Immunocompromised Groups Research Articles

Modelling cytomegalovirus replication patterns in the human host: factors important for pathogenesis

Human cytomegalovirus can cause a diverse range of diseases in different immunocompromised hosts. The pathogenic mechanisms underlying these diseases have not been fully elucidated, though the maximal viral load during infection is strongly correlated with the disease. However, concentrating on single viral load measures during infection ignores valuable information contained during the entire replication history up to the onset of disease. We use a statistical model that allows all viral load data sampled during infection to be analysed, and have applied it to four immunocompromised groups exhibiting five distinct cytomegalovirus-related diseases. The results show that for all diseases, peaks in viral load contribute less to disease progression than phases of low virus load with equal amount of viral turnover. The model accurately predicted the time of disease onset for fever, gastrointestinal disease and pneumonitis but not for hepatitis and retinitis, implying that other factors may be involved in the pathology of these diseases.

Herpes Zoster Mimicking Recurrence of Lymphoma on PET/CT

Herpes zoster is a relatively common disease characterized by the eruption of vesicles in a dermatomal distribution. It is postulated to occur when the cell-mediated immunity falls below a critical level, allowing dormant virus to replicate and infect the host. Herpes zoster is known to occur more frequently in immunocompromised groups such as oncology patients receiving chemotherapy and radiation. Patients after stem cell transplant have also been reported to be predisposed to herpes virus infection. F-18-FDG PET is widely used in oncology imaging to determine the presence of metabolic activity in certain malignancies, including lymphoma. However, inflammatory cells can also have high metabolic activity and display avid uptake of FDG. This case illustrates the importance of recognizing the possibility of an inflammatory process such as herpes zoster occurring on PET/CT imaging in an oncology patient being evaluated for malignant disease.

Travelling to Africa: Health risks reviewed

Africa's varied ecology presents a wide range of travel health threats: infections; accidents; envenomations; an uncertain drug supply; problematic access to competent medical care outside South Africa. Important vaccine preventable diseases include yellow fever, meningococcal disease, typhoid, polio, rabies, and hepatitis A and B; routine vaccinations should be up to date. Much, but not all, of sub-Saharan Africa is malarious with chloroquine resistant falciparum dominating; chemoprophylaxis and personal protection measures will often be indicated. Other threats are less obvious, e.g. helminth and protozoal infections. The immunocompromised and other high-risk groups may require special attention. Risk mitigation strategies may include education, vaccination, chemoprophylaxis, personal protection measures, provision of treatment and equipment packs, behaviour modification, and evacuation insurance.

Pneumocystis Pneumonia

In Brief Major controversies persist regarding the diagnosis and management of Pneumocystis pneumonia (PCP). Of considerable significance is the fact that much of the available evidence relates to human immunodeficiency virus (HIV)–infected subjects and may not be applicable to other immunocompromised groups. Induced sputum (IS) remains an important diagnostic test with a high specificity and good patient acceptability. Immunofluorescence improves the sensitivity of IS when compared with standard cytochemical staining. Nucleic acid amplification techniques may also increase sensitivity, although they remain predominantly a research tool. Bronchoscopy with bronchoalveolar lavage (BAL) is the optimum diagnostic test, with bilobar washing including an upper lobe reaching sensitivities of 95%. BAL, rather than IS, should be performed as the initial diagnostic investigation in non–HIV-infected subjects where the Pneumocystis pathogen load is low. Transbronchial biopsy is no more sensitive than bilobar lavage and is associated with considerable morbidity. Nonbronchoscopic lavage is an underused diagnostic resource offering a cheap alternative to fiberoptic bronchoscopy. Early diagnostic evaluation with BAL rather than empirical treatment is encouraged since the chance of detecting Pneumocystis after several days of anti-Pneumocystis treatment is reduced. In addition, multiple respiratory pathogens are common in patients with low CD4 counts. This strategy of early BAL is particularly important in non–HIV-infected immunocompromised patients where there is greater uncertainty regarding the clinical diagnosis of PCP. Pneumocystis pneumonia remains a serious infection in both human immunodeficiency virus (HIV)–infected and noninfected immunocompromised populations. This review explores controversies in both the diagnosis and management of Pneumocystis pneumonia (PCP); notably the advantages and disadvantages of induced sputum and bronchoalveolar lavage for diagnosis, the optimum methods for identifying Pneumocystis in specimens, and the timing of the introduction of highly active antiretroviral therapy following HIV-PCP coinfection.

Propagation and assay of BK virus.

BK virus (BKV), one of two human polyomaviruses, was first isolated in cell culture from the urine of an immunocompromised renal transplant patient in England in 1971 (). Seroprevalence studies have shown that BK infection is widespread in children throughout the world, and the virus thereafter persists latently in the kidney for life. Immunosuppression can lead to reactivation of the virus and prolonged viruria (). Although in immunocompetent individuals BK infection is generally asymptomatic, lowering of immunity can occasionally result in life-threatening renal disease (,). An association between active BKV infection and ureteric stenosis in renal transplant recipients, and hemorrhagic cystitis in bone marrow transplant patients has long been established (), and recent evidence suggests that BK may contribute to further complications arising in immunocompromised groups, e.g., interstitial pneumonia () and atypical retinitis ().

Low virulence of Escherichia coli strains causing urinary tract infection in renal disease patients.

The distribution of urinary bacterial species was determined and the virulence factors of Escherichia coli urinary strains analysed by molecular and phenotyping methods in episodes of urinary tract infection in renal disease patients (n =68) in comparison with other immunocompromised patients (n =59) and non-immunocompromised patients (n =21). Escherichia coli was isolated in 116 (78%) of the 148 patients, being the species most frequently isolated in all groups (75% of renal disease patients, 76% of other immunocompromised patients, 95% of non-immunocompromised patients). All other pathogens showed a similar distribution in the renal disease and other immunocompromised patient groups. All virulence factors of Escherichia coli tested for (genes for G adhesins, expression of MR adhesins, production of haemolysin, presence of certain O and K antigens) were found more often in non-immunocompromised than in immunocompromised patients. The factors allowing the highest degree of discrimination between immunocompromised and non-immunocompromised patients were the prevalence of genes for G adhesins (35% vs. 65%) and expression of MR adhesins (32% vs. 55%). It is concluded that there is a lower prevalence of G adhesins and MR adhesins in Escherichia coli strains from immunocompromised patients than non-immunocompromised patients, suggesting that less virulent Escherichia coli strains may cause urinary tract infections more frequently in renal disease patients and other immunocompromised patients. Moreover, the spectrum of urinary pathogens other than Escherichia coli is similar in both immunocompromised patient groups investigated.

Hepatitis G virus RNA is common in AIDS patients' plasma but is not associated with abnormal liver function tests or other clinical syndromes.

Hepatitis G virus (HGV) is a new virus found in 1% to 4% of blood from all donors but is more prevalent in some immunocompromised groups, with unclear clinical significance. Frozen plasma samples from 192 AIDS patients were tested for HGV RNA; 44 (23%) were positive. Positive patients did not differ from negative patients in age, gender, race, HIV infection risk factors, nor blood transfusion exposure. Hepatitis BsAg was associated with HGV infection (odds ratio [OR] = 7.7; 95% confidence interval [CI], 2.4-25.0) but hepatitis C antibody was not. Mean values for liver function tests and hematologic values did not differ significantly between the groups nor did the occurrence of certain recognized AIDS-related complications. Mean CD4+ cell counts and HIV-1 plasma RNA levels were comparable in the two groups, but the mean circulating CD8+ cell count in the HGV-positive group (853+/-458 cells/microL) was higher than in the negative group (682+/-457 cells/microL; p = .03). Hepatitis G virus, although common in AIDS patients, does not appear to alter the course of AIDS nor appear as a distinct hepatitis syndrome.

THE COMPROMISED TRAVELER

Compromised travelers represent a diverse and challenging group of individuals. They include HIV-infected patients who are at risk for potentially adverse reactions to immunizations, and new exposures to enteric water-borne opportunistic pathogens associated with chronic infections. Such travelers may encounter unfamiliar opportunistic fungi and classical tropical infections, such as leishmaniasis, whose pathogenesis can be enhanced by the presence of prior HIV infection. Other immunocompromised groups include those who are functionally or anatomically asplenic, and patients who are iatrogenically immunosuppressed from medications utilized for solid organ transplantation, chemotherapy, or treatment of malignancies. This population of travelers also includes those with diabetes mellitus who may require adjustments in their dosing, administration, and possibly even the types of insulin used on their trips. These patients are also at greater risk for acquisition of tuberculosis, severe community-acquired pneumonia, urinary tract infections, and pyomyositis. Older travelers present both the infectious disease and travel medicine specialist with issues such events, malignancy-related infections, myocardial infarction, and other forms of cardiopulmonary compromise, which the authors address in this article.

Significance of leukocyte concentration in the performance of the quantitative cytomegalovirus (CMV) antigenemia assay

Background: The quantitative cytomegalovirus-antigenemia (CMV-Ag) assay is an important technology in the regimen of tests utilized in the care and management of acquired immunodeficiency syndrome (AIDS) and other immunocompromised patient groups. Performance of this assay is contingent upon the appropriate processing of the polymorphonuclear leukocyte (PMNL) compartment of the peripheral blood. However, a cell input standard in the performance of the CMV-Ag assay, has not been established. Interpretive differences between laboratories utilizing the CMV-Ag assay may reflect this lack of test uniformity. Objectives: To determine the effect of different PMNL concentrations on the quantitation of CMV in peripheral blood. The leukocyte concentration resulting in optimal rates of viral detection, will be compared with the shell vial assay-indirect immunofluorescent assay (SVA-IFA), and conventional tube culture (TC-CPE). Study design: A total of 74 freshly collected blood specimens were tested by the CMV-Ag assay, using cytospin preparations consisting of 2×10 5, 4×10 5 and in preliminary experiments, 8×10 5 PMNLs/slide. Data obtained from these studies were compared to SVA-IFA and TC-CPE. Viral load was monitored among 11 symptomatic patients through sequential testing of these patients at the start of ganciclovir (GCV), foscarnet (PFA), or combination drug therapy. Results: Among 74 blood specimens tested by the CMV-Ag assay, cytospin preparations consisting of 4×10 5 compared with 2×10 5 PMNLs/slide, affected a mean positive cell increase of 215% ( P=0.03). PMNL slide preparations consisting 8×10 5 cells produced background levels which prevented accurate reading of slides. The CMV-Ag assay was more sensitive than the SVA-IFA, but equivalent to TC-CPE. Among 11 patients started on drug therapy, viral load was markedly reduced in 8 within 2–3 weeks; three patients (2 deceased within 3 weeks after receiving therapy), showed no decrease in viral load. One patient was identified as harboring a PFA resistant strain. Conclusions: A PMNL concentration of 4×10 5 cells facilitated the reading of CMV-Ag assay slide preparations. The modified CMV-Ag assay furthermore, is applicable in the monitoring of viral load for the tracking of susceptible or resistant CMV strains.

No Benefits from Repeat Pneumococcal Vaccine

The CDC now recommends repeat pneumococcal vaccination after six or more years for some immunocompromised groups. Should HIV-infected persons be among them? To approach this question, Houston investigators examined the longevity of vaccine-induced antibodies against the pneumococcal polysaccharides (PPS) in seropositive men and the utility of revaccinating nonresponders. The 23-valent pneumococcal vaccination was given to 104 HIV-infected men …

An unusual presentation of cat scratch encephalitis

Cat scratch disease is an infectious illness that has been recognized since the 1880s; however, our understanding and knowledge of it is still evolving (1). It was not until 1991 that the etiologic species, Rochalimaea, was finally confirmed (2,3). Only recently have the breadth of its clinical spectrum and the population at risk been appreciated. We now realize that signs and symptoms that had been considered cardinal for diagnosis may be absent. Cat scratch disease was known to afflict primarily children and adolescents; however, the incidence of CSD is increasing in immunocompromised groups, such as AIDS and transplant patients (3,4). The recent discovery of the infectious agent and improved understanding of the disease process have led to new approaches in diagnosis and treatment. We present a report of a patient with cat scratch disease who presented with seizure and altered mental status secondary to encephalitis.

Primary central nervous system lymphomas?New pathological developments

Primary central nervous system lymphomas (PCNSL) show increased incidence both in immunocompromised high-risk groups and in the general population. They are extranodal diffuse non-Hodgkin's lymphomas with a morphology similar to systemic lymphomas, but differ in their biological and molecular behaviour. The majority are large B-cell variants of high-grade malignancy; low-grade subtypes and T-cell lymphomas are rare; up to 50% remain unclassified according to the New Working Formulation and updated Kiel classification. Monoclonality of immunoglobulin receptor gene rearrangement can be diagnostically useful. The pathogenesis of PCNSL is obscure. Epstein-Barr virus (EBV) genome/proteins expression in two-thirds of HIV-related PCNSL but only in 15% of those in immunocompetent patients suggest different EBV latency stages in both types; human herpesvirus type 6 does not appear to play a pathogenic role. Comparison of expression patterns of integrin chains and adhesion molecules are very similar for PCNSL and nodal lymphomas suggesting that they are not selective mediators of lymphoma cell homing to the brain. In HIV-negative PCNSL they appear not to be influenced by EBV. Studies of protooncogenes (bcl-1 and bcl-2 genes) revealed no rearrangement in PCNSL, suggesting that they are not involved in the pathogenesis of PCNSL that probably do not differ cytogenetically from nodal B-cell lymphomas. Since most of the currently known molecular parameters are probably not the primary pathogenic events, the molecular genetics and pathogenesis of PCNSL are still to be elucidated.

Septic bursitis in immunocompromised patients

A retrospective analysis of 29 patients with septic bursitis was undertaken to ascertain if immunocompromised patients differed in their clinical presentations, type of organisms cultured, and outcome when compared with their non-immunocompromised cohorts. Thirty episodes of septic bursitis occurred in 29 patients, 43 percent of which occurred in immunocompromised patients. Despite similar clinical presentations, the bursae of immunocompromised patients took three times longer to sterilize and had a much higher bursal white blood cell count when compared with the bursae of non-immunocompromised patients. The bacteriologic spectrum was essentially identical in both groups; there were no cases in which gram-negative organisms were recovered from infected bursae. No cases of septic bursitis were seen in neutropenic patients. The most common factors contributing to an immunocompromised state were alcoholism or steroid therapy. A successful resolution of septic bursitis was seen in all the patients in the immunocompromised groups.