Factors associated with hospital admission and adverse outcome for COVID-19: Role of social factors and medical care.

BACKGROUND: Beyond sex, age, and various comorbidities, geographical origin and socioeconomic deprivation are associated with Coronavirus Disease (COVID-19) morbidity and mortality in the general population. We aimed to assess factors associated with severe forms of COVID-19 after a hospital emergency department visit, focusing on socioeconomic factors. METHODS: Patients with laboratory-confirmed COVID-19 attending the emergency department of Béclère Hospital (France) in March-April 2020 were included. Postal addresses were used to obtain two geographical deprivation indices at the neighborhood level. Factors associated with hospitalization and factors associated with adverse outcomes, i.e. mechanical ventilation or death, were studied using logistic and Cox analyses, respectively. RESULTS: Among 399 included patients, 321 were hospitalized. Neither geographical origin nor socioeconomic deprivation was associated with any of the outcomes. Being male, older, overweight or obese, diabetic, or having a neuropsychiatric disorder were independent risk factors for hospitalization. Among 296 patients hospitalized at Béclère Hospital, 91 experienced an adverse outcome. Older age, being overweight or obese, desaturation and extent of chest CT scan lesions>25% at admission (aHR: 2.2 [95% CI: 1.3-3.5]) and higher peak CRP levels and acute kidney failure (aHR: 2.0 [1.2-3.3]) during follow-up were independently associated with adverse outcomes, whereas treatment with hydrocortisone reduced the risk of mechanical ventilation or death by half (aHR: 0.5 [0.3-0.8]). CONCLUSION: No association between geographical origin or socioeconomic deprivation and the occurrence of a severe form of COVID-19 was observed in our population after arrival to the emergency department. Empirical corticosteroid use with hydrocortisone had a strong protective impact.

Dogs L. infantum infection from an endemic region of the north of Tunisia: a prospective study.

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.

[Description of the female of Phlebotomus (Larroussius) Chadlii, Rioux, Juminer & Gibily, 1966 (Diptera: Psychodidae). From an example captured from the area of Kef (Tunisia)]. / Description de la femelle de Phlebotomus (Larroussius) Chadlii Rioux, Juminer et Gibily, 1966 (Diptera : Psychodidae). D'après un exemplaire capturé aux environs du Kef (Tunisie).

The female of Phlebotomus chadlii Rioux, Jumminer & Gibily, 1966 is described and illustrated for the first time from a specimen collected in El Kef region, northwest Tunisia. It was distinguished from P. ariasi by several characters of the spermathecae: 1) the enlarged portion of P. chadlii spermathecae duct appears smooth and better developed than that of P. ariasi; 2) in P. chadlii, this part comprises three quarters of the duct whereas, in P. ariasi, it covers only the half; 3) the spermathecae neck of P. chadlii is shorter than that of P. ariasi. The duct base is compatible with the large aedeagus size of P. chadlii male. Besides, the assignment of this female to the species P. chadlii is supported by: 1) the presence of males in the same area, over the last three years; 2) the total absence in this area of P. ariasi; 3) the concomitant presence, in the same trap station, of the described female with P. chadlii males.

Leishmania major infection in the fat sand rat Psammomys obesus in Tunisia: interaction of host and parasite populations.

The causative agent of cutaneous leishmaniasis, Leishmania major, was studied in a Tunisian population of the fat sand rat, Psammomys obesus. Seasonal changes in the abundances of parasite and host were monitored in a longitudinal field survey lasting 21 months. Overall, 566 P. obesus, collected during 10 trapping sessions between May 1995 and January 1997, were examined. Analysis of prevalence, using logistic regression, revealed that extrinsic factors, such as season and climatic conditions, and intrinsic factors, such as host age, have a combined effect. Leishmania major showed a seasonal pattern, with most transmission occurring in late summer and in autumn, when prevalences were 7.5- and 6.6-fold higher, respectively, than in spring. Prevalence peaked, at 70%, in September 1995 and then decreased to 0% in June 1996. The same temporal fluctuation was observed during the second study year, albeit among prevalences that were relatively low because of unusually dry conditions. Prevalence was highly dependent on the age of the P. obesus, and season and age acted in synergy so that the rodents were highly infected in late summer and in autumn. Prevalence was not correlated with the relative density of the P. obesus and also appeared independent of gender. Although the ear lesions observed on 378 sand rats during a 1-year survey were closely associated with Leishmania infection, such lesions were not good predictors of infection, as 35% of the rodents found to be infected had no visible lesions on their ears. The prevalences of Leishmania infection observed in this study, among P. obesus living in monospecific colonies, were generally lower than those observed in other studies of P. obesus. It seems possible that P. obesus living in monospecific colonies could have a lesser role in propagating the parasite than those living in plurispecific colonies of rodents, and act as an 'epidemiological sink'.

[Leishmania infantum MON-1: the only zymodeme isolated in canine leishmaniasis in Tunisia]. / Leishmania infantum MON-1: seul zymodème isolé chez les chiens leishmaniens en Tunisie.

Iso-enzymatic characterization of 19 Leishmania strains isolated from Tunisian dogs revealed that all correspond to Leishmania infantum MON-1. This confirms the role of dog as a reservoir of the commonest zymodeme responsible for human visceral leishmaniasis in the Mediterranean basin. However, and in spite of the high number of identifications, many zymodemes, mainly the dermotropic ones as Leishmania infantum MON-24, frequently reported in humans, had never been isolated from dogs. The study of their cultural characteristics may contribute to explain the particular iso-enzymatic profile of dogs strains.

Patterns of the tapeworm Raillietina trapezoides infection in the fat sand rat Psammomys obesus in Tunisia: season, climatic conditions, host age and crowding effects.

The tapeworm Raillietina trapezoides was studied in a Tunisian population of the fat sand rat Psammomys obesus. Seasonal changes in the abundance of parasite and host were monitored in a longitudinal field survey lasting 20 months. In total 582 intestinal samples were collected during 10 trapping sessions between May 1995 and January 1997 and examined. The impact of abiotic and biotic factors on the prevalence and parasite burden were explored, using generalized linear models. R. trapezoides showed a seasonal pattern with most transmission occurring in summer and autumn. In August-September when the rodents were at low density and most adult (90-100%) were infected. In winter, infections with R. trapezoides were highly prevalent in the cohort of adults only. The worm burden by number was also high in late summer and autumn. Prevalence and parasite burden by number or by biomass were highly age dependent. Season and age act in synergy so that the rodents were highly infected in late summer and autumn. Unusually dry conditions in winter seemed to increase prevalence and to reduce the number of worms. There was no difference between males and females in prevalence or parasite burden (by number or by biomass). Prevalence was not correlated with the relative density of the hosts whereas parasite burden depended upon their densities. The more numerous the worms were, the smaller they were individually, reflecting a crowding effect. The possibility of an immune response regulating P. obesus is discussed, in regard to the very high natural prevalence and the variation in worm burden, and compared with other parasite-host systems.

[Sero-epidemiologic profile of toxoplasmosis in northern Tunisia]. / Profil séro-épidémiologique de la toxoplasmose au nord de la Tunisie.

Toxoplasma antibodies prevalence was studied in the north of Tunisia where a mild climate prevails. Two groups of individuals were investigated: 857 living in rural area and 564 living in urb town. Sera were analysed by ELISA and indirect immunofluorescence. The overall prevalence was 58.4%. It roses from 24.5% at ten years to 52.1% at 20 years of age. A maximum level, around 70%, was reached by about 30 years. The risk of acute infection after this age seemed low as judging by the proportion of high antibodies titers observed in this group (14.2% before 30 years vs 3.7% after). A significantly higher prevalence was detected in urban residents (67% vs 52.8%). In this group, the rate of seroconversion seems the highest between ten and 20 years of age and the majority of women are infected before reaching childbearing age. In the rural area, the seropositivity is lower between ten-20 years and many women at childbearing age still susceptible to toxoplasmosis. The risk of acute infection seems higher in the youngest ones as showed by the proportion of high antibodies titers observed in the 18-30 age group (9.2%) compared to the one observed after 30 years (1.9%).

[Evaluation of two DNA probes specific for Leishmania infantum in the diagnosis of canine leishmaniasis]. / Evaluation de deux sondes ADN spécifiques de Leishmania infantum dans le diagnostic de la leishmaniose canine.

This study reports on the evaluation of two L. infantum specific DNA probes for the diagnosis of canine leishmaniasis. The probes presented very satisfying performances in terms of specificity (100%) and predictive value of the positive result (100%). However, their sensitivity (35.3%) and the clinical complexity of canine infections render their use difficult in epidemiological surveys of visceral leishmaniasis aiming at measuring the prevalence of the dog infection by L. infantum. The sensitivity of these tools has improved (66.7%) when dogs presenting patent leishmaniasis were considered. Such probes constitute appropriate tools to confirm suspected cases of leishmaniasis. Unlike the classical parasitological and serological tools, this kind of tools allows a concomitant detection and identification of the causative agent. Therefore, despite their low sensitivity, these probes can still be of importance in epidemiological investigations.

[Concordance of leishmaniasis cutaneous tests in Tunisia]. / Concordance des tests cutanés à la leishmanine en Tunisie.

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.

Investigation of the spread of human visceral leishmaniasis in central Tunisia.

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.

[Epidemiologic and parasitologic data concerning sporadic cutaneous leishmaniasis in northern Tunisia]. / Données épidémiologiques et parasitologiques concernant la leishmaniose cutanée sporadique du nord tunisien.

This study refers to 23 patients presenting with the sporadic forms of cutaneous leishmaniasis encountered in northern most humid parts of Tunisia. Culture inoculation for parasitic isolation was processed using two media: the classical NNN and a rabbit serum based medium (SLC). Cultures were positive in 17 cases with SLC medium and 13 cases with NNN medium. Eight isolates were typed using 15 isoenzymes systems. Six isolates were identified as Leishmania infantum MON-24 which confirms the crucial role of this zymodeme in causing this form of cutaneous leishmaniasis. The other two isolates were identified as Leishmania infantum MON-1, which is the principal agent of visceral leishmaniasis in the Mediterranean area.

Patterns of infection of haemoparasites in the fat sand rat, Psammomys obesus, in Tunisia, and effect on the host.

Two bacterial and one protozoan blood parasite, belonging to the genera Bartonella, Borrelia and Babesia, were studied in a Tunisian population of Psammomys obesus. Seasonal changes in the abundance of the parasites and host were monitored in a longitudinal field survey lasting 17 months. Blood samples collected during eight rodent-trapping sessions, between September 1995 and January 1997, were examined microscopically. Bartonella sp. showed a seasonal pattern, with most transmission occurring in summer and autumn; most rodents (90%) were infected in August-September, when they were at low density and adult. Borrelia sp. showed low prevalences, with few seasonal fluctuations, and Babesia sp. showed an intermediate pattern, differing from one year to another. In the cohort of adult rats, infections with Bartonella sp. and Babesia sp. were less prevalent in winter than in the previous summer. Single and mixed infections were equally prevalent in females and males, and in sexually active and inactive adults. In addition, infection had no apparent effect on the weight of adult P. obesus. The observation that the proportion of erythrocytes infected with Bartonella sp. decreased with increasing host age is probably indicative of some acquired immunity to this micro-organism. The absence of detectable infections with Borrelia sp. in old rats indicates that the prevalence and/or intensity of infection declines with host age or that infected animals die selectively. However, there was no indication that any of these parasites combined sufficient pathogenicity and abundance to have any measurable effect on the rodent population.

[Role of direct agglutination test (DAT) in the diagnosis of visceral leishmaniasis in Tunisia]. / Apport du test d'agglination directe (DAT) dans le diagnostique de la leishmaniose viscerale en Tunisie.

Direct agglutination test (DAT) is a simple ans economical technique for visceral leishmaniasis diagnosis. An evaluation, held in Tunisia with 41 confirmed visceral leishmaniasis cases and 58 negative controls, showed a sensitivity of 95.1% and a specificity of 96.5%. These results were highly correlated with those of ELISA and fluorescent antibody test. The use of DAT in our country will be very relevant, mainly in district hospitals, where others classical tests are not available. It will also be useful during sero-epidemiological studies on both human and canine visceral leishmaniasis.

Leishmania infantum species-specific kDNA probes: isolation and evaluation.

The study refers to the isolation of specific DNA probes to the parasite species Leishmania (L) infantum according to different strategies using recombinant minicircles isolated from L. infantum kinetoplast DNAs. A first probe was identified following a classical procedure. One mini-circle selected for strong reactivity to L. infantum total DNA was used to identify specific subfragments to this species among which the 95bp fragment, 3B8HaeIII-2 was selected. For the obtention of the second probe, a strategy based on sequential screenings for specificity and sensitivity was applied. This allowed identification of a set of minicircles showing an increased specificity to L. infantum as compared to other species, and an increased sensitivity of reaction as compared to the other minicircles. Subclonings and screenings allowed a final selection of a 137bp-minicircle fragment: 3E9HaeIII-12. Reactivities of the 2 probes were assessed on a panel of total DNAs and promastigotes from 74 isolates pertaining to 9 species encountered in the Old World. Parasites isolated in Tunisia from different foci, different hosts after different transmission seasons were included. Hybridizations have shown the exquisite specificity of these probes to L. infantum in this country. Probe 3E9HaeIII-12 was found to be the more sensitive where down to 10 ng of total DNA and 10(3) promastigotes could be detected. From this study and as compared to data provided in the literature, the second procedure allowed at least 10-fold increase in sensitivity.

[Confirmation of the presence of Leishmania infantum MON-80 in Tunisia]. / Confirmation de la présence de Leishmania infantum MON-80 en Tunisie.

A definitive confirmation of the presence in Tunisia of the rare zymodem MON-80 of Leishmania infantum, as a causative agent of infantile visceral leishmaniasis, is reported.

[Efficacy of intra-lesional glucantime in the treatment of zoonotic cutaneous leishmaniasis in basic health care conditions]. / Efficacité du traitement de la leishmaniose cutanée zoonotique par le glucantime en intra-lésionnel, dans les conditions des soins de santé de base.

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.

[Imported malaria in Tunisia]. / Le paludisme d'importation en Tunisie.

Thanks to the national programme of malaria eradication carried out between 1968 and 1972, there has been no active transmission of the parasitosis in Tunisia since the last indigenous case in 1979. Since 1980, with the increase in international exchanges especially with sub-Saharian countries, only imported cases of malaria have been reported in Tunisia. A retrospective and thorough survey of malaria cases diagnosed in the laboratory of parasitology of the Pasteur Institute in Tunis from 1980 to 1995 determined the epidemiological characteristics of this imported parasitosis. All in all, during the sixteen years following eradication, 245 cases were registered. The majority of cases (86.2%) was diagnosed by a systematic control of groups at risk within the national programme of malaria eradication. The remaining 13.8% cases sought medical advice when clinical symptoms appeared after their return from endemic countries. The population most affected by imported malaria were men (sex-ratio: 6.8) aged between 20 and 40 years (76% of cases); 38% were Tunisians having sojourned in an endemic country, essentially students from sub-Saharian Africa. The presumed country of contamination was African in 92.7% of the cases. Entrance into Tunisia by patients was mainly by air; 4% of the registered cases had come by land from Algeria. Sound knowledge of the epidemiological characteristics of imported malaria would make for a better follow-up of the affected population and thus reduce the probability of repeated transmission.

Immunologic determinants of disease evolution in localized cutaneous leishmaniasis due to Leishmania major.

Localized cutaneous leishmaniasis caused by Leishmania major is polymorphic in its clinical presentation and evolution. Clinical and parasitologic features and disease evolution of 112 Tunisian patients was evaluated. The expression of interleukin (IL)-4, IL-6, IL-10, IL-12 (p40), interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha mRNA was analyzed by reverse transcription-polymerase chain reaction in 73 biopsies. Cytokine mRNA expression varied individually over a wide range; TNF-alpha, IL-6, and IFN-gamma were detectable in >90% of lesions, IL-12 and IL-10 in 40% and 70%, respectively, and IL-4 in only 9%. Statistical analysis demonstrated positive association between the level of IL-12 and IFN-gamma and the presence of parasites in the lesions. Unfavorable evolution of the lesions was positively associated with high IL-10, IL-12, and IFN-gamma mRNA expression. These results indicate that an unfavorable clinical outcome was not related to an inadequate Th1 cell response and suggest that the macrophage-activating effect of IFN-gamma may be inhibited by the concomitant expression of IL-10.

[Anthropologic research and understanding pediatric visceral leishmaniasis in Tunisia]. / Contribution de la recherche anthropologique à la connaissance de la leishmaniose viscérale infantile en Tunisie.

In order to determine the social and cultural factors which delay hospitalization of children suffering from visceral leishmaniasis (VL), a study was carried out in the rural area of Kairouan (Tunisia). Qualitative techniques were used to investigate beliefs and behaviours associated with the symptoms of VL. The study has demonstrated that the folk interpretation of the disease interferes largely with the choice of the therapy. Regarding VL, the subdivision of the disease into two groups of symptoms, fever and splenomegaly, incites parents to consult doctors in the presence of fever and use traditional healers when splenomegaly appears. This is responsible for long delays before the patients can have access to official health care. This investigation clearly demonstrated that a health education programme is needed in VL endemic areas in Tunisia in order to shorten delays between the appearance of symptoms and their diagnosis. For this objective to be achieved, it would also seem necessary to implement simple serodiagnostic techniques at the periphery level.

[Validation of DNA tools in the identification of Leishmania sp. parasites in Algeria]. / Validation d'outils ADN dans l'identification de parasites Leishmania sp. en Algérie.

The present study aimed at homogenizing the use of DNA tools for Leishmania parasite characterization in two endemic countries, Algeria and Tunisia. Two genomic DNA probes, pDK10 and pDK20, previously developped in Tunisia, were here applied to a collection of 41 isolates obtained from Algerian patients having cutaneous or visceral leishmaniases. These DNA tools allowed to discriminate among and to identify causal agents of cutaneous leishmaniasis, L. infantum and L. major. Apart from the pDK20--hybridization pattern obtained usually for the species L. infantum, new hybridization patterns were identified for isolates obtained from both visceral and cutaneous leishmaniases patients. Use of DNA probes in complement to isoenzyme typing offers interesting propects for a better description of transmission cycles.