Secondary Opportunistic Infections Research Articles

Polymicrobial Cholangitis and Liver Abscess in a Patient With the Acquired Immunodeficiency Syndrome

Cholangitis/cholangiopathy associated with the human immunodeficiency virus (HIV) infection is characterized by chronic abdominal pain, low-grade fever, cholestasis, and sometimes areas of focal or diffuse dilatation of the bile ducts that may be apparent on noninvasive imaging studies. Although the etiology of this biliary disease may be multifactorial, it appears to be the result of immunosuppression and/or secondary opportunistic infections rather than a direct cytopathic effect of HIV itself. Various opportunistic pathogens, including cytomegalovirus, Cryptosporidium, Campylobacter fetus, and Candida albicans, have been implicated as causes of HIV-associated cholangitis. We report an unusual case of polymicrobial cholangitis and liver abscess in a patient with HIV infection.

Human immunodeficiency virus type 1 and mucosal humoral defense.

Mucosal sites serve as the principle venues through which primary human immunodeficiency virus type 1 (HIV-1) infections are transferred from donor to host. These moist tissues, which provide the interface with the external environment, also provide access to many of the secondary opportunistic infections that aggravate and may accelerate HIV-1 disease. Antibodies to HIV-1, particularly of the IgG rather than the IgA class, have been detected in virtually all mucosal fluids from HIV-1-infected patients. However, the ability of such patients to generate de novo humoral responses to new mucosal pathogens is impaired. Current studies are directed to characterizing the functional role of natural and infection-derived antibodies in control of HIV-1 infection as well as the impact of HIV-1 disease on mucosal B cell responses to immunization and infection.

EHRLICHIOSIS AFTER PANCREAS TRANSPLANTATION

368 Human ehrlichioses are tick-borne infections caused by bacteria in the genus ehrlichia of the family Rickettsiaceae. Since it was first identified in 1987, two types have been found to exist; human monocytic ehrlichiosis (HME) and human granulocytic ehrlichiosis (HGE). To date there have been two cases of ehrlichiosis in the transplant population, an HME infection in a liver transplant patient and a case of HGE in a kidney recipient. We report herein three pancreas transplant patients who developed HGE post transplant within the last two years at a Southeastern center (Table).TableDespite uniform symptomatology none of the patients had another source of infection and bone marrow biopsies in each case revealed HGE. All three patients were treated with doxycycline for two weeks, filgrastim and a reduction in immunosuppression. Two patients experienced complete recovery. One patient (Pt#3) expired secondary to development of a secondary opportunistic infection with toxoplasmosis. Conclusion: In the setting of potent immunosuppression, ehrlichiosis should be included in the differential diagnosis when transplant patients present with persistent fever, pancytopenia, and abnormal liver function. Ehrlichiosis patients may be at risk of developing greater opportunistic or lymphoproliferative disease.

Induction and Expression of Intestinal Humoral Immunity in HIV-Infected Individuals: Prospects for Vaccination against Secondary Enteric Infections

In view of the high incidence and severity of AIDS-related mucosal complications and secondary mucosal infections, we have evaluated the impact of HIV infection on the mucosal humoral immune status. By measuring the number of total and specific antibody-secreting cells in duodenal biopsies, we could show that HIV infection induces a pronounced polyclonal B-cell activation already in the early stages of the disease. Furthermore, we could document normal mucosal B-cell responses following oral vaccination, also in the late stages of the disease, and despite a lack of concomitant systemic responses. The relevance of these observations will be discussed with respect to the possibility of vaccinating HIV-infected individuals against secondary opportunistic infections.

Cardiac transplant-related cutaneous malignancies in an australian recipient: Immunosuppression, friend or foe?

Cardiac transplantation now offers hope to those diagnosed with end stage cardiac failure. The consequences of such transplantation include the need for lifelong immunosuppression to avoid life-threatening rejection. The subsequent development of secondary malignancies and opportunistic infections often leads to significant morbidity and mortality. Cutaneous malignancies in particular represent a major concern to Australian transplant recipients. The case history is presented of a cardiac transplant recipient who developed multiple recurrent aggressive cutaneous squamous cell carcinomas of the head and neck. Despite surgery and radiotherapy, he experienced explosive in-field and distant relapse. The aggressiveness and atypical natural history of this disease, driven by the need for ongoing immunosuppression, highlights the inadequacies of current treatment approaches.

Therapeutic options for HIV-associated bodyweight loss. A risk-benefit analysis.

Involuntary bodyweight loss, a common complication of infection with HIV, is an indicator of poor prognosis and decreased survival. Because of the multifactorial pathogenesis of HIV-related wasting, emerging therapies are directed at the multiple proposed mechanisms of involuntary bodyweight loss. The initial evaluation and treatment of HIV-related bodyweight loss is focused on the identification and treatment of reversible causes of bodyweight loss, such as secondary opportunistic infections or endocrine dysfunction. Nutritional intervention should begin in the early stages of HIV infection and continue throughout the life of the patient. Of the appetite stimulants, megestrol most consistently promotes bodyweight gain, but with a predominance of fat, not lean, body mass. Anabolic therapies such as testosterone derivatives and recombinant human growth hormone (somatropin) stimulate the addition of lean body mass and are begin actively researched for the treatment of HIV-associated wasting. Finally, thalidomide, a potent inhibitor of tumour necrosis factor-alpha, is a potentially useful therapy that is still under investigation. New research into the treatment of HIV-related bodyweight loss is focusing on combination therapies.

Immunopathology of human immunodeficiency virus infection in the gastrointestinal tract.

The intestinal (in particular rectal) mucosa is an important portal of entry of HIV in homosexual men, who represent the vast majority of HIV-infected patients in Europe and North America. There are several possibilities for HIV to reach the CD4+ T cells, macrophages and follicular dendritic cells in the intestinal mucosa. HIV may be transported through M cells directly to mucosal lymphoid follicles. Alternatively, HIV may infect enterocytes via the Fc-receptor by antibody-bound HIV or via a CD4-independent receptor. By successive budding on the basal side of enterocytes HIV may be released into the lamina propria. Furthermore, in patients not infected by the intestinal route, HIV may also rapidly enter the intestinal mucosa by other mechanisms. Intestinal T lymphocytes are mainly activated memory T cells reentering the mucosal surfaces after circulating through the peripheral blood. In the periphery they may be preferentially infected by HIV. Accumulation of infected T cells could thus occur in the intestinal mucosa. The special phenotypical and functional characteristics of intestinal T lymphocytes may affect the replication and cytopathology of HIV, resulting in an accelerated loss of CD4+ T cells in the lamina propria. CD4 T cells play a critical role in antigen-dependent B cell differentiation, thus the pronounced CD4 T cell depletion in the intestinal mucosa may be responsible for the observed decrease of IgA plasma cells and a reduced secretion of IgA2. Depletion and functional impairment of activated mucosal LPL with consequent altered cytokine secretion in HIV infection could explain the breakdown of the mucosal immune barrier, leading to secondary opportunistic or nonopportunistic infections and secondary malignancies. Furthermore, several viral factors like thenef gene product may influence T cell activation and function, especially in the gastrointestinal tract contributing to the observed pronounced and early loss of CD4 T cells in the mucosal lamina propria. In addition, due to the interrelation between the mucosal immune system and epithelium, these changes might be responsible for the partial small intestinal mucosal atrophy and maturational defects in enterocytes observed in HIV-infected patients.

Induction of inflammatory cytokines in placental monocytes of gravidae infected with the human immunodeficiency virus type 1.

Placental mononuclear cells (PMC) are susceptible to infection with the human immunodeficiency virus (HIV). PMC secreted tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta), and IL-6 among other factors, which, in turn, regulate HIV replication in latently infected cells. We assessed the induction of these cytokines in PMC from HIV-infected (HIV+) and uninfected (control) gravidae following exposure to lipopolysaccharide (LPS), HIV lysate (iHIV), recombinant HIV env (GP160) and HIV gag (gag55), and synthetic HIV p17 (HGP30) antigens. In comparison to control PMC, HIV+ PMC constitutively secreted higher levels of IL-1beta and IL-6 and were refractory to stimulation by iHIV, GP160, gag55, and HGP30. Control PMC IL-1 beta levels were boosted by LPS; gag55 and HGP30 augmented IL-6 but not IL-1 beta. Both groups exhibited low basal TNF-alpha production that was augmented by LPS. HIV+ PMC exhibited higher constitutive levels of IL-1 beta, IL-6, and TNF-alpha gene transcription than control PMC. These levels could be further augmented by LPS, yet the incremental levels were lower than those obtained from PMC of uninfected women. The high basal constitutive secretion of cytokines by HIV+ PMC and their refractoriness to activation may reflect a virus-mediated dysregulation of cytokine expression culminating in compromised host defenses against secondary opportunistic infections associated with AIDS.

Infectious complications of corticosteroids as adjuvant treatment of Pneumocystis carinii pneumonia

Summary A retrospective chart search was lead for CDC stages B and C illnesses occuring up to one year after a PCP diagnosis : this search had for aim to evaluate the infectious complications of adjuvant steroid therapy in Pneumocystis carinii pneumonia (PCP). 56 patients presented 61 episodes of PCP. Steroids were given in 28 episodes (mean duration 17.8 days, mean dosage 1.3 mg/kg). No statistically significant difference in opportunistic infections among the two groups was noted at 1, 3 or 12 months. A short steroid treatment does not increase the risk of developing secondary opportunistic infections after PCP. Prospective studies are needed to confirm these results, before systematically extending steroid prescription to mild PCP.

Hodgkin's disease as an indicator of AIDS

Hodgkin's disease (HD) is not currently included within the Centers for Disease Control (CDC) classification system for AIDS. Upon HD diagnosis, HIV(human immunosuppressive virus)-positive patients are generally found within' Stages III or IV of the Ann Arbor HD classification system, already exacerbating the problem of treatment. In contrast, HIV-negative patients diagnosed with HD are generally found within Stages I or II. Epidemiology and the presence of secondary lymphomas, opportunistic infections, or aggressive pathologies, accompanied by low survival rate and timing of HD diagnosis suggest that HD should be included among conditions indicating AIDS manifestation.

Correlation of body mass index with urinary neopterin in individuals infected with human immunodeficiency virus.

We assessed correlations between body mass index and plasma lipids, immune activation markers and the CD4+ T-cell count. The subjects of this cross-sectional study were randomly selected and comprised all those who attended the AIDS Out-Patient Clinic at the University Hospital in Innsbruck in March and April 1992. Patients with signs and symptoms of acute bacterial and secondary opportunistic infections were excluded. We investigated 63 individuals with HIV infection of whom 35 were asymptomatic, 8 had oral candidiasis, 4 had constitutional signs and symptoms and 16 had AIDS, for an association among body mass index, urinary neopterin, soluble tumor necrosis factor receptors (sTNFRs), plasma lipids, and the numbers of CD4+ T cells. The body mass index correlated inversely with urinary neopterin (rs = -0.42, p = 0.0009) and weakly with the numbers of CD4+ T cells (rs = 0.29, p = 0.02) but not with plasma lipids, sTNFRs and beta 2-microglobulin. The results show that body mass index correlates with immune activation. The data suggest that endogenous formation of interferon-gamma may be an important mediator of wasting in HIV infection, since this cytokine is responsible for the observed elevation of neopterin concentrations in body fluids.

Gender differences in reported AIDS-indicative diagnoses.

To compare AIDS-defining conditions in women and men, US adult AIDS cases diagnosed between January 1988 and June 1991 and reported to the Centers for Disease Control and Prevention through June 1992 were examined. For most AIDS-defining conditions, the prevalence was similar for women and men when differences in race/ethnicity and mode of transmission were accounted for. Pneumocystis carinii pneumonia was the most prevalent condition (> 50%) regardless of gender, race/ethnicity, or mode of transmission. By logistic regression analysis, among injection drug users, conditions reported significantly more frequently in women than in men include esophageal candidiasis (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.40-1.62), herpes simplex virus (HSV) disease (OR, 1.68; CI, 1.46-1.94), and cytomegalovirus (CMV) disease (OR, 1.43; CI, 1.18-1.73). More knowledge of the interrelationships in women between HIV infection and secondary opportunistic infections, including candidiasis and sexually transmitted disease (e.g., HSV and CMV) is needed.

Serum increases and lymphoid cell surface losses of IL-2 receptor CD25 in HIV infection: Distinctive parameters of HIV-induced change

Lymphocyte activation induces production of soluble IL-2 receptor (sIL-2R) which is a large portion of the CD25 membrane molecule and which is detectable in serum. Serum sIL-2R is reported here to increase as a direct effect of the HIV infection and not to be due to secondary opportunistic infections. sIL-2R increased promptly after HIV seroconversion in 83% of 50 initially seronegative homosexual men. The sIL-2R serum levels stabilized in the third year after seroconversion and were then predictive of later CD4 T cell levels and development of AIDS. In two studies of 59 and 395 seropositive men, beta-2 microglobulin (B2M) and neopterin levels in serum correlated closely with each other but not with sIL-2R levels. Thus, increased production of sIL-2R may reflect pathological processes distinct from those determining B2M and neopterin increases. Membrane CD25 expression on peripheral blood lymphocytes, unexpectedly, was found to be decreased in HIV infection. This contrasted with the increased sIL-2R in serum. Investigations with sensitive flow cytometry technics showed that CD25 was expressed at reduced levels and averaged only 12% of lymphocytes from HIV-infected individuals in contrast to 25% in noninfected individuals. All major lymphoid populations showed reductions in CD25 positive cells. This reduction in lymphoid membrane CD25, however, was not inversely correlated with the increased serum levels of sIL-2R or with other parameters of immune deficiency or activation. Thus, surface CD25 loss and serum sIL-2R increase are separate and independent consequences of HIV infection.

AIDS in the Nervous System

ABSTRACT stated objective of the authors is to help physicians diagnose and manage the neurological complications of the acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection. reader will find that this book achieves the authors' goal and more.The nervous system is one of the most frequently involved organ systems affected by HIV infection. Disorders of the brain, meninges, spinal cord, peripheral nerve, and muscle have all been associated with primary HIV infection or HIV-related secondary opportunistic infections and tumors. Such nervous system disorders have appeared in diverse clinical settings, ranging from the initial manifestations of HIV infection to a myriad of opportunistic infections in persons with AIDS. In addressing the frequency and diversity of neurological disease associated with HIV infection, the authors, one a clinical neurologist and the other a neuropathologist, have skillfully combined their expertise.The book's seven chapters are The Character of AIDS, Epidemiology,

Clinical and immunologic aspects of FeLV-induced immunosuppression

Cats exposed to the feline leukemia virus (FeLV) may mount an effective immune response and eliminate the virus, develop a non-viremic, latent infection or become persistently infected and shed the virus. Persistently infected cats commonly die of secondary opportunistic infections that result from FeLV-induced immunosuppression. The acquired immunosuppression is the most frequent and most devastating consequence of FeLV infection in the cat. Immunosuppression is targeted primarily to the cell-mediated immune system and has been attributed to the viral p15e envelope protein. The decreased IgG response and proliferative response to T cell mitogens is thought to be due to a defect in the helper cell function. As a result of T helper cell immunosuppression, infected cats may also have defective cytotoxic lymphocyte and activated macrophage functions which are regulated by their lymphokines. Research has shown that the virus causes a general suppression in the production of T cell-derived lymphokines, including gamma interferon and interleukin 2. A decrease in the function of polymorphonuclear leukocytes has also been reported and may contribute to deaths due to opportunistic infections in FeLV-positive cats. There are numerous parallels between the acquired immunodeficiency syndrome (AIDS) in man and the FeLV-induced immunodeficiency syndrome in cats. Frequent deaths due to opportunistic infections, lymphopenia, depressed cell-mediated immune responses to T cell-dependent antigens despite hypergammaglobulinemia and the presence of a long period of time between infection and the onset of clinical signs are just a few of the syndromes that are similar between the 2 retroviral diseases. A new strain of FeLV, FeLV-FAIDS has been associated with a naturally occurring immunosuppressive syndrome that is strikingly similar to AIDS in man. In addition, a T-lymphotropic retrovirus has recently been identified from cats with an immunodeficiency-like syndrome; this feline lentivirus disease is morphologically similar, but antigenically distinct from the human immunodeficiency virus, the cause of AIDS. Treatment for FeLV immunosuppression is primarily supportive. The development of a soluble tumor cell antigen vaccine has been shown to be efficacious in preventing FeLV infections.