary infection and higher viremia were independent predictors of more severe thrombocytopenia, and higher viremia was associated with a small increase in hemoconcentration. Our findings identify clear serotype and immune-status related effects on the dynamics of dengue viremia and sNS1 responses, together with associations with important clinical parameters.

Background: he mechanism underlying the transient vascular leak syndrome of dengue hemorrhagic fever (DHF) is unknown. We aimed to determine whether molecular size and charge selectivity, which help restrict plasma proteins within the intravascular space, are altered in patients with DHF and whether a disturbance of the anionic glycosaminoglycan (GAG) layer on the luminal endothelial surface contributes to disease pathogenesis., Methods: We measured serial plasma levels and fractional clearances of proteins with different size and charge characteristics in 48 children with dengue shock syndrome (DSS) and urinary excretion profiles of heparan sulfate, chondroitin-4-sulfate, and chondroitin-6-sulfate in affected children and healthy control subjects., Results: Compared with convalescent values, acute plasma concentrations of all proteins were reduced, with increased fractional clearances. Smaller proteins were more affected than larger molecules. Albumin, which is normally protected from leakage by its strong negative charge, demonstrated a clearance pattern similar to that of transferrin, a neutral molecule of similar size. Urinary heparan sulfate excretion was significantly increased in children with DSS., Conclusions: The endothelial size-dependent sieving mechanism for plasma proteins is at least partially retained, whereas selective restriction based on negative charge is impaired. The increased heparan sulfate excretion suggests a role for GAGs in the pathogenesis of the vascular leak.

The pathophysiological basis of hemorrhage in dengue infections remains poorly understood, despite the increasing global importance of these infections. A large prospective study of 167 Vietnamese children with dengue shock syndrome documented only minor prolongations of prothrombin and partial thromboplastin times but moderate to severe depression of plasma fibrinogen concentrations. A detailed study of 48 children revealed low plasma concentrations of the anticoagulant proteins C, S, and antithrombin III, which decreased with increasing severity of shock, probably because of capillary leakage. Concurrent increases in the levels of thrombomodulin, tissue factor, and plasminogen activator inhibitor type 1 (PAI-1) indicated increased production of these proteins. Thrombomodulin levels suggestive of endothelial activation correlated with increasing shock severity, whereas PAI-1 levels correlated with bleeding severity. Dengue virus can directly activate plasminogen in vitro. Rather than causing true disseminated intravascular coagulation, dengue infection may activate fibrinolysis primarily, degrading fibrinogen directly and prompting secondary activation of procoagulant homeostatic mechanisms.

From 1992-1998, Burkholderia pseudomallei was isolated from only 9 (0.25%) of 3653 cultures of blood from febrile patients admitted to the Centre for Tropical Diseases in Ho Chi Minh City, an infectious disease referral center for southern Vietnam. Soil was sampled from 407 sites in 147 rice fields along the 5 major roads radiating from Ho Chi Minh City. B. pseudomallei was isolated from 73 sites (18%) in 39 rice fields (27%), but only 15 (21%) of the 71 isolates from 9 (6%) of 147 fields were the virulent l-arabinose (ara)-negative biotype. All except 1 of the fields with the ara-negative biotype were close to the homes of the patients with melioidosis. The low incidence of melioidosis in the provinces around Ho Chi Minh City may be explained by the restricted distribution of ara-negative B. pseudomallei in the soil in this area.

Objective: To investigate the relationship between serum vitamin A levels and conjunctival impression cytology and retinal whitening present in Malawian children with cerebral malaria., Methods: Standard retinal examination and conjunctival impression cytology were performed at hospital admission on 101 consecutively admitted children with cerebral malaria. Blood samples were drawn from 56 children at 24 hours, frozen at -20 degrees C, and transported for assessment of vitamin A levels by high-performance liquid chromatography. Associations among fundus findings and vitamin A measurements were sought., Results: The whitening of the retina that we have previously described in children with cerebral malaria was found to be associated with a mean+/-SD serum vitamin A level of 0.29+/-0.1 micromol/L, compared with a mean vitamin A level of 0.41+/-0.2 micromol/L in children without retinal whitening. Children with retinal whitening were 2.77 (95% CI, 1.06-7.3) times more likely to have abnormal conjunctival impression cytology results than those without whitening. No child had any clinical or ophthalmologic evidence of chronic vitamin A deficiency., Conclusions: The retinal whitening described in children with cerebral malaria is associated with low serum vitamin A levels and with abnormal conjunctival impression cytology results and may be due to acute vitamin A deficiency at the tissue level.

Objectives: To compare artemether (by intramuscular injection) and quinine (by intravenous infusion) as treatments for cerebral malaria in African children., Methods: An open, randomized trial conducted at the Queen Elizabeth Central Hospital in Blantyre, Malawi. This trial was part of a multicentre study designed to determine if treatment with artemether would significantly lower mortality rates compared with quinine. Data from 83 artemether recipients and 81 quinine recipients are reported here., Results: Overall mortality rates and coma resolution times were not significantly different in the two treatment groups. Parasite and fever clearance times were significantly more rapid in the artemether recipients. Analyses which took into account the possible confounding variables did not significantly alter the findings of these unadjusted analyses., Conclusion: These results do not suggest that treatment with artemether would confer a survival advantage in children with life-threatening malaria. The power and precision of the estimated treatment effects of artemether would be enhanced by a meta-analysis of all relevant clinical trials.

The pathogenesis of cerebral malaria is poorly understood. Direct and indirect ophthalmoscope examinations of 141 Malawian children with strictly defined cerebral malaria revealed 2 distinct and prognostically significant findings: papilloedema and extramacular retinal oedema. The relative risk of death in patients with papilloedema was 6.7 times that in patients without papilloedema. Extramacular retinal oedema was associated with a 2.9 fold increase in the relative risk of dying. The mortality rate in patients with neither of these signs was only 1.3% compared to an overall mortality rate of 9.2%. The clinical and laboratory features associated with each of these ophthalmological findings were different, suggesting that there may be at least 2 different pathogenetic processes in patients with cerebral malaria.

Background: Cerebral malaria is a major cause of mortality and morbidity in children in tropical regions. The pathogenesis of this important complication of Plasmodium falciparum infection is not well understood. A number of observers have commented on the presence of retinal pathology in various types of malaria. Previous reports have not demonstrated that fundus findings are significantly associated with outcome., Methods: The authors examined the ocular fundi, by direct and indirect ophthalmoscopy, of 56 children admitted consecutively with cerebral malaria., Results: Every child with a normal fundus on admission recovered fully, but two conditions were found to be associated with a poor outcome. Patients with papilledema had a relative risk of poor outcome 5.2 times greater than those without this finding (P < 0.01). Patients with retinal edema outside the posterior vascular arcades had a relative risk of poor outcome 3.9 times greater than those without this finding (P < 0.01). These two fundus findings were independently predictive of a poor outcome., Conclusion: Fundus findings are useful as predictors of outcome in children with cerebral malaria. The authors' findings suggest that there may be two distinct mechanisms associated with poor outcome in these children.

Artemisinin compounds clear parasitaemia more rapidly than other drugs do in both mild and severe malaria, but no advantage in clinical efficacy has been shown. We have compared artemether treatment with standard quinine treatment in Malawian children with cerebral malaria. 65 unconscious children were randomly allocated to intravenous quinine (n = 37) or intramuscular artemether (n = 28) treatment. The two groups were well matched for various prognostic features. Median parasite clearance times were shorter in the artemether group (28 [interquartile range 18-34] vs 40 [36-44] h in the quinine group, p = 0.0002). Coma resolution times were also shorter with artemether than with quinine (8 [4-15] vs 14 [10-36] h, p = 0.01).