LIGHT AND ELECTRON MICROSCOPIC STUDY OF SURFACES OF TEST-SPECIMENS TESTED IN WEAR APPARATUSES

Objective: Symptoms of acute retroviral syndrome (ARS) may be used to identify patients with acute HIV-1 infection who seek care. ARS symptoms in African adults differ by region. We assessed whether reporting of ARS was associated with HIV-1 subtype in a multicentre African cohort study representing countries with predominant HIV-1 subtypes A, C, and D. Methods: ARS symptoms were assessed in adults enrolling within 6 weeks after the estimated date of infection in an acute and early HIV-1 infection cohort study. HIV-1 subtype was determined by POL genotyping. We used log-binomial regression to compare ARS symptom prevalence among those with subtype A vs. C or D, adjusting for sex, time since enrolment, and enrolment viral load. Results: Among 183 volunteers ascertained within 6 weeks after estimated date of infection, 77 (42.0%) had subtype A, 83 (45.4%) subtype C, and 23 (12.6%) subtype D infection. Individuals with subtype A were 1.40 (95% confidence interval: 1.17, 1.68) times as likely as individuals with subtypes C or D to report any ARS symptoms; each individual symptom other than rash was also more prevalent in subtype A than in subtype C or D, with prevalence ratios ranging from 1.94 (1.40, 2.70) for headache to 4.92 (2.24, 10.78) for lymphadenopathy. Conclusion: Individuals with subtype A were significantly more likely than individuals with subtypes C or D to report any ARS symptoms. HIV-1 subtypes may help explain differences in ARS that have been observed across regions in Africa, and may impact the yield of symptom-based screening strategies for acute HIV infection detection

A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of Electroporated HIV DNA with or without Interleukin 12 in Prime-Boost Combinations with an Ad35 HIV Vaccine in Healthy HIV-Seronegative African Adults.

Strategies to enhance the immunogenicity of DNA vaccines in humans include i) co-administration of molecular adjuvants, ii) intramuscular administration followed by in vivo electroporation (IM/EP) and/or iii) boosting with a different vaccine. Combining these strategies provided protection of macaques challenged with SIV; this clinical trial was designed to mimic the vaccine regimen in the SIV study.Seventy five healthy, HIV-seronegative adults were enrolled into a phase 1, randomized, double-blind, placebo-controlled trial. Multi-antigenic HIV (HIVMAG) plasmid DNA (pDNA) vaccine alone or co-administered with pDNA encoding human Interleukin 12 (IL-12) (GENEVAX IL-12) given by IM/EP using the TriGrid Delivery System was tested in different prime-boost regimens with recombinant Ad35 HIV vaccine given IM.All local reactions but one were mild or moderate. Systemic reactions and unsolicited adverse events including laboratory abnormalities did not differ between vaccine and placebo recipients. No serious adverse events (SAEs) were reported. T cell and antibody response rates after HIVMAG (x3) prime-Ad35 (x1) boost were independent of IL-12, while the magnitude of interferon gamma (IFN-γ) ELISPOT responses was highest after HIVMAG (x3) without IL-12. The quality and phenotype of T cell responses shown by intracellular cytokine staining (ICS) were similar between groups. Inhibition of HIV replication by autologous T cells was demonstrated after HIVMAG (x3) prime and was boosted after Ad35. HIV specific antibodies were detected only after Ad35 boost, although there was a priming effect with 3 doses of HIVMAG with or without IL-12. No anti-IL-12 antibodies were detected.The vaccines were safe, well tolerated and moderately immunogenic. Repeated administration IM/EP was well accepted. An adjuvant effect of co-administered plasmid IL-12 was not detected.ClinicalTrials.gov NCT01496989

Baseline Morbidity in 2,990 Adult African Volunteers Recruited to Characterize Laboratory Reference Intervals for Future HIV Vaccine Clinical Trials

BACKGROUND: An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study. METHODS: Asymptomatic persons, aged 18-60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia). Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP). RESULTS AND CONCLUSIONS: Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis (52% men, 48% women). Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%), significant medical history (76, 13%) and inability to complete the informed consent process (73, 13%). Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38%) and antibodies against Hepatitis C (95, 34%). This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons

Ordinal-Level Phylogenomics of the Arthropod Class Diplopoda (Millipedes) Based on an Analysis of 221 Nuclear Protein-Coding Loci Generated Using Next-Generation Sequence Analyses

Background The ancient and diverse, yet understudied arthropod class Diplopoda, the millipedes, has a muddled taxonomic history. Despite having a cosmopolitan distribution and a number of unique and interesting characteristics, the group has received relatively little attention; interest in millipede systematics is low compared to taxa of comparable diversity. The existing classification of the group comprises 16 orders. Past attempts to reconstruct millipede phylogenies have suffered from a paucity of characters and included too few taxa to confidently resolve relationships and make formal nomenclatural changes. Herein, we reconstruct an ordinal-level phylogeny for the class Diplopoda using the largest character set ever assembled for the group. Methods Transcriptomic sequences were obtained from exemplar taxa representing much of the diversity of millipede orders using second-generation (i.e., next-generation or high-throughput) sequencing. These data were subject to rigorous orthology selection and phylogenetic dataset optimization and then used to reconstruct phylogenies employing Bayesian inference and maximum likelihood optimality criteria. Ancestral reconstructions of sperm transfer appendage development (gonopods), presence of lateral defense secretion pores (ozopores), and presence of spinnerets were considered. The timings of major millipede lineage divergence points were estimated. Results The resulting phylogeny differed from the existing classifications in a number of fundamental ways. Our phylogeny includes a grouping that has never been described (Juliformia+Merocheta+Stemmiulida), and the ancestral reconstructions suggest caution with respect to using spinnerets as a unifying characteristic for the Nematophora. Our results are shown to have significantly stronger support than previous hypotheses given our data. Our efforts represent the first step toward obtaining a well-supported and robust phylogeny of the Diplopoda that can be used to answer many questions concerning the evolution of this ancient and diverse animal group

Loneliness of Older Immigrant Groups in Canada: Effects of Ethnic-Cultural Background

This study aimed to explore the loneliness of several groups of older immigrants in Canadacompared to native-born older adults. Data from the Canadian General Social Survey, Cycle 22 (Nolder adults = 3,692) were used. The dependent variable is the 6 item De Jong Gierveld lonelinessscale. Determinants of loneliness included country of birth, ethnic background (cultural context);belongingness (community context) and social networks (social context). Results showed that onlysome immigrant groups are significantly lonelier than older adults born in Canada. Immigrants withsimilar language and culture are not lonelier; while those from countries that differ in nativelanguage/culture are significantly higher on loneliness. Multivariate analyses showed the importanceof cultural background, of composition of the network of relatives and friends, and of localparticipation and feelings of belonging to the Canadian society in explaining loneliness of olderimmigrants

Transfusion-transmitted infections

Although the risk of transfusion-transmitted infections today is lower than ever, the supply of safe blood products remains subject to contamination with known and yet to be identified human pathogens. Only continuous improvement and implementation of donor selection, sensitive screening tests and effective inactivation procedures can ensure the elimination, or at least reduction, of the risk of acquiring transfusion transmitted infections. In addition, ongoing education and up-to-date information regarding infectious agents that are potentially transmitted via blood components is necessary to promote the reporting of adverse events, an important component of transfusion transmitted disease surveillance. Thus, the collaboration of all parties involved in transfusion medicine, including national haemovigilance systems, is crucial for protecting a secure blood product supply from known and emerging blood-borne pathogens

Prediction of extended high viremia among newly HIV-1-infected persons in sub-Saharan Africa

Objective Prompt identification of newly HIV-infected persons, particularly those who are most at risk of extended high viremia (EHV), allows important clinical and transmission prevention benefits. We sought to determine whether EHV could be predicted during early HIV infection (EHI) from clinical, demographic, and laboratory indicators in a large HIV-1 incidence study in Africa. Design Adults acquiring HIV-1 infection were enrolled in an EHI study assessing acute retroviral syndrome (ARS) symptoms and viral dynamics. Methods Estimated date of infection (EDI) was based on a positive plasma viral load or p24 antigen test prior to seroconversion, or the mid-point between negative and positive serological tests. EHV was defined as mean untreated viral load ≥5 log10 copies/ml 130±330 days post-EDI. We used logistic regression to develop risk score algorithms for predicting EHV based on sex, age, number of ARS symptoms, and CD4 and viral load at diagnosis. Results Models based on the full set of five predictors had excellent performance both in the full population (c-statistic = 0.80) and when confined to persons with each of three HIV-1 subtypes (c-statistic = 0.80–0.83 within subtypes A, C, and D). Reduced models containing only 2–4 predictors performed similarly. In a risk score algorithm based on the final full-population model, predictor scores were one for male sex and enrollment CD4&lt;350 cells/mm3, and two for having enrollment viral load &gt;4.9 log10 copies/ml. With a risk score cut-point of two, this algorithm was 85% sensitive (95% CI: 76%-91%) and 61% specific (55%-68%) in predicting EHV. Conclusions Simple risk score algorithms can reliably identify persons with EHI in sub-Saharan Africa who are likely to sustain high viral loads if treatment is delayed. These algorithms may be useful for prioritizing intensified efforts around care linkage and retention, treatment initiation, adherence support, and partner services to optimize clinical and prevention outcomes.</p