MOLECULAR EPIDEMIOLOGY OF MULTIDRUG RESISTANT TUBERCULOSIS IN MONGOLIA AND EASTERN SIBERIA: TWO INDEPENDENT DISSEMINATION PROCESSES FOR DOMINANT STRAINS

Mongolia and Russia are among the countries with the high tuberculosis (TB) burden. The prevalence of tuberculosis, including multidrug-resistant tuberculosis (MDR), in Eastern Siberia bordering Mongolia is significantly higher than that of in the European part of Russia. In addition, unlike Mongolia, Eastern Siberia is characterized by a high prevalence of HIV infection. The cross-border spread of socially significant infections in these countries seems to be occur due to their wide-range cooperation and cultural exchange. Whereas the HIV infection has no epidemiological significance for Mongolia at the moment, tuberculosis, however, on both sides of the border has a similar prevalence. The aim was to evaluate the cross-border MDR M. tuberculosis distribution in Mongolia and Eastern Siberia by using molecular genetic data.Materials and methods: A total of 1045 M. tuberculosis strains isolated in Mongolia (291) and the three regions of Eastern Siberia (754) were studied by using the MIRU-VNTR - 24 loci genotyping. The CC2/W148 and CC1 subtype was identified by the specific deletion in the kdpD gene and SNP in the pks17 gene at position 1887060, respectively.Phylogenetic analysis of MIRU-VNTR patterns was carried out by generating UPGMA tree and maximum likelihood tree. Results. The Beijing genotype was found in 75.3% (219/291) and 69.0% (520/754) from Mongolian and East Siberian collect ion, respectively. Common minor genotypes were LAM (11.0% and 15.1%), T (10.3% and 4.5%), Haarlem (1.4% and 2.4%) found in Mongolia and Eastern Siberia, respectively. The genotype S (1.3%) and Ural (5.0%) was found solely in the Russia-derived samples. The main epidemic Beijing subtypes in each country belonged to different clonal complexes (CC): the majority of Mongolian Beijing strains displayed profiles 342-32, 3819-32, 1773-32 MLVA types and belonged to the CC4 subtype; Russian Beijing strains mainly belonged to the CC1 (43.7% - 227/520) and CC2/W148 (34.8% - 181/520) subtypes.The MDR level and distribution patterns differed significantly between Mongolia and Eastern Siberia. Modeling of Beijing strain expansion evidences about extremely subtle contribution of the M. tuberculosis cross-border transmission between Mongolia and Russia. The phylogenetic reconstruction of Beijing CC4 subtype evolution in Mongolia suggests that its distribution is primarily associated with China and other countries of the West Pacific region. Three main phylogenetic branches of CC4 subtype were traced, which probably spread throughout Mongolia in the 11-12th centuries. It may be assumed that spread of the epidemic Beijing CC4 subtype might occur in two stages: early period – emergence of ancestral CC4 variants in Mongolia or their introduction from China (they are homologous to the strains preserved in the Chinese population); later period – dissemination due to the active exchange of M. tuberculosis with countries of Southeast Asia, but not Russia.Conclusion. Using MIRU-VNTR 24 genotyping as well as classification according to specific single nucleotide polymorphisms specific to certain Beijing subtypes, it allowed to describe separate patterns of the epidemic variants spread in Mongolia and Russia. It has been demonstrated that emergence and spread of MDR-TB in Mongolia is entirely iatrogenic in nature, while the epidemic subtypes of the Beijing genotype (subtypes CC1 and CC2 / W148) contribute markedly into the MDR-TB spread in Eastern Siberia.

Download Full-text

A joint cross-border investigation of a cluster of multidrug-resistant tuberculosis in Austria, Romania and Germany in 2014 using classic, genotyping and whole genome sequencing methods: lessons learnt

Eurosurveillance ◽

10.2807/1560-7917.es.2017.22.2.30439 ◽

2017 ◽

Vol 22 (2) ◽

Cited By ~ 20

Author(s):

Lena Fiebig ◽

Thomas A Kohl ◽

Odette Popovici ◽

Margarita Mühlenfeld ◽

Alexander Indra ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Universal Access ◽

Multidrug Resistant ◽

Whole Genome ◽

The European Union ◽

Cross Border ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Molecular surveillance of multidrug-resistant tuberculosis (MDR-TB) using 24-loci MIRU-VNTR in the European Union suggests the occurrence of international transmission. In early 2014, Austria detected a molecular MDR-TB cluster of five isolates. Links to Romania and Germany prompted the three countries to investigate possible cross-border MDR-TB transmission jointly. We searched genotyping databases, genotyped additional isolates from Romania, used whole genome sequencing (WGS) to infer putative transmission links, and investigated pairwise epidemiological links and patient mobility. Ten isolates from 10 patients shared the same 24-loci MIRU-VNTR pattern. Within this cluster, WGS defined two subgroups of four patients each. The first comprised an MDR-TB patient from Romania who had sought medical care in Austria and two patients from Austria. The second comprised patients, two of them epidemiologically linked, who lived in three different countries but had the same city of provenance in Romania. Our findings strongly suggested that the two cases in Austrian citizens resulted from a newly introduced MDR-TB strain, followed by domestic transmission. For the other cases, transmission probably occurred in the same city of provenance. To prevent further MDR-TB transmission, we need to ensure universal access to early and adequate therapy and collaborate closely in tuberculosis care beyond administrative borders.

Download Full-text

Thyroid function in multidrug-resistant tuberculosis patients with or without human immunodeficiency virus (HIV) infection before commencement of MDR-TB drug regimen

African Health Sciences ◽

10.4314/ahs.v16i2.30 ◽

2016 ◽

Vol 16 (2) ◽

pp. 596 ◽

Cited By ~ 2

Author(s):

Olusoji Mayowa Ige ◽

Kehinde Sola Akinlade ◽

Sheu Kadiri Rahamon ◽

Victory Fabian Edem ◽

Olatunbosun Ganiyu Arinola

Keyword(s):

Human Immunodeficiency Virus ◽

Hiv Infection ◽

Thyroid Function ◽

Drug Regimen ◽

Multidrug Resistant ◽

Tuberculosis Patients ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Immunodeficiency Virus ◽

Mdr Tb

Download Full-text

Faculty Opinions recommendation of Development and evaluation of a pilot nurse case management model to address multidrug-resistant tuberculosis (MDR-TB) and HIV in South Africa.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725239549.793504303 ◽

2015 ◽

Author(s):

Rannakoe Lehloenya

Keyword(s):

South Africa ◽

Case Management ◽

Multidrug Resistant ◽

Management Model ◽

Nurse Case Management ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Download Full-text

Multidrug-Resistant Tuberculosis (MDR-TB) Control Activities in Kano State, North West Nigeria: Progress so Far

TEXILA INTERNATIONAL JOURNAL OF PUBLIC HEALTH ◽

10.21522/tijph.2013.se.19.02.art002 ◽

2019 ◽

pp. 6-12

Author(s):

Musa K. Bawa

Keyword(s):

Multidrug Resistant ◽

North West ◽

Tb Control ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Download Full-text

The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China

BMC Medicine ◽

10.1186/s12916-021-01932-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Chathika K Weerasuriya ◽

Rebecca C Harris ◽

C Finn McQuaid ◽

Fiammetta Bozzani ◽

Yunzhou Ruan ◽

...

Keyword(s):

Cost Effectiveness ◽

Cost Effective ◽

Multidrug Resistant ◽

Second Line ◽

Second Line Therapy ◽

China And India ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Line Therapy ◽

Mdr Tb

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

Download Full-text

PP581 Catastrophic Costs Of Multidrug-Resistant Tuberculosis: Estimation Based On The Cost Of Treatment In China

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462320002032 ◽

2020 ◽

Vol 36 (S1) ◽

pp. 43-43

Author(s):

Lijun Shen ◽

Shangshang Gu ◽

Fan Zhang ◽

Zhao Liu ◽

Yuehua Liu

Keyword(s):

Market Price ◽

Multidrug Resistant ◽

Policy Support ◽

World Health ◽

Chinese Patients ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Drug Affordability ◽

The Cost

IntroductionChina bears a considerably high burden of multidrug-resistant tuberculosis (MDR-TB). Second-line anti-TB drugs are urgently needed yet domestic MDR-TB drugs are expensive and lack policy support. Patients’ living conditions are closely related to the drug affordability. The national TB prevention programs should play a critical role. The purpose of this study is to measure the cost of treating MDR-TB patients under different treatment schemes and price sources. The results of this study are expected to inform the relevant drug protection policies and provide inputs for further cost-effectiveness analyses.MethodsBased on the treatment plan of China's Multidrug-Resistant Pulmonary Tuberculosis Clinical Path (2012 edition) and the World Health Organization (WHO) Drug-Resistant Tuberculosis Treatment Guide (2018 edition), the treatment costs of MDR-TB were measured under different scenarios. Catastrophic health expenditure was then calculated if the treatment cost exceeds 40 percent of the household's non-subsistence income. National, rural and disposable income per capita in 2018, were used to represent Chinese patients’ affordability.ResultsUnder varied treatment schemes and market price sources in China, the total costs for MDR-TB patients range from 19,401 to 126,703 CNY [2,853 to 18,633 USD] per person. Under current prices, all treatment schemes recommended by the WHO will incur catastrophic costs for Chinese MDR-TB patients. Significant differences were found between rural and urban areas as 52.8 percent of the treatment listed in the 2012 China Guideline would lead to catastrophic cost for rural patients but not urban ones.ConclusionsOur study concludes that the domestic drugs are more expensive than the international purchase price and the treatment of MDR-TB imposes substantial economic burden on patients, especially in the rural areas. The results of the study also indicate that it is urgent for the state to emphasize government responsibility and initiate centralized procurement for price negotiations to reduce the market price of MDR-TB drugs. The urban-rural gap should also be addressed in the design of future policies to ensure the drug affordability for all patients in need.

Download Full-text

Correction to: HIV infection and multidrug resistant tuberculosis: a systematic review and meta-analysis

BMC Infectious Diseases ◽

10.1186/s12879-021-05799-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zeeba Zahra Sultana ◽

Farhana Ul Hoque ◽

Joseph Beyene ◽

Md. Akhlak-Ul-Islam ◽

Md Hasinur Rahman Khan ◽

...

Keyword(s):

Systematic Review ◽

Hiv Infection ◽

Meta Analysis ◽

Multidrug Resistant ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis

An amendment to this paper has been published and can be accessed via the original article.

Download Full-text

Outcomes of Community-Based Systematic Screening of Household Contacts of Patients with Multidrug-Resistant Tuberculosis in Myanmar

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed5010002 ◽

2019 ◽

Vol 5 (1) ◽

pp. 2

Author(s):

Nang Thu Thu Kyaw ◽

Aung Sithu ◽

Srinath Satyanarayana ◽

Ajay M. V. Kumar ◽

Saw Thein ◽

...

Keyword(s):

Chest Radiography ◽

Multidrug Resistant ◽

Sputum Smear ◽

Community Based ◽

Household Contacts ◽

Resistant Tuberculosis ◽

Symptom Screening ◽

Multidrug Resistant Tuberculosis ◽

Screening Algorithm ◽

Mdr Tb

Screening of household contacts of patients with multidrug-resistant tuberculosis (MDR-TB) is a crucial active TB case-finding intervention. Before 2016, this intervention had not been implemented in Myanmar, a country with a high MDR-TB burden. In 2016, a community-based screening of household contacts of MDR-TB patients using a systematic TB-screening algorithm (symptom screening and chest radiography followed by sputum smear microscopy and Xpert-MTB/RIF assays) was implemented in 33 townships in Myanmar. We assessed the implementation of this intervention, how well the screening algorithm was followed, and the yield of active TB. Data collected between April 2016 and March 2017 were analyzed using logistic and log-binomial regression. Of 620 household contacts of 210 MDR-TB patients enrolled for screening, 620 (100%) underwent TB symptom screening and 505 (81%) underwent chest radiography. Of 240 (39%) symptomatic household contacts, 71 (30%) were not further screened according to the algorithm. Children aged <15 years were less likely to follow the algorithm. Twenty-four contacts were diagnosed with active TB, including two rifampicin- resistant cases (yield of active TB = 3.9%, 95% CI: 2.3%–6.5%). The highest yield was found among children aged <5 years (10.0%, 95% CI: 3.6%–24.7%). Household contact screening should be strengthened, continued, and scaled up for all MDR-TB patients in Myanmar.

Download Full-text