Neuromuscular stimulation causes muscle phenotype-dependent changes in the expression of the IGFs and their binding proteins in developing slow and fast muscle of chick embryos.

Insulin-like growth factor (IGF) -1 and -2 and binding protein (IGFBP-2, -4, and -5) expression can be affected by several environmental factors, but the impact of movement on the IGF axis during late embryogenesis has yet to be fully characterized. Movement was promoted in chick embryos during mid-embryogenesis using 4-aminopyridine (4-AP). The results indicate an increase in IGF-1 (P < 0.01) and a decrease in IGFBP-2 (P < 0.05) mRNA expression in slow muscle of the stimulated group compared with the control group. In fast muscle, there was a decrease in IGF-2 (P < 0.01) on embryonic day (ED) 16 and an increase in IGFBP-2 (P < 0.01) and IGFBP-4 (P < 0.05) and in IGFBP-5 (P < 0.05) expression on ED18 in the stimulated group compared with the control group. These results indicate that neuromuscular stimulation with 4-AP influences IGF axis gene expression in a muscle fiber type-dependent manner. Consequences of the changes in the IGF system for each muscle are discussed.     

Prevalence of rotavirus antibodies in a non-human primate colony

A total of 51 monkeys maintained in a colony at the Institute of Primate Research (Kenya) and housed in doors with natural lighting in a group cage were used in this study. Monkeys belonging to 3 species were selected at random and blood samples collected. The serum samples were screened for presence of neutralizing antibodies (VTN) to rhesus rotavirus (RRV) by virus neutralization assay. Virus neutralization was determined by 60% reduction in fluorescent focus units (ffu). 96% of the animals screened had naturally occurring antibodies to rhesus rotavirus. Another group of 11 lactating monkeys (5 baboons, 6 vervets) and their infants were screened further for presence of IgG and IgA antibodies in serum and breast milk (mothers). Overall, the mothers had higher titres of both IgG and IgA than the infants. Taken together, these results demonstrate rotavirus infection is endemic in this primate colony. This mimics the human situation, hence, captive non human primates (such as the baboons) could be a suitable model for testing rotavirus candidate vaccines and for investigating the possible application in humans of passive-active immunization strategy.     

Linkage to and retention in care following healthcare transition from pediatric to adult HIV care

Outcomes following healthcare transition (HCT) from pediatric to adult HIV care are not well described. We sought to describe clinical outcomes following HCT within our institution among young adults with behavioral-acquired (N?=?31) and perinatally-acquired (N?=?19) HIV. We conducted a retrospective cohort study among HIV-infected adults who attempted transition from pediatric to adult HIV care within our institution. The primary end point was retention in care, defined as the completion of at least two visits over 12 months following linkage to adult care. Additional end points include time to linkage to adult care, and changes in CD4?+?T cell count and HIV RNA across time. Outcomes were compared between perinatal and behavioral HIV cohorts. Binary data were analyzed using the Fisher exact test and continuous data were analyzed using the Mann–Whitney test. Forty-three (86%) of 50 patients were successfully linked to adult care. The median time to linkage was 98 days. Fifty percent of patients achieved full retention in care at 12 months post-linkage. Though those with behavioral-acquired HIV attempted transfer at an older age, the groups did not differ in rates of linkage and retention in adult care. CD4?+?T cell counts and rates of viral suppression did not differ between pre- and post-HCT periods. Despite high rates of successful linkage to adult care in our study population, rates of retention in adult HIV care following HCT were low. These results imply that challenges remain in the adult HIV care setting toward improving the HCT process.     

Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya

Although the alpha+ thalassemias almost certainly confer protection against death from malaria, this has not been formally documented. We have conducted a study involving 655 case patients with rigorously defined severe malaria and 648 controls, frequency matched on area of residence and ethnic group. The prevalence of both heterozygous and homozygous alpha+ thalassemia was reduced in both case patients with severe malaria (adjusted odds ratios [ORs], 0.73 and 0.57; 95% confidence intervals [95% CIs], 0.57-0.94 and 0.40-0.81; P = .013 and P = .002, respectively, compared with controls) and among the subgroup of children who died after admission with severe malaria (OR, 0.60 and 0.37; 95% CI, 0.37-1.00 and 0.16-0.87; P = .05 and P = .02, respectively, compared with surviving case patients). The lowest ORs were seen for the forms of malaria associated with the highest mortality-coma and severe anemia complicated by deep, acidotic breathing. Our study supports the conclusion that both heterozygotes and homozygotes enjoy a selective advantage against death from Plasmodium falciparum malaria.     

The burden and consequences of inherited blood disorders among young children in western Kenya

Although inherited blood disorders are common among children in many parts of Africa, limited data are available about their prevalence or contribution to childhood anaemia. We conducted a cross‐sectional survey of 858 children aged 6–35 months who were randomly selected from 60 villages in western Kenya. Haemoglobin (Hb), ferritin, malaria, C‐reactive protein (CRP) and retinol binding protein (RBP) were measured from capillary blood. Using polymerase chain reaction (PCR), Hb type, ?3.7 kb alpha‐globin chain deletion, glucose‐6‐phosphate dehydrogenase (G6PD) genotype and haptoglobin (Hp) genotype were determined. More than 2 out of 3 children had at least one measured blood disorder. Sickle cell trait (HbAS) and disease (HbSS) were found in 17.1% and 1.6% of children, respectively; 38.5% were heterozygotes and 9.6% were homozygotes for α⁺‐thalassaemia. The Hp 2‐2 genotype was found in 20.4% of children, whereas 8.2% of males and 6.8% of children overall had G6PD deficiency. There were no significant differences in the distribution of malaria by the measured blood disorders, except among males with G6PD deficiency who had a lower prevalence of clinical malaria than males of normal G6PD genotype (P = 0.005). After excluding children with malaria parasitaemia, inflammation (CRP > 5 mg L^?1), iron deficiency (ferritin < 12 μg L^?1) or vitamin A deficiency (RBP < 0.7 μg L^?1), the prevalence of anaemia among those without α⁺‐thalassaemia (43.0%) remained significantly lower than that among children who were either heterozygotes (53.5%) or homozygotes (67.7%, P = 0.03). Inherited blood disorders are common among pre‐school children in western Kenya and are important contributors to anaemia.     

Measurements of immune responses for establishing correlates of vaccine protection against HIV

Well-defined correlates of protective immunity are an essential component of rational vaccine development. Despite years of basic science and three HIV vaccine efficacy trials, correlates of immunological protection from HIV infection remain undefined. In December 2010, a meeting of scientists engaged in basic and translational work toward developing HIV-1 vaccines was convened. The goal of this meeting was to discuss current opportunities and optimal approaches for defining correlates of protection, both for ongoing and future HIV-1 vaccine candidates; specific efforts were made to engage young scientists. We discuss here the highlights from the meeting regarding the progress made and the way forward for a protective HIV-1 vaccine.     

Infection of Chinese Rhesus Monkeys with a Subtype C SHIV Resulted in Attenuated In Vivo Viral Replication Despite Successful Animal-to-Animal Serial Passages

Rhesus macaques can be readily infected with chimeric simian-human immunodeficiency viruses (SHIV) as a suitable virus challenge system for testing the efficacy of HIV vaccines. Three Chinese-origin rhesus macaques (ChRM) were inoculated intravenously (IV) with SHIVC109P4 in a rapid serial in vivo passage. SHIV recovered from the peripheral blood of the final ChRM was used to generate a ChRM-adapted virus challenge stock. This stock was titrated for the intrarectal route (IR) in 8 ChRMs using undiluted, 1:10 or 1:100 dilutions, to determine a suitable dose for use in future vaccine efficacy testing via repeated low-dose IR challenges. All 11 ChRMs were successfully infected, reaching similar median peak viraemias at 1–2 weeks post inoculation but undetectable levels by 8 weeks post inoculation. T-cell responses were detected in all animals and Tier 1 neutralizing antibodies (Nab) developed in 10 of 11 infected ChRMs. All ChRMs remained healthy and maintained normal CD4⁺ T cell counts. Sequence analyses showed >98% amino acid identity between the original inoculum and virus recovered at peak viraemia indicating only minimal changes in the env gene. Thus, while replication is limited over time, our adapted SHIV can be used to test for protection of virus acquisition in ChRMs.