HIV-related nontuberculous mycobacterial infection: incidence, survival analysis and associated risk factors.

To evaluate the incidence and survival time for AIDS-patients affected by different stages of nontuberculous mycobacterial (NTM) infection we performed a retrospective study. Data of 1540 hospitalised AIDS-patients was analyzed with respect to survival time and incidence rates. The overall incidence rate of NTM following AIDS was 16.6/100 person-years (PY), with an increase from 12.1/100PY (1987-1990) to 18.9/100PY (1991-1994). Antiretroviral therapy (ART) and toxoplasmosis prophylaxis reduced the risk of NTM disease whereas CD4 cells <40/ microl at time of the first AIDS defining illness led to a 2.5 fold higher risk. Pneumocystis carinii pneumonia (PCP), wasting syndrome and PCP prophylaxis increased the risk of progression from colonization to dissemination. Cryptococcus neoformans infection, wasting syndrome, PCP prophylaxis and CD4 cells <40/ microl were linked to immediate NTM dissemination. Though the incidence of NTM dissemination increased by the factor 1.56 in 1991-1994, survival did not differ between patients with and without NTM infection.

Sensitivity and specificity of indirect immunofluorescence and Grocott-technique in comparison with immunocytology (alkaline phosphatase anti alkaline phosphatase = APAAP) for the diagnosis of Pneumocystis carinii in broncho-alveolar lavage (BAL).

The purpose of the study was to compare the sensitivity and specificity of the indirect method of immunofluorescence with the immunocytological technique of alkaline phosphatase anti alkaline phosphatase complex (APAAP) for the detection of Pneumocystis carinii by bronchoalveolar lavage (BAL) in HIV-1 positive patients. - 83 HIV-1 positive patients with clinical presentations suggestive of Pneumocystis carinii pneumonia (PcP) were included in the study. 28 samples were found Pc-positive by immunofluorescence (IFT), 26 by Grocott and 29 by APAAP. In comparison to the lab results 33 patients were diagnosed as PcP according to the clinical course (i.e. therapeutic outcome, drugs used, and therapy changes). Compared to the clinical diagnoses, the following lab tests proved to be false positive and false negative: false positive: IF = 1, Grocott = 0, APAAP = 4 (3F6). false negative: IF = 5, Grocott = 7, APAAP = 4 (3F6). - Grocott stain shows insufficient correlation to the clinical diagnoses (p = 0.0156, McNemar-Test, two-tailed). - The two different detection methods (IFT and APAAP) showed no significant statistical difference with regard to their sensitivity (p = 0.3438, McNemar-Test, two tailed) and specificity. Considering cost and time the immunofluorescence technique seems to be the most suitable for the diagnosis of PcP in HIV-1 positive patients.

Malignant gastrointestinal lymphomas in patients with AIDS.

HIV-associated malignant lymphomas are a common complication in late HIV infection, and there is a high percentage of gastrointestinal tract involvement. Non-Hodgkin's lymphoma was found in 108 of 2,750 HIV-positive patients (3.9%) in our institution, whereas gastrointestinal manifestation was diagnosed in 48 of 108 patients (44.4%). 44 of these cases were found during endoscopy of the upper and lower gastrointestinal tract (or by laparotomy or laparoscopy in 4 cases). Endoscopy is a reliable procedure for the diagnosis of lymphoma. Unusual manifestations such as oral, esophageal or perianal lesions and multifocal disease were common findings. Life-threatening complications such as gastrointestinal bleeding, perforation, and obstruction occurred in 37.5%. High-grade B-cell lymphomas were found in all cases including mainly lymphoblastic, immunoblastic, centroblastic and Burkitt subtypes. 52% of the patients had disseminated lymphoma with Ann Arbor stage III or IV. Standard chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisone was started in 25 patients and resulted in a mean survival time of 4.8 months. The prognosis of AIDS patients presenting with malignant gastrointestinal lymphoma depends mainly on the presence or absence of previous AIDS-defining diseases, not CD4 cells, lymphoma-associated gastrointestinal complications or the histopathologic lymphoma type at the time of diagnosis.

Cryptococcosis in HIV infection of man: an epidemiological and immunological indicator?

Cryptococcosis is an epidemiological and immunological indicator due to the absence of Cryptococcus neoformans as a saprophyte in immunocompetent humans and the advantage of specific C. neoformans culture. On this basis, a report is presented on the CD4 lymphocyte count of 36 AIDS patients suffering from cryptococcosis and other concomitant or missing opportunistic AIDS-defining infections. In 26 out of 36 patients, i.e. 72%, a CD4 lymphocyte count of < or = 50/microL (mean value 39.5%) was found. Cryptococcosis as the sole opportunistic infection was diagnosed in 5 cases (13.9%). In 31 cases, various combinations of AIDS-associated diseases were found: Pneumocystis carinii pneumonia (PCP) (n = 19), cytomegalovirus infection (CMV) (n = 10), Kaposi's sarcoma (n = 6), Mycobacterium avium intracellulare infection (MAI) (n = 5), pneumonia (n = 2), toxoplasmosis (n = 2), Candida esophagitis (n = 1), tuberculosis (n = 1), lambliasis (n = 1), salmonellosis (n = 1) and wasting syndrome (n = 5). The conspicuous simultaneous occurrence or succession of pneumocystosis and cryptococcosis and the contrasting absence of aspergillosis and mucormycosis (zygomycosis) are commented. Based on the present observations in HIV-infected persons in Berlin, a CD4 lymphocyte count of < 150/microL may be used as a parameter indicating a predisposition for cryptococcosis as an airborne AIDS-defining infection. Attention is drawn to bird droppings as the sole habitat of C. neoformans and accidental niche of various other microorganisms.

Rifabutin versus placebo in combination with three drugs in the treatment of nontuberculous mycobacterial infection in patients with AIDS.

The aim of this double-blind, randomized, placebo-controlled, 12-week study was to assess the efficacy of rifabutin (450 or 600 mg/d) in the treatment of disseminated nontuberculous mycobacterial infection in patients with AIDS. Companion drugs in both arms of the study were ethambutol, clofazimine, and isoniazid. Because of low accrual, the study was prematurely terminated when a total of 382 patients had been enrolled, of which 200 were eligible (i.e., their specimens were culture-positive for Mycobacterium avium complex [MAC] or Mycobacterium xenopi at baseline) and 102 were evaluable (i.e., they were eligible, were treated for a minimum of 6 weeks, and had at least one culture assessment after baseline). The original protocol called for a total of 220 evaluable patients. At week 12, rifabutin treatment was associated with higher, although nonsignificant, rates of bacteriologic conversion than was the placebo arm, with regard to both the eligible patients (25% vs. 18%) and the evaluable patients (45% vs. 38%). Corresponding median times to culture conversion were 42 vs. 63 days (eligible patients) and 43 vs. 69 days (evaluable patients). No significant difference was observed in clinical improvement, mortality, or toxicity between the two treatment arms. The addition of rifabutin to a triple-drug regimen may contribute to the clearance of disseminated MAC infection in patients with AIDS, without causing additional toxicity.

[67Ga scintigraphy in retroperitoneal fibrosis (RPF): indications, application and clinical relevance--report of five patients]. / 67Ga-Szintigraphie bei retroperitonealer Fibrose (RPF): Indikation, Durchführung und klinische Bedeutung.

AIM: The aim of the study was to evaluate the indication for 67Ga-citrate imaging and its clinical impact on patients with retroperitoneal fibrosis (RPF). METHOD: The scanning with ventral and dorsal projections was done 48 an 72 h after i.v.-injection of 370 Mbq 67Ga-citrate. RESULTS: In the 5 patients with idiopathic RPF included in the study, there was a remarkably high correlation between the clinical symptoms, the surgical and histologic findings, the activity of the disease and the results of 67Ga-scintigraphy. CONCLUSION: While CT and--maybe even better--MRI might perfectly show the extension, shape and contour of the fibrotic tissue, Gallium-67 scan appears to be superior in assessing the intensity and activity of the disease process.

CD4 lymphocyte count in HIV-positive persons exposed to Cryptococcus neoformans.

A report is presented on four HIV-positive homosexual men examined after several months of exposure during cleaning of a flat from masses of pigeon droppings heavily colonized by Cryptococcus neoformans. Only one out of the four persons, with a CD4 lymphocyte count of 50/microL, fell sick from systemic cryptococcosis, but not the others, with CD4 lymphocyte counts of 180, 250, and 630/microL, respectively; they remained clinically and mycologically inconspicuous and free from C. neoformans. Open questions in view of the epidemiology of opportunistic pathogens in AIDS are discussed with regard to the CD4 cell count as a parameter indicating a predisposition for cryptococcosis as an airborne AIDS-defining opportunistic infection. This has been confirmed by specific cultural diagnosis of the agent in both the environment and the patient. Already in 1987/88, the probable source of infection had been the subject of epidemiological studies on C. neoformans in Berlin.

Disseminated toxoplasmosis in AIDS patients--report of 16 cases.

Between June 1986 and October 1992, disseminated toxoplasmosis was diagnosed in 16 AIDS patients. 13 cases were diagnosed at autopsy where multiple organ involvement was documented in all 13. Three patients were diagnosed intra vitam. All 3 survived with appropriate treatment. Clinical features indicative of disseminated toxoplasmosis were: fever of unknown origin between 39 degrees and 40 degrees C in 16 cases, clinical signs suggestive of sepsis or septic shock in 15, with progression to multiorgan failure in 10, disseminated intravascular coagulopathy in 6, confusion, disorientation or apathy in 13 and lack of a systemic pneumocystis carinii prophylaxis in all 16. Typical laboratory markers were: CD4 cell counts below 100 x 10(6)/l in 16 cases, elevation of serum lactic dehydrogenase in 16 and creatine phosphokinase (in 4/6), normal or only slightly elevated C-reactive protein (in 9/11), positive Toxoplasma gondii IgG antibodies in 15/16 and negative IgM antibodies in all 16. Lesions indicative of cerebral toxoplasmosis were visualized on cranial computerized tomography in only 3/10 evaluated patients. In patients with advanced HIV infection presenting with a systemic illness, including the clinical and laboratory features described above, systemic Toxoplasma gondii infection must be included in the differential diagnosis. In these patients, specific and if warranted, invasive diagnostic procedures followed by early vigorous therapeutic intervention should be considered.

Disseminated toxoplasmosis with sepsis in AIDS.

A 24-year-old woman with acquired immunodeficiency syndrome was admitted with septic fever of unknown origin and a 2-week history of diarrhea. Clinical diagnostic procedures did not reveal the cause of sepsis. Broad-spectrum antibiotics and intensive symptomatic therapy could not prevent progressive deterioration. The patient developed septic shock and consumptive coagulopathy and died 6 days after admission. Autopsy revealed disseminated infection with toxoplasma gondii and multiple organ manifestations. We conclude that disseminated toxoplasmosis should be considered in AIDS patients with septic disease of unknown origin. Extremely elevated lactate dehydrogenase may suggest disseminated toxoplasma gondii infection. New procedures such as polymerase chain reaction for detection of toxoplasmosis may be helpful diagnostic tools.

Gastrointestinal symptoms in patients infected with human immunodeficiency virus: relevance of infective agents isolated from gastrointestinal tract.

The correlation of gastrointestinal symptoms and infections in 186 consecutive patients with human immunodeficiency virus (HIV) infection undergoing diagnostic endoscopy (oesophagogastroduodenoscopy, n = 124; colonoscopy, n = 37; both, n = 25) was investigated. Biopsy and stool samples were examined for infective agents. Only weight loss (p = 0.003) and dysphagia (p = 0.027) were more common in patients at stage CDC IV compared with earlier stages. In three of 27 patients at stage II/III and in 93 of 159 patients at stage IV an infective agent was identified in stool or gastrointestinal biopsy specimen (p < 0.001). Cytomegalovirus (n = 35), Candida sp (n = 28), M avium complex (n = 10), and Cryptosporidium (eight) were the most frequent agents detected. At stage IV, diarrhoea was more frequent in infected compared with non-infected patients (p = 0.006); however, an infective agent was also found in 39 of 82 patients at stage IV without diarrhoea. The frequency of gastrointestinal symptoms was not consistently increased in patients harbouring specific infective agents compared with non-infected patients. Our findings indicate that the pathogenic relevance of a gastrointestinal infection in HIV infected patients has to be verified and indirectly support the existence of an HIV associated enteropathy.

Effects of zidovudine treatment on the small intestinal mucosa in patients infected with the human immunodeficiency virus.

Zidovudine is associated with hematologic toxicity and may also impair the rapidly proliferating intestinal epithelium. However, patients with human immunodeficiency virus (HIV) infection receiving zidovudine gain body weight, indicating improved absorptive function. In the present study, 33 HIV-infected patients with gastrointestinal symptoms who were undergoing duodenoscopy and who had no detectable secondary intestinal pathogens were investigated; 12 of them received zidovudine. HIV antigen p24 was detected in duodenal biopsy specimens by immunohistology in 3 of 12 patients with zidovudine treatment and in 10 of 21 patients without zidovudine treatment. Morphometry of duodenal specimens showed reduced villus surface area (P less than 0.05) without crypt hyperplasia independent of zidovudine therapy and reduced numbers of crypt mitoses in patients with mucosal HIV infection (P less than 0.001) compared with controls. In the duodenal brush border, patients with mucosal HIV infection (P = 0.006) and patients without zidovudine treatment (P = 0.009) had absent lactase/beta-glucosidase activity more frequently than controls, and all HIV-infected patients (P less than 0.025) except zidovudine recipients had decreased alkaline phosphatase activity compared with controls. These findings show a hyporegenerative atrophy of the small intestine and enterocyte dysmaturation associated with mucosal HIV infection. Improved enterocyte maturation, indicated by increased brush border enzyme activity, may contribute to the clinical benefit of HIV-infected patients from zidovudine therapy.

How do patients with HIV perceive their general practitioners?

OBJECTIVE: To study the perceptions of patients with HIV of their general practitioners in terms of knowledge, abilities, confidence, and satisfaction. DESIGN: Questionnaire survey of inpatients, outpatients, and members of a self help group. SETTING: Two city hospitals, three outpatient clinics, and one AIDS self help group in Munich and Berlin, Germany. SUBJECTS: All 402 patients available between 1 September 1988 and 31 May 1989. MAIN OUTCOME MEASURES: General practitioners' attitudes towards the patients' HIV status; patients' experience of treatment rejection; reception in the general practitioner's office; the doctor's perceived knowledge about HIV and AIDS. RESULTS: 394 of 402 patients consented to interview; 87% were registered with a general practitioner and 91% of those indicated that the doctor was aware of their HIV diagnosis. The overwhelming majority of patients (94%) had a friendly or at least neutral reception in the general practitioner's surgery and only six patients' general practitioner changed his or her behaviour for the worse because of the HIV diagnosis. Two thirds of patients said they would consult first with their primary care doctor for a physical problem, but only 13% would do so for psychological problems. Over a third of the patients did not routinely inform other doctors or medical staff about their HIV status, but there was no significant correlation between this concealment and ever having been rejected by a doctor (7%) or a dentist (12%). CONCLUSION: Most patients expressed a high degree of satisfaction with their general practitioners in terms of confidential issues, attitudes, knowledge, and management.

Hyaline globules reacting positively with zidovudine antibody in brain and spinal cord of AIDS patients.

Histology of the central nervous system in nine AIDS showed extracellular hyaline globules in the white matter of the brain and the spinal cord. In immunohistochemical studies with a battery of antibodies, the only positive reaction of these globules was with an antibody to zidovudine. High-performance liquid chromatography showed the presence of a zidovudine isomer in eluates of brain tissue from these patients.

[Manifestations of AIDS in the gastrointestinal tract]. / AIDS-Manifestationen im Gastrointestinaltrakt.

Besides central nervous system, pulmonary and cutaneous manifestations, the gastrointestinal tract and the hepatobiliary system are major organs in AIDS. Gastrointestinal symptoms due to opportunistic infections or HIV-associated tumours are common in AIDS patients. Nevertheless, a huge variety of endoscopically diagnosed mucosal lesions may not always be correlated to microbiological findings, clinical symptoms and histological aspects. Cytomegalovirus being the most important opportunistic infection in the GI tract in symptomatic AIDS patients, is correlated with erosive and ulcerative lesions, often accompanied by complications like perforation or bleeding. HIV-associated tumours in the GI tract like Non Hodgkin-lymphoma or Kaposi sarcoma may present with atypical endoscopic findings. Diagnostic procedures should include microbiological and histological investigations of biopsies looking for opportunistic infections. Besides, typical immunological changes involving the mucosa as direct target organ of the HIV virus, are important to understand morphological and functional abnormalities in HIV-patients with GI symptoms.

[Intestinal spirochetosis in HIV infection: prevalence, isolation and morphology of spirochetes]. / Intestinale Spirochätose bei HIV-Infektion. Vorkommen, Isolierung und Morphologie der Spirochäten.

The prevalence of intestinal spirochaetosis was investigated in 39 HIV-positive homosexual males (mean age 39 [24-65] years) in different stages of HIV infection (3 with the lymphadenopathy syndrome, 8 with AIDS-related complex and 28 with AIDS). Biopsies for cultural and histological demonstration of spirochaetes were obtained during routine ileoscopies. At the time of examination 35 of the 39 patients had intestinal symptoms. 27 patients had had no previous antimicrobial treatment. In 12 of the 27 previously untreated patients with intestinal symptoms spirochaetes were demonstrated, to different extent, from the terminal ileum to the rectum, while the treated group of eight and the control group of four were negative. There were no significant inflammatory changes histologically. Treatment with metronidazole in most cases improved symptoms. In their ultrastructure the microorganisms showed several complete convolutions, cone-shaped cell endings, cell length of 4-18 microns, cell diameter of 0.21-0.35 microns and five subterminal flagella. Morphological considerations favour the inclusion of these microorganisms in the genus Treponema rather than Brachyspira.

Persistence of Cryptococcus neoformans in seminal fluid and urine under itraconazole treatment. The urogenital tract (prostate) as a niche for Cryptococcus neoformans.

The open questions of the persistence of Cryptococcus neoformans in the urogenital tract under antimycotic treatment can be examined under optimal mycological-diagnostic conditions only. The example of a case of cryptococcosis in an AIDS patient diagnosed and treated with itraconazole in the early secondary stage of cryptococcosis is used to discuss the problems of the persistence of Cr. neoformans involvement in the urogenital tract (prostate). Data from a ten-week follow-up study are presented and discussed. The observations made have shown that itraconazole is effective in all regions of the body, with the exception of the urogenital tract. In addition to clinical examinations, cases treated with itraconazole should be finally subjected to cultural examination of prostatic secretion and/or seminal fluid, to exclude the possible presence of a symptom-free involvement of the prostate by Cr. neoformans.