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Biomedical subjects

J J Drabick

Publications and source records attributed to J J Drabick.

At least 19 recordsLinked to original sources

Dengue among United Nations mission in Haiti personnel, 1995: implications for preventive medicine.

The incidence of dengue infections has been increasing in the Caribbean, and cases have been identified among successive deployments of multinational peacekeepers to Haiti (1994-1997). In the absence of an effective vaccine or chemoprophylaxis to prevent dengue fever, vector-control operations and use of personal protection measures to prevent arthropod bites are the most effective means of limiting disease transmission. During our 5-month deployment as part of the United Nations Mission in Haiti, 79 cases of recent dengue fever were identified among 249 patients (32%) presenting with febrile illness to the 86th Combat Support Hospital. Further investigation revealed low unit readiness to perform standard vector-control activities and poor individual adherence to measures to prevent arthropod bites. Command enforcement of existing field preventive medicine doctrine is essential to prevent casualties caused by dengue, other arthropod-borne infections, and nuisance arthropod bites during military deployments.

Dengue

Covalent polymyxin B conjugate with human immunoglobulin G as an antiendotoxin reagent.

Polymyxin B (PMB) is a cyclic decapeptide antibiotic which also binds and neutralizes endotoxin. Unfortunately, PMB can be considerably nephrotoxic at clinically utilized doses, thereby limiting its utility as a therapeutic antiendotoxin reagent. We sought to change the pharmacokinetics and toxicity profile of PMB by covalently linking it to a human immunoglobulin G (IgG) carrier. Conjugates of PMB with IgG were prepared by EDAC [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide]-mediated amide formation. Analysis by dot enzyme-linked immunosorbent assay with an anti-PMB monoclonal antibody showed that the purified conjugate contained bound PMB. The IgG-PMB conjugate reacted with lipid A and J5 lipopolysaccharide in Western blot assays in a manner comparable to that of whole antiserum with anti-lipid A reactivity; unconjugated IgG had no reactivity. The PMB bound in the conjugate retained its endotoxin-neutralizing activity compared to that of unbound PMB as evidenced by its dose-dependent inhibition of tumor necrosis factor release by endotoxin-stimulated human monocytes in vitro; unconjugated IgG had no activity. By this assay, the PMB-IgG conjugate was determined to have approximately 3.0 microg of bound functional PMB per 100 microg of total protein of conjugate (five molecules of PMB per IgG molecule). The PMB-IgG conjugate was also bactericidal against clinical strains of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae relative to unconjugated IgG with MBCs of <4 microg of conjugate per ml for each of the tested strains. The conjugate appeared to be nontoxic at the highest doses deliverable and provided statistically significant protection from death to galactosamine-sensitized, lipopolysaccharide-challenged mice in a dose-dependent fashion when administered prophylactically 2 h before challenge. However, neither free PMB nor the PMB-IgG conjugate could protect mice challenged with endotoxin 2 h after administration. This suggests that these reagents can play a role in prophylaxis but not in therapy of sepsis. These experiments demonstrated that the PMB-IgG conjugate retains bound yet functional PMB as evidenced by its endotoxin-neutralizing activity both in vitro and in vivo. Further work is required to define the role that this or related conjugate compounds may play in the prophylaxis of endotoxin-mediated disease.

Anti-Bacterial Agents

Seroprevalence of hepatitis E virus among United Nations Mission in Haiti (UNMIH) peacekeepers, 1995.

Information about the prevalence of hepatitis E virus (HEV) infection is sparse in many countries. Following the identification of four cases of acute HEV infection among Bangladeshi soldiers, a serologic survey was conducted to determine the prevalence of HEV infection among other peacekeepers from the United Nations Mission in Haiti (UNMIH) and Haitian civilians. Of the 981 participants in the survey, 876 were soldiers from eight UNMIH-participating countries representing Asia, Africa, and the Americas, and 105 were Haitian civilians. The prevalence of HEV infection by country (from highest to lowest) included Pakistan (62%), India (37%), Nepal (37%), Bangladesh (27%), Djibouti (13%), Honduras (6%), Guatemala (5%), Haiti (3%), and the United States (2%). More than 90% of those surveyed from Guatemala, Haiti, and Honduras, where prevalence data has been scarce, appeared susceptible to HEV infection. Future multinational missions like the UNMIH might also present unique opportunities to study health threats of widespread interest.

Adult

Laboratory diagnosis of acute dengue fever during the United Nations Mission in Haiti, 1995-1996.

We evaluated laboratory methods to confirm a clinical diagnosis of dengue. Acute sera were collected from personnel (n = 414) supporting the United Nations Mission in Haiti and presenting with febrile illness consistent with dengue fever or no apparent underlying cause. Dengue virus was recovered from 161 of 379 acute sera by inoculation into C6/36 cell culture. While 93 of 414 acute sera had detectable IgM antibodies, the IgM capture ELISA (MAC ELISA) had a sensitivity of only 13% compared with the virus isolation gold standard. If presumptive dengue fever cases were identified by both virus isolation and the presence of IgM, virus isolation and the MAC ELISA had clinical sensitivities of 69% and 40%, respectively. This study suggests that a combination of laboratory methods that target virus or subviral components as well as anti-viral IgM antibodies may be necessary for sensitive laboratory diagnosis with acute sera.

Acute Disease

A randomized, placebo-controlled study of oral cimetidine as an immunopotentiator of parenteral immunization with a group B meningococcal vaccine.

Cimetidine (CIM) is an H2-receptor antagonist with a long history of clinical use in peptic ulcer disease. In addition to its inhibitory effect upon gastric acid secretion, CIM can also block histamine-mediated immunosuppression by inhibiting H2 receptors on suppressor T cells. CIM results in immunoaugmentation of both cellular and humoral immunity by this mechanism and has been used clinically in the treatment of chronic infectious and neoplastic diseases. We postulated that orally administered CIM, like an adjuvant, could augment the immunologic response to a parenteral vaccine. To test this hypothesis, a randomized placebo (PLB)-controlled, double-blinded study in 14 healthy volunteers was performed using a Group B meningococcal outer membrane protein (OMP) vaccine administered twice, 6 weeks apart. Volunteers were randomized within pairs defined by their screening OMP antibody titers to receive either CIM or PLB which was administered for 5 days, beginning 2 days before each of the two immunizations. All 14 volunteers completed the study with excellent compliance. Sera were tested for anti-OMP and bactericidal antibodies. The groups were comparable in terms of gender distribution, age and baseline anti-OMP titers. Reactogenicity to the vaccine was mild and comparable between groups. There was little effect of CIM (over PLB) on anti-OMP or functional bactericidal antibody levels over time. Geometric means of maximum OMP antibody increase over baseline was 3.3-fold (95% CI: 1.8-6.3) for CIM and 2.4 for PLB (CI: 1.6-3.7). CIM had a corresponding 3.9-fold increase (CI: 1.9-8.3) in bactericidal antibody level compared to 2.2 for PLB (CI: 1.4-3.4). We conclude that oral CIM was not effective as an immunopotentiator of immunization with this group B meningococcal vaccine.

Adjuvants, Immunologic

A cluster of acute hepatitis E infection in United Nations Bangladeshi peacekeepers in Haiti.

In the fall of 1995, within a month of deployment to Haiti for peacekeeping duty, four Bangladeshi soldiers developed acute icteric hepatitis in rapid succession. Hepatitis E virus (HEV) was found to be the etiology by demonstrating HEV genomic sequences in serum samples by the polymerase chain reaction (PCR) and serologically by the detection of elevated IgM titers to HEV. No case had serologic evidence of acute hepatitis A or C infection. The soldiers had probably acquired their infection while living in a cantonment area outside Dhaka, Bangladesh for one month prior to deployment. Cloning and sequencing of amplified PCR products demonstrated a single strain suggestive of a common source of infection. Furthermore, high genomic identity with Asian strains of HEV and dissimilarity with the Mexican strain was demonstrated, verifying that the strain had indeed been imported. Human waste management from the Bangladesh camp in Haiti was strictly controlled and no secondary cases were observed. A convenience sample of 105 (12%) soldiers from the Bangladesh battalion (850 men) revealed anicteric or asymptomatic HEV infection in seven (7%) of 105. This report contains the first demonstration of acute hepatitis E in natives of Bangladesh and demonstrates the power of the PCR in the rapid diagnosis and epidemiologic analysis of HEV infection. More importantly, this cluster demonstrates the importation of an important infectious disease by multinational peacekeepers to a potentially susceptible host country.

Acute Disease

Prostatodynia in United Nations peacekeeping forces in Haiti.

Prostatodynia is a clinical entity associated with voiding symptoms and pelvic pain suggestive of prostatitis but with a normal prostate examination and without evidence of inflammation or infection in expressed prostatic secretions. The problem tends to be chronic and is vexing in its management. Although thought to be a common condition, prevalence data are generally lacking. From June to October 1995, the U.S. Army's 86th Combat Support Hospital provided medical support to a multinational United Nations peacekeeping force in Haiti. Patients diagnosed with prostatodynia were more common (13 cases) than men with other urologic problems (urolithiasis, 6 cases; urinary tract infection, 6 cases; scrotal abscess/mass, 2 cases; epididymitis, 1 case). Patients tended to be young (mean age 29.8), had multiple visits, failed to respond to multiple courses of antibiotics for presumed "prostatitis," and denied recent sexual relations. Some patients reported having had similar symptoms on prolonged separation from their spouses in the past that resolved with resumption of normal intercourse. Masturbation, however, had no impact on symptoms and was painful in some individuals. Terazosin, an alpha-antagonist, and stress-reduction therapy led to improvement in some patients' symptoms. A discussion of these retrospective findings in light of what is known about the possible etiologies and treatment of prostatodynia is presented. Prostatodynia appears to be a common problem in deployed troops and can lead to frequent use of medical services. Physicians supporting long deployments need to be aware of this entity.

Abscess

Microbiological laboratory results from Haiti: June-October 1995.

From June to October 1995, the U.S. Army's 86th Combat Support Hospital was deployed in Haiti in support of the United Nations peacekeeping mission. The hospital's mission was to provide comprehensive health care to United Nations military and civilian personnel in Haiti. The hospital's laboratory, with microbiological and parasitological capability, was a critical asset in light of the infectious disease threats in Haiti. A total of 356 microbiological (5.4%) and 887 parasitological (13.4%) tests were performed, out of a total of 6628 laboratory tests. One finding was the discovery of antibiotic-resistant urinary isolates of Escherichia coli. These were from community-acquired infections and included strains resistant to ampicillin (6/15), trimethoprim+sulfamethoxazole (6/15), and ciprofloxacin (2/15). Ampicillin (8/15) and trimethoprim+sulfamethoxazole (3/15) resistance was also noted in Shigella spp. However, no chloroquine-resistant strains of malaria were encountered. Dengue virus, also mosquito borne, was a major pathogen. Antimicrobial-resistant nosocomial pathogens were also encountered. Deployed laboratories should be able to determine antimicrobial susceptibility and perform microbial identification to guide clinical management, conduct medical surveillance, and detect emerging resistance.

Communicable Diseases

Affinity-purified Escherichia coli J5 lipopolysaccharide-specific IgG protects neutropenic rats against gram-negative bacterial sepsis.

Antibodies were raised in rabbits by immunization with the heat-killed J5 mutant of Escherichia coli O111 (Rc chemotype). Serum antibodies were separated into purified IgG and IgM by sequential affinity chromatography on protein G-Sepharose and anti-rabbit IgG-Sepharose columns. J5 lipopolysaccharide (LPS)-specific IgG was prepared by affinity chromatography of purified IgG on a J5 LPS-EAH Sepharose 4B affinity column. Purified IgM, IgG, and J5 LPS-specific IgG protected neutropenic rats against lethal challenge with Pseudomonas aeruginosa 12:4:4 (Fisher Devlin immunotype 6). Nine of 16 rats treated with the IgM fraction were protected (P < .001). Thirteen of 20 rats treated with the purified IgG and 6 of 8 treated with J5 LPS-specific IgG were protected compared with none of 25 treated with IgG made from the preimmune serum of the same rabbit (P < .001). These results demonstrate that purified J5 LPS-specific IgG protects against the lethal consequences of gram-negative bacteremia.

Animals

Passive protection of mice against lethal Francisella tularensis (live tularemia vaccine strain) infection by the sera of human recipients of the live tularemia vaccine.

The relative role that humoral immunity plays in protection against infection with the intracellular bacterium, Francisella tularensis, remains controversial. Cellular immunity is thought to play the major and perhaps only role. The authors, in this article, investigate the immunologic and protective properties of immune serum collected from human recipients of the live tularemia vaccine (LVS). Sera of recipients of the vaccine demonstrated reactivity with the vaccine strain by enzyme-linked immunosorbent assay and Western blot analysis. This reactivity appeared to be directed primarily against the lipopolysaccharide of LVS and demonstrated complete cross-reactivity with fully virulent F. tularensis (Schu4). Pooled immune sera protected mice fully against a 10,000 LD50 challenge with the LVS strain relative to non-immune sera. The protection was abrogated by dilution or preadsorption with the LVS strain but not by preadsorption with Escherichia coli, which suggests specificity of protection. The authors conclude that antibodies to the LVS strain of F. tularensis are generated by live vaccination in humans and play a significant role in protection of mice against lethal challenge with the same organism. These antibodies crossreact completely with fully virulent F. tularensis, but whether they play a role in protection against fully virulent human tularemia strains requires further experimentation.

Animals

Hypereosinophilic syndrome associated with HIV infection. Military Medical Consortium for Applied Retroviral Research.

A hypereosinophilic syndrome associated with dermatitis has been observed rarely in association with HIV infection. We describe the case of a young man with AIDS who came to us with a diffuse cutaneous eruption, fever, angioedema, eosinophilia, and a mildly elevated serum IgE level. No allergic or infectious cause of this illness could be determined, and the patient was treated with corticosteroids and PUVA therapy, resulting in complete resolution of the dermatitis and associated findings. In this case, there were clinical and histopathologic similarities to the idiopathic hypereosinophilic syndrome and to acute graft-versus-host disease. The serum level of the cytokine interleukin-5 (IL-5), which is associated with eosinophil production, was found to be mildly elevated during the peak of the eruption, while samples drawn previously and subsequently were not. Although it appears that the syndrome we describe is associated with the measurably elevated level of IL-5, further investigation is required to determine whether there is a cause and effect relationship between IL-5 and this entity. A brief review of the literature concerning eosinophils and HIV infection is also presented in the context of this case.

Acquired Immunodeficiency Syndrome

Immunotherapy of tularemia: characterization of a monoclonal antibody reactive with Francisella tularensis.

An IgM monoclonal antibody (mAb) recognized surface antigens specific to Francisella tularensis wild-type (Schu4) and live vaccine strain (LVS), and reacted with both in ELISA and slide agglutination tests. This mAb also reacted with LVS microorganisms in tissues of infected mice as assessed by an indirect fluorescence technique. Western blot analysis showed the mAb to react with antigens associated with F. tularensis LPS.

Animals

Pasteurella multocida pneumonia in a man with AIDS and nontraumatic feline exposure.

A case of acute pneumonia due to Pasteurella multocida ssp multocida occurred in a young man with AIDS and chronic sinusitis. The pneumonia was diagnosed by bronchoscopy and responded to treatment with aztreonam. Epidemiologic investigation revealed the case was temporally related to nontraumatic exposure to cat secretions that the patient presumably had acquired via an aerosol. The cat's oral cavity was cultured and an isolate of P multocida ssp multocida with identical biochemical reactions, DNA restriction patterns, and nearly identical fatty acid profile to that of the patient's isolate was obtained suggesting they were identical strains and therefore epidemiologically linked. A control strain with identical biochemical reactions and antibiotic sensitivities exhibited different patterns. To our knowledge, this is the first such reported infection in a patient infected with human immunodeficiency virus.

AIDS-Related Opportunistic Infections

CD4 lymphocyte decline and survival in human immunodeficiency virus infection. The Military Medical Consortium for Applied Retroviral Research.

The loss of the CD4 lymphocyte is the central pathophysiologic event in the progression of human immunodeficiency virus (HIV) infection. This retrospective study, based on review of data from deceased HIV patients followed in a single HIV clinic, was conducted to determine if the rate of CD4 lymphocyte decline was predictive of survival. Forty of 172 patients met defined criteria for inclusion in this study. For each patient, CD4-cell counts showed approximate exponential decline over time. A Cox regression analysis was used to assess the association of CD4 cell decline (half-life), race, age, gender, initial CD4-cell count, and treatment (anti-Pneumocystis carinii pneumonia prophylaxis and/or zidovudine vs. no therapy) on total survival (from initial CD4 cell count) and on remaining survival time after reaching a CD4 cell count of 100 (estimated). For all patients, the rate of CD4 cell decline was predictive of total survival (p = .009) but not for survival after reaching a count of 100 (p = .6). For patients who had never received therapy (6 patients), however, the CD4 half-life remained associated with survival time from 100 CD4 cells (p < .05) as opposed to the treated patients. Therapy was the single variable most predictive of both survival endpoints, resulting in an increase in median total survival of 27.2 mo (p < .00001) and of 15.4 mo from a CD4 cell count of 100 (p < .00004). Nonwhites had a slight survival disadvantage compared to whites (p = .08 overall; p = .02 from CD4 cell count of 100).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Absence of retroviral sequences in Graves' disease.

An earlier report of HIV-1 gene sequences in thyroid cell genomic DNA from patients with Graves' disease prompted use of the polymerase chain reaction technique to identify such sequences in Graves' disease thyroid tissue and in white blood-cells from these patients. We were unable to confirm the existence of HIV-1-related DNA sequences in Graves' specimens.

DNA, Viral