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Opportunistic Infections in Hospitalized HIV-Infected Adults in Ho Chi Minh City, Vietnam: a Cross-Sectional Study

Posted on: Thursday, 9 December 2004, 03:00 CST

Summary: 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^sup 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.

Keywords: Vietnam, HIV, tuberculosis, Pneumocystis carinii, Pneumocystis jiroveci, cryptococcus, penicillium

Introduction

The HIV pandemic has emerged as a significant problem in Southeast Asia. Descriptions of the natural history of HIV infection in the region have predominantly originated from Thailand, where reports have identified the most common AIDS-defining conditions as wasting syndrome, tuberculosis, cryptococcosis and Pneumocystis jiroveci pneumonia (formerly known as Pneumocystis carinii pneumonia)1,2. Given that studies conducted in Africa led to the recommendation that HIVinfected persons in the region receive prophylaxis with trimethroprim/sulphamethoxazole, knowledge of the common HIV-related opportunistic infections in Vietnam may help dictate the local choice of prophylactic interventions3,4. We conducted a cross-sectional study to determine the prevalence of opportunistic infections in hospitalized HIV-infected adults in Ho Chi Minh City (HCMC), Vietnam and to assess both the usefulness of various diagnostic investigations and the value of currently recommended primary prophylaxis regimens.

Methods

Between July and September 2000, we collected clinical data for 100 HIV-infected adults consecutively admitted to the Hospital for Tropical Diseases (HTD), a 500-bed infectious diseases referral centre for southern Vietnam. Written informed consent was obtained. The study protocol was approved by the Scientific and Ethical Committee of HTD and the Committee on Human Research of the University of California, San Francisco, USA.

Within 48 hours of hospitalization, a detailed history and physical examination were performed. Data on admission clinical features, hospital course and outcome were collected. Laboratory tests and other diagnostic procedures were performed onsite and used to help guide clinical treatment. HIV infection was defined as two positive enzyme immunoassays (AxSYM HIV-1, Abbott Diagnostics, Abbott Park, IL, USA and Vironostika HIV-1, Organon Teknika, Durham, NC, USA). In all participants blood was examined for complete blood count, liver function tests, creatinine, CD4 cell count, three malaria blood smears and cultured for bacteria, fungi and mycobacteria (BACTEC Plus Aerobic/F and MYCO/F-lytic vials, Becton Dickenson Microbiology Systems, Sparks, MD, USA). Additional investigations were performed as clinically indicated, including microscopy and culture of cerebrospinal fluid, stool, urine, lymph node aspirates or skin lesions; sputum or induced sputum for Gram stain, acid-fast bacilli smear and culture and immunoflourescent antibody stain for P. jiroveci (Shield Diagnostics, Dundee, UK); fungal culture of oropharyngeal swabs, chest radiograph, abdominal ultrasound, and head computerized tomography scan. Identification of mycobacterial isolates and susceptibility tests were performed at the UK National Tuberculosis Reference Unit, Dulwich, UK. When possible, serological testing was performed for hepatitis BsAg and antibodies to hepatitis BsAg, hepatitis C and Toxoplasma gondii (AxSYM HbsAg (V2), HCV (V3.0), Abbott Diagnostics, Abbott Park, IL, USA; Toxo IgG EIA II and Toxo IgM EIA recomb, Roche, France).

Table 1. Diagnoses among HIV-infected adults in Ho Chi Minh City, Vietnam (AV= 100)*

The χ^sup 2^ test, or Fisher's exact test, where appropriate, were used to compare categorical variables. Calculations for odds ratios, relative risks, 95% confidence intervals and multivariate analysis using logistic regression were performed using STATA software (Version 6.0, Stata Corporation, College Station, Texas, USA).

Results

Of 100 patients enrolled, the mean age was 30.2 years (range 15- 58 years) and 82% were male. Risk factors for HIV acquisition were injection drug use (55%), sexual transmission (34%) and unknown (11%). The median CD4 count was 20 cells/mm3 (range 1-1051 cells/ mm^sup 3^). Sixty-two percent of patients were newly diagnosed with HIV infection at this hospitalization. At admission, 86 patients reported taking a therapeutic antimicrobial at the time of admission, four patients reported taking antiretroviral therapy (didanosine and stavudine), and four patients reported taking co- trimoxazole prophylaxis. In-hospital mortality was 28%. The principal diagnoses are shown in Table 1.

Mycobacterium tuberculosis was the most common diagnosis (pulmonary: 55% (21/38), extrapulmonary: 21% (8/38), both: 24% (9/ 38)), and was isolated in 50% (17/34) of patients with wasting syndrome. Of the 30 tuberculosis isolates, 10 (33%) demonstrated resistance to isoniazid (8), streptomycin (7), or both (5). All isolates were sensitive to pyrazinamide, rifampicin and ethambutol.

Sputum induction in 14 patients yielded a positive result in 11 (M. tuberculosis (5), P. jiroveci (4), both M. tuberculosis and P. jiroveci (1), Pseudomonas aeruginosa (1)). Thirteen patients were diagnosed with a primary lower respiratory tract infection (LRTI) other than tuberculosis or P. jiroveci pneumonia using clinical criteria and chest radiographic findings; poor quality of collected sputa precluded identification of a causative pathogen in all but the one patient with P. aeruginosa infection.

Blood cultures were performed in 81 patients. Clinically significant isolates included M. tuberculosis (10), Penicillium marneffei (6), Cryptococcus neoformans (5), Staphylococcus aureus (2), Shigella flexneri (1), Serratia marcescens (1), and Mycobacterium aviumintracellulare (1). In the 10 patients with positive blood cultures for M. tuberculosis, the diagnosis in eight had been made by prior examination of sputum, stool or lymph node aspirate smears. In the remaining two patients, neither had undergone thorough investigation of clinically relevant sites prior to the blood cultures becoming positive.

Serology results were available for 76 patients. Seventeen patients (22%) had results consistent with chronic hepatitis B infection, 45 patients (59%) with previous hepatitis B infection, and 43 patients (57%) with hepatitis C infection. Injection drug use was significantly associated with hepatitis C infection (P value <0.05). No patients tested seropositive for T. gondii IgM and five patients (7%) tested seropositive for T. gondii IgG.

Discussion

Ours is the first cross-sectional study characterizing HIV- related opportunistic infections in Vietnam. The results emphasize the variation in the range of opportunistic infections seen in different regions of the world. The most common AIDS-defining diagnoses seen in our study - tuberculosis, wasting syndrome, cryptococcosis and penicilliosis together accounted for nearly 80% of deaths. Furthermore, one-third of patients were diagnosed with multiple infections, which made treatment both difficult, with potential drug interactions and side effects, and expensive. Given the small sample size and the advanced stages of disease recorded, we cannot generalize our findings to the entire HIV-infected population in Vietnam. Nevertheless, some general observations can be made.

Studies from Thailand2 and Africa5-8 have demonstrated that bacteraemia with M. tuberculosis is common in HIV-infected adults, leading to the suggestion that routinely performing mycobacterial blood cultures in febrile HIV-infected patients who present with particular clinical syndromes will aid in more rapid detection of infection7. In contrast, we found that employing routine mycobacterial blood culture as a screen for infection is not necessary; improving the availability of chest radiographs, sputum smears, lymph node aspirates and induced sputum techniques would likely yield the same results but in a more rapid and costeffective manner8. While mycobacterial blood cultures might be useful to survey for unrecognized M. avium complex infection, our results suggest that infection with non-tuberculous mycobacteria occurs infrequently in HIV-infected persons in Vietnam.

Our study is notable for its low frequency of bacterial (other than tuberculosis) and parasitic infections. In contrast, non-typhi salmonellae is a common bacteraemic pathogen in Bangkok2, wh\ile infections due to non-typhi salmonellae and other Gram-negative rods, Streptococcus pneumoniae, T. gondii, Cryptosporidium parvum and Isospora bellii have been frequently identified in Africa5,6,9. HIV-infected patients have been seen at the HTD with invasive disease due to non-typhi salmonellae and S. pneumoniae outside of this study, but the numbers have been small. However, higher rates of bacterial infection (other than tuberculosis), in LRTI for example, may have been concealed by the frequent antibiotic use prior to hospitalization. The low prevalence of toxoplasmosis in Vietnam and Thailand1 may reflect the uncommon habit of having cats as household pets, and that meat is usually well-cooked.

The use of sputum induction enabled the diagnoses of the first cases of P. jiroveci pneumonia in Vietnam. While our findings are consistent with the low, but not insignificant, prevalences reported in Thailand3 and Africa9,10, some studies have used clinical case definitions for P. jiroveci pneumonia without microbiological confirmation, which may overestimate prevalences when compared to our study. Currently, based on studies from Cte d'Ivoire3,4, prophylactic co-trimoxazole is uniformly recommended for all HIV- infected persons in Africa with a CD4 cell count <500 cells/mm311. However, much of the clinical benefit in these studies was attributed to a decline in infections due to non-typhi salmonellae, S. pneumoniae, Isospora and malaria - pathogens unconfirmed in high frequencies in our population. Morbidity attributed to bacterial pneumonia was also decreased in the Cte d'Ivoire studies, and while LRTI was frequently diagnosed in our population, it is relevant to note that 47% of invasive pneumococcal isolates at HTD are co- trimoxazole resistant12. Likewise, the low frequency of toxoplasmosis we found suggests prophylaxis would convey little benefit in our population. Currently co-trimoxazole prophylaxis is recommended for HIV-infected persons in Vietnam with a CD4 count below 500. Our results suggest that its value, other than for preventing P. jiroveci pneumonia, which may occur infrequently, is questionable and requires further study.

As in Thailand, we found high prevalences of cryptococcal and penicillium infections, which were characterized by poor response rates, severe sequelae, and high mortality. In view of studies showing benefit in Thailand13, the feasibility and efficacy of primary itraconazole prophylaxis in HIV-infected persons in Vietnam merits further investigation.

The preponderance of active tuberculosis has significant public health implications. Our high resistance rates to isoniazid and streptomycin are consistent with recent reports detailing the emergence of the Beijing genotype in Vietnam14, which has been strongly associated with drug resistance. While chemoprophylaxis in purified protein derivative (PPD)-positive, HIV-infected persons may reduce development of active tuberculosis15,16, follow-up of completion rates and difficulty in determining whether failure is due to reactivation vs re-infection has made assessment of the efficacy of these regimens difficult. The high background levels of resistance and the logistic difficulties of instituting treatment for latent tuberculosis suggest that studies addressing the feasibility and longterm efficacy are required before routine recommendations can be made for the HIV-infected population in Vietnam.

Acknowledgements: We are indebted to the hospital leaders and the laboratory and clinical staff at the Hospital for Tropical Diseases, Cho Quan Hospital, Ho Chi Minh City, Vietnam for their support and assistance with this study. We thank The Diag Centre, Ho Chi Minh City, Vietnam; Professor Francis Drobieneski and staff of the UK Mycobacterial Reference Unit, Dulwich and Professor Tony Hart, Department of Medical Microbiology, University of Liverpool, UK for help with specific diagnostic tests. We also thank Estie Hudes for advice on statistical analysis and Drs Harry Lampiris, Dennis Osmond, Art Reingold, Charles Daley and Nick White for helpful discussion.

References

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4 Wiktor SZ, Sassan-Morokro M, Grant AD, et al. Efficacy of trimethoprim-sulfamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1 infected patients with tuberculosis in Abidjan, Cte d'Ivoire: a randomized controlled trial. Lancet 1999;353:1469- 75

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11 Joint United Nations Programme on AIDS and the World Health Organization. Press Release (7/00). Provisional WHO/UNAIDS Secretariat recommendations on the use of cotrimoxazole prophylaxis in adults and children living with HIV/AIDS in Africa. Available from URL: [www.who.int/inf-pr-2000/en/pr2000-23.html]

12 Parry CM, Duong NM, Zhou J, et al. Emergence in Vietnam of Streptococcus pneumoniae resistant to multiple antimicrobial agents as a result of dissemination of the multiresistant Spain 23F-1 clone. Antimicrob Agents Chemother 2002;46:3512-17

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16 Pape JW, Jean SS, Ho JL, Hafner A, Johnson WD. Effect of isoniazid prophylaxis on incidence of active tuberculosis and progression of HIV infection. Lancet 1993;342:268-72

(Accepted 31 July 2003)

Janice K Louie MD MPH1, Nguyen Huu Chi MD2, Le Thi Thu Thao MD2, Vo Minh Quang MD2, James Campbell AIBMS3, Nguyen Van Vinh Chau MD2, George W Rutherford MD1, Jeremy J Farrar DPhil FRCP3 and Christopher M Parry MB FRCPath3

1 Center for AIDS Prevention Studies, University of California, San Francisco, 74 New Montgomery Street, Suite 600, San Francisco, CA 94105, USA; 2 Hospital for Tropical Diseases, Cho Quan Hospital, Ho Chi Minh City; 3 Wellcome Trust Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

Correspondence to: Dr Janice K Louie

E-mail: JLouie@dhs.ca.gov

Copyright Royal Society of Medicine Press Ltd. Nov 2004

Source: International Journal of STD & AIDS

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