Philip Rice

Cytomegalovirus Infection in Immunocompetent Patients

Symptoms associated with cytomegalovirus (CMV) infection in immunocompetent patients are not well documented. From December 1998 through June 2001, serum samples obtained from 7630 patients in Cambridge and Chelmsford, United Kingdom, were tested for CMV immunoglobulin M. CMV immunoglobulin G avidity was used to confirm CMV infection. A total of 124 patients (106 patients treated by general practitioners [GPs] and 18 hospitalized patients) with CMV infection were identified. The most frequent symptoms were malaise (67%), fever (46%), and sweats (46%), and the most frequent finding was abnormal liver function test results (69%). Twelve percent of patients had a relapsing illness, and many had symptoms that lasted for up to 32 weeks (mean duration of symptoms, 7.8 weeks). GPs reported that there was a significant benefit in making the diagnosis of CMV infection; it provided reassurance and avoided the need for further investigations. We have identified symptoms associated with CMV infection in immunocompetent patients who present to GPs or who are admitted to the hospital.

Congenital cytomegalovirus: association between dried blood spot viral load and hearing loss

Aim: To investigate the relation between cytomegalovirus (CMV) viral load on dried blood spots (DBS) from newborn biochemical screening (“Guthrie”) cards, and sensorineural hearing loss (SNHL) in congenital CMV. Design: Cross-sectional study with retrospective case-note review. Setting: Seven paediatric audiology departments in the United Kingdom. Patients: 84 children, median age 7 years: 43 with known congenital CMV, 41 with unexplained SNHL. Interventions: Half a DBS was tested for CMV DNA viral load by quantitative real-time polymerase chain reaction (PCR). Main outcome measures: Pure tone average hearing thresholds (0.5–4 kHz). Results: DBS CMV DNA viral load significantly correlated with hearing thresholds for the worse and better hearing ears (Spearman’s rank correlations: r = 0.445, p = 0.008 and r = 0.481, p = 0.004 respectively). Multivariable logistic regression showed that the effect of DBS viral load on the risk of SNHL remained important, when age and central nervous system involvement had been taken into account (odds ratio (OR) 2.76, 95% confidence interval (CI) 1.14 to 6.63, p = 0.024). The mean log DBS viral load was significantly higher in children with SNHL than in those with normal hearing (2.69 versus 1.64, 95% CI −1.84 to −0.27, p = 0.01). 8/35 (23%) children with unexplained SNHL tested positive for CMV DNA on DBS. One false positive result was obtained. Conclusion: The risk of SNHL increased with DBS viral load. Further studies should investigate whether DBS CMV testing has a role in identifying asymptomatic congenitally infected neonates at risk of SNHL, and whether antiviral treatment can reduce this risk.

Dengue Hemorrhagic Fever with Fulminant Hepatic Failure in an Immigrant Returning to Bangladesh

An immigrant from Bangladesh living in the United Kingdom presented with a nonspecific febrile illness after visiting his homeland and subsequently developed fulminant hepatic failure accompanied by hypotension, ascites, a generalized coagulopathy, and thrombocytopenia. Serology and detection of dengue virus serotype 3 by PCR established a postmortem diagnosis of hepatic failure secondary to dengue hemorrhagic fever.

Enfurvitide prevents vertical transmission of multidrug-resistant HIV-1 in pregnancy but does not cross the placenta.

The use of previously successful antiretroviral regimens in mother-to-child transmission (MTCT) prevention will be increasingly challenged by the rising prevalence of multidrug-resistant (MDR) HIV. We used enfurvitide together with an optimized antiretroviral backbone to prevent the MTCT prevention of MDR HIV in two pregnant women. The measurement of maternal and foetal peripheral blood levels of enfurvitide showed no evidence of transplacental transfer.

Ultra-violet radiation is responsible for the differences in global epidemiology of chickenpox and the evolution of varicella-zoster virus as man migrated out of Africa

BackgroundOf the eight human herpes viruses, varicella-zoster virus, which causes chickenpox and zoster, has a unique epidemiology. Primary infection is much less common in children in the tropics compared with temperate areas. This results in increased adult susceptibility causing outbreaks, for example in health-care workers migrating from tropical to temperate countries. The recent demonstration that there are different genotypes of varicella-zoster virus and their geographic segregation into tropical and temperate areas suggests a distinct, yet previously unconsidered climatic factor may be responsible for both the clinical and molecular epidemiological features of this virus infection.Presentation of the hypothesisUnlike other human herpes viruses, varicella-zoster virus does not require intimate contact for infection to occur indicating that transmission may be interrupted by a geographically restricted climatic factor. The factor with the largest difference between tropical and temperate zones is ultra-violet radiation. This could reduce the infectiousness of chickenpox cases by inactivating virus in vesicles, before or after rupture. This would explain decreased transmissibility in the tropics and why the peak chickenpox incidence in temperate zones occurs during winter and spring, when ultra-violet radiation is at its lowest. The evolution of geographically restricted genotypes is also explained by ultra-violet radiation driving natural selection of different virus genotypes with varying degrees of resistance to inactivation, tropical genotypes being the most resistant. Consequently, temperate viruses should be more sensitive to its effects. This is supported by the observation that temperate genotypes are found in the tropics only in specific circumstances, namely where ultra-violet radiation has either been excluded or significantly reduced in intensity.Testing the HypothesisThe hypothesis is testable by exposing different virus genotypes to ultra-violet radiation and quantifying virus survival by plaque forming units or quantitative mRNA RT-PCR.Implications of the hypothesisThe ancestral varicella-zoster virus, most probably a tropical genotype, co-migrated with man as he left Africa approximately 200,000 years ago. For this virus to have lost the selective advantage of resistance to ultra-violet radiation, the hypothesis would predict that the temperate, ultra-violet sensitive virus should have acquired another selective advantage as an evolutionary trade-off. One obvious advantage could be an increased reactivation rate as zoster to set up more rounds of chickenpox transmission. If this were so, the mechanism responsible for resistance to ultra-violet radiation might also be involved in reactivation and latency. This could then provide the first insight into a genetic correlate of the survival strategy of this virus.

Recurrence of hepatitis B after single lung transplantation.

This study describes a patient who developed decompensated liver disease secondary to reactivation of hepatitis B infection 20 months after single lung transplantation following augmentation of immunosuppression to treat allograft rejection. Discussion focuses on the virologic and management issues of this case and reviews the approach taken when considering patients with chronic hepatitis B infection for lung transplantation.