Human papillomavirus genotypes and HPV-16 variants distribution among Tunisian women with normal cytology and squamous intraepithelial lesions.

BACKGROUND: Little is known about the epidemiological characteristics of papillomavirus (HPV) infection among North African countries. Herein, we conducted a molecular epidemiological study to investigate prevalence of HPV type and HPV-16 variants among cervical-screened unvaccinated Tunisian women. METHODS: Cross-sectional study was performed on 494 Tunisian women visiting Women's Healthcare Centers. HPV-DNA detection was carried out on cervical samples using real-time polymerase chain reaction. HPV genotyping and HPV-16 variants were characterized by direct sequencing of L1 viral capsid gene. RESULTS: The overall HPV prevalence was 34% (95% CI: 30-38%) with significantly higher prevalence among women with squamous intraepithelial lesions (SIL) than those with no intraepithelial lesions (NIL) 84% (95% CI: 76-92%) and 24.5% (95% CI: 20-29%) respectively. The distribution of HPV prevalence according to women's age shows a U-shaped curve and the highest HPV prevalence rates were observed among the youngest (≤25 years; 51.2%, 95% CI: 37-67%) and the oldest women (>55 years; 41.7%, 95% The HPV-16 prevalence was 32.8% (95% CI: 22-45%) among women with SIL and 9.2% (95% CI: 6-12%) among women with NIL. Whereas, the HPV-18 prevalence was 1.3% (95% CI: 0-5%) among women with SIL and 0.3% (95% CI: 0-1%) among women with NIL. Among HPV-16 positive women, European lineage (E) was identified as the predominant HPV-16 variant (85.7%, 95% CI: 76-95%). The frequency of E variant was lower among SIL than among NIL women (81%, 95% CI: 64-99%, and 88%, 95% CI: 77-100%, respectively). Conversely, the African-2 variant frequency was higher among SIL than among NIL women (18%, 95% CI: 1-36% and 6%, 95% CI: 2-14%, respectively). In multivariate analysis, young age was the only risk factor that is independently associated with HPV infection. Moreover, HPV infection and menopause were both found to be independently associated with SIL and HSIL. CONCLUSION: HPV DNA testing should be proposed to young and menopausal Tunisian women. Considering HPV prevalence, only 13% of the Tunisian women could be protected by the bivalent HPV vaccine. These results may be helpful for designing an adapted HPV testing and vaccination program in Tunisia.

Neuroendocrine tumours of the pancreas: a clinicopathological study of nine cases including six insulinomas.

BACKGROUND: Pancreatic neuroendocrine tumours (pNET) are relatively uncommon, accounting for 1-2% of all pancreatic neoplasms. They are characterised by varying clinical presentation, tumour biology and prognosis. AIM: To provide an updated overview on clinicopathological features, treatment and outcome of pNET. PATIENTS AND METHODS: In our retrospective study, we reviewed 9 cases of pNET that were diagnosed at the Pathology Department of Mongi Slim Hospital over an 11-year period (2003- 2013). Relevant clinical information and microscopic slides were available in all cases and were retrospectively reviewed. The latest WHO classification (2010) was adopted. RESULTS: Our study group included 3 men and 6 women (M/F ratio 0.5) with an age between 20 and 75 years (mean = 52 years). Pancreatic neuroendocrine tumours ranged in size from 0.5 to 10 cm (mean 4 cm). The sites of pNET were the head of the pancreas (n = 4), the body of the pancreas (n = 3) and the tail of the pancreas (n = 2). Enucleation of the tumour was performed in five cases, Three patients underwent distal pancreatectomy and splenectomy, whereas only one patient had central pancreatectomy. Histopathological examination of the surgical specimen coupled with immunohistochemical study established a diagnosis of pNET grade 1 (G1) in seven cases and grade 2 (G2) in two cases. CONCLUSION: Pancreatic neuroendocrine tumours are a heterogeneous group of neoplasms with distinct tumour genetics, biology and clinicopathological features. Accurate clinical and pathologic diagnosis is an important first step in developing an appropriate management plan.

Dual infection with Bordetella pertussis and Mycoplasma pneumoniae in three infants: case reports.

Studying pertussis-like respiratory infections, we report the cases of three infants with evidence of both Bordetella pertussis and Mycoplasma pneumoniae. Bordetella infection was identified by the real-time polymerase chain reaction (RT-PCR) of nasopharyngeal specimens. Neither B. pertussis nor B. parapertussis were recovered on the culture of nasopharyngeal aspirates (NPAs) from any subjects. M. pneumoniae etiology was diagnosed by culture and RT-PCR. The evolution was fatal for all of the subjects. We conclude that, among patients with Bordetella infection, co-infection with another respiratory pathogen is often probable, and these mixed infections might cause a more severe form of illness, sometimes leading to death.

Lack of effect of tumor necrosis factor-alpha -308 G/A polymorphism on severity of liver fibrosis in Tunisian hepatitis C virus (HCV)-infected patients.

OBJECTIVES: Tumor necrosis factor alpha (TNF-alpha) plays a key role in the immune response. An elevated plasma level of TNF-alpha was repeatedly observed in patients with active liver injury or cirrhosis regardless of the aetiology. The G/A transition at position -308 in the promoter region have been shown to influence TNF-alpha expression. In this study, we aimed to evaluate the impact of TNF-alpha -308 G/A functional polymorphism on fibrosis severity in Tunisian Hepatitis C Virus (HCV)-infected patients. METHODS: TNF-alpha -308 G/A polymorphism was evaluated by polymerase chain reaction (PCR) amplification followed by Restriction Fragment Length Polymorphism (RFLP) method in 53 chronic hepatitis C patients. Single-nucleotide polymorphism (SNP) frequencies were compared with regard to liver fibrosis severity as assessed by the METAVIR scoring system (F1-F2; n=22 versus F3-F4; n=31). RESULTS: The genotype distribution of the TNF-alpha -308 G/A polymorphism among the HCV-infected patients was as follows : GG : 67.9%, GA : 32.1%, AA : 0%. With regard to fibrosis score, no significant differences in TNF-alpha genotype distribution were observed between F1-F2 and F3-F4 patients (p=0.15). CONCLUSION: No significant association between TNF-alpha -308 polymorphism and and the severity of liver fibrosis was found in our Tunisian cohort.

NS5A(ISDR-V3) region genetic variability of Tunisian HCV-1b strains: Correlation with the response to the combined interferon/ribavirin therapy.

In the non-structural protein 5A (NS5A) of hepatitis C virus (HCV), mutations within the interferon sensitivity-determining region (ISDR), the PKR-binding domain (PKR-BD), the variable region 3 (V3), and the interferon/ribavirin resistance-determining region (IRRDR) have been correlated with the IFN-based therapy response. In Tunisia, where a high prevalence of HCV-1b has been found, no data regarding the implication of NS5A in treatment response were available. The current study examined the relationship between the pre-treatment mutation number within ISDR, PKR-BD, V3, IRRDR, as well as in the entire ISDR-V3 region of NS5A (aa 2209-2379) and the response to the 48-week course of combined IFN plus ribavirin therapy in 15 HCV-1b-infected Tunisian patients. Referring to HCV-J sequence, a significant high genetic variability was observed within PKR-BD in the sustained virological responder patients compared to non-responders (P = 0.040). More importantly, when considering the entire region from ISDR to V3, referred to as NS5A(ISDR-V3), a clear difference in the mutation number was observed between sustained virological responders (19.6 +/- 3.16) and non-responders (15.0 +/- 1.41) (P = 0.002). Additionally, a more detailed analysis of NS5A(ISDR-V3) region revealed an elevated degree of mutation rate within the region located between amino acids 2282 and 2308 (P = 0.0006). Interestingly, an analysis of specific amino acid variations defined proline and serine at position 2300 as signature patterns for sensitive and resistant strains, respectively. The genetic variability within the NS5A region of HCV-1b strains was associated with the response to the combined IFN plus ribavirin therapy in our Tunisian cohort.

Interleukin-10 and interferon-gamma gene polymorphisms in patients with nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a multifactorial disease. Cytokines driving the immune response seem to be disturbed in NPC patients. Since interleukin-10 (IL-10) is known to reduce the production of interferon-gamma (IFN-gamma), we supposed that genetic differences in IL-10 and IFN-gamma expression could be a mechanism by which NPC cells escape antitumour immune response. As the production of each cytokine is affected by the genetic background, we investigated the possible association between single nucleotide polymorphisms in genes of IL-10 and IFN-gamma with NPC. Different IL-10 -1082 G/A and IFN-gamma+874 Tau/Alpha genotypes were determined in 160 patients with nasopharyngeal carcinoma and 197 healthy controls. No association was found either for each SNP studied alone or for the combined analysis for both IL-10 and IFN-gamma polymorphisms among NPC patients in comparison with controls. Compared with individuals from high incidence countries, we noted huge significant differences in genotype distribution between individuals from low and intermediate NPC incidence countries. Polymorphisms of the IL-10 and IFN-gamma do not appear to be associated with NPC risk in the Tunisian population. Nevertheless, we strongly believe that the relationship between cytokines polymorphisms and NPC susceptibility deeply depends on the ethnicity.

Association of interleukin-18 polymorphisms and plasma level with the outcome of chronic HCV infection.

Hepatitis C virus (HCV) infection is the main cause of chronic liver disease throughout the world, and may progress to cirrhosis and hepatocellular carcinoma (HCC). Immunological factors, especially cytokines and some host genetic variations, rather than direct HCV action, seem to play an important role in the pathogenesis of HCV infection. Elevated levels of interleukin-18 (IL-18) were described previously for chronically (HCV)-infected patients. This study is aimed at investigating IL-18 promoter polymorphisms (-607C/A and -137G/C) in HCV-infected patients with different disease severities (chronic hepatitis C, liver cirrhosis and HCC) and establishing an association between these polymorphisms and IL-18 plasma concentration with the outcome of chronic HCV infection. The carriage of at least one C allele at position -607 (CC + CA) was associated with a higher risk of cirrhosis and HCC (P = 0.032). Compared with controls, HCV-infected patients had significantly higher levels of IL-18 (P = 0.0001) that correlate with disease severity (P = 0.01, P = 0.001, P = 0.0006, respectively). In conclusion, we supposed a possible implication of IL-18 promoter polymorphisms in the pathogenesis of chronic HCV infection.

[HFE gene mutations in Tunisian major beta-Thalassemia and iron overload]. / Mutations du gène HFE chez des beta-thalassémiques majeurs tunisiens et surcharge en fer.

OBJECTIVES: In this study we have determined the allele frequency of HFE mutations H63D and C282Y in a group of Tunisian beta-thalassemia major patients. These two mutations are implicated in hereditary hemochromatosis among Caucasians. In this study we wanted to correlate these mutations with the iron status in major beta-thalassemia patients. DESIGN AND METHODS: Fifty Tunisian major beta-thalassemia were screening for the C282Y and H63D by digestion of polymerase chain reaction products (RFLP). Serum ferritin level was measured by immunoenzymatic microparticular essay. RESULTS: The allele frequency of H63D mutation was 17%. C282Y mutation was not present in our studied patients. No statistically significant difference of serum ferritin level was found between major beta-thalassemia with and without HFE mutations. CONCLUSION: Our results suggest that H63D mutation is so frequent in Tunisian major beta-thalassemia patients than in the general population and that the coinheritance of H63D mutation does not influence the severity of iron overload in these patients.

Cervical human papillomavirus infection in Tunisian women.

BACKGROUND: It is well established that certain types of human papillomavirus (HPV) are the sexually transmitted agents etiologically linked to cervical cancer. Sexual habits have been shown to be a major determining factor for HPV infection. A large study was carried out to investigate the prevalence and risk factors associated with cervical infection with HPV in Tunisian women. MATERIALS AND METHODS: PCR and restriction enzyme digestion were used to characterize HPV cervical infection in 106 Tunisian married women and 51 legal prostitutes. Epidemiological data were collected and correlated with HPV molecular genotyping. RESULTS: There was a higher relative frequency of HPV-DNA in prostitutes (39%) than in married women (14%) (p = 0.001). Molecular analyses of HPV types showed the most prevalent type in prostitutes to be HPV-16, a high-risk oncogenic type. In married women, the most prevalent type was HPV-6 which is associated with a low risk for cervical cancer. HPV-DNA detection was markedly increased in young adult women and in those having recent sexual experience. CONCLUSION: Cervical HPV infection in Tunisia is less frequent than in other African countries, but far from uncommon. The decrease of HPV prevalence in older women, regardless of their sexual behavior, may result from an efficient immune response acquired with age.

[Detection and molecular typing of human papillomaviruses: prevalence of cervical infection in the Tunisian central region]. / Detection et typage moleculaire des Papillomavirus Humains: prevalence de l'infection cervicale dans la region du centre Tunisien.

There are compelling molecular and epidemiological data which indicate that infection with certain genital human papillomaviruses (HPVs), such as HPV 16 and HPV 18, has a critical role in initial changes that lead to cervical and probably other anogenital cancers. These observations prompted us to investigate the prevalence of cervical infection with genital human papillomaviruses in Tunisia. We used the polymerase chain reaction (PCR) to detect and type HPV DNA. The prevalence of HPV infection in a population of 106 Tunisian women recruited at the Offices Nationaux de la Famille et de Population (ONFP) was 13.6%. Molecular HPV typing indicated a high prevalence of HPV at high oncogenic risk; Our results indicate that the infection with genital human papillomaviruses is frequent in the Tunisian population.

[Group D streptococci and enterococci: identification, sensitivity to antibiotics and a study of the high level resistance to aminosides (Charles Nicolle Hospital in Tunis)]. / Les streptocoques du groupe D et les enterocoques: identification, sensibilite aux antibiotiques et etude de la resistance haut niveau aux aminosides (Hôpital Charles Nicolle de Tunis).

197 strains of enterococcus and group D Streptococcus were isolated from human material at Charles Nicolle Hospital (Tunis) and identified by biochemical tests: 174, Enterococcus faecalis, 6 Enterococcus faecium, 2 Enterococcus durans and 15 Streptococcus bovis. The sensitivity to antibiotics was studied: all Enterococcus faecium were resistant at least to one antibiotic, 15% of Enterococcus faecalis were sensitive for all antibiotics tested the other species were frequently sensitive. High level resistance to aminoglycosides were frequent in Enterococcus faecalis 40%: among these strains high level resistance to gentamicin accounts for 12% and 18 frequently associated with resistance to kanamycin and streptomycin, this situation present therapeutic problems in case of severe infection.

[Non-groupable streptococci: identification, sensitivity to antibiotics (Charles Nicolle Hospital in Tunis)]. / Les streptocoques non groupables: identification, sensibilite aux antibiotiques (Hôpital Charles Nicolle de Tunis).

50 strains of viridans streptococci isolated from human material are identified by biochemical tests (bile esculin, Cl Na 6,5%, acid production from lactose, mannitol, sorbitol, inulin, arginine, esculin and starch hydrolysis; production of levan and dextran in sucrose media) Streptococcus salivarius and Streptococcus mitis are predominant species. Susceptibility to antibiotics was studied: 70% of viridans streptococci were susceptible to all antibiotics tested, high level resistance to aminoglycoside was not present. The only resistance observed were to tetracycline, macrolides and related drugs.