In utero/peripartum antiretroviral therapy exposure and mental health outcomes at 8-18 years old: A longitudinal comparative study of children with perinatally acquired HIV, children perinatally HIV exposed but uninfected, and children unexposed uninfected from Uganda.

In utero/peripartum antiretroviral therapy (IPA) exposure type was examined in relationship to mental health symptoms among 577 children with perinatally acquired HIV (CPHIV), children perinatally HIV exposed but uninfected (CHEU), and children HIV unexposed uninfected (CHUU). IPA exposure was categorized for CPHIV and CHEU as none, single-dose nevirapine with or without zidovudine (sdNVP±AZT), sdNVP+AZT+lamivudine (3TC), or combination antiretroviral therapy (cART). Anxiety and depressive symptoms were reported at baseline, 6-, and 12-month follow-up per behavioral assessment system for children. Multivariable linear mixed models were used to estimate differences (b) with 95% confidence intervals (95% CI) for IPA exposure types versus CHEU without IPA exposure. Depressive and anxiety symptoms were lower in CHUU relative to CHEU and CPHIV but did not differ between CPHIV and CHEU. CHEU with sdNVP±AZT exposure had greater anxiety (b = 0.51, 95% CI: [0.06, 0.96]) and depressive symptoms (b = 0.48, 95% CI: [0.07, 0.89]) than CHEU without IPA exposure. CHEU with sdNVP+AZT+3TC exposure had higher anxiety (b = 0.0.45, 95% CI: [0.03, 0.86]) and depressive symptoms (b = 0.72, 95% CI: [0.27, 1.17]) versus CHEU without IPA exposure. Depressive and anxiety symptoms were not different for CHEU and CPHIV exposed to cART (b = 0.12-0.60, 95% CI: [-0.41, 1.30]) and CHEU and CHUU (b = -0.04 to 0.08, 95% CI: [-0.24, 0.29]) without IPA exposure. Among CHEU, peripartum sdNVP±AZT and sdNVP+AZT+3TC but not cART compared to no IPA exposure was associated with clinically important elevations in anxiety and depressive symptoms. Monitoring of mental health trajectory of HIV-affected children considering IPA is needed to inform mental health interventions. Patient Contribution: Caregivers and their dependents provided consent for participation and collaborated with study team to identify mutually convenient times for protocol implementation.

Association of serum PUFA and linear growth over 12 months among 6-10 years old Ugandan children with or without HIV.

OBJECTIVE: To quantify PUFA-associated improvement in linear growth among children aged 6-10 years. DESIGN: Serum fatty acids (FA), including essential FA (EFA) (linoleic acid (LA) and α-linolenic acid (ALA)) were quantified at baseline using GC-MS technology. FA totals by class (n-3, n-6, n-9, PUFA and SFA) and FA ratios were calculated. Height-for-age Z-score (HAZ) relative to WHO population reference values were calculated longitudinally at baseline, 6 and 12 months. Linear regression models estimated PUFA, HIV status and their interaction-associated standardised mean difference (SMD) and 95 % CI in HAZ over 12 months. SETTING: Community controls and children connected to community health centre in Kampala, Uganda, were enrolled. PARTICIPANTS: Children perinatally HIV-infected (CPHIV, n 82), or HIV-exposed but uninfected (CHEU, n 76) and community controls (n 78). RESULTS: Relative to highest FA levels, low SFA (SMD = 0·31, 95 % CI: 0·03, 0·60), low Mead acid (SMD = 0·38, 95 % CI: 0·02, 0·74), low total n-9 (SMD = 0·44, 95 % CI: 0·08, 0·80) and low triene-to-tetraene ratio (SMD = 0·42, 95 % CI: 0·07, 0·77) predicted superior growth over 12 months. Conversely, low LA (SMD = -0·47, 95 % CI: -0·82, -0·12) and low total PUFA (sum of total n-3, total n-6 and Mead acid) (SMD = -0·33 to -0·39, 95 % CI: -0·71, -0·01) predicted growth deficit over 12 months follow-up, regardless of HIV status. CONCLUSION: Low n-3 FA (ALA, EPA and n-3 index) predicted growth deficits among community controls. EFA sufficiency may improve stature in school-aged children regardless of HIV status. Evaluating efficacy of diets low in total SFA, sufficient in EFA and enriched in n-3 FA for improving child growth is warranted.

Correction to: Change in quality of life over eight years in a nationally representative sample of US adults with heart disease and type 2 diabetes: minority race and toxic stress as key social determinants.

An amendment to this paper has been published and can be accessed via the original article.

Change in quality of life over eight years in a nationally representative sample of US adults with heart disease and type 2 diabetes:minority race and toxic stress as keysocial determinants.

BACKGROUND: Toxic stress (TS), minority race and their interaction are evaluated as determinants of change in quality of life (QOL) over 8 years follow-up in a nationally representative sample of United States (US) adults (≥50 years old) with heart disease (HD) and/or type-2 diabetes (T2DM) diagnosed by 2006 as part of the Health and Retirement Study (HRS). METHODS: Recent and life-course stress plus experiences of lifetime discrimination were measured every 2 years using the stressful life experiences questionnaire. QOL was assessed by participant self-rated health (SRH) and operationally defined as improved, unchanged or declined in current year versus two years prior. Repeated measures multinomial logistic regressionusing generalized estimating equations (GEEs) was implemented to estimate race-, TS and their interaction- related odds of worse SRH from2006-2014. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with adjustment for time, age, sex and socio-economic status. RESULTS: Three thousand nine hundred four adults with HD/T2DM, mean age 71.1 ± 9.3 years old, 80.9, 14.7 and 4.4% that respectively self-identified as Caucasian, African-American and Other race, were included. Over the eight-year follow-up, the odds of worse SRH for African-American and Other race were respectively 1.46 (95% CI: 1.25-1.70) and 1.43 (95% CI, 1.10-1.86) times higher relative to Caucasians. Relative to older Americans that reported ≥2 lifetime discrimination events, the odds of poor SRH was respectively 33% (OR = 0.67, 95%CI: 0.50-0.89) and 17% (OR = 0.83, 95%CI: 0.59-1.17) lower for those that reported none vs one lifetime discrimination experience. Furthermore, the relationship of life-course stress to SRH decline over 8 years varied by race (time*stress*race, p = 0.1173). Specifically, increasing life-course stress predicted worse QOL among Caucasians (p = 0.0063) and among African-American (p = 0.0820) but not among Other race (p = 0.9943). CONCLUSION: Toxic stress and minority race are social determinants of deterioration in QOL among older Americans with chronic diseases (HD/T2DM). The types and prevalence of toxic stressors varied by race/ethnicity. Policy interventions to address root causes of TS while targeted at proximate drivers of TS by race/ethnicity represent a viable strategy for mitigating racial disparities in overall wellbeing and improving QOL in all aging Americans regardless of race.

Tracking Progress Toward Elimination of Mother to Child Transmission of HIV in Zambia: Findings from the Early Infant Diagnosis of HIV Program (2009-2017).

BACKGROUND: We carried out analyses of early infant testing results at Livingstone Central Hospital in Zambia to assess time of testing, linkages to care and availability of test results for clinical decision making. METHODS: We abstracted data from registers of HIV-exposed infants who had dried blood spots cards (DBS) collected for DNA-PCR from January 2009 to December 2017. Only those tested from 2014 to 2017 had additional data which were used to estimate risk factors for mother-to-child HIV transmission using logistic regression models. RESULTS: DBS were collected from 2630 children. The proportion of HIV-positive tests decreased from 21% in 2009 to 2% in 2016 and 2017. Median turnaround time for results was 9 weeks (IQR: 5, 15) for HIV-negative, 7 weeks (IQR: 5, 13) for HIV-positive children. Only 2% of infants whose mothers took antiretroviral therapy (ART) were HIV positive, while 18% of infants whose mothers took short course antiretroviral drugs (ARVs) were infected. Infants of mothers who did not take ARVs had 9 times the odds of an HIV positive test (OR = 8.9, 95% CI: 3.6, 22.6). Infants of mothers who received short course ARVs were 40% less likely to get an HIV test within the first 2 months of life (OR = 0.6, 95% CI: 0.4, 0.9) compared to infants of mothers who received ART. Only 52% had a third test at median age 52 weeks (IQR: 50, 54). CONCLUSIONS: Long turnaround time for test results and low retention in care after the initial HIV test were critical challenges to clinical decision making.

Toxic Stress and Quality of Life in Early School-Aged Ugandan Children With and Without Perinatal Human Immunodeficiency Virus Infection.

Caregiver's and child's self-reported quality of life (QOL) was defined using standardized questionnaires in a sample (N = 277) of 6-10 years old HIV-infected, HIV-exposed uninfected, and HIV-unexposed uninfected children from Uganda. Psychosocial stress (acute stress and cumulative lifetime adversity) and physiologic stress (dysregulations across 13 biomarkers), perinatal HIV status, and their interaction were related to child QOL via general linear models. Lower child- and caregiver-reported psychosocial stress were dose-dependently associated with higher QOL (acute stress: mean difference coefficient b = 8.1-14.8, effect size [ES] = 0.46-0.83). Lower allostasis was dose-dependently associated with higher QOL (b = 6.1-9.7, ES = 0.34-0.54). Given low caregiver acute stress, QOL for HIV-infected was similar to HIV-uninfected children; however, given high caregiver acute stress, a QOL disadvantage (b = -7.8, 95% CI: -12.8, -2.8; ES = -0.73) was evident for HIV-infected versus uninfected children. Testing of caregiver stress reduction interventions is warranted to increase wellbeing in dependent children.

Psychosocial Adjustment in Ugandan Children: Coping With Human Immunodeficiency Virus Exposure, Lifetime Adversity, and Importance of Social Support.

Cumulative lifetime adversity and social support were investigated as determinants of psychosocial adjustment (esteem, distress, hopefulness, positive outlook/future aspirations, and sense of purpose) over 12 months in 6-10-years-old HIV-infected, HIV-exposed uninfected and HIV-unexposed uninfected children from Uganda. Each determinant and psychosocial adjustment indicator was self-reported using standardized questionnaires administered at baseline, 6, and 12 months. Linear mixed effects models were used to relate time-varying lifetime adversity and social support to psychosocial adjustment over 12 months. Regardless of HIV status, higher adversity predicted lower esteem (coefficient b = -2.98, 95% confidence interval (CI): [-4.62, -1.35]) and increased distress (b =3.96, 95% CI: [1.29, 6.62]) but was not associated with hopefulness, positive outlook or sense of purpose. Low social support predicted higher distress (b =9.05, 95% CI: [7.36, 10.73]), lower positive outlook (b = -10.56, 95% CI: [-2.34, -8.79]) and low sense of purpose (b = -9.90, 95% CI: [-11.44, -8.36]) over 12 months. Pragmatic interventions that enhance coping with adversity and provide emotional/instrumental support should be tested for effectiveness in promoting resilient psychosocial adjustment trajectory in vulnerable children.

Caregiver socioemotional health as a determinant of child well-being in school-aged and adolescent Ugandan children with and without perinatal HIV exposure.

OBJECTIVE: Caregiver socio-emotional attributes are major determinants of child well-being. This investigation in vulnerable school-aged Ugandan children estimates relationships between children's well-being and their caregiver's anxiety, depression and social support. METHODS: Perinatally HIV-infected, HIV-exposed uninfected and HIV-unexposed Ugandan children and their caregivers were enrolled. Perinatal HIV status was determined by 18 months of age using DNA-polymerase chain-reaction test; status was confirmed via HIV rapid diagnostic test when children were 6-18 years old. Five indicators of child well-being (distress, hopelessness, positive future orientation, esteem and quality of life (QOL)) and caregivers' socioemotional status (depressive symptoms, anxiety and social support) were measured using validated, culturally adapted and translated instruments. Categories based on tertiles of each caregiver psychosocial indicator were defined. Linear regression analyses estimated percent differences (ß) and corresponding 95% confidence intervals (CI) for child well-being in relation to caregiver's psychosocial status. RESULTS: As per tertile increment, caregiver anxiety was associated with 2.7% higher distress (95%CI:0.2%, 5.3%) and lower self-esteem/QOL (ß = -1.3%/-2.6%; 95%CI: -5.0%,-0.2%) in their children. Child distress/hopelessness increased (ß = 3.3%/7.6%; 95%CI:0.4%, 14.7%) and self-esteem/QOL decreased 2.3% (ß = -2.3%/-4.4%; 95%CI: -7.2%, -1.3%) as per tertile increment in caregiver depression. Higher caregiver social support was associated with lower distress and higher positive outlook (ß = 3%; 95%CI:1.4%, 4.5%) in their children. HIV-infected/exposed children had most caregiver depression-related QOL deficit (ß = -5.2%/-6.8%; 95%CI: -12.4%, -0.2%) and HIV-unexposed children had most caregiver social support-related enhancements in positive outlook (ß=4.5%; 95%CI:1.9%, 7.1%). CONCLUSIONS: Caregiver anxiety, depressive symptoms and low social support were associated with worse well-being in school-aged and adolescent children. Improvement of caregiver mental health and strengthening caregiver social support systems may be a viable strategy for improving well-being of vulnerable children and adolescents in this setting.

OBJECTIF: Les attributs socio-affectifs des responsables d'enfants sont des déterminants majeurs du bien-être des enfants. Cette investigation menée auprès d'enfants ougandais vulnérables d'âge scolaire a estimé les relations entre le bien-être des enfants et l'anxiété, la dépression et le soutien social de leur responsable. MÉTHODES: Des enfants ougandais infectés par le VIH de manière périnatale, exposés au VIH mais non infectés, et non exposés au VIH ainsi que leurs responsables ont été inscrits. Le statut VIH périnatal a été déterminé à l'âge de 18 mois à l'aide du test de PCR de l'ADN; le statut a été confirmé par un test de diagnostic rapide du VIH chez les enfants âgés de 6 à 18 ans. Cinq indicateurs du bien-être de l'enfant (détresse, désespoir, orientation future positive, estime et qualité de vie (QV)), et le statut psychosocial des responsables (symptômes dépressifs, anxiété et soutien social) ont été mesurés à l'aide de méthodes validées, adaptées à la culture et respectées et d'outils traduits. Des catégories basées sur les tertiles de chaque indicateur psychosocial du responsable ont été définies. Des analyses de régression linéaire ont estimé les différences en pourcentage (ß) et les intervalles de confiance (IC) à 95% correspondants pour le bien-être de l'enfant par rapport au statut psychosocial de leurs responsables. RÉSULTATS: Par incrément de tertile, l'anxiété des responsables était associé à 2,7% de détresse plus élevé (IC95%: 0,2%, 5,3%) et de faible estime de soi/QV (ß = −1,3%/−2,6%; IC95%: −5,0%, −0,2%) chez leurs enfants. La détresse et le désespoir des enfants augmentaient (ß = 3,3%/7,6%; IC95%: 0,4%, 14,7%) et l'estime de soi/QV diminuait de 2,3% (ß = −2,3%/−4,4%; IC95%: −7,2%, −1,3%) par incrément de tertile de la dépression chez le responsable. Un soutien social plus élevé des responsables était associé à une détresse moindre et à une perspective positive plus élevée (ß = 3%; IC95%: 1,4%, 4,5%) chez leurs enfants. Les enfants infectés/exposés au VIH présentaient pour la plupart un déficit de QV lié à la dépression de leurs responsables (ß = −5,2%/−6,8%; IC95%: −12,4%, −0,2%), et ceux non exposés au VIH présentaient pour la plupart des améliorations en perspective positive liées au soutien social de leurs responsables (ß = 4,5%; IC95%: 1,9%, 7,1%). CONCLUSIONS: L'anxiété, les symptômes dépressifs et un faible soutien social du responsable étaient associés à un bien-être précaire chez les enfants d'âge scolaire et les adolescents. L'amélioration de la santé mentale des responsables et le renforcement des systèmes de soutien social pour les responsables peuvent constituer une stratégie viable pour améliorer le bien-être des enfants et des adolescents vulnérables dans cette région.

Predictors of loss to follow-up among children on long-term antiretroviral therapy in Zambia (2003-2015).

BACKGROUND: Retention in care is critical for children living with HIV taking antiretroviral therapy (ART). Loss to follow-up (LTFU) is high in HIV treatment programs in resource limited settings. We estimated the cumulative incidence of LTFU and identified associated risk factors among children on ART at Livingstone Central Hospital (LCH), Zambia. METHODS: Using a retrospective cohort study design, we abstracted data from medical records of children who received ART between 2003 and 2015. Loss to follow-up was defined as no clinical and pharmacy contact for at least 90 days after the child missed their last scheduled clinical visit. Non-parametric competing risks models were used to estimate the cumulative incidence of death, LTFU and transfer. Cause-specific Cox regression was used to estimate the hazard ratios of the risk factors of LTFU. RESULTS: A total of 1039 children aged 0-15 years commenced ART at LCH between 2003 and 2015. Median duration of follow-up was 3.8 years (95% CI: 1.2-6.5), median age at ART initiation was 3.6 years (IQR: 1.3-8.6), 179 (17%) started treatment during their first year of life. At least 167 (16%) were LTFU and we traced 151 (90%). Of those we traced, 39 (26%) had died, 71 (47%) defaulted, 20 (13%) continued ART at other clinics and 21 (14%) continued treatment with gaps. The cumulative incidence of LTFU for the entire cohort was 2.7% (95% CI: 1.9-3.9) at 3 months, 4.1% (95% CI: 2.9-5.4) at 6 months and 14.1% (95% CI: 12.4-16.9) after 5 years on ART. Associated risk factors were: 1) non-disclosure of HIV status at baseline, aHR = 1.9 (1.2-2.9), 2) No phone ownership, aHR = 2.1 (1.6-2.9), 3) starting treatment between 2013 to 2015, aHR = 5.6 (2.2-14.1). CONCLUSION: Among the children LTFU mortality and default were substantially high. Children who started treatment in recent years (2013-2015) had the highest hazard of LTFU. Lack of access to a phone and non-disclosure of HIV-status to the index child was associated with higher hazards of LTFU. We recommend re-enforcement of client counselling and focused follow-up strategies using modern technology such as mobile phones as adjunct to current approaches.

Long-term survival outcomes of HIV infected children receiving antiretroviral therapy: an observational study from Zambia (2003-2015).

BACKGROUND: In 2017, 64% of children living with HIV in Zambia accessed Antiretroviral Therapy (ART). Despite expanded ART coverage, there is paucity of information on effectiveness of pediatric ART in reducing mortality. The aim of this research is to describe treatment outcomes, measure mortality rates and assess predictors of mortality among children receiving ART. METHODS: Using a retrospective cohort study design, we abstracted routinely collected clinical data from medical records of children from birth to 15 years old, who had received ART for at least 6 months at Livingstone Central Hospital in Southern Province Zambia, between January 2003 and June 2015. The primary outcome was death. Cause of death was ascertained from medical records and death certificates. Distribution of survival times according to baseline covariates were estimated using Kaplan Meier and Cox Proportional Hazards methods. RESULTS: Overall, 1039 children were commenced on ART during the study period. The median age at treatment initiation was 3.6 years (IQR: 1.3-8.6) and 520 (50%) children were female. Of these, 71 (7%) died, 164 (16%) were lost to follow-up, 210 (20%) transferred and 594 (56%) were actively on treatment. After 4450 person years, mortality rate was 1.6/100 (95% CI: 1.4-1.8). Mortality was highest during the first 3 months of treatment (11.7/100 (95% CI: 7.6-16.3). In multivariable proportional hazards regression, the adjusted hazards of death were highest among children aged < 1 year (aHR = 3.1 (95% CI: 1.3-6.4), compared to those aged 6-15 years, WHO stage 4 (aHR =4.8 (95% CI: 2.3-10), compared to WHO stage 1 and 2. In the sensitivity analysis to address bias due to loss to follow-up, mortality increased 5 times when we assumed that all the children who were lost to follow up died within 90 days of their last visit. CONCLUSION: We observed low attrition due to mortality among children on ART. Loss to follow-up was high (16%). Mortality was highest during the first 3 months of treatment. Children aged less than one year and those with advanced WHO disease stage had higher mortality. We recommend effective interventions to improve retention in care and early diagnosis of HIV in children.

Gaining and sustaining schistosomiasis control: study protocol and baseline data prior to different treatment strategies in five African countries.

BACKGROUND: The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in 2008 to answer strategic questions about schistosomiasis control. For programme managers, a high-priority question is: what are the most cost-effective strategies for delivering preventive chemotherapy (PCT) with praziquantel (PZQ)? This paper describes the process SCORE used to transform this question into a harmonized research protocol, the study design for answering this question, the village eligibility assessments and data resulting from the first year of the study. METHODS: Beginning in 2009, SCORE held a series of meetings to specify empirical questions and design studies related to different schedules of PCT for schistosomiasis control in communities with high (gaining control studies) and moderate (sustaining control studies) prevalence of Schistosoma infection among school-aged children. Seven studies are currently being implemented in five African countries. During the first year, villages were screened for eligibility, and data were collected on prevalence and intensity of infection prior to randomisation and the implementation of different schemes of PZQ intervention strategies. RESULTS: These studies of different treatment schedules with PZQ will provide the most comprehensive data thus far on the optimal frequency and continuity of PCT for schistosomiasis infection and morbidity control. CONCLUSIONS: We expect that the study outcomes will provide data for decision-making for country programme managers and a rich resource of information to the schistosomiasis research community. TRIAL REGISTRATION: The trials are registered at International Standard Randomised Controlled Trial registry (identifiers: ISRCTN99401114 , ISRCTN14849830 , ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 and ISRCTN32045736 ).

Indicators of resilience and healthcare outcomes: findings from the 2010 health and retirement survey.

OBJECTIVE: To test the hypothesis that higher levels of resilience indicators are associated with lower overall healthcare utilization (HCU) as well as improvements in self-rated health (SRH), we analyzed a representative sample of 4562 adults 50-70 years old enrolled in the US 2010 health and retirement survey. METHODS: Multivariable logistic regression models estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for high versus low resilience in relation to HCU and SRH improvements over 2 years. Resilience indicators included: cumulative lifetime adversity, social support, global mastery and domain-specific mastery. Cumulative lifetime adversity was defined as 0, 1-2, 3-4 or 5+ events. HCU included hospitalization (any vs. none) and physician visits (< 20 vs. ≥ 20) over 2 years. FINDINGS: Hospitalization odds declined by 25 % (OR 0.75, 95 %CI 0.64-0.86), odds of ≥ 20 physician visits declined by 47 % (OR 0.53, 95 % CI 0.45-0.63) and the odds of SRH improvement increased by 49 % (OR 1.49, 95 % CI 1.17-1.88) for respondents with high versus low health mastery. Cumulative lifetime adversity manifested a dose-dependent positive relationship with HCU. Specifically, hospitalization odds was, respectively, 25, 80 and 142 % elevated for participants that reported 1-2, 3-4 and 5+ versus 0 lifetime adversities. High versus low global, financial and health mastery, respectively, predicted improved SRH, lower physician's visits and hospitalizations. CONCLUSION: In this sample of adults near or in retirement, resilience predicted lower HCU and improved SRH. Resilience is a dynamic state that can be enhanced in adults with positive impacts on subjective well-being and HCU.

Four Degrees of Separation: Social Contacts and Health Providers Influence the Steps to Final Diagnosis of Active Tuberculosis Patients in Urban Uganda.

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.

Prevalence of latent tuberculosis infection and associated risk factors in an urban African setting.

BACKGROUND: Nearly one third of the world is infected with latent tuberculosis infection (LTBI) and a vast pool of individuals with LTBI persists in developing countries, posing a major barrier to global TB control. The aim of the present study was to determine the prevalence of LTBI and the associated risk factors among adults in Kampala, Uganda. METHODS: We performed a secondary analysis from a door-to-door cross-sectional survey of chronic cough conducted from January 2008 to June 2009. Urban residents of Rubaga community in Kampala aged 15 years and older who had received Tuberculin skin testing (TST) were included in the analysis. The primary outcome was LTBI defined as a TST with induration 10 mm or greater. Multivariable logistic regression analyses were used to assess the risk factors associated with LTBI. RESULTS: A total of 290 participants were tested with TST, 283 had their tests read and 7 didn't have the TST read because of failure to trace them within 48-72 hours. Of the participants with TST results, 68% were female, 75% were 15-34 years, 83% had attained at least 13 years of education, 12% were smokers, 50% were currently married, 57% left home for school or employment, 21% were HIV positive and 65% reported chronic cough of 2 weeks or longer. The overall prevalence of LTBI was 49% [95% CI 44-55] with some age-and sex-specific differences. On multivariable analysis, leaving home for school or employment, aOR = 1.72; [95%CI: 1.05, 2.81] and age 25-34, aOR = 1.94; [95%CI: 1.12, 3.38]; 35 years and older, aOR = 3.12; [95%CI: 1.65, 5.88] were significant risk factors of LTBI. CONCLUSION: The prevalence of LTBI was high in this urban African setting. Leaving home for school or employment and older age were factors significantly associated with LTBI in this setting. This suggests a potential role of expansion of one's social network outside the home and cumulative risk of exposure to TB with age in the acquisition of LTBI. Our results provide support for LTBI screening and preventive treatment programs of these sub-groups in order to enhance TB control.

The effect of standard dose multivitamin supplementation on disease progression in HIV-infected adults initiating HAART: a randomized double blind placebo-controlled trial in Uganda.

BACKGROUND: Efficacy trials investigating the effect of multivitamin (MV) supplementations among patients on Highly Active Antiretroviral Therapy (HAART) have so far been inconclusive. We conducted a randomized, double blind, placebo controlled trial to determine the effect of one recommended daily allowance (RDA) of MV supplementation on disease progression in patients initiating HAART. METHODS: Eligible subjects were randomized to receive placebo or MV supplementation including vitamins B-complex, C and E. Participants were followed for up to 18 months. Primary endpoints were: change in CD4 cell count, weight and quality of life (QoL). Secondary endpoints were: i) development of a new or recurrent HIV disease progression event, including all-cause mortality; ii) switching from first- to second-line antiretroviral therapy (ART); and iii) occurrence of an adverse event. Intent-to-treat analysis, using linear regression mixed effects models were used to compare changes over time in the primary endpoints between the study arms. Kaplan-Meier time-to-event analysis and the log-rank test was used to compare HIV disease progression events and all-cause mortality. RESULTS: Four hundred participants were randomized, 200 onto MV and 200 onto placebo. By month 18, the average change in CD4 cell count in the MV arm was 141 cells/uL compared to 147 cells/uL in the placebo arm, a mean difference of -6 · 17 [95 % CI -29 · 3, 16 · 9]. The average change in weight in the MV arm was 3 · 9 kg compared to 3 · 3 kg in the placebo arm, a mean difference of 0 · 54 [95 % CI -0 · 40, 1 · 48]; whereas average change in QoL scores in the MV arm was 6 · 8 compared to 8 · 8 in the placebo arm, a mean difference of -2.16 [95 % CI -4 · 59,0 · 27]. No significant differences were observed in these primary endpoints, or in occurrence of adverse events between the trial arms. CONCLUSIONS: One RDA of MV supplementation was safe but did not have an effect on indicators of disease progression among HIV infected adults initiating HAART. TRIAL REGISTRATION: Clinical trials NCT01228578 , registered on 15th October 2010.

Prevalence and correlates of cytopenias in HIV-infected adults initiating highly active antiretroviral therapy in Uganda.

BACKGROUND: Cytopenias are the most common HIV-associated hematological abnormality. Cytopenias have been associated with several factors including sex, race/ethnicity, geographical location and comorbidities such as tuberculosis, hepatitis B infection, fever and oral candidiasis. Cytopenias become more prevalent as HIV progresses and are often fatal. Data from resource-limited settings about the prevalence and correlates of cytopenia are limited. Therefore we conducted this cross-sectional study to assess the prevalence and correlates of cytopenia among adult AIDS patients at initiation of HAART in Uganda. METHODS: 400 HIV-infected subjects who were HAART-naïve or on HAART for ≤ 6 months were enrolled into the Multivitamins, HAART and HIV/AIDS Trial. Anemia was defined according to WHO guidelines as any hemoglobin concentration < 12 g/dl for non-pregnant females and < 13 g/dl for males. Leucopenia and thrombocytopenia were defined using study site laboratory reference ranges for lack of generally accepted definitions for these 2 cell lines as leucopenia if white blood cell count < 2.75 × 109 cells/litre and thrombocytopenia if platelets < 125 × 109 cells/litre for females and < 156 × 109 cells/litre for males. Univariate and bivariate analyses were done to describe the patient population and log-binomial regression was used to quantify the correlates of cytopenia. RESULTS: Sixty five percent of the 400 subjects had at least one form of cytopenia. Anemia occurred in 47.8%, leucopenia in 24.3%, thrombocytopenia in 8.3%, bicytopenia in 21.9% and only 2 had a pancytopenia. Cytopenia was more prevalent in females (prevalence ratio [PR]:1.33, 95% confidence interval [CI]:1.12-1.59); CD4 count category 50 to <200 (PR: 0.75, 95% CI: 0.64 -0.88) and CD4 count category 200 to <350 (PR: 0.74, 95% CI: 0.59 - 0.92) compared to CD4 count category <50; normal BMI (PR: 0.82, 95% CI:0.68-1.00) and overweight BMI (PR: 0.64, 95% CI:0.50- 0.82) compared to underweight BMI and those with a history or presence of oral candidiasis. CONCLUSIONS: Cytopenias are a frequent complication in HIV-infected adults at initiation of HAART in Uganda. The presence of any cytopenia was associated with female sex, decreasing CD4 count and decreasing body mass index. Prospective studies in resource-limited settings on the trend in HIV-related cytopenias are needed.

The impact of mid- and late-life loss on insomnia: findings from the health and retirement study, 2010 cohort.

Bereavement and insomnia are both well-documented risk factors for illness. We use cohort data to estimate risk of insomnia after death of a family member among adults aged 50 to 70 years. Each day, 6700 persons die in the United States. During the next 20 years, this number will increase. In this cohort, any loss increases the likelihood of insomnia. The highest rates of insomnia occur among women aged 50 to 59 years; men aged 65 to 70 years, and persons reporting death of a spouse/partner or child. Physical activity reduces this risk by one-third. Bereavement is a public health issue requiring a targeted response.

HIV infection and the incidence of malaria among HIV-exposed children from Tanzania.

OBJECTIVE: To determine whether human immunodeficiency virus (HIV) infection is associated with increased risk of malaria incidence and recurrence in children. METHODS: Newborn infants of HIV-infected mothers were enrolled at 6 weeks and followed for 2 years. HIV status was assessed by enzyme-linked immunosorbant assay and confirmed by HIV DNA polymerase chain reaction. Malaria was defined as (1) physician-diagnosed clinical malaria; (2) probable malaria, in which laboratory testing is requested for parasitemia; and (3) blood smear-confirmed malaria. Cox proportional hazards models estimated hazard ratios (HRs) for development of first and second malaria episodes, and generalized estimating equation models estimated malaria rate differences per 100-child-years in relation to time-updated HIV status. RESULTS: Child HIV infection was associated with clinical (HR, 1.34; 95% confidence interval [CI], 1.12-1.61), probable (HR, 1.47; 95% CI, 1.19-1.81), and confirmed (HR, 1.67; 95% CI, 1.18-2.36) malaria episodes. Per 100 child-years, HIV-infected children experienced 88 (95% CI, 65-113), 36 (95% CI, 19-53), and 20 (95% CI, 9-31) more episodes of clinical, probable, and confirmed malaria episodes, respectively, than HIV-uninfected children. Among children with ≥1 malaria episodes, those with HIV infection developed second clinical (HR, 1.28; 95% CI, 1.04-1.57), probable (HR, 1.60; 95% CI, 1.26-2.14), and confirmed (HR, 2.27; 95% CI, 1.06-3.89) malaria sooner than HIV-uninfected children. CONCLUSIONS: HIV infection is a risk factor for the development of malaria. Proactive malaria disease prevention and treatment is warranted for all children, particularly those with HIV infection in settings of coendemicity.

New Perspectives on the Associations between Blood Fatty Acids, Growth Parameters, and Cognitive Development in Global Child Populations.

Malnutrition is prevalent in low-middle-income countries (LMICs), but it is usually clinically diagnosed through abnormal anthropometric parameters characteristic of protein energy malnutrition (PEM). In doing so, other contributors or byproducts of malnutrition, notably essential fatty acid deficiency (EFAD), are overlooked. Previous research performed mainly in high-income countries (HICs) shows that deficiencies in essential fatty acids (EFAs) and their n-3 and n-6 polyunsaturated fatty acid (PUFA) byproducts (also known as highly unsaturated fatty acids or HUFAs) lead to both abnormal linear growth and impaired cognitive development. These adverse developmental outcomes remain an important public health issue in LMICs. To identify EFAD before severe malnutrition develops, clinicians should perform blood fatty acid panels to measure levels of fatty acids associated with EFAD, notably Mead acid and HUFAs. This review demonstrates the importance of measuring endogenous fatty acid levels for measuring fatty acid intake in various child populations in LMICs. Featured topics include a comparison of fatty acid levels between global child populations, the relationships between growth and cognition and PUFAs and the possible mechanisms driving these relationships, and the potential importance of EFAD and HUFA scores as biomarkers of overall health and normal development.

Growth differences by school-age and adolescence according to in utero and peripartum antiretroviral therapy exposure among Ugandan children.

In utero/peripartum antiretroviral (IPA) drug exposure in human immunodeficiency virus (HIV)-exposed children has established benefit for prevention of HIV mother-to-child-transmission but its association with height-for-age by adolescence is unknown. Hence we quantify IPA-associated growth differences at 6 to 18 years old among children with perinatally acquired HIV (CPHIV) infection and children HIV exposed but uninfected (CHEU) relative to children HIV unexposed and uninfected (CHUU). Cohort study. Kampala, Uganda. Two hundred thirty eight community controls and 490 children of women living with HIV born between 2000 and 2011 in a community were enrolled at 6 to 18 years of age and followed every 6 months for 1 year. Height-for-age determined at enrollment, 6 and 12 months after enrollment using the World Health Organization reference. IPA exposure was retrospectively determined from medical records and categorized as: no IPA, single-dose nevirapine with/without zidovudine (sdNVP ±â€…AZT), sdNVP + AZT + lamivudine, or combination antiretroviral therapy (cART). Mean differences (ß) with 95% confidence intervals (CIs) in height-for-age over 12 months were evaluated according to IPA exposure for CPHIV and CHEU and relative to CHUU using longitudinal linear mixed effects models adjusted for caregiver factors (sex, age, education, functioning in caregiving role, and lifetime adversity) in Statistical Analysis Software (v.9.4). Regardless of IPA type, CPHIV grew worse than CHUU by school-age/adolescence (ß = -0.30, 95% CI: -0.48, -0.11). Relative to CHUU height-for-age was similar for CHEU exposed to sdNVP ±â€…AZT (ß = -0.16, 95% CI: -0.46, 0.14) and for CHEU exposed to sdNVP + AZT + lamivudine (ß = 0.08, 95% CI: -0.20, 0.35). However, CHEU without any IPA exposure had lower height-for-age (ß = -0.27, 95% CI: -0.52, -0.00) whereas CHEU with cART exposure had greater height-for-age (ß = 0.41, 95% CI: 0.10, 0.71) in comparison with CHUU by 6 to 18 years old. Our findings suggest that CHEU may achieve height-for-age parity with CHUU by school-age and adolescent years- especially if provided benefit of effective cART in the peripartum period. However, CPHIV regardless of IPA exposure type and CHEU without IPA exposure remain at a disadvantage and will benefit from intervention to support their growth.