Albert L. Vincent

Disseminated Mycobacterium bovis after intravesicular bacillus calmette-Gu rin treatments for bladder cancer.

Transitional-cell carcinoma of the bladder is an aggressive and potentially fatal malignancy. In 1990, the US Food and Drug Administration approved the use of intravesicular bacillus CalmetteGuérin (BCG) for the treatment of superficial bladder cancer.1 BCG is a live, attenuated strain of Mycobacterium bovis (M. bovis) that has been used to treat transitional-cell carcinoma since 1976 and has been reported to eradicate disease in more than 70% of patients with in situ and stage I disease.2 The precise mechanism by which BCG acts is unknown, but a local granulomatous inflammation, centered on a T-cell–mediated immunity response, is thought to play a role.3 While the majority of patients tolerate BCG intravesicular treatments well, a number of adverse reactions (eg, fever, hematuria, dysuria, nausea, and malaise) have been reported.4,5 More serious complications include granulomatous prostatitis, pneumonitis, and hepatitis. We report a case of disseminated BCG infection causing pneumonitis that required corticosteroids and antitubercular therapy for cure.

THE LYMPHATIC PATHOLOGY OF BRUGIA PAHANGI IN NUDE (ATHYMIC) AND THYMIC MICE C3H/HeN

The nude (congenitally athymic) mouse, C3H/HeN is highly susceptible to infection with Brugia pahangi (Nematoda: Filarioidea). Normal, hairy mice show a strong thymus-dependent resistance and usually terminate the infection in the larval stages. The present study examined chronological histopathologic changes in the lumbar lymph nodes and adjacent lymphatic vessels of both hosts. In thymic mice, lymphangitis and perilymphangitis reached a maximum 14 to 17 days PI, about the time of disappearance of live worms. The infiltrate showed characteristics of both acute and chronic inflammation: eosinophils, neutrophils, eosinophilic precipitates, and sometimes necrotizing lymphangitis, as well as macrophages and plasma cells. The cellular infiltrate in nude mice was weaker and developed more slowly. Inflammatory responses to identifiable dead worms were seen in both types of hosts but appeared more frequently in thymic mice. Although variable in both models, the granulomas of thymic mice generally showed more tendency to cavitation, greater macrophage or epithelioid cell infiltration, more granulocytes, and appeared to be more destructive than the foreign body responses of nude mice. Whereas lymphangiectasis was generally progressive in nude mice, it was arrested before the end of the third week in thymic mice. In thymic mice, at maximum lumbar lymph node size (17 days), there were large areas of lymphocyte hyperplasia and heavy infiltration of plasma cells. Most nodes returned to normal mean size by the end of the second month. Little or no reactivity was seen in athymic mouse nodes. Our results suggest that some lesions of lymphatic filariasis are potentially thymus-independent: lymphatic fibrosis, lymphangiectasis, accumulations of macrophages and giant cells around disintegrating worms, calcification of worms, intralymphatic thrombosis, and moderate vascular infiltrates including eosinophils.

The lymphatic pathology of Brugia pahangi in the Mongolian jird.

We studied the sequence of histopathologic changes associated with Brugia pahangi (Nematoda: Filarioidea) infections in lymphatic vessels in the spermatic cord of the Mongolian jird (gerbil), Meriones unguiculatus. Intravascular granulomas caused mainly by disintegrating worms were seen in 67% of jirds necropsied on, or after, 35 days postinoculation, whereas none of 20 jirds examined before this day showed dying larvae. These granulomas usually evolved without vascular occlusion. Other granulomatous foci, often with a thrombuslike core, sometimes harbored microfilariae or microfilarialike materials. The perilymphatic cellular infiltrate consisted mostly of eosinophils, lymphocytes, and plasma cells. Large numbers of eosinophils were seen in the early weeks, but later declined, while lymphocytes increased to become the predominant cell in old infections. Irregular fibrosis of some valves and portions of the lymphatic walls were seen as early as the 2nd wk postinoculation. Lymphatic changes in the jird are similar to those described in other hosts infected with filariae, but remained moderate. Living worms appeared to be the stimulus for many observed changes. Most pathologic alterations were well established by 3 or 4 mo and showed little qualitative change during the remaining 4 mo of the study.

Infectious complications of cutaneous t-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) is the most common primary lymphoma of the skin. As with most cancers, survival depends on the stage of disease. Infection is a common complication of CTCL, contributing significant morbidity and mortality. We report a patient with severe, generalized mycosis fungoides (MF) complicated by recurrent skin infections,and we review the infectious complications of patients with CTCL.

Mucormycosis in immunochallenged patients

Mucorales species are deadly opportunistic fungi with a rapidly invasive nature. A rare disease, mucormycosis is most commonly reported in patients with diabetes mellitus, because the favorable carbohydrate-rich environment allows the Mucorales fungi to flourish, especially in the setting of ketoacidosis. However, case reports over the past 20 years show that a growing number of cases of mucormycosis are occurring during treatment following bone marrow transplants (BMT) and hematological malignancies (HM) such as leukemia and lymphoma. This is due to the prolonged treatment of these patients with steroids and immunosuppressive agents. Liposomal amphotericin B treatment and posaconazole are two pharmacologic agents that seem to be effective against mucormycosis, but the inherently rapid onset and course of the disease, in conjunction with the difficulty in correctly identifying it, hinder prompt institution of appropriate antifungal therapy. This review of the literature discusses the clinical presentation, diagnosis, and treatment of mucormycosis among the BMT and HM populations.

Successful voriconazole therapy of disseminated Fusarium solani in the brain of a neutropenic cancer patient

Although Aspergillus remains the most common of the opportunistic molds in patients with hematologic malignancies,disseminated Fusarium infection is increasingly encountered as more aggressive chemotherapeutic regimens and bone marrow transplants lead to prolonged neutropenia.1-11 Most frequently pathogenic to man is F solani, followed by F oxysporum, F verticillioides, and F proliferatum as the next most common12 of a dozen other species that have been documented. Still other species are significant as pathogens of plants and animals. A fatal leukoencephalomalacia of horses is caused by fumonisins that contaminate corn and corn byproducts while in the field.13 The fungus is ubiquitous in the soil and has recently been found in water and wet surfaces within a hospital with known fusarial infections.14 However, some cancer hospital epidemiologists have concluded that the external environment is the more likely source of infection to patients.15 Entry is either airborne or through a breakdown in the skin barrier,10 but central venous catheters should not be underestimated as portals of entry.5,16

Lactobacillus Bacteremia in Febrile Neutropenic Patients in a Cancer Hospital

may cause serious infection in immunosuppressed patients. CliniEmpirical antibiotic therapy for patients with febrile neutropenia cal syndromes associated with L. casei infection include endocardihas resulted in a decrease in the number of cases of bacteremia tis [1, 2], sepsis [3–6], pneumonia [7], meningitis [4], mediastinitis caused by enteric gram-negative bacilli. However, gram-positive [8], liver abscess [9], endometritis [6], amnionitis [5], and urinary organisms have emerged as a major cause of bacteremia in this tract infection [4]. Risk factors for bacteremia include neutropenia, population. We report the occurrence of a microaerophilic, gramprior surgery, malignancy, diabetes, and prior therapy with antimipositive rod, Lactobacillus casei, that caused bacteremia among a crobials inactive against Lactobacillus [5]. Empirical antibiotics significant number of febrile neutropenic patients who were receivsuch as cephalosporins, aminoglycosides, and vancomycin are freing antimicrobials active against this organism. quently used to treat febrile neutropenia but do not eradicate LactoWe reviewed the charts of 22 patients admitted to the H. Lee bacillus [5]. Patel et al. [4] reported that the use of vancomycin Moffitt Cancer Center and Research Institute in Tampa, Florida, in liver transplant recipients promoted colonization of the gastroinbetween January 1988 and June 1996. There were nine males and testinal tract and may constitute a contributing factor in the devel13 females; the mean age was 45.2 years (range, 17–69 years). opment of lactobacillemia. Lactobacillus species are usually susL. casei was isolated from the blood of all patients and from the ceptible to penicillins [1], ampicillin [2], clindamycin [4, 5], and urine of one; the organisms were cultured on both blood agar erythromycin [5], antibiotics that are not commonly used for emincubated at 357C in room air and chocolate agar incubated at 357C pirical therapy for febrile neutropenia. Bayer et al. [3] reported in a 5% CO2 environment. Species identification was performed by that a synergistic effect existed in vitro when penicillin or ampiciluse of the Vitek ANI identification system (bioMérieux Vitek, lin and gentamicin/streptomycin were used in the treatment of Hazelwood, MO). lactobacillemia. Vancomycin, used either alone or in combination Multiple species, notably Escherichia coli, Staphylococcus epiwith gentamicin or streptomycin, did not have antimicrobial activdermidis, or Candida species, were also recovered from the blood ity against Lactobacillus plantarum or L. casei. In another study of 14 study subjects. Lactobacillus bacteremia occurred in 22 paL. casei was found to be resistant to cefoxitin and vancomycin, tients with 10 types of tumors. with synergy between vancomycin and penicillin [2]. Neither A test for independent proportions indicated that bacteremia was L. casei nor Lactobacillus acidophilus was effectively controlled significantly more frequent (9 [6.01%] of 162) among patients by the use of gentamicin alone [2]. with acute myelogenous leukemia (AML) than among all others Lactobacillus becomes a potential pathogen in patients with in the hospital registry (13 [0.1%] of 9,047; t Å 4.1, P Å .0001). cancer when empirical antibiotics used to treat episodes of febrile The underlying malignancy most frequently complicated by bacterneutropenia lack activity against this organism. Capnocytophaga emia was AML (9 [5.4%] of 168), followed by all other leukemias infection, also seen in febrile neutropenic patients with mucositis, (11 [4.4%] of 250) and, rarely, breast cancer (5 [0.33%] of 1,535). similarly requires therapy with penicillin or clindamycin [10]. The The distribution of probable risk factors for lactobacillemia was widespread use of third-generation cephalosporins, aminoglycoas follows: neutropenia, 91% of patients (20 of 22); both mucositis sides, and vancomycin as empirical therapy for febrile neutropenia and neutropenia, 36.4% (8 of 22); and vancomycin therapy, 95.5% facilitates the development of lactobacillus infections. Once dis(21 of 22). Antibiotics frequently used before lactobacillus bactercovered and treated promptly, however, lactobacillus bacteremia emia occurred included vancomycin (95.5% of patients), ceftazareadily responds to treatment with penicillin, clindamycin, or dime (63.8%), tobramycin (63.8%), metronidazole (59.1%), azerythromycin in combination with gentamicin. treonam (45.5%), acyclovir (45.5%), and fluconazole (40.9%). Use

DISSEMINATED CUTANEOUS MYCOBACTERIUM CHELONAE INFECTION

Over the last two decades, a rising proportion of mycobacterial infections have been caused by nontuberculous species such as Mycobacterium chelonae.1-3 Belonging to the M. fortuitum complex,4 M. chelonae is an acidfast bacillus (AFB) that grows rapidly compared with the more common M. tuberculosis. Disseminated cutaneous manifestations are the most common presentations and occur in patients who are immunosuppressed by malignancy, corticosteroid therapy, or the various immunomodulating drugs used in organ transplantation.5 After an indolent course, the extremities are usually involved with several to hundreds of nodules, abscesses, and/or ulcers that are erythematous or indurated.5-7 We present the case of an elderly woman with a long-standing M. chelonae infection and a history of protracted corticosteroid therapy (longer than 6 months). The basis of diagnosis and current treatment modalities are reviewed.

A Survey of Bancroftian Filariasis in the Dominican Republic

Albert L. Vincent, Department of Comprehensive Medicine, University of South Rorida, College of Medicine, 12901 North 30th Street, Box 41, Tampa, Florida, 33612-4799; Anerico Gonzalvo, Department of Pathology, Tampa General Hospital, Davis Island, Tampa, Florida, 33606; Bruce C. Cowell, Department of Biology, Life Sciences 169, University of South Florida, Tampa, Florida 33620; Jai K. Nayar, Florida Medical Entomology Laboratory, 200 9th Street S.E., Vero Beach, Rorida, 32962; and Luz Uribe, Primera Avenida 1477, Santiago, Chile

Immunity to Brugia pahangi in athymic nude and normal mice: eosinophilia, antibody and hypersensitivity responses

Summary Congenitally athymic nude (nu/nu) mice, immunologically reconstituted by thymus grafting before inoculation with infective larvae, and mice heterozygous for the nu gene (nu/+), mounted potent protective humoral and cellular immune responses to Brugia pahangi. Although responses were not identical, both groups of mice produced IgM, IgG and IgE antibodies specific for adult worm antigen (S‐Ag) present in a crude aqueous extract, made immediate and delayed hypersensitivity footpad swelling responses when challenged with S‐Ag and eliminated their infection in the early larval stages. Heterozygotes also exhibited a marked eosinophilia which peaked coincident with larval killing. In contrast, thymus grafting of patent nudes had no effect upon microfilaraemias or adult worm burdens and did not completely protect against a challenge larval inoculum although antibodies specific for S‐Ag were produced. With the occasional exceptions of moderate immediate footpad swelling and very low titres of IgM specific for S‐Ag, no specific immune responses to B. pahangi were found in ungrafted nude mice which allowed full development of adult worms and supported patent infections.