Parenting Expectations, NICU Experiences, and Maternal Psychological Outcomes: An Exploratory Mixed-Methods Study.

BACKGROUND: Infant neonatal intensive care unit (NICU) hospitalization increases maternal risk for psychological distress. However, no universal screening standards exist and predicting maternal risk remains challenging. Reconceptualizing maternal distress in relation to differences between parenting expectations and NICU experiences may illuminate commonalities across a range of experiences. PURPOSE: This study explored parenting expectation-experience differences (EEDs) among NICU mothers and assessed correlations between EED scores and psychological outcomes 1 to 5 years post-NICU hospitalization. METHODS: A 3-phase explanatory sequential mixed-methods design was used. Pearson's correlation coefficients were used to measure relationships between EED scores and maternal psychological outcomes. Reflexive thematic analysis of one-on-one, semi-structured interviews contextualized EED scores. RESULTS: Most participants (92.9%) reported negative EED scores, indicating NICU experiences fell short of parenting expectations. Significant inverse correlations were found between EED scores and maternal outcomes, including depression ( r = -0.25, P < .01), anxiety ( r = -0.25, P < .01) and posttraumatic stress disorder symptoms ( r = -0.41, P < .001), and perceived parenting self-efficacy ( r = -0.28, P < .01). Major qualitative themes included unexpected versus prepared, lost parenting experiences, and surviving and thriving. Data synthesis contextualized EED scores and revealed key differences in meaning ascribed to unmet parenting expectations. IMPLICATIONS FOR PRACTICE AND RESEARCH: Preparing mothers for infant NICU hospitalization and creating a NICU parenting environment, which better supports mothers and their engagement in parenting tasks, may help to reduce differences between parenting expectations and NICU experiences. Further research is needed to elucidate the impacts of parenting EEDs in this population.

Tuberculosis Variant with Rifampin Resistance Undetectable by Xpert MTB/RIF, Botswana.

GeneXpert MTB/RIF, a tool widely used for diagnosing tuberculosis, has limitations for detecting rifampin resistance in certain variants. We report transmission of a pre-extensively drug-resistant variant in Botswana that went undetected by GeneXpert. The public health impact of misdiagnosis emphasizes the need for comprehensive molecular testing to identify resistance and guide treatment.

Use of High-Resolution Geospatial and Genomic Data to Characterize Recent Tuberculosis Transmission, Botswana.

Combining genomic and geospatial data can be useful for understanding Mycobacterium tuberculosis transmission in high-burden tuberculosis (TB) settings. We performed whole-genome sequencing on M. tuberculosis DNA extracted from sputum cultures from a population-based TB study conducted in Gaborone, Botswana, during 2012-2016. We determined spatial distribution of cases on the basis of shared genotypes among isolates. We considered clusters of isolates with ≤5 single-nucleotide polymorphisms identified by whole-genome sequencing to indicate recent transmission and clusters of ≥10 persons to be outbreaks. We obtained both molecular and geospatial data for 946/1,449 (65%) participants with culture-confirmed TB; 62 persons belonged to 5 outbreaks of 10-19 persons each. We detected geospatial clustering in just 2 of those 5 outbreaks, suggesting heterogeneous spatial patterns. Our findings indicate that targeted interventions applied in smaller geographic areas of high-burden TB identified using integrated genomic and geospatial data might help interrupt TB transmission during outbreaks.

Using genetic data to identify transmission risk factors: Statistical assessment and application to tuberculosis transmission.

Identifying host factors that influence infectious disease transmission is an important step toward developing interventions to reduce disease incidence. Recent advances in methods for reconstructing infectious disease transmission events using pathogen genomic and epidemiological data open the door for investigation of host factors that affect onward transmission. While most transmission reconstruction methods are designed to work with densely sampled outbreaks, these methods are making their way into surveillance studies, where the fraction of sampled cases with sequenced pathogens could be relatively low. Surveillance studies that use transmission event reconstruction then use the reconstructed events as response variables (i.e., infection source status of each sampled case) and use host characteristics as predictors (e.g., presence of HIV infection) in regression models. We use simulations to study estimation of the effect of a host factor on probability of being an infection source via this multi-step inferential procedure. Using TransPhylo-a widely-used method for Bayesian estimation of infectious disease transmission events-and logistic regression, we find that low sensitivity of identifying infection sources leads to dilution of the signal, biasing logistic regression coefficients toward zero. We show that increasing the proportion of sampled cases improves sensitivity and some, but not all properties of the logistic regression inference. Application of these approaches to real world data from a population-based TB study in Botswana fails to detect an association between HIV infection and probability of being a TB infection source. We conclude that application of a pipeline, where one first uses TransPhylo and sparsely sampled surveillance data to infer transmission events and then estimates effects of host characteristics on probabilities of these events, should be accompanied by a realistic simulation study to better understand biases stemming from imprecise transmission event inference.

Correlates of SARS-CoV-2 anti-RBD IgG antibody titers among persons experiencing homelessness in Los Angeles.

OBJECTIVES: People experiencing homelessness (PEH) have been especially impacted by the COVID-19 pandemic, likely due to increased vulnerabilities stemming from chronic diseases, substance use, and mental health conditions. DESIGN: A case-control study to assess the presence of antibodies against SARS-CoV-2 among PEH and associations with key variables. SAMPLE: A convenience sample of 97 PEH in Skid Row, Los Angeles. MEASUREMENTS: A structured questionnaire assessing socio-demographic, mental health, drug and alcohol use, health care access, pandemic stress, and other COVID-19-specific questions. RESULTS: We found high anti-receptor binding domain (RBD) IgG titers among five of 15 PEH who reported no prior COVID-19 diagnosis or being vaccinated, suggesting undiagnosed and/or asymptomatic COVID-19. While anti-RBD IgG titers across vaccination categories were not statistically significant (p = .069), participants vaccinated with Janssen had the lowest mean anti-RBD IgG titers. In multivariable analysis, we found negative associations between level of SARS-CoV-2 antibody titers with the Janssen vaccine and depression; thus, a need for integrated care for PEH with depression and COVID-19. CONCLUSIONS: Further research is warranted to confirm the immune response, initial and over time, to SARS-CoV-2 infection and to COVID-19 vaccinations, particularly among PEH whose immune systems may be impacted by multiple health conditions.

Exploratory assessment: Nurse-led community health worker delivered HCV intervention for people experiencing homelessness.

BACKGROUND: Getting and maintaining Hepatitis C Virus (HCV) cure is challenging among people experiencing homelessness (PEH) as a result of critical social determinants of health such as unstable housing, mental health disorders, and drug and alcohol use. OBJECTIVES: The purpose of this exploratory pilot study was to compare a registered nurse/community health worker (RN/CHW)-led HCV intervention tailored for PEH, "I am HCV Free," with a clinic-based standard of care (cbSOC) for treating HCV. Efficacy was measured by sustained virological response at 12 weeks after stopping antivirals (SVR12), and improvement in mental health, drug and alcohol use, and access to healthcare. METHODS: An exploratory randomized controlled trial design was used to assign PEH recruited from partner sites in the Skid Row Area of Los Angeles, California, to the RN/CHW or cbSOC programs. All received direct-acting antivirals. The RN/CHW group received directly observed therapy in community-based settings, incentives for taking HCV medications, and wrap-around services, including connection to additional healthcare services, housing support, and referral to other community services. For all PEH, drug and alcohol use and mental health symptoms were measured at month 2 or 3 and 5 or 6 follow-up, depending on HCV medication type, while SVR12 was measured at month 5 or 6 follow-up. RESULTS: Among PEH in the RN/CHW group, 75% (3 of 4) completed SVR12 and all three attained undetectable viral load. This was compared with 66.7% (n = 4 of 6) of the cbSOC group who completed SVR12; all four attained undetectable viral load. The RN/CHW group, as compared to the cbSOC, also showed greater improvements in mental health, and significant improvement in drug use, and access to healthcare services. DISCUSSION: While this study shows significant improvements in drug use and health service access among the RN/-CHW group, the sample size of the study limits the validity and generalizability of the results. Further studies using larger sample sizes are necessitated.

Association Between Maternal HIV Stigma Among South Indian Mothers Living with HIV and the CD4 Count of Children Living with HIV.

HIV stigma takes a multidimensional toll on a mother's ability to care for herself and subsequently may impact her ability to care for her child, particularly when mother and child are seroconcordant. A cross-sectional analysis was conducted to examine the association between maternal HIV stigma and child CD4 count in rural India. We assessed 108 mother-child dyads and found that a one-unit increase in community stigma fear decreased child CD4 count by 352 cells (95% CI = - 603, - 102), highlighting the need to develop a better understanding of the consequences of HIV-related stigma on the compounded burden of care in households where mother and child both live with HIV.

The association of household food insecurity and HIV infection with common mental disorders among newly diagnosed tuberculosis patients in Botswana.

OBJECTIVE: To determine the association between food insecurity and HIV infection with depression and anxiety among new tuberculosis (TB) patients. DESIGN: Our cross-sectional study assessed depression, anxiety and food insecurity with Patient Health Questionnaire (PHQ-9), Zung Anxiety Self-Assessment Scale (ZUNG) and Household Food Insecurity Access Scale, respectively. Poisson regression models with robust variance were used to examine correlates of depression (PHQ-9 ≥ 10) and anxiety (ZUNG ≥ 36). SETTING: Gaborone, Botswana. PARTICIPANTS: Patients who were newly diagnosed with TB. RESULTS: Between January and December 2019, we enrolled 180 TB patients from primary health clinics in Botswana. Overall, 99 (55·0 %) were HIV positive, 47 (26·1 %), 85 (47·2 %) and 69 (38·5 %) indicated depression, anxiety and moderate to severe food insecurity, respectively. After adjusting for potential confounders, food insecurity was associated with a higher prevalence of depression (adjusted prevalence ratio (aPR) = 2·30; 95 % CI 1·40, 3·78) and anxiety (aPR = 1·41; 95 % CI 1·05, 1·91). Prevalence of depression and anxiety was similar between HIV-infected and HIV-uninfected participants. Estimates remained comparable when restricted to HIV-infected participants. CONCLUSIONS: Mental disorders may be affected by food insecurity among new TB patients, regardless of HIV status.

"I got tested at home, the help came to me": acceptability and feasibility of home-based TB testing of household contacts using portable molecular diagnostics in South Africa.

OBJECTIVE: The effectiveness of household contact investigations is limited by low referral uptake for clinic-based TB testing by symptomatic household contacts. We qualitatively investigated the acceptability and perceived benefits of home-based TB testing using a portable GeneXpert-I instrument (GX-I) in an urban South African township. METHODS: In-depth interviews were conducted with household contacts tested and those that observed testing. Semi-structured interviews explored household contact's understanding of TB, perceptions of the GX-I device and testing procedures, confidentiality, willingness to refer others, and views on home- vs. clinic-based testing. Focus group discussions with home-based TB testing implementing staff assessed operational considerations for scale-up. Data were analysed using a constant comparison approach to qualitatively evaluate the acceptability and feasibility of home-based TB testing. RESULTS: Thirty in-depth interviews and two focus group discussions were conducted. Observing one's own sputum being tested resulted in an emergent trust in home-based TB testing, the GX-I device and one's test results. Home-based TB testing was considered convenient, helped to overcome apathy towards testing and mitigated barriers to clinic-based testing. Perceptions that home-based TB testing contributes to improved household and community health resulted in an emergent theme of alleviation of health insecurities. Operational concerns regarding inadvertent disclosure of one's diagnosis to household members and time spent in people's homes were identified. CONCLUSIONS: Home-based TB testing was acceptable and feasible. Individuals expressed belief in the machine by being able to witness the testing process. Though most themes mirrored qualitative studies of home-based HIV testing, the alleviation of health insecurities theme is unique to home-based TB testing. Future research must evaluate the impact of home-based TB testing on case finding yield, time-to-treatment initiation and household outcomes.

OBJECTIF: L'efficacité des enquêtes sur les contacts familiaux est limitée par le faible taux de respect de l'orientation pour le dépistage de la tuberculose (TB) en clinique par les contacts familiaux symptomatiques. Nous avons investigué qualitativement l'acceptabilité et les avantages perçus du dépistage de la TB à domicile à l'aide d'un dispositif portable GeneXpert-I (GX-I) dans une ville urbaine sud-africaine. MÉTHODES: Des entretiens approfondis ont été menés avec des contacts familiaux testés et ceux qui ont observé la pratique des tests. Des entretiens semi-structurés ont permis d'explorer la compréhension de la TB par les contacts familiaux, les perceptions sur le dispositif GX-I et les procédures de test, la confidentialité, la volonté de référer d'autres personnes et les opinions sur le dépistage à domicile ou en clinique. Des discussions de groupe focalisées avec le personnel chargé de la mise en œuvre du dépistage de la TB à domicile ont évalué les considérations opérationnelles pour le déploiement. Les données ont été analysées en utilisant une approche de comparaison constante pour évaluer qualitativement l'acceptabilité et la faisabilité du dépistage de la TB à domicile. RÉSULTATS: Trente entretiens approfondis et deux discussions de groupe ont été menés. L'observation de ses propres expectorations testées a conduit à une émergente de confiance dans le dépistage de la TB à domicile, le dispositif GX-I et les résultats des tests. Le dépistage de la TB à domicile était considéré comme pratique, aidait à surmonter l'apathie envers le dépistage et atténuait les obstacles au dépistage en clinique. La perception selon laquelle le dépistage de la TB à domicile contribue à l'amélioration de la santé des ménages et de la communauté a donné lieu à l'émergence du thème de la réduction des insécurités sanitaires. Des préoccupations opérationnelles concernant la divulgation par inadvertance de son diagnostic aux membres du ménage et le temps passé au domicile des personnes ont été identifiées. CONCLUSION: Le dépistage de la TB à domicile était acceptable et faisable. Les individus ont exprimé leur croyance en la machine en étant en mesure d'assister au processus de test. Bien que la plupart des thèmes reflètent des études qualitatives sur le dépistage du VIH à domicile, le thème de l'atténuation des insécurités sanitaires est unique au dépistage de la TB à domicile. Les recherches futures doivent évaluer l'impact du dépistage de la TB à domicile sur le rendement de la recherche des cas, le délai de mise en route du traitement et les résultats au sein des ménages.

Vulvar cancer in Botswana in women with and without HIV infection: patterns of treatment and survival outcomes.

OBJECTIVES: Vulvar cancer is a rare gynecological malignancy. However, the incidence of human papillomavirus (HPV)-associated vulvar disease is increasing, particularly in low- and middle-income countries. HIV infection is associated with an increased risk of HPV-associated vulvar cancer. We evaluated treatment patterns and survival outcomes in a cohort of vulvar cancer patients in Botswana. The primary objective of this study was to determine overall survival and the impact of treatment modality, stage, and HIV status on overall survival. METHODS: Women with vulvar cancer who presented to oncology care in Botswana from January 2015 through August 2019 were prospectively enrolled in this observational cohort study. Demographics, clinical characteristics, treatment, and survival data were collected. Factors associated with survival including age, HIV status, stage, and treatment were evaluated. RESULTS: Our cohort included 120 women with vulvar cancer. Median age was 42 (IQR 38-47) years. The majority of patients were living with HIV (89%, n=107) that was well-controlled on antiretroviral treatment. Among women with HIV, 54.2% (n=58) were early stage (FIGO stage I/II). In those without HIV, 46.2% (n=6) were early stage (stage I/II). Of the 95 (79%) patients who received treatment, 20.8% (n=25) received surgery, 67.5% (n=81) received radiation therapy, and 24.2% (n=29) received chemotherapy, either alone or in combination. Median follow-up time of all patients was 24.7 (IQR 14.2-39.1) months and 2- year overall survival for all patients was 74%. Multivariate analysis demonstrated improved survival for those who received surgery (HR 0.26; 95% CI 0.08 to 0.86) and poor survival was associated with advanced stage (HR 2.56; 95% CI 1.30 to 5.02). Survival was not associated with HIV status. CONCLUSIONS: The majority of women with vulvar cancer in Botswana are young and living with HIV infection. Just under half of patients present with advanced stage, which was associated with worse survival. Improved survival was seen for those who received surgery.

Effect of a Nurse-Led Community Health Worker Intervention on Latent Tuberculosis Medication Completion Among Homeless Adults.

BACKGROUND: Tuberculosis (TB) disproportionately affects marginalized and impoverished homeless adults. Although active TB can be prevented by treating latent TB infection (LTBI), individual factors, such as high prevalence of depression and anxiety, drug and alcohol use, and unstable housing, lead to poor LTBI treatment adherence and completion among homeless adults. OBJECTIVES: We hypothesized that the delivery of a tailored nurse-led, community health worker (RN/CHW) program across the LTBI continuum of care (e.g., screening, diagnosis, and treatment) that delivers 3HP treatment (3HP: rifapentine plus isoniazid) for homeless adults (e.g., sheltered and unsheltered) and is tailored to their health and social service needs will overcome existing treatment completion barriers. We also hypothesized that mental health symptoms (e.g., depression and anxiety), drug use score, and problematic alcohol use will decline over time among clients receiving this treatment. METHODS: We assessed the effect of delivering a theoretically guided, RN/CHW-based, single-arm study among eligible LTBI-positive homeless adults (N = 50) on completion of a weekly, directly observed, 12-dose 3HP LTBI treatment in Central City East (Skid Row). Completing 3HP treatment was compared to the only known historical, clinic-based control that obtained 65% completion among homeless adults. Secondary outcomes included drug and alcohol use, depression, and anxiety. RESULTS: The RN/CHW program achieved a 91.8% 3HP treatment completion rate among homeless adults. Younger homeless adults (<50 years old) were less likely to complete 3HP treatment compared to those who were older. Neither drug use, depression, nor anxiety was associated with 3HP treatment completion. Decrease in anxiety was observed at 3 months, but not at 6 months, compared to baseline. DISCUSSION: To our knowledge, the pilot study is the first to evaluate an effective RN/CHW-delivered, community-based intervention, which can reduce the burden of active TB for homeless adults.

Engaging the Community in Designing a Hepatitis C Virus Treatment Program for Adults Experiencing Homelessness.

Despite the availability of cure for hepatitis C virus (HCV), people experiencing homelessness (PEH) are challenged with initiating and completing HCV treatment. The design of culturally sensitive HCV treatment programs is lacking. The objective was to employ community-based participatory research methods to understand perceptions of HCV-positive PEH, and providers, on the design and delivery of a culturally sensitive, nurse-led community health worker (RN/CHW) HCV initiation and completion program. Four focus group sessions were conducted with HCV-positive PEH (n = 30) as well as homeless service providers (HSP; n = 7) in Skid Row, Los Angeles. An iterative, thematic approach provided the themes of essentials of successful participant engagement and retention: Role of nurse-Led CHW in promoting: (a) tangible and emotional support; (b) cognitive and behavioral support; and (c) financial and structural resources. The goal of this study is to provide the groundwork for future research of HCV program design to support HCV cure among homeless populations.

The Effect of Community-Based Nutritional Interventions on Children of Women Living With Human Immunodeficiency Virus in Rural India: A 2 × 2 Factorial Intervention Trial.

BACKGROUND: Malnutrition is a common clinical concern among children in low-income communities affected by human immunodeficiency virus (HIV). We examined the effect of a community-based nutritional intervention on anthropometric and clinical outcomes of children of women living with HIV in rural India. METHODS: We assigned women living with HIV and their child (oldest 3-8 years) to 1 of 4 programs: (1) community-based HIV care program, (2) program 1 + nutrition education, (3) program 1 + food supplement, and (4) all elements of programs 1-3. Study data were collected at baseline and months 6, 12, and 18. We applied mixed-effects modeling with restricted maximum likelihood estimation to examine changes in weight (all children) and CD4+ T-cell counts (children with HIV only). RESULTS: Overall, 600 mother-child pairs were enrolled (150/group) with 100% retention at follow-up visits. Approximately 20% of children were living with HIV. Children in program 4 had higher weight gain than those in programs 1, 2, and 3 at all time points (adjusted P < .001). We found a higher increase in CD4+ T cells across all time points among participants in programs 3 and 4 compared with program 1 (adjusted P < .001). Factorial analysis suggested a synergistic effect of combining nutrition education and food supplements for weight gain but not for increase in CD4+ T cells. CONCLUSIONS: A combination of nutrition education and food supplements provided to women living with HIV significantly increased weight and CD4+ T cells, and such interventions can be integrated into HIV-care programs in low-income settings.

Possible Transmission Mechanisms of Mixed Mycobacterium tuberculosis Infection in High HIV Prevalence Country, Botswana.

Tuberculosis caused by concurrent infection with multiple Mycobacterium tuberculosis strains (i.e., mixed infection) challenges clinical and epidemiologic paradigms. We explored possible transmission mechanisms of mixed infection in a population-based, molecular epidemiology study in Botswana during 2012-2016. We defined mixed infection as multiple repeats of alleles at >2 loci within a discrete mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) result. We compared mixed infection MIRU-VNTR results with all study MIRU-VNTR results by considering all permutations at each multiple allele locus; matched MIRU-VNTR results were considered evidence of recently acquired strains and nonmatched to any other results were considered evidence of remotely acquired strains. Among 2,051 patients, 34 (1.7%) had mixed infection, of which 23 (68%) had recently and remotely acquired strains. This finding might support the mixed infection mechanism of recent transmission and simultaneous remote reactivation. Further exploration is needed to determine proportions of transmission mechanisms in settings where mixed infections are prevalent.

Human papillomavirus genotypes in women with invasive cervical cancer with and without human immunodeficiency virus infection in Botswana.

Cervical cancer remains a significant cause of morbidity and mortality in women worldwide and is the leading cause of cancer-related death in Botswana. It is well established that women with HIV have a higher risk of persistent HPV infection leading to cervical cancer. We assessed HPV prevalence and genotype distribution in 126 tissue specimens from confirmed invasive cervical cancer cases using Abbott real-time PCR assay. Overall, 88 (69.8%) women were HIV-infected. Fifty-seven (64.8%) of the HIV-infected women had a baseline CD4+ count ≥350 cells/µl, and 82 (93.2%) were on antiretroviral therapy at the time of cervical cancer diagnosis. The median age of HIV-infected patients was significantly younger than that of HIV-uninfected patients (p < 0.001). HPV DNA was detected in all of 126 (100%) of tissues analyzed in our study. The HPV genotypes identified included the HPV-16 (75.4%), HPV-18 (28.6%) and other high-risk (hr) HPV genotypes (16.7%). HIV infection was positively associated with the presence of the HPV-16 genotype (p = 0.036), but not with HPV-18 or with other high-risk (hr)-HPV genotypes. Thirty-three percent of the patients had multiple hr-HPV genotypes, with higher rates in HIV-infected women. These results highlight the importance and potential impact of large-scale HPV vaccination programs covering HPV-16 and HPV-18 genotypes in countries like Botswana with high burden of HIV infection.

HIV infection is not associated with the initiation of curative treatment in women with cervical cancer in Botswana.

BACKGROUND: Cervical cancer is the leading cause of cancer death in Sub-Saharan Africa. The risk of developing cancer is increased for women living with human immunodeficiency virus (HIV) infection. It is unknown which factors predict the initiation of curative chemoradiotherapy (CRT) in resource-limited settings and whether HIV is associated with initiating curative CRT in settings with a high HIV burden. METHODS: All women living with and without HIV infection who were initiating curative and noncurative CRT for locally advanced cervical cancer in Botswana were prospectively enrolled in an observational study. The factors associated with receiving CRT were evaluated in all patients and the subgroup of women living with HIV. RESULTS: Of 519 enrolled women, 284 (55%) initiated CRT with curative intent. The curative cohort included 200 women (70.4%) who were living with HIV and had a median CD4 count of 484.0 cells/µL (interquartile range, 342.0-611.0 cells/µL). In the noncurative cohort, 157 of 235 women (66.8%) were living with HIV and had a median CD4 count of 476.5 cells/µL (interquartile range, 308.0-649.5 cells/µL). HIV status was not associated with initiating curative CRT (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.58-1.56). The factors associated with receiving curative CRT treatment on multivariable analysis in all patients included baseline hemoglobin levels ≥10 g/dL (OR, 1.80; 95% CI, 1.18-2.74) and stage I or II versus stage III or IV disease (OR, 3.16; 95% CI, 2.10-4.75). Women aged >61 years were less likely to receive curative treatment (OR, 0.43; 95% CI, 0.24-0.75). Among women who were living with HIV, higher CD4 cell counts were associated with higher rates of CRT initiation. CONCLUSIONS: The initiation of CRT with curative intent does not depend on HIV status. Significant predictors of CRT initiation include baseline hemoglobin level, disease stage, and age.

Utility of Targeted, Amplicon-Based Deep Sequencing To Detect Resistance to First-Line Tuberculosis Drugs in Botswana.

Multidrug-resistant tuberculosis (TB) is an alarming threat, and targeted deep sequencing (DS) may be an effective method for rapid identification of drug-resistant profiles, including detection of heteroresistance. We evaluated the sensitivity and specificity of targeted DS versus phenotypic drug susceptibility testing (pDST) among patients starting first-line anti-TB therapy in Botswana. Overall, we found high concordance between DS and pDST. Lower sensitivity of DS, which targets established high-confidence resistance variants, was observed for detecting isoniazid resistance among HIV-infected patients.

Depression, social support, and stigma as predictors of quality of life over time: results from an Asha-based HIV/AIDS intervention in India.

Quality of life (QOL) is associated with better outcomes in HIV/AIDS populations. We explored predictors of improved QOL over time in 600 Women Living with HIV/AIDS (WLH/A) in India [mean age = 34.31, SD = 6.97], enrolled in a nurse-led-Asha (Accredited Social Health Activist) intervention. Trained local interviewers ascertained self-report data at baseline and six-month follow-up (post-intervention). Latent Class Analysis (LCA) identified constellations of responses on psychosocial indicators (depression, social support, internalized stigma and stigma fears); their relationship with QOL over time was examined. We identified three classes: Class 1) Highest Social Resources/Lowest Depression; Class 2) Some Social Resources/Highest Depression; and Class 3) Lowest Social Resources/Higher Depression. At baseline, Class 3 reported the lowest QOL (M = 0.25, SD = 0.26); Class 1 reported the highest (M = 0.37, SD = 0.33). Class 2's QOL did not differ from Class 3's QOL, likely due to the potent effects of high depression. At six-month follow-up, all groups reported improved QOL; class membership no longer predicted variability (contrast between Class 2 and 1 = -0.05, 95% CI = -0.14, 0.04; contrast between Class 3 and 1 = 0.01, 95% CI = -0.03, 0.05; contrast between Class 3 and 2 = 0.07, 95% CI = -0.02, 0.16). Psychosocial indicators are important predictors of QOL; an Asha-supported approach may have broad applicability to improve QOL in WLH/A in India.

Mixed Mycobacterium tuberculosis-Strain Infections Are Associated With Poor Treatment Outcomes Among Patients With Newly Diagnosed Tuberculosis, Independent of Pretreatment Heteroresistance.

Background: Heteroresistant Mycobacterium tuberculosis infections (defined as concomitant infection with drug-resistant and drug-susceptible strains) may explain the higher risk of poor tuberculosis treatment outcomes observed among patients with mixed-strain M. tuberculosis infections. We investigated the clinical effect of mixed-strain infections while controlling for pretreatment heteroresistance in a population-based sample of patients with tuberculosis starting first-line tuberculosis therapy in Botswana. Methods: We performed 24-locus mycobacterial interspersed repetitive unit-variable number tandem-repeat analysis and targeted deep sequencing on baseline primary cultured isolates to detect mixed infections and heteroresistance, respectively. Drug-sensitive, micro-heteroresistant, macro-heteroresistant, and fixed-resistant infections were defined as infections in which the frequency of resistance was <0.1%, 0.1%-4%, 5%-94%, and ≥95%, respectively, in resistance-conferring domains of the inhA promoter, the katG gene, and the rpoB gene. Results: Of the 260 patients with tuberculosis included in the study, 25 (9.6%) had mixed infections and 30 (11.5%) had poor treatment outcomes. Micro-heteroresistance, macro-heteroresistance, and fixed resistance were found among 11 (4.2%), 2 (0.8%), and 11 (4.2%), respectively, for isoniazid and 21 (8.1%), 0 (0%), and 10 (3.8%), respectively, for rifampicin. In multivariable analysis, mixed infections but not heteroresistant infections independently predicted poor treatment outcomes. Conclusions: Among patients starting first-line tuberculosis therapy in Botswana, mixed infections were associated with poor tuberculosis treatment outcomes, independent of heteroresistance.