268 research outputs found
Frequency of Drug Resistance Gene Amplification in Clinical Leishmania Strains
Experimental studies about Leishmania resistance to metal and antifolates have pointed out that gene amplification is one of the main mechanisms of drug detoxification. Amplified genes code for adenosine triphosphate-dependent transporters (multidrug resistance and P-glycoproteins P), enzymes involved in trypanothione pathway, particularly gamma glutamyl cysteine synthase, and others involved in folates metabolism, such as dihydrofolate reductase and pterine reductase. The aim of this study was to detect and quantify the amplification of these genes in clinical strains of visceral leishmaniasis agents: Leishmania infantum, L. donovani, and L. archibaldi. Relative quantification experiments by means of real-time polymerase chain reaction showed that multidrug resistance gene amplification is the more frequent event. For P-glycoproteins P and dihydrofolate reductase genes, level of amplification was comparable to the level observed after in vitro selection of resistant clones. Gene amplification is therefore a common phenomenon in wild strains concurring to Leishmania genomic plasticity. This finding, which corroborates results of experimental studies, supports a better understanding of metal resistance selection and spreading in endemic areas
Trichinella pseudospiralis outbreak in France.
Four persons became ill with trichinellosis after eating meat from a wild boar hunted in Camargue, France. Nonencapsulated larvae of Trichinella pseudospiralis were detected in meat and muscle biopsy specimens. The diagnoses were confirmed by molecular typing. Surveillance for the emerging T. pseudospiralis should be expanded
Identification des dermatophytes par spectrométrie de masse MALDI-TOF
Introduction
Lâidentification des dermatophytes par les mĂ©thodes microbiologiques conventionnelles est souvent longue et fastidieuse. La technique de spectromĂ©trie de masse et sa variante MALDI-TOF (Matrix Assisted Laser Desorption Ionisation-Time of Flight) est un nouvel outil utilisĂ© pour lâidentification des bactĂ©ries et des levures dans les laboratoires dâanalyses mĂ©dicales. Nous avons rĂ©cemment dĂ©veloppĂ© une mĂ©thode standardisĂ©e pour lâidentification en routine des champignons filamenteux Ă partir de culture en milieu solide. Lâobjectif de cette Ă©tude est dâĂ©tendre cette mĂ©thode standardisĂ©e Ă lâidentification des dermatophytes dans lâactivitĂ© de routine du laboratoire.
Matériel et méthode
Une banque de rĂ©fĂ©rence contenant les spectres de masse de 44 souches parfaitement caractĂ©risĂ©es correspondants Ă 13 espĂšces de dermatophytes a Ă©tĂ© gĂ©nĂ©rĂ©e sur un UltraFlex (BruckerDaltonics, Allemagne) couplĂ© au logiciel MaldiBiotyper v2.1. Par la suite, 133 souches isolĂ©es de prĂ©lĂšvements cliniques ont Ă©tĂ© identifiĂ©es en comparant leur spectre Ă ceux inclus dans la banque de rĂ©fĂ©rence : lâidentification dâespĂšce a Ă©tĂ© retenue si le Log Score (LS) obtenu Ă©tait supĂ©rieur ou Ă©gal Ă 1,7. Enfin, lâidentification par MALDI-TOF a Ă©tĂ© considĂ©rĂ©e comme correcte en cas de concordance avec lâidentification morphologique ou molĂ©culaire des isolats cliniques.
RĂ©sultats
Lâidentification par spectromĂ©trie de masse(SM) a Ă©tĂ© correcte pour 130 (97,8 %) des isolats. Pour 2 isolats identifiĂ©s conventionnellement comme Microsporum canis, lâidentification par SM nâa pas pu gĂ©nĂ©rer de spectre avec un LS valide. Pour un isolat correspondant Ă Microsporum audouinii, la SM a gĂ©nĂ©rĂ© une mauvaise identification. Tous les isolats ont pu ĂȘtre identifiĂ©s aprĂšs seulement 3 à 6 jours de culture avant lâapparition des caractĂšres morphologiques conventionnels dâidentification.
Conclusion
Le protocole de SM utilisĂ© pour lâidentification des champignons filamenteux au laboratoire est applicable aux dermatophytes. Une identification dâespĂšce peut ĂȘtre obtenue en 3 à 6 jours alors quâune identification conventionnelle qui nĂ©cessite notamment des milieux de cultures complĂ©mentaires demande 2 à 3 semaines
Evaluation of antigens for the serodiagnosis of kala-azar and oriental sores by means of the indirect immunofluorescence antibody test (IFAT)
Antigens and corresponding sera were collected from travellers with leishmaniasis returning to Germany from different endemic areas of the old world. The antigenicity of these Leishmania strains, which were maintained in Syrian hamsters, was compared by indirect immunofluorescence (IFAT). Antigenicity was demonstrated by antibody titres in 18 sera from 11 patients. The amastigotic stages of nine strains of Leishmania donovani and four strains of Leishmania tropica were compared with each other and with the culture forms of insect flagellates (Strigomonas oncopelti and Leptomonas ctenocephali). Eighteen sera from 11 patients were available for antibody determination with these antigens. The maximal antibody titres in a single serum varied considerably depending on which antigen was used for the test. High antibody levels could only be maintained when Leishmania donovani was employed as the antigen, but considerable differences also occurred between the different strains of this species. The other antigens were weaker. No differences in antigenicity between amastigotes and promastigotes of the same strain were observed. It is important to select suitable antigens. Low titres may be of doubtful specificity and are a poor baseline for the fall in titre which is an essential index of effective treatment.Wir sammelten Parasiten und Seren von Reisenden, die aus verschiedenen endemischen Gebieten der Alten Welt mit einer Leishmaniasis nach Deutschland zurĂŒckkehrten. Die AntigenaktivitĂ€ten der isolierten und fortlaufend in Goldhamstern gehaltenenLeishmania-StĂ€mme wurden im indirekten Immunofluoreszenztest (IFAT) verglichen. Die AntigenitĂ€t wurde an Hand von Antikörpertitern in 18 Serumproben von 11 Patienten bewiesen. Neun StĂ€mme desLeishmania donovani-Komplexes und vierLeishmania tropica-Isolate wurden in ihrem amastigoten Stadium miteinander verglichen. Hinzu kamen zwei Insekten-Flagellaten als Kulturformen:Strigomonas oncopelti undLeptomonas ctenocephali. 18 Serumproben von 11 Patienten standen fĂŒr die Antikörperbestimmung mit diesen Antigenen zur VerfĂŒgung. Die maximalen Titerhöhen variierten in ein- und derselben antiserumprobe zum Teil erheblich, je nachdem, welches Antigen fĂŒr den Test benutzt wurde. Hohe Antikörpertiter konnten nur erhalten werden, wennLeishmania donovani als Antigen vorlag, es ergaben sich aber auch zwischen den einzelnen StĂ€mmen dieser Leishmaniaart erhebliche Unterschiede in der AntigenaktivitĂ€t. Antigene anderer Art erwiesen sich als wenig wirksam. Zwischen amastigoten und promastigoten Entwicklungsformen einesLeishmania donovani-Stammes konnten keine Unterschiede in der AntigenaktivitĂ€t erkannt werden. FĂŒr den Nachweis möglichst hoher Antikörpertiter im IFAT ist die Auswahl geeigneter Antigene von ausschlaggebender Bedeutung. Niedrige Titer erschweren deren Beurteilung als spezifisch und sind eine schlechte Ausgangsposition fĂŒr die Beobachtung des obligatorischen Titerabfalles nach erfolgreicher Therapie
Ecology of Phlebotomine Sand Flies in the Rural Community of Mont Rolland (ThiĂšs Region, Senegal): Area of Transmission of Canine Leishmaniasis
BACKGROUND: Different epidemiological studies previously indicated that canine leishmaniasis is present in the region of ThiĂšs (Senegal). However, the risks to human health, the transmission cycle and particularly the implicated vectors are unknown. METHODOLOGY/PRINCIPAL FINDINGS: To improve our knowledge on the population of phlebotomine sand flies and the potential vectors of canine leishmaniasis, sand flies were collected using sticky traps, light traps and indoor spraying method using pyrethroid insecticides in 16 villages of the rural community of Mont Rolland (ThiĂšs region) between March and July 2005. The 3788 phlebotomine sand flies we collected (2044 males, 1744 females) were distributed among 9 species of which 2 belonged to the genus Phlebotomus: P. duboscqi (vector of cutaneous leishmaniasis in Senegal) and P. rodhaini. The other species belonged to the genus Sergentomyia: S. adleri, S. clydei, S. antennata, S. buxtoni, S. dubia, S. schwetzi and S. magna. The number of individuals and the species composition differed according to the type of trap, suggesting variable, species-related degrees of endophily or exophily. The two species of the genus Phlebotomus were markedly under-represented in comparison to the species of the genus Sergentomyia. This study also shows a heterogeneous spatial distribution within the rural community that could be explained by the different ecosystems and particularly the soil characteristics of this community. Finally, the presence of the S. dubia species appeared to be significantly associated with canine leishmaniasis seroprevalence in dogs. CONCLUSIONS/SIGNIFICANCE: Our data allow us to hypothesize that the species of the genus Sergentomyia and particularly the species S. dubia and S. schwetzi might be capable of transmitting canine leishmaniasis. These results challenge the dogma that leishmaniasis is exclusively transmitted by species of the genus Phlebotomus in the Old World. This hypothesis should be more thoroughly evaluated
Pre-hospital risk factors for inpatient death from severe febrile illness in Malian children.
BACKGROUND: Inpatient case fatality from severe malaria remains high in much of sub-Saharan Africa. The majority of these deaths occur within 24 hours of admission, suggesting that pre-hospital management may have an impact on the risk of case fatality. METHODS: Prospective cohort study, including questionnaire about pre-hospital treatment, of all 437 patients admitted with severe febrile illness (presumed to be severe malaria) to the paediatric ward in Sikasso Regional Hospital, Mali, in a two-month period. FINDINGS: The case fatality rate was 17.4%. Coma, hypoglycaemia and respiratory distress at admission were associated with significantly higher mortality. In multiple logistic regression models and in a survival analysis to examine pre-admission risk factors for case fatality, the only consistent and significant risk factor was sex. Girls were twice as likely to die as boys (AOR 2.00, 95% CI 1.08-3.70). There was a wide variety of pre-hospital treatments used, both modern and traditional. None had a consistent impact on the risk of death across different analyses. Reported use of traditional treatments was not associated with post-admission outcome. INTERPRETATION: Aside from well-recognised markers of severity, the main risk factor for death in this study was female sex, but this study cannot determine the reason why. Differences in pre-hospital treatments were not associated with case fatality
Prevalence of soil transmitted nematodes on Nukufetau, a remote Pacific island in Tuvalu
BACKGROUND: The population of Nukufetau, a remote coral atoll island in Tuvalu in the Western Pacific, received annual mass drug administration (MDA) of diethylcarbamazine and albendazole under the Pacific Elimination of Lymphatic Filariasis program in 2001, 2002 and 2003, with the last MDA occurring six months before a cross-sectional survey of the whole population for soil transmitted helminths (STH). METHODS: A cross-sectional survey in May 2004 recruited 206 residents (35.2% of the population) who provided a single faecal sample that was preserved, concentrated and examined microscopically. RESULTS: Overall prevalence of STH was 69.9%; only hookworm and Trichuris trichiura were diagnosed. Trichuris was present in 68.4% with intensity of infection being light in 56.3%, medium in 11.7% and heavy in 0.5%. Hookworm occurred in 11.7% with intensity of infection 11.2% being light and medium in 0.5%. Twenty individuals (9.7%) had dual infections. The prevalence of Trichuris was constant across all ages while the prevalence of hookworm was significantly lower in residents below 30 years of age. In the age group 5â12 years comparison of results with a 2001 survey [1] suggested that the prevalence of STH has declined minimally, due to sustained high prevalence of Trichuris, while hookworm has declined dramatically from 34.4% to 1.6%. CONCLUSION: The results of this survey suggest that although the MDA appears to have reduced hookworm prevalence in residents below 30 years of age, there has been minimal effect on Trichuris prevalence. An integrated program to control STH is required
Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial.
BACKGROUND: SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa. METHODS: A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three treatment regimens: 10 mg/kg single dose AmBisome plus 10 days of SSG (20 mg/kg/day), 10 mg/kg single dose AmBisome plus 10 days of miltefosine (2.5mg/kg/day) and miltefosine alone (2.5 mg/kg/day for 28 days). The primary endpoint was initial parasitological cure at Day 28, and secondary endpoints included definitive cure at Day 210, and pharmacokinetic (miltefosine) and pharmacodynamic assessments. RESULTS: In sequential analyses with 49-51 patients per arm, initial cure was 85% (95% CI: 73-92) in all arms. At D210, definitive cure was 87% (95% CI: 77-97) for AmBisome + SSG, 77% (95% CI 64-90) for AmBisome + miltefosine and 72% (95% CI 60-85) for miltefosine alone, with lower efficacy in younger patients, who weigh less. Miltefosine pharmacokinetic data indicated under-exposure in children compared to adults. CONCLUSION: No major safety concerns were identified, but point estimates of definitive cure were less than 90% for each regimen so none will be evaluated in Phase III trials in their current form. Allometric dosing of miltefosine in children needs to be evaluated. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov, number NCT01067443
Impact of Long-Term Treatment with Ivermectin on the Prevalence and Intensity of Soil-Transmitted Helminth Infections
Soil-transmitted helminth (intestinal worm) infections are very common in developing countries and are an important cause of illness. Mass de-worming treatments of school children are an important strategy to reduce illness caused by these infections in communities without access to clean water and sanitation. Few studies have examined the effect of repeated mass treatments in the long-term in controlling these infections. The objective of the present study was to assess the impact of the drug ivermectin used for the control of onchocerciasis (river blindness), that has important effects against intestinal worms, on the epidemiology of intestinal worms in children when administered repeatedly for 15â17 years. We compared the epidemiology of infections between children living in communities that received ivermectin with communities that never received the drug. The data suggest that ivermectin has important differential effects on intestinal worms with a greater impact on infections with Trichuris trichiura and little impact on Ascaris lumbricoides and hookworms infections. Our data suggest that long-term ivermectin treatments may provide health benefits through effects on T. trichiura infections but that the addition of second de-worming drug such as albendazole may be required for the control of other intestinal worm infections
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