Cryptococcal meningitis among HIV infected patients

Cryptococcal meningitis is an emerging opportunistic infection among HIV infected patients and an important cause of mortality among these patients. The incidence of cryptococcal meningitis varies from place to place. A total of 31 specimens of CSF out of 89 samples processed from known HIV positive cases yielded Cryptococcus neoformans during the period of 3 years. C.neoformans was the most common opportunistic pathogen isolated from CSF samples of these patients with an incidence of 34.8%     

Cutaneous cryptococcosis in a donkey

A 7-year-old indigenous male donkey presented with a 3-month history of non-healing ulcerated nodular lesions involving the skin and subcutaneous tissue of the ears. The affected ears were misshapen due to firm, small, often ulcerated nodules along with seropurulent discharge and some local. There was histopathologically granulomatous dermatitis composed of multinucleated giant cells, macrophages, lymphocytes, plasma cells, and eosinophils in the dermis. Numerous ovoid or spherical, yeast-like organisms in small clear halo or spaces were present both freely and in the cytoplasm of macrophages and giant cells. The capsule was stained by periodic acid schiff and Alcian blue stains. Based on lesion histopathology, it was diagnosed as cutaneous cryptococcosis. The following article documents previously unreported gross and histologic findings of cutaneous cryptococcosis in a donkey.     

Asymptomatic bearing of Leishmania infantum among Tunisian HIV infected patients

The number of visceral leishmaniasis (VL) cases is in continuous growth in Mediterranean countries. In Tunisia, in addition to the traditional infantile form, more and more cases in immunocompetent or immunocompromised adults have been reported. However, co-infection VL-HIV remains rare in Tunisia and diagnosis of all the cases up till now has been done using traditional techniques (serology, direct examination and culture of bone marrow). However, the last years, several studies proved the greatest sensitivity of PCR in VL diagnosis. We carried out a systematic detection of Leishmania in peripheral blood for 25 HIV infected patients (10 were asymptomatic, 6 presented a fever and/or a paleness and/or an asthenia, and 9 had an opportunist infection other than VL). In all cases, the culture on Novy-Nicolle-McNeal (NNN) medium was negative by the end of the month. Serology carried out for 22 patients was negative in IFI in 17 cases, positive at the 1/20 for four others and positive at the 1/40 for one patient (confirmed by Western Blot technique). A PCR using the primers Lei70L-Lei70R, specific of the gene of Leishmania infantum, allowed the display of the specific band of 345 bp for 17 samples. The higher sensitivity of PCR compared to conventional methods is subject to the difficulty of result interpretation in PCR positive testing among patients not having any other marker of the disease which raises the question of significance for this asymptomatic bearing.     

Cutaneous cryptococcosis in an immunocompetent host

An immunocompetent 62-year-old woman presented with cutaneous lesions over her right arm and the hypogastrium. The diagnosis of cutaneous cryptococcosis was made on the basis of the demonstration and isolation of Cryptococcus neoformans from the aspirated pus. The patient responded to fluconazole treatment.     

Generalized cryptococcosis in HIV infection

Two cases of generalized cryptococcosis in patients who died of HIV infection are described. The course of the disease was masked by other diseases and final diagnosis was established after necropsy. Leukemia was a clinical "mask" in one case and generalized tuberculosis in the other. Numerous cryptococci were found in different organs histologically with positive Shiff-reaction. Ultrastructurally, cryptococci were of variable forms this probably reflecting different stages of interaction between microorganisms and the host.     

Cutaneous cryptococcosis in athymic and beige-athymic mice.

The dermotropism of Cryptococcus neoformans SLHA in congenitally athymic (nu/nu) and doubly immunodeficient beige-athymic (bg/bg-nu/nu) mice is described. Both bg/bg-nu/nu and nu/nu mice developed cutaneous cryptococcosis within 7 to 12 days following intravenous challenge with 10(4) encapsulated yeast cells. Macroscopically, cutaneous lesions appeared as small subcutaneous nodules without ulceration. Cryptococcal skin lesions were observed primarily on the flank of nu/nu mice, whereas skin lesions in bg/bg-nu/nu mice were distributed over the trunk, abdomen, and face. While bg/bg-nu/nu mice had four times as many macroscopic skin lesions as nu/nu mice on day 14 after intravenous challenge, the skin lesions in nu/nu mice were larger. Histopathology revealed large foci of encapsulated yeasts extending from the basement membrane of the epidermis through the dermis to the underlying musculature. Yeasts in these lesions evoked a minimal inflammatory response that consisted primarily of macrophages. Interestingly, yeast cells appeared to be degrading collagen bundles located in the dermis. The dermotropic strain used in this study produced gelatinase and other proteases in vitro. These results indicate that C. neoformans can be dermotropic in a T-cell-deficient host and that proteases may be a virulence factor(s).     

Integrated therapy for HIV and cryptococcosis

Cryptococcosis has been one of the most common opportunistic infections and causes of mortality among HIV-infected patients, especially in resource-limited countries. Cryptococcal meningitis is the most common form of cryptococcosis. Laboratory diagnosis of cryptococcosis includes direct microscopic examination, isolation of Cryptococcus from a clinical specimen, and detection of cryptococcal antigen. Without appropriate treatment, cryptococcosis is fatal. Early diagnosis and treatment is the key to treatment success. Treatment of cryptococcosis consists of three main aspects: antifungal therapy, intracranial pressure management for cryptococcal meningitis, and restoration of immune function with antiretroviral therapy (ART). Optimal integration of these three aspects is crucial to achieving successful treatment and reducing the mortality. Antifungal therapy consists of three phases: induction, consolidation, and maintenance. A combination of two drugs, i.e. amphotericin B plus flucytosine or fluconazole, is preferred in the induction phase. Fluconazole monotherapy is recommended during consolidation and maintenance phases. In cryptococcal meningitis, intracranial pressure rises along with CSF fungal burden and is associated with morbidity and mortality. Aggressive control of intracranial pressure should be done. Management options include therapeutic lumbar puncture, lumbar drain insertion, ventriculostomy, or ventriculoperitoneal shunt. Medical treatment such as corticosteroids, mannitol, and acetazolamide are ineffective and should not be used. ART has proven to have a great impact on survival rates among HIV-infected patients with cryptococcosis. The time to start ART in HIV-infected patients with cryptococcosis has to be deferred until 5 weeks after the start of antifungal therapy. In general, any effective ART regimen is acceptable. Potential drug interactions between antiretroviral agents and amphotericin B, flucytosine, and fluconazole are minimal. Of most potential clinical relevance is the concomitant use of fluconazole and nevirapine. Concomitant use of these two drugs should be cautious, and patients should be monitored closely for nevirapine-associated adverse events, including hepatotoxicity. Overlapping toxicities of antifungal and antiretroviral drugs and immune reconstitution inflammatory syndrome are not uncommon. Early recognition and appropriate management of these consequences can reinforce the successful integrated therapy in HIV-infected patients with cryptococcosis.     

Brain cryptococcosis in HIV infection]

A 30-year-old female with HIV-infection (AIDS-stage) died with generalized, including meningoencephalitis, infection. Fungi found in the brain were identified as Cryptococcus neoformans. Fungal cells were also found in the lungs and in the necrotic phlegmon of soft tissue i. e. there was a generalized Cryptococcus infection.     

Oxidative imbalance in HIV infected patients.

We present an outline of the complex interplay of oxidants and antioxidants in infectious diseases in general, and in particular with reference to the HIV infection, and subsequent opportunistic infections. Viral and opportunistic infections may directly or indirectly cause an imbalance in prooxidant/antioxidant mechanisms and result in generation of increased steady state concentrations of reactive oxidants. In HIV patients a prooxidant state could lead to a self-perpetuation of infection via stimulated expression of genes carrying the virus genome, and subsequently to immunosuppression, and promotion of initiated cells to neoplastic growth.     

Prevalence of cryptococcosis among HIV-infected patients in Yaounde, Cameroon

Background

Cryptococcus neoformans is encapsulated yeast which causes life-threatening infections in up to 40% of AIDS patients in Africa.

Objective

To investigate the prevalence of cryptococcosis among HIV infected patients in Yaounde.

Methods

In a hospital-based surveillance study of cryptococcosis, the colonization of Cerebrospinal Fluid (CSF), urine and blood sample by C. neoformans was evaluated by direct microscopic examination and culture techniques. Data obtained were then analyzed based on the medical records of the patients.

Results

Among the105 patients sampled for the study, the CD4 counts varied between 31 and 304 lymphocytes/mm³. Direct specimens examination (n= 294) in India ink preparations revealed polysaccharide capsule in 25 (8.5%) of the samples. Upon culture, 29 (9.86 %) samples were positive of C. neoformans (23 from the CSFs and 6 from the urine). All the positive samples were obtained from patients who were not on Antiretroviral Therapy (ART). Meningo-encephalitis symptoms were observed in 13 patients with C. neoformans in CSFs.

Conclusion

This study reveals that cryptococcosis is rife in AIDS patients in Yaounde. Therefore, to minimize the death toll, we recommend that its routine check should be integrated in the management of HIV/AIDS patients.     

HIV antigen-induced release of histamine from basophils from HIV infected patients

Basophil leukocytes from 39 HIV-infected patients with various degrees of immunodeficiency and disease progression were stimulated with an HIV antigen preparation. Cells from 19 of 22 patients with AIDS and all of six patients with milder degrees of HIV-related disease showed significant histamine release. In contrast, cells from 11 asymptomatic HIV-infected patients and 11 healthy control persons released no histamine. The histamine release induced by HIV antigen was found to be inversely correlated to the number of CD4 positive T lymphocytes. These results indicate that the histamine release was related to both the clinical stage of disease and the degree of immunodeficiency. Passive sensitization experiments showed that IgE, but not IgG, was responsible for the induction of histamine release, indicating the reaction to be type 1 allergic. The histamine release caused by HIV might be involved in the development of disease because of the immunomodulating properties of this mediator.     

Pulmonary cryptococcosis in patients without HIV infection: factors associated with disseminated disease

Cryptococcus neoformans is an uncommonly recognized cause of pneumonia in HIV-negative patients. Because of its propensity to disseminate to the meninges and other sites, a lumbar puncture is recommended for patients with pulmonary cryptococcosis, regardless of other risk factors. This study explored clinical and laboratory features to help predict which patients had pulmonary disease alone versus those who had pulmonary plus extrapulmonary disease. A retrospective chart review at 15 medical centers was performed from 1990 to 2000 of all HIV-negative patients who had pulmonary cryptococcosis. Demographic, clinical, radiographic, and laboratory features were evaluated to determine factors that differentiated those patients who had extrapulmonary disease. Among 166 patients who had pulmonary cryptococcosis, 122 had pulmonary infection only and 44 had pulmonary plus extrapulmonary (disseminated) disease. A negative serum cryptococcal antigen titer was more common in patients with pulmonary disease alone (p < 0.01). Multivariate analysis demonstrated that patients who had disseminated disease were more likely than those who only had pulmonary disease to have cirrhosis (p = 0.049), headache (p < 0.001), weight loss (p = 0.003), fever (p = 0.035), altered mental status (p < 0.001), and to be receiving high-dose corticosteroids (p = 0.008). In this large cohort of HIV-negative patients with pulmonary cryptococcosis, there were easily distinguished clinical and laboratory features among patients with pulmonary disease alone versus those with pulmonary plus extrapulmonary disease. These findings may be helpful in the evaluation of HIV-negative patients with pulmonary cryptococcosis with regard to the need for lumbar puncture or to search for disseminated disease.