PROFILE OF RICKETTSIAL FEVER IN CHILDREN
Deepa Patil*, L. H. Bidari**, Nitin Tikare***, V. A. Revankar ****
Department of Pediatrics.*, Department of Pediatrics.**, Department of Pediatrics.***, Department of Pediatrics.****
Introduction
Rickettsial Fever is an acute febrile, zoonotic disease spread by bite of ticks or mites. The infection manifests as non-specific febrile illness which is sometimes accompanied by gastrointestinal, respiratory or central nervous system manifestations. Illness can be in apparent or severe and death is reported to occur in 1% to 30% of untreated cases. The presences of Rickettsial diseases in India have been documented in Jammu & Kashmir, Himachal Pradesh, Uttaranchal, Rajasthan, Assam, West Bengal, Maharashtra, Kerala and Tamil Nadu .(4) Recently the disease has reemerged in many areas of India.(2,8)

Diagnosis and surveillance of this disease can be challenging particularly in the absence of advanced laboratory techniques or expensive tests. Rickettsial diseases may pose a serious public health problem, if not diagnosed or misdiagnosed. Immuno-fluorescence assay (IFA) is the gold standard technique and is used as a reference technique in most laboratories.

Weil Felix (WF) test is based on the detection of antibodies to various proteus species which contains antigens with cross-reacting epitopes to antigens from members of the genus Rickettsia. Even though WF agglutination test is not very sensitive but when positive, it is rather specific test.(12) Good correlation between the results of WF test and detection of IgM antibodies by an Immuno-fluorescence assay has been demonstrated.(10) This study was done to see the clinical and hematological profile of patients suffering from Rickettsial Fever admitted in our hospital.

Type of Study:

Prospective study

Methodology:
All patients who were suspected clinically and supported by lab. investigations of Rickettsial Fever admitted in Dr. Bidari's Ashwini Hospital, Bijapur during the period of January 2006 to September 2006 were included in this study. Clinical suspicion of Rickettsial fever was based on history of fever, non-confluent maculopapular or purpuric rash involving palms and soles and supported with Weil Felix Test.

The WF proteus agglutination assay (P. vulgaris, OX-19, OX-2, OX-K strain agglutination; Wellcome; Dartford, England) was performed on each sample according to the manufacturers instructions by diluting each serum 1/20 to 1/1280. A Single WF titre of 1:320 or rise of four fold or more in titres on repeat testing starting from 1:40 was accepted as positive results.

On admission, a complete physical and laboratory examination (Complete blood count, Liver function test, WF, Widal & Malarial Parasites) were done. CSF, serum electrolytes, X-Ray, 2D-Echo were done as and when needed.

All patients were treated with chloramphenicol at the dosage of 50-100mg/kg/day in 3 divided doses for duration till the patient has been afebrile for at least 2-4 days along with Clarithromycin for 7 days, and Doxycycline in the dose of 2.5mg/kg/day once daily for 5 days in children above 8 years.

Observations:
In our study from January 2006 to September 2006, 48 patients satisfied our inclusion criteria. Age ranged from 2 ½ months to 9 years with maximum incidence in 1-5 years of age group (75%) with male predominance (M:F = 2.6:1).

Major presenting symptoms were fever and rash (100%), followed by oedema (77%), altered sensorium (52%), convulsions (46%) and joint pains (27%). Rash was seen in all children of which characteristic non-confluent maculopapular rash involving palms and soles was seen in 42 cases (87%) and purpuric rash was seen in 6 cases (13%). Other signs observed were oedema (87%), hepatosplenomegaly (85%), altered sensorium (50%), seizures (46%), upper GI bleeds (13%), peripheral gangrene (6%), myocarditis (4%) and pneumonia (4%).

Mean hemoglobin was 8.6gm/dl (5.2 to 14gm/dl), leucopenia (<5000 cells/mm3) seen in 1 case, where as leucocytosis (>10000 cells/mm3) seen in 43 cases (89.5%), thrombocytopenia (<1.5 lakh cells/mm3) in 18 cases (37.5%) and thrombocytosis (>4.5 lakh cells/mm3) in 8 cases (16.6%).

On WF test, 7 patients showed titres = 1:320 for OX2 antigen and 13 patients for OX-19 antigen, while 7 patients showed titre =1:320 for both the antigens at presentation. Of the 20 children whose titres were <1:320 had shown rise in titre >1:320 after one week.

CSF analysis was done in 22 children of which 13 (27%) were abnormal. CSF sugar was low in 8 cases. CSF protein was high in all 13 cases (100%) with mean CSF protein of 253mg/dl (65-340mg/dl), CSF pleocytosis was seen in all 13 abnormal CSF with mean cell count 143 cells/mm3 (10-265cells/mm3). Polymorphonuclear predominance was seen in 9 cases (69.2%) and lymphocytic predominance was seen in 4 cases (30.7%).

3 children required mechanical ventilation of which 2 expired and 1 left against medical advice.

44 cases (91.6%) improved, 2 cases (4.16%) expired and 2 cases (4.16%) left against medical advice.

Discussion
Rickettsial disease is an acute infectious disease caused by Rickettsial organism, which is transmitted to humans by ticks, mites or lice. Though, it was reported by Anton et. al. (15)14, no such age is found in pediatric age group. In our study age of presentation ranged from 2 ½ months to 9 years with maximum children from 1-5 years of age group. It was in comparison with Colomba et. al. who showed median age of presentation as 6 years with male preponderance (M:F-2.6:1). Majority of the patients presented with fever and rash (100%) and a characteristic non-confluent maculopapular rash involving palms and soles was seen in 87%, which was more in comparison to Colomba et. al. (94%) 15, and purpuric rash was seen in 13%, which was more in comparison with Colomba et.al. (2.3%)15, hepatosplenomegaly was seen in 85% which was far more in comparison to S K Mahajan et. al. (43%), altered sensorium was seen in 50% which was double in comparison to S K Mahajan et. al. (24%), seizures was seen in 46%. Hepatosplenomegaly (85%), altered sensorium (50%), seizures (46%) was double in comparison to S K Mahajan et. al. (43%, 24%, 19% respectively)1. Peripheral gangrene 6%, myocarditis 4% and pneumonia 4% were also seen in our study.

On WF test, 7 patients showed titres = 1 : 320 per OX-2 antigen and 13 patients for OX-19 antigen, while 7 patients showed titres = 1 : 320 for both the OX-2 and OX-19 antigens at presentation. In 20 patients the titre increased > 1 : 320 in the convalescent phase.

According to the WF titres, the most probable Rickettsial disease would be tick borne-spotted fever or epidemic typhus. Since no louse infestations (the scalp & body infestation, lymphadenopathy) was seen in any of the patients and most of them were below low socioeconomic status from rural area, there are more chances of tick infestation. Hence tick borne spotted fever is the most likely cause, but still further investigations like PCR should be done to detect the different Rickettsial organisms.

Even though the sensitivity WF has been claimed less, there are several reports which suggest good correlation of WF test with other standard tests used. Amano et. al. (11) 10 tested sera from 17 patients of Rickettsial disease in the acute and convalescent phases by indirect immuno-peroxidase test, WF test, Enzyme Linked Immuno Sorbent (ELISA) and immuno-blotting in the comparison of antibody titres in acute & convalescent phase sera, a parallelism of increment was noted between the titres in WF test and titres of immunoglobulin M (IgM) in ELISA. Amano et.al (12) 11 observed that of the sera which were positive to Rickettsia by indirect immuno-peroxidase approximately 80% sera were positive to antigens by WF test.

In the study conducted in South India (15) 13, the sensitivity to patients antigens was 30% at a titre breakpoint of 1 : 80 but the specificity and positive predictive value was 100%.

Saah A J et. al suggested that, even though WF test is not a very sensitive test but when positive it is rather specific test (14) 12.
Conclusions
  1. Rickettsial fever does exist in our area posing diagnostic difficulty and should be kept in mind in workup of PUO.
  2. The availability and the cost of Standard serological methods for Rickettsia are major problems in India. The diagnosis should be largely based on high index of suspicion and careful clinical, laboratory and epidemiological evaluation supported by cost effective tests like WF.
  3. WF test is still not entirely absolute but should be interpreted in the correct clinical contexts.
  4. Use of empirical treatment should also be considered to reduce the high mortality and morbidity observed with the disease.
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