Resource implications of the latent tuberculosis cascade of care: a time and motion study in five countries.

BACKGROUND: The End TB Strategy calls for global scale-up of preventive treatment for latent tuberculosis infection (LTBI), but little information is available about the associated human resource requirements. Our study aimed to quantify the healthcare worker (HCW) time needed to perform the tasks associated with each step along the LTBI cascade of care for household contacts of TB patients. METHODS: We conducted a time and motion (TAM) study between January 2018 and March 2019, in which consenting HCWs were observed throughout a typical workday. The precise time spent was recorded in pre-specified categories of work activities for each step along the cascade. A linear mixed model was fit to estimate the time at each step. RESULTS: A total of 173 HCWs in Benin, Canada, Ghana, Indonesia, and Vietnam participated. The greatest amount of time was spent for the medical evaluation (median: 11 min; IQR: 6-16), while the least time was spent on reading a tuberculin skin test (TST) (median: 4 min; IQR: 2-9). The greatest variability was seen in the time spent for each medical evaluation, while TST placement and reading showed the least variability. The total time required to complete all steps along the LTBI cascade, from identification of household contacts (HHC) through to treatment initiation ranged from 1.8 h per index TB patient in Vietnam to 5.2 h in Ghana. CONCLUSIONS: Our findings suggest that the time requirements are very modest to perform each step in the latent TB cascade of care, but to achieve full identification and management of all household contacts will require additional human resources in many settings.

Latent tuberculous infection in household contacts of multidrug-resistant and newly diagnosed tuberculosis.

BACKGROUND: Differences in the prevalence of latent tuberculous infection (LTBI) and tuberculosis (TB) disease among contacts of patients with multidrug-resistant TB (MDR-TB) and drug-susceptible TB are not well understood. OBJECTIVE: To compare the prevalence of tuberculin skin test (TST) positivity in household contacts of patients with MDR-TB and in contacts of patients never previously treated for TB ('new TB'). DESIGN: Consecutive patients with MDR-TB and their household contacts at nine urban district clinics in Viet Nam were screened for TB and LTBI, and followed up for 6 months. LTBI was defined as a TST result of at least 10 mm. RESULTS: A total of 167 patients with TB and their 337 household contacts were recruited. A total of 167/180 (25.8%) contacts of new TB patients and 60/147 (40.8%) contacts of MDR-TB patients were TST-positive (odds ratio [OR] 2.0, 95%CI 1.3-3.2). Contacts of MDR-TB patients were more likely to have baseline chest radiograph findings consistent with TB (OR 2.6, 95%CI 1.4-5.0). CONCLUSION: Contacts of MDR-TB patients have a high risk of developing TB. Measures to reduce Mycobacterium tuberculosis transmission and accelerate the detection of disease among high-risk contacts should be prioritised to curb the MDR-TB epidemic.

Characterisation of Mycobacterium tuberculosis isolates lacking IS6110 in Viet Nam.

SETTING: The molecular diagnosis of tuberculosis (TB) in Viet Nam is often based on the detection of insertion sequence (IS) 6110 in Mycobacterium tuberculosis. However, 8-11% of M. tuberculosis strains in South-East Asia do not contain this target and this undermines the validity of these molecular tests. OBJECTIVE: We quantified the frequency of M. tuberculosis strains lacking IS6110 in rural Viet Nam and studied their epidemiological and clinical characteristics. DESIGN: Consecutively diagnosed adult TB patients in rural Southern Viet Nam submitted two sputum samples for culture, IS6110 restriction fragment length polymorphism (RFLP) spoligotyping and 15-loci variable number tandem repeat typing. Polymerase chain reaction (PCR) was performed to confirm the absence of IS6110 elements in strains lacking IS6110 hybridisation in RFLP. RESULTS: Among 2664 TB patient isolates examined, 109 (4.1%) had no IS6110 element. Compared to other strains, these no-copy strains were less often resistant to anti-tuberculosis drugs, particularly to streptomycin (adjusted OR 0.2, 95%CI 0.1-0.5), and showed significant geographic variation. No associations with TB history or demographic factors were found. CONCLUSIONS: Strains without the IS6110 target pose a problem in Viet Nam as regards false-negative molecular TB diagnosis in PCR. Compared to other strains circulating in Viet Nam, no-copy strains are more susceptible to anti-tuberculosis drugs.

Decrease in risk of tuberculosis infection despite increase in tuberculosis among young adults in urban Vietnam.

OBJECTIVE: To assess whether the increase in tuberculosis (TB) notification rates among young adults in Vietnam reflects increased transmission in the population at large. METHOD: Trends of case notification rates of new smear-positive TB were calculated from routinely reported data of district TB units over the period 1996-2005. Results from repeated tuberculin surveys among children aged 6-9 years were obtained to calculate the trend in annual risk of TB infection (ARTI). FINDINGS: From 1996 to 2006, notification rates in the age group 15-24 years increased by 4.3% per year, and more so in highly urbanised (6.7%) than in rural districts (1.7%). The ARTI in urban districts declined from 2.4% in 1992 to 1.2% in 1998 and 0.9% in 2005. In rural districts, the ARTI increased from 0.7% in 1991 to 1.2% in 1997, and then declined to 0.9% in 2006. CONCLUSION: The increase in TB notification rates among young adults in Ho Chi Minh Province is accompanied by a decrease in ARTI in children. This suggests that the trend in TB notification among young adults reflects increased rates of progression from infection to disease and/or increased transmission within this age group, rather than increased transmission in the population at large.

The Beijing genotype is associated with young age and multidrug-resistant tuberculosis in rural Vietnam.

BACKGROUND: Associations between multidrug resistance and the Mycobacterium tuberculosis Beijing genotype have been described mainly in populations with poor tuberculosis (TB) control such as prisons and inner cities, and may reflect shared risk factors rather than a biological association. OBJECTIVE: To study the association between genotype and drug resistance among TB patients in a population with adequate TB control. SETTING: Three rural districts in Vietnam. The study was performed at the Pham Ngoc Thach Tuberculosis and Lung Disease Hospital, Ho Chi Minh City, and the Tien Giang Provincial Tuberculosis and Lung Disease Hospital, My Tho, Vietnam. METHODS: Pretreatment sputum specimens were collected for culture, drug susceptibility testing and spoligotyping of all sputum smear-positive pulmonary TB patients consecutively diagnosed over a 3-year period. RESULTS: Beijing genotype infections were observed in 614 of 1744 (35%) patients. Beijing strains were more common among female (adjusted odds ratio [aOR] 1.4, P = 0.005), young (aOR 2.8, P < 0.001) and previously treated patients (aOR 2.4, P < 0.001). The Beijing genotype was associated with any resistance (aOR 3.7, P < 0.001) and multidrug resistance (aOR 6.8, P < 0.001) among new patients, and with any resistance (aOR 2.7, P = 0.005) but not with multidrug resistance (aOR 1.4, P = 0.545) among previously treated patients. CONCLUSION: In Vietnam, Beijing genotype is associated with young age and in new patients with multidrug resistance despite adequate TB control, suggesting a biological association. This potentially undermines the effectiveness of TB control in countries where Beijing genotype infections are common.

Drug resistance among smear-positive tuberculosis patients in Ho Chi Minh City, Vietnam.

OBJECTIVES: To assess the pattern of drug resistance among smear-positive tuberculosis (TB) patients in an inner city area in Vietnam. METHODS: A random sample of patients diagnosed by the national TB programme (NTP) were offered HIV testing and submitted sputum for Mycobacterium tuberculosis drug sensitivity testing. RESULTS: Of 1433 isolates from new patients, 360 (25%) were resistant to isoniazid (INH), 57 (4.0%) to rifampicin (RMP), 421 (29%) to streptomycin (SM) and 28 (2.0%) to ethambutol. Among 401 previously treated patients, this was 218 (54%), 109 (27%), 217 (54%) and 26 (7%), respectively. Multidrug resistance (MDR) was observed in 55 (3.8%) new and 102 (25%) previously treated patients. RMP resistance was strongly associated with resistance to INH (OR 46) and INH plus SM (OR 91, P = 0.004). Prevalence of drug resistance tended to decrease with age. Neither any resistance nor MDR was significantly associated with HIV infection. CONCLUSIONS: In this inner city area, levels of drug resistance, in particular of MDR among previously treated patients, are high. This may be related to the use of NTP regimens in the context of highly prevalent combined SM and INH resistance which may favour acquisition of RMP resistance.

Treatment outcomes by drug resistance and HIV status among tuberculosis patients in Ho Chi Minh City, Vietnam.

OBJECTIVE: To assess the combined effects of drug resistance, HIV infection and treatment regimen on treatment outcomes of smear-positive tuberculosis patients in Ho Chi Minh City, Vietnam. METHODS: A representative sample of patients diagnosed in 1998-2000 in 12 urban districts was offered HIV testing and submitted sputum for Mycobacterium tuberculosis culture and drug susceptibility testing. New patients were treated with 2SHRZ/6HE in nine districts and with 2SHRZ/4RH in three districts. RESULTS: The cure rate was 87% (1240/1430) among new patients compared to only 73% (287/391) among previously treated patients. Failure was associated with multidrug resistance (adjusted odds ratios [aOR] 49.6 and 16.6, respectively) and combined resistance to isoniazid (INH) and streptomycin (SM) (aOR 13.4 and 4.8), but not with HIV infection. New patients had an increased risk of failure on treatment with 2SHRZ/4RH compared to 2SHRZ/6HE if the isolate was resistant to INH and SM (aOR 2.8, P = 0.016). Death during treatment occurred in 15 of 50 HIV-infected patients (30%). Mortality was significantly associated with HIV infection (aOR 29.9), multidrug resistance (aOR 4.7) and other resistance to two or more drugs (aOR 2.1). CONCLUSION: In Vietnam, adaptation of treatment regimens should be considered, and interventions are needed to reduce the high mortality among HIV-infected patients.

Treatment results among tuberculosis patients treated by private lung specialists involved in a public-private mix project in Vietnam.

SETTING: Ho Chi Minh City, Vietnam. OBJECTIVES: To determine treatment outcome among patients treated by private lung specialists in a public-private mix (PPM) project for improved TB control. METHODS: Cohorts of patients treated by private lung specialists within the PPM project and in National Tuberculosis Programme (NTP) facilities were followed for up to 12 months. The quality of case management and treatment outcome was determined based on information in treatment cards. As a complement, questionnaire surveys of private providers (PPs) and patients and focus group discussions with PPs were conducted. RESULTS: Among 400 patients treated by PPs, 36 different treatment regimens were used. Directly observed treatment was not used at all, and treatment evaluation with sputum smear microscopy and health education was inadequate. Overall treatment success was 60% and the default rate was 37%, which was considerably worse than in NTP facilities. CONCLUSION: This PPM project, which used a combination of training, supervision, standardised referral and information system and financial incentives, did not achieve sufficiently good treatment outcome by PPs. Possible reasons for the poor outcome include absence of subsidisation of drug costs and lack of regulatory enforcement.

Referring TB suspects from private pharmacies to the National Tuberculosis Programme: experiences from two districts in Ho Chi Minh City, Vietnam.

SETTING: Ho Chi Minh City, Vietnam. OBJECTIVE: To describe pharmacists' attitudes towards referring TB suspects to the National Tuberculosis Programme (NTP) and to evaluate the feasibility of a new referral system. METHODS: 1) Questionnaire survey of 150 private pharmacies; 2) qualitative interviews with 16 pharmacists; 3) monitoring the use of new referral forms for 21 months. RESULTS: Use of a simple referral form was thought to be manageable by 72% of the pharmacists. Pharmacists identified a number of different types of risks associated with referral of TB suspects to the NTP; clients could turn to another pharmacy (61% of respondents); criticise the pharmacist if it appears that they do not have TB (42%); or remain untreated because they are not able to visit the NTP (41%). Fifty-eight (39%) of eligible pharmacies referred at least one client. At least 373 suspects were referred, 149 were tested and 10 had TB. CONCLUSIONS: It is feasible to let pharmacies refer TB suspects. For there to be a significant impact on case detection, it is important to acknowledge a number of concerns expressed by pharmacists and attempt to change both clients' and providers' expectations with regard to the pharmacists' role.

Initial defaulting in the National Tuberculosis Programme in Ho Chi Minh City, Vietnam: a survey of extent, reasons and alternative actions taken following default.

SETTING: Ho Chi Minh City, Vietnam. AIM: To determine the extent of initial default in the NTP, the reasons for initial default, health seeking after initial default and treatment received at other health facilities. METHOD: Questionnaire-based interviews of patients who were diagnosed with sputum-positive TB in the NTP during 2000 and who did not register for treatment in the NTP. RESULTS: The initial default rate was 8.3%; 79% gave reasons related to the NTP working procedures or treatment strategy, while 17.5% gave reasons related to insufficient knowledge among patients about TB and/or the need for treatment. Sixty-five per cent had been treated with anti-tuberculosis drugs at other health facilities after default, of which 74% had been treated at fully private facilities. CONCLUSION: Initial default is mainly caused by some patients' negative perceptions of working procedures and/or treatment strategy in the NTP. The majority of these patients are treated in private clinics after default from the NTP. The NTP needs to improve patients' perceptions of the treatment strategy and develop more user-friendly services that enable more patients to access treatment and reduce the risk of patients receiving substandard treatment in the private sector.

Public-private mix for improved TB control in Ho Chi Minh City, Vietnam: an assessment of its impact on case detection.

SETTING: Ho Chi Minh City (HCMC), Vietnam. OBJECTIVE: To assess the impact on case detection of a public-private mix (PPM) project linking private providers (PPs) to the National Tuberculosis Programme (NTP). METHOD: Nine-month monitoring of referral and diagnostic data recorded in new referral forms and treatment cards for PPs and upgraded NTP registers. RESULTS: A total of 1549 TB suspects were referred, of whom 1090 (70%) actually went to the NTP for sputum examination. A total of 569 cases were detected through referrals or notification, of whom 45% were new sputum smear-positive cases. The case detection of new sputum smear-positive cases in PPM districts increased by 18% (21/100,000, 95%CI 0-42) compared to the previous year, while a slight decrease occurred in control districts. In HCMC as a whole, case detection increased by 7% (7/100,000, 95%CI 2-11/100,000). Among sputum smear-positive cases detected in NTP through referrals from PPs, 58% defaulted before initiating treatment. CONCLUSIONS: The tendency towards increased case detection associated with this PPM indicates a potential for utilising PPs to improve case detection. However, the NTP and PPs should jointly address the problem of initial default before considering expansion of this PPM model.