In this large study of HIV-infected persons in Southeast Asia, 1 in 35 outpatients had a BSI; the highest prevalence was in patients with low CD4 counts and clinical signs of infection. M. tuberculosis remains one of the most common causes of BSI in HIV-infected persons who live in resource-limited settings. In all analyses performed, several factors were consistently associated with BSI: self-reported fever or documented elevated temperature, low CD4 count, abnormalities on chest radiograph, and signs or symptoms of abdominal illness.
BSI correlated strongly with immunosuppression. In fact, 10% of outpatients with HIV and CD4 count <100 cells/mm3
had a BSI, a prevalence similar to that seen in a previous study of febrile, HIV-infected inpatients in Thailand (6
). No patients who received ART had a BSI, consistent with the observation from other settings that highly active ART may reduce the incidence of bacteremia in HIV-infected persons (26–28
). M. tuberculosis
was the most frequent pathogen isolated in our study, findings consistent with studies that have shown that undiagnosed TB disease is common in patients with newly diagnosed HIVinfection and that the invasiveness of TB increases with declining CD4 cell counts and with the absence of ART (29–31
). These findings are particularly valid in countries with a high incidence of TB, such as Thailand, Cambodia, and Vietnam; in these 3 countries, the estimated incidence is >140 TB cases (all forms) per 100,000 persons (32
). We found that strong predictors of M. tuberculosis
BSI included clinical features that suggest pulmonary TB, including difficulty breathing and adenopathy or a miliary pattern shown on a chest radiograph. In an analysis published separately, we demonstrated that the incremental yield of blood culture for detecting TB was extremely low in HIV-infected persons who have 3 sputum specimens cultured on liquid media (22
). Our study, therefore, further supports the World Health Organization policy of focusing on pulmonary, rather than extrapulmonary, TB case finding and of recommending routine, regular TB screening for HIV-infected patients (33
More than one fifth of all BSIs were attributable to fungi, but we were unable to identify any clinical characteristics independently associated with fungal BSI. Because cryptococcosis and penicilliosis are commonly associated with advanced immunosuppression and have high death rates if left untreated, further studies are needed to improve case finding for and prevention of these infections (34,35
). In contrast, we found that self-reported fever and the finding of jaundice on physical examination were strong predictors of bacterial infection. The reasons for an association with jaundice are unclear, but the association is consistent with our finding that most bacterial infections were of enteric origin. Symptoms of abdominal illness, such as loss of appetite and nausea or vomiting, also were associated with BSI caused by any pathogen. Our finding that non-Typhi Salmonella
spp. infections were the most common bacterial infection in HIV patients is consistent with results of other studies and provides further evidence that efforts are needed to prevent invasive salmonellosis in HIV-infected persons, through improvements in food and water safety and the development of new vaccines (36
Our study has several limitations. First, we collected only 1 blood culture per patient and used only 1 type of culture media, which potentially reduced the sensitivity for detection of bacteremia (37
). This limitation is a likely explanation for the lack of Streptococcus pneumoniae
detected in our study. Invasive pneumococcal disease is a common cause of bacteremia in HIV-infected patients throughout the world, but S. pneumoniae
is challenging to isolate from blood. In addition, 12% of study patients were receiving co-trimoxazole preventive therapy, and our study was conducted among outpatients, a population less likely to have undiagnosed severe disease caused by a virulent pathogen, such as pneumococcus. Although other investigators in Southeast Asia have found similarly low pneumococcal isolation rates and have speculated that this is attributable to low incidence, at least 1 high-quality study demonstrated that the incidence of invasive pneumococcal disease in Thailand is similar to that in other regions (19–21,38
A major strength of our study, however, is that, unlike all previous studies, which were conducted at single referral hospitals, our study was conducted at multiple urban and rural clinical facilities in 3 countries. Thus, our results can be broadly generalized to HIV-infected patients throughout Southeast Asia.
Mycobacterial, fungal, and bacterial BSIs remain a major health problem for HIV-infected persons in Southeast Asia. Any HIV-infected outpatients (regardless of whether they have newly diagnosed HIV, are newly seeking care, or are already receiving care) who report experiencing fever or abdominal symptoms in the previous day, have a temperature >38
C or jaundice on physical examination, or have a chest radiograph demonstrating paratracheal adenopathy or a miliary pattern, have a high likelihood of a BSI, particularly if their CD4 count is <100 cells/mm3
. In such patients, blood culture, when available, should be performed immediately to facilitate diagnosis and accelerate access to treatment of BSI. Regardless of blood culture availability, clinicians should place their highest priority on early diagnosis and treatment of pulmonary TB. Ultimately, increasing use of ART most likely will have the greatest effect on reducing BSIs.