Addition of doxycycline to ciprofloxacin for infection prophylaxis during autologous stem cell transplants for multiple myeloma.

BACKGROUND: The most commonly used antibacterial prophylaxis during autologous stem cell transplants (ASCT) for multiple myeloma (MM) involves a fluoroquinolone, such as ciprofloxacin or levofloxacin. We assessed the impact of adding doxycycline to ciprofloxacin as routine antibacterial prophylaxis in these patients. METHODS: We retrospectively reviewed electronic medical records and our ASCT database to analyze rates and types of bacterial infections in MM patients who underwent ASCT in our institution. RESULTS: Among 419 patients, 118 received ciprofloxacin alone (cipro group), and 301 ciprofloxacin and doxycycline (cipro-doxy group). Neutropenic fever (NF) developed in 63 (53%) and 108 (36%) patients of the cipro and cipro-doxy groups, respectively (p = 0.010). The number of documented bacteremic episodes was 13 (11%) and 14 (4.7%) in the two groups, respectively (p = 0.017). Antimicrobial resistance and Clostridium difficile infections were uncommon. Transplant-related mortality was 1% in both groups. CONCLUSIONS: The addition of doxycycline to standard prophylaxis with ciprofloxacin seems to reduce the number of NF episodes and documented bacterial infections in patients with MM undergoing ASCT, without increasing rate of serious complications.

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.

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)

The activities of thiol proteases in the rat visceral yolk sac increase during late gestation.

While the rat YVS has been shown to possess an active lysosomal proteolytic system, there are no published reports on the identity of these proteases nor on their changes in activity during the latter half of gestation. We have used specific synthetic substrates to show that cathepsins B, L and H are present in this organ from days 12.5 to 20.5 of gestation. Cathepsins B and L exhibit a marked increase in activity beginning on day 15.5 of gestation. By days 19.5-20.5, cathepsin B activity is increased tenfold over that observed on day 12.5. The activity of cathepsin L may be elevated on day 12.5, decreases more than half by day 14.5 and then increases fourfold by day 20.5. The activity of cathepsin H does not change throughout this period nor do the cathepsins exhibit marked changes in activity in the placenta during this same period or in the PYS from days 12.5 to 14.5 of gestation. These results indicate a specific increase in VYS cathepsin B and L activities late in gestation. These enzymes may be involved in meeting the nutritional needs of the embryo and/or in the degenerative changes which may occur in the VYS and PYS prior to parturition. Studies on the degradation of rat serum albumin by extracts of day 19.5 VYS indicate that cathepsin L may be the quantitatively most important protease in late gestation.

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.

Medical surveillance of multinational peacekeepers deployed in support of the United Nations Mission in Haiti, June-October 1995.

BACKGROUND: Multinational peacekeepers, both military and civilian, often deploy to areas of the world where significant health threats are endemic and host country public health systems are inadequate. Medical surveillance of deployed personnel enables leaders to better direct health care resources to prevent and treat casualties. Over a 5-month period, June to October 1995, a medical surveillance system (MSS) was implemented in support of the United Nations Mission in Haiti (UNMIH). Information obtained from this system as well as lessons learned from its implementation and management may help decrease casualty rates during future multinational missions. METHODS: Over 90% of UNMIH personnel (80% military from over 11 countries and 20% civilian from over 70 countries) stationed throughout Haiti participated in the MSS. A weekly standardized reporting form included the number of new outpatient visits by disease and non-battle injury (DNBI) category and number of personnel supported by each participating UN medical treatment facility (MTF). Previously, medical reporting consisted of simple counts of patient visits without distinguishing between new and follow-up visits. Weekly incidence rates were determined and trends compared within and among reporting sites. The diagnoses and numbers of inpatient cases per week were only monitored at the 86th Combat Support Hospital, the facility with the most sophisticated level of health care available to UN personnel. RESULTS: The overall outpatient DNBI incidence rate ranged from 9.2% to 13% of supported UN personnel/week. Of the 14 outpatient diagnostic categories, the three categories consistently with the highest rates included orthopaedic/injury (1.6-2.5%), dermatology (1.3-2.2%), and respiratory (0.9-2.2%) of supported UN personnel/week. The most common inpatient discharge diagnoses included suspected dengue fever (22.3%), gastro-enteritis (15%), and other febrile illness (13.5%). Of the 249 patients who presented with a febrile illness, 79 (32%) had serological evidence of recent dengue infection. Surveillance results helped lead to interventions that addressed issues related to field sanitation, potable water, food preparation and vector control. CONCLUSIONS: Despite hurdles associated with distance, language, and communications, the MSS was a practical and effective tool for UNMIH force protection. UN requirements for standardized medical surveillance during deployments should be developed and implemented. Furthermore, planners should recognize that if ongoing medical surveillance and related responses are to be effective, personnel should be trained prior to deployment and resources dedicated to a sustained effort in theatre.

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.

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.

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.

Disseminated Mycobacterium chelonae subspecies chelonae infection with cutaneous and osseous manifestations.

A 75-year-old man who had been receiving corticosteroids for treatment of chronic obstructive pulmonary disease presented with nodulopustular skin lesions, bone pain, and constitutional symptoms. Evaluation revealed a disseminated infection with Mycobacterium chelonae subspecies chelonae, with cutaneous and osseous involvement documented by histopathologic studies and cultures. The bone involvement is a novel observation for this subspecies. The patient was successfully treated with a three-drug regimen of tobramycin sulfate, erythromycin stearate, and ciprofloxacin hydrochloride. We present a discussion of the case in the context of the literature.

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.

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.

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.

A retrospective analysis of diseases associated with indeterminate HIV western blot patterns.

Some individuals possess antibodies which react to HIV-1 Western blot proteins in patterns not diagnostic for HIV infection. A retrospective chart review of patients exhibiting such indeterminate HIV Western blots was performed in comparison to a control cohort of sex- and age-matched individuals from the same population of HIV-negative blots to determine if such blots were associated with any specific disease states. Twenty such patients with 25 indeterminate blots among them were found in a total population of 816 (2.5%). GAG-only (core) Western blots comprised the majority 84% (21/25). An indeterminate blot was statistically associated with Hashimoto's thyroiditis (p less than 0.01) and non-Hodgkin's lymphoma (p less than 0.05). Kikuchi's disease and malignant histiocytosis were associated but the numbers were too small to reach statistical significance. The possibility that these diseases are caused by novel retroviruses, cross-reactive with HIV-1, is discussed in lieu of these findings.

BU and CY as conditioning regimen for autologous transplant in patients with multiple myeloma.

High-dose melphalan is considered the current standard of care among the preparative regimens used in peripheral blood autologous SCT (ASCT) for multiple myeloma (MM). We report the results of a single ASCT in 79 MM patients using the BU/CY conditioning regimen, with BU 1 mg/kg p.o. or 0.8 mg/kg i.v. every 6 h x 16 doses, and CY 60 mg/kg per day i.v. for 2 days. ASCT was carried out in first (62%) or subsequent remission/refractory disease (38%). For an overall RR of 86%, 48 and 20 patients achieved PR and CR, respectively. At a median follow-up of 41 months (range 2-132 months), the estimated median OS and PFS were 45 months (95% confidence interval (CI)=38-92) and 20 months (95% CI=15-25), respectively. The BU/CY regimen was well tolerated, and transplant-related mortality was 4%. Clinical outcomes of the BU/CY regimen are not superior to those obtained in historical controls with high-dose melphalan followed by a single ASCT. Therefore, considering even the greater complexity of administration of the BU/CY regimen compared with that of single-agent melphalan, we believe the latter should remain the conditioning regimen of choice for ASCT in MM.

Pentastomiasis.

Pentastomiasis is a parasitic zoonosis caused by pentastomes, members of an unusual phylum--Pentastomida--with characteristics of both arthropods and annelids. Adult pentastomes parasitize the respiratory tracts of reptiles or carnivorous mammals. The infection is generally limited to the tropics and subtropics, but ocular involvement has been reported in the southern United States. The majority of human pentastomiasis is caused by two species. The first, Armillifer armillatus, infects humans as secondary hosts. Infection is usually asymptomatic but has characteristic postmortem and radiologic features. The second, Linguatula serrata, can infect humans as does Armillifer or can cause a self-limited nasopharyngitis--the halzoun or marrara syndrome--with the human acting as a temporary definitive host. This article discusses the biology and parasitology of these metazoans as well as the clinical manifestations, pathology, diagnosis, and epidemiology of pentastomiasis.

Suppurative pylephlebitis.

Suppurative pylephlebitis is an unusual disease with an associated high mortality. Most cases are a complication of an intra-abdominal septic focus, but some may occur de novo. In the case we have presented, the diagnosis was made by modern imaging techniques that showed thrombus predominantly within the upper portal venous system. We hypothesize that the portal system was seeded through a gastric ulcer. The patient recovered completely with prolonged antibiotic therapy.

Concurrent pernicious anemia and myelodysplastic syndrome.

Megaloblastic anemia (MA) due to vitamin B12 deficiency is a reversible form of ineffective hematopoiesis. Myelodysplastic syndrome (MDS) is an acquired, irreversible disorder of ineffective hematopoiesis, characterized by stem cell dysfunction as a consequence of DNA damage manifested in part by karyotype anomalies. Importantly, MA and MDS are generally considered mutually exclusive diagnoses. We report the case of a 73-year-old woman with a profound macrocytic anemia, monocytosis and neurologic symptoms. Low cobalamin levels and the presence of anti-intrinsic-factor antibodies definitively established a diagnosis of pernicious anemia. Replacement therapy resulted in resolution of neurologic findings and macrocytosis; however, the anemia and monocytosis persisted. Bone marrow biopsy revealed trilineage myelodysplasia, which together with the peripheral monocytosis suggested a diagnosis of chronic myelomonocytic leukemia. Karyotype analysis revealed a clone with 45, XX, +der(1;7)(q10;p10)-7 [20]. Eighteen months after documented vitamin B12 replenishment her MDS transformed to terminal acute myeloid leukemia with the same clonal abnormality. Reversible cytogenetic abnormalities have been observed with MA, occasionally including karyotypes typically associated with MDS or myeloid leukemias. These abnormalities, like the anemia, resolve with vitamin replacement. This case suggests that MA and MDS can occur simultaneously; clinicians should be aware that this phenomenon occurs. Whether acquired karyotype abnormalities from the MA were related to the MDS and subsequent myeloid leukemia in this woman is a speculative but intriguing consideration that is discussed.