Arenaviridae: Third Year Notes DR Sulaiman Conteh

ARENAVIRIDAE
THIRD YEAR NOTES

Dr Sulaiman Conteh
02/15/22 Pharm K. 1
Properties
• An arenavirus is a negative-sense, single-
stranded RNA virus that is a member of
the family Arenaviridae.
• These viruses infect rodents and
occasionally humans; arenaviruses have
also been discovered which infect snakes.
• At least eight arenaviruses are known to
cause human disease.
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Diseases Caused by
Arenaviruses
• Aseptic meningitis, a severe human disease
that causes inflammation covering the brain
and spinal cord, can arise from the
lymphocytic choriomeningitis virus.
• Hemorrhagic fever syndromes, including
Lassa fever, are derived from infections such
as Guanarito virus, Junin virus, Lassa virus,
Lujo virus,[2] Machupo virus, Sabia virus, or
Whitewater Arroyo virus.
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LASSER FEVER
THIRD YEAR NOTES

Dr Sulaiman Conteh
02/15/22 Pharm K. 4
Introduction
• Lassa viral haemorrhagic fever is an acute illness of 1-4
weeks duration that occurs in West Africa.
• Though first described in the 1950s, the virus causing
the disease was not identified until 1969.
• Lassa fever is caused by the Lassa virus, a member of
the Arenaviridae family; it is an enveloped, single-
stranded, bisegmented RNA virus(+ and - ve)
• Lassa fever is known to be endemic in Guinea
(Conakry), Liberia, Sierra Leone and parts of Nigeria, but
probably exists in other West African countries as well.
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Transmission
• Humans usually become infected with Lassa virus from
exposure to excreta of infected Mastomys natalensis
(multimammate rat).
• Both direct exposure, (touching the excreta) and Lassa
virus may also be spread between humans through
direct contact with the blood, urine, faeces, or other
bodily secretions of a person with Lassa fever.
• There is no epidemiological evidence supporting
airborne spread between humans.
• Person-to-person transmission occurs in both community
and health care settings, where the virus may be spread
by contaminated medical equipment, such as re-used
needles.
• Sexual transmission of Lassa virus has been reported.
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Prevalence
The dissemination of the infection can be assessed by prevalence of
antibodies to the virus in populations of:
• Sierra Leone 8–52%
• Guinea 4–55%
• Nigeria approx. 21%
Some studies indicate that 300 000 to 500 000 cases of Lassa fever
and 5000 deaths occur yearly across West Africa. The overall case-
fatality rate is 1%, up to 15% among hospitalized patients.
Death usually occurs within 14 days of onset in fatal cases.
The disease is especially severe late in pregnancy, with maternal
death and/or fetal loss occurring in greater than 80% of cases
during the third trimester.
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Pathogenesis
• The Lassa virus gains entry into the host
cell by means of the cell-surface receptor
the alpha-dystroglycan (alpha-DG).
• Lassa virus will infect almost every tissue
in the human body. It starts with the
mucosa, intestine, lungs and urinary
system, and then progresses to the
vascular system.
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Signs and Symptoms
• About 80% of human infections are asymptomatic; the remaining
cases have severe multi-system disease, where the virus affects
several organs in the body, such as the liver, spleen and kidneys.
• The incubation period of Lassa fever ranges from 6-21 days. The
onset of the disease is usually gradual, starting with fever, general
weakness, and malaise.
• After a few days, headache, sore throat, muscle pain, chest pain,
nausea, vomiting, diarrhoea, cough, and abdominal may follow.
Severe cases may progress to show facial swelling, fluid in the lung
cavity, bleeding from mouth, nose, vagina or gastrointestinal tract,
and low blood pressure. Protein may be noted in the urine. Shock,
seizures, tremor, disorientation, and coma may be seen in the late
stages.
• Deafness occurs in 25% of patients of whom half recover some
function after 1-3 months. Transient hair loss and gait disturbance
may occur during recovery.
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Diagnosis
• Lassa fever is diagnosed by detection of
Lassa antigen, anti-Lassa antibodies, or
virus isolation techniques.
• 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.
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Treatment
• The antiviral drug ribavirin is effective
treatment for Lassa fever if given early on
in the course of clinical illness.
• There is no evidence to support the role of
ribavirin as post-exposure prophylactic
treatment for Lassa fever.
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Prevention
• community hygiene
• Infection control for health workers and
exposure community members
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Lymphocytic choriomeningitis
• It is a rodent-borne viral infectious disease
that presents as aseptic meningitis,
encephalitis or meningoencephalitis.
• Its causative agent is lymphocytic
choriomeningitis
mammarenavirus (LCMV), a member of
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Virology
• LCMV Armstrong-Acute infection
• LCMV Clone 13-Chronic infection
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Signs and symptoms
Congenital infection:
•For immunocompetent mothers, there is no
significant threat, but the virus has damaging
effects upon the fetus. If infection occurs during
the first trimester, LCMV results in an increased
risk of spontaneous abortion.
•Later congenital infection :malformations such
as intracranial calcifications, hydrocephalus,
microcephaly or macrocephaly, intellectual
disabilities, and seizures.
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Other congenital presentations
• chorioretinal scars, and optic atrophy.
• Mortality among infants is approximately
30%.
• Among the survivors, two thirds have
lasting neurologic abnormalities
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Organ donation
• Patients infected in solid organ transplants have
developed a severe fatal illness, starting within
weeks of the transplant.
• The initial symptoms included fever, lethargy,
anorexia and leukopenia, and quickly progressed
to multisystem organ failure, hepatic insufficiency
or severe hepatitis, dysfunction of the transplanted
organ, coagulopathy, hypoxia, multiple
bacteremias and shock.
• Localized rash and diarrhea were also seen in
some patients. Nearly all cases have been fatal.
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Diagnosis
• Clinical diagnosis:
History of prodrome symptoms and by
considering the period of time before the
onset of meningitis symptoms, typically
15–21 days for LCM
• Pathological:
Immunofluorescent antibody (IFA) test or an
enzyme immunoassay to detect specific
antibody in blood or cerebrospinal fluid
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Pathological diagnosis Cont:
• reverse transcription polymerase chain
reaction (RT-PCR) tests which may detect
nucleic acids in the blood and cerebrospinal
fluid.(CSF)
• LCMV can be grown in a variety of cell lines
including BHK21, L and Vero cells, and it
may be identified with immuno-fluorescence.
• A diagnosis can also be made by the
intracerebral inoculation of blood or CSF into
mice.
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Prevention
• Several measures can be taken to prevent
exposure to LCM from wild rodents in the home.
• A checklist of precautions is provided by the CDC,
providing tips for sealing the home to keep rodents
out, using traps to eliminate existing rodents, and
maintaining a clean, healthy home.
• Products include devices that emit ultrasonic
sound that allegedly irritates mice and drives them
away, and more swift, painless means of death
such as mini electrocution or gas chambers.
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Treatment
• Treatment is symptomatic and supportive. Children
with hydrocephalus often need a ventriculoperitoneal
shunt.
• ribavirin is used in some cases due to the inhibitory
effect the agent has in vitro on arenaviruses.
• Early and intravenous ribavirin treatment is required
for maximal efficacy, and it can produce considerable
side effects.
• Use of ribavirin during pregnancy is generally not
recommended, as some studies indicate the possibility
of teratogenic effects.
• mortality is less than one percent.
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CALICIVIRIDAE
NORWALK(NOROVIRUS)
Third Year
Dr Sulaiman Conteh
02/15/22 Pharm K. 22
Properties
• Norovirus (formerly Norwalk agent) is a
single-stranded RNA, nonenveloped viruses (
Caliciviridae) that causes approximately 90%
of epidemic nonbacterial outbreaks of
gastroenteritis around the world.
• Norovirus is rapidly inactivated by either
sufficient heating or by chlorine-based
disinfectants, but the virus is less susceptible
to alcohols and detergents, as it does not have
a lipid envelope.
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Properties Cont:
• After infection, immunity to norovirus is usually
incomplete and temporary.
• There is an inherited predisposition to infection, and
individuals with blood type AB are more often
infected, while blood types O and AB can confer
partial protection against symptomatic infection.
• A single nucleotide mutation (G428A) in the
fucosyltransferase gene on chromosome 19 provides
strong protection from infection in 20% of the white
population.
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Transmission
• The viruses are transmitted by three modes:
1. fecally contaminated food or water:Shellfish
and salad ingredients are the foods most
often implicated in norovirus outbreaks
2. person-to-person contact, and via
aerosolization of the virus and
3. contamination of surfaces.
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Pathophysiology
• When a person becomes infected with
norovirus, the virus begins to multiply within
the small intestine.
• After approximately one to two days,
norovirus symptoms can appear.
• The principal symptom is acute gastroenteritis
that develops between 24 and 48 hours after
exposure, and lasts for 24–60 hours.
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Pathophysiology Cont:
• The disease is usually self-limiting, and characterized
by nausea, forceful vomiting, watery diarrhea, and
abdominal pain, and in some cases, loss of taste.
General lethargy, weakness, muscle aches, headache,
coughs, and low-grade fever may occur.
• Severe illness is rare but can occur in the very young,
elderly, and persons with weakened immune
systems.
• Symptoms may become life-threatening in these
groups if dehydration is ignored or not treated.
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Diagnosis
• Specific diagnosis of norovirus is routinely
made by polymerase chain reaction (PCR)
assays or real-time PCR assays, which give
results within a few hours.
• ELISA that use antibodies against a mixture of
norovirus strains are available commercially,
but lack specificity and sensitivity.
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Prevention
• Hand washing is an effective method to
reduce the spread of norovirus pathogens.
• Detection in foods: Routine protocols to
detect norovirus (norovirus RNA) in clams and
oysters by reverse transcription polymerase
chain reaction can be done.
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02/15/22
Dr Conteh
DEPARTMENT OF MEDICAL
MICROBIOLOGY
COMAHS
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PHARM K.
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OUTLINE
 Introduction
 Replication
 Transmission and Epidemiology
 Pathogenesis and Immunity
 Clinical features
 Laboratory
 prevention
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PHARM K.
02/15/22
INTRODUCTIO
• Dengue is, at present, the most important arboviral

cause of death and disease in man (Gubler and
CostaValez, 1991).
• The infection has spread widely from south-east

Asia to the Americas, the Pacific and Africa.
• In all major tropical areas of the world the incidence

of DF, DHF and DSS has increased dramatically
over the past few years.
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PHARM K.
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INTR.
Important properties
•The dengue viruses form a subgroup of the genus
Flavivirus.
•Its genome and capsid is typical of the genus flavirus.
•extensive cross-reactivity is seen with HI-test. This

Makes it difficult to distinguish bwt. Dengue virus and
many other members of flavivirus.
•However, NT- serologic test has helped in identifying

dengue virus as a distinct antigenic
33 subgroup.
PHARM K.
02/15/22
INTR.
• There are four serotypes of dengue based on

neutralization tests.
• Dengue serotypes 1,2,3,4. with all the serology tests,

the four serotypes are highly cross reactive with each
other. They are however, distinguishable with the high
specific PRNT.
• Dengue serotypes 1, 3 and 4 show a closer antigenic

and genetic relationship to34 each other than dengue 2.
PHARM K.
02/15/22
REPLICATION
• Replication is similar to Yellow fever virus.
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PHARM K.
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TRASNMISSION AND
EPIDEMIOLGY
• Dengue displays many epidemiological similarities to

yellow fever and chikungunya viruses.
• There is considerable overlap in the ecologies of

these three virus infections.
• Essentially there are three transmission cycles of

dengue virus infection.
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PHARM K.
02/15/22
TRANS &EPIDEMIOLOGY
• a forest cycle in primates and involving forest species of

Aedes.
• a rural or semi-rural cycle in humans, with the peri-
domestic Aedes species being the vectors.
• an urban cycle in humans involving domesticated

Aedes species.
• By far the most important of these three for both

endemic and epidemic human37
dengue is the urban cycle
PHARM K.
02/15/22
PATHOGENESIS AND
IMMNUNITY
• Essentially, there are two hypotheses involving

immunological or virological mechanisms.
• The immunological theory of DHF/DSS is based on the

phenomenon of antibody-mediated enhancement of
infection.
• Three elements partake in the process of antibody-mediated

enhancement: antibody, virus and the receptor for the Fc
portion of IgG(I.e FcgRI molecule and the FcgRII
38
molecule). PHARM K.
02/15/22
PATH AND IMMUNITY
• The alternative hypothesis of Rosen (1986) and

colleagues, indicates that the severe complications of
DHF/DSS are the direct results of properties of the virus.
• that is, the aftermath of infection with unusually virulent

strains of dengue circulating in a particular area and giving
rise to outbreaks of DHF/ DSS.
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PHARM K.
02/15/22
CLINICAL FEATURES
• The majority of infections with dengue virus, based on the

extent of population seropositivity, are asymptomatic.
• Clinical manifestations of dengue however, occur in two
forms- classical dengue fever and DHF/DSS.
• Classical dengue fever is an acute disease characterized by-
sudden onset of fever, severe headache which is typically
frontal in distribution.
• together with retroorbital pain, nausea and vomiting. Severe

muscle and bone pain and arthralgia
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PHARM K.
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CLINICAL FEATURES
• There is frequently a diffuse, discrete maculopapular

rash which appear at the recovery phase of the illness.
• The grave complication of DHF/DSS is governed by

two factors, prior infection and age.
• DHF and DSS % occurrence in primary infection

less when compared with secondary infection(i.e
primary infection 0.18% and 0.007% respectively,
secondary 2.0% and 1.1% respectively).
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PHARM K.
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CLINICAL FEATURES
• It is also rare in individuals over the age of 15 years.

• DHF/DSS resembles yellow fever in its biphasic
presentation.
• The severity of DHF/DSS has also been graded by
the WHO from I to IV (Anonymous, 1980).
• Grade 1& II are similar in their presentation with

slight difference in their hemorrhagic manifestations.
• Grade III- Circulatory failure, Grade IV- profound

shock with pulse and BP undetectable.
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PHARM K.
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PHARM K.
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PHARM K.
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LABORATORY DIAGNOSIS
• The clinical diagnosis of dengue, both the UCDF form and

DHF/DSS, if often unreliable.
• The febrile illness in Dengue is similar to many viral

infection although muscle and bone pain is suggestive of
dengue.
• Similarly the DHF may resembles other causes of HF.
although thrombocytopenia with haemoconcentration and
signs of a moderate consumptive coagulopathy is
suggestive of dengue.
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PHARM K.
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LAB. DIAGNOSIS.
• The most widely used serological test is the HI test,

detecting antibodies as early as 4 days post-onset.
• ELISA (MAC ELISA)-to detect IgM is used during
outbreaks.
• Immuno- fluorescent assays have been used successfully to

detect dengue IgG and IgM antibodies.(this determine
secondary infection).
• The CF test is also used and 46is more specific than HI-test
PHARM K.
02/15/22
LAB. DIAGNOSIS.
• The NT and PRNT tests are the most specific and

sensitive but are difficult to perform and thus tend to
be used only for specific purposes.
• Virus isolation is difficul.t
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PHARM K.
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PREVENTION
• There is, at present, no licensed dengue vaccine. Current

strategy is to develop a vaccine against all four serotypes.
• Successful trials of monovalent vaccines have been reported,

but, as yet, not for experimental tetravalent vaccines.
• control of dengue depends on (a) surveillance to obtain early

warning of epidemics or preferably to be able to predict
impending epidemics, 48
PHARM K.
02/15/22
PREVENTION
• And (b) effective vector control.

• Epidemiological surveillance may be of two types:
a. proactive surveillance.
b. reactive surveillance. This surveillance type is more
insensitive because several cases may occur that are
not dengue.
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PHARM K.
02/15/22
THE END
THANKS
50
PHARM K.
Eastern equine encephalitis
Dr Sulaiman Gbonnie Conteh

Third Year
COMAHS
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Eastern equine encephalitis (EEE)
Triple E or sleeping sickness (not to be confused
with African trypanosomiasis), is a disease
caused by a zoonotic mosquito vectored
Togavirus that is present in North, Central, and
South America, and the Caribbean.
EEE was first recognized in Massachusetts,
United States, in 1831, when 75 horses died
mysteriously of viral encephalitis.
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Epidemiology of EEE
• Epizootics in horses have continued to occur regularly in the
United States.
• It can also be identified in donkeys and zebras.
• Due to the rarity of the disease, its occurrence can cause
economic impact beyond the cost of horses and poultry.
• EEE is found today in the eastern part of the United States
and is often associated with coastal plains.
• It can most commonly be found in East Coast and Gulf
Coast states.
• In Florida, about one to two human cases are reported a
year, although over 60 cases of equine encephalitis are
reported.
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VIRUS
• The causative agent, later identified as a togavirus, was first isolated from
infected horse brains in 1933.
• In 1938, the first confirmed human cases were identified when 30 children
died of encephalitis in the Northeastern United States.
• These cases coincided with outbreaks in horses in the same regions.
• The fatality rate in humans is 33%, and currently no cure is known for
human infections.
• This virus has four variations in the types in lineage.
• The most common to the human disease is group 1, which is considered
to be endemic in North America and the Caribbean, while the other three
lineages, groups IIA, IIB, and III, are typically found in Central and South
America, causing equine illness
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Life Cycle
In Birds and Mosquito
• EEEV is capable of infecting a wide range of animals,

including mammals, birds, reptiles, and amphibians.
• The virus is maintained in nature through a bird—
mosquito cycle. Two mosquito species are primarily
involved in this portion of the cycle; they are
Culiseta melanura and Culiseta morsitans.
• These mosquitoes feed on the blood of birds. The
frequency of the virus found in nature increases
throughout the summer as more birds and more
mosquitoes become infected.
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Life Cycle
In Mosquito and Humans
• Transmission of EEEV to mammals (including humans)

occurs via other mosquito species, which feed on the
blood of both birds and mammals.
• These other mosquitoes are referred to as "bridge
vectors" because they carry the virus from the avian
hosts to other types of hosts, particularly mammals.
• The bridge vectors include Aedes taeniorhynchus[7],
Aedes vexans, Coquillettidia perturbans,
Ochlerotatus canadensis, and Ochlerotatus sollicitans.
Ochlerotatus canadensis also frequently bites turtles.
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Life Cycle Cont:
In Mosquito and Humans
• Humans, horses, and most other infected

mammals do not circulate enough viruses in
their blood to infect additional mosquitoes.
• Some cases of EEE have been contracted
through laboratory exposures or from
exposure of the eyes, lungs, or skin wounds to
brain or spinal cord matter from infected
animals.
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EBOLA VIRUS FEVER
Dr Sulaiman Conteh
02/15/22 Pharm K. 58
Introduction
• The Ebola virus can cause severe viral
haemorrhagic fever (VHF) outbreaks in humans
with a case fatality rate of up to 90%.
• Ebola first appeared in 1976 in two simultaneous
outbreaks, in Nzara, Sudan, and in Yambuku,
Democratic Republic of Congo (DRC).
• The latter was in a village situated near the
Ebola River, from which the disease takes its
name.
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Cause
The Ebola virus is comprised of five distinct
species:
• Bundibugyo,
• Ivory Coast,
• Reston,
• Sudan and
• Zaire.
Bundibugyo, Sudan and Zaire species have been
associated with large Ebola haemorrhagic fever
(EHF) outbreaks in Africa, while the Ivory Coast
and Reston species have not.
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Prognosis
• EHF is a febrile haemorrhagic illness
which causes death in 25-90% of all cases
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Transmission
• Ebola is introduced into the human
population through close contact with the
blood, secretions, organs or other bodily
fluids of infected animals.
• In Africa, infection has been documented
through the handling of infected
chimpanzees, gorillas, fruit bats, monkeys,
forest antelope and porcupines found
dead or ill in the rainforest.
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Transmission Cont:
• Ebola spreads in the community through human-
to-human transmission, resulting from close
contact with the blood, secretions, organs or
other bodily fluids of infected people.
• Burial ceremonies where mourners have direct
contact with the body of the deceased person
can also play a role in the transmission of Ebola.
• Transmission via infected semen can occur up
to seven weeks after clinical recovery.
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Signs and symptoms
• The incubation period (interval from infection to
onset of symptoms) varies between 2 to 21 days.
• EVD begins with a sudden onset of an influenza-
like stage characterized by general malaise, fever
with chills, arthralgia and myalgia, and chest pain.
Nausea is accompanied by abdominal pain,
anorexia, diarrhea, and vomiting. Respiratory tract
involvement is characterized by pharyngitis with
sore throat, cough, dyspnea, and hiccups.
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Signs and symptoms Cont:
• The central nervous system with severe
headaches, agitation, confusion, fatigue,
depression, seizures, and sometimes coma.
• The circulatory system is also frequently
involved, with the most prominent signs being
edema and conjunctivitis. Hemorrhagic
symptoms are infrequent,hematemesis,
hemoptysis, melena, and bleeding from mucous
membranes (gastroinestinal tract, nose, vagina
and gingiva).
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• Cutaneous presentation may include:
maculopapular rash, petechiae, purpura,
ecchymoses, and hematomas.
• Development of hemorrhagic symptoms is
generally indicative of a negative prognosis.
However, contrary to popular belief, hemorrhage
does not lead to hypovolemia and is not the
cause of death.
• Death occurs due to multiple organ dysfunction
syndrome due to fluid redistribution,
hypotension, disseminated intravascular
coagulation, and focal tissue necroses.
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Differential diagnosis
• malaria, typhoid fever, shigellosis, cholera,
leptospirosis, plague, rickettsiosis,
relapsing fever, meningitis, hepatitis and
other VHFs.
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Diagnosis
• enzyme-linked immunosorbent assay
(ELISA)
• antigen detection tests
• serum neutralization test
• reverse transcriptase polymerase chain
reaction (RT-PCR) assay
• virus isolation by cell culture.
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Treatment and vaccine
• Severe cases require intensive supportive care.
Patients are frequently dehydrated and in need
of intravenous fluids or oral rehydration with
solutions containing electrolytes.
• No specific treatment or vaccine is yet available

for EHF. New drug therapies have shown
promising results in laboratory studies and are
currently being evaluated. Several vaccines are
being tested but it could be several years before
any are available.
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Prevention
• Controlling Ebola Reston in domestic animals:
There is no animal vaccine available against Ebola
Reston.
Routine cleaning and disinfection of pig or monkey farms
(with sodium hypochlorite or other detergents) is
expected to be effective in inactivating the virus.
As Ebola Reston outbreaks in pigs and monkeys have
preceded human infections, the establishment of an
active animal health surveillance system to detect new
cases is essential in providing early warning for
veterinary and human public health authorities.
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Reducing the risk of Ebola infection
in people
• Reducing the risk of wildlife-to-human transmission from contact with
infected fruit bats or monkeys/apes and the consumption of their raw meat.
Animals should be handled with gloves and other appropriate protective
clothing. Their products (blood and meat) should be thoroughly cooked before
consumption.
• Reducing the risk of human-to-human transmission in the community arising
from direct or close contact with infected patients, particularly with their bodily
fluids. Close physical contact with Ebola patients should be avoided. Gloves
and appropriate personal protective equipment should be worn when taking
care of ill patients at home. Regular hand washing is required after visiting sick
relatives in hospital, as well as after taking care of ill patients at home.
• Communities affected by Ebola should inform the population about the
nature of the disease and about outbreak containment measures, including
burial of the deceased. People who have died from Ebola should be promptly
and safely buried.
• Precautionary measures are needed in Africa to avoid that pig farms
infected through contact with fruit bats amplify the virus and cause EHF
outbreaks.
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Controlling infection in health-care
settings
• Human-to-human transmission of the Ebola virus is primarily associated
with direct contact with blood and body fluids. Transmission to healthcare
workers has been reported when appropriate infection control measures
have not been observed.
• Health-care workers caring for patients with suspected or confirmed Ebola

virus should apply infection control precautions to avoid any exposure to the
patient’s blood and body fluids and/or direct unprotected contact with the
possibly contaminated environment. Therefore the provision of health care
for suspected or confirmed Ebola patients requires specific control
measures and the reinforcement of standard precautions, particularly basic
hand hygiene, the use of personal protective equipment, safe injections
practices and safe burial practices.
• Laboratory workers are also at risk. Samples taken from suspected human
and animal Ebola cases for diagnosis should be handled by trained staff and
processed in suitably-equipped laboratories.
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ECHOVIRUS
THIRD YEAR
Dr Sulaiman Conteh
02/15/22 Pharm K. 73
Properties
• An echovirus has a naked protein capsid,
which makes up 75% of the virus particle that
encloses a dense central core of single-
stranded RNA.
• This RNA contains an RNA replicase, viral-
coded proteins, and a single polyprotein.
• The structural proteins determine host range
and play a very important role in delivering
the RNA genome into the cytoplasm of new
host cells.
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Pathogenesis
• Viral replication of an echovirus occurs in the
nasopharynx after infection and then spreads to
regional lymph nodes.
• However, most viral particles are swallowed and they
reach the lower gut tract, where the virus is
presumed to bind to specific receptors.
• The virus then spreads to the lower intestinal tract,
replicating but not causing any major cellular effects
along the way.
• Next, the virus spreads to many secondary sites in
the body such as the central nervous system, liver,
spleen, bone marrow, heart and finally the lungs
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Symptoms
• Echovirus disease occurs disproportionately in
males and children.
• Infection within the first two weeks of birth
can cause devastating and potentially fatal
disease. In this population, death usually
results from overwhelming liver failure or
myocarditis, rather than infection of the
central nervous system.
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Symptoms Cont:
• Older children and adults have a better
prognosis. Myocarditis is the most frequent
complication in adults.
• Echovirus may also produce a rash that
spreads from the face down to the neck,
upper extremities, and chest.
02/15/22 Pharm K. 77
Laboratory Diagnosis
•Laboratory diagnosis is made with acute and
convalescent titers of serum antibodies to
Echovirus.
02/15/22 Pharm K. 78
Treatment
• No specific treatment for echovirus infection is
currently available.
• Care is directed at relief of symptoms.
02/15/22 Pharm K. 79
Escherichia Coli
Third Year
Dr Sulaiman Gbonnie Conteh
02/15/22 Pharm K. 80
Introduction
• Escherichia coli is a Gram-negative,
facultative anaerobic, rod-shaped,
coliform bacterium of the genus Escherichia.
• found in the lower intestine of warm-blooded
organisms (endotherms).
• Most E. coli strains are harmless, but some
serotypes (EPEC, ETEC etc.) can cause serious
food poisoning in their hosts, and are
occasionally responsible for food contamination
incidents that prompt product recalls.
02/15/22 Pharm K. 81
Introduction
• The harmless strains are part of the
normal microbiota of the gut, and can benefit
their hosts by producing vitamin K2,(which helps
blood to clot) and preventing colonisation of the
intestine with pathogenic bacteria, having a
mutualistic relationship.
• E. coli is expelled into the environment within
fecal matter. The bacterium grows massively in
fresh fecal matter under aerobic conditions for 3
days, but its numbers decline slowly afterwards.
02/15/22 Pharm K. 82
Classification
Domain: Bacteria
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Escherichia
Species:
02/15/22 Pharm E. coli
K. 83
Serotypes
• Based on major surface antigens (O antigen:
part of lipopolysaccharide layer; H: flagellin; K
antigen: capsule), e.g. O157:H7).
• At present, about 190 serogroups are known.
02/15/22 Pharm K. 84
Strains of E. coli and their role in diseases
• Most E. coli strains do not cause disease, naturally living in the gut.
• Virulent strains can cause gastroenteritis, urinary tract infections,
neonatal meningitis, hemorrhagic colitis, and Crohn's disease.
• Virulent strains are also responsible for bowel necrosis (tissue
death) and perforation without progressing to
hemolytic-uremic syndrome, peritonitis, mastitis, sepsis, and Gram-
negative pneumonia.
• Very young children are more susceptible to develop severe illness,
such as hemolytic uremic syndrome.
• Healthy individuals of all ages are at risk to the severe
consequences that may arise as a result of being infected with E.
coli
02/15/22 Pharm K. 85
Strains of E. coli and their role in diseases Cont:
• Uropathogenic E. coli (UPEC) is one of the main causes

of urinary tract infections.
• It is part of the normal microbiota in the gut and can
be introduced in many ways.
• In particular for females, the direction of wiping after
defecation (wiping back to front) can lead to fecal
contamination of the urogenital orifices.
• Anal intercourse can also introduce this bacterium into
the male urethra, and in switching from anal to vaginal
intercourse, the male can also introduce UPEC to the
female urogenital system.
02/15/22 Pharm K. 86
• Enterotoxigenic E. coli (ETEC) is the most

common cause of traveler's diarrhea.
• The bacteria, typically transmitted through
contaminated food or drinking water, adheres
to the intestinal lining, where it secretes either
of two types of enterotoxins, leading to
watery diarrhea.
• The rate and severity of infections are higher
among children under the age of five,
02/15/22 Pharm K. 87
• Enteroinvasive Escherichia coli (EIEC) causes

an illness indistinguishable from shigellosis.
• Definitive diagnosis is made by stool culture
but most cases are probably treated
empirically as shigellosis.
02/15/22 Pharm K. 88
• Enterohaemorrhagic Escherichia coli (EHEC; usually serotype O157:H7 and also
known as verotoxin-producing E. coli, or VTEC) is a well-recognized cause of
gastroenteritis in humans.
• It is a zoonosis that is usually associated with cattle and there have been a number
of major outbreaks associated with contaminated food.
• A variety of modes of transmission have been reported and EHEC is a paradigm for
all enteric livestock associated zoonoses.
• EHEC secretes a toxin (Shiga-like toxin 1), which affects vascular endothelial cells in
the gut and in the kidney.
• After an incubation period of 12–48 h.
• It causes diarrhoea (frequently bloody), associated with abdominal pain and
nausea. Some days after the onset of symptoms, the patient may develop
thrombotic thrombocytopenic purpura or haemolytic uraemic syndrome.
• This is more common in children and may lead to permanent renal damage or
death.
• Non-O157 serotypes are of increasing concern.
02/15/22 Pharm K. 89
Diagnosis
• Diagnosis of infectious diarrhea and identification of
antimicrobial resistance is performed using a stool culture
with subsequent antibiotic sensitivity testing.
• It requires a minimum of 2 days and maximum of several
weeks to culture gastrointestinal pathogens.
• The sensitivity (true positive) and specificity (true
negative) rates for stool culture vary by pathogen,
although a number of human pathogens can not be
cultured.
• For culture-positive samples, antimicrobial resistance
testing takes an additional 12–24 hours to perform.
02/15/22 Pharm K. 90
Treatment
• The mainstay of treatment is the assessment of dehydration
and replacement of fluid and electrolytes.
• Administration of antibiotics has been shown to shorten
the course of illness and duration of excretion of
enterotoxigenic E. coli (ETEC) in adults in endemic areas and
in traveller's diarrhea, though the rate of resistance to
commonly used antibiotics is increasing and they are
generally not recommended.
• The antibiotic used depends upon susceptibility patterns in
the particular geographical region.
• Currently, the antibiotics of choice are fluoroquinolones or
azithromycin, with an emerging role for rifaximin.
02/15/22 Pharm K. 91
Treatment
• Don’t take over-the-counter medications that
fight diarrhea. You don’t want to slow down
your digestive system, because that will delay
your body’s shedding of the infection.
• When you start to feel better, stick to low-fiber
foods
• Dairy products and foods that are high in fat
or fiber can make your symptoms worse.
02/15/22 Pharm K. 92
Prevention
• ETEC is the type of E. coli that most vaccine
development efforts are focused on.
• There are currently no licensed vaccines for
ETEC, though several are in various stages of
development.
• One of the most important things you can do
to protect yourself and your family against E.
coli is wash your hands.
02/15/22 Pharm K. 93
Prevention Cont:
You can also prevent E. coli infections by being
careful about the foods that carry the greatest
chance of contamination:
•Cook hamburgers until they’re 160 F inside.
•Drink only pasteurized milk, juice, and cider.
•Wash all of your produce before you eat it. Be
especially careful to get dirt off leafy greens such
as lettuce and spinach.
02/15/22 Pharm K. 94
Prevention Cont:
• When you're swimming, try not to swallow
the water, whether it's a pool, a lake, or the
ocean. It may be tainted with E. coli from
feces.
02/15/22 Pharm K. 95
LASSER FEVER
THIRD YEAR NOTES
Dr Sulaiman Conteh
02/15/22 Pharm K. 96
Introduction
• Lassa viral haemorrhagic fever is an acute illness of 1-4
weeks duration that occurs in West Africa.
• Though first described in the 1950s, the virus causing
the disease was not identified until 1969.
• Lassa fever is caused by the Lassa virus, a member of
the Arenaviridae family; it is an enveloped, single-
stranded, bisegmented RNA virus(+ and - ve)
• Lassa fever is known to be endemic in Guinea
(Conakry), Liberia, Sierra Leone and parts of Nigeria, but
probably exists in other West African countries as well.
02/15/22 Pharm K. 97
Transmission
• Humans usually become infected with Lassa virus from
exposure to excreta of infected Mastomys natalensis
(multimammate rat).
• Both direct exposure, (touching the excreta) and Lassa
virus may also be spread between humans through
direct contact with the blood, urine, faeces, or other
bodily secretions of a person with Lassa fever.
• There is no epidemiological evidence supporting
airborne spread between humans.
• Person-to-person transmission occurs in both community
and health care settings, where the virus may be spread
by contaminated medical equipment, such as re-used
needles.
• Sexual transmission of Lassa virus has been reported.
02/15/22 Pharm K. 98
Prevalence
The dissemination of the infection can be assessed by prevalence of
antibodies to the virus in populations of:
• Sierra Leone 8–52%
• Guinea 4–55%
• Nigeria approx. 21%
Some studies indicate that 300 000 to 500 000 cases of Lassa fever
and 5000 deaths occur yearly across West Africa. The overall case-
fatality rate is 1%, up to 15% among hospitalized patients.
Death usually occurs within 14 days of onset in fatal cases.
The disease is especially severe late in pregnancy, with maternal
death and/or fetal loss occurring in greater than 80% of cases
during the third trimester.
02/15/22 Pharm K. 99
Pathogenesis
• The Lassa virus gains entry into the host
cell by means of the cell-surface receptor
the alpha-dystroglycan (alpha-DG).
• Lassa virus will infect almost every tissue
in the human body. It starts with the
mucosa, intestine, lungs and urinary
system, and then progresses to the
vascular system.
02/15/22 Pharm K. 100

Signs and Symptoms
• About 80% of human infections are asymptomatic; the remaining
cases have severe multi-system disease, where the virus affects
several organs in the body, such as the liver, spleen and kidneys.
• The incubation period of Lassa fever ranges from 6-21 days. The
onset of the disease is usually gradual, starting with fever, general
weakness, and malaise.
• After a few days, headache, sore throat, muscle pain, chest pain,
nausea, vomiting, diarrhoea, cough, and abdominal may follow.
Severe cases may progress to show facial swelling, fluid in the lung
cavity, bleeding from mouth, nose, vagina or gastrointestinal tract,
and low blood pressure. Protein may be noted in the urine. Shock,
seizures, tremor, disorientation, and coma may be seen in the late
stages.
• Deafness occurs in 25% of patients of whom half recover some
function after 1-3 months. Transient hair loss and gait disturbance
may occur during recovery.
02/15/22 Pharm K. 101

Diagnosis
• Lassa fever is diagnosed by detection of
Lassa antigen, anti-Lassa antibodies, or
virus isolation techniques.
• 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.
02/15/22 Pharm K. 102

Treatment
• The antiviral drug ribavirin is effective
treatment for Lassa fever if given early on
in the course of clinical illness.
• There is no evidence to support the role of
ribavirin as post-exposure prophylactic
treatment for Lassa fever.
02/15/22 Pharm K. 103

Prevention
• community hygiene
• Infection control for health workers and
exposure community members
02/15/22 Pharm K. 104

Lymphocytic choriomeningitis
• It is a rodent-borne viral infectious disease
that presents as aseptic meningitis,
encephalitis or meningoencephalitis.
• Its causative agent is lymphocytic
choriomeningitis
mammarenavirus (LCMV), a member of
02/15/22 Pharm K. 105

Virology
• LCMV Armstrong-Acute infection
• LCMV Clone 13-Chronic infection
02/15/22 Pharm K. 106

Signs and symptoms
02/15/22 Pharm K. 107

Marburg virus
THIRD YEAR
Dr Sulaiman Conteh
02/15/22 Pharm K. 108

Introduction
• The Marburg virus in the Filoviridae family
was first noticed and described during a
small epidemic in the city of Marburg,
Germany in 1967.
02/15/22 Pharm K. 109

Virology
• Marburgvirions contain non-infectious, linear
nonsegmented, single-stranded RNA genomes
of negative polarity
• Marburgvirus genomes are approximately 19 kb
long and contain seven genes in the order 3'-
UTR-NP-VP35-VP40-GP-VP30-VP24-L-5'-UTR.
• The genomes of the two different
marburgviruses ( marburgviruses Marburg virus
(MARV) and Ravn virus (RAVV)) differ in
sequence.
02/15/22 Pharm K. 110

Replication
• The marburgvirus life cycle begins with virion attachment
to specific cell-surface receptors, followed by fusion of
the virion envelope with cellular membranes and the
concomitant release of the virus nucleocapsid into the
cytosol.
• The virus RdRp partially uncoats the nucleocapsid and
transcribes the genes into positive-stranded mRNAs,
which are then translated into structural and
nonstructural proteins.
• Marburgvirus L binds to a single promoter located at the
3' end of the genome. Transcription either terminates
after a gene or continues to the next gene downstream.
02/15/22 Pharm K. 111

Replication Cont:
• This means that genes close to the 3' end of the genome are
transcribed in the greatest abundance, whereas those toward
the 5' end are least likely to be transcribed. The gene order is
therefore a simple but effective form of transcriptional
regulation. The most abundant protein produced is the
nucleoprotein, whose concentration in the cell determines
when L switches from gene transcription to genome
replication.
• Replication results in full-length, positive-stranded
antigenomes that are in turn transcribed into negative-
stranded virus progeny genome copies. Newly synthesized
structural proteins and genomes self-assemble and
accumulate near the inside of the cell membrane. Virions bud
off from the cell, gaining their envelopes from the cellular
membrane they bud from. The mature progeny particles then
infect other cells to repeat the cycle.
02/15/22 Pharm K. 112
Signs and symptoms
• Incubation: 2–21 days
• Generalization Phase: Day 1 up to Day 5 from onset of clinical
symptoms.
• High fever (~40˚C) and a sudden, severe headache, with
accompanying chills, fatigue, nausea, vomiting, diarrhea,
pharyngitis, maculopapular rash, abdominal pain,
conjunctivitis, & malaise.
• Early Organ Phase: Day 5 up to Day 13.
• Symptoms include prostration, dyspnea, edema, conjunctival
injection, viral exanthema, and CNS symptoms, including
encephalitis, confusion, delirium, apathy, and aggression.
Hemorrhagic symptoms typically occur late and herald the
end of the early organ phase, leading either to eventual
recovery or worsening & death.
• Symptoms include bloody stools, ecchymoses, blood leakage
from venipuncture sites, mucosal & visceral hemorrhaging,
and possibly hematemesis.
02/15/22 Pharm K. 113
• Late Organ Phase: Day 13 up to Day 21+. Symptoms
bifurcate into two constellations for survivors & fatal
cases.
• Survivors will enter a convalescence phase,
experiencing myalgia, fibromyalgia, hepatitis, asthenia,
ocular symptoms, & psychosis.
• Fatal cases continue to deteriorate, experiencing
continued fever, obtundation, coma, convulsions, diffuse
coagulopathy, metabolic disturbances, shock and death,
with death occur in Days 8 and 16.
02/15/22 Pharm K. 114

Diagnosis
• History of the patient, in particular the travel and occupational
history (which countries and caves were visited?) and the patient's
exposure to wildlife (exposure to bats or bat excrements?).
• MVD can be confirmed by isolation of marburgviruses from or by
detection of marburgvirus antigen or genomic or subgenomic RNAs
in patient blood or serum samples during the acute phase of MVD.
• Marburgvirus isolation is usually performed by inoculation of grivet
kidney epithelial Vero E6 or MA-104 cell cultures or by inoculation of
human adrenal carcinoma SW-13 cells, all of which react to
infection with characteristic cytopathic effects.
• Immunofluorescence assays are used to confirm marburgvirus
presence in cell cultures. During an outbreak, virus isolation and
electron microscopy are most often not feasible options.
• The most common diagnostic methods are therefore RT-PCR in
conjunction with antigen-capture ELISA,which can be performed in
field or mobile hospitals and laboratories.
02/15/22 Pharm K. 115

REOVIRIDAE
ROTAVIRUS
THIRD YEAR
Dr Sulaiman Conteh
02/15/22 Pharm K. 116

Reoviridae
• They have a wide host range, including vertebrates
, invertebrates, plants, protists and fungi.
• They lack lipid envelopes and package their
genomes of discrete
double-stranded segments of RNA within multi-
layered capsids. Lack of a lipid envelope has
allowed three-dimensional structures of these large
complex viruses (diameter,∼60–100 nm) to be
obtained, revealing a structural and likely
evolutionary relationship to the Cystovirus family of
Bacteriophage.
02/15/22 Pharm K. 117

Properties
• There are currently 87 species in this family,
divided among 30 genera.
• Reoviruses can affect the gastrointestinal system
(Rotavirus) and respiratory tract.
• The name "Reo-" is derived from respiratory e
nteric orphan viruses.
• The term "orphan virus" refers to the fact that
some of these viruses have been observed not
associated with any known disease.
02/15/22 Pharm K. 118

ROTAVIRUS
• Rotavirus is the most common cause of
severe diarrhoea among infants and young children, and
is one of several viruses that cause infections often called
stomach flu, despite having no relation to influenza.
• By the age of five, nearly every child in the world has
been infected with rotavirus at least once.
• However, with each infection, immunity develops, and
subsequent infections are less severe; adults are rarely
affected.
• There are five species of this virus, referred to as A, B, C,
D, and E. Rotavirus A, the most common, causes more
than 90% of infections in humans.
02/15/22 Pharm K. 119

Properties
REO: Respiratory Enteric Orphan
Structure:
•The genome of rotavirus consists of 11 double helix
molecules of RNA which are 18,555 nucleotides in
total.
•Each helix, is a gene, numbered 1 to 11 by
decreasing size. Each gene codes for one protein,
except genes 9, which codes for two.
•The RNA is surrounded by a three-layered
icosahedral protein capsid. Viral particles are up to
76.5 nm in diameter and are not enveloped.
02/15/22 Pharm K. 120
Properties Cont:
Proteins: There are six viral proteins (VPs)
that form the virus particle.
These structural proteins are called VP1,
VP2, VP3, VP4, VP6 and VP7.
In addition to the VPs, there are six
nonstructural proteins (NSPs), that are only
produced in cells infected by rotavirus.
These are called NSP1, NSP2, NSP3, NSP4
, NSP5 and NSP6.
02/15/22 Pharm K. 121
Functions of Viral Proteins
RNA Segment Size ( Molecular Copies per
Protein Location Function
(Gene) base pairs) weight kDa particle
RNA-
At the vertices dependent
1 3302 VP1 125 <25
of the core RNA
polymerase
Forms inner Stimulates
2 2690 VP2 102 shell of the 120 viral RNA
core replicase
Guanylyl
At the vertices transferase
3 2591 VP3 88 <25
of the core mRNA capping
enzyme
Cell
4 2362 VP4 87 Surface spike 120 attachment,
virulence
5 1611 NSP1 59 Nonstructural 0 5'RNA binding
Structural and
species-
6 1356 VP6 45 Inner Capsid 780
specific
antigen
Enhances viral
mRNA activity
and shut-offs
02/15/22
7 1104 NSP3 37 Pharm K. Nonstructural 0
cellular
122
protein
Structural proteins
• VP1: In an infected cell this enzyme
produces mRNA transcripts for the
synthesis of viral proteins and produces
copies of the rotavirus genome RNA
segments for newly produced virus
particles.
• VP2 forms the core layer of the virion and
binds the RNA genome
02/15/22 Pharm K. 123

Structural Proteins Cont:
• VP6 forms the bulk of the capsid. It is
highly antigenic and can be used to
identify rotavirus species. This protein is
used in laboratory tests for rotavirus A
infections.
02/15/22 Pharm K. 124

Pathogenesis and Replication
• Rotaviruses replicate mainly in the gut,
and infect enterocytes of the villi of the
small intestine, leading to structural and
functional changes of the epithelium.
• The triple protein coats make them
resistant to the acidic pH of the stomach
and the digestive enzymes in the gut.
02/15/22 Pharm K. 125

Cont:
• The virus enter cells by receptor mediated
endocytosis and form a vesicle known as
an endosome.
• Proteins in the third layer (VP7 and the
VP4 spike) disrupt the membrane of the
endosome, creating a difference in the
calcium concentration. This causes the
breakdown of VP7 trimers into single
protein subunits, leaving the VP2 and VP6
protein coats around the viral dsRNA,
forming a double-layered particle (DLP).
02/15/22 Pharm K. 126
Cont:
• The eleven dsRNA strands remain within
the protection of the two protein shells and
the viral RNA-dependent RNA polymerase
creates mRNA transcripts of the double-
stranded viral genome.
• By remaining in the core, the viral RNA
evades innate host immune responses
called RNA interference that are triggered
by the presence of double-stranded RNA.
02/15/22 Pharm K. 127

Cont:
• During the infection, rotavirus produces mRNA for
both protein biosynthesis and gene replication.
• Most of the rotavirus proteins accumulate in
viroplasm, where the RNA is replicated and the
DLPs are assembled.
• Viroplasm is formed around the cell nucleus as
early as two hours after virus infection, and consists
of viral factories thought to be made by two viral
nonstructural proteins: NSP5 and NSP2.
02/15/22 Pharm K. 128

Cont:
•Inhibition of NSP5 by RNA interference
results in a sharp decrease in rotavirus
replication. The DLPs migrate to the
endoplasmic reticulum where they obtain
their third, outer layer (formed by VP7 and
VP4). The progeny viruses are released
from the cell by lysis.
02/15/22 Pharm K. 129

Mechanism of Disease
• The diarrhoea is caused by multiple activities of the virus. Malabsorption
occurs because of the destruction of gut cells called enterocytes.
 The toxic rotavirus protein NSP4 induces age- and
 calcium ion-dependent chloride secretion,
 disrupts SGLT1 transporter-mediated reabsorption of water, apparently
reduces activity of brush-border membrane disaccharidases, and
 activates the calcium ion-dependent secretory reflexes of the enteric
nervous system.
• Healthy enterocytes secrete lactase into the small intestine; milk
intolerance due to lactase deficiency is a symptom of rotavirus infection,
which can persist for weeks. A recurrence of mild diarrhoea often
follows the reintroduction of milk into the child's diet, due to bacterial
fermentation of the disaccharide lactose in the gut.
02/15/22 Pharm K. 130

Epidemiology
• Rotavirus is transmitted by the faecal-oral
route, via contact with contaminated hands,
surfaces and objects, and possibly by the
respiratory route.
• Sanitary measures adequate for eliminating
bacteria and parasites seem to be
ineffective in control of rotavirus, as the
incidence of rotavirus infection in countries
with high and low health standards is
similar.
02/15/22 Pharm K. 131
Signs and symptoms
• Rotavirus gastroenteritis is a mild to
severe disease characterised by vomiting,
watery diarrhoea, and low-grade fever.
• Once a child is infected by the virus, there
is an incubation period of about two days
before symptoms appear. Symptoms often
start with vomiting followed by four to eight
days of profuse diarrhoea.
• Dehydration is the most common cause of
death related to rotavirus infection.
02/15/22 Pharm K. 132
• Rotavirus A infections can occur throughout life: the
first usually produces symptoms, but subsequent
infections are typically mild or asymptomatic, as the
immune system provides some protection.
• Symptomatic infection rates are highest in children
under two years of age and decrease progressively
towards 45 years of age.
• The most severe symptoms tend to occur in
children six months to two years of age, the elderly,
and those with compromised or absent immune
system functions.
02/15/22 Pharm K. 133

• Due to immunity acquired in childhood,
most adults are not susceptible to
rotavirus; gastroenteritis in adults usually
has a cause other than rotavirus, but
asymptomatic infections in adults may
maintain the transmission of infection in
the community
02/15/22 Pharm K. 134

DIAGNOSTIC
• Specific diagnosis of infection with
rotavirus A is made by finding the virus in
the child's stool by enzyme immunoassay.
• Electron microscopy and PCR.
• Reverse transcription-polymerase chain
reaction (RT-PCR) can detect and identify
all species and serotypes of human
rotavirus.
02/15/22 Pharm K. 135
Treatment and prognosis
• Treatment of acute rotavirus infection is
nonspecific and involves management of
symptoms and, most importantly,
maintenance of hydration.
• If untreated, children can die from the
resulting severe dehydration. Depending on
the severity of diarrhoea, treatment
consists of oral rehydration and intravenous
fluids
02/15/22 Pharm K. 136
THANK
YOU
02/15/22 Pharm K. 137
RHINOVIRUS
THIRD YEAR
Dr Sulaiman Conteh
02/15/22 Pharm K. 138

Properties
• There are 100 serotypes of human
rhinoviruses
• They replicate better at 33–35°C than at
37°C.
• They are acid labile
02/15/22 Pharm K. 139

Replication
• Attach by ICAM-1
• They have the same replication like
poliovirus
02/15/22 Pharm K. 140

Transmission
• There are two modes of transmission:
 aerosols of respiratory droplets
 contaminated surfaces, including direct
person-to-person contact.
02/15/22 Pharm K. 141

Pathogenesis
• The primary route of entry for Human
rhinoviruses is the upper respiratory tract.
Afterward, the virus binds to ICAM-1 also
known as CD54 receptors on respiratory
epithelial cells.
• As the virus replicates and spreads, infected
cells release distress signals known as
chemokines and cytokines (which in turn
activate inflammatory mediators).
02/15/22 Pharm K. 142
Pathogenesis cont:
• Immunity is serotype-specific and is a
function of nasal secretary IgA rather than
the humoral antibody
02/15/22 Pharm K. 143

Clinical Features
• Incubation period is 2-4 days
• Human rhinoviruses occur worldwide and are the
primary cause of common colds. Symptoms include
 sore throat,
 runny nose,
 nasal congestion,
 sneezing and
 cough;
 sometimes accompanied by muscle aches, fatigue,
malaise, headache, muscle weakness, or
loss of appetite.
02/15/22 Pharm K. 144

Diagnosis
• Isolation from the nasal discharge and cell
culture.
02/15/22 Pharm K. 145

Treatment and Prevention
• No antivirals
• Vaccine not possible because the 100
serotypes do not cross react for protection.
02/15/22 Pharm K. 146

Salmonella Spp
THIRD YEAR
Dr Sulaiman Conteh
02/15/22 Pharm K. 147

Classification
Domain : Bacterium
Kingdom : monera
Phylum : Proteobacteria
Class : Gammaproteobacteria
Order : Enterobacterials
Family : Enterobacteriaceae
Gender : Salmonella
Lignieres 1900
02/15/22 Species
Pharm K. 148
Properties
• They are gram-negative bacteria , in the form of a
bacillus , mostly mobile (with peritrichal flagella),
non-sporulating, non-capsulated, and most of
them do not ferment lactose .
• Salmonella is an extremely heterogeneous genus,
composed of three species,
Salmonella subterranea , Salmonella bongori and
Salmonella enterica
• Samonella enterica sp has 2610 serotypes .
• The classification into serogroups depends on
the antigen O, while the serotypes classification
depends on the antigen H.
02/15/22 Pharm K. 149
Epidemiology
• Salmonella spp. can colonize all animals, whereas
in Salmonella Typhi, the human is the only reservoir.
• Typhoid fever salmonellosis is endemic in
underdeveloped countries. Although resistances have
been found via plasmids to chloramphenicol ,
ampicillin , Salmonella Typhi has a low infectious dose
(unlike other Salmonella serotypes ).
• Most reptiles are parasitized by salmonella, and
contact with their feces or fecal traces can lead to
contamination, Therefore, personal hygienic care and
cleaning of the environment are important when
handling pet reptiles, as tortoises , aquarium turtles ,
iguanas and snakes
02/15/22 Pharm K. 150

Epidemiology
• The incidence of salmonellosis has markedly increased in many
countries; however, a paucity of good surveillance data exists.
• In 2000, approximately 21.6 million worldwide cases of typhoid fever
caused 216,500 deaths. By other estimates, a total of 26.9 million
typhoid fever episodes occurred in 2010.
• The geographical distribution of the disease differs widely. Incidence
of typhoid fever in south-central Asia, Southeast Asia, and, possibly,
southern Africa was high (>100 cases per 100,000 population per
year).
• The rest of Asia, Africa, Latin America, and Oceania (except for
Australia and New Zealand) typically see intermediate rates of
typhoid fever (10-100 cases per 100,000 population), while the
incidence is low in the other parts of the world (< 10 cases per
100,000 population).
• In countries where typhoid fever is endemic, most cases of the
disease occur in children aged 5-19 years and young adults. [
02/15/22 Pharm K. 151

Comorbidities to Salmonella
• In a 2001 study of 129
nonfecal Salmonella isolates at Massachusetts
General Hospital, the most common risk
factors were found to be corticosteroid use,
malignancy, diabetes, HIV infection, prior
antimicrobial therapy, and immunosuppressive
therapy.
• Sickle cell disease, malaria, schistosomiasis,
bartonellosis, and pernicious anemia have been
mentioned in the literature as other
comorbidities that predispose to salmonellosis.
02/15/22 Pharm K. 152

Pathogenesis of Salmonella sp
• Although the infectious dose varies
among Salmonella strains, a large inoculum is thought
to be necessary to overcome stomach acidity and to
compete with normal intestinal flora.
• Large inoculate are also associated with higher rates
of illness and shorter incubation periods.
• In general, about 106 bacterial cells are needed to
cause infection.
• Low gastric acidity, which is common in elderly
persons and among individuals who use antacids, can
decrease the infective dose to 103 cells, while prior
vaccination can increase the number to 109 cells.
02/15/22 Pharm K. 153

cont:
• The Salmonella infection cycle starts after the ingestion of
microbes. Through the stomach, the bacteria reach the small
intestine.
• Infection with salmonellae is characterized by attachment of
the bacteria by fimbriae or pili to cells lining the intestinal
lumen.
• Salmonellae selectively attach to specialized epithelial cells
(M cells) of the Peyer patches. The bacteria are then
internalized by receptor-mediated endocytosis and
transported within phagosomes to the lamina propria, where
they are released.
• Once there, salmonellae induce an influx of macrophages
(typhoidal strains) or neutrophils (nontyphoidal strains).
02/15/22 Pharm K. 154

cont:
• The Vi antigen of S typhi is important in preventing antibody-
mediated opsonization and complement-mediated lysis.
Through the induction of cytokine release and via
mononuclear cell migration, S typhi organisms spread through
the reticuloendothelial system, mainly to the liver, spleen, and
bone marrow.
• Within 14 days, the bacteria appear in the bloodstream,
facilitating secondary metastatic foci (eg, splenic abscess,
endocarditis).
• In some patients, gallbladder infection leads to long-term
carriage of S typhi or S paratyphi in bile and secretion to the
stool. As a rule, infection with nontyphoidal salmonellae
generally precipitates a localized response, while S typhi and
other especially virulent strains invade deeper tissues via
lymphatics and capillaries and elicit a major immune
response.
02/15/22 Pharm K. 155
cont:
• Virulence factors of salmonellae are
complex and encoded both on the
organism's chromosome and on large (34-
120 kd) plasmids.
02/15/22 Pharm K. 156

Clinical features
• The onset of illness is insidious and non-specific, with
intermittent fever, headache and abdominal pain.
• Physical findings in the early stages include abdominal
tenderness, hepato splenomegaly, lymphadenopathy and a
scanty maculopapular rash (‘rose spots’).
• Without treatment (and occasionally even after treatment),
serious complications can arise, usually in the third week of
illness. These include meningitis, lobar pneumonia,
osteomyelitis, intestinal perforation and intestinal
haemorrhage.
• The fourth week of the illness is characterized by gradual
improvement but, in developing countries, up to 30% of those
infected will die and 10% of untreated survivors will relapse.
This compares with a mortality rate of 1–2% in the USA.
02/15/22 Pharm K. 157

C.F cont:
• After clinical recovery, 5–10% of patients will continue
to excrete S. typhi for several months: these are
termed convalescent carriers.
• Between 1% and 4% will continue to carry the
organism for more than a year: this is chronic carriage.
• The usual site of carriage is the gall bladder and
chronic carriage is associated with the presence of
gallstones.
• However, in parts of the Middle East and Africa where
urinary schistosomiasis is prevalent, chronic carriage
of S. typhi in the urinary bladder is also common.
02/15/22 Pharm K. 158

C.F. Paratyphi
• associated with a milder and shorter
illness, and complications are uncommon.
02/15/22 Pharm K. 159

C.F Nontyphodoid
• Infection with nontyphoidal salmonellae usually causes
enterocolitis similar to that caused by other bacterial
enteric pathogens.
• The incubation period depends on the host and the
inoculum is generally 6-72 hours. In most cases,
stools are loose and bloodless.
• In rare cases, Salmonella infections cause large-
volume choleralike diarrhea or may be associated with
tenesmus. The diarrhea is typically self-limiting and
resolves within 3-7 days.
• Fever, abdominal cramping, chills, headache, and
myalgia are common. Fever usually resolves within 48
hours.
02/15/22 Pharm K. 160

C.F Nontyphoidal focal disease
• Focal disease is due to transient or persistent bacteremia.
Almost any organ can be affected, with sites of preexisting
structural abnormalities being the most vulnerable.
• Although postoperative Non-typhoidal Salmonellosis
infections (NTS) are rare, patients with malignant brain tumors
who require tumor resections and receive corticosteroids are
at great risk.
• The diagnosis of brain abscess should be considered in all
cases of NTS meningitis after surgery for brain tumor.

Adequate drainage (if possible), early isolation of the
pathogens, and control of the infection via antibiotic therapy
guided by antimicrobial susceptibility testing are vital
components in preventing this potentially fatal condition.
02/15/22 Pharm K. 161

C.F -Bacteremia
• Approximately 5% of patients with NTS gastroenteritis
develop bacteremia, and the incidence of extra-intestinal focal
infection in patients with NTS bacteremia is about 40%. The
organism can reach an extra-intestinal focus via blood
dissemination, direct extension from the surrounding organs,
and direct bacterial inoculation (eg, invasive medical
procedures).
• Invasive Salmonella infection can develop even in previously
healthy adults. Chronic Salmonella carriage is a predisposing
factor for invasive infection, and influenza infection may
contribute to such "breakthrough infections." The diagnosis
may be challenging since there may be no clear exposure or
focal physical signs.
02/15/22 Pharm K. 162

Diagnosis
• The definitive diagnosis of enteric fever requires the culture of
S. typhi or S. paratyphi from the patient.
• Blood culture is positive in most cases in the first 2 weeks.
• Culture of intestinal secretions, faeces and urine is also used,
although care must be taken to distinguish acute infection
from chronic carriage.
• Bone marrow culture is more sensitive than blood culture but
is rarely required, except in patients who have already
received antibiotics.
• Leucopenia is common but non-specific.
• Serological investigations, such as the Widal antigen test, are
of little practical value, are easily misinterpreted and should
not be used.
02/15/22 Pharm K. 163

Treatment
• Supportive
• Ciprofloxacin, azithromycin, ceftriaxone,
or trimethoprim/sulfamethoxazole (TMP/SMX) only
for high-risk patients and patients with systemic or
focal infections
• Azithromycin is the best choice in
quinoloneresistant
• cases; ceftriaxone has also been shown to be
effective.
• The patient's temperature may remain elevated for
several days after antibiotics are started and this
alone is not a sign of treatment failure.
02/15/22 Pharm K. 164
Treatment cont:
• Prolonged antibiotic therapy may eliminate
the carrier state, but in the presence of gall
bladder disease it is rarely effective.
• Cholecystectomy is not usually justified on
clinical or public health grounds.
02/15/22 Pharm K. 165

• TMP/SMX 5 mg/kg (of the TMP component)
orally every 12 hours for children
• Ciprofloxacin 500 mg orally every 12 hours
for adults
• Azithromycin 500 mg orally on day 1 followed
by 250 mg once a day for 4 days for adults
• Ceftriaxone 2 g IV once a day for 7 to 10
days for adults
02/15/22 Pharm K. 166

Carriers
• Asymptomatic carriage is usually self-limited,
and antibiotic treatment is rarely required.
• In unusual cases (eg, in food handlers or
health care workers), eradication may be
attempted with oral ciprofloxacin 500 mg
every 12 hours for 1 month.
• Follow-up stool cultures should be obtained
in the weeks after drug administration to
document elimination of Salmonella.
02/15/22 Pharm K. 167
Prevention
• Preventing contamination of foodstuffs by
infected animals and humans is paramount.
• Preventive measures for travelers also apply
to most other enteric infections.
• This is mainly through improved sanitation
and clean water
• Vaccination with either injectable inactivated
or oral live attenuated vaccines gives partial
protection.
02/15/22 Pharm K. 168
Shigella Spp
THIRD YEAR
Dr Sulaiman Conteh
02/15/22 Pharm K. 169

Introduction
• Shigella is a genus of bacteria that is Gram-negative,
facultative anaerobic, non-spore-forming, nonmotile, rod-shaped
and genetically closely related to E. coli.
• The genus is named after Kiyoshi Shiga, who first discovered it in
1897.
• The causative agent of human shigellosis, Shigella causes disease
in primates, but not in other mammals.
• It is only naturally found in humans and gorillas.
• During infection, it typically causes dysentery.
• Shigella is one of the leading bacterial causes of diarrhea
worldwide, causing an estimated 80–165 million cases.
• The number of deaths it causes each year is estimated at between
74,000 and 600,000.
• It is one of the top four pathogens that cause moderate-to-severe
diarrhea in African and South Asian children.[
02/15/22 Pharm K. 170

Domain:
Classification
Bacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Shigella
Castellani & Chalmers 1919
Species
S. boydii
S. dysenteriae
S. flexneri
02/15/22 Pharm K. 171
S. sonnei
Classification
• Serogroup A: S. dysenteriae (15
serotypes)
• Serogroup B: S. flexneri (9 serotypes)
• Serogroup C: S. boydii (19 serotypes)
• Serogroup D: S. sonnei (one serotype)[
02/15/22 Pharm K. 172

Pathogenesis
• Shigella infection is typically by ingestion.
• Depending on the health of the host, fewer than 100 bacterial cells
can be enough to cause an infection.
• Shigella species generally invade the epithelial lining of the colon,
causing severe inflammation and death of the cells lining the colon.
• This inflammation results in the diarrhea and even dysentery that
are the hallmarks of Shigella infection.
• Some strains of Shigella produce toxins which contribute to disease
during infection. S. flexneri strains produce ShET1 and ShET2,
which may contribute to diarrhea.[
• S. dysenteriae strains produce Shiga toxin, which is hemolytic
similar to the verotoxin produced by enterohemorrhagic E. coli.
• Both Shiga toxin and verotoxin are associated with causing
potentially fatal hemolytic-uremic syndrome.
02/15/22 Pharm K. 173

Pathogenesis Cont:
• Shigella species invade the host through the M-cells
interspersed in the gut epithelia of the small intestine, as they
do not interact with the apical surface of epithelial cells,
preferring the basolateral side.
• Shigella uses a type-III secretion system, which acts as a
biological syringe to translocate toxic effector proteins to the
target human cell.
• The effector proteins can alter the metabolism of the target
cell, for instance leading to the lysis of vacuolar membranes
or reorganization of actin polymerization to facilitate
intracellular motility of Shigella bacteria inside the host cell.
• For instance, the IcsA effector (which is an autotransporter
instead of type III secretion system effector) protein triggers
actin reorganization by N-WASP recruitment of
Arp2/3 complexes, helping cell-to-cell spread.
02/15/22 Pharm K. 174

Pathogenesis Cont:
• After infection, Shigella cells multiply
intracellularly and spread to neighboring
epithelial cells, resulting in tissue
destruction and characteristic pathology of
shigellosis.
02/15/22 Pharm K. 175

Clinical Feature
• Diarrhea, fever, nausea, vomiting, stomach cramps,
and flatulence.
• It is also commonly known to cause large and painful
bowel movements.
• The stool may contain blood, mucus, or pus.
• Hence, Shigella cells may cause dysentery.
• In rare cases, young children may have seizures.
• Symptoms can take as long as a week to appear, but
most often begin two to four days after ingestion.
Symptoms usually last for several days, but can last
for weeks.
• Shigella is implicated as one of the pathogenic causes
of reactive arthritis worldwide.
02/15/22 Pharm K. 176
Diagnosis
• The diagnosis of shigellosis is made by isolating the organism
from diarrheal fecal sample cultures.
• Shigella species are negative for motility and are generally not
lactose fermenters, but S. sonnei can ferment lactose.
• They typically do not produce gas from carbohydrates (with
the exception of certain strains of S. flexneri) and tend to be
overall biochemically inert.
• Shigella should also be urea hydrolysis negative. When
inoculated to a triple sugar iron slant, they react as follows:
K/A, gas -, and H2S -. Indole reactions are mixed, positive and
negative, with the exception of
• S. sonnei, which is always indole negative.
• Growth on Hektoen enteric agar produces bluish-green
colonies for Shigella and bluish-green colonies with black
centers for Salmonella
02/15/22 Pharm K. 177
Treatment
• Treatment consists mainly of replacing fluids and salts
lost because of diarrhea.
• Replacement by mouth is satisfactory for most people,
but some may need to receive fluids intravenously.
• Antidiarrheal drugs (such as diphenoxylate or
loperamide) may prolong the infection and should not
be used
• Antibiotics: Antibiotics, such as
trimethoprim-sulfamethoxazole, ciprofloxacin may be
given when the person is very young or very old, when
the disease is severe, or when the risk of the infection
spreading to other people is high.
02/15/22 Pharm K. 178

Prevention
• Simple precautions can be taken to prevent
getting shigellosis: wash hands before handling
food and thoroughly cook all food before eating.
• The primary prevention methods are improved
sanitation and personal and food hygiene, but a
low-cost and efficacious vaccine would
complement these methods.
• Since shigellosis is spread very quickly among
children, keeping infected children out of daycare
for 24 hours after their symptoms have
disappeared, will decrease the occurrence of
shigellosis in daycares
02/15/22 Pharm K. 179

VIBRO SPECIES
THIRD YEARS
Dr SULAIMAN G CONTEH
02/15/22 Pharm K. 180

Introduction
• Vibrio is a genus of Gram-negative bacteria, possessing a curved-
rod (comma) shape, several species of which can cause
foodborne infection, usually associated with eating undercooked
seafood.
• Typically found in salt water, Vibrio species are
facultative anaerobes that test positive for oxidase and do not form
spores.
• All members of the genus are motile. They are able to have polar or
lateral flagellum with or without sheaths.
• Vibrio species typically possess two chromosomes, which is
unusual for bacteria.
• Each chromosome has a distinct and independent origin of
replication, and are conserved together over time in the genus.
• Recent phylogenies have been constructed based on a suite of
genes (multilocus sequence analysis).
02/15/22 Pharm K. 181

Classification
Domain: Bacteria
Order: Vibrionales
Family: Vibrionaceae
Genus: Vibrio
Pacini 1854
02/15/22 Pharm K. 182

Vibro sp
• V. adaptatus
V. aerogenes • V. chagasii
V. aestivus
V. aestuarianus V. cholerae
V. agarivorans V. cincinnatiensis
V. albensis V. coralliilyticus
V. alfacsensis V. crassostreae
V. alginolyticus V. cyclitrophicus
V. anguillarum V. diabolicus
V. areninigrae V. diazotrophicus
V. artabrorum V. ezurae
V. atlanticus V. fluvialis
V. atypicus V. fortis
V. azureus V. furnissii
V. brasiliensis
V. gallicus
V. bubulus
V. calviensis V. gazogenes
V. campbellii V. gigantis
V. casei V. halioticoli
02/15/22 Pharm K. 183

• V. harveyi
V. hepatarius
• V. parahaemolyticus
V. hippocampi
V. pectenicida
V. hispanicus
V. penaeicida
V. ichthyoenteri
V. pomeroyi
V. indicus
V. ponticus
V. kanaloae
V. proteolyticus
V. lentus
V. rotiferianus
V. litoralis
V. ruber
V. logei
V. rumoiensis
V. mediterranei
V. salmonicida
V. metschnikovii
V. scophthalmi
V. mimicus
V. splendidus
V. mytili
V. superstes
V. natriegens
V. tapetis
V. tasmaniensis
V. navarrensis
V. tubiashii
V. neonatus
V. neptunius
V. nereis
V. vulnificus
V. wodanis
V. nigripulchritudo V. xuii
V. ordalii Moved:
V. orientalis V. fischeri to Aliivibrio fischeri
V. pacinii V. hollisae to Grimontia hollisae
02/15/22 Pharm K. 184

Pathogenic Sp
• V. cholerae (the causative agent of cholera
),
• V. parahaemolyticus, and
• V. vulnificus.
• V. alginolyticus
02/15/22 Pharm K. 185

Vibro sp xteristics
• Vibrio is considered to be among the
natural dwellers of aquatic environments
which play essential roles in maintaining
the aquatic ecosystem.
02/15/22 Pharm K. 186

Structure of V. cholerae
02/15/22 Pharm K. 187

Cholera
• The organism is killed by temperatures of
100°C in a few seconds but can survive in
ice for up to 6 weeks.
• One major pathogenic serogroup
possesses a somatic antigen (O1) with
two biotypes: classical and El Tor.
02/15/22 Pharm K. 188

Transmission
• V. cholerae is generally transmitted by
contaminated water.
• Pathogenic Vibrio species can cause foodborne
illness (infection), usually associated with eating
undercooked seafood.
• When ingested Vibrio bacteria can primarily result in
watery diarrhea along with other secondary
symptoms.
• The pathogenic features can be linked to
quorum sensing, where bacteria are able to express
their virulence factor via their signaling molecules.
02/15/22 Pharm K. 189

Transmission 1
• V. vulnificus outbreaks commonly occur in
warm climates and small, generally lethal,
outbreaks occur regularly.
• An outbreak occurred in New Orleans
after Hurricane Katrina, and several lethal
cases occur most years in Florida.
• Foodborne Vibrio infections are most often
associated with eating raw shellfish.
02/15/22 Pharm K. 190
Transmission 2
• V. parahaemolyticus is also associated
with the Kanagawa phenomenon, in which
strains isolated from human hosts (clinical
isolates) are hemolytic on
blood agar plates, while those isolated
from nonhuman sources are not hemolytic.
02/15/22 Pharm K. 191

Pathogenesis of Vibro
• Transmission is by the faeco-oral route. Contaminated
water plays a major role in the dissemination of
cholera, although contaminated foodstuffs and contact
carriers may contribute in epidemics.
• Achlorhydria or hypochlorhydria facilitates passage of
the cholera bacilli into the small intestine.
• Here they proliferate, elaborating an exotoxin that
produces massive secretion of isotonic fluid into the
intestinal lumen.
• Cholera toxin also releases serotonin (5-
hydroxytryptamine, 5-HT) from enterochromaffin cells
in the gut, which activates a neural secretory reflex in
the enteric nervous system.
02/15/22 Pharm K. 192

Pathogenesis of Vibro-1
• V. cholerae also produces other toxins
(zona occludens toxin (ZOT) and
accessory cholera toxin (ACT)), which
contribute to its pathogenic effect.
02/15/22 Pharm K. 193

Cellular pathologic effect
• The cholera toxin (CTX or CT) is an oligomeric
complex made up of six protein subunits:
• single copy of the A subunit (part A), and
• five copies of the B subunit (part B), connected by a
disulfide bond.
• The five B subunits form a five-membered ring that
binds to GM1 gangliosides on the surface of the
intestinal epithelium cells. The A1 portion of the A
subunit is an enzyme that ADP-ribosylates G proteins,
while the A2 chain fits into the central pore of the B
subunit ring. Upon binding, the complex is taken into
the cell via receptor-mediated endocytosis.
02/15/22 Pharm K. 194

Cellular pathologic effect Cont:
• Once inside the cell, the disulfide bond is reduced, and
the A1 subunit is freed to bind with a human partner
protein called ADP-ribosylation factor 6 (Arf6).
• Binding exposes its active site, allowing it to permanently
ribosylate the Gs alpha subunit of the
heterotrimeric G protein.
• This results in constitutive cAMP production, which in
turn leads to the secretion of water, sodium, potassium,
and bicarbonate into the lumen of the small intestine and
rapid dehydration.
• The gene encoding the cholera toxin was introduced
into V. cholerae by horizontal gene transfer. Virulent
strains of V. cholerae carry a variant of a temperate
bacteriophage called CTXφ.
02/15/22 Pharm K. 195
Clinical Presentation
• The incubation period varies from a few hours to 6 days. The
majority of patients with cholera have a mild illness that cannot be
distinguished clinically from diarrhoea due to other infective causes.
• In severe cases, there is abrupt onset of profuse painless diarrhoea,
followed by vomiting.
• As the illness progresses, the typical ‘rice water’ stool, flecked with
mucus, may be seen. There is massive fluid loss, and if this is not
replaced, the features of hypovolaemic shock (cold clammy skin,
tachycardia, hypotension and peripheral cyanosis) and dehydration
(sunken eyes, hollow cheeks and a diminished urine output) appear.
• The patient, though apathetic, is usually lucid. Muscle cramps may
be severe.
• Children may present withconvulsions owing to hypoglycaemia.
02/15/22 Pharm K. 196

Clinical Presentation Cont:
• With adequate treatment the prognosis is
good, with a gradual return to normal
clinical and biochemical parameters in 1–3
days.
02/15/22 Pharm K. 197

Risk for clinical presentation of
Vibro Cholerae
• uncontrolled diabetes,
• elevated iron levels (cirrhosis,
sickle cell disease, hemochromatosis)
• Patients with type O blood being the most
susceptible.
• cancer or
• other immunocompromised states.
02/15/22 Pharm K. 198

Non-cholera Vibrio infections
• Patients with noncholera Vibrio wound
infection or sepsis are much more ill and
frequently have other medical
conditions. Like
02/15/22 Pharm K. 199

Diagnosis
• This is largely clinical. Examination of freshly passed
stools may demonstrate rapidly motile organisms
(although this is not diagnostic, as Campylobacter
jejuni may give a similar appearance).
• A rapid dipstick test is also available.
• Stool and rectal swabs should be taken for culture to
confirm the diagnosis and to establish antibiotic
sensitivity.
• FilmArray GI Panel can detect low level V.
cholerae organism not recovered by culture.
• Cholera should always be reported to the appropriate
public health authority as a priority disease.
02/15/22 Pharm K. 200

FilmArray GI Panel
• The FilmArray GI Panel contains two
sensitive PCR assays for the detection
of V. cholerae; one targets the gyrB gene
for genus-level Vibrio identification
(focused on detection of V.
parahaemolyticus, V. vulnificus, and V.
cholerae) and the second targets
the toxR gene for specific identification
of V. cholerae.
02/15/22 Pharm K. 201
Management
• Supportive with rehydration of the patient
• Antibiotic
• Zinc
02/15/22 Pharm K. 202

02/15/22 Pharm K. 203
Prevention of V. Cholera infection
• Good hygiene and improved sanitation.
• The World Health Organization (WHO) has
prequalified three bivalent cholera vaccines:
• Dukoral (SBL Vaccines), containing a non-
toxic B-subunit of cholera toxin and providing
protection against V. cholerae O1
• ShanChol (Shantha Biotec)
• Euvichol (EuBiologics Co.), which have
bivalent O1 and O139 oral killed cholera
vaccines.[
02/15/22 Pharm K. 204

Flaviviridae
Third Year Medicine and Pharmacy
Dr Sulaiman G Conteh
02/15/22 Pharm K. 205

Properties
• Flaviviridae is a family of enveloped linear single-stranded RNA
genomes of positive polarity, which mainly infect mammals and
birds.
• They are primarily spread through arthropod vectors (mainly ticks
and mosquitoes).
• The family gets its name from the yellow fever virus; flavus is Latin
for "yellow", and yellow fever in turn was named because of its
propensity to cause jaundice in victims.
• There are 89 species in the family divided among four genera.
• Diseases associated with the group include:
• hepatitis C (hepaciviruses), hemorrhagic syndromes,
fatal mucosal disease (pestiviruses), hemorrhagic fever,
encephalitis, and the birth defect microcephaly (flaviviruses).
02/15/22 Pharm K. 206

Life Cycle
• Viral replication is cytoplasmic.
• Entry into the host cell is achieved by attachment of
the viral envelope protein E to host receptors, which
mediates clathrin-mediated endocytosis.
• Replication follows the positive-stranded RNA virus
replication model.
• Positive-stranded RNA virus transcription is the
method of transcription.
• Translation takes place by viral initiation.
• The virus exits the host cell by budding.
• Humans and mammals serve as the natural hosts.
The virus is transmitted via vectors (ticks and
mosquitoes).
02/15/22 Pharm K. 207
Genuses
• Genus Flavivirus (includes Yellow fever virus,
West Nile virus, Dengue virus, and Zika virus)
• Genus Hepacivirus (includes Hepacivirus C (
hepatitis C virus) and Hepacivirus B (GB virus B)
• Genus Pegivirus (includes Pegivirus A (GB virus
A), Pegivirus C (GB virus C), and Pegivirus B (GB
virus D))
• Genus Pestivirus (includes Pestivirus A (
bovine viral diarrhea virus 1) and Pestivirus C (
classical swine fever virus, previously hog cholera
virus)). Viruses in this genus infect nonhuman
mammals.
02/15/22 Pharm K. 208

Clinically importance Flavivirus
• Yellow fever
• Dengue fever
• Zika fever
• Hepatitis C
• Japanese encephalitis
• Kyasanur Forest disease
• Murray Valley encephalitis
• St. Louis encephalitis
• Tick-borne encephalitis
• West Nile encephalitis
02/15/22 Pharm K. 209

YELLOW FEVER
THIRD YEAR
Dr Sulaiman Conteh
02/15/22 Pharm K. 210

Yellow fever
• Yellow (slang term "Yellow Jack") is an acute
viral hemorrhagic disease. The virus is a 40
to 50 nm enveloped RNA virus with positive
sense of the Flaviviridae family.
• The yellow fever virus is transmitted by the
bite of female mosquitoes (the yellow fever
mosquito, Aedes africanus in Africa and the
Haemagogus species in South and Central
America. and other species) and is found in
tropical and subtropical areas in South
America between latitudes 15°N and 15°S
and Africa(90% of cases).
• It is not found in Asia even though the
climate condition is suitable and Aedes
mosquito is present.
02/15/22 Pharm K. 211
Transmission cont
• A. aegypti, a domestic mosquito that lives in
close relationship to humans, is responsible
for human-to-human transmission in urban
areas (urban yellow fever).
• Once infected, a mosquito remains so for
life.
• The only known hosts of the virus are
primates and several species of mosquito.
02/15/22 Pharm K. 212

Transmission cycles
There are three types of transmission cycles.
• Sylvatic (or jungle) yellow fever: In tropical

rainforests, yellow fever occurs in monkeys that
are infected by wild mosquitoes. The infected
monkeys then pass the virus to other
mosquitoes that feed on them. The infected
mosquitoes bite humans entering the forest,
resulting in occasional cases of yellow fever. The
majority of infections occur in young men
working in the forest (e.g. for logging).
02/15/22 Pharm K. 213
Transmission cycles Cont:
• Intermediate yellow fever: In humid or semi-humid
parts of Africa, small-scale epidemics occur. Semi-
domestic mosquitoes (that breed in the wild and
around households) infect both monkeys and humans.
Increased contact between people and infected
mosquitoes leads to transmission. Many separate
villages in an area can suffer cases simultaneously.
This is the most common type of outbreak in Africa. An
outbreak can become a more severe epidemic if the
infection is carried into an area populated with both
domestic mosquitoes and unvaccinated people.
02/15/22 Pharm K. 214

Transmission cycles Cont:
• Urban yellow fever: Large epidemics occur
when infected people introduce the virus
into densely populated areas with a high
number of non-immune people and Aedes
mosquitoes. Infected mosquitoes transmit
the virus from person to person.
02/15/22 Pharm K. 215

Pathogenesis
• After infection, the viruses replicate in the
lymph nodes and infect dendritic cells in
particular.
• From there they reach the liver and infect
hepatocytes (probably indirectly via Kupffer
cells), which leads to eosinophilic
degradation of these cells and to the release
of cytokines.
• Necrotic masses (Councilman bodies)
appear in the cytoplasm of hepatocytes.
02/15/22 Pharm K. 216
Complications
• Cardiovascular shock and multi organ
failure with strongly increased cytokine
levels (cytokine storm) follow.
02/15/22 Pharm K. 217

Signs and symptoms
•Yellow fever begins after an incubation
period of three to six days.
•Three phases in the severe (classical)
illness are recognized
02/15/22 Pharm K. 218

First Phase of clinical
presentation
• Initial symptoms are mostly a mild infection with fever
(39 to 40 °C),
• headache mostly retrobulbar, chills, back pain,
myalgia, althragia, loss of appetite, flushed face and
suffused conjunctivae,
• Epigastric discomfort and vomiting are present when
the illness is severe.
• Relative bradycardia (Faget's sign) is present from the
second day of illness.
• The patient then makes an apparent recovery and
feels well for several days.
• In these cases the infection lasts only three to four
days.
02/15/22 Pharm K. 219
Second phase of clinical
presentation Cont:
• In 15% of cases, however, sufferers enter
a second, toxic phase of the disease
which occur 24hrs after the initial phase
with recurring fever,
• jaundice due to liver damage,
• abdominal pain.
• Bleeding in the mouth, the eyes and in the
• gastrointestinal tract will cause
vomitus containing blood (giving the name
black vomit).
02/15/22 Pharm K. 220
Third Phase
• Coma, which is usually a result of uraemia
or haemorrhagic shock, occurs for a few
hours preceding death.
• Death occurs in 40% of severe cases
• Overall fatality rate 3%.
02/15/22 Pharm K. 221

Surviving the infection
• Surviving the infection causes life-long
immunity and normally there is no
permanent organ damage.
02/15/22 Pharm K. 222

Diagnosis
• History of travel to endemic zones and vaccination
status
• clinical diagnosis-location-Sierra Leone South East
• Reverse transcription polymerase chain reaction
where the genome of the virus is amplified.
• isolation of the virus and its growth in cell culture
using blood plasma; this can take one to four weeks
• Serologically:ELISA during the acute phase of the
disease using specific IgM against yellow fever or
an increase in specific IgG-titer (compared to an
earlier sample) can confirm yellow fever.
02/15/22 Pharm K. 223
Treatment
• No treatment-supportive
02/15/22 Pharm K. 224

Prevention
• Vaccination as well as avoidance of mosquito bites
in areas where yellow fever is endemic using good
hygiene.
• Attenuated live (stem 17D) chick embryo vaccine
• WHO recommends routine vaccinations for people
living in endemic areas between the 9th and 12th
month after birth.
• Compulsory vaccination for people coming endemic
areas-Vaccination has to be proven in a vaccination
certificate which is valid 10 days after the
vaccination and lasts for 10 years, but protection
lasts much longer than this and probably for life.
02/15/22 Pharm K. 225
Vaccine facts
Facts about the 17D-vaccine;
1 should be stored frozen or at least kept at
temperatures of not more than 58C
2 After reconstitution it should be used
immediately and any remnants discarded
within an hour.
3 A single dose of 0.5 ml given
subcutaneously provides excellent, long-
lasting immunity to 99% of vaccinees
02/15/22 Pharm K. 226
Vaccine Complications
The risk of death from yellow fever is far greater than the
risks related to the vaccine. People who should not be
vaccinated include:
• children aged less than 9 months for routine

immunization (or less than 6 months during an epidemic);
• pregnant women – except during a yellow fever outbreak
when the risk of infection is high;
• people with severe allergies to egg protein; and
• people with severe immunodeficiency due to
symptomatic HIV/AIDS or other causes, or in the
presence of a thymus disorder.
02/15/22 Pharm K. 227
Dengue fever
Third Year Medicine and

Pharmacy
02/15/22 Pharm K. 228

Introduction
• Dengue fever is a mosquito-borne tropical disease caused by
the dengue virus. arboviruses (arthropod-borne viruses).
• The dengue virus genome (genetic material) contains about
11,000 nucleotide bases, which code for the three different
types of protein molecules (C, prM and E) that form the
virus particle and seven other non-structural protein
molecules (NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5) that
are found in infected host cells only and are required for
replication of the virus.
• There are five strains of the virus, called serotypes, of which
the first four are referred to as DENV-1, DENV-2, DENV-3 and
DENV-4.
• The fifth type was announced in 2013.The distinctions
between the serotypes are based on their antigenicity.
02/15/22 Pharm K. 229
Transmission
• Dengue virus is primarily transmitted by
Aedes mosquitos, particularly A. aegypti
. These mosquitos usually live between the
latitudes of 35° North and 35° South below
an elevation of 1,000 metres (3,300 ft).
• They typically bite during the early morning
and in the evening, but they may bite and
thus spread infection at any time of day.
02/15/22 Pharm K. 230

Transmission Cont:
• Other Aedes species that transmit the disease include A. albopictus
, A. polynesiensis and A. scutellaris.
• Humans are the primary host of the virus, but it also circulates in
nonhuman primates.
• An infection can be acquired via a single bite.
• A female mosquito that takes a blood meal from a person infected
with dengue fever, during the initial 2- to 10-day febrile period,
becomes itself infected with the virus in the cells lining its gut.
• About 8–10 days later, the virus spreads to other tissues including
the mosquito's salivary glands and is subsequently released into its
saliva.
• The virus seems to have no detrimental effect on the mosquito,
which remains infected for life.
• Aedes aegypti is particularly involved, as it prefers to lay its eggs in
artificial water containers, to live in close proximity to humans, and
to feed on people rather than other vertebrates.
02/15/22 Pharm K. 231

Transmission cont:
• Dengue can also be transmitted via infected
blood products and through organ donation.
• In countries such as Singapore, where dengue is
endemic, the risk is estimated to be between 1.6
and 6 per 10,000 transfusions.
• Vertical transmission (from mother to child) during
pregnancy or at birth has been reported.
• Other person-to-person modes of transmission,
including sexual transmission, have also been
reported, but are very unusual.
02/15/22 Pharm K. 232

Predisposition to Dengue
infection
• Severe disease is more common in babies and young children, and
in contrast to many other infections, it is more common in children
who are relatively well nourished.
• Other risk factors for severe disease include female sex, high
body mass index, and viral load.
• While each serotype can cause the full spectrum of disease, virus
strain is a risk factor.
• Infection with one serotype is thought to produce lifelong immunity
to that type, but only short-term protection against the other three.
• The risk of severe disease from secondary infection increases if
someone previously exposed to serotype DENV-1 contracts
serotype DENV-2 or DENV-3, or if someone previously exposed to
DENV-3 acquires DENV-2.
• Dengue can be life-threatening in people with chronic diseases such
as diabetes and asthma.[3
02/15/22 Pharm K. 233

Predisposition to Dengue
infection Cont:
• Polymorphisms (normal variations) in particular genes
have been linked with an increased risk of severe
dengue complications. Examples include the genes
coding for the proteins TNFα, mannan-binding lectin,
CTLA4, TGFβ, DC-SIGN, PLCE1, and particular forms
of human leukocyte antigen from gene variations of
HLA-B.
• A common genetic abnormality, especially in Africans,
known as
glucose-6-phosphate dehydrogenase deficiency,
appears to increase the risk.
• Polymorphisms in the genes for the vitamin D receptor
and FcγR seem to offer protection against severe
disease in secondary dengue infection
02/15/22 Pharm K. 234
Pathogenesis
• When a mosquito carrying dengue virus bites
a person, the virus enters the skin together
with the mosquito's saliva. It binds to and
enters white blood cells, and reproduces
inside the cells while they move throughout
the body. The white blood cells respond by
producing several signaling proteins, such
as cytokines and interferons, which are
responsible for many of the symptoms, such
as the fever, the flu-like symptoms, and the
severe pains.
02/15/22 Pharm K. 235

Pathogenesis Cont:
• In severe infection, the virus production
inside the body is greatly increased, and
many more organs (such as the liver and
the bone marrow) can be affected.
• Fluid from the bloodstream leaks through
the wall of small blood vessels into body
cavities due to capillary permeability.
02/15/22 Pharm K. 236

Pathogenesis Cont:
• As a result, less blood circulates in the blood
vessels, and the blood pressure becomes so
low that it cannot supply sufficient blood to vital
organs.
• Furthermore, dysfunction of the bone marrow
due to infection of the stromal cells leads to
reduced numbers of platelets, which are
necessary for effective blood clotting; this
increases the risk of bleeding, the other major
complication of dengue fever.
02/15/22 Pharm K. 237
Classification
• The World Health Organization's 2009
classification divides dengue fever into two
groups: uncomplicated and severe.
• Severe dengue is defined as that
associated with severe bleeding, severe
organ dysfunction, or severe plasma
leakage
• while all other cases are uncomplicated.
02/15/22 Pharm K. 238

World Health Organization's
1997
• Undifferentiated fever,
• dengue fever, and
• dengue hemorrhagic fever.
02/15/22 Pharm K. 239

Dengue hemorrhagic fever
• Dengue hemorrhagic fever was subdivided
further into grades I–IV.
• Grade I is the presence only of easy
bruising or a positive tourniquet test in
someone with fever,
• grade II is the presence of spontaneous
bleeding into the skin and elsewhere,
02/15/22 Pharm K. 240

World Health Organization's 1997
cont:
• grade III is the clinical evidence of shock,
and
• grade IV is shock so severe that blood
pressure and pulse cannot be detected.
• Grades III and IV are referred to as
"dengue shock syndrome".
02/15/22 Pharm K. 241

Signs and symptoms
• The incubation period ranges from 3 to 14 days, but most
often it is 4 to 7 days.
• Typically, people infected with dengue virus are asymptomatic
(80%) or have only mild symptoms such as an uncomplicated
fever.
• Others have more severe illness (5%), and in a small
proportion it is life-threatening.
• Ttravelers returning from endemic areas are unlikely to have
dengue fever if symptoms start more than 14 days after
arriving home.
• Children often experience symptoms similar to those of the
common cold and gastroenteritis (vomiting and diarrhea) and
have a greater risk of severe complications, though initial
symptoms are generally mild but include high fever
02/15/22 Pharm K. 242

Clinical presentation
• The characteristic symptoms of dengue are
sudden-onset fever, headache (typically
located behind the eyes), muscle and joint
pains, and a rash. An alternative name for
dengue, "breakbone fever", comes from the
associated muscle and joint pains.
• The course of infection is divided into three
phases: febrile, critical, and recovery.
02/15/22 Pharm K. 243

Signs and symptoms Cont
02/15/22 Pharm K. 244

febrile phase
• The febrile phase involves high fever, potentially over 40 °C
(104 °F), and is associated with generalized pain and a
headache; this usually lasts two to seven days.
• Nausea and vomiting may also occur. A rash occurs in 50–
80% of those with symptoms in the first or second day of
symptoms as flushed skin, or later in the course of illness
(days 4–7), as a measles-like rash.[
• A rash described as "islands of white in a sea of red" has also
been observed.
• Some petechiae (small red spots that do not disappear when
the skin is pressed, which are caused by broken capillaries)
can appear at this point, as may some mild bleeding from the
mucous membranes of the mouth and nose.
• The fever itself is classically biphasic or saddleback in nature,
breaking and then returning for one or two days.
02/15/22 Pharm K. 245

critical phase
• During this period, there is leakage of plasma from the blood
vessels, typically lasting one to two days.
• This may result in fluid accumulation in the chest
and abdominal cavity as well as depletion of fluid from the
circulation and decreased blood supply to vital organs.
• There may also be organ dysfunction and severe bleeding,
typically from the gastrointestinal tract.
• Shock (dengue shock syndrome) and hemorrhage (dengue
hemorrhagic fever) occur in less than 5% of all cases of
dengue;however, those who have previously been infected
with other serotypes of dengue virus ("secondary infection")
are at an increased risk.
• This critical phase, while rare, occurs relatively more
commonly in children and young adults
02/15/22 Pharm K. 246

recovery phase
• There is resorption of the leaked fluid into the
bloodstream.
• This usually lasts two to three days. The improvement
is often striking, and can be accompanied with
severe itching and a slow heart rate.
• Another rash may occur with either
a maculopapular or a vasculitic appearance, which is
followed by peeling of the skin.
• During this stage, a fluid overload state may occur; if
it affects the brain, it may cause a reduced level of
consciousness or seizures. A feeling of fatigue may
last for weeks in adults.
02/15/22 Pharm K. 247

Associated problems
• Dengue can occasionally affect several other body
systems,either in isolation or along with the classic dengue
symptoms.
• A decreased level of consciousness occurs in 0.5–6% of
severe cases, which is attributable either to inflammation of
the brain by the virus or indirectly as a result of impairment of
vital organs, for example, the liver.
• Other neurological disorders have been reported in the
context of dengue, such as transverse myelitis and Guillain–
Barré syndrome. Infection of the heart and acute liver
failure are among the rarer complications.
• A pregnant woman who develops dengue is at higher risk
of miscarriage, low birth weight birth, and premature birth.
02/15/22 Pharm K. 248

Diagnosis-Clinical
• The diagnosis of dengue is typically made clinically, on the
basis of reported symptoms and physical examination; this
applies especially in endemic areas.
• However, early disease can be difficult to differentiate from
other viral infections.
• A probable diagnosis is based on the findings of fever plus
two of the following: nausea and vomiting, rash, generalized
pains, low white blood cell count, positive tourniquet test, or
any warning sign in someone who lives in
an endemic area. Warning signs typically occur before the
onset of severe dengue.
• The diagnosis should be considered in anyone who develops
a fever within two weeks of being in the tropics or subtropics.
02/15/22 Pharm K. 249

The tourniquet test
• The tourniquet test, which is particularly useful
in settings where no laboratory investigations
are readily available, involves the application of
a blood pressure cuff at or between
the diastolic and systolic pressure for five
minutes, followed by the counting of
any petechial hemorrhages; a higher number
makes a diagnosis of dengue more likely with
the cut off being more than 10 to 20 per
1 inch2 (6.25 cm2).
02/15/22 Pharm K. 250
Warning signs
• Worsening abdominal pain
• Ongoing vomiting
• Liver enlargement
• Mucosal bleeding
• High hematocrit with low platelets
• Lethargy or restlessness
• Serosal effusions
02/15/22 Pharm K. 251

• low white blood cell count, which may then be followed by low
platelets and metabolic acidosis.
• A moderately elevated level of aminotransferase (AST and ALT) from the
liver is commonly associated with low platelets and white blood cells.
• In severe disease, plasma leakage results in hemoconcentration (as
indicated by a rising hematocrit) and hypoalbuminemia. Pleural
effusions or ascites can be detected by physical examination when large,
but the demonstration of fluid on ultrasound may assist in the early
identification of dengue shock syndrome.
• Dengue shock syndrome is present if pulse pressure drops to ≤ 20 mm Hg
along with peripheral vascular collapse.
• Peripheral vascular collapse is determined in children via delayed capillary
refill, rapid heart rate, or cold extremities. While warning signs are an
important aspect for early detection of potential serious disease, the
evidence for any specific clinical or laboratory marker is weak.[
02/15/22 Pharm K. 252

• Virus isolation in cell cultures, nucleic acid detection by PCR,
viral antigen detection (such as for NS1) or specific antibodies
(serology).
• Virus isolation and nucleic acid detection are more accurate
than antigen detection, but these tests are not widely
available due to their greater cost.
• Detection of NS1 during the febrile phase of a primary
infection may be greater than 90% sensitive however is only
60–80% in subsequent infections.
• All tests may be negative in the early stages of the disease.
• PCR and viral antigen detection are more accurate in the first
seven days.
• In 2012 a PCR test was introduced that can run on equipment
used to diagnose influenza; this is likely to improve access to
PCR-based diagnosis.
02/15/22 Pharm K. 253

Arenaviridae: Third Year Notes DR Sulaiman Conteh

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Arenaviridae: Third Year Notes DR Sulaiman Conteh

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ARENAVIRIDAE

THIRD YEAR NOTES

THIRD YEAR NOTES

• Dengue is, at present, the most important arboviral

• The infection has spread widely from south-east

• In all major tropical areas of the world the incidence

•extensive cross-reactivity is seen with HI-test. This

•However, NT- serologic test has helped in identifying

• There are four serotypes of dengue based on

• Dengue serotypes 1,2,3,4. with all the serology tests,

• Dengue serotypes 1, 3 and 4 show a closer antigenic

• Replication is similar to Yellow fever virus.

• Dengue displays many epidemiological similarities to

• There is considerable overlap in the ecologies of

• Essentially there are three transmission cycles of

• a forest cycle in primates and involving forest species of

• an urban cycle in humans involving domesticated

• By far the most important of these three for both

• Essentially, there are two hypotheses involving

• The immunological theory of DHF/DSS is based on the

• Three elements partake in the process of antibody-mediated

PATH AND IMMUNITY

• The alternative hypothesis of Rosen (1986) and

• that is, the aftermath of infection with unusually virulent

• The majority of infections with dengue virus, based on the

• together with retroorbital pain, nausea and vomiting. Severe

• There is frequently a diffuse, discrete maculopapular

• The grave complication of DHF/DSS is governed by

• DHF and DSS % occurrence in primary infection

• It is also rare in individuals over the age of 15 years.

• Grade 1& II are similar in their presentation with

• Grade III- Circulatory failure, Grade IV- profound

• The clinical diagnosis of dengue, both the UCDF form and

• The febrile illness in Dengue is similar to many viral

• The most widely used serological test is the HI test,

• Immuno- fluorescent assays have been used successfully to

• The NT and PRNT tests are the most specific and

• Virus isolation is difficul.t

• There is, at present, no licensed dengue vaccine. Current

• Successful trials of monovalent vaccines have been reported,

• control of dengue depends on (a) surveillance to obtain early

• And (b) effective vector control.

Dr Sulaiman Gbonnie Conteh

• EEEV is capable of infecting a wide range of animals,

• Transmission of EEEV to mammals (including humans)

• Humans, horses, and most other infected

• No specific treatment or vaccine is yet available

• Health-care workers caring for patients with suspected or confirmed Ebola

• Uropathogenic E. coli (UPEC) is one of the main causes

• Enterotoxigenic E. coli (ETEC) is the most

• Enteroinvasive Escherichia coli (EIEC) causes

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