Herpesvirus hominis Infection in Patients with Myeloproliferative and Lymphoproliferative Disorders

Infection with Herpesvirus hominis, often associated with oral ulceration, was found to be more frequent in patients with myeloproliferative and lymphoproliferative disorders than in normal populations or patients with other diseases. This increased frequency was not associated with any deficiency of the humoral antibody response, suggesting a possible impairment of cell-mediated immunity. The otherwise untreatable oral lesions appeared to respond effectively to local irradiation.     

Diagnosing Invasive Mold Infections: What Is Next

Purpose of Review

Currently, microbiological diagnosis of invasive mold infections is based largely on culture, direct microscopy, PCR, or antigen (such as β-D-glucan or galactomannan)-based tests. In this review, we look at novel and experimental diagnostic tests for invasive mold infections.

Recent Findings

Several new techniques have been proposed, and are in different stages of development. The JF5-antibody-based lateral flow device has recently been commercialized, and is closest to uptake in routine care. Other tests, such as the MAb476-antibody-based urine lateral flow device, gliotoxin or bis(methylthio)gliotoxin, mold-specific T cells, exhaled breath analysis, siderophores, mass spectrometry serum disaccharide, or cytokine analysis, are at an earlier stage of development.

Summary

Most proposed diagnostic tests for invasive mold infections are in the experimental stage and are not ready for routine clinical use. They still require further characterization and analytical and clinical validation by independent research groups.

     

Invasive Fungal Infections in the Child with Chronic Granulomatous Disease

Invasive fungal infections (IFI) are a major threat for patients with chronic granulomatous disease (CGD) which is an inherited disorder of NADPH oxidase. The absence of a functional NADPH oxidase complex affects the display of an efficient antimicrobial effect as well as a controlled inflammatory response. Invasive aspergillosis caused by either Aspergillus fumigatus or A. nidulans is the most common IFI. Aspergillus nidulans infections seem to display a unique interaction with the CGD host and are seldom reported in other immunocompromised hosts. The occurrence of mucormycosis in the CGD host is mainly noted in the setting of treatment of inflammatory complications with immunosuppressive drugs. Candida infections are infrequently seen and show an age-dependent clinical presentation mainly affecting infants and young children. Furthermore, the child with CGD is susceptible to a wide range of fungal pathogens, indicating the need to determine the causative fungus, often by invasive diagnostic approaches, to guide optimal and rational treatment. Currently, it is becoming more and more clear that the exaggerated inflammatory response to fungal infection in the CGD host is leading in the pathogenesis, and antiinflammatory treatment might become as important as antifungal treatment in this specific host.     

Breakthrough Invasive Fungal Infections in Patients with Acute Myeloid Leukemia

Mycopathologia - We sought to determine the occurrence, risk factors, effect of antifungal prophylaxis, and outcomes of invasive fungal infections (IFIs) in patients with acute myeloid leukemia...     

Challenges in Diagnosing Invasive Pulmonary Aspergillosis in Patients With COPD and Other Chronic Lung Disorders

Invasive pulmonary aspergillosis (IPA) is a necrotizing pneumonia caused by airborne opportunistic fungi of Aspergillus species. Patients with chronic obstructive pulmonary disease (COPD) or other chronic lung disorders (CLD) have emerged to be at risk for IPA, with a related mortality rate greater than 70%. Host factors playing a role in the occurrence of IPA in CLD patients differ from those in patients with hematologic disorders and may be largely responsible for a distinct pattern of the disease. Furthermore, these host factors affect the results of standard diagnostic procedures recommended for IPA. Therefore, the diagnosis of IPA in patients with COPD and other CLD remains challenging for physicians. This review puts into perspective the host factors contributing to the pathogenesis of IPA in CLD patients and discusses the use and interpretation of the main diagnostic tools currently available.     

Chromosomes and Transformation of Lymphocytes in Lymphoproliferative Disorders

In chronic lymphocytic leukaemia the majority of circulating lymphocytes which responded to phytohaemagglutinin in vitro were found to have normal karyotypes. A minor population of cells in patients treated with chemotherapy had an increased number of chromosomal rearrangements as compared with cells from normal controls and untreated patients with chronic lymphocytic leukaemia. Probably bonemarrow and lymph-node cells also had a normal karyotype.In the other lymphoproliferative disorders the peripheral blood lymphocytes had either normal karyotypes or chromosomal abnormalities attributable to treatment, even in those cases where the tumour cells of involved lymph nodes were known to have abnormal karyotypes.It was possible that circulating tumour cells were present in one case.     

Japanese Patients with Chronic Fatigue Syndrome Are Negative for Known Retrovirus Infections

Although chronic fatigue syndrome (CFS) is known to be the syndrome that begins with an acute flu-like illness that may be due to the exposure to an infectious agent, there has been no convincing evidence on the causative agents. Recently, human T-lymphotropic virus type II (HTLV-II)-like virus has been reported to be associated with the CFS by using HTLV Western blot analysis and polymerase chain reaction. However, some investigators could not detect HTLV-II by indirect immunofluorescence analysis. Lately, CFS patients have been reported in Japan. We detected all 30 tested patients with CFS were seronegative for HTLV-II, HTLV-I and HIV by specific peptide ELISA and Western blot. Further, PCR analysis was negative for HTLV-II and retrovirus was not detected by coculture method with patients' PBMC. Thus, known human retrovirus infections do not cause a CFS in Japan.     

Malassezia Species: A Rare Cause of Invasive Fungal Infections in Immunocompromised Patients

The members of Malassezia species, which may cause skin disorders in healthy individuals, are associated with both cutaneous and systemic disorders in immunocompromised patients. These disorders include folliculitis, seborrheic dermatitis, catheter-related fungemia, and deeply invasive infections. This review examines not only the risk factors and pathogenesis of this rare fungal infection but also the clinical manifestations, diagnosis, and treatment of Malassezia infections in immunocompromised patients. Reports from several series of immunocompromised patients have shown low mortality rates with appropriate treatment.     

Identification by PCR of Non-typhoidal Salmonella enterica Serovars Associated with Invasive Infections among Febrile Patients in Mali

Background

In sub-Saharan Africa, non-typhoidal Salmonella (NTS) are emerging as a prominent cause of invasive disease (bacteremia and focal infections such as meningitis) in infants and young children. Importantly, including data from Mali, three serovars, Salmonella enterica serovar Typhimurium, Salmonella Enteritidis and Salmonella Dublin, account for the majority of non-typhoidal Salmonella isolated from these patients.

Methods

We have extended a previously developed series of polymerase chain reactions (PCRs) based on O serogrouping and H typing to identify Salmonella Typhimurium and variants (mostly I 4,[5],12:i:-), Salmonella Enteritidis and Salmonella Dublin. We also designed primers to detect Salmonella Stanleyville, a serovar found in West Africa. Another PCR was used to differentiate diphasic Salmonella Typhimurium and monophasic Salmonella Typhimurium from other O serogroup B, H:i serovars. We used these PCRs to blind-test 327 Salmonella serogroup B and D isolates that were obtained from the blood cultures of febrile patients in Bamako, Mali.

Principal Findings

We have shown that when used in conjunction with our previously described O-serogrouping PCR, our PCRs are 100% sensitive and specific in identifying Salmonella Typhimurium and variants, Salmonella Enteritidis, Salmonella Dublin and Salmonella Stanleyville. When we attempted to differentiate 171 Salmonella Typhimurium (I 4,[ 5],12:i:1,2) strains from 52 monophasic Salmonella Typhimurium (I 4,[5],12:i:-) strains, we were able to correctly identify 170 of the Salmonella Typhimurium and 51 of the Salmonella I 4,[5],12:i:- strains.

Conclusion

We have described a simple yet effective PCR method to support surveillance of the incidence of invasive disease caused by NTS in developing countries.     

Invasive Candidiasis in Patients with Implants

Implantable device infections are an important cause of invasive candidiasis and carry high rates of morbidity and mortality. Central vascular access catheters are by far the most commonly infected type of device. Infections associated with peritoneal dialysis catheters, cardiac devices, prosthetic joints, and other implantable devices are much less common but can have devastating consequences for affected patients. Central to the pathogenesis of these infections is the interplay between altered anatomic barriers due to device implantation, host immune factors, and the tendency of Candida to form biofilms upon inanimate surfaces. Once infection develops, current treatment options nearly always necessitate removal of the device, so major efforts are under way to prevent infection by implementing innovative infection control strategies and developing implants that are less susceptible to biofilm formation. This review focuses on recent developments in our understanding of the epidemiology, pathogenesis, treatment options, and prevention of implant-associated invasive candidiasis.     

Invasive Pulmonary Fungal Infections in Cystic Fibrosis

Invasive pulmonary mycosis is after allergic bronchopulmonary aspergillosis (ABPA) a frequent and severe complication of CF lung disease. Among CF caregivers, there is an insecurity when and how to treat infections of the lung parenchyma caused by different fungi in patients with CF. This case series provides a multicenter experience on diagnostic, manifestation, and treatment of non-ABPA cases of pulmonary. Non-ABPA cases of pulmonary mycoses in patients with CF have been collected from the CF Centers in Berlin, Essen, Worms, Frankfurt (Germany), Leeds (UK), and Barcelona (Spain). Non-ABPA was defined as total serum IgE level <500 kU/L. Scedosporium and Lomentospora species seem to be more virulent in patients with CF and have been successfully treated with triple antifungal drug regimens in several cases. Rare fungi including yeasts can have pathogenic potential in CF. In this series, antibiotic treatment failure was the main indicator for the initiation of antifungal treatment. For an early and effective treatment of pulmonary mycoses in CF, the identification of biomarkers and of risk factors beyond antibiotic treatment failure is crucial and urgently needed. Furthermore, treatment efficacy studies are necessary for the different causative agents of these infections.     

Combination Therapy for Invasive Fungal Infections

The purpose of this review is to summarize and evaluate relevant literature on combination antifungal therapy for invasive fungal infections (IFIs). Cryptococcal meningitis has the largest body and highest quality in support of combination therapy with amphotericin B and flucytosine. More recent data in treatment of invasive aspergillosis suggest combination therapy with voriconazole and echinocandins may be effective in select patients. Quality studies are needed to define combination therapy in rare mold infections. Multiple strategies have been employed to optimize treatment of the growing incidence of IFIs. With exceptions as noted above, justification for the use of combination antifungal therapy is most often based on uncontrolled and/or underpowered studies, in vitro data, and case reports.     

Prevalence and Clinical Course in Invasive Infections with Meningococcal Endotoxin Variants

Background

Meningococci produce a penta-acylated instead of hexa-acylated lipid A when their lpxL1 gene is inactivated. Meningococcal strains with such lipid A endotoxin variants have been found previously in adult meningitis patients, where they caused less blood coagulopathy because of decreased TLR4 activation.

Methods

A cohort of 448 isolates from patients with invasive meningococcal disease in the Netherlands were screened for the ability to induce IL-6 in monocytic cell Mono Mac 6 cells. The lpxL1 gene was sequenced of isolates, which show poor capacity to induce IL-6.. Clinical characteristics of patients were retrieved from hospital records.

Results

Of 448 patients, 29 (6.5%) were infected with meningococci expressing a lipid A variant strain. Lipid A variation was not associated with a specific serogroup or genotype. Infections with lipid A variants were associated with older age (19.3 vs. 5.9 (median) years, p = 0.007) and higher prevalence of underlying comorbidities (39% vs. 17%; p = 0.004) compared to wild-type strains. Patients infected with lipid A variant strains had less severe infections like meningitis or shock (OR 0.23; 95%CI 0.09–0.58) and were less often admitted to intensive care (OR 0.21; 95%CI 0.07–0.60) compared to wild-type strains, independent of age, underlying comorbidities or strain characteristics.

Conclusions

In adults with meningococcal disease lipid A variation is rather common. Infection with penta-acylated lipid A variant meningococci is associated with a less severe disease course.     

Epidemiology of Invasive Fungal Infections in Patients with Acquired Immunodeficiency Syndrome at a Reference Hospital for Infectious Diseases in Brazil

Invasive fungal infections (IFIs) represent one of the main causes of morbimortality in immunocompromised patients. Pneumocystosis, cryptococcosis and histoplasmosis are the most frequently occurring IFIs in patients with acquired immunodeficiency syndrome (AIDS). Fungi, such as Candida spp. and Aspergillus spp., may cause severe diseases during the course of an HIV infection. Following the introduction of highly active anti-retroviral therapy, there has been a marked reduction of opportunistic fungal infections, which today is 20–25 % of the number of infections observed in the mid-1990s. This study is an observational and retrospective study aimed at the characterising IFI incidence and describing the epidemiology, clinical diagnostic and therapeutic features and denouement in HIV/AIDS patients. In HIV/AIDS patients, the IFI incidence is 54.3/1,000 hospitalisation/year, with a lethality of 37.7 %. Cryptococcosis represents the main opportunistic IFI in the population, followed by histoplasmosis. Nosocomial pathogenic yeast infections are caused principally by Candida spp., with a higher candidemia incidence at our institution compared to other Brazilian centres.     

Epidemiology of Invasive Fungal Infections in Latin America

The pathogenic role of invasive fungal infections (IFIs) has increased during the past two decades in Latin America and worldwide, and the number of patients at risk has risen dramatically. Working habits and leisure activities have also been a focus of attention by public health officials, as endemic mycoses have provoked a number of outbreaks. An extensive search of medical literature from Latin America suggests that the incidence of IFIs from both endemic and opportunistic fungi has increased. The increase in endemic mycoses is probably related to population changes (migration, tourism, and increased population growth), whereas the increase in opportunistic mycoses may be associated with the greater number of people at risk. In both cases, the early and appropriate use of diagnostic procedures has improved diagnosis and outcome.     

血液恶性肿瘤患者化疗治疗预防侵袭性真菌感染的临床分析与研究

目的:侵袭性真菌感染在血液恶性肿瘤化疗患者中时常出现,其感染周期较长,且易产生抗药性,给患者带来极大痛苦,为了探讨血液恶性肿瘤患者侵袭性真菌感染的最佳临床预防方案,我院进行了相关研究.方法:选取2009年3月-2012年1月入住我院并接受治疗的血液恶性肿瘤患者156例,将所有患者随机分为观察组和对照组,每组患者78例,其中对照组传统预防方案,观察组采用伊曲康唑预防方案.两组患者化疗治疗后对两组患者的侵袭性真菌感染状况及药物不良反应,不良反应包括血压升高、转氨酶升高、肾功能衰竭、腹泻、皮疹、气胸、药物过敏等.同时对两组患者进行满意度调查.结果:观察组感染率低于对照组27个百分点(P＜0.05),不良反应低于对照组5.1个百分点(P＜0.05),观察组的满意度高于对照组6.4个百分点(P＜0.05),均具有显著性差异,具有统计学意义.结论:观察组由于在传统预防方案的基础上额外采用了伊曲康唑预防对患者进行预防,使得观察组的化疗感染率、不良反应状况均低于对照组,而满意度明显高于对照组,因此对血液恶性肿瘤患者化疗时应用伊曲康唑预防方案可以起到明显的侵袭性真菌感染预防效果,该方案值得进一步推广.