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Murine typhus in children: clinical and laboratory features from 41 cases in Crete, Greece

2009; Elsevier BV; Volume: 15; Linguagem: Inglês

10.1111/j.1469-0691.2008.02133.x

1469-0691

Achilleas Gikas, Sofia Kokkini, Constantinos Tsioutis, D. Athenessopoulos, E. Balomenaki, S. Blasak, C. Matheou, Yiannis Tselentis, Anna Psaroulaki,

Leptospirosis research and findings

Murine typhus, also known as endemic typhus, is a flea-borne infectious disease with a worldwide distribution, caused by an obligate intracellular, gram-negative microorganism, Rickettsia typhi [1Chaniotis B Psaroulaki A Chaliotis G Gozalo Garcia G Gozadinos T Tselentis Y Transmission cycle of murine typhus in Greece.Ann Trop Med Parasitol. 1994; 88: 645-647PubMed Google Scholar]. The transmitting agent of R. typhi is the rat flea, Xenopsylla cheopis, although the cat flea, Ctenocephalides felis, has also been implicated [1Chaniotis B Psaroulaki A Chaliotis G Gozalo Garcia G Gozadinos T Tselentis Y Transmission cycle of murine typhus in Greece.Ann Trop Med Parasitol. 1994; 88: 645-647PubMed Google Scholar, 2Gikas A Doukakis S Pediaditis J Kastanakis S Psaroulaki A Tselentis Y Murine typhus in Greece: epidemiological, clinical, and therapeutic data from 83 cases.Trans R Soc Trop Med Hyg. 2002; 96: 250-253Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 3Bitsori M Galanakis E Gikas A Scoulica E Sbyrakis S Rickettsia typhi infection in childhood.Acta Paediatr. 2002; 91: 59-61Crossref PubMed Google Scholar, 4Koliou M Psaroulaki A Georgiou C Ioannou I Tselentis Y Gikas A Murine typhus in Cyprus: 21 paediatric cases.Eur J Clin Microbiol Infect Dis. 2007; 26: 491-493Crossref PubMed Scopus (25) Google Scholar]. Main reservoirs are rats, house mice, opossums, skunks and cats [1Chaniotis B Psaroulaki A Chaliotis G Gozalo Garcia G Gozadinos T Tselentis Y Transmission cycle of murine typhus in Greece.Ann Trop Med Parasitol. 1994; 88: 645-647PubMed Google Scholar, 2Gikas A Doukakis S Pediaditis J Kastanakis S Psaroulaki A Tselentis Y Murine typhus in Greece: epidemiological, clinical, and therapeutic data from 83 cases.Trans R Soc Trop Med Hyg. 2002; 96: 250-253Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 3Bitsori M Galanakis E Gikas A Scoulica E Sbyrakis S Rickettsia typhi infection in childhood.Acta Paediatr. 2002; 91: 59-61Crossref PubMed Google Scholar]. The actual incidence of murine typhus is unclear, as the common clinical manifestations of the disease are non-specific [1Chaniotis B Psaroulaki A Chaliotis G Gozalo Garcia G Gozadinos T Tselentis Y Transmission cycle of murine typhus in Greece.Ann Trop Med Parasitol. 1994; 88: 645-647PubMed Google Scholar, 2Gikas A Doukakis S Pediaditis J Kastanakis S Psaroulaki A Tselentis Y Murine typhus in Greece: epidemiological, clinical, and therapeutic data from 83 cases.Trans R Soc Trop Med Hyg. 2002; 96: 250-253Abstract Full Text PDF PubMed Scopus (58) Google Scholar]. In children, only a small number of studies have focused on the occurrence and on clinical profiles of the disease [3Bitsori M Galanakis E Gikas A Scoulica E Sbyrakis S Rickettsia typhi infection in childhood.Acta Paediatr. 2002; 91: 59-61Crossref PubMed Google Scholar, 4Koliou M Psaroulaki A Georgiou C Ioannou I Tselentis Y Gikas A Murine typhus in Cyprus: 21 paediatric cases.Eur J Clin Microbiol Infect Dis. 2007; 26: 491-493Crossref PubMed Scopus (25) Google Scholar, 5Whiteford SF Taylor JP Dumler JS Clinical, laboratory, and epidemiologic features of murine typhus in 97 Texas children.Arch Pediatr Adolesc Med. 2001; 155: 396-400Crossref PubMed Scopus (73) Google Scholar]. The aim of this study was to confirm the presence and to assess the clinical and laboratory characteristics of R. typhi infection among children in the area of Chania, Crete, Greece. Forty-one children were hospitalised with acute R. typhi infection in the Pediatric Department of the General Hospital of Chania, from 2001 through to 2006. All other causes included in the differential diagnosis were ruled out. Diagnosis of acute R. typhi infection was considered positive by the combination of compatible clinical features and an indirect immunofluorescence test (Biomerieux, Lyon, France), when specific IgM and/or IgG titres on admission were >1/400 and >1/960, respectively. All cases were reviewed retrospectively for demographic, clinical and laboratory findings, treatment and outcome. Most admissions (87.8%) occurred between May and October. The mean age was 9.8 years old (range, 1–15 years old). Twenty children (48.8%) were males. History of recent contact with animals was positive in 13 children (31.7%); all 13 children reported contact with cats and 10/13 reported contact with dogs. On admission all patients had fever. Common clinical characteristics were fever, rash, hepatomegaly, splenomegaly and anorexia. Main laboratory features included elevated aspartate aminotransferase and alanine aminotransferase, abnormal chest radiography, thrombocytopenia and leucopenia. CSF analysis in one patient with confusion did not reveal any abnormalities. Clinical and laboratory manifestations found on admission are presented in Table 1.TABLE 1Clinical, epidemiological and laboratory characteristics of murine typhus in 41 children in Chania, CreteClinical characteristicFever41 (100.0)Rash26 (63.4)Macular14 (34.9)Maculopapular12 (27.9)Hepatomegaly25 (61.0)Chills25 (60.0)Perspiration20 (48.8)Splenomegaly19 (46.3)Anorexia17 (41.5)Malaise15 (36.6)Myalgia13 (31.7)Joint pain11 (26.8)Abdominal pain6 (14.6)Headache6 (14.6)Lymphadenopathy5 (12.2)Cervical4 (9.8)Submandibular1 (2.4)Diarrhoea4 (9.8)Cough4 (9.8)Vomiting4 (9.8)Confusion1 (2.3)Laboratory findingsAST > one-foldanormal value, 0–40 U/L30 (73.0)ALT > one-foldanormal value, 0–40 U/L27 (65.6)Abnormal chest radiography22 (53.7)Thrombocytopeniabnormal value, 150–450 × 109/L16 (39.0)Leucopeniacnormal value, 5–10 × 109/L10 (24.4)Proteinuria7 (17.0)Haematuria6 (14.6)Hyponatraemiadnormal value, 135–145 mEq/L.4 (9.8)Other characteristicsMale sex20 (48.8)Recent contact with animals13 (31.7)Mean duration of fever before admission (range) Mean duration of fever (range) after admission5.7 days (1–15 days) 9.1 days (3–17 days)Rash onset after fever (mean, range)3.6 days (1–8 days)Total rash duration (mean, range)4.7 days (2–9 days)AST, aspartate aminotransferase; ALT, alanine aminotransferaseValues given are n (%).a normal value, 0–40 U/Lb normal value, 150–450 × 109/Lc normal value, 5–10 × 109/Ld normal value, 135–145 mEq/L. Open table in a new tab AST, aspartate aminotransferase; ALT, alanine aminotransferase Values given are n (%). Serologic testing through IFA performed on admission was diagnosed for all 41 children, with a median IgM titre of 1/3200 (range, 1/400 to 1/31200) and a median IgG titre of 1/2880 (range, 1/480 to 1/30720). All children were treated upon admission. Combination therapy was administered to two of them. Antibiotics administered were doxycycline in 19 children (46.3%), chloramphenicol in 12 (29.3%), quinolones in five (12.2%), cephalosporins in three children (7.3%), and a combination of trimethoprim/sulfamethoxazole and b-lactams in two children (4.9%). The outcome was favourable for all 41 patients; apyrexia was recorded on a mean of 4.9 days after admission (range, 2–12 days). The mean total duration of fever was 9.1 days (range, 3–17 days). No complication or relapse was observed within 1 month of follow-up. The temperate climate of the Mediterranean basin is a major contributing factor to the endemicity of murine typhus in the area [1Chaniotis B Psaroulaki A Chaliotis G Gozalo Garcia G Gozadinos T Tselentis Y Transmission cycle of murine typhus in Greece.Ann Trop Med Parasitol. 1994; 88: 645-647PubMed Google Scholar, 2Gikas A Doukakis S Pediaditis J Kastanakis S Psaroulaki A Tselentis Y Murine typhus in Greece: epidemiological, clinical, and therapeutic data from 83 cases.Trans R Soc Trop Med Hyg. 2002; 96: 250-253Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 3Bitsori M Galanakis E Gikas A Scoulica E Sbyrakis S Rickettsia typhi infection in childhood.Acta Paediatr. 2002; 91: 59-61Crossref PubMed Google Scholar, 4Koliou M Psaroulaki A Georgiou C Ioannou I Tselentis Y Gikas A Murine typhus in Cyprus: 21 paediatric cases.Eur J Clin Microbiol Infect Dis. 2007; 26: 491-493Crossref PubMed Scopus (25) Google Scholar]. Only a few studies have described flea-borne typhus in children, and differences in the clinical presentation of the disease among children and adults need further investigation [2Gikas A Doukakis S Pediaditis J Kastanakis S Psaroulaki A Tselentis Y Murine typhus in Greece: epidemiological, clinical, and therapeutic data from 83 cases.Trans R Soc Trop Med Hyg. 2002; 96: 250-253Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 3Bitsori M Galanakis E Gikas A Scoulica E Sbyrakis S Rickettsia typhi infection in childhood.Acta Paediatr. 2002; 91: 59-61Crossref PubMed Google Scholar, 4Koliou M Psaroulaki A Georgiou C Ioannou I Tselentis Y Gikas A Murine typhus in Cyprus: 21 paediatric cases.Eur J Clin Microbiol Infect Dis. 2007; 26: 491-493Crossref PubMed Scopus (25) Google Scholar, 5Whiteford SF Taylor JP Dumler JS Clinical, laboratory, and epidemiologic features of murine typhus in 97 Texas children.Arch Pediatr Adolesc Med. 2001; 155: 396-400Crossref PubMed Scopus (73) Google Scholar]. In our study, the main clinical manifestations were fever, rash, chills, perspiration, anorexia and hepatosplenomegaly, which is in agreement with other studies involving children [3Bitsori M Galanakis E Gikas A Scoulica E Sbyrakis S Rickettsia typhi infection in childhood.Acta Paediatr. 2002; 91: 59-61Crossref PubMed Google Scholar, 4Koliou M Psaroulaki A Georgiou C Ioannou I Tselentis Y Gikas A Murine typhus in Cyprus: 21 paediatric cases.Eur J Clin Microbiol Infect Dis. 2007; 26: 491-493Crossref PubMed Scopus (25) Google Scholar, 5Whiteford SF Taylor JP Dumler JS Clinical, laboratory, and epidemiologic features of murine typhus in 97 Texas children.Arch Pediatr Adolesc Med. 2001; 155: 396-400Crossref PubMed Scopus (73) Google Scholar]. In contrast to adults, headache (14.6%), the classic triad of fever, headache and rash (12.2%), and conjunctivitis (none), were uncommon in our study [2Gikas A Doukakis S Pediaditis J Kastanakis S Psaroulaki A Tselentis Y Murine typhus in Greece: epidemiological, clinical, and therapeutic data from 83 cases.Trans R Soc Trop Med Hyg. 2002; 96: 250-253Abstract Full Text PDF PubMed Scopus (58) Google Scholar]. Pulmonary involvement was much more common in children (53.7%), while hyponatraemia was observed only in a small number of children (9.8%), compared with adults [2Gikas A Doukakis S Pediaditis J Kastanakis S Psaroulaki A Tselentis Y Murine typhus in Greece: epidemiological, clinical, and therapeutic data from 83 cases.Trans R Soc Trop Med Hyg. 2002; 96: 250-253Abstract Full Text PDF PubMed Scopus (58) Google Scholar]. The clinical course of the disease in our cases was mild and without complications. A possible explanation is the early administration of the appropriate therapy, due to increased medical awareness in Crete, where murine typhus is endemic [2Gikas A Doukakis S Pediaditis J Kastanakis S Psaroulaki A Tselentis Y Murine typhus in Greece: epidemiological, clinical, and therapeutic data from 83 cases.Trans R Soc Trop Med Hyg. 2002; 96: 250-253Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 3Bitsori M Galanakis E Gikas A Scoulica E Sbyrakis S Rickettsia typhi infection in childhood.Acta Paediatr. 2002; 91: 59-61Crossref PubMed Google Scholar]. In conclusion, murine typhus in children causes a mild disease, presenting with non-specific clinical features. Clinical and laboratory characteristics of the disease present certain diversities when compared with murine typhus in adults. Therefore, when related epidemiological information is available, fever, rash, anorexia and hepatosplenomegaly in children should raise suspicion for R. typhi infection.