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Scrub typhus in a tertiary care hospital in the eastern part of Odisha
a p o l l o m e d i c i n e 1 2 ( 2 0 1 5 ) 2 e6
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/apme
Original Article
Scrub typhus in a tertiary care hospital in the eastern part of Odisha Suneeta Sahu a,*, Sudhi Ranjan Misra b, Prasant Padhan c, Samir Sahu d a Sr Consultant and HOD, Clinical Microbiologist, Dept of Clinical Microbiology and Immunoserology Apollo Hospitals, Bhubaneswar, India b Sr Consultant, Clinical Microbiologist, Dept of Clinical Microbiology and Immunoserology Apollo Hospitals, Bhubaneswar, India c Sr Consultant, Rheumatologist, Dept of Rheumatology, Apollo Hospitals, Bhubaneswar, India d Sr Consultant, Pulmonologist and Intensivist, Dept of Critical Care, Apollo Hospitals, Bhubaneswar, India
article info
abstract
Article history:
Aim: Our hospital, tertiary care hospital in the capital of the State of Odisha, had been
Received 3 January 2015
witnessing pyrexia of unknown origin, associated with breathlessness, renal and liver
Accepted 3 February 2015
impairment, which did not respond to high antibiotics like Carbapenems but to Doxycy-
Available online 7 March 2015
cline therefore, the present study was undertaken to identify whether scrub typhus is the aetiological agent and thereafter their characteristic features were further evaluated as an
Keywords:
effort in supporting its diagnoses and treating patients accordingly.
Scrub typhus
Methods: 150 Adult patients (age >12 yrs) admitted with pyrexia of unknown origin between
Orientia tsutsugamushi
April 2011 and October 2013, were evaluated. Weil Felix test was done in all these patients.
Weil Felix
Weil Felix positive samples were tested for Scrub Typhus IgM ELISA. Results: Of the 150 patients included in the study 50 (33.33%) were found to be positive for IgM antibodies against Orientia Tsutsugamushi. The cases were seen mainly in the months between September and November. The common symptoms found were fever, myalgia, breathlessness, rash and abdominal pain and clouding of memory. The diagnostic features like eschar were found in 32% patients. Nearly two thirds of patients had fever >30 days and myalgia (62.5%), breathlessness (64%). Most common complications was ARDS (62.5%) followed by liver and renal failure (50%). Conclusion: Our results showed that Scrub typhus should be considered in the differential diagnosis of POU associated with breathlessness, myalgia, rash, gastrointestinal symptoms, hepatorenal syndrome or ARDS. Empirical treatment with Doxycycline may be given in the cases with strong suspicion of Scrub typhus. Copyright © 2015, Indraprastha Medical Corporation Ltd. All rights reserved.
* Corresponding author. E-mail addresses: [email protected], [email protected] (S. Sahu). http://dx.doi.org/10.1016/j.apme.2015.02.003 0976-0016/Copyright © 2015, Indraprastha Medical Corporation Ltd. All rights reserved.
3
a p o l l o m e d i c i n e 1 2 ( 2 0 1 5 ) 2 e6
1.
Introduction
Scrub typhus, caused by Orientia (formerly Rickettsia) tsutsugamushi, is an acute infectious disease of variable severity that is transmitted to humans by an arthropod vector of the Trombiculidae family. “Tsutsuga” means small and dangerous and “mushi” means insect or mite. It affects people of all ages including children. Humans are accidental hosts in this zoonotic disease. While scrub typhus is confined geographically to the Asia Pacific region, a billion people are at risk and nearly a million cases are reported every year.1 Scrub typhus was first described from Japan in 1899. It was a dreaded disease in pre-antibiotic era and a militarily important disease that affected thousands of soldiers in the far east during the second World War.2 The rickettsia is transmitted by bite from an infected mite to human, after which it grows at the location of the bite and a characteristic skin lesion known as an eschar is formed. The rickettsia then spreads systemically via the hematogenous and lymphatogenous routes. The infected human then develops various systemic symptoms and reactions including fever, rash, lymphadenopathy, elevations of C-Reacting Protein (CRP) and liver enzymes.3 In India, scrub typhus broke out in an epidemic form in Assam and West Bengal during the Second World War. Later, the presence of this disease was found throughout India in humans, trombiculid mites and rodents.4 The term “scrub” is used because of the type of vegetation (terrain between woods and clearings) that harbors the vector; however, the name is not entirely correct because certain endemic areas can also be sandy, semiarid and mountain deserts. The word “typhus” is derived from the Greek word “typhus”, which means “fever with stupor” or smoke.5 Scrub typhus is a diagnostic dilemma because it has non specific presentations, limited awareness, low index of suspicious among clinicians and lack of diagnostic facilities.6 O. tsutsugamushi is an obligatory intra-cellular gram negative bacterium, and is a Zoonotic disease. Man is accidentally infected when he encroaches the mite infected areas, known as the mite islands. These areas consist of areas with secondary scrub growth, which grows after the clearance of primary forest, and hence the term scrub typhus. However the infection can occur in disease habitats like sea shore, ricefields and even semideserts.7 If the diagnosis is delayed or patient is not treated with appropriate antibiotics, the scrub typhus can present with serious complications such as renal failure, mycocarditis, septic shock, meningitis. Scrub Typhus broke out in an epidemic form in Assam and West Bengal during world war II. Outbreak of scrub typhus in southern India has been reported in 2003.8 However cases in the state of Odisha has not been reported so far.
2.
Materials & methods
150 Adult patients (age more than 12 yrs) admitted with pyrexia of unknown origin to our hospital which is a 350 bedded hospital between April 2011 and October 2013, were evaluated. Detailed clinical examination including careful search for
eschar was made in all patients. Basic laboratory tests were done in these cases (complete blood count, peripheral smear, urine analysis, urea, creatinine, glucose, liver function tests). Additional investigations including blood culture, chest X-ray, Widal, rapid card test for malarial antigen, serology for leptospirosis and serology for dengue were also done in the majority of patients. In addition Weil Felix test was done in all these patients. Kit Progen, Proteus Antigen suspension for Weil Felix by Tulip Diagnostics was used. All Weil Felix positive samples were tested for Scrub Typhus IgM by InBios International Inc. Other investigations were done as indicated (USG abdomen, urine culture) to establish the cause of fever. Patients diagnosed to have scrub typhus on the basis of eschar and/or positive Weil Felix test were included in the study.
3.
Results
50 patients were diagnosed to have scrub typhus during the study period of 2 and ½ years. The age ranged from 16 to 65 yrs. There were 17 females and 33 males. Most of the patients were from the nearby districts of Bhubaneswar. Maximum numbers were seen between April and October. Table 1 shows the signs and symptoms in these 50 cases, Breathlessness, being the commonest (64%), other symptoms were headache (25%), diarrhea (35.7%), skin rash (50%), abdominal pain, nausea, vomiting was complained by 37.5% patients. Myalgia was seen in 62.5% patients. 12.5% patients presented with fever <7 days and same number of patients were admitted after 15e29 days of fever, whereas fever for 7e14 days was present in 37.5% patients. Common sign seen were pleural effusion (43%) hepatomegaly (27%) and splenomegaly (13%). Eschar was seen in 18 patients. Associated enteric fever was seen in 4/50 patients. Common sites of eschar was in lower abdomen and back region. Other sites involved were cheek, vulva and thigh region. Table 2 shows the lab parameters in these patients. Total leucocyte count was raised in majority 50% of patients. Thrombocytopenia was seen in 19 patients (37.5%). SGOT & or SGPT were elevated in 87% patients. Raised bilirubin (1.2 mg/ d) was found in 50% of patients and renal failure (Creatinine >1.5 mg/dl) was present in 53%. 50% patients had pleural effusion on admission. Hepatomegaly and splenomegaly was seen in 27% and 13% respectively. Widal test positive in 1: 360
Table 1 e Signs and symptoms. Fever <7 days Fever 7e14 days Fever 15e29days Fever >30 days Myalgia Headache Cough Breathlessness Nausea Vomiting Abd. pain Diarrhea Skin rash
12.5% 37.5% 12.5% 62.5% 62.5% 25% 28.57% (64%) 37.5% 37.5% 37.5% 35.7% 50%
4
a p o l l o m e d i c i n e 1 2 ( 2 0 1 5 ) 2 e6
40% in Malaysia.4 The major clinical symptoms for scrub typhus are eschar, fever and rash. Tsay and Chang3 documented fever as a characteristic symptoms of scrub typhus patients in a study of 33 patients where all 33 had fever. Eschar was present in 60%, rash was present is 21%. Cases may have been missed if the specific symptoms of scrub typhus eschar, fever and rash were not present.10 The occurrence of scrub typhus varies with age, gender, and activity.11 Our results show that the rates of infection in males is same as females in 2012e2013. Eschar at the site of attachment of the larval mite or chigger, is the most characteristic feature of scrub typhus, but not seen in all patients. Eschar is a black necrotic lesion resembling a cigarette burn usually found in areas where skin is thin, moist or wrinkled and, where the clothing is tight. Eschar formation in the cheek after the bite of mite has been shown in Fig. 1. The common sites involved were axilla, groin and cheek. In our series eschar was found in 23 out of the 50 cases. Often patients were not aware of the presence of the eschar, as it hardly produced any symptoms of discomfort. In other reports from India very few patients were found to have eschar.2,4 Among the laboratory parameters, the most consistent abnormality noticed was elevation of liver enzymes, which was present in 95.9% of the cases (Table 2).6 Similar abnormalities have been observed in other studies.8 In the present study one patient had cyanosis of distal phalanges which is depicted in Fig. 2. One-third (18/50) of our patients had multisystem involvement (Table 5). These patients presented with significant breathlessness and 32/50 (64%) of these had evidence of acute respiratory distress syndrome (ARDS) with diffuse infiltrates in the chest X-ray. Fourteen of these patients required ventilatory support and two of them expired due to Multi Organ Failure. Choi et al reported that radiography demonstrated abnormalities in 54/72 (72%) patients of scrub typhus. The most frequent findings were parenchymal abnormalities with lower lung predilection including bilateral reticulonodular opacities ground glass opacities, consolidation, septal lines, and hilar lymph nodes enlargement.6 Hypotension was present in 35/50 (70%) patients at admission and 28/ 50 (57%) of these patients required inotropic support, with others responding to intravenous fluids. Renal function impairment was seen in 28/50 patients and, 32/50 patients had clinical jaundice with bilirubin values more than 1.2 mg/dl. Table 5 shows the comparison of clinical features of our series with other reported series. Scrub typhus is known to produce serious complications and has a mortality rate of 7e30%.12e15 (Deaths are attributable to late presentation, delayed diagnosis and drug resistance).16 Tsay et al from Taiwan found 8 cases of ARDS, 3 cases of acute renal failure and one case each of myocarditis and septic shock.10 These authors also analyzed the features associated with multiple organ involvement in scrub typhus and compared
Table 2 e Laboratory investigations. Tests name
SD
TLC
50%
Platelets <1.0 lac
37.5%
[SGOT/SGPT [Alk. Phosphal
87% 73%
Albuminuria
Trace
[ Creatinine (1.5 mg/dl) [ Bilirubin (1.2 mg/dl) Weil Felix test
53% 50% 1:80 (1%) 1:160 (60%) 1:320 (30%) 27% 13% 50% 4/50
Hepatomegaly Splenomegaly Pleural Effusion Widal test positive 1:320
titer in 4 patients was observed. The titer of Weil Felix out of the 40 tests done was 1: 320 or more in 12 patients 1: 160 in 24 patients and 1:80 in 4 patients. Table 3 shows the diagnostic criteria used in this study. Eschar alone was seen in 37.8%, Eschar þ Weil Felix was present in 50% cases, Weil Felix came positive in 37.5% patients and breathlessness was seen in as high as 64% of patients. Table 4 shows the complications in the patients suffering from scrub typhus in this study. Major complications like ARDS (62.5%), Shock (62.5%), Renal impairment, Liver impairment and myocarditis (50% each) were seen, Similar number of patients showed features of multi organ dysfunction. 25% of patients had features of meningitis and meningoencephalitis. Though a significant number had multiorgan dysfunction 93% patients had recovery after appropriate treatment and were discharged. Table 5: It shows the comparison of various clinical features of different studies. It shows that maximum number of patients were having deranged liver function test followed by rash, presence of Eschar, & myalgia.
4.
Discussion
Increasing prevalence of scrub typhus has been reported from some Asian countries and may coincide with improved diagnostic facilities and/or more urbanization into rural areas. Most patients with scrub typhus present with acute fever of unknown origin. Scrub typhus is caused by O. tsutsugamushi which is transmitted to humans by the bite of larval stage of trombiculide mites or chiggers. The percentage of positive findings in sera from the general population varies from 2% in India to
Table 3 e Criteria for diagnosis. Symptomps Percentage
Eschar alone
Eschar þ Weil Felix
Weil Felix
Breathlessness
37.8%
50%
37.5%
64%
93% Discharged 50% 25% 50% 25%
MODS Myocarditis
50% 50% 25% 62.5% Percentage
62.5%
ARDS
Table 4 e Complications.
5
Fig. 1 e Eshar formation after mite bite on the check.
Fig. 2 e Cyanosis of distal phalanges.
Complications
Shock
Meningitis
Renal impairment
Bilirubin > 1:2
Thrombocytopenia
Meningoencephalitis
Results
a p o l l o m e d i c i n e 1 2 ( 2 0 1 5 ) 2 e6
them with the scrub typhus cases who had undifferentiated fever. They found higher mean white cell count and longer duration of fever and lower albumin levels in patients with multiple organ involvement. Weil Felix test was positive in 39/50 patients in titers 1:160. In two of these cases Weil Felix test was negative on admission, but when repeated in the convalescent period became positive. Weil Felix test has not been found to be a sensitive test to detect scrub typhus in the community by other studies also, but when positive, it is highly specific.17e19 Weil Felix test is usually positive during the second week of illness. This test is based on the detection of antibodies to various Proteus species which contain antigens with cross reacting epitopes to antigens from members of the genus Rickettsia. Positive test with OXK strain of Proteus mirabilis is suggestive of scrub typhus. Positive test with OX2 and OX19 strains of Proteus suggests infection by typhus and spotted fever groups of Rickettsiae. Criteria suggested for the diagnosis of scrub typhus is a single titer of 1:320 or greater, or a fourfold rise in titer starting from 1:80 for OXK. A good correlation between the results of Weil Felix test and the detection of IgM antibodies by an immunofluorescence assay has been observed.9 According to Issac et al, from Christian Medical College, Vellore, the specificity of the test is high, even at a titer as low as 1/20.17 Hence, they suggested that patients with low titers also should be evaluated for scrub typhus. However the test lacks sensitivity.
6
a p o l l o m e d i c i n e 1 2 ( 2 0 1 5 ) 2 e6
Table 5 e Comparison of various clinical features.
No. of cases No. of days of fever Myalgia Cough Nausea/vomiting Lymphadenopathy Hepatomegaly Jaundice Altered sensorium Rash Eschar Mortality Weil Felix positive
Vellore (Ref7)
Shimla (Ref2)
South Vietnam (Ref9)
Pondicherry
(Present series)
27 5e20 52% 44% 48% NA NA 26% 19% 22% 4% 11.10% 77%
21 5e25 38% NA 43% 53% 43% 53% 24% 10% 10% 14.20% NA
87 NA 32% 45% 28% 85% 43% NA NA 34% 46% NA 57%
50 3e60 38% 40% 58% 30% 28% 10% 20% 14% 46% 2% 78%
50 3e29 36% 29% 29% 33% 27% 50% 25% 36% 38% 7% 90%
In a different study from the same institution which evaluated various serological tests for scrub typhus, Weil Felix test was found to have a sensitivity of only 43% but a specificity of 98% for titers 1:80 or more.19 Several studies have shown that Weil Felix test has high specificity.17e19 In a rural Malaysian hospital, the usefulness of two serological tests for scrub typhus namely, Weil Felix test and IFA were compared.18 It was found that, at a cut off value of greater than or equal to 1:400 titer, the IFA test had a specificity of 96% and at a cut off value of greater than or equal to 1:320 of OXK had a specificity of 97%. The probability value for the correct diagnosis for scrub typhus was found to be 78% for IFA titer of 1:400 or more and 79% for OXK titer 1:320 or more. When both tests were positive in a single sample, the probability of correct diagnosis increases to 96%.18 All the reports of scrub typhus from South India have been from Christian Medical College, Vellore. In one of their studies referred to earlier, Weil Felix test had a specificity of 98% for titers 1:80 or more.19 It is noteworthy that the serological tests for Rickettsial diseases including the specific IgM antibody tests become positive only in the second week and a second sample at a later time is often required; serological tests cannot provide early diagnosis and a specific diagnosis may not be available until after the patient has died or recovered.10 This study was done in order to have a thorough knowledge of the clinical features of scrub typhus including its symptoms and signs so that diagnosis of scrub typhus can be done with this awareness at the earliest and help the patient get proper treatment in this part of the state.
Conflicts of interest All authors have none to declare.
references
1. Watt G, Parola P. Scrub typhus and tropical rickettsioses. Curr Opin Infect Dis. 2003;16(5):429e436. 2. Groves MG, Harrington KS. Scrub typhus. In: Beran GW, ed. Handbook of Zoonoses. 2nd ed. Florida: CRC Press; 1994:663e668.
3. Allen AC, Spitz S. A Comparative Study of the Pathology of Scrub Typhus (Tsutsugamushi Disease) and Other Rickettsial Diseases. 1945. 4. Park K. Epidemiology of communicable diseases. In: Park's Textbook of Preventive and Social Medicine. 15th ed. Jabalpur, India: Banarsidas Bhanot Publishers; 1998:228e229. 5. Medicine update scrub typhus. 6. Vivekanandan M, Mani A, Priya YS, Singh AP, Jayakumar S, Purty S. Outbreak of scrub typhus in Pondicherry. J Assoc Physicians India. 2010;58:24e28. 7. Mahajan SK. Scrub typhus. J Assoc Physicians India. 2005;53:954e958. 8. Mathai E, Rolain JM, Verghese GM, et al. Outbreak of scrub typhus in southern India during the cooler months. Ann N Y Acad Sci. 2003;990:359e364. 9. Amano K, Suzuki N, Fujita M, et al. Serological reactivity of sera from scrub typhus patients against Weil-Felix test antigen. Microbiol Immunol. 1993;37:927e933. 10. Tsay RW, Chang FY. Serious complications in scrub typhus. J Microbiol Immunol Infect. 1998;31:240e244. 11. Am J Trop Med Hyg. 2002;67(2):162e165. Motohiko Ogawa, Toshikatsu Hagiwara, Toshio Kishimoto, Sadashi Shiga, Yoshiya Yoshida, Yumiko Furuya, Ikuo Kaiho, Tadahiko Ito, Haruyasu Nemoto, Norishige Yamamoto, and Kunihiko Masukawa. 12. Wang CC, Liu SF, Liu JW, et al. Acute respiratory distress syndrome in scrub typhus. Am J Trop Med Hyg. 2007;76:1148e1152. 13. Yen TH, Chang CT, Lin JL, et al. Scrub typhus a frequently overlooked cause of acute renal failure. Ren Fail. 2003;25:397e410. 14. Thap LC, Supanarnond W, Treeprasertsuk S, et al. Septic shock secondary to scrub typhus. Characteristics and complications. Southeast Asian J Trop Med Public Health. 2002;330:780e786. 15. Cracco G, Delafosse C, Baril L, et al. Multiple organ failure complicating probable scrub typhus. Clin Infect Dis. 2000;31:191e192. 16. Pandey et al from Himachal Pradesh reported 3 cases of ARDS due to scrub typhus. 17. Issac R, Varghese GM, Mathai E, et al. Scrub typhus: prevalence and diagnostic issues in rural Southern India. Clin Infect Dis. 2004;39:1395e1396. 18. Brown GW, Shirai A, Rogers C, Groves MG. Diagnostic criteria for scrub typhus probability values for immunoflourescent antibody and proteus OXK agglutinin titres. Am J Trop Med Hyg. 1983;32:1101e1107. 19. Prakash JA, Abraham OC, Mathai E. Evaluation of tests for serological diagnosis of scrub typhus. Trop Doct. 2006;36:212e213.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/apme
Original Article
Scrub typhus in a tertiary care hospital in the eastern part of Odisha Suneeta Sahu a,*, Sudhi Ranjan Misra b, Prasant Padhan c, Samir Sahu d a Sr Consultant and HOD, Clinical Microbiologist, Dept of Clinical Microbiology and Immunoserology Apollo Hospitals, Bhubaneswar, India b Sr Consultant, Clinical Microbiologist, Dept of Clinical Microbiology and Immunoserology Apollo Hospitals, Bhubaneswar, India c Sr Consultant, Rheumatologist, Dept of Rheumatology, Apollo Hospitals, Bhubaneswar, India d Sr Consultant, Pulmonologist and Intensivist, Dept of Critical Care, Apollo Hospitals, Bhubaneswar, India
article info
abstract
Article history:
Aim: Our hospital, tertiary care hospital in the capital of the State of Odisha, had been
Received 3 January 2015
witnessing pyrexia of unknown origin, associated with breathlessness, renal and liver
Accepted 3 February 2015
impairment, which did not respond to high antibiotics like Carbapenems but to Doxycy-
Available online 7 March 2015
cline therefore, the present study was undertaken to identify whether scrub typhus is the aetiological agent and thereafter their characteristic features were further evaluated as an
Keywords:
effort in supporting its diagnoses and treating patients accordingly.
Scrub typhus
Methods: 150 Adult patients (age >12 yrs) admitted with pyrexia of unknown origin between
Orientia tsutsugamushi
April 2011 and October 2013, were evaluated. Weil Felix test was done in all these patients.
Weil Felix
Weil Felix positive samples were tested for Scrub Typhus IgM ELISA. Results: Of the 150 patients included in the study 50 (33.33%) were found to be positive for IgM antibodies against Orientia Tsutsugamushi. The cases were seen mainly in the months between September and November. The common symptoms found were fever, myalgia, breathlessness, rash and abdominal pain and clouding of memory. The diagnostic features like eschar were found in 32% patients. Nearly two thirds of patients had fever >30 days and myalgia (62.5%), breathlessness (64%). Most common complications was ARDS (62.5%) followed by liver and renal failure (50%). Conclusion: Our results showed that Scrub typhus should be considered in the differential diagnosis of POU associated with breathlessness, myalgia, rash, gastrointestinal symptoms, hepatorenal syndrome or ARDS. Empirical treatment with Doxycycline may be given in the cases with strong suspicion of Scrub typhus. Copyright © 2015, Indraprastha Medical Corporation Ltd. All rights reserved.
* Corresponding author. E-mail addresses: [email protected], [email protected] (S. Sahu). http://dx.doi.org/10.1016/j.apme.2015.02.003 0976-0016/Copyright © 2015, Indraprastha Medical Corporation Ltd. All rights reserved.
3
a p o l l o m e d i c i n e 1 2 ( 2 0 1 5 ) 2 e6
1.
Introduction
Scrub typhus, caused by Orientia (formerly Rickettsia) tsutsugamushi, is an acute infectious disease of variable severity that is transmitted to humans by an arthropod vector of the Trombiculidae family. “Tsutsuga” means small and dangerous and “mushi” means insect or mite. It affects people of all ages including children. Humans are accidental hosts in this zoonotic disease. While scrub typhus is confined geographically to the Asia Pacific region, a billion people are at risk and nearly a million cases are reported every year.1 Scrub typhus was first described from Japan in 1899. It was a dreaded disease in pre-antibiotic era and a militarily important disease that affected thousands of soldiers in the far east during the second World War.2 The rickettsia is transmitted by bite from an infected mite to human, after which it grows at the location of the bite and a characteristic skin lesion known as an eschar is formed. The rickettsia then spreads systemically via the hematogenous and lymphatogenous routes. The infected human then develops various systemic symptoms and reactions including fever, rash, lymphadenopathy, elevations of C-Reacting Protein (CRP) and liver enzymes.3 In India, scrub typhus broke out in an epidemic form in Assam and West Bengal during the Second World War. Later, the presence of this disease was found throughout India in humans, trombiculid mites and rodents.4 The term “scrub” is used because of the type of vegetation (terrain between woods and clearings) that harbors the vector; however, the name is not entirely correct because certain endemic areas can also be sandy, semiarid and mountain deserts. The word “typhus” is derived from the Greek word “typhus”, which means “fever with stupor” or smoke.5 Scrub typhus is a diagnostic dilemma because it has non specific presentations, limited awareness, low index of suspicious among clinicians and lack of diagnostic facilities.6 O. tsutsugamushi is an obligatory intra-cellular gram negative bacterium, and is a Zoonotic disease. Man is accidentally infected when he encroaches the mite infected areas, known as the mite islands. These areas consist of areas with secondary scrub growth, which grows after the clearance of primary forest, and hence the term scrub typhus. However the infection can occur in disease habitats like sea shore, ricefields and even semideserts.7 If the diagnosis is delayed or patient is not treated with appropriate antibiotics, the scrub typhus can present with serious complications such as renal failure, mycocarditis, septic shock, meningitis. Scrub Typhus broke out in an epidemic form in Assam and West Bengal during world war II. Outbreak of scrub typhus in southern India has been reported in 2003.8 However cases in the state of Odisha has not been reported so far.
2.
Materials & methods
150 Adult patients (age more than 12 yrs) admitted with pyrexia of unknown origin to our hospital which is a 350 bedded hospital between April 2011 and October 2013, were evaluated. Detailed clinical examination including careful search for
eschar was made in all patients. Basic laboratory tests were done in these cases (complete blood count, peripheral smear, urine analysis, urea, creatinine, glucose, liver function tests). Additional investigations including blood culture, chest X-ray, Widal, rapid card test for malarial antigen, serology for leptospirosis and serology for dengue were also done in the majority of patients. In addition Weil Felix test was done in all these patients. Kit Progen, Proteus Antigen suspension for Weil Felix by Tulip Diagnostics was used. All Weil Felix positive samples were tested for Scrub Typhus IgM by InBios International Inc. Other investigations were done as indicated (USG abdomen, urine culture) to establish the cause of fever. Patients diagnosed to have scrub typhus on the basis of eschar and/or positive Weil Felix test were included in the study.
3.
Results
50 patients were diagnosed to have scrub typhus during the study period of 2 and ½ years. The age ranged from 16 to 65 yrs. There were 17 females and 33 males. Most of the patients were from the nearby districts of Bhubaneswar. Maximum numbers were seen between April and October. Table 1 shows the signs and symptoms in these 50 cases, Breathlessness, being the commonest (64%), other symptoms were headache (25%), diarrhea (35.7%), skin rash (50%), abdominal pain, nausea, vomiting was complained by 37.5% patients. Myalgia was seen in 62.5% patients. 12.5% patients presented with fever <7 days and same number of patients were admitted after 15e29 days of fever, whereas fever for 7e14 days was present in 37.5% patients. Common sign seen were pleural effusion (43%) hepatomegaly (27%) and splenomegaly (13%). Eschar was seen in 18 patients. Associated enteric fever was seen in 4/50 patients. Common sites of eschar was in lower abdomen and back region. Other sites involved were cheek, vulva and thigh region. Table 2 shows the lab parameters in these patients. Total leucocyte count was raised in majority 50% of patients. Thrombocytopenia was seen in 19 patients (37.5%). SGOT & or SGPT were elevated in 87% patients. Raised bilirubin (1.2 mg/ d) was found in 50% of patients and renal failure (Creatinine >1.5 mg/dl) was present in 53%. 50% patients had pleural effusion on admission. Hepatomegaly and splenomegaly was seen in 27% and 13% respectively. Widal test positive in 1: 360
Table 1 e Signs and symptoms. Fever <7 days Fever 7e14 days Fever 15e29days Fever >30 days Myalgia Headache Cough Breathlessness Nausea Vomiting Abd. pain Diarrhea Skin rash
12.5% 37.5% 12.5% 62.5% 62.5% 25% 28.57% (64%) 37.5% 37.5% 37.5% 35.7% 50%
4
a p o l l o m e d i c i n e 1 2 ( 2 0 1 5 ) 2 e6
40% in Malaysia.4 The major clinical symptoms for scrub typhus are eschar, fever and rash. Tsay and Chang3 documented fever as a characteristic symptoms of scrub typhus patients in a study of 33 patients where all 33 had fever. Eschar was present in 60%, rash was present is 21%. Cases may have been missed if the specific symptoms of scrub typhus eschar, fever and rash were not present.10 The occurrence of scrub typhus varies with age, gender, and activity.11 Our results show that the rates of infection in males is same as females in 2012e2013. Eschar at the site of attachment of the larval mite or chigger, is the most characteristic feature of scrub typhus, but not seen in all patients. Eschar is a black necrotic lesion resembling a cigarette burn usually found in areas where skin is thin, moist or wrinkled and, where the clothing is tight. Eschar formation in the cheek after the bite of mite has been shown in Fig. 1. The common sites involved were axilla, groin and cheek. In our series eschar was found in 23 out of the 50 cases. Often patients were not aware of the presence of the eschar, as it hardly produced any symptoms of discomfort. In other reports from India very few patients were found to have eschar.2,4 Among the laboratory parameters, the most consistent abnormality noticed was elevation of liver enzymes, which was present in 95.9% of the cases (Table 2).6 Similar abnormalities have been observed in other studies.8 In the present study one patient had cyanosis of distal phalanges which is depicted in Fig. 2. One-third (18/50) of our patients had multisystem involvement (Table 5). These patients presented with significant breathlessness and 32/50 (64%) of these had evidence of acute respiratory distress syndrome (ARDS) with diffuse infiltrates in the chest X-ray. Fourteen of these patients required ventilatory support and two of them expired due to Multi Organ Failure. Choi et al reported that radiography demonstrated abnormalities in 54/72 (72%) patients of scrub typhus. The most frequent findings were parenchymal abnormalities with lower lung predilection including bilateral reticulonodular opacities ground glass opacities, consolidation, septal lines, and hilar lymph nodes enlargement.6 Hypotension was present in 35/50 (70%) patients at admission and 28/ 50 (57%) of these patients required inotropic support, with others responding to intravenous fluids. Renal function impairment was seen in 28/50 patients and, 32/50 patients had clinical jaundice with bilirubin values more than 1.2 mg/dl. Table 5 shows the comparison of clinical features of our series with other reported series. Scrub typhus is known to produce serious complications and has a mortality rate of 7e30%.12e15 (Deaths are attributable to late presentation, delayed diagnosis and drug resistance).16 Tsay et al from Taiwan found 8 cases of ARDS, 3 cases of acute renal failure and one case each of myocarditis and septic shock.10 These authors also analyzed the features associated with multiple organ involvement in scrub typhus and compared
Table 2 e Laboratory investigations. Tests name
SD
TLC
50%
Platelets <1.0 lac
37.5%
[SGOT/SGPT [Alk. Phosphal
87% 73%
Albuminuria
Trace
[ Creatinine (1.5 mg/dl) [ Bilirubin (1.2 mg/dl) Weil Felix test
53% 50% 1:80 (1%) 1:160 (60%) 1:320 (30%) 27% 13% 50% 4/50
Hepatomegaly Splenomegaly Pleural Effusion Widal test positive 1:320
titer in 4 patients was observed. The titer of Weil Felix out of the 40 tests done was 1: 320 or more in 12 patients 1: 160 in 24 patients and 1:80 in 4 patients. Table 3 shows the diagnostic criteria used in this study. Eschar alone was seen in 37.8%, Eschar þ Weil Felix was present in 50% cases, Weil Felix came positive in 37.5% patients and breathlessness was seen in as high as 64% of patients. Table 4 shows the complications in the patients suffering from scrub typhus in this study. Major complications like ARDS (62.5%), Shock (62.5%), Renal impairment, Liver impairment and myocarditis (50% each) were seen, Similar number of patients showed features of multi organ dysfunction. 25% of patients had features of meningitis and meningoencephalitis. Though a significant number had multiorgan dysfunction 93% patients had recovery after appropriate treatment and were discharged. Table 5: It shows the comparison of various clinical features of different studies. It shows that maximum number of patients were having deranged liver function test followed by rash, presence of Eschar, & myalgia.
4.
Discussion
Increasing prevalence of scrub typhus has been reported from some Asian countries and may coincide with improved diagnostic facilities and/or more urbanization into rural areas. Most patients with scrub typhus present with acute fever of unknown origin. Scrub typhus is caused by O. tsutsugamushi which is transmitted to humans by the bite of larval stage of trombiculide mites or chiggers. The percentage of positive findings in sera from the general population varies from 2% in India to
Table 3 e Criteria for diagnosis. Symptomps Percentage
Eschar alone
Eschar þ Weil Felix
Weil Felix
Breathlessness
37.8%
50%
37.5%
64%
93% Discharged 50% 25% 50% 25%
MODS Myocarditis
50% 50% 25% 62.5% Percentage
62.5%
ARDS
Table 4 e Complications.
5
Fig. 1 e Eshar formation after mite bite on the check.
Fig. 2 e Cyanosis of distal phalanges.
Complications
Shock
Meningitis
Renal impairment
Bilirubin > 1:2
Thrombocytopenia
Meningoencephalitis
Results
a p o l l o m e d i c i n e 1 2 ( 2 0 1 5 ) 2 e6
them with the scrub typhus cases who had undifferentiated fever. They found higher mean white cell count and longer duration of fever and lower albumin levels in patients with multiple organ involvement. Weil Felix test was positive in 39/50 patients in titers 1:160. In two of these cases Weil Felix test was negative on admission, but when repeated in the convalescent period became positive. Weil Felix test has not been found to be a sensitive test to detect scrub typhus in the community by other studies also, but when positive, it is highly specific.17e19 Weil Felix test is usually positive during the second week of illness. This test is based on the detection of antibodies to various Proteus species which contain antigens with cross reacting epitopes to antigens from members of the genus Rickettsia. Positive test with OXK strain of Proteus mirabilis is suggestive of scrub typhus. Positive test with OX2 and OX19 strains of Proteus suggests infection by typhus and spotted fever groups of Rickettsiae. Criteria suggested for the diagnosis of scrub typhus is a single titer of 1:320 or greater, or a fourfold rise in titer starting from 1:80 for OXK. A good correlation between the results of Weil Felix test and the detection of IgM antibodies by an immunofluorescence assay has been observed.9 According to Issac et al, from Christian Medical College, Vellore, the specificity of the test is high, even at a titer as low as 1/20.17 Hence, they suggested that patients with low titers also should be evaluated for scrub typhus. However the test lacks sensitivity.
6
a p o l l o m e d i c i n e 1 2 ( 2 0 1 5 ) 2 e6
Table 5 e Comparison of various clinical features.
No. of cases No. of days of fever Myalgia Cough Nausea/vomiting Lymphadenopathy Hepatomegaly Jaundice Altered sensorium Rash Eschar Mortality Weil Felix positive
Vellore (Ref7)
Shimla (Ref2)
South Vietnam (Ref9)
Pondicherry
(Present series)
27 5e20 52% 44% 48% NA NA 26% 19% 22% 4% 11.10% 77%
21 5e25 38% NA 43% 53% 43% 53% 24% 10% 10% 14.20% NA
87 NA 32% 45% 28% 85% 43% NA NA 34% 46% NA 57%
50 3e60 38% 40% 58% 30% 28% 10% 20% 14% 46% 2% 78%
50 3e29 36% 29% 29% 33% 27% 50% 25% 36% 38% 7% 90%
In a different study from the same institution which evaluated various serological tests for scrub typhus, Weil Felix test was found to have a sensitivity of only 43% but a specificity of 98% for titers 1:80 or more.19 Several studies have shown that Weil Felix test has high specificity.17e19 In a rural Malaysian hospital, the usefulness of two serological tests for scrub typhus namely, Weil Felix test and IFA were compared.18 It was found that, at a cut off value of greater than or equal to 1:400 titer, the IFA test had a specificity of 96% and at a cut off value of greater than or equal to 1:320 of OXK had a specificity of 97%. The probability value for the correct diagnosis for scrub typhus was found to be 78% for IFA titer of 1:400 or more and 79% for OXK titer 1:320 or more. When both tests were positive in a single sample, the probability of correct diagnosis increases to 96%.18 All the reports of scrub typhus from South India have been from Christian Medical College, Vellore. In one of their studies referred to earlier, Weil Felix test had a specificity of 98% for titers 1:80 or more.19 It is noteworthy that the serological tests for Rickettsial diseases including the specific IgM antibody tests become positive only in the second week and a second sample at a later time is often required; serological tests cannot provide early diagnosis and a specific diagnosis may not be available until after the patient has died or recovered.10 This study was done in order to have a thorough knowledge of the clinical features of scrub typhus including its symptoms and signs so that diagnosis of scrub typhus can be done with this awareness at the earliest and help the patient get proper treatment in this part of the state.
Conflicts of interest All authors have none to declare.
references
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