A hospital based study of rickettsial diseases evidenced by Weil Felix test in a tertiary care hospital
Uttam Udayan, Meena Dias, Santosh Machado
Department of Microbiology, Father Muller Medical College, Mangalore, Karnataka, India
Meena Dias
Associate Professor, S 3, Casa Leila, S.L Mathias Road, Falnir, Mangalore - 575 002, Karnataka
Introduction: Rickettsial infections, one of the re-emerging diseases are increasingly underdiagnosed due to nonspecific symptoms, absence of reliable and affordable diagnostic test and contribute substantially to the acute febrile burden and preventive illness in many populations. A delay in diagnosis and therapy are associated with increased morbidity and mortality. Objectives: To determine and categorize rickettsial disease titers by Weil Felix test, and to know the frequency of rickettsial diseases in febrile patients presenting to a tertiary hospital. Materials and Methods: In a prospective study, a total of 100 samples were tested by Weil Felix test from patients with fever and results were analyzed. Results: Out of 100 samples 64 were positive. Male preponderance was seen. The most common clinical symptom were fever, rash followed by hepatomegaly and splenomegaly. One patient with a high titer of more than 1280 died of encephalitis. Conclusion: In the absence of availability of a good reliable serological or molecular evidence, Weil Felix test can be used in the laboratories mainly due to cost and technical aspects of other reliable tests for diagnosis.
Keywords: Rickettsial disease, Weil Felix test, PUO
Udayan U, Dias M, Machado S. A hospital based study of rickettsial diseases evidenced by Weil Felix test in a tertiary care hospital. CHRISMED J Health Res 2014;1:150-3
Udayan U, Dias M, Machado S. A hospital based study of rickettsial diseases evidenced by Weil Felix test in a tertiary care hospital. CHRISMED J Health Res [serial online] 2014 [cited 2023 Jan 30];1:150-3. Available from: https://www.cjhr.org/text.asp?2014/1/3/150/138883
Rickettsiae are aerobic gram-negative cocobacilli, obligate intracellular organisms associated with arthropod which acts as mechanical vectors for the transmission of diseases in mammals. [1] These organisms usually cause fever and other associated morbidities, if not diagnosed and may be a threat to public health.
The geographical distribution is dependent on the vector responsible for transmission of disease. Rickettsial diseases are prevalent in India. The disease has been reported from Jammu and Kashmir in the north to Kerala in south. [2],[3] Information about research on rickettsial diseases in India is negligible which accounts for the under diagnosis of the disease as these reported cases form only tip of the iceberg leading to public health problem. Treating physicians should be aware of the disease condition and its presentation to include in differential diagnosis of many Pyrexia of Unknown Origin (PUO) cases. [4]
The nonspecific symptoms and lack of data on the geographical distribution and low index of suspicion makes it difficult for physician to include in differential diagnosis. In a tertiary hospital, these easily treatable diseases can go unnoticed if not properly suspected and diagnosed. Hence an attempt has been made to use Weil Felix test in the diagnosis of rickettsial infections in the absence of reliable serological tests especially in a resource-limited settings and to know the presence of this disease in this area. Weil Felix test is a nonspecific tube agglutination test in which antibodies against rickettsiae are detected using Proteus antigens.
A prospective hospital based study conducted in the Department of Microbiology of a teaching hospital, in which 100 patient samples with history of fever for more than a week with or without rashes presenting to out-patient services and admitted in our hospital were included in this study.
With proper aseptic precautions, patient's blood was collected in a BD™ (Becton Dickinson) vacutainer by venepuncture and then transported to the laboratory. The patient's serum was tested for Weil Felix test (PROGEN, Tulip diagnostics Pvt Ltd.) by qualitative slide agglutination and quantitative tube agglutination test according to standard protocol with double dilution of 1:20-1:160 for initial screening followed by further dilutions to achieve end titer. [5] Positive samples were also correlated with other tests like Widal test, Dengue IgM Enzyme Linked Immunosorbent Assay (ELISA) and presence of Proteus infection by urine culture in the same patient.
Results and Analysis
As there is no data regarding the baseline titer of rickettsial diseases in this geographical area, OX-K, OX-19, and OX-2 titers 160 and above were considered significant.
Out of 100, 64 blood samples showed agglutination. The 51 (79.68%) of 64 samples were regarded significant based on titers. Out of 51 significant titers, 11 (21.56%) samples were significant for OX-K antigen and thus for scrub typhus. The significant titers for OX-2 and OX-19 were 45 (88.23%) and 10 (19.60%) respectively. OX-K titers are usually raised in scrub typhus while OX-19 and OX-2 in tick typhus. Mixed antigen titers were seen in 11 (17.18%) blood samples among the 64 samples analyzed, making it too difficult to interpret [Table 1]. Mixed antigen titers were mostly seen with OX-K. In one case with OX-K titer of >1280, OX 19 had 640 and in others it was OX-2 with titer of 320.
Table 1: Mixed antigen titers
Among 64 samples, 46 (71.87%) were males and 18 (28.13%) were females. [Table 2] explains the relationship between clinical presentation and test positivity. One patient with a high titer of more than 1280 died of encephalitis. No other complications were noted. Two patients showed rise in titer in repeat samples.
Table 2: Clinical features and Weil Felix in samples tested
[Table 3] shows the results of other tests performed on positive samples. Only five samples were positive for Salmonella and two for dengue. [Table 4] shows titers of five Widal positive samples. All the patients tested negative for Proteus.
Table 3: Correlation of Weil Felix with tests to rule out other causes
Table 4: Titers of 5 samples which showed Widal positivity
All the patients with significant titers were treated with doxycycline and they responded very well to treatment except six patients. Out of whom one patient died of encephalitis and others left against medical advice. Others who had positive Widal test were started on third generation cephalosporins and they recovered uneventful [Table 5]. Patients showing significant titers with various antigens are shown in [Table 6].
Table 5: Response to treatment with doxycycline and
other antimicrobials
Table 6: Number of patients showing signifi cant titers
In a developing country like India, there is lack of data on rickettsial diseases and insufficient research, diagnosis of Rickettsiae is complicated as laboratory culture of organism is not recommended due to high chances of transmission of infection to the persons handling in the laboratory. A lot depends on serological evidence and molecular techniques for the diagnosis of rickettsial infection. Serological test includes latex agglutination [6] , immunofluorescence, indirect hemagglutination, ELISA, and Weil Felix test. [7] Polymerase chain reaction (PCR) for detection of rickettsial DNA is available but it is not feasible with every institution to do it.
Weil Felix test is a test with one too many pitfalls and irrelevant results can be seen in many other conditions. False positive results have been obtained with infection by Salmonellae, small pox, Streptococcus pyogenes, and Proteus.[8] The importance of this test, though being not a standard test, is still reasonably good when it comes to evaluating a fever of unknown origin (FUO). This test when performed in conjunction with other tests, which can falsely report Weil Felix test as positive, such as Widal, Dengue IgM ELISA and presence of Proteus infection in the body, can eliminate the possibility of reporting false positive and increase the value of this tube agglutination test. In our study, out of 51 positive samples only seven were positive for typhoid and dengue, but we could not rule out false positivity due to the absence of specific test. These patients were treated with both doxycycline and third generation cephalosporins.
The associated symptoms with fever also play a role in not only ordering the test for confirmation but also choosing the appropriate antimicrobial therapy. In our study we had all the patients suffering from fever, as it is being the major inclusion criteria. Among the tested samples, rashes and eschars were seen in 29 (61.70%) patients making it easy for the physician to suspect rickettsial fever. But rash may not be present in all cases. We noticed in 18 patients who had fever and rash showed negative result with Weil Felix test. Hepatomegaly and splenomegaly was seen in scrub typhus patients all of whom had titers of OX-K more than 320. One patient with high titers for OX-K >1280, died in intensive care unit (ICU) due to encephalitis, before any therapeutic intervention could be done. While one patient with high titers of OX-K showed a big eschar on thigh and also diagnosed to be suffering from Acute Myeloid Leukemia. Additional results of hyponatremia, thrombocytopenia, and low to near normal leukocyte count may help in the diagnosis. In our study thrombocytopenia was seen in 22% of cases and hyponatremia in 18.75% cases. In addition to these, other information like exposure to tick should also be considered. We could elicit the history only in few patients. Persistence of fever even after 48 hours, presence of rash and tick exposure with altered biochemical parameters should alert the clinician to test for rickettsial antibodies.
The frequency of appearance of agglutination of OX-K and OX-19, seen in 11 (17.18%) and 9 (14.06%) patients respectively was less compared to OX-2 which was seen in 44 (68.75%) of patients. The total sample size in this study may be not sufficient enough to say definitely regarding the frequency of appearance of OX-2 antigen titers.
In our study there were totally nine significant titers for OX-19 with four being significant with only OX-19 and remaining five being mixed with other antibodies titers. Out of 100 samples tested, 13 samples gave a titer less than 80 and below which indicates that it is prevalent in this part. This gives us an idea that typhus fever group cases are presenting to outpatient departments and many at times it goes undiagnosed or under diagnosed. With appropriate investigations and clinical correlation with patient's signs and symptoms, there can be successful diagnosis and treatment.
The appearance of OX-2 agglutination in the tests was seen in 34 tested samples. The highest dilution recorded is >1280. This antigenic agglutination is basically seen in spotted fever groups and can also be seen in typhus group. Patients suffering from spotted fever are presenting to hospitals and needs to be evaluated appropriately. Appearance of this category of antibodies in high numbers and high titers needs to be evaluated further. With such small number of sample it is inappropriate to jump into conclusion. Patients whose sample showed significant titers were treated with doxycycline, most of them improved over time and they were relieved of fever and associated symptoms.
Finally, this study just gives an insight of the rickettsial fevers presenting to our hospital and clearly indicates that there are genuine cases presenting with fever, associated with rashes or any other atypical presentations and physicians should be aware of this disease. Rickettsial diseases have become a potential differential diagnosis of any FUO presenting to our hospital.
Limitation of the present study was that the test could not be compared with ELISA or other specific tests. But most of our laboratories lack these facilities except few elite laboratories situated in urban areas.
As stated earlier, evaluation with more number of samples and for longer duration is the need of the hour to know the exact magnitude of the problem. Comparative studies using different diagnostic techniques are essential for proper work up of any case, but dependency on Weil Felix test alone, especially in a tertiary care hospital, is not recommended. In spite of all the drawbacks associated with it, the Weil Felix test still serves as a useful and cheapest available tool for the laboratory diagnosis of rickettsial diseases.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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