BackgroundInfectious diseases of the central nervous system (CNS) remain common and life-threatening, especially in developing countries. Knowledge of the aetiological agents responsible for these infections is essential to guide empiric therapy and develop a rational public health policy. To date most data has come from patients admitted to tertiary referral hospitals in Asia and there is limited aetiological data at the provincial hospital level where most patients are seen.MethodsWe conducted a prospective Provincial Hospital-based descriptive surveillance study in adults and children at thirteen hospitals in central and southern Viet Nam between August 2007– April 2010. The pathogens of CNS infection were confirmed in CSF and blood samples by using classical microbiology, molecular diagnostics and serology.ResultsWe recruited 1241 patients with clinically suspected infection of the CNS. An aetiological agent was identified in 640/1241 (52%) of the patients. The most common pathogens were Streptococcus suis serotype 2 in patients older than 14 years of age (147/617, 24%) and Japanese encephalitis virus in patients less than 14 years old (142/624, 23%). Mycobacterium tuberculosis was confirmed in 34/617 (6%) adult patients and 11/624 (2%) paediatric patients. The acute case fatality rate (CFR) during hospital admission was 73/617 (12%) in adults and to 42/624 (7%) in children.ConclusionsZoonotic bacterial and viral pathogens are the most common causes of CNS infection in adults and children in Viet Nam.

BackgroundThe increasing frequency and intensity of dengue outbreaks in endemic and non-endemic countries requires a rational, evidence based response. To this end, we aimed to collate the experiences of a number of affected countries, identify strengths and limitations in dengue surveillance, outbreak preparedness, detection and response and contribute towards the development of a model contingency plan adaptable to country needs.MethodsThe study was undertaken in five Latin American (Brazil, Colombia, Dominican Republic, Mexico, Peru) and five in Asian countries (Indonesia, Malaysia, Maldives, Sri Lanka, Vietnam). A mixed-methods approach was used which included document analysis, key informant interviews, focus-group discussions, secondary data analysis and consensus building by an international dengue expert meeting organised by the World Health Organization, Special Program for Research and Training in Tropical Diseases (WHO-TDR).ResultsCountry information on dengue is based on compulsory notification and reporting (“passive surveillance”), with laboratory confirmation (in all participating Latin American countries and some Asian countries) or by using a clinical syndromic definition. Seven countries additionally had sentinel sites with active dengue reporting, some also had virological surveillance. Six had agreed a formal definition of a dengue outbreak separate to seasonal variation in case numbers. Countries collected data on a range of warning signs that may identify outbreaks early, but none had developed a systematic approach to identifying and responding to the early stages of an outbreak. Outbreak response plans varied in quality, particularly regarding the early response. The surge capacity of hospitals with recent dengue outbreaks varied; those that could mobilise additional staff, beds, laboratory support and resources coped best in comparison to those improvising a coping strategy during the outbreak. Hospital outbreak management plans were present in 9/22 participating hospitals in Latin-America and 8/20 participating hospitals in Asia.ConclusionsConsiderable variation between countries was observed with regard to surveillance, outbreak detection, and response. Through discussion at the expert meeting, suggestions were made for the development of a more standardised approach in the form of a model contingency plan, with agreed outbreak definitions and country-specific risk assessment schemes to initiate early response activities according to the outbreak phase. This would also allow greater cross-country sharing of ideas.

BackgroundAs dengue spreads to new geographical regions and the force of infection changes in existing endemic areas, a greater breadth of clinical presentations is being recognised. Clinical experience suggests that adults manifest a pattern of complications different from those observed in children, but few reports have described the age-related spectrum of disease in contemporaneous groups of patients recruited at the same geographical location.Methodology/Principal FindingsUsing detailed prospectively collected information from ongoing studies that encompass the full spectrum of hospitalised dengue cases admitted to a single hospital in southern Vietnam, we compared clinical and laboratory features, management, and outcome for 647 adults and 881 children with confirmed dengue. Signs of vascular leakage and shock were more frequent and more severe in children than adults, while bleeding manifestations and organ involvement were more common in adults. Additionally, adults experienced significantly more severe thrombocytopenia. Secondary infection but not serotype was independently associated with greater thrombocytopenia, although with a smaller effect than age-group. The effect of age-group on platelet count was also apparent in the values obtained several weeks after recovery, indicating that healthy adults have intrinsically lower counts compared to children.Conclusions/SignificanceThere are clear distinctions between adults and children in the pattern of complications seen in association with dengue infection, and these depend partly on intrinsic age-dependent physiological differences. Knowledge of such differences is important to inform research on disease pathogenesis, as well as to encourage development of management guidelines that are appropriate to the age-groups at risk.

Azithromycin is an effective treatment for uncomplicated infections with Salmonella enterica serovar Typhi and serovar Paratyphi A (enteric fever), but there are no clinically validated MIC and disk zone size interpretative guidelines. We studied individual patient data from three randomized controlled trials (RCTs) of antimicrobial treatment in enteric fever in Vietnam, with azithromycin used in one treatment arm, to determine the relationship between azithromycin treatment response and the azithromycin MIC of the infecting isolate. We additionally compared the azithromycin MIC and the disk susceptibility zone sizes of 1,640 S. Typhi and S. Paratyphi A clinical isolates collected from seven Asian countries. In the RCTs, 214 patients who were treated with azithromycin at a dose of 10 to 20 mg/ml for 5 to 7 days were analyzed. Treatment was successful in 195 of 214 (91%) patients, with no significant difference in response (cure rate, fever clearance time) with MICs ranging from 4 to 16 μg/ml. The proportion of Asian enteric fever isolates with an MIC of ≤16 μg/ml was 1,452/1,460 (99.5%; 95% confidence interval [CI], 98.9 to 99.7) for S. Typhi and 207/240 (86.3%; 95% CI, 81.2 to 90.3) (P < 0.001) for S. Paratyphi A. A zone size of ≥13 mm to a 5-μg azithromycin disk identified S. Typhi isolates with an MIC of ≤16 μg/ml with a sensitivity of 99.7%. An azithromycin MIC of ≤16 μg/ml or disk inhibition zone size of ≥13 mm enabled the detection of susceptible S. Typhi isolates that respond to azithromycin treatment. Further work is needed to define the response to treatment in S. Typhi isolates with an azithromycin MIC of >16 μg/ml and to determine MIC and disk breakpoints for S. Paratyphi A.