DNA hybridisation of 309 consecutive Staphylococcus aureus clinical isolates with oligonucleotide probes specific for genes encoding Panton-Valentine leucocidin (luk-PV) and gamma-haemolysin (hlg) revealed that 99% of randomly selected strains carried the hlg locus whereas only 2% harboured the luk-PV as well as the hlg loci. Only 1% of the strains did not possess either gene. In a clinical prospective study of independent S. aureus strains, 58 Panton-Valentine leucocidin (PVL)-producing isolates were shown to be responsible for primary skin infections, mainly furuncles (86%). Phage susceptibility patterns and pulsed field gel electrophoresis (PFGE) profiles of DNA were shown to be polymorphic epidemiological markers of PVL-producing strains. In eight patients with recurrent furuncles, the PVL-producing strains isolated either from furuncles or from the anterior nares were considered to be identical in each based upon phage sensitivity profiles or PFGE patterns.

Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (TL). Such complications are seen frequently in Leishmania guyanensis infections, in which patients respond variously to first-line antileishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently, we reported that a double-stranded RNA virus, Leishmania RNA virus 1 (LRV1), nested within L. guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyperinflammatory response. This report investigates the prevalence of LRV1 in human L. guyanensis infection and its effect on treatment efficacy, as well as its correlation to symptomatic relapses after the completion of first-line treatment. In our cohort of 75 patients with a diagnosis of primary localized American TL, the prevalence of LRV1-positive L. guyanensis infection was elevated to 58%. All patients infected with LRV1-negative L. guyanensis were cured after 1 dose (22 of 31 [71%]) or 2 doses (31 of 31 [100%]) of pentamidine. In contrast, 12 of 44 LRV1-positive patients (27%) presented with persistent infection and symptomatic relapse that required extended therapy and the use of second-line drugs. Finally, LRV1 presence was associated with a significant increase in levels of intra-lesional inflammatory markers. In conclusion, LRV1 status in L. guyanensis infection is significantly predictive (P = .0009) of first-line treatment failure and symptomatic relapse and has the potential to guide therapeutic choices in American TL.

Background: Infection with human herpesvirus 8 (HHV8), also termed Kaposi's sarcoma (KS)-associated herpesvirus, is associated with all forms of KS, with primary effusion lymphoma (PEL), and with some forms of multicentric Castleman's disease (MCD), but the pathogenic role of HHV8 in these tumors and the clonal nature of KS are still unclear. The purpose of this study was to examine whether the number of terminal repeats (TRs) contained in the fused TR region of HHV8 could be used as a marker of clonality in HHV8-associated tumors. Methods: Pulsed-field gel electrophoresis (PFGE) and multiple-probe Southern blot analysis of the HHV8 TR region were performed on high-molecular-weight DNA obtained from tumoral KS, PEL, and MCD lesions. Results: These analysis showed that the fused TR region contains a large but variable number of TR units (ranging from 16 to 75) and that the viral genome is present as extrachromosomal circular DNA in these tumors in vivo, with occasional ladders of heterogeneous linear termini reflecting lytic replication. All PEL tumors and PEL-derived cell lines as well as some KS tumors contained monoclonal or oligoclonal fused TR fragments; however, the TR region appeared polyclonal in MCD tumors and in a few KS lesions. Conclusion: Several KS and PEL lesions are monoclonal expansions of a single infected cell, suggesting that HHV8 infection precedes tumor growth and thus supporting an etiologic role of latent HHV8 in these proliferations. Our finding that nodular KS lesions display all possible patterns of clonality supports the model according to which KS begins as a polyclonal disease with subsequent evolution to a monoclonal process.

Histoplasmosis due to Histoplasma capsulatum var capsulatum is a frequent systemic fungal infection in the Americas. Diagnostic and therapeutic options differ between North and South America. Disseminated histoplasmosis is an AIDS-defining infection. Prognostic factors of potentially severe presentations must be evaluated in order to facilitate the initial therapeutic choice. Patients with HIV with disseminated infections presenting with severe pulmonary and renal impairment have a poor prognosis. Cutaneous presentations are more frequent in HIV patients in South America than in North America. A murine model has shown that South American isolates have a greater virulence that North American isolates. These differences are due in part to diagnostic delays in resource-poor countries. Direct examination of May-Grünwald-Giemsa-stained smears or tissues in suspected histoplasmosis is a simple means of confirming the diagnosis in resource-poor settings. Studies of prognostic factors should further refine indication criteria to guide first-line treatment choice between amphotericin B and itraconazole. The association of tuberculosis and histoplasmosis is frequent in HIV patients and presents diagnostic and therapeutic challenges that may be difficult to resolve in resource-poor settings. It is important that affordable generic drugs for treating histoplasmosis be made widely available in resource-poor countries.

Histoplasma capsulatum var. capsulatum infection is a major AIDS-defining illness in French Guiana. Although it affects South and Central American countries, the number of published cases is low. We present the largest series of AIDS-related histoplasmosis. The aim of this work is to describe clinical features and to help optimize investigations in settings where antigen detection methods are not available. Two hundred cases of AIDS-related histoplasmosis, diagnosed in the hospitals of French Guiana, were included retrospectively between 1982 and 2007. At the time of diagnosis, 92% of patients did not receive highly active antiretroviral therapy. CD4 cell count was less than 100 cells/microl for 80% of them. Most patients had fever, lymphadenopathies, and pulmonary and digestive symptoms. Neurological signs and skin/mucosal locations were less common. Other opportunistic infections were associated in 36.6% of cases (mostly tuberculosis). In most of the patients, lactic dehydrogenase was at least four times the normal value, and there was a moderate increase of aspartate aminotransaminase but not alanine aminotransaminase levels. Bone marrow aspirations were useful, but cultures of liver and lymphadenopathy specimens were the most contributive. Following treatment initiation, 17.5% died within a month. Presumptive treatment was started before diagnostic confirmation in 14.3% of the cases. In high prevalence settings, histoplasmosis often revealed AIDS in severely immunodeficient and poorly followed patients. In the absence of a quick sensitive technique, skin smear and fungal tissue cultures are contributive. Nevertheless, given the diagnostic delays and the poor prognosis, presumptive treatment with amphotericin B-containing regimens should be recommended when clinical and epidemiological contexts are evocative.