Lydia Feinstein

Antenatal and delivery services in Kinshasa, Democratic Republic of Congo: care-seeking and experiences reported by women in a household-based survey.

Increasing coverage of quality reproductive health services, including prevention of mother‐to‐child transmission services, requires understanding where and how these services are provided. To inform scale‐up, we conducted a population‐based survey in Kinshasa, Democratic Republic of Congo.

Implementation and Operational Research: Maternal Combination Antiretroviral Therapy Is Associated With Improved Retention of HIV-Exposed Infants in Kinshasa, Democratic Republic of Congo.

Background:Programs to prevent mother-to-child HIV transmission are plagued by loss to follow-up (LTFU) of HIV-exposed infants. We assessed if providing combination antiretroviral therapy (cART) to HIV-infected mothers was associated with reduced LTFU of their HIV-exposed infants in Kinshasa, DR Congo. Methods:We constructed a cohort of mother–infant pairs using routinely collected clinical data. Maternal cART eligibility was based on national guidelines in effect at the time. Infants were considered LTFU after 3 failed tracking attempts after a missed visit or if more than 6 months passed since they were last seen in clinic. Statistical methods accounted for competing risks (eg, death). Results:A total of 1318 infants enrolled at a median age of 2.6 weeks (interquartile range: 2.1–6.9), at which point 24% of mothers were receiving cART. Overall, 5% of infants never returned to care after enrollment and 18% were LTFU by 18 months. The 18-month cumulative incidence of LTFU was 8% among infants whose mothers initiated cART by infant enrollment and 20% among infants whose mothers were not yet on cART. Adjusted for baseline factors, infants whose mothers were not on cART were over twice as likely to be LTFU, with a subdistribution hazard ratio of 2.75 (95% confidence limit: 1.81 to 4.16). The association remained strong regardless of maternal CD4 count at infant enrollment. Conclusions:Increasing access to cART for pregnant women could improve retention of HIV-exposed infants, thereby increasing the clinical and population-level impacts of prevention of mother-to-child HIV transmission interventions and access to early cART for HIV-infected infants.

Effect of baseline immune suppression on growth recovery in HIV positive South African children receiving antiretroviral treatment.

Background:Growth failure is common among children infected with HIV. The degree of growth recovery and its determinants in children initiating combination antiretroviral therapy (cART) are not well understood. Methods:We conducted a cohort study of children who initiated cART between 2004 and 2008 at a pediatric HIV clinic in Johannesburg, South Africa. To determine the effect of severe immunodeficiency at cART initiation on growth recovery (defined as attaining a z-score > −2), we generated Kaplan–Meier survival functions and fit a Cox proportional hazards model. In sensitivity analyses, we assessed selection bias due to loss to follow-up or death. Results:Of the 2399 children who initiated cART, 71% presented with growth failure. Within 2 years of cART, only 81% of underweight children achieved normal weight, and 64% of stunted children achieved length/height recovery. Severe immunodeficiency at cART initiation was not associated with weight recovery [hazards ratio: 1.05, 95% CI: 0.83 to 1.32] or length/height recovery (hazards ratio: 1.06, 95% CI: 0.83 to 1.34) in overall analyses, and modification by baseline growth failure and age were modest. Older children and those with severe growth failure were less likely to achieve growth recovery, regardless of baseline immunodeficiency status. Conclusions:A substantial proportion of children fail to achieve growth recovery despite 2 years of cART. Our analysis did not support an association between baseline immunodeficiency and growth recovery. Younger age and less-severe growth failure at cART initiation are strong predictors of achieving growth recovery. These findings support early initiation of cART, before the presence of growth failure, and independent of level of immunodeficiency.

Economic impacts of child marriage: global synthesis report.

Background As the number of deaths among children younger than 5 years of age continues to decline globally through programs to address the health of older infants, neonatal mortality is becoming an increasingly large proportion of under–5 deaths. Lack of access to safe delivery care, emergency obstetric care and postnatal care continue to be challenges for reducing neonatal mortality. This article reviews the available evidence regarding the effectiveness of community–based primary health care (CBPHC) and common components of programs aiming to improve health during the first 28 days of life. Methods A database comprising evidence of the effectiveness of projects, programs and field research studies (referred to collectively as projects) in improving maternal, neonatal and child health through CBPHC has been assembled and described elsewhere in this series. From this larger database (N = 548), a subset was created from assessments specifically relating to newborn health (N = 93). Assessments were excluded if the primary project beneficiaries were more than 28 days of age, or if the assessment did not identify one of the following outcomes related to neonatal health: changes in knowledge about newborn illness, care seeking for newborn illness, utilization of postnatal care, nutritional status of neonates, neonatal morbidity, or neonatal mortality. Descriptive analyses were conducted based on study type and outcome variables. An equity assessment was also conducted on the articles included in the neonatal subset. Results There is strong evidence that CBPHC can be effective in improving neonatal health, and we present information about the common characteristics shared by effective programs. For projects that reported on health outcomes, twice as many reported an improvement in neonatal health as did those that reported no effect; only one study demonstrated a negative effect. Of those with the strongest experimental study design, almost three–quarters reported beneficial neonatal health outcomes. Many of the neonatal projects assessed in our database utilized community health workers (CHWs), home visits, and participatory women’s groups. Several of the interventions used in these projects focused on health education (recognition of danger signs), and promotion of and support for exclusive breastfeeding (sometimes, but not always, including early breastfeeding). Almost all of the assessments that included a measurable equity component showed that CBPHC produced neonatal health benefits that favored the poorest segment of the project population. However, the studies were quite biased in geographic scope, with more than half conducted in South Asia, and many were pilot studies, rather than projects at scale. Conclusions CBPHC can be effectively employed to improve neonatal health in high–mortality, resource–constrained settings. CBPHC is especially important for education and support for pregnant and postpartum mothers and for establishing community–facility linkages to facilitate referrals for obstetrical emergencies; however, the latter will only produce better health outcomes if facilities offer timely, high–quality care. Further research on this topic is needed in Africa and Latin America, as well as in urban and peri–urban areas. Additionally, more assessments are needed of integrated packages of neonatal interventions and of programs at scale.

PTSD is associated with an increase in aged T cell phenotypes in adults living in Detroit

BACKGROUND Psychosocial stress is thought to play a key role in the acceleration of immunological aging. This study investigated the relationship between lifetime and past-year history of post-traumatic stress disorder (PTSD) and the distribution of T cell phenotypes thought to be characteristic of immunological aging. METHODS Data were from 85 individuals who participated in the community-based Detroit Neighborhood Health Study. Immune markers assessed included the CD4:CD8 ratio, the ratio of late-differentiated effector (CCR7-CD45RA+CD27-CD28-) to naïve (CCR7+CD45RA+CD27+CD28+) T cells, the percentage of KLRG1-expressing cells, and the percentage of CD57-expressing cells. RESULTS In models adjusted for age, gender, race/ethnicity, education, smoking status, and medication use, we found that past-year PTSD was associated with statistically significant differences in the CD8+ T cell population, including a higher ratio of late-differentiated effector to naïve T cells, a higher percentage of KLRG1+ cells, and a higher percentage of CD57+ cells. The percentage of CD57+ cells in the CD4 subset was also significantly higher and the CD4:CD8 ratio significantly lower among individuals who had experienced past-year PTSD. Lifetime PTSD was also associated with differences in several parameters of immune aging. CONCLUSIONS PTSD is associated with an aged immune phenotype and should be evaluated as a potential catalyzer of accelerated immunological aging in future studies.

Temporal changes in the outcomes of HIV-exposed infants in Kinshasa, Democratic Republic of Congo during a period of rapidly evolving guidelines for care (2007–2013)

Objective:Guidelines for prevention of mother-to-child transmission of HIV have developed rapidly, yet little is known about how outcomes of HIV-exposed infants have changed over time. We describe HIV-exposed infant outcomes in Kinshasa, Democratic Republic of Congo, between 2007 and 2013. Design:Cohort study of mother–infant pairs enrolled in family-centered comprehensive HIV care. Methods:Accounting for competing risks, we estimated the cumulative incidences of early infant diagnosis, HIV transmission, death, loss to follow-up, and combination antiretroviral therapy (cART) initiation for infants enrolled in three periods (2007–2008, 2009–2010, and 2011–2012). Results:1707 HIV-exposed infants enrolled at a median age of 2.6 weeks. Among infants whose mothers had recently enrolled into HIV care (N = 1411), access to EID by age two months increased from 28% (95% confidence limits [CL]: 24,34%) among infants enrolled in 2007-2008 to 63% (95% CL: 59,68%) among infants enrolled in 2011–2012 (Grays p-value <0.01). The 18-month cumulative incidence of HIV declined from 16% (95% CL: 11,22%) for infants enrolled in 2007–2008 to 11% (95% CL: 8,16%) for infants enrolled in 2011–2012 (Grays p-value = 0.19). The 18-month cumulative incidence of death also declined, from 8% (95% CL: 5,12%) to 3% (95% CL: 2,5%) (Grays p-value = 0.02). LTFU did not improve, with 18-month cumulative incidences of 19% (95% CL: 15,23%) for infants enrolled in 2007-2008 and 22% (95% CL: 18,26%) for infants enrolled in 2011–2012 (Grays p-value = 0.06). Among HIV-infected infants, the 24-month cumulative incidence of cART increased from 61% (95% CL: 43,75%) to 97% (95% CL: 82,100%) (Grays p-value <0.01); the median age at cART decreased from 17.9 to 9.3 months. Outcomes were better for infants whose mothers enrolled before pregnancy. Conclusions:We observed encouraging improvements, but continued efforts are needed.

Income and markers of immunological cellular aging

Objective Socioeconomic disadvantage may contribute to poor health through immune-related biological mechanisms. We examined the associations between socioeconomic status, as measured by annual household income, and T-cell markers of aging, including the ratios of CD4 and CD8 effector cells to naïve cells (E/N ratio) and the CD4/CD8 T-cell ratio. We hypothesized that participants with a lower income would have higher E/N ratios and lower CD4/CD8 ratios compared with participants with a higher income, and that these associations would be partially mediated by elevated cytomegalovirus (CMV) IgG antibody levels, a virus implicated in aging and clonal expansion of T cells. Methods Data were from 79 individuals who participated in the population-based Detroit Neighborhood Health Study. We used linear regression to quantify the association between a

Implementation and Operational Research: Decentralization Does Not Assure Optimal Delivery of PMTCT and HIV-Exposed Infant Services in a Low Prevalence Setting.

10,000 decrease in income and each ratio outcome. Results After adjustment for age, sex, race, smoking, medication use, and lifetime history of mental health conditions, lower income was associated with a 0.41 (95% confidence interval = 0.09–0.72) log-unit increase in the CD4 E/N ratio and a 0.20 (95% confidence interval = 0.02–0.39) log-unit increase in the CD8 E/N ratio. CMV immunoglobulin G antibody level partially mediated these associations. Conclusions Our study suggests that low socioeconomic status is associated with immunological aging as measured by the E/N ratio and that impaired immune control of CMV may partially mediate these associations.

Does cytomegalovirus infection contribute to socioeconomic disparities in all-cause mortality?

Background:The consequences of decentralizing prevention of mother-to-child HIV transmission and HIV-exposed infant services to antenatal care (ANC)/labor and delivery (L&D) sites from dedicated HIV care and treatment (C&T) centers remain unknown, particularly in low prevalence settings. Methods:In a cohort of mother–infant pairs, we compared delivery of routine services at ANC/L&D and C&T facilities in Kinshasa, Democratic Republic of Congo from 2010–2013, using methods accounting for competing risks (eg, death). Women could opt to receive interventions at 90 decentralized ANC/L&D sites, or 2 affiliated C&T centers. Additionally, we assessed decentralizations population-level impacts by comparing proportions of women and infants receiving interventions before (2009–2010) and after (2011–2013) decentralization. Results:Among newly HIV-diagnosed women (N = 1482), the 14-week cumulative incidence of receiving the package of CD4 testing and zidovudine or antiretroviral therapy was less at ANC/L&D [66%; 95% confidence interval (CI): 63% to 69%] than at C&T (88%; 95% CI: 83% to 92%) sites (subdistribution hazard ratio, 0.62; 95% CI: 0.55 to 0.69). Delivery of cotrimoxazole and DNA polymerase chain reaction testing to HIV-exposed infants (N = 1182) was inferior at ANC/L&D sites (subdistribution hazard ratio, 0.84; 95% CI: 0.76 to 0.92); the 10-month cumulative incidence of the package at ANC/L&D sites was 89% (95% CI: 82% to 93%) versus 97% (95% CI: 93% to 99%) at C&T centers. Receipt of the pregnancy (20% of 1518, to 64% of 1405) and infant (16%–31%) packages improved post decentralization. Conclusions:Services were delivered less efficiently at ANC/L&D sites than C&T centers. Although access improved with decentralization, its potential cannot be realized without sufficient and sustained support.

The impact of pathogen burden on leukocyte telomere length in the Multi-Ethnic Study of Atherosclerosis

The social patterning of cytomegalovirus (CMV) and its implication in aging suggest that the virus may partially contribute to socioeconomic disparities in mortality. We used Cox regression and inverse odds ratio weighting to quantify the proportion of the association between socioeconomic status (SES) and all-cause mortality that was attributable to mediation by CMV seropositivity. Data were from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994), with mortality follow-up through December 2011. SES was assessed as household income (income-to-poverty ratio ≤1.30;>1.30 to≤1.85;>1.85 to≤3.50;>3.50) and education (high school). We found strong associations between low SES and increased mortality: hazard ratio (HR) 1.80; 95% confidence interval (CI): 1.57, 2.06 comparing the lowest versus highest income groups and HR 1.29; 95% CI: 1.13, 1.48 comparing high school education. 65% of individuals were CMV seropositive, accounting for 6-15% of the SES-mortality associations. Age modified the associations between SES, CMV, and mortality, with CMV more strongly associated with mortality in older individuals. Our findings suggest that cytomegalovirus may partially contribute to persistent socioeconomic disparities in mortality, particularly among older individuals.