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Background We determined the frequency of genetic polymorphisms in three anti‐TB drug metabolic proteins previously reported: N‐acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1), and arylacetamide deacetylase (AADAC) within a Peruvian population in a cohort of TB patients. Methods We genotyped SNPs rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931 for NAT2; rs3813867 and rs2031920 for CYP2E1; and rs1803155 for AADAC in 395 participants completed their antituberculosis treatment. Results Seventy‐four percent of the participants are carriers of slow metabolizer genotypes: NAT2*5, NAT2*6, and NAT2*7, which increase the sensitivity of INH at low doses and increase the risk of drug‐induced liver injuries. Sixty‐four percent are homozygous for the wild‐type CYP2E1*1A allele, which could increase the risk of hepatotoxicity. However, 16% had a NAT2 fast metabolizer phenotype which could increase the risk of acquiring resistance to INH, thereby increasing the risk of multidrug‐resistant (MDR) or treatment failure. The frequency of rs1803155 (AADAC*2 allele) was higher (99.9%) in Peruvians than in European American, African American, Japanese, and Korean populations. Conclusions This high prevalence of slow metabolizers for isoniazid in the Peruvian population should be further studied and considered to help individualize drug regimens, especially in countries with a great genetic diversity like Peru. These data will help the Peruvian National Tuberculosis Control Program develop new strategies for therapies., High prevalence of slow metabolizers for isoniazid in the Peruvian population should be further studied and considered to help individualize drug regimens, especially in countries with a great genetic diversity like Peru.

Background Tuberculosis (TB) prevention through the use of preventive treatment is a critical activity in the elimination of TB. In multiple settings, limited staffing has been identified as a barrier to managing preventive treatment for TB contacts. This study aims to determine how health center staffing, service type, and TB caseload affects implementation of isoniazid preventive therapy (IPT) for TB contacts in southern Lima. Methods We conducted an ecological study in 2019 in southern Lima, Peru. Through the review of medical records, we identified contacts of TB patients who initiated IPT during 2016–2018, and who were 0–19 years old, the age group eligible for IPT according to Peruvian guidelines. We assessed bivariate associations between health center characteristics (numbers of physicians and nurses, types of services available, annual TB caseload) and IPT initiation and completion using binomial logistic regression. Results Among 977 contacts, 69% took more than a week to start IPT and 41% did not complete IPT. For those who successfully completed IPT, 58% did not complete full medical follow-up. There was no significant difference in IPT completion or adherence based on whether health centers had more physicians and nurses, more comprehensive services, or higher TB caseloads. Among contacts, female sex was associated with delay in initiating IPT (P = 0.005), age 5–19 years old was associated with completion of IPT (P = 0.025) and age P = 0.041). Conclusions There are significant gaps in IPT implementation in health centers of southern Lima, Peru, but insufficient staffing of health centers may not be responsible. Further research is needed to identify how IPT implementation can be improved, potentially through improving staff training or monitoring and supervision. Graphic abstract

Forty-six health centers in south Lima, Peru.To assess the association between caregivers' knowledge and perceptions around isoniazid preventive therapy (IPT) and whether their children complete IPT.We conducted a retrospective medical record review of children who initiated IPT during 2017-2018. We administered structured surveys to caregivers of the children about their knowledge about and perceptions of IPT. We used a modified Poisson regression to determine factors associated with IPT completion.We included 550 children, of whom 31% did not complete IPT. Independent factors associated with not completing IPT were low caregiver knowledge about TB and IPT (adjusted risk ratio [aRR] 1.41, 95% CI 1.06-1.78), low caregiver perception of the importance of IPT (aRR 1.76, 95% CI 1.30-2.39), low caregiver satisfaction with the health services (aRR 1.57, 95% CI 1.14-2.16), experience of adverse events (aRR 2.08, 95% CI 1.51-2.87), and living in a household with moderate or severe family dysfunction (aRR 1.53, 95% CI 1.07-2.19).IPT completion among children was associated with the knowledge and perceptions of their caregivers, as well as the experience of adverse events. To improve IPT completion among children, health care providers should prioritize education and counseling for caregivers, promote positive interpersonal relationships with them, and monitor adverse events.Quarante-six centres de santé au Sud de Lima, Pérou.Evaluer l’association entre les connaissances et les perceptions relatives au traitement préventif par l’isoniazide (TPI) des responsables des enfants et le fait que leurs enfants aient achevé le TPI.Nous avons réalisé une revue rétrospective des dossiers médicaux des enfants qui ont démarré le TPI entre 2017 et 2018. Nous avons administré aux responsables des enfants des questionnaires structurés relatifs à leurs connaissances et perceptions du TPI. Nous avons utilisé une régression de Poisson modifiée afin de déterminer les facteurs associés à l’achèvement du TPI.Nous avons inclus 500 enfants dont 31% n’ont pas achevé le TPI. Les facteurs indépendants associés au non achèvement étaient faibles connaissances relatives à la TB et au TPI (risque relatif ajusté [RRa] 1,41 ; IC 95% 1,06–1,78), faibles perception par les responsables de l’importance du TPI (RRa 1,76 ; IC 95% 1,30–2,39), faible taux de satisfaction des responsables par rapport aux services de santé (RRa 1,57 ; IC 95% 1,14–2,16), survenue d’effets secondaires (RR 2,08 ; IC 95% 1,51–2,87) et dysfonction familiale modérée ou grave (RRa 1,53 ; IC 95% 1,07–2,19).L’achèvement du TPI chez les enfants a été associé aux connaissances et perceptions de leurs responsables, ainsi qu’à la survenue d’effets secondaires. Pour améliorer l’achèvement du TPI chez les enfants, les prestataires de soins de santé devraient accorder la priorité à l’éducation des responsables, promouvoir des relations inter personnelles positives avec eux et surveiller les effets secondaires.

Background: Giving preventive therapy to children living in the households of TB patients to prevent them from developing TB themselves is important for reducing morbidity and mortality in this high-risk group. Children’s adherence to medications is likely dependent on their caregivers. We conducted a study to assess the association between caregivers’ knowledge and perceptions around isoniazid preventive therapy (IPT) and whether their children completed IPT. Methods: We conducted a retrospective medical record review of children who initiated IPT during 2017-2018 in 50 health facilities in south Lima, Peru. We administered structured surveys to caregivers of the children and about their knowledge and perceptions around IPT. To determine factors associated with IPT completion, we used a modified Poisson regression with generalized estimating equations to account for clustering by household. Results: We included in the study 550 children, of whom 31% did not complete IPT. Independent factors associated with not completing IPT were: low caregiver knowledge about TB and IPT (adjusted risk ratio [aRR]: 1.41; 95% confidence interval [CI]: 1.06-1.78), low caregiver perception of the importance of IPT (aRR: 1.76; 95% CI: 1.30-2.39), low caregiver satisfaction with the health services (aRR: 1.57; 95% CI: 1.14-2.16), experiencing adverse events (aRR: 2.08; 95% CI: 1.51-2.87), and living in a household with moderate or severe family dysfunction (aRR: 1.53; 95% CI: 1.07-2.19). Conclusions: IPT completion among children was associated with the knowledge and perceptions of their caregivers, as well as whether they experienced adverse events. To improve IPT completion among children, health care providers should prioritize education and counseling for caregivers, promote positive interpersonal relationships with them, and monitor adverse events.