Central role of interleukin-15 in human immunodeficiency virus (HIV)-infected patients with visceral leishmaniasis

To evaluate clinical and immunological parameters, interleukin (IL)-15 production and outcome of patients with visceral leishmaniasis (VL), including HIV positive patients, we analyzed 48 cases of VL. Clinical manifestations and response to therapy were similar in VL/HIV- and VL/HIV+ patients. However, relapses were more frequent in patients with HIV infection. Low levels of IL-15 concentrations were found in HIV+ patients without VL. These levels were comparable to concentrations obtained in healthy donors. We found a relationship between response to therapy and IL-15 levels. We found increased levels of IL-15 in VL/HIV- and VL/HIV+ patients with clinical and parasitological response to therapy. Our data demonstrate that VL in HIV-infected patients occurs in subjects with severe immunodeficiency and presents high rate of relapses. Low levels of IL-15 in illness patients and restored production in cured persons suggest that this cytokine could play a central role in immune responses during Leishmania/HIV co-infection.     

Visceral leishmaniasis in human immunodeficiency virus (HIV)-infected and non-HIV-infected patients. A comparative study

Visceral leishmaniasis is an endemic infection in Mediterranean countries, where it has become a frequent complication of acquired immunodeficiency syndrome (AIDS). The incidence of visceral leishmaniasis is increasing in Spain due to human immunodeficiency virus (HIV)-related cases, but some aspects of its epidemiology, clinical features, and management remain unknown. In addition, no comparative clinical studies about the disease in HIV-infected and non-HIV-infected patients have been reported. During a 24-year period, 120 cases of visceral leishmaniasis were diagnosed at our institution and 80 (66%) were associated with HIV infection. The mean age at diagnosis was higher in HIV-infected that in non-HIV-infected patients (33.2 versus 23.2 yr; p = 0.002), but the male/female ratio was similar in both groups. The main risk factor for HIV infection was intravenous drug abuse (78.7%). The clinical presentation of leishmaniasis was similar in both groups, but HIV-infected patients had a lower frequency of splenomegaly than HIV-negative individuals (80.8% versus 97.4%; p = 0.02). HIV-infected patients had a greater frequency and degree of leukopenia, lymphocytopenia, and thrombocytopenia. Most of them were profoundly immunosuppressed (mean CD4+ lymphocyte count, 90 cells/mm3) at the time of diagnosis of leishmaniasis, and 53.7% had AIDS. The sensitivity of serologic studies for Leishmania was significantly lower in HIV-infected than in non-HIV-infected patients (50% versus 80%; p < 0.001), but the diagnostic yield of bone marrow aspirate (67.1% versus 79.4%) and bone marrow culture (62.9% versus 66.6%) was similar in both groups. After initial treatment, the response rate was significantly lower in HIV-infected than in non-HIV-infected individuals (54.8% versus 89.7%; p = 0.001). The relapse rate was 46.2% and 7.5%, respectively (p < 0.001). Secondary prophylaxis with antimonial compounds or amphotericin B seems to be useful in preventing relapses in HIV-infected patients. The mortality rate was higher (53.7% versus 7.5%; p < 0.001) and the median survival time shorter (25 versus > 160 mo; p < 0.001) in AIDS patients than in HIV-negative individuals. Although leishmaniasis could contribute to death in a significant number of HIV-infected patients, it was the main cause of death in only a few of them. The CD4+ lymphocyte count and the use of highly active antiretroviral therapy and secondary prophylaxis for leishmaniasis were the most significant prognostic factors for survival in AIDS patients. Visceral leishmaniasis behaves as an opportunistic infection in HIV-infected individuals and should be considered as an AIDS-defining disease.     

Visceral leishmaniasis in patients infected with human immunodeficiency virus (HIV)

In an 8-month period nine patients with human immunodeficiency virus (HIV) infection were diagnosed as having visceral leishmaniasis; all diagnoses were based on cultures (eight from bone marrow and one from the skin). Visceral leishmaniasis developed before full-blown acquired immunodeficiency syndrome (AIDS) in seven patients and at the same time as or after AIDS in the other two patients. Three patients had a history of leishmaniasis. Clinical manifestations and laboratory findings were atypical. Leishmania species were cultured from samples taken from all patients; however, six patients had an insignificant antileishmanial antibody titer and Leishmania amastigotes were not seen in their bone marrow smears. Four isolates were identified by isoenzyme analysis as Leishmania donovani infantum. Five patients died, including two patients who had completed at least one 3-week course of therapy with N-methylglucamine antimoniate. Screening should be done for visceral leishmaniasis in patients with HIV infection who live or travel in areas where the disease is endemic. The diagnosis of visceral leishmaniasis may frequently be missed if cultures are not done.     

In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic, human immunodeficiency virus (HIV)-infected patients with and without lipodystrophy. We studied 18 HIV-infected patients with lipodystrophy (LIPO) on antiretroviral therapy and 25 HIV-infected patients without lipodystrophy (controls) of whom 18 were on antiretroviral therapy and 7 were not. Posthepatic insulin clearance rate was estimated as the ratio of posthepatic insulin appearance rate to steady-state plasma insulin concentration during a euglycemic hyperinsulinemic clamp (40 mU.m-2 .min-1). Posthepatic insulin appearance rate during the clamp was calculated, taking into account the remnant endogenous insulin secretion, which was estimated by deconvolution of C-peptide concentrations. Hepatic extraction of insulin was calculated as 1 minus the ratio of fasting posthepatic insulin delivery rate to fasting endogenous insulin secretion rate. Compared with controls, LIPO displayed increased fasting insulin (130%, P < .001), impaired insulin sensitivity index (M value, -29%, P < .001), and reduced MCRi (-17%, P < .01). Hepatic extraction of insulin was similar between groups (LIPO, 55%; controls, 57%; P > .8). In LIPO, HEXi and MCRi correlated inversely with fasting insulin (r = -0.56, P < .02 and r = -0.68, P < .002) and positively with M value (r = 0.63, P < .01 and r = 0.65, P < .004). In controls, MCRi correlated inversely with fasting insulin (r = -0.47, P < .02) and positively with M value (r = 0.57, P < .004); however, the correlations between HEXi and these parameters were insignificant (P > .1). Our data suggest that HEXi and MCRi are decreased in proportion to the degree of insulin resistance in nondiabetic HIV-infected patients with lipodystrophy.     

Platelet antibodies in serum of patients with human immunodeficiency virus (HIV) infection

Between 10 and 15% of human immunodeficiency virus (HIV) seropositive individuals develop an immune thrombocytopenic purpura; however, the mechanism involved in platelet destruction is not yet established. In the present work, we have analyzed 208 sera from HIV seropositive individuals, including 85 thrombocytopenic patients, for the presence of autoantibodies against platelet proteins by using the Western blot technique. Our results indicate that: (1) antibodies against platelet proteins were found in 8 of 123 (6.5%) nonthrombocytopenic patients, as compared with 17 of 85 (20%) of thrombocytopenic patients (p less than 0.03); (2) these antibodies appeared to be more frequently found in advanced stages of disease (p less than 0.02); (3) the reactivity of positive sera with antigenic determinants implicated several distinct platelet proteins; (4) antigens thus recognized are unrelated to the major membrane glycoproteins IIb and IIIa, as well as absent in vero cells and trypsin-sensitive cells. Such results underscore the difficulties in establishing the mechanisms involved in platelet destruction during HIV infection.     

Non-cryptosporidial diarrhoea in human immunodeficiency virus (HIV) infected patients.

Thirty of 81 consecutive HIV antibody positive patients referred with non-cryptosporidial diarrhoea had no potential infectious cause; most had AIDS related complex rather than the full blown syndrome. Opportunistic infections with cytomegalovirus (CMV), mycobacterium avium-intracellulare (MAI), and herpes simplex virus (HSV), which allowed a diagnosis of AIDS to be made, were found in 19 patients and were the presenting features of AIDS in five. Other potential pathogenic species included entamoeba, giardia, campylobacter, and salmonella (without septicaemia). Cytomegalovirus infection was often accompanied by abdominal pain. Severe weight loss (greater than 10 kg) at presentation was found in patients with CMV infection and MAI. Bloody diarrhoea was confined to the group with HSV procitis. Malignant causes of diarrhoea were rare. Two patients developed a squamous carcinoma of the anorectal margin and one a non-Hodgkin's lymphoma. In only two of 12 patients who had Kaposi's sarcoma was this considered as a cause of diarrhoea. Rigid sigmoidoscopy showed macroscopic abnormalities in over a third (32) of the 81 patients with non-cryptosporidial diarrhoea. Most commonly this was severe inflammation (17) or discrete ulceration (four) [three of whom had CMV colitis]. Kaposi's sarcoma was identified in 11 patients. Non-specific inflammation was seen histologically in 40 of the 60 patients with no sigmoidoscopic inflammatory changes. Barium enema only revealed an abnormality in a minority of the patients and a colonoscopy only revealed information additional to rigid sigmoidoscopy in two patients--one with CMV ulcers in the transverse colon and the other with evidence of Kaposi's sarcoma not seen in the rectum. Ten patients had a rectal biopsy examined by electron microscopy as no infective cause of diarrhoea was uncovered. In four of these microtubular structures which are commonly seen in viral infections were found and two had prelymphomatous changes and in one of these frank lymphoma has developed. We recommend multiple stool analysis, sigmoidoscopy and rectal biopsy as the initial investigations in these patients reserving tests of malabsorption, colonoscopy, and barium enema for the small number of more difficult cases.     

Cryptococcal meningitis in human immunodeficiency virus (HIV)-positive and HIV-negative patients

This study compared clinical manifestations, blood biochemistry and cerebrospinal fluid (CSF) results of HIV-positive and HIV-negative patients with cryptococcal meningitis. We collected 57 cases of cryptococcal meningitis from cytological specimens submitted to the Department of Tropical Pathology, Faculty of Tropical Medicine. Pertinent clinical data were analyzed retrospectively in 47 cases for clinical manifestations, laboratory features and outcomes of 38 HIV-positive and 9 HIV-negative patients. Headache was the most common symptom seen in all cases, of which 70.2% occurred with fever. CSF examination of both groups revealed elevated opening pressure. Increased CSF protein and depressed CSF glucose levels were seen in HIV-negative cases, which differed from HIV-positive cases, where a slight change was noted. CSF pleocytosis in HIV-positive patients was variable. Forty-eight percent of HIV-positive patients had CSF leukocyte counts below 20 cells/ mm3. None was found in the HIV-negative patients. Specific treatments with amphotericin B and fluconazole were given. Five fatal cases of cryptococcal meningitis were noted, all of which were HIV-positive. There were statistically significant differences in blood neutrophils, blood eosinophils, CSF leukocyte counts, CSF neutrophils, CSF lymphocytes, CSF glucose, and CSF total protein, in HIV-positive and HIV-negative patients (p = 0.050, p = 0.022, p = 0.002, p = 0.016, p = 0.047, p = 0.031, p = 0.009, respectively).     

HIV (human immunodeficiency virus) and HIV-associated diseases

The discovery of the Human Immunodeficiency Virus (HIV), the characterization of its molecular biology and the development of serologic methods for detecting antibodies have led to a better understanding of HIV-associated clinical syndromes. Recently, the Centre of Disease Control has proposed a classification of HIV-related conditions. This classification forms the basis for this review. It is completed by remarks on antiviral and immunomodulating drugs and its effects on HIV. Difficulties in development of vaccines are discussed.     

Analysis of lymphocytes, monocytes, and neutrophils from human immunodeficiency virus (HIV)-infected persons for HIV DNA

The human immunodeficiency virus (HIV) infects and depletes or alters the function of cells involved in immune responsiveness. While both T helper lymphocytes and monocyte/macrophages can be infected via cell-surface CD4 in vitro, previous studies showed that few blood cells express HIV RNA in vivo. This study used DNA amplification to determine the levels of HIV DNA in purified lymphocytes, monocytes, and neutrophils from HIV-infected asymptomatic individuals and persons with AIDS. The average numbers of HIV DNA copies in lymphocytes from AIDS patients and asymptomatic individuals were similar (approximately 100-140 copies/150,000 cells). However, when expressed on the basis of numbers of CD4+ T cells, AIDS patients' cells contained approximately 2.5 times more HIV DNA. While HIV DNA was present in lymphocytes from all 27 subjects, little or no HIV DNA was observed in monocytes or neutrophils. Only 1 asymptomatic person contained levels of HIV DNA in monocytes (125 proviral copies/150,000 cells) that were comparable to levels expressed in lymphocytes (160/150,000). While expression of monocyte HIV DNA in this person was persistent over at least 8 months, it was not observed in neutrophils, suggesting that monocyte HIV DNA did not originate in myeloid precursors. This study shows that in AIDS or asymptomatic HIV infection, lymphocytes are the predominant infected cell found in blood.     

42例HIV感染/艾滋病患者的心脏表现

目的　总结 42例人免疫缺陷病毒 ( HIV)感染 /艾滋病患者的心脏表现。方法　对 42例 HIV感染 /艾滋病患者进行回顾性分析。结果　 42例 HIV感染 /艾滋病心脏表现有 :心律失常 5 0 .0 % ( 2 1/ 4 2 ) ,感染性心内膜炎 4.8% ( 2 / 4 2 ) ,心包积液 2 .4% ( 1/ 4 2 ) ,扩张型心肌病合并心功能不全 14 .3% ( 6 / 4 2 )。结论　心脏亦为 HIV感染 /艾滋病的受累器官之一。艾滋病患者可因自身突出的全身症状掩盖而使心脏病变隐匿 ,心电图、胸片、超声心动图有助早期诊断并指导治疗     

Persistent Campylobacter jejuni infections in patients infected with the human immunodeficiency virus (HIV)

We identified Campylobacter jejuni infections in four patients infected with the human immunodeficiency virus (HIV); three had persistent and severe C. jejuni infections. Multiple isolates obtained from each patient had the same biochemical and serotypic characteristics, indicating recurrent infection rather than reinfection with unrelated strains. Serum antibody responses to C. jejuni group antigens by enzyme-linked immunosorbent assay were markedly impaired in the three patients with persistent infection compared with forty-two immunocompetent C. jejuni-infected controls and with the HIV-infected patient who readily cleared the organism. One patient was bacteremic; his blood isolate was killed by normal serum but was resistant to his own serum, whereas a simultaneous stool isolate of a different serotype was sensitive. Failure of two patients to eradicate the organism and long-term administration of erythromycin therapy led to the in-vivo development of resistance to this antibiotic, which is most frequently used to treat C. jejuni infections.