A. Letaief

Seroepidemiological survey of rickettsial infections among blood donors in central Tunisia

In this report we attempt to evaluate the prevalence of antibodies against Rickettsia conorii, R. typhi, Coxiella burnettii, and Ehrlichia chaffeensis in central Tunisia. Five hundred sera from blood donors, collected between March and June 1993, were tested for these 4 antibodies using an indirect immunofluorescence antibody assay (IFA). Nine percent of the sera had antibodies against R. conorii (IgG > 1:32) by IFA, and 8% by Western blotting; with IFA, 3.6% had antibodies to R. typhi, 26% to C. burnetii (> 1:50), and none to E. chaffeensis. Infection rates with R. conorii and R. typhi did not differ significantly between the sexes, but fewer young people had antibodies to R. typhi. A significantly higher prevalence of antibodies to C. burnetii was noted for males with no difference between age classes. No significant difference was detected between urban and rural areas. This study confirmed the endemicity of rickettsioses, and revealed a high seroprevalence of Q fever, in central Tunisia.

Serologic Study of Rickettsioses among Acute Febrile Patients in Central Tunisia

Abstract:  Although Mediterranean spotted or “boutonneuse” fever (MSF) has been documented in central Tunisia, other spotted fever group rickettsioses (SFGR) and typhus group rickettsioses (TGR) have received little attention in our region. We sought to determine the role of rickettsioses, Q fever, ehrlichioses, and bartonelloses among patients with acute fever. The results of this study of 47 persons with acute fever of undetermined origin are reported in this paper. We concluded that SFGR, murine typhus, and acute Q fever are common causes of acute isolate fever in summer in central Tunisia and should be investigated systematically in patients with acute fever of unknown origin.

Epidemiological and clinical features of giant cell arteritis in Tunisia

BACKGROUND Giant cell arteritis (GCA) is a systemic vasculitis of the elderly that could result in vision loss or even be life threatening. Unlike western countries, this disease is considered exceptional in Tunisia. OBJECTIVE The aims of this study were to determine epidemiological and clinical features of GCA in Tunisian population and to identify management difficulties. PATIENTS AND METHODS A multicentric study of 96 patients in whom GCA was diagnosed between 1986 and 2003. All patients fulfilled the ACR criteria for classification of GCA. RESULTS The majority of cases (77%) were diagnosed since 1994. The male/female ratio was 0.88 and the mean age at the time of diagnosis was 70.8+/-7.7 years. Clinical features were characterized by gradual onset in 64.4% of cases. The most frequent clinical manifestations were headache (91.7%), abnormalities in temporal arteries (85.4%), severe ischemic manifestations (80.2%), constitutional symptoms (75%), and polymyalgia rheumatica (56.3%). Biological inflammatory syndrome was noted in all patients. Temporal artery biopsy established histological diagnosis in 73% of cases. All patients were treated by corticosteroids. Remission was obtained in 45.6%. Relapses occurred in 40.4% of cases and 30 patients were still receiving corticosteroids at the time of study. Four patients died and irreversible ischemic complications were noted in 15.6% of cases. Steroid adverse effects occurred in 56 patients. CONCLUSION GCA is not exceptional to Tunisia. It occurs amongst elderly patients with no female predominance noticed. Clinical features are similar to those reported in other series.

Evaluation of Clinical Diagnosis Scores for Boutonneuse Fever

Abstract: Mediterranean spotted fever (MSF) is endemic in Tunisia. Diagnosis is confirmed retrospectively based on serology. Clinical features are suggestive of diagnosis if the triad (fever, rash, and eschar) is present. Otherwise clinical diagnosis could be difficult. A diagnosis score was already proposed by Raoult et al. The aim of this study was to evaluate this score, considering only clinical parameters, in order to help clinicians in diagnosing MSF before confirmation. We retrospectively analyzed 62 consecutive charts of patients with diagnosis of suspected MSF. Diagnosis confirmation was made by serology (IgG anti‐R. conorii exceeding 128 or seroconversion). Epidemiological and clinical features and total score for each patient were reviewed. To validate the clinical score, we calculated sensitivity, specificity and the Youden index for each score in order to establish the ROC curve. SPSS was used for these statistical tests. Area under curve was 0.70 (P= 0.02). The cutoff score with the most predictive value of MSF diagnosis was 18, according to our study (sensitivity 60%, specificity 84,6% and Youden index 0.44). The MSF diagnosis score is a helpful tool to aid the clinician with presumptive management before confirmation. In our study we demonstrated that a score based only on epidemiological and clinical features could be sufficient, but we have to indicate that these results and cutoff score of 18 were from a retrospective study and should be confirmed by a well‐designed prospective one.

Characterization of Rickettsial Diseases in a Hospital-Based Population in Central Tunisia

In Tunisia, 2 rickettsial groups, spotted fever group and typhus group, have been described since the beginning of the 20th century. Mediterranean spotted fever (MSF), also known as Boutonneuse fever, caused by Rickettsia conorii and transmitted by the dog tick Rhipicephalus sanguineus, is the most frequent rickettsial infection observed. Its seroprevalence in our region is 9% among blood donors and 23% in hospitalized febrile patients. Typhus group rickettsioses, caused by R. typhi and R. prowazekii, are less frequently reported than in the 1970s. Only sporadic cases of typhus were reported in the last decade. However, R. typhi antibodies were present in 3.6% among healthy people and 40% in patients with acute fever of undetermined origin. In the unit of Infectious Diseases at Farhat Hached University Hospital in Sousse, during 2007, 5% of hospitalized patients had eruptive fever, and half of the cases met clinical criteria of MSF and/or were confirmed by rickettsial serology. The majority of cases (90%) were noted in hot seasons, and contact with domestic animals was found in 76%. The most common symptoms were fever (present in all cases), skin rash (in 85% to 98% of cases), and headache (in 69.5% of cases). The clinical triad (fever + rash +“tache noire”) was noted in 32 to 61%. Normal blood cells or leukopenia, cytolysis, and thrombopenia were the most frequent biological abnormalities. Complications and malignant forms of rickettsial infections were reported in 3.5 to 6% among hospitalized adult patients. When specific serology was performed, MSF was confirmed in 15%, and we noted an emergence of murine typhus (MT) mistaken for R. conorii or viral infection. Rickettsia felis was identified in 1 patient, whereas 17% of cases remained undetermined. Rickettsia conorii Malish was identified by PCR in skin biopsies. Doxycycline was the antibiotic of choice for rickettsial infections; it was prescribed in the majority of patients, associated with fever defervescence, in a mean of 72 hours. The mean length of stay among hospitalized patients with rickettsial infections was 5.9 days. In conclusion, in our region, MSF and murine typhus are endemic. Doxycycline should be prescribed in patients with acute fever and skin rash, especially in hot seasons. These rickettsioses were characterized by benign prognosis. More skin biopsies are needed to identify other SFG rickettsies.

Comparison of Two Quantitative Real Time PCR Assays for Rickettsia Detection in Patients from Tunisia

Background and objectives Quantitative real time PCR (qPCR) offers rapid diagnosis of rickettsial infections. Thus, successful treatment could be initiated to avoid unfavorable outcome. Our aim was to compare two qPCR assays for Rickettsia detection and to evaluate their contribution in early diagnosis of rickettsial infection in Tunisian patients. Patients and methods Included patients were hospitalized in different hospitals in Tunisia from 2007 to 2012. Serology was performed by microimmunofluorescence assay using R. conorii and R. typhi antigens. Two duplex qPCRs, previously reported, were performed on collected skin biopsies and whole blood samples. The first duplex amplified all Rickettsia species (PanRick) and Rickettsia typhi DNA (Rtt). The second duplex detected spotted fever group Rickettsiae (RC00338) and typhus group Rickettsiae DNA (Rp278). Results Diagnosis of rickettsiosis was confirmed in 82 cases (57.7%). Among 44 skin biopsies obtained from patients with confirmed diagnosis, the first duplex was positive in 24 samples (54.5%), with three patients positive by Rtt qPCR. Using the second duplex, positivity was noted in 21 samples (47.7%), with two patients positive by Rp278 qPCR. Among79 whole blood samples obtained from patients with confirmed diagnosis, panRick qPCR was positive in 5 cases (6.3%) among which two were positive by Rtt qPCR. Using the second set of qPCRs, positivity was noted in four cases (5%) with one sample positive by Rp278 qPCR. Positivity rates of the two duplex qPCRs were significantly higher among patients presenting with negative first serum than those with already detectable antibodies. Conclusions Using qPCR offers a rapid diagnosis. The PanRick qPCR showed a higher sensitivity. Our study showed that this qPCR could offer a prompt diagnosis at the early stage of the disease. However, its implementation in routine needs cost/effectiveness evaluation.

Association of an HLA-G 14-bp Insertion/Deletion polymorphism with high HBV replication in chronic hepatitis.

Identification of an HLA‐G 14‐bp Insertion/Deletion (Ins/Del) polymorphism at the 3′ untranslated region of HLA‐G revealed its importance in HLA‐G mRNA stability and HLA‐G protein level variation. We evaluated the association between the HLA‐G 14‐bp Ins/Del polymorphism in patients with chronic Hepatitis B virus (HBV) infection in a case–control study. Genomic DNA was extracted from 263 patients with chronic HBV hepatitis and 246 control subjects and was examined for the HLA‐G 14‐bp Ins/Del polymorphism by PCR. The polymorphic variants were genotyped in chronic HBV seropositive cases stratified according to HBV DNA levels, fibrosis stages and in a control population. There was no statistical significant association between the 14‐bp Ins/Del polymorphism and increased susceptibility to HBV infection neither for alleles (P = 0.09) nor for genotypes (P = 0.18). The stratification of HBV patients based on HBV DNA levels revealed an association between the 14‐bp Ins/Del polymorphism and an enhanced HBV activity with high HBV DNA levels. In particular, the Ins allele was significantly associated with high HBV DNA levels (P = 0.0024, OR = 1.71, 95% CI 1.2–2.4). The genotype Ins/Ins was associated with a 2.5‐fold (95% CI, 1.29–4.88) increased risk of susceptibility to high HBV replication compared with the Del/Del and Ins/Del genotypes. This susceptibility is linked to the presence of two Ins alleles. No association was observed between the 14‐bp Ins/Del polymorphism and fibrosis stage of HBV infection. We observed an association between the 14‐bp Ins/Del polymorphism and high HBV replication characterized by high HBV DNA levels in chronic HBV patients. These results suggest a potential prognostic value for disease outcome evaluation.

Granulocytic sarcoma of the rectum: Report of one case that presented with rectal bleeding

Granulocytic sarcoma is an uncommon and localized extramedullary tumor composed of immature granulocytic cells. It may present in association with acute myeloid leukaemia, myelodysplastic syndrome and chronic myelogenous leukaemia. Granulocytic sarcoma may occur in any anatomical site but involvement of the gastrointestinal tract is rare, especially in the rectum. We report on the case of a 17 year old female who presented with rectal bleeding, abdominal pain and weight loss one mo prior to admission. Rectosigmoidoscopy revealed a rectal polypoid and ulcerated mass. The histological examination of the mass showed granulocytic sarcoma. Bone marrow examination was compatible with acute promyelocytic leukaemia (FAB type M3). This case report is a reminder of this peculiar sign of tumoral syndrome in acute myeloid leukaemia. We also discuss diagnostic methods and analyze the disease course.

First molecular detection of R. conorii subsp. conorii 99 years after the Conor description of Mediterranean spotted fever, in Tunisia.

and in the Paediatric Unit of the University Hospital of Mahdia (35� 30¢15.84¢¢N, 11� 03¢57.96¢¢E) in the centre of Tunisia, were investigated for rickettsial infection. Sera were collected and cutaneous biopsies (two from eschar and two from maculopapular rash) were obtained from four patients. Sera were tested by IFA and Western blot with crossadsorption studies for identification of rickettsial strains at the species level. DNA of blood was extracted by using the QIAamp Tissue Kit (Qiagen GMBH, Hilden, Germany), according to the manufacturer’s instructions, in the Laboratory of Medical Entomology in the Institut Pasteur of Tunis. DNA of cutaneous biopsies was extracted in Marseille, France. Rickettsial DNA was detected by PCR using the primers targeting the gltA gene and the primers targeting the OmpA gene [4]. PCR products were purified and sequenced as previously described [4]. All obtained sequences were assembled and edited with Auto Assembler software (version 1.4; Perkin-Elmer). Sequences were analysed by BLAST sequencing analysis of the sequences in the GenBank database (see http:// www.ncbi.nlm.nih.gov/blast/).

La maladie de Takayasu dans la région centre de la Tunisie. À propos de 27 cas

BACKGROUND Takayasus arteritis is a rare inflammatory disease and few data are available in Tunisia. The aim of this study is to evaluate clinical and radiological features of the disease in the centre of Tunisia. METHODS We retrospectively studied medical records of patients treated in departments of internal medicine or cardiology from three university hospitals in Sousse and Monastir over the period 1985-2005. The criteria for inclusion were those proposed by the American College of Rheumatology. RESULTS Twenty-seven patients were identified. The mean age at presentation was 33.2 years (range 16-68 years) and 88.9% were female. The mean delay from the onset of the symptoms to the time of diagnosis was 4.2 years. Intermittent claudication was the most common presentation (81.5%) and hypertension was noted in 40.7% of cases. Arterial localization most frequently involved was subclavian artery. The aorta was involved in 52.3% and renal arteries in 36.3% of cases. Stenosis or occlusions was constant but aneurysms were noted in 7.4%. Functional difficulty was the main complaint in the follow-up, death related to Takayasus disease was noted in 3.7%. The mean follow-up time was 75.8 months (6.3 years). CONCLUSION There is no epidemiologic particularity of Takayasus disease in Tunisia, however involvement of the subclavian artery was more frequent than the aortic localization.