Cat scratch disease, Bartonella hensalae infection

1. CAT SCRATCH DISEASE
Dr. Dadimi Bhargavi
Division of VPE
P-2389

2. CAT SCRATCH DISEASE
Bartonellla henselae
Pleomorphic gram negative rod.
Facultative intracellular parasite
Fastidious.
Opportunistic pathogen.
Named after Diane Hensel, who contributed greatly to the initial isolation
of the organism.
Two major serotypes/genotypes
TypeI (Houston 1)
Type II (BA-TF/Marseille)

3. Epidemiology
Geographical distribution: Worldwide distrbution
B. Henselae Type I
Easter U.S
Asia
B. Henselae type II
Europe
Temperate climates
Seasonal variation
Peak August to October (North)
 Morbidity and mortality:
22,000 to 24,000 annual cases in U.S.
3 to 6% of general population are seropositive
Most common in children.
Most infections are self-limiting
Death is rare.

4. History
1950: Clinical syndrome describes in France by Debre et al.,1950
1983: Bacterial cause described by Wear et al.
Gram negative bacillus
Found in lymph nodes of patients (Warthin Starry silver stain)
1988: Organism successfully isolated and cultured.
1991: CSD bacillus named Afipia felis (Birkness et al.,)
1992: Rochalemaea henselae isolated
Pateints with bacillary angiomatosis
Refuted the role of A. felis in CSD
1993: Genera Rochamlimea and Bartonella united by Brenner and co-workers
B. henselae currently recognized as causative agent of CSD

5. Transmission
Cat fleas- Ctenocephalids felis-between cats
Scratch, bite/lick of cats contaminated with flea faeces- zoonotic
Rubbing eyes after cotact with cat- Oculoglandular syndrome
No human to human cotact. (SOT)

6. Cat Scratch disease
First described as a clinical entity in 1950 by Debre et al., 1950.
Incubation poeriod : 3-10 days.
Self-limiting.
CLINICAL SIGNS
Skin rashes- small erythematus papules, pustules, macules, vesicules or ulcers at
the site of inoculation in days to 1 week.
Lymph nodes- Ipsilateral regional lymphadenopathy after 1 to 2 weeks.
46%- upper extremities
26%-neck & jaw
18%- groin region
10%-other areas.
L.Nodes become tender and eventually suppurate.
Lymphadenipathy may persist for several months.
Myalgia, arthalgia, arthritis -10% of patients.

7. Complications
Immunocompromised individuals
Endocarditis- most commonly by Bartonella quintana.
Meningoencephalistis-severe head ache& acute cnfusion
Perinauds oculoglandular syndrome
Purulent unilateral conjunctivitis
Conjunctival granulomas
Ipsilateral perauricular lymphadinopathy
Bacillary angiomatosis & Bacillary peliosis
•Rare
•B.Henselae
•Blood-filled cycsts and sinusoidal dilatation of
liver.
•Fever, nausea, vomiting, diarrhoea
•B.Henselae, B. quinatana.
•Vascular proliferative disease of skin
and/or other interal organs.
•Usually an AIDS related disease.

8. 130 patients including those with fever and lymphadenopathy, infective endocarditis
and neuroretinitis were enrolled in the study.
Whole blood, serum, and lymph node aspirate and valvular vegetations if available
were obtained.
Indirect fluorescence assay (IFA) was performed and
Polymerase chain reaction (PCR) done for the citrate synthase gene (glt A).
Cultural isolation was attempted.
Results:
IFA was positive in 11 (8.46%) patients and PCR was positive in 3 (2.3%) patients.
Culture was negative in all the cases.
A higher incidence of Bartonella infection was seen in patients with fever and
lymphadenopathy i.e. 9/39 (23.07%) eight of whom were children.
Studies in India
Prevalence Bartonella hensalae infection in teritiary care hospital in North India-2016
Chaudhry et al., 2016
There are only 2 studies till now in Humans. These two studies were conducted by AIIMS,
Delhi

10. Prevalence Bartonella hensalae infection in teritiary care hospital in North India-2016
Chaudhry et al., 2018
145 patients including those with fever and lymphadenopathy, infective endocarditis
and neuroretinitis were enrolled in the study.
Whole blood, serum, and lymph node aspirate and valvular vegetations if available
were obtained.
Indirect fluorescence assay (IFA) was performed and
Polymerase chain reaction (PCR) done for the citrate synthase gene (glt A).
Cultural isolation was attempted.
Results:
IFA was positive in 11 (7.85%) patients and PCR was positive in 3 (2.14%) patients.
Culture was negative in all the cases.
A higher incidence of Bartonella infection was seen in patients with fever and
lymphadenopathy . 7 of whom were children.

12. Case reports in India
A case report in Pondicherry-2013 (12 year old boy)
• Presented with swelling of right side of neck
• Differential diagnosis for TB was done-Negative (no history of weight loss,
no abnormality in chest x-ray, no chronic cough, culture was negative and
Montoux test was negative, Ziehl Neelsen Staining was negative).
CSD diagnosis:
• Warthin Starry staining of Lymphnode biopsy
• History of catscratch.
Patel et al., 2018

13. Case report from Karnataka- 2018
A 17 year old male was presented with a single swelling on
inguinal region for 15days.
Diagnosis:
Staining of lumphnode tissues with Gomori methneamine silver
stain: rod shaped L shaped organism.
Giriyan et al., 2018
Case reports in India

14. Case report from Chennai-2007 (18 year old male)
• presented with swelling on right side of neck for 30 days, and
associated with evening rise in temperature.
• No history of recurrent cough, weight loss and contact with cat or any
other pet animal.
• Differential diagnosis for Tb was made- negative
CSD diagnosis:
• By histopathological examination
• Warthin starry silver staining of lymphnode tissue
• Seological examination in Center for Disease Control (CDC) in Delhi.
The titre was 1:130
Sheja et al., 2007
Case reports in India

15. Bartonella Endocarditis: a case series in Chennai
• Blood Culture Negative endocarditis (BCNE)- accounts for upto 76% of
Infective Endocarditis cases in developing countries.
• 0.2 to 12.7% of these cases are attributed to Bartonella spp.
• Study: 2016 to 2019, Chennai.
• 76 BCNE patients were screened for Bartonella Endocarditis by realtime PCR,
IFA, Western blot.
• 4 cases of were found to be because of Bartonella spp., among these 1 case was
attributed to Bartonella hensalae.
Rayvathy Balasubramaniam et al., 2020

17. Work in IVRI on Bartonella hensalae infection
Division of Veterinary Public Health-IVRI
• An occurrence study on Bartonella hensalae infection in Cats and
humans was carried out.
• Conventional PCR targeting ribC gene and IgG based IFAT was
performed.
• Risk factors associated with its occurrence were studied.
• Results are yet to be publised.

18. Diagnosis
Historically the diagnosis of a case of typical CSD required fulfillment
of three of the four following criteria:
1.History of an animal (usually cat) contact, with the presence of scratch or primary
skin or eye lesion.
2. Aspiration of “sterile pus” from lymph node or culture and other laboratory testing
that excluded other etiologic possibilities.
3.A positive CSD skin test.
4.A lymph node biopsy revealing pathology consistent with CSD.

19. Direct examination of blood smears
Bartonella are gram negative ,non-acid fast and stain poorly
Can be stained by silver staining (Warthin-Starry stain)
Low titres of bacteremia associated with B. henselae during infection make it
difficult for direct observation in blood smears.
Can be detected in early stages of lymphadenopathy but not during late stages.
Direct immunofluoroscence and acridine orange staining can also be used.
Diagnosis

20. Culture & Isolation
Generally attempted from blood and tissue.
Collected in EDTA vials.
Brain Heart Infusion agar, 5% defibrinated rabbit sheep blood agar.
Requires more than 7 days of incubation before colonies appear on agar plates.
Incubated at 35-37ºC, under conditions of 5-10% CO2 and >40% humidity.
This environment can be created in candle jars.
Diagnosis

21. Colony morphology:
1. Irregular, raised, whitish, rough and dry in appearance.
Characterized as “Cauliflower”, “molar tooth”, or “verrucous” with
pitting and strong adherence to agar.
2. Flat, circular, moist in appearance and less adherent.
Bartonella henselae typically displays a greater proportion of rough
colonies.
 Prolonged incubation time, curved gram negative bacilli on staining and
negative catalase and oxidase reaction-Preliminary identification.
Diagnosis

22. MALDI-TOFF
Matrix-assisted laser desorption /ionization time of flight mass spectrometry.
Useful tool for rapid detection of Bartonella spp. culture from a positive clincal culture.
Limitations are
Lack of availability of MALDI-TOFF technology in at most clinical laboratories
Testing requires isolation of positive cultures.
Diagnosis

23. PCR assay:
Real time or conventional PCR assays.
Bartonella DNA is rarely detected in sera from CSD patients.
Gene fragment specific for citrate synthase, heat shock proteins, and groEL or 16s
rRNA gene segments can be amplified from lymphnode tissue by PCR.
Amplification of rRNA gene fragments with universal primers, followed by nucleotide
sequencing of the amplified product-used in refernce laboratories.
PCR testing of excised cardiac valves has become one of the most important modalities
for Bartonella culture-negative diagnosis.
Diagnosis

24. Immuno Fluoroscence assay (IFA)
Most widely adapted test for diagnosis of Bartonella infection.
CDC developed an IFA that uses B. henselae bacteria cocultivated with Vero cells on
slides and then fixed.
Preparation of slides, dilution of serum and time consuming reading of
immunofluoroscence on each slide affectb affect the ability to make rapid, cost effective
diagnosis.
Sensitivity is high-84% (upto 95% when using the strictest criteria for CSD)
Diagnosis

25. Diagnosis
IFA IgG titres:
1. 1:60- Possible infection
2. >1:256- strongly suggests recent or acute infection.
3. A four fold rise in titre between acute and convalascent specimen is
definitive.
4. For culture negative endocarditis patients, titre >1:1024 is US labs and
>1:800 in unite des Rickettsies in France- supportive
evidence of Bartonella endocarditis.

26. Some patients with CSD may have low titers that subsequently increase as late as 3 weeks
after presentation; thus obtaining repeat serology as late as 3-4 weeks after presentation can
increase IFA sensitivity.
IFA tests often show extensive cross reactivity between antibodies of Bartonella quintana
and B. henselae.
Also serologic cross reaction with antibiodies of Chlamydia spp. and Coxiella burnetti.
Use of specific fractions or purified proteins may enhance the standardization and
interpretaion efficiency of serological testing of Bartonella.
Diagnosis

29. Vaccination
Currently there are no vaccines available either for cats or humans.
(Pal et al., 2021; CDC, 2019)

30. Treatment
Self-limiting and lymphadenopathy lasts for 2-8 weeks (No antibiotics required).
Azithromycin- 5 days (helps in faster resolution of lymphadenopathy).
>100 lb b.wt- 500mg on day 1 followed by 250 mg for 4 subsequent
days.
<100 lb b.wt-250mg.
Rifampin, ciprofloxacin, Tetracycline, Trimiethoprim-sulfamethoxazole, gentamicin
also used.
Bacillary angiomatosis and Bacillary Peliosis- high rates of relapse- treatment
proloned for 3-4 months

31. Prevention
Rough play with cats should be avoided.
Bites or scratches should be immediately washed with soap and water.
Keeping the cat nails trimmed.
Flea control