Frank G. J. Cobelens

Directly observed therapy (DOT) remains the cornerstone of the global tuberculosis (TB) control strategy. Tanzania, one of the 22 high-burden countries regarding TB, changed the first-line treatment regimen to contain rifampicin-containing fixed-dose combination for the full 6 months of treatment. As daily health facility-based DOT for this long period is not feasible for the patient, nor for the health system, Tanzania introduced patient centred treatment (PCT). PCT allows patients to choose for daily DOT at a health facility or at their home by a supporter of choice. The introduction of fixed dose combinations in the intensive and continuation phase made PCT feasible by eliminating the risk of selective drug taking by patients and reducing the number of tablets to be taken. The approach was tested in three districts with the objective to assess the effect of this strategy on TB treatment outcomes

Frank Cobelens and colleagues outline key research questions that need to be addressed to maximize the impact of programmatic management of drug-resistant tuberculosis.

In Ho Chi Minh City, Vietnam, reporting rates for tuberculosis (TB) are rising in an emerging HIV epidemic. To describe the HIV epidemic among TB patients and quantify its impact on rates of reported TB, we performed a repeated cross-sectional survey from 1997 through 2002 in a randomly selected sample of inner city TB patients. We assessed effect by adjusting TB case reporting rates by the fraction of TB cases attributable to HIV infection. HIV prevalence in TB patients rose exponentially from 1.5% to 9.0% during the study period. Young (<35 years), single, male patients were mostly affected; injection drug use was a potent risk factor. After correction for HIV infection, the trend in TB reporting rates changed from a 1.9% increase to a 0.4% decrease per year. An emerging HIV epidemic, concentrated in young, male, injection drug users, is responsible for increased TB reporting rates in urban Vietnam.

Background: HIV testing on sputum using the QraQuick HIV1/2^® assay has high sensitivity and specificity, and holds promise for application in tuberculosis surveys. Its performance under conditions that may occur during surveys in resource-poor countries is however, unknown. We assessed, in a blinded comparison with HIV serum testing, the sensitivity and specificity of the OraQuick^® assay for detecting HIV antibody in sputum specimens kept at ambient temperature for up to 7 days, with and without decontaminant. Methods: Paired sputum and blood specimens from consecutively diagnosed smear-positive tuberculosis patients were tested with OraQuick^® and 2 HIV-1/2 ELISA's. Sputum was tested within 24 hours of collection, split into 2 aliquots with and without addition of cetylpyridium chloride, and tested again after 4 and 7 days. Results: Complete data was available for 377/435 (87%) enrolled patients; 132 (35%) tested HIV positive on serum. The sensitivity of the sputum test was 94.7% (95% CI 89.4–97.8) on day 1, 93.2% on day 4 and 92.9% on day 7. The specificity was 92.9% (95% CI 88.9–95.8) on day 1, and declined to 76.7% on day 4 (p < 0.001) and to 62.7% on day 7 (p < 0.001). Adding cetylpyridium chloride further decreased the specificity to 67.8% on day 4 (p = 0.04) and to 49.6% on day 7 (p = 0.004). Conclusion: Transportation of sputum specimens at ambient temperatures for 4 days or more, and addition of decontaminant, strongly affect the specificity of the OraQuick^® assay. Unless applied within one day, this assay is not suitable for estimation of HIV-prevalence among tuberculosis patients in survey settings.

Delay in tuberculosis diagnosis and treatment initiation may increase disease severity and mortality. In evaluations of tuberculosis control programmes high fatality rates during tuberculosis treatment, are used as an indicator of long delays in low HIV-prevalence settings. However, data for this presumed association between delay and fatality are lacking. We assessed the association between diagnostic delay and mortality of new smear-positive pulmonary tuberculosis patients in Vietnam.

Tuberculosis treatment failure and death rates are low in the Western Pacific Region, including Vietnam. However, failure or death may also occur among patients who did not complete treatment, i.e. reported as default or transfer-out. We aimed to assess the proportion failures and deaths among new smear-positive pulmonary tuberculosis patients with reported default or transfer-out.

Background: Treatment delay is an important indicator of access to tuberculosis diagnosis and treatment. Analyses of patient delay (i.e. time interval between onset of symptoms and first consultation of a health care provider) and health care delay (i.e. time interval between first consultation and start of treatment) can inform policies to improve access. This study assesses the patient, health care provider and total delay in diagnosis and treatment of new smear-positive pulmonary tuberculosis patients, and the risk factors for long delay, in Vietnam. Methods: A cross-sectional survey of new patients treated by the National Tuberculosis Control Programme was conducted in 70 randomly selected districts in Vietnam. All consecutively registered patients in one quarter of 2002 were interviewed using a pre-coded structured questionnaire. Results: Median (range) delay was 4 weeks (1–48) for total, 3 (1–48) weeks for patient and 1 (0–25) week for health care delay. Patients with long total delay (≥ 12 weeks, 15%) accounted for 49% of the cumulative number of delay-weeks. Independent risk factors (p < 0.05) for long total delay were female sex, middle age, remote setting, residence in the northern or central area, and initial visit to the private sector. For long patient delay (≥ 6 weeks) this was female sex, belonging to an ethnic minority, and living at > 5 km distance from a health facility or in the northern area. For long health care delay (≥ 6 weeks) this was urban setting, residence in the central area and initial visit to a communal health post, TB hospital or the private sector. Conclusion: Analyses of patient and treatment delays can indicate target groups and areas for health education and strengthening of the referral system, in particular between the private sector and the NTP.

In the Netherlands during 1993–2001, multidrug-resistant tuberculosis among newly diagnosed patients was more frequent in those with HIV coinfection (5/308, 1.6%) than in those with no HIV infection (39/646, 0.6%; adjusted odds ratio 3.43, p = 0.015). Four of the 5 patients coinfected with multidrug-resistant tuberculosis and HIV were foreign-born. DNA fingerprint analysis suggested that transmission had occurred outside the Netherlands.

Potential conflicts of interest.F.G.J.C.: no conflicts.

BackgroundThere is limited evidence that the DOTS (directly observed therapy, short course) strategy for tuberculosis (TB) control can contain the emergence and spread of drug resistance in the absence of second-line treatment. We compared drug-resistance levels between 1996 and 2001 in the south of Vietnam, an area with a well-functioning DOTS program MethodsSputum specimens were collected from consecutively diagnosed patients with smear-positive TB at 40 randomly selected public TB clinics. Mycobacterium tuberculosis isolates were tested for susceptibility to first-line drugs ResultsAmong 888 new patients in 2001, resistance to any drug was observed in 238 (26.3%), resistance to isoniazid was observed in 154 (16.6%), resistance to rifampin was observed in 22 (2.0%), resistance to ethambutol was observed in 12 (1.1%), resistance to streptomycin was observed in 173 (19.4%), and resistance to both isoniazid and rifampicin (multidrug resistance [MDR]) was observed in 20 (1.8% [95% confidence interval, 1.0%–3.3%]). Among 136 previously treated patients in 2001, any resistance was observed in 89 (62.9%), and MDR was observed in 35 (23.2%). The prevalence of any drug resistance and of streptomycin resistance among new patients had decreased significantly (P<.01) since 1996; there was no increase in the prevalence of MDR ConclusionThe prevalence of drug resistance decreased despite high initial levels of resistance to isoniazid and streptomycin and despite the absence of second-line treatment. Therefore, a DOTS program can contain drug-resistant TB in this setting