Especially Dangerous Infection

1. ESPECIALLYESPECIALLY
DANGEROUSDANGEROUS
INFECTIONSINFECTIONS
Infectious diseasesInfectious diseases
Department of infectious diseasesDepartment of infectious diseases

2. Especially dangerous infections – it is as heavy as
lead sharply contagious infections which are able mass to
spread as epidemics and pandemics and give high % lethality.
Especially dangerous infections (EDI): plague,
cholera, natural pox (pox of marmosets), yellow fever and
other. They are named «quarantine infections» or
“convention”, so as prophylactic and against epidemic
measures on these infections are regulated by the
“International sanitary rules”(ISR, 1969, 1973), by the
international agreements – by conventions.

3. These rules are directed on prevention of import EDI
and guard of territory of the states from distribution EDI. They
are executed by every country which enters to WHO.
In obedience to ISR:
1) every country during 24 hours must report WHO about the
cases of disease or exposure of exciter EDI on its territory;
2) about the amount of cases, about the amount of lethal
cases;
3) about mechanisms and ways of transmission;
4) about the sizes of cell;
5) about liquidation of cell.
WHO reports all other countries about the cases EDI in
a world, gives out information about the flashes, publishes
reports, results of scientific researches, and gives help in
conducting of quarantine measures.

4. In obedience to the order of Ministry of health of Ukraine №133,
from 19.07.95 to EDI is equated 38 infections:
Plague Brucellosis Legyonelosis
Cholera Rabbit-fever Illness of Hat
Natural pox Siberia Ku-fever
Yellow fever Sap Mouse typhus
AIDS Myloidosis Topsail fever
Pasterelosis Psittacosis Tuberculosis
Illness of Marburg Circling Pseudotuberculosis
Fever is Tasty Hydrophobia Hemorrhagic fevers
Fever Ebola Erizopeloid Crimean fever
Leptospirosis Omsk fever Illness of Lime
The Contagions viruses of fever Denge,
Chicoungounya, Valleys Rift, Western to
Nile
Encephalitis: Californian,
Sent-Louis, valleys Moor.
The epidemic spotted
fever
Encephalomyelitis’s: Western and East
American, Venezuelan
Hemorrhagic fever with a
kidney syndrome
Tick to turning typhus
Foot-and-mouth disease Tick encephalitis

5. Sponsored
Medical Lecture Notes – All Subjects
USMLE Exam (America) – Practice

6. PlaguePlague
Plague is a deadly infectious disease caused by the
enterobacteria Yersinia pestis. Plague is a zoonotic,
primarily carried by rodents (most notably rats) and spread
to humans via fleas. Plague is notorious throughout history,
due to the unprecedented scale of death and devastation it
brought. Plague is still endemic in some parts of the world.
The epidemiological use of the term plague is currently
applied to bacterial infections that cause buboes, although
historically the medical use of the term plague has been
applied to pandemic infections in general. Plague is often
synonymous with "bubonic plague" but this only describes
one of its manifestations. Other names have been used to
describe this disease, such as "The Black Plague" and
"The Black Death", the latter is now used primarily to
describe the second, and most devastating pandemic of
the disease.

7. Bubonic plague is mainly a
disease in rodents and
fleas (Xenopsylla cheopis).
Infection in a human occurs
when a person is bitten by
a flea that has been infec-
ted by biting a rodent that
itself has been infected by
the bite of a flea carrying
the disease. The bacteria multiply inside the flea, sticking
together to form a plug that blocks its stomach and causes
it to begin to starve. The flea then voraciously bites a host
and continues to feed, even though it cannot quell its
hunger, and consequently the flea vomits blood tainted with
the bacteria back into the bite wound. The bubonic plague
bacterium then infects a new victim, and the flea eventually
dies from starvation. Serious outbreaks of plague are
usually started by other disease outbreaks in rodents, or a
rise in the rodent population.

8. Etiology
Yersinia pestis (bacillus pestis),
the etiological agent of plague
was first described by A. Yersen
in 1894 in Hong-Hong, the
International committee of
systematization of bacteria (1982) referred it to Yersinia
genus together with bacillus pseudotuberculosis and
yersiniosis.
In its characteristic form this organism is a short, oval
bacillus with rounded ends - i.e. coccobacillary. In the
tissues a typical capsule may be observed; in cultures
grown at 37°C material can be demonstrated by means
of India ink preparations, but it no well-defined.
The organism is Gram-negative, and when stained with a
weak stain (e.g. methylene blue) shows characteristic
bipolar staining which is an important feature in
identification.

9. Geographic Distribution of Plague
Worldwide, there are 1,000 to 2,000 cases each year.
During the 1980s epidemic plague occurred each year in
Africa, Asia, or South America. Epidemic plague is
generally associated with domestic rats. Almost all of the
cases reported during the decade were rural and occurred
among people living in small towns and villages or
agricultural areas rather than in larger, more developed,
towns and cities.

11. The following information provides a worldwide
distribution pattern:
There is no plague in Australia.
There is no plague in Europe; the last reported cases
occurred after World War II.
In Asia and extreme southeastern Europe, plague is
distributed from the Caucasus Mountains in Russia,
through much of the Middle East, eastward through China,
and then southward to Southwest and Southeast Asia,
where it occurs in scattered, localized foci. Within these
plague foci, there are isolated human cases and occasional
outbreaks. Plague regularly occurs in Madagascar, off the
southeastern coast of Africa.

12. In Africa, plague foci are distributed from Uganda south on
the eastern side of the continent, and in southern Africa. Severe
outbreaks have occurred in recent years in Kenya, Tanzania,
Zaire, Mozambique, and Botswana, with smaller outbreaks in
other East African countries. Plague also has been reported in
scattered foci in western and northern Africa.
In North America, plague is found from the Pacific Coast
eastward to the western Great Plains and from British Columbia
and Alberta, Canada southward to Mexico. Most of the human
cases occur in two regions; one in northern New Mexico,
northern Arizona, and southern Colorado, another in California,
southern Oregon, and far western Nevada.
In South America, active plague foci exist in two regions;
the Andean mountain region (including parts of Bolivia, Peru,
and Ecuador) and in Brazil.

13. Clinical manifestations
Incubation Period. The incubation period of human plague
varies usually from 2 to 10 days, but is generally from 3
to 4 days. In primary pneumonic plague it may not be
over 2 or 3 days.
Clinical plague infection manifests itself in three forms
depending on the route of infection:
 bubonic,
 septicaemic
 pneumonic.

14. Bubonic plague is the best-known
manifestation of the bacterial disease
plague. The term "bubonic plague" was
often used synonymously for plague,
but it does in fact refer specifically to
an infection that enters through the
skin and travels through the
lymphatics, as is often seen in flea-
borne infections. Bubonic plague kills
about 50% of infected patients in 3–7
days without treatment, and is believed
by many to be the Black Death that
swept through Europe in the 1340s,
killing millions of people.The bubonic
plague may have originated in ancient
Egypt, according to a new study.

15. Pathology and transmission
The bubonic plague is an infection of the lymphatic
system, usually resulting from the bite of an infected flea.
The fleas are often found on rodents, such as rats and
mice, and seek out other prey when their rodent hosts die.
Once established, bacteria rapidly spread to the lymph
nodes and multiply. Yersinia pestis can resist phagocytosis
and even reproduce inside phagocytes and kill them. As
the disease progresses, the lymph nodes can hemorrhage
and become necrotic. Bubonic plague can progress to
lethal septicemic plague in some cases. The plague is also
known to spread to the lungs and become the disease
known as the pneumonic plague.

16. Symptoms
The most famous symptom of bubonic plague is swollen
lymph glands, called buboes. These are commonly found in
the armpits, groin or neck. The bubonic plague was the first
step of the ongoing plague. Two other forms of the plague,
pneumonic and septicemic, resulted after a patient with the
bubonic plague developed pneumonia or blood poisoning.
Other symptoms include spots on the skin that are red at
first and then turn black, heavy breathing, continuous blood
vomiting, aching limbs, coughing and terrible pain. The pain
is usually caused by the actual decaying, or decomposing
of the skin while the infected person is still alive. Upon
death, the cadaver will spasm for a period of time.

17. Clinical manifestations
Incubation period is 10 – 14 days, but it may be from 3 till
60 days.
The onset of the disease is an acute, with high temperature
till 40,0 – 41,00
C. The disease is accompanied by chill,
severe headache, pains in the loin, region pains in the
eye’s balls.
In the some cases short prodromal period occurs:
weakness, fatigue, headache, sleeplessness, sometimes
psychic violations.
The next phases are differented in the course of the
disease: initial phase with predominance of general toxic
syndrome; the phase of neurological disorders with
different variants of the lesion of the central nervous
system; the phase of outcomes (recovery or residual
manifestations – pareses, paralyses).

18. Treatment
In modern times, several classes of antibiotics are
effective in treating bubonic plague. These include the
aminoglycosides streptomycin and gentamicin, the
tetracyclines tetracycline and doxycycline and the
fluoroquinolone ciprofloxacin. Patients with plague in the
modern era usually recover completely with prompt
diagnosis and treatment.

19. Pneumonic plague is the
most virulent and least
common form of plague.
Typically, pneumonic form is
due to a secondary spread
from advanced infection of
an initial bubonic form.
Primary pneumonic plague
results from inhalation of
aerosolized infective droplets
and can be transmitted from
human to human without
involvement of fleas or
animals. Untreated
pneumonic plague has a
very high case-fatality ratio.

20. Pathology and transmission
Pneumonic plague can be caused in two ways: primary, which
results from the inhalation of aerosolised plague bacteria, or
secondary, when septicemic plague spreads into lung tissue
from the bloodstream. Pneumonic plague is not vector-borne
like bubonic plague; instead it can be spread from person to
person. There have been cases of pneumonic plague
resulting from the dissection or handling of contaminated
animal tissue. This is one type of the formerly known Black
Plague. It could kill 90%-100% if they coughed and passed on
the bacteria.
Symptoms
The most apparent symptom of pneumonic plague is coughing,
often with hemoptysis.
With pneumonic plague, the first signs of illness are fever,
headache, weakness, and rapidly developing pneumonia with
shortness of breath, chest pain, cough, and sometimes
bloody or watery sputum. The pneumonia progresses for 2 to
4 days and may cause respiratory failure and shock. Without
early treatment, patients will die.

21. Prognosis and treatment
Pneumonic plague is a very aggressive infection requiring
rapid antibiotic treatment within around 24 hours of
infection.
Early treatment of pneumonic plague is essential. To
reduce the chance of death, antibiotics must be given
within 24 hours of first symptoms. Streptomycin,
gentamicin, the tetracyclines, and chloramphenicol are all
effective against pneumonic plague.
Antibiotic treatment for 7 days will protect people who have
had direct, close contact with infected patients. Wearing
a close-fitting surgical mask also protects against
infection.
Without treatment, the mortality rate from pneumonic
plague approaches 100%.

22. Septicaemic plague
The disease can result from bubonic and pneumonic plague.
Lymphatics ultimately drain into the bloodstream, so the plague
bacteria may enter the blood and travel to almost any part of the
body. In septicemic plague, bacterial endotoxins cause
disseminated intravascular coagulation (DIC), causing tiny clots
throughout the body and possibly ischaemic necrosis (tissue
death due to lack of circulation/perfusion to that tissue) from the
clots. DIC results in depletion of the body's clotting resources, so
that it can no longer control bleeding. Consequently, there is
bleeding into the skin and other organs, which can cause red
and/or black patchy rash and hemoptysis/haemoptysis (coughing
up or vomiting of blood). There are bumps on the skin that look
somewhat like insect bites; these are usually red, and
sometimes white in the center.
Untreated, septicemic plague is usually fatal. Early treatment
with antibiotics reduces the mortality rate to between 4 and 15
percent. People who die from this form of plague often die on the
same day symptoms first appear.

23. Other forms
There are a few other rare manifestations of plague,
including asymptomatic plague and abortive plague.
Cellulocutaneous plague sometimes results in infection
of the skin and soft tissue, often around the bite site of a
flea.
Plague meningitis can occur in very rare cases of
septicemic plague.

24. Laboratory testing
Diagnosis and confirmation of plague requires laboratory
testing. Recovery and identification of Y. pestis culture from
a patient sample is optimum for confirmation.
Depending on the presentation of the form on plague:
bubo aspirates, blood, and sputum are the most
appropriate specimens for rapid testing and culture. Serum
taken during the early and late stages of infection can be
examined to confirm infection. Rapid dipstick tests have
been validated for field use to quickly screen for Y. pestis
antigen in patients. Specimens should be collected and
forwarded to laboratories for plague testing.

25. Laboratory Test Criteria for Diagnosis of Plague
SUSPECTED PLAGUE SHOULD BE CONSIDERED IF
THE FOLLOWING CONDITIONS ARE MET:
1. Clinical symptoms that are compatible with plague, i. e.,
fever and lymphadenopathy in a person who resides in
or recently traveled to a plague-endemic area.
2. If small gram-negative and/or bipolar-staining
coccobacilli are seen on a smear taken from affected
tissues, e.g.:
 Bubo (bubonic plague)
 Blood (septicemic plague)
 Tracheal/lung aspirate (pneumonic plague)

26. Laboratory Test Criteria for Diagnosis of Plague
PRESUMPTIVE PLAGUE SHOULD BE CONSIDERED
WHEN ONE OR BOTH OF THE FOLLOWING
CONDITIONS ARE MET:
1. If immunofluorescence stain of smear or material is
positive for the presence of Yersinia pestis F1 antigen.
2. If only a single serum specimen is tested and the anti-
F1 antigen titer by agglutination is >1:10.*
*Agglutination testing must be shown to be specific to Y. pestis F1 antigen by
hemagglutination inhibition.

27. Laboratory Test Criteria for Diagnosis of Plague
CONFIRMED PLAGUE IS DIAGNOSED IF ONE OF THE
FOLLOWING CONDITIONS IS MET:
1. If a culture isolated is lysed by specific bacteriophage.
2. If two serum specimens demonstrate a four fold anti-F1
antigen titer difference by agglutination testing.*
3. If a single serum specimen tested by agglutination has
a titer of >1:128 and the patient has no known previous
plague exposure or vaccination history.*
*Agglutination testing must be shown to be specific to Y. pestis F1 antigen by
hemagglutination inhibition.

28. Vaccination
Plague vaccines at one time were widely used but have
not proven to be an approach that could prevent plague
effectively. Vaccines are not recommended for immediate
protection in outbreak situations. Vaccination is only
recommended as a prophylactic measure for high-risk
groups (e.g. laboratory personnel who are constantly
exposed to the risk of contamination).

29. Surveillance and control
Conduct investigation to identify animals and flea
species that are implicated in the plague enzootic cycle in
the region and develop a programme on environmental
management to limit its potential spread.
Active long-term surveillance of zoonotic foci and rapid
response to reduce exposure during epizootic outbreaks
have been successful in reducing human plague.

30. Prophylactic (preventive) antibiotics: Health
authorities advise that antibiotics be given for a brief
period to people who have been exposed to the bites of
potentially infected rodent fleas (for example, during a
plague outbreak) or who have handled an animal known
to be infected with the plague bacterium. Such experts
also recommend that antibiotics be given if a person has
had close exposure to a person or an animal (for
example, a house cat) with suspected plague
pneumonia.
Persons who must be present in an area where a
plague outbreak is occurring can protect themselves for
2 to 3 weeks by taking antibiotics. The preferred
antibiotics for prophylaxis against plague are the
tetracyclines or the sulfonamides.

31. Viral hemorrhagic feversViral hemorrhagic fevers (VHFs) are caused by viruses
from four distinct families and range in severity from
relatively mild to life-threatening.
These highly infectious viruses lead to a potentially lethal
disease syndrome characterized by fever, malaise,
vomiting, mucosal and gastrointestinal (GI) bleeding,
edema, and hypotension.
The 4 viral families known to cause VHF disease in
humans include the Arenaviridae, Bunyaviridae,
Filoviridae, and Flaviviridae. General characteristics of
these viral families can be found in the table below.

32. Etiologic agents
 The Arenaviridae include the viruses responsible for
Lassa fever and Argentine, Bolivian, and Venezuelan
hemorrhagic fevers.
 The Bunyaviridae include the members of the Hantavirus
genus that cause hemorrhagic fever with renal syndrome
(HFRS), the Crimean-Congo hemorrhagic fever (CCHF)
virus from the Nairovirus genus, and the Rift Valley fever
(RVF) virus from the Phlebovirus genus.
 The Filoviridae include Ebola and Marburg viruses.
 Finally, the Flaviviridae include dengue, yellow fever, and
two viruses in the tick-borne encephalitis group that
cause VHF: Omsk hemorrhagic fever virus and
Kyasanur Forest disease virus. The viral conditions have
also been described by Bryan, and his opinion on the
subject should be considered authoritative.

33. Virus FamilyVirus Family Disease (Virus)Disease (Virus) Natural DistributionNatural Distribution
Usual Source ofUsual Source of
Human InfectionHuman Infection
Incubation (Days)Incubation (Days)
ArenaviridaeArenaviridae
ArenavirusArenavirus Lassa feverLassa fever AfricaAfrica RodentRodent 5-165-16
Argentine HF (Junin)Argentine HF (Junin) South AmericaSouth America RodentRodent 7-147-14
Bolivian HF (Machupo)Bolivian HF (Machupo) South AmericaSouth America RodentRodent 9-159-15
Brazilian HF (Sabia)Brazilian HF (Sabia) South AmericaSouth America RodentRodent 7-147-14
Venezuelan HF (Guanarito)Venezuelan HF (Guanarito) South AmericaSouth America RodentRodent 7-147-14
BunyaviridaeBunyaviridae
PhlebovirusPhlebovirus Rift Valley feverRift Valley fever AfricaAfrica MosquitoMosquito 2-52-5
NairovirusNairovirus Crimean-Congo HFCrimean-Congo HF Europe, Asia, AfricaEurope, Asia, Africa TickTick 3-123-12
HantavirusHantavirus
Hemorrhagic fever with renalHemorrhagic fever with renal
syndrome, hantavirus pulmonarysyndrome, hantavirus pulmonary
syndromesyndrome
Asia, Europe,Asia, Europe,
worldwideworldwide
RodentRodent 9-359-35
FiloviridaeFiloviridae
FilovirusFilovirus Marburg and EbolaMarburg and Ebola AfricaAfrica UnknownUnknown 3-163-16
FlaviviridaeFlaviviridae
FlavivirusFlavivirus Yellow feverYellow fever
Tropical Africa, SouthTropical Africa, South
AmericaAmerica
MosquitoMosquito 3-63-6
Dengue HFDengue HF Asia, Americas, AfricaAsia, Americas, Africa MosquitoMosquito
Unknown for dengueUnknown for dengue
HF, 3-5 for dengueHF, 3-5 for dengue
Viral Families Causing Viral Hemorrhagic FeverViral Families Causing Viral Hemorrhagic Fever

34. Symptoms
The VHF designation includes a broad range of diseases.
Signs and symptoms can vary widely, even among
members of the same viral family. But VHFs do have
some common characteristics, especially in their effects
on your vascular system — the network of arteries, veins
and capillaries that circulates blood throughout your
body.
Hemorrhagic fevers make blood vessels more permeable
— that is, more likely to leak — causing bleeding that
can range from relatively minor to massive. Bleeding
may occur under your skin, in internal organs, and from
your mouth, eyes, ears and rectum. People with severe
bleeding may experience potentially lethal signs and
symptoms such as shock and coma, but rarely die of
blood loss.

35. Symptoms
In general, signs and symptoms of most VHFs begin two
days to two weeks after you've been exposed to the
virus. Typically, VHFs begin with fever and muscle
aches; many cause vomiting and diarrhea; and all create
problems in a number of organ systems, especially your
liver, lymphatic system, lungs and sometimes your
kidneys.
Problems more specific to diseases within each of the four
families of viruses that cause viral hemorrhagic fevers
are listed below.

36. Lassa fever
Lassa fever is an acute viral hemorrhagic fever first described in
1969 in the town of Lassa, in Borno State, Nigeria located in
the Yedseram river valley at the south end of Lake Chad.
Clinical cases of the disease had been known for over a decade
earlier but not connected with this viral pathogen. The
infection is endemic in West African countries, and causes
300-500,000 cases annually with ~5,000 deaths. Outbreaks of
the disease have been observed in Nigeria, Liberia, Sierra
Leone, Guinea, and the Central African Republic, but it is
believed that human infections also exist in Democratic
Republic of the Congo, Mali, and Senegal. Its primary animal
host is the Natal Multimammate Mouse (Mastomys
natalensis), an animal indigenous to most of Sub-Saharan
Africa. Although the rodents are also a source of protein for
peoples of these areas, the virus is probably transmitted by
the contact with the feces and urine of animals accessing
grain stores in residences.

37. Etiology
Lassa fever is caused by the Lassa virus, a
member of the Arenaviridae family; it is an enveloped,
single-stranded, bisegmented RNA virus.
Virus classification
Group: Group V ((-)ssRNA)
Family: Arenaviridae
Genus: Arenavirus
Species: Lassa virus

38. Epidemiology
Lassa virus is zoonotic (transmitted from
animals), in that it spreads to man from rodents,
specifically multimammate rats (Mastomys
natalensis). This is probably the most common
rodent in equatorial Africa, ubiquitous in human
households and eaten as a delicacy in some
areas. In these rats infection is in a persistent
asymptomatic state.
The virus is shed in their excreta (urine and
feces), which can be aerosolized. In fatal cases,
Lassa fever is characterized by impaired or
delayed cellular immunity leading to fulminant
viremia.

39. Epidemiology
Infection in humans typically occurs via
exposure to animal excrement through the
respiratory or gastrointestinal tracts. Inhalation of
tiny particles of infective material (aerosol) is
believed to be the most significant means of
exposure. It is possible to acquire the infection
through broken skin or mucous membranes that
are directly exposed to infective material.
Transmission from person to person has also
been established, presenting a disease risk for
healthcare workers. Frequency of transmission via
sexual contact has not been established.

40. Symptoms
In 80% of cases the disease is inapparent, but in
the remaining 20% it takes a complicated course. It is
estimated that the virus is responsible for about 5,000
deaths annually. The fever accounts for up to ⅓ of
deaths in hospitals within the affected regions and 10
to 16% of total cases.
After an incubation period of six to twenty-one
days, an acute illness with multiorgan involvement
develops. Non-specific symptoms include fever, facial
swelling, and muscle fatigue, as well as conjunctivitis
and mucosal bleeding.

41. Gastrointestinal tract
o Nausea
o Vomiting (bloody)
o Diarrhea (bloody)
o Stomach ache
o Constipation
o Dysphagia (difficulty
swallowing)
o Hepatitis
Cardiovascular system
o Pericarditis
o Hypertension
o Hypotension
o Tachycardia
(abnormally high heart
rate)
The other symptoms arising from the affected organs are:
Symptoms

42. Nervous system
o Encephalitis
o Meningitis
o Unilateral or bilateral
hearing deficit
o Seizures
Respiratory tract
o Cough
o Chest pain
o Dyspnoea
o Pharyngitis
o Pleuritis
The other symptoms arising from the affected organs are:
Symptoms
Clinically, Lassa fever infections are difficult to distinguish
from other viral hemorrhagic fevers such as Ebola and
Marburg, and from more common febrile illnesses such as
malaria.
The virus is excreted in urine for three to nine weeks and in
semen for three months.

43. Diagnosis
There is a range of laboratory investigations
that are performed to diagnose the disease and
assess its course and complications. ELISA test
for antigen and IgM antibodies gives 88%
sensitivity and 90% specificity for the presence of
the infection. Other laboratory findings in Lassa
fever include lymphopenia (low white blood cell
count), thrombocytopenia (low platelets), and
elevated aspartate aminotransferase (AST) levels
in the blood.

44. Treatment
All persons suspected of Lassa fever infection should
be admitted to isolation facilities and their body fluids and
excreta properly disposed of.
Early and aggressive treatment using Ribavirin was
pioneered by Joe McCormick in 1979. After extensive
testing, it was determined that early administration is critical
to success. Additionally, Ribavirin is almost twice as
effective when given intravenously as when taken by
mouth. Ribavirin is a prodrug which appears to interfere
with viral replication by inhibiting RNA-dependent nucleic
acid synthesis, although the precise mechanism of action is
disputed. The drug is relatively inexpensive, but the cost of
the drug is still very high for many of those in poverty-
stricken West African states. Fluid replacement, blood
transfusion and fighting hypotension are usually required.
Intravenous interferon therapy has also been used.

45. Treatment
When Lassa fever infects pregnant women late in their
third trimester, it is necessary to abort the pregnancy for
the mother to have a good chance of survival. This is
because the virus has an affinity for the placenta and other
highly vascular tissues. The fetus has only a one in ten
chance of survival no matter what course of action is taken;
hence focus is always on saving the life of the mother.
Following abortion, women should receive the same
treatment as other Lassa fever patients.

46. Prevention
Control of the Mastomys rodent population is impractical, so
measures are limited to keeping rodents out of homes and food
supplies, as well as maintaining effective personal hygiene.
Gloves, masks, laboratory coats, and goggles are advised while
in contact with an infected person.
No vaccine against Lassa fever is currently available,
though development is underway. The Mozambique virus closely
resembles Lassa fever, while lacking its deadly effects. This
virus is being considered for possible use as a vaccine.
Researchers at the USAMRIID facility, where military
biologists study infectious diseases, have a promising vaccine
candidate. They have developed a replication-competent
vaccine against Lassa virus based on recombinant vesicular
stomatitis virus vectors expressing the Lassa virus glycoprotein.
After a single intramuscular injection, test primates have
survived lethal challenge, while showing no clinical symptoms.

47. Prognosis
About 15%-20% of hospitalized Lassa fever patients
will die from the illness. It is estimated that the
overall mortality rate is 1%, however during
epidemics mortality can climb as high as 50%. The
mortality rate is greater than 80% when it occurs in
pregnant women during their third trimester; fetal
death also occurs in nearly all those cases. Abortion
decreases the risk of death to the mother.
Thanks to treatment with Ribavirin, fatality rates are
continuing to decline. Work on a vaccine is
continuing, with multiple approaches showing
positive results in animal trials.

48. Hemorrhagic fever with renal syndrome
The disease associated with Hantaan virus is called
hemorrhagic fever with renal syndrome (HFRS), a term
that is accepted by the World Health Organization. It was
formerly called Korean hemorrhagic fever (a term that is
no longer in use).
Hantaviruses belong to the
Bunyaviridae family of viruses.
The name hantavirus is derived
from the Hantan River, where
the Hantaan virus (the etiologic
agent of Korean hemorrhagic
fever) was first isolated by Dr.
Ho-Wang Lee and colleagues.

49. Epidemiology
The cotton rat
Sigmodon hispidus is a
hantavirus carrier that
becomes a threat when
it enters human
habitation in rural and
suburban areas.
Regions especially affected by HFRS include China,
the Korean Peninsula, Russia (Hantaan, Puumala and
Seoul viruses), and northern and western Europe
(Puumala and Dobrava virus).

50. Epidemiology
Regions with the highest incidences of HCPS include
Patagonian Argentina, Chile, Brazil, the United States,
Canada, and Panama, where a milder form of disease that
spares the heart has been recognized. The two agents of
HCPS in South America are Andes virus (also called Oran,
Castelo de Sonhos, Lechiguanas, Juquitiba, Araraquara, and
Bermejo viruses, among many other synonyms), which is the
only hantavirus that has shown (albeit uncommonly) an
interpersonal form of transmission, and Laguna Negra virus,
an extremely close relative of the previously-known Rio
Mamore virus. In the U.S., minor cases of HCPS include New
York virus, Bayou virus, and possibly Black Creek Canal
virus.

51. Symptoms
Renal syndrome
Hantavirus has an incubation time of 2–4 weeks in humans,
before symptoms of infection occur. These symptoms can be
split into five phases:
Febrile phase: Symptoms include fever, chills, malaise,
headaches, nausea, abdominal and back pain, respiratory
problems such as the ones common in the influenza virus, as
well as gastro-intestinal problems. These symptoms normally
occur for 3–7 days.
Hypotensive phase: This occurs when the blood platelet levels
drop and symptoms can lead to tachycardia and hypoxemia.
This phase can last for 2 days.
Oliguric phase: This phase lasts for 3–7 days and is
characterised by the onset of renal failure and proteinuria
occurs.
Diuretic phase: This is characterized by diuresis of 3–6L per
day, which can last for a couple of days up to weeks.
Convalescent phase: This is normally when recovery occurs
and symptoms begin to improve.

52. Symptoms
Hantavirus (cardio-)pulmonary syndrome
Hantavirus pulmonary syndrome (HPS) is a deadly disease
transmitted by infected rodents through urine, droppings,
or saliva. Humans can contract the disease when they
breathe in aerosolized virus. HPS was first recognized in
1993 and has since been identified throughout the
United States. Although rare, HPS is potentially deadly.
Rodent control in and around the home remains the
primary strategy for preventing hantavirus infection.
These symptoms, which are very similar to HFRS, include
tachycardia and tachypnea. Such conditions can lead to
a cardiopulmonary phase, where cardiovascular shock
can occur, and hospitalization of the patient is required.

53. Diagnosis
Blood tests are the main method for diagnosing.
These are laboratory tests that analyze samples of
your blood for the presence of certain antibodies that
your body produces as a defense against disease-
causing agents (pathogens). For people with
hantavirus infection, antibodies of the IgM and IgG
classes are nearly always present in the blood by the
time signs and symptoms appear.

54. Treatment
Supportive therapy is the mainstay of care for
patients with hantavirus infections. Care includes
careful management of the patient’s fluid
(hydration) and electrolyte (e.g., sodium,
potassium, chloride) levels, maintenance of correct
oxygen and blood pressure levels, and appropriate
treatment of any secondary infections. Dialysis
may be required to correct severe fluid overload.
Intravenous ribavirin, an antiviral drug, has been
shown to decrease illness and death associated
with HFRS.

55. Prevention
Minimize or eliminate contact with rodents to help prevent
exposure to the hantavirus. Although only certain rodent species
are known to carry hantavirus, it's best to minimize contact with
all rodents, because others may carry pathogens that cause
various illnesses.
Take these steps to help prevent hantavirus infection:
Keep dwellings clean and rodent-free.
Avoid contact with all rodents — including urban rats —
and their droppings.
Disinfect dead rodents before handling and disposing of
them.
Neutralize rodent droppings or urine with household
disinfectants before sweeping or vacuuming.
Take special precautions, such as wearing a respirator,
when cleaning buildings with heavy rodent infestations.

56. Ebola and Marburg haemorrhagic fever
Ebola virus and Marburg virus are
related viruses that cause severe, often
fatal, disease. Ebola virus and Marburg
virus originate primarily in the tropical
forests of Africa and cause hemorrhagic
fevers that can lead to extensive bleeding
(hemorrhage), organ failure and shock.
Ebola virus and Marburg virus initially
move from animals to humans, then can
spread from person to person through
direct contact with blood and other body
fluids.An electron micrograph
of an Ebola virus

57. Epidemiology
In 1967, isolated cases of hemorrhagic fever
occurred among laboratory workers handling tissues
from African green monkeys (Cercopithecus aethiops)
from Uganda and in medical personnel who attended
the laboratory workers. This was a new virus named
Marburg virus after the city in Germany where it was
first characterized. In 1976, epidemics of severe
haemorrhagic fever occurred simultaneously in Zaire
and Sudan and a new filovirus was identified,
serologically different from the Marburg virus. This
new virus, Ebola, was named after a small river in
Democratic Republic of Congo. Later studies clarified
the specific nature of these viruses and defined a
separate family, the Filoviridae.

58. Epidemiology
Multiple outbreaks of both Ebola and Marburg
have been identified since their initial discovery.
The most recent outbreaks of Ebola virus were in
2007 in the Democratic Republic of Congo with
372 cases, which of 166 (45%) were fatal and in
2008 in Uganda where there were three cases
detected among mine workers from Kakasi Forest
Reserve in Kamwenge District. The most recent
outbreaks of Marburg virus were in 2004-2005 in
Angola when there were 252 cases, of which 227
(90%) were fatal and in Uganda in 2007 when two
mine co-workers were infected, one died.

59. Epidemiology
The natural reservoir for both diseases is unknown although
it is presumed there is an animal reservoir. Ebola virus has been
isolated from cynomolgus monkeys and Marburg from green
monkeys and bats.
Transmission modes
Ebola and Marburg viruses are highly transmissible by
direct contact with blood, secretions, organs or other body fluids
of dead or living infected persons.
Sexual contact transmission can occur up to 7 weeks after
clinical recovery.
Transmission can also occur by contact with dead or living
infected animals (e.g., monkeys, chimpanzees, forest antelopes,
and bats).
Nosocomial transmission can occur. Health care workers
can be infected through close contact with infected patients. The
risk for infection can be significantly reduced through the
appropriate use of infection control precautions and adequate
barrier procedures. This is especially important when performing
invasive procedures.

60. Clinical presentation
The typical incubation period for these viruses is from 2 to
21 days. In most cases, an infected patient experiences sudden
onset of fever, malaise (weakness), muscle and joint pains and
headache followed by progressive weakness, anorexia (lack of
appetite), diarrhoea (watery stools sometimes containing blood
and mucus), nausea and vomiting. Some patients progress to
develop impaired kidney and liver function, and haemorrhagic
symptoms. These manifest by bleeding from the nose, gums and
skin (like bruising), bloody vomiting and stools, and prolonged
bleeding from needle puncture sites. Other symptoms include
skin rash, conjunctival injection, inflamed throat and difficulty
swallowing.
Depending on the filovirus and subtypes, risk of death
ranges from 30% to 90%.

61. Tests and diagnosis
Ebola and Marburg hemorrhagic fevers are hard to diagnose
initially because many of the early signs and symptoms
resemble those of other infectious diseases, such as typhoid or
malaria. But if doctors believe that someone may have been
exposed to Ebola or Marburg, they can use specialized
laboratory tests to identify the viruses within a few days.
Most people with Ebola or Marburg fever have high
concentrations of the virus in their blood. Blood tests known as
ELISA (enzyme-linked immunosorbent assay) and reverse
transcriptase polymerase chain reaction (PCR) can detect
antibodies to or specific genes of the viruses. Testing blood or
tissue samples poses a high risk and must be done under
controlled conditions at a "biosafety level 4" lab. Newer
diagnostic techniques include testing saliva and urine samples or
testing samples in which the virus has been inactivated.

62. Complications
Both Ebola and Marburg hemorrhagic fevers lead to death
for a high percentage of people affected. As the illness
progresses, it can cause organ failure, severe bleeding,
jaundice, delirium, seizures, coma and shock. Death often
occurs less than 10 days from the start of signs and symptoms.
The fatality rate for Ebola fever ranges from 50 percent to 90
percent. In most Marburg outbreaks, about 25 percent of people
who got it died. But the fatality rate reached nearly 90 percent in
recent large outbreaks in Angola and the Democratic Republic of
Congo. One reason the viruses are so deadly is that they
hamper the immune system's ability to mount a defense. But
scientists don't understand why some people recover from Ebola
and Marburg and others don't.
For people who survive, recovery is slow. It may take
months to regain weight and strength. Studies show that the
viruses remain in the body for many weeks after the illness.
Survivors may experience hair loss, sensory changes, eye
problems, liver inflammation (hepatitis), weakness, fatigue,
headaches and testicular inflammation.

63. Treatments and drugs
No antiviral medications have proved effective in
treating Ebola virus or Marburg virus infection. As a
result, treatment consists of supportive care in a
hospital. This includes providing fluids, maintaining
adequate blood pressure, replacing blood loss and
treating any other infections that develop. Some
people receive transfusions of plasma to replace blood
proteins that improve clotting.
Public health officials urge hospitals to keep
people with Ebola or Marburg hemorrhagic fever
isolated from others. Health care workers should follow
strict infection-control precautions.

64. Prevention
Prevention efforts focus on avoiding contact with the viruses.
The following precautions can help prevent infection and
spread of Ebola and Marburg.
 Don't travel to areas of known outbreaks. Before traveling
to Africa, find out about any current epidemics. To date,
human cases of Ebola and Marburg have occurred in
Democratic Republic of Congo, Angola, Uganda, Sudan and
Gabon. One case of Ebola was reported in Cote d'Ivoire and
one in Liberia. Two cases of Marburg occurred in Kenya (in
people who had visited Kitum Cave in Mount Elgon National
Park). Another person may have acquired the Marburg virus
in Zimbabwe.
 Avoid all contact with dead primates in areas where
infections have occurred. To meet the demand for exotic
meats and "bush meat," some hunters enter remote forests
and kill monkeys, chimpanzees and other primates. The
hunters sometimes scavenge dead chimpanzees.

65. Prevention
 Avoid close physical contact with someone infected with
Ebola or Marburg. In particular, caregivers should avoid
contact with the person's body fluids and tissues, including
blood, semen, vaginal secretions and saliva.
 Health care workers should follow strict infection-control
procedures. This includes wearing protective clothing, such
as gloves, masks, gowns and leg and shoe coverings; and
properly using, disinfecting and disposing of needles and
other instruments. Injection needles and syringes should not
be reused.
 Don't handle the remains of anyone suspected of dying of
Ebola or Marburg fever. Specially organized and trained
teams should bury the remains using appropriate safety
equipment.

66. Vaccine development
Although no vaccines are available yet to prevent
Ebola or Marburg diseases, several are in
development. Recently the first clinical trial of a
human DNA vaccine for Ebola virus showed that it
was safe and produced an immune system
response. This vaccine uses genetically engineered
portions of the virus's DNA — proteins designed to
trigger an immune system response to Ebola.
Potential vaccines for Marburg virus have proved
effective in nonhuman primates. Further studies are
under way.

67. Dengue fever
Dengue fever and
dengue hemorrhagic
fever (DHF) are acute
febrile diseases, found in
the tropics and Africa, and
caused by four closely
related virus serotypes of
the genus Flavivirus,
family Flaviviridae. It is
also known as
breakbone fever.
Dengue virus
A TEM micrograph showing Dengue virus
virions (the cluster of dark dots near the center).

68. Epidemiology
The geographical spread includes northern Australia,
Singapore, Malaysia, Taiwan, Thailand, Vietnam, Indonesia,
Honduras, Costa Rica, Philippines, Pakistan, India,
Bangladesh, Puerto Rico, Bolivia, Brazil, Guyana, Venezuela,
Barbados, Trinidad and Samoa. Unlike malaria, dengue is just
as prevalent in the urban districts of its range as in rural
areas. Each serotype is sufficiently different that there is no
cross-protection and epidemics caused by multiple serotypes
(hyperendemicity) can occur. Dengue is transmitted to
humans by the Aedes aegypti or more rarely the Aedes
albopictus mosquito, which feed during the day.
The WHO says some 2.5 billion people, two fifths of the
world's population, are now at risk from dengue and estimates
that there may be 50 million cases of dengue infection
worldwide every year. The disease is now epidemic in more
than 100 countries.

69. Epidemiology
Worldwide dengue distribution, 2006.
Red: Epidemic dengue. Blue: Aedes aegypti.

70. Signs and symptoms
The disease manifests as a sudden onset of severe
headache, muscle and joint pains (myalgias and arthralgias—
severe pain that gives it the nick-name break-bone fever or
bonecrusher disease), fever, and rash. The dengue rash is
characteristically bright red petechiae and usually appears first
on the lower limbs and the chest; in some patients, it spreads to
cover most of the body. There may also be gastritis with some
combination of associated abdominal pain, nausea, vomiting, or
diarrhea.
Some cases develop much milder symptoms which can be
misdiagnosed as influenza or other viral infection when no rash
is present. Thus travelers from tropical areas may pass on
dengue in their home countries inadvertently, having not been
properly diagnosed at the height of their illness. Patients with
dengue can pass on the infection only through mosquitoes or
blood products and only while they are still febrile.

71. Signs and symptoms
The classic dengue fever lasts about six to seven days, with
a smaller peak of fever at the trailing end of the disease (the so-
called biphasic pattern). Clinically, the platelet count will drop
until the patient's temperature is normal.
Cases of DHF also show higher fever, variable
haemorrhagic phenomena, thrombocytopenia, and
haemoconcentration. A small proportion of cases lead to dengue
shock syndrome (DSS) which has a high mortality rate.
DHF combined with a cirrhotic liver has been suspected in
rapid development of Hepatocellular Carcinoma. Given the DEN
virus is related to the Hepatitis C virus this is an avenue for
further research as HCC is among the top five leading cancerous
causes of death outside of Europe and North America. Normally
HCC does not occur in a cirrhotic liver for ten or more years after
the cessation of the poisoning agent. DHF patients can develop
HCC within one year of cessation of abuse.

72. Diagnosis
The diagnosis of dengue is usually made clinically. The classic
picture is high fever with no localising source of infection, a
petechial rash with thrombocytopenia and relative
leukopenia - low platelet and white blood cell count. Care
has to be taken as diagnosis of DHF can mask end stage
liver disease and vice versa.
1. Fever, bladder problem, constant headaches, severe
dizziness and loss of appetite.
2. Hemorrhagic tendency (positive tourniquet test,
spontaneous bruising, bleeding from mucosa, gingiva,
injection sites, etc.; vomiting blood, or bloody diarrhea)
3. Thrombocytopenia (<100,000 platelets per mm³ or
estimated as less than 3 platelets per high power field)
4. Evidence of plasma leakage (hematocrit more than 20%
higher than expected, or drop in haematocrit of 20% or more
from baseline following IV fluid, pleural effusion, ascites,
hypoproteinemia)
5. Encephalitic occurrences.

73. Diagnosis
Dengue shock syndrome is defined as dengue hemorrhagic
fever plus:
 Weak rapid pulse,
 Narrow pulse pressure (less than 20 mm Hg)
 Cold, clammy skin and restlessness.
Serology and polymerase chain reaction (PCR) studies are
available to confirm the diagnosis of dengue if clinically
indicated.

74. Treatment
The mainstay of treatment is timely supportive therapy
to tackle shock due to haemoconcentration and bleeding.
Close monitoring of vital signs in critical period (between
day 2 to day 7 of fever) is vital. Increased oral fluid intake is
recommended to prevent dehydration. Supplementation
with intravenous fluids may be necessary to prevent
dehydration and significant concentration of the blood if the
patient is unable to maintain oral intake. A platelet
transfusion is indicated in rare cases if the platelet level
drops significantly (below 20,000) or if there is significant
bleeding. The presence of melena may indicate internal
gastrointestinal bleeding requiring platelet and/or red blood
cell transfusion.
Aspirin and non-steroidal anti-inflammatory drugs
should be avoided as these drugs may worsen the bleeding
tendency associated with some of these infections.
Patients may receive paracetamol preparations to deal with
these symptoms if dengue is suspected.

75. Prevention. Vaccine development
There is no commercially available vaccine for the
dengue flavivirus. However, one of the many ongoing
vaccine development programs is the Pediatric Dengue
Vaccine Initiative which was set up in 2003 with the aim of
accelerating the development and introduction of dengue
vaccine(s) that are affordable and accessible to poor
children in endemic countries. Thai researchers are testing
a dengue fever vaccine on 3,000–5,000 human volunteers
after having successfully conducted tests on animals and a
small group of human volunteers. A number of other
vaccine candidates are entering phase I or II testing.

76. Prevention. Mosquito control
Primary prevention of dengue mainly resides in
mosquito control. There are two primary methods: larval
control and adult mosquito control. In urban areas, Aedes
mosquitos breed on water collections in artificial containers
such as plastic cups, used tires, broken bottles, flower pots,
etc. Periodic draining or removal of artificial containers is
the most effective way of reducing the breeding grounds for
mosquitos. Larvicide treatment is another effective way to
control the vector larvae but the larvicide chosen should be
long-lasting and preferably have World Health Organization
clearance for use in drinking water. There are some very
effective insect growth regulators (IGRs) available which
are both safe and long-lasting (e.g. pyriproxyfen). For
reducing the adult mosquito load, fogging with insecticide is
somewhat effective.

77. Yellow fever
Yellow fever (also called
yellow jack, or sometimes
black vomit or American
Plague) is an acute viral
disease. It is an important
cause of hemorrhagic illness in
many African and South
American countries despite
existence of an effective
vaccine. The yellow refers to
the jaundice symptoms that
affect some patients.TEM micrograph: Multiple yellow fever
virions (234,000x magnification).

78. Yellow fever has been a source of several devastating
epidemics. Yellow fever epidemics broke out in the 1700s in
Italy, France, Spain, and England. 300,000 people are believed
to have died from yellow fever in Spain during the 19th century.
French soldiers were attacked by yellow fever during the 1802
Haitian Revolution; more than half of the army perished from the
disease. Outbreaks followed by thousands of deaths occurred
periodically in other Western Hemisphere locations until
research, which included human volunteers (some of whom
died), led to an understanding of the method of transmission to
humans (primarily by mosquitos) and development of a vaccine
and other preventive efforts in the early 20th century.
Despite the breakthrough research of Cuban physician
Carlos Finlay, American physician Walter Reed, and many
others over 100 years ago, unvaccinated populations in many
developing nations in Africa and Central/South America continue
to be at risk. As of 2001, the WHO estimates that yellow fever
causes 200,000 illnesses and 30,000 deaths every year in
unvaccinated populations.
Epidemiology

79. Endemic range of yellow fever (2005)

80. Etiology. Clinical simptoms.
Yellow fever is caused by a flavivirus of the family
Flaviviridae, a positive sense single-stranded RNA virus.
Human infection begins after deposition of viral particles
through the skin in infected arthropod saliva, hence it is
considered an arbovirus. The mosquitos involved are
Aedes simpsaloni, A. africanus, and A. aegypti in Africa,
the Haemagogus genus in South America, and the
Sabethes genus in France. Yellow fever is frequently
severe but moderate cases may occur as the result of
previous infection by another flavivirus. After infection the
virus first replicates locally, followed by transportation to
the rest of the body via the lymphatic system. Following
systemic lymphatic infection 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.
Necrotic masses (Councilman bodies) appear in the
cytoplasm of hepatocytes.

81. Yellow fever begins suddenly after an incubation
period of three to five days in the human body. In mild
cases only fever and headache may be present.
Within 24 hours about 15% develop a more severe
form, in which they enter the "toxic phase"
characterized by fever, chills, bleeding into the skin,
paradoxically slow heartbeat, headache, back pains,
and extreme prostration. Nausea, vomiting, and
constipation are common. Jaundice usually appears
on the second or third day. After the third day the
symptoms recede, only to return with increased
severity in the final stage, during which there is a
marked tendency to hemorrhage internally; the
characteristic “coffee ground” vomitus contains blood.
The patient then lapses into delirium and coma,
followed by death in about 50% of those who enter the
toxic phase.

82. During epidemics a much higher proportion have
entered the toxic phase, and the fatality rate has been
as high as 85%. Although the disease still occurs, it is
usually confined to sporadic outbreaks.
There is a difference between disease outbreaks in
rural or forest areas and in towns. Disease outbreaks
in towns and non-native people may be more serious
because of higher densities of mosquito vectors and
higher population densities.

83. Treatment
There is no true cure for yellow fever, therefore
vaccination is important. Treatment is
symptomatic and supportive only. Fluid
replacement, fighting hypotension and
transfusion of blood derivates is generally
needed only in severe cases. In cases that
result in acute renal failure, dialysis may be
necessary.

84. Prevention
In 1937, Max Theiler, working at the Rockefeller
Foundation, developed a safe and highly efficacious
vaccine for yellow fever that gives a ten-year or more
immunity from the virus.