Congenital cytomegalovirus infection is associated with high maternal socio-economic status and corresponding low maternal cytomegalovirus seropositivity.

AIMS: Human cytomegalovirus (CMV) is the leading infectious cause of congenital infection in developed countries. Globally, CMV seropositivity has been associated with low socio-economic status (SES); however, Australian data are lacking. Therefore, we examined the association between SES and CMV seroprevalence in children and pregnant women. METHODS: Three groups were examined: 1, a prospective cohort of Australian children aged 0-15 years (n = 220); 2, a clinic-based sample of pregnant women (n = 778); and 3, a case series of infants and children (n = 219) with symptomatic congenital CMV infection. SES was determined using a postcode-based score from the Australian Bureau of Statistics.Group 1 was recruited from endocrinology clinics and follow-up at Prince of Wales Hospital and Children's Hospital at Westmead. Group 2 was recruited at the Royal Hospital for Women. Congenitally infected infants were identified through the Australian Paediatric Surveillance Unit. RESULTS: CMV seroprevalence among all children was 20% (95% confidence interval (CI) 15-25%), and there was no association with SES (P = 0.58). Seroprevalence among pregnant women was 57% (53-60%), and higher rates of CMV seropositivity were associated with lower SES (P < 0.001). More congenital CMV cases were reported in the highest socio-economic groups (55%) than the lowest (9%) (P < 0.001). CONCLUSIONS: A marked socio-economic gradient in CMV seroprevalence is evident in Australian pregnant women and cases of congenital CMV but not in unselected Australian children. These findings highlight the importance of a community-wide approach to CMV awareness and the potential for hygienic measures to reduce the burden of congenital CMV in Australia.

Human cytomegalovirus infection is detected frequently in stillbirths and is associated with fetal thrombotic vasculopathy.

BACKGROUND: Human cytomegalovirus (CMV) is the most common congenital infection in developed countries and is a known cause of intrauterine fetal death. We examined CMV infection in stillbirths and the relationship with histopathological findings at autopsy. METHODS: We collected liver, kidney, and placenta specimens from 130 stillbirths. CMV DNA and protein were detected using polymerase chain reaction and immunohistochemistry, along with routine autopsy of stillborn infants. RESULTS: Overall, CMV DNA was detected in 15% of singleton, >20-week stillborn infants. CMV DNA was detected in kidney (9%), liver (11%), and placenta (5%) specimens, with 75% of infections confirmed by immunohistochemistry. Fetal thrombotic vasculopathy was the only histopathological abnormality associated with CMV infection (in 60% CMV-infected vs 28% uninfected stillbirths P = .010). CONCLUSIONS: Stillbirth has multiple etiologies. However, the detection of CMV DNA in 15% of fetal tissues or placentae suggests a strong association between CMV infection in pregnancy and stillbirth. Molecular testing during postmortem investigation has an important role to determine the contribution of CMV infection.

Outbreaks of pandemic (H1N1) 2009 and seasonal influenza A (H3N2) on cruise ship.

To determine the extent and pattern of influenza transmission and effectiveness of containment measures, we investigated dual outbreaks of pandemic (H1N1) 2009 and influenza A (H3N2) that had occurred on a cruise ship in May 2009. Of 1,970 passengers and 734 crew members, 82 (3.0%) were infected with pandemic (H1N1) 2009 virus, 98 (3.6%) with influenza A (H3N2) virus, and 2 (0.1%) with both. Among 45 children who visited the ship's childcare center, infection rate for pandemic (H1N1) 2009 was higher than that for influenza A (H3N2) viruses. Disembarked passengers reported a high level of compliance with isolation and quarantine recommendations. We found 4 subsequent cases epidemiologically linked to passengers but no evidence of sustained transmission to the community or passengers on the next cruise. Among this population of generally healthy passengers, children seemed more susceptible to pandemic (H1N1) 2009 than to influenza (H3N2) viruses. Intensive disease control measures successfully contained these outbreaks.

Enhanced diagnosis of pandemic (H1N1) 2009 influenza infection using molecular and serological testing in intensive care unit patients with suspected influenza.

During the 2009 outbreak of pandemic (H1N1) 2009 influenza (pH1N1) in Australia, acute and convalescent serum specimens were collected from 33 patients with severe respiratory disease admitted to intensive care units. Using hemagglutination inhibition of pH1N1, 29 paired serum samples showed significant increases in specific antibody titers. Of these 29 patients, 18 had pH1N1 RNA detected by routine nucleic acid testing. These results indicate that up to one-third of pH1N1 cases may not have laboratory confirmation of infection unless serological testing is included for suspected cases.

Successful valganciclovir treatment of post-transplant cytomegalovirus infection in the presence of UL97 mutation N597D.

Mutations in the human cytomegalovirus (CMV) UL97 protein kinase are the most common mechanism of ganciclovir (GCV) resistance in the clinical setting. A CMV strain with a previously unrecognized UL97 mutation N597D was identified in the blood of a heart transplant recipient who experienced a persistent CMV infection with high viral loads accompanying pain and fever while receiving valganciclovir (valGCV) therapy. The N597D mutation was transferred by mutagenesis to an antiviral sensitive CMV strain for analysis of antiviral susceptibility by standardized phenotypic assay. Recombinant phenotyping showed N597D conferred a less than twofold increase in GCV IC(50) compared to the sensitive control strain. Despite the presence of this mutation, valGCV eventually resolved the infection after 6 weeks of therapy. A subsequent CMV reactivation was also responsive to valganciclovir. This case illustrates the diversity of UL97 mutations in the codon segment 590-607 usually associated with GCV resistance, with some mutations producing minimal levels of resistance that do not preclude a therapeutic response to the drug. Accurate interpretation of genotypic test results ultimately requires experimental determination of the level of resistance conferred by newly discovered UL97 mutations.

Emergence and persistence of multiple antiviral-resistant CMV strains in a highly immunocompromised child.

BACKGROUND: The emergence of human cytomegalovirus (CMV) antiviral resistance plays a significant role in disease progression in immunocompromised patients who have received antiviral therapy. OBJECTIVES: To determine the pattern of antiviral-resistant CMV strains in a highly immunocompromised child. STUDY DESIGN: Retrospective specimens of blood and urine were analysed using PCR-sequencing to identify antiviral-resistant CMV strains containing UL97 or UL54 mutations. RESULTS: CMV strains resistant to antiviral agents contributed to disease in a bone marrow transplant recipient with X-linked severe combined immunodeficiency (SCID) treated with ganciclovir (GCV) and foscarnet (FOS). Retrospective analyses detected GCV-resistant CMV (L595S) in a specimen taken after disease progression. This GCV-resistant CMV strain persisted for 1 year, after which time it was no longer detected even though the patient continued to receive GCV. A FOS-resistant strain (T700A) then emerged even though no FOS had been administered in the preceding year. CONCLUSION: The detection of antiviral-resistant CMV did not follow the patterns found in other patients tested for antiviral resistance, including emergence of a FOS-resistant strain in the absence of antiviral-selective pressure. These findings indicate the patient's underlying immunosuppressive condition should be considered for diagnosis and management of resistant CMV.