Fever

Non-specific but essential to know

  Dengue
 Malaria
 Typhoid
Outline  Typhus
 HIV
 Leptospirosis
Dengue
fever
Aetiology and
Pathophysiology
 Caused by the dengue virus
(DENV 1-4) - Flaviviridae
 Main vector is Aedes aegypti
(urban) and albopictus
(suburban/rural)
 Incubation period 4-14 days
(commonly 5-7 days)
 Notifiable disease in Malaysia
Antibody dependent enhancement

 First infection is known as

primary dengue, results in
lifelong immunity to a specific
serotype
 Second infection known as
secondary dengue and has a
higher risk of severe dengue due
to antibody dependent
enhancement (ADE)
 Third and fourth infection known
as post-secondary dengue –
Severe infection is rare
Clinical Features of Dengue
Tourniquet Test
(Hess Test)
Phases of Dengue
Warning Signs
Indications for
Admission
Outpatient Management

 Outpatient management involves ensuring adequate fluid intake (7-8 glasses

of 200ml of fluids)
 Encourage ORS and fruit juice to restore electrolyte
 Ensure patient is able to pass urine every 6 hours
 Daily monitoring of warning signs, vitals, urine output, oral intake, mental
status, perfusion and full blood count
 Refer to hospital if no clinical improvement, deterioration during
defervescence, or development of warning signs
 Discharge after 24-48 hours afebrile
Outpatient management
Inpatient
monitoring – Stable
Patient
Inpatient
monitoring – Stable
Patient
Management of
Unstable Patient
Malaria
Malaria
 Caused by intracellular obligate
protozoan plasmodium
(falciparum, malariae, vivax,
ovale, knowlesi)
 Transmitted by Anopheles
mosquitos, or less commonly by
blood transfusion, contaminated
needles, and transplacentally.
 Common in forested areas
 Fever pattern (Tertian – vivax,
ovale; Malignant tertian –
Falciparum; Quartan – Malariae;
Quotidian – Knowlesi)
 Incubation 7-30 days
Plasmodium life cycle
 Bitten by infected female Anopheles mosquito and
Plasmodium species parasites in the form of
sporozoites are injected into bloodstream
 Sporozoites travel to the liver, multiplying asexually
for the next 7-10 days. This part of the life cycle
produces no symptoms.
 Merozoites are released into the bloodstream to
penetrate erythrocytes. Clinical sx begin after the
rupture of mature schizont-infected erythrocytes,
releasing the merozoites and toxic products of
parasite’s metabolism in the blood.
 Release toxins induce release of cytokines from
macrophages → fever etc happens.

 Some merozoites mature within erythrocytes into

sexual forms called gametocytes, which reproduce
sexually if they are ingested by a mosquito. If left
untreated, the parasite count in a malaria patient
keeps increasing every 24, 48 or 72 hours, depending
on the Plasmodium species.
Clinical Features - Uncomplicated

 Nonspecific sx  -Fatigue  Mild jaundice

 Fever, chills: Early  -Headache  Anaemia
course - febrile
 -Cough  Splenomegaly
paroxysms occur at
irregular intervals  -Arthralgia and
each day myalgia
 Quartan: Malariae  -Sweating
 Tertian: Vivax,  Nausea/vomiting/d
Ovale, Falciparum iarrhea
 Quotidian:  -Abdominal pain
Knowlesi
Clinical Features –
Complicated/Severe
 Cerebral malaria
 Splenic rupture
 Renal failure
 Severe haemolysis (Blackwater fever)
 Non-cardiogenic pulmonary oedema
 Hypoglycemia
 Thrombocytopenia
 Algid Malaria (Sepsis with vascular
collapse)
 Death
Diagnosis

 Diagnosis established by blood film for malaria

parasite (BFMP)
 Thick smears – Diagnosis of malaria; Thin smears –
Diagnosis of species and percentage of infected
erythrocytes
 Rapid diagnostic tests also available
 FBC
 Blood urea and serum electrolyte
 CRP
 Liver profile
 Blood glucose
Management – Uncomplicated
falciparum
 Artemisinin combination
therapy (ACT) preferred –
Artemether and Lumefantrine
(Riamet), Artesunate and
Mefloquine (ASMQ) or
Choloroquine for 3 days
 Add on primaquine for 14 days
if Plasmodium Vivax
 Chemoprophylaxis with
Atovaquone/Proguanil,
Mefloquine, and Doxycycline
Management –Severe falciparum
Management – Non falciparum
 Typhoid Fever
(Enteric Fever)
 Caused by Salmonella enterica
(typhi/paraytyphi)
 Risk factors include poverty,
overcrowding, poor hygiene, and
unsanitary food handling
 Fecal-oral transmission. Humans
are the only reservoir
 Incubation period of 5-21 days
 Salmonella organisms are able to
survive gastric acid, penetrate
intestinal epithelium, invade
lymphoid tissue and disseminate
Clinical Features and Diagnosis

 1st week: Stepladder fever pattern, relative

bradycardia
 2nd week: Abdominal pain, Rose Spots
 3rd week: Hepatosplenomegaly, intestinal bleeding,
perforation due to ileocecal necrosis of Peyer’s patches,
peritonitis, and septic shock.
 Diagnosed with blood and stool culture. The most
sensitive is bone marrow culture.
 Blood investigations may reveal anemia, leukopenia,
leukocytosis, and transaminitis
Pulse-temperature dissociation (Faget’s
Sign) and Liebermeister's rule
 Normally there will be an increase in pulse rate by 10 bpm for every 1 degree
increase in temperature. Certain infections may cause temperature-pulse
dissociation (relative bradycardia in association with fever).
 Any intracellular organism has the potential to cause a relative bradycardia
(Faget's sign)
 Infections that cause dissociation:
 Salmonella typhi
 C burnetii (agent of Q fever)
 Chlamydia infections
 Dengue fever
Severe Disease
 Gastrointestinal bleeding (10–20%) and
intestinal perforation (1–3%) most
commonly occur in the third and fourth
weeks of illness and result from
hyperplasia, ulceration, and necrosis of
the ileocecal Peyer’s patches at the
initial site of Salmonella infiltration

 Neurologic manifestations occur in 2–

40% of patients and include meningitis,
Guillain-Barré syndrome, neuritis, and
neuropsychiatric symptoms (described
as “muttering delirium” or “coma vigil”),
with picking at bedclothes or imaginary
objects.
 Management
 Treatment with empirical antibiotics (ceftriaxone, ciprofloxacin +/- dexamethasone)
 Relapse in 2-3 weeks
 Chronic carriage is detected as presence of organism in stool for > 12 months
 Stool culture for screening for food handlers, healthcare personnel, and during outbreaks.
 Eradication includes 4 weeks of antibiotics and cholecystectomy
 Vaccines available include live attenuated oral vaccine, polysaccharide vaccine and typhoid conjugate
vaccine
Scrub Typhus

 Caused by Orientia tsuttugamushi which is carried by a vector

Chigger (Trombiculid bug)
 Found in oil palm estates
 Incubation period of 7-10 days
 Presents with fever, headache, myalgia, anorexia and malaise
 Nonpruritic, macular or maculopapular rash on the abdomen
and spreads to the extremities
 Pathognomonic rash is the eschar - A painless papule often
appears at the site of the infecting chigger bite, central
necrosis then occurs, which in turns into a black crust
Diagnosis and Management

 Complicated form may cause multi-organ failure (ARDS,

myocarditis, hepatitis, AKI, meningoencephalitis, septic
shock)
 Indirect fluorescent antibody (IFA) with a four-fold rise in
titers over a 14-day period is conclusive
 Eschar biopsy shows lymphohistiocytic vasculitis
 Uncomplicated treated with PO doxycycline 100mg BD X
1/52 (azithromycin in pregnancy and paeds)
 Complicated treated with IV azithromycin 500mg OD x
5/7
 Leptospirosis

 Zoonotic disease caused by

Risk factors
Leptospira interrogans,
Gram -ve spirochaete  Swimming in river
 Ingestion of contaminated
 Incubation period 7-14 days water
 Cycling through puddles
Hosts & Causative organisms  Farm workers
 Fish farmers
 Rodents
 Miner
 Dogs
 Sewage workers
 Cattle  Soldiers
 Pigs  Abbatoir workers
Clinical Features

 Mild infections probably go undiagnosed

 Majority (90-95%) are subclinical or mild
fever
 Two phases are leptospiremic phase (acute
phase) and Weil's disease (immune phase
Diagnosis

 Serology
ELISA: Leptospira IgM Ab (appear from the end of first week)
PCR: Leptospira DNA in blood and urine

 Microscopic agglutination test (MAT) is gold standard (1-

400; positive / 4 fold increase) as it is more specific but
less sensitive than Leptospira IgM Ab

 Blood / CSF culture for leptospires during first week of

illness but takes several weeks.
Other investigations

 FBC
- Leukocytosis
- Thrombocytopenia due to activation of endothelial cells leading to PLT
agglutination and adhesion
- Prolonged prothrombin time in hepatitis

 Raised creatine kinase due to myositis

Management

 Mild to moderate cases treated with Doxycycline or azithromycin (pregnancy)

 Severe cases treated with ceftriaxone or Benzylpenicillin
 Prophylaxis by taking doxycycline or azithromycin weekly throughout stay
HIV Seroconversion Illness
 HIV is a retrovirus which infects and replicates in human lymphocytes (CD4 + T-
cells) and macrophages.
 This leads to progressive immune system dysfunction, opportunistic infection, and
malignancy = Acquired Immunodeficiency Syndrome (AIDS).
 The virus is transmitted via blood, sexual fluids, and breast milk. Virus subtypes
include HIV1 (global epidemic) and HIV2 (predominantly West Africa).
 HIV binds, via its GP120 envelope glycoprotein, to CD4 receptors on helper T
cells, monocytes, and macrophages. These ‘CD4 cells’ migrate to lymphoid tissue
where the virus replicates, producing billions of new virions.
 These are released, and in turn infect new CD4 cells. As infection progresses,
depletion or impaired function of CD4 cells leads to immune function. HIV is a
retrovirus: it encodes reverse transcriptase, allowing DNA copies to be produced
from viral RNA. This is error prone, meaning a significant mutation rate, which
contributes to treatment resistance.
Prevention
 Sexual transmission: Consistent and correct use of (male and
female) condoms transmission by ~90%. Serosorting is the
restriction of (unprotected) sex depending on HIV status. It is
unsafe due to inaccuracies in HIV status (which is only as reliable
as a person’s last test) and failure to disclose. It does not consider
transfer of treatment resistance, other STIs, or hepatitis.
 Post-exposure prophylaxis (PEP): The short-term use of
antiretroviral therapy (ART) after potential HIV exposure (sexual
or occupational) should be considered an emergency method of
HIV prevention. Can be given up to 72h (ideally <24h) after
exposure.
 Pre-exposure prophylaxis (PrEP): The use of ART in those at high
risk of acquiring HIV including serodifferent relationships without
suppression of viral load, condomless anal sex in MSM.
Clinical Features

 Primary HIV infection is symptomatic in ~80%,

typically 2–4 weeks after infection (=
seroconversion illness, acute retroviral syndrome).
 Flu-like symptoms and an
eythematous/maculopapular rash.
 Fever, rash, myalgia, pharyngitis, mucosal
ulceration, lymphadenopathy, and headache/aseptic
meningitis.
 Persistant generalized lymphadenopathy =
swollen/enlarged lymph nodes >1cm in two or more
non-contiguous sites (not inguinal) persisting for >3
months.
Treatment
 Anti-retroviral therapy.
 Need to emphasize adherence (Poor adherence may cause resistance)
 Monitor CD4 and viral load
 Contact tracing and offer prophylaxis where required
 Acquired immunodeficiency syndrome (AIDS) is defined as an HIV infection with either a CD4+ T cell count
below 200 cells per µL or the occurrence of specific diseases associated with HIV infection
Opportunistic Infections
Needle stick injury
Thank you 