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1.
Nat Med ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816609

ABSTRACT

Accurately predicting functional outcomes for unresponsive patients with acute brain injury is a medical, scientific and ethical challenge. This prospective study assesses how a multimodal approach combining various numbers of behavioral, neuroimaging and electrophysiological markers affects the performance of outcome predictions. We analyzed data from 349 patients admitted to a tertiary neurointensive care unit between 2009 and 2021, categorizing prognoses as good, uncertain or poor, and compared these predictions with observed outcomes using the Glasgow Outcome Scale-Extended (GOS-E, levels ranging from 1 to 8, with higher levels indicating better outcomes). After excluding cases with life-sustaining therapy withdrawal to mitigate the self-fulfilling prophecy bias, our findings reveal that a good prognosis, compared with a poor or uncertain one, is associated with better one-year functional outcomes (common odds ratio (95% CI) for higher GOS-E: OR = 14.57 (5.70-40.32), P < 0.001; and 2.9 (1.56-5.45), P < 0.001, respectively). Moreover, increasing the number of assessment modalities decreased uncertainty (OR = 0.35 (0.21-0.59), P < 0.001) and improved prognostic accuracy (OR = 2.72 (1.18-6.47), P = 0.011). Our results underscore the value of multimodal assessment in refining neuroprognostic precision, thereby offering a robust foundation for clinical decision-making processes for acutely brain-injured patients. ClinicalTrials.gov registration: NCT04534777 .

2.
Rev Epidemiol Sante Publique ; 68(1): 37-43, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31874725

ABSTRACT

BACKGROUND: The relationship between thermal stress and health has been only marginally investigated in North Africa. This study aimed to estimate the short-term effect of heat on total mortality, in the city of Tunis in 2005-2007, using time series analysis. METHODS: The study period was restricted to the summer season (May-October) and heat effect was assessed using maximum temperature as exposure variable. We estimated the breakpoint above which heat-related mortality begins to increase using a segmented linear regression. A Poisson Generalized Estimating Equations (GEE) model was then used to estimate the impact of heat on daily mortality. Models were adjusted for nitrogen dioxide (NO2), trend, calendar month, day of the week, the Ramadan period, and holidays. RESULTS: The estimated breakpoint was 31.5°C (standard deviation: 0.9°C). After adjustment for potential confounders, the daily mortality increased significantly by 2.00% [95% confidence interval: 0.68-3.16] for a 1°C increase in daily maximum temperature above the breakpoint. An increase of 10mg/m3 in NO2 was associated with a significant increase in daily mortality (0.48% [0.08-0.88]). CONCLUSION: There is an important effect of heat on daily mortality in the city of Tunis. This is the first evaluation of such an association in a North African city with hot and dry summers and a lower middle economy.


Subject(s)
Environmental Exposure/adverse effects , Environmental Exposure/statistics & numerical data , Heat-Shock Response/physiology , Hot Temperature/adverse effects , Mortality , Adolescent , Adult , Aged , Aged, 80 and over , Air Pollutants/adverse effects , Air Pollution/adverse effects , Air Pollution/statistics & numerical data , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Cause of Death , Child , Child, Preschool , Cities , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Particulate Matter/adverse effects , Seasons , Time Factors , Tunisia/epidemiology , Young Adult
3.
East. Mediterr. health j ; 22(7): 459-466, 2016-07.
Article in English | WHO IRIS | ID: who-260096

ABSTRACT

The burden of influenza was estimated from surveillance data in Tunisia using epidemiological parameters of transmission with WHO classical tools and mathematical modelling. The incidence rates of influenza-associated influenza-like illness [ILI] per 100 000 were 18 735 in 2012/2013 season; 5536 in 2013/14 and 12 602 in 2014/15. The estimated proportions of influenza-associated ILI in the total outpatient load were 3.16%; 0.86% and 1.98% in the 3 seasons respectively. Distribution of influenza viruses among positive patients was: A[H3N2] 15.5%; A[H1N1] pdm2009 39.2%; and B virus 45.3% in 2014/2015 season. From the estimated numbers of symptomatic cases, we estimated that the critical proportions of the population that should be vaccinated were 15%, 4% and 10% respectively. Running the model for the different values of R0, we quantified the number of symptomatic clinical cases, the clinical attack rates, the symptomatic clinical attack rates and the number of deaths. More realistic versions of this model and improved estimates of parameters from surveillance data will strengthen the estimation of the burden of influenza


En Tunisie, la charge de la grippe a été estimée à partir des données de surveillance, en utilisant les paramètres épidémiologiques de la transmission avec les outils classiques de l'OMS et la modélisation mathématique. Les taux d'incidence des syndromes de type grippal [STG] associés à la grippe étaient 18 735 pour 100 000 pour la saison 2012-2013 ; 5 536 pour 2013-2014 et 12 602 pour 2014-2015. La part estimée de STG associés à la grippe pour la charge totale de patients externes était respectivement de 3,16%, 0,86% et 1,98% pour les trois saisons. Parmi les patients positifs au virus de la grippe, la répartition était la suivante pour la saison 2014-2015 : 15,5% pour le virus A[H3N2] ; 39,2% pour le virus A[H1N1]pdm2009 ; et 45,3% pour le virus B. A partir du nombre estimé de cas symptomatiques, nous avons calculé que la proportion critique de la population devant être vaccinée était respectivement de 15%, 4% et 10%. L'exécution du modèle avec les différentes valeurs de R0 nous a permis de déterminer le nombre de cas cliniques symptomatiques, les taux d'attaque clinique, les taux d'attaque clinique pour les cas symptomatiques et le nombre de décès. Des versions plus réalistes de ce modèle ainsi que des estimations améliorées des paramètres issus des données de surveillance permettront d'accroître l'utilité des modèles mathématiques


Subject(s)
Communicable Diseases , Influenza, Human , Seasons , Influenza A Virus, H1N1 Subtype
4.
Annu Int Conf IEEE Eng Med Biol Soc ; 2016: 3910-3913, 2016 Aug.
Article in English | MEDLINE | ID: mdl-28269140

ABSTRACT

Automatic parasite segmentation in fluorescent images is of high importance as it serves as an easier and faster tool for detecting and counting parasites in each focus. In this paper we present a hybrid segmentation for the Promastigote form of Leishmania parasites in Indirect Immunofluorescence (IIF) images, combining edge and region-based techniques through the morphological algorithm of watershed. The proposed approach deals first with a pre-processing step to correct illumination non-uniformities in the fluorescence Leishmania-infected images before performing the initial segmentation by means of the watershed algorithm. A merging step using joint region homogeneity and edge integrity criteria is then applied to improve the segmentation results. Segmentation tests of 1438 parasites from 40 collected IIF images illustrate the efficiency of our approach.


Subject(s)
Fluorescent Antibody Technique, Indirect , Leishmania/cytology , Leishmaniasis/parasitology , Algorithms , Animals , Cluster Analysis , Dogs , Fluorescent Dyes , Image Processing, Computer-Assisted , Leishmaniasis/diagnosis , Leishmaniasis/veterinary
5.
Rev Med Brux ; 36(5): 410-4, 2015.
Article in French | MEDLINE | ID: mdl-26749630

ABSTRACT

INTRODUCTION: Hospital morbidity studies allow us to draw the hospital pathological profile of a region and to follow its evolution. This study aims to describe the profile and the main trends of pediatric diseases within public structures in the region of Monastir between 2000 and 2010. MATERIEL AND METHODS: A descriptive study which concerns all pediatric hospitalizations of public structures in the region of Monastir between 2000 and 2010. Informations were collected from the regional register of hospital morbidity implanted at the Department of Preventive Medicine and Epidemiology of the University Hospital of Monastir. RESULTS: A total of 52.443 hospitalizations were collected between 2000 and 2010 with a means annual hospitalization rate of 3,9 %. The mean age was 7,2 ± 5,4 years and 15,3 % had not exceeded the first year of life. Major diagnostic categories (MDC) were dominated by diseases of the digestive and respiratory systems with 14,4 and 14 % respectively. Main chronological trends have shown that the rate of childhood asthma rise significantly from 0,2 %. in 2000 to 2,5 %. in 2010 and Hydatid Cyst whose rate increased also from 0,2 %. in 2000 to 1,8 %. in 2010 (P < 0,05). CONCLUSION: This morbidity profile incites managers to focus their efforts to improve the management of most important diseases.


Subject(s)
Hospitalization/trends , Adolescent , Asthma/epidemiology , Child , Child, Preschool , Diabetes Mellitus, Type 1/epidemiology , Echinococcosis/epidemiology , Female , Hospitalization/statistics & numerical data , Humans , Infant , Infant, Newborn , Male , Tunisia/epidemiology
6.
East. Mediterr. health j ; 21(8): 584-590, 2015.
Article in English | WHO IRIS | ID: who-255256

ABSTRACT

Data on the economic burden of rotavirus infection in Tunisia are needed to inform the decision to include rotavirus in routine childhood immunizations. This study aimed to describe the epidemiological profile of rotavirus disease in central-east Tunisia and to estimate its hospital cost.In the first stage - the prospective collection of epidemiological data - we enrolled all patients < 5 years old who were hospitalized for acute diarrhoea at 5 university paediatric departments in central-east Tunisia during the period 2009-2011. Rotavirus was responsible for 65 [23.3%] of the 279 cases enrolled. In the second stage, cost data were collected retrospectively using an activity-based costing method from the medical records of the children who were positively diagnosed with rotavirus. The average cost of care per child was TD 433 [SD 134]. This is a significant economic burden in Tunisia, where a safe and effective vaccine is available but not yet introduced to the immunization schedule


Des données sur le fardeau économique de l'infection à rotavirus en Tunisie sont nécessaires pour décider ou non d'inclure le rotavirus dans les vaccinations infantiles systématiques. La présente étude visait à décrire le profil épidémiologique de l'infection à rotavirus dans le centre-est de la Tunisie et l'estimation de son coût hospitalier. Lors de la première phase, à savoir le recueil prospectif de données épidémiologiques, nous avons recruté tous les patients de moins de cinq ans ayant été hospitalisés pour une diarrhée aiguë dans cinq services pédiatriques universitaires du centre-est de la Tunisie entre 2009 et 2011. Le rotavirus était responsable de 65 cas sur 279 recrutés [23,3 %]. Lors de la deuxième phase, des données sur les coûts ont été recueillies rétrospectivement à partir des dossiers médicaux des enfants qui étaient positifs au rotavirus, en utilisant une méthodologie de gestion des coûts par activité.Le coût moyen des soins par enfant était de 433 dinars tunisiens [ET 134]. Ce montant représente un fardeau économique important en Tunisie, où un vaccin sûr et efficace existe mais n'est pas encore intégré dans le programme de vaccination


Subject(s)
Rotavirus Infections , Gastroenteritis , Child , Retrospective Studies , Health Care Costs , Rotavirus
7.
Article in English | MEDLINE | ID: mdl-25571049

ABSTRACT

This paper describes the first steps for the automation of the serum titration process. In fact, this process requires an Indirect Immunofluorescence (IIF) diagnosis automation. We deal with the initial phase that represents the fluorescence images segmentation. Our approach consists of three principle stages: (1) a color based segmentation which aims at extracting the fluorescent foreground based on k-means clustering, (2) the segmentation of the fluorescent clustered image, and (3) a region-based feature segmentation, intended to remove the fluorescent noisy regions and to locate fluorescent parasites. We evaluated the proposed method on 40 IIF images. Experimental results show that such a method provides reliable and robust automatic segmentation of fluorescent Promastigote parasite.


Subject(s)
Fluorescent Antibody Technique, Indirect/methods , Image Processing, Computer-Assisted , Leishmaniasis/parasitology , Parasites/cytology , Algorithms , Animals , Automation , Cluster Analysis , Dogs , Fuzzy Logic
8.
Arch Inst Pasteur Tunis ; 89(1-4): 23-31, 2012.
Article in English | MEDLINE | ID: mdl-24834658

ABSTRACT

This study aimed at investigating whether the efficiency of the leishmanin skin test (LST) to evaluate the immune status of individuals exposed to Leishmania (L.) infantum is age-related. It was conducted in two districts of the governorate of Kairouan, an endemic region for L. infantum infection in Tunisia. Healthy individuals (n = 119) were selected according to two criteria: no current or past history of visceral or cutaneous leishmaniasis, and their age range: 1-6 years (group I), 7-14 years (group II), and 20-66 years old (group III). Assessments comprised LSTs, in vitro lymphoproliferative response, and interferon-gamma (IFN-gamma) productions induced by soluble leishmanial antigens (SLA). LST recorded an overall of 89.07% and 89.9% concordance with T cell proliferation and IFN-gamma production induced by SLA, respectively. Using in vitro tests as gold standards, LST was found more sensitive for screening individuals from group I (96% and 100%, considering T cell proliferation and IFN-gamma production results, respectively), than group II (91% and 97%) and group III (70% and 74%,). Conversely, LST was less specific in group I (84% and 77%) than group II (100% and 94%) and group III (100% for both in vitro tests). Our results suggested that the strength of LST resided in its higher sensitivity, to unravel asymptomatic injections and cell mediated immunity to L. infantum parasite in infants and its higher specificity for screening adult individuals. Negative LST in adults and positive LST in children < 5 years, the population at risk of developing visceral leishmaniasis, remain the weaknesses of LST and should be interpreted with caution.


Subject(s)
Leishmaniasis, Cutaneous/immunology , Skin Tests , Adolescent , Adult , Age Factors , Aged , Child , Child, Preschool , Humans , Infant , Interferon-gamma/metabolism , Lymphocyte Activation , Middle Aged , T-Lymphocytes/metabolism , Young Adult
9.
Arch Inst Pasteur Tunis ; 87(1-2): 25-33, 2010.
Article in French | MEDLINE | ID: mdl-21604458

ABSTRACT

The influence of thermal stress on health is proved. In the light of the current climate change this relationship should be extensively investigated. This study aims to describe the relationship between temperature and total mortality in the city of Tunis over a period of three years, from 2005 to 2007 using time series analysis. The form of the relation (crude and adjusted) between mortality and temperatures was investigated using Poisson generalized additive models (GAM). Confounders included in the models were pollutant, trend, calendar month, day of the week, the period of Ramadan, and holidays. The adjusted relationship between mortality and temperature was "V" shaped with a steeper slope for low temperatures than for high temperatures. The impact of heat on mortality will be further analyzed to refine our findings and to contribute to the elaboration of guidelines for preventive strategies.


Subject(s)
Climate , Mortality/trends , Temperature , Cause of Death , Humans , Time Factors , Tunisia/epidemiology , Urban Health
10.
Arch Inst Pasteur Tunis ; 85(1-4): 55-61, 2008.
Article in English | MEDLINE | ID: mdl-19469416

ABSTRACT

A follow-up study of 917 dogs was undertaken between 1994 and 1995 in the focus of visceral leishmaniasis in northern Tunisia. It permitted to assess the demography of the dog population, the importance of canine leishmaniasis (CL) and the determinants of seropositivity and mortality of dogs. Canine population was stable through time with an input of 231 dogs and an output of 218 dogs per year. The prevalence of seropositivity was 18% and 22.3% in 1994 and 1995 respectively and 90% of dogs were asymptomatic. Among 525 negative dogs in 1994 and reassessed in 1995, 78 seroconverted revealing an annual cumulative incidence of 14.74%. On the other hand, 23.47% (27/115) of seropositive dogs became negative in 1995. Age, presence of symptoms and density of dogs were independently associated with CL seropositivity. These results demonstrate the difficulty of control strategies of visceral leishmaniasis targeting the dog population.


Subject(s)
Dog Diseases/epidemiology , Endemic Diseases/statistics & numerical data , Leishmania infantum , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/veterinary , Animals , Antibodies, Protozoan/blood , Disease Reservoirs/parasitology , Disease Reservoirs/statistics & numerical data , Disease Reservoirs/veterinary , Dog Diseases/immunology , Dog Diseases/parasitology , Dogs , Enzyme-Linked Immunosorbent Assay , Female , Fluorescent Antibody Technique, Indirect , Follow-Up Studies , Incidence , Leishmania infantum/immunology , Leishmaniasis, Visceral/immunology , Leishmaniasis, Visceral/parasitology , Logistic Models , Male , Population Surveillance , Prospective Studies , Risk Factors , Seroepidemiologic Studies , Tunisia/epidemiology
11.
Arch Inst Pasteur Tunis ; 84(1-4): 21-7, 2007.
Article in English | MEDLINE | ID: mdl-19388580

ABSTRACT

A matched case-control study was undertaken in 2004 in Béja, north-western Tunisia, to evaluate potential risk factors for hepatitis C infection. Cases were anti-HCV positive subjects screened in 1996 serosurvey. HCV seronegative controls (5 per case) were selected in the proximity of cases and matched for age and gender. A standardized questionnaire was used to collect demographic, socioeconomic, social behavior, medical and surgical history information. Matched odds ratios (OR) and adjusted OR (AOR) and their 95% CI were calculated in multivariate analysis using logistic regression. 57 HCV positive cases (mean age 61.63 +/- 14,84; 68.4 % female) and 285 HCV negative controls (mean age 60.95 +/- 14.66; 68.4 % female) were enrolled. Multivariate analysis revealed that intravenous drug injections (AOR=1.96; 95%CI[1.02-3.8] p=0.045), past history of invasive procedures (AOR=2.53; 95%CI[1.21-5.29] p=0.0014) and medical history of hypertension (AOR=2.31; 95%CI [1.17-4.56]p=0.015) were significantly associated to HCV infection. These results suggest that nosocomial transmission of HCV infection in north-west Tunisia is common.


Subject(s)
Endemic Diseases/statistics & numerical data , Hepatitis C/epidemiology , Hepatitis C/etiology , Risk Assessment , Age Distribution , Case-Control Studies , Cross Infection/epidemiology , Female , Hepatitis C/transmission , Humans , Hypertension/complications , Logistic Models , Male , Mass Screening , Multivariate Analysis , Population Surveillance , Risk Factors , Seroepidemiologic Studies , Sex Distribution , Socioeconomic Factors , Substance Abuse, Intravenous/complications , Surveys and Questionnaires , Tunisia/epidemiology
12.
J Virol Methods ; 114(2): 151-8, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14625050

ABSTRACT

Matching serum and oral fluid (saliva) samples were collected from 369 subjects in Tunisia in 2002, from a city in the north and a rural district in the south. Rubella-specific IgG was detected in sera by commercial ELISA (Dade Behring) and in matching oral fluids by two methods, a previously described IgG-capture ELISA (GACELISA) [J. Clin. Microbiol. 37 (1999) 391] and the Dade Behring ELISA with the assay protocol modified for use with oral fluids. Total IgG concentration of oral fluids was also measured. Rubella-specific IgG was detected in 289 (78.3%) sera overall. Differences in the age distribution of the study population in the north and south led to a higher prevalence being found in the north (86.2%) than in the south (71.8%). This difference was reflected in the oral fluid rubella-specific IgG results. With GACELISA, rubella-specific IgG was detected in 79.4% of oral fluids from the north and 69.7% from the south and with the modified Dade Behring assay, in 81.4% of oral fluids from the north and in 64.9% from the south. The sensitivity and specificity of GACELISA in comparison to results from the matching sera were 92.4 and 93.2%, respectively. The sensitivity and specificity of the modified Dade Behring ELISA were 89.8 and 92.0%, respectively. Total IgG concentration in oral fluid showed a weak correlation (r=0.19) with the modified Dade Behring results and with samples where total IgG was >7.5 mg/l, the sensitivity and specificity were 94.4 and 90.0%, respectively. Twenty-nine oral fluids, which gave false negative rubella-specific IgG results with the modified Dade Behring ELISA, had a lower mean total IgG concentration than 256 oral fluids which gave concordant positive results (7.0mg/l versus 15.8 mg/l, P<0.001). The study validated the modified Dade Behring ELISA, providing an alternative to the GACELISA for assessing levels of rubella immunity for population studies using oral fluid samples.


Subject(s)
Antibodies, Viral/analysis , Immunoglobulin G/analysis , Rubella virus/immunology , Rubella/epidemiology , Saliva/immunology , Adolescent , Adult , Age Distribution , Antibodies, Viral/blood , Antibody Specificity , Child , Child, Preschool , Female , Humans , Immunoglobulin G/blood , Infant , Infant, Newborn , Male , Middle Aged , Reagent Kits, Diagnostic , Sensitivity and Specificity , Seroepidemiologic Studies , Tunisia/epidemiology
13.
Arch Inst Pasteur Tunis ; 80(1-4): 17-27, 2003.
Article in French | MEDLINE | ID: mdl-15941064

ABSTRACT

This work aims to estimate prevalence and evaluate risk factors of leishmanin-skin test positivity. A cross-sectional leishmanin skin test study was carried out on a sample of 3190 healthy volunteers living in the gouvernorates of Kairouan and Kasserine. Age standardized prevalence of leishmanin-skin test positivity was 45.9% (CI95% = [43.9-47.9]) confirming the hyper endemicity of this region. The rate of leishmanin-skin test positivity ranged from 75.9% (CI95% = [71.9-79.5]) in Zaghdoud (Kairouan) to 6.5% (CI95% = [3.7-11.01) in Abdeladhim (Kasserine). There is no significant difference between men and women suggesting a similar exposure to infection. In the districts of Zaghdoud, Sidi Amor, El Hajeb and chbika, age specific rates showed a rapid increasing positive prevalence with age reaching a proportion exceeding 80% after the age of 15 years. However, the age specific prevalence from other delegations showed a progressive increasing trend with age, with a low rate for younger children and a plateau of 75% after 45 years. Multivariate analysis of leishmanin-skin test positivity risk factors showed that only district and age are determinants of this infection.


Subject(s)
Antigens, Protozoan , Leishmania infantum/immunology , Leishmaniasis, Visceral , Skin Tests , Adolescent , Adult , Age Distribution , Age Factors , Animals , Child , Child, Preschool , Cross-Sectional Studies , Endemic Diseases , Female , Humans , Infant , Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/immunology , Leishmaniasis, Visceral/transmission , Male , Middle Aged , Multivariate Analysis , Population Surveillance , Prevalence , Residence Characteristics/statistics & numerical data , Risk Factors , Sex Distribution , Skin Tests/methods , Socioeconomic Factors , Surveys and Questionnaires , Tunisia/epidemiology
14.
Biochimie ; 83(6): 463-9, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11506890

ABSTRACT

Rhizopus oryzae lipase (ROL) was found to be a true lipase. This enzyme presents the interfacial activation phenomenon. The N-terminal amino acid sequence of ROL was compared to those of rhizopus lipases. Purified ROL possesses the same N-terminal sequence as the mature Rhizopus niveus lipase (RNL). This sequence was found in the last 28 amino acids of the propeptide sequence derived from the cDNA of Rhizopus delemar lipase (RDL). Using the baro-stat method, we have measured the hydrolysis rate of dicaprin films by ROL as a function of surface pressure. Our results show that Rhizopus oryzae lipase is markedly stereoselective of the sn-3 position of the 2,3 enantiomer of dicaprin. Polyclonal antibodies (PAB) directed against ROL have been produced and purified by immunoaffinity. The effects of these PAB on the interfacial behavior of ROL were determined. The immunoblot analysis with polyclonal antibodies anti-ROL (PAB anti-ROL) and various lipases shows a cross-immunoreactivity between the lipase from the rhizopus family (Rhizopus delemar lipase and Rhizopus arrhizus lipase).


Subject(s)
Diglycerides/metabolism , Lipase/chemistry , Lipase/metabolism , Rhizopus/enzymology , Amino Acid Sequence , Antibodies/immunology , Antibodies/pharmacology , Atmospheric Pressure , Cross Reactions , Diglycerides/chemistry , Hydrolysis , Immunoblotting , Isoelectric Focusing , Isoelectric Point , Kinetics , Lipase/immunology , Molecular Sequence Data , Stereoisomerism , Substrate Specificity
15.
Infect Immun ; 69(8): 4906-15, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11447167

ABSTRACT

Virulence variability was investigated by analyzing the experimental pathogenicity of 19 Leishmania major strains in susceptible BALB/c mice. Twelve strains were isolated from Tunisian patients with zoonotic cutaneous leishmaniasis; seven strains were isolated in Syria (n = 1), Saudi Arabia (n = 2), Jordan (n = 2), or Israel (n = 2). BALB/c mice were injected in the hind footpad with 2 x 10(6) amastigotes of the various isolates, and lesion progression was recorded weekly for 9 weeks. Interleukin-4 (IL-4) and gamma interferon (IFN-gamma) production of lymph node mononuclear cells activated in vitro with parasite antigens were evaluated 5 weeks after infection. We show that disease progression induced by different L. major isolates was largely heterogeneous although reproducible results were obtained when using the same isolate. Interestingly, isolates from the Middle East induced a more severe disease than did the majority of Tunisian isolates. Strains with the highest virulence tend to generate more IL-4 and less IFN-gamma in vitro at week 5 postinfection as well as higher levels of early IL-4 mRNA in the lymph node draining the inoculation site at 16 h postinfection. These results suggest that L. major isolates from the field may differ in virulence, which influences the course of the disease induced in mice and the type of immune response elicited by the infected host.


Subject(s)
Genetic Heterogeneity , Leishmania major/pathogenicity , Leishmaniasis, Cutaneous/parasitology , Adult , Animals , Antigens, Protozoan/genetics , Bone Marrow Cells/parasitology , Cells, Cultured , Disease Models, Animal , Humans , Interferon-gamma/biosynthesis , Interleukin-4/biosynthesis , Leishmania major/genetics , Leishmania major/immunology , Leishmania major/isolation & purification , Leishmaniasis, Cutaneous/immunology , Macrophages/parasitology , Mice , Mice, Inbred BALB C , Protozoan Proteins/genetics , RNA, Messenger , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Virulence/genetics
16.
Hum Immunol ; 62(5): 509-17, 2001 May.
Article in English | MEDLINE | ID: mdl-11334675

ABSTRACT

HLA-DRB1, -DQB1, TNFalpha, TNFbeta, HSP70-2 and HSP70-hom genetic polymorphisms were analyzed in 156 unrelated patients who developed mediterranean visceral leishmaniasis (MVL) due to Leishmania infantum, and 154 unrelated healthy controls, who have got asymptomatic infection with this parasite and were selected on the basis of a positive leishmanin skin test (LST). A significantly reduced frequency of HLA-DR2 was observed among MVL patients (16.1%), compared with controls (26.3%) (relative risk = 0.54; p = 0.04). HLA-DR2/DR13 as well as HLA-DQB1*0201/- genotype frequencies were significantly lower in patients vs controls (relapse rate = 0.17 and 0.46, respectively; p < 0.05). However, using Bonferroni correction, none of these associations remained significant. No association was found, between either the -308 base pair TNFalpha gene polymorphism or the NcoI polymorphism in the first intron of the TNFbeta gene and susceptibility to MVL. Analysis of PstI and NcoI polymorphisms in the coding region of HSP70-2 and HSP70-hom genes, respectively, revealed a significantly higher frequency of homozygotes for the HSP70-2/PstI negative allele, among patients (21.8%) vs controls (12.6%) (relapse rate = 1.94; p = 0.04). Again, this result was not significant after using Bonferroni correction. These results do not support association between susceptibility to MVL and the MHC class II and class III loci analyzed in this study.


Subject(s)
HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , HSP70 Heat-Shock Proteins/genetics , Leishmania infantum , Leishmaniasis, Visceral/genetics , Lymphotoxin-alpha/genetics , Polymorphism, Genetic , Tumor Necrosis Factor-alpha/genetics , Animals , Child, Preschool , Genetic Predisposition to Disease/genetics , HLA-DQ beta-Chains , HLA-DRB1 Chains , Haplotypes , Humans , Infant , Infant, Newborn , Leishmaniasis, Visceral/immunology , Mediterranean Region
17.
Arch Inst Pasteur Tunis ; 78(1-4): 11-6, 2001.
Article in French | MEDLINE | ID: mdl-14658234

ABSTRACT

A cross sectional study aimed to evaluate the effect of antigenic preparation (Leishmania infantum versus Leishmania major) and dose of leishmania antigens (5 x 10(6) versus 2.5 x 10(6) parasites in the same volume) on the reproducibility of delayed type hypersensitivity leishmania skin test. Results showed that among 34 individuals involved from visceral leishmaniasis endemic area. 26 (76.5%) had a positif Leishmania infantum leishmania (L-L. infantum) test and 27 (79.4%) to Leishmania major leishmania (L-L. major). Mean size of cutaneous reaction was 5.94 +/- 2.86 mm for L-L. infantum and 5.41 +/- 3.23 mm for L-L. major, with a significant positive linear association (p < 10-3). Intra-class correlation coefficient was 0.80 (CI95% = [0.64-0.93]) and concordance Kappa (kappa) was 0.57 (CI95% = [0.40-0.74]). Among 153 individuals from zoonotic cutaneous leishmaniasis. 92.9% revealed a positive test for both types of leishmanin (L-L. major full dose versus L-L. major half dose). Mean size of cutaneous reaction was 12.61 +/- 4.65 mm for the reference test and 11.30 +/- 3.95 mm for diluted one, with a positive linear association (p < 10-3). Intra-class correlation coefficient was 0.78 (IC95% = [0.71-0.84]) and concordance Kappa (kappa) was 0.82 (IC95% = [0.73-0.91]). These results demonstrate a limited effect of leishmania antigenic variation and antigen dose on the reproducibility of delayed type hypersensitivity induced by the leishmanin test.


Subject(s)
Antigens, Protozoan , Leishmania infantum/immunology , Leishmania major/immunology , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Visceral/diagnosis , Skin Tests/methods , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Antigenic Variation/genetics , Antigens, Protozoan/genetics , Child , Child, Preschool , Cross-Sectional Studies , Endemic Diseases/statistics & numerical data , Female , Humans , Hypersensitivity, Delayed/etiology , Leishmaniasis, Cutaneous/epidemiology , Leishmaniasis, Cutaneous/parasitology , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/parasitology , Linear Models , Male , Middle Aged , Sensitivity and Specificity , Skin Tests/standards , Statistics, Nonparametric , Tunisia/epidemiology , Zoonoses/epidemiology , Zoonoses/parasitology
18.
Trans R Soc Trop Med Hyg ; 94(4): 382-6, 2000.
Article in English | MEDLINE | ID: mdl-11127239

ABSTRACT

The epidemiology, clinical patterns, and spatial spread of Mediterranean visceral leishmaniasis were retrospectively studied in central Tunisia. The clinical profile of the disease was typical of the Mediterranean infantile form. Malnutrition and associated infectious diseases were observed in 62.5% and 55% of cases, respectively. The case-fatality rate was 6.2% and resistance to meglumine antimonate was observed in 1.6% of patients. The annual incidence of cases increased from approximately 10 cases per year before 1991 to approximately 50 cases per year between 1992 and 1994. The cumulative incidence was 133.7/100,000 among children aged < 15 years. This increase was preceded by 3 years of high mean annual rainfall in the region. The spatial distribution of the incidence of the infection through time showed an aggregation of cases in the northern part of the area where intensive agriculture projects took place during the last 10 years, leading to the establishment of a stable Leishmania infantum transmission cycle below the Atlas mountain chains, and an evident tendency to a progressive extension to the south.


Subject(s)
Leishmaniasis, Visceral/epidemiology , Meglumine/therapeutic use , Adolescent , Child , Child, Preschool , Drug Resistance , Female , Humans , Incidence , Infant , Infant, Newborn , Leishmaniasis, Visceral/drug therapy , Leishmaniasis, Visceral/transmission , Male , Retrospective Studies , Tunisia/epidemiology
19.
Clin Exp Immunol ; 116(1): 127-32, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10209516

ABSTRACT

Resistance to Leishmania parasite infection requires the development of a cellular immune response that activates macrophage leishmanicidal activity. In this study we have investigated the lymphoproliferative responses and in vitro cytokine production of peripheral blood mononuclear cells (PBMC) from individuals living in an endemic area for L. major infection in Tunisia. The results were compared with the DTH reaction of the leishmanin skin test (LST). Sixty-seven individuals were included in the study: 22 persons (age range 9-60 years) who developed, 2 years before the present study, a parasitologically confirmed localized cutaneous leishmaniasis (LCL) that healed spontaneously, and 45 individuals (age range 18-20 years) born and living in the same area, with no previous history of LCL. LST was positive (skin induration > or = 5 mm) in 20/22 cured cases of LCL and in 75% of healthy individuals without history of LCL. LST+ individuals expressed vigorous Leishmania-specific lymphoproliferative responses associated with in vitro production of interferon-gamma (IFN-gamma) but not IL-4. Interestingly, IL-10 was detected in parallel with the highest levels of IFN-gamma in PBMC supernatants from 3/20 cured LCL and 8/25 individuals without history of LCL. Our results showed a 98% concordance between the DTH reaction assessed by LST and the in vitro proliferative assay induced by soluble leishmanial antigens. Moreover, proliferative assays as well as cytokine analysis did not show any significant difference of the immune memory to parasite antigens developed by patients who had overt cutaneous leishmaniasis and those who had apparently asymptomatic infection.


Subject(s)
Antigens, Protozoan/immunology , Cytokines/metabolism , Hypersensitivity, Delayed , Leishmaniasis, Cutaneous/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Animals , Child , Humans , Interferon-gamma/metabolism , Interleukin-10/metabolism , Interleukin-4/metabolism , Leishmaniasis, Cutaneous/epidemiology , Lymphocyte Activation , Middle Aged , Skin Tests , Tunisia/epidemiology
20.
Arch Inst Pasteur Tunis ; 76(1-4): 13-8, 1999.
Article in French | MEDLINE | ID: mdl-14666752

ABSTRACT

A randomized placebo-controlled trial treating cutaneous lesions due to Leishmania major with intralesionnel glucantime, was conducted in El Guettar between december 1994 and June 1995, in order to assess efficacy of this therapy under field conditions. It included 109 patients: 52 were administrated glucantime and 57 received local treatment (eosin 5% and alcohol 95%). Prognostic factors were similar in both groups. Results did not reveal a significant difference between glucantime and eosin regarding the rapidity of the healing of lesions. However, scars seem to be of better quality among the glucantime group. Bacterial super infection was noticed among 57.6% of humid lesions sampled among 33 patients. Isolated strains included group A streptococcus (22%), staphylococcus aureus (16.7%) or an association of both agents (61.1%). Resistance profile indicated that streptococcus and staphylococcus respond well to macrolids compared to other antibiotic groups.


Subject(s)
Antiprotozoal Agents/administration & dosage , Leishmania major , Leishmaniasis, Cutaneous/drug therapy , Meglumine/administration & dosage , Organometallic Compounds/administration & dosage , Zoonoses , Animals , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial , Eosine Yellowish-(YS)/administration & dosage , Female , Humans , Injections, Intralesional , Leishmaniasis, Cutaneous/complications , Leishmaniasis, Cutaneous/parasitology , Male , Meglumine Antimoniate , Primary Health Care , Prognosis , Single-Blind Method , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcal Infections/parasitology , Streptococcal Infections/drug therapy , Streptococcal Infections/microbiology , Streptococcal Infections/parasitology , Streptococcus pyogenes , Superinfection/drug therapy , Superinfection/microbiology , Superinfection/parasitology , Treatment Outcome , Tunisia , Zoonoses/parasitology
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