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Mediterranean spotted fever in Algerian children

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

10.1111/j.1469-0691.2008.02241.x

1469-0691

Nadjet Mouffok, Philippe Parola, D. Abdennour, A. Aouati, F. Razik, A. Benabdellah, Didier Raoult,

Vector-Borne Animal Diseases

Mediterranean spotted fever (MSF) is a potentially life-threatening zoonosis caused by Rickettsia conorii and transmitted by the brown dog tick Rhipicephalus sanguineus [1Parola P Paddock C Raoult D Tick-borne rickettsioses around the world: emerging diseases challenging old concepts.Clin Microbiol Rev. 2005; 18: 719-756Crossref PubMed Scopus (752) Google Scholar]. Although MSF is one of the oldest recognised rickettsioses, there have been few reports about this rickettsiosis in North Africa [1Parola P Paddock C Raoult D Tick-borne rickettsioses around the world: emerging diseases challenging old concepts.Clin Microbiol Rev. 2005; 18: 719-756Crossref PubMed Scopus (752) Google Scholar, 2Mouffok N Parola P Lepidi H Raoult D New trends of Mediterranean spotted fever in Algeria.Int J Infect Dis. 2008; (In press.)PubMed Google Scholar]. The present work on MSF cases occurring in children is a subset of a larger study conducted within all age categories. Patients younger than 15 years old who were seen at the Oran Teaching Hospital in 2004–2005 with suspicion of rickettsioses were prospectively included in this study. Informed consent was obtained from all parents. For each child, the study involved obtaining an acute-phase serum sample within 2 weeks of the onset of the symptoms and, when possible, a convalescent-phase serum sample. IgG and IgM antibody titres were estimated by an immunofluorescence (IF) assay, using 10 rickettsial antigens [2Mouffok N Parola P Lepidi H Raoult D New trends of Mediterranean spotted fever in Algeria.Int J Infect Dis. 2008; (In press.)PubMed Google Scholar].When cross-reactions were noted between several rickettsial antigens, Western blotting and cross-adsorption studies were used to complement the IF assay [2Mouffok N Parola P Lepidi H Raoult D New trends of Mediterranean spotted fever in Algeria.Int J Infect Dis. 2008; (In press.)PubMed Google Scholar]. A total of 36 children were included in the study. Most of them (75%) were taken to healthcare providers before being seen at the Oran University Hospital. During a previous consultation they were prescribed a first-line antibiotics regimen, in particular amoxicillin (56%) or amoxicillin-clavulanate (22%); a few of them also received penicillin G, erythromycin, spiramycin or cotrimoxazole. A total of 24 cases were diagnosed as MSF. Most (16 children) of them were encountered in July (seven cases) and August (nine cases). The median age was 4.5 years old (15 days to 14 years old). A history of tick-bite was given in nine (37.5%) cases. Contact with dogs was reported in 20 (83.3%) cases. Patients were seen at the hospital after a median of 6 days (range 3–10 days) of fever. All children but one had fever (Table 1). A rash was observed in all the children but one. It was maculopapular and included the palms and soles in 23 (92%) of the cases. One child had a petechial rash. An inoculation eschar was observed in 20 (83.3%) children. In the majority (16/20) of the cases it was localised in the cephalic region (retro-auricular, the lobule of the ear, scalp). For four other children, it was respectively localized on the trunk, on the buttocks, in the inguinal area, and between two toes. Eighteen patients (90%) presented with a single eschar, while two patients presented with two eschars. Two children presented with seizure and were considered as a severe form of MSF. Leucopenia was found in eight cases (33.3%), leucocytosis in five (20%), thrombocytopenia in four cases (16.6%) and anaemia in 16 cases (66.6%).TABLE 1Clinical findings in 24 children with confirmed Mediterranean spotted fever (MSF) in Oran, Algeria, in 2004–2005, compared with three other published studies from France, Sicily and SpainMSFPresent study[3Raoult D Arnolds M Garnier JM De Micco P Giraud E Fièvre boutonneuse méditerranéenne de l'enfant (à propos de 41 observations).Med Hyg. 1983; 41: 1013-1016Google Scholar][4Colomba 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: 60Crossref PubMed Scopus (56) Google Scholar][5Lopez-Pares P Munoz-Espin T Espejo-Arenas E et al.Fiebre botonosa mediterranéa en la infancia. Estudio prospectivo de 130 casos.An Esp Pediatr. 1988; 28: 293-296PubMed Google Scholar]Clinical manifestationsn = 24aCases definitely confirmed to be caused by R. conorii, using immunofluoresence with a panel of rickettsial antigens, completed by Western blot and cross-absorption studies. (%)n = 41 (%)n = 415bTwo hundred and thirty-two cases were confirmed by IF serology, using R. conorii antigen only. (%)n = 130cImmunofluorescence to R. conorii was positive in 75% of the cases. (%)Fever23 (96)41 (100)386 (93)130 (100) Moderate14 (58) High9 (38)Rash23 (96)41 (100)392 (95)127 (98)Eschar (Tache noire)20 (83)33 (80)263 (63.4)113 (87) Unique18257 Multiple26Local lymphoadenopathy12 (50)214 (51.6)79 (61)Headache9 (38)6 (15)122 (29)82 (63)Arthralgia/myalgia10 (42)4 (10)158 (38)Diarrhea4 (17)4 (10)Vomiting3 (13)2 (5)37 (28)dNausea or vomiting.Splenomegaly5 (20)9 (22)10 (8)Hepatomegaly2 (8)3 (7.5)21 (16)Seizures2 (8)3 (7.5)Meningism4 (17)8 (20)3 (0.7)Coma0000Cough2 (8)2 (5)2 (2)Epistaxis1 (4)a Cases definitely confirmed to be caused by R. conorii, using immunofluoresence with a panel of rickettsial antigens, completed by Western blot and cross-absorption studies.b Two hundred and thirty-two cases were confirmed by IF serology, using R. conorii antigen only.c Immunofluorescence to R. conorii was positive in 75% of the cases.d Nausea or vomiting. Open table in a new tab Intravenous chloramphenicol was used as a first-line drug in eight children who presented with vomiting. It was switched to oral josamycine (macrolid, five cases), doxycycline (two cases) or thiophenicol (one case). The 13 other children received josamycine as a first-line oral regimen. We report here the largest prospective study conducted on MSF in children in North Africa. Although other spotted fever group rickettsioses exist in Algeria [1Parola P Paddock C Raoult D Tick-borne rickettsioses around the world: emerging diseases challenging old concepts.Clin Microbiol Rev. 2005; 18: 719-756Crossref PubMed Scopus (752) Google Scholar], our cases have been confirmed to be caused by R. conorii using immunofluorescence methods completed by Western blot and cross-absorption studies. Cases were encountered in the summer, a classic pattern for MSF [1Parola P Paddock C Raoult D Tick-borne rickettsioses around the world: emerging diseases challenging old concepts.Clin Microbiol Rev. 2005; 18: 719-756Crossref PubMed Scopus (752) Google Scholar], because Rh. sanguineus ticks are highly active and more aggressive during the warmest months. Of interest, two children presented with two eschars. This is quite unusual in MSF, for which the typical inoculation eschar at the tick-bite site is usually unique [1Parola P Paddock C Raoult D Tick-borne rickettsioses around the world: emerging diseases challenging old concepts.Clin Microbiol Rev. 2005; 18: 719-756Crossref PubMed Scopus (752) Google Scholar, 2Mouffok N Parola P Lepidi H Raoult D New trends of Mediterranean spotted fever in Algeria.Int J Infect Dis. 2008; (In press.)PubMed Google Scholar]. However, particular climatic circumstances, including higher temperature, that were reported in Oran in recent years, may have led to an increased proclivity of ticks to bite humans (Parola et al., unpublished). Although 62.5% of the children in the present series were hospitalised, only two (those with seizures) were considered to have a severe form. During the same period in Oran, cases were particularly severe in adults; 49% of 167 patients diagnosed with MSF were hospitalised with a severe form [2Mouffok N Parola P Lepidi H Raoult D New trends of Mediterranean spotted fever in Algeria.Int J Infect Dis. 2008; (In press.)PubMed Google Scholar]. Therefore, cases of MSF seem to be milder in children than in adults. Also, in adults, the eschar is most often observed on the trunk and legs [2Mouffok N Parola P Lepidi H Raoult D New trends of Mediterranean spotted fever in Algeria.Int J Infect Dis. 2008; (In press.)PubMed Google Scholar]. Herein, the eschar is frequently localised on the cephalic area, even in babies who were not of walking age. When they initially sought medical care, children were prescribed drugs that were ineffective to treat rickettsioses. It should be remembered that doxycycline remains the treatment of choice for all patients, including young children with life-threatening rickettsioses [1Parola P Paddock C Raoult D Tick-borne rickettsioses around the world: emerging diseases challenging old concepts.Clin Microbiol Rev. 2005; 18: 719-756Crossref PubMed Scopus (752) Google Scholar]. The risk of dental staining by doxycycline is negligible when a single, relatively short course of therapy is administered. Chloramphenicol continues to be used as the empirical parenteral treatment of severe cases if it is the sole available drug or in children presenting with vomiting and lack of intravenous doxycycline. Josamycin can be used in children, but newer macrolides are also of interest, particularly azithromycin [1Parola P Paddock C Raoult D Tick-borne rickettsioses around the world: emerging diseases challenging old concepts.Clin Microbiol Rev. 2005; 18: 719-756Crossref PubMed Scopus (752) Google Scholar]. MSF seems to be still misdiagnosed in children as other eruptive febrile diseases. The consequences of this include delays in appropriate therapy and a risk of a severe form and even a fatal outcome.