Infection In Immunocompetent Individuals Research Articles

New insights into the natural history of hepatitis E virus infection through a longitudinal study of multitransfused immunocompetent patients in France.

Little is known about the natural history of Hepatitis E virus (HEV) infection in immunocompetent individuals. The prevalence, the course of infection and the occurrence of transmission by transfusion were investigated in multitransfused immunocompetent patients/blood donor pairs included in a longitudinal sample repository collection and followed up between 1988 and 2010. Ninety-eight subjects aged 6-89 years and suffering from acquired haemoglobinopathies were tested for HEV markers (IgM, IgG and RNA) in serial samples collected every 2 or 3 years. Eighteen patients (18.4%) were positive for HEV-IgG at baseline with a prevalence increasing from 12.5% below 26 years to 32% above 56 years. Nine patients remained IgG positive along the study and nine lost their antibodies after a mean follow-up of 7.4 years (1-22 years). One seropositive patient showed an increase of IgG level and RNA-HEV reappearance 1 year after inclusion, suggesting a reinfection and one seroconversion, probably acquired through blood transfusion was observed. This first longitudinal study including immunocompetent individuals confirms that HEV infection is common in Western Europe and that transfusion transmission occurs probably less frequently than expected. In addition, seroreversion and reinfection seem to be common. This suggests that the anti-HEV may not persist overtime naturally. However, repeat exposure to the virus related to the high prevalence of HEV infection may result in a sustainable specific IgG response.

Immunoproteomics-Based Analysis of the Immunocompetent Serological Response to Lomentospora prolificans.

The filamentous fungus Lomentospora prolificans is an emerging pathogen causing severe infections mainly among the immunocompromised population. These diseases course with high mortality rates due to great virulence of the fungus, its inherent resistance to available antifungals, and absence of specific diagnostic tools. Despite being widespread in humanized environments, L. prolificans rarely causes infections in immunocompetent individuals likely due to their developed protective immune response. In this study, conidial and hyphal immunomes against healthy human serum IgG were analyzed, identifying immunodominant antigens and establishing their prevalence among the immunocompetent population. Thirteen protein spots from each morph were detected as reactive against at least 70% of serum samples, and identified by liquid chromatography tandem mass spectrometry (LC-MS/MS). Hence, the most seroprevalent antigens were WD40 repeat 2 protein, malate dehydrogenase, and DHN1, in conidia, and heat shock protein (Hsp) 70, Hsp90, ATP synthase β subunit, and glyceraldehyde-3-phosphate dehydrogenase, in hyphae. More interestingly, the presence of some of these seroprevalent antigens was determined on the cell surface, as Hsp70, enolase, or Hsp90. Thus, we have identified a diverse set of antigenic proteins, both in the entire proteome and cell surface subproteome, which may be used as targets to develop innovative therapeutic or diagnostic tools.

Specific K39 antibody response and its persistence after treatment in patients with imported leishmaniasis

The sensitivity of a K39 ELISA (Leishmania IgG, Virion/Serion) for the detection of antibodies in patients with imported leishmaniasis was compared with an immunofluorescence assay (IFA), which was applied as “golden standard”. The retrospective study comprised 93 IFA-positive or borderline sera from 42 patients with visceral (n = 16) or cutaneous (n = 26) leishmaniasis. Patients had acquired infection predominately in the Mediterranean area or the Middle East. The Leishmania species (Leishmania donovani/infantum, Leishmania tropica, Leishmania major) were identified by real-time PCR. The majority (94 %) of first samples from patients with visceral leishmaniasis (VL) tested positive by K39 ELISA. Antibody levels ranged from low to very high (33.19–1990.00 U/ml; median 596.66 U/ml) but did not correlate with the respective IFA titers. High K39 ELISA values correlated with acute infection in immunocompetent individuals. K39 antibodies declined in all individuals after clinically successful therapy, but time to seronegativity varied considerably (51 weeks to >6 years). In patients with cutaneous leishmaniasis (CL), the sensitivity of the K39 ELISA was low (23 %) compared to IFA (92 % positive). Antibody levels ranged from low to medium (10.85–524.77 U/ml; median 19.77 U/ml). The highest antibody concentrations were seen in L. infantum-infected individuals. Summarizing, a high K39 ELISA value indicates active VL. The assay is, like IFA, not a measure for effective therapy but may support post-treatment monitoring. Low level positivity can indicate subclinical, previous or clinically cured VL or even CL. The K39 ELISA can supplement highly sensitive screening tests in the diagnosis and follow-up of imported leishmaniasis.

BK polyomavirus: virus-cell interactions, host immune response, and viral pathogenesis.

The BK polyomavirus (BKPyV) is one of the main human polyomaviruses. After primary infection, it establishes a persistent infection, and acts as an opportunistic pathogen, innocuous in immunocompetent hosts, but causing potentially serious pathology in the context of immunosuppression, in particular in kidney and hematopoietic stem cell graft recipients. Much progress has been made in recent years in the description of virus-cell interactions, but many aspects of viral physiopathology remain mysterious, principally due to the asymptomatic nature of infection in immunocompetent individuals and the lack of an animal model. The characteristics of the antiviral immune response are beginning to become more clearly understood, particularly in kidney transplant patients. Work in these areas is important in order to identify patients at high risk of developing a severe infection. Indeed, in the absence of an effective antiviral therapy few therapeutic options are available, and patient management remains based on modulation of immunosuppressive therapy.

NONTUBERCULOUS TUBERCULOSIS CAUSED BY MYCOBACTERIUM GORDONAE - CLINICAL CASE REPORT

Background: Mycobacterium gordonae is a slow growing mycobacterium usually found in soil, tap water, and as laboratory contaminant. It is occasionally implicated in different infections in immunosuppressed patients. In contrast, there have been few case reports of active infection in immunocompetent individuals. Case Description: We report a case of a 46-old immunocompetent patient with long-term cough and poor expectoration. A computed tomography of the chest revealed punctiform lesions and fibrosis formation in the upper right lobe. It did not show any infiltrate in lung parenchyma. Mycobacterium gordonae was definitively diagnosed by genetic method. After antituberculosis treatment the toxic infectious syndrome was overcome. Conclusion: Mycobacterium gordonae is reported to cause clinically significant nontuberculosis infection in both immunocompetent and immunosuppressed individuals. Mycobacterium gordonae is hardly diagnosed with traditional laboratory methods, but the latest molecular techniques allow successful isolation and identification of slow growing Mycobacterium gordonae.

Human Nocardia Infections: A Review of Pulmonary Nocardiosis.

Human nocardiosis may present as an acute or a chronic infection. Although a saprophyte Nocardia spp are responsible for superficial skin infections, pulmonary infections, and disseminated nocardiosis usually involving patients who are immunosuppressed and debilitated. Infections in immunocompetent individuals are usually chronic and present non-specific symptoms. Invasive and disseminated nocardiosis is common among patients with weakened cellular immune systems. Clinical diagnosis of pulmonary nocardiosis is difficult owing to the similarity of its presentation with other respiratory pathogens that include Actinomycetes members and Mycobacterium tuberculosis. Laboratory diagnosis of human nocardiosis is plagued by the fact that a culture of Nocardia spp requires prolonged incubation periods for isolation which most laboratories fail to follow. The lack of clinical, laboratory, and epidemiological data on the incidence of nocardiosis in humans undermines its significance as a potential pathogen. This review attempts to reexamine the pathogenic potential of Nocardia in human infections

Efficacy of Adjunctive Tofacitinib Therapy in Mouse Models of Tuberculosis

The global tuberculosis (TB) epidemic and the spread of multi- and extensively-drug resistant strains of Mycobacterium tuberculosis (M.tb) have been fueled by low adherence to following lengthy treatment protocols, and the rapid spread of HIV (Human Immunodeficiency Virus). Persistence of the infection in immunocompetent individuals follows from the ability of M.tb to subvert host immune responses in favor of survival within macrophages. Alternative host-directed strategies are therefore being currently sought to improve treatment efficacy and duration. In this study, we evaluated tofacitinib, a new oral Janus kinase (JAK) blocker with anti-inflammatory properties, in shortening tuberculosis treatment. BALB/c mice, which are immunocompetent, showed acceleration of M.tb clearance achieving apparent sterilization after 16weeks of adjunctive tofacitinib therapy at average exposures higher than recommended in humans, while mice receiving standard treatment alone did not achieve clearance until 24weeks. True sterilization with tofacitinib was not achieved until five months. C3HeB/FeJ mice, which show reduced pro-inflammatory cytokines during M.tb infection, did not show improved clearance with adjunctive tofacitinib therapy, indicating that the nature of granulomatous lesions and host immunity may influence responsiveness to tofacitinib. Our findings suggest that the JAK pathway could be explored further for host-directed therapy in immunocompetent individuals.

Respiratory Syncytial Virus in Hematopoietic Stem Cell Transplantation and Solid-Organ Transplantation.

Respiratory syncytial virus (RSV), one of the most common causes of respiratory infections in immunocompetent individuals, can cause significant pulmonary morbidity and mortality in hematopoietic stem cell (HSCT) and less often in solid-organ transplant recipients. Early diagnosis and medical intervention prior to the progression from upper to lower respiratory tract viral involvement is essential to positively affect the clinical course. The greatest risk of disease progression from upper to lower respiratory tract disease is during the early posttransplant period for HSCT recipients, with lymphopenia being an important risk factor. Polymerase chain reaction has become the preferred method for rapidly diagnosing infection in this population because of higher sensitivity compared to traditional viral culture and direct viral antigen methods. Despite the lack of prospective randomized trials, retrospective pooled analyses have suggested that systemically delivered ribavirin (either aerosolized, oral, or IV; with or without immunomodulator therapy) can decrease the risk of progression of disease. Additionally, there are a number of clinical trials currently in process to evaluate several new agents that target RSV in the high-risk HSCT patient population.

Molecular detection of hepatitis E virus (HEV) in liver biopsies after liver transplantation

We aimed to determine the rate of hepatitis E virus (HEV) infection, a recently increasingly recognized disease in the Western world, in liver transplant patients by direct molecular testing of liver tissue. A RT-PCR assay was designed for detecting the HEV open reading frame (ORF) 2/3 gene region in formalin-fixed, paraffin-embedded tissues, and applied to all liver biopsies (n=683) taken 4 weeks or later from all patients (n=282) after liver transplantation of two large academic centers. HEV-RNA was detected in ten biopsies from four different patients (rate: 1%). Histology in early HEV infection was variable including cases with only few hepatocellular apoptoses, no or only minute inflammation. Hepatitis lasted for at least 6 months in 3/4 patients. Serologic testing for HEV-RNA in a subcohort (159 patients) was positive in five patients (rate: 3%), resulting in an overall HEV detection rate of 3% (8/282). In case both liver tissue and sera of a patient were available from the same time period, all cases tested positive in one material were also tested positive in the other material, respectively. All patients had de novo autochthonous infection with HEV genotype 3. Our data confirm that HEV infection is a relevant cause of liver injury after liver transplantation. Molecular testing for HEV in routinely processed transplant liver biopsies is powerful for evaluating patients with elevated transaminases of unknown origin. Histology of HEV infection under immunosuppression in the early phase is distinct from HEV infection in immunocompetent individuals.

Frequency and genotype of human parvovirus B19 among Iranian patients infected with HIV.

The human parvovirus B19 (B19) usually causes a subclinical infection in immunocompetent individuals. Whereas immunocompromised individuals such as patients infected with HIV are at risk of persistent anemia due to B19 infection. Only few studies have been carried out on distribution and molecular epidemiology of B19 in Iran. We aimed to determine the frequency and genotype of B19 among Iranian patients infected with HIV. We conducted a survey on 99 HIV patients and 64 healthy controls. IgG and IgM antibodies against B19 were detected by ELISA and B19 DNA was assessed by nested PCR. PCR products were subjected to direct sequencing and classified after phylogenetic analysis. The prevalence of B19 immunoglobulin was 11.1% for IgG and 1% for IgM. B19 DNA was detected in 13.1% of cases. The prevalence of B19 IgG, IgM, and DNA in control group was 25%, 1.6%, and 9.4%, respectively. B19 IgG was significantly lower in HIV group than in normal controls. There was no significant difference regarding anemia between cases and controls. All sequenced B19 isolates belonged to genotype 1A with low genetic diversity. Our findings indicated that in the HAART era, the importance of B19 infections in HIV patients may be limited whereas persistent B19 viremia in the circulation of healthy controls raises a potential concern in blood donations.

A clinical significance of assessing cytomegalovirus infection status in patients with ulcerative colitis.

A clinical significance of assessing cytomegalovirus infection status in patients with ulcerative colitis.

Rahnella aquatilis Sepsis in a Premature Newborn.

Rahnella aquatilis is an infrequently isolated Gram-negative rod within the Enterobacteriaceae family. The organism's natural habitat is water. The organism is rarely isolated from clinical specimens and it seldom causes infection in immunocompetent individuals. Here we present a one-month-old boy who was born prematurely at 27th week of gestation by cesarean section with a birth weight of 730 g. He developed sepsis caused by Rahnella aquatilis during the treatment for ventilator associated pneumonia due to Stenotrophomonas maltophilia with ciprofloxacin. He was successfully treated with a combination of amikacin plus meropenem. Although R. aquatilis is one of the saprophyticus organisms, it may cause life-threatening infection in newborn.

Detection of Encephalitozoon spp. from human diarrheal stool and farm soil samples in Korea.

Microsporidia are eukaryotic organisms that cause zoonosis and are major opportunistic pathogens in HIV-positive patients. However, there is increasing evidence that these organisms can also cause gastrointestinal and ocular infections in immunocompetent individuals. In Korea, there have been no reports on human infections with microsporidia to date. In the present study, we used real-time PCR and nucleotide sequencing to detect Encephalitozoon intestinalis infection in seven of 139 human diarrheal stool specimens (5%) and Encephalitozoon hellem in three of 34 farm soil samples (8.8%). Genotype analysis of the E. hellem isolates based on the internal transcribed spacer 1 and polar tube protein genes showed that all isolates were genotype 1B. To our knowledge, this is the first report on human E. intestinalis infection in Korea and the first report revealing farm soil samples as a source of E. hellem infection. Because microsporidia are an important public health issue, further large-scale epidemiological studies are warranted.

Mycobacterium abscessus: An environmental mycobacteria being a human pathogen

BackgroundMycobacterium abscessus is an opportunistic organism common in the environment. This species rarely cause infections in immunocompetent individuals. Certain patient groups, however, can get severe infections, e.g., in skin, soft tissues or lungs, as well as disseminated infections. During the last years, this organism has emerged as a major pathogen in patients with cystic fibroses. M. abscessus exhibits two different colony types: one with smooth and shining morphology, the other with rough and dry morphology. The smooth strains are considered wild-types, which become rough due to mutation. These features make the M. abscessus variants particularly interesting for scientific studies, since the results of such analyses can be a basis for creating theories also concerning other mycobacteria. AimThe aim of this study is to analyze potential differences between smooth and rough strains of M. abscessus concerning human host response. MethodsM. abscessus strains isolated at the Mycobacterial Laboratory in Gothenburg, Sweden were analyzed morphologically. The ability of monocytes to internalize the two colony variants of M. abscessus was studied, as well as the cytokine response. ResultsThe analyses showed that isolates from the wound mainly exhibit smooth colony formation, while those from airways generally are of the rough phenotype. Human monocytes easily internalized the smooth varieties of M. abscessus, whereas the rough ones rarely were internalized. Differences between the two types, concerning the capacity to induce cytokines, were also revealed. Discussion and conclusionsThe wound isolates of M. abscessus were mainly smooth, while the lung isolates were rough. The rough variants that lack certain surface glycolipids are likely to be more hydrophobic and aerosol transmissible than the smooth strains, which might explain why the rough ones are more often associated with infections in the airways than are the smooth ones. Studies on other mycobacteria have also shown a link between hydrophobicity and aerosol transmission.These studies showed that human monocytes easily internalize smooth M. abscessus cells, but rarely the rough ones. This capacity of the rough cells to avoid internalization is in all probability also due to absence or reduction of certain surface glycolipids. The lack of these surface lipids makes the rough bacteria stick to each other forming so-called cords, which are aggregates of many cells and thus difficult to internalize. The absence of glycolipids exposing other surface structures of the bacteria cell may also contribute to prevent internalization. Even if intracellular survival is regarded as the most important virulence factor of mycobacteria, it is nevertheless likely that the capacity to avoid internalization can contribute to pathogenesis at several mycobacterioses. It is possible that this phenomenon is important at tuberculosis, since Mycobacterium tuberculosis cells form rough colonies.

Prevalence of toxoplasmosis and related risk factors among humans referred to main laboratories of Urmia city, North West of Iran, 2013.

Toxoplasmosis is mostly asymptomatic infection in immunocompetent individuals while it can cause a severe infection in human fetusduring pregnancy and immunocompromised patients. This study aimed to determine the prevalence of anti-Toxoplasma IgM and IgG seropositivity and potential risk factors of the infection in humans referred to Urmia City maindiagnostic laboratories, Urmia, Iran. Totally 195 blood samples were collected from the individuals referred to maindiagnostic laboratories of Urmia City, 2013. Serum concentration of anti-Toxoplasma IgG and IgM were determined using ELISA method. Demographic variables of the participants were collected by interviewing, which are including sex, age, occupation, educational and residential status, eating undercooked meat, consumption of raw vegetable and the method of washing raw vegetables. None of all 200 serum sample were anti-Toxoplasma IgM positive, but different concentrations of anti-Toxoplasma IgG were observed in 88 (45.12%) of samples. The significant higher rate of anti-Toxoplasma IgG seropositivitywere observed in people with soil related jobs (P=0.005, OR=2.266; 95% CI 1.260, 4.078) and history of eating raw vegetables at restaurant (P=0.036, OR=1.985; 95% CI 0.991, 3.978). Also anti-Toxoplasma IgG concentrationmean was significantly higher in people whowere commonly eaten raw vegetable at restaurants (P<0.001, t=7.918). The prevalence of chronic toxoplasmosis is considerably high while the acute infection is very low in the studied area. Having soil related jobs and eating raw vegetables at restaurants increases the risk of acquiring the infection.

Localized cutaneous infections in immunocompetent individuals due to rapidly growing mycobacteria.

Rapidly growing mycobacteria (RGM) cause skin infections that are refractory to standard antibiotic regimens. Although typically associated with disseminated cutaneous or other systemic infections in immunocompromised patients, RGM sometimes cause localized cutaneous infections in immunocompetent hosts. These infections are almost always associated with precedent skin trauma and inoculation, and therefore have been implicated in outbreaks involving contaminated tattoo ink and inadequately sterilized acupuncture needles. Histologic features often include suppurative granulomatous inflammation, and microorganisms are rarely visualized with stains for acid-fast bacilli. The differential diagnosis includes granulomatous fungal and non-RGM bacterial infections as well as noninfectious suppurative or sarcoidlike conditions. Because no pathognomonic histologic features exist for cutaneous RGM infections, clinical suspicion and appropriate workup are essential to reach an accurate and timely diagnosis. Most localized cutaneous RGM infections in immunocompetent individuals respond well to either clarithromycin or amikacin, in combination with surgical debridement.

Molluscum contagiosum in a pediatric American Indian population: incidence and risk factors.

BackgroundMolluscum contagiosum virus (MCV) causes an innocuous yet persistent skin infection in immunocompetent individuals and is spread by contact with lesions. Studies point to atopic dermatitis (AD) as a risk factor for MCV infection; however, there are no longitudinal studies that have evaluated this hypothesis.MethodsOutpatient visit data from fiscal years 2001–2009 for American Indian and Alaska Native (AI/AN) children were examined to describe the incidence of molluscum contagiosum (MC). We conducted a case-control study of patients <5 years old at an Indian Health Service (IHS) clinic to evaluate dermatological risk factors for infection.ResultsThe incidence rate for MC in children <5 years old was highest in the West and East regions. MC cases were more likely to have a prior or co-occurring diagnosis of eczema, eczema or dermatitis, impetigo, and scabies (p<0.05) compared to controls; 51.4% of MC cases had a prior or co-occurring diagnosis of eczema or dermatitis.ConclusionsThe present study is the first demonstration of an association between AD and MC using a case-control study design. It is unknown if the concurrent high incidence of eczema and MC is related, and this association deserves further investigation.

Toxoplasmosis as a travel risk.

Toxoplasma gondii is a protozoan parasite with worldwide distribution that infects more than one third of the global population. Primary infection in immunocompetent individuals is usually asymptomatic; however, different organs can be affected in immunocompromised individuals leading to the development of encephalitis, myocarditis or pneumonitis. The prevalence of infection with Toxoplasma as well as its genetic structure varies geographically and for that reason travel may be considered as a risk factor to acquire the infection. As toxoplasmosis is a foodborne disease, health care providers should give health education on prevention measures to all prospective travelers in order to decrease the risk of infection in endemic areas. This review presents an overview of the infection with T. gondii with some considerations for travelers to and from endemic zones.

Immunotherapeutic Approaches To Prevent Cytomegalovirus-Mediated Disease.

Human cytomegalovirus (CMV) is the major cause of congenital neurological defects in the United States and also causes significant morbidity and mortality for hematopoietic and solid organ transplant patients. Primary infection in immunocompetent individuals rarely causes disease but resolves as a life-long latent infection, characterized by sustained antibody and cellular responses. Despite considerable efforts over the last 40 years to develop live attenuated and subunit vaccines, none is close to receiving regulatory approval. However, there is evidence that antibodies can prevent primary infection and cytotoxic T cells can suppress secondary infection. Prior maternal infection decreases the risk a fetus will contract CMV, while adoptive transfer of virus-specific CD8+ T cells is highly protective against CMV disease in hematopoietic stem cell transplant recipients. As a result, three polyclonal immunoglobulin preparations are approved for clinical use and one monoclonal antibody has reached phase III trials. Enhanced understanding of the viral life cycle from a biochemical perspective has revealed additional targets for neutralizing antibodies in the gH/gL/UL128-131 pentamer. Until an effective vaccine is licensed, passive immunotherapeutics may present an alternative to maintain viral loads and prevent CMV disease in susceptible populations. This review summarizes the progress and potential of immunotherapeutics to treat CMV infection.

Identification of Past and Recent Parvovirus B19 Infection in Immunocompetent Individuals by Quantitative PCR and Enzyme Immunoassays: a Dual-Laboratory Study

Parvovirus B19 (B19V) is a member of the family Parvoviridae, genus Erythrovirus. B19V-specific IgG and IgM react differently against conformational and linear epitopes of VP1 and VP2 antigens, leading to the development of IgG avidity and epitope type specificity (ETS) enzyme immunoassays (EIAs) for distinguishing past from recent infection. Additionally, B19V viral load determination (by quantitative PCR [qPCR]) is increasingly used in the staging of B19V infection. In this study, the utility of these methods is compared. A panel of 78 sera was jointly tested by the Virus Reference Department (VRD), London, United Kingdom, and the Haartman Institute (HI), Helsinki, Finland, using a number of EIAs, e.g., B19V-specific IgG and IgM, IgG avidity, and ETS EIAs. At VRD, the sera were also tested by a B19V viral load PCR (qPCR). By consensus analysis, 43 (55.1%) sera represented past infection, 28 (35.9%) sera represented recent infection, and 7 (9.0%) sera were indeterminate. Both VRD B19V qPCR and HI B19V VP2 IgM EIA gave the highest agreement with consensus interpretation for past or recent infection, with an overall agreement of 99% (95% confidence interval [CI], 92 to 100) and positive predictive value (PPV) of 100% (95% CI, 87 to 100). Nine sera designated as representing past infection by consensus analysis were B19V IgM positive by a commercial VRD B19V IgM EIA and B19V IgM negative by a new HI in-house B19V VP2 IgM EIA. A new VRD B19V IgG avidity EIA showed good (>95%) agreement (excluding equivocal results) with consensus interpretations for past or recent infection. Correct discrimination of past from recent B19V infection was achieved through application of qPCR or by appropriate selection of EIAs.