Delays and loss to follow-up before treatment of drug-resistant tuberculosis following implementation of Xpert MTB/RIF in South Africa: A retrospective cohort study

Abstract

BackgroundSouth Africa has a large burden of rifampicin-resistant tuberculosis (RR-TB), with 18,734 patients diagnosed in 2014. The number of diagnosed patients has increased substantially with the introduction of the Xpert MTB/RIF test, used for tuberculosis (TB) diagnosis for all patients with presumptive TB. Routine aggregate data suggest a large treatment gap (pre-treatment loss to follow-up) between the numbers of patients with laboratory-confirmed RR-TB and those reported to have started second-line treatment. We aimed to assess the impact of Xpert MTB/RIF implementation on the delay to treatment initiation and loss to follow-up before second-line treatment for RR-TB across South Africa.Methods and findingsA nationwide retrospective cohort study was conducted to assess second-line treatment initiation and treatment delay among laboratory-diagnosed RR-TB patients. Cohorts, including approximately 300 sequentially diagnosed RR-TB patients per South African province, were drawn from the years 2011 and 2013, i.e., before and after Xpert implementation. Patients with prior laboratory RR-TB diagnoses within 6 mo and currently treated patients were excluded. Treatment initiation was determined through data linkage with national and local treatment registers, medical record review, interviews with health care staff, and direct contact with patients or household members. Additional laboratory data were used to track cases. National estimates of the percentage of patients who initiated treatment and time to treatment were weighted to account for the sampling design.There were 2,508 and 2,528 eligible patients in the 2011 and 2013 cohorts, respectively; 92% were newly diagnosed with RR-TB (no prior RR-TB diagnoses). Nationally, among the 2,340 and 2,311 new RR-TB patients in the 2011 and 2013 cohorts, 55% (95% CI 53%–57%) and 63% (95% CI 61%–65%), respectively, started treatment within 6 mo of laboratory receipt of their diagnostic specimen (p < 0.001). However, in 2013, there was no difference in the percentage of patients who initiated treatment at 6 mo between the 1,368 new RR-TB patients diagnosed by Xpert (62%, 95% CI 59%–65%) and the 943 diagnosed by other methods (64%, 95% CI 61%–67%) (p = 0.39). The median time to treatment decreased from 44 d (interquartile range [IQR] 20–69) in 2011 to 22 d (IQR 2–43) in 2013 (p < 0.001). In 2013, across the nine provinces, there were substantial variations in both treatment initiation (range 51%–73% by 6 mo) and median time to treatment (range 15–36 d, n = 1,450), and only 53% of the 1,448 new RR-TB patients who received treatment were recorded in the national RR-TB register.This retrospective study is limited by the lack of information to assess reasons for non-initiation of treatment, particularly pre-treatment mortality data. Other limitations include the use of names and dates of birth to locate patient-level data, potentially resulting in missed treatment initiation among some patients.ConclusionsIn 2013, there was a large treatment gap for RR-TB in South Africa that v...

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“…With the establishment of molecular approaches in the detection of anti-TB drug resistance, the delay in the diagnosis of MDR-TB could be fundamentally reduced to hours, facilitating early treatment. In South Africa, the time to treatment was reported as 44 days in 2011 and as 22 days in 2013, after Xpert MTB/RIF was introduced (15). Unfortunately, in many countries with a high TB burden, such as China, rapid MDR-TB diagnostic approaches have not been widely implemented.…”

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“…In low-and middle-income countries, 4-38% of patients with laboratory-detected sputum smear-positive or culture-positive TB fail to start treatment (MacPherson et al, 2014), with pre-treatment losses to follow-up being no better with molecular technology. For those who are treated, turnaround times between confirmed diagnosis and treatment initiation can be lengthy, compromising individual care and increasing the risk of Mtb transmission (Cox et al, 2017).…”