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Ethiopian Journal of Health Sciences Sep 2023Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar... (Review)
Review
BACKGROUND
Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar clinical presentations to tuberculosis, leading to inappropriate treatment and increased morbidity and mortality rates. This literature review aims to provide an overview of the prevalence, clinical manifestations, diagnosis, and management of NTM infections in Africa.
METHODS
A systematic search was performed using various electronic databases including PubMed, Scopus, and Web of Science. The search was limited to studies published in the English language from 2000 to 2021. The following keywords were used: "non-tuberculous mycobacteria", "NTM", "Africa", and "prevalence". Studies that focused solely on the Mycobacterium tuberculosis complex or those that did not report prevalence rates were excluded. Data extraction was performed on eligible studies. Overall, a total of 32 studies met the inclusion criteria and were included in this review.
RESULTS
In our literature review, we identified a total of 32 studies that reported non-tuberculosis mycobacteria (NTM) in Africa. The majority of these studies were conducted in South Africa, followed by Ethiopia and Nigeria. The most commonly isolated NTM species were Mycobacterium avium complex (MAC), Mycobacterium fortuitum, and Mycobacterium abscessus. Many of the studies reported a high prevalence of NTM infections among HIV-positive individuals. Other risk factors for NTM infection included advanced age, chronic lung disease, and previous tuberculosis infection.
CONCLUSION
In conclusion, this literature review highlights the significant burden of non-tuberculosis mycobacteria infections in Africa. The prevalence of these infections is high, and they are often misdiagnosed due to their similarity to tuberculosis. The lack of awareness and diagnostic tools for non-tuberculosis mycobacteria infections in Africa is a major concern that needs to be addressed urgently. It is crucial to improve laboratory capacity and develop appropriate diagnostic algorithms for these infections.
Topics: Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Africa; Prevalence
PubMed: 38784502
DOI: 10.4314/ejhs.v33i5.21 -
Microbiology Spectrum Aug 2023We evaluated the clinical characteristics and treatment outcomes of 35 patients diagnosed with Mycobacterium fortuitum-pulmonary disease (M. fortuitum-PD). Prior to...
We evaluated the clinical characteristics and treatment outcomes of 35 patients diagnosed with Mycobacterium fortuitum-pulmonary disease (M. fortuitum-PD). Prior to treatment, all isolates were sensitive to amikacin and 73% and 90% were sensitive to imipenem and moxifloxacin, respectively. Approximately two-thirds of the patients (24 of 35) remained stable without antibiotic treatment. Of 11 patients requiring antibiotic treatment, the majority (81%, 9 of 11) achieved a microbiological cure with susceptible antibiotics. Mycobacterium fortuitum (M. fortuitum) is a rapidly growing mycobacterium that causes M. fortuitum-pulmonary disease (PD). It is common among individuals with preexisting lung conditions. Limited data exist regarding treatment and prognosis. Our study examined patients with M. fortuitum-PD. Two-thirds of them remained stable without antibiotics. Among those requiring treatment, 81% achieved a microbiological cure with suitable antibiotics. In many cases, M. fortuitum-PD follows a stable course without antibiotics, and when necessary, a favorable treatment response can be achieved with the appropriate antibiotics.
Topics: Humans; Mycobacterium fortuitum; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; Treatment Outcome; Microbial Sensitivity Tests; Lung Diseases
PubMed: 37428038
DOI: 10.1128/spectrum.02051-23 -
Frontiers in Cellular and Infection... 2023Mycobacteriophages are viruses that infect members of genus . Because of the rise in antibiotic resistance in mycobacterial diseases such as tuberculosis,...
Mycobacteriophages are viruses that infect members of genus . Because of the rise in antibiotic resistance in mycobacterial diseases such as tuberculosis, mycobacteriophages have received renewed attention as alternative therapeutic agents. Mycobacteriophages are highly diverse, and, on the basis of their genome sequences, they are grouped into 30 clusters and 10 singletons. In this article, we have described the isolation and characterization of a novel mycobacteriophage Kashi-VT1 (KVT1) infecting mc 155 () and isolated from Varanasi, India. KVT1 is a cluster K1 temperate phage that belongs to family as visualized in transmission electron microscopy. The phage genome is 61,010 base pairs with 66.5% Guanine/Cytosine (GC) content, encoding 101 putative open reading frames. The KVT1 genome encodes an immunity repressor, a tyrosine integrase, and an excise protein, which are the characteristics of temperate phages. It also contains genes encoding holin, lysin A, and lysin B involved in host cell lysis. The one-step growth curve demonstrated that KVT1 has a latency time of 90 min and an average burst size of 101 phage particles per infected cell. It can withstand a temperature of up to 45°C and has a maximum viability between pH 8 and 9. Some mycobacteriophages from cluster K are known to infect the pathogenic (); hence, KVT1 holds potential for the phage therapy against tuberculosis, and it can also be engineered to convert into an exclusively lytic phage.
Topics: Humans; Mycobacteriophages; Genome, Viral; Mycobacterium tuberculosis; Mycobacterium smegmatis; Tuberculosis; Bacteriophages
PubMed: 37545854
DOI: 10.3389/fcimb.2023.1173894 -
Tropical Medicine and Health Sep 2023CNS manifestations represent an emerging facet of NTM infection with significant mortality. Due to protean presentation and low index of suspicion, many cases are often... (Review)
Review
BACKGROUND
CNS manifestations represent an emerging facet of NTM infection with significant mortality. Due to protean presentation and low index of suspicion, many cases are often treated erroneously as tubercular meningitis or fungal infections.
OBJECTIVES
Literature on NTM CNS disease is scarce, with most available data on pulmonary disease. This systematic review aimed to evaluate the epidemiology, clinical presentation, diagnostic modalities, and predictors of outcome in CNS NTM infection.
METHODS
The literature search was performed in major electronic databases (PubMed, Google Scholar, and Scopus) using keywords "CNS," "Central nervous system," "brain abscess," "meningitis," "spinal," "Nontuberculous mycobacteria," "NTM". All cases of CNS NTM infection reported between January 1980 and December 2022 were included.
RESULTS
A total of 77 studies (112 cases) were included in the final analysis. The mean age of all patients was 38 years, with most patients male (62.5%). Mycobacterium avium complex (MAC) was the most common aetiology, followed by M. fortuitum and M. abscessus (34.8%, 21.4% and 15.2%, respectively). The disseminated disease was found in 33% of cases. HIV (33.9%) and neurosurgical hardware (22.3%) were the common risk factors. Intracranial abscess (36.6%) and leptomeningeal enhancement (28%) were the most prevalent findings in neuroimaging. The overall case fatality rate was 37.5%. On multivariate analysis, male gender (adjusted OR 2.4, 95% CI 1.2-7.9) and HIV (adjusted OR 3.7, 95% CI 1.8-6.1) were the independent predictors of mortality). M. fortuitum infection was significantly associated with increased survival (adjusted OR 0.18, 95% CI (0.08-0.45), p value 0.012).
CONCLUSIONS
Current evidence shows the emerging role of rapid-grower NTM in CNS disease. Male gender and HIV positivity were associated with significant mortality, while M fortuitum carries favourable outcomes.
PubMed: 37749661
DOI: 10.1186/s41182-023-00546-4 -
South African Journal of Botany :... Jul 2023Tuberculosis (TB) is currently rated as the 13th leading cause of mortality and the second leading cause of death after COVID-19, and above AIDS. Existing challenges...
Tuberculosis (TB) is currently rated as the 13th leading cause of mortality and the second leading cause of death after COVID-19, and above AIDS. Existing challenges relating to the development of multidrug-resistant strains and dangerous side effects of currently used drugs add impetus to the search for additional TB treatments. Hence, interest has grown in the use of medicinal plants as a source of bioactive preparations with efficacy against TB-causing organisms, and also with the ability to ameliorate the negative effects of TB drugs. This study aimed to evaluate the antimycobacterial and hepatoprotective potentials of extracts and isolated flavonoid compounds from invasive Test organisms used were pathogenic and H37RV, and the fast-growing and . The selectivity index (SI) values of the test substances were determined through cytotoxicity assays to promote these extracts and compounds as leads for the development of effective and safe anti-tubercular drugs. The antimycobacterial activity was evaluated using a serial microdilution method, and the SI was calculated from the 50% lethal concentrations calculated from cytotoxicity tests. Hepatoprotective activity was determined using HepG2 liver cells treated with rifampicin as a toxin. The extracts and compounds had a range of antimycobacterial activity with minimum inhibitory concentration (MIC) values ranging from 0.031 to 2.5 mg/mL. Two flavonoid compounds, 5,7,4'-trimethoxy flavanone and 5‑hydroxy-3,7,4'-trimethoxyflavone showed promising antimycobacterial potential, and minimal toxicity was observed, as most SI values were higher than 1. The flavonoid compound 5,7,4'-trimethoxy flavanone had the highest SI (6.452), which was against H37RV. The HepG2 cells were reduced to 65% due to toxicity by rifampicin, however, the flavonoid compounds were able to improve cell viability to between 81 and 89% at different concentrations tested. Results obtained indicate that may serve as a lead for the development of safe and effective antimycobacterial and hepatoprotective drugs.
PubMed: 37206481
DOI: 10.1016/j.sajb.2023.05.002 -
Microbiology Spectrum Aug 2023Tuberculosis (TB) is an ongoing threat to public health, and furthermore, the incidence of infections by nontuberculous mycobacteria (NTM), whose symptoms are not...
Tuberculosis (TB) is an ongoing threat to public health, and furthermore, the incidence of infections by nontuberculous mycobacteria (NTM), whose symptoms are not distinguishable from TB, is increasing globally, thus indicating a need for accurate diagnostics for patients with suspected mycobacterial infections. Such diagnostic strategies need to include two steps, (i) detecting the mycobacterial infections and, if the case is an NTM infection, (ii) identifying the causative NTM pathogen. To eliminate a false-positive TB diagnosis for a host vaccinated by the bacillus Calmette-Guérin (BCG) strain of Mycobacterium bovis, a new target specific for M. tuberculosis species was selected, together with the species-specific targets for the six dominant NTM species of clinical importance, i.e., M. intracellulare, M. avium, M. kansasii, M. massiliense, M. abscessus, and M. fortuitum. Using sets of primers and probes, a two-step real-time multiplex PCR method was designed. The diagnostic performance was assessed by using a total of 1,772 clinical specimens from patients with suspected TB or NTM infection. A total of 69.4% of M. tuberculosis and 28.8% of NTM infections were positive for the primary step of the real-time PCR corresponding to the culture within 10 weeks, and mycobacterial species of 75.5% of the NTM-positive cases were identified by the secondary step. The two-step method described herein presented promising results and similar diagnostic sensitivity and specificity to commercially available real-time PCR kits for detecting TB and NTM infections. The method also enabled the identification of mycobacterial species in three-quarters of NTM infection cases, thus providing a better treatment strategy. Tuberculosis (TB) is an ongoing threat to public health. In addition, infection by nontuberculous mycobacteria (NTM) is a nonnegligible issue for global public health, with increasing incidences. Since the antimicrobial treatment strategy needs to be differed by the causative pathogen, a rapid and accurate diagnostic method is necessary. In this study, we developed a two-step molecular diagnostic method using clinical specimens of TB and NTM infection-suspected patients. The diagnostic power of the new method using the novel target was similar to the widely used TB detection kit, and, among the NTM-positive specimens, three-quarters of the NTM species were able to be identified. This simple and powerful method will be useful as it is, and it could be applied easily to a point-of-care diagnostic apparatus for better application to patients, especially those living in developing countries.
Topics: Humans; Real-Time Polymerase Chain Reaction; Tuberculosis; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Mycobacterium tuberculosis; Mycobacterium bovis
PubMed: 37378523
DOI: 10.1128/spectrum.01606-23 -
Microbiology Spectrum Sep 2023The clinical utility of rifamycins against non-tuberculous mycobacterial (NTM) disease is limited by intrinsic drug resistance achieved by ADP-ribosyltransferase Arr. By...
The clinical utility of rifamycins against non-tuberculous mycobacterial (NTM) disease is limited by intrinsic drug resistance achieved by ADP-ribosyltransferase Arr. By blocking the site of ribosylation, we recently optimized a series of analogs with substantially improved potency against . Here, we show that a representative member of this series is significantly more potent than rifabutin against major NTM pathogens expressing Arr, providing a powerful medicinal chemistry approach to expand the antimycobacterial spectrum of rifamycins. IMPORTANCE Lung disease caused by a range of different species of non-tuberculous mycobacteria (NTM) is difficult to cure. The rifamycins are very active against which causes tuberculosis (TB), but inactive against many NTM species. Previously, we showed that the natural resistance of the NTM to rifamycins is due to enzymatic inactivation of the drug by the bacterium. We generated chemically modified versions of rifamycins that prevent inactivation by the bacterium and thus become highly active against Here, we show that such a chemically modified rifamycin is also highly active against several additional NTM species that harbor the rifamycin inactivating enzyme found in , including , , and . This finding expands the potential therapeutic utility of our novel rifamycins to include several currently difficult-to-cure NTM lung disease pathogens beyond
PubMed: 37681986
DOI: 10.1128/spectrum.01900-23