Classical fever of unknown origin in 21 countries with different economic development: an international ID-IRI study.

Fever of unknown origin (FUO) is a serious challenge for physicians. The aim of the present study was to consider epidemiology and dynamics of FUO in countries with different economic development. The data of FUO patients hospitalized/followed between 1st July 2016 and 1st July 2021 were collected retrospectively and submitted from referral centers in 21 countries through ID-IRI clinical research platform. The countries were categorized into developing (low-income (LI) and lower middle-income (LMI) economies) and developed countries (upper middle-income (UMI) and high-income (HI) economies). This research included 788 patients. FUO diagnoses were as follows: infections (51.6%; n = 407), neoplasms (11.4%, n = 90), collagen vascular disorders (9.3%, n = 73), undiagnosed (20.1%, n = 158), miscellaneous diseases (7.7%, n = 60). The most common infections were tuberculosis (n = 45, 5.7%), brucellosis (n = 39, 4.9%), rickettsiosis (n = 23, 2.9%), HIV infection (n = 20, 2.5%), and typhoid fever (n = 13, 1.6%). Cardiovascular infections (n = 56, 7.1%) were the most common infectious syndromes. Only collagen vascular disorders were reported significantly more from developed countries (RR = 2.00, 95% CI: 1.19-3.38). FUO had similar characteristics in LI/LMI and UMI/HI countries including the portion of undiagnosed cases (OR, 95% CI; 0.87 (0.65-1.15)), death attributed to FUO (RR = 0.87, 95% CI: 0.65-1.15, p-value = 0.3355), and the mean duration until diagnosis (p = 0.9663). Various aspects of FUO cannot be determined by the economic development solely. Other development indices can be considered in future analyses. Physicians in different countries should be equally prepared for FUO patients.

Cat scratch disease neuroretinitis: A case report.

INTRODUCTION: Cat scratch disease (CSD) is a ubiquitous infectious disease caused by a Gram-negative intracellular bacillus, Bartonella henselae. Neuroretinitis is a classical but rare manifestation of CSD. CASE PRESENTATION: A 20-year-old woman presented with a 5-day-history of reduced vision in the left eye (LE). Two weeks before eye symptoms, she complained from fever, fatigue and arthromyalgia which resolved spontaneously. In the LE, visual acuity (VA) was 7/10, fundus photography showed optic disc edema with macular exudates arranged in incomplete macular star. Serologic test for Bartonella henselae using indirect immunofluorescent assay (IFA) was highly positive (1:2560 UI/L) for immunoglobulin G (Ig G). The diagnosis of CSD associated neuroretinitis has been made and the patient was treated with doxycycline, rifampicin and oral prednisolone. Twelve months after the end of therapy, VA was 10/10, fundus photography and Macular OCT were normal. DISCUSSION: In CSD, neuroretinitis occurs 2-3 weeks after systemic symptoms. The clinical features of CSD are not specific hence the need for bacteriological diagnosis which is based mainly on serologic testing by the detection of Ig G and Ig M by IFA or ELISA. The treatment of CSD-associated neuroretinitis is not standardized. Antibiotics active against intracellular bacteria, with or without systemic corticosteroids, should be prescribed especially in severe cases. The outcome of Bartonella henslae neuroretinitis is usually favourable. CONCLUSION: Despite rarely reported in Tunisia, CSD should be considered in patients with presence of typical neuroretinitis with macular star and of a history of contact with cats.

Neurological manifestations following cured malaria: don't forget post-malaria neurological syndrome.

INTRODUCTION: Cerebral malaria which occurs during the active infection is the most common neurological complication of malaria. Other complications including post-malaria neurological syndrome (PMNS) can rarely occur following complete recovery from the disease. We report a case of post-malaria neurological syndrome in a Tunisian patient. CASE PRESENTATION: A 26-year-old Tunisian man with no past medical history was admitted in 2016 for a muscle weakness of the 4 limbs, seizures, tetraparesis and myoclonus which appeared after he returned from Côte d'Ivoire where he had been treated three weeks ago for Plasmodium falciparum malaria with favorable outcome. Blood smears for malaria were negative. Brain MRI showed multiple hypersignal cerebral lesions. Investigations didn't show any infectious, metabolic, toxic, vascular or tumoral etiology. Thus, the diagnosis of PMNS was considered. The patient was treated with methylprednisolone with favorable outcome. Two years later, he was completely asymptomatic. CONCLUSION: PMNS should be considered in patients with neurological symptoms occurring within two months of cured acute disease in which blood smears for malaria are negative and other etiologies have been ruled out. In most cases, the disease is self-limited while in severe cases corticosteroid therapy should be prescribed with favorable outcome.

Molecular diagnosis of Rickettsia infection in patients from Tunisia.

Diagnosis of rickettsioses had largely benefited from the development of molecular techniques. Unfortunately, in Tunisia, despite the large number of rickettsial cases registered every year, the Rickettsia species remain unidentified. In this study, we aimed to detect the Rickettsia species in clinical samples using molecular tests. A study was established to analyze skin biopsies, cutaneous swabs, and cerebrospinal fluid samples taken from clinically suspected patients to have rickettsial infection. Two molecular techniques were used to detect Rickettsia DNA: quantitative real time PCR (qPCR) and reverse line blot test (RLB). An analysis of the RLB hybridization assay results revealed the presence of Rickettsia DNA in skin biopsies (40.6%) and swabs (46.7%). Rickettsia conorii was the most prevalent identified species among tested samples. Other species of interest include Rickettsia typhi and Rickettsia massiliae. Using qPCR positivity rates in skin biopsies was 63.7% against 80% in swabs. R. conorii was the most frequently detected species, followed by R. typhi. The agreement between the two techniques was 68.6% (kappa=0.33). Molecular tests, especially using specific probes qPCR, allow for a rapid, better and confident diagnosis in clinical practice. They improve the survey of Mediterranean spotted fever which is considered to be the most important rickettsial infection in humans in Tunisia.

[Causes of death in patients with HIV infection in two Tunisian medical centers]. / Causes de décès des patients infectés par le VIH dans le Centre tunisien.

Antiretroviral tritherapy has contributed to a considerable reduction in HIV-related mortality. The causes of death are dominated by opportunistic infections in developing countries and by cardiovascular diseases and cancer in developed countries. To determine the causes and risk factors associated with death in HIV-infected patients in two Tunisian medical centers. cross-sectional study of HIV-infected patients over 15 years treated at Sousse and Monastir medical centers between 2000 and 2014. Death was considered related to HIV if its primary cause was AIDS-defining illness or if it was due to an opportunistic infection of unknown etiology with CD4 < 50 cells/mm3; it was considered unrelated to HIV if its primary cause wasn't an AIDS defining illness or if it was due to an unknown cause if no information was available. Two hundred thirteen patients, 130 men (61%) and 83 women (39%), average age 40 ± 11 years were enrolled in the study. Fifty four patients died, the mortality rate was 5.4/100 patients/year. Annual mortality rate decreased from 5.8% in 2000-2003 to 2.3% in 2012-2014. Survival was 72% at 5 years and 67% at 10 years. Death events were associated with HIV in 70.4% of cases. The leading causes of death were pneumocystis carinii pneumonia and cryptococcal meningitis in 6 cases (11%) each. Mortality risk factors were a personal history of opportunistic infections, duration of antiretroviral therapy < 12 months and smoking. Strengthening screening, early initiation of antiretroviral therapy and fight against tobacco are needed to reduce mortality in patients infected with HIV in Tunisia.

Bloom syndrome complicated by colonic cancer in a young Tunisian woman.

Bloom syndrome (BS) is an autosomal recessive inherited disorder characterized by chromosomal instability leading to a high risk of cancer at an early age. The diagnosis should be considered in patients with short stature, photosensitivity, variable degrees of immunodeficiency, and hypogonadism. We report a 19-year-old woman, with history of dysmorphic features and recurrent infections. The diagnosis of bloom syndrome was made and confirmed cytogenetically at the age of 14 years. She developed a colon cancer revealed by venous thrombosis and anemia. She died after 15 days of the cancer diagnosis. This is the first registrated case of confirmed Bloom syndrome in Tunisian population.

Fatal allopurinol-induced hypersensitivity syndrome associated with pancreatic abnormalities.

Allopurinol hypersensitivity syndrome is a severe adverse reaction characterized by rash, fever, and internal organ involvement. We report a case of fatal allopurinol-induced hypersensitivity syndrome associated with acute pancreatitis.A 46-year-old man was treated by allopurinol for asymptomatic hyperuricemia. The patient developed a diffuse erythrodermic maculopapular eruption and fever. Laboratory analysis revealed cytolysis and cholestasis, amylases and lipases were highly elevated. Computed tomography scans revealed pancreatitis Grade C. The treatment of asymptomatic hyperuricemia should only be initiated when there is a clear indication to reduce the incidence and the severe consequences of allopurinol hypersensitivity syndrome.

A case of primary biliary cirrhosis associated with pernicious anemia: a case report.

Primary biliary cirrhosis is often associated with autoimmune diseases. However, its association with pernicious anemia has rarely been reported.We report a case of a 68-year-old woman who presented jaundice and pruritus. Mildly elevated serum levels of alkaline phosphatase and gamma-glutamyl transpeptidase were detected. The titer of anti-mitochondrial M(2 )anti-body was elevated. Histology of liver biopsy showed features of primary biliary cirrhosis. In addition, aregenerative macrocytic anemia was found in the full blood count. The diagnosis of pernicious anemia was established by megaloblastosis in bone marrow, atrophic gastritis without Helicobacter pylori, low level of vitamin B(12 )and good response to treatment regimen of vitamin B(12). The association of primary biliary cirrhosis and pernicious anemia is unlikely to be casual and may be explained by autoimmune mechanism commonly shared by the diseases.

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.

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.

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.

Epidemiology of infective endocarditis in Tunisia: a 10-year multicenter retrospective study.

BACKGROUND: Since the first description of infective endocarditis, the profile of the disease has evolved continuously with stable incidence. However, epidemiological features are different in developing countries compared with western countries. OBJECTIVE: To describe epidemiological, microbiological and outcome characteristics of infective endocarditis in Tunisia. PATIENTS AND METHODS: This was a descriptive multicenter retrospective study of inpatients treated for infective endocarditis from 1991 to 2000. Charts of patients with possible or definite infective endocarditis according to the Duke criteria were included in the study. RESULTS: Four hundred and forty episodes of infective endocarditis among 435 patients (242 males, 193 females; mean (SD) age=32.4 (16.8) years, range 1-78 years) were reviewed. The most common predisposing heart disease was rheumatic valvular disease (45.2%). Infective endocarditis occurred on prosthetic valves in 17.3% of cases. Causative microorganisms were identified in 50.2% of cases: streptococci (17.3%), enterococci (3.9%), staphylococci (17.9%), and other pathogens (11.1%). Blood cultures were negative in 53.6% and no microorganism was identified in 49.8%. Early valve surgery was performed in 51.2% of patients. The in-hospital mortality was 20.6%. CONCLUSION: Infective endocarditis is still frequently associated with rheumatic disease among young adults in Tunisia, with a high frequency of negative blood cultures and high in-hospital mortality, given that the population affected is relatively young.