Acute Febrile illness(AFI)

Hansa H.(MD)
 Fever

Defn: elevation in body temp that exceeds the normal daily

variation and occurs in conjunction with an increase in the
hypothalamic set point
Fever and Hyperthermia ??
• Body temperature fluctuates in a defined normal range (36.5-
37.9°C rectally)….Axillary temperature lowers by 0.5°C
• With The highest point is reached in early evening and the
lowest in the morning.
• Fever is defined as a rectal temperature ≥38°C( if it is axillary
> 37.5 °C considered as fever)
Characteristics
Incubation period
Pattern
Duration
Associated symptoms and signs
 Incubation period

-Short <10 days

-Bacillary dysentery, Rickettsia infections, RF, Plague
-Intermediate: 10-21 days
-Typhoid, Malaria, Typhus, HIV, Brucellosis
-Long: >21 days
-Viral hepatitis, Malaria, Amebic liver abscess, VL
 Pattern

• Intermittent fever-is an exaggerated circadian rhythm that

includes a period of normal temperatures on most days;
extremely wide fluctuations may be termed septic or hectic
fever.
• Sustained fever- is persistent and does not vary by more than
0.5°C /day
• Remittent fever- is persistent and varies by more than
0.5°C /day.
• Relapsing fever- is characterized by febrile periods that are
separated by intervals of normal temperature for days
• tertian fever- occurs on the 1st and 3rd days (malaria caused
by Plasmodium vivax)
• quartan fever- occurs on the 1st and 4th days (malaria caused
by Plasmodium malariae).
• periodic fever -is used narrowly fever syndromes with a
regular periodicity (cyclic neutropenia)
 Duration

 Acute : <2 weeks

-Typhoid, Malaria, Meningitis, RF, Typhus
 -Chronic fever: > 2 weeks
-Tb, VL, Brucellosis, HIV
 AFI?

• Def: An acute onset of fever lasting for less than 2 weeks and
no cause found after full history and physical examination,
needs disease specific investigation for diagnosis.
• It is also called acute undifferentiated febrile
illness.
-Meningitis(bacterial)
-Relapsing Fever
-Malaria
-Typhoid fever
 Bacterial meningitis

• Acute &diffuse bacterial infection of the CNS with primary

involvement of the meninges
• Etiology
● Pathogen is influenced by :
-Age of the host
-Immune status of the host
-Epidemiology of the pathogen
1) Based on the age
a)First 2-3 month
-Gram negative, Group B-streptococus
- Listeria Monocytogenes
-Group D streptococci (Enterococcus)
-Beyond 1 month of age
-Streptococcus pneumoniae
- Neisseria meningitidis
b) 2 month - 12 years
-N. Meningitidis…..the most commo
-S. Pneumoniae -In those with incomplete vaccination and
developing countries
-H.. influenza type B
2) Based on the host immunity status
- ( anatomic defect or immune deficits) less common
pathogens can cause meningitis
-P. aeruginosa ,
-S. aureus , CONS ,
-Salmonella spp. , L.monocytogenes
3) Epidemiology of the pathogen
-N.menegitidis is the most common cause of epidemics
(With serotype A the most common)
 Risk factors

• Young age due to Lack of immunity to specific

pathogens
-95% of cases occur between 1 month – 5 yrs of age .
• Recent colonization with pathogenic bacteria
• Close contact
• Black race
• Male sex
• Crowded living conditions
• Poverty
• Splenic dysfunction….capsulated MOS( N.M,
H.Influenza, S.P)
CSF leak ( congenital or acquired )……Pneumococcal
meningitis
T-lymphocyte defects ( congenital or acquired )
- Listeria Monocytogenes
Lumbosacral dermal sinus and meningomyelocele
- Staphylococcal and gram negative enteric bacterial
meningitis
CSF shunt infections
- Staphylococci (especially CONS)
- Low virulence bacteria that colonize the skin
 Pathology and Pathophysiology

• A meningeal purulent exudate of varying thickness may be

distributed around
-the cerebral veins
- venous sinuses
-convexity of the brain, and cerebellum
- in the sulci, sylvian fissures, basal cisterns, and S. cord.
• Ventriculitis with bacteria and inflammatory cells in
ventricular fluid may be present (more often in neonates), as
may subdural effusions and, rarely, empyema.
• Vascular and parenchymal cerebral changes
- vasculitis,
-thrombosis of small cortical veins
-occlusion of major venous sinuses
-necrotizing arteriti producing subarachnoid hemorrhage
• Cerebral infarction, resulting from vascular occlusion because of-
-Inflammation
-vasospasm
- thrombosis
N.B-Infarct size ranges from microscopic to involvement of an entire
hemisphere.
• Inflammation of spinal nerves and roots produces meningeal
signs
• Inflammation of the cranial nerves produces -cranial
neuropathies-CN-2,3,7,8
• Increased intracranial pressure (ICP) also produces CN-3 palsy
and CN-6
• Increased ICP
-Cytotoxic cerebral edema-cell death
-Vasogenic cerebral edema-cytokine-induced increased
capillary vascular permeability
-Interstitial cerebral edema-increased hydrostatic pressure
after obstruction of reabsorption of CSF in the arachnoid villus or
obstruction of the flow of fluid from the ventricles.
• Hydrocephalus
 communicating
• It is due to inflammation associated with adhesive thickening
of the arachnoid villi and the cisterns at the base of the brain.
 obstructive (non-communicating)
• After fibrosis and gliosis of the aqueduct of Sylvius or the
foramina of Magendie and Luschka
 Pathogenesis

 Hematogenous dissemination-common
- Bacteremia- precedes the meningitis or concomitantly (with
the usual sources of Bacterial colonization of the nasopharynx
with a potentially pathogenic MOS.
 Contiguous focus of infection (E.g- Para nasal sinusitis, otitis
media, mastoiditis, orbital cellulitis, or cranial or vertebral
osteomyelitis)
 Clinical manifastations

Two patterns of onset :

a ) Dramatic onset ( fulminant )-less common
• Shock , purpura ,DIC ,reduced level of consciousness,
death with in 24 hour.
b )Gradual onset or sub acute (more common )
• Meningitis is preceded by several days of fever
accompanied by URT or GI symptoms
-followed by nonspecific signs of CNS
infection like increased lethargy &
irritability
 • Non-specific findings
fever ,anorexia ,poor feeding ,symptoms of URTI,
myalgia , arthralgia , tachycardia, hypotension,
petechial , purpura , erythematous macular rash

• Signs of meningeal irritation

- Back pain ,neck stiffness , kerning sign,
brudzinski sign.
• Papilledema , photophobia
• Focal neurologic signs (10-20%)
• Cranial neuropathies
 Symptoms and Signs of Increased ICP
-Head ache, Emesis, bulging fontanel, sutural diathesis
-CN-3, CN-6 palsy
-Cushing triad-HTN
-Bradycardia Late sign of Inc. ICP
-Respiratory depression
-Alteration of mental status (Stupor, Coma)
-Decerebrate or decorticate posturing
 Seizures-(20 -30 % )
 DIAGNOSIS

• Clinical suspicion
• CBC
• ESR, C-reactive proteins
• Blood culture is +ve in 80-90%
• CSF analysis…..
1) Lumbar puncture
• Between L3 & L4 or L4 & L5
• CSF
– Pressure …..usually elevated to 100-300 mmH2O ( Nl =50-80
mmH2O )
– Gross appearance……turbid (WBC >200-400 /mm3)
– WBC count (Nl =less than 5, lymphocyte > 75% or monocytes )
» Usually elevated to >1000/mm3 (>100 – 10,000/mm3 )
» In 20 % of cases WBC < 250/mm3
» Neutrophil predominance ( 75- 95% )
» Pleocytosis with lymphocyte predominance…….during
-early stages(first 8-24 hrs)….
-Partialy treated menegitis
– Elevated protein …usually 100-500 mg/dl (N-20 - 45 mg/dl )
 – Reduced glucose….usually <40 mg/dl (or <50% of serum
glucose ) ( Nl =>50mg/dl or 75 %of serum glucose )
– Gram stain : positive in 70-90 % of cases
– Culture :positive in 80-90 %
2) Latex particle agglutination
- Highly sensitive but less specific
3) Countercurrent immuno electrophoresis (CIE)
-Rapid & very specific
• Gram-positive diplococci suggest pneumococcal
infection ( picture 1 )
• Gram-negative diplococci suggest meningococcal
infection ( picture 2 )
• Small pleomorphic gram-negative coccobacilli
suggest Haemophilus influenzae infection ( 
image 1 )
• Gram-positive rods and coccobacilli suggest
listerial infection ( p
 Contraindications for LP

- Increased ICP
- Sever cardiopulmonary compromise
- Infection of the skin overlying the site of the LP
-Thrombocytopenia( < 20,000/mm3 )
 TREATMENT

 Fluid Management
 Mx of complications
-Seizure
-ICP
-SIADH…other complications
 Antibiotics
 Steroid
 fluid management

• Restrict to 1/3-2/3 till ICP and/ or SIDH is R/o

• If there is shock/hypotension-aggressively managed with
fluid.
• Septic shock add vasoactive agents….if patient is having fluid
refractory hypotension
• ICP MX
-Elevate the head
-Fluid restriction
-Mannitol (preferred) or furosemide
Seizure Mx
-Monitor serum glucose ,Na ,Ca
-IV diazepam or lorazepam
-Phenytoin 15 -20 mg/Kg loading dose ,then 5 mg /Kg /24 hr
maintenance dose
Or
Phenobarbitone 20 mg /Kg IV loading dose, then 5 mg/Kg /24 hr
maintenance dose
Corticosteroids
 Use above 6 weeks of age
 Dexamethasone 0.15 mg/Kg/dose every 6 hrs for 2 days
 Maximum benefit if given 1-2 hours before antibiotics are
initiated
 Limit inflammatory mediators that worsen neurologic injury
and CNS symptoms & signs
• Antibiotics
 Always use high dose ,parenteral (IV) antibiotics
 Initial (empirical )choice of therapy
-Vancomycin 60 mg/kg/24 hr, given every 6 hr
-Ceftriaxone 100 mg /Kg /24 day for 7 – 10 days
-Cefotaxime 200 mg /Kg /24 hr every 6 hr for 7- 10 days
 If patient is immuno compromised
-Ceftazidime or aminoglycoside need to be included
because of risk of gram –ve bacterial meningitis
e.g. P.aeruginosa ,E .coli
 PRACTICE IN ETHIOPIA
Crystalline Na penicillin 250,000 IU /Kg IV stat…..loading dose,
then, 500,000 IU /Kg/24hr in 8 divided doses
and
CAF 50 mg/Kg IV stat ..loading dose then, 100 mg /Kg /24 hrs.
in 4 divided doses for 10 days
OR
Ceftriaxone 50 mg /Kg /dose every 12 hrs. for 7- 10 days
 N.B
Duration of Antibiotics depends on
1-Age of the patient
2-Etiologic agent
Age of the patient ( with out etiologic diagnosis)
-Neonates ……..03 weeks
-Older children 10-14 days
• 1) Etiology agent
-N .meningitidis…….5 -7 days
-H .influenzae type b……….7 10 days
-S .Pneumoniae………..10-14 days
-CSF culture –ve………7- 10 days
-Gram –ve bacilli……03 weeks or 2 weeks after CSF
sterilization
 COMPLICATIONS

Acute
– Seizures
– Increased ICP
– Cranial nerve palsies
– Stroke
– Cerebral or cerebellar herniation
– Thrombosis of the dural venous sinuses
– Subdural effusions
– Hydrocephalus
– Shock ,DIC
– Symmetric peripheral gangrene
-sever hypotension + End toxemia + On going thrombosis
• Chronic
-Sensor neural Hearing loss(S.P-30%,H.I-5-20%,N.M-10%)
-Visual impairment
-Behavioral problems
-Mental retardation
-Epilepsy
-Delay in acquisition of language
 OUTCOME

 Mortality …< 10 % with antibiotic therapy and supportive

care
 Sever neurodevelopmental sequalae …10 -20 % of cases
 Neurobehavioral morbidity ….50 % of cases
POOR PROGNOSTIC FACTORS
• Pneumococcal meningitis
• Age < 6 months
• >106 colony – forming units of bacteria / ml of CSF
• Seizure occurring after 4days of therapy
• Coma or focal neurological signs on presentation
• Absence of pleocytosis in CSF analysis
 PREVENTION

• Vaccination
• Chemoprophylaxis
-Antibiotic prophylaxis of susceptible at-risk contacts
 Relapsing Fever
• As the name implies, relapsing fever is characterized by
recurrent episodes of fever, which accompanies
spirochetemia.
• The disease relapses are due to antigenic variation by the
spirochetes.
• Caused by spirochetes of the Borrelia genus, is an arthropod-
borne infection
 Risk factors

 Overcrowding, impoverishment, unhygienic condition

 Prisoners, war, famine
 Cool, rainy season
 Close contacts
 Accidental needle prick
 Pathogenesis

 Relapsing fever is cyclical because the Borrelia organisms

undergo antigenic (phase) variation
 Spirochetes isolated during the primary febrile episode differs
antigenically from those recovered during a subsequent relapse.
 Two phase
-Multiplication in blood- (febrile period)
-Sequestration at liver, spleen, BM & CNS- (remission)
 Activation of mediators of inflammation
-Hageman factor, complement system
-Cytokines: IL-6, IL-8, CRP, TNF-responsible for JHR
 Clinical presentation

 RF is characterized by febrile episodes lasting 2-9 days,

separated by afebrile intervals of 2-7 days.
-Sudden high grade fever(>40 )
- Chills, rigor, sweats, myalgia, arthralgia
-Delirium, prostration, photophobia
-Pneumonia, myocarditis
-Meningismus
-Abdominal pain, a productive cough, mild respiratory distress
and bleeding manifestations
-Diffuse, erythematous, macular, or petechial rash lasting up to 2
days may develop over the trunk and shoulders.
-Icterus, petechial in 1/3 of patients
-Tender Hepatosplenomegaly
-DIC, hepatic failure
 The initial symptomatic period characteristically ends with a
crisis in 2-9 days, marked by
- Abrupt diaphoresis,
- Hypothermia, hypotension,
- Bradycardia, profound muscle weakness, and prostration.
 In untreated patients, the first relapse occurs within 1 wk,
followed by usually 3 but up to 10 relapses, with symptoms
during each relapse becoming milder and shorter as the
afebrile remission period lengthens.
• There are two forms of RF
-Louse born(epidemics)
-Tick born(Endemic)
Differences b/n Tick(endemic) and louse(epidemics) Relapsing fever)
Epidemics(Louse) Epedemic(tick)
IP 2-14 days, 7 days (range: 2-9
days)
Period of pyrexia long Short
Number of relapse few Frequent
Remission period long short
Vector Human peduculosis tick
Mechanism of Human occurs as a result of When saliva, coxal fluid, or
infection crushing lice during excrement is released by the
scratching, facilitating entry tick during feeding,
of infected hemolymph thereby permitting
through abraded or normal spirochetes to penetrate the
skin or mucous membranes skin and mucous
membranes.
Neurologic manifestations Less common More common
Etiology Borrelia recurrentis Borrelia dugesii, Borrelia
hermsii and Borrelia
turicatae
 Dx
• Demonstration of spirochetes by dark field
• microscopy or in thin or thick blood smears stained with
Giemsa or Wright stain
• blood culture
• Serologic tests have not been standardized, are generally not
available, and produce cross reactions with other spirochetes
 Treatment

• For children's >8 yrs.

-Tetracycline 500 mg po QID or Doxycycline 100 mg po BID for
10 days
N.B. Do not administer to children <8 years of age due to
permanent discoloration of teeth and retardation of skeletal
development and bone growth (risk being greatest for children
<4 years and in those receiving high doses).
• Less than 8yrs
-Erythromycin 50 mg/kg/day PO QID
OR
-Procaine penicillin at 200,000 to 400,000 units IM stat.
 Jarisch-Herxheimer reaction(JHR)

• Resolution of each febrile episode either by natural crisis or as

a result of antimicrobial treatment is
• It is associated by massive antigen release results in release
of mediators-TNF
Two phases
1) Chill phase:
-Toxic T>41, rigors, hyper metabolism
-Increase PVR & decrease in Pul. arterial pressure
-Lasts 10-30 min
2) Flush phase:
-Decrease in PVR & increase in Pul. Arterial pressure
-Decrease in T, diaphoresis,
-Decreased effective circulatory volume
-Lasts<8 hrs
-Sleep, exhaustion, recovery with disappearance of
spirochetes
Mx-Supportive( Fluid, anti-paretics)
Mortality reaches 20% in malnourished & stressed population
 Prognosis

• majority of patients recover from their illness with or without

treatment after the appearance of anti-Borrelia antibodies,
which agglutinate,kill, or opsonize the spirochete
• With adequate therapy, the mortality rate for relapsing fever
is <5%.
Poor prognostic factors
-pregnant mothers
-Neonates(mortality may reach—33%)
 Prevention

• No vaccine is available
• Disease control requires
- Avoidance or elimination of the arthropod vectors
-Good personal hygiene and delousing of persons
 Malaria

 It causes acute and chronic illness characterized by paroxysms

of fever, chills, sweats, fatigue, anemia, and splenomegaly
 Malaria is caused by intracellular Plasmodium protozoa
transmitted to humans by female Anopheles mosquitoes.
Types- P. falciparum
- P. vivax
- P. ovale
- P. malariae
-P. knowlesi
• Transmission is via:-
– Female anopheles mosquito bite
– Blood transfusion
– Use of contaminated needles
– Vertical-Mother to child transmission
 Epidemiology

• Its a major world wide problem occurring in more than 100

countries with a combined population of more than 1.6 billion
people
• Principle areas of transmission are Africa, Asia and South
America
• P. falciparum and P. malaria are found in most malaria's areas
• P.F is the most common in Africa, P.V-out side Africa, P-ovale is
the least cause
• Ethiopia is among the few countries with unstable malaria
transmission
• In Ethiopia, 52 million (68%) people live in malarial risk area
primarily at altitudes below 2000 m.
• Malaria is mainly seasonal with unstable transmission in the
highlands and relatively longer transmission duration in the
lowlands.
• Historically there have been an estimated 10 million clinical
malarial cases annually however cases have reduced
substantially since 2006
• 60-70% of malarial cases is due to P. falciparum with the
remainder caused by P. vivax
• Sporozoites(from mosquito)- liver
schizont/hypnozoit- merozoites-Infect RBC and
mature to trophozoit----schizont—rupture to release
merozoit---Gametocyte and taken by mosquito + and
other merozites infect other RBC
 Life Cycle
1. Transmission

Female anopheles Infection Sporozoites 2. Pre-erythrocytic phase

mosquito bites and
releases sporozoites into Also called the “tissue” or “hepatic” phase
the blood stream. These
circulate for about 30 mins Takes place in hepatocytes. The sporozoites
and then invade the liver. mature into schizonts which rupture to
release merozoites. Duration of this phase
depends on the species.

In P. vivax and P. ovale, the schizont may

also differentiate into hypnozoites. These
are dormant forms of the parasite which
may remain in the liver for several months
Liver
or years and cause relapse in the human
host.

Merozoites Asexual
cycle

Transmission
to mosquito

Gametocytes

Nebyou 67
 Cont.
Infection Sporozoites

3a. Asexual phase (Erythrocytic schizogony)

Merozoites invade red blood cells. Here they

grow and mature into trophozoites which appear
as ring forms. The trophozoites develop into
schizonts. The infected red blood cells then
rupture to release numerous merozoites from the
schizont to infect other red cells. Merozoite
release results in fever, chills, rigours and other
symptoms of malaria infection.
Liver

Merozoites Asexual
cycle 3b. Sexual phase

Transmission Some merozoites differentiate into male and

to mosquito female gametocytes, the forms of Plasmodia
infective to mosquitoes. These are taken up
by a mosquito during another blood meal.
Gametocytes These fuse to form an ookinette in the gut
lumen of the mosquito. The ookinette invades
the stomach wall to form the oocyst. This in
turn develops and releases sporozoites which
migrate to the salivary gland of the mosquito.
This mosquito then goes on to infect another
Nebyou human host. 68
 Clinical manifestation
• Depends on
-Malaria-specific immune status of the host
- The infecting species of Plasmodium
 Immune vs. non-immune
1. Immune or semi immune
- Recently residing in an endemic area and >5 years
2. Non-immune
- From endemic area but younger than 5 yrs
- Not residing in an endemic area for more than 1 yr
- Travel/visitor to an endemic area
 Type of species
-Falciparum cause more sever than the others
• Usual incubation periods are
-P. falciparum, 9–14 days
-P. vivax, 12–17 days
- P. ovale, 16–18 days
- P. malariae, 18–40 days
• P. falciparum infection in young children and non-immune
adults, falciparum malaria may become a severe life-
threatening disease.
• P.Knowlsy similarly cause sever disease
• P. ovale, P. malariae, and P. vivax infection, on the other hand,
rarely result in severe disease or death except in cases of
splenic rupture.
 The classic presentation of malaria is seldom noted with other
infectious
Diseases
 Consists of paroxysms of fever alternating with periods of
fatigue but otherwise relative wellness.
 Febrile paroxysms are characterized by
- high fever, sweats, and headache, myalgia, back pain,
abdominal pain, nausea, vomiting, diarrhea, pallor, and jaundice.
 Paroxysms coincide with the rupture of schizonts that occurs
every 48 hrs. with P. vivax and P. ovale, resulting in fever spikes
every other day.
(“tertian” malaria)
 Rupture of schizonts occurs every 72 hrs. with P. malaria,
resulting in fever spikes every fourth day.
(“quartan” malaria
 But Periodicity is less apparent with P. falciparum and mixed
infections-2nd day or more frequently in P. falciparum (“sub-
tertian” malaria)
 P.knowlesi ,fever spikes every 24 hrs (daily)
 Diagnosis of Malaria

 There are no pathognomonic clinical signs or symptoms for

the dx of malaria.
Clinical Diagnosis
 A patient who has fever or hx of fever in the last 48 hrs. and
lives in malaria endemic areas
 Has travel with in the last 30 days to malarias areas.
 Laboratory DX
1. peripheral BF examination:-is the gold standard for the dx
of malaria.
1.1:-Thick blood smear
-Used for determining parasite density
- Monitoring the response to treatment.
-Helps to identify the plasmodium
1.2 Thin blood smear
-Used for positive identification of specific malarial spp.
• Two methods are used to establish the parasite count.
• Method 1: parasites per microlitre of blood
• Method 2: the plus system
1)+ = 1-10 parasites per 100 thick film fields
2)+ + = 11-100 parasites per 100 thick film field
3)+ + + = 1-10 parasites per single thick film field
4)+ + + + = more than 10 parasites per single thick film field
2) Rapid diagnostic test
-Identify Falciparum vs. non-Plasmodium falciparum
3) PCR
4) Other Ix
-RBS
-Electrolyte
-HCT
-OFT
 Severe Malaria
• Severe malaria ,is due to P. falciparum which is serious can
lead to immediate life threatening condition.
• Usually starts with fever and vomiting.
• Children can deteriorate rapidly over 1–2 days, going into
coma or shock, or manifesting convulsions, severe anemia and
acidosis
 Diagnosis of Sever Malaria

 It is diagnosed as presence of Asexual form of P.Falciparum,

and presence of one or more of the following in the absence
of other cause
1-prostration(unable to sit unsupported(>1yr)or in ability to
drink or BF(<1yr).
2-Cerebral malaria
3-Convelsion
4-Sever anemia (Hgb<5 gm/dl)
5-Algid malaria
6-Hypoglycemia (<40mg/dl)
7-Metabolic acidosis:HCO3 (<15mmol/l)
8-Renal impairment (Cr.>3g/dl)
9-Hyperlactatimia (>5mmol/l)
10-Hyperparasitemia (>10% in P.F and >2% in P.knowlesi)
(N.B to define hyperparasitemia >4%..WHO2015)
11-Black water fever
12-Pulmnary Edema
13-Others
-Bleeding disorder , Hyperparexia
• N.B-P.vivax and P.Knowlesi can cause sever and complicated
malaria
 Management

• Uncomplicated malaria
-First line treatment to uncomplicated P. falciparum
Arthemesinin derivatives(artemether lumefantrine (Coartum)
for three days
-First line treatment to P. vivax is chloroquine
-First line treatment for mixed infection (Pf+Pv) is Coartum(AL)
-Second line treatment for uncomplicated Pf or mixed infection
is PO Quinine
-Second line treatment for P.vivax is COARTUM. if both
chloroquine or AL not available use PO quinine
-Radical treatment for P.vivax using primaquine:(for Hypnozoit)
• Severe Malaria
-Pre referral treatment to severe malaria at health post
-Rectal artesunate
-Artemether IM 3.2mg/kg
 Severe Malaria treatment

-ABCD of life
-Establish IV line
-Take blood for laboratory tests
-Treat hypoglycemia
-Start specific antimalaria treatment
-Treat fever
-Assess for need of blood transfusion
-Provide good nursing care
 Treatment of severe malaria at Hospital

• IV or IM Artesunate (preferred)
OR
• IM Artemether (alternate)
OR
• IV Quinine infusion (If Artesunate not available)-Followed by
oral coartum therapy
• Rx for P.V and P.K similar.
 Poor prognostic factors

• Age<3 yrs
• Acidosis
• Hypoglycemia
• Papilledema
• Hyperparasitemia
• Deep coma
• Convulsion
• Organ dysfunction(pul and rnal)
• Sever anemia
• Peripheral leukocytosis
• Elevation of liver enzymes to >3X
 Prevention
• Avoid Mosquito breeding area
• Use insecticides
• Chemoprophylaxis
 Chronic complications

-Quartan nephropathy
-Nephrotic syndrome….associated with P.M
-Hyper reactive malarial splenomegaly syndrome (HMS)
-Burkits lymphoma
-Residual neurologic deficit
 Typhoid fever
• Typhus abdominalis
• Enteric fever
 A systemic disease characterized by fever and abdominal pain
 Exclusively human disease caused by an organism of genus

salmonella, family of enerobacterisae-

-S.Typhi
-S.Paratyphi
 S.Typhi- more common with ratio of 10:1

-More sever
-Needs low infective dose
 Epidemiology

• It is estimated that more than 26.9 million typhoid fever cases

occur annually, of which 1% result in death.
• In most developed countries, the incidence of typhoid fever is
<15 cases per 100,000 population, with most cases occurring
in travelers.
• The incidence may vary considerably in the developing world,
with estimated rates ranging from 100-1,000 cases per
100,000 population.
• There are significant differences in the age distribution and
population at risk.
• Population-based studies from South Asia also indicate that
the age-specific incidence of typhoid fever may be highest in
children younger than 5 yrs. of age, in association with
comparatively higher rates of complications and
hospitalization.
Transmission:
• direct or indirect contact with an infected person (sick or
chronic carrier) is a prerequisite for infection.
(Feco-oral)
• Ingestion of foods or water contaminated with S. Typhi from
human feces is the most common mode of transmission,
although waterborne outbreaks as a consequence of poor
sanitation or contamination have been described in
developing countries.
 Pathogenesis
• Infecting dose of about 105-109 organisms, with an
incubation period ranging from 4-14 days, depending on
the inoculating dose of viable bacteria
• After ingestion, S. Typhi organisms are thought to invade the
body through the gut mucosa in the terminal ileum, possibly
through specialized antigen-sampling cells known as M cells
that overlie gut-associated lymphoid tissues, through
enterocytes, or via a Para cellular route
• S.Typhi crosses the intestinal mucosal barrier after attachment
to the microvilli
• After passing through the intestinal mucosa, S. Typhi
organisms enter the mesenteric lymphoid system and then
pass into the bloodstream via the lymphatic's-Primary
bacteremia
• This primary bacteremia is usually asymptomatic, and blood
culture results are frequently negative at this stage of the
disease.
• The blood borne bacteria are disseminated throughout the
body and are thought to colonize the organs of the
reticuloendothelial system, where they may replicate within
macrophages.
• After a period of bacterial replication, S. Typhi organisms are
shed back into the blood, causing a secondary bacteremia
that coincides with the onset of clinical symptoms and marks
the end of the incubation period.
• Infection with S. Typhi produces an inflammatory response in
the deeper mucosal layers and underlying lymphoid tissue,
with hyperplasia of Peyer patches and subsequent necrosis
and sloughing of overlying epithelium
• The resulting ulcers can bleed but usually heal without
scarring or stricture formation
• The inflammatory lesion may occasionally penetrate the
muscularis and serosa of the intestine and produce
perforation
• The mesenteric lymph nodes, liver, and spleen are hyperemic
and generally have areas of focal necrosis as well.
• The clinical syndrome of fever and systemic symptoms is
produced by a release of proinflammatory cytokines (IL-6, IL-
1β, and TNF-α) from the infected cells.
 Summary of pathogenesis
-Multiplication in the SI lumen.
-First 4 days-stool culture could be positive.
-Proliferation in the mesenteric LN
-Through thoracic duct reaches the blood stream– primary
bacteremia.
-Dissemination to liver and spleen
-Massive multiplication- secondary bacteremia.
-Invasion of most organs
-Gall bladder-chronic carriers
-Peyer’s patches-hyperplasia and necrosis, perforation
 Clinical presentation

• The incubation period of typhoid fever is usually 7-14 days but

depends on the infecting dose and ranges between 3 and 30
days.
• The clinical presentation varies from a mild illness with low-
grade fever, malaise,and slight, dry cough to a severe clinical
picture with abdominal discomfort and multiple
complications.
• Many factors influence the severity and overall clinical
outcome of the infection.
• Which include
-the duration of illness before the initiation
-of appropriate therapy
- choice of antimicrobial treatment, age, previous similar Hx
-exposure or vaccination history
-virulence of the bacterial strain
-Quantity of inoculum ingested
-several host factors affecting immune status
• In those patient with classical presentation
• First week of illness
-Rising ("stepwise(ladderr)") fever and bacteremia develop
-Chills are typical, frank rigors are rare
- Relative bradycardia ( pulse-temperature dissociation )may
be observed
• second week of illness
-Sustained high grade fever
-Toxic and apathetic
-Abdominal pain develops
-“Rose spots” (faint salmon-colored macules on the trunk and
abdomen)
• Third week of illness
-Hepato-splenomegaly
-Intestinal bleeding, and Perforation due to ileocecal lymphatic
hyperplasia of the Peyer's patches
-With secondary bacteremia and peritonitis.
-More toxic, delirious & confusional state( typhoid state)
-Septic shock
-Death due to toxemia, myocarditis, intestinal hemorrhage &
perforation
Fourth week:
-Fever, mental state and abdominal distension improves
-Intestinal complication may still occur
 Laboratory

-CBC-mild leukocytosis
-Later neutropenia, anemia, thrombocytopenia..pancytopenia
-Culture:
-Definitive Dx-blood or BM culture
-Blood culture: Yield -1st WK 90% and 3rd wk 50%
-Stool culture is positive in up to 30 to 40 percent of cases,
but is often negative by the time that systemic symptoms
bring patients to medical attention
-BM culture positive-90% despite treatment
-Duodenal string test
Serology:
-Ab against flagella (H) and somatic (O) Ag –widal test
-False positive
-Immunization, early infection-serology scar, anamnestic
reaction
-Serologic tests are neither sensitive nor
specific…no more use
 Treatment
 There are general principles of typhoid fever management.
-Adequate rest, hydration
-Correct fluid and electrolyte imbalance
-Blood transfusion and supportive care for hemorrhage
-Surgical intervention for perforation
-Antipyretic therapy
-Antibiotic therapy-CAF
-Ceftriaxone
-Erythromycin
-Floroquinoloes
 Prognosis

• The prognosis depends on

-The rapidity of diagnosis
- Institution of appropriate antibiotic therapy.
-Patient’s age,
-General state of health
-Nutrition
- The causative Salmonella serotype
 Prevention

-Personal and environmental hygiene

-Vaccine
-Whole cell killed vaccine, Ty21a attuenated, Vicps
polysaccharide
-Monitoring of food handlers
Thank you
 References

 Nelson 20th edition

 National malaria guideline 2012

 up-to-date
 Malaria WHO 2015