Human Cytomegalovirus Pneumonia Research Articles

Complexity of Human Cytomegalovirus Infection in South African HIV-Exposed Infants with Pneumonia.

Human cytomegalovirus (HCMV) can cause significant end-organ diseases such as pneumonia in HIV-exposed infants. Complex viral factors may influence pathogenesis including: a large genome with a sizeable coding capacity, numerous gene regions of hypervariability, multiple-strain infections, and tissue compartmentalization of strains. We used a whole genome sequencing approach to assess the complexity of infection by comparing high-throughput sequencing data obtained from respiratory and blood specimens of HIV-exposed infants with severe HCMV pneumonia with those of lung transplant recipients and patients with hematological disorders. There were significantly more specimens from HIV-exposed infants showing multiple HCMV strain infection. Some genotypes, such as UL73 G4B and UL74 G4, were significantly more prevalent in HIV-exposed infants with severe HCMV pneumonia. Some genotypes were predominant in the respiratory specimens of several patients. However, the predominance was not statistically significant, precluding firm conclusions on anatomical compartmentalization in the lung.

Human cytomegalovirus pneumonia and intestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a case report and literatures review

Human cytomegalovirus pneumonia and intestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a case report and literatures review

Deaths due to respiratory tract infections in Africa

According to the WHO, lower respiratory tract infections are one of the most prevalent causes of death in Africa. Estimates based on verbal autopsies are inaccurate compared with the gold standard for determining cause of death, the anatomical postmortem. Here, we review all respiratory postmortem data available from Africa and assess disease prevalence by HIV status in both adults and children. Pulmonary and extrapulmonary tuberculosis was detected in over 50% of HIV-infected adults, four to five-fold more prevalent than in HIV-uninfected cases. Overall tuberculosis was less prevalent in children, but was more prevalent in HIV-uninfected compared with HIV-infected children. Bacterial pneumonia was more prevalent in children than adults and was relatively unaffected by HIV status. Pneumocystis jirovecci and human cytomegalovirus pneumonia were detected almost exclusively in HIV-infected mortalities, twice as prevalent in children as in adults. Coinfections were common and correlation with premortem clinical diagnoses was low. Respiratory tract infections are important causes of mortality in Africa. Of the 21 reviewed studies, only four studies (all adults) were undertaken in the last decade. There is hence an urgent need for new postmortem studies to monitor cause of death in new and emerging patient groups, such as those on antiretroviral therapy and HIV exposed uninfected children.

Detection of human cytomegalovirus in transbronchial biopsies from lung transplant recipients

The role of human cytomegalovirus (HCMV) in lung transplantation (LT) and drawbacks related to viral quantification in bronchoalveolar lavage (BAL) underline the potential usefulness of investigating other specimens. Thirty-three LT recipients were prospectively studied by HCMV quantitative real time PCR on matched transbronchial biopsy (TBB), BAL, and whole blood specimens. Overall, 27/33 patients turned out HCMV-positive in at least one specimen: 7.1%, 37.1%, and 13.5% of TBB, BAL, and blood samples, respectively. No significant association between HCMV on all types of specimens and acute rejection, lymphocytic bronchiolitis, bronchiolitis obliterans and bronchiolitis obliterans syndrome was found. HCMV pneumonia was associated to HCMV detection on TBB (p=0.003) and whole blood (p=0.008), not on BAL (p=0.47). The highest mean viral load was detected in TBB from cases with HCMV pneumonia in comparison to all other cases, suggesting the potential use of HCMV investigation in TBB for evaluating posttransplant complications.

The Lack and Cytomegalovirus-Specific Cellular Immune Response May Contribute to the Onset of Organ Infection and Disease in Lung Transplant Recipients

Cellular immune response has been demonstrated to play a role in the control of human cytomegalovirus (HCMV) replication in organ transplant recipients. Herein, HCMV-specific T-cell response and association to the onset of organ infection/disease were prospectively evaluated by EliSPOT assay in a population of 46 lung transplant (LT) recipients at 1, 3, 6, 9 and 12 months post-transplantation. According to our centre?s practice, a combined prolonged antiviral prophylaxis (HCMV-IG for 12 months and ganciclovir or valganciclovir for 3 weeks from postoperative day 21) was given to all LT recipients. HCMV-DNA was concomitantly detected on bronchoalveolar lavage (BAL) and whole blood by real-time PCR. Approximately one third of patients resulted HCMV persistently non-responder; the rate of HCMV infection, as evaluated by HCMV-DNA positivity, tended to be higher in non-responders. Mean viral load on BAL was significantly higher in non-responders vs other patients (p < 0.001). Temporal profile of infections appeared related to the HCMV responder status with a shorter time to onset of infection post-transplantation and a longer duration in non-responders. The occurrence of organ disease (i.e. pneumonia) tended to be higher in non-responders, with poor prognosis, as death occurred in one of three non-responder patients that developed HCMV pneumonia. The lack of HCMV-specific cellular response can contribute to the onset of organ infection and disease also in patients in which antiviral prophylaxis was adopted; this could be due to the potential occurrence of incomplete control of replication in lungs or a delayed priming of T-cell reconstitution.

Evaluation of HCMV on transbronchial biopsies in lung transplant recipients

Introduction. Human cytomegalovirus (HCMV) can cause direct and indirect effects in lung transplant recipients. Virological monitoring is usually performed by evaluation of viral load on bronchoalveolar lavage (BAL). However, few centers perform surveillance bronchoscopies with transbronchial biopsy (TBB) for investigating the occurrence of HCMV infection/disease, in addition to rejection. In this study, prevalence and clinical role of HCMV quantification on TBB have been studied. Methods. HCMV has been quantified by real-time PCR on 87 serial TBB specimens from 30 lung transplant recipients (all receiving anti-HCMV prophylaxis) and on the corresponding BAL and whole blood specimens. Results have been related to available histopathological features (including pneumonia, acute rejection, chronic rejection) and immunohistochemistry. Results. HCMV has been detected in 8%, 32.2%, and 16.7% of TBB, BAL, and whole blood specimens, respectively. Interstitial pneumonia has been diagnosed in 14.9% of cases, with a significant association to HCMV positivity on TBB (viral load 103-104 copies/104 cells), but not on BAL and whole blood. No significant association between HCMV positivity on TBB and acute or chronic rejection has been found, although previous episodes of HCMV pneumonia had occurred in two patients with chronic rejection. Conclusions. Evaluation of HCMV on TBB could be useful to identify episodes of local reactivation with subsequent organ disease. Although sampling errors on TBB must always be considered, this could allow to overcome problems in BAL dilution. Surveillance TBB in lung transplant recipients allows for early identification of rejection episodes or HCMV reactivation, thus suggesting the initiation of antiviral therapy and optimizing clinical management.

Incidence and clinical outcome of cytomegalovirus transmission via breast milk in preterm infants ≤31 weeks

To evaluate incidence, timing and clinical relevance of acquired human cytomegalovirus (HCMV) infection in preterm infants. The prospective longitudinal study included preterm infants </=31 weeks. Congenital HCMV infection was excluded by negative HCMV culture from urine or by HCMV-PCR-negative umbilical cord blood. Infants from HCMV-IgG-positive mothers received thawed frozen breast milk until 33 weeks. Urine samples were obtained weekly for HCMV culture. Data were collected regarding clinical course and milk-intake. Twenty-nine mothers (29/48, 60%) of 35 infants were HCMV-IgG-positive. Five of 35 infants (14%) excreted HCMV in urine. Three of five children remained asymptomatic. One child developed a respirator-dependent HCMV pneumonia, the other child an upper airway infection and a transient thrombocytopenia. HCMV infected children had a significant longer hospital stay (median 96 vs. 73 days, p = 0.025) and received more formula milk (89 vs. 44 mL/kg/day, p = 0.04). Mothers of infected children had significantly higher HCMV-IgG levels than those of non-infected children (mean 1557 vs. 921 AU/mL, p = 0.048). Nineteen of 48 mothers (40%) with 23 infants were HCMV-IgG-negative. These children remained HCMV negative. Feeding preterm infants </=31 weeks of HCMV-IgG-positive mothers with thawed frozen breast milk until 33 completed weeks does not prevent symptomatic HCMV infection in all cases. These infections can be associated with a prolonged hospital stay.

Pneumonitis in human cytomegalovirus infection

Human cytomegalovirus (HCMV) is a beta herpes virus with a double stranded DNA genome of 240kbp. The virus is prevalent and establishes a latent infection in most adults. HCMV is an opportunistic pathogen for patients with impaired cellular immunity. HCMV pneumonia is a common presentation of HCMV disease in immunocompromised patients. The incidence of HCMV pneumonitis can be as high as 90% in lung transplant recipients. This paper takes a fresh look at the challenging perspectives of molecular, immunologic, cellular, diagnostic, clinical, and therapeutic characteristics of HCMV infection as future targets for development of antiviral strategies.

Human Cytomegalovirus Resistance to Antiviral Drugs

Human cytomegalovirus (HCMV) infections are common and lead to lifelong infections. In immunocompetent individuals, primary infections are mostly subclinical or they may be associated with a self-limited mononucleosis-like syndrome. In contrast, infections in immunocompromised hosts (either primary infections, reactivations from latency, or reinfections) are associated with important morbidity and mortality. In patients with AIDS, the introduction of highly active antiretroviral therapy (HAART) has decreased the overall incidence of HCMV disease, mainly retinitis and gastrointestinal infections, by about 80% (50, 105). However, the functional benefit of HAART (i.e., restoration of specific HCMV-specific immune responses) may take up to 3 to 6 months to occur, and some patients do not have access to or do not respond to HAART (3, 40, 67, 104). Thus, HCMV still remains a concern in AIDS patients with CD4 counts <50 to 100 cells/μl. A specific HCMV syndrome consisting of fever, malaise, arthralgia, and neutropenia may occur in solid-organ transplant (SOT) patients, in particular, those developing a primary HCMV infection (i.e., HCMV-seronegative recipient from a HCMV-seropositive donor [D+/R−]) during the first 3 months posttransplantation. In addition, invasive HCMV disease may involve different organs, such as the lungs, liver, and gastrointestinal tract. In the absence of antiviral intervention, symptomatic HCMV infections occur in approximately 39 to 41% of heart-lung transplant recipients, 9 to 35% of heart transplant recipients, 22 to 29% of liver and pancreas transplant recipients, 8 to 32% of kidney transplant recipients, 50% of kidney-pancreas transplant recipients, and 22% of small-bowel transplant recipients (114), with the highest incidence seen in D+/R− patients. Finally, active HCMV infections have been associated with indirect effects, such as dysfunction or rejection of the transplanted organ, an increased risk for bacterial or fungal opportunistic infections, and accelerated atherosclerosis in heart transplant recipients (109). Among allogeneic bone marrow transplant (BMT) or hematopoietic stem cell transplant (HSCT) recipients, pneumonia and enteritis are the most common clinical manifestations of HCMV disease. In HCMV-seropositive recipients, active HCMV infections occur in 70 to 80% of patients; and in the absence of antiviral intervention, disease develops in 20 to 35% of those individuals, whereas active infections occur in only 15% of seronegative recipients of marrow from a seropositive donor (102). HCMV pneumonia remains associated with a significant risk of mortality, even when specific antiviral treatment is administered (18, 101). Gastrointestinal disease, alone or in association with pulmonary disease, is the second most common clinical manifestation of HCMV infections in that setting (85). In addition to AIDS patients and transplant recipients, HCMV infections have been associated with serious complications in other immunocompromised hosts, such as cancer patients, mostly those suffering from hematologic malignancies (48), and children with congenital primary immunodeficiencies (135). Finally, congenital HCMV infections can result in severe sequelae in newborns or during the first years of life (22).

Early Diagnosis and Monitoring of Human Cytomegalovirus Pneumonia in Patients With Adult T-cell Leukemia by DNA Amplification in Serum

A nested polymerase chain reaction (PCR) was used to detect human cytomegalovirus (HCMV) DNA in serum of patients with adult T-cell leukemia (ATL). Serum samples were collected consecutively from 11 patients with HCMV pneumonia diagnosed histopathologically and 7 HCMV-seropositive patients without HCMV disease. Serum samples obtained from 24 HCMV-seropositive healthy volunteers were used as controls. The HCMV DNA was detected in serum a mean of 14 days before the onset of HCMV pneumonia, which suggests that DNAemia exists prior to the development of HCMV pneumonia. The amount of viral DNA in serum increased with disease progression and decreased with disease improvement. Thus, the detection of HCMV DNA in serum by nested PCR is useful for monitoring and the early diagnosis of HCMV pneumonia in patients with ATL. In addition, quantitation of HCMV DNA may be useful for monitoring HCMV infection, because it appears to correlate with the activity of the disease.

Spontaneous dissecting aneurysms of coronary arteries in a cardiac allograft

Dissecting aneurysms of coronary arteries are a rare finding and have never been reported in a cardiac allograft. We found two spontaneous dissecting aneurysms on the middle third of both the left anterior descending and the right coronary arteries in a female cardiac transplantation recipient. She died 43 days after cardiac transplantation after developing human cytomegalovirus pneumonia and pancreatitis. Dissecting coronary aneurysms, microfoci of subendocardial coagulative necrosis, and area of subepicardial dystrophic calcifications were discovered at necropsy examination.