RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
PG DISSERTATION SYNOPSIS
CLINICAL PROFILE OF RICKETTSIAL INFECTION


1 .Name of the candidate and Address : Dr. Kurian Thomas

Residential address : Koilparambil House

Arpookara East. P. O

Kottayam

Kerala

2. Name of the institution : St. John’s Medical College,

Bangalore - 560034

3. Course of the study and subject : M.D (General Medicine)

4. Date of admission : 16th April 2011

5. Title of the topic :

“CLINICAL PROFILE OF RICKETTSIAL INFECTION”

6. BRIEF RESUME OF THE INTENDED WORK

6.1 NEED FOR THE STUDY

The incidence of rickettsial infection had seen a significant decline in the nineties secondary to widespread use of insecticides. But the past decade has again witnessed a resurgence in the incidence of rickettsial infection.

Though varieties of rickettsial infections are described in literature the main agent that we come across is rickettsial typhus caused by Orientia tsutsugamushi. In most clinical scenarios the presentation of rickettsial infection refuses to fit into a particular pattern. The clinical presentation of rickettsial infection is wide and varied and the severity also varies from mild to severe

Today rickettsial infection can be accurately diagnosed by immunofluresence and ELISA. But these tests are very expensive and are not easily available. As a result the main diagnostic tool in the clinicians hand is still the weil-felix test. Weil felix test has less sensitivity but the specificity has been proven to be quite acceptable.

In view of this it is imperative that the wide and varied clinical presentations of rickettsial infections be studied in detail because if intervened at an appropriate stage rickettsial infection has excellent prognosis

6.2 REVIEW OF LITERATURE

Rickettsial infection is endemic in the tropical and sub tropical regions of the Asian continent. The main agent causing rickettsial infection in our country is Orientia tsutsugamushi,which is the etiological agent for scrub typhus.[1] Multiple studies conducted in India and abroad have validated the re-emerging trend of rickettsial infection.[1,2,3,4]

The clinical presentation of rickettsial infection is varied and refuses to fit into a particular pattern. Various clinical conditions where the diagnosis of rickettsial infection should be considered are fever without source, pyrexia of unknown origin (PUO), fever with rash (rash which is petechial, involving palms and soles, having centripetal spread), fever with eschar, meningoencephalitis or aseptic meningitis, acute renal insufficiency with eschar, and infective vasculitides.[5]

The clinical features of rickettsial infection in general include fever with chills and rigour (100%), vomiting (43%), headache and myalgias (38%), lymphadenopathy (53%), jaundice (53%), congested eyes (34%), hepato-splenomegaly (43%), pain abdomen (29%), diarrhea (18%)[6], dyspnea (18%)[6], altered sensorium (24%), seizures (19%), abnormal bleeding (14%), rash (10%) and eschar (10%).[3] Rickettsial infection can lead onto serious end organ which includes pneumonitis, ARDS, acute renal failure, myocarditis, disseminated intravascular coagulation (DIC)[7] and septic shock.[6]

Doxycycline is the drug of choice for most rickettsial infections.[8] With early intervention, extremely favourable response is seen. No significant morbidity or mortality has been reported in patients who receive early and appropriate treatment.[7]

The gold standard test for the diagnosis of rickettsial infection is immunofluorescent assay. However, as it is highly expensive and not freely available in India, it is seldom used. Also there is little consensus apparent in the choice of IFA methodology (i.e., antigenic strains and antibody isotype) and of the positivity cutoff limits for diagnostic purposes. Hence in an endemic country like India, the seroprevalence in the normal population has to be estimated before IFA can be used as a diagnostic method.[9]

Weil – felix test is still the widely used test for diagnosis of rickettsial infection. Even though the sensitivity of the weil – felix test is low, it has high specificity and positive predictive value. In a study by Isaac R et al, it was shown that the sensitivity for Ox-K was 30% at a titre breakpoint of 1:80, but the specificity and positive predictive value were 100%. At a breakpoint of 1:20, the sensitivity was 61%, the specificity was 94%, and positive predictive value was 84%. At a breakpoint of 1:40, the sensitivity was 49%, the specificity was 96%, and positive predictive value was 88%.[1]

Considering the endemicity of rickettsial infection in our country and the inexpensive yet effective treatment options available, it is highly unlikely that the weil – felix test will be replaced anytime soon by an expensive investigation such as the IFA. Hence it is imperative that the clinical profile of rickettsial infection be studied in detail so as to assist the clinician in making an early diagnosis.

6.3 AIMS AND OBJECTIVES

1.  To assess the clinical profile of rickettsial infection

2.  To assess organ dysfunction in rickettsial infection with special focus on renal manifestations

7. MATERIALS AND METHODS

7.1 SOURCE OF DATA

Place of Study : St. John’s Medical College Hospital, Bangalore

Study period : 1st August 2012 to 31st October 2013

Method : Descriptive study design

Sample size : 75

INCLUSION CRITERIA

1.  Weil felix positivity in dilutions greater than 1 in 160

2.  Typical clinical presentations with eschar

EXCLUSION CRITERIA

1.  Subjects who do not consent for the study.

2.  Subjects less than 18 years of age

3.  Cases with other established causes of infection

7.2 METHOD OF COLLECTION OF DATA

Cases of fever admitted in the study period in our hospital will be followed up on the basis of weil felix positivity. The clinical presentation and multiple organ dysfunction in these patients will be evaluated with special focus on the renal manifestations. In possible cases a paired serology will be done to further validate the diagnosis of rickettsial infection. Cases in which a more sensitive investigation such as blood or urine culture comes positive will be excluded even if there is a high probability of rickettsial disease coexisting so as to prevent dilution of data. The renal manifestations in normal patients and those with baseline renal impairment will be studied and compared in detail. The treatment protocol adopted and the response to treatment will also be scrutinised

CLINICAL ASSESSMENT PROFORMA

Name:

MRD No:

Age: IP No:

Sex:

Residence :

Occupation :

Similar ailment in relatives :

Co morbidities if any :

Yes / No /

History of tick bite :

Clinical features

Yes / No /

Fever

Yes / No /

Chills and Rigor

Yes / No /
Yes / No /

Malaise

Myalgia

Yes / No /

Rash

Yes / No /

Eschar

Yes / No /

Headache

Yes / No /

Giddiness

Yes / No /

Altered sensorium

Yes / No /

Seizures

Yes / No /

Cough

Yes / No /

Sore throat

Yes / No /

Difficulty in breathing

Yes / No /

Chest pain

Yes / No /

Palpitation

Yes / No /

Nausea

Yes / No /

Vomiting

Yes / No /

Diarrhoea

Yes / No /

Abdominal pain

Yes / No /

Oliguria / Decreased urine output

Yes / No /

Facial puffiness

Yes / No /

Congestion of eyes

Yes / No /

Pedal edema

Yes / No /

Any bleeding manifestations

Vitals at admission

a.  Pulse

b.  Blood pressure

c.  Respiratory rate

d.  Temperature

General examination

Yes / No /

Pallor

Yes / No /
Yes / No /

Icterus

Yes / No /

Cyanosis

Clubbing

Yes / No /

Lymphadenopathy

Yes / No /

Edema

Yes / No /

Elevated JVP

Yes / No /

Rash

Extent of rash (if present):

Yes / No /

Eschar

Any other notable findings:

Systemic findings

a.  Respiratory

b.  Cardiovascular

c.  Gastrointestinal

d.  Nervous system

Provisional diagnosis :

Vitals at admission

a.  Pulse

b.  Blood pressure

c.  Respiratory rate

d.  Temperature

General examination

Yes / No /

Pallor

Yes / No /
Yes / No /

Icterus

Yes / No /

Cyanosis

Clubbing

Yes / No /

Lymphadenopathy

Yes / No /

Edema

Yes / No /

Elevated JVP

Yes / No /

Rash

Extent of rash (if present):

Yes / No /

Eschar

Any other notable findings:

Systemic findings

a.  Respiratory

b.  Cardiovascular

c.  Gastrointestinal

d.  Nervous system

Provisional diagnosis :

Laboratory investigations

Weil felix titre :

ü  Hb :

ü  Leukocyte count :

P / L / E

ü  Differential count

ü  Platelet count :

ü  ESR :

ü  Blood urea :

ü  Serum creatinine :

ü  Serum electrolytes

a.  S. Na+ :

b.  S. K+ :

ü  Liver function test

a.  AST :

b.  ALT :

c.  ALP :

ü  Routine urine :

ü  Specific fever workup for infection –

Yes / No /

a.  MP

Yes / No /

b.  Dengue

Yes / No /

c.  Leptospirosis

Yes / No /

d.  Widal

Yes / No /

e.  Blood culture

Yes / No /

f.  Urine culture

g.  Others

ü  Chest x-ray

ü  ECG

ü  Ultrasound abdomen

Treatment

Choice of antibiotic :

Details

Other significant management:

Renal dysfunction

Yes / No /

History of renal dysfunction

Yes / No /

Renal dysfunction

Oliguric / Non oliguric /

If yes,

Yes / No /

Haematuria

Macroscopic / af / Microscopic / a
Yes / No /

Proteinuria

Baseline serum creatinine (if available):

Serum creatinine at admission :

Dialysis

Yes / No /

Is dialysis required

No of times dialyzed :

Response to treatment :

Yes / No /

Renal scan

Renal function at the time of discharge

8. LIST OF REFERENCES

1.  Isaac R, Verghese GM, Mathai E et al, Scrub typhus : prevalence and diagnostic issues in rural southern india, Clinical Infectious diseases, 2004 Nov, vol 39, pp. 1395 – 1396

2.  Mathai E., Rolain JM, Verghese GM et al, Outbreak of scrub typhus in southern India during the cooler months, Annals of the New York Academy of Sciences, June 2003, Vol 990, pp. 359 – 364. Available from www.pubmed.com (PMID 12860654)

3.  SK Mahajan, R Kashyap, A Kanga,V Sharma, BS Prasher, LS Pal, Relevance of Weil-Felix test in the diagnosis of scrub typhus in India, Journal of The Association of Physicians of India, Aug 2006, Vol 54, pp. 619 – 621

4.  Paddock CD, The science and fiction of emerging rickettsioses, Annals of the New York Academy of Sciences, May 2009, Vol 1166, pp.133 – 143

5.  Narendra Rathi, Akanksha Rathi, Rickettsial infections : Indian perspective, Indian Paediatrics, Feb 17 2010, vol 47, pp.157 - 164

6.  Tsay RW, Chang F Y, Serious complications in scrub typhus, Journal of Microbiology, Immunology and Infection, 1998, vol 31(4), pp. 240 - 244

  1. Mohd Ashraf, Arshad Farooq, Saika Bashia et al, Renal failure association with scrub typhus, JK Science, 2010 april-june, vol 12 (2), Available from http://jkscience.org/archive/volume122/Renal%20Failure%20Associated%20with%20Scrub%20Typhus11.pdf

8.  David H. Walker, J. Stephen Dumler, Thomas Marrie. Harrison’s Principles of Internal Medicine 18th edition. McGraw-Hill Companies Inc.; 2012. Chapter 174 The Rickettsial Diseases. pp.1407 – 1417

9.  Stuart D Blacksell, Naomi J Bryant, Daniel H Paris et al, Scrub typhus serological testing with the indirect immunofluorescence method as diagnostic gold standard: A lack of consensus leads to a lot of confusion, Clinical Infectious Diseases, 2007, vol 44, pp.391-401

9. SIGNATURE OF CANDIDATE :

10. REMARKS OF THE GUIDE :

11. NAME AND DESIGNATION OF

11.1 Guide : DR. SEENA SANKAR

ASSOCIATE PROFESSOR

DEPT. OF GENERAL MEDICINE

11.2 Signature :

11.3 Co-guide : DR. PRASHANTH G KEDALYA

ASSOCIATE PROFESSOR

DEPT. OF NEPHROLOGY

11.4 Signature :

11.5 Head of Department : DR. G D RAVEENDRAN

PROFESSOR & HOD

DEPT. OF GENERAL MEDICINE

11.6 Signature :

12.1. REMARKS OF PRINCIPAL:

12.2. Signature :