Why do Nigerian manufacturing firms take action on AIDS?

Objective: To identify differences between manufacturing firms in Nigeria that have undertaken HIV/AIDS prevention activities and those that have not as a step toward improving the targeting of HIV policies and interventions. Methods: A survey of a representative sample of registered manufacturing firms in Nigeria, stratified by location, workforce size, and industrial sector. The survey was administered to managers of 232 firms representing most major industrial areas and sectors in March-April 2001. Results: 45.3 percent of the firms’ managers received information about HIV/AIDS from a source outside the firm in 2000; 7.7 percent knew of an employee who was HIV-positive at the time of the survey; and 13.6 percent knew of an employee who had left the firm and/or died in service due to AIDS. Only 31.7 percent of firms took any action to prevent HIV among employees in 2000, and 23.9 percent had discussed the epidemic as a potential business concern. The best correlates of having taken action on HIV were knowledge of an HIV-positive employee or having lost an employee to AIDS (odds ratio [OR] 6.36, 95% confidence interval [CI]: 2.30, 17.57) and receiving information about the disease from an outside source (OR 7.83, 95% CI: 3.46, 17.69). Conclusions: Despite a nationwide HIV seroprevalence of 5.8 percent, as of 2001 most Nigerian manufacturing firm managers did not regard HIV/AIDS as a serious problem and had neither taken any action on it nor discussed it as a business issue. Providing managers with accurate, relevant information about the epidemic and practical prevention interventions might strengthen the business response to AIDS in countries like Nigeria

Community Case Management of Fever Due to Malaria and Pneumonia in Children Under Five in Zambia: A Cluster Randomized Controlled Trial

In a cluster randomized trial, Kojo Yeboah-Antwi and colleagues find that integrated management of malaria and pneumonia in children under five by community health workers is both feasible and effective. BACKGROUND. Pneumonia and malaria, two of the leading causes of morbidity and mortality among children under five in Zambia, often have overlapping clinical manifestations. Zambia is piloting the use of artemether-lumefantrine (AL) by community health workers (CHWs) to treat uncomplicated malaria. Valid concerns about potential overuse of AL could be addressed by the use of malaria rapid diagnostics employed at the community level. Currently, CHWs in Zambia evaluate and treat children with suspected malaria in rural areas, but they refer children with suspected pneumonia to the nearest health facility. This study was designed to assess the effectiveness and feasibility of using CHWs to manage nonsevere pneumonia and uncomplicated malaria with the aid of rapid diagnostic tests (RDTs). METHODS AND FINDINGS. Community health posts staffed by CHWs were matched and randomly allocated to intervention and control arms. Children between the ages of 6 months and 5 years were managed according to the study protocol, as follows. Intervention CHWs performed RDTs, treated test-positive children with AL, and treated those with nonsevere pneumonia (increased respiratory rate) with amoxicillin. Control CHWs did not perform RDTs, treated all febrile children with AL, and referred those with signs of pneumonia to the health facility, as per Ministry of Health policy. The primary outcomes were the use of AL in children with fever and early and appropriate treatment with antibiotics for nonsevere pneumonia. A total of 3,125 children with fever and/or difficult/fast breathing were managed over a 12-month period. In the intervention arm, 27.5% (265/963) of children with fever received AL compared to 99.1% (2066/2084) of control children (risk ratio 0.23, 95% confidence interval 0.14–0.38). For children classified with nonsevere pneumonia, 68.2% (247/362) in the intervention arm and 13.3% (22/203) in the control arm received early and appropriate treatment (risk ratio 5.32, 95% confidence interval 2.19–8.94). There were two deaths in the intervention and one in the control arm. CONCLUSIONS. The potential for CHWs to use RDTs, AL, and amoxicillin to manage both malaria and pneumonia at the community level is promising and might reduce overuse of AL, as well as provide early and appropriate treatment to children with nonsevere pneumonia.United States Agency for International Development (GHSA-00-00020-00) with Boston University; President's Malaria Initiativ

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

Differential Effects of Early Weaning for HIV-Free Survival of Children Born to HIV-Infected Mothers by Severity of Maternal Disease

BACKGROUND. We previously reported no benefit of early weaning for HIV-free survival of children born to HIV-infected mothers in intent-to-treat analyses. Since early weaning was poorly accepted, we conducted a secondary analysis to investigate whether beneficial effects may have been hidden. METHODS. 958 HIV-infected women in Lusaka, Zambia, were randomized to abrupt weaning at 4 months (intervention) or to continued breastfeeding (control). Children were followed to 24 months with regular HIV PCR tests and examinations to determine HIV infection or death. Detailed behavioral data were collected on when all breastfeeding ended. Most participants were recruited before antiretroviral treatment (ART) became available. We compared outcomes among mother-child pairs who weaned earlier or later than intended by study design adjusting for potential confounders. RESULTS. Of infants alive, uninfected and still breastfeeding at 4 months in the intervention group, 16.1% who weaned as instructed acquired HIV or died by 24 months compared to 16.0% who did not comply (p=0.98). Children of women with less severe disease during pregnancy (not eligible for ART) had worse outcomes if their mothers weaned as instructed (RH=2.60 95% CI: 1.06-6.36) compared to those who continued breastfeeding. Conversely, children of mothers with more severe disease (eligible for ART but did not receive it) who weaned early had better outcomes (p-value interaction=0.002). In the control group, weaning before 15 months was associated with 3.94-fold (95% CI: 1.65-9.39) increase in HIV infection or death among infants of mothers with less severe disease. CONCLUSION. Incomplete adherence did not mask a benefit of early weaning. On the contrary, for women with less severe disease, early weaning was harmful and continued breastfeeding resulted in better outcomes. For women with more advanced disease, ART should be given during pregnancy for maternal health and to reduce transmission, including through breastfeeding. TRIAL REGISTRATION. Clinical trials.gov NCT00310726National Institute of Child Health and Human Development (NICHD); National Institutes of Health (R01 HD 39611, R01 HD 40777

Breast milk and in utero transmission of HIV-1 select for envelope variants with unique molecular signatures

Additional file 5: Figure S5. Representative CD4 infectivity curves using Affinofile cells for IUT (top) and BMT (bottom) maternal–infant pairs. Affinofile cells were induced to generate a 100-fold range of CD4 surface density (ABS/cell) and infected with 2000 IU pseudotyped virus. Percent infection was measured as the percent luciferase relative to infected and maximally induced Affinofile cells. Data shown are representative curves among 3–4 experimental replicates

Hubble Space Telescope and Ground-Based Observations of the Type Iax Supernovae SN 2005hk and SN 2008A

We present Hubble Space Telescope (HST) and ground-based optical and near-infrared observations of SN 2005hk and SN 2008A, typical members of the Type Iax class of supernovae (SNe). Here we focus on late-time observations, where these objects deviate most dramatically from all other SN types. Instead of the dominant nebular emission lines that are observed in other SNe at late phases, spectra of SNe 2005hk and 2008A show lines of Fe II, Ca II, and Fe I more than a year past maximum light, along with narrow [Fe II] and [Ca II] emission. We use spectral features to constrain the temperature and density of the ejecta, and find high densities at late times, with n_e >~ 10^9 cm^-3. Such high densities should yield enhanced cooling of the ejecta, making these objects good candidates to observe the expected "infrared catastrophe," a generic feature of SN Ia models. However, our HST photometry of SN 2008A does not match the predictions of an infrared catastrophe. Moreover, our HST observations rule out a "complete deflagration" that fully disrupts the white dwarf for these peculiar SNe, showing no evidence for unburned material at late times. Deflagration explosion models that leave behind a bound remnant can match some of the observed properties of SNe Iax, but no published model is consistent with all of our observations of SNe 2005hk and 2008A.Comment: 20 pages, 15 figure

4E10-Resistant HIV-1 Isolated from Four Subjects with Rare Membrane-Proximal External Region Polymorphisms

Human antibody 4E10 targets the highly conserved membrane-proximal external region (MPER) of the HIV-1 transmembrane glycoprotein, gp41, and has extraordinarily broad neutralizing activity. It is considered by many to be a prototype for vaccine development. In this study, we describe four subjects infected with viruses carrying rare MPER polymorphisms associated with resistance to 4E10 neutralization. In one case resistant virus carrying a W680G substitution was transmitted from mother to infant. We used site-directed mutagenesis to demonstrate that the W680G substitution is necessary for conferring the 4E10-resistant phenotype, but that it is not sufficient to transfer the phenotype to a 4E10-sensitive Env. Our third subject carried Envs with a W680R substitution causing variable resistance to 4E10, indicating that residues outside the MPER are required to confer the phenotype. A fourth subject possessed a F673L substitution previously associated with 4E10 resistance. For all three subjects with W680 polymorphisms, we observed additional residues in the MPER that co-varied with position 680 and preserved charged distributions across this region. Our data provide important caveats for vaccine development targeting the MPER. Naturally occurring Env variants described in our study also represent unique tools for probing the structure-function of HIV-1 envelope

Eff ectiveness of 4% chlorhexidine umbilical cord care on neonatal mortality in Southern Province, Zambia (ZamCAT): a cluster-randomised controlled trial

Background Chlorhexidine umbilical cord washes reduce neonatal mortality in south Asian populations with high neonatal mortality rates and predominantly home-based deliveries. No data exist for sub-Saharan African populations with lower neonatal mortality rates or mostly facility-based deliveries. We compared the eff ect of chlorhexidine with dry cord care on neonatal mortality rates in Zambia. Methods We undertook a cluster-randomised controlled trial in Southern Province, Zambia, with 90 health facilitybased clusters. We enrolled women who were in their second or third trimester of pregnancy, aged at least 15 years, and who would remain in the catchment area for follow-up of 28 days post-partum. Newborn babies received clean dry cord care (control) or topical application of 10 mL of a 4% chlorhexidine solution once per day until 3 days after cord drop (intervention), according to cluster assignment. We used stratifi ed, restricted randomisation to divide clusters into urban or two rural groups (located <40 km or ≥40 km to referral facility), and randomly assigned clusters (1:1) to use intervention (n=45) or control treatment (n=45). Sites, participants, and fi eld monitors were aware of their study assignment. The primary outcomes were all-cause neonatal mortality within 28 days post-partum and all-cause neonatal mortality within 28 days post-partum among babies who survived the fi rst 24 h of life. Analysis was by intention to treat. Neonatal mortality rate was compared with generalised estimating equations. This study is registered at ClinicalTrials.gov (NCT01241318). Findings From Feb 15, 2011, to Jan 30, 2013, we screened 42 356 pregnant women and enrolled 39 679 women (mean 436·2 per cluster [SD 65·3]), who had 37 856 livebirths and 723 stillbirths; 63·8% of deliveries were facility-based. Of livebirths, 18 450 (99·7%) newborn babies in the chlorhexidine group and 19 308 (99·8%) newborn babies in the dry cord care group were followed up to day 28 or death. 16 660 (90·0%) infants in the chlorhexidine group had chlorhexidine applied within 24 h of birth. We found no signifi cant diff erence in neonatal mortality rate between the chlorhexidine group (15·2 deaths per 1000 livebirths) and the dry cord care group (13·6 deaths per 1000 livebirths; risk ratio [RR] 1·12, 95% CI 0·88–1·44). Eliminating day 0 deaths yielded similar fi ndings (RR 1·12, 95% CI 0·86–1·47). Interpretation Despite substantial reductions previously reported in south Asia, chlorhexidine cord applications did not signifi cantly reduce neonatal mortality rates in Zambia. Chlorhexidine cord applications do not seem to provide clear benefi ts for newborn babies in settings with predominantly facility-based deliveries and lower (<30 deaths per 1000 livebirths) neonatal mortality rates