Immunological serotype interactions and their effect on the epidemiological pattern of dengue.

Long-term epidemiological data reveal multi-annual fluctuations in the incidence of dengue fever and dengue haemorrhagic fever, as well as complex cyclical behaviour in the dynamics of the four serotypes of the dengue virus. It has previously been proposed that these patterns are due to the phenomenon of the so-called antibody-dependent enhancement (ADE) among dengue serotypes, whereby viral replication is increased during secondary infection with a heterologous serotype; however, recent studies have implied that this positive reinforcement cannot account for the temporal patterns of dengue and that some form of cross-immunity or external forcing is necessary. Here, we show that ADE alone can produce the observed periodicities and desynchronized oscillations of individual serotypes if its effects are decomposed into its two possible manifestations: enhancement of susceptibility to secondary infections and increased transmissibility from individuals suffering from secondary infections.

Prevalence of Gnathostoma spinigerum infection in wild and cultured swamp eels in Vietnam.

Human infections with Gnathostoma spinigerum frequently occur in southern Vietnam. Previous investigations have implicated infected swamp eels (Monopterus albus) as an important source of infection to humans. Because aquaculture of M.

Quantification of artemisinin in human plasma using liquid chromatography coupled to tandem mass spectrometry.

A liquid chromatographic tandem mass spectroscopy method for the quantification of artemisinin in human heparinised plasma has been developed and validated. The method uses Oasis HLB mu-elution solid phase extraction 96-well plates to facilitate a high throughput of 192 samples a day. Artesunate (internal standard) in a plasma-water solution was added to plasma (50 microL) before solid phase extraction.

Diagnostic accuracy of NS1 ELISA and lateral flow rapid tests for dengue sensitivity, specificity and relationship to viraemia and antibody responses.

Background: Dengue is a public health problem in many countries. Rapid diagnosis of dengue can assist patient triage and management. Detection of the dengue viral protein, NS1, represents a new approach to dengue diagnosis.

Patterns of gene transcript abundance in the blood of children with severe or uncomplicated dengue highlight differences in disease evolution and host response to dengue virus infection.

DNA microarrays and specific reverse-transcription polymerase chain reaction assays were used to reveal transcriptional patterns in the blood of children presenting with dengue shock syndrome (DSS) and well-matched patients with uncomplicated dengue. The transcriptome of patients with acute uncomplicated dengue was characterized by a metabolically demanding "host-defense" profile; transcripts related to oxidative metabolism, interferon signaling, protein ubiquination, apoptosis, and cytokines were prominent. In contrast, the transcriptome of patients with DSS was surprisingly benign, particularly with regard to transcripts derived from apoptotic and type I interferon pathways.

Development and validation of a high-throughput zwitterionic hydrophilic interaction liquid chromatography solid-phase extraction-liquid chromatography-tandem mass spectrometry method for determination of the anti-influenza drug peramivir in plasma.

An assay for the analysis for the quantification of the anti-influenza drug peramivir in human plasma using high-throughput zwitterionic (ZIC) hydrophilic interaction liquid chromatography (HILIC) solid-phase extraction (SPE) in a 96-wellplate format and liquid chromatography coupled to positive tandem mass spectroscopy has been developed and validated. The ZIC-HILIC SPE efficiently removed sources of interference present in the supernatant after protein precipitation of plasma proteins. The main advantage of the ZIC-HILIC SPE sample preparation step was that it allowed load and elution conditions to be optimised to extract only peramivir and minimize co-extraction of lipophilic phospholipids.

Dengue in Vietnamese infants--results of infection-enhancement assays correlate with age-related disease epidemiology, and cellular immune responses correlate with disease severity.

The pathogenesis of severe dengue is not well understood. Maternally derived subneutralizing levels of dengue virus-reactive IgG are postulated to be a critical risk factor for severe dengue during infancy. In this study, we found that, in healthy Vietnamese infants, there was a strong temporal association between the Fc-dependent, dengue virus infection-enhancing activity of neat plasma and the age-related epidemiology of severe dengue.

Preservation of a critical epitope core region is associated with the high degree of flaviviral cross-reactivity exhibited by a dengue-specific CD4+ T cell clone.

Dengue is a member of the Flaviviridae, a large group of related viruses some of which co-circulate in certain regions (e.g. dengue and Yellow fever in South America).

The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis.

The factors that govern the development of tuberculosis disease are incompletely understood. We hypothesized that some strains of Mycobacterium tuberculosis (M. tuberculosis) are more capable of causing disseminated disease than others and may be associated with polymorphisms in host genes responsible for the innate immune response to infection.

Clinical and microbiological features of HIV-associated tuberculous meningitis in Vietnamese adults.

Methods: The aim of this prospective, observational cohort study was to determine the clinical and microbiological features, outcome, and baseline variables predictive of death, in Vietnamese adults with HIV-associated tuberculous meningitis (TBM). 58 patients were admitted to the Hospital for Tropical Diseases in Ho Chi Minh City and underwent routine clinical and laboratory assessments. Treatment was with standard antituberculous therapy and adjunctive dexamethasone; antiretroviral therapy was not routinely available.

A randomized controlled pilot study of artesunate versus triclabendazole for human fascioliasis in central Vietnam.

Human fascioliasis caused by Fasciola hepatica or Fasciola gigantica is an increasing global problem. The mainstay of current treatment is triclabendazole, but resistance in animals has been described, and it is not available in many countries. The antimalarial artesunate has an excellent safety profile, and there is increasing evidence of its efficacy against other parasites both in vitro and in vivo.

Streptococcus suis meningitis in adults in Vietnam.

Background: Streptococcus suis infection is an emerging zoonosis in Asia. We determined the detailed epidemiological, clinical, and microbiological characteristics of S. suis meningitis in adults.

Relationship between Mycobacterium tuberculosis genotype and the clinical phenotype of pulmonary and meningeal tuberculosis.

We used large sequence polymorphisms to determine the genotypes of 397 isolates of Mycobacterium tuberculosis from human immunodeficiency virus-uninfected Vietnamese adults with pulmonary (n = 235) or meningeal (n = 162) tuberculosis. We compared the pretreatment radiographic appearances of pulmonary tuberculosis and the presentation, response to treatment, and outcome of tuberculous meningitis between the genotypes. Multivariate analysis identified variables independently associated with genotype and outcome.

Human case of Streptococcus suis serotype 16 infection.

Streptococcus suis infection is an emerging zoonosis in Southeast Asia. We report a fatal case of S. suis serotype 16 infection in a Vietnamese man in 2001.

Specimens and culture media for the laboratory diagnosis of typhoid fever.

Background: Culture of S. Typhi is necessary for the definitive diagnosis of typhoid fever and provides isolates for antibiotic susceptibility testing and epidemiological studies. However, current methods are not fully optimised and sourcing culture media and bottles for culture media may be problematic.

Antibodies to the Vi capsule of Salmonella Typhi in the serum of typhoid patients and healthy control subjects from a typhoid endemic region.

Background: There is very little published data on the antibody response to the Vi capsular polysaccharide (Vi-CPS) of S. Typhi during naturally acquired typhoid fever in an endemic area.

Methodology: An indirect ELISA, using tyraminated, purified Vi-CPS, was used to assay anti-Vi-CPS antibodies from typhoid fever cases and controls living in the Ho Chi Minh City and Mekong Delta region of Viet Nam.

High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic T-cells during the course of secondary dengue virus infection.

Background: Dengue is one of the most important human diseases transmitted by an arthropod vector and the incidence of dengue virus infection has been increasing - over half the world's population now live in areas at risk of infection. Most infections are asymptomatic, but a subset of patients experience a potentially fatal shock syndrome characterised by plasma leakage. Severe forms of dengue are epidemiologically associated with repeated infection by more than one of the four dengue virus serotypes.

Antimicrobial drug resistance of Salmonella enterica serovar typhi in asia and molecular mechanism of reduced susceptibility to the fluoroquinolones.

This study describes the pattern and extent of drug resistance in 1,774 strains of Salmonella enterica serovar Typhi isolated across Asia between 1993 and 2005 and characterizes the molecular mechanisms underlying the reduced susceptibilities to fluoroquinolones of these strains. For 1,393 serovar Typhi strains collected in southern Vietnam, the proportion of multidrug resistance has remained high since 1993 (50% in 2004) and there was a dramatic increase in nalidixic acid resistance between 1993 (4%) and 2005 (97%). In a cross-sectional sample of 381 serovar Typhi strains from 8 Asian countries, Bangladesh, China, India, Indonesia, Laos, Nepal, Pakistan, and central Vietnam, collected in 2002 to 2004, various rates of multidrug resistance (16 to 37%) and nalidixic acid resistance (5 to 51%) were found.

A quantitative ultrastructural study of renal pathology in fatal Plasmodium falciparum malaria.

Objective: To use electron microscopy to examine the role of parasitized red blood cell (PRBC) sequestration in the pathogenesis of acute renal failure in severe falciparum malaria.

Methods: Ultrastructural pathological examination of renal tissues from Southeast Asian adults (n = 63) who died from severe falciparum malaria. Qualitative and quantitative determination of the major pathological features of disease, including PRBC and leukocyte sequestration.

Genetic analysis of the dihydrofolate reductase-thymidylate synthase gene from geographically diverse isolates of Plasmodium malariae.

Plasmodium malariae, the parasite responsible for quartan malaria, is transmitted in most areas of malaria endemicity and is associated with significant morbidity. The sequence of the gene coding for the enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) was obtained from field isolates of P. malariae and from the closely related simian parasite Plasmodium brasilianum.

Maternal antibody and viral factors in the pathogenesis of dengue virus in infants.

The pathogenesis of dengue in infants is poorly understood. We postulated that dengue severity in infants would be positively associated with markers of viral burden and that maternally derived, neutralizing anti-dengue antibody would have decayed before the age at which infants with dengue presented to the hospital. In 75 Vietnamese infants with primary dengue, we found significant heterogeneity in viremia and NS1 antigenemia at hospital presentation, and these factors were independent of disease grade or continuous measures of disease severity.

A common human TLR1 polymorphism regulates the innate immune response to lipopeptides.

Toll-like receptors (TLR) are critical mediators of the immune response to pathogens and human polymorphisms in this gene family regulate inflammatory pathways and are associated with susceptibility to infection. Lipopeptides are present in a wide variety of microbes and stimulate immune responses through TLR1/2 or TLR2/6 heterodimers. It is not currently known whether polymorphisms in TLR1 regulate the innate immune response.

A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis.

Tuberculous meningitis (TBM) results from the haematogenous dissemination of Mycobacterium tuberculosis from the lung to the brain. Dissemination is believed to occur early during infection, before the development of adaptive immunity. Toll-like receptor 2 (TLR2) mediates recognition of M.

Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza.

Background: New prophylactic and therapeutic strategies to combat human infections with highly pathogenic avian influenza (HPAI) H5N1 viruses are needed. We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs) and tested their efficacy for prophylaxis and therapy in a murine model of infection.

Methods And Findings: Using Epstein-Barr virus we immortalized memory B cells from Vietnamese adults who had recovered from infections with HPAI H5N1 viruses.

Transparent development of the WHO rapid advice guidelines.

Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies.