New Players in the Same Old Game: Disturbance of Group 2 Innate Lymphoid Cells in HIV-1 and Mycobacterium leprae Co-infected Patients.

Leprosy control is achieved through a fine-tuning of TH1 and TH2 immune response pattern balance. Given the increasing epidemiological overlay of HIV and M. leprae infections, immune response in co-infected patients consists in an important contemporary issue. Here we describe for the first time the innate lymphoid cells compartment in peripheral blood of leprosy and HIV/M. leprae co-infected patients, and show that co-infection increases group 2 innate lymphoid whilst decreasing group 1 innate lymphoid cells frequencies and function.

No association of cryptococcal antigenemia with poor outcomes among antiretroviral therapy-experienced HIV-infected patients in Addis Ababa, Ethiopia.

INTRODUCTION: There are limited data on clinical outcomes of ART-experienced patients with cryptococcal antigenemia. We assessed clinical outcomes of a predominantly asymptomatic, ART-experienced cohort of HIV+ patients previously found to have a high (8.4%) prevalence of cryptococcal antigenemia. METHODS: The study took place at All Africa Leprosy, Tuberculosis and Rehabilitative Training Centre and Black Lion Hospital HIV Clinics in Addis Ababa, Ethiopia. A retrospective study design was used to perform 12-month follow-up of 367 mostly asymptomatic HIV-infected patients (CD4<200 cells/µl) with high levels of antiretroviral therapy use (74%) who were previously screened for cryptococcal antigenemia. Medical chart abstraction was performed approximately one year after initial screening to obtain data on clinic visit history, ART use, CD4 count, opportunistic infections, and patient outcome. We evaluated the association of cryptococcal antigenemia and a composite poor outcome of death and loss to follow-up using logistic regression. RESULTS: Overall, 323 (88%) patients were alive, 8 (2%) dead, and 36 (10%) lost to follow-up. Among the 31 patients with a positive cryptococcal antigen test (titers ≥1∶8) at baseline, 28 were alive (all titers ≤1∶512), 1 dead and 2 lost to follow-up (titers ≥1∶1024). In multivariate analysis, cryptococcal antigenemia was not predictive of a poor outcome (aOR = 1.3, 95% CI 0.3-4.8). A baseline CD4 count <100 cells/µl was associated with an increased risk of a poor outcome (aOR 3.0, 95% CI 1.4-6.7) while an increasing CD4 count (aOR 0.1, 95% CI 0.1-0.3) and receiving antiretroviral therapy at last follow-up visit (aOR 0.1, 95% CI 0.02-0.2) were associated with a reduced risk of a poor outcome. CONCLUSIONS: Unlike prior ART-naïve cohorts, we found that among persons receiving ART and with CD4 counts <200 cells/µl, asymptomatic cryptococcal antigenemia was not predictive of a poor outcome.

Lower numbers of natural killer T cells in HIV-1 and Mycobacterium leprae co-infected patients.

Natural killer T (NKT) cells are a heterogeneous population of lymphocytes that recognize antigens presented by CD1d and have attracted attention because of their potential role linking innate and adaptive immune responses. Peripheral NKT cells display a memory-activated phenotype and can rapidly secrete large amounts of pro-inflammatory cytokines upon antigenic activation. In this study, we evaluated NKT cells in the context of patients co-infected with HIV-1 and Mycobacterium leprae. The volunteers were enrolled into four groups: 22 healthy controls, 23 HIV-1-infected patients, 20 patients with leprosy and 17 patients with leprosy and HIV-1-infection. Flow cytometry and ELISPOT assays were performed on peripheral blood mononuclear cells. We demonstrated that patients co-infected with HIV-1 and M. leprae have significantly lower NKT cell frequencies [median 0.022%, interquartile range (IQR): 0.007-0.051] in the peripheral blood when compared with healthy subjects (median 0.077%, IQR: 0.032-0.405, P < 0.01) or HIV-1 mono-infected patients (median 0.072%, IQR: 0.030-0.160, P < 0.05). Also, more NKT cells from co-infected patients secreted interferon-γ after stimulation with DimerX, when compared with leprosy mono-infected patients (P = 0.05). These results suggest that NKT cells are decreased in frequency in HIV-1 and M. leprae co-infected patients compared with HIV-1 mono-infected patients alone, but are at a more activated state. Innate immunity in human subjects is strongly influenced by their spectrum of chronic infections, and in HIV-1-infected subjects, a concurrent mycobacterial infection probably hyper-activates and lowers circulating NKT cell numbers.

Atypical presentation of leprosy in HIV.

Atypical presentations can be expected when leprosy, a mycobacterial disease is associated with HIV. We report a case of a 28 year old male driver with a high risk behavior, who came for evaluation of hypoaesthetic, scaly erythematous plaques over face, trunk, upper extremity; verrucous lesions over elbows and necrotic lesions over the neck and lower extremities since 6 months. No other systemic complaints were present. Nerve examination showed grossly thickened left greater auricular nerve and cord like thickening of bilateral ulnar and lateral popliteal nerves. His investigations revealed anemia, a reactive ELISA for HIV-1 and CD4 of 400 cell/cmm. Ultrasonography of the thickened nerves revealed an abscess in the left ulnar nerve whereas the left greater auricular nerve showed neuritis. Histopathology from an erythematous plaque was suggestive of borderline tuberculoid leprosy in reaction. Final diagnosis was borderline tuberculoid leprosy in type 1 reaction with atypical and varied morphology in an immunocompromised male with neuritis of the left greater auricular nerve, a silent left ulnar nerve abscess with early left ulnar nerve palsy. Our case highlights the atypical morphology of leprosy lesions and the unexpected protective cellular response as suggested by formation of nerve abscess in a HIV positive patient.

Non-familial multiple keratoacanthomas in a 70 year-old long-term non-progressor HIV-seropositive man.

We describe here multiple keratoacanthomas in an Human Immunodeficiency Virus (HIV)-seropositive 70 year-old man. The patient had multiple epithelial tumors of the skin showing rapid growth, histopathological features of a keratoacanthoma and a conspicuous tendency toward spontaneous remission. A diagnosis of nonfamilial multiple keratoacanthoma was established. The patient had a CD4 count of 633 cells/microL. The HIV disease in our patient was of a nonprogressive nature with CCR5-positive T cells.

Western blot profile in HIV infection.

BACKGROUND: Although the overall sensitivity and specificity of the western blot (WB) test for detection of antibodies to various viral proteins is high, there has been a substantial difference in the timing of the appearance of antibody bands and their intensities during different stages of HIV infection. AIMS: Mapping different band patterns of Western blot results and correlating them with stages of HIV infection. METHODS: We performed a retrospective study with 1,467 HIV-1 infected cases confirmed by WB test between January 2002 to July 2005, with the objective of mapping different band patterns of western blot results and determining whether the presence or absence of certain bands was associated with any specific stage of HIV infection. For the interpretation of the WB results in this study, the guidelines recommended by NACO, India were followed. RESULTS: Reactivity with all the bands was the most commonly observed WB pattern, occurring in 92.91% (1363/1467) of cases, whereas the other 7.09% showed uncommon band patterns. Of all individual bands, p31 band was the most frequently missing one, absent in 7.09% cases. On classifying the WB reactive cases by the WHO clinical staging system, 38.45% (564/1467) were in Stage 1, 47.99% (704/1467) in stages 2 and 3 and 13.56% in stage 4. Correlation of CD4 cell counts with the various uncommon band patterns showed that only 5.56% (4/72) had counts in the 200-500 cells/microl range, whereas 45.83% and 48.61% had counts of < 200 and> 500 cells/microl respectively. CONCLUSION: Interpretation of the WB band pattern in combination with clinical features may be occasionally useful in predicting the stage of HIV infection.

AIDS vaccine: present status and future challenges.

Development of a preventive vaccine for HIV is the best hope of controlling the AIDS pandemic. HIV has, however, proved a difficult pathogen to vaccinate against because of its very high mutation rate and capability to escape immune responses. Neutralizing antibodies that can neutralize diverse field strains have so far proved difficult to induce. Adjuvanting these vaccines with cytokine plasmids and a "prime-boost," approach is being evaluated in an effort to induce both CTL and antibody responses and thereby have immune responses active against both infected cells and free viral particles, thereby necessitating fewer doses of recombinant protein to reach maximum antibodies titers. Although obstacles exist in evaluation of candidate HIV vaccines, evidence from natural history studies, new molecular tools in virology and immunology, new adjuvants, new gene expression systems, new antigen delivery systems, recent discoveries in HIV entry and pathogenesis, and promising studies of candidate vaccines in animal models have provided reasons to hope that developing a safe and effective AIDS vaccine is possible and within reach.

Testing for antibody to human immunodeficiency virus type 1 in a population in which mycobacterial diseases are endemic.

During a large epidemiologic study in the Karonga District of northern Malawi, serum samples from 139 patients with incident leprosy, 124 with newly diagnosed leprosy, 277 patients with incident tuberculosis, and 2296 controls were tested for antibodies to human immunodeficiency virus. Sera were tested according to a four-test protocol using two ELISAs and two particle agglutination assays. Overall, 188 samples were considered positive, 2634 were considered negative, and 14 were indeterminate. All 18 available positive specimens from leprosy patients, a random sample of 14 positive specimens from tuberculosis patients, and 15 positive specimens from controls were tested by Western blot. There was no evidence of substantial numbers of ELISA false-positives in any patient group or among controls.

Cellular immune response to Mycobacterium leprae infection in human immunodeficiency virus-infected individuals.

The immune responses to Mycobacterium leprae and other mycobacterial antigens were studied in 11 leprosy patients with concurrent human immunodeficiency virus type 1 (HIV-1) infection. Three patients manifested borderline lepromatous leprosy, and eight patients had borderline tuberculoid (BT) leprosy. Despite the low CD4+ T-cell count in the peripheral blood, no histologic or phenotypic change in the cellular infiltrate in either the lepromatous or tuberculoid lesions was observed when compared with HIV-1-negative patients. Lepromatous lesions contained heavily parasitized macrophages and few CD8+ T cells. Lesions from the patients with BT leprosy showed extensive CD4+ T-cell infiltration despite a significant reduction in CD4+ T-cell counts in the peripheral blood. No acid-fast bacilli were detected in the tuberculoid lesions. HIV-1 infection did not alter the lack of response in lepromatous leprosy to M. leprae antigens either in vitro or in vivo. In contrast, the skin test response to M. leprae antigens as well as the in vitro lymphoproliferative responses to mycobacterial antigens that are usually seen in patients with tuberculoid leprosy were abrogated in the BT HIV-1+ patients. However, production of gamma interferon in response to the same stimuli was preserved in most of the patients. Analysis of cytokine gene expression showed activation of additional cytokine genes in the unstimulated peripheral blood cells of patients with both leprosy and HIV-1 infections as compared with cells from patients with leprosy alone. These results suggest that granuloma formation in leprosy can be independent of the impaired CD4+ T-cell response of the HIV-1 infection. Furthermore, in HIV-1+ individuals with M. leprae infection, activation of cytokine genes is observed even when the circulating CD4+ T-cell count is significantly reduced.

Prevalence of HIV infection and high-risk characteristics among leprosy patients of south India; a case-control study.

With the observation of the occurrence of the human immunodeficiency virus (HIV) infection among leprosy patients in our pilot study carried out in Tamil Nadu, South India, a case-control study was planned to explore whether HIV infection is a risk factor for leprosy and to understand the characteristics of HIV infection and high-risk behaviors among leprosy patients. We screened 556 patients and 1004 nonleprosy controls (matching 502 cases for age, sex and area of residence) for HIV-1 and HIV-2 antibodies. They also were interviewed for personal information on history of blood transfusion, intravenous drug abuse, high-risk sexual behavior, and sexually transmitted diseases. Of the 1019 total cases screened (of both pilot and extended studies), 5 were found to be position for HIV antibodies (HIV-1 = 4, HIV-2 = 1); of the 1019 nonleprosy controls, 6 were positive for HIV-1 antibodies. An analysis by odds ratio revealed no association between leprosy and HIV infection (OR = 0.824, 95% CI = 0.201-3.593). A strong association was found only between high-risk behavior and HIV infection (OR = 5.186, 95% CI = 1.717-15.667). However, unmarried, unmarried after 30 years of age, exposure to spouses of the leprosy patients, and a history of surgery were all observed to be significantly more common among leprosy patients than the controls.

HIV-1 infection as a risk factor for leprosy; a case-control study in Tanzania.

A case-control study was carried out in Tanzania to determine the relative risk of those with HIV-1 infection for getting leprosy. Cases were 93 consecutively diagnosed patients with leprosy aged 15-54 years from the Mwanza Region. Controls were a representative population sample of 4161 people drawn from a stratified cluster sample from urban areas, roadside settlements, and rural villages. HIV-1 infection was determined by enzyme-linked immunosorbent assay (ELISA); Western blot was used when the ELISA result was indeterminate. The HIV-1 prevalence in leprosy cases was 10% in rural (7 of 72) and in roadside and urban areas (2 of 21); in controls these prevalences were 3.4% and 9.9%, respectively. The relative risk of HIV-1 infection for the development of leprosy was estimated to be 2.2 [95% confidence interval (CI) = 1.0-4.7; p = 0.07]. HIV-1 infection was significantly associated with multibacillary (MB) leprosy (odds ratio 4.6; CI = 1.3-13.2) but not with paucibacillary leprosy (odds ratio 1.4; 95% CI = 0.4-3.8). The population etiological fraction for the development of MB leprosy attributable to HIV-1 infection in this population is estimated to be 13% (95% CI = 4%-23%). We conclude that HIV-1 is a risk factor for the development of MB leprosy. The impact of the HIV-1 epidemic on the incidence of leprosy so far has been limited since HIV-1 occurs mainly in urban areas and leprosy in rural areas.

Leprosy reversal reaction in HIV-positive patients.

We report two cases of leprosy in HIV-infected patients who, by their clinical, histological and immunological features, enhance the evidence that HIV-positive leprosy does not differ from nonHIV-positive leprosy. Moreover, extensive studies of reversal reactions in HIV-positive patients might be of great interest in determining the exact pathogenesis of this leprosy reactional state.

Mechanisms of immunosuppression.

Immunosuppresive disease is a major economic concern in domestic poultry production. Although many immunosuppressive agents have been described, mechanisms of how infectious and noninfectious agents compromise the immune system are poorly understood in avian species. Two categories, generalized and antigen-specific immunosuppression have been described in mammals. Generalized immunosuppression produces overall reduced responsiveness and increased susceptibility to a wide variety of infectious and neoplastic diseases. The best characterized immunosuppressive mechanisms are described in HIV-1 infections that lead to acquired immune deficiency syndrome (AIDS) in humans. In contrast, the antigen-specific suppression observed in human leprosy illustrates how an infecting agent selectively suppresses host responses against itself favoring bacterial spread. Both diseases have well-defined clinical staging classifications that correlate with specific immunological defects. An approach to studying immunosuppressive mechanisms in the avian suggests the need for relating pathogenesis with tests of immune responsiveness using a series of increasingly more specific immunological assays to pinpoint defects.