1) The document discusses viral hemorrhagic fevers (VHFs), including Ebola virus disease and Marburg virus disease. It covers the classification, epidemiology, pathogenesis, clinical presentation, diagnosis, treatment and prevention of these diseases. 2) Ebola virus specifically is discussed in detail, including its structure and genome, life cycle within the host, risk factors and methods of transmission between humans. Symptoms can include fever, bleeding and organ dysfunction leading to shock. 3) Prevention of Ebola and other VHFs is focused on avoiding contact with body fluids, proper hygiene and isolation of infected individuals. There are currently antiviral treatments available for Ebola virus disease.

1. DR.HAMISI MKINDI,MD.
TO DOWNLOAD CONTACT: hermyc@live.com

2. TABLE OF CONTENTS:
 INTRODUCTION
 CLASSIFICATION
 EBOLA VIRUS DISEASE
 EPIDEMIOLOGY
 LIFE CYCLE OF EBOLA VIRUS
 PATHOGENESIS
 SYMPTOMS AND SIGNS & COMPLICATIONS
 INVESTIGATIONS
 TREATMENT AND PROGNOSIS
 PREVENTION AND CONTROL
 OTHERS HEMORRHAGIC VIRUS
 REFERNCES

3. I- INTRODUCTION
Viral Hemorrhagic Fevers (VHF) are
a group of febrile illnesses caused by RNA viruses from
several viral families infecting human and non human
primates.
These highly infectious viruses lead to a potentially lethal
disease syndrome characterized by;
 Fever, malaise, vomiting,
 Mucosal and gastrointestinal (GI) bleeding,
 Oedema, and hypotension.

4. II- CLASSIFICATION
4 FAMILIES
1) Arenaviridae
2) Bunyaviridae
3) Filoviridae
4) Flaviviridae
5) OTHERS; Chikungunya (alpha virus)

5. SUMMARY OF PATHOGENIC AGENTS FOR VHF
VIRUS FAMILY VIRUS/SYNDROME GEOGRAPHIC
OCCURRENCE
RESERVOIR OR
VECTOR
HUMA-HUMAN
TRANSMISSION
ARENAVIRIDAE
Junin (Argentine HF) S. America
Rodents
Lassa Fever- yes, via
body fluid; others- not
usually
Machupo (Bolivia HF) S. America
Guanarito (Brazilia HF) S. America
Sabia (Venezuela HF) S. America
Lassa (Lassa Fever) West Africa
FLAVIVIRIDAE
Yellow fever Tropical Africa,
Latin America
Mosquitoes Yellow fever – blood
infective up to 5 days of
illness; others –No
Dengue Fever Tropical areas
Kynasur Forest Disease India
Ticks
OMSK HF Siberia
BUNYAVIRIDAE
Congo-Crimean HF Crimea, parts of Africa,
Europe & Asia
Ticks Congo-Crimean HF –
yes, through body fluids;
Rift Valley Fever,
Hantaviruses – No
Rift Valley Fever Africa Mosquitoes
Hantaviruses (Hemorrhagic Renal
syndrome/ Hantavirus Pulmonary
Syndrome)
Diverse Rodents
FILOVIRIDAE
Ebola HF Africa FRUIT BATS Yes, body fluid
transmission
Marburg Africa
Virus Family

6. III- EBOLA VIRUS DISEASE (EVD)
FORMERLY EBOLA HEMORRHAGIC FEVER (EHF)
 Ebola virus disease (EVD) is a zoonotic disease caused by an RNA virus
of the family Filoviridae and genus Ebola virus leading to severe
hemorrhagic fever and fulminant septic shock.
 It spreads in the human population is through human-to-human
transmission. Incubation period ranges between 2 – 21 days.
 The virus is characterised by a long, filamentous morphology, surrounded
by a lipid viral envelope .
 It morphologically similar to the Marburg virus, and share similar disease
symptoms.

7. (A) STRUCTURE & GENOME OF EBOV
 Ebola virus contains single‐stranded negative RNA linear genome,
encoding seven genes
[NP, VP35, VP40, VP30, VP24, L, and GP]
 Five genetically distinct EBOV species within the genus Ebola
virus are known
• Zaire Ebola virus (ZEBOV),
• Sudan Ebola virus (SEBOV),
• Tai Forest Ebola virus,
• Bundibugyo Ebola virus (BEBOV), and
• Reston Ebola virus (REBOV).

8. The five EBOVs differ in sequence, number, and location of
gene overlaps in their genomes .
REBOV species is reported to cause disease only in
nonhuman primates;
ZEBOV, SEBOV, and BEBOV are responsible for most of the
Ebola hemorrhagic fever (EHF) outbreaks
But ZEBOV constitutes a particularly serious threat to both
human and animals in sub‐Saharan Africa with case fatality
rates as high as 90%.

9. https://www.researchgate.net/figure/Structure-and-the-Genome-of-EbolaVirus24_fig1_303833379

10. (B) EPIDEMIOLOGY
Ebola was discovered in 1976, several outbreaks have occurred, primarily in
Africa.
According to WHO, the 2014 outbreak of Ebola virus in West Africa was the
“largest, most severe and most complex Ebola epidemic” in history.
More than 28,000 people were infected with 11,000 deaths.
 On average, 50% of people who contract Ebola will die. Case fatality rates in past outbreak
varied btn 25 -90%, and
 In current outbreaks which began in 2018 in Kivu DRC, the overall fatality rate was around
67%
 EVD is a public health problem mainly in tropical countries, but imposing global
security and threat.
[Ebola Virus Disease | WHO | Regional Office for Africa ]

11. https://www.google.com/url?q=https://ethiopiaobservatory.com/2014/08/27/eb
ola-virus disease-outbreaks-its reach/&sa=U&ved=2ahUKEwj-
8enFw6f1AhWbiVwKHdcFBsYQr4kDegQIERAC&usg=AOvVaw2wzJPwH2BA

12. Jacob et al., Ebola Nat Rev Dis Primers. 2020 Feb 20;6(1)13

13. (C) LIFE CYCLE OF EBOLA VIRUS
http://www.southsudanmedicaljournal.com/archive/november-2018/ebola-virus-disease-epidemiology-management-
prevention-and-control.htm

14.  RESERVOIR;
Fruit bats of the Pteropodidae Family are considered to be the natural reservoirs of
Ebola virus.
 TRANSMISSION;
The virus is transmitted from wildlife to people through contact with infected fruit bats
and through intermediate hosts such as monkeys, apes, or pigs.
Human‐to‐human transmission;
 Bodily organs and fluid contact
 Poor IPC (infected syringes and needles)
 Direct contact with the body of a deceased person during burial ceremonies is another classic
way by which Ebola can be transmitted.
 No evidences show that pet cat/ dogs, mosquitoes, or other insects can transmit
Ebola virus.

15. (D) PATHOGENESIS:
Entry Point; Mucus membranes, Skin breaks, or Parental
Targets Cell; Monocytes, macrophages, dendritic cells, endothelial cell,
fibroblasts, hepatocytes, adrenal cortical cells & epithelial cells.
Within 6 to 10 days migrates to regional lymph nodes, then to liver
spleen and adrenal gland
• Apoptosis of lymphocytes  Lymphocytopenia
• Hepatocellular necrosis  Dysregulation of clotting factors  coagulopathy
• Adrenocortical necrosis  Impaired steroid synthesis  Hypotension
EBV also Trigger Release of pro-inflammatory Cytokines  Vascular
leak and impaired clotting resulting in MODS and SHOCK.
[www.cdc.gov/vhf/clinicians/evd]

16. i) ENVIRONMENT FACTORS
SEASONS
 Human EVD outbreaks in Africa suggest that the onset
of these outbreaks was associated with conditions with
high absolute humidity and low temperature.
 Seasonal migrations of fruit bat increases contact with
animals and humans
 But EBVD can happen in both dry and wet season.

17. ii) HOST FACTORS
RISK FACTORS
• Age & Sex -all ages and both sexes show an equal preponderance for
the disease.
• Immunity -immunocompetent VS Immunocompromised +/- the same
 Wild animal and plant products consumption is probably the risk fact for
nonhuman to human transmission
 Socio- cultural and taboos in handling the dead is the risk factor for
human-human transmission in the community
 Poor IPC practice among hospital staff is the risk factor of transmission
among healthcare workers

18. iii) VIRULENCE FACTORS
1) High viral load in body fluids .
2) Glycoprotein [GP] causes reduction of integrins  reduced cell adhesion of
Intracellular structure
Endothelial damage
 Liver damage
3) VP24 & VP 35 are structural proteins of EBOV which blunt the human immune
system response by blocking the ability to produce and respond to interferon
proteins (interferon alpha, beta and gamma)
• VP 24 prevention of STAT 1 signaling
• VP 35 directly inhibit the production of interferon-beta .
IMPROPER
CLOTTING

19. [https://www.researchgate.net/figure/Fig-3-Pathogenesis-of-ebola-virus_fig1_273438825]

20. (E) CLINICAL PRESENTATION
 Non specific
Fever, myalgia & malaise
 GIT: Watery diarrhea, nausea, vomiting and abdominal pain
 RS: cough, SOB
 CNS: headache or confusion may develop, seizures +/- , cerebral
edema
 Hematological: bleeding +/- (petechiae, ecchymosis, mucosal
bleeding)

21. Jacob et al., Ebola Nat Rev Dis Primers. 2020 Feb 20;6(1)13
www.nature.com

22. (F) INVESTIGATION
 FBP
- Leucopenia with
lymphopenia
- Later on elevated
neutrophils and left shift
- Thrompcytopenia
 LFT;
- AST>>ALT
- Prolonged PT & PTT
- FDP elevated
- URINALYSIS
=>Proteinuria
Specimens:
-Blood, semen, other body fluid
 PCR
 ELISA
- Antigen detection
- IgM antibodies detection
 CULTURE
Is positive during acute stage.
Virus isolation: requires Biosafety
Level 4 laboratory.
Can take several days

23. Caleo et al, Lancet Infect Dis 2020; 20: 1324–38 Published Online June 25, 2020
https://doi.org/10.1016/ S1473-3099(20)30193-6

24. (G) TREATMENT
i) Antiviral therapy:
Currently two antiviral therapy approved for ZEBOV
1) Inmazeb
2) Ebanga (mAbs)
Act on Glycoprotein( GP) => Preventing entry into human cells.
Efficacy has not been established for species other than ZEBOV

25. ii) Supportive care;
 Oxygen therapy
 Fluid therapy & BT
 Vasopressors
iii) Secondary infection treatment
iv) Vaccine
 A replication-competent, live, attenuated recombinant vesicular stomatitis
virus (rVSV) virus
 ZEBOV-GP Ebola vaccine (Ervebo) contain a gene for zebov glycoprotein
 It does not provide protection against other species of ebolavirus or
marburgvirus

26. (H) PREVENTION
 Hand washing
 Wear PPE
 Avoid contact with blood
or body fluid
 The incubation period of
Ebola virus is 2‐21 days
and therefore, it is
recommended that
infected individuals be
isolated for at least 21
days.
http://www.myk104.com/prevention-ebola

27. (I) PROGNOSIS
Death
Survival
The person remains infectious as long as the virus is present in the
blood and body fluids while those who have completely recovered
from EBV cannot spread it further.
Ebola virus has been detected in the semen of recovered patients
and such patients are advised to abstain from sex or use condoms
for three months after being cured.
There is no evidence yet on when women recovering from the
Ebola virus can resume breastfeeding.

29. 1- MARBURG HF
 Marburg virus disease (MVD) is a hemorrhagic fever virus
caused by Filovirus of Filoviridae family
 Marburg virus disease in humans and primates.
 The virus is considered to be extremely dangerous
 The average MVB case fatality rate is around 50% according
to WHO.
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30. Epidemiology &Transmission
First outbreak was in German 1967,was associated with
lab work using infected African green monkey imported
from Uganda.
Other cases were reported from Uganda, Kenya, DRC,
Angola, and Zimbabwe
Human-to-human transmission occurs by direct contact
with an infected person's bodily fluids.
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31. Clinical features
 Incubation period is 5-10 days
 Presents with fever, chills, headache, and muscle aches, rash
occurs on the chest, back, and abdomen
 Nausea, vomiting chest pain, sore throat, abdominal pain, and
diarrhea may appear.
 In severe forms jaundice, pancreatic inflammation, severe weight
loss, delirium, liver failure, and massive hemorrhaging with organ
dysfunction occurs.
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32. Diagnosis
Enzyme–linked immunosorbent assay
(ELISA)
Serum neutralization test.
Reverse-transcriptase polymerase chain
reaction (RT-PCR) assay and
Virus isolation cell culture
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33. Treatment &Prevention
No specific treatment or vaccine available
Supportive hospital therapy should be utilized
Intensive care ,barrier nursing techniques
wearing of protective gowns, gloves, and masks
Placing the infected individual in strict isolation
and sterilization or proper disposal of needles,
equipment, and patient excretions.
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34. 2- ARENAVIRIDAE
Is a virus spread by
rodents and cause either
neurological or
hermorrhagic fever.
Enveloped virus with two
beaded single-stranded
RNA segments.
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Wild rodents is the
main source of Lassa
virus infection.
LASSA FEVER

35. Epidemiology and Transmission
Lassa fever is endemic in rural West Africa
Transimmision is by rodents to human ,
Virus is transmitted through inhalation of aerosols
from rodent urine, ingestion of rodent-contaminated
food, or direct contact of broken skin or mucosa with
rodent excreta.
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36. PATHOGENESIS
 Unclear
 Main target of virus are
dendritic cells and endothelial
cells
 Virus prevents host innate
immunity by nucleoprotein
(NP) activity .
 When a pathogen entered
into a host innate defense
system recognize pathogen
associated molecular pattern
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 NP encoded in Lassa
virus is essential in viral
replication and
transription but also
suppresses host innate
interferon response by
inhibit translocation of
interferon regulatory
factor 3 (IRF3).

37. Upon entry the Lassa virus infects almost every tissue in
the human body and progress to the vascular system .
Small focal hemorrhages is present, primarily in
mucosal surfaces, and hepatic necrosis is more severe.
 Levels of circulating proinflammatory cytokines are
present as well and these are candidates for the
mediators of arenavirus HF.
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38. Clinical features
Typically occur 1-3weeks after the patient comes
into contact with the virus.
Mild symptoms 80% general malaise fever and
weakness
20% presents with bleeding gums, eyes , nose
,respiratory distress and severe vomiting.
Neurological symptoms and multi organ failure.
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39. Diagnosis
Enzyme-linked immunosorbent assay (ELISA) test for
antigen
Igm antibodies give 88% sensitivity and 90% specificity
RT- RNA PCR is highly sensitive
Other lab findings –lymphopenia, thrombocytopenia and
elevated liver enzymes
Throat culture
Biopsy or autopsy specimens of lymphoid tissues, marrow,
and liver usually yield virus.
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40. Treatment &Prevention
Aggressive intravenous fluid resuscitation
Aggressive electrolyte repletion
Correction of acid-base derangements
Ribavirin
Control of rodents
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41. 3- BUNYAVIRIDAE
-
 Bunyaviridae is a family of Arthropod-borne or
Rodent-borne spherical enveloped RNA.
 It involve:
Congo-Crimean HF
Rift Valley Fever
Hantaviruses (Hemorrhagic Renal syndrome/
Hantavirus Pulmonary Syndrome)
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42.  RIFT VALLEY FEVER
 RVF primarily affects animals,
especially sheep, cattle, camels
and goat
 But it can also cause severe
disease in humans.
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 Rift valley virus cause RVHF
 Form spherical RNA with
diameters of 90–100 nm.
 Consisting of a large (L),
medium (M), and small (S) RNA
segment.
 1st outbreak was on 1977 –
Egypty, caused by sheep that
were imported from Sudan.

43. Epidemiology&Transmission
RVF is endemic to sub-Saharan Africa.
Sporadic outbreaks have occurred in humans
RVF virus is transmitted by mosquito, percutaneous
inoculation, and slaughter or consumption of infected
animals.
 Direct Contact-Tissues or body fluids of
infected animals
Does not spread from person- to-person
Two outbreaks reported in Tanzania, the recent
being in 2006/07
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https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-3183-9

44. Mechanism of disease
Caused by cytopathic virus that target the liver and
the brain.
The virus escape from the skin to the draining
lymphnodes where it replicate and spread
throughout the body
Nonstructural protein (NSs) expression, thus
providing some initial inhibition of alpha/beta
interferon (INF-α/β)-mediated responses.
It also cross the BBB and infect neurones and glia
leading to meningoencephalitis and retinitis
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45. Clinical features
 Period of time from exposure to signs of disease: 2-6 days
 No signs to flu-like symptoms
- Fever, headache, muscle and joint pain, nausea, vomiting
- Recovery in 4-7 days
 In severe form
- Ocular manifestation (0.5-2%) of patients
- Meningoencephalitis <1%
- Haemorrhagic fever<1%
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DIAGNOSIS
A suspected or probable case with Laboratory confirmation of Rift
Valley Fever by
- ELISA
- PCR.

46. Treatment and prevention
 No specific treatment, control is very important
 Quarantine domestic animals
 Animal vaccines exist for areas where RFV is endemic.
 Vector control (mosquito) prevent spread of the disease.
46
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47. 4- FLAVIVIRIDAE
Includes Dengue virus and yellow fever virus
Linear single-stranded RNA genomes of positive
polarity
Enveloped
Non-segmented.
47
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48.  YELLOW FEVER
 Epidemic, yellow fever is spread
from one infected human host to
the next by Aedes aegypti
 A mosquito that inhabits human
settlements in Africa, South
America, and North America
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A mosquito that bites an infected human during the viremic phase of
his or her illness may transmit the infection to other hosts after the
virus has incubated for 1-2 weeks in the mosquito.
Mosquitoes survive the infection and may serve as a vector for life.

49. Pathogenesis
 Infection occurs after deposition of viral particles through the skin from infected
mosquito saliva .
 The E protein help in viral-cellular attachment endosomal membrane fusion, and
the display of sites mediating hemagglutination and viral neutralization
 Nonstructural protein (NS1) is expressed on the surface of infected cells and is
also excreted as a complement-fixing antigen.
 Although antibodies to NS1 do not neutralize the virus, they contribute to
protective immunity, probably by complement and cell mediated responses against
infected cells
 The virus first replicates locally, followed by transportation to the rest of the body
via the lymphatic system
 The virus proceeds to establish itself throughout organ systems, including the heart,
kidneys, adrenal glands, and the parenchyma of the liver; high viral loads are also present in the
blood.
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50. Clinical features
 The majority of persons have mild illness
 In initial symptoms includes fever ,chills ,headache nausea and
vomiting
 Severe forms presents with jaundice ,bleeding and eventually
shock and multi organ failure
Diagnosis
Lab test includes :-
 IgM –capture ELISA
 IgG –ELISA performed on blood sampled during acute illness.
 PCR ,immunohistochemical stains ,and viral culture .
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51. Treatment & Prevention
Symptomatic and
supportive only.
Fluid replacement
Transfusion of blood is
generally needed only
in severe cases.
Vaccine developed in
1930s that gives a 10-
year or more immunity
from the disease
Effectively protects people
traveling to affected
areas, while at the same
time being a means to
control the disease.
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52.  DENGUE FEVER
 Dengue fever is a common mosquito-borne illness in many tropical
and subtropical countries.
 Since 1970 the virus has been spread dramatically , in Africa has
epidemics and DF is known to be present in 19 countries on the
African continent .
 In Tanzania 2014 outbreak reported 1,018 confirmed cases out of a
total of 2129 suspected cases including 4 deaths.
 4 serotypes are known to be circulating in the continent.
 Vector: A. aegypti (mosquito)
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53. People at higher risk include:
 infants and small children
 pregnant women (the virus may be passed from mother to fetus)
 older adults
 those with compromised immune systems
 TRANSMISSION
 Four different dengue viruses serotypes are known to cause
dengue hemorrhagic fever.
 Dengue hemorrhagic fever occurs when a person is bitten by a
mosquito that is infected with the virus.
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54. Pathogenesis of bleeding in DHF
Thrombocytopaenia is due to bone marrow suppression
during the febrile viraemic phase of the illness.
The low plasma fibrinogen due to reflection of loss into the
interstitial spaces in increased vascular permeability.
Haemorrhages are triggered by trauma in this setting of
coagulopathy.
Development of antibodies potentially cross-reactive to
plasminogen could have a role in causing haemorrhage in
DHF
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55. Clinical features
Early symptoms include:
- Decreased appetite
- Fever
- Headache
- Joint or muscle aches
- General ill feeling
- Vomiting
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LATER ON patient
presents with
- Patches of blood under
the skin
- Tiny spots of blood on
the skin
- Generalized rash
- Worsening early
symptoms

56. Diagnosis
Antibody test –two different classes of
antibodies produced by the body in
response to DF i.e IgG and IgM
Molecular testing -Polymerase chain
reaction (PCR).
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57. Treatment & Prevention
No specific treatment hydration status is important
Pain relievers given with caution since they may
worsened the bleeding .avoid NSAID
Ongoing vaccine development against Dengue virus
.
Eliminating or reducing the mosquito.
The use of mosquito nets, repellents ,and avoiding
endemic areas.
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58. REFERENCE
1. Lange medical microbiology 24th edition
2. World Health Organization. Interim infection prevention and control guidance for care
of patients with suspected or confirmed filovirus haemorrhagic fever in health-care
settings, with focus on Ebola. 2014;1-24.
3. CDC Center for Disease Control Ebola virus page http://www.cdc.gov/vhf/ebola/
4. Bray M. Pathogenesis of viral hemorrhagic fever. Current Opinion in Immunology
2005;17: 399-403.
5. Beer B, Kurth R, Bukreyev A. Characteristics of Filoviridae: Marburg and Ebola
viruse. Naturwissenschaften. 1999; 86: 8-17.
6. Baron RC, McCormick JB, Zubeir OA. Ebola virus disease in southern Sudan:
hospital dissemination and intrafamilial spread. Bull World Health Organ 1983;
61:997–1003.
7. Nigeria Centre for Disease Control (2020) Lassa fever situation report.
https://reliefweb.int/sites/reliefweb.int/files/resources/9f755119d0c
6e28f2747ace79a1bb4f8.pdf
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