High prevalence of phenotypic pyrazinamide resistance and its association with pncA gene mutations in Mycobacterium tuberculosis isolates from Uganda

Naluyange, Resty; Mboowa, Gerald; Komakech, Kevin; Semugenze, Derrick; Kateete, David Patrick; Ssengooba, Willy

doi:10.1371/journal.pone.0232543

Cited by 14 publications

(9 citation statements)

References 27 publications

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“…PZA was always controversial in the treatment of MDR-TB and XDR-TB, some studies showed that PZA resistant or not did not impact its anti-microbial activity (21,26,27), however, the high resistant rate of PZA had been considered its application in the future (28). In the present study, we tested PZA resistance by MIC value, the resistance rate was 50.9%.…”

Section: Discussionmentioning

confidence: 82%

An inexpensive, efficient and safe regimen containing Pasiniazid for MDR-TB in high Tuberculosis epidemic areas – A prospective study in China

Sun

Tang

Wang

et al. 2020

Preprint

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Background: MDR-TB（multidrug-resistant tuberculosis） remains the challenge with low success rate of treatment. Pasiniazid had been applied in China for two decades, but relevant clinical studies are rare. To verify the efficacy and safety of a regimen containing pasiniazid on MDR-TB, a prospective clinical study was conducted in China. Methods: Patients with MDR-TB satisfied with inclusion criteria were prospectively enrolled into the study from 2017 June to 2018 Dec, given the regimen and followed up, observed the treatment outcome and adverse effect of drugs made up the regimen.Results: A total of 114 patients diagnosed as MDR Pulmonary tuberculosis(MDR-PTB) were enrolled into the study and given the regimen with six months of Capremycin(Cm), Levofloxacin(Lfx), Cycloserine(Cs), Protionamide(Pto), Pyrazinamide(Z) and Pasiniazid（Pa）, followed by 12 months of LfxCsPtoZPa. The overall treatment success rate in all enrolled patients was 79.8% (91/114) while it was significantly higher in newly treated MDR-PTB (91.7%, 33/36) than that in retreated MDR-PTB(74.4%，58/78, p value was 0.03); Patients infected with strains resistant to fluoroquinolones impacted the treatment outcome (P<0.05) while other drugs did not (P >0.05). Pasiniazid was taken safely without adverse reaction during the course of treatment.Conclusions: The long term of anti-MDR-PTB regimen containing Pasiniazid was proved to be effective, safe and inexpensive although it contained injectable agents. This regimen is suited to be applied in areas with poor resource and high TB burden.

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Section: Discussionmentioning

confidence: 82%

An inexpensive, efficient and safe regimen containing Pasiniazid for MDR-TB in high Tuberculosis epidemic areas – A prospective study in China

Sun

Tang

Wang

et al. 2020

Preprint

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“…However, Allana et al [ 52 ] reported that 70% of multidrug-resistant and 96% of extensively drug-resistant M. tuberculosis isolates in South Africa and Georgia were positive for the pncA gene. Detection of this gene in clinical M. tuberculosis isolates has been published from other countries, such as Pakistan [ 53 ] and Uganda [ 54 ]. The data obtained in our study, therefore, show that the environmental abundance of this gene could be driven by bacteria carrying this resistance gene in the wastewater environment or a prevalence within the local population/communities.…”

Section: Discussionmentioning

confidence: 99%

Wastewater-Based Surveillance of Antibiotic Resistance Genes Associated with Tuberculosis Treatment Regimen in KwaZulu Natal, South Africa

et al. 2021

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Essential components of public health include strengthening the surveillance of infectious diseases and developing early detection and prevention policies. This is particularly important for drug-resistant tuberculosis (DR-TB), which can be explored by using wastewater-based surveillance. This study aimed to use molecular techniques to determine the occurrence and concentration of antibiotic-resistance genes (ARGs) associated with tuberculosis (TB) resistance in untreated and treated wastewater. Raw/untreated and treated (post-chlorination) wastewater samples were taken from three wastewater treatment plants (WWTPs) in South Africa. The ARGs were selected to target drugs used for first- and second-line TB treatment. Both conventional polymerase chain reaction (PCR) and the more advanced droplet digital PCR (ddPCR) were evaluated as surveillance strategies to determine the distribution and concentration of the selected ARGs. The most abundant ARG in the untreated wastewater was the rrs gene, associated with resistance to the aminoglycosides, specifically streptomycin, with median concentration ranges of 4.69–5.19 log copies/mL. In contrast, pncA gene, associated with resistance to the TB drug pyrazinamide, was the least detected (1.59 to 2.27 log copies/mL). Resistance genes associated with bedaquiline was detected, which is a significant finding because this is a new drug introduced in South Africa for the treatment of multi-drug resistant TB. This study, therefore, establishes the potential of molecular surveillance of wastewater for monitoring antibiotic resistance to TB treatment in communities.

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“…The review further demonstrated that a great number of infectious diseases have been shown to resist available and routine therapy in the Ugandan context, for example, tuberculosis [19][20][21], pneumonia [22,23], salmonellosis [24,25], malaria [26,27], gonorrhea [28][29][30] and other urinary tract infections and respiratory infections, as well as important viral and fungal infections. There has been detection of wide spread beta lactam and non-beta lactam antibiotic resistance reported in district referral hospitals [31] as well as multidrug resistance amongst clinical isolates [32,33].…”

Section: Discussionmentioning

confidence: 99%

Efforts to Identify and Combat Antimicrobial Resistance in Uganda: A Systematic Review

Kivumbi

Standley

2021

TropicalMed

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The global burden of antimicrobial resistance is on the rise, resulting in higher morbidity and mortality in our communities. The spread of antimicrobial resistance in the environment and development of resistant microbes is a challenge to the control of antimicrobial resistance. Approaches, such as antimicrobial stewardship programmes and enhanced surveillance, have been devised to curb its spread. However, particularly in lower- and middle-income countries, the overall extent of antimicrobial resistance and knowledge on ongoing surveillance, stewardship or investigation efforts, are often poorly understood. This study aimed to look at the efforts that have been undertaken to detect and combat antimicrobial resistance in Uganda as a means of establishing an overview of the situation, to help inform future decisions. We conducted a systematic literature review of the PubMed database to assess these efforts. A search combining keywords associated with antimicrobial resistance were used to find relevant studies between 1995 and 2020 on surveillance of antimicrobial resistance in Uganda, and susceptibility of microbes to different drugs. The search yielded 430 records, 163 of which met the inclusion criteria for analysis. The studies were categorized according to country and region, the type of antimicrobial resistance, context of the study, study design and outcome of the study. We observed that antibacterial resistance and antimalarial resistance had the most published studies while antiviral and antifungal resistance were represented by very few studies each. Most studies were conducted in humans and hospital settings, with few in veterinary and One Health contexts, and only one that included environmental sampling. The majority of studies have focused on surveillance, susceptibility testing or resistance genes; none of our included papers had a policy or stewardship focus. The results from our work can inform public health policy on antimicrobial stewardship as it contributes to understanding the status of antimicrobial resistance surveillance in Uganda, and can also help to guide future research efforts. Notably, a One Health approach needs to be followed with respect to surveillance of antimicrobial resistance to better understand the mechanisms of resistance transfer across the human-animal–environment interface, including additional investigation in antiviral and antifungal resistance.

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High prevalence of phenotypic pyrazinamide resistance and its association with pncA gene mutations in Mycobacterium tuberculosis isolates from Uganda

Cited by 14 publications

References 27 publications

An inexpensive, efficient and safe regimen containing Pasiniazid for MDR-TB in high Tuberculosis epidemic areas – A prospective study in China

An inexpensive, efficient and safe regimen containing Pasiniazid for MDR-TB in high Tuberculosis epidemic areas – A prospective study in China

Wastewater-Based Surveillance of Antibiotic Resistance Genes Associated with Tuberculosis Treatment Regimen in KwaZulu Natal, South Africa

Efforts to Identify and Combat Antimicrobial Resistance in Uganda: A Systematic Review

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