The Quest for an AIDS Vaccine

More than fifty thousand cases of AIDS have been reported in the United States since the disease wasfirst described in 1981. Many times this number of people are infected with human immunodeficiency virus (HIV), which has been identified as the agent responsible for the illness. The seriousness of the disease, coupled with the relatively rapid spread of HIV, has fueled the effort for development of an effective vaccine. Much is now known about the life cycle of the virus, and about its structural components. This information, and information about methods of transmission of the virus, form the basis for a rational vaccine development program. A successful program depends both on technological advances and on the political will to create a climate in which interpretable vaccine trials can be undertaken. This review will focus on some of the impediments to rapid development and licensure of an AIDS vaccine

The Evolution of Mentorship Capacity Development in Low- and Middle-Income Countries: Case Studies from Peru, Kenya, India, and Mozambique.

Following the Fogarty International Center-supported "Mentoring the Mentors" workshops in South America, Africa, and Asia, approaches and guidelines for mentorship at institutions within these low- and middle-income country (LMIC) contexts, appropriate for the respective regional resources and culture, were implemented. Through the presentation of case studies from these three geographic regions, this article illustrates the institutional mentorship infrastructure before the workshop and the identified gaps used to implement strategies to build mentorship capacity at the Universidad Peruana Cayetano Heredia (Peru), Kenya Medical Research Institute (Kenya), Saint John's Research Institute (India), and Eduardo Mondlane University (Mozambique). These case studies illustrate three findings: first, that mentorship programs in LMICs have made uneven progress, and institutions with existing programs have exhibited greater advancement to their mentoring capacity than institutions without formal programs before the workshops. Second, mentoring needs assessments help garner the support of institutional leadership and create local ownership. Third, developing a culture of mentorship that includes group mentoring activities at LMIC institutions can help overcome the shortage of trained mentors. Regardless of the stage of mentoring programs, LMIC institutions can work toward developing sustainable, culturally effective mentorship models that further the partnership of early career scientists and global health

Predictors of Acute Liver Failure in Patients With Acute Hepatitis A: An Analysis of the 2016-2018 San Diego County Hepatitis A Outbreak.

Background:Between 2016 and 2018, San Diego County experienced a hepatitis A outbreak with a historically high mortality rate (3.4%) that highlighted the need for early recognition of those at risk of developing acute liver failure (ALF). Methods:A retrospective case series of adult hospitalized patients with acute hepatitis A. Results:One hundred six patients with hepatitis A were studied, of whom 11 (10.4%) developed ALF, of whom 7 (6.6%) died. A history of alcohol abuse, hyperbilirubinemia, hypoalbuminemia, hyponatremia, and anemia were associated with increased odds of developing ALF. Initial Maddrey's and Model of End-Stage Liver Disease Sodium (MELD-Na) scores were also associated with the development of ALF. Multivariable analysis showed that a higher initial MELD-Na score (odds ratio [OR], 1.205; 95% confidence interval [CI], 1.018-1.427) and a lower initial serum albumin concentration (OR, 9.35; 95% CI, 1.15-76.9) were associated with increased odds of developing ALF. Combining serum albumin and MELD-Na (SAM; C-statistic, 0.8878; 95% CI, 0.756-0.988) yielded a model that was not better than either serum albumin (C-statistic, 0.852; 95% CI, 0.675-0.976) or MELD-Na (C-statistic, 0.891; 95% CI, 0.784-0.968; P = .841). Finally, positive blood cultures were more common among patients with ALF compared with those without ALF (63.6% vs 4.3%; P < .00001). Conclusions:Hypoalbuminemia was associated with an increased risk of ALF in patients with acute hepatitis A. Positive blood cultures and septic shock as a cause of death were common among patients with ALF. Providers caring for patients with acute hepatitis A should monitor for early signs of sepsis and consider empiric antibiotics, especially in patients presenting with hypoalbuminemia

Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique

Introduction: Leptospirosis is a neglected zoonotic disease caused by a bacteria of the genus Leptospira. In Africa, it is frequently mistaken for frequently occurring conditions such as malaria. The aim of this study was to identify rodent species involved in the transmission of the disease, the prevalence of pathogenic Leptospira spp. in selected rodent species and risk factors for human leptospirosis. Material and Methods: We conducted a descriptive and exploratory epidemiological and molecular study in Mozambique Island city in 2015. Six neighborhoods, comprising 30 households each were randomly selected. People from the selected 180 households were interviewed regarding their awareness of the disease, the presence of rodents in their houses, chemicals used to eliminate them, sewage disposal, water supply system, and other key issues related to the disease. In each neighborhood, we trapped 10 rodents for a morphometric study to identify their species and for molecular isolation of Leptospira DNA. We extracted kidneys from 57/60 of rodents trapped and performed nested polymerase chain reaction targeting rrs 16S ribosomal RNA and lipL32 genes for identification of Leptospira genus and pathogenic Leptospira spp. respectively. Results: Of the 180 participants 92 (51%) reported having heard of leptospirosis;107 (59%) have had the disease; 151 (83%) reported the existence of rats in their house; 100 (56%) had latrines; 118 (66%) used chemicals to kill the rats; 102 (57%) used well water and 114 (63%) used trash containers. The most prevalent rodent species captured was Rattus norvegicus 36/60 (60%), followed by Rattus rattus 19/60 (31.67%) and Mus musculus 3/60 (5%). Sequences of rrs 16S rRNA gene were identified rrs 16S ribosomal DNA RNA was identified in 20/57 (35.%) rodents. Out these two were positive for lipL32 gene, giving an overall pathogenic Leptospira infection of 3.5% (2/57). The rodent species identified as carriers of pathogenic Leptospira were Rattus norvegicus (1) and R. rattus (1). Conclusion: This is the first study in Mozambique to identify the presence of pathogenic species of Leptospira using molecular tools. Leptospirosis risk factors in Mozambique Island city are rodent’s infestation, limited disease awareness, lack of access to clean water, insufficient resources for waste collection, greater clustering of households, poor sanitation environment and degradation of living conditions. Pathogenic Leptospira spp. are present in the area studied and at least two species of rodents, the R. rattus and R. norvegicus are potentially involved in the transmission of the causal agents of the disease.publishersversionpublishe

The Virome of Cerebrospinal Fluid: Viruses Where We Once Thought There Were None.

Traditionally, medicine has held that some human body sites are sterile and that the introduction of microbes to these sites results in infections. This paradigm shifted significantly with the discovery of the human microbiome and acceptance of these commensal microbes living across the body. However, the central nervous system (CNS) is still believed by many to be sterile in healthy people. Using culture-independent methods, we examined the virome of cerebrospinal fluid (CSF) from a cohort of mostly healthy human subjects. We identified a community of DNA viruses, most of which were identified as bacteriophages. Compared to other human specimen types, CSF viromes were not ecologically distinct. There was a high alpha diversity cluster that included feces, saliva, and urine, and a low alpha diversity cluster that included CSF, body fluids, plasma, and breast milk. The high diversity cluster included specimens known to have many bacteria, while other specimens traditionally assumed to be sterile formed the low diversity cluster. There was an abundance of viruses shared among CSF, breast milk, plasma, and body fluids, while each generally shared less with urine, feces, and saliva. These shared viruses ranged across different virus families, indicating that similarities between these viromes represent more than just a single shared virus family. By identifying a virome in the CSF of mostly healthy individuals, it is now less likely that any human body site is devoid of microbes, which further highlights the need to decipher the role that viral communities may play in human health

Pandemic (H1N1) 2009 Surveillance in Marginalized Populations, Tijuana, Mexico

To detect early cases of pandemic (H1N1) 2009 infection, in 2009 we surveyed 303 persons from marginalized populations of drug users, sex workers, and homeless persons in Tijuana, Mexico. Six confirmed cases of pandemic (H1N1) 2009 were detected, and the use of rapid, mobile influenza testing was demonstrated

Characteristics and Outcomes of Initial Virologic Suppressors during Analytic Treatment Interruption in a Therapeutic HIV-1 gag Vaccine Trial

Background: In the placebo-controlled trial ACTG A5197, a trend favoring viral suppression was seen in the HIV-1-infected subjects who received a recombinant Ad5 HIV-1 $gag$ vaccine. Objective: To identify individuals with initial viral suppression (plasma HIV-1 RNA set point <3.0 $log_{10}$ copies/ml) during the analytic treatment interruption (ATI) and evaluate the durability and correlates of virologic control and characteristics of HIV sequence evolution. Methods: HIV-1 $gag$ and $pol$ RNA were amplified and sequenced from plasma obtained during the ATI. Immune responses were measured by flow cytometric analysis and intracellular cytokine expression assays. Characteristics of those with and without initial viral suppression were compared using the Wilcoxon rank sum and Fisher's exact tests. Results: Eleven out of 104 participants (10.6%) were classified as initial virologic suppressors, nine of whom had received the vaccine. Initial virologic suppressors had significantly less CD4+ cell decline by ATI week 16 as compared to non-suppressors (median 7 CD4+ cell gain vs. 247 CD4+ cell loss, P = 0.04). However, of the ten initial virologic suppressors with a pVL at ATI week 49, only three maintained pVL <3.0 log10 copies/ml. HIV-1 Gag-specific CD4+ interferon-γ responses were not associated with initial virologic suppression and no evidence of vaccine-driven HIV sequence evolution was detected. Participants with initial virologic suppression were found to have a lower percentage of CD4+ CTLA-4+ cells prior to treatment interruption, but a greater proportion of HIV-1 Gag-reactive CD4+ TNF-α+ cells expressing either CTLA-4 or PD-1. Conclusions: Among individuals participating in a rAd5 therapeutic HIV-1 $gag$ vaccine trial, initial viral suppression was found in a subset of patients, but this response was not sustained. The association between CTLA-4 and PD-1 expression on CD4+ T cells and virologic outcome warrants further study in trials of other therapeutic vaccines in development. Trial Registration: ClinicalTrials.gov NCT0008010

Crosssectional study to evaluate factors associated with adherence to antiretroviral therapy by Brazilian HIV-infected patients.

ABSTRACT Antiretroviral therapy success is highly dependent on the ability of the patient to fully adhere to the prescribed treatment regimen. We present the results of a cross-sectional study that evaluates the predictive value of a self-administered questionnaire of adherence to antiretroviral (ARV) therapy. Study participants were interviewed using a 36-item Patient Medication Adherence Questionnaire (PMAQ) designed to assess knowledge about ARV therapy, motivation to adhere to treatment, and behavioral skills. Plasma HIV-1 RNA levels were correlated with the results obtained from the PMAQ. Of the 182 study participants, 82 (45%) were receiving their initial ARV regimen. Of the remaining patients, 39 (21%) and 61 (34%) were on a second or additional ARV regimen, respectively. An undetectable viral load was documented in 47/62 (76%) patients on their first regimen who reported missing medication on less than 4 days in the last 3 months. The PMAQ had a higher predictive value of plasma viral suppression for patients in the initial regimen than for patients in salvage therapy. The overall predictive value of the PMAQ to identify adherence was 74%, and 59% for nonadherence, with an overall efficacy of 64%. Of the 74 patients (45%) who did not understand the concept of antiretroviral therapy, 80% were failing or had previously failed the ARV treatment. Of 35 patients with doubts about their HIV status or skeptical of the benefits of ARV therapy, 29 (84%) were nonadherent. Despite the positive predictive value of PMAQ in identifying adherence, self-reported adherence is not a sufficiently precise predictor of treatment success to substitute for viral load monitoring. On the other hand, the use of such an instrument to identify factors associated with nonadherence provides an excellent opportunity to apply early intervention designed to specifically address factors that might be contributing to the lack of adherence prior to regimen failure

The Medical Education Partnership Initiative Effect on Increasing Health Professions Education and Research Capacity in Mozambique

Background: Mozambique is an emerging lower income country (LIC) on the southeast coast of Africa. There are significant workforce shortages in medical and health professions in the country. Mozambique was one of 12 countries in Africa that was awarded a grant through the Medical Education Partnership Initiative (MEPI) in 2010. The overarching goal of MEPI Mozambique was to enhance the capacity of medical schools to train the medical and scientific leadership corps that the country required to facilitate the training of doctors and other health professionals, and thus to strengthen the national health system. Objective: The aim of this article is to provide an overview of MEPI Mozambique activities, its outcomes and successes, lessons learned, and how these have sustainably strengthened the health sector in the country. What Was Done: The Eduardo Mondlane University (UEM) formed a partnership with the University of California, San Diego (UCSD) to implement MEPI Mozambique. A range of activities in medical education, research capacity development, electronic connectivity and information technology, and developing relationships among medical education stakeholders, were performed. Outcomes and Effects: The activities and innovations introduced under MEPI became part of the daily routine in medical education in Mozambique, dramatically influencing attitudes and perceptions. Joint research with partners leveraged research capabilities. The creation of a research support center offered a mechanism to sustainably build on MEPI achievements. Scientific knowledge generated through research has been translated into practice and policy, and has improved the working environment for health professionals. The use of interactive communication technologies enabled the scaling up of training and research in sustainable ways, and created communities of practice. Conclusion: MEPI Mozambique developed transformational long-term partnerships between UEM, UCSD and other partners. These are changing the trajectory of medical and health professions education in Mozambique and creating sustainable capacity for research