Xpert(®) MTB/RIF for smear-negative presumptive TB: impact on case notification in DR Congo.

SETTING: The impact of Xpert(®) MTB/RIF as a follow-on diagnostic test after smear microscopy on tuberculosis (TB) notification has not yet been well defined. DESIGN: Quasi-experimental design with 86 evaluation and 49 control clinics in Kinshasa, Democratic Republic of Congo. Smear microscopy was supported at all 135 clinics, Xpert was placed in 15 evaluation clinics and a sputum transport system was implemented for 25 satellite clinics. The number of cases notified before and during the project (July 2012-June 2013) was obtained from the National TB Program. RESULTS: Of 27,147 presumptive TB cases presenting in clinics with access to Xpert, 5922 (21.8%) were smear-positive. Of 18,636 individuals with ⩾ 3 negative microscopy results, 6920 (37.1%) underwent Xpert testing, 991 (14.3%) of whom tested positive. The number of bacteriologically positive cases increased equally in evaluation clinics (15.1%, 95%CI -2.3 to 32.6) and control clinics (13.6%, 95%CI 2.6-29.3), for a difference in increase of 1.5% (95%CI -28.8 to 31.8). There was no difference in the change in smear-negative cases (-42.4%, 95%CI -111.5 to 26.6), nor in all types of TB notified (-6.1%, 95%CI -32.5 to 20.4) between the evaluation and control clinics. CONCLUSION: In part due to a restrictive algorithm, Xpert as follow-on to smear microscopy did not increase the overall number of TB notifications, nor the number of bacteriologically positive cases.

Delayed antiretroviral therapy despite integrated treatment for tuberculosis and HIV infection.

SETTING: Five primary health care clinics in Kinshasa, Democratic Republic of Congo. OBJECTIVE: To examine timing and predictors of delayed initiation of antiretroviral therapy (ART) during anti-tuberculosis treatment. DESIGN: Prospective observational cohort of adult patients receiving integrated treatment for tuberculosis (TB) and human immunodeficiency virus (HIV) who are expected to initiate ART at 1 month if CD4 count is <100 cells/mm(3) or if patient is World Health Organization (WHO) Clinical Stage 4 for reasons other than extra-pulmonary TB, at 2 months if CD4 count is 100-350 cells/mm(3), or at completion of anti-tuberculosis treatment if subsequently CD4 count is ≤ 350 cells/mm(3) or patient has WHO Clinical Stage 4. RESULTS: Of 492 patients, 235 (47.8%) experienced delayed initiation of ART: 171 (72.8%) initiated ART late, after a median delay of 12 days (interquartile range [IQR] 4-27) and 64 (27.2%) never initiated ART. Contraindication to any antiretroviral drug (aOR 2.91, 95%CI 1.22-6.95), lower baseline CD4 count (aOR 1.20, 95%CI 1.08-1.33/100 cells/mm(3)), TB drug intolerance (aOR 1.93, 95%CI 1.23-3.02) and non-disclosure of HIV infection (aOR 1.50, 95%CI 1.03-2.18) predicted delayed ART initiation. CONCLUSION: Despite fully integrated treatment, half of all patients experienced delayed ART initiation. Pragmatic approaches to ensure timely ART initiation in those at risk of delayed ART initiation are needed.

Impact of HIV on clinical presentation and outcomes of tuberculosis treatment at primary care level.

Little is known on how human immunodeficiency virus (HIV) infection impacts pediatric tuberculosis (TB) in primary care. We compared TB type, HIV care and case fatality rates between 5685 adults and 830 children with TB treated at primary care clinics in Kinshasa, Democratic Republic of Congo. Children represented a substantial burden (13%) of TB, and presented predominantly with difficult to diagnose smear-negative TB and extra-pulmonary TB. The HIV co-infection rate was lower in children than in adults, and fewer children than adults received antiretroviral therapy during anti-tuberculosis treatment. Case fatality was four times higher in HIV-infected than non-infected children. Child-friendly point-of-care TB diagnostics and decentralized pediatric TB-HIV care should receive greater attention.

Mortality among tuberculosis patients in the Democratic Republic of Congo.

SETTING: Kinshasa, Democratic Republic of Congo. OBJECTIVE: To identify programmatic interventions for improved survival in patients receiving treatment for tuberculosis (TB) at primary care clinics. DESIGN: Retrospective cohort of adult patients initiating anti-tuberculosis treatment between January 2006 and May 2007. RESULTS: Among 5685 patients, 390 deaths occurred during anti-tuberculosis treatment, of which half (52%) did so during the first 2 months. Patients with smear-negative pulmonary TB were at greater risk of death in the first 2 months of treatment (human immunodeficiency virus [HIV] positive HR 1.49, 95%CI 0.89-2.49; HIV-negative HR 1.77 95%CI 1.06-2.95), but not thereafter. Patients with extra-pulmonary TB were at increased risk of death in the first 2 months of anti-tuberculosis treatment if they were non-HIV-infected (HR 2.42, 95%CI 1.52-3.85), and were half as likely to die during the remainder of treatment (HIV-positive HR 0.46, 95%CI 0.22-0.97; HIV-negative HR 0.47, 95%CI 0.23-0.94). Antiretroviral therapy (ART) reduced the risk of death by an estimated 36% (HR 0.64, 95%CI 0.37-1.11). CONCLUSION: High mortality in the first months of anti-tuberculosis treatment could be reduced by addressing diagnostic delays, particularly for extra-pulmonary and smear-negative TB cases and, in HIV-infected patients, by initiation of ART soon after starting anti-tuberculosis treatment.

Sputum smear microscopy: evaluation of impact of training, microscope distribution, and use of external quality assessment guidelines for resource-poor settings.

Sputum smear microscopy is the main and often only laboratory technique used for the diagnosis of tuberculosis in resource-poor countries, making quality assurance (QA) of smear microscopy an important activity. We evaluated the effects of a 5-day refresher training course for laboratory technicians and the distribution of new microscopes on the quality of smear microscopy in 13 primary health care laboratories in Kinshasa, Democratic Republic of Congo. The 2002 external QA guidelines for acid-fast bacillus smear microscopy were implemented, and blinded rechecking of the slides was performed before and 9 months after the training course and microscope distribution. We observed that the on-site checklist was highly time-consuming but could be tailored to capture frequent problems. Random blinded rechecking by the lot QA system method decreased the number of slides to be reviewed. Most laboratories needed further investigation for possible unacceptable performance, even according to the least-stringent interpretation. We conclude that the 2002 external QA guidelines are feasible for implementation in resource-poor settings, that the efficiency of external QA can be increased by selecting sample size parameters and interpretation criteria that take into account the local working conditions, and that greater attention should be paid to the provision of timely feedback and correction of the causes of substandard performance at poorly performing laboratories.