Isoniazid Preventive Treatment Research Articles

Predictors of positive tuberculin skin test in neonates exposed to pulmonary tuberculosis.

Neonates are at risk of nosocomial tuberculosis (TB) infection from health care workers (HCWs) in neonatal care facilities, which can progress to severe TB diseases. Tuberculin skin test (TST) is commonly used for TB diagnosis, but its accuracy in neonates is influenced by various factors, including bacilli Calmette-Guérin (BCG) vaccination. This study aimed to identify predictors of positive TSTs in neonates exposed to HCWs with pulmonary TB. A retrospective observational study was conducted to compare the frequency of predictors between TST-positive and TST-negative neonates. Demographic, epidemiological, and clinical data of neonates exposed to TB, along with that of HCW and household contacts, were collected retrospectively through contact investigations with the Korean National TB Surveillance System (KNTSS) database. TSTs using 2 tuberculin units of purified protein derivative RT23 were performed on exposed neonates at the end of preventive TB treatment. Firth logistic regression was performed to identify predictors of TST positivity. Contact investigations revealed that 152 neonates and 54 HCWs were exposed to infectious TB index cases in 3 neonatal care facilities. Of 152 exposed neonates, 8 (5.3%) had positive TST results. Age of 6 days or more at the initial exposure is a statistically significant predictor of positive TST (Firth coefficient 2.1, 95% confidence interval 0.3-3.9, P = 0.024); BCG vaccination showed no statistical significance in both univariable and multivariable analysis. Sex, prematurity, exposure duration, duration from initial exposure to contact investigation, and isoniazid preventive treatment duration were not significant predictors. Age at the initial exposure is a significant predictor of positive TST in neonates exposed to active pulmonary TB. Given the complexities of TST interpretation, including false positives due to BCG vaccination, careful risk assessment is necessary for appropriate decision-making and resource allocation in the management of neonatal TB exposure.

Izoniazidom navodené poškodenie pečene sprevádzané ikterom

Summary: Isoniazid belongs to the first line antituberculosis drugs and can be used for the treatment of both active and latent tuberculosis infections. It is a part of combined regimens, for the preventive treatment of tuberculosis isoniazid can be used in monotherapy as well. Even though elevations in serum aminotransferases levels during isoniazid therapy are seen frequently, the development of symptomatic hepatitis is rare, according to specialised literature. This article describes a case of a patient who developed drug-induced liver injury accompanied by jaundice during the isoniazid preventive treatment of tuberculosis. It also provides a summary of the currently known risk factors, pathogenesis, and incidence of hepatotoxicity observed throughout therapy with this antituberculosis drug. We also illustrate the process of diagnosing drug--induced liver injury in clinical practice settings with the utilisation of the updated RUCAM score. Key words: jaundice – isoniazid – drug-induced liver injury – tuberculosis preventative therapy – updated RUCAM score.

Community-supported self-administered tuberculosis treatment combined with active tuberculosis screening: a pilot experience in Conakry, Guinea

ABSTRACT Directly observed treatment (DOT) for tuberculosis (TB) is recommended by the World Health Organization. However, DOT does not always meet patients’ preferences, burdens health facilities, and is hard to implement in settings where access to healthcare services is regularly interrupted. A model addressing these limitations of DOT is community-supported self-administered treatment (CS-SAT), in which patients who self-administer TB treatment receive regular visits from community members. Guinea is a country with a high TB burden, recurrent epidemics, and periodic socio-political unrest. We piloted a CS-SAT model for drug-susceptible TB patients in Conakry, led by community volunteers, who also conducted active TB case finding among household contacts and referrals for isoniazid preventive treatment (IPT) in children below 5 years old. We aimed to assess TB treatment outcomes of patients on CS-SAT and describe the number of patients identified with TB case finding and IPT provision. Prospectively enrolled bacteriologically confirmed TB patients, presenting to two facilities, received monthly TB medication. Community volunteers performed bi-weekly (initiation phase) and later monthly (continuation phase) home visits to verify treatment adherence, screen household contacts for TB, and assess IPT uptake in children under five. Among 359 enrolled TB patients, 237 (66.0%) were male, and 37 (10.3%) were HIV-positive. Three hundred forty (94.7%) participants had treatment success, seven (1.9%) died, seven (1.9%) experienced treatment failure, and five (1.4%) were lost-to-follow-up. Among 1585 household contacts screened for TB, 26 (1.6%) had TB symptoms, of whom five (19.2%) were diagnosed with pulmonary TB. IPT referral was done for 376 children from 198 households. In a challenging setting, where DOT is often not feasible, CS-SAT led to successful TB treatment outcomes and created an opportunity for active TB case finding and IPT referral. We recommend the Guinean CS-SAT model for implementation in similar settings.

Factors associated with isoniazid preventive treatment interruption and completion among PLHIV in Gombe Hospital, Uganda, 2017–2019

BackgroundTuberculosis (TB) is the leading cause of death in persons living with HIV (PLHIV). PLHIV carry a disproportionate burden of TB infection with risks 20–37 times greater than HIV-negative populations. While isoniazid preventive treatment (IPT) is regarded as a crucial component of HIV care to prevent active TB, the uptake among PLHIV remains very poor. Studies on the factors associated withIPT interruption and completion among PLHIV in Uganda are scarce. Thus, in Gombe Hospital in Uganda, this study assessed the factors associated withIPT interruption and completion among PLHIV. MethodsThis was a hospital-based cross-sectional study that used both quantitative and qualitative methods of data collection from January 3rd, 2020 to February 28th, 2020. We reviewed the medical records of 686 PLHIV who received IPT at Gombe Hospital from January 1st, 2017 to December 31st, 2019. Binary logistic and modified Poisson regression were used to analyze factors associated with IPT completion and interruption. We conducted 7 key informant interviews and 14 in-depth interviews. ResultsSecond-line antiretroviral therapy (AOR = 46, p < 0.001) and age ≥ 45 years (AOR = 0.2, p = 0.040) were significantly associated with IPT interruption, while attending routine ART counseling sessions (APR = 1.5, p < 0.001) and prescription for ≥ 2 months at the start of IPT (APR = 1.1, p = 0.010) were associated with IPT completion. Barriers to IPT completion included pill burden, forgetfulness, poor integration of IPT in HIV healthcare services, and lack of awareness of IPT, while facilitators were easy accessibility of IPT and support from implementing partners. ConclusionsSide effects and pill burden were the major barriers to the long-term completion of IPT. Supplying ≥ 2 months IPT drugs, using IPT drugs with fewer side effects, and counseling during IPT could improve IPT completion and reduce IPT interruption.

Completion of 6-mo isoniazid preventive treatment among eligible under six children: A cross-sectional study, Lagos, Nigeria.

Nigeria is one of the thirty high burden countries with significant contribution to the global childhood tuberculosis epidemic. Tuberculosis annual risk for children could be as high as 4% particularly in high tuberculosis (TB) prevalent communities. Isoniazid (INH) Preventive Therapy has been shown to prevent TB incidence but data on its implementation among children are scarce. To determine the completion of INH among under six children that were exposed to adults with smear positive pulmonary TB in Lagos, Nigeria. This was a hospital-based retrospective cross-sectional review of 265 medical records of eligible children < 6 years old enrolled for INH across 32 private hospitals in Lagos, Nigeria. The study took place between July and September 2020. Data was collected on independent variables (age, gender, type of facility, TB screening, dose and weight) and outcome variables (INH outcome and proportion lost to follow up across months 1-6 of INH treatment). About 53.8% of the participants were female, 95.4% were screened for TB and none was diagnosed of having TB. The participants' age ranged from 1 to 72 mo with a mean of 36.01 ± 19.67 mo, and 40.2% were between the ages of 1-24 mo. Only 155 (59.2%) of the 262 participants initiated on INH completed the six-month treatment. Cumulatively, 107 (41.0%) children were lost to follow-up at the end of the sixth month. Of the cumulative 107 loss to follow-up while on INH, largest drop-offs were reported at the end of month 2, 52 (49%) followed by 20 (19%), 17 (16%), 11 (10.2%) and 7 (6.5%) at months 3, 4, 5 and 6 respectively. The analysis showed that there was no significant association between age, gender, type of facility and completion of INH treatment (P > 0.005). This study demonstrated suboptimal INH completion rate among children with only 6 out of 10 children initiated on INH who completed a 6-mo treatment in Lagos, Nigeria. The huge drop-offs in the first 2 mo of INH calls for innovative strategies such as the use of 60-d INH calendar that would facilitate reminder and early engagement of children on INH and their caregivers in care and across the entire period of treatment.

Health workers' knowledge and practice of Isoniazid preventive treatment guidelines in health facilities in Ebonyi State, Nigeria.

Isoniazid preventive therapy is recommended as part of a comprehensive HIV and AIDS care strategy. IPT is used as prophylaxis to reduce the incidence of TB in HIV-infected persons. However, its implementation has been very slow and has been influenced by several factors. This study assessed health workers' knowledge and adherence to Isoniazid Preventive Therapy guidelines. This was a cross-sectional study in six health facilities providing HIV care in Ebonyi State using a semi-structured, self-administered questionnaire. Data were collected from 85 health workers working in the HIV clinics. Data were also extracted from 200 patient treatment cards. Data analysis was carried out using SPSS version 20 software. Chi-square statistics and logistic regression were carried out to determine the association between socio-demographic characteristics and knowledge as well as self-reported practice of the guideline. Slightly over half of the respondents (58.8%) had good knowledge of the guideline, and the majority (75.3%) self-reported that they practiced the guideline. Only 17% of the treatment cards had isoniazid prescribed and only 11% of these had patient adherence assessed. The most common challenges to implementation of the guideline cited by health workers were unavailability of isoniazid, poor awareness, patient non-adherence, poor resources, high pill burden, and lack of training. Being a doctor and more than 3 years duration of work in the clinic were predictors of good knowledge. There was no predictor of practice. There was good knowledge and practice of the guideline from health worker self-reports, however, review of treatment card showed prescription was low. Further studies to explore and understand why there is such low prescription of INH/IPT to HIV patients despite good knowledge of healthcare professionals are recommended.

Costs of implementing universal test and treat in three correctional facilities in South Africa and Zambia

Universal test and treat (UTT) is a population-based strategy that aims to ensure widespread HIV testing and rapid antiretroviral therapy (ART) for all who have tested positive regardless of CD4 count to decrease HIV incidence and improve health outcomes. Little is known about the specific resources required to implement UTT in correctional facilities for incarcerated people. The primary aim of this study was to describe the resources used to implement UTT and to provide detailed costing to inform UTT scale-up in similar settings. The costing study was a cross-sectional descriptive study conducted in three correctional complexes, Johannesburg Correctional Facility in Johannesburg (>4000 inmates) South Africa, and Brandvlei (~3000 inmates), South Africa and Lusaka Central (~1400 inmates), Zambia. Costing was determined through a survey conducted between September and December 2017 that identified materials and labour used for three separate components of UTT: HIV testing services (HTS), ART initiation, and ART maintenance. Our study participants were staff working in the correctional facilities involved in any activity related to UTT implementation. Unit costs were reported as cost per client served while total costs were reported for all clients seen over a 12-month period. The cost of HIV testing services (HTS) per client was $ 92.12 at Brandvlei, $ 73.82 at Johannesburg, and $ 65.15 at Lusaka. The largest cost driver for HIV testing at Brandvlei were staff costs at 55.6% of the total cost, while at Johannesburg (56.5%) and Lusaka (86.6%) supplies were the largest contributor. The cost per client initiated on ART was $917 for Brandvlei, $421.8 for Johannesburg, and $252.1 for Lusaka. The activity cost drivers were adherence counselling at Brandvlei (59%), and at Johannesburg and Lusaka it was the actual ART initiation at 75.6% and 75.8%, respectively. The annual unit cost for ART maintenance was $2,640.6 for Brandvlei, $710 for Johannesburg, and $385.5 for Lusaka. The activity cost drivers for all three facilities were side effect monitoring, and initiation of isoniazid preventive treatment (IPT), cotrimoxazole, and fluconazole, with this comprising 44.7% of the total cost at Brandvlei, 88.9% at Johannesburg, and 50.5% at Lusaka. Given the needs of this population, the opportunity to reach inmates at high risk for HIV, and overall national and global 95-95-95 goals, the UTT policies for incarcerated individuals are of vital importance. Our findings provide comparator costing data and highlight key drivers of UTT cost by facility.

Preventing pellagra during isoniazid preventive treatment

An estimated 1·7 billion people globally are latently infected with Mycobacterium tuberculosis.1 Latent M tuberculosis infection is defined by WHO as a state of persistent immune response to M tuberculosis antigens with no clinical evidence of active disease. During their lifetime, up to 10% of people with latent M tuberculosis infection are at risk of progressing to active tuberculosis disease.1 In 2018, the UN General Assembly End TB targets included the specific goal to give tuberculosis preventive treatment for all people with latent M tuberculosis infection.

Isoniazid-associated pellagra during mass scale-up of tuberculosis preventive therapy: a case-control study

Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and might induce niacin deficiency. In 2017, Malawi scaled up continuous isoniazid preventive treatment (IPT) for tuberculosis prevention among people living with HIV. In addition, an under-diversified diet based on subsistence maize, as is commonly the case in Malawi, is a risk factor for pellagra. We aimed to investigate whether large-scale isoniazid exposure in Malawi contributed to the cumulative risk for pellagra in a nutritionally vulnerable population. We did a matched case-control study to evaluate the association between daily, continuous isoniazid exposure and pellagra. We matched sequentially enrolled patients with pellagra each with four control participants by sex and age from referral dermatology centres in three IPT scale-up districts in Malawi (Lilongwe, Blantyre, and Zomba) to evaluate isoniazid as a risk for pellagra using multivariable conditional logistic regression. We established a community clinic referral system surrounding the dermatology clinic in each district to enhance case-finding and included all patients with pellagra, regardless of referral status. The primary outcome was dermatologist-diagnosed pellagra. We calculated the interval between isoniazid initiation and rash onset and assessed 30-day clinical outcomes after multi-B vitamin treatment containing 300 mg nicotinamide daily. Between Feb 5 and Aug 9, 2019, we enrolled 197 patients with pellagra and 781 matched controls. Isoniazid exposure was associated with an increased risk of pellagra (adjusted odds ratio 42·6 [95% CI 13·3-136·6]). Significant covariates included HIV infection, referral status, food insecurity, underweight, excess alcohol consumption, and, among women, lactation. The median time from isoniazid initiation to rash onset was shorter during the season of food scarcity (5 months [IQR 3-7]) compared with the harvest season (9 months [8-11]; hazard ratio 7·2 [95% CI 3·2-16·2], log-rank p<0·0001). Those with isoniazid-associated pellagra who discontinued isoniazid and adhered to multi-B vitamin treatment showed 30-day clinical improvement. Continuous IPT scale-up and the annual period of food scarcity both increased the risk of pellagra in Malawi. Use of shorter rifamycin-based regimens for tuberculosis prevention and food fortification in populations with undernutrition might reduce this risk. Niacin-containing multi-B vitamin co-administration with isoniazid as pellagra prevention is worth exploring further. This study was supported by the President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention under project 7173.

Factor associated with treatment noncompletion during implementation of isoniazid-preventive therapy in ten pilot sites of Lome, Togo

BACKGROUND: Tuberculosis (TB) represents the leading cause of death among people living with HIV (PLHIV). Several studies have proven the effectiveness of isoniazid-preventive treatment (IPT) in reducing the incidence and mortality of TB. The study aims to identify the factors associated with noncompletion of the treatment during the pilot phase of IPT implementation.METHODS: This was a retrospective cohort study using data routinely collected in ten PLHIV care centers in Lomé, Togo, conducted between June 1, 2019, and March 31, 2020. All confirmed PLHIV newly enrolled in care who gave consent were included. IPT tolerance and signs of TB were checked at each appointment. To identify the factors associated with noncompletion of treatment, a logistic regression model was developed.RESULTS: Sixty-five percent of the 301 patients were female. The mean age was 39.8 ± 13.2 years. Respectively, 43.8% and 41.9% of the patients were at clinical stages 1 and 2. The mean completion rate was 42.9% with extremes depending on the center ranging from 9.5% to 90.0%. The main causes of noncompletion were isoniazid stockouts (45.9%), lost to follow-up (37.8%), and noncompliance (12.8%). Multivariate analysis identified stockouts, public type of center, and poor general condition at the inclusion as risk factors for noncompletion.CONCLUSIONS: Good results obtained by some centers prove that the implementation of the intervention is indeed possible, as long as good management of drug stocks and better follow-up of patients are ensured.

Factors Associated with Isoniazid Preventive Treatment Interruption and Completion Among PLHIV in Gombe Hospital, Uganda, 2017–2019

Factors Associated with Isoniazid Preventive Treatment Interruption and Completion Among PLHIV in Gombe Hospital, Uganda, 2017–2019

Factors Associated with Isoniazid Preventive Treatment Interruption and Completion Among PLHIV in Gombe Hospital, Uganda, 2017–2019

Factors Associated with Isoniazid Preventive Treatment Interruption and Completion Among PLHIV in Gombe Hospital, Uganda, 2017–2019

The Effect of Long-Term HAART on the Incidence of Tuberculosis Among People Living with HIV in Addis Ababa, Ethiopia: A Matched Nested Case-Control Study.

BackgroundThe introduction of antiretroviral therapy (ART) significantly decreases the incidence of tuberculosis (TB) in people living with human immunodeficiency virus (PLWHIV). However, a considerable proportion is still co-infected with TB after ART initiation. Thus, this study aimed to assess the effect of long-term HAART on the incidence of TB among PLWHIV in Addis Ababa, Ethiopia.MethodsA matched nested case–control study was conducted among PLWHIV who were enrolled in ART clinics in Addis Ababa, Ethiopia from 2013 up to 2018. Cases were HIV-TB co-infected individuals who were taking antiretroviral treatment, while controls were PLWHIV without TB who were taking antiretroviral treatment. The cases and controls are matched exactly in age and sex. Data were entered in Epi Info version 7.1 and analyzed using SPSS version 20. Bi-variable and multivariable conditional logistic regression were employed along with 95% CI. A P-value <0.05 in the multivariable analysis was considered statistically significant.ResultsFifty-seven cases were compared with 114 controls. Accordingly, previous TB history (X2; 13.790, P < 0.001), baseline functional status (X2; 9.120, P = 0.010), baseline WHO clinical stage (X2; 10.083, P = 0.001), baseline hemoglobin value (X2; 6.985, P = 0.008), baseline body mass index (X2; 3.873, P = 0.049), isoniazid preventive treatment (X2; 8.047, P = 0.005), baseline CD4 value (X2; 12.741, P < 0.001) and length of stay on ART (X2; 53.359, P < 0.001) were associated with developing TB. Length of stay on ART was found to be the statistically significant determinant of TB infection after ART initiation (aOR = 5.925, 95% CI = 2.649–13.250).ConclusionAdvanced clinical stages at the baseline, previous TB history, and not taking IPT were associated with TB infection. The long-term ART exposure significantly decreases tuberculosis incidence in PLWHIV. Thus, retaining PLWHIV on ART would be important to decrease the incidence of TB in this group of individuals.

Prediction Tool to Identify Children at Highest Risk of Tuberculosis Disease Progression Among Those Exposed at Home.

BackgroundThere is a dearth of research to understand which children, among those who are exposed at home to tuberculosis (TB), are at the highest risk of TB disease, to tailor care. We sought to identify predictors of TB progression in children.MethodsWe conducted a prospective cohort study of children living with adults with pulmonary TB in Lima, Peru (2009–2012). We applied classification and regression tree analysis to examine potential predictors of incident TB disease during 12 months in 3 age groups (0–4, 5–9, and 10–14 years). We calculated the relative risk (RR) for top predictors in each age group.ResultsAmong 4545 children 0–14 years old, 156 (3.4%) were diagnosed with TB within 1 year of household exposure to TB (3.4%, 2.3%, and 4.7% in children 0–4, 5–9, and 10–14 years old, respectively). The most important predictor of TB was having a positive tuberculin skin test (TST) result, with RRs of 6.6 (95% CI, 4.0–10.7), 6.6 (95% CI, 3.2–13.6), and 5.2 (95% CI, 3.0–9.0) in the age groups 0–4, 5–9, and 10–14 years, respectively. In young children with a positive TST, not using isoniazid preventive treatment further increased risk of disease (RR, 12.2 [95% CI, 3.8–39.2]).ConclusionsWe present a tool that identifies child household contacts at high risk of TB disease progression based on data collected during contact tracing. In addition to the use of TB preventive therapy for all children exposed at home to TB, those children at highest risk of progressing to TB disease may benefit from more frequent follow-up.

Nosocomial TB in two neonatal intensive care units at a tertiary care centre: infection risk and outcomes.

BACKGROUND: Sick neonates in TB endemic areas are at risk of nosocomial TB exposure.OBJECTIVE: To evaluate outcomes following contact investigation and isoniazid preventive treatment (IPT) in sick neonates exposed to healthcare personnel (HCP) with pulmonary TB.METHODS: Investigations were conducted following two exposure events in different neonatal intensive care units (NICUs). Details of the infants´ physical examination, chest X-ray and exposure history were recorded. Infants without TB disease were prescribed a 9-month course of IPT and followed for ≥1 year.RESULTS: Ninety infants were exposed in NICU A and 231 in NICU B (n = 321). The overall proportions of completing the 9-month IPT was 164/265 (61.8%): 40/79 (50.6%) in NICU A and 124/186 (66.7%) in NICU B (P = 0.01). The overall incidence of TB was 10.2% (24/236): 7.5% in NICU A and 11.2% in NICU B (P = 0.39). Contact investigation beginning >111 days after exposure was a risk factor for TB infection (P = 0.02).CONCLUSION: The risk of TB following nosocomial exposure in sick neonates was high, particularly when contact investigation was delayed. Our findings underscore the importance of hospital policies that promote early detection of TB in HCP, reduce transmission in NICUs, and facilitate rapid case investigation.

Integrated TB and HIV care for Mozambican children: temporal trends, site-level determinants of performance, and recommendations for improved TB preventive treatment

BackgroundPediatric tuberculosis (TB), human immunodeficiency virus (HIV), and TB-HIV co-infection are health problems with evidence-based diagnostic and treatment algorithms that can reduce morbidity and mortality. Implementation and operational barriers affect adherence to guidelines in many resource-constrained settings, negatively affecting patient outcomes. This study aimed to assess performance in the pediatric HIV and TB care cascades in Mozambique.MethodsA retrospective analysis of routine PEPFAR site-level HIV and TB data from 2012 to 2016 was performed. Patients 0–14 years of age were included. Descriptive statistics were used to report trends in TB and HIV indicators. Linear regression was done to assess associations of site-level variables with performance in the pediatric TB and HIV care cascades using 2016 data.ResultsRoutine HIV testing and cotrimoxazole initiation for co-infected children in the TB program were nearly optimal at 99% and 96% in 2016, respectively. Antiretroviral therapy (ART) initiation was lower at 87%, but steadily improved from 2012 to 2016. From the HIV program, TB screening at the last consultation rose steadily over the study period, reaching 82% in 2016. The percentage of newly enrolled children who received either TB treatment or isoniazid preventive treatment (IPT) also steadily improved in all provinces, but in 2016 was only at 42% nationally. Larger volume sites were significantly more likely to complete the pediatric HIV and TB care cascades in 2016 (p value range 0.05 to < 0.001).ConclusionsMozambique has made significant strides in improving the pediatric care cascades for children with TB and HIV, but there were missed opportunities for TB diagnosis and prevention, with IPT utilization being particularly problematic. Strengthened TB/HIV programming that continues to focus on pediatric ART scale-up while improving delivery of TB preventive therapy, either with IPT or newer rifapentine-based regimens for age-eligible children, is needed.

Protocol for a Case-Control Study to Investigate the Association of Pellagra With Isoniazid Exposure During Tuberculosis Preventive Treatment Scale-Up in Malawi.

Background: Pellagra is caused by niacin (vitamin B3) deficiency and manifested by a distinctive dermatitis. Isoniazid is critical for treating tuberculosis globally and is a component of most regimens to prevent tuberculosis. Isoniazid may contribute to pellagra by disrupting intracellular niacin synthesis. In 2017, Malawian clinicians recognized a high incidence of pellagra-like rashes after scale-up of isoniazid preventive treatment (IPT) to people living with HIV (PLHIV). This increase in pellagra incidence among PLHIV coincided with a seasonal period of sustained food insecurity in the region, which obscured epidemiological interpretations. Although isoniazid has been implicated as a secondary cause of pellagra for decades, no hypothesis-driven epidemiological study has assessed this relationship in a population exposed to isoniazid. We developed this case-control protocol to assess the association between large-scale isoniazid distribution and pellagra in Malawi.Methods: We measure the relative odds of having pellagra among isoniazid-exposed people compared to those without exposure while controlling for other pellagra risk factors. Secondary aims include measuring time from isoniazid initiation to onset of dermatitis, comparing niacin metabolites 1-methylnicotinamide (1-MN), and l-methyl-2-pyridone-5-carboxamide (2-PYR) in urine as a proxy for total body niacin status among subpopulations, and describing clinical outcomes after 30-days multi-B vitamin (containing 300 mg nicotinamide daily) therapy and isoniazid cessation (if exposed). We aim to enroll 197 participants with pellagra and 788 age- and sex-matched controls (1:4 ratio) presenting at three dermatology clinics. Four randomly selected community clinics within 3–25 km of designated dermatology clinics will refer persons with pellagra-like symptoms to one of the study enrollment sites for diagnosis. Trained study dermatologists will conduct a detailed exposure questionnaire and perform anthropometric measurements. A subset of enrollees will provide a casual urine specimen for niacin metabolites quantification and/or point-of-care isoniazid detection to confirm whether participants recently ingested isoniazid. We will use conditional logistic regression, matching age and sex, to estimate odds ratios for the primary study aim.Discussion: The results of this study will inform the programmatic scale-up of isoniazid-containing regimens to prevent tuberculosis.

Screening program for latent tuberculosis infection in asylum seekers - a single center experience in Pavia, Italy.

The management of Latent Tuberculosis Infection is crucial in fighting Tuberculosis worldwide, and particularly in low incidence European Countries. While guidelines for the management of Tuberculosis in newly arrived immigrants have been issued by the European Center for Disease Control and Prevention and by the National Health Authorities in Italy, these are not widely implemented yet at local level. We report our program for the screening of Latent Tuberculosis Infection and active Tuberculosis in asylum seekers, jointly implemented by Public Health Authorities and the Infectious Diseases Department of a tertiary care, teaching hospital in Northern Italy. We reviewed records of the asylum seekers who were screened at our center via Tuberculin Skin Test and/or Interferon Gamma Release Assay plus chest X-ray and either treated with Isoniazid Preventive Treatment or for active Tuberculosis Disease in case of positive results. We screened 726 migrants, mostly males (97.3%) and from Sub-Saharan Africa (82.2%) and found a high adherence rate for both screening (98.2%) and Isoniazid Preventive Treatment (90.1%). In addition, we found seven cases of active Tuberculosis. Latent Tuberculosis Infection screening and treatment proved feasible in our program, which should be systematically implemented in asylum seekers reaching Europe.

Adherence to Isoniazid Preventive Therapy among Under-Five Children in Contact with Adult Bacteriologically Confirmed Pulmonary Tuberculosis Patients: A Mixed-Method Study.

Background The World Health Organization recommends that all children below the age of five who have household contact with an infectious tuberculosis case should receive isoniazid preventive treatment for at least six months after the active tuberculosis disease has been ruled out. This research aims to determine the adherence of children, eligible for isoniazid preventive treatment, to the treatment who had contact with pulmonary tuberculosis patients. Methods A mixed study design was used to prospectively assess the adherence to IPT among children under the age of 5 in contact with pulmonary TB patients through the quantitative study design and barriers of adherence in view of health care professionals and the family of children through a descriptive qualitative study. The study was conducted from July 2019 to December 2019 in Addis Ababa. Data were collected by a structured datasheet from the selected health center registration book. Data were entered into Epi Data software and analyzed by using SPSS version 20. Descriptive statistical methods were used to summarize the sociodemographic characteristics of the study participants. Result The ratio of the total number of pulmonary tuberculosis index cases recruited into the study to the number of child contacts aged less than 5 years was 1 : 1.32. The total isoniazid preventive treatment uptake in this study was 75.2%; one-fifth (21.3%) of the children who started IPT did not complete the full course of six-month isoniazid preventive treatment. Except for HIV not to be tested (P < 0.001), there was no significant association of the listed risk factors in default to complete the full six months of preventive treatment. Conclusion Enrolment of eligible children for isoniazid preventive treatment in the urban city Addis Ababa was still below the target of the World Health Organization End tuberculosis strategy by 2030. The treatment adherence rate also needs a great deal of effort to achieve the strategy. Child default after the first visit indicates a lack of understanding about the benefit and safety of preventive therapy in young children among families of TB patients, and awareness-creating efforts by health extension workers will help to improve the outcomes.

Incidence of Tuberculosis During the First Year of Antiretroviral Treatment in West African HIV-Infected Adults.

We estimated tuberculosis incidence during the first year on antriretroviral therapy without isoniazid-preventive treatment in 6938 West African HIV-infected adults at 3.33 cases per 100 person-years (95% CI, 2.85–3.80). In multivariate Poisson models, sites in Cote d’Ivoire, male gender, low body mass index, low hemoglobin, low CD4 count, and young age were significantly associated with higher incidence.