Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques

Background: Mucosally transmissible and pathogenic CCR5 (R5)-tropic simian-human immunodeficiency virus (SHIV) molecular clones are useful reagents to identity neutralization escape in HIV-1 vaccine experiments and to study the envelope evolutionary process and mechanistic basis for coreceptor switch during the course of natural infection. Results: We observed progression to AIDS in rhesus macaques infected intrarectally with molecular clones of the pathogenic R5 SHIVSF162P3N isolate. Expansion to CXCR4 usage was documented in one diseased macaque that mounted a neutralizing antibody response and in another that failed to do so, with the latter displaying a rapid progressor phenotype. V3 loop envelop glycoprotein gp120 sequence changes that are predictive of a CXCR4 (X4)-using phenotype in HIV-1 subtype B primary isolates, specifically basic amino acid substations at positions 11 (S11R), 24 (G24R) and 25 (D25K) of the loop were detected in the two infected macaques. Functional assays showed that envelopes with V3 S11R or D25K mutation were dual-tropic, infecting CD4+ target cells that expressed either the CCR5 or CXCR4 coreceptor. And, consistent with findings of coreceptor switching in macaques infected with the pathogenic isolate, CXCR4-using variant was first detected in the lymph node of the chronically infected rhesus monkey several weeks prior to its presence in peripheral blood. Moreover, X4 emergence in this macaque coincided with persistent peripheral CD4+ T cell loss and a decline in neutralizing antibody titer that are suggestive of immune deterioration, with macrophages as the major virus-producing cells at the end-stage of disease. Conclusions: The data showed that molecular clones derived from the R5 SHIVSF162P3N isolate are mucosally transmissible and induced disease in a manner similar to that observed in HIV-1 infected individuals, providing a relevant and useful animal infection model for in-depth analyses of host selection pressures and the env evolutionary changes that influence disease outcome, coreceptor switching and vaccine escape

The South African Rea Phela Health Study : a randomized controlled trial of communication retention strategies

Epidemiological transitions are occurring throughout Africa. To inform public health programs and policies, longitudinal cohorts investigating non-communicable diseases are needed. However, loss-to-follow up is a major problem. In preparation for a longitudinal study, we conducted a randomized controlled trial to test communication-based retention strategies (message content and delivery methods) among a pilot cohort of South African healthcare workers (n = 1536; median age = 36; women = 1270). Two messaging formats across three delivery modes were tested. Response rates were analyzed by intervention, survey return date and method using chi-square tests and univariate logistic regression. Sixty-seven of 238 (17.4%) control group participants and 238 of 1152 (24.6%) intervention group participants were retained (OR 1.54: CI 1.15–2.07; P = 0.004). Odds of being retained were 1.68 times greater for participants who received regular contact and themed messages compared to control (CI 1.22–2.32; P = 0.001). Neither health status nor clinical condition affected response rates (P>0.05). Time-to-first contact did not impact response rates (P>0.05). Message content and delivery method influenced response rates compared to the control, however no difference was found between intervention groups. Although greater retention is required for valid cohort studies, these findings are the first to quantitatively assess retention factors in AfricaS1 Appendix. Follow-up questionnaire sample.S1 Table. Differences in health status between responders and non-responders.S2 Table. Differences in method of survey return between interventions.S3 Table. Differences in response by email provided and method of survey return.S4 Table. Differences in length of time to first contact between responders and non-responders.S5 Table. Differences in response within interventions associated with response to first Madmaker.The Foundation for Professional Development (JMR, AMM) and the University of Pretoria School of Health Systems and Public Health Research Committee (JMR).http://www.plosone.orgInternal MedicineSchool of Health Systems and Public Health (SHSPH

The South African Rea Phela Health Study: A randomized controlled trial of communication retention strategies.

Epidemiological transitions are occurring throughout Africa. To inform public health programs and policies, longitudinal cohorts investigating non-communicable diseases are needed. However, loss-to-follow up is a major problem. In preparation for a longitudinal study, we conducted a randomized controlled trial to test communication-based retention strategies (message content and delivery methods) among a pilot cohort of South African healthcare workers (n = 1536; median age = 36; women = 1270). Two messaging formats across three delivery modes were tested. Response rates were analyzed by intervention, survey return date and method using chi-square tests and univariate logistic regression. Sixty-seven of 238 (17.4%) control group participants and 238 of 1152 (24.6%) intervention group participants were retained (OR 1.54: CI 1.15-2.07; P = 0.004). Odds of being retained were 1.68 times greater for participants who received regular contact and themed messages compared to control (CI 1.22-2.32; P = 0.001). Neither health status nor clinical condition affected response rates (P>0.05). Time-to-first contact did not impact response rates (P>0.05). Message content and delivery method influenced response rates compared to the control, however no difference was found between intervention groups. Although greater retention is required for valid cohort studies, these findings are the first to quantitatively assess retention factors in Africa

Determinants of late antenatal care presentation in rural and peri-urban communities in South Africa: A cross-sectional study

<div><p>Objective</p><p>To investigate and compare determinates for delayed first presentation to antenatal care (ANC) services.</p><p>Methods</p><p>A cross-sectional study was conducted amongst pregnant women attending their first ANC visit in rural Capricorn District and peri-urban Tlokwe sub-district communities in South Africa. Data collection included questionnaires and medical record abstraction. Bivariate and multivariate analyses assessed factors associated with late ANC presentation.</p><p>Results</p><p>We recruited 807 pregnant women. Of these, 51% of rural women and 28% of peri-urban women presented late for first ANC. Rural women were more likely to present late for first ANC (AOR = 2.65; 95% CI 1.98–3.55) and report barriers to accessing ANC services (<i>P</i><0.0001). Late ANC presentation in rural communities was associated with being married (AOR = 2.36; 95% CI 1.33–4.19), employed (AOR = 1.90; 95% CI 1.03–3.50), <20 years of age (AOR = 2.19; 95% CI 1.10–4.37), and reporting an unplanned pregnancy (AOR = 2.21; 95% CI 1.40–3.50). Late presentation in peri-urban communities was associated with unplanned pregnancy (AOR = 1.67; 95% CI 1.01–2.74), being told to come back later to initiate ANC after presenting early (AOR 0.51; 95% CI 0.30–0.89) and being pregnant for the first time (AOR = 0.56; 95% CI 0.34–0.94)</p><p>Conclusion</p><p>Both rural and peri-urban women had high rates of late presentation for first ANC. However, women in the rural communities were more likely to present late. Unplanned pregnancy was an independent risk factor in both rural and peri-urban communities. Interventions around family planning, especially for adolescent girls and young women, are needed to improve early presentation for ANC.</p></div

Logistic regression analysis (with fixed effects) of determinants of late presentation in rural Capricorn District and peri-urban Tlokwe sub-district.

<p>Logistic regression analysis (with fixed effects) of determinants of late presentation in rural Capricorn District and peri-urban Tlokwe sub-district.</p

Socio-demographic, obstetric and health seeking characteristics of study participants.

<p>Socio-demographic, obstetric and health seeking characteristics of study participants.</p

ANC knowledge, attitudes and practices of study participants.

<p>ANC knowledge, attitudes and practices of study participants.</p

Difficulties with coming to the clinic for ANC and first ANC entry time (n = 227).

<p>Difficulties with coming to the clinic for ANC and first ANC entry time (n = 227).</p

Pooled logistic regression analysis (with fixed effects) of determinants of late presentation.

<p>Pooled logistic regression analysis (with fixed effects) of determinants of late presentation.</p

National map of South Africa with highlighted study locations.

<p>National map of South Africa with highlighted study locations.</p