Publications by authors named "Mohamed Ali Ben Hadj Kacem"

9 Publications

  • Page 1 of 1

Evaluation of the influenza-like illness surveillance system in Tunisia, 2012-2015.

BMC Public Health 2019 Jun 6;19(1):694. Epub 2019 Jun 6.

Laboratory of Transmission, Control and Immunobiology of Infections (LR11IPT02), Institut Pasteur de Tunis, 13, Place Pasteur, BP 74, 1002, Tunis-Belvédère, Tunisia.

Background: This study was initiated to evaluate, for the first time, the performance and quality of the influenza-like illness (ILI) surveillance system in Tunisia.

Methods: The evaluation covered the period of 2012-2015 and used different data sources to measure indicators related to data quality and completeness, representativeness, timeliness, simplicity, acceptability, flexibility, stability and utility.

Results: During the evaluation period, 485.221 ILI cases were reported among 6.386.621 outpatients at 268 ILI sentinel sites. To conserve resources, cases were only enrolled and tested for influenza during times when the number of patients meeting the ILI case definition exceeded 7% (10% after 2014) of the total number of outpatients for the week. When this benchmark was met, five to 10 patients were enrolled and sampled by nasopharyngeal swabs the following week. In total, The National Influenza Center (NIC) received 2476 samples, of which 683 (27.6%) were positive for influenza. The greatest strength of the system was its representativeness and flexibility. The timeliness of the data and the acceptability of the surveillance system performed moderately well; however, the utility of the data and the stability and simplicity of the surveillance system need improvement. Overall, the performance of the Tunisian influenza surveillance system was evaluated as performing moderately well for situational awareness in the country and for collecting representative influenza virologic samples.

Conclusions: The influenza surveillance system in Tunisia provided pertinent evidence for public health interventions related to influenza situational awareness. To better monitor influenza, we propose that ILI surveillance should be limited to sites that are currently performing well and the quality of data collected should be closely monitored and improved.
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http://dx.doi.org/10.1186/s12889-019-7035-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555026PMC
June 2019

Genetic Diversity of HIV-1 in Tunisia.

AIDS Res Hum Retroviruses 2017 01 19;33(1):77-81. Epub 2016 Sep 19.

1 Unit Virology, Microbiology Laboratory, Charles Nicolle University Hospital , Tunis, Tunisia .

In this study, the genetic diversity of HIV-1 in Tunisia was analyzed. For this, 193 samples were collected in different regions of Tunisia between 2012 and 2015. A protease and reverse transcriptase fragment were amplified and sequenced. Phylogenetic analyses were performed through maximum likelihood and recombination was analyzed by bootscanning. Six HIV-1 subtypes (B, A1, G, D, C, and F2), 5 circulating recombinant forms (CRF02_AG, CRF25_cpx, CRF43_02G, CRF06_cpx, and CRF19_cpx), and 11 unique recombinant forms were identified. Subtype B (46.4%) and CRF02_AG (39.4%) were the predominant genetic forms. A group of 44 CRF02_AG sequences formed a distinct Tunisian cluster, which also included four viruses from western Europe. Nine viruses were closely related to isolates collected in other African or in European countries. In conclusion, a high HIV-1 genetic diversity is observed in Tunisia and the local spread of CRF02_AG is first documented in this country.
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http://dx.doi.org/10.1089/AID.2016.0164DOI Listing
January 2017

Loss and gain of N-linked glycosylation sites in globular head and stem of HA found in A/H3N2 flu fatal and severe cases during 2013 Tunisia flu seasonal survey.

Virus Genes 2014 Feb 31;48(1):189-92. Epub 2013 Oct 31.

National Influenza Centre-Tunis, Microbiology Laboratory, Charles Nicolle's Hospital, Bvd 9 avril, Tunis, Tunisia,

Glycosylation on the globular head of the hemagglutinin (HA) protein of influenza virus acts as an important target for recognition and destruction of virus by innate immune proteins of the collectin family. In the current study, we have characterized the dynamic amino acid changes at N-linked glycosylation sites of full length sequences of HA genes of 5 A/H3N2 Tunisian strains isolates from mild, severe, and fatal cases. Compared to the reference strain, A/Perth/16/2009 substitutions in potential N-glycosylation sites were observed in 5 HA genes at five different positions (45, 124, 128, 144, and 145) generating the losses and gains of N-linked glycosylation sites. Also the mutation N145S was presented in the receptor-binding site of all segments analyzed. Point mutations in several positions in the gene encoding the H3 of Tunisian strains were shown to ablate a glycan attachment site and also loss of a potential glycosylation site. The relation between these mutations and virulence of influenza A/H3N2 virus needed to be verified in the further experiments.
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http://dx.doi.org/10.1007/s11262-013-0993-0DOI Listing
February 2014

Virological Surveillance of Influenza Viruses during the 2008-09, 2009-10 and 2010-11 Seasons in Tunisia.

PLoS One 2013 19;8(9):e74064. Epub 2013 Sep 19.

Unit Virology, Microbiology Laboratory, National Influenza Centre, Charles Nicolle's Hospital, Tunis, Tunisia.

Background: The data contribute to a better understanding of the circulation of influenza viruses especially in North-Africa.

Objective: The objective of this surveillance was to detect severe influenza cases, identify their epidemiological and virological characteristics and assess their impact on the healthcare system.

Method: We describe in this report the findings of laboratory-based surveillance of human cases of influenza virus and other respiratory viruses' infection during three seasons in Tunisia.

Results: The 2008-09 winter influenza season is underway in Tunisia, with co-circulation of influenza A/H3N2 (56.25%), influenza A(H1N1) (32.5%), and a few sporadic influenza B viruses (11.25%). In 2010-11 season the circulating strains are predominantly the 2009 pandemic influenza A(H1N1)pdm09 (70%) and influenza B viruses (22%). And sporadic viruses were sub-typed as A/H3N2 and unsubtyped influenza A, 5% and 3%, respectively. Unlike other countries, highest prevalence of influenza B virus Yamagata-like lineage has been reported in Tunisia (76%) localised into the clade B/Bangladesh/3333/2007. In the pandemic year, influenza A(H1N1)pdm09 predominated over other influenza viruses (95%). Amino acid changes D222G and D222E were detected in the HA gene of A(H1N1)pdm09 virus in two severe cases, one fatal case and one mild case out of 50 influenza A(H1N1)pdm09 viruses studied. The most frequently reported respiratory virus other than influenza in three seasons was RSV (45.29%).

Conclusion: This article summarises the surveillance and epidemiology of influenza viruses and other respiratory viruses, showing how rapid improvements in influenza surveillance were feasible by connecting the existing structure in the health care system for patient records to electronic surveillance system for reporting ILI cases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0074064PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777972PMC
May 2014

Frequency of D222G haemagglutinin mutant of pandemic (H1N1) pdm09 influenza virus in Tunisia between 2009 and 2011.

Diagn Pathol 2013 Jul 31;8:124. Epub 2013 Jul 31.

National Influenza Centre-Tunis, Unit Virology, Microbiology Laboratory, Charles Nicolle’s Hospital, Tunis, Tunisia.

Background: The novel pandemic A (H1N1) pdm09 virus was first identified in Mexico in April 2009 and since then it spread worldwide over a short period of time. Although the virus infection is generally associated with mild disease and a relatively low mortality, it is projected that mutations in specific regions of the viral genome, especially within the receptor binding domain of the haemagglutinin (HA) protein could result in more virulent virus stains, leading to a more severe pathogenicity.

Methods: To monitor the genetic polymorphisms at position 222 of Haemagglutinin of influenza A(H1N1)pdm09 viruses from both outpatients with mild influenza and individuals with severe disease requiring hospitalization, during 2009-2010 and 2010-2011 seasons, a sequence-based genotypic assessment of viral populations to understand the prevalence of D222G mutation.

Results: The D222G was identified in clinical specimens from 3 out of 42 cases analyzed in Tunisia with severe outcome (7%). Interestingly, in one fatal case out of four viruses taken from fatal cases studied (25%). Also this mutation was found in one mild case out of 8 mild cases studied (0.1%). D222E substitution was found in virus taken from one patient with severe clinical syndrome (2%) out of 42 severe cases analyzed and E374K substitution was found in two severe cases (4%) out of 42 severe cases studied.

Conclusions: A specific mutation in the viral haemagglutinin (D222G) was found in fatal, severe and mild case. Further virological, clinical and epidemiological investigations are needed to ascertain the role of this and other mutations that may alter the virulence and transmissibility of the pandemic influenza A (H1N1)pdm09.

Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1027334947811255.
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http://dx.doi.org/10.1186/1746-1596-8-124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751102PMC
July 2013

Genetic diversity of HA1 domain of heammaglutinin gene of influenza A(H1N1)pdm09 in Tunisia.

Virol J 2013 May 16;10:150. Epub 2013 May 16.

National Influenza Centre-Tunis, Unit Virology, Microbiology Laboratory, Charles Nicolle's Hospital, Tunis, Tunisia.

We present major results concerning isolation and determination of the nucleotide sequence of hemagglutinin (HA1) of the pandemic (H1N1)pdm09 influenza viruses found in Tunisia. Amino acid analysis revealed minor amino acid changes in the antigenic or receptor-binding domains. We found mutations that were also present in 1918 pandemic virus, which includes S183P in 4 and S185T mutation in 19 of 27 viruses analyzed from 2011, while none of the 2009 viruses carried these mutations. Also two specific amino acid differences into N-glycosylation sites (N288T and N276H) were detected. The phylogenetic analysis revealed that the majority of the Tunisian isolates clustered with clade A/St. Petersburg/27/2011 viruses characterized by D97N and S185T mutations. However it also reveals a trend of 2010 strains to accumulate amino acid variation and form new phylogenetic clade with three specific amino acid substitutions: V47I, E172K and K308E.
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http://dx.doi.org/10.1186/1743-422X-10-150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663686PMC
May 2013

HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naïve and first-line treatment failures in Djiboutian patients.

Diagn Pathol 2012 Oct 8;7:138. Epub 2012 Oct 8.

Laboratoire de la Caisse Nationale de Sécurité Sociale, Djibouti, Republic of Djibouti.

Unlabelled: In this study we report the prevalence of antiretroviral drug resistant HIV-1 genotypes of virus isolated from Djiboutian patients who failed first-line antiretroviral therapy (ART) and from ART naïve patients.

Patients And Methods: A total of 35 blood samples from 16 patients who showed first-line ART failure (>1000 viral genome copies/ml) and 19 ART-naïve patients were collected in Djibouti from October 2009 to December 2009. Both the protease (PR) and reverse transcriptase (RT) genes were amplified and sequenced using National Agency for AIDS Research (ANRS) protocols. The Stanford HIV database algorithm was used for interpretation of resistance data and genotyping.

Results: Among the 16 patients with first-line ART failure, nine (56.2%) showed reverse transcriptase inhibitor-resistant HIV-1 strains: two (12.5%) were resistant to nucleoside (NRTI), one (6.25%) to non-nucleoside (NNRTI) reverse transcriptase inhibitors, and six (37.5%) to both. Analysis of the DNA sequencing data indicated that the most common mutations conferring drug resistance were M184V (38%) for NRTI and K103N (25%) for NNRTI. Only NRTI primary mutations K101Q, K103N and the PI minor mutation L10V were found in ART naïve individuals. No protease inhibitor resistant strains were detected. In our study, we found no detectable resistance in ∼ 44% of all patients who experienced therapeutic failure which was explained by low compliance, co-infection with tuberculosis and malnutrition. Genotyping revealed that 65.7% of samples were infected with subtype C, 20% with CRF02_AG, 8.5% with B, 2.9% with CRF02_AG/C and 2.9% with K/C.

Conclusion: The results of this first study about drug resistance mutations in first-line ART failures show the importance of performing drug resistance mutation test which guides the choice of a second-line regimen. This will improve the management of HIV-infected Djiboutian patients.

Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2051206212753973.
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http://dx.doi.org/10.1186/1746-1596-7-138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488517PMC
October 2012

Haemagglutinin D222G mutation found in a fatal case of pandemic (H1N1) flu in Tunisia.

Arch Virol 2012 Sep 9;157(9):1813-4. Epub 2012 Jun 9.

Unit Virology, Microbiology Laboratory, Charles Nicolle's Hospital, National Influenza Centre-Tunis, Tunis, Tunisia.

Recently, the D222G substitution was observed in the HA of pandemic (H1N1) 2009 viruses isolated from fatal cases in several countries. We made a similar observation in one fatal case in Tunisia showing a D222G substitution in a virus isolate. The man was 47 years old and had no other subjacent pathologies or any known risk factors. He died after three days, suffering from severe respiratory symptoms of flu. The causal link of the D222G substitution in Tunisia with virulence must be verified. Further study is warranted to elucidate the intriguing relationship between the D222G substitution and severe disease. Constant molecular surveillance is important to monitor the pathogenicity of circulating strains and evaluate vaccine efficacy.
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http://dx.doi.org/10.1007/s00705-012-1349-0DOI Listing
September 2012

[Analysis of antibiotics as a curative measure in four hospital units].

Tunis Med 2006 Sep;84(9):556-62

Département de médecine préventive et sociale, Faculté de Médecine de Tunis.

In order to analyse the methods of curative prescription of antibiotics in four units of hospitalization of the hospital Charles Nicolle of Tunis, a descriptive study of prescriptions was carried out during the first five months of year 2001. On the whole, 165 prescriptions delivered to patients were included in the study. The average age of the patients was 44 years, the sex ratio of 1.45 and the average duration of 15.1 days. Approximately two thirds of the initially probabilist prescriptions were not documented secondarily. Those secondarily documented (n = 51) were essentially related to nosocomial pneumonias and septicaemias (29 and 10 prescriptions). The two germs most frequently isolated during nosocomial pneumonias were Acinetobacter baumannii and, Pseudomonas aeruginosa (17 and 8 strains). Only imipenem, netilmicin and colistin remain active on A. baumannii. The bitherapy was the most used treatment (87.5%). It was generally an association beta-lactamin-aminosid (52.9%). The average cost of a documented prescription varied from 943,6 to 1184,9 TD (Tunisian Dinars) according as the prescription were secondarily documented or not.
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September 2006