Multidrug-resistant  Mycobacterium tuberculosis : a report of cosmopolitan microbial migration and an analysis of best management practices

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Abstract

Background

Tuberculosis (TB) control is a primary global health priority but the goal to eliminate TB is being threatened by the increase in incidence of multidrug-resistant tuberculosis (MDR-TB). With this series of seven MDR-TB cases in migrant patients with identical Mycobacterium tuberculosis strains we aim to illustrate the challenges encountered during therapy and follow-up: language barriers, access to care for migrant patients, depression due to isolation, adverse reactions to the treatment, management of pediatric TB, further contact tracing. We also discuss best practices for the management of complex MDR-TB cases in settings with low overall TB incidence focusing on modern diagnostic assays and an individualized and an interdisciplinary therapeutic approach.

Methods

We describe a case series of seven consecutively diagnosed MDR-TB patients, six of them treated at our tertiary care hospital between May 2018 and March 2020. Epidemiologic data was gained by semi-structured patient interviews and reconstruction of the migration route. The origin of the cluster was confirmed by genotyping of the TB-strains.

Results

Six related patients were diagnosed with pulmonary MDR-TB between May and August 2018. All had a positive Interferon-Gamma-Release Assay (IGRA), in five patients sputum microscopy was positive for acid-fast bacilli (AFB). The genetic and phenotypical drug susceptibility test did not match with MDR-TB strains from an East-African origin. The index patient was identified through genetical fingerprinting. By changing the therapy to a modern MDR-TB regime and using an interdisciplinary and culture-sensitive approach, all patients improved clinically and radiologically.

Conclusion

Human migration plays an important role for the global spread of MDR-TB in low incidence countries. Early case detection and adequate treatment are key to prevention of outbreaks. Especially language barriers and complex migration routes make genotyping of TB-strains a crucial tool to identify cases clusters, the potential index patient and transmission dynamics. We are fortunate enough to experience times in which new TB-antibiotics were made available and in which molecular assays revolutionized TB-diagnostics. We need to take advantage of that and develop personalized therapies for patients suffering from drug resistant TB.

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Most cited references 25

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Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis

Parvaneh Baghaei, Mathilde Fréchet-Jachym, Gregory Fox … (2018)

Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis.

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The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era.

B J Marais, R Gie, H Schaaf … (2004)

The pre-chemotherapy literature documented the natural history of tuberculosis in childhood. These disease descriptions remain invaluable for guiding public health policy and research, as the introduction of effective chemotherapy radically changed the history of disease. Specific high-risk groups were identified. Primary infection before 2 years of age frequently progressed to serious disease within the first 12 months without significant prior symptoms. Primary infection between 2 and 10 years of age rarely progressed to serious disease, and such progression was associated with significant clinical symptoms. In children aged >3 years the presence of symptoms represented a window of opportunity in which to establish a clinical diagnosis before serious disease progression. Primary infection after 10 years of age frequently progressed to adult-type disease. Early effective intervention in this group will reduce the burden of cavitating disease and associated disease transmission in the community. Although the pre-chemotherapy literature excluded the influence of human immune deficiency virus (HIV) infection, recent disease descriptions in HIV-infected children indicate that immune-compromised children behave in a similar fashion to immune immature children (less than 2 years of age). An important concept deduced from the natural history of tuberculosis in childhood is that of relevant disease. Deciding which children to treat may be extremely difficult in high-prevalence, low-resource settings. The concept of relevant disease provides guidance for more effective public health intervention.

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DNA Sequencing Predicts 1st-Line Tuberculosis Drug Susceptibility Profiles

Caroline Allix-Beguec, Irena Arandjelovic, Lijun Bi … (2018)

Background The World Health Organization recommends universal drug susceptibility testing for Mycobacterium tuberculosis complex to guide treatment decisions and improve outcomes. We assessed whether DNA sequencing can accurately predict antibiotic susceptibility profiles for first-line anti-tuberculosis drugs. Methods Whole-genome sequences and associated phenotypes to isoniazid, rifampicin, ethambutol and pyrazinamide were obtained for isolates from 16 countries across six continents. For each isolate, mutations associated with drug-resistance and drug-susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These were predicted to be pan-susceptible if predicted susceptible to isoniazid and to other drugs, or contained mutations of unknown association in genes affecting these other drugs. We simulated how negative predictive value changed with drug-resistance prevalence. Results 10,209 isolates were analysed. The greatest proportion of phenotypes were predicted for rifampicin (9,660/10,130; (95.4%)) and the lowest for ethambutol (8,794/9,794; (89.8%)). Isoniazid, rifampicin, ethambutol and pyrazinamide resistance was correctly predicted with 97.1%, 97.5% 94.6% and 91.3% sensitivity, and susceptibility with 99.0%, 98.8%, 93.6% and 96.8% specificity, respectively. 5,250 (89.5%) drug profiles were correctly predicted for 5,865/7,516 (78.0%) isolates with complete phenotypic profiles. Among these, 3,952/4,037 (97.9%) predictions of pan-susceptibility were correct. The negative predictive value for 97.5% of simulated drug profiles exceeded 95% where the prevalence of drug-resistance was below 47.0%. Conclusions Phenotypic testing for first-line drugs can be phased down in favour of DNA sequencing to guide anti- tuberculosis drug therapy.

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Author and article information

Contributors

Oana Joean:

ORCID: http://orcid.org/0000-0002-5995-4605

Joean.Oana@mh-hannover.de

Journal

Journal ID (nlm-ta): BMC Infect Dis

Journal ID (iso-abbrev): BMC Infect. Dis

Title: BMC Infectious Diseases

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2334

Publication date (Electronic): 17 September 2020

Publication date PMC-release: 17 September 2020

Publication date Collection: 2020

Volume: 20

Electronic Location Identifier: 678

Affiliations

[1 ]GRID grid.10423.34, ISNI 0000 0000 9529 9877, Department for Rheumatology and Clinical Immunology, , Hannover Medical School, ; Hannover, Germany

[2 ]GRID grid.10423.34, ISNI 0000 0000 9529 9877, Department of Respiratory Medicine, , Hannover Medical School, ; Carl-Neuberg-Str 1, 30625 Hannover, Germany

[3 ]GRID grid.10423.34, ISNI 0000 0000 9529 9877, Department of Pediatric Pneumology, Allergy and Neonatology, , Hannover Medical School, ; Hannover, Germany

[4 ]GRID grid.10423.34, ISNI 0000 0000 9529 9877, Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, ; Hannover, Germany

[5 ]GRID grid.418187.3, ISNI 0000 0004 0493 9170, Division of Clinical Infectious Diseases, Research Center Borstel, ; Borstel, Germany

[6 ]GRID grid.452463.2, German Center for Infection Research, Clinical Tuberculosis Center, ; Borstel, Germany

Author information

Oana Joean http://orcid.org/0000-0002-5995-4605

Article

Publisher ID: 5381

DOI: 10.1186/s12879-020-05381-0

PMC ID: 7499973

PubMed ID: 32942990

SO-VID: 0c76baf0-6d9d-491f-85e1-df965a4e08d0

License:

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