Improved identification and enrolment into care of HIV-exposed and -infected infants and children following a community health worker intervention in Lilongwe,Malawi

Background

Early identification and entry into care is critical to reducing morbidity and mortality in children with HIV. The objective of this report is to describe the impact of the Tingathe programme, which utilizes community health workers (CHWs) to improve identification and enrolment into care of HIV-exposed and -infected infants and children.

Methods

Three programme phases are described. During the first phase, Mentorship Only (MO) (March 2007–February 2008) on-site clinical mentorship on paediatric HIV care was provided. In the second phase, Tingathe-Basic (March 2008–February 2009), CHWs provided HIV testing and counselling to improve case finding of HIV-exposed and -infected children. In the final phase, Tingathe-PMTCT (prevention of mother-to-child transmission) (March 2009–February 2011), CHWs were also assigned to HIV-positive pregnant women to improve mother-infant retention in care. We reviewed routinely collected programme data from HIV testing registers, patient mastercards and clinic attendance registers from March 2005 to March 2011.

Results

During MO, 42 children (38 HIV-infected and 4 HIV-exposed) were active in care. During Tingathe-Basic, 238 HIV-infected children (HIC) were newly enrolled, a six-fold increase in rate of enrolment from 3.2 to 19.8 per month. The number of HIV-exposed infants (HEI) increased from 4 to 118. During Tingathe-PMTCT, 526 HIC were newly enrolled over 24 months, at a rate of 21.9 patients per month. There was also a seven-fold increase in the average number of exposed infants enrolled per month (9.5–70 patients per month), resulting in 1667 enrolled with a younger median age at enrolment (5.2 vs. 2.5 months; p<0.001).During the Tingathe-Basic and Tingathe-PMTCT periods, CHWs conducted 44,388 rapid HIV tests, 7658 (17.3%) in children aged 18 months to 15 years; 351 (4.6%) tested HIV-positive. Over this time, 1781 HEI were enrolled, with 102 (5.7%) found HIV-infected by positive PCR. Additional HIC entered care through various mechanisms (including positive linkage by CHWs and transfer-ins) such that by February 2011, a total of 866 HIC were receiving care, a 23-fold increase from 2008.

Conclusions

A multipronged approach utilizing CHWs to conduct HIV testing, link HIC into care and provide support to PMTCT mothers can dramatically improve the identification and enrolment into care of HIV-exposed and -infected children.     

Association of maternal and infant inflammation with neurodevelopment in HIV-exposed uninfected children in a South African birth cohort

HIV-exposed uninfected (HEU) children may have altered immune regulation and poorer neurodevelopment outcomes compared to their HIV-unexposed (HU) counterparts. However, studies investigating the association of maternal and infant inflammation with neurodevelopment in HEU children are limited and longitudinal data are lacking. This study investigated serum inflammatory markers in women living with HIV vs. HIV-uninfected women during pregnancy and in their children, as well as associations with neurodevelopmental outcomes at two years of age in an African birth cohort study. A sub-group of mother–child dyads from the Drakenstein Child Health Study had serum inflammatory markers measured at ≈26 week’s gestation (n = 77 HIV-infected mothers; n = 190 HIV-uninfected mothers), at 6–10 weeks (n = 63 HEU infants and n = 159 HU infants) and at 24–28 months (n = 77 HEU children and n = 190 HU children). Serum inflammatory markers [granulocyte–macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), interleukin IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor-α (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL) and metalloproteinase-9 (MMP-9)] were analyzed with a multiplex bead array and ELISA assays. The Bayley Scales of Infant and Toddler Development, third edition, was used to assess neurodevelopment at 24–28 months. After correcting for multiple comparisons, HIV infection during pregnancy was associated with lower serum levels of inflammatory markers in mothers at 26 weeks gestation (GM-CSF and MMP-9, p < 0.05) and HEU children at 6–10 weeks (IFN-γ and IL-1β, p < 0.01), and at 24–28 months (IFN-γ, IL-1β, IL-2 and IL-4, p < 0.05) compared to HIV-uninfected mothers and HU children. In HEU infants at 6–10 weeks, inflammatory markers (GM-CSF, IFN-γ, IL-10, IL-12p70, IL-1β, IL-2, IL-4, IL-6 and NGAL, all p < 0.05) were associated with poorer motor function at two years of age. This is the first study to evaluate the associations of follow-up immune markers in HEU children with neurodevelopment. These findings suggest that maternal HIV infection is associated with immune dysregulation in mothers and their children through two years of age. An altered immune system in HEU infants is associated with poorer follow-up motor neurodevelopment. These data highlight the important role of the immune system in early neurodevelopment and provide a foundation for future research.     

Evaluation and treatment of the human immunodeficiency virus-1-exposed infant

In developed countries, care and treatment are available for pregnant women and infants that can decrease the rate of perinatal human immunodeficiency virus type 1 (HIV-1) infection to 2% or less. The paediatrician has a key role in the prevention of mother-to-child transmission of HIV-1 by identifying HIV-exposed infants whose mothers’ HIV infection was not diagnosed before delivery, prescribing antiretroviral prophylaxis for these infants to decrease the risk of acquiring HIV-1 infection, and promoting avoidance of HIV-1 transmission through human milk. In addition, the paediatrician can provide care for HIV-exposed infants by monitoring them for early determination of HIV-1 infection status and for possible short- and long-term toxicities of antiretroviral exposure, providing chemoprophylaxis for Pneumocystis pneumonia, and supporting families living with HIV-1 infection by providing counselling to parents or caregivers.     

Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses in HIV-2-infected and in HIV-2-exposed but uninfected individuals in Guinea-Bissau

Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses were determined in cultures of peripheral blood mononuclear cells from HIV-2-exposed uninfected individuals, HIV-2-infected individuals and HIV-negative controls in Guinea-Bissau. Increased HIV-2-specific T lymphocyte proliferative responses were detected in both groups compared to HIV-negative controls (healthy HIV-uninfected individuals without known exposure to an HIV-infected person); five out of 29 of the HIV-2-exposed uninfected and half (16 of 32) of the HIV-2-infected individuals had stimulation indexes >2, compared to one out of 49 of the HIV-negative controls (P = 0.003 and P < 0.0001, respectively). The exposed uninfected individuals had reactivity to a HIV-2 V3-peptide corresponding to amino acids 311-326 of the envelope glycoprotein, while the HIV-2-infected people reacted mainly to HIV-2 whole viral lysate. Thus, this study demonstrates a high degree of HIV-2-specific T helper cell activity, as measured by lymphocyte proliferation, in HIV-2-exposed uninfected individuals as well as in HIV-2-infected subjects. These immune responses could be important for resistance to the infection and for the control of established infection and, thus, play a role in the lower transmission and progression of HIV-2 compared to HIV-1.     

HIV暴露婴儿预防接种免疫效果报告

目的为评估经HIV母婴阻断措施后该类婴儿群对卡介苗、乙肝疫苗的免疫反应能力,为相关部门制定此类婴儿的预防接种政策提供依据。方法为HIV感染孕妇提供综合性母婴阻断措施,将其婴儿设为观察组,母亲HIV阴性婴儿为对照组。对2组婴儿按常规进行预防接种,在接种卡介苗3～6个月后作结核菌素（PPD）试验、乙肝疫苗7～10个月后作乙肝抗体（抗-HBs）水平检测。结果 HIV感染孕妇经孕期规范抗病毒治疗后母婴阻断效果明显,其婴儿感染率远低于未治疗者。2组婴儿的PPD阳性率及卡痕阳性率均达90%以上;抗-HBs水平,观察组为296.83±3.10mIU/mL,对照组为354.30±2.37mIU/mL。结论本组资料显示,HIV阳性孕妇经综合性HIV母婴阻断措施后其所娩婴儿对乙肝疫苗和卡介苗具有类似于普通婴儿的免疫反应能力。     

Kinetics of pneumococcal antibodies among HIV-exposed,uninfected infants in Botswana

BackgroundStreptococcus pneumoniae is a leading cause of severe infections among children. Despite vaccination, HIV-exposed, uninfected (HEU) children have a higher incidence of invasive pneumococcal disease than HIV-unexposed, uninfected (HUU) children. We sought to compare the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV-13) in HEU and HUU infants.MethodsWe conducted a prospective cohort study of 134 mother-infant dyads in Botswana. Infants received PCV-13 doses at 2, 3, and 4 months through routine clinical care. We measured IgG antibodies specific to vaccine serotypes in sera collected from infants at 0, 5, and 12 months of age. We calculated the proportion of infants with protective IgG levels (≥0.35 µg/mL) to specific pneumococcal serotypes.ResultsAt birth, fewer than half of infants had protective IgG levels to serotypes 1 (38%), 3 (46%), 4 (33%), 5 (23%), 6B (40%), 7F (44%), 9 V (44%), and 23F (46%). Compared to HUU infants (n = 97), HEU infants (n = 37) had lower antibody concentrations at birth to serotypes 5 (p = 0.046) and 19A (p = 0.008) after adjustment for maternal age and infant birth weight. More than 80% of HEU and HUU infants developed protective antibody levels to each of the 13 vaccine serotypes following PCV-13 vaccination. Median concentrations of antibodies to pneumococcal serotypes declined by 55–93% between 5 and 12 months of age, with fewer than half of infants having protective antibody levels to serotypes 1 (47%), 3 (28%), 9 V (44%), 18C (24%), and 23F (49%) at 12 months of age.ConclusionsBoth HEU and HUU infants developed protective antibody responses to PCV-13 administered in a 3 + 0 schedule. However, antibody concentrations to many pneumococcal serotypes waned substantially by 12 months of age, suggesting that a PCV-13 booster dose in the second year of life may be needed to maintain protective pneumococcal antibody levels in older infants and young children.     

Association of maternal HIV-1 severity with dental caries: an observational study of uninfected 5- to 7-yr-old children of HIV-1-infected mothers without severe immune suppression

Treatment programs to prevent perinatal and postnatal HIV-1 transmission have become available in sub-Saharan Africa, leading to an emerging population of HIV-1 exposed uninfected (HEU) children. Exposure to HIV-1 in utero and during breastfeeding may increase the risk of morbidity and mortality in HEU children. This study estimated the association of the severity of maternal HIV-1 infection as assessed by CD4 count and viral load at baseline (7 d postpartum), with  dmft count of their 5- to 7-yr-old HEU offspring. A follow-up study was conducted of HIV-1-infected mother–HEU children pairs (n = 164) from the Ugandan site of the ANRS 12341-PROMISE- PEP trial (ClinicalTrials.gov, number NCT00640263). HIV-1-infected mothers were interviewed and the HEU children were examined for caries using the World Health Organization's survey methods for field conditions and the dmft index. Directed acyclic graphs and negative binomial regression were used for analyses. The prevalence of 1 or more dmft was 48%. Negative binomial regression showed no association between the dmft count and maternal CD4 counts 7 d postpartum but a 10% lower dmft count with longer breastfeeding duration was found. Maternal CD4 count at birth was not associated with the dental caries experience in uninfected children born to women without severe immune suppression, while there appeared to be a protective effect of high viral load and breastfeeding duration.