Thursday, September 1, 2016
Ahead of Print Exposure Specific and Age Specific Attack Rates for Ebola Virus Disease in Ebola Affected Households Sierra Leone Volume 22 Number 8—August 2016 Emerging Infectious Disease journal CDC
Ahead of Print Exposure Specific and Age Specific Attack Rates for Ebola Virus Disease in Ebola Affected Households Sierra Leone Volume 22 Number 8—August 2016 Emerging Infectious Disease journal CDC
Ahead of Print -Exposure-Specific and Age-Specific Attack Rates for Ebola Virus Disease in Ebola-Affected Households, Sierra Leone - Volume 22, Number 8—August 2016 - Emerging Infectious Disease journal - CDC
Threat from Emerging Vectorborne Viruses — (Length: 7:32)
Volume 22, Number 8—August 2016
Research
Exposure-Specific and Age-Specific Attack Rates for Ebola Virus Disease in Ebola-Affected Households, Sierra Leone
On This Page
- Methods
- Results
- Discussion
- Suggested Citation
Hilary Bower, Sembia Johnson, Mohamed S. Bangura, Alie Joshua Kamara, Osman Kamara, Saidu H. Mansaray, Daniel Sesay, Cecilia Turay, Francesco Checchi, and Judith R. Glynn
Suggested citation for this article
Abstract
Using histories of household members of Ebola virus disease (EVD) survivors in Sierra Leone, we calculated risk of EVD by age and exposure level, adjusting for confounding and clustering, and estimated relative risks. Of 937 household members in 94 households, 448 (48%) had had EVD. Highly correlated with exposure, risk ranged from 83% for touching a corpse to 8% for minimal contact and varied by age group: 43% for children <2 years of age; 30% for those 5–14 years of age; and >60% for adults >30 years of age. Compared with risk for persons 20–29 years of age, exposure-adjusted relative risks were lower for those 5–9 (0.70), 10–14 (0.64), and 15–19 (0.71) years of age but not for children <2 (0.92) or 2–4 (0.97) years of age. Lower risk for 5–19-year-olds, after adjustment for exposure, suggests decreased susceptibility in this group.
In Ebola epidemics in West Africa and elsewhere, children appear to have been relatively spared (1–5). Published notification data for the West Africa outbreak that began in 2013 show a linear increase in incidence of Ebola virus disease (EVD) with age in persons up to ?35 years of age, followed by a plateau in incidence for older age groups (6). Among children, the World Health Organization has reported a slightly increasing incidence with increasing age in Liberia and Sierra Leone but no clear pattern in Guinea (4). In contrast, published case-fatality rates for EVD are lowest for persons 10–15 years of age and highest for young children and older adults (4,7).
These age patterns could result from bias in recognizing, diagnosing, or reporting cases; differences in exposure; or differences in susceptibility to disease. Official data from the West Africa outbreak are known to be inaccurate (8,9). In previous, smaller outbreaks, case ascertainment could have been more complete because of the smaller scale, but EVD cases might have been missed, especially mild cases; deaths may also have been missed because the elderly and very young are more likely to sicken and die from other causes. Children with fever are less likely than adults to visit health facilities for care, and children may be underreported as contacts (10).
Exposure patterns are likely to differ by age and sex. Women may be more at risk from caring for the sick and men from carrying sick persons to the hospital. Children may be deliberately kept away from sick persons and funeral rites, and lower incidence among children has been attributed to these factors (1,11). However, preventing exposure of young children in Ebola-affected households is difficult. Children need to be held, fed, and cared for and often share beds with adults or other children; they may also be exposed through breastfeeding (12).
The high case-fatality rate observed in children <5 years of age and especially in those <1 year of age (4) suggests that young children are particularly susceptible to Ebola; consequently, low incidence in young children may reflect low exposure or low ascertainment. In a study of 27 Ebola-affected households after the Kikwit outbreak in 1995, children <18 years of age had lower risks of disease than adults, after adjustment for reported exposures (13).
Assessing whether risk by age depends on exposure or susceptibility requires a comparison of exposures in persons with and without EVD. A recent systematic review of risk factors for transmission of Ebola virus found few studies reporting data on risks (14) and no previous study large enough to stratify in detail by age (3,13,15–19). We interviewed a large cohort of EVD survivors and their household members to determine exposure levels of all members, living and dead, and to calculate attack rates and relative risks by age, sex, and type of exposure. The Sierra Leone Ethics and Scientific Review Committee and the Ethics Committee of the London School of Hygiene and Tropical Medicine approved the study.
Methods
All survivors who were discharged from Kerry Town Ebola Treatment Centre (ETC), Sierra Leone, during November 2014–March 2015 and who lived in the Western Area were eligible for the study. During July–August 2015, members of the study team, which had assisted in survivor reintegration into the community, contacted survivors or their parents or guardians and asked them to bring all household members who were present at the time Ebola was affecting their household to an interview to be conducted at 1 of various locations. To make contact, the field team went to addresses of all survivors when addresses were available and complete enough to locate. We also used telephone numbers when available. Team members were university graduates, nurses, and paramedics and included Ebola survivors; they received extensive training in interview techniques and were supervised by the first 2 authors (H.B. and S.J.), 1 or both of whom attended all interviews.
After obtaining individual written informed consent from each participant or parents or guardians of participants <18 years of age, the interviewers compiled a list of all members in each household and included information on age, sex, and household members who had had EVD and those who had died of EVD. Households were defined as persons eating from the same pot at the time EVD was in the household, regardless of how much time had been spent in the household, and included persons who joined the household to assist someone who was ill.
We asked household members to describe in their own words what had occurred in the household. For each person reported as having had EVD, we asked what symptoms occurred at home and which persons had helped that person during his or her EVD illness, shared a bed or had contact with the person, or had contact with the body if the person died. Adults spoke for young children and corroborated information from older children. Using probing questions and predefined exposure levels, we assigned a maximum exposure for persons who had been present in the household. The levels, which we developed on the basis of the literature and discussion with ETC staff, included touching the corpse of someone who died from EVD; direct contact with body fluids of a wet patient (i.e., with diarrhea, vomiting, or bleeding); direct contact with a wet patient; direct contact with a dry patient (i.e., without diarrhea, vomiting, or bleeding); indirect contact with a wet patient (e.g., washing clothes); indirect contact with a dry patient; minimal contact (e.g., shared meals); or no known contact (Table 1). We also asked about exposures outside the home and classified these exposures by using the same scale. For those reported as not having had EVD, we asked about any symptoms at the same time that others in the household had EVD. Study team members, all of whom are multilingual, conducted interviews in the participants’ language and recorded key outcomes in English.
Definitions
Laboratory-confirmed EVD survivors who were reported from Kerry Town ETC, survivors from other ETCs, and all persons reported by the family as having died of EVD were counted as EVD case-patients. Deaths for which the family was unsure of the cause and symptomatic persons who were not tested or did not receive a diagnosis of EVD were classified as probable EVD case-patients if they fit the Sierra Leone case definition for probable cases (20).
For each household, the first person who became ill was identified as the likely primary case-patient. Some households reported 2 people who became ill at the same time, and they are counted as co-primary case-patients. No household described >1 period when Ebola occurred in the household. To avoid overburdening participants, we did not collect time sequences or dates and defined all nonprimary case-patients in a household as subsequent case-patients.
Analysis
Our initial descriptive analysis of outcomes by age and sex included all household members. We subsequently analyzed primary case-patients separately because their exposure occurred outside the household, and we compared their characteristics with those of all other household members.
In the analysis of risks for disease by age, sex, and exposure level, we excluded primary case-patients and household members who were alive but not present for the interview and unable to consent to individual data collection. We explored the following variables for their effects on disease risk and as confounders of the associations of other variables and disease risk: having a spouse who contracted EVD first; occupation; being household head versus household member; and household-level variables (i.e., household size; crowding [number of persons/number of rooms]; and access to water, soap, and latrine). Our analysis used logistic regression and adjusted for household clustering by using random effects. Because risks were large, we used marginal standardization to estimate risk ratios (RRs) and the delta method to estimate 95% CIs (21,22). All analyses used Stata 14 (http://www.stata.com). We also performed a sensitivity analysis that excluded case-patients and deaths classified as probable EVD cases.
Results
Study Population
Figure 1. Flow diagram showing the population composition for study of Ebola-affected households related to survivors from the Kerry Town Ebola Treatment Centre (ETC), Sierra Leone, 2014–2015. EVD, Ebola virus disease. *Includes 23...
Of 151 EVD survivors discharged from Kerry Town ETC, we included 123 survivors from 94 households in the study. The other 28 survivors had a similar age distribution to those included (39% of survivors not included vs. 36% of those included were <15 years of age) and a slightly higher proportion of males (54% of those not included vs. 38% of included survivors). We collected detailed information for 937 persons, including exposure histories for 909 (Figure 1).
Overall, 448 persons were reported as having had EVD or probable EVD, of whom 238 (53%) died; 227 deaths were reported as caused by EVD, and the 11 other deaths fit the EVD case definition. Among survivors, 123 were EVD patients at the Kerry Town ETC, and 45 were at other ETCs. An additional 42 household members had probable EVD; the remaining 485 household members had no evidence of EVD.
Figure 2. Risk for Ebola virus disease in Ebola-affected households of Kerry Town Ebola Treatment Centre survivors, by age and sex, Sierra Leone, 2014–2015. A) Risk by age group; bars indicate 95% CIs....
Risk for EVD was lowest for children 5–14 years of age but higher for children <2 years of age and for adults (Table 2). Risk increased with age for adults up to ?35 years of age and then plateaued for older adults (Figure 2, panel A). Because most probable case-patients were children, the lower risk for children was more extreme when probable case-patients were excluded (Table 2). EVD risk was similar for male and female study participants, even when results were stratified by age (Figure 2, panel B).
Primary Case-Patients
Primary case-patients were identified for 91 households and co-primary case-patients in 3 households. Compared with all other household members, primary case-patients were older, usually >30 years of age; slightly more likely to be male; and more likely to be household heads, healthcare or EVD front-line workers, or religious or community leaders (Table 3). Children or students were least likely to be primary case-patients. In 5 households, primary case-patients joined the household when they were already ill.
Likely sources of infection were identified for 68 (70%) of 97 primary case-patients. When >1 source of infection was possible, we selected the highest exposure level (Table 1). Thirty primary case-patients visited a household with an EVD patient; 16 of those 30 went to help the ill patient. Eight prepared bodies for burial or touched the corpse; 6 attended funerals; 4 carried a person with EVD symptoms; 8 attended healthcare facilities; and 12 worked as healthcare or front-line workers, 5 of whom were known to have treated an EVD patient.
Subsequent Case-Patients
The overall risk for acquiring EVD was 43% and was similar for male and female participants (Table 4); the risk by age was J-shaped, as for the full study population. Among household members, 60% reported direct contact with a wet patient or their fluids or with a person who died of EVD (Table 4). Only 10 (1.2%) household members had a substantially higher level of exposure outside the household than inside.
Figure 3. Distribution of levels of exposure to Ebola virus disease in Ebola-affected households, excluding primary case-patients, by age and sex, Sierra Leone, 2014–2015. A) Male participants; B) female participants. Levels of exposure...
Attack rates increased steeply and linearly with the predefined exposure levels. Exposure levels were high at all ages and for males and females (Figure 3), but exposure to EVD corpses increased with age, and direct exposure to fluids was higher for children <2 years of age, largely because of breastfeeding, and for older adults. After adjustment for age and sex, attack rates varied by occupation and were higher in larger and more crowded households. We found no clear associations with household-level measures of sanitation nor with having a spouse who developed EVD first (Table 4).
A multivariable analysis (Table 4) showed that developing EVD as a subsequent case-patient was strongly associated with age (p = 0.004), level of exposure (p<0.001), not being a household head (p = 0.03), and household size (p = 0.01). Sex was kept in the model a priori but was not associated with EVD risk. Occupation was not associated with EVD risk after adjustment for exposure level (p = 0.2). In the full model, the association with age was still J-shaped. The lowest risk was for persons 5–19 years of age, and risks were higher for older than younger adults. Additional adjustment for other available variables had little effect on associations. In the sensitivity analysis that excluded probable EVD cases, associations with exposure levels were stronger, and the J-shaped association with age was more marked (Table 5).
Discussion
In Ebola-affected households in our study, the age pattern for EVD incidence in children differed from that reported for the overall epidemic by the World Health Organization (4) and was closer to the age pattern of reported case-fatality rates; children <5 years of age had higher risks than older children (4,7). Among adults, the pattern was similar to previous findings (6), with a plateau occurring >35 years of age. This pattern was similar whether probable case-patients were included or not. Children were less likely than adults to be primary case-patients, and among child primary case-patients, no particular trend by age occurred (Table 3). The higher risk for EVD among children <5 years of age than among older children may suggest that very young children have been disproportionately missed in notification data.
Our study included only survivor households because it was conducted by building on survivor-support links; consequently, it missed households with only fatal cases and those in which no one sought care. Compared with all Ebola-affected households, households in our study were likely to be larger; to include more case-patients, which increases the chance that >1 household member survived; and to include more children >5 years of age, who have a lower case-fatality rate than younger children. These characteristics would tend to increase attack rates and may explain the high attack rate overall and th
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