Treatment of cryptococcosis with liposomal amphotericin B (AmBisome) in 23 patients with AIDS.

OBJECTIVE: To determine the safety and efficacy of liposomal amphotericin B (AmBisome) in the primary treatment of AIDS-associated cryptococcosis. DESIGN: A Phase II, multicentre, European, non-comparative, open study to assess the use of AmBisome in 23 patients (26 enrolments) with cryptococcosis. Dose requirements, mycological response and toxicity were documented. SETTING: Hospital-based HIV units. PATIENTS: Twenty-three HIV-1-seropositive patients. RESULTS: Drug toxicity, assessed in 25 enrolments, was well-tolerated with little renal, hepatic or haematological toxicity. Eighteen out of 23 (78%) enrolments responded clinically. Nineteen enrolments had cryptococcal meningitis: sterilization of spinal fluid was achieved in 12 out of the 18 (67%) who were mycologically evaluable. Fourteen out of the 19 (74%) responded clinically. CONCLUSION: AmBisome is well-tolerated and may be an effective formulation in the treatment of cryptococcosis.

The efficacy of halofantrine in the treatment of acute malaria in nonimmune travelers.

A multicenter prospective trial was performed to investigate the efficacy and the tolerability of halofantrine in nonimmune patients with malaria imported from areas with drug-resistant falciparum parasites (mainly Africa). Forty-five of the 74 subjects were treated with a one-day regimen (3 x 500 mg) of halofantrine, and the other 29 received the same regimen with an additional treatment on day 7. In the second group, a 100% efficacy rate was demonstrated, but in the group receiving the one-day regimen, four recrudescences were observed in patients with falciparum malaria. Only five mild adverse reactions were seen, which disappeared spontaneously after the end of the treatment. We conclude that halofantrine is highly effective in curing malaria in nonimmune subjects. The treatment scheme for such persons should include an additional treatment on day 7 for nonimmune individuals. This drug was well tolerated in our patients, indicating that halofantrine will be useful in the treatment of multidrug-resistant malaria in nonimmune persons.

Neuropsychiatric side effects after the use of mefloquine.

This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep-wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8,000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13,000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended.

Immunoglobulin G subclass preference of intrathecally produced HIV-specific oligoclonal antibodies.

Cerebrospinal fluid (CSF) and serum samples from 16 HIV-seropositive subjects were examined by ELISA and isoelectric focusing for the presence of HIV-specific immunoglobulin G (IgG) subclass antibodies. Autochthonous synthesis of IgG in the CSF was demonstrated in 11 patients. Intrathecally synthesized antibodies specific for individual HIV structural proteins were largely restricted to IgG1 (10 of 11 patients). One patient revealed additional local synthesis of IgG2 antibodies related to HIV-p15. In another patient locally produced antibodies specific for HIV consisted entirely of IgG4. In this patient amounts of locally produced antibodies were too low to be detected by routine procedures (calculation from an evaluation graph). No local synthesis of HIV-related IgG3 was demonstrated in any patient. Further studies will be needed to show whether determination of IgG-subclass-restricted antibodies to HIV is of prognostic value.

Analysis of oligoclonal antibody bands against individual HIV structural proteins in the CSF of patients infected with HIV.

Intrathecal antibody responses to HIV were investigated by a highly sensitive immunoblot assay. Serum and CSF specimens were tested for reactivity with the recombinant HIV gag proteins p15, p17 and p24 and with the recombinant transmembrane protein p41. Autochthonous production of virus-specific IgG to one or more HIV structural proteins was seen in 8 of 10 asymptomatic seropositive subjects, in 3 of 4 men with AIDS-related complex, and in 9 of 13 patients with AIDS. These results were consonant with an elevated CSF/serum antibody ratio to total HIV antigen. The high frequency of local HIV-specific antibody synthesis in seropositive individuals without related clinical symptoms indicates an early involvement of the CNS in HIV infections.

Cryptococcosis in AIDS patients: observations concerning CNS involvement.

The clinical course and response to therapy of seven patients with cryptococcosis and AIDS were reviewed. One patient was still in the primary stage of cryptococcosis in AIDS, i.e. the stage that is characterized by the sole cultural detection of Cryptococcus neoformans in the respiratory tract. The other six patients were in the secondary stage, where C. neoformans can be detected from the cerebrospinal fluid (CSF), blood, urine, faeces and other body sites. The main presenting features (headache, fever, nausea) were due to central nervous system involvement, although meningism and mental changes were rarely present, and CSF changes were very subtle. Treatment with amphotericin B and flucytosine was very effective, there being no more growth of fungi in cultures in most cases. Adverse reactions to the drugs used occurred frequently and consisted mainly of anaemia, hepatosis and fever. Diagnosis in the primary stage of cryptococcosis may improve the prognosis.

Meningovascular neurosyphilis in human immunodeficiency virus infection as a differential diagnosis of focal CNS lesions: a clinicopathological study.

The acquired immunodeficiency syndrome (AIDS) appears to alter the course of syphilis and particularly neurosyphilis. We report the case of an HIV-positive patient with two CNS lesions due to vascular complications of neurosyphilis of the meningovascular type, 18 months after he had developed a penile chancre. On admission, CT scans were inconsistent with cerebral toxoplasmosis or CNS lymphoma. At necropsy, histopathological examination showed typical Heubner's endarteritis of the basilar and posterior cerebral arteries. In AIDS patients, superadded meningovascular syphilis must be suspected, especially when CT scanning reveals the presence of multi-focal, low density lesions with the particular characteristics of infarction.

Malaria therapy in 452 patients, with special reference to the use of quinine.

We investigated the efficacy and toxic potential of antimalarial therapy regimens in 452 malaria patients treated between 1980 and 1990. Drug regimens in 330 non-immune travellers were compared with those of 122 semi-immunes with acute malaria; 71% patients acquired their infection in tropical Africa, and the 288 Plasmodium falciparum infections were the most prevalent species. Because of increasing drug resistance or toxicity of chloroquine, pyrimethamine-sulfadoxine and even mefloquine, quinine proved to be the most effective antimalarial against P. falciparum and the only one which did not lead to recrudescences. These occurred in 10% patients after chloroquine and 6% after mefloquine. Cinchonism occurred in 25% of those treated with quinine, but it was fully reversible and never necessitated withdrawal of the drug. We conclude that quinine is highly effective in the treatment of P. falciparum infection and is mandatory if the clinical condition requires a fast-acting blood schizonticide, in cases of hyper-parasitaemia and if multi-drug resistance occurs; its use should not be restricted by reversible side-effects such as cinchonism.

Isolation of atypical mycobacteria from tap water in hospitals and homes: is this a possible source of disseminated MAC infection in AIDS patients?

Infections caused by mycobacteria other than tuberculosis (MOTT), especially Mycobacterium avium complex (MAC), are common in AIDS patients, but rare in immunocompetent persons. The route of transmission is unknown, but tap water could provide a possible source of infection: MAC was isolated from tap water in the U.S.A. but this has not been reported in Germany. We therefore investigated tap water in Berlin for the presence of mycobacteria and compared radiometric (Bactec) and standard plate culture methods processing large volumes of water samples. The Bactec method yielded equal results compared to standard methods but had the advantage of easy handling. Mycobacteria were isolated from 50/118 (42.4%) samples and from 21/30 (70%) sites. The most frequently isolated species was Mycobacterium gordonae (from 28% samples and from 53.3% sites); MAC was isolated from two samples only (1.7%).

Thoracic computed tomography of patients infected with the human immunodeficiency virus: relevance for the course of disease.

To determine the diagnostic accuracy and prognostic implications of thoracic computed tomography (CT) in patients with human immunodeficiency virus infection (HIV), CT scans of 154 HIV-infected patients (mean age, 41 years; range 23-65 years; 18 female) with suspicion of pulmonary disease were retrospectively reviewed for signs of disease by two investigators blinded to clinical data other than positive HIV serology. Abnormal CT features were correlated with CD4-T lymphocyte count, histologic or microbiologic diagnosis, and survival. Computed tomography detected features of pulmonary disease in 133 patients. A recent chest film was available in 96 patients, and it was normal in 16. In 17 of 99 patients (17%) with histologic or microbiologic correlation, pathologic CT features could be demonstrated, though histologic and microbiological studies were unrevealing. Median survival was 649 days. Confluent pulmonary infiltrates and bilateral masses on CT indicated advanced disease with a median survival of 115 days (n = 11, p = 0.0005) and 174 days (n = 15, p < 0.0001), respectively. The authors concluded that thoracic CT detects pulmonary lesions in an appreciable portion of HIV-infected patients in whom chest radiographs, microbiologic methods, or histology failed to establish a diagnosis, and that CT findings allow for an estimation of patient survival in acquired immunodeficiency syndrome.

Impairment of cranio-facial nerves due to AIDS. Report of 2 cases.

2 cases of disorders of craniofacial nerves resulting from progressive multifocal leucoencephalopathy are described. Clinical symptoms occurred as facial paralysis, hypaesthesia, hemianopsia and deafness. In both patients, the impairment of the central nervous system (CNS) preceded indicative AIDS symptoms. Both patients died about 3 months after the first CNS symptoms had been diagnosed. Clinical and neurohistopathological findings as well as differential diagnoses are discussed.

Primary intraosseous AIDS-associated Kaposi's sarcoma. Report of two cases with initial jaw involvement.

AIDS-associated Kaposi's sarcoma (KS), which in 80% of cases occurs in the oral cavity, usually presents with characteristic clinical features such as brown-bluish pigmented macules or tumorous lesions. In later stages the tumor, most probably originating from the vascular endothelium, may secondarily induce erosion of the underlying bone. The primary, intraosseous occurrence of KS has prompted the present 2 case reports. The tumor presented as extensive, diffuse osteolysis within the mandible without causing clinical symptoms. Although rare, intraosseous KS must be included in the differential diagnosis of isolated bone defects in HIV-infected patients.

Oral manifestations in a patient with idiopathic CD4+ lymphocytopenia.

A 56-year-old patient with idiopathic CD4+ lymphocytopenia (ICL) is described. In addition to a complex medical history and clinical course, he presented with oral manifestations including episodic erythematous candidiasis, persistent angular cheilitis, lingua exfoliativa areata, and teleangiectasia of facial skin and buccal mucosa. Light microscopy and transmission electron microscopy (TEM) revealed vascular structures similar to findings in clinically uninvolved oral mucosa of patients with HIV infection. Further observations of patients with ICL are warranted to clarify the significance of oral findings made in the present case.

Oral manifestations of AIDS-associated non-Hodgkin's lymphomas.

While B-cell lymphomas are frequently found in AIDS patients, reports on oral manifestations are rare. Among a group of 465 HIV-infected patients 5 presented with primary oral manifestations of a malignant B-cell lymphoma. The primary site of manifestation was the maxilla in 3 cases and the mandible in 2 cases. Based on the histological and immunohistochemical examination the tumors were differentiated as Burkitt's lymphoma (n = 1), as anaplastic large cell (ALC) lymphoma of the B-cell type (n = 1), as high-grade non-Hodgkin's lymphoma not classifiable according to the Kiel classification (n = 1), as immunoblastic-plasmoblastic lymphoma (n = 1), and as centroblastic lymphoma (n = 1). Serum samples were negative for HTLV-I antibodies in 5/5 cases.

Human immunodeficiency virus-associated squamous cell carcinomas of the head and neck presenting as oral and primary intraosseous squamous cell carcinomas.

Six cases of squamous cell carcinoma arising in the head and neck of patients infected with the human immunodeficiency virus are described. This article reports the first two cases of primary intraosseous squamous cell carcinoma associated with infection with human immunodeficiency virus. Clinical presentation, results of imaging studies, histologic characteristics, therapies applied, and the clinical follow-up are described in detail for each of the six cases. These data are evaluated through a review of the current literature.

[Hyperpigmentation of the oral mucosa in HIV infection]. / Hyperpigmentierung der oralen Mukosa bei HIV-Infektion.

In ten HIV-infected patients oral hyperpigmentations (HP) were observed, which seemed to be unrelated to any of the known endogenous or exogenous etiological factors. Light microscopy revealed accumulation of Fe-negative pigment in keratinocytes of the stratum basale as well as extra- and intracellularly within the subepithelial connective tissue. The ultrastructure of HP was characterised by the occurrence of melanosomes and premelanosomes within keratinocytes, melanocytes, macrophages and occasionally in fibroblasts, while especially in keratinocytes of the superficial cell layers immature melanosomes were found. Immunohistochemical examination pointed to an increase of HLA-DR positive cells and an altered distribution pattern of immunocompetent cells within the hyperpigmented mucosa. The finding of oral HP in HIV-infected patients may occur due to an increased activity of melanocytes, an increased production of melanosomes and their increased transfer to keratinocytes.