Multidrug-resistant TB and HIV in Thailand: overlapping, but not independently associated, risk factors.

The HIV and multi-drug resistant tuberculosis (MDR-TB) epidemics are closely linked. In Thailand as part of a sentinel surveillance system, we collected data prospectively about pulmonary TB cases treated in public clinics. A subset of HIV-infected TB patients identified through this system had additional data collected for a research study. We conducted multivariate analysis to identify factors associated with MDR-TB. Of 10,428 TB patients, 2,376 (23%) were HIV-infected; 145 (1%) had MDR-TB. Of the MDR-TB cases, 52 (37%) were HIV-infected. Independent risk factors for MDR-TB included age 18-29 years old, male sex, and previous TB treatment, but not HIV infection. Among new patients, having an injection drug use history was a risk factor for MDR-TB. Of 539 HIV-infected TB patients in the research study, MDR-TB was diagnosed in 19 (4%); the only significant risk factors were previous TB treatment and previous hepatitis. In Thailand, HIV is common among MDR-TB patients, but is not an independent risk factor for MDR-TB. Populations at high risk for HIV-young adults, men, injection drug users - should be prioritized for drug susceptibility testing.

Social stigma and knowledge of tuberculosis and HIV among patients with both diseases in Thailand.

INTRODUCTION: Disease-related stigma and knowledge are believed to be associated with patients' willingness to seek treatment and adherence to treatment. HIV-associated tuberculosis (TB) presents unique challenges, because TB and HIV are both medically complex and stigmatizing diseases. In Thailand, we assessed knowledge and beliefs about these diseases among HIV-infected TB patients. METHODS: We prospectively interviewed and examined HIV-infected TB patients from three provinces and one national referral hospital in Thailand from 2005-2006. At the beginning of TB treatment, we asked patients standardized questions about TB stigma, TB knowledge, and HIV knowledge. Responses were grouped into scores; scores equal to or greater than the median score of study population were considered high. Multiple logistic regression analysis was used to identify factors associated with scores. RESULTS: Of 769 patients enrolled, 500 (65%) reported high TB stigma, 177 (23%) low TB knowledge, and 379 (49%) low HIV knowledge. Patients reporting high TB stigma were more likely to have taken antibiotics before TB treatment, to have first visited a traditional healer or private provider, to not know that monogamy can reduce the risk of acquiring HIV infection, and to have been hospitalized at enrollment. Patients with low TB knowledge were more likely to have severe TB disease, to be hospitalized at enrollment, to be treated at the national infectious diseases referral hospital, and to have low HIV knowledge. Patients with low HIV knowledge were more likely to know a TB patient and to have low TB knowledge. DISCUSSION: We found that stigma and low disease-specific knowledge were common among HIV-infected TB patients and associated with similar factors. Further research is needed to determine whether reducing stigma and increasing TB and HIV knowledge among the general community and patients reduces diagnostic delay and improves patient outcomes.

HIV care and treatment factors associated with improved survival during TB treatment in Thailand: an observational study.

BACKGROUND: In Southeast Asia, HIV-infected patients frequently die during TB treatment. Many physicians are reluctant to treat HIV-infected TB patients with anti-retroviral therapy (ART) and have questions about the added value of opportunistic infection prophylaxis to ART, the optimum ART regimen, and the benefit of initiating ART early during TB treatment. METHODS: We conducted a multi-center observational study of HIV-infected patients newly diagnosed with TB in Thailand. Clinical data was collected from the beginning to the end of TB treatment. We conducted multivariable proportional hazards analysis to identify factors associated with death. RESULTS: Of 667 HIV-infected TB patients enrolled, 450 (68%) were smear and/or culture positive. Death during TB treatment occurred in 112 (17%). In proportional hazards analysis, factors strongly associated with reduced risk of death were ART use (Hazard Ratio [HR] 0.16; 95% confidence interval [CI] 0.07-0.36), fluconazole use (HR 0.34; CI 0.18-0.64), and co-trimoxazole use (HR 0.41; CI 0.20-0.83). Among 126 patients that initiated ART after TB diagnosis, the risk of death increased the longer that ART was delayed during TB treatment. Efavirenz- and nevirapine-containing ART regimens were associated with similar rates of adverse events and death. CONCLUSION: Among HIV-infected patients living in Thailand, the single most important determinant of survival during TB treatment was use of ART. Controlled clinical trials are needed to confirm our findings that early ART initiation improves survival and that the choice of non-nucleoside reverse transcriptase inhibitor does not.

Characteristics of HIV-infected tuberculosis patients in Thailand.

To improve understanding about the epidemiology and clinical features of HIV-associated tuberculosis (TB) infection we conducted a prospective, multi-center observational study of HIV-infected TB patients in Thailand. We enrolled HIV-infected patients diagnosed with TB at public health facilities from three provinces and the national infectious diseases referral hospital in Thailand. Patients underwent standardized interviews, evaluations, and laboratory testing at the beginning of TB treatment. We analyzed demographic and clinical characteristics of patients and stratified our findings by level of immune-suppression and whether antiretroviral therapy (ART) was used before TB diagnosis. Of 769 patients analyzed, pulmonary TB was diagnosed in 461 (60%). The median CD4+ T-lymphocyte (CD4) count was 63 cells/microl [interquartile range (IQR), 23-163.5] and the median HIV RNA viral load was 308,000 copies/ml (IQR, 51,900-759,000) at the time of TB diagnosis. Methamphetamine use was reported by 304 patients (40%), marijuana by 267 patients (35%), and injection drug use by 199 patients (26%). Three hundred three patients (40%) reported having been previously incarcerated. Among sexually active patients, 142 (42%) reported never using condoms at all. Patients with CD4 counts <200 cells/microl were significantly more likely than patients with CD4 counts > or =200 cells/microl to have extra-pulmonary TB, fever, fatigue, muscle weakness, no hemoptysis, tachycardia, low body mass index, jaundice, or no pleural effusion. Of the 94 patients that received ART before TB diagnosis, the median time from ART initiation to TB diagnosis was 105 days (IQR, 31-468). HIV-infected patients who developed TB after ART initiation were more likely than other HIV-infected TB patients to have extra-pulmonary TB, a normal chest radiograph, low HIV RNA viral load, or a history of previous TB treatment.

HIV-associated extrapulmonary tuberculosis in Thailand: epidemiology and risk factors for death.

BACKGROUND: We conducted a prospective, multicenter observational cohort study in Thailand to characterize the epidemiology of extrapulmonary tuberculosis (TB) in HIV-infected persons and to identify risk factors for death. METHODS: From May 2005 to September 2006, we enrolled, interviewed, examined, and performed laboratory tests on HIV-infected adult TB patients and followed them from TB treatment initiation until the end of TB treatment. We conducted multivariate proportional hazards analysis to identify factors associated with death. RESULTS: Of the 769 patients, pulmonary TB only was diagnosed in 461 (60%), both pulmonary and extrapulmonary TB in 78 (10%), extrapulmonary TB at one site in 223 (29%), and extrapulmonary TB at more than one site in seven (1%) patients. Death during TB treatment occurred in 59 of 308 patients (19%) with any extrapulmonary involvement. In a proportional hazards model, patients with extrapulmonary TB had an increased risk of death if they had meningitis, and a CD4+ T-lymphocyte count <200 cells/microl. Patients who received co-trimoxazole, fluconazole, and antiretroviral therapy during TB treatment had a lower risk of death. CONCLUSIONS: Among HIV-infected patients with TB, extrapulmonary disease occurred in 40% of the patients, particularly in those with advanced immune suppression. Death during TB treatment was common, but the risk of death was reduced in patients who took co-trimoxazole, fluconazole, and antiretroviral therapy.

Causes of death in HIV-infected persons who have tuberculosis, Thailand.

Up to 50% of persons with HIV and a diagnosis of tuberculosis (TB) in Thailand die during TB treatment. In a prospective observational study, a team of physicians ascribed the cause of death after reviewing verbal autopsies (interviews of family members about events preceding death), laboratory data, and medical records. Of 849 HIV-infected TB patients enrolled, 142 (17%) died. The cause of death was TB for 38 (27%), including 6 with multidrug-resistant TB and 20 with disseminated TB; an HIV-associated condition other than TB for 50 (35%); and a condition unrelated to TB or HIV for 22 (15%). Twenty-three patients (16%) were judged not to have had TB at all. Death from all causes except those unrelated to TB or HIV was less common in persons receiving antiretroviral therapy (ART). In addition to increasing the use of ART, death rates may be reduced through expanded use of modern TB diagnostic techniques.

Factors associated with tuberculosis treatment default among HIV-infected tuberculosis patients in Thailand.

Ensuring completion of tuberculosis (TB) treatment remains a major public health problem. In HIV-infected patients, TB is the most common severe opportunistic infection. Few studies have evaluated risk factors for TB treatment default in HIV-infected patients. We conducted a prospective, observational study of HIV-infected TB patients in Thailand. Patients underwent standardised evaluations at the beginning of TB treatment, at the end of the intensive phase and at the end of TB treatment. TB treatment outcomes were assessed according to WHO guidelines. The analysis was limited to patients who defaulted or who had treatment success. Of the 554 patients analysed, 61 (11%) defaulted. In multivariate analysis, factors associated with TB treatment default included incarceration history [adjusted odds ratio (AOR) 2.0, 95% CI 1.1-3.7), smoking (AOR 2.3, 95% CI 1.3-4.1) and having a symptom complaint score >15 (AOR 3.4, 95% CI 1.4-8.0); one marker of wealth, namely owning a refrigerator, was protective (AOR 0.4, 95% CI 0.2-0.8). Default during TB treatment was a significant problem in HIV-infected patients. Reducing default may require enhancing services for patients with a history of incarceration or smoking and designing patient-centred systems to address poverty and patient wellness.

Multi-drug resistant TB and HIV in Thailand: overlapping, but not independently associated risk factors.

The HIV and multi-drug resistant tuberculosis (MDR-TB) epidemics are closely linked. In Thailand as part of a sentinel surveillance system, we collected data prospectively about pulmonary TB cases treated in public clinics. A subset of HIV-infected TB patients identified through this system had additional data collected for a research study. We conducted multivariate analysis to identify factors associated with MDR-TB. Of 10,428 TB patients, 2,376 (23%) were HIV-infected; 145 (1%) had MDR-TB. Of the MDR-TB cases, 52 (37%) were HIV-infected. Independent risk factors for MDR-TB included age 18-29 years old, male sex, and previous TB treatment, but not HIV infection. Among new patients, having an injection drug use history was a risk factor for MDR-TB. Of 539 HIV-infected TB patients in the research study, MDR-TB was diagnosed in 19 (4%); the only significant risk factors were previous TB treatment and previous hepatitis. In Thailand, HIV is common among MDR-TB patients, but is not an independent risk factor for MDR-TB. Populations at high risk for HIV-young adults, men, injection drug users - should be prioritized for drug susceptibility testing.

Health-seeking behavior among HIV-infected patients treated for TB in Thailand.

In Asia, patients increasingly seek tuberculosis (TB) treatment in the private sector; however, few private sector practices follow international TB management guidelines. We conducted a study to measure the frequency and predictors of seeking TB diagnosis in the private sector among 756 HIV-infected TB patients in four Thai provinces during 2005-2006. Of enrolled patients, 97 (13%) first sought care at a private provider and 83 (11%) at a pharmacy. In multivariable analysis, the only factor independently associated with seeking care at a private provider was having a high TB stigma score. Factors independently associated with seeking care at a pharmacy included not knowing that TB can be cured and that TB care can be provided close to home. Patients reported that the most influential factor in choosing a provider was confidentiality (468; 62%). Further research is needed to evaluate whether educating the community about the confidentiality, availability, and success of curing TB at government health facilities can promote prompt utilization of public TB treatment services by HIV-infected patients in Thailand.

Improvements in physical and mental health among HIV-infected patients treated for TB in Thailand.

We conducted a prospective, observational study of human immunodeficiency virus (HIV) infected patients diagnosed with tuberculosis (TB) at public health facilities in Thailand to evaluate the impact of TB and HIV treatment on overall physical and mental health. Standardized data were collected from patients at the time of TB diagnosis, two months into TB treatment, and at completion of TB treatment. We calculated composite physical and mental health scores for patients that completed treatment, compared scores during treatment, and analyzed factors associated with improvements in these scores. Of 493 patients analyzed, 488 (99%) reported at least one physical health complaint and 210 (43%) had at least one mental health complaint at baseline. Improvement in physical health occurred in 377 (76%) and improvement in mental health occurred in 182 (37%). In a multivariable analysis, factors strongly associated with improvement in physical health were receiving TB treatment in Bangkok, age greater than 50 years, and improved mental health. Improvement in mental health was strongly associated with alleviation of physical symptoms, including bloody urine, foot pain, headache, muscle weakness, difficulty sleeping, chest pain, and dizziness.

Viral hepatitis and HIV-associated tuberculosis: risk factors and TB treatment outcomes in Thailand.

BACKGROUND: The occurrence of tuberculosis (TB), human immunodeficiency virus (HIV), and viral hepatitis infections in the same patient poses unique clinical and public health challenges, because medications to treat TB and HIV are hepatotoxic. We conducted an observational study to evaluate risk factors for HBsAg and/or anti-HCV reactivity and to assess differences in adverse events and TB treatment outcomes among HIV-infected TB patients. METHODS: Patients were evaluated at the beginning, during, and at the end of TB treatment. Blood samples were tested for aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (BR), complete blood count, and CD4+ T lymphocyte cell count. TB treatment outcomes were assessed at the end of TB treatment according to international guidelines. RESULTS: Of 769 enrolled patients, 752 (98%) had serologic testing performed for viral hepatitis: 70 (9%) were reactive for HBsAg, 237 (31%) for anti-HCV, and 472 (63%) non-reactive for both markers. At the beginning of TB treatment, 18 (26%) patients with HBsAg reactivity had elevated liver function tests compared with 69 (15%) patients non-reactive to any viral marker (p = 0.02). At the end of TB treatment, 493 (64%) were successfully treated. Factors independently associated with HBsAg reactivity included being a man who had sex with men (adjusted odds ratio [AOR], 2.1; 95% confidence interval [CI], 1.1-4.3) and having low TB knowledge (AOR, 1.8; CI, 1.0-3.0). Factors most strongly associated with anti-HCV reactivity were having injection drug use history (AOR, 12.8; CI, 7.0-23.2) and living in Bangkok (AOR, 15.8; CI, 9.4-26.5). The rate of clinical hepatitis and death during TB treatment was similar in patients HBsAg reactive, anti-HCV reactive, both HBsAg and anti-HCV reactive, and non-reactive to any viral marker. CONCLUSION: Among HIV-infected TB patients living in Thailand, markers of viral hepatitis infection, particularly hepatitis C virus infection, were common and strongly associated with known behavioral risk factors. Viral hepatitis infection markers were not strongly associated with death or the development of clinical hepatitis during TB treatment.

Assessing the sensitivity of surveillance for pneumonia in rural Thailand.

We conducted a household survey among Sa Kaeo residents to characterize self-reported health-seeking behavior for pneumonia and the proportion of individuals who seek care at a hospital to determine the coverage of a surveillance system. A 2-stage cluster sample was used to select households. A case of pneumonia was defined as a self-reported history of cough and difficulty breathing for at least 2 days or being given a diagnosis of pneumonia by a healthcare provider in the 12-month period beginning February 1, 2002, and ending January 31, 2003. Interviewers administered a structured questionnaire that asked about clinical illness and utilization of healthcare services. Among 1,600 households, 5,658 persons were surveyed, of whom 62 persons met the case definition. Of the 59 persons with complete data, 53 (90%, 95% CI: 79-96) sought medical care and 47 (80%, 95% CI: 67-89) sought care at a hospital facility in the province. Neither distance nor cost was reported as a barrier to seeking care. Most individuals with self-reported pneumonia sought care at the hospital level. Population-based surveillance can provide reliable estimates of hospitalized, chest radiograph-confirmed pneumonia in Sa Kaeo if adjustments are made to account for the proportion of individuals who access a hospital where radiologic assessment is available.

A household survey to assess the burden of influenza in rural Thailand.

Little is known about the disease burden of influenza in middle-income tropical countries like Thailand. The recent outbreak of avian influenza (H5N1) and studies on influenza from neighboring countries highlight the need for data on incidence, access to care, and health care cost. In May/ June 2003, we conducted a province-wide household survey using two-stage cluster sampling to determine the burden of influenza-like illness in Sa Kaeo Province. We used the total number of reported influenza that occurred in May 2003 and a prospective study of outpatient influenza in clinic patients to develop an estimate of the annualized incidence of influenza. Of 718 subjects, 16 (2.2%) suffered an episode of influenza-like illness in the preceding month; 14 sought care, of whom 7 went to a hospital facility. Fifty percent reported missing on average 3 days of work or school. The total individual cost per illness episode was 663 baht (15.78 US dollars). The proportion of outpatients with influenza-like illness caused by an influenza virus in May was 16% and the annualized influenza incidence was estimated to be 5,941/100,000 in Sa Kaeo Province. This survey adds to information indicating that in rural Thailand, the burden of influenza is substantial and costs associated with an illness episode are up to 20% of an average monthly income.