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Epidemiology:
Human beings are the only hosts for S. typhi and
S.paratyphi. Thus enteric fever is transmitted only
thorough close contact with acutely infected
individuals or chronic carriers through ingestion of
contaminated food or water.
Chronic carriers are the source of infection
harboring the organisms in their gall bladder
(especially in the presence of gall stones) and rarely
at other sites. It affects people of all ages and both
sexes. Enteric fever is endemic in most developing
countries.
Currently the disease is observed at a great
frequency in AIDS patients than the general population.
Pathogenesis:
Following ingestion of the organism in contaminated
food or drink, Salmonella typhi passes the gastric
barrier and reach the upper small intestine where the
bacilli invade the intestinal epithelium and they are
engulfed by phagosome which reside in the Peyers
patches. The bacilli multiply and enter the blood
Clinical Manifestation:
The incubation period varies from 3-60 days. The
manifestation is dependent on inoculums size, state of
host defense and the duration of the disease. The
Severity of the illness may range from mild, brief
illness to acute, severe disease with central nervous
system involvement and death.
First week;
Fever is high grade, with a daily increase in a
step-ladder pattern for the 1st one week and then
becomes persistent.
Headache , malaise , Abdominal pain
Second week;
Fever becomes continuous
The patient becomes very ill and withdrawn confused,
delirious and sometimes may be even comatose.
Third Week;
The patient goes to a pattern of typhoidal state"
characterized by extreme toxemia, disorientation, and
pea-soup diarrhea and sometimes may be complicated by
intestinal perforation and hemorrhage.
Fourth Week;
Fever starts to decrease and the patient may
deferveresce with resolution of symptoms. At this
point patient may lose weight.
Relapse may occur in 10% of cases.
Chronic Carriers:
Approximately 1- 5 % of patient with Enteric fever
become asymptomatic chronic carriers
They shed S.typhi in either urine or stool for
year
> 1
Diagnosis:
Treatment:
Antibiotic therapy is curative. These drugs can be
given either orally or intravenous, depending on
patient condition (able to take orally or not),
severity of the disease. One should note that fever may
persist for 4-6 days despite effective antibiotic
treatment .
Oral drugs:
First Line;
Nowadays 4-amino quinolones are the drugs of choice
because of their effectiveness on multidrug resistant
typhoid, and low relapse and carrier rates.
Ciprofloxacin, norfloxacin, ofloxacin, and pefloxacin
are all equally effective.
Ciprofloxacin: 500mg PO BID for 10 days
Ceftriaxone 1-2 gm IM or IV for 10 -14 days 4- amino
quinolones are not recommended for use in children and
pregnant women because of their observed potential
Alternatives;
Azithromycin
Chloramphenicol
Prevention and
control:
PHARMACOLOGY (TUESDAY)
Cell membrane phospholipids:
cellular infiltration
iii. Inspissations in the airway lumen of abnormally
thick, viscid plugs of excessive mucus.
PHARMACOTHERAPY OF BRONCHIAL ASTHMA
Drug used in the treatment of bronchial asthma can be
grouped into three main categories:
1. Bronchodilators
a. Adrenergic agonists which include: Non selective
agonists e.g. adrenaline, Selective agonists e.g.
salbutamol
b. Methylxanthines; theophylline derivatives
c. Muscranic receptor antagonists e.g. Ipratropium
bromide
2.Mast cell stabilizers, e.g. cromolyn sodium,
nedocromil, ketotifen
3.Antinflammatory agents: corticosteroids
1.ADRENERGIC AGONISTS (SYMPATHOMIMETIC AGENTS)
(a) Non- selective agonists - Epinephrine, ephedrine,
isoprotenerol
(b). Selective agonists - Salbutamol, terbutaline,
metaproterenol, salmeterol, formaterol and etc
Mechanism of Action:
?Agonists stimulate adenyl cyclase and increase
formation of cAMP in the airway tissues. They have got
several pharmacological actions important in the
treatment of asthma. Relax smooth muscles. Inhibit
release of inflammatory mediator or broncho
constricting substances from mast cells. Inhibit
microvasculature leakage Increase mucociliary transport
a. Non-selective ?agonists: Cause more cardiac
stimulation,they should be reserved for special
situation.
Epinephrine: very effective, rapidly acting
2. METHYLXANTHINES
The three important methylxanthines are theophylline,
theobromine, and caffeine. The theophylline
preparations most commonly used for therapeutic
purposes is aminophylline (theophylline plus
diethylamine).
Mechanism of Action
i. Competitively inhibit phosphodiesterase (PDE) enzyme
leading to increased cAMP level.
ii. They competitively inhibit the action of adenosine
on adenosine (A1 and A2) receptors (adenosine has been
shown to cause contraction of isolated airway smooth
muscle and to provoke histamine release from airway
mast cells.
iii. Inhibit the release of histamines and leukotriens
from the mast cells Of the three natural xanthines,
agents theophylline is most selective in its smooth
muscle effect, while caffeine has the most marked
central effect.
Pharmacokinetics
Only slightly soluble in water so has been administered
as several salts containing varying amounts of
theophylline base. Most preparations are well absorbed
from gastro intestinal tract and metabolized by liver.
Doses should be decreased in cases of liver disease and
heart failure.
Adverse Effects: Anorexia, nausea vomiting, abdominal
discomfort, headache, anxiety, insomnia, seizures,
arrhythmias.
Theophylline is now largely reserved for patients in
whom symptoms remain poorly controlled despite the
combination of regular treatment with an inhaled antiinflammatory agent and as needed use of a agonist.
3. MUSCRANIC RECEPTOR ANTAGONISTS
Mechanism of Action: Muscarinic antagonist
or an IV administration.
Because of severe adverse effects when given
chronically, oral and parenteral corticosteroids are
reserved for patient who need urgent treatment and
those who have not improved with
Bronchodilator:Aerosol treatment is the most effective
way to decrease the systemic adverse effect of
corticosteroid therapy. Abrupt discontinuation should
be discouraged because of the fear of adrenal
insufficiency. Doses should be decreased after
improvement. Regular or controlled therapy is better
maintained with aerosol corticosteroids.
Clinical uses in bronchial asthma: Urgent treatment of
severe asthma not improved with bronchodilator;IV,
inhalation or oral.
Side effects: Suppression of the hypothalamicpituitary-adrenal axis . Sodium retention and
hypertension. Cataract. Impairment of growth in
children Susceptibility to infection like oral
candidiasis and tuberculosis.
5. MAST CELL STABILIZERS
e.g cromolyn sodium.
Mechanism of action: Stabilize the mast cells so that
release of histamine and other mediators is inhibited
through alteration in the function of delayed chloride
channel in cell membrane. It has no role once mediator
is released and is used for casual prophylaxis.
Clinical uses; Exercise and antigen induced asthma.
Side effects; Poorly absorbed so minimal side effect.
Throat irritation, cough, dryness of mouth, chest
tightness and wheezing.
ADULT HEALTH (WEDNESDAY)
Relapsing Fever:
Definition: Relapsing fever is an acute febrile
illness caused by Borrelia species, presenting with
recurrence of characteristic febrile periods lasting
for days alternating with afebrile periods.
Transmission:
LBRF: Body lice become infected by B. recurrentis while
feeding on spirochetemic human blood, the only
reservoir of infection. Humans acquire infection when
infected body lice are crushed and their fluids
contaminate mucous membrane or breaks in the skin (such
as abrasions caused by scratching of pruritic louse
Pathophysiology:
In humans, Borrelia after entering the body multiply
in the blood and circulate in great number during
febrile periods. They are also found in the spleen,
liver, central nervous system, bone marrow, and may be
sequestered in these organs during periods of
remission. Severity is related to spirochetal density
in blood but systemic manifestations are related to
release of various cytokines.
The disease is characterized by sub capsular and
parenchymal hemorrhage with infarcts of spleen, liver,
heart and brain is seen. Thus, patients will have
enlarged spleen and liver with variable edema and
swelling of brain, lung and kidneys. Relapsing fever in
pregnancy can result abortion, still birth and fatal
neonatal infection Death from TBRF is rare. In contrast
fatality rate of LBRF may reach up to 20 % during out
Clinical Features:
The manifestation of both LBRF and TBRF are similar.
Incubation period is 7 days (ranging from 2-18 days).
The onset is sudden with high grade irregular fever,
headache, chills, myalgias, arthralgias, and insomnia.
Patient will be withdrawn, disinterested to food and
other stimuli and thirsty. Patient will have delirium
associated with high grade fever, tachycardia and dry
tongue, injected conjunctiva and photophobia
Summation gallop , occasionally resulting from
myocardial involvement
Upper abdominal tenderness with hepatosplenomegally,
Scattered petechiae over the trunk, extremities and
mucous membrane in 1/3 LBRF and fewer TBRF
Symptoms and signs of meningeal irritation may be
seen in some patients.
Icteric sclera may be found in late stage of the
disease.
LBRF
B. recurrentis
Parasite in
the vector
Found in
endolymph of lice
Transmission
Contamination of
mucous membrane
or breaks or
abrasions on the
skin by body
fluids of lice,
released during
crushing
- Not transmitted
by the bite of
lice or
inoculation of
louse feces
No
Vertical
transmission
(TransOvarian)
TBRF
B. duttoni + many
others(all zoonotic)
Found in all tissues,
including salivary
glands & ovaries
By bite of tick
during blood meal
(organisms in the
saliva & coaxal fluid
of Borrelia)
Yes
Distribution
East Africa
Occurrence
Epidemics are
frequent in
homeless people
living in
unhygienic
crowded condition
Short life span
Vector
longevity
Jarisch
Herxheimer
Reaction
Eradication
Sub-Saharan Africa,
Mediterranean
littoral, middle
east, Russia, India,
China, USA
Sporadic or in small
often familial
clusters
More severe
Less severe
Easy
Diagnosis:
Diagnosis of relapsing fever is made based on
demonstration of the organisms in blood, bone marrow,
CSF etc Blood Film:
Giemsa or Wright stained peripheral blood smear is an
ideal test in the resource limited setting.
Spiral organisms can be demonstrated on peripheral
blood taken during febrile period preceding the crisis.
Other Tests:
Dark field microscopy of unstained blood/CSF
Serologic tests.
Treatment:
Relapsing fever is treated with antibiotics. In LBRF
single dose of erythromycin, tetracycline, doxycycline
or chloramphenicol, produces rapid clearance of
Borrelia from the blood & remission of symptoms. TBRF
is less sensitive to these antibiotics and requires a 7
days course of treatment.
Adult Dosage:
Medication
(Oral)
Erythromycin
Tetracycline
Doxycycline
LBRF (single
dose)
500mg
500mg
100mg
TBRF (7 days
schedule)
500mg every 6 hrs
500mg every 6 hrs
100mg every 12
hrs
Chloramphenicol
Parenteral:
Penicillin G
(procaine)
500mg
600,000 I.M
stat
accompanied by
Flush phase:
Fall in body temperature, drenching sweating,
Potential dangerous fall in Systemic blood pressure
( as peripheral vascular resistance falls )
Clinical and ECG evidence of myocarditis may be
seen , S3 gallop and prolonged QT interval
Vital signs must be monitored closely during this
time which usually lasts for <or = 8 hrs.
Treatment of JHR:
Close monitoring of vital signs
PHARMACOLOGY (THURSDAY)
ANTI-TUSSIVES
DEXTROMETROPHAN
Dextromethorphan is an opoid synthetic antitussive,
essentially free of analgesic and addictive properties
and the main side effects are respiratory depression.
Expectorants are drugs that removes thick tenacious
mucus from respiratory passages, e.g. Ipecac alkaloid,
sodium citrate, saline expectorant, guanfenesin,
potassium salts Mucolytics are agents that liquefy
mucus and facilitate expectoration, e.g.acetylcysteine.
DECONGESTANTS
Decongestants are the drugs that reduce congestion of
nasal passages, which in turn open clogged nasal
passages and enhances drainages of the sinuses.
Clinical uses: Used in congestion associated with
rhinitis, hay fever, allergic rhinitis and to a lesser
extent common cold. Drugs can be administered nasally
Rickettsial diseases
Definition: Rickettsiae are small intracellular
bacteria that are spread to man by arthropod vectors,
namely human body lice, fleas, ticks & larval mites.
The organisms inhabit the gastrointestinal tract of
these arthropods & spread to human host by the direct
bite of the vector or the inoculation of the organism
contained in the feces of the vector by bite induced
body itching. These infections are characterized by
persistence in the body, widespread vasculitis
(invading endothelial cells of small blood vessels) &
multi-system involvement. Except in louse borne typhus
humans are accidental hosts in most rickettsial
diseases.
Classification:
Rickettsial diseases are classified into five general
groups;
Tick
Pathophysiology:
In man rickettsiae multiply in the endothelial cells
of capillaries causing lesions in the skin, brain,
lung, heart, kidneys and skeletal muscles. Endothelial
proliferation coupled with peri-vascular reaction
causes thromboses and small hemorrhages. However,
tissue and organ injury is commonly due to increased
vascular permeability with resulting edema, hypovolemia
and organ ischemia. This leads to multi-system
involvement with complications such as non-cardiogenic
pulmonary edema, cardiac dysrhythemia, encephalitis,
renal and hepatic failure and bleeding.
Clinical Features:
Signs and symptoms;
Incubation period of 1 week
Abrupt onset of illness with prostration, severe
headache and rapidly rising fever of 38.8 to 40.0 C
Cough s seen in 70 % of patients , myalgia may also
occur which may be severe Rash, begins on upper trunk
around 5th day and then becomes generalized, involving
the entire body except face, palms and soles; at first,
rash is macular, becoming maculopapular, petechial and
confluent without treatment, although in black people,
rash may be absent (spotless epidemic typhus)
Photophobia, with conjunctival injection and eye
pain; frequent
Tongue may be dry, brown, furred
The signs of central nervous system involvement,
commonly as meningo-encephalitis, appear towards the
end of the 1st week progressing to seizure and coma.
Laboratory investigations:
Serologic tests;
Epidemic typhus;
*Doxycycline 200mg as single dose
patient is afebrile for 24 hours.
PO until the
Prognosis:
Untreated disease is fatal in 7 to 40 % of cases,
depending on condition of host. In untreated survivors,
renal insufficiency, multiorgan involvement and
neurologic manifestations (12 %) are common. However,
endemic typhus has better prognosis with a mortality of
only 1 2%. Serious neurological, renal and other
complications are unusual.