Hepatic and pulmonary pneumocystosis during primary prophylaxis for Pneumocystis carinii pneumonia with dapsone/pyrimethamine.
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Biomedical subjects
Publications and source records attributed to D Podzamczer.
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OBJECTIVE: To compare the efficacy and safety of two intermittent regimens for the simultaneous primary prevention of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis in HIV-infected patients. DESIGN: Prospective randomized open trial. SETTING: HIV outpatient clinic of an Infectious Disease Service and a 1000-bed university teaching hospital. PATIENTS: A total of 166 HIV-infected patients with a CD4 cell count < 200 x 10(6)/l or a CD4 percentage < 20%, without previous PCP or toxoplasmosis. INTERVENTION: Patients were randomized to oral (1) cotrimoxazole [160 mg trimethoprim (TMP) and 800 mg sulphamethoxazole (SMX)] twice a day on Mondays, Wednesdays and Fridays (n = 81), or (2) dapsone (100 mg) plus pyrimethamine (25 mg) (DP) once a week (n = 85). MAIN OUTCOME MEASURES: Clinical and biological evaluation was performed every 30-60 days. End-points were PCP, toxoplasmosis and death. Adverse reactions were considered as defined in the protocol. RESULTS: After a mean follow-up of 380 days, intention-to-treat analysis revealed that DP patients had a higher rate of PCP [13 out of 85 (15.2%) versus three out of 81 (3.7%); P = 0.01]. The cumulative rates of PCP at 12 and 24 months were 5 and 42% for DP patients and 3 and 10% for TMP-SMX patients, respectively (Mantel-Cox, P = 0.0007). Of the 29 patients who died during follow-up, 14 were in the TMP-SMX group and 15 in the DP group (not significant). Two patients in the TMP-SMX group and three in the DP group developed toxoplasmosis (not significant). Adverse reactions were common (66.7% of TMP-SMX patients and 42.4% of DP patients; P = 0.001). However, only 12.3% of TMP-SMX patients and 2.3% of DP patients (P = 0.01) had to discontinue therapy because of toxicity. CONCLUSIONS: At the given doses, DP was inferior to TMP-SMX in preventing first episodes of PCP. Although more patients and a longer follow-up are required, the regimens appeared to prevent toxoplasmosis equally well.
OBJECTIVE: To evaluate the risk of developing active tuberculosis (TB) in a cohort of HIV-1-infected patients. METHODS: Prospective longitudinal follow-up of 839 HIV-infected patients, of whom 505 (60%) were parenteral drug users and 269 (32%) homosexual men. Tuberculin skin tests were performed at baseline and annually thereafter. Prophylaxis with isoniazid (300 mg daily for 9 months) was offered to those with a positive tuberculin test (induration > or = 5 mm). Diagnosis of TB was accepted if it could be confirmed microbiologically (acid-fast bacilli seen in Ziehl-Neelsen stains or grown in Lowenstein-Jensen cultures) or pathologically (presence of caseating granulomas) and patients had consistent clinical manifestations. RESULTS: Active TB developed in 23 out of the 733 (3.1%) patients with a negative tuberculin skin test after a mean follow-up of 16 +/- 11 months (range, 2-52 months), with an estimated cumulative probability of 1.5 and 7% after 1 and 3 years, respectively (or 2.4 per 100 patient-years). None of the 87 patients with a negative tuberculin test but a positive Multitest developed TB. Conversely, 106 patients had a positive tuberculin skin test (97 at baseline and nine who converted during follow-up). Active TB developed in seven out of the 26 not receiving prophylaxis or in whom prophylaxis had to be discontinued (16.2 per 100 patient-years), in four out of 61 patients 3-27 months after having completed 9 months of prophylaxis with isoniazid (8.9 per 100 patient-years) and in none of the 19 still receiving isoniazid. When TB was diagnosed, the mean CD4 lymphocyte count of the 34 patients who developed it during follow-up was 77 +/- 103 x 10(6)/l (range, 1-400 x 10(6)/l). CONCLUSIONS: Among HIV-infected patients in whom the tuberculin skin test is negative, the risk of developing active TB is sufficient to consider prophylaxis if the CD4 count falls below 400 x 10(6)/l, at least in those patients with skin anergy living in high-risk geographical areas such as Spain. When the tuberculin skin test was positive, isoniazid (9 months) provided a 45% protection beyond the period of its administration.
Forty patients with AIDS-associated Kaposi's sarcoma (KS) treated with the combination of interferon alpha-2b (IFN-alpha) 10-20 MU day-1 and zidovudine (ZDV), 500-800 mg day-1, were evaluated for safety and efficacy. Eighteen patients (45%) had an overall response (CR+PR) at 3 months and a response persisting for a median of 14 (3-27) months. Patients with a CD4 count of less than 300 mm-3, prior to opportunistic infections or constitutional symptoms, were less likely to respond. However, between 28.5% and 36% of patients with a low CD4 count did respond to combined therapy. This is higher than would be predicted from single agent IFN-alpha therapy. Twelve of 28 patients (42.8%) receiving 10 MU day-1 of IFN-alpha (low dose) had an overall response. In addition, patients tolerated this dose of IFN-alpha better, presenting fewer flu-like symptoms and displayed a trend toward less anaemia. p24 antigen decreased in six out of nine evaluable cases, four of whom were treated with low-dose IFN-alpha. Low-dose IFN-alpha plus ZDV seems to be a useful and well-tolerated therapy for KS with antitumoral and antiviral activity. Patients without 'bad prognostic markers' are most likely to show improvement.
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Esophageal ulcers are often found in patients with human immunodeficiency virus infection. We have retrospectively reviewed the upper endoscopies performed in these patients during the last four years. 149 examinations were realized in 73 patients. Fourteen patients with esophageal ulcers were diagnosed. A severe immunological impairment was present in all patients (CD4 24.4 +/- 31.1 cells/ul). Symptoms were non-specific, with prevailing dysphagia and odynophagia. The etiological diagnosis was reached by histological studies and cultures in 5 cases (36%), three due to Herpes virus type I, one due to Cytomegalovirus and another one to Mycobacterium tuberculosis. Patients with multiple ulcers or small ones were successfully treated with antiviral drugs, even when the etiological studies were negative. Corticosteroids were useful in single and large ulcers in which diagnostic tests were negative.
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The case of a HIV positive patient with lumbosacral polyradiculomyelitis by cytomegalovirus (PLS-CMV) is presented. The patient was a homosexual male receiving maintainance treatment with foscarnet for previous corioretinitis by CMV who consulted for paraparesia and sphincter disorders of a 3 week evolution. Neutrophilic pleocytosis and high levels of glucose and proteins were observed on LCR and CMV isolated discarding other entities. The LCR normalized upon treatment with gancyclovir although serious residual paraparesia persisted. PLS-CMV is an infrequent entity of typical clinic and liquoral characteristics. Recognition of the same is important since favorable response depends on early anti-CMV treatment.
We present here three AIDS patients with disseminated cryptococcal infection and lung involvement. Two patients presented with respiratory symptoms and in the third one, pulmonary disease was only a radiologic finding. Chest X-ray films showed an interstitial pattern in two cases and pulmonary cavitation in one case. One patient has also simultaneous infection by P. carinii. Diagnosis was established by culture from bronchoalveolar lavage in all cases and also by non-induced sputum exam in two cases. All patients were treated with amphotericin B, with good clinical outcome, and without relapses under maintenance therapy with fluconazole. Cryptococcosis must be included in differential diagnosis of AIDS patients with diffuse interstitial lung infiltrates. The presence of C. neoformans in respiratory samples does not rule out the existence of other opportunistic infections, and therefore bronchoalveolar lavage is advisable.
A series of eight patients with cerebral tuberculoma seen between 1980 and 1990 is reported. Headache was the leading clinical finding, followed by focal neurological findings and seizures. Papilledema was the most uniform examination finding associated with intracranial hypertension. Five patients had another localization of tuberculosis: three had tuberculous meningitis, one had tuberculous pericarditis and only one had associated active pulmonary involvement. Cerebrospinal fluid was investigated in seven patients. In three patients data of tuberculous meningitis were found, with positive culture in Löwenstein medium. Two patients had the acquired immunodeficiency syndrome. All patients received medical treatment with good response, except in one who developed paradoxical expansion of the lesions after two months of therapy.
Ocular toxoplasmosis is an uncommonly reported complication in patients with acquired immunodeficiency syndrome. Three patients with human immunodeficiency virus (HIV) infection and ocular toxoplasmosis are reported. In two of them, cerebral toxoplasmosis was associated. Ocular involvement presented as exudative chorioretinitis, bilateral in 2 cases and unilateral in 1. The diagnosis was made on the basis of ocular disease associated with lesions consistent with toxoplasmosis of central nervous system (CNS) and response to antitoxoplasma treatment in one case, and ocular disease with rising antitoxoplasma serologic titers in the remaining two. Initial therapy included pyrimethamine plus sulfadiazine in 2 cases and pyrimethamine plus clindamycin in 1. The 2 patients treated with sulfadiazine showed hypersensitivity features, and clindamycin had to be substituted. The response to therapy was favorable, although one patient died few days after the development of CNS lesions. When chorioretinitis develops in a patient with HIV infection, ocular toxoplasmosis should be considered. As CNS involvement is commonly associated and relapse after the withdrawal of therapy is likely, these patients should be treated as those with isolated toxoplasma encephalitis.
We describe 40 HIV-seropositive patients who developed visceral leishmaniasis. All the patients lived in areas endemic for visceral leishmaniasis and belonged to groups at risk for AIDS. Twenty-three patients (57.2%) had definitive AIDS before or after diagnosis of leishmaniasis and 77.5% were classified as belonging to CDC group IV. Fever was present in 95% patients and enlargement of the liver and/or spleen in 92.5%. Lymphopenia was found in 78.3%, depression of the absolute number of CD4 lymphocytes in 90% and depression of the CD4 to CD8 ratio in all evaluated cases but leishmania antibodies were found in only 35.2%. Parasites were demonstrated in the bone marrow or liver in every case. Thirty patients (75%) showed an initial good response to antimonial drugs, although the leishmaniasis followed a chronic or relapsing course in 17 (42.5%). HIV-related mortality was 40%. A significant correlation was found only between the relapsing course of the disease and mortality. In a multivariate linear regression model, the relapsing course was the only variable that influenced mortality. Visceral leishmaniasis is an opportunistic disease that should be suspected in HIV-infected patients. We suggest that it should be included in the CDC group IV C-1 and considered as a disease indicative of AIDS.
We have studied gallium-67 citrate scan (Ga-67) in the diagnosis of lymphadenopathy in patients with HIV-associated symptoms. Thirty HIV-infected patients with lymphadenopathy, fever and/or weight loss were evaluated with Ga-67. Lymph-node biopsy and/or needle aspirations were done in all patients. Twelve of 17 patients with grade 2 or 3 Ga-67 (uptake equal to or greater than that in the liver) had mycobacteriosis, three had lymphoma, one had Kaposi's sarcoma plus Castleman's disease and one had follicular hyperplasia. The three patients with grade 1 Ga-67 (uptake greater than that in soft tissue but less than that in the liver) had follicular hyperplasia. Of the 10 patients with grade 0 Ga-67 (less than or equal to that in soft tissue), nine had follicular hyperplasia and one had Kaposi's sarcoma. Sixteen of 17 patients with grade 2 or 3 Ga-67 versus one of 13 with Ga-67 grade 1 or 0 had diseases other than follicular hyperplasia (P less than 0.0001). Ga-67 may be a practical diagnostic tool in HIV-infected patients with lymphadenopathy and constitutional symptoms. A grade 1 or 0 Ga-67 suggests the presence of follicular hyperplasia, and lymph-node biopsy may be avoided unless Kaposi's sarcoma is suspected.
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In 23 out of 227 patients with positive serological tests for the human immunodeficiency virus (10%), seen between June 1987 and May 1988, lingual lesions of hairy leukoplakia (HL) were found. HL was present in 16/188 drug abusers (9%) and in 7/19 homosexuals (32%). In 3 cases HL was the only clinical manifestation of disease, in 11 it was associated with other symptoms of acquired immunodeficiency syndrome related complex (ARC), and in 9 it was found in patients with a previous or concomitant diagnosis of acquired immunodeficiency syndrome. The mean count of CD4 lymphocytes in the 23 patients was 0.22 X 10(9)/l. The diagnosis was made on the basis of the characteristic clinical features. In 3 cases biopsy was carried out, and parakeratosis and vacuolization of the spinous layer cells were found. Remarkably, particles of the herpesvirus group were also found. The lesions oscillated in size or even spontaneously disappeared, at least transiently; however, in the patients treated with zidovudine the improvement appeared to be more significant. The detection of HL discloses a likely infection by the HIV; it is usually associated with other features of ARC and/or severe immune depression, and it requires the institution of antiretroviral treatment.
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