Opportunistic infections in hospitalized HIV-infected adults in Ho Chi Minh City, Vietnam: a cross-sectional study.

The HIV epidemic is emerging rapidly in Vietnam. We studied the prevalence of opportunistic infections by performing clinical and microbiological investigations in 100 hospitalized HIV-infected adults in Ho Cho Minh City, Vietnam. The median CD4 count was 20 cells/mm(3) and in-hospital mortality was 28%. The most frequent diagnoses were oral candidiasis (54), tuberculosis (37), wasting syndrome (34), lower respiratory tract infection (13), cryptococcosis (9), and penicilliosis (7). Bacterial (other than tuberculosis) and parasitic infections were uncommon. Regional differences should be considered when deciding which diagnostic procedures and prophylactic measures to implement. In Vietnam, routine mycobacterial blood cultures do not provide greater yield than chest radiography and sputum and lymph node aspirate smears. Prophylactic trimethoprim/sulphamethoxazole against Pneumocystis jiroveci pneumonia may confer little benefit, and high rates of isoniazid resistance may affect the efficacy and feasibility of tuberculosis chemoprophylaxis. However, the usefulness of itraconazole prophylaxis for cryptococcosis and penicilliosis merits further consideration

Early T-cell responses to dengue virus epitopes in Vietnamese adults with secondary dengue virus infections.

T-cell responses to dengue viruses may be important in both protective immunity and pathogenesis. This study of 48 Vietnamese adults with secondary dengue virus infections defined the breadth and magnitude of peripheral T-cell responses to 260 overlapping peptide antigens derived from a dengue virus serotype 2 (DV2) isolate. Forty-seven different peptides evoked significant gamma interferon enzyme-linked immunospot (ELISPOT) assay responses in 39 patients; of these, 34 peptides contained potentially novel T-cell epitopes. NS3 and particularly NS3200-324 were important T-cell targets. The breadth and magnitude of ELISPOT responses to DV2 peptides were independent of the infecting dengue virus serotype, suggesting that cross-reactive T cells dominate the acute response during secondary infection. Acute ELISPOT responses were weakly correlated with the extent of hemoconcentration in individual patients but not with the nadir of thrombocytopenia or overall clinical disease grade. NS3556-564 and Env414-422 were identified as novel HLA-A*24 and B*07-restricted CD8+ T-cell epitopes, respectively. Acute T-cell responses to natural variants of Env414-422 and NS3556-564 were largely cross-reactive and peaked during disease convalescence. The results highlight the importance of NS3 and cross-reactive T cells during acute secondary infection but suggest that the overall breadth and magnitude of the T-cell response is not significantly related to clinical disease grade

Seizures and raised intracranial pressure in Vietnamese patients with Japanese encephalitis.

Japanese encephalitis (JE) causes at least 10 000 deaths each year. Death is presumed to result from infection, dysfunction and destruction of neurons. There is no antiviral treatment. Seizures and raised intracranial pressure (ICP) are potentially treatable complications, but their importance in the pathophysiology of JE is unknown. Between 1994 and 1997 we prospectively studied patients with suspected CNS infections referred to an infectious disease referral hospital in Ho Chi Minh City, Vietnam. We diagnosed Japanese encephalitis virus (JEV), using antibody detection, culture of serum and CSF, and immunohistochemistry of autopsy material. We observed patients for seizures and clinical signs of brainstem herniation, measured CSF opening pressures (OP) and, on a subset of patients, performed EEGs. Of 555 patients with suspected CNS infections, 144 (26%) were infected with JEV (134 children and 10 adults). Seventeen (12%) patients died and 33 (23%) had severe sequelae. Of the 40 patients with witnessed seizures, 24 (62%) died or had severe sequelae, compared with 26 (14%) of 104 with no witnessed seizures [odds ratio (OR) 4.50, 95% confidence interval (CI) 1.94-10.52, P < 0.0001]. Patients in status epilepticus (n = 25), including 15 with subtle motor seizures, were more likely to die than those with other seizures (P = 0.003). Patients with seizures were more likely to have an elevated CSF OP (P = 0.033) and to develop brainstem signs compatible with herniation syndromes (P < 0.0001). Of 11 patients with CSF OP > or =25 cm, five (46%) died, compared with seven (9%) of 80 patients with lower pressures [OR 8.69, 95% CI 1.73-45.39, P = 0.005). Of the 50 patients with a poor outcome, 35 (70%) had signs compatible with herniation syndromes (including 19 with signs of rostro-caudal progression), compared with nine (10%) of those with better outcomes (P < 0.0001). Of 11 patients with CSF OP > or =25 cm, five (46%) died, compared with seven (9%) of 80 patients with lower pressures (OR 8.69, 95% CI 1.73-45.39, P = 0.005). The combination of coma, multiple seizures, brainstem signs and illness for 7 or more days was an accurate predictor of outcome, correctly identifying 42 (84%) of 50 patients with a poor outcome and 82 (87%) of 94 with a better outcome. These findings suggest that in JE, seizures and raised ICP may be important causes of death. The outcome may be improved by measures aimed at controlling these secondary complications

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). Immune responses cross-reactive between different dengue serotypes are important in the pathogenesis of dengue disease but it is not known whether previous infection with one flavivirus might affect the clinical course of subsequent infections with other members of the family. CD4+ T cells have been shown to be important in the production of cytokines in response to dengue infection and can demonstrate significant epitope cross-reactivity. Here, we describe the generation and characterisation of CD4+ T cell clones from a patient experiencing acute dengue infection. These clones were DRB1*15+ and recognised epitope variants not only within other dengue viruses but certain other flaviviruses. This cross-reactivity was dependent upon the presence of a five-amino acid core region, consistent with structural observations of class II MHC binding to TCR demonstrating that only a subset of residues within an epitope bound to a class II molecule are "read out" by the TCR. This capacity of CD4+ T cell clones to recognise a given epitope despite considerable variation between viruses may be of pathological significance, particularly in regions where related viruses co-circulate

Patterns of host genome-wide gene transcript abundance in the peripheral blood of patients with acute dengue hemorrhagic fever.

Responses by peripheral blood leukocytes may contribute to the pathogenesis of dengue hemorrhagic fever (DHF). We used DNA microarrays to reveal transcriptional patterns in the blood of 14 adults with DHF. Acute DHF was defined by an abundance of transcripts from cell cycle- and endoplasmic reticulum (ER)-related genes, suggesting a proliferative response accompanied by ER stress. Transcript-abundance levels for immunoresponse-associated genes, including cell surface markers, immunoglobulin, and innate response elements, were also elevated. Twenty-four genes were identified for which transcript abundance distinguished patients with dengue shock syndrome (DSS) from those without DSS. All the gene transcripts associated with DSS, many of which are induced by type I interferons, were less abundant in patients with DSS than in those without DSS. To our knowledge, these data provide the first snapshot of gene-expression patterns in peripheral blood during acute dengue and suggest that DSS is associated with attenuation of selected aspects of the innate host response

An observational study of breakthrough SARS-CoV-2 Delta variant infections among vaccinated healthcare workers in Vietnam

Background Data on breakthrough SARS-CoV-2 Delta variant infections in vaccinated individuals are limited. Methods We studied breakthrough infections among Oxford-AstraZeneca vaccinated healthcare workers in an infectious diseases hospital in Vietnam. We collected demographic and clinical data alongside serial PCR testing, measurement of SARS-CoV-2 antibodies, and viral whole-genome sequencing. Findings Between 11th–25th June 2021 (7-8 weeks after the second dose), 69 staff tested positive for SARS-CoV-2. 62 participated in the study. Most were asymptomatic or mildly symptomatic and all recovered. Twenty-two complete-genome sequences were obtained; all were Delta variant and were phylogenetically distinct from contemporary viruses obtained from the community or from hospital patients admitted prior to the outbreak. Viral loads inferred from Ct values were 251 times higher than in cases infected with the original strain in March/April 2020. Median time from diagnosis to negative PCR was 21 days (range 8–33). Neutralizing antibodies (expressed as percentage of inhibition) measured after the second vaccine dose, or at diagnosis, were lower in cases than in uninfected, fully vaccinated controls (median (IQR): 69.4 (50.7-89.1) vs. 91.3 (79.6-94.9), p=0.005 and 59.4 (32.5-73.1) vs. 91.1 (77.3-94.2), p=0.043). There was no correlation between vaccine-induced neutralizing antibody levels and peak viral loads or the development of symptoms. Interpretation Breakthrough Delta variant infections following Oxford-AstraZeneca vaccination may cause asymptomatic or mild disease, but are associated with high viral loads, prolonged PCR positivity and low levels of vaccine-induced neutralizing antibodies. Epidemiological and sequence data suggested ongoing transmission had occurred between fully vaccinated individuals