Ben Lopman

Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant

BACKGROUND Highly publicised outbreaks of norovirus gastroenteritis in hospitals in the UK and Ireland and cruise ships in the USA sparked speculation about whether this reported activity was unusual. METHODS We analysed data collected through a collaborative research and surveillance network of viral gastroenteritis in ten European countries (England and Wales were analysed as one region). We compiled data on total number of outbreaks by month, and compared genetic sequences from the isolated viruses. Data were compared with historic data from a systematic retrospective review of surveillance systems and with a central database of viral sequences. FINDINGS Three regions (England and Wales, Germany, and the Netherlands) had sustained epidemiological and viral characterisation data from 1995 to 2002. In all three, we noted a striking increase in norovirus outbreaks in 2002 that coincided with the detection and emergence of a new predominant norovirus variant of genogroup II4, which had a consistent mutation in the polymerase gene. Eight of nine regions had an annual peak in 2002 and the new genogroup II4 variant was detected in nine countries. Also, the detection of the new variant preceded an atypical spring and summer peak of outbreaks in three countries. INTERPRETATION Our data from ten European countries show a striking increase and unusual seasonal pattern of norovirus gastroenteritis in 2002 that occurred concurrently with the emergence of a novel genetic variant. In addition to showing the added value of an international network for viral gastroenteritis outbreaks, these observations raise questions about the biological properties of the variant and the mechanisms for its rapid dissemination.

Norovirus Disease in the United States

Although recognized as the leading cause of epidemic acute gastroenteritis across all age groups, norovirus has remained poorly characterized with respect to its endemic disease incidence. Use of different methods, including attributable proportion extrapolation, population-based surveillance, and indirect modeling, in several recent studies has considerably improved norovirus disease incidence estimates for the United States. Norovirus causes an average of 570–800 deaths, 56,000–71,000 hospitalizations, 400,000 emergency department visits, 1.7–1.9 million outpatient visits, and 19–21 million total illnesses per year. Persons >65 years of age are at greatest risk for norovirus-associated death, and children <5 years of age have the highest rates of norovirus-associated medical care visits. Endemic norovirus disease occurs year round but exhibits a pronounced winter peak and increases by ≤50% during years in which pandemic strains emerge. These findings support continued development and targeting of appropriate interventions, including vaccines, for norovirus disease.

Viral gastroenteritis outbreaks in Europe, 1995-2000

To gain understanding of surveillance and epidemiology of viral gastroenteritis outbreaks in Europe, we compiled data from 10 surveillance systems in the Foodborne Viruses in Europe network. Established surveillance systems found Norovirus to be responsible for >85% (N=3,714) of all nonbacterial outbreaks of gastroenteritis reported from 1995 to 2000. However, the absolute number and population-based rates of viral gastroenteritis outbreaks differed markedly among European surveillance systems. A wide range of estimates of the importance of foodborne transmission were also found. We review these differences within the context of the sources of outbreak surveillance information, clinical definitions, and structures of the outbreak surveillance systems.

Clinical Manifestation of Norovirus Gastroenteritis in Health Care Settings

Noroviruses are generally believed to cause relatively mild gastroenteritis of short duration in otherwise healthy adults. However, outbreaks in health care settings are common and affect vulnerable populations. During 2002-2003, a total of 4 major hospitals, 11 community hospitals, and 135 nursing homes in the county of Avon, England, were prospectively monitored for outbreaks of gastroenteritis. For 482 hospital staff, 166 nursing home staff, and 266 nursing home residents, the median duration of norovirus gastroenteritis was 2 days, with 75% achieving complete recovery within 3 days. The median duration of norovirus gastroenteritis for 730 hospital patients was 3 days (75% of the patients achieved complete recovery within 5 days), which was significantly longer than that for all other groups (P<.001). Therefore, infection in hospitalized persons may be more severe than that in other groups in the community at large. This increased duration of acute illness should be considered when implementing measures to prevent transmission in hospital settings.

Voluntary counselling and testing: uptake, impact on sexual behaviour, and HIV incidence in a rural Zimbabwean cohort

Objectives:To examine the determinants of uptake of voluntary counselling and testing (VCT) services, to assess changes in sexual risk behaviour following VCT, and to compare HIV incidence amongst testers and non-testers. Methods:Prospective population-based cohort study of adult men and women in the Manicaland province of eastern Zimbabwe. Demographic, socioeconomic, sexual behaviour and VCT utilization data were collected at baseline (1998–2000) and follow-up (3 years later). HIV status was determined by HIV-1 antibody detection. In addition to services provided by the government and non-governmental organizations, a mobile VCT clinic was available at study sites. Results:Lifetime uptake of VCT increased from under 6% to 11% at follow-up. Age, increasing education and knowledge of HIV were associated with VCT uptake. Women who took a test were more likely to be HIV positive and to have greater HIV knowledge and fewer total lifetime partners. After controlling for demographic characteristics, sexual behaviour was not independently associated with VCT uptake. Women who tested positive reported increased consistent condom use in their regular partnerships. However, individuals who tested negative were more likely to adopt more risky behaviours in terms of numbers of partnerships in the last month, the last year and in concurrent partnerships. HIV incidence during follow-up did not differ between testers and non-testers. Conclusion:Motivation for VCT uptake was driven by knowledge and education rather than sexual risk. Increased sexual risk following receipt of a negative result may be a serious unintended consequence of VCT. It should be minimized with appropriate pre- and post-test counselling.

The Roles of Clostridium difficile and Norovirus Among Gastroenteritis-Associated Deaths in the United States, 1999–2007

BACKGROUND Globally, gastroenteritis is recognized as an important contributor to mortality among children, but population-based data on gastroenteritis deaths among adults and the contributions of specific pathogens are limited. We aimed to describe trends in gastroenteritis deaths across all ages in the United States and specifically estimate the contributions of Clostridium difficile and norovirus. METHODS Gastroenteritis-associated deaths in the United States during 1999-2007 were identified from the National Center for Health Statistics multiple-cause-of-death mortality data. All deaths in which the underlying cause or any of the contributing causes listed gastroenteritis were included. Time-series regression models were used to identify cause-unspecified gastroenteritis deaths that were probably due to specific causes; seasonality of model residuals was analyzed to estimate norovirus-associated deaths. RESULTS Gastroenteritis mortality averaged 39/1000000 person-years (11 255 deaths per year) during the study period, increasing from 25/1 000 000 person-years in 1999-2000 to 57/1 000 000 person-years in 2006-2007 (P < .001). Adults aged ≥ 65 years accounted for 83% of gastroenteritis deaths (258/1 000 000 person-years). C. difficile mortality increased 5-fold from 10/1 000 000 person-years in 1999-2000 to 48/1 000 000 person-years in 2006-2007 (P < .001). Norovirus contributed to an estimated 797 deaths annually (3/1 000 000 person-years), with surges by up to 50% during epidemic seasons associated with emergent viral strains. CONCLUSIONS Gastroenteritis-associated mortality has more than doubled during the past decade, primarily affecting the elderly. C. difficile is the main contributor to gastroenteritis-associated deaths, largely accounting for the increasing trend, and norovirus is probably the second leading infectious cause. These findings can help guide appropriate clinical management strategies and vaccine development.

Epidemiology and cost of nosocomial gastroenteritis, Avon, England, 2002-2003.

Implementing control measures rapidly may be effective in controlling gastroenteritis outbreaks.

Human caliciviruses in Europe

Caliciviruses are single-stranded RNA viruses, which are divided into four genera based on their morphology and genomic structure. Viruses from two genera, the Norwalk like viruses and Sapporo like viruses, are a common cause of acute, nonbacterial gastroenteritis in humans. Although the first human calicivirus discovered nearly 30 years ago, much of the epidemiological and biological character of these viruses is only now beginning to unfold. Investigation has been difficult due to a number of factors, the viruses cannot be amplified by in vitro cell culture or animal models and electron microscopy (EM) is often not sensitive enough to detect the viruses in stool samples. Recent advances in molecular diagnostic techniques and the advent of a baculovirus expression system have highlighted the clinical and public health importance of calicivirus in all age groups, their ability to cause infection via a number of transmission routes as well as their considerable genetic diversity. These characteristics, in conjunction with the inability of humans to develop long-term immunity make HuCV an important public health issue in Europe and worldwide.

Decline in Diarrhea Mortality and Admissions after Routine Childhood Rotavirus Immunization in Brazil: A Time-Series Analysis

A time series analysis by Manish Patel and colleagues shows that the introduction of rotavirus vaccination in Brazil is associated with reduced diarrhea-related deaths and hospital admissions in children under 5 years of age.

HIV-associated orphanhood and children's psychosocial distress: theoretical framework tested with data from Zimbabwe.

OBJECTIVES We measured the psychosocial effect of orphanhood in a sub-Saharan African population and evaluated a new framework for understanding the causes and consequences of psychosocial distress among orphans and other vulnerable children. METHODS The framework was evaluated using data from 5321 children aged 12 to 17 years who were interviewed in a 2004 national survey in Zimbabwe. We constructed a measure of psychosocial distress using principle components analysis. We used regression analyses to obtain standardized parameter estimates of psychosocial distress and odds ratios of early sexual activity. RESULTS Orphans had more psychosocial distress than did nonorphans. For both genders, paternal, maternal, and double orphans exhibited more-severe distress than did nonorphaned, nonvulnerable children. Orphanhood remained associated with psychosocial distress after we controlled for differences in more-proximate determinants. Maternal and paternal orphans were significantly more likely than were nonorphaned, nonvulnerable children to have engaged in sexual activity. These differences were reduced after we controlled for psychosocial distress. CONCLUSIONS Orphaned adolescents in Zimbabwe suffer greater psychosocial distress than do nonorphaned, nonvulnerable children, which may lead to increased likelihood of early onset of sexual intercourse and HIV infection. The effect of strategies to provide psychosocial support should be evaluated scientifically.