Presentazione standard di PowerPoint...Factors Contributing to the Emergence or Re-Emergence of Infectious Diseases (2) Economic development and changes in the use of land, including

Implemented by In collaboration with

Ebola (1)DR. GIULIANO RIZZARDINI AND DR. MARIA V IT TORIA COSSU

ASST FATEBENEFRATELL I L .SACCO HOSPITAL

GIULIANO.RIZZARDINI@ASST -FBF-SACCO. IT & MARIA .COSSU@ASST -FBF-SACCO. IT


OutlineINTRODUCTION

VIRUS

RESERVOIRS

TRANSMISSION

PREVIOUS OUTBREAKS

EBOLA 2013-2016 IN WEST AFRICA

SIGNS AND SYMPTOMS

DIAGNOSIS

TREATMENT

ITALIAN EXPERIENCE

PREVENTION

TtT: BACK UP SLIDES


INTRODUCTION

VIRUS

RESERVOIRS

TRANSMISSION

PREVIOUS OUTBREAKS


SIGNS AND SYMPTOMS

DIAGNOSIS

TREATMENT

ITALIAN EXPERIENCE

PREVENTION

TtT: BACK UP SLIDES

Outline


Epidemics and Pandemics have shaped our history…

Middle Ages

20th Century

1st Millenium


…and they continue to threaten us…and place sudden intense demands on national and international health systems

…on some occasions have brought health and social systems to the point of collapse

…the diseases of most concern are those that may have international significance –either as a possible global epidemic or pandemic, or because they pose a risk for travellers with high case fatality rates or have trade implications. Most of these diseases tend to be emerging diseases.


So, in the context of emerging/epidemic disease at the beginning of the 21st. century:

We have seen the emergence of new or newly recognizedpathogens (e.g. Highly Pathogenic Avian Influenza [H5N1], SARS, Nipah, pandemic influenza [H1N1], novel coronavirus ……)

The resurgence of well characterized outbreak-prone diseases (e.g. dengue, measles, yellow fever, chickungunya, Ebola - also cholera, TB, meningitis, shigellosis)

Human-made "bio-risk" also increasing: accidental and deliberate release of infectious agents as smallpox, SARS, Ebola, anthrax, tularaemia, etc.


61% of all Emerging Infectious Diseases are Zoonosesaffecting Humans

Frequency of all EID events has significantly increased since 1940, reaching a peak in 1980-1990

61% of EID events are caused by the transmission from animals (zoonoses)

74% of these from wildlife

Zoonotic EIDs from wildlife reach highest proportion in recent decade

Wildlife

Domestic

Animal Human

Translocation

Human

encroachment

Ex situ contact

Ecological

manipulation

Global travel

Urbanization

Biomedical

manipulation

Technology

And Industry

Agricultural

Intensification

Encroachment

Introduction

“Spill over” &

“Spill back”


SARS; the First Pandemic of 21st Century Changed the World...


H5N1 avian influenza: A New Global Concern…



Factors Contributing to the Emergence or Re-Emergence of Infectious Diseases (1)

Human demographic change by which persons begin to live in previously uninhabited remote areas of the world and are exposed to new environmental sources of infectious agents, insects and animals.

Unsustainable urbanization causes breakdowns of sanitary and other public health measures in overcrowded cities (e.g., slums).



Economic development and changes in the use of land, including deforestation, reforestation, and urbanization.

Global warming , climate changes cause changes in geographical distribution of agents and vectors.

Changing human behaviours, such as increased use of child-care facilities, sexual and drug use behaviours, and patterns of outdoor recreation.


International travel and commerce that quickly transport people and goods vast distances.

Changes in food processing and handling, including foods prepared from many different individual animals and countries, and transported great distances.



Evolution of pathogenic infectious agents by which they may infect new hosts, produce toxins, or adapt by responding to changes in the host immunity (e.g. influenza, HIV).

Development of resistance by infectious agents such as Mycobacterium tuberculosis and Neisseria gonorrhoeae to chemoprophylactic or chemotherapeutic medicines.



Resistance of the vectors of vector-borne infectious diseases to pesticides.

Immunosuppression of persons due to medical treatments or new diseases that result in infectious diseases caused by agents not usually pathogenic in healthy hosts (e.g. leukemia patients).



Deterioration in surveillance systems for infectious diseases, including laboratory support, to detect new or emerging disease problems at an early stage (e.g. Indonesian resistance to “scientific colonialism”).

Illiteracy limits knowledge and implementation of prevention strategies.

Lack of political will – corruption, other priorities.



Biowarfare/bioterrorism – an unfortunate potential source of new or emerging disease threats (e.g. anthrax and letters).

War, civil unrest – creates refugees, food and housing shortages, increased density of living, etc.

Famine causing reduced immune capacity, etc.

Manufacturing strategies; e.g., pooling of plasma, etc.



Public Health Emergency of International Concern (PHEIC)

Defined in IHR 2005 as

‘an extraordinary public health event which constitutes a public health risk to other States through the international spread of disease and may require a coordinated international response’.

Such events are required to be assessed for notification to WHO using a decision instrument


(PHEIC)4 decision criteria used in assessment of a public health event are :

(a) The seriousness of the event’s public health impact.

(b) The unusual or unexpected nature of the event.

(c) The risk of international spread.

(d) The risk that travel or trade restrictions will be imposed by other countries.

Any 2 criteria Notify WHO

A single case of smallpox, poliomyelitis (WPV), human influenza caused by a new subtype and SARS must be immediately notified to WHO, irrespective of the context in which it occurs.


The magic word: PREPAREDNESS


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Outbreak Detection and Response without PreparednessDelayed Response

Day

CasesOpportunity

for control

Late Detection

First Case


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Early Detection

Cases

Rapid Response

Outbreak Detection and Response with Preparedness


WHO RESPONSE

-International Health Regulations

-Global Outbreak Alert and Response Network (GOARN)◦ 120 technical institutions participating

◦ 2000-02 -- Responded to 34 events in 26 countries


Purpose and scope of the IHR

From three diseases to all public health hazards, irrespective of origin or source

From control of borders to containment at source

From preset measures to adapted response

“to prevent, protect against, control and provide a public health response to the international spread of disease in ways that are commensurate with and restricted to public health risks, and which avoid unnecessary interference with international traffic and trade“ (Article 2)


No single institution has all the capacity!

Coordinate and support rapid international team deployment to countries for outbreak response

To focus and coordinate global resources - local > regional > global


WHO global alert and response systems


PHEIC


PAHO

AFROWPRO

EMROSEARO

EURO

OperationsStatesWHO Portal

Event Management

System

Information Sharing at WHO


Strategy for Preventing and Control Ebola Outbreaks


Fundamental Role of the Public Health Professional

Establish surveillance for: ◦ Unusual diseases

Assure laboratory capacity to investigate new agents (e.g., high-throughput labs)

Develop plans for handling outbreaks of unknown agents


INTRODUCTION

VIRUS

RESERVOIRS

TRANSMISSION

PREVIOUS OUTBREAKS


SIGNS AND SYMPTOMS

DIAGNOSIS

TREATMENT

ITALIAN EXPERIENCE

PREVENTION

TtT: BACK UP SLIDES

Outline


What is Ebola virus disease (EDV)?Ebola virus disease (EVD), formerly known as Ebola haemorrhagic

fever, is a severe, often fatal illness in humans.


Viral hemorragic fever


Hemorrhagic Fevers◦ Definition: a severe multi-system syndrome.

◦ Vascular System Damaged

◦ Body regulation Impaired

◦ Accompanied by hemorrhage

◦ MOF

◦ Four families of viruses

◦ Arenaviruses (Junin Virus)

◦ Bunyaviruses (Nariovirus )

◦ Flaviviruses (ie. Yellow Fever)

◦ Filoviruses (Marburg & Ebola)

◦ RNA viruses covered in a lipid coating

◦ Viruses are geographically restricted to areas where host species (reservoir) live

◦ Humans are not natural reservoirs for these viruses

◦ CDC Classification: BSL-4 Agent


Viral Hemorrhagic Fevers (VHFs)

The severity and clinical presentation of VHFs maysignificantly change according to several differentfactors related to the type of the causative agent, and the host epidemiological and clinical features. In general, patients with VHFs show fever and coagulation abnormalities that may progress towardsdisseminated intravascular coagulation, multiorganfailure, shock and, eventually, death

The VHFs are a diverse group of animal and human illnesses that are caused by fourdistinct families of RNA viruses: Filoviridae, Arenaviridae, Bunyaviridae, and Flaviviridae.


Filoviridae

Marburgvirus was the first ever filovirus recognized, discovered in 1967 when laboratory workers in

Marburg, Germany developed hemorrhagic feverafter handling tissue of African green monkeys from

Uganda.

The 1967 outbreak proved fatal in seven of the 37 cases.

Filoviridae are a family of enveloped, non-segmented, negative-strand RNA viruses that share a similar filamentous structure.


Structure

Filovirus: like other members of this family, Ebola is thread-like in structure

◦ Variable shapes

◦ “U” shaped

◦ Coiled

◦ Circular

◦ Branched

http://bepast.org/docs/photos/Ebola/em_ebola.jpg


Genus Ebolavirus is 1 of 3 members of the Filoviridae family (filovirus), along with genus Marburgvirus and genus Cuevavirus.

Genus Ebolavirus comprises 5 distinct species:

- Bundibugyo ebolavirus (BDBV)

- Zaire ebolavirus (EBOV)

- Sudan ebolavirus (SUDV)

- Taï Forest ebolavirus (TAFV)

- Reston ebolavirus (RESTV)*


*Reston Ebolavirus (RESTV) The Good Cousin

Found in Philippines and China

Causes respiratory disease in pigs

Infects humans, but no disease

Pig farmers, abattoir workers, others have antibodies

Some cross-reaction with Zaire EBOV

Are people with RESTV antibodies immune?

Can RESTV antibodies be used for therapy?

Will RESTV antibodies from natural infections confuse diagnosis of Ebola virus disease?

39

*Miranda & Miranda 2011; Pan et al 2014


Infectious disease terminology

Inoculating dose = the number of viral particles that enter the host; minimum inoculating dose of Ebolavirus is very low (1-10 viruses)

Incubation period = days from when the person was exposed and symptoms first develop; aver. EBOV = 11 days (2 – 21 days)


Survival outside hostDried – 24 hr at 25°C; 14 days at 4°C

In fluids – up to 46 days at 25°C

Ebolavirus is killed by:

◦ Heat 60ºC for 1 hr

◦ Hypochlorite (Chlorine solution)

◦ Alcohols

◦ 3% acetic acid

◦ 1% glutaraldehyde

Piercy et al J Appl Microbiol 2010;109:1531; Sagripanti et al Arch Virol 2010; 155:2035; Health Canada –PDSS - http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/ebola-eng.php


Environmental contamination in isolation ward

Sudan Ebolavirus outbreak – Uganda 2000

2 positives from 33 environmental specimens

Ebolavirus was detected on a bloody glove and a bloody IV insertion site

Not isolated on bedframes, chairs, stethoscopes, clean gloves, food bowl, spit bowl, body bag cleaned with bleach, body louse.

Bausch et al. J Inf Dis 2007


Natural history

Virus enters the cell – any cell, but particularly uses macrophages, dendritic cells and monocytes

Spreads to lymph nodes via lymphatics and then to liver and spleen via blood

Secondary spread to all organs

Exits the body in faeces, saliva, sweat, tears, sputum, skin cells, breast milk, semen, urine, vomitus

The WHO states that only people who are very sick are able to spread Ebola disease in saliva, and whole virus has not been reported to be transmitted through sweat. Most people spread the virus through blood, feces and vomit.Entry points for the virus include the nose, mouth, eyes, open wounds, cuts and abrasions


EVD: a short history

Ebola first appeared in 1976 in 2 simultaneous outbreaks, in Nzara, Sudan, and in Yambuku, Democratic Republic of Congo a village situated near the Ebola River, from which the disease takes its name.

The first known case of EVD was a 44-year old school teacher who presented himself, on 26 August 1976, with a febrile illness at the Yambuku Mission Hospital and died after 13 days the onset of the symptoms.

He started an epidemic that killed 280 of the 313 infected persons (88%).


Ebola

River

EBOLA: the origin


Mar 12, 1977 Volume 309 Number 8011p555-614Originally published as Volume 1, Issue 8011

ISOLATION AND PARTIAL CHARACTERISATION OF A NEW VIRUS CAUSING ACUTE HÆMORRHAGIC FEVER IN ZAIRE: K.M Johnson, J.V Lange, P.A Webb, F.A Murphy

VIRAL HÆMORRHAGIC FEVER IN SOUTHERN SUDAN AND NORTHERN ZAIRE: Preliminary Studies on the Aetiological AgentE.T.W. Bowen, G. Lloyd, W.J. Harris, G.S. Platt, A. Baskerville, E.E. Vella

ISOLATION OF MARBURG-LIKE VIRUS FROM A CASE OF HÆMORRHAGIC FEVER IN ZAIRES: Pattyn, G.vanderGroen, W. Jacob, P. Piot, G. Courteille


571

TABLE !!—COMPARISON OF I.F.A. TITRES OF GUINEAPIGS

IMMUNISED (SINGLE INJECTION) AGAINST MARBURG (’67) ANDMARBURG-LIKE (’76) VIRUSES

they have diagnostic significance. Plastic-embedded formalin-fixed necropsy specimens were examined with the electron

microscope. Although preservation of liver tissue was poor,large numbers of filamentous virus particles and inclusionbodies (masses of tubules) were found (fig. 5) which were indis-

tinguishable from those in Marburg virus-infected human and

guineapig livers studied in 1967 and 1975.6-8

ANTIGENIC COMPARISON WITH MARBURG

An antigenic difference between this isolate and Marburg’67 was demonstrated by indirect immunofluorescence (I.F.A.).An infected Vero-cell suspension was placed in drops on slides,air dried, and then acetone-fixed for 10 min at room tempera-ture. Slides were stored at -T0°C until tested. Marburg ’67

antigen slides, prepared in like manner, were used for compari-son. Reciprocal titres obtained with convalescent human seradrawn during the 1967, 1975, and 1976 outbreaks are listedin table I. With the exception of a weak reaction to Marburgantigen at a 1/4 dilution of the Zaire convalescent serum, thenew isolate was distinct from Marburg virus. The homologous

Marburg titres of 128 and 64 obtained with ’67 and ’75

antigens and antisera were comparable to those reported byWulff and Conrad.9 9

A single-injection immune serum to the new agent was pre-pared in guineapigs, and reciprocal I.F.A. tests were performedwith available similar reagents for Marburg virus. Reciprocaltitres (table n) further confirmed the distinctness of the twoviruses. Although one of two early convalescent sera fromSudan gave a positive reaction with the Zaire antigen (table I)further work is needed to determine whether the haemorrhagic-disease agents from the two countries are identical.

EBOLA VIRUS

With the concurrence of Prof. S. R. Pattyn, Institute of

Tropical Medicine, Antwerp, and Mr E. T. W. Bowen, Micro-

biological Research Establishment, Porton Down, the nameEbola virus is proposed for this new agent. Ebola is a smallriver in Zaire which flows westward, north of Yambuku, the

village of origin of the patient from whom the first isolate wasobtained. In deference to the countries involved and to the lack

of specific knowledge of the original natural source of the

virus, it is also suggested that no names of countries or specifictowns be used.

REFERENCES

1. Wld Hlth Org. wkly epidem. Rec. 1976, 51, (42), p. 325.2. Center for Disease Control. Morbidity and Mortality Weekly Report, 1976,

vol. 25, p. 378.3. Pattyn, S. R., Jacob, W., Van der Groen, G., Piot, P., Courteille, Lancet,

1977, i, 573.4. Bowen, E. T. W., Platt, G. S., Lloyd, G., Baskerville, A., Harris, W. J.,

Vella, E. E. ibid. p. 571.5. Kissling, R. E., Robinson, R. Q., Murphy, F. A., Whitfield, S. G. Science,

1968, 160, 888.6. Center for Disease Control. Morbidity and Mortality Weekly Report, 1975,

vol. 24, p. 89.7. Gear, J. S. S., Cassell, G. A., Gear, A. J., Trappler, B., Clansen, L., Meyers,

A. M., Kew, M. C., Bothwell, T. H., Sher, R., Miller, G. B., Schneider,J., Koormhof, H. J., Gomperts, E. D., Isaacson, M., Gear, J. H. S. Br.med. J. 1975, iv, 489.

8. Murphy, F. A., Simpson, D. I. H., Whitfield, S. G., Zlotnik, I., Carter, G. B.Lab. Invest. 1971, 24, 279.

9. Wulff, H., Conrad, L. J. in Comparative Diagnosis of Viral Diseases. NewYork (in the press).

VIRAL HÆMORRHAGIC FEVER IN SOUTHERN

SUDAN AND NORTHERN ZAIRE

Preliminary Studies on the Aetiological Agent

E. T. W. BOWEN

G. LLOYD

W. J. HARRIS

G. S. PLATT

A. BASKERVILLE

E. E. VELLA

Microbiological Research Establishment, Porton, Salisbury,Wiltshire, England

BETWEEN July and September, 1976, sporadic cases offever with haemorrhagic manifestations were reported inthe areas of Nzara, Maridi, and Lirangu in the southernSudan. The first cases are believed to have been in agri-cultural settlements. An outbreak of a similar disease

was also reported from the zone of Bumba in northernZaire.1 As the epidemic increased in intensity, the dis-

turbingly high percentage of cases reported among hos-

pital personnel suggested direct person-to-person spreadof infection. The illness began with an acute fever,malaise, sore throat, muscular pains, vomiting, and

diarrhoea. Those severely affected had epistaxis, subcon-

junctival haemorrhages, haemoptysis, hsematemeses, andmelaena. Some patients also had a body rash, tremors,and convulsions.

SOURCES OF SPECIMENS

Specimens from the northern Zaire outbreak were referredto the Microbiological Research Establishment, Porton, byProf. S. R. Pattyn of the Institute of Tropical Medicine,

Antwerp. They were an acute-phase serum (no. 718), cell-culturematerials and brains from suckling mice which had alreadybeen inoculated with the serum. We later received a specimenof liver from the same patient and also 5 acute-phase blood

specimens from Zaire via Professor Pattyn. Specimens fromthe southern Sudan were mainly collected at Maridi Hospitaland sent to us directly by Dr Babiker el Tahir, Dr D. H.

Smith, Dr K. Jones, and Dr M. Cornet, who were there to in-

vestigate. They consisted of 3 throat swabs, 3 urine specimens,6 acute-phase blood specimens, and convalescent serum speci-mens. These specimens were sent on dry ice or in liquidnitrogen. Three laboratories engaged in preliminary studies onthe xtiological agent reported the isolation of a virus whichwas morphologically similar to Marburg virus.2

RESULTS OF ATTEMPTS AT VIRUS ISOLATION

Virus isolation from the original human material was

attempted in : (1) culture preparations of Vero cells; (2)suckling mice inoculated intraperitoneally (i.p.) and in-

tracerebrally (i.c.); and (3) young guineapigs (200-250g) inoculated i.p.

Isolation in Guineapigs

So far 5 isolations of the aetiological agent have been

obtained in guineapigs: 4 from specimens from northern Zaireand 1 from a specimen from southern Sudan. Guineapigs in-oculated with these specimens became febrile 105°F (40-5°C)after an incubation period of 4-7 days. The febrile illnesslasted 4-5 days during which the guineapigs failed to thriveand looked ill. 1 of the 12 guineapigs inoculated with originalmaterial died on the 12th day after inoculation. The other 11

guineapigs slowly recovered and were subsequently shown tohave antibodies detectable by fluorescent antibody tests at

titres ranging from 1/64 to 1/128. When whole heparinisedblood from febrile guineapigs was inoculated !.p. into other

guineapigs it produced a similar febrile illness.


Piot, now 67, was the youngestmember of the original Ebola investigative team and is still

active professionally; some of the others have retired and some

have died.

Health officials go over data collected during the Ebola

outbreak of 1976 in Zaire, nowknown as the Democratic

Republic of Congo.


Since the first case, over the course of 28 years, 30 outbreaks have been enumerated before the last one

in 2014 in West Africa


INTRODUCTION

VIRUS

RESERVOIRS

TRANSMISSION

PREVIOUS OUTBREAKS


SIGNS AND SYMPTOMS

DIAGNOSIS

TREATMENT

ITALIAN EXPERIENCE

PREVENTION

TtT: BACK UP SLIDES

Outline


How do people become infected with the virus?


Gretchen Vogel


Fruit bats and Ebola virus

Several bat species can host EBOV

Differences in the prevalence of the infection in different bat species and in different

geographical areas are probable.

It has been hypothesized that EBOV infection is a seasonal relatively mild infection in

bats, and climatic factors may influence the size of seasonal epidemics.

EBOV infection would be more prevalent in young animals and in pregnant females

Food shortages in the dry season may promote contacts between bats and humans


Fruit bats

Hypsignathus

monstrosus


.

Many bat species live in large colonies

They have the ability to move quickly and spread viruses over considerable distances.

They enjoy great longevity

Increasing human activity leads to interactionsbetween bats, humans, and livestock, thus

increasing the zoonotic potential.

For all these reasons, bats are a potentialsource of emerging diseases.


INTRODUCTION

VIRUS

RESERVOIRS

TRANSMISSION

PREVIOUS OUTBREAKS


SIGNS AND SYMPTOMS

DIAGNOSIS

TREATMENT

ITALIAN EXPERIENCE

PREVENTION

TtT: BACK UP SLIDES

Outline


Transmission

There is no conclusive evidence for how wild animals contract an EBOV infection.



Filovirus Cycle of Transmission

P Formenty, World Health Organization, April 2014


The spillover theory

•The sequences of the virus strains responsible of the different outbreaks in humans differ significantly, suggesting multiple emergences of the infection from the primary animal reservoir.

•The comparison of sequences of different geographical origin and the data of the last epidemic further support the spillover theory.

Wittmann et al PNAS 2007, 104: 17123-27

Baize et al. NEJM 2104


EBOV transmission


Monkeys infected with the Ebola virus: the presence of the virus

In the pharynx after 2-4 days after the appearance of the fever

In conjunctions after 5-6 days

In rectal swabs after 5-6 days

In the nasal mucosa after 5-10 days


Transmission (1): from the animal reservoires

Ebola is introduced into the human population through close contact with the blood, secretions, organs or other bodily fluids of infected animals.

In Africa, infection has been documented through the handling of infected chimpanzees, gorillas, fruit bats, monkeys, warthogs, forest antelope and porcupines found ill or dead or in the rainforest.


Ebola and bushmeat

Brazzaville market

http://www.tropicalforests.ox.ac.uk/bushmeat2

http://www.tropicalforests.ox.ac.uk/bushmeat2


Bat soup



Transmission (2): human-to-human transmission

Ebola then spreads in the community through human-to-human transmission, with infection resulting from direct contact (through broken skin or mucous membranes) with the blood, secretions, organs or other bodily fluids of infected people, and indirect contact with environments contaminated with such fluids.

Burial ceremonies in which mourners have direct contact with the body of the deceased person can also play a role in the transmission of Ebola.


Airborne transmission has not been documented during EVD outbreaks. Spread by water or food other than

bushmeat has also not been observed, nor has spread by mosquitos or other insects.


Human-to-Human transmission

Direct contact (through broken skin or mucous membranes) with the blood, secretions, organs or other bodily fluids of infected people

Indirect contact with environments contaminated with fluids.

Burial ceremonies (mourners direct contact with corps)

The patients become contagious once symptoms begin. They are not contagious during incubation period.

Virus transmitted through the semen for up to 7 weeks after recovery from illness.

Health-care workers have frequently been infected .


Body fluids that may contain ebolaviruses include saliva, mucus, vomit, feces, sweat, tears, breast milk, urine, and semen. The WHO states that only people who are very sick are able to spread Ebola in saliva, and whole virus has not been transmitted through sweat. Most people spread the virus through blood, feces, and vomit. Entry points include the nose, mouth, eyes, or open wounds, cuts and abrasions. Contact with objects contaminated by the virus, particularly needles and syringes, may also transmit the infection. The virus is able to survive on objects for a few hours in a dried state and can survive for a few days within body fluids. Ebola virus may be able to persist in the semen of survivors for up to seven weeks after recovery, which could give rise to infections via sexual intercourse. Otherwise, people who have recovered are not infectious. The potential for widespread infections in countries with medical systems capable of observing correct medical isolation procedures is considered low. Usually when someone has symptoms, they are sufficiently unwell that they are unable to travel without assistance.

Dead bodies remain infectious, thus people who engage in practices ranging from traditional burial rituals to more modern processes such as embalming are at risk. Nearly two thirds of the cases of Ebola infections in Guinea during the 2014 outbreak are believed to have been contracted via unprotected (or unsuitably protected) contact with infected corpses during certain Guinean burial rituals.


Timeline for how a person with Ebola becomes more infectious over time:

Source: Public Health England


EVD in health-care workers

Health-care workers have frequently been infected while treating patients with suspected or confirmed EVD. This has occurred through close contact with patients when infection control precautions are not strictly practiced.


Is sexual transmission possible ?

Men who have recovered from the disease can still transmit the virus through their semen for up to 7 weeks after recovery from illness.


Infectious disease terminology

Attack rate = Percent of people in an exposed group who develop the disease; EBOV = 16-40%

Case fatality rate = Percent of infected people who die; EBOV West Africa = 40% (11310/28616)

Reproduction number = Average number of new cases that occur from a single case; EBOV = 1.3


The basic reproduction number

R0 = Average number of new cases that occur from a single case

C = the number of susceptible people in the population that the affected patients are in contact with

= the infectiousness of the organism

D = duration of infectivity of affected patients

R0 = C x x D


Values of R0 of well-known infectious diseases

Disease Transmission R0

Measles Airborne 12–18

Pertussis Airborne droplet 12–17

Diphtheria Saliva 6–7

Smallpox Airborne droplet 5–7

Polio Fecal-oral route 5–7

Rubella Airborne droplet 5–7

Mumps Airborne droplet 4–7

HIV/AIDS Sexual contact 2–5

SARS Airborne droplet 2–5[2]

Influenzae

(1918 Pandemic Strain)Airborne droplet 2–3[

2014 Ebola Outbreak Bodily fluid1-2

Unless noted R0 values are from: History and Epidemiology of Global Smallpox Eradication From the training course titled "Smallpox: Disease, Prevention, and Intervention". The CDC and the World Health Organization. Slide 16-17.

http://www.cdc.gov/vhf/ebola/transmission/human-transmission.html

http://www.cdc.gov/vhf/ebola/diagnosis/index.html

http://www.cdc.gov/vhf/ebola/hcp/interim-guidance-specimen-collection-submission-patients-suspected-infection-ebola.html


The importance of Effective Reproduction Number (Rt)

If one case of EVD (on average) infects greater than one other person, Rt is >1 and the epidemic grows; e.g., as in West Africa where Rt was initially 3 decreasing to 1.3

If one case of EVD (on average) infects less than one other person, Rt is <1 and the epidemic slows and stops; e.g., as in DRC where Rt is 0.84

The aim of outbreak control is to reduce Rt to less than 1


Looking at past outbreaks, estimates of R0 for:

Ebola Zaire ranged from 1.4-4.7 and for

Ebola Sudan ranged from 1.3-2.7

R0 has not been estimated for Ebola Bundibugyo


What about serosurveys?


Niche modelling suggests that Ebola virus should be widely distributed over equatorial Africa, including countries from which Ebola virus infections have

not been reported.

The most confusing results, however, stem from a myriad of serosurveys, which revealed anti-Ebola virus antibodies in human beings from all over

Africa.

Many of these studies were done during the 1980s and 1990s and varied in quality: different assays were used to detect antibodies (eg,

immunofluorescence assay, ELISA, western blot); seemingly arbitrary cutoffswere sometimes used to differentiate negative from positive results; differentEbola virus antigens were used for assay development (eg, whole inactivatedvirions vs individual viral proteins); sample cohort sizes diverged; and proper

controls were or could often not be included.


Asymptomatic EbolaIt is not known how frequently asymptomatic Ebola virus infection occurs, yetit could affect the course of epidemics. High rates of asymptomatic infection

would reduce incidence through herd immunity, radically altering model predictions of epidemic spread.

If those with asymptomatic infection are infectious, perhaps with persistentviral shedding, it would help explain some failures in control and the

emergence of new chains of transmission.

The extent of asymptomatic infection is unclearbecause previous findings have varied widely (eg, from 1% to 46% of household contacts), with positive results

reported in some populations unlikely to have beenexposed to filoviruses.


Plausible explanations for these discrepant serosurvey results are:

The serosurveys are artifacts due to cross- reaction of Ebola virus antigenswith non-anti- Ebola virus antibodies;

the detected antibodies stem from contact with undiscovered, non-pathogenic filoviruses that are endemic in Africa and that are closely relatedto Ebola virus;

or Ebola virus causes widespread subclinical infection in human beings


Lancet Infect Dis 2017 Published Online February 27, 2017 http://dx.doi.org/10.1016/ S1473-3099(17)30111-1

This new highly specific and sensitive assay showed asymptomaticinfection with Ebola virus was uncommon despite high exposure. The low prevalence suggests asymptomatic infection contributes little to herd immunity in Ebola, and even if infectious, would account for few

transmissions.


Thank you for your attention

DR. GIULIANO RIZZARDINI AND DR. MARIA V IT TORIA COSSU

ASST FATEBENEFRATELL I L .SACCO HOSPITAL

GIULIANO.RIZZARDINI@ASST -FBF-SACCO. IT & MARIA .COSSU@ASST -FBF-SACCO. IT

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