Establishing Quality Assurance for HIV-1 Rapid Test for Recent Infection in Thailand through the Utilization of Dried Tube Specimens.

The present study focuses on establishing the quality assurance of laboratories for recent infections (RTRI) in Thailand. We developed a cold-chain independent method, using fully characterized plasma obtained from the Thai Red Cross Society, and prepared as dried tube specimens (DTS). Twenty microliters of HIV-seronegative, recent, and long-term infected samples were aliquoted into individual tubes and dried at room temperature, 20-30 degrees Celsius, in a biosafety cabinet overnight to ensure optimal preservation. The DTS external quality control and external quality assessment were tested for homogeneity and stability following the ISO/Guide 35 guidelines. The DTS panels were distributed to 48 sites (FY 2022) and 27 sites (FY 2023) across 14 and 9 provinces, respectively, in Thailand. The results from participating laboratories were collected and evaluated for performance. The results were scored, and acceptable performance criteria were defined as the proportion of panels correctly tested, which was set at 100%. The satisfactory performance ranged from 96% to 100% and was not significantly different among the 13 health regions. The developed and implemented DTS panels can be used to monitor the quality of RTRI testing in Thailand.

An algorithm for tuberculosis screening and diagnosis in people with HIV.

BACKGROUND: Tuberculosis screening is recommended for people with human immunodeficiency virus (HIV) infection to facilitate early diagnosis and safe initiation of antiretroviral therapy and isoniazid preventive therapy. No internationally accepted, evidence-based guideline addresses the optimal means of conducting such screening, although screening for chronic cough is common. METHODS: We consecutively enrolled people with HIV infection from eight outpatient clinics in Cambodia, Thailand, and Vietnam. For each patient, three samples of sputum and one each of urine, stool, blood, and lymph-node aspirate (for patients with lymphadenopathy) were obtained for mycobacterial culture. We compared the characteristics of patients who received a diagnosis of tuberculosis (on the basis of having one or more specimens that were culture-positive) with those of patients who did not have tuberculosis to derive an algorithm for screening and diagnosis. RESULTS: Tuberculosis was diagnosed in 267 (15%) of 1748 patients (median CD4+ T-lymphocyte count, 242 per cubic millimeter; interquartile range, 82 to 396). The presence of a cough for 2 or 3 weeks or more during the preceding 4 weeks had a sensitivity of 22 to 33% for detecting tuberculosis. The presence of cough of any duration, fever of any duration, or night sweats lasting 3 or more weeks in the preceding 4 weeks was 93% sensitive and 36% specific for tuberculosis. In the 1199 patients with any of these symptoms, a combination of two negative sputum smears, a normal chest radiograph, and a CD4+ cell count of 350 or more per cubic millimeter helped to rule out a diagnosis of tuberculosis, whereas a positive diagnosis could be made only for the 113 patients (9%) with one or more positive sputum smears; mycobacterial culture was required for most other patients. CONCLUSIONS: In persons with HIV infection, screening for tuberculosis should include asking questions about a combination of symptoms rather than only about chronic cough. It is likely that antiretroviral therapy and isoniazid preventive therapy can be started safely in people whose screening for all three symptoms is negative, whereas diagnosis in most others will require mycobacterial culture.

Nontuberculous mycobacterial disease in patients with HIV in Southeast Asia.

RATIONALE: Although nontuberculous mycobacteria (NTM) are widely documented as a cause of illness among HIV-infected people in the developed world, studies describing the prevalence of NTM disease among HIV-infected people in most resource-limited settings are rare. OBJECTIVES: To evaluate the prevalence of mycobacterial disease in HIV-infected patients in Southeast Asia. METHODS: We enrolled people with HIV from three countries in Southeast Asia and collected pulmonary and extrapulmonary specimens to evaluate the prevalence of mycobacterial disease. We adapted American Thoracic Society/Infectious Disease Society of America guidelines to classify patients into NTM pulmonary disease, NTM pulmonary disease suspects, NTM disseminated disease, and no NTM categories. MEASUREMENTS AND MAIN RESULTS: In Cambodia, where solid media alone was used, NTM was rare. Of 1,060 patients enrolled in Thailand and Vietnam, where liquid culture was performed, 124 (12%) had tuberculosis and 218 (21%) had NTM. Of 218 patients with NTM, 66 (30%) were classified as NTM pulmonary disease suspects, 9 (4%) with NTM pulmonary disease, and 10 (5%) with NTM disseminated disease. The prevalence of NTM disease was 2% (19 of 1,060). Of 51 patients receiving antiretroviral therapy (ART), none had NTM disease compared with 19 (2%) of 1,009 not receiving ART. CONCLUSIONS: Although people with HIV frequently have sputum cultures positive for NTM, few meet a strict case definition for NTM disease. Consistent with previous studies, ART was associated with lower odds of having NTM disease. Further studies of NTM in HIV-infected individuals in tuberculosis-endemic countries are needed to develop and validate case definitions.

Bloodstream infections among HIV-infected outpatients, Southeast Asia.

Bloodstream infections (BSIs) are a major cause of illness in HIV-infected persons. To evaluate prevalence of and risk factors for BSIs in 2,009 HIV-infected outpatients in Cambodia, Thailand, and Vietnam, we performed a single Myco/F Lytic blood culture. Fifty-eight (2.9%) had a clinically significant BSI (i.e., a blood culture positive for an organism known to be a pathogen). Mycobacterium tuberculosis accounted for 31 (54%) of all BSIs, followed by fungi (13 [22%]) and bacteria (9 [16%]). Of patients for whom data were recorded about antiretroviral therapy, 0 of 119 who had received antiretroviral therapy for ≥14 days had a BSI, compared with 3% of 1,801 patients who had not. In multivariate analysis, factors consistently associated with BSI were fever, low CD4+ T-lymphocyte count, abnormalities on chest radiograph, and signs or symptoms of abdominal illness. For HIV-infected outpatients with these risk factors, clinicians should place their highest priority on diagnosing tuberculosis.

Yield of acid-fast smear and mycobacterial culture for tuberculosis diagnosis in people with human immunodeficiency virus.

RATIONALE: The World Health Organization recently revised its recommendations for tuberculosis (TB) diagnosis in people with HIV. Most studies cited to support these policies involved HIV-uninfected patients and only evaluated sputum specimens. OBJECTIVES: To evaluate the performance of acid-fast bacilli smear and mycobacterial culture on sputum and nonsputum specimens for TB diagnosis in a cross-sectional survey of HIV-infected patients. METHODS: In Thailand and Vietnam, we enrolled people with HIV regardless of signs or symptoms. Enrolled patients provided three sputum, one urine, one stool, one blood, and, for patients with palpable peripheral adenopathy, one lymph node aspirate specimen for acid-fast bacilli microscopy and mycobacterial culture on solid and broth-based media. We classified any patient with at least one specimen culture positive for Mycobacterium tuberculosis as having TB. MEASUREMENTS AND MAIN RESULTS: Of 1,060 patients enrolled, 147 (14%) had TB. Of 126 with pulmonary TB, the incremental yield of performing a third sputum smear over two smears was 2% (95% confidence interval, 0-6), 90 (71%) patients were detected on broth-based culture of the first sputum specimen, and an additional 21 (17%) and 12 (10%) patients were diagnosed with the second and third specimens cultured. Of 82 lymph nodes cultured, 34 (42%) grew M. tuberculosis. In patients with two negative sputum smears, broth-based culture of three sputum specimens had the highest yield of any testing strategy. CONCLUSIONS: In people with HIV living in settings where mycobacterial culture is not routinely available to all patients, a third sputum smear adds little to the diagnosis of TB. Broth-based culture of three sputum specimens diagnoses most TB cases, and lymph node aspiration provides the highest incremental yield of any nonpulmonary specimen test for TB.

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.

Diagnostic performance and costs of Capilia TB for Mycobacterium tuberculosis complex identification from broth-based culture in Bangkok, Thailand.

OBJECTIVES: Broth-based culture (BBC) systems are increasingly being used to detect Mycobacterium tuberculosis complex (MTBC) in resource-limited. We evaluated the performance, time to detection and cost of the Capilia TB identification test from broth cultures positive for acid-fast bacilli (AFB) in Thailand. METHODS: From October-December 2007, broth cultures that grew AFB from specimens submitted by district TB clinics to the Bangkok city laboratory were tested for MTBC using Capilia TB and standard biochemical tests. Isolates that were identified as MTBC by biochemical tests but not by Capilia TB underwent repeat testing using Capilia TB, Accuprobe (Gen-Probe, San Diego, CA, USA) and sequencing. Costs of time, labour, infrastructure and consumables for all procedures were measured. RESULTS: Of 247 isolates evaluated, the sensitivity of Capilia TB was 97% and its true specificity 100% compared with biochemical testing. The median time from specimen receipt to confirmed MTBC identification was 20 days (range 7-53 days) for Capilia TB and 45 days (range 35-79 days) for biochemical testing (P < 0.01). Six isolates that were Capilia TB negative but positive by biochemical testing were confirmed as MTBC and mutations in the mpb64 gene were detected in all. The unit cost of using Capilia TB was 2.67 USD that of biochemical testing was 8.78 USD. CONCLUSIONS: In Thailand, Capilia TB had acceptable sensitivity and specificity, was lower in cost and had shorter turn-around times. Laboratories investing in BBC should consider Capilia TB for identification of MTBC, after validation of performance in their setting.

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.

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.

TB, HIV-associated TB and multidrug-resistant TB on Thailand's border with Myanmar, 2006-2007.

OBJECTIVE: To measure the burden and improve management of tuberculosis (TB), HIV-associated TB and MDR TB in Tak Province, Thailand, which borders Myanmar. METHODS: From September 2006 to August 2007, we collected uniform data about TB cases and enhanced human immunodeficiency virus (HIV) counselling and testing. We provided mycobacterial culture and drug-susceptibility testing in public or non-governmental organization facilities. Patients were classified by nationality and, for non-Thais, by migration status. RESULTS: Of 1662 TB cases in the 12-month period, 1087 (65%) occurred in non-Thais. Of non-Thais, 415 (38%) lived in Myanmar but crossed the border for healthcare. HIV infection was diagnosed in 18% of Thais compared with 12% of non-Thais (P < 0.01); HIV status was unknown for 22% of Thais and 27% of non-Thais (P = 0.02). Overall, multidrug-resistant (MDR) TB was diagnosed in 27 patients, 19 (70%) in non-Thais. Among TB cases never previously treated for TB, no MDR cases were diagnosed in Thais or in Myanmar refugees, but six cases were diagnosed in migrants from Myanmar. CONCLUSIONS: In Thailand, TB, HIV-associated TB and MDR TB in migrants from Myanmar are important public health problems; they need to be resolved in both the countries.

Using tuberculin skin test as an entry point to screen for latent and active tuberculosis in Thai people living with HIV.

BACKGROUND: Tuberculin skin test (TST) identifies patients highly likely to benefit from isoniazid preventive therapy and tuberculosis (TB) prevalence may differ by TST status. We evaluated latent and active TB screening and diagnosis strategies among people living with HIV (PLHIV) incorporating TST as the initial screening step. METHODS: PLHIV attending services at the Thai Red Cross Anonymous Clinic during September 2006 to January 2008 were enrolled. TB disease was defined as any positive Mycobacterium tuberculosis (MTB) specimen culture from sputum, urine, stool, lymph node aspiration, and blood. The performance of symptom screening (>1 of: any cough, any fever, night sweats lasting 3 or more weeks in the preceding 4 weeks) and laboratory screening (sputum smear followed by chest radiography and CD4 count) for active TB disease were evaluated according to TST status. RESULTS: We enrolled 604 PLHIV. TST was positive in 151 PLHIV (25.0%). TB disease was diagnosed in 33 PLHIV, including 22 (14.6%) TST-positive and 11 (2.4%) TST-negative PLHIV. We found that an approach of performing MTB culture for all TST-positive PLHIV and symptom screening followed by laboratory screening for all TST-negative PLHIV would identify 196 (32.4%) of 604 PLHIV who would need MTB culture to correctly diagnose 29 (87.9%) of 33 active TB cases. CONCLUSIONS: TST can be used as an initial screening test among PLHIV to identify those at highest risk of active TB disease. Access to MTB culture or other sensitive tests to exclude TB disease is urgently needed to improve TB screening and prevention in resource-limited settings.