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Ebola cases flare up in Liberia
WHO confirmed that three people contracted Ebola virus in Liberia after the country was twice declared free of transmission, underscoring the virus’s ability to persist in patients who have recovered.
“It’s a rare event, but we have seen it happen about a half a dozen times,” Bruce Aylward, MD, WHO director-general for the Ebola response, said during a press briefing. “And so as the virus dies out of the community, or the individuals clear the virus over the coming 6 to 9 months, we have to make sure that we have the ability to rapidly detect it and rapidly respond to stop the flares.”
Bruce Aylward
All three patients are from the same family, according to WHO. Nearly 150 contacts are being monitored, including 10 health care workers.
Caring for family members increases risk for transmission
The greatest risk for transmission of filoviruses such as Ebola is close personal contact with an infected patient during later stages of disease, according to a systematic review recently published in the International Journal of Epidemiology.
Paul R. Hunter, MD, MPH, from Norwich Medical School at the University of East Anglia, United Kingdom, and colleagues extracted data from 31 studies and opinion papers published between 1967 and 2015 that assessed the dynamics of transmission, including the odds of developing filovirus infection (n = 8) and anecdotal observations (n = 23). The sources primarily focused on Ebola transmission in 10 African countries; however, Marburg virus and Sudan ebolavirus transmission were also included in the analysis.
People who cared for an actively ill patient significantly increased their risk for transmission (minimum OR = 0.99; 95% CI, 0.56-1.76, maximum OR = 8.9; 95% CI, 3.1-25.4). The trend was even more evident among those who cared for patients at home until death (OR = 13.33; 95% CI, 3.2-55.6). Visitors of ill patients receiving care also were at high risk for transmission (OR = 8.7; 95% CI, 3-26.3; matched odds ratio [MOR] = 10.6; 95% CI, 3.8-36.3).
According to researchers, 32% of household contacts who had direct contact (n = 254) with an infected patient contracted disease vs. 1% of household contacts who had no direct contact (n = 135). They found no evidence of risk associated with casual community contact with asymptomatic patients in early stages of disease.
“Many forms of contact such as conversation, sharing a meal, sharing a bed and direct or indirect touching are unlikely to result in disease transmission during incubation or early illness,” Hunter said in a press release. “We found that infection risk is highest among those caring for a sick person at home…or preparing the recently deceased for burial.”
Although the risk is low, sexual partners of recovering patients are at a “chronic” risk for transmission, Hunter and colleagues wrote.
Ebola virus persists in semen
A preliminary report published in The New England Journal of Medicine by WHO, the CDC and the Sierra Leone Ministry of Health and Sanitation showed that Ebola virus RNA was detectable in semen at least 9 months after the onset of illness.
An investigation was launched after an EVD survivor likely transmitted the disease to his partner through unprotected vaginal intercourse approximately 179 days after EVD onset. Genomic data of semen and vaginal-secretion samples obtained from the EVD survivor and his partner were similar, but distinct from sequences from patients in neighboring countries. A nearly completed genome assembly suggested infectious particles were present in the survivor’s semen specimen.
Gibrilla F. Deen, MD, from the Sierra Leone Ministry of Health and Sanitation, and colleagues assessed semen samples from 93 EVD survivors aged older than 18 years from Freetown, Sierra Leone, and found that almost half of them had detectable levels of Ebola virus RNA in their semen.
Additional samples from nine participants were tested after 3 months illness onset, all of which were positive for EVD. Furthermore, 65% of those samples had viral reservoir after 4 to 6 months and 26% had viral reservoir after 7 to 9 months of illness onset.
Effectiveness of molecular diagnostics
WHO officials believe the recent cluster of EVD cases in Liberia likely stemmed from contact with a virus persisting in an individual; therefore, any residual viruses from a survivor or the convalescent population must be rapidly detected to prevent future outbreaks, Aylward said during the press briefing. A pair of studies recently demonstrated the efficacy of diagnostic assays that investigators currently use in West Africa to detect EVD RNA.
In one study, researchers from the National Institute of Allergy and Infectious Diseases used the The Qiagen QIAamp Viral RNA mini kit to extract RNA samples from six seminal fluid samples and six whole blood samples spiked with live Ebola viruses (Ebola virus/H.sapiens-tc/GIN/14/WPG-C05). Ebola virus RNA was then analyzed with EZ1 RT-PCR reagents and assay parameters, as well as CRP Ribonuclease P (RNAseP) and Major Goove Binder (MGB) reagents and assay parameters. Multiple grouped t tests and the Holm-Sidak method were used to determine significance.
No significant disparities were observed in the extractions using the RNAseP assay, which targeted the housekeeping gene. There was consistency in donor cycle threshold values across the spiked concentrations, which enabled accurate comparisons between sample matrices. There were no significant differences between semen and whole blood sample types.
“This study now opens the door to test semen from [Ebola virus] survivors for the presence of residual viral RNA as well as to facilitate epidemiological investigations to rapidly identify sources of new cases as well as potential at-risk contacts,” researchers wrote in The Journal of Infectious Diseases. “In the interim, public health officials and laboratorians can be confident that the existing EZ1-EUA assay performs as well on semen as they do on whole blood.”
In another study led by Robert Fischer, PhD, of the Virus Ecology Unit at Rocky Mountain Laboratories in Hamilton, Montana, CDC researchers used the QlAamp Viral RNA Mini Kit to cull spiked samples, which were then analyzed with Roche LightCycler 480 RNA Master Hydroloysis Probes (Roche) reagents with primers and probes that targeted the L gene of EBOV on the SmartCycler (Cepheid). PCR efficacy was similar in semen, blood and tissue cultures; however, the mean C value was 1.2 times higher for semen vs. blood samples (P < .0001). Ebola virus RNA was detected during all 8 days of the observation period with no decrease in C values, demonstrating the viruses’ ability to persist in semen over an extended period of time, researchers wrote.
Due to the possibility of transmitting disease through sexual intercourse, WHO and the CDC recommend screening semen samples in male survivors and educating survivors on the use and proper disposal of condoms. Aylward also said rapid response teams must be employed in Liberia, Sierra Leone and Guinea.
“With that in place, countries will be able to prevent, detect and respond and ensure that Ebola no longer causes the kind of horrific consequences we saw over the last years in these countries.”
Disclosure: The researchers report no relevant financial disclosures.
References:
Deen GF, et al. N Engl J Med.2015;doi:10.1056/NEJMoa1511410.
Fischer R, et al. Emerg Infect Dis.2015;doi: 10.3201/eid2202.151278.
Hunter PR, et al. Int J Epidemiol.2015;doi:10.1093/ije/dyv307.
Mate SE, et al. N Engl J Med.2015;doi:10.1056/NEJMoa1509773.
Pettitt J, et al. J Infect Dis. 2015;doi:10.1093/infdis/jiv454.