Edmund Tramont

National Institutes of Health | NIH · Division of Clinical Research (DCR)

Candida albicans causes debilitating, often azole-resistant, infections in patients with chronic mucocutaneous candidiasis (CMC). Amphotericin B (AMB) resistance is rare, but AMB use is limited by parenteral administration and nephrotoxicity. In this study, we evaluated cochleated AMB (CAMB), a new oral AMB formulation, in mouse models of oropharyn...

Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) affects around 20–50% of people living with HIV (PLWH). Although batteries of tests are used to identify neurocognitive impairment (NCI), they are long and difficult to perform during a routine clinic visit, thus impairing the ability to diagnose HAND. Therefore, a brief y...

This chapter focuses on meningococcal infection, which was first recognized over two centuries ago as epidemic cerebrospinal fever. It explains how meningococcal infection occurs worldwide as endemic sporadic cases that have the potential to spread and expand into an epidemic. It also investigates the transmission of meningococcal infection that oc...

Objective To test the hypothesis that brain white matter hyperintensities (WMH) are more common in people living with HIV (PLWH), even in the setting of well-controlled infection, and to identify clinical parameters that correlate with these abnormalities. Methods Research brain MRI scans, acquired within longitudinal studies evaluating neurocogni...

Background Candida albicans causes debilitating mucosal infections in patients with inherited susceptibility to chronic mucocutaneous candidiasis (CMC), often requiring long-term azole-based treatment. Due to increasing azole resistance, alternative treatments are desirable. Acquired resistance to amphotericin B (AMB) is rare but AMB use is limited...

Risk behaviors associated with sexually transmitted infections (STIs) among people living with HIV (PLWH) have not been well characterized in the US military. We identified risk behaviors associated with a new STI in this population after the repeal of "Don't Ask, Don't Tell." US Military HIV Natural History Study participants who completed the ris...

Although atovaquone is effective in treating and preventing Pneumocystis pneumonia (PCP), it’s use is limited by nonlinear absorption and adverse events. The current study was undertaken to examine the activity of encochleated atovaquone (eATQ), a novel lipid-crystal nanoparticle formulation, in a mouse model of PCP. eATQ 100 to 200 mg was superior...

Introduction In October 1985, 4 years after the initial descriptions of the acquired immunodeficiency syndrome (AIDS), the U.S. Department of Defense (DoD) began routine screening for human immunodeficiency virus (HIV) infection to prevent infected recruits from exposure to live virus vaccines, implemented routine active-duty force screening to ens...

Background In spite of viral suppression with antiretroviral therapy (ART), neurocognitive impairment (NCI) affects ~20% of those infected with HIV; most are asymptomatic or only mildly impaired based on instrumental activity of daily living (IADL) self-reported questionnaires. Previous studies have shown a strong association between depression, co...

Purpose: This study sought to assess the frequency of refractive surgery complications in human immunodeficiency virus-positive (HIV+) individuals and related risk factors. Settings: Multiple centers in the United States. Design: Prospective observational cohort study. Methods: The U.S. Military HIV Natural History Study is a prospective obs...

Objective: To characterize cerebral arterial remodeling in HIV-infected (HIV+) individuals in-vivo, and to study its clinical and immunological associations. Methods: T2*-weighted magnetic resonance imagining sequences was used to determine cross-sectional area (vascular caliber) of the anterior (A1 segment) and middle (M1 segment) cerebral arterie...

Background Current oral therapeutic options for chronic mucocutaneous candidiasis (CMC) are often associated with resistance and toxicity. Amphotericin B (AMB) has broad fungicidal activity and markedly resists emergence of resistance but requires parenteral administration and monitoring for significant nephrotoxicity, which worsens with chronic tr...

Background Candida albicans causes debilitating mucosal infections in patients with inherited susceptibility to chronic mucocutaneous candidiasis (CMC) such as oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC), which often require long-term azole-based treatment. Due to the high incidence of azole resistance in these patients, alte...

Objective: To quantitatively measure brain glucose metabolism in treated HIV-positive individuals with [18F]-labeled fluorodeoxyglucose (FDG) PET/CT. Methods: We performed a cross-sectional comparison of FDG uptake in 47 treated HIV+ individuals, 10 age-matched controls (HIV-) sharing many of the comorbid conditions seen in the HIV+ group, and 1...

As globalization progressively connects and impacts the health of people across the world, collaborative research partnerships provide mutual advantages by sharing knowledge and resources to address locally and globally relevant scientific and public health questions. Partnerships undertaken for scientific research are similar to business collabora...

Background: D-dimer blood levels in persons with HIV infection are associated with risk of serious non-AIDS conditions and death. Black race has been correlated with higher D-dimer levels in several studies. We examined the effects of race and HIV on D-dimer over time and the impact of viral load suppression by longitudinally comparing changes in...

Meningococcal infection, first recognized over 2 centuries ago as epidemic cerebrospinal fever, occurs worldwide as endemic sporadic cases but with the potential to spread and expand into an epidemic. Humans are the only natural host for the bacteria. Transmission of the organism occurs from person to person by direct contact with colonized respira...

Syphilis is a complex systemic disease caused by the spirochete Treponema pallidum. Syphilis is transmitted sexually or congenitally and can involve nearly every organ system. Its clinical progression involves several well-characterized stages: (1) an incubation period of 1 week to 3 months; (2) a primary stage characterized by a chancre (an indura...

Background: HIV-infected persons are at increased risk for age-related, non-AIDS-defining conditions. The development of multimorbidity, defined as the presence two or more chronic conditions, has not been evaluated among a young cohort of recently diagnosed HIV seroconverters with open access to care. Methods: Documented HIV-seroconverters as pa...

The Department of Defense (DoD) and the Department of Veterans Affairs (VA) provide comprehensive HIV treatment and care to their beneficiaries with open access and few costs to the patient. Individuals who receive HIV care in the VA have higher rates of substance abuse, homelessness and unemployment than individuals who receive HIV care in the DoD...

The relationship between CD4 T-cell counts determined soon after seroconversion with HIV-1 (baseline CD4), nadir CD4, and CD4 levels attained during highly active antiretroviral therapy (HAART) is unknown. Longitudinal, including baseline (at or soon after HIV diagnosis), intermediate (nadir), and distal (post-HAART) CD4 T-cell counts were assessed...

Attachment AntigensHost Cell Properties (Tropisms)Kinetics of Attachment of Gonococci to Buccal CellsReferencesDiscussionReferences

Conclusions Despite the rapid increase in knowledge regarding the epidemiology, pathogenesis, and molecular virology of HIV-1 and the continued advances in chemotherapy, HIV/AIDS will be with us for a long time to come. In that vein, it is winning the host-pathogen battle. It is likely that the much-anticipated breakthrough will involve a heretofor...

The U.S. military has a long and illustrious history of involvement with vaccines against infectious diseases. For more than 200 years, the military has been actively engaged in vaccine research and has made many important contributions to the development of these products for use in disease prevention and control. Through the efforts of military r...

Sexually transmitted diseases have posed a threat to military service members throughout history. Among these diseases, syphilis, gonorrhea, and human immunodeficiency virus infections have accounted for the most significant morbidity and mortality rates in the U.S. military. In response, military researchers have made significant contributions to...

Until the advent of penicillin and the antibiotic era in the mid-20th century, syphilis was a prevalent disease, infecting between 8% and 14% of the population living in urban areas. The disease progressed to a chronic illness in up to 25% of patients, and its late neurologic manifestations had a profound affect on Western history when it infected...

In this Policy Forum, the authors respond to Burton et al. by asserting that the ongoing efficacy trial of ALVAC-HIV (vCP1521) and AIDSVAX B/E in Thailand is scientifically justified, morally correct, and strategically important. No laboratory assay or animal model has been validated as a predictor of the efficacy of HIV vaccines in humans, thus e...

A new collaborative model of research is needed to increase resources, to prioritize the R (ii) to increase the pace, reduce the overlap, and more systematically explore the elements of and delivery systems for vaccines; (iii) to use common standards for the prompt comparative testing of vaccine candidates; (iv) to expand resources for manufacturin...

Despite the remarkable advances that have been made in the last 20 years regarding the molecular virology, pathogenesis and epidemiology of HIV, the development of an effective HIV vaccine remains an elusive goal. The major reason for this is that we have not determined a correlate of immunity. The various explantations for this include integration...

The consultation was jointly organized by the WHO-UNAIDS HIV Vaccine Initiative and the Quality Assurance and Safety of Biologicals Team of the World Health Organization (WHO). Thirty-four experts from 16 developed and developing countries attended the meeting, bringing together expertise from academic institutions, clinical trial centres, national...

A phase II efficacy trial was conducted with recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein gp160 (rgp160) in 608 HIV-infected, asymptomatic volunteers with CD4+ cell counts >400 cells/mm3. During a 5-year study, volunteers received a 6-shot primary series of immunizations with either rgp160 or placebo over 6 months, fo...

We will be focusing this presentation on a few selected aspects regarding novel biological means of conrolling HIV disease with an emphasis on research that we have been conducting in our laboratory.

HIV infection (AIDS) burst upon the scene a decade ago. Because it is a sexually transmitted disease that infects blood and kills its victim, it is military relevant and will impact on all aspects of the military. The US Army Medical Research and Development Command as 'Lead Agent for Infectious Disease Research' in the Department of Defense has de...

There has been controversy about whether cognitive changes occur in early human immunodeficiency virus (HIV) disease. In those studies reporting cognitive changes, these are typically subclinical, and their relationship to daily and/or occupational functioning has not been addressed. The potential effects of changes may vary as a function of occupa...

Since syphilis and HIV infection are associated with each other at a higher rate than expected by chance, all HIV-infected persons and persons with syphilis should be tested for syphilis and vice versa. Because the immunological dysfunction of HIV-infected patients can interfere in clearing of T. pallidum, concomitant infection with T. pallidum req...

HIV-infected individuals in both early and late stages of HIV disease were evaluated over 2 years to assess temporal trends and determinants of disease progression. The Walter Reed (WR) staging system was used to categorize patients into an early-stage cohort (WR Stages 1 and 2. N = 1183) and a late-stage cohort (WR Stage 5, N = 260) based on the i...

HIV is a complex retrovirus. Like some other viruses it infects host cells for life, but unlike other viruses it appears to do so every time. Its elaborate genetic regulation enables it to remain relatively dormant, replicating steadily but slowly. On appropriate stimulation, it is capable of explosive up-regulation, releasing high numbers of new i...

Despite multiple antiviral humoral and cellular immune responses, infection with the human immunodeficiency virus (HIV) results in a progressively debilitating disease. We hypothesized that a more effective immune response could be generated by post-infection vaccination with HIV-specific antigens. We performed a phase I trial of the safety and imm...

As the focus of the management of human immunodeficiency virus (HIV) infection turns from the treatment of AIDS to the entire continuum of the disease, projection of long-term healthcare costs becomes increasingly important. Rather than a fulminant disease treated primarily inside the hospital, HIV infection will become a chronic condition requirin...

Whenever Americans spend time in foreign lands, they may become infected with pathogens alien to the United States and bring these pathogens back with them. Mass deployments of the U.S. Armed Forces abroad amplify this risk since military personnel are more intimately exposed than ordinary travelers to each other, to local people, and to the natura...

A randomized, placebo-controlled, double-blind efficacy trial of a purified gonococcal pilus vaccine composed of a single pilus type was tested in 3123 men and 127 women volunteers. Either 100 micrograms of vaccine or a placebo was given intradermally on day 1 and day 14. Each group was evenly matched with respect to age, sex, prior history of a se...

Because of the immunologic dysfunction of HIV-infected patients, concomitant infection with T. pallidum requires that maximal doses of appropriate antibiotics be given, and the expected falls in nontreponemal antibody titer cannot be relied upon to certify a cure. Genital ulcer disease appears to increase the risk of acquiring HIV. Therefore, all H...

In 1983, a gonococcal pilus vaccine failed to show protection in a large, placebo-controlled, double-blind field trial. The epitopic response to this vaccine was investigated in a random subgroup of 20 vaccine recipients. Using Western blot analysis of the immunizing pilus and its cyanogen bromide (CNBr) fragments, IgG antibody to pilin was detecte...

A bivalent vaccine consisting of Salmonella typhi strain Ty21a containing the 120 MDa plasmid of Shigella sonnei and expressing both S. typhi and S. sonnei lipopolysaccharides (LPS) on its surface was previously shown to protect significantly against S. sonnei disease in experimental challenge studies. However, protective efficacy could not be reco...

Macrophages are major viral reservoirs in the brain, lungs, and lymph nodes of HIV-infected patients. But not all HIV isolates infect macrophages. The molecular basis for this restrictive target cell tropism and the mechanisms by which HIV infects macrophages are not well understood: virus uptake by CD4-dependent and -independent pathways have both...

Recombinant soluble CD4 (rsCD4) offers a promising innovative approach for treating patients infected with human immunodeficiency virus

Prescription drug profiles of 116 human immunodeficiency virus (HIV)-infected patients taking zidovudine in 1988 were surveyed. Patients received the drug an average of 236 days. About one-third (32 percent) required reduced dosage presumably because of hematologic toxicity and this was associated with length of time on the drug. Zidovudine dosage...

Having a useful classification system is critical to understanding and treating any complex disease process. Some classification systems help with diagnosis, such as the Jones criteria for acute rheumatic fever. Some describe the natural history of a disease, such as the primary, secondary, and tertiary stages of syphilis. Others emphasize prognosi...

One hundred fourteen men with uncomplicated urethritis were randomized to receive 1 week of therapy with either doxycycline (100 mg twice daily) or ofloxacin (300 mg twice daily). Of the 109 men completing the post-treatment visit, 56 received ofloxacin and 52 (93%) were clinically cured. Forty four (83%) of the 53 men treated with doxycycline were...

Reagin and treponemal antibody tests are highly reliable in diagnosing secondary syphilis. However, patients infected with the human immunodeficiency virus (HIV) respond abnormally to antigenic stimulation and may fail to develop typical serologic responses to infections. We report the case of an HIV-infected man with Kaposi sarcoma and secondary s...

Because of the high prevalence of penicillinase-producing Neisseria gonorrhoeae in the Republic of Korea, spectinomycin has been used there in the primary treatment of gonococcal infections in U.S. military personnel since 1981, but there have been increasingly frequent reports of treatment failures with spectinomycin. We conducted a clinical study...

IT is difficult for those of us practicing modern-day medicine to comprehend how pervasive syphilis was in the pre-antibiotic era. For example, medical textbooks commonly divided the discussion of organ systems into sections on congenital defects, tumors, trauma, and infections, but listed syphilis as a separate category. Sir William Osier was ofte...

Gonorrhea is one of the oldest recorded diseases of mankind (1). Over the past 15 years it has reached epidemic proportions, afflicting principally the most sexually active 15–30 years old age group at a rate of 12/1000/yr. The reasons for such high rates are multifactorial. Increased promiscuity among sexually active adults, the propensity of gono...

Patients with acquired immunodeficiency syndrome (AIDS) represent a minority of those who have been infected with human T-lymphotropic virus type III (HTLV-III). The clinical presentation of patients with HTLV-III infections can range from asymptomatic through chronic generalized lymphadenopathy, to subclinical and clinical T-cell deficiency. The U...

A serum amoxycillin concentration of 0.11 g/l was established as being treponemicidal in a rabbit model with orchitis. Seventeen patients treated with amoxycillin 2 g by mouth three times a day plus 500 mg probenecid twice a day attained treponemicidal CSF amoxycillin concentrations. Thus amoxycillin by mouth offers an effective alternative method...

Thirty-six patients with American cutaneous leishmaniasis were randomized to receive intravenous sodium stibogluconate for 10 days at a dose of 600 mg antimony (Sb) per day by one of three schedules: once daily by rapid infusion (A), by continuous 24 hr infusion (B), or in divided doses every eight hours by rapid infusion (C). Patients not cured af...

Bacterial pili (fimbriae) are protein appendages which extend from the cell surface and serve to adhere the microorganism to body surfaces. These appendages have been isolated, purified and characterized as vaccine candidates. These vaccines stimulate an immune response which serves at least with regards to Neisseria gonorrhoeae to block the adhere...

The form-l antigen of Shigella sonnei was transferred to the avirulent Shigella typhi strain 21a and the resulting 5076-1C transconjugate strain was tested for safety and immunogenicity as a candidate oral vaccine. The transconjugant strain was shown to be well tolerated and safe in 19 human volunteers who were fed from 1 × 107 to 1 × 1010 organism...

Penicillinase-producing Neisseria gonorrhoeae has increased in the Far East to the point that penicillin can no longer be recommended as the drug of choice, mandating a change to spectinomycin. As part of an ongoing surveillance of antibiotic susceptibilities, minimal inhibitory concentrations of penicillin, tetracycline, spectinomycin, trimethopri...

Eighty-five patients undergoing cardiac surgery with cardiopulmonary bypass were given either cephalothin or ceforanide perioperatively in randomized, blinded fashion. The incidence of surgically related, postoperative infections was 23% for the cephalothin- and 26% for the ceforanide-treated groups. There were no statistically significant differen...

A parenteral gonococcal pilus vaccine which has previously been shown to be safe and antigenic also results in the production of specific local genital antibody. All three major antibody classes were present in the local secretions, but immunoglobulin A predominated, a portion of which is dimeric 11S immunoglobulin A. This mucosal antibody is also...

A gonococcal pilus vaccine or placebo was injected subcutaneously or intramuscularly into 71 human volunteers. The vaccine was found to be safe. The principal adverse reaction was a complaint of a sore arm, which was caused, at least in part, to the volume of material injected. 6 of 64 (9%) volunteers receiving the larger doses also complained of m...

Adhesion of gonococci to mucosal epithelial cells appear to be a critical step in the pathogenesis of gonococcal infection. Parameters affecting adhesion, the antigens involved in adhesion and the human antibody response that blocks adhesion have been studied. Gonococci adhere to a variety of human cells grown either in tissue culture or organ cult...

Antibacterial activity of 65 2-acetylpyridine thiosemicarbazones and related compounds was determined by using clinical isolates of nine bacterial genera. Minimal inhibitory concentrations (MICs) of 0.002 to 0.062 micrograms/ml were obtained with 23% of the compounds for Neisseria gonorrhoeae and 0.016 to 0.062 micrograms/ml with 17% of the compoun...

Antibodies in genital secretions of patients with gonorrhea have been shown to inhibit the attachment of gonococci to epithelial cells. The gonococcal antigens for which these antibodies are specific were studied by adsorption of the genital secretions from a patient infected with gonorrhea with purified lipopolysaccharide, outer membrane complex,...

On the basis of bacterial typing, pyocin typing, and antibiotic sensitivity tests, two consorts appeared to have been reinfected 34 and 41 days later, respectively, with the same gonococcal strain, suggesting a failure in these patients to develop effective immunity to reinfection. However, these tests do not measure antigens which mediate attachme...