HIV-2 infection is associated with preserved GALT homeostasis and epithelial integrity despite ongoing mucosal viral replication.

The mechanisms that enable preservation of gut mucosal integrity during persistent viral replication and inherent inflammation remain unclear. Here, we investigated, for the first time, gut homeostasis in HIV-2 infection, a naturally occurring form of attenuated HIV disease. We found viral replication in both sigmoid and ileum of asymptomatic HIV-2+ patients (range: 240-851 circulating CD4+T-cells per µl) despite their undetectable viremia, accompanied by interferon-γ-producing CD8 T-cell expansion, irrespective of antiretroviral treatment. Nevertheless, there was no CD4 T-cell depletion, and Foxp3+ and IL-17- or IL-22-producing CD4 T-cell numbers were unaffected. Moreover, IL-22-producing innate lymphoid cells and IL-22-induced antimicrobial peptides and mucins were maintained. In agreement, the epithelium histology was preserved, including tight junction protein zonula occludens (ZO-1) levels. Furthermore, in vitro infection of colon epithelia with primary isolates revealed no HIV-2 impact on ZO-1 expression. Notably, sigmoid transcriptional levels of CCL20 and CCL28 were significantly increased, in direct correlation with GM-CSF, indicating a local response able to enhance CD4 T-cell recruitment. In conclusion, maintenance of mucosal integrity in HIV-2 infection was associated with T-cell recruitment responses, potentially counteracting CD4 T-cell depletion due to HIV-2 replication. These data have unique implications for the design of therapies targeting gut homeostasis in HIV-1 infection and other chronic inflammatory settings.

Population mobility and the changing epidemics of HIV-2 in Portugal.

INTRODUCTION: Portugal is the European country with the highest frequency of HIV-2 infection, which is mainly concentrated in West Africa. The cumulative number of notified HIV-2 infections in Portugal was 1813 by the end of December 2008. To better characterize the dynamics of HIV-2 infection in the country and to obtain data that may be of use in the prevention of the spread of HIV-2, we evaluated a large pooled sample of patients. PATIENTS AND METHODS: Five Portuguese hospitals provided data on HIV-2-infected patients from 1984 to the end of 2007. Data concerning demographic characteristics and clinical variables were extracted. Patients were stratified according to date of diagnosis in approximately 5-year categories. RESULTS: The sample included 442 patients, accounting for 37% of all HIV-2 infections notified in Portugal during that period. HIV-2-infected patients showed clearly different characteristics according to the period of diagnosis. Until 2000, the majority of HIV-2-infected patients were Portuguese-born males living in the north of the country. From 2000 to 2007, most of the patients diagnosed with HIV-2 infection had a West African origin, were predominantly female and were living in the capital, Lisbon. The average age at diagnosis and loss to follow-up significantly increased over time. CONCLUSION: HIV-2 infection has been documented in Portugal since the early 1980s and its epidemiology appears to reflect changes in population movement. These include the movements of soldiers and repatriates from African territories during the independence wars and, later, migration and mobility from high-endemicity areas. The findings of this study stress the importance of promoting migrant-sensitive health care.

Smear microscopy to diagnose tuberculosis early and prevent further transmission in a population with a high prevalence of HIV infection.

In western Europe, Portugal has the highest incidence of tuberculosis (TB). The quickest way to diagnose TB is with a positive smear. To evaluate the usefulness of smear microscopy in a population with a high HIV seroprevalence, TB patients admitted during the year 2000 were retrospectively analyzed. Of the 74 TB patients admitted, 45 (61%) had pulmonary TB, 11 having multiresistant (MR)-TB. Considering that only half of the patients with pulmonary TB had a positive smear, a high degree of clinical suspicion is of great importance. Appropriate isolation facilities for TB are much needed, in order to prevent nosocomial TB spread.

Automated malaria diagnosis using pigment detection.

Several new methods of malaria diagnosis have recently been developed, but these all rely on clinical suspicion and, consequently, an explicit clinical request. Although some methods lend themselves to automation (eg. PCR), no technique can yet be used for routine clinical automated screening. Detection of birefringent haemozoin has been used to diagnose malaria since the turn of the 20th century. A new generation of full blood count analysers, used widely in clinical laboratories, have the potential to detect haemozoin in white blood cells and probably erythrocytes. Thomas Hänscheid, Emilia Valadas and Martin Grobusch here describe this novel technique for malaria diagnosis and discuss its potential applications.

Monocyte-derived macrophage cytokine responses induced by M. bovis BCG.

SETTING: One important aspect of macrophage function is the production of inflammatory and anti-inflammatory cytokines, which in turn affect the survival of intracellular organisms such as mycobacteria. OBJECTIVE: To determine the relationship between phagocytosis of mycobacteria and expression of intracellular cytokines. DESIGN: Phagocytosis and cytokine production were studied simultaneously within human monocyte-derived macrophages (MDMs) from healthy donors using fluorescent labelling of M. bovis BCG and flow cytometry. RESULTS: At a range of infection ratios (5:1, 1:1, 0.2:1) TNF- alpha, IL-10, IL-6 and IL-12 were all produced in a dose-dependent manner. At an infection ratio representative of the in vivo situation (1:1), cytokine production was induced in both MDMs containing intracellular M. bovis BCG and in uninfected bystander MDMs. Phagocytosis increased over time, but there was considerable donor variation: the proportions of cells containing one or more mycobacterium were 15.4+/-14.8% (mean+/-SD) at 4 h and 32.7+/-21.1% at 24 h (n=19). Analysis of cytokine production by MDMs not containing mycobacteria (bystander cells) at 4 h revealed that these uninfected cells produced 79+/-6.6% of the TNF- alpha, 53.9+/-40.0% of the IL-10 and 64.2+/-12.4% of the IL-12. By 20 h these proportions had decreased to 57+/-13.5%, 30.9+/-7.4% and 45.5+/-13.3% respectively. CONCLUSION: Both infected and bystander MDMs can be stimulated to produce cytokines in response to M. bovis BCG, indicating that the ability of MDMs to produce cytokines is not necessarily dependent on the ability to phagocytose mycobacteria.

Usefulness of immunochromatographic detection of antibodies to Mycobacterium tuberculosis as an adjunct to auramine staining for rapid diagnosis of tuberculosis in a low-prevalence setting.

A novel immunochromatographic membrane-based assay for the detection of specific IgG antibodies to Mycobacterium tuberculosis was evaluated in patients with active tuberculosis in a low-prevalence population. The sensitivity of the test for detecting active tuberculosis was 41.5% (17/41 patients positive); its specificity in a group of patients with other lung diseases was 91.4% (3/35 false positive), while in a group of 47 healthy controls it was 100%. The sensitivity of the immunochromatographic test equaled that of auramine staining, but different subsets of tuberculosis patients were detected by the two tests. The suboptimal sensitivity of this immunochromatographic test implies that, even though it could be a useful adjunct, it cannot be a replacement for the diagnosis of tuberculosis by other microbiological methods along with clinical and radiological data.

[Neurosyphilis and AIDS]. / Neurossífilis e SIDA.

Syphilis in HIV-infected patients reveals some particular aspects which are clinically relevant and disturbing: it is more frequent and develops more quickly to late stages, namely neurosyphilis; this progression may happen even if classic therapy in the early stages has been undertaken; the diagnosis of neurosyphilis is rather complex, the serological tests being of no definite credit; high doses of intravenous penicillin should be administered for a long period. We report a case that exemplifies the aspects described above.