Appendix 4: Studies excluded based on suspected overlapping datasets
Forty-twostudies were excluded because an overlap with another dataset was suspected (e.g., two studies were conducted in the same hospital in the same time period). The study with the largest sample was always included.
For scrub typhus, 38 studies were excluded: two studies from China,1,212 from India,3-14 ten from South Korea,15-24five from Taiwan,25-29 one from Sri Lanka,30 seven from Thailand,31-37 and one from Vietnam.38
For Mediterranean Spotted fever, nine studies were excluded: three from Algeria,39-41 one from Croatia,42 two from Italy,43,44 two from Portugal,45,46 and one study from Tunesia.47
References
1.Liu YX, Suo JJ, Xing YB, et al. Characteristics of pediatric scrub typhus in a new endemic region of Northern China. Pediatr Infect Dis J 2009; 28(12): 1111-4.
2.Zhang L, Bi Z, Kou Z, et al. Scrub typhus caused by Orientia tsutsugamushi Kawasaki-related genotypes in Shandong Province, northern China. Infect Genet Evol 2015; 30: 238-43.
3.Venkategowda PM, Rao SM, Mutkule DP, Rao MV, Taggu AN. Scrub typhus: Clinical spectrum and outcome. Indian J Crit Care Med 2015; 19(4): 208-13.
4.Sankhyan N, Saptharishi LG, Sasidaran K, Kanga A, Singhi SC. Clinical profile of scrub typhus in children and its association with hemophagocytic lymphohistiocytosis. Indian Pediatr 2014; 51(8): 651-3.
5.Kalita J, Mani VE, Bhoi SK, Misra UK. Status epilepticus in scrub typhus. Epilepsia 2016; 57(7): e125-e8.
6.Mani VE, Chauhan PS, Kalita J, Bhoi SK, Misra UK. Is VEGF a marker of severity of scrub typhus infection? Eur J Clin Microbiol Infect Dis 2016; 35(2): 305-10.
7.Inamdar S, Thunga G, Acharya R, Vijayanarayana K, Shridharan N, Bhrugu P. Study of clinical characteristics and treatment pattern of scrub typhus in tertiary care hospital. J Pharm Sci Res 2013; 5(5): 107-10.
8.Jamil MD, Hussain M, Lyngdoh M, Sharma S, Barman B, Bhattacharya PK. Scrub typhus meningoencephalitis, a diagnostic challenge for clinicians: A hospital based study from North-East India. J Neurosci Rural Pract 2015; 6(4): 488-93.
9.Abhilash K, Mannam PR, Rajendran K, John RA, Ramasami P. Chest radiographic manifestations of scrub typhus. J Postgrad Med 2016; 62: 235-8.
10.Abhilash KPP, Gunasekaran K, Mitra S, et al. Scrub typhus meningitis: An under-recognized cause of aseptic meningitis in India. Neurol India 2015; 63(2): 209-14.
11.Chrispal A, Boorugu H, Gopinath KG, et al. Scrub typhus: an unrecognized threat in South India - clinical profile and predictors of mortality. Trop Doct 2010; 40(3): 129-33.
12.Griffith M, Peter J, Karthik G, et al. Profile of organ dysfunction and predictors of mortality in severe scrub typhus infection requiring intensive care admission. Indian J Crit Care Med 2014; 18(8): 497-502.
13.Mitra S, Gautam I, Jambugulam M, Abhilash K, Jayaseeelan V. Clinical score to differentiate scrub typhus and dengue: A tool to differentiate scrub typhus and dengue. J Global Infect Dis 2017; 9(1): 12-7.
14.Varghese GM, Mathew A, Kumar S, Abraham OC, Trowbridge P, Mathai E. Differential diagnosis of scrub typhus meningitis from bacterial meningitis using clinical and laboratory features. Neurol India 2013; 61(1): 17-20.
15.Jang HC, Choi SM, Jang MO, et al. Inappropriateness of quinolone in scrub typhus treatment due to gyrA mutation in Orientia tsutsugamushi Boryong strain. J Korean Med Sci 2013; 28(5): 667-71.
16.Jang MO, Jang HC, Kim UJ, et al. Outcome of intravenous azithromycin therapy in patients with complicated scrub typhus compared with that of doxycycline therapy using propensity-matched analysis. Antimicrob Agents Chemother 2014; 58(3): 1488-93.
17.Kim DM, Kim HL, Park CY, et al. Clinical usefulness of eschar polymerase chain reaction for the diagnosis of scrub typhus: a prospective study. Clin Infect DIs 2006; 43(10): 1296-300.
18.Kim DM, Kim SW, Choi SH, Yun NR. Clinical and laboratory findings associated with severe scrub typhus. BMC Infect Dis 2010; 10: 108.
19.Kim DM, Won KJ, Park CY, et al. Distribution of eschars on the body of scrub typhus patients: a prospective study. Am J Trop Med Hyg 2007; 76(5): 806-9.
20.Kim DM, Yun NR, Neupane GP, et al. Differences in clinical features according to Boryoung and Karp genotypes of Orientia tsutsugamushi. PloS One 2011; 6(8): e22731.
21.Lee J, Kim DM, Yun NR, et al. A comparative study of hepatitis caused by scrub typhus and viral hepatitis A in South Korea. Am J Trop Med Hyg 2011; 85(5): 873-7.
22.Lee J, Kim DM, Yun NR, Kim YD, Park CG, Kim MW. The Correlation of Endoscopic Findings and Clinical Features in Korean Patients with Scrub Typhus: A Cohort Study. PloS One 2016; 11(5): e0155810.
23.Yoon HJ, Lee MS, Ki M, et al. Does IL-17 play a role in hepatic dysfunction of scrub typhus patients? Vector Borne Zoonotic Dis 2010; 10(3): 231-5.
24.Sun IO, Kim MC, Park JW, et al. Clinical characteristics of acute kidney injury in patients with scrub typhus--RIFLE criteria validation. J Infect Chemother 2014; 20(2): 93-6.
25.Tsai CC, Lay CJ, Ho YH, Wang LS, Chen LK. Intravenous minocycline versus oral doxycycline for the treatment of noncomplicated scrub typhus. J Microbiol Immunol Infect 2011; 44(1): 33-8.
26.Hu ML, Liu JW, Wu KL, et al. Short report: Abnormal liver function in scrub typhus. Am J Trop Med Hyg 2005; 73(4): 667-8.
27.Lee CH, Liu JW. Coinfection with leptospirosis and scrub typhus in Taiwanese patients. Am J Trop Med Hyg 2007; 77(3): 525-7.
28.Su TH, Liu CJ, Chen DS, Kao JH. Milder clinical manifestation of scrub typhus in Kinmen, Taiwan. J Formos Med Assoc 2013; 112(4): 201-7.
29.Huang CT, Chi H, Lee HC, Chiu NC, Huang FY. Scrub typhus in children in a teaching hospital in eastern Taiwan, 2000-2005. Southeast Asian J Trop Med 2009; 40(4): 789-94.
30.Angelakis E, Munasinghe A, Yaddehige I, et al. Detection of rickettsioses and Q fever in Sri Lanka. Am J Trop Med Hyg 2012; 86(4): 711-2.
31.Sriwongpan P, Krittigamas P, Tantipong H, Patumanond J, Tawichasri C, Namwongprom S. Clinical risk-scoring algorithm to forecast scrub typhus severity. Risk Manag Healthc Policy 2014; 7: 11-7.
32.Lim C, Paris DH, Blacksell SD, et al. How to determine the accuracy of an alternative diagnostic test when it is actually better than the reference tests: A re-evaluation of diagnostic tests for scrub typhus using Bayesian LCMs. PloS One 2015; 10 (5) (no pagination)(e0114930).
33.Watt G, Strickman D, Kantipong P, Jongsakul K, Paxton H. Performance of a dot blot immunoassay for the rapid diagnosis of scrub typhus in a longitudinal case series. J Infect Dis 1998; 177(3): 800-2.
34.Charoensak A, Chawalparit O, Suttinont C, et al. Scrub typhus: chest radiographic and clinical findings in 130 Thai patients. J Med Assoc Thai 2006; 89(5): 600-7.
35.Thap LC, Supanaranond W, Treeprasertsuk S, Kitvatanachai S, Chinprasatsak S, Phonrat B. Septic shock secondary to scrub typhus: characteristics and complications. Southeast Asian J Trop Med Public Health 2002; 33(4): 780-6.
36.McGready R, Ashley EA, Wuthiekanun V, et al. Arthropod borne disease: the leading cause of fever in pregnancy on the Thai-Burmese border. PLoS Negl Trop Dis 2010; 4(11): e888.
37.Sonthayanon P, Chierakul W, Wuthiekanun V, et al. Association of high Orientia tsutsugamushi DNA loads with disease of greater severity in adults with scrub typhus. J Clin Microbiol 2009; 47(2): 430-4.
38.Hamaguchi S, Cuong NC, Tra DT, et al. Clinical and Epidemiological Characteristics of Scrub Typhus and Murine Typhus among Hospitalized Patients with Acute Undifferentiated Fever in Northern Vietnam. Am J Trop Med Hyg 2015; 92(5): 972-8.
39.Benabdellah A, Mouffok N, Bensaad M, Belkadi Kouied A, Razik F, Raoult D. Mediterranean-spotted fever: clinical and laboratory characteristics of 34 children in Oran (Algeria). Pathol Biol 2007; 55(10): 539-42.
40.Mouffok N, Benabdellah A, Richet H, et al. Reemergence of rickettsiosis in Oran, Algeria. Ann NY Acad Sci 2006; 1078: 180-4.
41.Mouffok N, Parola P, Abdennour D, et al. Mediterranean spotted fever in Algerian children. Clin Microbiol Infect 2009; 15 Suppl 2: 290-1.
42.Punda-Polic V, Klismanic Z, Capkun V, Bradaric N. Demographic and epidemiologic features of Mediterranean spotted fever cases in the region of split, Croatia. Ann NY Acad Sci 2003; 990: 143-8.
43.Giammanco GM, Vitale G, Mansueto S, Capra G, Caleca MP, Ammatuna P. Presence of Rickettsia conorii subsp. israelensis, the causative agent of Israeli spotted fever, in Sicily, Italy, ascertained in a retrospective study. J Clin Microbiol 2005; 43(12): 6027-31.
44.Colomba C, Saporito L, Polara VF, Rubino R, Titone L. Mediterranean spotted fever: clinical and laboratory characteristics of 415 Sicilian children. BMC Infect Dis 2006; 6: 60.
45.de Sousa R, Ismail N, Dória-Nóbrega S, et al. The presence of eschars, but not greater severity, in Portuguese patients infected with Israeli spotted fever. Ann N Y Acad Sci 2005; 1063: 197-202.
46.de Sousa R, Nóbrega SD, Bacellar F, Torgal J. Mediterranean spotted fever in Portugal: risk factors for fatal outcome in 105 hospitalized patients. Ann N Y Acad Sci 2003; 990: 285-94.
47.Khairallah M, Ladjimi A, Chakroun M, et al. Posterior segment manifestations of Rickettsia conorii infection. Ophthalmology 2004; 111(3): 529-34.