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BACKGROUND: The rate of pulmonary tuberculosis (TB) recurrence is substantial. Identifying risk factors can support the development of prevention strategies. METHODS: We retrieved studies published between 1 January 1980 and 31 December 2022 that assessed factors associated with undifferentiated TB recurrence, relapse or reinfection. For factors reported in at least four studies, we performed random-effects meta-analysis to estimate a pooled relative risk (RR). We assessed heterogeneity, risk of publication bias and certainty of evidence. RESULTS: We included 85 studies in the review; 81 documented risk factors for undifferentiated recurrence, 17 for relapse and 10 for reinfection. The scope for meta-analyses was limited given the wide variety of factors studied, inconsistency in control for confounding and the fact that only few studies employed molecular genotyping. Factors that significantly contributed to moderately or strongly increased pooled risk and scored at least moderate certainty of evidence were: for undifferentiated recurrence, multidrug resistance (MDR) (RR 3.49; 95% CI 1.86 to 6.53) and fixed-dose combination TB drugs (RR 2.29; 95% CI 1.10 to 4.75) in the previous episode; for relapse, none; and for reinfection, HIV infection (RR 4.65; 95% CI 1.71 to 12.65). Low adherence to treatment increased the pooled risk of recurrence 3.3-fold (95% CI 2.37 to 4.62), but the certainty of evidence was weak. CONCLUSION: This review emphasises the need for standardising methods for TB recurrence research. Actively pursuing MDR prevention, facilitating retention in treatment and providing integrated care for patients with HIV could curb recurrence rates. The use of fixed-dose combinations of TB drugs under field conditions merits further attention. PROSPERO REGISTRATION NUMBER: CRD42018077867.

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Tuberculosis (TB) is the leading cause of death among people living with HIV (PLWH). Limited TB knowledge has been associated with delayed TB diagnosis and low adherence to TB treatment. A cross-sectional study was conducted among PLWH at the largest HIV-referral center in Lima, Peru, to describe TB knowledge among PLWH and potential associated sociodemographic factors. Participants answered a self-administered survey on TB knowledge, which consisted of five questions about TB cure, transmission, treatment, symptoms, and prevention. Of 179 PLWH enrolled, most participants did not know that isoniazid (85%) and antiretrovirals (78%) are preventive measures for TB, and 56 (31.3%) knew that TB can be asymptomatic in PLWH. We did not find statistical differences in TB knowledge based on gender, education, marital status, and time on HIV care. We identified important gaps in TB knowledge among PLWH. Addressing these gaps could empower PLWH to reduce their TB risk.

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OBJECTIVE: The objective of this study was to identify trajectories of depressive symptoms (DSs) during the first half of drug-sensitive pulmonary tuberculosis (PTB) treatment and examine their association with loss to follow-up (LTFU) in the second half. DESIGN: This study involved a secondary analysis of longitudinal data to identify potential trajectories of DS and their relationship with LTFU. SETTING: The study was conducted in first and second-level health centres located in San Juan de Lurigancho, Lima, Peru. PARTICIPANTS: Anonymised data from 265 individuals, including monthly measures of DSs from diagnosis to the completion of treatment, initiation of treatment for multidrug resistant TB, LTFU or death, were collected. RESULTS: Three trajectories were identified: 'declining', 'growth' and 'high'. These trajectories were observed in 182 (68.7%), 53 (20%) and 30 (11.3%) of the 265 individuals, respectively, during the first half of PTB treatment. Compared with those with a 'declining' trajectory, individuals with a 'growth' trajectory had a higher likelihood of experiencing LTFU during the second half of PTB treatment, after controlling for sociodemographic factors and at least weekly alcohol use (OR 3.9; 95% CI 1.09 to 13.97, p=0.036). CONCLUSIONS: The findings suggest that a trajectory of increasing DSs during the first half of PTB treatment is associated with a higher risk of LTFU during the second half.

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INTRODUCTION: The sequelae of COVID-19 have been described as a multisystemic condition, with a great impact on the cardiovascular and pulmonary systems with abnormalities in pulmonary function tests, such as lower diffusing capacity of the lung for carbon monoxide (DLco) levels and pathological patterns in spirometry; persistence of radiological lesions; cardiac involvement such as myocarditis and pericarditis; and an increase in mental disorders such as anxiety and depression. Several factors, such as infection severity during the acute phase as well as vaccination status, have shown some variable effects on these post-COVID-19 conditions, mainly at a clinical level such as symptoms persistence. Longitudinal assessments and reversibility of changes across the spectrum of disease severity are required to understand the long-term impact of COVID-19. METHODS AND ANALYSIS: A prospective cohort study aims to assess the impact of SARS-CoV-2 infection on cardiopulmonary function and quality of life after the acute phase of the disease over a 6-month follow-up period. Sample size was calculated to recruit 200 participants with confirmatory COVID-19 tests who will be subsequently classified according to infection severity. Four follow-up visits at baseline, month 1, month 3 and month 6 after discharge from the acute phase of the infection will be scheduled as well as procedures such as spirometry, DLco test, 6-minute walk test, chest CT scan, echocardiogram, ECG, N-terminal pro-B-type natriuretic peptide measurement and RAND-36 scale. Primary outcomes are defined as abnormal pulmonary function test considered as DLco <80%, abnormal cardiovascular function considered as left ventricular ejection fraction <50% and abnormal quality of life considered as a <40 score for each sphere in the RAND-36-Item Short Form Health Survey. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Ethics Committee of the Universidad Peruana Cayetano Heredia (SIDISI 203725) and the Ethics Committee of the Hospital Cayetano Heredia (042-2021). Protocol details were uploaded in ClinicalTrials.gov. Findings will be disseminated through peer-reviewed journals, scientific conferences and open-access social media platforms. TRIAL REGISTRATION NUMBER: NCT05386485.

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INTRODUCTION: People with tuberculosis experience long-term health effects beyond cure, including chronic respiratory diseases. We investigated whether tuberculosis is a risk factor for subsequent lung cancer. METHODS: We searched PubMed, Scopus, Cochrane, Latin American and Caribbean Health Sciences Literature and the Scientific Electronic Library Online for cohort and case-control studies providing effect estimates for the association between tuberculosis and subsequent lung cancer. We pooled estimates through random-effects meta-analysis. The study was registered in PROSPERO (CDR42020178362). RESULTS: Out of 6240 records, we included 29 cohort and 44 case-control studies. Pooled estimates adjusted for age and smoking (assessed quantitatively) were hazard ratio (HR) 1.51 (95% CI 1.30-1.76, I2=81%; five studies) and OR 1.74 (95% CI 1.42-2.13, I2=59%; 19 studies). The occurrence of lung cancer was increased for 2 years after tuberculosis diagnosis (HR 5.01, 95% CI 3.64-6.89; two studies), but decreased thereafter. Most studies were retrospective, had moderate to high risk of bias, and did not control for passive smoking, environmental exposure and socioeconomic status. Heterogeneity was high. CONCLUSION: We document an association between tuberculosis and lung cancer occurrence, particularly in, but not limited to, the first 2 years after tuberculosis diagnosis. Some cancer cases may have been present at the time of tuberculosis diagnosis and therefore causality cannot be ascertained. Prospective studies controlling for key confounding factors are needed to identify which tuberculosis patients are at the highest risk, as well as cost-effective approaches to mitigate such risk.

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This study aims to describe knowledge on HIV and antiretroviral (ARV) treatment and psychosocial factors among people living with HIV (PLWH) in Lima, Perú, to explore characteristics associated to this knowledge, and determine its impact on sustained viral suppression. A cross-sectional survey was conducted among 171 PLWH at the largest referral health care center in Lima. The psychosocial factors measured were depression, risk of alcoholism, use of illegal drugs and disclosure. A participant had "poor knowledge" when less than 80% of replies were correct. Sustained viral suppression was defined as two consecutive viral loads under 50 copies/mL. A total of 49% and 43% had poor HIV and ARV knowledge respectively; 48% of the study population screened positive for depression and 27% reported feeling unsupported by the person they disclosed to. The largest gaps in HIV and ARV knowledge were among 98 (57%) that did not recognize that HIV increased the risk of cancer and among 57 (33%) participants that did not disagree with the statement that taking a double dose of ARV if they missed one. Moderate depression was significantly associated to poor HIV and ARV knowledge. Non-disclosure and being on ARVs for less than 6 months were associated with not achieving sustained viral suppression. Our findings highlight important HIV and ARV knowledge gaps of PLWH and a high burden of psychosocial problems, especially of depression, among PLWH in Lima, Peru. Increasing knowledge and addressing depression and disclosure could improve care of PLWH.

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BACKGROUND: A recurrent tuberculosis (TB) episode results from exogenous reinfection or relapse after cure. The use of genotyping allows the distinction between both. METHODS: We did a systematic review and meta-analysis, using four databases to search for studies in English, French and Spanish published between 1 January 1980 and 30 September 2020 that assessed recurrences after TB treatment success and/or differentiated relapses from reinfections using genotyping. We calculated person years of follow-up and performed random-effects model meta-analysis for estimating pooled recurrent TB incidence rates and proportions of relapses and reinfections. We performed subgroup analyses by clinical-epidemiological factors and by methodological study characteristics. FINDINGS: The pooled recurrent TB incidence rate was 2.26 per 100 person years at risk (95% CI 1.87 to 2.73; 145 studies). Heterogeneity was high (I2=98%). Stratified pooled recurrence rates increased from 1.47 (95% CI 0.87 to 2.46) to 4.10 (95% CI 2.67 to 6.28) per 100 person years for studies conducted in low versus high TB incidence settings. Background HIV prevalence, treatment drug regimen, sample size and duration of follow-up contributed too. The pooled proportion of relapses was 70% (95% CI 63% to 77%; I²=85%; 48 studies). Heterogeneity was determined by background TB incidence, as demonstrated by pooled proportions of 83% (95% CI 75% to 89%) versus 59% (95% CI 42% to 74%) relapse for studies from settings with low versus high TB incidence, respectively. INTERPRETATION: The risk of recurrent TB is substantial and relapse is consistently the most frequent form of recurrence. Notwithstanding, with increasing background TB incidence the proportion of reinfections increases and the predominance of relapses among recurrences decreases. PROSPERO REGISTRATION NUMBER: CRD42018077867.

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BACKGROUND: Active case finding (ACF) in household contacts of tuberculosis (TB) patients is now recommended for National TB Programs (NTP) in low- and middle-income countries. However, evidence supporting these recommendations remains limited. This study evaluates the effectiveness and cost-effectiveness of ACF for household contacts of TB cases in a large TB endemic district of Lima, Peru. METHODS: A pragmatic stepped-wedge cluster randomized controlled trial was conducted in 34 health centers of San Juan de Lurigancho district. Centers were stratified by TB rate and randomly allocated to initiate ACF in groups of eight or nine centers at four-month intervals. In the intervention arm, NTP providers visited households of index patients to screen contacts for active TB. The control arm was routine passive case finding (PCF) of symptomatic TB cases. The primary outcomes were the crude and adjusted active TB case rates among household contacts. Program costs were directly measured, and the cost-effectiveness of the ACF intervention was determined. FINDINGS: 3222 index TB cases and 12,566 household contacts were included in the study. ACF identified more household contact TB cases than PCF, 199.29/10,000 contacts/year vs. 132.13 (incidence rate ratio of 1.51 (95% CI 1.21-1.88)). ACF was associated with an incremental cost-effectiveness ratio of US $16,400 per disability-adjusted life year averted and not cost-effective assuming a willingness-to-pay threshold for Peru of US $6360. CONCLUSION: ACF of TB case household contacts detected significantly more secondary TB cases than PCF alone, but was not cost-effective in this setting. In threshold analyses, ACF becomes cost-effective if associated with case detection rates 2.5 times higher than existing PCF programs.

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OBJECTIVE: Contacts of pulmonary tuberculosis (TB) cases are at high risk of TB infection and progression to disease. Close and household contacts and those <5 years old have the highest risk. Isoniazid preventive therapy (IPT) can largely prevent TB disease among infected individuals. International and Peruvian recommendations include TB contact investigation and IPT prescription to eligible contacts. We conducted a study in Lima, Peru, to determine the number of close and household contacts who were evaluated, started on IPT, and who completed it, and the factors associated to compliance with national guidelines. METHODS: We conducted a longitudinal retrospective study including all TB cases diagnosed between January 2015 and July 2016 in 13 health facilities in south Lima. Treatment cards, TB registers and clinical files were reviewed and data on index cases (sex, age, smear status, TB treatment outcome), contact investigation (sex, age, kinship to the index case, evaluations at month 0, 2 and 6) and health facility (number of TB cases notified per year, proportion of TB cases with treatment success) were extracted. We tabulated frequencies of contact evaluation by contact and index case characteristics. To investigate determinants of IPT initiation and completion, we used generalised linear mixed models. RESULTS: A total of 2323 contacts were reported by 662 index cases; the median number of contacts per case was four (IQR, 2-5). Evaluation at month 0 was completed by 99.2% (255/257) of contacts <5 and 98.1% (558/569) of contacts aged 5-19 years. Of 191 eligible contacts <5 years old, 70.2% (134) started IPT and 31.4% (42) completed it. Of 395 contacts 5-19 years old, 36.7% (145) started IPT and 32.4% (47) completed it. Factors associated to not starting IPT among contacts <5 years old were being a second-degree relative to the index case (OR 6.6 95CI% 2.6-16.5), not having received a tuberculin skin test (TST) (OR 3.9 95%CI 1.4-10.8), being contact of a smear-negative index case (OR 5.5 95%CI 2.0-15.1) and attending a low-caseload health facility (OR 2.8 95%CI 1.3-6.2). Factors associated to not starting IPT among 5-19 year-olds were age (OR 13.7 95%CI 5.9-32.0 for 16-19 vs. 5-7 years old), being a second-degree relative (OR 3.0 95%CI 1.6-5.6), not having received a TST (OR 5.4, 95%CI 2.5-11.8), being contact of a male index case (OR 2.1 95CI% 1.2-3.5), with smear-negative TB (OR 1.9 95%CI 1.0-3.6), and attending a high-caseload health facility (OR 2.1 95%CI 1.2-3.6). Factors associated to not completing IPT, among contacts who started, were not having received a TST (OR 3.4 95%CI 1.5-7.9 for <5 year-olds, and OR 4.3 95%CI 1.7-10.8 for those 5-19 years old), being contact of an index case with TB treatment outcome other than success (OR 9.3 95%CI 2.6-33.8 for <5 year-olds and OR 15.3 95%CI 1.9-125.8 for those 5-19 years old), and, only for those 5-19 years old, attending a health facility with high caseload (OR 3.2 95%CI 1.4-7.7) and a health facility with low proportion of TB cases with treatment success (OR 4.4 95%CI 1.9-10.2). CONCLUSIONS: We found partial compliance to TB contact investigation, and identified contact, index case and health facility-related factors associated to IPT start and completion that can guide the TB programme in increasing coverage and quality of this fundamental activity.

OBJECTIF: Les contacts des cas de tuberculose (TB) pulmonaire présentent un risque élevé d'infection à la TB et d'évolution vers la maladie. Les contacts étroits et familiaux et ceux de moins de 5 ans sont les plus à risque. Le traitement préventif à l'isoniazide (TPI) peut largement prévenir la maladie TB chez les personnes infectées. Nous avons mené une étude à Lima, au Pérou, pour déterminer le nombre de contacts proches et familiaux qui ont été évalués, qui ont commencé le TPI et qui l'ont achevé, ainsi que les facteurs associés au respect des directives nationales. MÉTHODES: Etude longitudinal rétrospective de tous les cas de TB diagnostiqués entre janvier 2015 et juillet 2016 dans 13 établissements de santé dans le sud de Lima. Les cartes de traitement, les registres de TB et les dossiers cliniques ont été examinés et des données sur les cas indice, l'investigation des contacts et les établissements de santé ont été extraites. Nous avons tabulé les fréquences d'évaluation des contacts par les caractéristiques des contacts et des cas indice. Pour étudier les déterminants de l'initiation et de l'achèvement du TPI, nous avons utilisé des modèles linéaires mixtes généralisés. RÉSULTATS: Au total, 2.323 contacts ont été rapportés par 662 cas indice; 70,2% des contacts âgés de moins de 5 ans ont commencé le TPI et 31,4% l'ont terminé, tandis que 36,7% des contacts âgés de 5 à 19 ans ont commencé le TPI et 32,4% l'ont terminé. Les facteurs associés au fait de ne pas commencer ou de terminer le TPI étaient: être un parent de second degré du cas indice, ne pas avoir reçu le test tuberculinique, être le contact d'un cas indice à frottis négatif et fréquenter un établissement de santé à faible charge de travail pour les moins de cinq ans contre fréquenter un établissement de santé à charge de travail élevée pour les contacts plus âgés. CONCLUSIONS: Nous avons constaté une compliance partielle à l'enquête sur les contacts de la TB, et avons identifié les facteurs liés aux contacts, aux cas indice et aux établissements de santé associés au début et à la fin du TPI qui peuvent guider le programme de TB dans l'augmentation de sa couverture et de sa qualité.

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