Isoniazid Prophylaxis Research Articles

Latent Tuberculosis Infection in Haematopoietic Stem Cell Transplant Recipients: A Retrospective Italian Cohort Study in Tor Vergata University Hospital, Rome.

The results of tuberculosis (TB) screening and reactivation in a cohort of 323 adult patients undergoing haematopoietic stem cell transplantation (HSCT) from 2015 to 2019 at the University Hospital of Tor Vergata, Rome, Italy, were reported. A total of 260 patients, 59 (18.3%) autologous and 264 (81.7%) allogeneic transplants, underwent Interferon Release (IFN)-γ (IGRA) test screening: 228 (87.7%) were negative, 11 (4.2%) indeterminate and 21 (8.1%) positive. Most of the IGRA-positive patients were of Italian origin (95.2%) and significantly older than the IGRA-negative (p < 0.001); 22 (8.5%) patients underwent a second IGRA during the first year after transplantation, and 1 tested positive for IGRA. Significantly lower monocyte (p = 0.044) and lymphocyte counts (p = 0.009) were detected in IGRA negative and IGRA indeterminate patients, respectively. All latent TB patients underwent isoniazid prophylaxis, and none of them progressed to active TB over a median follow-up period of 63.4 months. A significant decline in TB screening practices was shown from 2015 to 2019, and approximately 19% of patients were not screened. In conclusion, 8.1% of our HSCT population had LTBI, all received INH treatment, and no reactivation of TB was observed during the follow-up period. In addition, 19% escaped screening and 8% of these came from countries with a medium TB burden, therefore at higher risk of possible development of TB.

Incidence and predictors of Tuberculosis among patients enrolled in Anti-Retroviral Therapy after universal test and treat program, Addis Ababa, Ethiopia. A retrospective follow -up study.

IntroductionTuberculosis (TB) is the leading killer of people living with HIV (PLHIV) and almost one-third of deaths in the world are attributed to it and many of these deaths occur in developing countries. Despite these evidences, after the implementation of universal test and treat (UTT) strategy, information regarding the incidence and predictors of tuberculosis among PLHIV is limited in Ethiopia. Therefore, this study aimed to assess the incidence and predictors of tuberculosis among patients enrolled in Anti-Retroviral Therapy (ART) after universal test and treat program at St. Peter hospital and Zewditu Memorial Hospital, Addis Ababa, Ethiopia.MethodsInstitutional-based retrospective cohort study was conducted from November 1 to 30, 2020. Simple random sampling was used to select a total of 539 adults records which was enrolled on ART. Data was collected and entered into EPI DATA 3.1 and analyzed using STATA version 14.1. Time-to-event distributions were estimated using Kaplan–Meier estimates. Hazards across different categories were compared using log-rank tests. Predictors were identified using the Cox proportional hazards model. The hazard ratio (HR) and 95% confidence interval (CI) were computed. Variables having P-value < 0.05 from the multivariable analysis were considered as a statistically significant.ResultAmong 539 records reviewed, 529 (98%) were included in the final analysis. The total follow-up period was 1529 Person-Year (PY). The incidence rate in this cohort was found to be 4.84 per 100-person year (95%CI,3.83–6.11). CD4 count<200 (AHR: 3.14,95% CI:1.64–7.10), poor adherence (AHR:2.16, 95% CI:1.21–3.85), underweight (AHR:2.42, 95% CI: 1.30–4.51), not taking isoniazid prophylaxis therapy (AHR: 2.78,95% CI: 1.06–7.30), being bedridden 3.06; (AHR: 3.06, 95% CI: 1.50–6.24), and baseline WHO stage three or four (AHR:2.33, 95% CI:1.08–5.02) were independent predictors for the incidence of TB among HIV positive patients.ConclusionIn this study, the incidence of tuberculosis is relatively low as compared to studies done before the initiation of test and treat program in Ethiopia. low CD4count, poor level of adherence, low BMI, not taking IPT prophylaxis, bedridden functional status, and being on baseline WHO stage III or IV were found to increase the hazard of tuberculosis. Hence, close follow up, reminders, surveillance, and tracing mechanisms targeting this higher risk group would decrease Tuberculosis among PLHIV.

Effectiveness and safety of available preventive tuberculosis treatment regimens for children and adolescents: protocol for a systematic review and network meta-analysis

IntroductionApproximately 5%–10% of individuals with untreated latent tuberculosis infection (LTBI) will progress to active tuberculosis (TB). Children are at a higher risk for progression to TB disease than adults. Isoniazid...

Isoniazid prophylaxis in liver transplant recipient with latent tuberculosis: Is it harmful for transplanted liver?

Liver transplantation (LT) is considered the only treatment for patients with end-stage liver disease and, despite its incredible impacts on the patients' health status, places them in an immunocompromised state in which opportunistic infection would find a way to present. Latent tuberculosis infection (LTBI) is the most common form of TB and can be diagnosed through tuberculin skin test (TST) or Interferon-Gamma Release Assays (IGRA). LT recipients are at significant risk of TB activation. There is no strict guideline to approaching these cases though, in most centers, Isoniazid (INH) would be prescribed prophylactically. INH is a hepatotoxic medication and can have adverse effects on the transplanted liver. There is no consensus on this issue; therefore, we aimed to survey the potential hepatotoxic effects of INH among LT recipients in Shiraz, Iran. A retrospective cohort study was conducted among LT candidates and recipients at Abu Ali Sina Organ Transplantation Center between 1993 and 2019. All the cases underwent TST and chest X-ray to detect LTBI. All the LTBI were treated with INH from 6-9 months and followed by the level of liver enzymes for quick detection of hepatotoxicity. A control group was selected among LT recipients and matched for age, gender, MELD score, and donor age. Among 4895 medical records reviewed, 55 (1.12%) cases had LTBI. Neither INH-related hepatotoxicity, nor signs and symptoms that were suspicious to TB reactivation were reported. Overall, three deaths were reported, two because of myocardial infarction and one due to pneumonia. Ten patients (18.2%) experienced acute rejection as confirmed with pathology and responded to methylprednisolone. Aspartate aminotransferase (AST) was diminished from pre-LT time to the first time after transplantation; after that, it showed a steady pattern. Meanwhile, Alanine transaminase (ALT) was constant before and one stage later and decreased after that. Statistical analyses only showed significant changes in the total bilirubin titer between the case and control groups. This survey showed prophylactic management of LTBI with INH in LT candidates and recipients was associated with no hepatotoxicity or related death. It seems that INH prophylaxis is safe in LT settings and can efficiently prevent TB activation; however, careful monitoring for adverse effects and liver enzymes elevation is highly recommended.

Treatment in Latent Tuberculosis Uveitis-Is Immunosuppression Effective or Is Conventional 3- or 4-Drug Antituberculosis Therapy Mandatory?

Background/Aims: Controversy exists regarding 3- or 4 drug antituberculosis therapy (conventional ATT) in uveitis patients having latent tuberculosis (LTB), especially while initiating therapy with corticosteroids and/or other immunosuppressants. Methods: We performed a monocentral retrospective analysis of posterior uveitis patients with latent TB. Latent TB was diagnosed, in case of a positive QuantiFERON®-TB-Gold test and normal chest imaging, after ruling out other causes of infectious and noninfectious uveitis. Patients with active TB were excluded. From 2016 to 2020 we included 17 patients. Ophthalmological evaluation consisted of Best corrected visual acuity (BCVA), slit lamp examination, fundoscopy, OCT, and fluorescein- and indocyaningreen- angiography before and at months 3, 6, 12, 24, and the last follow-up after treatment. Results: Initially, all patients had active posterior uveitis with occlusive (n = 5 patients) and nonocclusive retinal vasculitis (n = 12 patients). Mean follow up was 28 ± 15 months. Therapy was started with systemic corticosteroids (mean prednisolone equivalent 71.3 mg/d) and already after 3 months it could be tapered to a mean maintenance dosage of 8.63 mg/d. Additional immunosuppressive treatment with cs- or bDMARDs was initiated in 14 patients (82%) due to recurrences of uveitis while tapering the corticosteroids <10 mg per/day or because of severe inflammation at the initial visit. While being on immunosuppression, best corrected visual acuity increased from 0.56 logMAR to 0.32 logMAR during follow-up and only three patients had one uveitis relapse, which was followed by switch of immunosuppressive treatment. As recommended, TB prophylaxis with 300 mg/d isoniazid was administered in 11 patients for at least 9 months while being on TNF-alpha-blocking agents. No patient developed active tuberculosis during immunosuppressive therapy. Conclusion: Mainly conventional ATT is strongly recommended—as monotherapy or in combination with immunosuppressives—for effective treatment in patients with uveitis due to latent TB. Although in our patient group no conventional ATT was initiated, immunosuppression alone occurred as an efficient treatment. Nevertheless, due to possible activation of TB, isoniazid prophylaxis is mandatory in latent TB patients while being on TNF-alpha blocking agents.

Tuberculosis and isoniazid prophylaxis among adult HIV positive patients on ART in Northwest Ethiopia.

Although antiretroviral therapy (ART) can avert tuberculosis (TB) incidence among human immunodeficiency virus (HIV) infected patients, the concomitant use of ART with isoniazid (INH) has a paramount effect. Despite this evidence, there is a paucity of data regarding TB incidence among HIV patients on ART with and without isoniazid prophylaxis and its predictors. Thus, this study sought to assess the incidence and predictors of TB among adult HIV positive patients on ART. This was a hospital based retrospective study including 368 adult HIV positive patients on ART in Gondar comprehensive specialized hospital between January 1, 2016, and April 30, 2019. Data was extracted from clinical laboratory and HIV care ART follow up clinic. The bi-variable and multivariable regression models were used to ascertain predictors of incident TB. Data was analyzed using SPSS version 20 software. A total of 335 adult HIV positive patients were included in the analysis, of whom, 56 (16.7%) were developed incident TB. Being ambulatory and bedridden (AOR: 2.2, 95% CI: 1.1, 4.6), advanced WHO clinical HIV disease stage (III and IV) (AOR: 3.2, 95% CI: 1.6, 6.1), not taking INH (AOR: 2.8, 95% CI: 1.3, 5.9), and baseline CD4+ T cell count ≤ 200 cell/mm3 (AOR: 3.6, 95% CI: 1.8, 7.2) were found to be the predictors of tuberculosis incidence. The study indicated a high TB incidence among HIV positive patients in Gondar. Therefore, scaling up the isoniazid preventive therapy program and its strict compliance is necessary to avert HIV fueled tuberculosis in HIV endemic areas.

Impact of COVID-19 pandemic on TB prevention and care in Addis Ababa, Ethiopia: a retrospective database study

ObjectiveThe current COVID-19 pandemic in Ethiopia could cause severe dysfunction in tuberculosis (TB) treatment, diagnostic services, and prevention and control efforts. In this study, we evaluated the effect of COVID-19...

Time to death among HIV-infected under-five children after initiation of anti-retroviral therapy and its predictors in Oromiya liyu zone, Amhara region, Ethiopia: a retrospective cohort study

BackgroundHuman Immunodeficiency Virus (HIV) is infection which mainly attacks immune system of an individual. Its disease progress is rapid in children and if treatment is not initiated nearly half of infected children will die by the second year of infection. In Ethiopia, nearly twenty four percent of HIV related death is happen to under-five children; however studies done in this specific age group are limited are with poor evidence of predictors.ObjectivesTo determine time to death and identify predictors of death in HIV infected under- five children on antiretroviral therapy in Amhara regional state, Oromia ‘liyu’ zone, Northeast Ethiopia, from 2014 to 2019.MethodsInstitution based retrospective follow up study was conducted in 376 under-five HIV- infected children on antiretroviral therapy from January 2014 to December 2019 in health institutions in Oromia Liyu Zone, Amhara region, Ethiopia. Multivariable Cox-proportional hazard regression model was used to identify independent predictors of mortality in HIV- infected under-five children on antiretroviral therapy.ResultAt the end of follow up, 304 (80.85%) of HIV-infected children were alive, 39 (10.95%) were lost to follow up, 12 (3.19%) were transferred out and 21 (5.59%) were reported dead due to HIV/AIDS. The cumulative survival probabilities of children after 3, 6, 12, 24 and 36 months were 0.99, 0.98, 0.97, 0.89 and 0.87 respectively. The overall mean time to death was 19.7 months (95%CI = 18.74–20.67) with incidence of 5.9 deaths per 100 child-months (95%CI: 3.89–9.09). Children with severe malnutrition at baseline (AHR = 4.9; 95 CI: 1.04, 23.50), advanced WHO clinical stage at enrolment (AHR = 3.9; CI: 1.37, 10.88), poor adherence to ART (AHR = 6.56; CI: 3.33, 10.14) and with no history of Isoniazide prophylaxis were significantly associated to higher mortality events (AHR = 3.6; CI: 1.24, 10.18).ConclusionDeath of HIV-infected under-five children on ART is high within the first one year after enrolment. The risk of death increased if the child was malnourished at beginning of treatment, had poor ART adherence, with advanced WHO clinical stages and lack of Isoniazide prophylaxis during their age of infancy.

Association between 9-month isoniazid prophylaxis of latent tuberculosis and severe hepatitis in patients treated with TNF inhibitors

To investigate associations between isoniazid for latent tuberculosis and risk of severe hepatitis, affecting patients with rheumatoid arthritis or ankylosing spondylitis whose treatment includes tumor necrosis factor inhibitors. Our self-controlled case series study analyzed Taiwan’s National Health Insurance Database from 2003 to 2015 to identify RA or AS patients, aged ≥ 20 years, receiving TNF inhibitors and a 9-month single isoniazid treatment. The outcome of interest was hospitalization due to severe hepatitis. We defined risk periods by isoniazid exposure (days): 1–28, 29–56, 57–84, 85–168, 169–252, and 253–280. To compare risk of severe hepatitis in exposed and non-exposed periods, we performed conditional Poisson regressions to generate incidence rate ratios (IRR) and 95% confidence intervals, with adjustment of patients’ baseline covariates including age, sex, HBV, HCV and related medication. Of 54,267 RA patients and 137,889 AS patients identified between 2000 and 2015, 11,221 (20.7%) RA and 4,208 (3.1%) AS patients underwent TNFi therapy, with 722 (5%) receiving isoniazid for latent tuberculosis. We identified 31 incident cases (4.3%) of hospitalization due to severe hepatitis. Of these hospitalization events, 5 occurred in the exposed periods, 25 occurred in the INH unexposed periods, and 1 occurred in the pre-exposure period. Compared with non-exposure, the risk of severe hepatitis was higher in exposed periods (incidence rate ratio [IRR]: 5.1, 95% CI: 1.57–16.55), especially 57–84 days (IRR: 17.29, 95% CI: 3.11–96.25) and 85–168 days (IRR:10.55, 95% CI: 1.90–58.51). The INH related fatal hepatotoxicity was not identified in our study. Our findings suggest an association between risk of severe hepatitis and exposure to isoniazid in patients with RA or AS under TNFi therapy, particularly within the exposed period 57–168 days. A close monitoring of liver function is mandatory to minimize the risk, especially within the first 6 months after initiation of 9 months isoniazid.

Risk of tuberculosis is increased in Behçet’s disease compared to other rheumatological disorders after anti-TNFα treatments: a case series and review of the literature

Background/aimTumor necrosis factor-alfa (TNF-a) antagonists are extensively utilized in the treatment of inflammatory rheumatic diseases and also shown to be effective in Behçet’s disease (BD) patients with major organ involvement. In this study, we aimed to re-evaluate the incidence of tuberculosis (TB) infection after anti-TNFa treatments and to reveal the risk of TB in BD.MethodsData of patients who received anti-TNFa treatment between 2005 and 2018 were assessed retrospectively. Demographic features, TNF-a antagonist type/treatment time, tuberculosis skin test (TST) and QuantiFERON results, isoniazid prophylaxis status, and concomitant corticosteroid (CS) treatments were collected. ResultsA total of 1277 (male/female = 597/680; median age = 49 years) patients were treated with TNF-a antagonist for a median of 33 months (Q1:12, Q3:62). Thirteen (1%) patients developed TB during the follow-up period. Within 13 TB-positive patients, 7 of them had pulmonary, and 7 had extrapulmonary TB. Although, the median time of (month) TNF-a antagonist treatment was higher in TB-positive patients than negative ones, the difference was not statistically significant (48 and 33 months, respectively, p = 0.47). Similarly, TB-positive patients were treated with CSs more than TB-negative patients (80% vs. 60%). Time from the initiation of TNF-a antagonist treatment to the diagnosis of TB had a median of 40 months (Q1-Q3: 22-56). There was a statistically significant increase of TB development in BD patients than non-BD patients after TNF-a antagonists (7.5% vs. 0.8%, respectively, p = 0.007). When we combined our patients with the other series from Turkey, among 12928 patients who received TNF-a antagonists, TB was positive in 12 (3.9%) of 305 BD patients compared to 112 (0.9%) of 12623 non-BD patients (p < 0.00001).ConclusionOur results suggest a higher frequency of TB infections in BD patients with TNF-a antagonists. As biologic agents are increasingly used for major organ involvement in current practice for BD, screening mechanisms should be carefully implemented.

The efficacy of isoniazid prophylaxis in renal transplant recipients in a high tuberculosis burden country.

Renal transplant recipients are at high risk of tuberculosis (TB). We started isoniazid (INH) prophylaxis of 1 year duration in all renal transplant recipients from April 2009. Our aim was to assess the incidence of TB on INH prophylaxis and its tolerability. This was a retrospective observational study. The files of renal transplant recipients from April 2009 to December 2011 were reviewed till June 2015. We noted the incidence of TB, INH tolerability, and development of resistance. We compared the incidence of TB with the historical controls who never received the prophylaxis. A total of 910 patients were reviewed and followed up for 4.8 years. INH prophylaxis was completed by 825 (91%) patients. A total of 46 patients (5%) developed active TB as compared to 15% in the historical controls. The median time of TB diagnosis from transplantation was 2.8 years. In the first-year post transplant, out of total TB cases, 52% occurred in the historical controls whereas 13% occurred in study cohort. Around 67% had TB>2 years after transplant. Overall 1.43% had hepatotoxicity. There was a significant reduction in TB among those who completed prophylaxis to those who did not (p<0.001). Of 14 cultures, one isolate was INH resistant (7%). INH prophylaxis was well tolerated. The incidence of TB decreased in the first 2 years. However there was a surge in TB cases 1 year after stopping INH therapy. We should consider prolonging the duration of INH prophylaxis in high TB burden countries in renal transplant recipients.

Incidence and predictors of mortality among children co-infected with tuberculosis and human immunodeficiency virus at public hospitals in Southern Ethiopia.

BackgroundTuberculosis and human immune deficiency virus co-infections remained the most common cause of child mortality for the last ten years. Globally, 1.2 million cases of tuberculosis occurred in patients living with HIV/AIDS, of which 1.0 million cases occurred in children. The public health impact of tuberculosis and human immune deficiency virus co-infection among children is high in developing countries and Sub-Saharan Africa accompanied three fourth of the global burden. However, there are limited studies that assess the incidence and predictors of mortality among tuberculosis and human immune deficiency virus co-infected children in Ethiopia.MethodsA facility-based retrospective cohort study was conducted at Public hospitals in Southern Ethiopia with a total of 286 randomly selected records of ART enrolled children from 1st January 2009 to 31stDecember 2018. Data were entered into Epi Data version 3.1 and exported to STATA version 14 for analysis. Bivariate and multivariable Cox proportional hazards model was fitted to identify the predictors of mortality. Variables that had a p-value<0.05 at 95%CI in the multivariable cox proportional hazard model were considered as statistically significant.ResultsA total of 274 tuberculosis and human immunodeficiency virus co-infected children’s records were reviewed. The incidence of mortality among tuberculosis and human immunodeficiency virus co-infected children was 17.15 per 100 children. The overall incidence density rate of mortality was 2.97(95%CI: 2.2, 3.9) per 100 child year of observation and being anemic (AHR: 2.6; 95%CI: 1.28, 5.21), not initiating isoniazid prophylaxis therapy (AHR: 2.8; 95%CI: 1.44, 5.48), developing extrapulmonary tuberculosis (AHR: 5.7; 95%CI: 2.67, 12.56) and non-adherence (AHR: 5.2; 95%CI: 2.19, 12.39) were independent predictors of mortality.ConclusionMortality rate was high among TB/HIV co-infected children at the public hospitals in Southern Ethiopia. Extra-pulmonary tuberculosis, anemia, non-adherence, and isoniazid preventive therapy use were statistically significant predictors of mortality among TB/HIV co-infected children. Therefore, extra pulmonary tuberculosis, and anemia should be closely monitored to increase their adherence as well as they should be provided with isoniazid preventive therapy.

Effect of Isoniazid Prophylaxis Therapy on the Prevention of Tuberculosis Incidence and Associated Factors Among HIV Infected Individuals in Northwest Ethiopia: Retrospective Cohort Study.

BackgroundTreating latent tuberculosis (TB) infection with Isoniazid (INH) among human immune virus (HIV) infected patients reduces active TB occurrence and death by 62% and 26%, respectively. Even though other studies show aforementioned evidence, TB incidence and its associated factors among HIV-infected individuals who were on INH and never on INH is not well studied in northwest Ethiopia. Therefore, this study tried to assess the effect of INH prophylaxis in TB prevention and associated factors among HIV-infected individuals.MethodsData were extracted from charts of HIV-infected clients who completed INH (193) and were never on INH (198) after a simple random sampling selection was done among newly diagnosed patients on follow-up from 2008 to 2015. After data were collected, it was entered into Epi info version 7 and exported to SPSS version 22 for analysis. Cox regression model was fitted and the hazard ratio was reported.ResultsIn this study, the overall TB incidence rate among HIV patients was 3.5/100 person-years (PY) [95% CI: 2.55, 4.82]. But it was 7.1/100 PY among patients who were never on INH and 0.35/100 PY among patients who completed INH. INH completed [adjusted hazard ratio (AHR) = 0.08, 95% CI: 0.02–0.37], on anti-retroviral therapy (ART) [AHR = 0.02, 95% CI: 0.01–0.04], baseline World Health Organization (WHO) stage I & II [AHR =0.22, 95% CI: 0.08–0.62] and baseline CD4 ≤ 350 [AHR=3.76, 95% CI: 1.39–10.18] were significantly associated with TB incidence.ConclusionPutting patients on INH for 6 months and ART were protective factors against TB. Therefore, health institutions are recommended to provide INH after ruling out active TB and contraindications for HIV-infected individuals.

Evaluation of a serum-based antigen test for tuberculosis in HIV-exposed infants: a diagnostic accuracy study

BackgroundNon-sputum methods are urgently needed to improve tuberculosis diagnosis and treatment monitoring in children. This study evaluated the ability of a serum assay quantifying a species-specific peptide of the Mycobacterium tuberculosis CFP-10 virulence factor via nanotechnology and matrix-assisted laser desorption ionization time-of-flight mass spectrometry to diagnose tuberculosis in HIV-infected and HIV-uninfected infants.MethodsSerum CFP-10 peptide signal was blinded evaluated in cryopreserved sera of 519 BCG-immunized, HIV-exposed infants (284 HIV-infected, 235 HIV-uninfected) from a multi-center randomized placebo-controlled isoniazid prophylaxis trial conducted in southern Africa between 2004 and 2008, who were followed up to 192 weeks for Mtb infection and TB. Children were classified as confirmed, unconfirmed, or unlikely tuberculosis cases using 2015 NIH diagnostic criteria for pediatric TB.ResultsIn HIV-infected infants, CFP-10 signal had 100% sensitivity for confirmed TB (5/5, 95% CI, 47.8–100) and 83.7% sensitivity for unconfirmed TB (36/43, 95% CI 69.3–93.2), with 93.1% specificity (203/218, 95% CI 88.9–96.1). In HIV-uninfected infants, CFP-10 signal detected the single confirmed TB case and 75.0% of unconfirmed TB cases (15/20; 95% CI 50.9–91.3), with 96.2% specificity (177/184, 95% CI, 92.3–98.5). Serum CFP-10 achieved 77% diagnostic sensitivity for confirmed and unconfirmed TB (13/17, 95% CI, 50–93%) at ≤ 24 weeks pre-diagnosis, and both CFP-10-positivity and concentration declined following anti-TB therapy initiation.ConclusionsSerum CFP-10 signal exhibited high diagnostic sensitivity and specificity for tuberculosis in HIV-infected and HIV-uninfected infants and potential utility for early TB detection and monitoring of anti-TB treatment responses.

POS-748 TUBERCULOSIS IN PAEDIATRIC KIDNEY TRANSPLANT RECIPIENTS – A SINGLE CENTRE EXPERIENCE.

Tuberculosis (TB) remains a major challenge in transplant patients particularly in endemic countries with frequent loss of transplanted kidneys. Importantly, many of the features for TB, specifically in the paediatric post-kidney transplant population, have not yet been adequately defined. The aim of the study was to describe the incidence, clinical presentation and outcomes in our paediatric kidney transplant recipients. This was a retrospective descriptive study of 212 paediatric kidney transplant recipients at Red Cross War Memorial Children`s Hospital from 1995 to 2019. Among the 212 kidney transplant patients, 20 (9%) were diagnosed with tuberculosis (TB) of which two thirds (n=13) were diagnosed during the first two years post-transplant. TB was confirmed bacteriologically in 12 (60%) children, and the remaining 8(40%) were clinically diagnosed. The main presenting symptoms were fever (n=13, 65%), weight loss (n=12, 60%) and cough (n=10, 50%). Acute rejection of the transplanted kidney was confirmed at diagnosis in nine children. Immunosuppression had been intensified with pulsed intravenous steroids for a rejection episode within the 3 months before the diagnosis of tuberculosis in 8 (40%) children. Tuberculin skin test was done in all children and was positive in 4 (20%) whilst chest radiography showed abnormalities suggestive of TB in 16 (80%) children. Among the children with TB, 15 (75%) were pulmonary, five (25%) extra-pulmonary among whom three with the TB foci in the allograft. A coinfection with Ebstein Barr virus was found in three cases, Cytomegalovirus in two children and Staphylococcus in another two children. Due to drug interactions, up to three fold increase in cyclosporine or tacrolimus dose was required to maintain therapeutic blood levels which was regularly monitored in the weeks after commencing TB treatment. Isoniazid (INH) prophylaxis appeared protective against development of TB (p=0.04). Other factors such as gender (p=0.25), age group above 15 years (p=0.59) ,10-14 years(p= 0.76), 5-9 years (p=0.81), and type of allograft (p= 0.73) were not significant risk factors for developing TB post kidney transplantation. All the TB infections were successfully treated with a graft and patient survival of 100%. Kidney transplant recipients have a high risk of TB. Chest radiography is a sensitive TB screening tool. A high index of suspicion is required due to its atypical presentation in these patients and frequent association with other infections. Frequent and meticulous monitoring of immunosuppression drug levels during treatment of TB is required to avoid loss of patient or graft. Isoniazid prophylaxis protects against development of TB in this population.

Evaluation of latent tuberculosis infection in liver transplant recipients.

Background and Objectives:Tuberculosis is one of the main reasons for mortality in liver transplant recipients. Since Iran is considered as a tuberculosis-endemic country, the present study aims to evaluate the outcome of latent tuberculosis infection in transplant recipients after liver transplantation.Materials and Methods:The present analytical cross-sectional study was performed on transplanted patients in Imam Khomeini Complex Hospital in Tehran Iran from 2006 to 2016. All patients with positive tuberculin skin test were enrolled. Variables including demographic information, therapeutic and outcome data were gathered and analyzed.Results:Among 675 transplant recipients, 100 patients had positive tuberculin skin test (14.8%). Sixty seven percent of recipients were men and the mean age was 72.67 ± 1.3 years. All patients’ received Isoniazid prophylaxis before transplantation. The mean duration of anti-tuberculosis prophylaxis before and after transplant were 2.7 ± 1.9 and 3.6 ± 5.5 months, respectively. Tuberculosis has not been occurred in none of these patients after a mean follow up time of 45.21 ± 3 months. During the study period, four subjects infected by Mycobacterium tuberculosis, while their skin test was negative before transplant.Conclusion:According to our study, tuberculin skin test is a reliable and sensitive test for diagnosis of latent tuberculosis in liver transplant candidates. Isoniazid prophylaxis is well tolerated in patients with end stage liver diseases and liver transplant recipients.

Pellagra a review exploring causes and mechanisms, including isoniazid-induced pellagra.

Pellagra is a clinical syndrome caused by a deficiency of niacin (nicotinic acid) and/or its precursor tryptophan. The cardinal manifestations are 4 D's: dermatitis, diarrhoea, dementia and in worst case death. Increased use of isoniazid prophylaxis along with antiretroviral therapy in countries where latent tuberculosis is common has been associated with increased presentations with pellagra.

Adherence to international standards of tuberculosis care guidelines among private practitioners, Chennai, Tamilnadu, India, 2016–2017

Background: Tuberculosis (TB) prevalence in Indian city of Chennai, located in Tamil Nadu, is higher than national average. Around 80% of TB patients in Chennai, approach private practitioners for first consultation. International standards for TB care (ISTC) recommends sputum examination as gold standard for diagnostics, contact tracing, screening for HIV, diabetes comorbidities, case notification and Isoniazid prophylaxis treatment (IPT). We did a study to describe the adherence to ISTC recommended treatment practices among private doctors and factors associated with adherence. Methods and materials: We did a cross-sectional analytical study between August 2016 and August 2017. We did multistage cluster sampling in the 15 zones of Chennai. We needed a sample of 225 doctors, assuming prevalence of adherence to ISTC diagnostic practices as 63%, with 10% as margin of error and 95% confidence level. We used semi-structured questionnaire for interview. We calculated proportions for adherence to ISTC guidelines. We did a multivariate analysis to calculate adjusted odd ratio (AOR) with 95% confidence interval (95% CI) to identify factors associated with adherence to ISTC guidelines. Results: Among 225 doctors interviewed, 140 were males (62%) and majority were in 30–39 years (44%) age group. Sputum examination as gold standard for diagnosis was practised by 58% (n = 130) of doctors and was associated with exposure to RNTCP training (AOR = 1.9, 95% CI = 1.1–3.5). Contact tracing was practiced by 38% (n = 85) and adherence was associated with age of doctors above 40 years (AOR = 3.1, 95% CI = 1.2–7.9). While screening for HIV and Diabetes was practiced by 63% (n = 142) and 65% (n = 146) respectively, being in government service (AOR = 2, 95% CI = 1.04–3.9) and exposure to RNTCP training (AOR = 2, 95% CI = 1.03–3.9) were associated with screening. Case notification was practiced by 65% (n = 146) and adherence was associated with RNTCP training (AOR = 3, 95% CI = 1.5–6.1) and awareness about mandatory notification (AOR = 8, 95% CI = 2.4–26.6). Awareness about IPT prophylaxis was 32% (n = 73) and was associated with exposure to RNTCP training (AOR = 2.2, 95% CI = 1.1–4.3). Conclusion: Adherence to ISTC guidelines among private practitioners was low. Training in RNTCP was associated with adherence. We recommend RNTCP training for all private practitioners.

Chest roentgenography is complementary to interferon-gamma release assay in latent tuberculosis infection screening of rheumatic patients

BackgroundA study of latent tuberculosis infection (LTBI) burden by chest roentgenography (CXR) with reference to interferon-gamma release assay (IGRA) is still lacking in rheumatic patients of an intermediate tuberculosis burden area.MethodsWe retrospectively reviewed clinical data of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) receiving LTBI screening for biologics from Jan 2013 to April 2014.ResultsA total of 238 rheumatic patients who underwent LTBI screening were included in this study, of whom 46 (19.3%) had positive IGRA tests, 178 (74.8%) had negative results, and 14 (5.9%) had indeterminate results. Radiological findings suggesting healed tuberculosis (CXR-old-TB) were found in 18.1% of all patients, 23.9% in the IGRA -positive patients vs 16.9% in the IGRA-negative patients (OR 1.55 95% CI: 0.71–3.39, p = 0.27). Forty (40/46, 87.0%) IGRA-positive patients received isoniazid prophylaxis and 77.5% of them finished treatment. Six patients developed adverse effects of isoniazid treatment, resulting in an overall number needed to harm (NNH) of 6.7 (40/6). IGRA-non-positive patients with old TB-suggestive CXR comprised 13.4% (32/238) of all our rheumatic patients, and one of them developed pulmonary tuberculosis within one year after screening.ConclusionsLTBI disease burden in rheumatic patients is substantial according to the estimation of CXR and IGRA screening. Correlation between CXR and IGRA is not significant in rheumatic patients, which implies their complementary roles. IGRA-non-positive patients with old TB-suggestive CXR comprise a significant portion in rheumatic patients and merit cautious follow-up by rheumatologists, tuberculosis specialists, and pulmonologists.

Management Issues in Myasthenia Gravis Patients Living With HIV: A Case Series and Literature Review.

South Africa is home to more than seven million people living with human immunodeficiency virus (HIV) and a high prevalence of tuberculosis. Human immunodeficiency virus–infected individuals may develop myasthenia gravis (MG), which raises questions regarding their management. An MG database, with 24 years of observational data, was audited for HIV-infected persons. Case reports of MG in HIV-infected persons were reviewed. We identified 17 persons with MG and HIV infection. All had generalized MG with a mean age at onset of 37.8 years. Eleven had acetylcholine receptor antibody–positive MG; one had antibodies against muscle-specific kinase. Six developed MG prior to HIV infection (mean CD4+ 361 cells/mm3); four worsened <6 months of starting antiretrovirals. Eleven developed MG while HIV-infected (mean CD4+ 423 cells/mm3); five presented with mild MG; three in MG crisis requiring rescue therapies (intravenous immune globulin or plasma exchange and/or intravenous cyclophosphamide). Two were diagnosed with HIV infection and MG at the same time. Fifteen required maintenance steroid-sparing immune therapies, predominantly azathioprine, or methotrexate. Plasma HIV viral loads remained below detectable levels on antiretrovirals during immunosuppressant treatment. Over the average follow-up of 6 years, 10 achieved minimal manifestation status, and the remainder improved to mild symptoms. Three cases had tuberculosis before MG, but none developed tuberculosis reactivation on immunosuppressive therapy; one used isoniazid prophylaxis. Herpes zoster reactivation during treatment occurred in one. Conclusions include the following: MG in HIV-infected patients should be managed similarly to individuals without HIV infection; half develop moderate–severe MG; MG symptoms may worsen within 6 months of antiretroviral initiation; safety monitoring must include plasma HIV viral load estimation. Isoniazid prophylaxis may not be indicated in all cases.