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The Lancet: Symptomless infection with Ebola virus

Re: Human asymptomatic Ebola infections

Re: Human asymptomatic Ebola infections

http://www.ncbi.nlm.nih.gov/pubmed/9988171

Abstract (emphasis mine):

J Infect Dis. 1999 Feb;179 Suppl 1:S98-101.
Serologic survey among hospital and health center workers during the Ebola hemorrhagic fever outbreak in Kikwit, Democratic Republic of the Congo, 1995.
Tomori O1, Bertolli J, Rollin PE, Fleerackers Y, Guimard Y, De Roo A, Feldmann H, Burt F, Swanepoel R, Killian S, Khan AS, Tshioko K, Bwaka M, Ndambe R, Peters CJ, Ksiazek TG.
Author information
Abstract
From May to July 1995, a serologic and interview survey was conducted to describe Ebola hemorrhagic fever (EHF) among personnel working in 5 hospitals and 26 health care centers in and around Kikwit, Democratic Republic of the Congo. Job-specific attack rates estimated for Kikwit General Hospital, the epicenter of the EHF epidemic, were 31% for physicians, 11% for technicians/room attendants, 10% for nurses, and 4% for other workers. Among 402 workers who did not meet the EHF case definition, 12 had borderline positive antibody test results; subsequent specimens from 4 of these tested negative. Although an old infection with persistent Ebola antibody production or a recent atypical or asymptomatic infection cannot be ruled out, if they occur at all, they appear to be rare. This survey demonstrated that opportunities for transmission of Ebola virus to personnel in health facilities existed in Kikwit because blood and body fluid precautions were not being universally followed.

Full text:

http://jid.oxfordjournals.org/content/179/Supplement_1/S98.long

Unfortunately, I cannot find any recent study on this subject.
 
Ebola control: effect of asymptomatic infection and acquired immunity

Ebola control: effect of asymptomatic infection and acquired immunity

10 16 2014

Ebola may be quietly immunizing many

A Canadian researcher is one of four scientists raising the issue that Ebola may be silently immunizing large numbers of people, who never fall ill or infect others yet become protected from future infection. Their letter was published in the medical journal The Lancet.

If true, this finding could have significant ramifications for both projections of how widespread the disease will be, and strategies policy makers and health workers should use to contain the disease, say the authors.

McMaster University's Jonathan Dushoff, an associate professor of biology and an investigator with the Michael G. DeGroote Institute for Infectious Disease Research, is one of the authors with principal author Steve Bellan of The University of Texas at Austin and others from UT Austin and the University of Florida. They call on public health authorities to determine how commonplace it is for people to be infected by Ebola without ever developing symptoms or spreading the disease and whether these individuals are then protected from future infection.

"Although resources on the ground are scarce, now is the best time to learn more about immunity to Ebola, and the sooner we know the sooner the knowledge can be used to stop the epidemic," said Dushoff.

Read more: Medical News Today

Link to full article in The Lancet: Ebola control: effect of asymptomatic infection and acquired immunity, Steve E Bellan, Juliet R C Pulliam, Jonathan Dushoff, Lauren Ancel Meyers, The Lancet, DOI: 10.1016/S0140*6736(14)61839*0, published online 14 October 2014.
 
Re: Ebola control: effect of asymptomatic infection and acquired immunity

Re: Ebola control: effect of asymptomatic infection and acquired immunity

Thank you. This is an interesting read putting together some past and present knowledge about Ebola.

I have a question with regard to the very last part of the article, here:

Burnouf and colleagues6
have advocated for randomised
controlled clinical trials comparing
the treatment efficacy of transfusions
from survivors with those from
control donors. By including a third
study group in which patients receive
transfusions from asymptomatic
seropositive individuals, this design
could simultaneously assess the
therapeutic value of these transfusions
from asymptomatic individuals, and
indicate whether such individuals
have protective immunity.

Would such a proposal be first submitted to some group analysing the ethics of such experiments?

Does such a group exist?

Preferably an international group, a group independent from any pharmaceutical concerns, or at least not under the dependence of any one government, that could review, accept or reject, or modify the design of such experiments?
 
Re: The Lancet: Symptomless infection with Ebola virus

This study may also be interesting.

Clin Exp Immunol. Jun 2001; 124(3): 453?460.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1906073/

Early immune responses accompanying human asymptomatic Ebola infections

E M Leroy,? S Baize,? P Debre,* J Lansoud-Soukate, and E Mavoungou

Abstract

In a recent study we identified certain asymptomatic individuals infected by Ebola virus (EBOV) who mounted specific IgG and early and strong inflammatory responses. Here, we further characterized the primary immune response to EBOV during the course of asymptomatic infection in humans. Inflammatory responses occurred in temporal association with anti-inflammatory phase composed by soluble antagonist IL-1RA, circulating TNF receptors, IL-10 and cortisol. At the end of the inflammatory process, mRNA expression of T-cell cytokines (IL-2 and IL-4) and activation markers (CD28, CD40L and CTLA4) was up-regulated, strongly suggesting T-cell activation. This T-cell activation was followed by EBOV-specific IgG responses (mainly IgG3 ang IgG1), and by marked and sustained up-regulation of IFNγ, FasL and perforin mRNA expression, suggesting activation of cytotoxic cells. The terminal down-regulation of these latter markers coincided with the release of the apoptotic marker 41/7 NMP in blood and with the disappearance of viral RNA from PBMC, suggesting that infected cells are eliminated by cytotoxic mechanisms. Finally, RT-PCR analysis of TCR-Vβ repertoire usage showed that TCR-Vβ12 mRNA was never expressed during the infection. Taken together, these findings improve our understanding about immune response during human asymptomatic Ebola infection, and throw new light on protection against Ebola virus.

Keywords: Ebola, asymptomatic, immunity, cytokine, TCR
 
Re: The Lancet: Symptomless infection with Ebola virus

And this

The Lancet, Volume 384, Issue 9953, Pages 1499 - 1500, 25 October 2014
<Previous Article|Next Article>
doi:10.1016/S0140-6736(14)61839-0

Ebola control: effect of asymptomatic infection and acquired immunity

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61839-0/fulltext


Evidence suggests that many Ebola infections are asymptomatic,1, 2 a factor overlooked by recent outbreak summaries and projections.3 Particularly, results from one post-Ebola outbreak serosurvey1 showed that 71% of seropositive individuals did not have the disease; another study2 reported that 46% of asymptomatic close contacts of patients with Ebola were seropositive. Although asymptomatic infections are unlikely to be infectious,2 they might confer protective immunity and thus have important epidemiological consequences.

snip to end

We propose that launching of an immediate investigation of asymptomatic immunity, by coupling serological testing to ongoing intervention efforts in west Africa, is warranted and feasible, and might ultimately save lives.
 
Re: The Lancet: Symptomless infection with Ebola virus

Sci Transl Med 31 October 2012:
Vol. 4, Issue 158, p. 158ra146
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3004582

Immune Parameters Correlate with Protection Against Ebola Virus Infection in Rodents and Nonhuman Primates

http://stm.sciencemag.org/content/4/158/158ra146.abstract?intcmp=collection-ebola


Abstract

Ebola virus causes severe hemorrhagic fever in susceptible hosts. Currently, no licensed vaccines or treatments are available; however, several experimental vaccines have been successful in protecting rodents and nonhuman primates (NHPs) from the lethal Zaire ebolavirus (ZEBOV) infection. The objective of this study was to evaluate immune responses correlating with survival in these animals after lethal challenge with ZEBOV. Knockout mice with impaired ability to generate normal T and/or B cell responses were vaccinated and challenged with ZEBOV. Vaccine-induced protection in mice was mainly mediated by B cells and CD4+ T cells. Vaccinated, outbred guinea pigs and NHPs demonstrated the highest correlation between survival and levels of total immunoglobulin G (IgG) specific to the ZEBOV glycoprotein (ZGP). These results highlight the relevance of total ZGP-specific IgG levels as a meaningful correlate of protection against ZEBOV exposure.
 
Re: The Lancet: Symptomless infection with Ebola virus

A co-worker sent this to me. It's from June 2000

In today's Lancet, E M Leroy and colleagues report evidence of symptomless Ebola virus infection in 11 individuals who had been in direct contact with affected patients.


http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)02394-1/fulltext

Summary of above

Summary
Background


Ebola virus is one of the most virulent pathogens, killing a very high proportion of patients within 5?7 days. Two outbreaks of fulminating haemorrhagic fever occurred in northern Gabon in 1996, with a 70% case-fatality rate. During both outbreaks we identified some individuals in direct contact with sick patients who never developed symptoms. We aimed to determine whether these individuals were indeed infected with Ebola virus, and how they maintained asymptomatic status.
Methods
Blood was collected from 24 close contacts of symptomatic patients. These asymptomatic individuals were sampled 2, 3, or 4 times during a 1-month period after the first exposure to symptomatic patients. Serum samples were analysed for the presence of Ebola antigens, virus-specific IgM and IgG (by ELISA and western blot), and different cytokines and chemokines. RNA was extracted from peripheral blood mononuclear cells, and reverse-transcriptase-PCR assays were done to amplify RNA of Ebola virus. PCR products were then sequenced.
Findings
11 of 24 asymptomatic individuals developed both IgM and IgG responses to Ebola antigens, indicating viral infection. Western-blot analysis showed that IgG responses were directed to nucleoprotein and viral protein of 40 kDa. The glycoprotein and viral protein of 24 kDa genes showed no nucleotide differences between symptomatic and asymptomatic individuals. Asymptomatic individuals had a strong inflammatory response characterised by high circulating concentrations of cytokines and chemokines.
Interpretation
This study showed that asymptomatic, replicative Ebola infection can and does occur in human beings. The lack of genetic differences between symptomatic and asymptomatic individuals suggest that asymptomatic Ebola infection did not result from viral mutations. Elucidation of the factors related to the genesis of the strong inflammatory response occurring early during the infectious process in these asymptomatic individuals could increase our understanding of the disease.
 
Re: The Lancet: Symptomless infection with Ebola virus

more snips from the lancet paper above(394-1):

.....Irrespective of explanation, the findings reported today imply that a similar carrier state may occur in people who have not been overtly ill..

If symptomless Ebola carriage posed a significant risk of infection, evidence of sporadic cases of haemorrhagic fever associated with, but not directly linked to, major outbreaks of Ebola infection should be identifiable by standard epidemiological techniques. Unfortunately, social and political conditions in central Africa seriously impede contact tracing.3 However, within these limitations, transmission of Ebola has been observed to occur only after close personal contact with affected patients or by exposure to infected body fluids or organs.6 Every outbreak of Ebola to date has been contained by the institution of standard infection-control measures: effective body disposal, barrier nursing, destruction or sterilisation of contaminated equipment, and the appropriate use of gloves, masks, and gowns.7 This degree of containment would be virtually impossible if symptom-free carriers posed a significant threat of infection.

.
 
Re: The Lancet: Symptomless infection with Ebola virus

> Ebola survivors are immune to the virus for as long as three months

> Antibodies make them immune for months.


Does a person who has had it and survived develop lifelong immunity? That is
unknown at this point.

Of these, Lassa fever, Marburg HF and Ebola HF are the most significant. ....
infections have long-lasting immunity but lifelong immunity has not ...

It is not certain if a patient would develop lifelong immunity after recovering.
Previous outbreaks have

Haemorrhagic diseases, such as Ebola haemorrhagic fever, are diseases ...
Survivors do seem to gain lifelong immunity against the virus that

Ebola, Virus Disease (EVD), previously known as Ebola haemorrhagic fever ...
this confers lifelong immunity to the Ebola virus in an individual

but unlike a vaccine, they do not confer lifelong immunity to the virus.

Development of antibodies last at least 10 years but it is unknown if this confers lifelong
immunity or if infection with other strains is possible.

that survivors of Lassa fever infection have lifelong immunity against the disease

all the time, so that it's impossible to build a lifelong immunity to it.

Currently, once you have Ebola, you have lifelong immunity from that viral strain;
if the virus were to mutate too much, our bodies wouldn't ...

infections have long-lasting immunity but lifelong immunity has not.

A vaccine provides lifelong immunity to the disease

Infection due to 1 of the 4 serotypes grants lifelong immunity to that serotype only

Since survivors of a particular strain of Ebola have a lifelong immunity from ...

The virus has four different serotypes; infection with one type usually gives lifelong
immunity

.
 
Re: The Lancet: Symptomless infection with Ebola virus

Ebola: fever definitions might delay detection in non-epidemic areas

Cédric Dananché a, Thomas Bénet a b, Philippe Vanhems a bEmail Address

snip

Few cases with detailed measurements of fever have been reported: only five confirmed Ebola cases have been described so far,1—3 with descriptions totalling a cumulative symptomatic period of 31 days and 80 temperature measurements (figure). Median body temperature was 38·6°C (IQR 38·0—38·8), ranging from 36·5°C to 40·1°C. Median temperature was between 38·2°C (38·0—38·7) on day 5 and 38·8°C (38·8—39·3) on day 7. Sensitivity values were 79%, 61%, and 53% for the thresholds of 38·0°C, 38·3°C, and 38·6°C, respectively....Early case detection in non-epidemic areas is crucial to avoid Ebola transmission. Body temperature changes substantially throughout the day and so a threshold that is too high could lead to cases being missed. Thus, lowering of the temperature threshold might increase sensitivity of case finding. WHO has chosen “sudden onset of fever” as defining suspected Ebola cases.
4 This criterion seems to be more relevant than is fever higher than a predetermined threshold—87% of patients with confirmed or probable Ebola have presented with fever or a feeling of fever.5 The history of previous exposures remains essential to optimise case management. Various definitions of patients at risk of infection might hamper detection in this public health emergency of international concern.
:tiphat:http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61787-6/fulltext?rss=yes
 
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