Norovirus transmission mediated by asymptomatic family members in households

Abstract

The transmission of human norovirus excreted from infected persons occasionally causes sporadic infections and outbreaks. Both symptomatic patients and asymptomatic carriers have been reported to contribute to norovirus transmission, but little is known about the magnitude of the contribution of asymptomatic carriers. We carried out a 1-year survey of residents of a district of Bangkok, Thailand to determine the percentage of norovirus transmissions originating from asymptomatic individuals. We screened 38 individuals recruited from 16 families from May 2018 to April 2019 for GI and GII genotypes. Norovirus was detected every month, and 101 of 716 stool samples (14.1%) from individuals with no symptoms of acute gastroenteritis were norovirus-positive. The average infection frequency was 2.4 times per person per year. Fourteen genotypes were identified from the positive samples, with GII.4 being detected most frequently. Notably, 89.1% of the norovirus-positive samples were provided by individuals with no diarrhea episode. Similar to cases of symptomatic infections in Thailand, asymptomatic infections were observed most frequently in December. We detected 4 cases of NV infection caused by household transmission, and 3 of the 4 transmissions originated from asymptomatic individuals. We also identified a case in which norovirus derived from an asymptomatic individual caused diarrhea in a family member. These results suggest that asymptomatic individuals play a substantial role in both the maintenance and spreading of norovirus in a community through household transmission.

Fig 1. The primary survey of NV infections from May–July 2018.

(A) Age distribution of the participants. (B) Gender distribution of the participants. (C) NV positivity in the primary survey. The numbers of NV-positive samples in each month were 2/128 (P1, collected at May 25), 12/123 (P2, collected at June 22), and 5/118 (P3, collected at July 20). (D) Diarrhea episodes among subjects providing NV-positive samples. The numbers of individuals with (black bars) and without (white bars) a diarrheal episode within 1 month prior to the sample collection among the NV-positive samples are shown. (E) The detection frequency of each genotype. The total number of samples with each genotype was counted.

Fig 2. NV infections in the 1-year survey.

(A) Age distribution of the participants. (B) Gender distribution of the participants. (C) The detection frequency of each genotype. The total number of samples with each genotype was counted. (D) The genotype distribution in the 1-year survey. (E) The number of participants infected with each genotype. (F) The ratio of participants infected with each genotype among the total participants.

Fig 3. The monthly distribution of NV and individuals with diarrhea.

(A) The monthly distribution of NV in the total samples. The NV positivity in samples collected each month is shown. (B) Diarrhea episodes of the NV-positive samples. The numbers of individuals with (black bars) or without (white bars) a diarrheal episode within 1 month prior to the sample collection are shown. (C) The monthly distribution of the incidence of diarrhea. The numbers of individuals who had an episode of diarrhea within 1 month prior to the sample collection among the NV-negative (white bars) and NV-positive individuals (black bars) in each month are shown.

Fig 4. The NV infection frequency and the number of genotypes for each individual.

(A) The frequency of NV infection. Infections of the same genotype that occurred more than 1-month interval were counted as 2 independent infections. When the same genotype was detected in consecutive periods, it was counted as one infection. Co-infection with 2 distinct genotypes during the same period was counted as 2 independent infections. The y-axis indicates the number of individuals who were infected with NV 0–5 times per year. (B) The number of genotypes detected for each individual. Infection was counted as described in panel A. The y-axis indicates the number of individuals who were infected with 0–4 genotypes per year. (C) The frequency of infection of each genotype in the same individual. Infection was counted as described in panel A. The y-axis indicates the number of individuals who were infected once 1 (white bar), 2 (gray bar), or 3 times (black bar) with each genotype. (D) The incidence of diarrhea of each genotype. The incidence of diarrhea is indicated by the percentage of samples associated with diarrhea among the total samples for each genotype.

Fig 5. The phylogenetic tree of the GII.4 strains and possible transmission routes.

The evolutionary history was inferred using the neighbor-joining method. The optimal tree with the sum of branch length = 0.06918009 is shown. The percentages of replicate trees in which the associated taxa clustered together in the bootstrap test (1,000 replicates) are shown next to the branches. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. Transmission routes with high probability (solid arrows) and low probability (dashed arrows) are indicated.