UNASSIGNED: Accumulation of chemicals including drugs in hair has been used in forensic investigations. Studies have reported isoniazid drug levels in the hair of TB patients.
UNASSIGNED: To review literature for evidence on isoniazid hair drug levels as a tool to monitor adherence, exposure, and TB treatment outcomes and the acceptability of using human hair for medical testing.
UNASSIGNED: We reviewed literature through Pubmed, Embase, Medline, google scholar, and google grey literature. The search terms focused on isoniazid/TB hair drug levels, adherence, treatment outcomes, and acceptability of using hair for medical testing. We kept refining our search terms at each step of our search.
UNASSIGNED: The initial search yielded 186859 articles, which dropped to 88 after removing duplicates and irrelevant articles and eventually to 14 on further refining our search terms. On full review,2 out of 14 and 1 out of 14 articles touched the area of Isoniazid hair drug levels; adherence, exposure, TB treatment outcomes, and acceptability respectively. Further scrutiny showed that none of the articles had addressed our research question.
UNASSIGNED: Literature on Isoniazid hair drug levels among TB patients as a tool to monitor adherence, exposure, and TB treatment outcomes, and its acceptability is limited and more research is needed.

BACKGROUND: Isoniazid-induced pancreatitis is a potentially serious adverse drug reaction, however, the frequency of its occurrence is unknown. We conducted a systematic review to explore this adverse drug reaction comprehensively.
METHODS: We performed an advanced search in PubMed, Web of Science, Scopus, Ovid, and Embase for studies that reported isoniazid-induced pancreatitis. From the extracted data of eligible cases, we performed a descriptive analysis and a methodological risk of bias assessment using a standardized tool.
RESULTS: We included 16 case reports from eight countries comprising 16 patients in our systematic review. Most of the isoniazid-induced pancreatitis cases were extrapulmonary tuberculosis cases. We found the mean age across all case reports was 36.7 years. In all the cases, discontinuation of isoniazid resulted in the resolution of pancreatitis.
CONCLUSIONS: We found the latency period for isoniazid-induced pancreatitis to be ranged from 12 to 45 days after initiation of isoniazid therapy. A low threshold for screening of pancreatitis by measuring pancreatic enzymes in patients on isoniazid presenting with acute abdominal pain is recommended. This would facilitate an early diagnosis and discontinuation of isoniazid, thus reducing the severity of pancreatitis and preventing the complications of pancreatitis.

BACKGROUND: Tuberculosis (TB), one of the deadliest infectious diseases globally, is increasingly exacerbated in China by the emergence of resistant Mycobacterium tuberculosis (MTB) strains. Drug-resistant TB, including mono-drug resistant TB, multidrug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB), presents significant public health challenges.
METHODS: We conducted a systematic literature review from January 2010 to February 2024 using databases such as PubMed, Embase, Web of Science, and Google Scholar. Our focus was on empirical data related to drug resistance patterns in newly diagnosed TB cases. Non-empirical studies were excluded through meticulous filtering. For meta-analysis, we used Review Manager (RevMan) 5.2 and assessed evidence quality using the Newcastle-Ottawa Scale (NOS).
RESULTS: Our search strategy identified 40 studies that met the inclusion criteria, encompassing a total sample size of 87,667 participants. Among new TB cases, the estimated prevalence of MDR-TB in China was 6.9% (95% CI: 5.6-8.1%). Prevalence rates for mono-drug resistance to first-line anti-TB medications were as follows: isoniazid at 18.2% (95% CI: 16.4-20.6%), rifampicin at 10.5% (95% CI: 8.6-12.8%), and ethambutol at 5.7% (95% CI: 4.1-7.3%). The prevalence of streptomycin resistance, a former first-line anti-TB drug, was 17.1% (95% CI: 14.6-19.1%). The prevalence of other types of mono-drug resistance was 15.2% (95% CI: 13.9-17.3%), and for XDR-TB, it was 0.9% (95% CI: 0.6-1.4%).
CONCLUSIONS: The high prevalence of drug-resistant TB in China poses a significant public health challenge. There is an urgent need for targeted interventions and continued surveillance to combat the spread of drug-resistant TB.

BACKGROUND: Screening for tuberculosis (TB) and providing TB preventive treatment (TPT) along with antiretroviral therapy is key components of human immune deficiency virus (HIV) care. The uptake of TPT during the coronavirus disease 2019 (COVID-19) period has not been adequately assessed in Addis Ababa City Administration. This study aimed at assessing TPT uptake status among People living with HIV (PLHIV) newly initiated on antiretroviral therapy during the COVID-19 period at all public hospitals of Addis Ababa City Administration, Ethiopia.
METHODS: A retrospective data review was conducted from April-July 2022. Routine District Health Information System 2 database was reviewed for the period from April 2020-March 2022. Proportion and mean with standard deviation were computed. Logistic regression analysis was conducted to assess factors associated with TPT completion. A p-value of < 0.05 was considered statistically significant.
RESULTS: A total of 1,069 PLHIV, aged 18 years and above were newly initiated on antiretroviral therapy, and of these 1,059 (99.1%) underwent screening for TB symptoms. Nine hundred twelve (86.1%) were negative for TB symptoms. Overall, 78.8% (719) of cases who were negative for TB symptoms were initiated on TPT, and of these 70.5% and 22.8% were completed and discontinued TPT, respectively. Of 719 cases who were initiated on TPT, 334 (46.5%) and 385 (53.5%) were initiated on isoniazid plus rifapentine weekly for three months and Isoniazid preventive therapy daily for six months, respectively. PLHIV who were initiated on isoniazid plus rifapentine weekly for three months were more likely to complete TPT (adjusted odds ratio [AOR],1.68; 95% confidence interval [CI], 1.01, 2.79) compared to those who were initiated on Isoniazid preventive therapy daily for six months.
CONCLUSIONS: While the proportion of PLHIV screened for TB was high, TPT uptake was low and far below the national target of achieving 90% TPT coverage. Overall a considerable proportion of cases discontinued TPT in this study. Further strengthening of the programmatic management of latent TB infection among PLHIV is needed. Therefore, efforts should be made by the Addis Ababa City Administration Health Bureau authorities and program managers to strengthen the initiation and completion of TPT among PLHIV in public hospitals.

N-acetyltransferase 2 (NAT2) genetic polymorphisms might alter isoniazid metabolism leading to toxicity. We reviewed the impact of NAT2 genotype status on the pharmacokinetics, efficacy, and safety of isoniazid, a treatment for tuberculosis (TB). A systematic search for research articles published in Scopus, PubMed, and Embase until August 31, 2023, was conducted without filters or limits on the following search terms and Boolean operators: \"isoniazid\" AND \"NAT2.\" Studies were selected if NAT2 phenotypes with pharmacokinetics or efficacy or safety of isoniazid in patients with TB were reported. Patient characteristics, NAT2 status, isoniazid pharmacokinetic parameters, early treatment failure, and the prevalence of drug-induced liver injury were extracted. If the data were given as a median, these values were standardized to the mean. Forty-one pharmacokinetics and 53 safety studies were included, but only one efficacy study was identified. The average maximum concentrations of isoniazid were expressed as supratherapeutic concentrations in adults (7.16 ± 4.85 μg/mL) and children (6.43 ± 3.87 μg/mL) in slow acetylators. The mean prevalence of drug-induced liver injury was 36.23 ± 19.84 in slow acetylators, which was significantly different from the intermediate (19.49 ± 18.20) and rapid (20.47 ± 20.68) acetylators. Subgroup analysis by continent showed that the highest mean drug-induced liver injury prevalence was in Asian slow acetylators (42.83 ± 27.61). The incidence of early treatment failure was decreased by genotype-guided isoniazid dosing in one study. Traditional weight-based dosing of isoniazid in most children and adults yielded therapeutic isoniazid levels (except for slow acetylators). Drug-induced liver injury was more commonly observed in slow acetylators. Genotype-guided dosing may prevent early treatment failure.

BACKGROUND: The treatment strategy for latent tuberculosis infection is to reduce the number of tuberculosis cases and consequently reduce the transmission of pathogenic bacteria. This study aimed to determine the safety, effectiveness, and adherence of isoniazid use for latent tuberculosis infection treatment.
METHODS: To identify studies on isoniazid use for latent tuberculosis infection, five electronic databases were searched. The methods and results are presented in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS: Most studies (53) used isoniazid for 9 months. The prevalence of use and adherence to treatment varied considerably (18% to 100%), and were evaluated by participant completion of isoniazid treatment for latent tuberculosis infection. The adverse events most frequently reported were hepatotoxicity, gastric intolerance, and neuropathy; the rates of occurrence ranged from < 1% to 48%. In the studies that evaluated the effectiveness of isoniazid for latent tuberculosis infection, the rate varied from 0 to 19.7% for patients who did not have active tuberculosis after the follow-up period.
CONCLUSIONS: The importance of maintaining follow up for patients using isoniazid should be emphasized due to the risk of developing adverse events. Despite the treatment challenges, the rates of patients who used isoniazid and developed active tuberculosis during the follow-up period were low. We believe that isoniazid continues to contribute to tuberculosis control worldwide, and better care strategies are required.

Generalized perforating granuloma annulare (GPGA) is a very rare form of granuloma annulare, with only 31 reported cases to the best of our knowledge. Furthermore, GPGA is a chronic disease that mimics many diseases, with no known exact etiology, resulting in a lack of specific clinical criteria leading to a lack of guidelines for diagnosis and therapy. In GPGA, papules are the predominant lesions followed by central crusting/scaling or umbilication; pustules, plaques, annular lesions or nodules are less frequent. We report a 66-year-old woman who presented with a 7-month history of mostly asymptomatic generalized infiltrated, flesh-colored to red-brown umbilicated or crusted papules. Histopathological findings were compatible with perforating granuloma annulare. Diagnostic workup revealed latent tuberculosis. To the best of our knowledge, this is the second published case of GPGA associated with latent tuberculosis and the first one that was successfully treated by isoniazid monotherapy. From our case we can speculate and support the theory that GPGA is a phenotypic granulomatous response to multiple etiologies and/or antigenic stimulation and that testing for tuberculosis should be seriously considered in the evaluation of patients with GPGA.

The Directly Observed Treatment-Short Course (DOTS) Programme was implemented by WHO and includes a combination of four anti-tuberculosis (TB) drugs (isoniazid, pyrazinamide, ethambutol and rifampicin) for a period of six months to eradicate the TB infection completely. Diabetes mellitus (DM) is recognized as one of a strong contributor of TB according to World Health Organization (WHO). The presence of diabetes mellitus type 2 (DM type 2) makes TB treatment complicated. Thus, the objective of the current meta-analysis was to identify and quantify the impact of type 2 DM on treatment outcomes of TB patients treated under the DOTS Programme.
This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Through a systematic review of relevant literature, we focused on studies investigating treatment outcomes including extended treatment duration and recurrence for individuals with both TB and DM undergoing DOTS therapy. The extracted information included study designs, sample sizes, patient characteristics and reported treatment results.
In 44 studies from different parts of the world, the pooled HR for the impact of DM on extended treatment duration and reoccurrence were HR 0.72, 95% CI 0.56-0.83, p < .01 and HR 0.93, 95% CI 0.70-1.04, p = .08, respectively. The pooled HR for impact of DM on composite TB treatment outcomes was calculated as 0.76 (95% CI 0.60-0.87), p < .01 with an effect size of 41.18. The heterogeneity observed among the included studies was moderate (I2 = 55.79%).
A negative impact of DM was found on recurrence and extended treatment duration in TB patients treated with DOTS therapy. DM type 2 is responsible for the TB treatment prolongation and TB recurrence rates. By implementing effective management strategies and advancing research, the challenges can be mitigated, arising due to the complex interaction between DM and TB.

Objectives: Accumulating evidence are available on the efficacy of high-dose isoniazid (INH) for multidrug-resistant tuberculosis (MDR-TB) treatment. We aimed to perform a systematic review and meta-analysis to compare clinical efficacy and safety outcomes of high-dose INH- containing therapy against other regimes. Methods: We searched the following databases PubMed, Embase, Scopus, Web of Science, CINAHL, the Cochrane Library, and ClinicalTrials.gov. We considered and included any studies comparing treatment success, treatment unsuccess, or adverse events in patients with MDR-TB treated with high-dose INH (>300 mg/day or >5 mg/kg/day). Results: Of a total of 3,749 citations screened, 19 studies were included, accounting for 5,103 subjects, the risk of bias was low in all studies. The pooled treatment success, death, and adverse events of high-dose INH-containing therapy was 76.5% (95% CI: 70.9%-81.8%; I2: 92.03%), 7.1% (95% CI: 5.3%-9.1%; I2: 73.75%), and 61.1% (95% CI: 43.0%-77.8%; I2: 98.23%), respectively. The high-dose INH administration is associated with significantly higher treatment success (RR: 1.13, 95% CI: 1.04-1.22; p < 0.01) and a lower risk of death (RR: 0.45, 95% CI: 0.32-0.63; p < 0.01). However, in terms of other outcomes (such as adverse events, and culture conversion rate), no difference was observed between high-dose INH and other treatment options (all p > 0.05). In addition, no publication bias was observed. Conclusion: In MDR-TB patients, high-dose INH administration is associated with a favorable outcome and acceptable adverse-event profile. Systematic review registration: identifier CRD42023438080.

BACKGROUND: People with radiographic evidence for pulmonary tuberculosis (TB), but negative sputum cultures, have increased risk of developing culture-positive TB. Recent expansion of X-ray screening is leading to increased identification of this group. We set out to synthesise the evidence for treatment to prevent progression to culture-positive disease.
METHODS: We conducted a systematic review and meta-analysis. We searched for prospective trials evaluating the efficacy of TB regimens against placebo, observation, or alternative regimens, for the treatment of adults and children with radiographic evidence of TB but culture-negative respiratory samples. Databases were searched up to 18 Oct 2022. Study quality was assessed using ROB 2·0 and ROBINS-I. The primary outcome was progression to culture-positive TB. Meta-analysis with a random effects model was conducted to estimate pooled efficacy. This study was registered with PROSPERO (CRD42021248486).
RESULTS: We included 13 trials (32,568 individuals) conducted between 1955 and 2018. Radiographic and bacteriological criteria for inclusion varied. 19·1% to 57·9% of participants with active x-ray changes and no treatment progressed to culture-positive disease. Progression was reduced with any treatment (6 studies, risk ratio [RR] 0·27, 95%CI 0·13-0·56), although multi-drug TB treatment (RR 0·11, 95%CI 0·05-0·23) was significantly more effective than isoniazid treatment (RR 0·63, 95%CI 0·35-1·13) (p = 0·0002).
CONCLUSIONS: Multi-drug regimens were associated with significantly reduced risk of progression to TB disease for individuals with radiographically apparent, but culture-negative TB. However, most studies were old, conducted prior to the HIV epidemic and with outdated regimens. New clinical trials are required to identify the optimal treatment approach.