^{1}

^{1}

Enhanced hygiene measures can reduce norovirus transmission potential by 85%.

Control of norovirus outbreaks relies on enhanced hygiene measures, such as handwashing, surface cleaning, using disposable paper towels, and using separate toilets for sick and well persons. However, little is known about their effectiveness in limiting further spread of norovirus infections. We analyzed norovirus outbreaks in 7 camps at an international scouting jamboree in the Netherlands during 2004. Implementation of hygiene measures coincided with an 84.8% (95% predictive interval 81.2%–86.6%) reduction in reproduction number. This reduction was unexpectedly large but still below the reduction needed to contain a norovirus outbreak. Even more stringent control measures are required to break the chain of transmission of norovirus.

Gastroenteritis is one of the most common causes of illness (

Norovirus infection can cause serious medical complications, such as dehydration, in persons with underlying illness (

We investigated the effect of enhanced hygiene measures on reducing norovirus transmission during an outbreak. We measured the effectiveness of enhanced hygiene measures as the relative reduction in the reproduction number—defined as the average number of secondary cases caused by 1 typical case—in the absence of and after enhanced hygiene measures. The value of this reproduction number provides crucial information about transmission potential: if the reproduction number exceeds the threshold value of 1, the number of new cases will increase over time; if it is <1, the number of new cases will decline over time, and eventually the chain of transmission will break.

The time course of the reproduction number during an outbreak can be inferred from the epidemic curve (

An outbreak of norovirus infection occurred at an international scout jamboree in the Netherlands during the summer of 2004 (

The jamboree was held on a large site, ≈600 m × 1,000 m. Jamboree participants were divided into 7 camps according to age: 3 camps each for participants 11–14 and 15–17 years of age and 1 camp for staff

Epidemic curve of an outbreak of norovirus at an international scout jamboree in the Netherlands, starting July 26, 2004 (day 0).

Day of onset | Camp, no. new cases/d | Total (n = 4,500) | |||||||
---|---|---|---|---|---|---|---|---|---|

A (n = 485) | B (n = 721) | C (n = 729) | D (n = 499) | E (n = 735) | F (n = 825*) | G (n = 506) | Unknown | ||

0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |

1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 4 |

2 | 0 | 2 | 2 | 1 | 1 | 3 | 0 | 1 | 10 |

3 | 2 | 7 | 9 | 0 | 2 | 1 | 0 | 1 | 22 |

4 | 3 | 4 | 2 | 1 | 2 | 2 | 4 | 0 | 18 |

5 | 0 | 10 | 1 | 2 | 1 | 1 | 2 | 2 | 19 |

6 | 0 | 12 | 3 | 2 | 2 | 0 | 0 | 1 | 20 |

7 | 2 | 19 | 14 | 2 | 3 | 3 | 6 | 3 | 52 |

8 | 3 | 5 | 8 | 2 | 2 | 1 | 1 | 0 | 22 |

9 | 7 | 10 | 14 | 0 | 2 | 10 | 24 | 2 | 69 |

10 | 5 | 4 | 3 | 2 | 0 | 16 | 8 | 11 | 49 |

11 | 3 | 2 | 4 | 1 | 0 | 1 | 1 | 3 | 15 |

12 | 4 | 1 | 4 | 2 | 1 | 1 | 0 | 2 | 15 |

13 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 3 |

14 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 3 |

15 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 3 |

Total† | 31 | 77 | 68 | 15 | 17 | 41 | 47 | 30 | 326 |

*This number is estimated. †Overall attack rate: 7.2. Attack rate by camp: A, 6.4; B, 10.7; C, 9.3; D, 3.0; E, 2.3; F, 5.0; G, 9.3.

On July 29 (day 3 of the jamboree), the Municipal Health Service “Hart voor Brabant” in ’s-Hertogenbosch provided advice on enhanced hygiene measures (

Norovirus was epidemiologically implicated as the causative agent (

During the outbreak, the Municipal Health Service assessed the number of new cases from typical gastroenteritis symptoms self-reported by participants and staff. After the jamboree, participants and staff were given a questionnaire asking them to report to the Municipal Health Service whether gastroenteritis had developed within a week after departure. The questionnaire asked the date of symptom onset, symptoms, camp label, and hospital admission.

We estimated the reproduction number for every case during the norovirus outbreak at the jamboree. Using the date of symptom onset for each case, we applied statistical methods to reconstruct likely patterns of who infected whom (

Generation time distribution for norovirus infections. Generation time is the time between onset of symptoms in successive case-patients. The histogram gives the relative frequency in norovirus outbreaks in Sweden in 1999 (

We incorporated additional information about the camp label of almost all case-patients and the pathogen genotype for 7 case-patients into the estimation procedure by adding a ”weight” to the transmission probabilities between pairs of cases. Here we considered 2 extreme cases for mixing between camps. The first extreme case was homogeneous mixing between all participants of the jamboree, as we assumed in the analysis described above; to achieve this, we assigned a weight of 1 to any pair of cases. The second extreme case was mixing within camps only and no mixing between camps. In this instance, the transmission probabilities for pairs of case-patients that stayed in different camps were assigned a weight of 0, and the transmission probabilities for pairs of case-patients that stayed in the same camp were given a weight of 1. The transmission probabilities for pairs of cases with known different genotypes were assigned a weight of 0, and the transmission probabilities for pairs of cases with known identical genotypes were assigned a weight of 1.

If the enhanced hygiene measures resulted in a sudden decline in transmission, the expected decline of the reproduction number would be gradual. Four factors determined the expected time course: the day enhanced hygiene measures began, the cumulative frequency distribution of generation times, the reproduction number without enhanced hygiene measures, and the relative reduction of the reproduction number attributed to hygiene measures. We express the reproduction number as a function of these 4 factors (

We tested the estimation procedure by simulating epidemic curves with known reproduction numbers. The interval estimates for reproduction numbers covered the actual values for days 0–7. We detected a slight downward bias for the estimated value of reproduction numbers and a slight downward bias for the estimated relative reduction of reproduction numbers after implementation of enhanced hygiene measures, indicating that the values obtained by the estimation procedure are conservative (

The estimated reproduction numbers decreased over time as the norovirus outbreak spread through the international scout jamboree (

Time course of the reproduction number for norovirus at an international scout jamboree, starting July 26, 2004 (day 0), in the Netherlands. Black diamonds show the mean value for the reproduction number over all sampled transmission matrices; vertical lines, mean minimum and maximum values for the reproduction number over all sampled transmission matrices. The dark gray area shows the uncertainty range (0.025 and 0.975 quantiles) in the mean reproduction number; light gray are, the uncertainty range (0.025 and 0.975 quantiles) of the maximum and minimum estimates of the reproduction number. The solid black line represents the fitted time course of reproduction numbers if decrease in the mean reproduction number results from an instantaneous decline in transmission when enhanced hygiene measures began; dashed line, the threshold value of 1, below which the outbreak was controlled.

The disease attack rate varied among different camps, from 2.3% to 10.7%; overall attack rate was 7.2% (

Time course of the reproduction number for norovirus for 7 camps of an international scout jamboree. Black diamonds show the mean value of the reproduction number without additional information about population structure and genotypes. Gray boxes show the mean value of the reproduction number when additional information about population structure and genotypes is used. The vertical lines show the mean minimum and maximum reproduction number over all sampled transmission matrices. The solid black line represents the time course of reproduction numbers if decrease in the mean reproduction number results from an instantaneous decline in transmission when enhanced hygiene measures begin. The camps are in order of the day of symptom onset of the first case-patient. Top panels indicate first introduction, bottom panels the last introduction.

We have shown that during an outbreak of norovirus, implementation of enhanced hygiene measures coincided with an 85% reduction of norovirus transmission, from 14.05 secondary cases per primary case before enhanced hygiene measures to 2.13 secondary cases per primary case after enhanced hygiene measures. This estimate is consistent with the time course of reproduction numbers in different camps in which infection was introduced at different times. Our estimates confirm the alleged high epidemic potential of norovirus and suggest that the enhanced hygiene measures were not sufficient to reduce the reproduction number below the threshold value of 1. This estimate explains why the number of new cases per day continued to increase and why norovirus infection spread to new camps, even after implementation of enhanced hygiene measures. It is tempting to speculate that our findings could be extrapolated to other hygiene measures to explain the typical pattern in several subsequent norovirus outbreaks on cruise ships and in hotels (

The estimation procedure for the time course of the reproduction number has several limitations. It requires a frequency distribution for the generation time, which may be unknown for many diseases that are less well studied than norovirus. The procedure also requires reporting of symptom onset of case-patients over intervals on the order of the mean generation time or smaller. Here, because the mean generation time was 3.6 days, we cannot use weekly reports of time of symptom onset. The procedure also requires a large outbreak so the effects of chance events on the course of the epidemic are minimized. Small outbreaks would lead to estimates of reproduction numbers that are highly uncertain and have questionable value for making generalizations about transmission.

Our main result is that the observed decline in the reproduction number coincided with implementation of enhanced hygiene measures. This extrapolation is highly suggestive of a causal relationship, which implies that hygiene measures can effectively reduce transmission of norovirus. However, several alternatives can explain the declining reproduction number, as discussed below.

First, the decrease in reproduction number may be due to chance events. Here we explicitly estimated the reproduction numbers from times of symptom onset and the generation time distribution for norovirus infections, whereas earlier work relied on transforming epidemic curves to reproduction numbers (

Second, it might be that jamboree participants differed in susceptibility, and the pool of highly susceptible persons was depleted during the first days of the outbreak. However, preexisting immunity for the genotypes involved seems highly unlikely: GI.5 and GI.4 rarely are detected in Europe, and the GII.4–2004 genotype caused a large epidemic during the winter after the jamboree (

Third, the decline in reproduction number could be because many infections were asymptomatic and many symptomatic cases were not reported. The request to report any symptoms might not have reached all participants because of the event’s large size and because participants came from many different countries. During norovirus outbreaks, asymptomatic cases occur; in almost half of the outbreaks in the Netherlands during 2002, stool samples from

Fourth, different genotypes of norovirus could have spread at different times during the outbreak. From genotyping data of 7 cases of the norovirus outbreak during the jamboree, we know that 3 different norovirus genotypes circulated during this outbreak from genogroup I and II. Recent work (

Finally, a change of the generation time distribution during the outbreak could explain the decline in reproduction number. The method we used to estimate the time course of reproduction number depends crucially on a correct specification of the generation time distribution. Here we obtained this distribution from a study of a norovirus outbreak in child daycare centers in Sweden (

We have quantitatively estimated the effectiveness of enhanced hygiene measures in containing an outbreak of norovirus. Because the reproduction number did not fall below the threshold value of 1, implementation of the hygiene measures was not sufficient to effectively break the chain of person-to-person transmission of norovirus during this outbreak. To contain an outbreak of norovirus, more rigorous interventions are required. These might range from better compliance with hygiene protocols to strict isolation of case-patients and quarantine of their contacts. We recommend quantifying the effectiveness of interventions against norovirus to provide the necessary evidence to justify use of existing hygiene protocols during outbreaks and to direct the development of better intervention measures. Although such quantifying would require analysis of more norovirus outbreaks with different sets of intervention measures, it would enable identification of the best possible intervention strategies to control the spread of one of the most common pathogens of humans.

Methods

Testing the Estimation Procedures with Simulated Outbreaks

We thank Harry Vennema and Bas van der Veer for performing the norovirus diagnostic testing and Nicola Low for commenting on the final version.

Ms Heijne is an infectious disease epidemiologist, formerly at the National Institute for Public Health and the Environment in the Netherlands and now at the Institute of Social and Preventive Medicine, University of Bern in Switzerland. Her work focuses on analyzing time series of infectious diseases.