Recent Publications (from our May 2020 newsletter)

1. Progress in the roll-out of multidrug-resistant tuberculosis (MDR-TB) treatments.
Int J Tuberc Lung Dis. 2020 May 1;24(5):535-536. doi: 10.5588/ijtld.19.0717.

Heng M(1), Allmendinger S(1), Chiang CY(2), Trébucq A(2), Horsburgh CR(1).

Please see this document. Corrections to this publication are in-press for next month’s IJTLD issue.

2. Challenges in TB regimen development: preserving evidentiary standards for regulatory decisions and policymaking.
Expert Rev Anti Infect Ther. 2020 Apr 28:1-3. doi:
10.1080/14787210.2020.1756776. Online ahead of print.

Guglielmetti L(1)(2)(3), Low M(4)(5)(6), McKenna L(5)(7).

DOI: 10.1080/14787210.2020.1756776
PMID: 32345064

Read the full article here.

3. High prevalence of hepatitis C infection among multidrug-resistant tuberculosis patients.
J Hepatol. 2020 May;72(5):1028-1029. doi: 10.1016/j.jhep.2019.10.018. Epub 2020
Mar 6.

Seung KJ(1), Franke MF(2), Hewison C(3), Huerga H(4), Khan U(5), Mitnick CD(6);
end TB Study Group.

DOI: 10.1016/j.jhep.2019.10.018
PMID: 32147086

Conflict of interest statement: Conflict of interest The endTB Consortium
coordinated donations of delamanid (Otsuka Pharmaceutical) and bedaquiline
(Janssen) to be used for treatment by some of the patients included in the endTB
Observational Study. All authors report no additional potential conflicts of
interest. Please refer to the accompanying ICMJE disclosure forms for further
details. 

Read the full article here.
4. Challenges in Tuberculosis Clinical Trials in the Face of the COVID-19 Pandemic: A Sponsor’s PerspectiveTrop. Med. Infect. Dis.20205(2), 86; https://doi.org/10.3390/tropicalmed5020086 (registering DOI)

I.D. Rusen

The COVID-19 pandemic has caused unforeseen and extreme changes in societal and health system functioning not previously experienced in most countries in a lifetime. The impact of the pandemic on clinical trials can be especially profound given their complexities and operational requirements. The STREAM Clinical Trial is the largest trial for MDR-TB ever conducted. Currently operating in seven countries, the trial had 126 participants on treatment and 312 additional participants in active follow up as of March 31, 2020. Areas of particular concern during this global emergency include treatment continuity, supply chain management and participant safety monitoring. This commentary highlights some of the challenges faced due to the pandemic and the steps taken to protect the safety of trial participants and the integrity of the trial.

Read the full article here.

5. Neurocognitive functioning in MDR-TB patients with and without HIV in KwaZulu-Natal, South Africa.
Trop Med Int Health. 2020 May 19. doi: 10.1111/tmi.13444. Online ahead of print.

Ramlall S(1), Lessells RJ(2)(3), Naidu T(4), Sandra Mthembu S(5), Padayachi
N(3), Burns JK(1)(6), Tomita A(2)(7).

OBJECTIVES: Optimizing medication adherence is one of the essential factors in
reversing the tide of a TB-HIV syndemic in sub-Saharan Africa, especially South
Africa. Impairment in key neurocognitive domains may impair patients’ ability to
maintain adherence to treatment, but the level of cognition and its relationship
to HIV status has not been examined in individuals with drug-resistant TB. We
therefore investigated performance on several key neurocognitive domains in
relationship to HIV status in a sample of multi-drug resistant (MDR-TB).
METHODS: We enrolled microbiologically confirmed MDR-TB inpatients at a
TB-specialist referral hospital in KwaZulu-Natal province, South Africa. We
collected cross-sectional data on sociodemographic, clinical, and neurocognitive
function (e.g. attention, memory, executive functioning, language fluency,
visual-spatial, eye-hand coordination). For the primary analysis, we excluded
participants with major depressive episode/substance use disorder (MDE/SUD). We
fitted adjusted Poisson regression models to explore the association between HIV
and neurocognitive function.
RESULTS: We enrolled 200 people with MDR-TB; 33 had MDE/SUD, and data of 167
were analyzed (151 HIV+, 16 HIV-). The mean age of participants was 34.2 years;
the majority were female (83%), and 53% had not completed secondary school.
There was evidence of impaired neurocognitive functioning across all domains in
both HIV+/- study participants. Based on the regression analyses, individuals
with co-infection (MDR-TB/HIV+), as well as those who had longer duration of
hospital stays experienced significantly lower cognitive performance in several
domains. Poor cognitive performance was significantly related to older age and
lower educational attainment. The presence of major depression or substance use
disorders did not influence the significance of the findings.
CONCLUSIONS: Adults with MDR-TB have significant neurocognitive impairment,
especially if HIV positive. An integrated approach is necessary in the
management of MDR-TB as cognitive health influences the ability to adhere to
chronic treatment, clinical outcomes and functionality.

This article is protected by copyright. All rights reserved.

DOI: 10.1111/tmi.13444
PMID: 32428324

This article is not available via OpenAccess.

6. Pattern of InhA and KatG mutations in isoniazid monoresistant Mycobacterium tuberculosis isolates.
Lung India. 2020 May-Jun;37(3):227-231. doi: 10.4103/lungindia.lungindia_204_19.

Charan AS(1), Gupta N(1), Dixit R(1), Arora P(1), Patni T(2), Antony K(1), Singh
M(3).

AIMS AND OBJECTIVES: The aim of the study is to detect the pattern of genetic
mutation, i.e., Inh A or Kat G or both (Inh A and kat G) in isoniazid (INH)
monoresistant mycobacteria and to correlate with the pattern in
multidrug-resistant (MDR) isolates.
MATERIALS AND METHODS: In this study, a quantitative research approach was used.
The research design was descriptive observational study. The study was conducted
at the Department of Respiratory Medicine, JLN Medical College, Ajmer,
Rajasthan, and Intermediate Referral Laboratory, State TB Demonstration Centre,
Ajmer. A total of 298 samples found to have resistant strains of Mycobacterium
tuberculosis were enrolled with purposive sampling.
RESULTS: The mean age of patients was 40.27 ± 13.82 years. There were 250
(83.9%) males, while 48 (16.1%) were females. One hundred ninety-two (64.4%)
were resistant for INH only, while the rest were resistant to both INH as well
as rifampicin (MDR-tuberculosis). The most common mutation in INH monoresistance
was kat G (125; 65.1%) as compared to inh A (54; 28.1%) and both inh A and kat G
(13; 6.7%). Among kat G mutations, the most common gene pattern was the absence
of WT (S315T) and the presence of MUT1 (S315T1).
CONCLUSION: Knowledge about mutation patterns of different INH resistant strains
is important in the present era where there is a provision of separate regimens
for INH monoresistant TB. Since these mutations are very closely related to
high- or low-degree resistance to INH, the therapeutic regimens cannot be
generalized.

DOI: 10.4103/lungindia.lungindia_204_19
PMID: 32367844

Read the full article here.