From our December 2019 Newsletter


1. Projecting the impact of variable MDR-TB transmission efficiency on long-term epidemic trends in South Africa and Vietnam.
Sci Rep. 2019 Dec 2;9(1):18099. doi: 10.1038/s41598-019-54561-9.

Salvatore PP(1), Kendall EA(2), Seabrook D(3), Brown J(3), Durham GH(3), Dowdy

Whether multidrug-resistant tuberculosis (MDR-TB) is less transmissible than
drug-susceptible (DS-)TB on a population level is uncertain. Even in the absence
of a genetic fitness cost, the transmission potential of individuals with MDR-TB
may vary by infectiousness, frequency of contact, or duration of disease. We used
a compartmental model to project the progression of MDR-TB epidemics in South
Africa and Vietnam under alternative assumptions about the relative transmission
efficiency of MDR-TB. Specifically, we considered three scenarios: consistently
lower transmission efficiency for MDR-TB than for DS-TB; equal transmission
efficiency; and an initial deficit in the transmission efficiency of MDR-TB that
closes over time. We calibrated these scenarios with data from drug resistance
surveys and projected epidemic trends to 2040. The incidence of MDR-TB was
projected to expand in most scenarios, but the degree of expansion depended
greatly on the future transmission efficiency of MDR-TB. For example, by 2040, we
projected absolute MDR-TB incidence to account for 5% (IQR: 4-9%) of incident TB
in South Africa and 14% (IQR: 9-26%) in Vietnam assuming consistently lower
MDR-TB transmission efficiency, versus 15% (IQR: 8-27%)and 41% (IQR: 23-62%),
respectively, assuming shrinking transmission efficiency deficits. Given future
uncertainty, specific responses to halt MDR-TB transmission should be

DOI: 10.1038/s41598-019-54561-9
PMID: 31792289

Read the full article here.

2. Drug-resistant tuberculosis in eastern Europe and central Asia: a time-series analysis of routine surveillance data.
Lancet Infect Dis. 2019 Nov 26. pii: S1473-3099(19)30568-7. doi:
10.1016/S1473-3099(19)30568-7. [Epub ahead of print]

Dadu A(1), Hovhannesyan A(1), Ahmedov S(2), van der Werf MJ(3), Dara M(4).

BACKGROUND: Among all WHO regions, the WHO European Region has the highest
proportion of drug-resistant tuberculosis among new and retreated cases. The 18
high-priority countries in eastern Europe and central Asia account for 85% of the
tuberculosis incidence and more than 90% of drug-resistant tuberculosis cases
emerging in the region. We aimed to analyse time-series trends in notification
rates of drug-resistant tuberculosis among new tuberculosis cases in the 18
high-priority countries in the WHO European Region.
METHODS: We used country data stored in WHO’s global tuberculosis database. For
each country, we calculated annual notification rates per 100 000 population of
new tuberculosis cases and of drug-resistant tuberculosis among new cases
reported from Jan 1, 2000, to Dec 31, 2017. We computed annual percentage changes
of notification rates and identified time-points of significant change in trends
using the joinpoint regression method.
FINDINGS: All 17 countries with data (no data available from Turkmenistan) showed
a significant decline in new tuberculosis notification rates in the most recent
years since the last joinpoint if one was identified. Notification rates of
drug-resistant tuberculosis showed diverse trends, with substantial year-to-year
variation. In the most recent years, notification rates of drug-resistant
tuberculosis among new tuberculosis cases were decreasing in two countries
(Estonia and Latvia), increasing in eight countries (Azerbaijan, Kyrgyzstan,
Moldova [Republic of Moldova], Romania, Russia [Russian Federation], Tajikistan,
Ukraine, and Uzbekistan), and stable in seven countries (Armenia, Belarus,
Bulgaria, Georgia, Kazakhstan, Lithuania, and Turkey).
INTERPRETATION: Our findings suggest that countries in the WHO European Region
are more successful in controlling drug-susceptible tuberculosis than
drug-resistant forms, and as a result, the proportion of drug-resistant strains
among newly notified patients with tuberculosis is increasing in many settings.
Two countries showed that it is possible to decrease incidence of both
drug-susceptible and drug-resistant tuberculosis. If no additional efforts are
made in prevention and care of patients with drug-resistant tuberculosis, further
decline of the tuberculosis burden will be halted. Further studies are needed to
investigate the success stories and document the most effective interventions to
reach the target to end tuberculosis by 2030.
FUNDING: United States Agency for International Development.

Copyright © 2019 World Health Organization. Published by Elsevier Ltd. All rights
reserved. Published by Elsevier Ltd.. All rights reserved.

DOI: 10.1016/S1473-3099(19)30568-7
PMID: 31784371

This article is not available via open access.

3. Clinical Characteristics of Active Tuberculosis Diagnosed after Starting Treatment for Latent Tuberculosis Infection.
Clin Infect Dis. 2019 Nov 27. pii: ciz1157. doi: 10.1093/cid/ciz1157. [Epub ahead
of print]

Flynn AG(1)(2), Aiona K(3), Haas MK(2)(3), Reves R(2), Belknap R(2)(3).

BACKGROUND: Efforts to expand treatment of latent tuberculosis infection (LTBI)
raise concerns for missed subclinical active tuberculosis (TB) and acquired
METHODS: We conducted a retrospective cohort review of patients who began LTBI
therapy between January 1, 2006 and December 31, 2017 at the Denver Metro TB
Clinic, Colorado, USA. Electronic databases and chart review were used for data
collection. Subsequent active TB diagnoses in this cohort were determined using
the state of Colorado TB database through June 30, 2018.
RESULTS: 8472 patients started LTBI treatment during the study period with 46%
prescribed nine months of isoniazid and 43% four months of rifampin. 24 (0.28%)
developed active TB, 10 during and 14 after LTBI therapy. Culture confirmation
was obtained for 13 (54%) and none had acquired drug-resistance. Patients
diagnosed during (n=10) versus after treatment (n=14) were less likely to be
culture-confirmed (30% versus 71%) and less likely to have pulmonary disease (20%
vs 57%).
CONCLUSIONS: Subclinical TB missed by symptom screening and chest radiography was
rare in our mostly HIV-negative cohort. Culture negative, extrapulmonary disease
was more common with TB diagnosed during than after LTBI treatment. We found no
evidence for acquired drug resistance in LTBI patients subsequently diagnosed
with active TB.

© The Author(s) 2019. Published by Oxford University Press for the Infectious
Diseases Society of America. All rights reserved. For permissions, e-mail:

DOI: 10.1093/cid/ciz1157
PMID: 31773132

This article is not available via open access.

4. Treatment of multidrug-resistant tuberculosis using therapeutic drug monitoring: first experiences with sub-300 mg linezolid dosages using in-house made capsules.
Eur Respir J. 2019 Dec 4;54(6). pii: 1900580. doi: 10.1183/13993003.00580-2019.
Print 2019 Dec.

Bolhuis MS(1), van der Werf TS(2)(3), Kerstjens HAM(2)(4), de Lange WCM(2)(4),
Alffenaar JC(5)(6), Akkerman OW(2)(4).

Despite all our efforts, the disease burden of tuberculosis (TB) is not falling fast enough to reach the 2030 milestone of the End TB strategy [1]. Multidrug-resistant tuberculosis (MDR-TB) remains a public health crisis, with low treatment success rates [1]. The repurposed drug linezolid has emerged as a core drug in MDR-TB treatment regimens [2, 3], despite its toxicity, e.g. anaemia, peripheral neuropathy and gastrointestinal disorders, optic neuritis, and thrombocytopenia [4, 5]. Currently, linezolid is used off-label, as part of Group A “Medicines to be prioritised” of the World Health Organization (WHO) MDR-TB treatment guideline [2] and in several large trials [6], such as the NIX-TB and END-TB trials.

DOI: 10.1183/13993003.00580-2019
PMID: 31439686

This article is not available via open access.