Medium matters: modeling the impact of solid medium performance on tuberculosis trial sample size requirements.

SETTING: Two-month solid medium culture conversion is a commonly used, if suboptimal, endpoint for phase 2 anti-tuberculosis treatment trials. OBJECTIVE AND DESIGN: To model the effect of the performance characteristics (sensitivity and contamination rate) of solid medium on required sample size for a two-arm clinical trial with 85% true (gold standard) culture conversion in the control and 95% in the experimental arm. RESULTS: Increasing sensitivity and decreasing contamination reduced the sample size from 239 subjects/arm (60% sensitivity, 30% contamination) to 138 subjects/arm (95% sensitivity, 1% contamination). CONCLUSION: Optimizing solid medium has significant potential to reduce sample size and increase the efficiency of tuberculosis clinical trials.

Syphilitic hepatitis in HIV-infected patients: a report of 7 cases and review of the literature.

BACKGROUND: A recent resurgence of primary and secondary syphilis has been observed in certain population groups, particularly among persons infected with human immunodeficiency virus (HIV). Liver involvement is an infrequently recognized complication of early syphilis, with no previous reports among HIV-infected patients. METHODS: We describe 7 cases of syphilitic hepatitis in HIV-positive individuals and review the literature. RESULTS: At our institutions, all patients presented with a rash consistent with secondary syphilis. Each case was characterized by a conspicuous increase in serum alkaline phosphatase level (mean level +/- standard deviation, 905 +/- 523.6 IU/L) and milder elevations in serum transaminase levels. The mean CD4+ absolute T cell count was 317 cells/mm3, and the median rapid plasma reagin (RPR) titer was 1 : 128. There was a significant correlation between higher CD4+ cell counts and the RPR titers (R=0.93; P=.002). Symptomatic resolution and biochemical improvement, particularly a significant decrease in serum alkaline phosphatase levels (P=.02), occurred following antibiotic therapy. CONCLUSIONS: Hepatic dysfunction is not uncommon in HIV-infected persons and is attributable to multiple causes. In the appropriate clinical setting, syphilitic hepatitis is an easily diagnosed and reversible etiology of liver dysfunction. The recognition of this entity will prevent unnecessary evaluation of abnormal liver enzyme levels in HIV-positive patients.

Successful treatment of human immunodeficiency virus-related Castleman's disease with interferon-alpha.

Multicentric Castleman's disease is an atypical lymphoproliferative disorder for which multiple chemotherapeutic regimens have been used without much success. Role of biological response modifiers like interferon used as a single agent is discussed in this case report.

Mycobacterium szulgai infection of the lung: case report and review of an unusual pathogen.

The nontuberculous mycobacteria are responsible for considerable morbidity in the immunocompromised and immunocompetent host, especially in the older patient with chronic fibrotic or cavitary disease of the lung. Mycobacterium szulgai is a slow growing mycobacterium infrequent in nature and man. Except from a snail and a tropical fish, it has been isolated only from humans and nearly always represents a true pathogen. Three-drug therapy using in vitro susceptibilities as a guide for 12 to 18 months increases the likelihood of success. We present a patient who developed M szulgai pulmonary infection 30 years after an episode of pulmonary tuberculosis. After successful therapy for his M szulgai infection, this patient developed chronic pulmonary histoplasmosis. We review the 25 years of clinical experience with this mycobacteria; particular emphasis is on the presentation and treatment of this very unusual infection.

Nontuberculous mycobacterial infections.

The acquired immunodeficiency syndrome (AIDS) pandemic has led to greater understanding and respect for the pathogenic potential of non-tuberculous mycobacteria. Mycobacterium avium complex (MAC) has emerged as the most common systemic bacterial infection in AIDS, causing debilitating disseminated disease in late-stage HIV-infected patients. With the release of the macrolide antibiotics, clarithromycin and azithromycin, effective and well-tolerated therapeutic regimens for MAC have been developed which prolong survival and increase quality of life. The macrolides and rifabutin are also effective as preventive therapy for MAC in patients with AIDS. Mycobacterium kansasii, which causes pulmonary disease similar to tuberculosis as well as disseminated disease in AIDS, is treatable with isoniazid, rifampin and ethambutol. Clinical syndromes and therapeutic options for other non-tuberculous mycobacteria in AIDS are also reviewed.

Nontuberculous mycobacteria in patients with human immunodeficiency virus infection.

Because of their often profound immune suppression, persons with HIV-infection are, increasingly, being identified as having morbidity related to mycobacteria. Indeed, mycobacterial disease is now the second most frequent cause of illness in AIDS patients receiving PCP prophylaxis with the majority of these patients in the United States having disease caused by M. avium complex (MAC). This section reviews the epidemiology, clinical presentation, treatment protocols, and prophylaxis strategies for MAC, as well as the other species of nontuberculosis mycobacteria being diagnosed in the setting of HIV infection. These organisms typically cause extrapulmonary, often disseminated disease in HIV infected persons, although pulmonary disease may occur. The prompt diagnosis and successful treatment of these infections can prolong the life and enhance its quality for affected patients with HIV coinfections.

Cholecystectomy in patients with AIDS: clinicopathologic correlations in 107 cases.

The etiologic and clinical features of cholecystisis in infection due to human immunodeficiency virus (HIV) were studies retrospectively. The charts and histopathologic specimens of 136 HIV-infected patients who underwent cholecystectomy between February 1987 and May 1993 at a large tertiary care center were reviewed. Opportunistic pathogens infecting the 107 patients with AIDS included microsporidia (eight cases-- Enterocytozoon bieneusi in six and Septata intestinalis in two); cytomegalovirus alone (six cases); Cryptosporidium alone (eight cases); cytomegalovirus plus Cryptosporidum (15 cases); and Pneumocystis carinii and Isospora belli (one case each). In addition, histopathologic changes characteristic of Kaposi's sarcoma were seen in one case. Thirty-eight patients with AIDS had acalculous cholecystitis for which no etiologic agent was found. Twenty-eight AIDS patients had cholelithiasis, six with coexistent opportunistic gallbladder infection. In the 107 AIDS patients, no specific symptom was found to be predictive of opportunistic infection of the gallbladder, but such infection was significantly associated with an abnormal abdominal ultrasound (P = .017) and with nonvisualization of the gallbladder by radionucleotide biliary scan (P < .001).

Disseminated toxoplasmosis and acquired immunodeficiency syndrome: diagnosis by transmission electron microscopy.

A 43-year-old, bisexual, black man with acquired immunodeficiency syndrome (AIDS), detected by CD4 lymphocyte criteria alone, presented with low-grade fever, chills, malaise, and watery diarrhea of 2 days' duration. Over the next 5 days, he developed a fulminant septicemia-like illness with progressive hypotension, disseminated intravascular coagulation, and very high serum lactic acid dehydrogenase (2,150 U/L) and serum creatine phosphokinase (5,395 U/L) levels, and died. The cause of this illness was not clinically apparent. A bone marrow biopsy performed on the day of his death revealed intracytoplasmic clusters of 3 microns long, oval, basophilic organisms, the exact nature of which was not evident by light microscopy. The diagnosis of disseminated toxoplasmosis (DT) was made only after electron microscopic study of the bone marrow revealed organisms with features typical of Toxoplasma gondii tachyzoites. These features included a multilayered pellicle, a pointed anterior end containing a conoid, up to nine rhoptries, sparse micronemes, and a posterior end containing a nucleus. Some of the organisms had divided by internal budding or endodyogeny. This case illustrates the value of transmission electron microscopy in making the diagnosis of DT.

Intestinal spirochetosis and acquired immunodeficiency syndrome: ultrastructural studies of two cases.

Two cases of intestinal spirochetosis (IS) with acquired immunodeficiency syndrome are reported. In case 1, a 48-year-old homosexual black man presented with a 1-month history of alternating watery diarrhea and constipation, which dissipated following the removal of two colonic hyperplastic polyps containing IS. In case 2, a 26-year-old homosexual black man presented with a 3-month history of persistent bloody diarrhea and was found to have chronic shigellosis and IS. Pathologic findings of IS were similar in both cases. Basophilic fringes typical of IS covered the surfacing colonic epithelium and consisted of dense growths of spirochetes adherent to and oriented perpendicular to the plasma membranes of the surfacing epithelium. The spirochetes measured 3 to 5 microns in length and 0.2 micron in width, contained four to eight axial fibrils, and closely resembled Brachyspira aalborgi ultrastructurally. These cases are notable because the histopathologic changes of IS were more extensive than generally described. There was involvement of both the right colon and rectum by IS in case 2, and in both cases there was extension of the IS down into the crypts of Lieberkühn, spirochetal invasion of the colonic mucosa, and a conspicuous inflammatory response by macrophages in the underlying lamina propria.