BackgroundPatients with tuberculosis require retreatment if they fail or default from initial treatment or if they relapse following initial treatment success. Outcomes among patients receiving a standard World Health Organization Category II retreatment regimen are suboptimal, resulting in increased risk of morbidity, drug resistance, and transmission.. In this study, we evaluated the risk factors for initial treatment failure, default, or early relapse leading to the need for tuberculosis retreatment in Morocco. We also assessed retreatment outcomes and drug susceptibility testing use for retreatment patients in urban centers in Morocco, where tuberculosis incidence is stubbornly high.MethodsPatients with smear- or culture-positive pulmonary tuberculosis presenting for retreatment were identified using clinic registries in nine urban public clinics in Morocco. Demographic and outcomes data were collected from clinical charts and reference laboratories. To identify factors that had put these individuals at risk for failure, default, or early relapse in the first place, initial treatment records were also abstracted (if retreatment began within two years of initial treatment), and patient characteristics were compared with controls who successfully completed initial treatment without early relapse.Results291 patients presenting for retreatment were included; 93% received a standard Category II regimen. Retreatment was successful in 74% of relapse patients, 48% of failure patients, and 41% of default patients. 25% of retreatment patients defaulted, higher than previous estimates. Retreatment failure was most common among patients who had failed initial treatment (24%), and default from retreatment was most frequent among patients with initial treatment default (57%). Drug susceptibility testing was performed in only 10% of retreatment patients. Independent risk factors for failure, default, or early relapse after initial treatment included male gender (aOR = 2.29, 95% CI 1.10-4.77), positive sputum smear after 3 months of treatment (OR 7.14, 95% CI 4.04-13.2), and hospitalization (OR 2.09, 95% CI 1.01-4.34). Higher weight at treatment initiation was protective. Male sex, substance use, missed doses, and hospitalization appeared to be risk factors for default, but subgroup analyses were limited by small numbers.ConclusionsOutcomes of retreatment with a Category II regimen are suboptimal and vary by subgroup. Default among patients receiving tuberculosis retreatment is unacceptably high in urban areas in Morocco, and patients who fail initial tuberculosis treatment are at especially high risk of retreatment failure. Strategies to address risk factors for initial treatment default and to identify patients at risk for failure (including expanded use of drug susceptibility testing) are important given suboptimal retreatment outcomes in these groups.

SettingPublic tuberculosis (TB) clinics in urban Morocco.ObjectiveExplore risk factors for TB treatment default and develop a prediction tool. Assess consequences of default, specifically risk for transmission or development of drug resistance.DesignCase-control study comparing patients who defaulted from TB treatment and patients who completed it using quantitative methods and open-ended questions. Results were interpreted in light of health professionals’ perspectives from a parallel study. A predictive model and simple tool to identify patients at high risk of default were developed. Sputum from cases with pulmonary TB was collected for smear and drug susceptibility testing.Results91 cases and 186 controls enrolled. Independent risk factors for default included current smoking, retreatment, work interference with adherence, daily directly observed therapy, side effects, quick symptom resolution, and not knowing one’s treatment duration. Age >50 years, never smoking, and having friends who knew one’s diagnosis were protective. A simple scoring tool incorporating these factors was 82.4% sensitive and 87.6% specific for predicting default in this population. Clinicians and patients described additional contributors to default and suggested locally-relevant intervention targets. Among 89 cases with pulmonary TB, 71% had sputum that was smear positive for TB. Drug resistance was rare.ConclusionThe causes of default from TB treatment were explored through synthesis of qualitative and quantitative data from patients and health professionals. A scoring tool with high sensitivity and specificity to predict default was developed. Prospective evaluation of this tool coupled with targeted interventions based on our findings is warranted. Of note, the risk of TB transmission from patients who default treatment to others is likely to be high. The commonly-feared risk of drug resistance, though, may be low; a larger study is required to confirm these findings.

BackgroundStandard 24-locus Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat (MIRU-VNTR) typing allows to get an improved resolution power for tracing TB transmission and predicting different strain (sub) lineages in a community.MethodologyDuring 2010–2012, a total of 168 Mycobacterium tuberculosis Complex (MTBC) isolates were collected by cluster sampling from 10 different Moroccan cities, and centralized by the National Reference Laboratory of Tuberculosis over the study period. All isolates were genotyped using spoligotyping, and a subset of 75 was genotyped using 24-locus based MIRU-VNTR typing, followed by first line drug susceptibility testing. Corresponding strain lineages were predicted using MIRU-VNTRplus database.Principal FindingsSpoligotyping resulted in 137 isolates in 18 clusters (2–50 isolates per cluster: clustering rate of 81.54%) corresponding to a SIT number in the SITVIT database, while 31(18.45%) patterns were unique of which 10 were labelled as “unknown” according to the same database. The most prevalent spoligotype family was LAM; (n = 81 or 48.24% of isolates, dominated by SIT42, n = 49), followed by Haarlem (23.80%), T superfamily (15.47%), >Beijing (2.97%), > U clade (2.38%) and S clade (1.19%). Subsequent 24-Locus MIRU-VNTR typing identified 64 unique types and 11 isolates in 5 clusters (2 to 3isolates per cluster), substantially reducing clusters defined by spoligotyping only. The single cluster of three isolates corresponded to two previously treated MDR-TB cases and one new MDR-TB case known to be contact a same index case and belonging to a same family, albeit residing in 3 different administrative regions. MIRU-VNTR loci 4052, 802, 2996, 2163b, 3690, 1955, 424, 2531, 2401 and 960 were highly discriminative in our setting (HGDI >0.6).Conclusions24-locus MIRU-VNTR typing can substantially improve the resolution of large clusters initially defined by spoligotyping alone and predominating in Morocco, and could therefore be used to better study tuberculosis transmission in a population-based, multi-year sample context.

BackgroundTuberculosis (TB) remains a major health problem in Morocco. Characterization of circulating Mycobacterium tuberculosis genotypic lineages, important to understand the dynamic of the disease, was hereby addressed for the first time at a national level.Methodology/Principal FindingsSpoligotyping was performed on a panel of 592 M. tuberculosis complex strains covering a 2-year period (2004–2006). It identified 129 patterns: 105 (n = 568 strains) corresponded to a SIT number in the SITVIT2 database, while 24 patterns were labeled as orphan. A total of 523 (88.3%) strains were clustered vs. 69 or 11.7% unclustered. Classification of strains within 3 large phylogenetical groups was as follows: group 1– ancestral/TbD1+/PGG1 (EAI, Bovis, Africanum), group 2– modern/TbD1−/PGG1 group (Beijing, CAS), group 3– evolutionary recent/TbD1−/PGG2/3 (Haarlem, X, S, T, LAM; alternatively designated as the Euro-American lineage). As opposed to group 3 strains (namely LAM, Haarlem, and T) that predominated (86.5% of all isolates), 6 strains belonged to group 2 (Beijing n = 5, CAS n = 1), and 3 strains (BOV_1 n = 2, BOV_4-CAPRAE) belonged to ancestral group 1 (EAI and AFRI lineage strains were absent). 12-loci MIRU-VNTR typing of the Casablanca subgroup (n = 114 strains) identified 71 patterns: 48 MITs and 23 orphan patterns; it allowed to reduce the clustering rate from 72.8% to 29.8% and the recent transmission rate from 64% to 20.2%.ConclusionThe M. tuberculosis population structure in Morocco is highly homogeneous, and is characterized by the predominance of the Euro-American lineages, namely LAM, Haarlem, and T, which belong to the “evolutionary recent” TbD1−/PGG2/3 phylogenetic group. The combination of spoligotyping and MIRUs decreased the clustering rate significantly, and should now be systematically applied in larger studies. The methods used in this study appear well suited to monitor the M. tuberculosis population structure for an enhanced TB management program in Morocco.

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