Evidence Briefs

Provide a synthesis of the best available evidence on a variety of priority topic areas as identified by leading infectious disease experts. We systematically explore the published literature using a comprehensive search strategy to identify relevant research on infection prevention, management, and control. For more information on our search strategy of the published literature, click here.
McMaster University
NCCMT

Risk Factors

Mar 28, 2017

Author(s): Stephanie Vendetti-Hastie, RN, CIC, Kristin Read, MPH, & Dr. Maureen Dobbins, PhD, RN
Expert Reviewer(s): Dr. Mark Loeb, MD, MSc, FRCPC & Dr. Dominik Mertz, MD, MSc

The OutbreakHelp Evidence Briefs aim to provide short summaries of the available evidence related to priority topic areas identified by leading infectious disease experts. Content for the Evidence Briefs were developed using a comprehensive and systematic search of the academic literature from inception to December 31st 2015 (more recently published information on this topic may be available here). All results were screened for relevance using pre-defined inclusion and exclusion criteria. Included articles must have met the following criteria: 1) specific to the topic of Ebola Virus Disease (EVD), 2) human research or research with real-world applicability, 3) study in a peer reviewed journal, and 4) published in either English or French. Articles identified as relevant were tagged with priority topic areas and assessed for quality using abbreviated versions of appropriate critical appraisal tools; a 5-star rating scheme was applied to articles as relevant. Relevance screening, category tagging, and critical appraisal were independently conducted by two raters and conflicts were resolved through discussion. A thematic analysis was performed on included articles by charting and then categorizing common concepts and topics discussed in the literature. Results are summarized in a narrative. The following Evidence Brief discusses human transmission focusing specifically on EVD persistence in body fluids, seroprevalence by setting of residence and risk factors for infection.

Main Message

Evidence suggests that risk of human to human EVD transmission is primarily associated with unprotected direct contact with infected individuals, particularly in the later stages of infection.

Attack rates among family members with direct contact are reported as 32% versus 1% for those without direct contact; and 9% in hospital in the absence of effective protective measures.

While some body fluids such as semen and breastmilk contain detectable EVD, there is no data in the literature on the extent to which positivity on real-time polymerase change reaction (RT-PCR) in these body fluids is associated with virus infectivity. 

In some provinces in Africa, prevalence of Zaire Ebola virus (ZEBOV) specific IgG in studied populations is approximately 15% (ranging from 1-19%) and is highest in rural forested areas.

EVD persistence in body fluids

A variety of human body fluids contain viable virus during the period of illness, with persistence in some fluids into convalescence or post-mortem periods (Table 1). Three studies examined various acute and/or convalescent body fluids (blood, urine, feces, tears, sweat, saliva, nasal blood, skin, semen and vaginal secretions) for presence of EVD by culture and/or RT-PCR. One study also examined whether convalescent transmission occurred among household contacts (Rowe et al., 1999). Refer to Table 1 for results. No direct evidence of transmission from convalescent patients to household contacts was found, although 5 household contacts who reported no previous signs or symptoms of EVD were found to be antibody positive, suggesting mild EVD in these patients that were not diagnosed (Rowe et al., 1999). There are no data in the literature on the extent to which positivity on RT-PCR is associated with virus infectivity. 

Table 1: EVD detection in human specimen

Study Details

Total Participants

Period of Illness

Fluid Type/# samples

RT-PCR Positive Results Days (d)

Comments

Rowe, et al., 1999

(Prospective cohort)

 

Follow up period of 21 months

 

Cases = 29

Household contacts = 152

 

 

Convalescent

 

First 6 months PSO and final at 21 months PSO

Blood - Antigen

E= 3 d (3-6); L=16 d (7-16)

All samples tested negative by virus isolation and for antigen by ELISA

Blood

IgM: E=2 d (2-9) PSO;

L=168 d (30-168) PSO (no further testing done)

 

IgG: E= 6d (6-18) PSO;

L= ﹥749 (661-749) d PSO (no further testing done after this time period)

Semen

E= 47 d PSO

L= 91d PSO

Bausch, et al., 2007

(Cross sectional)

 

Cases = 26

Acute

Acute

Acute

Convalescent

Acute

Acute

Acute

Convalescent

Saliva*

Skin

Breastmilk*

Breastmilk*

Stool

Tears

Nasal Blood

Semen*

L= 8 d PSO

L=6 d PSO

L=7 d PSO

L=15 d PSO

L=12 d PSO

L=6 d PSO

L=10 d PSO

L=40 d PSO

 

Deen, et al., 2015

(Cross-

sectional)

 

 

Convalescent cases = 93

 

 

 

Convalescent

Semen

● 9 sampled at 2-3 months

● 40 sampled at 4-6 months

● 43 sampled at 7-9 months

E = 128 d PSO (shortest time positive)

L=284 d PSO

● 9/9 sampled at 2-3 months positive (100%)

● 26/40 sampled at 4-6 months positive (65%)

● 11/43 sampled at 7-9 months positive (26%)

PSO – post symptom onset; E – earliest day; L – last day

Bold* indicates culture positive in addition to RT-PCR positive

 

Risk Factors for Infection

Within the provinces of Gabon and Democratic Republic of Congo (DRC), two cross-sectional studies examined seroprevalence of EVD IgG in different populations by setting of residence (Table 2).

Table 2: Prevalence of EVD IgG by Setting of Residence

Study

Virus Subtype

Environment

+/Total participants

IgG Seroprevalence (%)

Risk Factors for infection

Results

Moyen, et al., 2015

 

EBOV

Urban

8/509

1.6

 

 

EBOV

Rural

3/75

9/225

4

4

Exposure to bats vs. no exposure

 

p< 0.0001

Nkoghe, et al., 2011

ZEBOV

Province

667/4349

15.3

 

 

ZEBOV

Lakeland

12/443

2.7

Had butchered game vs. did not butcher game

p = .02

ZEBOV

Savannah

47/448

10.5

 

 

ZEBOV

Forest

608/3458

17.6

 

 

ZEBOV

Grassland

114/918

12.4

Being male vs. not being male

 

Ate bats vs. not eating bats

OR 1.75 (95% CI: 1.16-2.63; p=.007)

 

 

OR, 1.74 (95% CI: 1.09 – 2.75; p=.02)

ZEBOV

Deep forest

494/2540

19.4

 

 

 

Among the male population, being a hunter (OR 5.6, 95% CI: 1.4-22.6) having exposure to bats (OR 9.2, 95% CI: 3.5-24.1) or monkeys (OR 5.2, 95% CI: 1.3-21.3), or consuming birds (OR 4.1, 95% CI: 1.5-11.02) was statistically associated with EVD IgG positivity. In multivariate analysis the only variables independently associated with Ebola antibody detection were contact with bats (OR 7.5; 90% CI: 2.26-21.7) and bird consumption (OR 2.6; 95% CI: 1.1 – 6.9) (Moyen, et al., 2015). In Gabon, increasing age was an important risk factor, with a statistically significant difference (p = .02) across the age groups (Nkoghe, et al., 2011).

EVD can be spread to susceptible contacts directly and possibly indirectly through a variety of exposures across the household, community, hospital and other settings. Five studies examined risk factors for disease transmission and provided numerical odds, risk or prevalence ratios for filovirus disease transmission or IgG seropositivity (Table 2) (Baron, McCormick, & Zubeir, 1983; Brainard, Hooper, Pond, Edmunds, & Hunter, 2015; Dowell, et al., 1999; Francesconi, et al., 2003; Roels, et al., 1999).

One systematic review and meta-analysis described risk factors for transmission of EVD (Brainard, et al., 2015). Using data from three papers, the authors calculated incidence rates in household contacts with and without a history of direct contact. The meta-analysis included a total of 254 direct contacts and 135 indirect contacts. Among household contacts reporting direct contact with a case, the attack rate was 32% (95% CI: 26-38%) among those with no history of direct contact the attack rate was 1% (95% CI: 0-5%) (Brainard, et al., 2015).

Table 3: Risk Factors for Infection

Risk Factor

Unadjusted effect size (95% CI)*

Adjusted effect size (95% CI)

Direct contact Touched a sick person

During incubation period

During early illness

During late illness

With a person who had fever/bleeding at work/market

Touched but no nursing care

PPR 3.53 (0.52 -24.11)1

PRR 2.92

PRR 12.52

PRR 12.52

MOR 24.0 (3.2-1065)3

OR 0.40 (0.11-1.45)4

PPR 1.56 (0.19 -13.04)

PRR 0.8 (0.4-1.8)

Funeral related activities Viewed body only

Attended special rituals

Attended funeral itself

Touched body before/during funeral

Touched body before/during ceremony

Prepared a cadaver for burial

PRR 4.82

MOR 0.8 (0.2 - 3.2) 3

MOR 3.0 (1.2 - 7.6) 3

PPR 1.95 (0.91- 4.17) 1

PRR 4.92

MOR 13.1 (1.4-631) 3

PRR 1.6 (0.5 - 4.9)

 

 

PPR 1.84 (0.95 - 3.55)

PRR 2.1 (1.1 - 4.2)

Ritual handwashing at funeral

PPR 2.25 (1.08 - 4.72) 1

PPR 1.16 (0.54 - 2.49)

Communal meal during funeral

PPR 2.84 (1.35 - 5.98) 1

PPR 1.5 (0.98 - 2.28)

Contact with body fluids

In early illness

In late illness

PPR 5.30 (2.14 -13.14) 1

PRR 6.12

PRR 5.92

PPR 4.61 (1.7 - 12.3)

Shared mealDuring early illness

During late illness

With index patient

PRR 2.52

PRR 7.02

PPR 1.94 (0.89 - 4.22) 1

PRR 1.2 (0.5 - 2.7)

PRR 2.2 (1.2 - 4.0)

PPR 1.69 (1.0 - 2.8)

Washed clothes of a case

PPR 1.68 (0.78 - 3.60)1

PPR 1.02 (0.47-2.2)

Slept in the same hut Without sharing/bed sleeping mat

Entered the same room/no direct contact

PPR 2.16 (0.90 - 5.19) 1

OR 0.06 (0.00 - 1.06) 3

PPR 2.34 (1.13 - 4.8)

Shared bed/ sleeping matDuring incubation

During early illness

During late illness

Point of disease onset unclear

PRR 2.92

PRR 3.82

PRR 7.42

PPR 2.78 (1.15 - 6.70) 1

PRR 1.4 (0.8 - 2.4)

PRR 1.3 (0.7 - 2.5)

PRR 2.2 (1.2 - 4.2)

PPR 2.93 (1.2 - 7.4)

Likely sexual contact/spouse of index case

PRR 3.82

PRR 1.3 (0.7 - 2.5)

Caring for a patientAt home/early illness

At hospital until death

In home until death

PPR 6.00 (1.33 - 27.10) 1

PPR 8.57 (1.9 - 37.7) 1

PPR 13.33 (3.2 - 55.6) 1

p for trend of all three0.001

# of types of direct contactNo direct contact

One type of direct contact

Two types of direct contact

Three types of direct contact

PPR 1.01

PPR 0.18 (0.01 - 2.45) 1

PPR 1.94 (0.30 - 12.44) 1

PPR 4.00 (0.64 - 25.02) 1

p for trend of all four

0.001

Admitted to hospital (prior to outbreak recognition)

In 3 weeks prior to symptom onset

Receipt of injection in hospital

 

MOR 9.9 (3.1- 41) 3

MOR 30.0 (4.3 - 1302) 3

 

Visit to ill friend/relative (fever and bleeding) in own home

MOR 10.6 (3.8-36.3) 3

 

*PRR - prevalence rate ratio; PPR - prevalence proportion ratio; MOR- matched odds ratio: OR- odds ratio.

Bold: (CI 95% that is entirely above 1.0).

Missing data not provided or not able to be calculated.

1 Francesconi, et al., 2003

2 Dowell, et al., 1999

3 Roels, et al., 1999

4 Baron, et al., 1983

As presented in Table 2, risk of human to human EVD transmission was found be primarily associated with three behaviours: direct contact, particularly in the later stages of infection; caring for a sick person; and preparing the recently deceased for burial. No evidence of risk was associated with casual contact with asymptomatic individuals outside the home. The risk of contracting the disease during the incubation period was negligible and low during early symptomatic illness. Visiting or caring for EVD cases in hospital raised transmission risk. There was strong evidence that risk of transmission to family members is high when caring for an individual up to death and the risk is much higher when this is in the home environment (Brainard, Hooper, Pond, Edmunds, & Hunter, 2015; Dowell et al., 1999; Francesconi et al., 2003; Roels et al., 1999).

Risk behaviours also play a role in the transmission of EVD within hospital/treatment centre environments. Two cross sectional studies examined hospital exposures to EVD. The first described exposures and outcomes of 7 out of 84 contacts (8.4%) who contracted Ebola and had some form of contact with the index patient. Contacts who developed EVD reported the following exposures: sharing a ward/latrine, direct contact with patient, cleaned linens, cleaned body fluids, moved patient, placed intravenous line, general patient touching. All exposures occurred with no or inadequate personal protective equipment (PPE) (Dunn, et al., 2015). A similar attack rate of 9% in hospitals and health centers was described in the second study at the height of the EVD epidemic in Kikwit in 1995 where physicians were disproportionately affected at 31%. Among workers without infection (n=402) 73% had direct contact and/or indirect contact (33%) with EVD cases or suspect cases. PPE use was examined among a subset of workers in a hospital (n=48); 24% used complete protection (gloves, mask, gown, goggles); 8% used only gloves; and 32% used neither gloves nor complete protection during exposure (Tomori, et al., 1999).

Conclusion

Direct contact with a case (particularly in the late stages of infection), caring for a person with EVD, or preparing the recently deceased for burial are the three most commonly referenced risk factors for EVD transmission. There was no indication within included studies of transmission between convalescent patients and household contacts although traces of viral persistence of EVD (tested by RT-PCR) was found in blood, semen and breastmilk for varying timeframes from 2 days to 284 days post symptoms onset in the convalescent period of illness.

When looking at risk factors for EVD IgG positivity in the Democratic Republic of Congo and Gabon, several factors are mentioned as significant including exposure to bats and monkeys as well as consumption of birds.

REFERENCES

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Bausch, D. G., Towner, J. S., Dowell, S. F., Kaducu, F., Lukwiya, M., Sanchez, A., … Rollin, P. E. (2007). Assessment of the risk of Ebola virus transmission from bodily fluids and fomites. Journal of Infectious Diseases, 196(Suppl 2), S142-S147. [OutbreakHelp Star Rating: 4]

Brainard, J., Hooper, L., Pond, K., Edmunds, K., Hunter, P.R. (2015). Risk factors for transmission of Ebola or Marburg virus disease: A systematic review and meta-analysis. International Journal of Epidemiology, DOI: 10.1093/ije/dyv307. [OutbreakHelp Star Rating: 2.5]

Deen, G.F., Knust, B., Broutet, N., Sesay, F.R., Formenty, P., Ross, C., … Sahr, F. (2015). Ebola RNA persistence in semen of Ebola virus disease survivors: Preliminary report. The New England Journal of Medicine, DOI: 10.1056/NEJMoa1511410. [OutbreakHelp Star Rating: 4.5]

Dowell, S. F., Mukunu, R., Ksiazek, T. G., Khan, A. S., Rollin, P. E., Peters, C. J. (1999). Transmission of Ebola hemorrhagic fever: A study of risk factors in family members, Kikwit, Democratic Republic of the Congo, 1995. Journal of Infectious Diseases, 179(Suppl 1), S87-S91. [OutbreakHelp Star Rating: 4]

Dunn, A.C., Walker, T.A., Redd, J., Sugerman, D., McFadden, J., Singh, T., … Kilmarx, P.H. (2015). Nosocomial transmission of Ebola Virus Disease on pediatric and maternity wards: Bombali and Tonkolili, Sierra Leone, 2014. American Journal of Infection Control, 44(3), 269-272. [OutbreakHelp Star Rating: 4]

Francesconi, P., Yoti, Z., Declich, S., Onek, P.A., Fabiani, M., Olango, J., … Salmaso, S. (2003). Ebola hemorrhagic fever transmission and risk factors of contacts, Uganda. Emerging Infectious Diseases, 9(11), 1430-1437. [OutbreakHelp Star Rating: 4]

Moyen, N., Thirion, L., Emmerich, P., Dzia-Lepfoundzou, A., Richet, H., Boehmann, Y., … de Lamballerie, X. (2015). Risk factors associated with Ebola and Marburg viruses seroprevalence in blood donors in the Republic of Congo. PLoS Neglected Tropical Diseases, 9(6), e0003833. [OutbreakHelp Star Rating: 4]

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Roels, T.H., Bloom, A.S., Buffington, J., Muhungu, G.L., Mac Kenzie, W.R., Khan, A.S., … Ksiazek, T.G. (1999). Ebola hemorrhagic fever, Kikwit, Democratic Republic of the Congo, 1995: Risk factors for patients without a reported exposure. Journal of Infectious Diseases, 179(Suppl 1), S92-S97. [OutbreakHelp Star Rating: 4]

Rowe, A.K., Bertolli, J., Khan, A.S., Mukunu, R., Muyembe-Tamfum, J.J., Bressler, D., … Ksiazek, T.G. (1999). Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Journal of Infectious Diseases, 179(Suppl 1), S28-S35. [OutbreakHelp Star Rating: 4.5]

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