P02-07. High Concentrations of Interleukin-15 and Low Concentrations of CCL5 in Breast Milk are Associated with Protection against Postnatal HIV Transmission

Background: Natural variations in IL-15 concentration have not been investigated for an association with an immune-protection against HIV. Given IL-15's central role in anti-HIV immunity, we hypothesized that higher concentrations of IL-15 in breast milk may protect against postnatal mother-to-child HIV transmission. Methods: In a case-control study nested within a clinical trial in Zambia, we compared IL-15 concentrations in breast milk of 22 HIV-infected women who transmitted HIV to their infants through breastfeeding with those of 72 who did not, as well as 18 HIV-uninfected women. Breast milk HIV RNA quantity, sodium, CXCL12, CCL5, and IL-8 concentrations were measured as well as maternal plasma HIV RNA concentrations and CD4 cell count. We used logistic regression modeling to adjust for potential confounders. Results: Higher concentrations of IL-15 in breast milk (adjusted odds ratio [AOR]: 0.01 per log10 pg/ml increase, 95% confidence interval [CI]: <0.001 to 0.3) were associated with protection against postnatal HIV transmission in univariate analysis and after adjusting for maternal CD4 cell counts, breast milk HIV RNA, CCL5, CXCL12, and IL-8 concentrations. Breast milk IL-15 concentration correlated with breast milk sodium, the other cytokines and HIV RNA concentration. It was inversely correlated with infant birth weight and tended to be higher in 1 week than in 1 month post-partum samples. Breast milk CCL5 concentrations were associated with increased risk of HIV transmission (AOR: 12.7 95% CI: 1.6 to 102.0) in adjusted analysis. Breast milk CXCL12 and IL-8 concentrations were not independently associated with transmission. Conclusion: High concentration of IL-15 were associated with a protection against breastfeeding HIV transmission after adjusting for other pro-inflammatory cytokines, HIV RNA in breast milk, and maternal CD4 cell count. These results corroborate a protective role of IL-15-mediated cellular immunity against HIV transmission during breastfeeding. They are informative for vaccination studies using IL-15 as an adjuvant

Integration of Services for Victims of Child Sexual Abuse at the University Teaching Hospital One-Stop Centre

Objective. To improve care of sexually abused children by establishment of a "One Stop Centre" at the University Teaching Hospital. Methodology. Prior to opening of the One Stop Centre, a management team comprising of clinical departmental heads and a technical group of professionals (health workers, police, psychosocial counselors lawyers and media) were put in place. The team evaluated and identified gaps and weaknesses on the management of sexually abused children prevailing in Zambia. A manual was produced which would be used to train all professionals manning a One Stop Centre. A team of consultants from abroad were identified to offer need based training activities and a database was developed. Results. A multidisciplinary team comprising of health workers, police and psychosocial counselors now man the centre. The centre is assisted by lawyers as and when required. UTH is offering training to other areas of the country to establish similar services by using a Trainer of Trainers model. A comprehensive database has been established for Lusaka province. Conclusion. For establishment of a One Stop Centre, there needs to be a core group comprising of managers as well as a technical team committed to the management and protection of sexually abused children.Centre for Disease Control and Prevention Zambia; Zambia Society for the Prevention of Child Abuse and Neglect; Zambia Victim Support Unit; UNICEF Zambi

Effect of using HIV and infant feeding counselling cards on the quality of counselling provided to HIV positive mothers: a cluster randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Counselling human immunodeficiency virus (HIV) positive mothers on safer infant and young child feeding (IYCF) options is an important component of programmes to prevent mother to child transmission of HIV, but the quality of counselling is often inadequate. The aim of this study was to determine the effect the World Health Organization HIV and infant feeding cards on the quality of counselling provided to HIV positive mothers by health workers about safer infant feeding options.</p> <p>Method</p> <p>This was a un-blinded cluster-randomized controlled field trial in which 36 primary health facilities in Kafue and Lusaka districts in Zambia were randomized to intervention (IYCF counselling with counselling cards) or non- intervention arm (IYCF counselling without counselling cards). Counselling sessions with 10 HIV positive women attending each facility were observed and exit interviews were conducted by research assistants.</p> <p>Results</p> <p>Totals of 180 women in the intervention group and 180 women in the control group were attended to by health care providers and interviewed upon exiting the health facility. The health care providers in the intervention facilities more often discussed the advantages of disclosing their HIV status to a household member (RR = 1.46, 95% CI [1.11, 1.92]); used visual aids in explaining the risk of HIV transmission through breast milk (RR = 4.65, 95% CI [2.28, 9.46]); and discussed the advantages and disadvantages of infant feeding options for HIV positive mothers (all p values < 0.05). The differences also included exploration of the home situation (p < 0.05); involving the partner in the process of choosing a feeding option (RR = 1.38, 95% CI [1.09, 1.75]); and exploring how the mother will manage to feed the baby when she is at work (RR = 2.82, 95% CI [1.70, 4.67]). The clients in the intervention group felt that the provider was more caring and understanding (RR = 1.81, 95% CI [1.19, 2.75]).</p> <p>Conclusion</p> <p>The addition of counselling cards to the IYCF counselling session for HIV positive mothers were a valuable aid to counselling and significantly improved the quality of the counselling session.</p

Prevalence of clinical, immunological and irological failure among children on Haart at the university teaching hospital, Lusaka, Zambia

Background: There is increasing evidence that the current clinical and immunological monitoring tools are not sufficient to identify early enough patients who are failing on treatment. Development of resistance to the limited treatment options for children and premature switching are the dangers. The objective of this study was to review patient records to see how well WHO staging, CD4 profiles and viral load estimations relate in children on treatment at the University Teaching Hospital (UTH).Methods: A retrospective chart review of all children aged between 0-19 years that started treatment between January 2004 and Dec 2010 was carried out at the UTH. Systematic sampling was done of every second child who received HAART for more than 24 weeks, with at least one viral load (VL) reading beyond 24 weeks of treatment. Six-monthly clinical (WHO staging) immunological (age- related CD4 count/%) and virological data were collected until last follow-up review or five years on treatment. The 2010 Zambian Pediatric Guidelines were used to gauge age-related clinical, immunological and virological failure (VL&gt; 1,000).Results: A total of 517 patient records were reviewed (table 1). Mean age at ART initiation was 7 years ((SD 4.7yrs). Mean time after ART initiation when first viral load test was done was 2.7 years (SD 1.5yrs). Of all the viral loads done, 64% (328) had a routine indication for patients on treatment nearing the 3 year mark (mean 2.7 years). In 40% of children the first viral load test result was above 1,000 after 24 weeks or more of treatment. A total of 482 patients had WHO staging done at the time first VL test was done. Of the 359 patients (table 2) with a clinical stage I/II (not severely immunosuppressed), 41% were failing virologically. On the other hand, 63% of the patients with clinical stage III/IV had a VL below 1,000. Table 3 shows that there were 509 patients who had an immunological staging done at the time first VL was done. Of the 106 patients who were failing immunologically, 28% were virologically well suppressed. On the other hand of the 403 who were immunologically doing fine, 32% were failing virologically.Conclusions: Clinical staging and Immunological monitoring in children on ART does not accurately identify those that are failing. A push for routine, affordable virological testing is needed to identify treatment failures early to prevent development of ART resistance and to avoid premature switches to second line in those who are actually well suppressed

Early Childhood Infection of Kaposi’s Sarcoma-associated Herpesvirus in Zambian Households: a Molecular Analysis

Sub-Saharan Africa is endemic for Kaposi’s sarcoma-associated herpesvirus (KSHV) and there is a high rate of early childhood infection; however, the transmission sources are not well characterized. We examined household members as potential KSHV transmission sources to young children in the KSHV-endemic country of Zambia. To this end, we enrolled and followed Zambian households with at least one KSHV-seropositive child and collected longitudinal buccal swab samples. KSHV burden was evaluated and K1 sequences from the children were determined and analyzed for differences to K1 sequences from household members. The K1 sequences were also analyzed for evolution over time. We generated K1 sequences from 31 individuals across 16 households. Nine households contained multiple KSHV-positive members, including at least one child. In 6 of 9 households, the child had 100% sequence identity to all household members. However, in two households the child and mother had distinct K1 sequences. In the remaining household, the children were the only KSHV-infected individuals. Furthermore, we report that 1 of 18 individuals had K1 sequence variation within the timespan analyzed. In the present study, we provide evidence that (1) early childhood KSHV transmission occurs from both within and outside the household, (2) intra-household transmission can occur via non-maternal sources, (3) viral shedding in the buccal cavity is highly variable, and (4) the dominant K1 sequence within an individual did not rapidly evolve over time. These results are important for developing KSHV intervention strategies

Seroprevalence of Human Herpesvirus 8 among Zambian Women of Childbearing Age without Kaposi’s Sarcoma (KS) and Mother-Child Pairs with KS

The seroprevalence of human herpesvirus 8 (HHV-8) among a group of Zambian women of reproductive age and among mother-child pairs in which either one of them has Kaposi’s sarcoma (KS) was determined. A cross-sectional group of 378 pregnant women was randomly recruited into the study, and 183 (48.4%) had HHV-8 antibodies. Among the human immunodeficiency virus (HIV)-1–infected women, 51.1% were HHV-8–seropositive, whereas of HIV- 1–negative women, 47.3% were HHV-8–seropositive. In addition, 21 women index patients with KS and 5 young children index patients with KS were studied. All children with KS had mothers who were HHV-8–seropositive, while not all children whose mothers had KS were infected with HHV-8. Our study suggests that there is a high HHV-8 seroprevalence among Zambian women, and the rate is almost the same in HIV-1–positive and –negative women. This high seroprevalence may be a contributing factor toward the increased frequency of KS in this population

Genetic Variation in Mother-Child Acute Seroconverter Pairs from Zambia

Objective: To characterize the envelope (env) glycoprotein of HIV-1 in mother-infant pairs (MIP) that underwent near simultaneous or acute-phase seroconversion, we examined the env sequence of the transmitted viruses and compare viral evolution within the pair. Design: Three MIP from a Zambian cohort that seroconverted at the same sampling time were identified and followed longitudinally. Methods: The V1-V5 region of the HIV-1 env gene was sequenced for each sample collected. Phylogenetic and population genetics analyses were carried out to subtype the viruses, estimate relationships among viral genotypes, and compare molecular evolution between the viral populations. Results: Genetic analyses demonstrated a close intrapair relationship between viral sequences from each MIP. Transmission involved several closely related viral genotypes and did not result in a reduction in viral diversity. Amino acid changes were not evenly distributed along env V1-V5 but concentrated in concordant areas within each MIP. Several positions under positive selection were shared between the MIP viruses. Interestingly, selective pressure on the virus was higher in the infants than in the mothers. Conclusions: In contrast to most cases of perinatal transmission of HIV-1 from chronically infected mothers, there is no evidence of a genetic bottleneck in the transmitted viruses in these three instances of acute seroconversion. The longitudinal changes in the amino acids are in similar positions in env for the MIP, suggesting shared evolutionary constrains among the closely related viruses infecting the MIP; such constrains may lead to similar genetic changes in the virus in two different hosts

Cost of individual peer counselling for the promotion of exclusive breastfeeding in Uganda

<p>Abstract</p> <p>Background</p> <p>Exclusive breastfeeding (EBF) for 6 months is the recommended form of infant feeding. Support of mothers through individual peer counselling has been proved to be effective in increasing exclusive breastfeeding prevalence. We present a costing study of an individual peer support intervention in Uganda, whose objective was to raise exclusive breastfeeding rates at 3 months of age.</p> <p>Methods</p> <p>We costed the peer support intervention, which was offered to 406 breastfeeding mothers in Uganda. The average number of counselling visits was about 6 per woman. Annual financial and economic costs were collected in 2005-2008. Estimates were made of total project costs, average costs per mother counselled and average costs per peer counselling visit. Alternative intervention packages were explored in the sensitivity analysis. We also estimated the resources required to fund the scale up to district level, of a breastfeeding intervention programme within a public health sector model.</p> <p>Results</p> <p>Annual project costs were estimated to be US$56,308. The largest cost component was peer supporter supervision, which accounted for over 50$139 and the cost per visit was US$26. The cost per week of EBF was estimated to be US$15 at 12 weeks post partum. We estimated that implementing an alternative package modelled on routine public health sector programmes can potentially reduce costs by over 60%. Based on the calculated average costs and annual births, scaling up modelled costs to district level would cost the public sector an additional US$1,813,000.</p> <p>Conclusion</p> <p>Exclusive breastfeeding promotion in sub-Saharan Africa is feasible and can be implemented at a sustainable cost. The results of this study can be incorporated in cost effectiveness analyses of exclusive breastfeeding promotion programmes in sub-Saharan Africa.</p

Restriction of HIV-1 Genotypes in Breast Milk Does Not Account for the Population Transmission Genetic Bottleneck That Occurs following Transmission

BACKGROUND. Breast milk transmission of HIV-1 remains a major route of pediatric infection. Defining the characteristics of viral variants to which breastfeeding infants are exposed is important for understanding the genetic bottleneck that occurs in the majority of mother-to-child transmissions. The blood-milk epithelial barrier markedly restricts the quantity of HIV-1 in breast milk, even in the absence of antiretroviral drugs. The basis of this restriction and the genetic relationship between breast milk and blood variants are not well established. METHODOLOGY/PRINCIPAL FINDINGS. We compared 356 HIV-1 subtype C gp160 envelope (env) gene sequences from the plasma and breast milk of 13 breastfeeding women. A trend towards lower viral population diversity and divergence in breast milk was observed, potentially indicative of clonal expansion within the breast. No differences in potential N-linked glycosylation site numbers or in gp160 variable loop amino acid lengths were identified. Genetic compartmentalization was evident in only one out of six subjects in whom contemporaneously obtained samples were studied. However, in samples that were collected 10 or more days apart, six of seven subjects were classified as having compartmentalized viral populations, highlighting the necessity of contemporaneous sampling for genetic compartmentalization studies. We found evidence of CXCR4 co-receptor using viruses in breast milk and blood in nine out of the thirteen subjects, but no evidence of preferential localization of these variants in either tissue. CONCLUSIONS/SIGNIFICANCE. Despite marked restriction of HIV-1 quantities in milk, our data indicate intermixing of virus between blood and breast milk. Thus, we found no evidence that a restriction in viral genotype diversity in breast milk accounts for the genetic bottleneck observed following transmission. In addition, our results highlight the rapidity of HIV-1 env evolution and the importance of sample timing in analyses of gene flow.National Institute of Child Health and Human Development; National Institutes of Health (R01 HD 39611, R01 HD 40777); International Maternal Pediatric Adolescent AIDS Clinical Trials Group (U01 AI068632-01); National Institutes of Health Cellular, Biochemical; Molecular Sciences Training Program Grant (T 32 067587

The Mucosae-Associated Epithelial Chemokine (MEC/CCL28) Modulates Immunity in HIV Infection

BACKGROUND. CCL28 (MEC) binds to CCR3 and CCR10 and recruits IgA-secreting plasma cells (IgA-ASC) in the mucosal lamina propria (MLP). Mucosal HIV-specific IgA are detected in HIV-infection and exposure. The CCL28 circuit was analyzed in HIV-infected and-exposed individuals and in HIV-unexposed controls; the effect of CCL28 administration on gastrointestinal MLP IgA-ASC was verified in a mouse model. METHODOLOGY/FINDINGS. CCL28 was augmented in breast milk (BM) plasma and saliva of HIV-infected and –exposed individuals; CCR3+ and CCR10+ B lymphocytes were increased in these same individuals. Additionally: 1) CCL28 concentration in BM was associated with longer survival in HIV vertically-infected children; and 2) gastro-intestinal mucosal IgA-ASC were significantly increased in VSV-immunized mice receiving CCL28. CONCLUSIONS. CCL28 mediates mucosal immunity in HIV exposure and infection. CCL28-including constructs should be considered in mucosal vaccines to prevent HIV infection of the gastro-intestinal MLP via modulation of IgA-ASC.Istituto Superiore di Sanita' "Programma Nazionale di Ricerca sull' AIDS"; DG Right to Health and Solidarity Policy; EMPRO and AVIP EC WP6 Projects; Japan Health Science Foundation; National Institutes of Child Health and Human Development (HD 39611, HD 40777