INFECTIOUS DISEASES
ABDI SOLOMON(MD)
 Generally infectious diseases result from bacteria, viruses, fungi, and
parasites.
 Infectious diseases remain a major cause of death and are responsible
for worsening the living conditions of many millions of people
 Infectious diseases often do not occur in isolated cases
 Many factors affect the likelihood of acquiring infections which
include, host, environment and microbial factors.
 Many factors affect the likelihood of acquiring infections which
include
 host
 environment
 Infectious agents.
Host factor
 Many specific host factors influence the likelihood of acquiring an
infectious disease.
 Age, immunization history, prior illnesses, level of nutrition,
pregnancy, coexisting illness, and perhaps emotional state all have
some impact on the risk of infection after exposure to a potential
pathogen.
 Defense-immunity-innate/adaptive
 Immune response:
 Is a defense mechanism developed by the host for recognizing and
responding to microorganisms.
 two major classes. Innate and Acquired Immunity.
Innate immunity (Natural Immunity) :
 Is first line of defense and serves to protect the host with out prior exposure
to the infectious agent.
 is nonspecific and has no memory.eg phagocytoses by macrophages and
nutrophils, complement system etc
 Acquired (Adaptive) Immunity:
specific immune mechanism developed against a particular
organism.takes long time to develop
It has two major arms:
.Cellular immunity: comprising T- lymphocytes, NK cells
. Humeral Immunity : comprises of B-Lymphocytes and antibodies
produced by plasma cells.
 Enviromental factors
 Factors such as geography (e.g. altitude and malaria), environment (e.g.
mosquito breeding site and malaria), disease vectors
 Cleans of the environment
 Over crowding
Infectious agent
 Viruses
 Viruses contain two types of macromolecule: proteins and nucleic acids,
the latter of only one type (either DNA or RNA).
 Bacteria
 Long known as 'prokaryotes', bacteria share the following essential
features: they contain both RNA and DNA, have facilities for protein
metabolism and are generally free living.
 Eukaryotes
 These organisms exhibit subcellular compartmentalisation with
intracellular functions being achieved by specific organelles, e.g. nucleus,
chloroplasts, mitochondria and Golgi apparatus.Fungi,Protozoa,parasites
 Incubation period:
 The incubation period is the period between the invasion of the
tissues by pathogens and the appearance of clinical features of
infection.
 The period of infectivity is the time that the patient is infectious to
others
Typhoid (Enteric) Fever
 Definition: Typhoid fever is a systemic infection caused by dissemination of
Salmonella typhi and occasionally by S. paratyphi A and B and
S.typhimarium
 non capsulated, gram negative motile and rod shaped bacteria.
 Antigens:
 H-located in the cell capsule H (flagellar antigen).
 O- (Somatic or cell wall antigen).
 Vi -(polysaccharide virulence)
“widel test”
A schematic diagram of a single Salmonella typhi cell
showing the locations of the H (flagellar), 0 (somatic), and
Vi (K envelope) antigens.
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Epidemiology
 Continues to be a global health problem
 Areas with a high incidence include Asia, Africa and
Latin America
 Affects about 6000000 people with more than 600000
deaths a year. 80% in Asia
Transmission

fecal-oral route

close contact with patients or carriers

contaminated water and food

flies and cockroaches.
13
Pathogenesis
Ingested orally
Stomach barrier (some Eliminated)
enters the small intestine
Penetrate the mucus layer
 enter mononuclear phagocytes of ileal peyer's
patches and mesenteric lymph nodes
 proliferate in mononuclear phagocytes
spread to blood. initial bacteremia (Incubation
period).
14
PATHOGENESIS
 enter spleen, liver and bone marrow (reticuloendothelial system)
further proliferation occurs
 A lot of bacteria enter blood again-(second
bacteremia).
 Recovery
15
S.Typhi.
2nd bacteremia
liver、spleen、gall、
BM ,ect
early stage&acme stage
(1-3W）
stomach
(mono
Bac. In gall
nuclea
r
phago
cytes )
Bac. In
feces
Lower
ileum
16
LN Proliferate,swell
necrosis
defervescence stage
Enterorrhagia,i
ntestinal
perforation
S.Typhi eliminated
convalvescence stage
(4-5w)
peyer's patches &
mesenteric lymph nodes
（3-4w）
thoracic
duct
1st bacteremia
(Incubation stage)
10-14d
CLINICAL MANIFESTATION
The incubation period varies from 3-60 days.
 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
Initially diarrhea or loss stole followed by constipation in adults,
diarrhea is dominate feature in children
Relative bradycardia
Splenomegally Hepatomegaly
“Rose spots”
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
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.

18

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.


fatal complication
intestinal hemorrhage(serious blding 2-8%)
 intestinal perforation (1-4%)
 severe toxemia

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LABORATORY
FINDINGS
Routine examinations:


White blood cell count is normal or decreased.
Leukocytopenia

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BACTERIOLOGICAL EXAMINATIONS:

Blood culture -mostly (up to 90%) patients have positive culture
in the 1stweek, and only 50% by the 3rdweek.

The yield is much lower if patient has taken antibiotics prior to
the test.

Stool culture is negative in the first week and becomes positive
in 75%of patients in the 3rdweek.

Urine culture parallels stool culture.
21
WIDAL TEST

"O" agglutinin antibody titer ≥1:80 and "H" ≥1:160 or "O" 4 times
higher supports a diagnosis of typhoid fever.

"O" rises alone, not "H", early of the disease.

Only "H" positive, but "O" negative, often nonspecifically elevated
by immunization or previous infections

Antibody level maybe lower when have used antibiotics early.
22

Limitations of Widal test
It is non specific and a positive test could be due to
 Infection by other salmonellae (as the antigen used for the test is also
shared by other salmonellae)
 Recent vaccination for typhoid
 Past typhoid (already treated)
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ENTERIC (TYPHOID) FEVER: TREATMENT
 Prompt
administration of appropriate antibiotic
therapy prevents severe complications of enteric
fever and results in a case-fatality rate of <1%.
 The initial choice of antibiotics depends on the
susceptibility of the S. Typhi and S. Paratyphi
strains in the area of residence or travel.
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RX…
25

1st line
• Ciprofoxacin: 500mg PO BID for 5-7days
 • Ceftriaxone 1-2 gm IM or IV for 10 -14 days


Alternative
• Azithromycine 1 gm PO daily for 5 days
 • Chloramphenicol 500 mg Po QID for 14 days
 • Norfloxacin 400mg twice daily for 10 days

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2.4 RICKETTISIAL DISEASES: (EPIDEMIC AND ENDEMIC
TYPHUS)
Rickettisiae are small intracellular bacteria that are spread to
man by arthropod vectors, namely human body lice, fleas, ticks &
larval mites.
 Epidemic Typhus (Louse born ): is caused by R.prowazekii and
transmitted by human body louse (Pediculus humanus corporis).
 Endemic Typhus (Flea born) / Murine Typhus: is cause by R.
thyphi which is transmitted by fleas.

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PATHOPHYSIOLOGY
In man rickettsia multiply in the endothelial cells of capillaries
 causing lesions in the skin, brain, lung, heart, kidneys and skeletal
muscles.
 causes thromboses and small hemorrhages.
 However, tissue and organ injury is commonly due to increased
vascular permeability with resulting edema, hypovolemia and
organ ischemia.

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
Clinical Features (epidemic typhus)





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 5thday 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 infection and eye pain
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
signs of central nervous system involvement,may occur at the end
of 1st week (meningo-encephalitis)
30

Endemic typhus (Flea borne typhus)
Endemic typhus (also known as muri ne typhus) is a relatively milder.
 The incubation period is 1 - 3 weeks and followed by sudden onset of
fever,
 rigors, frontal headache, pain in the back and limbs, constipation and
cough (due to bronchitis).
 The fever becomes constant after the third day and associated with
conjunctivitis and orbital pain.

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Laboratory investigations;
 Serologic tests:

• Indirect fluorescent antibody test
 • Weil-Felix agglutination test: nonspecific or sensitive


Isolation of the organism by inoculation into laboratory animals
32

Complications of Endemic and Epidemic Typhus






Skin necrosis, gangrene of digits,
Venous thrombosis
Interstitial pneumonia in severe cases
Myocarditis
Oliguric renal failure
Parotitis
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
Treatment of rickettsial diseases






Endemic Typhus
Doxycycline 100mg bid PO for 7-15 days
Chloramphenicol 500mg QID PO for7-15 days
Epidemic typhus
Doxycycline 200mg as single dose PO until the patient is afebrile for 24
hours.
Delousing louse borne typhus
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RELAPSING FEVER

Definition


Relapsing fever is an acute febrile illness caused by Borrelia species,
presenting with recurrence of characteristic febrile periods last ing for
days alternating with afebrile periods.
Relapsing fever describes two distinct diseases:


• Louse borne (Endemic) relapsing fever (LBRF):- transmitted by body
louse( Pediculus humanis var corporis)
• Tick borne (Epidemic) relapsing fever (TBRF)- transmitted by tick
(Ornithodoros)
35

Etiology
Relapsing fever is caused by Borrelia species, which are spirochetal gram
negative helical bacteria.
 B. recurrentis is the only species that cause LBRF
 B. duttoni is the commonest causes of TBRF in sub-Saharan Africa

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PATHOGENESIS
Portal of entry, infected lice crushed into
abraded skin.
 Incubation period, 5-10 days.
 High level spirochetemia.
 Patients’ producing neutralizing antibodies,

clearing of the circulating strain Borrelia in 3-5 days

New ANTIGENIC VARIANTS appear


.
Recurrence of clinical symptom/signs;
up to 3-5 relapses may occur
CLINICAL FEATURES
Incubation period, 5-10 days, average 7 days.
The range of clinical symptoms/ signs is wide.
 In a typical sever case there is abrupt onset of
fever, 39-40.
The following is the dominant clinical features:

CLINICAL FEATURES,
contd.
SYMPTOMS





Fever
Headaches
Arthralgia/myalgia
Dry cough
Epistaxis/gum bleeding
SIGNS







Temperature
Tachycardia
Hepatomegaly
Splenomegaly
Petichea/ Subconjunctival
bleeding
Jaundice
Confusion/Meningism
COMPLICATIONS
Congestive heart failure
 Jaundice
 Bleeding diathesis
Jarish- Herxheimer reaction:
 The first dose of appropriate antibiotic causes
transient worsening of clinical
symptoms/signs.
 Frequency, 35-100%,
 associated with increased mortality.

COMPLICATIONS
CONTD.
Physiologic change:
 chills phase,


rise in BP, pulse,and respiratory rate;

BP falls dramatically .
flush phase,
There
is a marked, but transient rise in circulating
level of :

TNF, IL-6, and IL-8 at the peak of the reaction (figure 2).
DIAGNOSIS
Demonstration of the organism; blood film.
MANAGEMENT
Aims of Management:
 Clinical cure
 Prevention of relapse
 Prevention/treatment of complications
Antibiotic treatment:
A number of antibiotics are effective:
 Anticipate the occurrence of Jarish- Herxheimer like
reaction.
 In our setting we simply start with procaine penicillin
400,000IU IM and then observe for 12 hours and repeat
blood film.
Management of complications
Supportive


treatment:
IV fluids for hypotension,
diuretics for pulmonary edema.
Prevention and control
Better housing,
reliable water supply,
good personal hygiene.
Insecticides like DDT for killing lice.
MALARIA
Defn: Is a protozoan disease transmitted by the bite of A. mosquito
 Transmission in 107 countries
 Affect 3 billion ppls worldwide


ETOLOGY
Four sp. Of the genus Plasmodium
 Others – rare

P. falciparum – malignant malaria
 P. vivax – tertian malaria
 P. ovale – Tertian malaria
 P. malariae – quartian malaria


NB: almost all deaths are caused by falciparum malaria
EPIDEMOLOGY


Is complex and varies considerably even within relatively small
geographic area
Endemicity: defined interms of parasitemia rates or palpable
spleen rates in childern 2 – 9 yrs of age as
Hypoendemic - < 10%
 Mesoendemic – 11 – 50%
 Hyperendemic – 51 – 75%
 Holoendemic - > 75%

EPIDEMOLOGY
Stable transmission – is constant frequent round infection
 Unstable transmission

transmission is low, erratic or focal
 Full protective immunity is not acquired
 Symptomatic disease occurs at all ages
 Usually occurs in hypoendemic area

EPIDEMOLOGY

Principal determinants are
The density of the vector
 Human biting habit
 Life span of A. mosquito

Common in both low and highland and epidemics is commonly
observed in highlands
 Temprature – < 16 -18 oc sporogony is inhibted

stable
unstable
Mosquito life
long
short
Mosquito bites
frequent
rare
Human immunity
high
low
epidemics
No
yes
Eradication/ control
difficult
possible
TRANSMISSION
Is by the bite of mosquito(female anophilous)
 Transfusion malaria – blood transfusion, needle stick injury,
sharing of needles, organ transplantation

Incubation Period – short (no preerritrocitic cycle)
 c\f & mgt-same

LIFE CYCLE AND PATHOGENSIS
Divided into asexual and sexual
 sexual - Occurs inside a mosquito(definitive host)
 Asexual – it occurs in human body
 Two phases
 exoerytrocytic
 erytrocytic
 Life cycle (fig)

HOST RESPONSE




Activated nonspecific defense mechanism
Because of rapture of erythrocytes and release of parasites –
activation of the microphage and release of proitory mononuclear
cell derived cytokines causes fever (> 40 oc)
Sickle cell disease – decreased risk of infection (six fold)
Impaired parasite growth at low oxygen tension
CLINICAL FEATURE

IP






18 days to six weeks (P. malarae)
10 to 14 day (others)
Types and clinical features (tab)
None specific symptoms followed by fever N\V.
Febrile paroxysms – have three stages
Cold stage :
patient feels cold and has shivering
 Lasts for 30’ to 1 hr
 Characterized by vasoconstriction of vessels and rapid rise temperature

CLINICAL …

Hot stage
Patient feels hot and uncomofortable
 Become delirious, lasts 2 – 6 hrs


Sweating stage


Physical Examination


Will have profuse sweating and become very much exhausted
Uncomplicated – fever, mild anemia, palpable spleen and liver
Severe and complicated malaria (tab)
CHRONIC COMPLICATIONS




Tropical spleenomegally
syndrome(HSM)
It’s a syndrome resulting from unabnormal immunologic response
to repeated infection
Seen in some residents of endemic area (Tropical Africa and Asia)
Characterized by





Huge spleen (> 10 cm BLCM) with/out HM
Hyperspleenism (anemia and pancytopenia)
Marked elevation of serum IGM and antimalarial antibody
Hepatic sinusoidal lymphocytes
Peripheral B cell lyphocytosis
TSM

C/F: abdominal mass or drugging sensation in LUQ




•
Abdominal pain
Patients are vulnerable to respiratory and skin infection and die of
overwelming sepsis due to pancytopenia
Parasite may not be detected and
May evolve to malignant disorder
Rx:




Prophlaxes for long time usually for duration of exposure
Commonly used are Chloroquin and myphyloquin
Enlarged spleen and liver will regresss with effective prophylaxes
Spleneoctomy is only indicated for these with failure of anti-malarial prophylaxes
atleast given for six month
DIAGNOSIS
Peripheral blood film – Giemsa/wright’s stain
 Thin and thick film
 Thin film

Rapidly air dried
 Fixed in anhyderous methanol and stained
 Intact RBCs could be seen

Advantage
 spicious identification is simple
 Percent of RBC parasitized can be estimated

DIAGN….

Thick blood film
Dried throughly and stained without fixing
 Many RBCs lyzed during procedure







Advantage
Concentrates RBC (40 to 100 fold)
Helps to determine parasite concentration
NB – single BF doesn’t rule out malaria
Preferably done during febrile episoides
If and if blood smear negative in endemic araes repeat at least
every 12 to 24 hrs for 2 days
DIAGN…

Other IX:
cbc
 Blood glucose
 LP and CSF analysis (on indication)
 BUN/CR, LFT

TX

A. Benign forms of malaria (Plasmodium malariae, vivax, ovale):
Chloroquine is effective
 Dose: Initial dose is 600 mg PO followed by 300mg after 6, 24 and 48 h
subsequently.


Treatment of uncomplicated falciparum malaria

A)Artemether-Lumefantrine: (Coartem 20/120):
Adult Dosage: < 35 kg: 3 tabs PO BID for 3 days

> 35 Kg: 4 tabs PO BID for 3 days


B)Quinine:


Adult dose : 600 mg PO TID for 5 – 7 days alone or in combination with +
Tetracycline 500 mg PO QID or Doxycycline 100mg PO /day for the same period
other option mefloquine& fansidar
TREATMENT OF SEVERE AND COMPLICATED FALCIPARUM
MALARIA:
Admit patient
 i) Quinine : is drug of choice for severe and complicated malaria.
 Dosage and Adminstration:
 Where IV administration of quinine is possible
 Loading dose: Quinine 20 mg salt/kg of body weight by infusion
over 4 hours, in 5 % dextrose in saline (5-10 ml/kg of body weight
depending on the patient's overall fluid balance).
 Maintenance does: Twelve hours after the start of the loading dose,
give quinine 10 mg
 salt/kg of body weight in dextrose saline over 4 hours. Repeat the
same dose of quinine until pt is able to take orally.

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







ii) Artesunate injection (if available) : 2.4 mg/kg IV or IM stat followed
by 1.2 mg/kg at 12 and 24 hrs and then daily.
B) Supportive treatment:
• Bring down fever (cold sponges, paracetamol)
• Administer glucose IV or PO to prevent hypoglycaemia and encourage
early PO intake of food
• Ensure adequate fluid intake, check input and output and control
water and electrolyte balance (beware of pulmonary edema due to fluid
overload).
• Consider transfusion in severe falciparum malaria with high
parasitemia (> 20% of erythrocytes affected by plasmodium)
• Check renal function tests and blood sugar (beware of hypoglycemia).
• For comatose or unconscious patients proper nursing care mandatory
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