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Background: Globally, tuberculosis disease (TB) is more common among males than females. Recent research proposes that differences in social mixing by sex could alter infection patterns in TB. We examine evidence for two mechanisms by which social-mixing could increase men's contact rates with TB cases. First, men could be positioned in social networks such that they contact more people or social groups. Second, preferential mixing by sex could prime men to have more exposure to TB cases., Methods: We compared the networks of male and female TB cases and healthy matched controls living in Kampala, Uganda. Specifically, we estimated their positions in social networks (network distance to TB cases, degree, betweenness, and closeness) and assortativity patterns (mixing with adult men, women, and children inside and outside the household)., Results: The observed network consisted of 11,840 individuals. There were few differences in estimates of node position by sex. We found distinct mixing patterns by sex and TB disease status including that TB cases have proportionally more adult male contacts and fewer contacts with children., Conclusions: This analysis used a network approach to study how social mixing patterns are associated with TB disease. Understanding these mechanisms may have implications for designing targeted intervention strategies in high-burden populations., (© 2021. The Author(s).)

Background: The risk of infection from respiratory pathogens increases according to the contact rate between the infectious case and susceptible contact, but the definition of adequate contact for transmission is not standard. In this study we aimed to identify factors that can explain the level of contact between tuberculosis cases and their social networks in an African urban environment., Methods: This was a cross-sectional study conducted in Kampala, Uganda from 2013 to 2017. We carried out an exploratory factor analysis (EFA) in social network data from tuberculosis cases and their contacts. We evaluated the factorability of the data to EFA using the Kaiser-Meyer-Olkin Measure of Sampling Adequacy (KMO). We used principal axis factoring with oblique rotation to extract and rotate the factors, then we calculated factor scores for each using the weighted sum scores method. We assessed construct validity of the factors by associating the factors with other variables related to social mixing., Results: Tuberculosis cases (N = 120) listed their encounters with 1154 members of their social networks. Two factors were identified, the first named "Setting" captured 61% of the variance whereas the second, named 'Relationship' captured 21%. Median scores for the setting and relationship factors were 10.2 (IQR 7.0, 13.6) and 7.7 (IQR 6.4, 10.1) respectively. Setting and Relationship scores varied according to the age, gender, and nature of the relationship among tuberculosis cases and their contacts. Family members had a higher median setting score (13.8, IQR 11.6, 15.7) than non-family members (7.2, IQR 6.2, 9.4). The median relationship score in family members (9.9, IQR 7.6, 11.5) was also higher than in non-family members (6.9, IQR 5.6, 8.1). For both factors, household contacts had higher scores than extra-household contacts (p < .0001). Contacts of male cases had a lower setting score as opposed to contacts of female cases. In contrast, contacts of male and female cases had similar relationship scores., Conclusions: In this large cross-sectional study from an urban African setting, we identified two factors that can assess adequate contact between tuberculosis cases and their social network members. These findings also confirm the complexity and heterogeneity of social mixing.

Background: Delay in tuberculosis (TB) diagnosis adversely affects patients' outcomes and prolongs transmission in the community. The influence of social contacts on steps taken by active pulmonary TB patients to seek a diagnosis has not been well examined., Methods: A retrospective study design was use to enroll TB patients on treatment for 3 months or less and aged ≥18 years from 3 public clinics in Kampala, Uganda, from March to July 2014. Social network analysis was used to collect information about social contacts and health providers visited by patients to measure the number of steps and time between onset of symptoms and final diagnosis of TB., Results: Of 294 TB patients, 58 % were male and median age was 30 (IQR: 24-38) years. The median number of steps was 4 (IQR: 3, 7) corresponding to 70 (IQR: 28,140) days to diagnosis. New patients had more steps and time to diagnosis compared retreatment patients (5 vs. 3, P < 0.0001; 84 vs. 46 days P < 0.0001). Fifty-eight percent of patients first contacted persons in their social network. The first step to initiate seeking care accounted for 41 % of the patients' time to diagnosis while visits to non-TB providers and TB providers (without a TB diagnosis) accounted for 34 % and 11 % respectively. New TB patients vs. retreatment (HR: 0.66, 95 % CI; 1.11, 1.99), those who first contacted a non-TB health provider vs. contacting social network (HR: 0.72 95 % CI; 0.55, 0.95) and HIV seronegative vs. seropositive patients (HR: 0.70, 95 % CI; 0.53, 0.92) had a significantly lower likelihood of a timely final diagnosis., Conclusions: There were four degrees of separation between the onset of symptoms in a TB patient and a final diagnosis. Both social and provider networks of patients influenced the diagnostic pathways. Most delays occurred in the first step which represents decisions to seek help, and through interactions with non-TB health providers. TB control programs should strengthen education and active screening in the community and in health care settings to ensure timely diagnosis of TB.

Background: Despite sustained exposure to a person with pulmonary tuberculosis (TB), some M. tuberculosis (Mtb) exposed individuals maintain a negative tuberculin skin test (TST). Our objective was to characterize these persistently negative TST (PTST-) individuals and compare them to TST converters (TSTC) and individuals who are TST positive at study enrollment., Methods: During a TB household contact study in Kampala, Uganda, PTST-, TSTC, and TST + individuals were identified. PTST- individuals maintained a negative TST over a 2 year observation period despite prolonged exposure to an infectious tuberculosis (TB) case. Epidemiological and clinical characteristics were compared, a risk score developed by another group to capture risk for Mtb infection was computed, and an ordinal regression was performed., Results: When analyzed independently, epidemiological risk factors increased in prevalence from PTST- to TSTC to TST+. An ordinal regression model suggested age (p < 0.01), number of windows (p < 0.01) and people (p = 0.07) in the home, and sleeping in the same room (p < 0.01) were associated with PTST- and TSTC. As these factors do not exist in isolation, we examined a risk score, which reflects an accumulation of risk factors. This compound exposure score did not differ significantly between PTST-, TSTC, and TST+, except for the 5-15 age group (p = 0.009)., Conclusions: Though many individual factors differed across all three groups, an exposure risk score reflecting a collection of risk factors did not differ for PTST-, TSTC and TST + young children and adults. This is the first study to rigorously characterize the epidemiologic risk profile of individuals with persistently negative TSTs despite close exposure to a person with TB. Additional studies are needed to characterize possible epidemiologic and host factors associated with this phenotype.

Background: Nutritional changes during and after tuberculosis treatment have not been well described. We therefore determined the effect of wasting on rate of mean change in lean tissue and fat mass as measured by bioelectrical impedance analysis (BIA), and mean change in body mass index (BMI) during and after tuberculosis treatment., Methods: In a prospective cohort study of 717 adult patients, BMI and height-normalized indices of lean tissue (LMI) and fat mass (FMI) as measured by BIA were assessed at baseline, 3, 12, and 24 months., Results: Men with wasting at baseline regained LMI at a greater rate than FMI (4.55 kg/m2 (95% confidence interval (CI): 1.26, 7.83 versus 3.16 (95% CI: 0.80, 5.52)) per month, respectively during initial tuberculosis therapy. In contrast, women with wasting regained FMI at greater rate than LMI (3.55 kg/m2 (95% CI: 0.40, 6.70) versus 2.07 (95% CI: -0.74, 4.88)), respectively. Men with wasting regained BMI at a rate of 6.45 kg/m2 (95% CI: 3.02, 9.87) in the first three months whereas women, had a rate of 3.30 kg/m2 (95% CI: -0.11, 6.72). There were minimal changes in body composition after month 3 and during months 12 to 24., Conclusion: Wasted tuberculosis patients regain weight with treatment but the type of gain differs by gender and patients may remain underweight after the initial phase of treatment.