Estimating the burden of fungal disease in Vietnam.

Data regarding the prevalence of fungal infections in Vietnam are limited yet they are likely to occur more frequently as increasingly sophisticated healthcare creates more iatrogenic risk factors. In this study, we sought to estimate baseline incidence and prevalence of selected serious fungal infections for the year 2012. We made estimates with a previously described actuarial method, using reports on the incidence and prevalence of various established risk factors for fungal infections from Vietnam, or similar environments, supplemented by personal communications. Global data were used if local data were unavailable. We estimated 2,352,748 episodes of serious fungal infection occurred in Vietnam in 2012. Frequent conditions included recurrent vaginal candidiasis (3893/100,000 women annually), tinea capitis (457/100,000 annually) and chronic pulmonary aspergillosis (61/100,000/5 year period). We estimated 140 cases of cryptococcal meningitis, 206 of penicilliosis and 608 of Pneumocystis jirovecii pneumonia. This is the first summary of Vietnamese fungal infections. The majority of severe disease is due to Aspergillus species, driven by the high prevalence of pulmonary tuberculosis. The AIDS epidemic highlights opportunistic infections, such as penicilliosis and cryptococcosis, which may complicate immunosuppressive treatments. These estimates provide a useful indication of disease prevalence to inform future research and resource allocation but should be verified by further epidemiological approaches.

A polymorphism in human CD1A is associated with susceptibility to tuberculosis.

CD1 proteins are antigen-presenting molecules that evolved to present lipids rather than peptides to T cells. However, unlike major histocompatibility complex genes, CD1 genes show low rates of polymorphism and have not been clearly associated with human disease. We report that an intronic polymorphism in CD1A (rs411089) is associated with susceptibility to tuberculosis in two cohorts of Vietnamese adults (combined cohort odds ratio 1.78; 95% confidence interval: 1.24-2.57; P=0.001). These data strengthen the hypothesis that CD1A-mediated lipid antigen presentation is important for controlling tuberculosis in humans.

Epiregulin (EREG) variation is associated with susceptibility to tuberculosis.

Although host genetics influences susceptibility to Mycobacterium tuberculosis, the human genes regulating pathogenesis remain largely unknown. We used M. tuberculosis-stimulated macrophage gene expression profiling in conjunction with a case-control genetic association study to discover epiregulin (EREG), as a novel candidate tuberculosis (TB) susceptibility gene. Using a genome-wide association study dataset, we found that among the 21 genes with greater than 50-fold induction, EREG had the most polymorphisms associated with TB. We genotyped haplotype-tagging polymorphisms in discovery (N = 337 cases, N = 380 controls) and validation (N = 332 cases) datasets and an EREG polymorphism (rs7675690) was associated with susceptibility to TB (genotypic comparison; corrected P = 0.00007). rs7675690 was also associated more strongly with infections caused by the Beijing lineage of M. tuberculosis when compared with non-Beijing strains (controls vs Beijing, OR 7.81, P = 8.7 × 10(-5); non-Beijing, OR 3.13, P = 0.074). Furthermore, EREG expression was induced in monocytes and peripheral blood mononuclear cells stimulated with M. tuberculosis as well as TLR4 and TLR2/1/6 ligands. In murine macrophages, EREG expression induced by M. tuberculosis was MYD88- and TLR2-dependent. Together, these data provide the first evidence for an important role for EREG as a susceptibility gene for human TB.

Improving the diagnosis of pulmonary tuberculosis in HIV-infected individuals in Ho Chi Minh City, Viet Nam.

SETTING: District 6, An Hoa Clinic in Ho Chi Minh City (HCMC), Viet Nam. OBJECTIVE: To evaluate the performance of various algorithms in tuberculosis (TB) screening and diagnosis in a human immunodeficiency virus (HIV) infected population in HCMC, Viet Nam. DESIGN: A cross-sectional study of 397 consecutive HIV-infected patients seeking care at the An Hoa Clinic from August 2009 to June 2010. Data on participant demographics, clinical status, chest radiography (CXR) and laboratory results were collected. A multiple logistic regression model was developed to assess the association of covariates and pulmonary TB (PTB). RESULTS: The prevalence of sputum culture-confirmed PTB, acid-fast bacilli (AFB) positive TB, and multidrugresistant TB among the 397 HIV-infected patients was respectively 7%, 2%, and 0.3%. Adjusted odds ratios for low CD4+ cell count, positive sputum smear, and CXR to positive sputum culture were respectively 3.17, 32.04 and 4.28. Clinical findings alone had poor sensitivity, but combining CD4+ cell count, AFB sputum smear and CXR had a more accurate diagnostic performance. CONCLUSION: Results suggest that symptom screening had poor clinical performance, and support the routine use of sputum culture to improve the detection of TB disease in HIV-infected individuals in Viet Nam. However, when routine sputum culture is not available, an algorithm combining CD4+ cell count, AFB sputum smear and CXR is recommended for diagnosing PTB.