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

Autor: Mark P. Nicol, Wendy S. Stevens, Frank Cobelens, Alison D. Grant, Lindy Dickson-Hall, Helen Cox, Norbert Ndjeka, Anja van’t Hoog
Přispěvatelé: APH - Quality of Care, APH - Global Health, AII - Infectious diseases, Global Health, Infectious diseases, APH - Methodology
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Bacterial Diseases
Male
Pediatrics
Research Facilities
Extensively Drug-Resistant Tuberculosis
Drug resistance
Geographical locations
Cohort Studies
South Africa
0302 clinical medicine
Clinical Protocols
Interquartile range
Tuberculosis
Multidrug-Resistant
Medicine and Health Sciences
030212 general & internal medicine
Medical record
HIV diagnosis and management
General Medicine
Middle Aged
3. Good health
Infectious Diseases
Medicine
Tuberculosis Diagnosis and Management
Female
Research Laboratories
Cohort study
Research Article
Adult
medicine.medical_specialty
Tuberculosis
030106 microbiology
Research and Analysis Methods
03 medical and health sciences
Diagnostic Medicine
Drug Resistance
Bacterial
medicine
Humans
Antibiotics
Antitubercular
Retrospective Studies
business.industry
Drug resistant tuberculosis
Extensively drug-resistant tuberculosis
Retrospective cohort study
medicine.disease
Tropical Diseases
Specimen Preparation and Treatment
Africa
People and places
business
Government Laboratories
Zdroj: PLoS medicine, 14(2). Public Library of Science
PLoS Medicine
PLoS Medicine, Vol 14, Iss 2, p e1002238 (2017)
ISSN: 1549-1277
Popis: Background South 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 findings A 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. Conclusions In 2013, there was a large treatment gap for RR-TB in South Africa that varied significantly across provinces. Xpert implementation, while reducing treatment delay, had not contributed substantially to reducing the treatment gap in 2013. However, given improved case detection with Xpert, a larger proportion of RR-TB patients overall have received treatment, with reduced delays. Nonetheless, strategies to further improve linkage to treatment for all diagnosed RR-TB patients are urgently required.
Helen Cox and colleagues investigate whether the treatment gap for rifampicin-resistant tuberculosis has changed following implementation of Xpert MTB/RIF in South Africa.
Author Summary Why was this study done? Tuberculosis (TB) that is resistant to rifampicin, one of the most important first-line TB drugs, is more difficult to treat than drug-susceptible TB and requires treatment with second-line TB drugs. South Africa diagnoses close to 20,000 patients with rifampicin-resistant TB each year, but routine data suggest that a large proportion of these patients do not receive adequate treatment (treatment gap). South Africa has implemented the Xpert MTB/RIF test (a rapid test for TB and rifampicin resistance) for all individuals being investigated for TB. Prior to this, only a subset of TB patients received drug susceptibility testing, and the diagnosis of drug-resistant TB was often delayed, resulting in delayed treatment initiation. In South Africa, the number of diagnosed rifampicin-resistant TB patients is derived from laboratory data, while the number of patients who receive second-line treatment is derived from a separate treatment register. As both of these data sources provide aggregate numbers that are not linked, we do not have an accurate estimate of the proportion of patients who receive second-line treatment. Use of Xpert was expected to both increase case detection for rifampicin-resistant TB and reduce the delay to second-line treatment initiation, thereby increasing the proportion of diagnosed patients who receive treatment. What did the researchers do and find? A retrospective cohort study was conducted to quantify the proportion of diagnosed patients who received second-line treatment and the delay to treatment. Two cohorts of approximately 2,500 patients each were identified: the first in 2011 prior to Xpert implementation and the second in 2013 after Xpert implementation. While treatment initiation increased from 55% in 2011 to 63% in 2013, the percentage of patients starting second-line treatment was low overall and varied considerably across the nine provinces of South Africa. Xpert contributed to a reduction in treatment delay from a median of 44 days in 2011 to 22 days in 2013, but did not significantly improve the proportion receiving treatment. What do these findings mean? Use of Xpert contributes to reduced delays to treatment initiation but does not reduce the treatment gap. However, given improved case detection, a larger proportion of the total population of individuals with rifampicin-resistant TB will receive treatment. Further strategies to improve linkage to treatment for all patients diagnosed with rifampicin-resistant TB are required.
Databáze: OpenAIRE
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