Transmission of Respiratory Syncytial Virus in Households: Who Acquires Infection From Whom?

Households represent a setting of frequent and intense contacts and hence are conducive to the spread of respiratory viruses, such as respiratory syncytial virus (RSV). Infants are most vulnerable to severe RSV disease but a vaccine is not yet available hence the need to explore alternate strategies of protecting them. Such strategies would require better understanding of who infects the infants. During the RSV season of 2009/2010, we undertook a prospective study in rural Kenya involving 493 members of 47 households each with a child bom after the preceding RSV epidemic and at least one elder sibling. Throughout the epidemic a nasopharyngeal swab (NPS) was collected every 3-4 days irrespective of symptoms, from all household members, and tested for a range of respiratory viruses including RSV using a molecular diagnostic assay. Partial sequencing of the attachment protein (G) gene from positive swabs was used to compare RSV strains within the household. In addition, once-a-week a specimen of oral fluid (OF) from around the gums was collected for RSV-specific antibodies screening and for assessment of sensitivity of the OF in detection of RSV using molecular diagnostics. This is the first prospective study to investigate introduction and transmission of RSV in families using molecular techniques over a complete RSV season. Analysis of RSV infection data is reported in this thesis with particular interest to identifying from where infants derive their infection, estimating the duration of RSV shedding and identity factors influencing the recovery rates, and estimating parameters of RSV susceptibility and transmission probability. In addition, data on diagnostic performance of OF in detection of RSV by molecular methods is presented. A total of 16,924 NPS were collected, representing 86% of planned. RSV was detected in 40 (85%) households and 179 (36%) of the participants. In 28 of the 44 households with complete data, there was transmission of RSV to the infants experiencing their first epidemic. The probable source of RSV infection of the naive infants was a household member in at least 54% of the cases. Co-primary infection between a household member and the RSV-naive infant was ascribed in 4 of the cases. Older children were assigned the primary case for 11 (39%) of the infant cases and 10 (91%) of these were attending school. The infants appeared to play a role transmitting the introduced infections to the other members of the household including to the mothers. These findings support vaccination strategies that target school age children and pregnant women. Both of these vaccination strategies can have profound benefits to RSV naive infants directly by augmenting neutralizing antibodies against RSV (immunization of the pregnant women) and indirectly by reducing transmission from siblings to RSV-naive infants. Results from this study provide increased confidence in the rationale for RSV vaccination of individuals who are not the key targets for protection

Quantifying social contacts in a household setting of rural Kenya using wearable proximity sensors

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Quantifying age-related rates of social contact using diaries in a rural coastal population of Kenya

Background Improved understanding and quantification of social contact patterns that govern the transmission dynamics of respiratory viral infections has utility in the design of preventative and control measures such as vaccination and social distancing. The objective of this study was to quantify an age-specific matrix of contact rates for a predominantly rural low-income population that would support transmission dynamic modeling of respiratory viruses. Methods and Findings From the population register of the Kilifi Health and Demographic Surveillance System, coastal Kenya, 150 individuals per age group (50 years) exhibited the highest inter-generational contacts. Rural contact rates were higher than semiurban (18.8 vs 15.6, p = 0.002), with rural primary school students having twice as many assortative contacts as their semiurban peers. Conclusions and Significance This is the first age-specific contact matrix to be defined for tropical Sub-Saharan Africa and has utility in age-structured models to assess the potential impact of interventions for directly transmitted respiratory infections

The source of respiratory syncytial virus infection in infants : a household cohort study in rural Kenya

Background. Respiratory syncytial virus (RSV) vaccine development for direct protection of young infants faces substantial obstacles. Assessing the potential of indirect protection using different strategies, such as targeting older children or mothers, requires knowledge of the source of infection to the infants. Methods. We undertook a prospective study in rural Kenya. Households with a child born after the preceding RSV epidemic and ≥1 elder sibling were recruited. Nasopharyngeal swab samples were collected every 3–4 days irrespective of symptoms from all household members throughout the RSV season of 2009–2010 and tested for RSV using molecular techniques. Results. From 451 participants in 44 households a total of 15 396 nasopharyngeal swab samples were samples were collected, representing 86% of planned sampling. RSV was detected in 37 households (84%) and 173 participants (38%) and 28 study infants (64%). The infants acquired infection from within (15 infants; 54%) or outside (9 infants; 32%) the household; in 4 households the source of infant infection was inconclusive. Older children were index case patients for 11 (73%) of the within-household infant infections, and 10 of these 11 children were attending school. Conclusion. We demonstrate that school-going siblings frequently introduce RSV into households, leading to infection in infants

Influence of age, severity of infection, and co-infection on the duration of respiratory syncytial virus (RSV) shedding

RSV is the most important viral cause of pneumonia and bronchiolitis in children worldwide and has been associated with significant disease burden. With the renewed interest in RSV vaccines, we provide realistic estimates on duration, and influencing factors on RSV shedding which are required to better understand the impact of vaccination on the virus transmission dynamics. The data arise from a prospective study of 47 households (493 individuals) in rural Kenya, followed through a 6-month period of an RSV seasonal outbreak. Deep nasopharyngeal swabs were collected twice each week from all household members, irrespective of symptoms, and tested for RSV by multiplex PCR. The RSV G gene was sequenced. A total of 205 RSV infection episodes were detected in 179 individuals from 40 different households. The infection data were interval censored and assuming a random event time between observations, the average duration of virus shedding was 11·2 (95% confidence interval 10·1–12·3) days. The shedding durations were longer than previous estimates (3·9–7·4 days) based on immunofluorescence antigen detection or viral culture, and were shown to be strongly associated with age, severity of infection, and revealed potential interaction with other respiratory viruses. These findings are key to our understanding of the spread of this important virus and are relevant in the design of control programmes

Map of the study area.

<p>The inset shows the location of the KHDSS in relation to the former Kilifi District (part of Kilifi County). The study area locations are conventionally categorised as semiurban (Kilifi Township [denoted A] and Tezo [B]), and rural (Ngerenya [C], Roka [D] and Matsangoni [E]).</p

Contact mixing patterns.

<p>Part A: Distribution of overall number of contacts (with mean shown as a dashed line). Part B: Mean (dashed line) contact rate per person per day, with boxplots showing median (centre line) and interquartile range (IQR) of contact rates per age group per day. Part C: Contact rate surface (heat map) expressing the mean number of contacts between an individual participant in each age group with individuals in each age group. Part D: Population level numbers of contacts per day within and between age groups (estimated from the matrix defined in (C) scaled by the age-specific resident population size).</p

Age group specific contact rates with 95% CI^‡.

‡<p>Confidence intervals based on 2,000 bootstraps.</p><p>^*Age group in years.</p

Mean number of contacts per day stratified by gender, age group (years), presence of shadow, season, residence, days of week of 568 diary participants from the Kilifi Health and Demographic Surveillance System, Kenya.

‡<p>95% CI: 95% confidence intervals derived from 2,000 bootstraps.</p>$<p>Season: Dry  =  January, August, December; Wet  =  September – November</p>&<p>Location. Rural: Ngerenya, Roka, Matsangoni; Semiurban: Kilifi Township, Tezo.</p