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Table of Contents
July-September 2021
Volume 10 | Issue 3
Page Nos. 217-348
Online since Friday, September 3, 2021
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REVIEW ARTICLE
Nontuberculous mycobacterium: An emerging pathogen: Indian perspective
p. 217
Priya Rajendran, Chandrasekaran Padmapriyadarsini, Rajesh Mondal
DOI
:10.4103/ijmy.ijmy_141_21
PMID
:34494559
Nontuberculous mycobacteria (NTM), considered as mere contaminants, are off late, being reported as potential pathogens through various studies. The infections due to NTM range from pulmonary to extra pulmonary including skin and soft-tissue infections, traumatic and surgical wound infections, and catheter and implant-associated infections. Although extrapulmonary infections are extensively explored, pulmonary infections are scarcely reported due to their misdiagnosis as tuberculosis caused by
M. tuberculosis
(MTB). Appropriate detection methods are essential in order to facilitate the differential diagnosis of NTM from MTB infections. We aimed to collate the data available on NTM diagnosis and its epidemiology in India in this review. While diagnosis of MTB itself is more challenging in India, for appropriate treatment of NTM, special training and attention is needed for differential diagnosis of the former from latter. Currently, in India, in addition to the available techniques for identification of NTM, line probe assay (Hains life sciences) is proving to be a promising tool for the detection of NTM (common mycobacteria/additional species kit) and their antimicrobial resistance (Genotype NTM-DR VER 1.0). In future, with the price of sequencing steadily coming down, with proper monitoring, whole-genome sequencing could be the test of choice to predict the species, drug resistance, outbreaks in hospitals, and transmission dynamics.
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ORIGINAL ARTICLES
Evaluation of intracranial vasculitis in tuberculous meningitis using magnetic resonance vessel wall imaging technique
p. 228
Harshad Arvind Vanjare, Karthik Gunasekaran, Abi Manesh, Ajay Kumar Mishra, Pavithra Mannam, Ramya Iyadurai, Anitha Jasper, Sunithi Mani
DOI
:10.4103/ijmy.ijmy_117_21
PMID
:34494560
Background:
Tuberculous meningitis (TBM) is a global health problem with important complications such as acute infarcts secondary to vasculitis contributing to adverse outcomes. The objective of this study is to assess intracranial vasculitis in patients with TBM, either during their initial diagnosis or during follow-up while on standard antituberculous therapy.
Methods:
Ten patients with TBM underwent magnetic resonance (MR) based vessel wall imaging (VWI) to identify intracranial vasculitis (five patients during their initial presentation and the other five patients during their follow-up visit).
Results:
Vasculitis was seen in 60% of the patients wherein 70% of their intracranial vessels were affected. Acute and chronic infarcts were seen in four and two patients respectively, one of whom had both acute and chronic infarcts. Leptomeningeal enhancement and basal cisternal tuberculomas were frequently seen in patients with vasculitis. Vasculitis was also seen many days after the commencement of the antituberculous therapy thus explaining late-onset infarcts in this disease.
Conclusion:
Intracranial vasculitis is common in the patient with TBM. MR-based VWI technique has the potential for infarct risk assessment and to help guide the treatment for its possible prevention.
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Spatiotemporal analysis and seasonality of tuberculosis in Algeria
p. 234
Schehrazad Selmane, Mohamed L’hadj
DOI
:10.4103/ijmy.ijmy_111_21
PMID
:34494561
Background:
This study aimed to describe the spatiotemporal distribution, to build a forecasting model, and to determine the seasonal pattern of tuberculosis (TB) in Algeria.
Methods:
The Box–Jenkins methodology was used to develop predictive models and GeoDa software was used to perform spatial autocorrelation.
Results:
Between 1982 and 2019, the notification rate per 100,000 population of smear-positive pulmonary TB (SPPTB) has dropped 62.2%, while that of extrapulmonary TB (EPTB) has risen 91.3%. For the last decade, the mean detection rate of PTB was 82.6%. At around, 2% of PTB cases were yearly reported in children under 15 years old, a peak in notification rate was observed in the elderly aged 65 and over, and the sex ratio was in favor of men. Between 52% and 59% of EPTB cases were lymphadenitis TB and between 15% and 23% were pleural TB. About two-third of EPTB cases were females and around 10% were children under the age of 15. The time series analysis showed that (1,1, 2) × (1, 1, 0)4 (respectively (0, 1, 2) × (1, 1, 0)4, (3, 1, 0) × (1, 1, 0)4) offered the best forecasting model to quarterly TB (respectively EPTB, SPPTB) surveillance data. The most hit part was the Tell followed by high plateaus which accounted for 96.6% of notifications in 2017. Significant hot spots were identified in the central part for EPTB notification rate and in the northwestern part for SPPTB.
Conclusions:
There is a need to reframe the set objectives in the state strategy to combat TB taking into account seasonality and spatial clustering to ensure improved TB management through targeted and effective interventions.
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Ethnicity based comprehensive evaluation of polymorphism in interferon-gamma gene and its association with pulmonary and extra-pulmonary tuberculosis risk: An updated trial sequential meta-analysis
p. 243
Priyanka , Monika Sharma, Sadhna Sharma
DOI
:10.4103/ijmy.ijmy_108_21
PMID
:34494562
Background:
Host genetic background plays an important role in susceptibility to intracellular infectious pathogens like
Mycobacterium tuberculosis
(Mtb). Cellular immune response activation is vital for protection to these pathogens. Interferon-gamma (IFN-γ) plays a crucial role in this activation and preventing the intracellular growth of Mtb. A mutation in the IFN-γ gene, therefore, may lead to increased susceptibility to tuberculosis (TB) that may vary in different ethnic groups and its consequence also varies in pulmonary and extra-pulmonary TB (EPTB). Several IFN-γ gene polymorphisms are investigated for susceptibility to TB, but their associations are not always consistent as its impact may vary from one ethnicity to the other as well as with the type of TB. Hence, we performed a meta-analysis to overcome this problem. The present study involves comprehensive meta-analysis of + 874T/A polymorphism in the IFN-γ gene based on type of TB within five different ethnic groups to show its association with increased susceptibility to TB.
Methods:
Using PubMed and Google Scholar databases, a total of 50 case-control studies were retrieved having 8152 cases and 9755 controls in this meta-analysis. Thirty-eight studies of + 874T/A polymorphism of IFN-γ gene were correlated for Pooled odds ratios with 95% confidence intervals. The polymorphism was analyzed for six genetic models for five major ethnic groups accounting for heterogeneity among studies. Moreover, the sub-group analysis was based on the type of TB within each ethnic group. Trial sequential analysis was also performed for all the sub-groups to estimate the statistical consistency.
Results:
IFN-γ +874 T/A polymorphism analysis clearly confirmed the increased association of + 874AA genotype with increased TB risk. This polymorphism also showed significant association in East Asian, European, American, and African ethnic groups whereas no such association was found in Asians. Patients with pulmonary TB (PTB) confirmed the association in East Asians, Africans, and Americans, whereas patients with EPTB showed association in Asian and East Asian populations only.
Conclusions:
This study reaffirms the association of IFN-γ+874 T/A polymorphism with TB risk. It specifically confirms that IFN-γ+874 T/A polymorphism increases the susceptibility of pulmonary infection in Africans and Americans, while the East Asian population is more susceptible to both, pulmonary and EPTB.
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Programmatic challenges in managing multidrug-resistant tuberculosis in Malawi
p. 255
Loveness Charlie, Bibie Saidi, Emnet Getachew, Cathreen Lydiah Wanjiru, Mekdelawit Abebe, Hanna Amanuel Tesfahunei, Mary Gorret Atim, Tsegahun Manyazewal, Ronald Nachipo Mlera
DOI
:10.4103/ijmy.ijmy_47_21
PMID
:34494563
Background:
Multidrug-resistant tuberculosis (MDR-TB) is one of the most urgent challenges that Malawi tends to take a firm public health action. A recent increase in multidrug MDR-TB cases, a decrease in treatment success rate, and a double increase of lost-to-follow-up call into question the country's programmatic management of MDR-TB (PMDT). As such, the study aimed at exploring programmatic challenges in managing MDR-TB in Malawi.
Methods:
A comprehensive and nonsystematic search was made in PubMed and Google Scholar using mainly the keywords “MDR-TB” “extensively drug-resistant TB,” Malawi. The study reviewed existing guidelines and gray literature and reviewed data obtained from the national TB program (NTP) as well.
Results:
The study found the following challenges affecting PMDT: decrease in funding, partial access to GeneXpert, delay in diagnosis, long treatment duration, lack of adequate personal protective equipment, the long turnaround time of culture results, failure to initiate all diagnosed patients on treatment, absence of alternative second-line medicines, and lack of transport from health facilities to patient homes.
Conclusion:
If the Malawi NTP is to achieve a vision of a “TB-free Malawi,” rigorous efforts at all levels must be made, including mobilizing domestic resources for improved MDR-TB program performance. Developing partners should continue providing the much-needed funding to the Malawi government to stand in the wake of the MDR-TB crisis.
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Microbiome in sputum as a potential biomarker of chronicity in pulmonary resistant to rifampicin-tuberculosis and multidrug-resistant-tuberculosis patients
p. 260
Nurul Wiqoyah, Ni Made Mertaniasih, Wayan Tunas Artama, Sohkichi Matsumoto
DOI
:10.4103/ijmy.ijmy_132_21
PMID
:34494564
Background:
Cases of tuberculosis (TB) and multidrug-resistant TB (MDR-TB) in South-east Asia including Indonesia are still high. The presence of mixed infections in TB cases has been reported. Several studies revealed the role of the human microbiome in TB. This study purposes to characterize microbiome which can be a potential biomarker of chronicity in TB or MDR-TB.
Methods:
Sputum samples of pulmonary TB patients confirmed MDR-TB and resistant to rifampicin TB (RR-TB) were conducted Metagenomic next-generation sequencing. Principal coordinate analysis of UniFrac's showing the community structure of microbiome in MDR-TB comorbid diabetes mellitus (DM) is different from RR-TB noncomorbid DM (
P
= 0.003).
Results:
Proteobacteria microbiome in MDR-TB comorbid DM was more abundant than in RR-TB noncomorbid DM.
Actinobacteria
found in the small quantity in RR-TB and MDR-TB. Diversity of microbiome genera was greater in RR-TB. The linear discriminant analysis effect size analysis represents a genus biomarker whose abundance shows significant differences between groups, genus Rothia as a potential biomarker for RR-TB noncomorbid DM.
Conclusions:
Interesting findings is the community structure of microbiome in MDR-TB and RR-TB. In chronic TB such as recurrent, associated MDR-TB should attention to the findings of a small number of
Actinobacteria
could be a biomarker of TB which is also a determinant in patient taking combined anti-TB drugs of choice.
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The effect of glycemic control on clinico-radiological manifestations of pulmonary tuberculosis in patients with diabetes mellitus
p. 268
Kavin Mani Saalai, Anita Mohanty
DOI
:10.4103/ijmy.ijmy_133_21
PMID
:34494565
Background:
The association between diabetes mellitus (DM) and tuberculosis (TB) and their synergistic role in causing human disease has been recognized for centuries. Despite the known synergy between DM and TB, the importance of atypical clinical, radiological presentation and DM as a risk factor for TB is largely unknown. This study was undertaken to know the effect of glycemic control on TB manifestations as it will contribute to the opportunities for detection and treatment of both disease conditions appropriately.
Methods:
This cross-sectional study included 50 patients attending the pulmonary medicine department in Ispat General Hospital with pulmonary TB and DM during 6 months' period. Clinical data, chest-X ray, HbA1c values were obtained and the effect of glycemic control studied and analyzed.
Results:
Five patients had good glycemic control (HbA1c ≤7%), 45 patients had poor glycemic control (HbA1c >7%). Cough was present in all patients. Weight loss and night sweats were present in poor glycemic group and sputum smear grade was higher in higher HbA1c patients and both were statistically significant. None of the good glycemic group had lower zone lesion. The commonest type of lesion was nonhomogenous opacity, followed by cavities in both poor and good glycemic groups. Cavities were usually present in lower zones. Size and number of cavities were more as the glycemic control is poor. So, that glycemic control did have an effect on pulmonary TB manifestations, hence achieving and maintaining glycemic control is necessary for DM with pulmonary TB.
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Sera from patients with tuberculosis increase the phagocytic-microbicidal activity of human neutrophils, and ESAT-6 is implicated in the phenomenon
p. 271
Oscar Rojas-Espinosa, Miguel Angel Rivero-Silva, Alejandro Hernández-Solís, Patricia Arce-Paredes, Alma Yolanda Arce-Mendoza, Sergio Islas-Trujillo
DOI
:10.4103/ijmy.ijmy_134_21
PMID
:34494566
Background:
It has been reported that sera from patients with active pulmonary tuberculosis (APT) induced nuclear changes in normal neutrophils that included pyknosis, swelling, apoptosis, and production of extracellular traps (NETs). Similar changes were observed with some sera from their household contacts but not with sera from healthy, unrelated individuals. It was suggested that those sera from household contacts that induced neutrophil nuclear changes might correspond to people with subclinical tuberculosis. Thus, our experimental approach might serve to identify individuals with early, ongoing disease.
Methods:
Nuclear changes in neutrophils were fully evident by 3 h of contact and beyond. Circulating mycobacterial antigens were the most likely candidates for this effect. We wanted to know whether the nuclear changes induced on neutrophils by the sera of APT patients would negatively affect the phagocytic/microbicidal ability of neutrophils exposed to APT sera for short periods.
Results:
We now provide evidence that short-term contact (30 min) with sera from patients with pulmonary tuberculosis increases several phagocytic parameters of normal neutrophils, including endocytosis, myeloperoxidase levels, production of free reactive oxygen species, phagolysosome fusion, and microbicidal activity on
Staphylococcus aureus
, with these effects not being observed with sera from healthy donors. We also give evidence that suggests that ESAT-6 and CFP-10 are involved in the phenomenon.
Conclusion:
We conclude that activation is a stage that precedes lethal nuclear changes in neutrophils and suggests that autologous neutrophils must circulate in an altered state in the APT patients, thus contributing to the pathology of the disease.
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Prediction of treatment failure of tuberculosis using support vector machine with genetic algorithm
p. 279
Keethansana Kanesamoorthy, Maheshi B Dissanayake
DOI
:10.4103/ijmy.ijmy_130_21
PMID
:34494567
Background:
Tuberculosis (TB) is a disease that mainly affects human lungs. It can be fatal if the treatment is delayed. This study investigates the prediction of treatment failure of TB patients focusing on the features which contributes mostly for drug resistance.
Methods:
Support vector machine (SVM) is a relatively novel classification model that has shown promising performance in regression applications. Genetic algorithm (GA) is a method for solving the optimization problems. We have considered lifestyle and treatment preference-related data collected from TB-positive patients in Yangon, Myanmar to obtain a clear picture of the TB drug resistance. In this article, TB drug resistance is analyzed and modelled using SVM classifier. GA is used to enhance the overall performance of SVM, by selecting the most suitable 20 features from the 35 full feature set. Further, the performance of four different kernels of SVM model is investigated to obtain the best performance.
Results:
Once the model is trained with SVM and GA, we have feed unseen data into the model to predict the treatment resistance of the patient. The results have shown that SVM with GA is capable of achieving 67% of accuracy in predicting the treatment resistance in unseen data with only 20 features.
Conclusion:
The findings would in turn, assist to develop an effective TB treatment plan in future based on patients' lifestyle choices and social settings. In addition, the model developed in this research can be generalized to predict the outcome of drug therapy for many diseases in future.
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The effect of collaborative care on treatment outcomes of newly diagnosed tuberculosis patients with Type-2 diabetes mellitus and adverse drug reaction presentations: A prospective study
p. 285
Foluke Adenike Ayeni, Olubukola O Oyetunde, Bolajoko A Aina
DOI
:10.4103/ijmy.ijmy_124_21
PMID
:34494568
Background:
The burdens of tuberculosis (TB) and diabetes mellitus (DM) in Nigeria are high. DM often goes unrecognized in TB patients, resulting in poorer treatment outcomes compared with TB patients only. This study set out to compare TB treatment outcomes and associated factors in TB only and TBDM patients when a collaborative care (CC) model is in place.
Methods:
A prospective quasi-experimental study, modeled after the World Health Organization and The Union's Collaborative Framework for Care and Control of TB and DM was carried out among TB patients in two chest clinics in Lagos state. Patients were grouped into TB only, who received the usual TB care, directly observed treatment, short course (DOTS), and TBDM, who received DOTS and CC. Data were analyzed with IBM Statistical Package for the Social Sciences, version 23.0. Chi-square and multivariate analysis determined the association between treatment success and CC. Statistical tests were calculated at 95% confidence intervals and considered significant when
P
value is < 0.05.
Results:
Of 671 participants in the study, 52 (7.7%) had DM. At TB treatment completion, there was no statistically significant difference in outcomes between TBDM and TB-only patients (
P
= 0.40). Patients who received CC were about 32 (OR: 31.60, 95% CI: 3.38-293), and 5 times (OR: 5.08, 95% CI: 1.35-19.17) more likely to achieve success and cure, respectively, compared to those who did not.
Conclusion:
Provision of CC with DOTS ensured improved TB treatment outcomes in TBDM patients. Recommendations of WHO/The Union are feasible in our setting.
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Skin and soft-tissue infections due to rapidly growing mycobacteria: An overview
p. 293
Chanchal Kumar, Kamal Shrivastava, Anupriya Singh, Varsha Chauhan, Mandira Varma-Basil
DOI
:10.4103/ijmy.ijmy_110_21
PMID
:34494569
Background:
Rapidly growing mycobacteria (RGM) are increasingly being recognized as potential pathogens. RGM, particularly
Mycobacterium abscessus, Mycobacterium fortuitum,
and
Mycobacterium chelonae,
have been observed in both pulmonary and extrapulmonary infections including cutaneous, soft-tissue, and wound infections. However, there are limited reports of these potential pathogens from skin and soft-tissue infections. Moreover, the drug susceptibility profile of RGM is largely unknown in several regions of the world.
Methods:
We analyzed reports on RGM isolated from skin and soft-tissue infections globally for details of RGM species and drug susceptibility profile. We also analyzed the drug susceptibility profile of four RGM isolates, obtained from skin and soft-tissue infections in our laboratory, by broth microdilution method.
Results:
In the reports reviewed, the most common RGM isolated from skin and soft-tissue infections were
M. abscessus
(184/475, 38.7%),
M. fortuitum
(150/475, 31.5%),
M. chelonae
(72/475, 15%), and
M. chelonae–M. abscessus
complex (46/475, 9.6%). However, drug susceptibility was tested only in 26/39 (66.6%) reports. In our own laboratory, we obtained three isolates of
M. abscessus
and one isolate of
M. fortuitum
from one case of breast abscess and three cases of postsurgical wound infections. Maximum susceptibility of
M. abscessus
was observed to clarithromycin, amikacin, and linezolid. The
M. fortuitum
isolate was susceptible to clarithromycin, amikacin, clofazimine, and linezolid.
Conclusion:
Paucity of information available on RGM isolated from skin and soft-tissue infections highlights the need to be aware of the pathogenic potential and the drug susceptibility profile of these organisms.
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Survival of
Mycobacterium abscessus
complex organisms on coins
p. 301
John E Moore, Beverley Cherie Millar
DOI
:10.4103/ijmy.ijmy_138_21
PMID
:34494570
Background:
To date, there have been no reports on the occurrence of nontuberculous mycobacterial (NTM) organisms (nor tuberculosis [TB]) on money, currency, banknotes, or coins, where these may act as fomites in the potential transmission of mycobacterial organisms around communities, especially in developing nations, where physical currency is still the popular mainstay of the economy, compared to electronic and digital forms of currency transaction. It was therefore the aim of this study to examine the survival of the
Mycobacterium abscessus
complex organisms on coins.
Methods:
Coins from 17 countries were examined for the presence of
M. abscessus
complex organisms by broth enrichment in Middlebrook 7H9 for 2 months. Nickel-plated steel and copper-plated steel coins were artificially contaminated individually with
M. abscessus
complex (
circa
10
7
[7 log
10
] organisms/coin), including
M. abscessus
subsp.
massiliense
(
n
= 2),
M. abscessus
subsp.
bolletti
(
n
= 2), and
M. abscessus
subsp.
abscessus
(
n
= 1) and their surviving cells enumerated at weekly period up to 5-week postinoculation.
Results:
NTM organisms were not isolated from coins from the 17 currencies examined. In all three subspecies of
M. abscessus
, the copper-plated steel coins caused a more rapid decline in organism numbers, which were statistically very significant (
P
< 0.0001), compared to the paired survival on the nickel-plated steel coins, whereby organisms were none detectable after 3-week storage on the copper-plated coins. NTM organisms survived better on the nickel-plated coins, with a mean count across all subspecies of log
10
1.84 colony forming units per coin after 5 weeks of storage (range: 0.6–2.69 log
10
cfu/coin). There was no statistically significant difference (
P
> 0.05; 5%) in the survival dynamics among the three subspecies with storage on either coin type.
Conclusions:
Health-care professionals should be aware of the survival of
M. abscessus
complex organisms on coins for up to 12 weeks, which may be particular relevant in high-risk areas of health-care institutions where TB or NTM is prevalent and where there are opportunities for the transmission of such organisms through contaminated fomites, including coins, through opportunities including payment for treatments/medicines/dressings, coin-operated payment facilities, such as hospital car parking, self-service vending machines, hospital canteens, coffee shops and dining halls and hospital shops, whether static or mobile onward visits. To mitigate potential infection consequences of handling coins contaminated with
M. abscessus
complex organisms, other NTMs organisms and TB, the authors support re-establishing the principles of basic hygiene, including proper handwashing and the avoidance of handling money when working with food or dressing wounds and skin lesions, as well as when working with respiratory devices, including nebulizers.
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Computer-assisted screening of mycobacterial growth inhibitors: Exclusion of frequent hitters with the assistance of the multiple target screening method
p. 307
Kohei Kuriki, Junichi Taira, Masato Kuroki, Hiroshi Sakamoto, Shunsuke Aoki
DOI
:10.4103/ijmy.ijmy_137_21
PMID
:34494571
Background:
The emergence of frequent hitters (FHs) remains a challenge in drug discovery. We have previously used
in silico
structure-based drug screening (SBDS) to identify antimycobacterial candidates. However, excluding FHs has not been integrated into the SBDS system.
Methods:
A dataset comprising 15,000 docking score (protein–compound affinity matrix) was constructed by multiple target screening (MTS): DOCK–GOLD two-step docking simulations with 154,118 compounds versus the 30 target proteins essential for mycobacterial survival. After extraction of 141 compounds from the protein–compound affinity matrix, compounds determined to be FHs or false positives were excluded. Antimycobacterial properties of the top nine compounds selected through SBDS were experimentally evaluated.
Results:
Nine compounds designated KS1–KS9 were selected for experimental evaluation. Among the selected compounds, KS3, identified as adenosylhomocysteinase inhibitor, showed a potent inhibitory effect on antimycobacterial growth (inhibitory concentration [IC]
50
= 1.2 M). However, the compound also showed potent cytotoxicity.
Conclusion:
The MTS method is applicable in SBDS for the identification of enzyme-specific inhibitors.
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REVIEW ARTICLE
Safety and efficacy of high-dose rifampicin in the management of tuberculosis meningitis: Systematic review and meta-analysis
p. 312
Loveness Charlie, Solomon Mequante Abay, Abraham Tesfaye, Ronald Nachipo Mlera, Samuel Mwango, Mary Goretti
DOI
:10.4103/ijmy.ijmy_135_21
PMID
:34494572
Background:
Mycobacterium tuberculosis
(TB) practically affects any part of the body, but when the brain is involved, the consequences are devastating. Tuberculous meningitis (TBM) is the most severe form of drug-susceptible TB, with an estimation of more than 100,000 new cases occurring every year and a high mortality rate globally. The treatment strategy is based on pulmonary TB (PTB) management regimens which consider rifampicin as the backbone. Optimal treatment regimens for PTB may not be the most effective option for TBM due to difference in TB drug penetration across the blood–cerebrospinal fluid barrier, hence the need for other treatment options. This study aims to review the efficacy and safety of higher doses of rifampicin (>10 mg/kg) compared to 10 mg/kg rifampicin as part of standard therapy for the treatment of TBM.
Methods:
A systematic review and meta-analysis was conducted to assess the efficacy and safety of high-dose rifampicin for TBM. A search was done on PubMed, Google Scholar, and Cochrane library databases without publication date limit to identify studies providing data on the use of high-dose rifampicin for the treatment of TBM. Titles and abstracts were screened for relevance by three reviewers. Two reviewers used a predefined checklist on the inclusion criteria to assess full text for their eligibility in the review. A heterogeneity test was conducted to assess the variations among study outcomes. The risk ratio (RR) with a 95% confidence interval (CI) was calculated as a measure of intervention effect. The study is registered on PROSPERO and the registration number is CRD42020212737.
Results:
Five Phase 2 trials with a total of 1028 participants were included in this meta-analysis. All the five trials were used to analyze safety data, which found that there was no significant increase in the risk of Grade 3–5 adverse events in high-dose rifampicin (RR = 1.05; 95% CI = 0.95–1.18). Only four of them were included for the analysis of efficacy. The findings indicated that exposure to high-dose rifampicin is not associated with a reduced risk of mortality (RR = 0.95; 95% CI = 0.78–1.16).
Conclusions:
It can be concluded from this meta-analysis that there is no significant relation of high-dose rifampicin with adverse events and the reduction of mortality in TBM patients. Whether in future optimized TBM treatment regimen will include high-dose rifampicin or not should be determined by a large-scale clinical trial.
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CASE REPORTS
Primary tubercular granulomatous hepatitis presenting as fluctuating jaundice
p. 320
Arkadeep Dhali, Gopal Krishna Dhali, Ranajoy Ghosh, Avik Sarkar
DOI
:10.4103/ijmy.ijmy_92_21
PMID
:34494573
Granulomatous hepatitis is an uncommon presentation of tuberculosis (TB). It is even more peculiar to have TB confined to the liver alone with no pulmonary or a disseminated form. In either form, there is the usual presentation of nonprogressive cholestatic jaundice, but no documented case with fluctuating jaundice in the literature was found. In order to highlight this rare presentation aiding the right diagnosis, we present one such case of a 46-year-old woman with no known comorbidities, who complained of fluctuating and painless type of jaundice, associated with fatiguability, pruritus, and weight loss. Preliminary blood investigations showed anemia and cholestatic pattern of jaundice. Ultrasonography and computed tomography imaging showed hepatomegaly with heterogeneous texture. Magnetic resonance cholangiopancreatography further revealed features of cholecystitis with hepatic ducts near proximal common bile duct showing postinflammatory change. The periampullary region was normal. Sputum acid-fast staining and cartridge-based nucleic acid amplification test were negative. Eventually, liver biopsy was done which showed caseating granulomas with Langhans giant cells. The tissue was abundant in acid-fast bacilli. The patient was started on a 9-month course of first-line Antitubercular treatment (ATT) and responded well. Fluctuating jaundice is a rare and undocumented presentation of primary hepatic TB and can cause diagnostic dilemmas.
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Tuberculous peritonitis complicated by immunologic cerebral vasculitis
p. 324
Mansoor C Abdulla
DOI
:10.4103/ijmy.ijmy_112_21
PMID
:34494574
A 53-year-old female was admitted with ascites for 3 weeks, decreased response, and weakness of right upper and lower limbs for 1 day. Peritoneal biopsy showed necrotizing granulomatous inflammation, and cartridge-based nucleic acid amplification test for tuberculosis (TB) of biopsy was positive without rifampicin resistance. Magnetic resonance imaging brain showed multiple foci of diffusion restriction in bilateral cerebral hemisphere and cerebellum, suggestive of acute infarcts. After ruling out the secondary causes of cerebral infarction by appropriate tests and demonstrating that there was no evidence for tuberculous meningitis or direct injury, it was concluded that the reason for multiple cerebral infarctions in this patient is likely to be immunologic injury secondary to TB. Multiple cerebral infarctions secondary to immunologic injury in TB were reported only once previously.
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Tuberculosis presenting as metastatic lung cancer
p. 327
Sarfraz A Saleemi, Bader Alothman, Mohammed Alamer, Sultan Alsayari, Abdulaziz Almogbel, Shamayel Mohammed
DOI
:10.4103/ijmy.ijmy_89_21
PMID
:34494575
Mycobacterium tuberculosis
infection (TB) masquerading as lung tumor is well reported, but its mimicry as metastatic thoracic cancer is rare. We report the case of a young male who presented with clinical and radiological picture of lung cancer but investigations confirmed it as TB. A 35-year-old male, with 18-pack year of smoking history, presented with dry cough, anorexia, weight loss, and lower back and left hip pain. Chest imaging showed right upper lobe speculated mass with mediastinal and hilar lymphadenopathy and a lytic lesion in the left sacral area. Magnetic resonance imaging of the spine and pelvis revealed lytic lesion in the left sacrum. Fluorodeoxyglucose positron emission tomography computed tomography scan of the whole body showed hypermetabolic lung lesion with ipsilateral mediastinal, supraclavicular, splenic, and bone metastasis in the left aspect of the sacrum. Computed tomography (CT)-guided biopsy of the lung lesion showed necrotizing granuloma and tissue culture was positive for pan-susceptible
M. tuberculosis
. Follow-up CT scan showed complete resolution of the lung lesion and lymph nodes after anti-TB treatment with significant reduction in the sacral lesion. Mycobacterial infection may mimic metastatic lung cancer and should always be considered a differential diagnosis.
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Concomitant disseminated tuberculosis and lepromatous leprosy in a previously healthy male
p. 330
Baldeep Kaur, Daljinderjit Kaur, Monica Gupta, Nandini Agrawal, Sarabmeet Singh Lehl
DOI
:10.4103/ijmy.ijmy_25_21
PMID
:34494576
Tuberculosis (TB) and leprosy are two chronic mycobacterial infections caused by intracellular Gram-positive aerobic acid-fast bacilli. Both have highly variable presentations depending on immunological milieu of the host and account for significant disease morbidity. The burden of these age-old infections of humanity still remains high in India. Regardless of the same geographical endemicity of the two, coinfections are sparsely reported. Indeed, studies have revealed an antagonism between them. Of the few coinfections reported in the past, majority were diagnosed over a temporal sequence, with one occurring after the other, and most of these were localized forms of TB associated with leprosy. Only a single case of disseminated TB and lepromatous leprosy has been reported in the medical literature till date. Here, we report another rare case of disseminated TB and lepromatous leprosy that ultimately proved fatal for the patient. The diagnosis of the two diseases was made simultaneously which is again infrequent in the reported literature.
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Iliopsoas gravity abscess secondary to a tuberculous empyema
p. 335
Kazuya Tone, Yuta Hirano, Kazuyoshi Kuwano
DOI
:10.4103/ijmy.ijmy_129_21
PMID
:34494577
A 29-year-old Japanese man with a history of right-sided tuberculous pleurisy presented with fever and right flank pain. Computed tomography images revealed a right pleural effusion and an area of low attenuation in the right iliopsoas muscle. Percutaneous drainage of the iliopsoas lesion resulted in a bloody pyogenic discharge that tested positive for
Mycobacterium tuberculosis
by both acid-fast staining and polymerase chain reaction. Enhanced fluoroscopy revealed a perforation of the diaphragm between the thoracic region and the psoas muscle. The patient was diagnosed with an iliopsoas abscess secondary to tuberculous empyema.
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Tuberculosis with multiarticular involvement diagnosed by positive acid-fast staining in synovial fluid: An unusual case report
p. 338
Diego Chemello, Raissa Massaia Londero Chemello, Giovana Thomasi Jahnke
DOI
:10.4103/ijmy.ijmy_144_21
PMID
:34494578
Osteoarticular tuberculosis (TB) is an uncommon form of extrapulmonary TB, comprising approximately 5% of all TB and 10%–15% of extrapulmonary TB cases. Multifocal skeletal TB is rare and accounts for 10% of all osteoarticular TB cases. Sometimes, the diagnosis is difficult. The potential delay in the clinical diagnosis may be critical for patients since it can cause the spread of the infection from the bone to the adjacent joints and surrounding tissues. We present a rare case of military TB with multiarticular involvement in a patient with chronic tophaceous gout. The initial diagnosis was confirmed throughout the positive analysis for Ziehl–Nielsen acid-fast staining in synovial fluid of two different joints, which is unusual. The patient was treated with antituberculosis drugs and presented good recovery signs.
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Co-existence of pulmonary tuberculosis with sarcoidosis
p. 341
Harveen Kaur, Dilbag Singh, Naveen Pandhi
DOI
:10.4103/ijmy.ijmy_145_21
PMID
:34494579
Tuberculosis (TB) and sarcoidosis are multisystem, chronic granulomatous diseases. Although characterized by similar clinical manifestations, these disease entities vary significantly in etiologies and management. Sarcoidosis is an immunological disorder of unknown etiology, characterized by the presence of noncaseating granulomas in the tissues involved. TB is the infectious disease caused by
Mycobacterium tuberculosis
, characterized by granulomas with caseous necrosis. It is rare to have both the diseases concomitantly. We present the case of a 38-year-old male with microbiological confirmation of coexistent pulmonary TB and sarcoidosis.
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LETTERS TO EDITOR
Mind the gap!: Need for improved harmonization of antibiotic susceptibility testing of the nontuberculous mycobacteria between cystic fibrosis clinical guidelines and
Mycobacterium
antibiotic susceptibility testing laboratories
p. 344
John Edmund Moore, Mark Smyth, Steven Caskey, Beverley Cherie Millar
DOI
:10.4103/ijmy.ijmy_113_21
PMID
:34494580
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Differences in tuberculosis incidence among patients with hematological malignancies and general population, Santander, Colombia, 2015–2019
p. 346
Yeimer Ortiz-Martínez, Javier Enrique Fajardo-Rivero, Tania Mendoza-Herrera, Carlos E Ruiz-González, Yuderleys Masias-León, Camila Luna, Alfonso J Rodriguez-Morales
DOI
:10.4103/ijmy.ijmy_90_21
PMID
:34494581
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