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Libby Burch
March 9, 2012
Lassa, Ebola, & Marburg Viruses
Objectives:
During the course of this presentation, we will focus on three viral diseases: Lassa Virus,
Ebola Virus, and Marburg Virus. You will gain a greater understanding of how these
diseases apply to a humanitarian crisis situation or a resource poor setting, and explore
some strategies for diagnosis, treatment, and outbreak avoidance and control that are
appropriate for these circumstances. Each of these diseases will be described in turn, and
you will learn the biological basis of these viruses, their modes of transmission, symptoms,
global prevalence, and associated epidemiology. By the end of this presentation, you will
recognize the risk factors inherent to these viral diseases in humanitarian crises, and have
an understanding of the strategies necessary to combat these diseases.
Disease Background: Viral Hemorrhagic Fevers (VHFs)
 Viral Hemorrhagic fevers are a diverse group of viral diseases that are characterized
by widespread systemic symptoms that in their most severe manifestations can
cause vessel and organ damage and bleeding (hence the name “hemorrhagic”).
(WHO/CDC 1996).
 Symptoms are often extremely similar and hard to distinguish and include fever,
headache, malaise, nausea, vomiting blood and hemorrhage from mucus membranes
such as the nose, gingiva (gums), rectum, and conjunctiva (CDC 2006; WHO; SFDPH
2005). Death occurs due to blood loss through widespread hemorrhage or
associated organ failure (Cohen 2004). Incubation periods vary from disease to
disease and from outbreak to outbreak, but fall within the range 2 to 20 days postexposure (GIDEON Informatics: Lassa, Marburg, Ebola).
 Although found elsewhere, VHF diseases are most commonly found in Africa and
cause sporadic outbreaks and epidemics in endemic areas. This presentation will
cover Ebola hemorrhagic fever, Lassa virus, and Marburg virus, but Rift Valley fever,
Yellow Fever, Dengue hemorrhagic fever, and Crimean-Congo hemorrhagic fever are
also VHF diseases (SFDPH 2005).
 For the three diseases focused on today, human-to-human transmission is high after
initial infection from the animal reservoir. Transmission occurs readily via direct
contact with infected urine, blood, sweat, saliva, secretions, vaginal fluids, and
semen (Lamunu 2004). For these reasons, any contaminated objects or samples of
virus from these diseases are classified as Biohazard Safety Level 4 (the highest
designation) by the United States CDC (CDC).
 Risk of transmission of VHFs in hospitals, health care settings, and in areas of
crowding is extremely high. All bodily fluids from an infected person are possible
modes of transmission; health care workers must take utmost care to practice
barrier nursing and other outbreak control strategies (SFDPH 2005).
 International virologist Nathan Wolfe describes pathogen evolution in stages
leading up to exclusively infecting humans, with no need for an animal reservoir. A
disease like rabies is classified as Stage 2 because although human-to-human
transmission is possible, no cases occur because rabies is so easily identified and
transmission to another human is relatively difficult. Lassa, Ebola, and Marburg
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outbreaks are Stage 3 diseases because they are highly infectious, but have such
high mortality rates that the outbreaks invariably are contained and burn
themselves out. HIV is a classic example of a Stage 5 pathogen that originated in an
animal, but now exclusively infects humans (Wolfe et al. 2007).
Distribution in Africa
 All three VHFs that we will focus on today are endemic to central, west, or eastern
Africa (CDC).
 Lassa virus is found commonly in Nigeria, Sierra Leone, Guinea, Liberia, the Central
African Republic, and adjacent regions (McCormick 1987; CDC). Outbreaks are
projected to expand in distribution as logging routes and inter-regional travel
become more widespread (Wolfe 2011).
 Ebola Virus occurs in humid rain forests of central and western Africa, such as in
Zaire, Republic of the Congo, Gabon, Sudan, and Uganda. (GIDEON Informatics:
Ebola).
 Marburg is found in drier areas of Africa, such as regions in Kenya, Uganda,
Democratic Republic of the Congo, and Angola (GIDEON Informatics: Marburg).
 As you can see by the disease distributions [Pictured: Maps of Lassa, Ebola, Marburg
viruses. Photos courtesy of Travel Approved and Mehedi et al. 2011], extensive
overlap of endemic regions means diagnosis cannot be based on location.
Furthermore, as you will hear about later, new cases in new areas are being
identified as better diagnostics are designed and human mobility continues to
increase (Geisbert 2011).
Lassa Virus: Biological Background
 Lassa Virus (or Lassa fever) is transmitted to humans by a species of wild rodent
called the multimammate rat (Mastomys natalensis) and is therefore a zoonotic
disease (GIDEON Informatics: Lassa; Ogby et al. 2007).
 The actual virus is classified as an arenavirus, which is characterized by its
spherical, sand-like appearance (Emonet et al. 2011).
 Current estimates state that the annual caseload is between 300,000 and 500,000
cases, with about 5,000 deaths yearly across West Africa (Ogbu et al 2007).
 The overall mortality rate is about 1%, but increases to 15-20% in hospitalized
patients. Death rates are highest for pregnant women and fetuses have a 95%
mortality rate (CDC Lassa).
 Symptoms are varied, but include fever, muscle aches, nausea, vomiting, abdominal
pain, hemorrhagic symptoms in severe cases, and deafness in one or both ears
(Carey et al. 1972; CDC Lassa 2004).
Lassa Virus: A Zoonotic Disease
 Multimammate rats (Mastomys natalensis), or bush rats, are wild rodents that are
extremely common in most of sub-Saharan Africa (Werner 2004). Infected rats
show no averse symptoms, and shed the virus in their urine in concentrations
upwards of 1000-10,000 infectious viral particles per milliliter of urine and feces
throughout their lifetimes (GIDEON Informatics: Lassa; Kernéis et al. 2009).
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Transmission to humans can occur when aerosolized particles of rat urine or feces
are inhaled or with direct contact with rodent excreta with open wounds or mucous
membranes. Eating rodent meat is also a risk factor, as preparation of the infected
rodent can make viral transmission more likely, and undercooked meat will be
infective in ingested (Kernéis et al. 2009).
Again, with all of these diseases, after initial human infection from a rodent
reservoir, human-to-human transmission is high and results in the characteristic
sporadic outbreak pattern (Ogbu et al. 2011).
Lassa Virus: Risk Factors
 Contact with infected or possibly infected bush rat populations increases risk of
rodent-to-human transmission. Rat infiltration in homes and around food stores
increases the likelihood of rodent excreta being inhaled or ingested. This is
especially true in dry regions where dust and excreta are more easily kicked up into
the air (GIDEON Informatics: Lassa).
 However, the most at-risk population is associated with human-to-human
transmission: the health workers and family members that care for the infected
person. With high viral loads in symptomatic (and possibly hemorrhaging)
hospitalized or bedridden patients, the risk of infection for people in contact with
bodily fluids and contaminated materials is elevated. This is one reason why
nosocomial (hospital or clinically acquired) infections are so common and outbreaks
often start in hospitals (CDC).
Ebola Virus: Biological Background
 Ebola virus (or Ebola hemorrhagic fever) is a rare but extremely severe
hemorrhagic fever that has a mortality rate of 50-90% (GIDEON Informatics: Ebola).
 Ebola virus belongs to the viral family filoviridae, and is caused by 5 species of
filovirus, four of which have been seen to cause disease in humans. Filoviruses are
characterized by causing severe viral hemorrhagic fevers, infecting pigs, bats, or
primates in nature, and by their characteristic filamentous appearance when viewed
at high magnification. [Pictured: A strand-like viron of Ebola virus, with
characteristic looping at one end, as seen with a electron microscope. Photo
courtesy of the CDC Public Health Image Library].
 Although an animal reservoir must exist, it is currently unknown. Initial infection is
speculated to occur with contact with an infected animal and then spread
throughout human populations. Human-to-human transmission is just like with
Lassa (through blood, urine, secretions, contaminated objects like syringes). The
fifth species of Ebola virus, the one that has not been seen in humans (only in
primates), was observed to spread through airborne particles (CDC fact sheet). This
could have implications for containment should this species be found in humans in
the future.
 Ebola is typically found in regions of humid rainforest in central and western Africa
(GIDEON Informatics: Ebola).
Ebola Virus: A mysterious reservoir
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Researchers have been searching for an animal reservoir but have not conclusively
identified one yet. Gorillas, chimpanzees, and other non-human primates have been
seen to be infected with Ebola virus, but it is inconclusive whether this is just an
intermediate reservoir and the primates are getting infected via another animal.
Bats have been implicated as a possibility, but no definitive species have been found
and the mechanism of transmission is still unknown. (CDC: Ebola).
Ebola Virus: Risk factors
 Interaction with non-human primates increases the likelihood of animal-to-human
transmission. This is especially true for bush hunters that hunt primates and
prepare the meat for consumption, and therefore have extended contact with the
blood and bodily fluids of the animal (Wolfe 2011).
 Again, health care workers and family members that are caring for sick patients are
also at elevated risk.
Marburg Virus: Biological Background
 Marburg virus is a highly severe hemorrhagic fever with a typical mortality of 2330%, but that can increase to upwards of 80% in extreme outbreaks (CDC; Towner
2006). Marburg is clinically indistinguishable from Ebola virus.
 Like Ebola hemorrhagic fever, Marburg is a filovirus. [pictured: Marburg viron,
showing the characteristic ‘6’ and ‘U’ shaped filaments. Photo courtesy of the CDC
Public Health Image Library].
 Marburg is found mostly areas of dry climate in central and eastern Africa (Peterson
2004).
 Although a definitive animal reservoir is still being researched, recent studies show
that Marburg virus has been found in a species of bat common to Africa (Towner
2007) and strongly implicate that this bat (Rousettus aegyptiacus) might be the
animal reservoir that initially transmits the virus to primates and humans
(Manganga 2011).
Marburg Virus: Risk Factors
 Human activities in caves, especially mining projects, has been associated with
outbreaks in the past, and supports the recent research that bats could be the
animal reservoir (Swanepoel 2007).
 [Pictured: Egyptian Fruit Bats (Rousettus aegyptiacus), the possible zoonotic
reservoir of Marburg, in a human home. Photo courtesy of Dietmar Nill and
naturepl.com.]
 As with all three of these diseases, contact with infected humans (or primates, in the
case of Ebola and Marburg) is extremely risky and requires proper barrier nursing
techniques and extreme care when handling infectious material (CDC).
 Marburg outbreaks are typically sporadic but spread quickly throughout
communities if not contained (CDC; Towner 2006).
Diagnosis & Treatment
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All three diseases are diagnosed with laboratory tests due to their non-specific
symptoms. Again, they are characterized by fever, malaise, diarrhea, headache, sore
throat, vomiting, and hemorrhage.
Characteristic diagnostics for Lassa virus include inflammation of the throat with
while tonsilar patches (GIDEON Informatics: Lassa).
Laboratory diagnostic tests consist of immunoglobulin (IgG) antibody serology,
positive PCR from serum or autopsy tissues, or isolation of the virus itself in
biosafety level 4 laboratories (Harper 2010).
There is only a specific treatment for Lassa Virus, which consists of intravenous
Ribavirin for 10 days. The mechanisms of Ribivarin therapy are unknown, but are
highly effective (GIDEON Informatics).
Treatment for Ebola and Marburg (and Lassa after Ribivarin) consists of strict
isolation while implementing supportive care. This entails intravenous fluids to
maintain electrolytes, oxygen and breathing devices, or medications that could
control fever or maintain blood pressure (CDC Fact Sheets).
Ebola Outbreak: A case study
 The most recent large outbreak of Ebola occurred in Uganda between October 2000
and January 2001. During these four and a half months, a total of 425 cases and 224
deaths were recorded and attributed to Ebola hemorrhagic fever. This results in a
mortality rate for this outbreak of 53% (Lamunu et al. 2004; Cohen 2007).
 The outbreak was first reported to the Ministry of Health on October 8, 2000 by a
non-governmental hospital in the Gulu district of Uganda, at which point there were
three deaths and eight critically ill patients with symptoms characteristic of viral
hemorrhagic fever. Upon investigation by the Minitsry of Health team, most of the
patients had a history of attending a funeral just days before fever symptoms
appeared.
 A limited isolation unit was set up in the hospital on October 10, and barrier nursing
techniques were introduced and medical workers were provided with masks,
gloves, plastic aprons, gum boots, and head ware.
 Outreach to the public was started a week after initial reports, and consisted of
widespread educational posters, documentary films, and, radio programs were
distributed. Cultural practices such as handshaking, large gatherings (funerals and
dances) and traditional healing techniques were halted throughout effected
districts.
 Burial of infected corpses was delegated to trained burial teams of volunteers and
military personnel. [Pictured: Proper burial technique by trained teams, wearing
extensive barrier clothing. Photo courtesy of CDC Public Health Image Library.]
 Extensive cooperation between the health workers, military, community leaders,
teams from the CDC, and the public helped minimize spread and contain the
outbreak.
 The outbreak was declared to be over at the end of February 2001, after two
incubation periods after the last case sero-converted and had passed without
further infection. (Lamunu et al. 2004).
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[Pictured: The epidemic curve and timeline of the Uganda 2000 Ebola outbreak.
Graphic courtesy of Scott Harper and the CDC].
Containment and Control in a typical non-crises outbreak
 Steps in an outbreak situation are focused on containment and control of the
epidemic. This includes several steps (Harper 2010; CDC/WHO):
 (1) Logistics and Coordination: Supplies for barrier nursing, body disposal, medical
supplies, transportation of personnel. Coordination between international response
teams is necessary to plan resupply needs and make sure adequate professionals
are informed and participating. [Pictured: barrier nursing strategies]
 (2) Social Mobilization: All levels of the effected areas, including community leaders,
civilians, and the military must be constantly communicating. Outreach education to
the public must occur early and be widespread, and collaboration with the media is
ideal. [Pictured: A poster used for public education about the spread of Ebola virus]
 (3) Laboratory Diagnosis: Diagnosis of the species of virus should occur for as many
patients as possible through antibody detection, immunoglobulin detection, PCR
correlation, and serology tests.
 (4) Epidemiology and Surveillance: Cases and contacts must be maintained (ideally
in a database) such that daily checkups can be made by surveillance teams.
Coordination with burial teams and community outreach teams should be reported
to the Ministry of Health to better assess what needs to be added to the strategies.
Humanitarian Crises: A risk-enhanced situation
 Humanitarian crises situations add a whole new set of dimensions to the already
complicated field of outbreak control. With internally displaced persons due to
conflict, natural disaster, or other factors, population densities increase while
standards of living plummet.
 Access to sterile or even clean medical supplies are lacking, and personnel trained in
all aspects of infectious disease outbreaks are probably rare.
 Logistical coordination of medical teams and surveillance of the outbreak is
complicated by refugee camps, widespread disorganization, and a myriad of other
factors.
 Diagnosis is difficult because symptoms are common to many diseases associated
with resource poor settings (malaria, dengue, other fevers), and laboratory
diagnostic tests are unavailable or limited. Therefore, outbreaks can go
unmonitored and uncontained for longer period of time before officials take notice.
 Furthermore, in food-limited situations, bush meat may become the best option.
This can increase the likelihood that animal-to-human transmission occurs if
primates, bats, or rodents are hunted, slaughtered, and eaten.
Key Strategies in Humanitarian Crises
 Isolation: infected or suspected cases should be isolated from others as soon as
possible. This is especially important in crowded living situations where spread of
disease is extremely fast.
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Identification without laboratory resources can be hard, especially if there is only on
case. Look for headache, high fever, unexplained bleeding, and treat accordingly.
Fortunately most of these patients will have other fever-causing diseases that are
less infectious, such as dysentery, malaria, or typhoid fever. Should multiple similar
cases arise and treatment for other suspected diseases fails, immediately notify
other health care providers and start isolation precautions.
Isolation precautions in a crisis setting may be difficult: even setting aside a corner
of a large room for suspected cases can help reduce nosocomial outbreaks. In
settings where separate rooms are not possible, put screens or tarps between
patients to reduce transmission via spills or splashes. Assign one set of medical
equipment (blood pressure cuff, stethoscope, thermometer) for the isolation ward
or area. Disinfect after each use with alcohol.
Reduce transmission: This can be both preventative and post-infection. Infected
corpses should be buried properly and as soon as possible, ideally away from the
refugee camp or other volatile area. Infective agents and contaminated bedding,
clothing, or bandages should be burned. Injections and other invasive procedures
should be minimized to limit the opportunity for contamination or accidental
infection of health care workers. Use disposable needles and scalpels only once, and
dispose of them in a puncture-resistant burnable container. A good replacement for
a standard sharps container is a plastic water, oil, or bleach bottle.
If disposable syringes are not available, disinfect reusable syringes and needles with
full strength bleach several times and let air dry.
Low-tech disinfection is effective with soap and water and bleach. Sterilization
without an autoclave or steam sterilizer consists of boiling items in water for 20
minutes. This is effective to kill VHF viruses.
Barrier nursing supplies may be limited. Ideally a thin and thick pair of gloves
should be worn at all times, but in short supply substitute plastic bags and regular
kitchen gloves for latex medical gloves and thick rubber gloves. HEPA-filters or
biosafety masks are ideal, but surgical masks, and cotton masks are good substitutes
and can be reused if not contaminated.
More detailed instructions for each of these strategies can be found on the CDC
website where they have a public document called Infection Control for Viral
Hemorrhagic Fevers in the African Health Care Setting.
Future Directions
 Vaccines for Lassa, Ebola, and Marburg are currently in development and are being
tested on animal models. The Lassa vaccine prevented symptoms and death of three
primate specimens (Geisbert, et al. 2005), while the Ebola and Marburg live
attenuated vaccines prevented disease with only light fever symptoms (Jones et al.
2005).
 The non-profit organization Global Viral Forecasting Initiative is working to develop
systems that prevent novel pandemics before they are already established. Based on
the observation that most major human diseases start in animals, they have started
monitoring animals, humans, and pathogens to make insights into how diseases
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move from animals to humans, and how that data can be used to predict future
disease outbreaks (GVFI.org/about).
Hunting bushmeat is a huge opportunity for possible cross over of a pathogen due to
the extensive contact with wild animal carcasses, blood, and viscera. Nathan Wolfe,
head of GVFI, writes in his book The Viral Storm, “from the perspective of a microbe,
hunting and butchering represent the ultimate intimacy, a connection between one
species and all of the various tissues of another, along with the particular microbes
that inhabit each one of them” (Location 641). Hunting higher-level primates such
as the chimpanzee that are hunters themselves increases this risk even further due
to the accumulation of pathogens in the chimp’s tissues.
GVFI is using the unique role of the bushmeat hunter to monitor viral crossover as
they occur by having hunters act as “sentinels”. Hunters are given small pieces of
filter paper to drip the animal’s blood onto and return to the researchers for
analysis. In this way, many new viruses are being discovered before they are causing
widespread outbreaks, and the animal reservoirs of these viruses are already
known. Therefore, preventative measure can be taken, and outbreaks can be
avoided.
Instead of the current strategy of waiting for an outbreak and reacting to it, GVFI
hopes to prevent or at least predict outbreaks before they happen. “Reduce time to
insight, reduce time to action” –Lucky Gunasekara, GVFI virologist
Summary
 Lassa, Ebola, and Marburg viruses are Viral Hemorrhagic fevers characterized by a
set of symptoms, high infectivity, high mortality, and existence of an animal host.
 Transmission risks include interaction with the animal host, especially in hunting
situations where blood and bodily fluids are ubiquitous. Transmission is extremely
likely in hospital and patient-care situations, so proper barrier nursing, isolation,
and disinfection of supplies must be used.
 In resource poor settings or during humanitarian crises, alternative but effective
strategies can be used to contain and control an outbreak. These strategies include
coordination of task forces and use of non-standard equipment like tarps, plastic
bottles, and hand washing stations to minimize transmission.
 Current research in viral outbreak prediction will hopefully reduce epidemic
severity in the future by allowing for greater preparedness before the outbreak is
underway.
References
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