Syndromic approach inDiagnostic virology

What we discus here?

• Why do syndromic approach? • Different types of syndromes• One syndrome - related viral infection

Why do syndromic approach?

• No technique – identify broad group of viral pathogen.. Like Bacterial culture

• Numerous pathogenic viruses

Syndrome• A syndrome is a set of medical signs and

symptoms that are correlated with each other and, often, with a specific disease.

• There is no single step diagnostic procedure in viral disease – we rule out a viral disease in syndrome based testing.

Major clinical syndromes related to viral infection

1.Fever of unknown origin

2. Influenza like illness (ILI)

3. Severe acute respiratory illness (SARI)

4. Acute respiratory distress syndrome (ARDS)

5. Dengue like illness DLI (fever +myalgia)

6. Fever + Arthralgia

7. Fever + rash(measles like)

8. Acute encephalitis syndrome(AES)

9. Fever + Parotitis (mumps like)

10. Acute jaundice syndrome (AJS)

11. Acute diarrhoea syndrome (ADS)

12. Acute hemorrhagic fever syndrome (AHFS)

13. Syndromes with conjunctivitis

Syndromes

Diagnostic Approach• Test to be done is choose based on an algorithm by a

panel after thorough discussion.• Following factors are observed1. Age of patients.2. All presenting clinical symptoms3. History/Job/Travel etc..4. Season5. Epidemiological factors6. Any other relevant information7. Cause suspected by Clinician also checked.8. Very detailed request form.

Examples

Fever of unknown origin• Diagnostic challenge• Fever may be due to many reason• Bacteraemia/Sepsis• Secondary to a focal infection• Any non specific presentation of a disease• Parasitic, Fungal infection• Viral _ Diagnosis is very difficult.

Diagnostic steps- FUO

• Blood/Serum

• Most of FUO are bacterial.• Leptospira/Scrub typhus

• Dengue – IgM detection by ELISA

INFLUENZA LIKE ILLNESS (ILI)

Case Definition: Sudden onset of fever>100 0F

with

•Cough and or/ sore throat AND•An absence of other diagnosis

Severe Acute Respiratory Illness (SARI)

Case definition •for persons > 5years - Sudden onset of fever, and Cough or sore throat, AND Shortness of breath/difficulty in breathing

OR•Any child <5yrs old clinically suspected of having pneumonia or severe /very severe pneumonia

Causes of ILI & SARI

Acute Respiratory Distress Syndrome (ARDS)

• Acute respiratory distress syndrome (ARDS) occurs when fluid builds up in the air sacs (alveoli) of lungs. less oxygen can reach bloodstream.

•Acute onset•PaO2 /FiO2 (fraction of inspired oxygen) <200mmHg.•X-ray bilateral infiltrates.•Pulmonary arterial occlusion.

ARDS causing agents

Diagnostic Approach to ILI, SARI and ARDS

• Syndrome is classified into two classes.

• More symptoms seen in URT eg: ILI

• More symptoms seen in LRT eg: SARI & ARDS

Sample URT – Throat swab – Ideal• Nasopharyngeal swab – Ventilator patientSample LRT – ET Aspirate, Bronchial Washing/BALBlood – For rule out other cause. Eg: Dengue mimic

ILI – IgM dengue can be detected.

Testing pattern• Throat swab/Respiratory specimen

PCR for Influenza A and B and sub typing by PCR

If patient 6 months – 1 year age RSV – PCR then InfV A&B PCR

if negative, PCR for adenoV, RhV, coronaV, enteroV, RSV, hMPV,

parainfluenza virus.

Multiplex PCR – panel available: Kit.

Blood sample: Rule out Dengue/Lepto mimicry-IgM detection

ImmunoFlu : possible but not usually employed in diagnosis.

? Any bacterial or other cause?

DLI(fever+myalgia)

Definition:

• A diagnosis of DLI is established on the basis of clinical features and supporting non serologic laboratory investigations •With negative /incomplete serologic testing can be included

Conditions that mimic febrile phase of dengue viral infection

FLU LIKESYNDROMES

FEVER WITH DIARRHEARASH

Iillnesses with Neurological manifestations

Others

INFLUENZA CHIKUNGUNYAHIV(seroconversionstate)

Rubella Measles Chikungunya Drug reactions

Meningococcal infection

Rota virus other enteric infections

causes of meningoencephalitis

Febrile seizures

Leptospirosis Rickettsial infection Enteric fever MalariaViral hepatitis Brucellosis

Conditions that mimic critical phase

Bacterial Viral Parasitic

LeptospirosisRickettsial infections

Acute gastero enteritis

Typhoid

Bacterial sepsis

Septic shock

Viral hepatitis

Other causes of Viral hemorrhagic fevers like Kayasanur forest disease ,Crimean congo hemorrhagic fever

Malaria

Others-acute leukemia-other malignancies-other causes of acute

abdomen-platelet disorders

Diagnostic approach to DLI

• Sample : Blood• IgM ELISA – Dengue, CHIK V, Leptospira, • Dengue NS1 ELISA• KFD PCR• IgG ELISA _ Dengue- Second infection? Any other cause further studied.

Diagnostic approach – Fever with arthralgia

• Sample: Blood• IgM ELISA: Chikungunya, Dengue, Lepto.• KFD - PCR

Fever with rash (measles like illness)rash is an area of skin that has become redden/swollen/irritated

Diagnostic approach – fever with rashMaculo – papular rash• Sample: blood, Throat swab• IgM ELISA – Dengue, Measles, Corona,

Rubella, Any seasonal/endemic pathogen.• Throat swab – PCR for measles, rubella,

enteroV, coronaV, ParvoV, KFD (season)• IgM – ELISA - HHV 6/7, CHIK V.

Diagnostic approach.. continues

Vesicular rashLocation of vesicle, age, geographic area are

importantEg: HSV 1 facial/HSV 2 genital• Blood : HSV and VZV IgM - ELISA• Vesicle swab : PCR for – HSV 1&2, VZV, HFMD

Virus

Fever with parotitis (mumps like infection)

Fever with parotitis – Diagnosis• Sample: Blood, Salive, Urine, CSF• Blood: IgM mumps• Other samples: PCR – both monoplex and

multiplex PCR• Eg: Saliva PCR for mumps, parainfluenza, EBV,

Coxsackie virus, AdenoV parvo, HIV.• PCR in Urine and CSF – Positive in many cases.

Eg: mumps.

Acute encephalitis syndrome(AES)Definition• A person of any age, at any time of the year with acute onset of fever, a change in mental status (confusion, disorientation, coma, inability to talk)

AND/OR

New onset seizures(excluding simple febrile seizure)

Acute encephalitis syndrome causing agents

AES in immunocompromised

AES - Diagnosis• CSF• BloodCSF – IgM ELISA – JE and WNF. CSF – PCR for HSV 1&2, VZV, enteroV, other

suspected pathogen based on patient history age,seson etc..

Blood: IgM ELISA - Dengue, Lepto, Scrub, and other suspected pathogen based on patient history age etc..

PCR with blood for KFD

Acute Jaundice syndrome

• Definition :acute onset of jaundice and severe illnessAND

• Absence of known predisposing factors

Causes acute Jaundice syndrome

Diagnosis - AJS

• Sample: Blood

• HBsAg Detection By ELISA• IgM ELISA – HAV and HEV• IgM/IgG ELISA for HCV• Leptospira IgM

Acute Diarrhea Syndrome

• Definition :Acute diarrhea and severe illness ANDabsence of known predisposing factors

•Diarrhea :Increased frequency of defecation or recent change in consistency and character of stools

•If lasts more than 3 weeks it is known as chronicdiarrhea .

Viral infections cause watery diarrhea

Causes of watery diarrhoea

Diagnosis _ ADS

• Sample: Stool, Rectal swabPCR_ Ist line: Rota, Noro, Adeno, Astro._ second line: Corona, Entero, any other

suspiciousStool sample: Rota Ag ELISA

• Blood: Dengue, Lepto IgM ELISA

Acute hemorrhagic fever syndrome

DEFINITION: Acute onset of fever of less than 3 weeks duration And any two of the following.•Hemorrhagic or purpuric rash•Epistaxis (bleeding from nose)•Hemoptysis (coughing up of blood)•Blood in stool•Other hemorrhagic symptomsAND •absence of known predisposing factors

Diagnosis - AHFS

• Sample: BloodGeographic location/Travel history….• ELISA for IgM/(IgG secondary infection as in

case of DHF)• Dengue, KFD, YF, Hunta• Lepto, Malaria, Rickettsial • PCR in Blood

Syndromes with conjunctivitis

Acute hemorrhagic conjunctivitis

• Complication of conjunctivitis

• Enterovirus, CoxsackieA24, A24v

• Diffuse patchy conjunctival haemorrhage

• Hemorrhagic patches diffusely distribute in the bulbar conjunctiva -3 days after onset

Complication of AHC

• Moderate epithelial keratitis and conj. hyperaemia

Diagnosis of syndromes with conjunctivitis

• Sample: Conjunctival swab, Corneal impression smear, Blood

• Monoplex and Multipples PCR – Swab• Direct immuno fluorescence – Smear• IgM against virus detection: Blood

Comment: Many other techniques like culture, Animal inoculation,

Direct and indirect immuno fluorescence, HA, HIA, VNA are not employed as a diagnostic technique

- since are not reliableNowadays lab diagnosis of Viral

infection is greatly depended on PCR and ELISA

Thank you all…