An outbreak of acute pulmonary histoplasmosis in members of a trekking trip in Martinique, French West Indies.

BACKGROUND: Thirteen clustered cases of American histoplasmosis, a deep mycosis caused by Histoplasma capsulatum and acquired through inhalation of airborne spores was reported. Twenty-five persons traveled in Martinique, French West Indies. Thirteen underwent trekking and passed through a mountain tunnel full of bats (tunnel group). The 12 others performed canyoning and did not go through the tunnel (control group). Fifteen days after exposure, 1 patient of the tunnel group developed fever, chills, and cough. METHODS: The index case was diagnosed in the hospital, but 12 cases where initially diagnosed as prolonged influenza. All individuals were contacted and submitted to a phone questionnaire. They were asked about eventual occurrence of influenzalike symptoms, about activities practiced, and the notion of contact with bats. All were invited to have clinical examinations, chest x-ray films, and blood samplings. Serologic testing for histoplasmosis was performed by immunodiffusion. Clinical evidence of infection with H. capsulatum was obtained in all the remaining patients of the tunnel group and in none in the control group. Symptoms occurred with an acute onset in 11 to 23 days: fever and chills, severe asthenia, headaches, digestive tract involvement, and then cough, dyspnea, hepatic involvement. Pulmonary micro- or macronodules and mediastinal adenopathies were seen on radiograph and/or computed tomography scan. RESULTS: H. capsulatum serologic tests were positive in all 13 cases with presence of specific M and or H precipitins, 5 to 13 weeks after exposure, and were negative in control group. All patients were treated with itraconazole 200 mg per day during at least 2 months. Treatment was well tolerated; patients progressively recovered. Clinical and serologic follow-up was obtained for some patients at 1 and 4 years. The present study reports the first large outbreak of histoplasmosis acquired in Martinique. CONCLUSION: Histoplasmosis still occurs and is potentially serious. In patients returning from endemic areas, presenting prolonged influenzalike symptoms, clinicians should look for previous possible exposure to Histoplasma.

Outcome of multi-drug-resistant tuberculosis in France: a nationwide case-control study.

The factors related to the outcome of 51 cases of multi-drug-resistant tuberculosis (MDR-TB) reported in 1994 to the French National Reference Center were retrospectively analyzed. The patients (median age, 45 yr) were mainly male (75%), foreign-born (63%), and had pulmonary involvement (95%). Sixteen percent were human immunodeficiency virus (HIV)-coinfected. The number of drugs to which the Mycobacterium tuberculosis isolates were susceptible was four. Only 82% of the patients have been hospitalized at any time (median duration, 33 d). Five patients (9%) received no antituberculosis drugs, although three had drug susceptibility results, indicating that two or more active drugs were available; 46 (91%) received drugs, including 37 who received two or more active drugs. Among the nine cases who received only one active drug, three had drug susceptibility results, indicating that two or more active drugs were available. By December 1996, 10 patients were lost before treatment completion, 24 had treatment failure, and 17 had a favorable outcome. The median survival time was 31 mo. Factors related to a poorer outcome were HIV-coinfection (hazard ratio [HR] = 41), treatment with less than two active drugs (HR = 9.9), and MDR status knowledge at the time of diagnosis (HR = 3.3). The country of birth was not associated with a poorer outcome. The management and outcome of MDR-TB in France has to be improved. A solution would be to develop a specialized unit or team for the treatment of MDR-TB, as recommended by the World Health Organization (WHO).

JC virus detection in the cerebrospinal fluid of AIDS patients with progressive multifocal leucoencephalopathy and monitoring of the antiviral treatment by a PCR method.

Twenty-four cerebrospinal fluid (CSF) samples from 19 AIDS patients with neurological signs were analysed by the polymerase chain reaction (PCR) for the presence of JC virus (JCV). Eleven of the 19 patients tested presented with progressive multifocal leucoencephalopathy (PML). Two specific JCV target sequences were used for the PCR analysis: a sequence specific for the T antigen genes from both BK virus (BKV) and JCV (PCR1) and a sequence specific for the large T antigen gene from JCV (PCR2). The JCV genome was detected in 10 of 11 patients with PML by the PCR1 method and in all 11 patients by the PCR2 method. With samples from the eight patients without PML, one positive result was obtained with the PCR1 method and this sample and another gave positive results with PCR2. Multiple CSF samples were collected from three patients with PML at different times, including after intrathecal cytarabine treatment, and were tested by the PCR2 method for the presence of the JCV genome. The PCR result became negative for two of the three patients during the cytarabine treatment. However, the absence of a PCR signal was not associated with clinical improvement in these patients. The PCR method is useful for the detection of JCV in CSF samples and in the diagnosis of PML. However, the application of PCR for monitoring the effect of treatment remains to be established.

[Central nervous system mycoses in AIDS with the exception of cryptococcosis. Apropos of 3 anatomo-clinical cases]. / Les mycoses du système nerveux central au cours du SIDA à l'exception de la cryptococcose. A propos de 3 observations anatomo-cliniques.

Fungal infections of the central nervous system are uncommon in human immunodeficiency virus infected patients. The most frequently encountered is cerebromeningeal cryptococcosis. We report 3 clinicopathological cases of rarer fungal infections of the central nervous system in AIDS patients due to Candida and Aspergillus genders. In most cases, a systemic candida infection or aspergillus pulmonary infection preceded the onset of cerebral granulomas or abscesses. These infections usually occurred at the terminal stage of the disease and were associated with other neuropathologies. Neutropenia associated with lymphopenia represents a frequent risk factor along with intravenous catheter.

[The natural history of tuberculosis infection and skin tuberculin reaction]. / Histoire naturelle de l'infection tuberculeuse et réaction cutanée tuberculinique.

Though most often asymptomatic, tuberculous infection induces a delayed hypersensitivity reaction in the host by activating cellular immunity thus rendering the host refractory, "a priori", to a new infection; at least provided that the infecting dose is not massive or that the immune system of the host is not compromised. Less that ten per cent of immuno-competent individuals infected by Mycobacterium tuberculosis will develop tuberculous disease during their life. The intradermal reaction (IDR to tuberculin) in revealing delayed hypersensitivity to Mycobacterial antigens is in the absence of obvious signs, the only means of diagnosing a tuberculous infection in an individual. It is performed in France by an intradermal injection of 0.1 mls (10 U) of Merieux tuberculin. The response is read at 72 hours. In those who have not had BCG vaccination, an area of induration with a diameter of greater than or equal to 10 mm gives a positive result and is evidence of a tuberculous infection. The test is negative if the diameter is less than 5 mm and indeterminate between 5 and 9 mm. These indeterminate reactions may be the consequence of previous BCG vaccination or of a contact with atypical Mycobacteria in the environment. An IDR of greater than or equal to 10 mm less than ten years after BCG vaccination would not permit any discrimination between a reaction to the vaccine or an authentic tuberculous infection. On the other hand, an IDR of greater than 10 mm ten years after BCG vaccination is evidence of renewed contact with wild tubercle bacilli in 88 per cent of cases. In individuals whose immune defence is altered in particular in patients infected with HIV the threshold of positivity for IDR is lowered to 5 mm.

Herpes simplex virus type 1 encephalitis in acquired immunodeficiency syndrome.

Herpes simplex (HSV) infection of the central nervous system is uncommon in AIDS and usually has an atypical topography. This review is centred around the case of a 49-year-old homosexual patient with AIDS who died from diffuse encephalopathy. Neuropathological examination revealed necrotic and haemorrhagic changes involving both temporal lobes, insulae and cingulate gyri. Cowdry type A intranuclear inclusion bodies were abundant but inflammation was minimal. Electron microscopy confirmed characteristic herpes virus particles. Immunocyto-chemistry was positive for HSV type 1 and 2. In situ hybridization and PCR, however, were positive for HSV type 1 but excluded HSV type 2. There was associated cytomegalovirus ventriculitis but clearly separated from HSV encephalitis. There were no histological features of HIV encephalitis and HIV could not be demonstrated by immunocytochemistry or by PCR to demonstrate proviral DNA. Apoptotic neurons were numerous in areas with a severe macrophage reaction. Only two pathological cases with characteristic limbic distribution and necrotic haemorrhagic histologic have been reported previously. The rarity of these reports suggests that in advanced AIDS, the immune reaction causing a typical necrotizing encephalitis cannot be mounted. Distinction between HSV type 1 and 2 infection may be difficult by immunocytochemistry and usually requires in situ hybridization, tissue culture or PCR. In AIDS patients, HSV-1 has been identified as responsible for encephalitis whereas HSV-2 has been more responsible for myelitis. Associated productive HIV infection of the CNS was found in none of the cases. In contrast, cytomegalovirus encephalitis was found in nine of 11 cases of AIDS-associated HSV encephalitis.

Varicella-zoster virus infection of the central nervous system in the acquired immune deficiency syndrome.

Productive varicella-zoster virus (VZV) infection of the central nervous system (CNS) was demonstrated in 11 acquired immune deficiency syndrome (AIDS) patients using immunocytochemistry and in situ hybridization. A characteristic zoster skin eruption was seen in only four cases. From our own series and 11 other cases in the literature, we identified five clinico-pathological patterns of VZV infection of the CNS in AIDS patients which could occur simultaneously. (i) Multifocal encephalitis predominantly involving the white matter, likely to be due to haematogenous spread of the infection was found in four cases. (ii) Ventriculitis was found in three cases. In two cases there was complete acute or chronic necrosis of the ventricular wall with marked vasculitis; in the third, the ependymal lining appeared irregular with foci of VZV-infected ependymal cells, some of which protruded into the ventricular lumen. (iii) Acute haemorrhagic meningo-myeloradiculitis with necrotizing vasculitis was observed in two cases. In one, this was associated with ventriculitis and was possibly due to shedding of infected ependymal cells into the ventricular lumen and secondary seeding of the CSF. (iv) Focal necrotizing myelitis was seen in one case. It followed cutaneous herpes zoster and was considered to result from neural spread from the diseased dorsal root ganglion similar to cases previously described of encephalitis limited to the visual system following VZV ophthalmicus, or bulbar encephalitis following a trigeminal zoster. (v) Vasculopathy involving leptomeningeal arteries and causing cerebral infarcts was seen in four cases, it was associated with meningitis in most cases. These findings are in keeping with the observation in non-AIDS patients that VZV spread to the CNS may follow different routes. Our study tends to show that VZV infection of the CNS occurs more frequently in AIDS than previously suspected and suggests that it must be considered as a diagnosis in cases of encephalitis, ventriculitis, focal myelitis, acute myeloradiculitis and cerebral infarcts in these patients.

[Intramedullary localization of a primary cerebral lymphoma in AIDS]. / Localisation intramédullaire d'un lymphome cérébral primitif au cours du SIDA.

A 36 years-old male with AIDS, presented with left hemiparesis revealing a right parietal tumour. Stereotactic biopsy demonstrated a malignant non-Hodgkin's lymphoma. His condition partially improved following radiotherapy and chemotherapy. Three months later he was re-admitted with progressive bilateral root pain and urinary incontinence resulting in paraplegia with sensory loss below T10. He died one month later from generalized sepsis. Neuropathology confirmed an immunoblastic B-cell malignant non-Hodgkin's lymphoma in the white matter of the right parietal lobe and revealed a centrospinal localisation of the lymphoma in the thoracic cord at T10. There was no visceral localisation of the tumour. Secondary spread to the spinal cord of malignant non Hodgkin's lymphomas, usually causes meningo-myelo-radiculitis. Intraspinal deposits of primary cerebral lymphomas are uncommon and have never been previously described in AIDS, to our knowledge. Their pathogenesis is unclear. In our case, neuropathological findings are consistent with diffusion of the primary tumour to leptomeninges and secondary infiltration of the spinal cord along the perivascular spaces.