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AUFI IMA infectious diseases.............
1. Dr.Hari krishna Revuri MD(Int med)
CONSULTANT PHYSICIAN& INFECTION SPECIALIST
DHRUTHI HEALTH CARE
Area of interest :Infectious diseases with special focus on complicated HIV and PrEP
Memberships: International society of infectious diseases(ISID)
Clinical infectious disease society (CIDS)
International AIDS society
International diabetic federation.
Speaker and organiser for various state conferences and national faculty in HIV
society.
3. Life is short, and Art long,
opportunity fleeting,
experiment perilous,
decision difficult-
-Hippocrates
Mankind has three great
enemies: fever,
famine and war; of these by far
the greatest, by far the most
terrible, is fever.
– Sir William Osler
6. Non-malarial AUFI
Parasitic
Viral Bacterial Hepatic amebiasis
Arboviral*
Dengue,
Chikungunya
Other viruses:
Influenza
Blood stream
infections
Bacterial
zoonoses
Enteric
Fever
Spirochetal
infections. E.g.
Rickettsial
infections e.g.
Leptospirosis Scrub typhus
7. A mnemonic to sum up AUFIs: SMEAR
Disease group
M alaria
A rboviral
E nteric Fever
S pirochetal
R ickettsial
Examples
P.V. P.F.
Dengue, Chik, Zika
Typhoid, paratyphoid
Leptospirosis , Borreliosis
Scrub typhus, Murine
typhus,
Spotted fever
Diagnosis
Demonstration of
Organism
NS1 antigen, IgM
Culture , Serology
Serology
Serology
8. Step 1: Collect epidemiological information
Step 2: Evaluate clinical features
Step 3: Perform first-line and wherever possible confirmatory tests
Step 4: Integrate information from 1,2,3 to formulate a confirmed or probable diagnosis. Initiate therapy.
Step 5: Monitor therapeutic response, follow up test results
9. Step 1 : Epidemiological information
A.Agent of disease: Local disease prevalence, seasonality : Most
diseases in post-monsoon season.
B.Environment and exposures : Vectors, contaminated food, water,
animals and their excretions.
C. Host and Risk factors: Age, Comorbidities, immunosuppression,
pregnancy
10. “Scrub typhus is probably the single most prevalent, under-
recognized, neglected and severe but easily treatable disease
in the world.”-
Paris D.H. etal. Am.J.Trop.Med.Hyg 2013; 89(2): 301-307
11. Leptotrombidium Chigger’s Habitats
Dry Habitats
Scrub Area
Wet Habitats
The term scrub of scrub typhus
came from the type of
vegetations (terrain between
woods & clearings) that harbor
the vectors.
Rice Field
Moist Areas: Swamp & Bog
Areas Around Houses
Edges of Dense Forest
16. Some other viral zoonotic diseases can begin with AUFI
Viral hemorrhagic fever group :
• Crimean –Congo Hemorrhagic fever: Tick borne infections, Gujarat,
Rajasthan.
• Kyasanur Forest Disease: Karnataka, Goa, and other states.
Nipah virus : Fruit bats, encephalitis
COVID-19
17. Step 2: Evaluate clinical features
A.Assess severity of illness
B.Rule out localised infections
C. Assess key clinical features
- Onset, duration, progression
- Rule in and rule out features
- Characteristic pattern of organ involvement.
18. A.Red flag features:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Altered mental status (Glasgow coma scale <13), convulsions/positive meningeal
signs.
Breathless/RR> 22/minute /cyanosis /arterial oxygen saturation < 92 on room air,
BP < 100 mm Hg systolic /cold clammy extremities/capillary refill > 3 secs.
Hyperpyrexia (temperature > 41.5 c) or hypothermia (temperature < 36 C) or
rigors.
Prostration: Unable to stand or sit or walk without support.
Severe pallor.
Jaundice on examination of sclera (except mild jaundice which can occur in
uncomplicated malaria)
Abdominal pain severe/persistent vomiting.
Petechial or purpuric rash.
Significant bleeding from nose, gums or venepuncture sites/hematemesis/melena.
WHO : Guidelines for treatment of Malaria. 2015, Seymour CW etal. JAMA. 2016. WHO : Dengue . 2009.
19. B.Rule out localised infections
Clinical pearl 1:
Some localised infections may present like AUFI early in the course
e.g. Influenza
Clinical pearl 2:
Some AUFIs may present later in the course with s/o localised infections
Malaria – encephalopathy
Scrub typhus – Pneumonia, ARDS
Leptospirosis – Jaundice : Hepatobiliary infections
20.
21. C. Assess key clinical features
Onset ,progression and duration of illness
• Malaria, dengue, scrub, lepto: abrupt onset with often rapid
progression to complications in 1 week.
• Enteric fever: less abrupt onset with complications in 2 /3 week
Duration :
Dengue 7-12 days
Influenza : 3-8 days.
22. Potential diagnostic clues: Rule in and rule out
features
Rule in features: signs which alone or in combination indicate
moderate or high likelihood of disease ~ Good predictors
Rule out features: signs which alone or in combination indicate low to
very low likelihood of a disease ~ Good excluders
23. Rule-in features
• Malaria: Fever > 40 C , splenomegaly, ↓ platelets, ↑bilirubin
• Arboviral infections: Rash +/- arthritis.
• Enteric Fever: None
• Leptospirosis: Suffusion + jaundice + conjunctival hemorrhage + muscle
tenderness
• Scrub typhus: Eschar
Bhargava A, Ralph R, Chatterjee B etal BMJ 2018
0
24. Eschar: A pathognomonic sign of scrub
typhus
• Painless, non-pruritic ulcer at site of bite with black scab and
erythematous halo.
• > Frequent in primary infections
• Frequency 10-45% in Indian case series. 17% in our case series.
25.
26.
27.
28. Rule out features :
which suggest alternative diagnoses
• Malaria: Rash , lymphadenopathy.
• Dengue : Fever > 12 days, Normal tourniquet test and leukocyte
count suggest alternative diagnosis.
• Enteric Fever: Rash, lymphadenopathy, complications in first week.
• High fever with jaundice: Viral hepatitis is less likely
29. Clinical examination
General appearance and vitals
• Acutely ill patient: Severe forms of SMEAR.
• Relative bradycardia: Enteric fever, dengue fever, scrub typhus
• Hypotension in the first week: Dengue, scrub typhus, Malaria, Lepto Enteric fever
less likely
Eyes
• Jaundice : Malaria, lepto, scrub typhus, enteric fever
• Conjunctival suffusion: lepto, scrub typhus
• Non-purulent conjunctivitis: Zika, chikungunya
• Conjunctival hemorrhage: Lepto.
• Roth spots
Neck
Lymphadenopathy: Dengue, Scrub typhus.
33. The General Physical examination holds the key
•M uscle tenderness
•A denopathy, arthritis
•E schar
•S uffusion ( conjunctival)
•R ash
•J aundice
34.
35. Characteristic pattern of systemic involvement:
Lung, kidney, brain, CVS, bleeding
• Dengue: Jaundice, renal involvement less common. Bleeding
common.
• Enteric fever: acute renal failure and lung involvement less common.
• Malaria: thrombocytopenia + but bleeding rare. Transaminases n.
36.
37. SMEAR as a mnemonic for complications of
AUFI
• M ultiorgan failure
• A RDS
• E ncephalopathy
• S hock
• R enal failure
38. Step 3 : Perform basic and confirmatory
tests
• Perform microscopy or RDT for malaria, CBC, Urinalysis : In all
• Biochemical ( localised symptoms, complications)
• Imaging ( localised symptoms, complications)
• Demonstration of organism by culture, DNA:
• Demonstration of antibody: by serology
39. Leukocytosis
Leukopenia
Diagnostic value Prognostic value
Leptospirosis, scrub typhus, amebiasis In enteric fever, leptospirosis
Early leukopenia + thrombocytopenia Falling TLC +
: Dengue
thrombocytopenia + Rising hematocrit: Severe dengue
No discriminant value
Hematuria, proteinuria in lepto
Malaria Vs. dengue
Poor discriminant value. May be
modest elevation despite large
increases in bilirubin in Lepto
AKI + hypokalemia in leptospirosis
In association with bleeding
Hemoglobinuria in malaria
In all AUFIs except malaria.
Dengue
Thrombocytopenia
Urine
Bilirubin
Liver enzymes
Renal function and
electrolytes
Prognostic value in all severe
forms of AUFI
40.
41. Imaging in AUFI
X ray chest :
• Scrub typhus, Leptospirosis, occ. Malaria:-Bilateral pneumonia/ARDS
Pneumonia occasionally in Enteric fever. Pleural effusion in Dengue
Nodular shadows, cavities: Melioidosis
Ultrasound abdomen:
Ascites, pleural effusion, gall bladder wall edema: Dengue fever
Mesenteric adenopathy: Enteric Fever
Acalculous cholecystitis : Dengue, other AUFIs
Hepatic amebiasis: abscess
Multiple hepatic and splenic abscess : Melioidosis.
42. Confirmatory tests:
Microscopy: Malaria
Culture : Enteric Fever, Leptospirosis.
Nucleic acid amplification: Dengue, Leptospirosis, Scrub typhus
Serology
Immunochromatographic tests : Rapid Diagnosic Tests (RDTs)
ELISA based : IgM
Widal test: Not useful. Weil-Felix test: Low sensitivity
Available only in reference labs: Immunofluorescence based: IFA IgM
for Scrub typhus, Microscopic agglutination test for Leptospirosis
43. Comments on confirmatory tests
Malaria : Caveats with RDTs
• Low sensitivity to low level parasitemia
• Variable performance, deterioration at high temp. humidity
• Populations of P.falciparum with deletion in PfHRP2 genes
Serological confirmation:
IgM seroconversion or More than 4 fold rise in IgG titer alone diagnostic
Dengue, Scrub typhus, Leptospirosis: IgM based tests:
• Rapid but not early
• Persistence after infection.
• Cross reactivity: dengue, leptospirosis.
Best combination would be : PCR(+ in early disease) + Serology (+ later)
44. IgM positive for 2 pathogens
OR Smear positive for malaria + positive serology
Coinfections possible : malaria , dengue/chikungunya
scrub typhus, leptospirosis
Background positivity : Scrub typhus, leptospirosis.
Cross-infections: chikungunya, dengue.
45.
46. Step 4 : Probable diagnosis
Initiate therapy based on setting and severity of illness.
Ceftriaxone 2 g OD + Doxycycline 100 mg BD- severe bacterial AUFI
Enteric fever
(10-14d)
Leptospirosis
(7 days)
Scrub typhus
(7 days)
Singhi S etal. Indian journal of critical care medicine 2014;18(2):62-9
Thompson CN etal. The American journal of tropical medicine and hygiene.
2015;92(4):875-8.
47. Ceftriaxone + doxycycline
• Could serve in patients with AUFI complicated by Acute lung injury,
renal failure and encephalopathy.
• No dosage modification required in renal failure.
• Patients with severe falciparum often complicated by blood stream
infections.
48. Uncomplicated AUFIs
• Enteric Fever: Azithromycin, Cephalosporins (No Cefixime). NO
Fluoroquinolone.
• Scrub typhus: Doxycycline, Azithromycin.
• Leptospirosis : Ampicillin, Doxycycline, Azithromycin.
• Azithromycin in Enteric Fever: 1 g OD x 5 days or 1 g on day 1 ---500
mg OD x 6 days
• Azithromycin in Scrub typhus or Leptospirosis: 500 mg OD x 3-5 days
49. Step 5 : Monitor response, review results
• Monitor responses
• Follow up test results
• Consider alternative diagnosis: Amebiasis, endocarditis, TB,
brucellosis.
50. Summary
• 5 major disease groups cause AUFIs in India : SMEAR. This is also a mnemonic for
key clinical findings and complications
• A step-wise epidemiological and clinical approach can be useful in reaching a
probable diagnosis, initiating therapy and saving lives. Rule in and rule out features
should be seen in all patients, and look, you may find an eschar.
• Basic tests can provide information of diagnostic and prognostic value.
• A positive confirmation of diagnosis is easiest with malaria and dengue. Serology in
the other AUFIs should be cautiously interpreted.
• Ceftriaxone and Doxycycline is recommended as presumptive antibacterial therapy in
patients with severe possible bacterial AUFIs. Azithromycin may offer choice of
appropriate Rx for probable bacterial AUFIs which are uncomplicated.
