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Rationale: The persistent burden of tuberculosis (TB) disease emphasizes the need to identify individuals with TB for treatment and those at a high risk of incident TB for prevention. Targeting interventions toward those at high risk of developing and transmitting TB is a public health priority. Objectives: We aimed to identify characteristics of individuals involved in TB transmission in a community setting, which may guide the prioritization of targeted interventions. Methods: We collected clinical and sociodemographic data from a cohort of patients with TB in Lima, Peru. We used whole-genome sequencing data to assess the genetic distance between all possible pairs of patients; we considered pairs to be the result of a direct transmission event if they differed by three or fewer SNPs, and we assumed that the first diagnosed patient in a pair was the transmitter and the second was the recipient. We used logistic regression to examine the association between host factors and the likelihood of direct TB transmission. Measurements and Main Results: Analyzing data from 2,518 index patients with TB, we identified 1,447 direct transmission pairs. Regardless of recipient attributes, individuals less than 34 years old, males, and those with a history of incarceration had a higher likelihood of being transmitters in direct transmission pairs. Direct transmission was more likely when both patients were drinkers or smokers. Conclusions: This study identifies men, young adults, former prisoners, alcohol consumers, and smokers as priority groups for targeted interventions. Innovative strategies are needed to extend TB screening to social groups such as young adults and prisoners with limited access to routine preventive care. [ABSTRACT FROM AUTHOR]

We explored the utility of brief Mycobacterium tuberculosis whole-genome sequencing (WGS) "snapshots" at a sentinel site within Lima, Peru, for evaluating local transmission dynamics over time. Within a 17-km2 area, 15 of 70 (21%) isolates with WGS collected during 2011–2012 and 22 of 81 (27%) collected during 2020–2021 were clustered (P =.414), and additional isolates clustered with those from outside the area. Isolates from the later period were disproportionately related to large historic clusters in Lima from the earlier period. WGS snapshots at a sentinel site may not be useful for monitoring transmission, but monitoring the persistence of large transmission clusters might be. [ABSTRACT FROM AUTHOR]

Mathematical models have suggested that spatially-targeted screening interventions for tuberculosis may efficiently accelerate disease control, but empirical data supporting these findings are limited. Previous models demonstrating substantial impacts of these interventions have typically simulated large-scale screening efforts and have not attempted to capture the spatial distribution of tuberculosis in households and communities at a high resolution. Here, we calibrate an individual-based model to the locations of case notifications in one district of Lima, Peru. We estimate the incremental efficiency and impact of a spatially-targeted interventions used in combination with household contact tracing (HHCT). Our analysis reveals that HHCT is relatively efficient with a median of 40 (Interquartile Range: 31.7 to 49.9) household contacts required to be screened to detect a single case of active tuberculosis. However, HHCT has limited population impact, producing a median incidence reduction of only 3.7% (Interquartile Range: 5.8% to 1.9%) over 5 years. In comparison, spatially targeted screening (which we modeled as active case finding within high tuberculosis prevalence areas 100 m2 grid cell) is far less efficient, requiring evaluation of ≈12 times the number of individuals as HHCT to find a single individual with active tuberculosis. Furthermore, the addition of the spatially targeted screening effort produced only modest additional reductions in tuberculosis incidence over the 5 year period (≈1.3%) in tuberculosis incidence. In summary, we found that HHCT is an efficient approach for tuberculosis case finding, but has limited population impact. Other screening approaches which target areas of high tuberculosis prevalence are less efficient, and may have limited impact unless very large numbers of individuals can be screened. [ABSTRACT FROM AUTHOR]

Spatially targeted interventions may be effective alternatives to individual or populationbased prevention strategies against tuberculosis (TB). However, their efficacy may depend on the mechanisms that lead to geographically constrained hotspots. Local TB incidence may reflect high levels of local transmission; conversely, they may point to frequent travel of community members to high-risk areas. We used whole-genome sequencing to explore patterns of TB incidence and transmission in Lima, Peru. Between 2009 and 2012, we recruited incident pulmonary TB patients and their household contacts, whom we followed for the occurrence of TB disease. We used whole-genome sequences of 2,712 Mycobacterial tuberculosis isolates from 2,440 patients to estimate pariwise genomic distances and compared these to the spatial distance between patients’ residences. Genomic distances increased rapidly as spatial distances increased and remained high beyond 2 km of separation. Next, we divided the study catchment area into 1 × 1 km grid-cell surface units and used household spatial coordinates to locate each TB patient to a specific cell. We estimated cell-specific transmission by calculating the proportion of patients in each cell with a pairwise genomic distance of 10 or fewer single-nucleotide polymorphisms. We found that cell-specific TB incidence and local transmission varied widely but that cell-specific TB incidence did not correlate closely with our estimates of local transmission (Cohen’s k = 0.27). These findings indicate that an understanding of the spatial heterogeneity in the relative proportion of TB due to local transmission may help guide the implementation of spatially targeted interventions. [ABSTRACT FROM AUTHOR]

Objective: To use routinely collected data, with the addition of geographic information and census data, to identify local hot spots of rates of reported tuberculosis cases. Design: Residential locations of tuberculosis cases identified from eight public health facilities in Lima, Peru (2013–2018) were linked to census data to calculate neighborhood-level annual case rates. Heat maps of tuberculosis case rates by neighborhood were created. Local indicators of spatial autocorrelation, Moran's I, were used to identify where in the study area spatial clusters and outliers of tuberculosis case rates were occurring. Age- and sex-stratified case rates were also assessed. Results: We identified reports of 1,295 TB cases across 74 neighborhoods during the five-year study period, for an average annual rate of 124.2 reported TB cases per 100,000 population. In evaluating case rates by individual neighborhood, we identified a median rate of reported cases of 123.6 and a range from 0 to 800 cases per 100,000 population. Individuals aged 15–44 years old and men had higher case rates than other age groups and women. Locations of both hot and cold spots overlapped across age- and gender-specific maps. Conclusions: There is significant geographic heterogeneity in rates of reported TB cases and evident hot and cold spots within the study area. Characterization of the spatial distribution of these rates and local hot spots may be one practical tool to inform the work of local coalitions to target TB interventions in their zones. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic caused considerable burden on mental health worldwide. To address this emergency in Peru, Socios en Salud (SES) implemented an innovative digital system for the diagnosis and psychological therapy in vulnerable populations. We describe the development, implementation, and participant outcomes of this intervention. Methods: We conducted an intervention in a general population of Lima, Peru using a digital tool, ChatBot-Juntos, incorporating the abbreviated Self-Reporting Questionnaire (SRQ) to screen psychological distress. Participants positive for psychological distress received remote Psychological First Aid (PFA) and grief therapy if needed. Participants with a mental health condition or safety concern were referred to mental health services. SRQ scores were collected 3 months after PFA sessions. Differences between screening and follow-up scores were compared using Wilcoxon sign-rank test. Results: In total, 2027 people were screened; 1581 (77.9%) screened positive for psychological distress. Nine hundred ninety-seven (63%) people with psychological distress received PFA, and 320 (32.1%) of those were also referred for mental health care. At 3 months after follow-up, SRQ scores were collected for 579 (58%) participants. Significant reduction in SRQ scores was observed 3 months after PFA [median SRQ score changed from 9 to 5 (p < 0.001)], and after PFA plus referral to mental health services [median SRQ score changed from 11 to 6 (p < 0.001)]. Conclusion: Digital technology can be used to screen for psychological distress and deliver mental health support for populations affected by the COVID-19 pandemic. More research is needed to determine whether technology contributes to improved mental health outcomes. [ABSTRACT FROM AUTHOR]

Background There 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. Methods We 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. Results Among 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]). Conclusions We 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. [ABSTRACT FROM AUTHOR]

Because within-host Mycobacterium tuberculosis diversity complicates diagnosis and treatment of tuberculosis (TB), we measured diversity prevalence and associated factors among 3,098 pulmonary TB patients in Lima, Peru. The 161 patients with polyclonal infection were more likely than the 115 with clonal or the 2,822 with simple infections to have multidrug-resistant TB. [ABSTRACT FROM AUTHOR]

The Peruvian National Tuberculosis Control Program issued guidelines in 2006 specifying criteria for culture and drug-susceptibility testing (DST), including district-level rapid DST. All patients referred for culture and DST in 2 districts of Lima, Peru, during January 2005-November 2008 were monitored prospectively. Of 1,846 patients, 1,241 (67.2%) had complete DST results for isoniazid and rifampin; 419 (33.8%) patients had multidrug-resistant (MDR) TB at the time of referral. Among patients with new smear-positive TB, household contact and suspected category I failure were associated with MDR TB, compared with concurrent regional surveillance data. Among previously treated patients with smear-positive TB, adult household contact, suspected category II failure, early relapse after category I, and multiple previous TB treatments were associated with MDR TB, compared with concurrent regional surveillance data. The proportion of MDR TB detected by using guidelines was higher than that detected by a concurrent national drug-resistance survey, indicating that the strategy effectively identified patients for DST. [ABSTRACT FROM AUTHOR]

To determine whether spatiotemporal information could help predict multidrug resistance at the time of tuberculosis diagnosis, we investigated tuberculosis patients who underwent drug susceptibility testing in Lima, Peru, during 2005-2007. We found that crude representation of spatial location at the level of the health center improved prediction of multidrug resistance. [ABSTRACT FROM AUTHOR]

Background: There is limited research to guide TB treatment specifically in pregnant women and few studies have described the presentation of TB in pregnant women. We aimed to understand TB presentation and treatment outcomes in pregnant women in a low HIV burden setting. We describe a cohort of women of childbearing age treated for TB disease in Lima, Peru, and compare clinical presentation and treatment outcomes among pregnant and non-pregnant women between 2009 and 2012, including 36 pregnant women.Methods: This is a prospective cohort study. Subjects were recruited from across 106 public health centers in Lima, Peru. Baseline demographic, medical history, and drug-susceptibility test results were collected. We used descriptive statistics to describe demographic and clinical characteristics of the women using Pearson chi-squared, Fisher's exact tests, or Kruskal-Wallis.Results: Among 4500 individuals with pulmonary TB disease, 1334 women were included in analysis with 36 (2.69%) pregnant women. Pregnant women had similar demographics, past medical histories, and clinical presentation to non-pregnant women, except being more likely to be married (p = 0.01) and have cardiac disease (p = 0.04) and less likely to have weight loss (p = 0.05). Twenty (71.4%) pregnant women had pan-susceptible TB compared with 616 (63.1%) non-pregnant women; four (14.3%) pregnant women had mono-resistant TB compared with 154 (15.8%) non-pregnant women; and four (14.3%) pregnant women had multi-drug-resistant TB compared with 140 (14.3%) of non-pregnant women (p = 0.53). Twenty-eight (96.6%) pregnant women had a successful outcome (cure, completed treatment, treatment ended early by clinical team) while one (3.4%) had an unsuccessful outcome (treatment failed) and 1074 (97.3%) non-pregnant women had a successful outcome while 30 (2.7%) had an unsuccessful outcome (p = 0.56).Conclusion: In this cohort with low HIV co-infection, we found high TB treatment success rates in both pregnant and non-pregnant women, irrespective of drug-susceptibility profiles. If treated appropriately, pregnant women with TB disease can have successful outcomes. [ABSTRACT FROM AUTHOR]

Background: Identifying hotspots of tuberculosis transmission can inform spatially targeted active case-finding interventions. While national tuberculosis programs maintain notification registers which represent a potential source of data to investigate transmission patterns, high local tuberculosis incidence may not provide a reliable signal for transmission because the population distribution of covariates affecting susceptibility and disease progression may confound the relationship between tuberculosis incidence and transmission. Child cases of tuberculosis and other endemic infectious disease have been observed to provide a signal of their transmission intensity. We assessed whether local overrepresentation of child cases in tuberculosis notification data corresponds to areas where recent transmission events are concentrated.Methods: We visualized spatial clustering of children < 5 years old notified to Peru's National Tuberculosis Program from two districts of Lima, Peru, from 2005 to 2007 using a log-Gaussian Cox process to model the intensity of the point-referenced child cases. To identify where clustering of child cases was more extreme than expected by chance alone, we mapped all cases from the notification data onto a grid and used a hierarchical Bayesian spatial model to identify grid cells where the proportion of cases among children < 5 years old is greater than expected. Modeling the proportion of child cases allowed us to use the spatial distribution of adult cases to control for unobserved factors that may explain the spatial variability in the distribution of child cases. We compare where young children are overrepresented in case notification data to areas identified as transmission hotspots using molecular epidemiological methods during a prospective study of tuberculosis transmission conducted from 2009 to 2012 in the same setting.Results: Areas in which childhood tuberculosis cases are overrepresented align with areas of spatial concentration of transmission revealed by molecular epidemiologic methods.Conclusions: Age-disaggregated notification data can be used to identify hotspots of tuberculosis transmission and suggest local force of infection, providing an easily accessible source of data to target active case-finding intervention. [ABSTRACT FROM AUTHOR]

Introduction:Tuberculosis, reported as the second most common infectious cause of death worldwide, is a key mortality contributor in developing countries and globally. The disease is endemic in Peru and while relative success was achieved during the 1990s in its control, this slowed as new complications, such as multi drug resistant TB arose. Health centre workers participating in the national DOTS program, create the front-line TB work-force in Peru meaning their knowledge and attitudes about the disease are key in its control. Methods:A Spanish language, multiple choice knowledge and attitudes survey was designed based on previous successful studies and the national Peruvian TB control guidelines. It was applied to two health networks in Lima, Peru amongst 301health workers participating in the national TB control program from 66 different health centres. The study results were analysed to test mean knowledge scores amongst different groups, overall gaps in key areas of TB treatment and control knowledge, and attitudes towards the disease and the national TB control program. Results:A mean knowledge score of 10.1 (+/- 1.7) out of 15 or 67.3% correct was shown. Demographics shown to have an effect on knowledge score were age and level of education. Major knowledge gaps were noted primarily in themes relating to treatment and diagnostics. Greater community involvement including better patient education about TB was seen as important in implementing the national TB control program. Participants were in disagreement about the current distribution of health resources throughout the study area. Discussion Serious knowledge gaps were identified from the survey; these reflect findings from a previous study in Lima and other studies from TB endemic areas throughout the world. Understanding these gaps and observations made by front-line TB workers in Lima may help to improve the national TB control program and other control efforts globally. [ABSTRACT FROM AUTHOR]

Introduction. Diffusely adherent E. coli (DAEC) is the sixth recognized group of diarrheagenic E. coli. However, its association with diarrhea remains controversial. Variability in the adherence patterns of clinical strains is unknown. Objectives. To compare the adherence patterns between strains isolated from children with and without diarrhea. Materials and methods. A total of 31 DAEC strains were analyzed, 25 from children with diarrhea and 6 from asymptomatic (control) children, isolated from a cohort study of children under one year of age in the southern districts of Lima. DAEC were identified by PCR (daaD gene). The pattern and adherence score in HEp-2 cell culture were evaluated, Actin polimerization was determined by fluorescence actin staining (fAS) and motility was evaluated by conventional microbiology methods. Results. Diffuse adherence pattern was found in 88% of diarrhea samples and in the total of control strains. The number of bacteria adhered per cell was significantly lower in diarrhea samples (p<0.05). However, actin polymerization was greater in diarrhea samples (60% vs. 17%). Motility test was positive in 60% of the diarrhea samples and in all control samples. Conclusions. Our findings suggest a difference between adherence patterns, actin polymerization and motility between DAEC strains corresponding to diarrhea and control groups. The significance of these results must be confirmed with a bigger number of strains and determining the presence of virulence genes in the strains. [ABSTRACT FROM AUTHOR]

Introduction. Diarrheagenic E. coli (DEC) are a major cause of diarrhea in children in developing countries. However, they are not part of routine diagnosis in clinical laboratories. Objectives. To determine the DEC prevalence in Peruvian children and to describe the genetic variability of these strains. Materials and methods. A total of 8 003 E. coli strains previously isolated from eight different studies of diarrhea in children, mainly from peri-urban areas of Lima, were analyzed. Diagnosis of DEC was done with Multiplex real-time PCR using genes for each of the 6 DEC groups. Conventional PCR was performed for the detection of additional virulence genes. Results. Globally, the mean prevalence in diarrhea samples (n=4,243) was: enteroaggregative E. coli (EAEC) 9.9%, enteropathogenic E. coli (EPEC) 8.5%, enterotoxigenic E. coli (ETEC) 6.9%, diffusely adherent E. coli (DAEC) 4.8%, Shiga toxin-producing E. coli (STEC) 0.8% and enteroinvasive E. coli (EIEC) 0.6%. The relative frequency of each pathogen varies according to the age and the type of study. The main pathotypes in control samples (n=3,760) were EPEC (10.9%) and EAEC (10.4%). An important variability in the virulence genes frequency and molecular resistance mechanisms for each pathotype was found, without differences between diarrhea and control groups. Conclusions. DEC are a major cause of diarrhea in Peruvian children. These pathogens are highly heterogeneous. Additional studies are required to determine the prevalence in rural areas of Peru and in severe diarrhea cases. [ABSTRACT FROM AUTHOR]