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1.
Pediatr Nephrol ; 39(6): 1893-1900, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38212419

RESUMO

BACKGROUND: Schistosomiasis affects approximately 230 million people worldwide. There is an increased incidence of schistosomiasis cases in France acquired from outside the country. This increases the risk of schistosomiasis outbreaks as observed in Corsica. Clinicians from non-endemic regions are not accustomed to diagnosing and managing this pathology. The objective of this study is to provide a better description of the clinical and paraclinical characteristics and disease evolution of affected children. METHODS: Through the French Pediatric Nephrology Society and the Pediatric Infectious Pathology Group, we contacted all French pediatric centers that may have treated children with urinary schistosomiasis between 2013 and 2019. Age, sex, comorbidities, and clinical, biological, and radiological data (at discovery and follow-up) were collected retrospectively. RESULTS: A total of 122 patients from 10 different centers were included. The median age was 14 years and the sex ratio M/F was 4:1. Hematuria was present in 82% of the patients while urinary tract abnormality was found in 36% of them. Fourteen patients (11%) displayed complicated forms of urinary schistosomiasis including 10 patients with chronic kidney disease. A total of 110 patients received treatment with praziquantel, which was well-tolerated and led to clinical resolution of symptoms in 98% of cases. CONCLUSION: Patients with schistosomiasis present frequent kidney, urinary, or genital involvement. Systematic screening of patients returning from endemic areas is therefore recommended, especially since treatment with antiparasitic drugs is effective and well-tolerated. Enhancing medical knowledge of this pathology among all practitioners is essential to improve care and outcomes.


Assuntos
Esquistossomose Urinária , Humanos , Criança , Adolescente , Animais , Esquistossomose Urinária/diagnóstico , Esquistossomose Urinária/tratamento farmacológico , Esquistossomose Urinária/epidemiologia , Estudos Retrospectivos , Praziquantel/uso terapêutico , Hematúria , França/epidemiologia , Schistosoma haematobium
2.
J Antimicrob Chemother ; 78(3): 665-668, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36611259

RESUMO

BACKGROUND: A new mutation in the Plasmodium falciparum dihydropteroate synthetase gene (pfdhps), I431V, has been identified in several countries of Central and West Africa. This mutation is mostly found in association with four other SNPs on pfdhps (S436A, A437G, A581G and A613S), forming a quintuple mutant (vagKgs) and almost always associated with the Plasmodium falciparum dihydrofolate reductase gene (pfdhfr) CirnI (C50R, N51I, S108N) triple mutant. To date, nothing is known about the impact of this new pfdhps genotype on sulfadoxine-pyrimethamine (SP) resistance. OBJECTIVES: We sought to assess the prevalence of this pfdhps vagKgs quintuple mutant in two groups of pregnant women with malaria, one that took intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and one that did not. METHODS: The pfdhfr and pfdhps genes from Plasmodium falciparum isolates collected in Yaoundé (Cameroon) from pregnant women with symptomatic malaria under IPTp-SP or not, were sequenced. RESULTS: Of 159 patients evaluated, 70 had already taken SP during pregnancy and 89 had never taken SP. Only the vagKgs allele was significantly overrepresented in the SP+ group (21.4% versus 3.4%; P < 0.001), whereas the ISgKAA mutant, widely distributed in this area and known to be less susceptible to SP, tended to be less abundant in this group (48.6% versus 64.0%; P = 0.0503). CONCLUSIONS: We found a strong overrepresentation of the CirnI/vagKgs haplotype in the IPTp-SP pregnant group, suggesting a high level of resistance of this mutant to SP. This could compromise not only the effectiveness of IPTp-SP but also the seasonal malaria chemoprevention of young children, now widely implemented.


Assuntos
Antimaláricos , Malária Falciparum , Pirimetamina , Sulfadoxina , Criança , Pré-Escolar , Feminino , Humanos , Gravidez , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Camarões , Quimioprevenção/métodos , Di-Hidropteroato Sintase/genética , Combinação de Medicamentos , Resistência a Medicamentos/genética , Malária Falciparum/tratamento farmacológico , Mutação , Plasmodium falciparum/genética , Gestantes , Pirimetamina/farmacologia , Pirimetamina/uso terapêutico , Sulfadoxina/farmacologia , Sulfadoxina/uso terapêutico
3.
BMC Infect Dis ; 23(1): 317, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37165325

RESUMO

BACKGROUND: Sickle cell trait (SCT) refers to the carriage of one abnormal copy of the ß-globin gene, the HbS allele. SCT offers protection against malaria, controlling parasite density and preventing progression to symptomatic malaria. However, it remains unclear whether SCT also affects transmission stages and mosquito infection parameters. Deciphering the impact of the SCT on human to mosquito malaria transmission is key to understanding mechanisms that maintain the trait in malaria endemic areas. METHODS: The study was conducted from June to July 2017 among asymptomatic children living in the locality of Mfou, Cameroon. Blood samples were collected from asymptomatic children to perform malaria diagnosis by microscopy, Plasmodium species by PCR and hemoglobin typing by RFLP. Infectiousness of gametocytes to mosquitoes was assessed by membrane feeding assays using blood from gametocyte carriers of HbAA and HbAS genotypes. A zero-inflated model was fitted to predict distribution of oocysts in mosquitoes according to hemoglobin genotype of the gametocyte source. RESULTS: Among the 1557 children enrolled in the study, 314 (20.16%) were of the HbAS genotype. The prevalence of children with P. falciparum gametocytes was 18.47% in HbAS individuals and 13.57% in HbAA, and the difference is significant (χ2 = 4.61, P = 0.032). Multiplicity of infection was lower in HbAS gametocyte carriers (median = 2 genotypes/carrier in HbAS versus 3.5 genotypes/carrier in HbAA, Wilcoxon sum rank test = 188, P = 0.032). Gametocyte densities in the blood donor significantly influenced mosquito infection prevalence in both HbAS and HbAA individuals. The HbAS genotype had no significant effect on mosquito infection outcomes when using immune or naïve serum in feeding assays. In AB replacement feeding experiments, the odds ratio of mosquito infection for HbAA blood as compared to HbAS was 0.56 (95% CI 0.29-1.10), indicating a twice higher risk of infection in mosquitoes fed on gametocyte-containing blood of HbAS genotype. CONCLUSION: Plasmodium transmission stages were more prevalent in SCT individuals. This may reflect the parasite's enhanced investment in the sexual stage to increase their survival rate when asexual replication is impeded. The public health impact of our results points the need for intensive malaria control interventions in areas with high prevalence of HbAS. The similar infection parameters in feeding experiments where mosquitoes received the original serum from the blood donor indicated that immune responses to gametocyte surface proteins occur in both HbAS and HbAA individuals. The higher risk of infection in mosquitoes fed on HbAS blood depleted of immune factors suggests that changes in the membrane properties in HbAS erythrocytes may impact on the maturation process of gametocytes within circulating red blood cells.


Assuntos
Anopheles , Malária Falciparum , Traço Falciforme , Criança , Animais , Humanos , Plasmodium falciparum/genética , Traço Falciforme/genética , Traço Falciforme/parasitologia , Malária Falciparum/parasitologia , Hemoglobinas , Anopheles/parasitologia
4.
Antimicrob Agents Chemother ; 66(8): e0018822, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35862750

RESUMO

Malaria control relies on passive case detection, and this strategy fails detecting asymptomatic infections. In addition, infections in endemic areas harbor multiple parasite genotypes that could affect case management and malaria epidemiology. Here, we performed AmpSeq genotyping to capture polymorphisms associated with antimalarial resistance and the genetic diversity within natural Plasmodium falciparum infections. Known genetic polymorphisms associated with altered drug susceptibility were screened for the five most common marker genes, pfdhfr, pfdhps, pfmdr1, pfcrt, and pfK13, and genetic diversity was established from two known AmpSeq markers, cpmp and csp. Relative abundance of the different genotypes within mixed infections was calculated from the number of reads per genotype. Genotyping was performed on 117 samples, 63 from asymptomatic and 54 from symptomatic individuals. We identified up to 15 genotypes within an infection, and the median multiplicity of infection was higher in asymptomatic infections (median MOI = 5 in asymptomatics versus median MOI = 2 in symptomatics, P < 0.001). No genetic differentiation on parasites from asymptomatic and symptomatic individuals was found. No mutation associated with ART resistance was identified. Prevalence of the P. falciparum chloroquine resistance wild-type genotype (CVMNK) reached 80%, confirming a return to chloroquine (CQ) sensitive parasites in Cameroon. In addition, the CQ-associated resistant genotype (CVIET) was present at very low density in polyclonal infections. Persistence of low-density chloroquine resistant parasites indicates competition-survival trade-offs may contribute to maintaining genetic diversity in natura. Thus, monitoring the expansion of these low-density genotypes in different immune backgrounds will be critical to evaluate drug policy changes.


Assuntos
Antimaláricos , Antagonistas do Ácido Fólico , Malária Falciparum , Malária , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Infecções Assintomáticas/epidemiologia , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Resistência a Medicamentos/genética , Genótipo , Humanos , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Mutação , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/uso terapêutico
5.
J Antimicrob Chemother ; 76(11): 3037-3044, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34453535

RESUMO

BACKGROUND: Dihydroartemisinin/piperaquine is increasingly used for the treatment of uncomplicated Plasmodium falciparum malaria in Africa. The efficacy of this combination in Cameroon is poorly documented, while resistance to dihydroartemisinin/piperaquine readily spreads in Southeast Asia. OBJECTIVES: This study evaluated the clinical efficacy of dihydroartemisinin/piperaquine in Cameroon, as well as the molecular profile and phenotypic susceptibility of collected isolates to dihydroartemisinin and piperaquine. PATIENTS AND METHODS: Dihydroartemisinin/piperaquine efficacy in 42 days was followed-up for 138 patients presenting non-complicated falciparum malaria. Piperaquine concentration was determined at day 7 for 124 patients. kelch13 gene polymorphisms (n = 150) and plasmepsin2 gene amplification (n = 148) were determined as molecular markers of resistance to dihydroartemisinin and piperaquine, respectively. Parasite susceptibility to dihydroartemisinin and piperaquine was determined using validated in vitro survival assays. RESULTS: The efficacy of dihydroartemisinin/piperaquine treatment was 100% after PCR correction. The reinfections were not associated with a variation of piperaquine concentration at day 7. Ninety-six percent (144/150) of the samples presented a WT allele of the kelch13 gene. Two percent (3/150) presented the non-synonymous mutation A578S, which is not associated with resistance to dihydroartemisinin. No duplication of the plasmepsin2 gene was observed (0/148). All the samples tested in vitro by survival assays (n = 87) were susceptible to dihydroartemisinin and piperaquine. CONCLUSIONS: Dihydroartemisinin/piperaquine has demonstrated excellent therapeutic efficacy with no evidence of emerging artemisinin or piperaquine resistance in Yaoundé, Cameroon. This observation suggests that dihydroartemisinin/piperaquine could be a sustainable therapeutic solution for P. falciparum malaria if implemented in areas previously free of artemisinin- and piperaquine-resistant parasites, unlike Southeast Asia.


Assuntos
Antimaláricos , Artemisininas , Malária Falciparum , Malária , Quinolinas , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Camarões , Humanos , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/genética , Quinolinas/uso terapêutico
6.
Eur J Clin Microbiol Infect Dis ; 40(6): 1191-1198, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33411170

RESUMO

In the non-AIDS group, several underlying conditions and immune defects could lead to different PCP presentations. This study compared PCP presentation and outcome according to the underlying disease. A secondary analysis of a previously published prospective observational study including 544 PCP patients was done. Only non-AIDS patients were included. Underlying disease was defined as chronic lymphocytic leukemia (CLL), organ transplantation, solid cancer, allogeneic hematopoietic stem cell transplant (AHSCT), other hematological diseases, and immunosuppressive treatment. Clinical characteristics and outcomes were compared between groups. Multiple correspondent analyses compared clinical characteristics at diagnosis. Day 30 mortality was analyzed. Three hundred and twenty-one patients were included in the study. The underlying diseases were hematological malignancy (n = 75), AHSCT (n = 14), CLL (n = 19), solid organ transplant (n = 94), solid tumor (n = 39), and immunosuppressive treatment (n = 57). Compared with other underlying diseases, PCP related to CLL was closer to PCP related to AIDS presentation (long duration of symptoms before diagnosis, high level of dyspnea, and low oxygen saturation at diagnosis). Day 30 mortality was associated with underlying disease, oxygen flow, and shock at ICU admission. PCP presentations may vary according to the underlying reason for immunosuppression. Response to treatment and adjuvant steroid therapy should be analyzed regarding this result.


Assuntos
Pneumonia por Pneumocystis/complicações , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Doença Aguda , Idoso , Feminino , Doenças Hematológicas/complicações , Humanos , Leucemia Linfoide/complicações , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/diagnóstico , Estudos Prospectivos
7.
Nature ; 505(7481): 50-5, 2014 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-24352242

RESUMO

Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread.


Assuntos
Antimaláricos/farmacologia , Artemisininas/farmacologia , Resistência a Medicamentos/genética , Malária Falciparum/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Alelos , Animais , Células Sanguíneas/parasitologia , Camboja , Resistência a Medicamentos/efeitos dos fármacos , Marcadores Genéticos/genética , Meia-Vida , Humanos , Malária Falciparum/tratamento farmacológico , Mutação/genética , Testes de Sensibilidade Parasitária , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/isolamento & purificação , Polimorfismo de Nucleotídeo Único/genética , Estrutura Terciária de Proteína/genética , Proteínas de Protozoários/química , Fatores de Tempo
8.
N Engl J Med ; 374(25): 2453-64, 2016 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-27332904

RESUMO

BACKGROUND: Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale. METHODS: We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci. RESULTS: We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay. CONCLUSIONS: No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).


Assuntos
Artemisininas/farmacologia , Resistência a Medicamentos/genética , Lactonas/farmacologia , Mutação , Plasmodium falciparum/genética , Polimorfismo Genético , Proteínas de Protozoários/genética , Algoritmos , Artemisininas/uso terapêutico , Sudeste Asiático , China , Doenças Endêmicas , Genótipo , Humanos , Lactonas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Análise de Sequência de DNA
9.
Euro Surveill ; 23(4)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29382413

RESUMO

Seven cases of urogenital schistosomiasis occurred in Corsica in 2015 and 2016. The episodes were related to exposure to the same river and involved the same parasite strain as an outbreak with 106 cases in summer 2013. The connection calls for further investigations on the presence of an animal reservoir and the survival of infested snails during winter. However, recontamination of the river from previously infected bathers remains the most likely hypothesis.


Assuntos
Bulinus/parasitologia , Schistosoma haematobium/isolamento & purificação , Schistosoma/isolamento & purificação , Esquistossomose Urinária/transmissão , Animais , Notificação de Doenças , Monitoramento Ambiental , Água Doce , Humanos , Schistosoma haematobium/genética , Esquistossomose Urinária/parasitologia , Esquistossomose Urinária/urina , Caramujos/parasitologia
10.
Malar J ; 16(1): 345, 2017 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-28818084

RESUMO

BACKGROUND: The measure of new drug- or vaccine-based approaches for malaria control is based on direct membrane feeding assays (DMFAs) where gametocyte-infected blood samples are offered to mosquitoes through an artificial feeder system. Gametocyte donors are identified by the microscopic detection and quantification of malaria blood stages on blood films prepared using either capillary or venous blood. However, parasites are known to sequester in the microvasculature and this phenomenon may alter accurate detection of parasites in blood films. The blood source may then impact the success of mosquito feeding experiments and investigations are needed for the implementation of DMFAs under natural conditions. METHODS: Thick blood smears were prepared from blood obtained from asymptomatic children attending primary schools in the vicinity of Mfou (Cameroon) over four transmission seasons. Parasite densities were determined microscopically from capillary and venous blood for 137 naturally-infected gametocyte carriers. The effect of the blood source on gametocyte and asexual stage densities was then assessed by fitting cumulative link mixed models (CLMM). DMFAs were performed to compare the infectiousness of gametocytes from the different blood sources to mosquitoes. RESULTS: Prevalence of Plasmodium falciparum asexual stages among asymptomatic children aged from 4 to 15 years was 51.8% (2116/4087). The overall prevalence of P. falciparum gametocyte carriage was 8.9% and varied from one school to another. No difference in the density of gametocyte and asexual stages was found between capillary and venous blood. Attempts to perform DMFAs with capillary blood failed. CONCLUSIONS: Plasmodium falciparum malaria parasite densities do not differ between capillary and venous blood in asymptomatic subjects for both gametocyte and trophozoite stages. This finding suggests that the blood source should not interfere with transmission efficiency in DMFAs.


Assuntos
Capilares/parasitologia , Malária Falciparum/epidemiologia , Parasitemia/epidemiologia , Plasmodium falciparum/isolamento & purificação , Veias/parasitologia , Adolescente , Camarões/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Malária Falciparum/parasitologia , Masculino , Parasitemia/parasitologia , Prevalência
11.
Value Health ; 20(10): 1319-1328, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29241891

RESUMO

BACKGROUND: Mortality from intra-abdominal candidiasis in intensive care units (ICUs) is high. It takes many days for peritoneal-fluid fungal culture to become positive, and the recommended empirical antifungal therapy involves excessive costs. Polymerase chain reaction (PCR) should produce results more rapidly than fungal culture. OBJECTIVES: To perform a cost-effectiveness analysis of the combination of several diagnostic and therapeutic strategies to manage Candida peritonitis in non-neutropenic adult patients in ICUs. METHODS: We constructed a decision tree model to evaluate the cost effectiveness. Cost and effectiveness were taken into account in a 1-year time horizon and from the French National Health Insurance perspective. Six strategies were compared: fluconazole or echinocandin as an empirical therapy, plus diagnosis by fungal culture or detection by PCR of all Candida species, or use of PCR to detect most fluconazole-resistant Candida species (i.e., Candida krusei and Candida glabrata). RESULTS: The use of fluconazole empirical treatment and PCR to detect all Candida species is more cost effective than using fluconazole empirical treatment without PCR (incremental cost-effectiveness ratio of €40,055/quality-adjusted life-year). Empirical treatment with echinocandin plus PCR to detect C. krusei and C. glabrata is the most effective strategy, but has an incremental cost-effectiveness ratio of €93,776/quality-adjusted life-year. If the cost of echinocandin decreases, then strategies involving PCR plus empirical echinocandin become more cost-effective. CONCLUSIONS: Detection by PCR of all Candida species and of most fluconazole-resistant Candida species could improve the cost-effectiveness of fluconazole and echinocandin given to non-neutropenic patients with suspected peritoneal candidiasis in ICUs.


Assuntos
Antifúngicos/administração & dosagem , Candida/isolamento & purificação , Candidíase/diagnóstico , Peritonite/diagnóstico , Reação em Cadeia da Polimerase/métodos , Adulto , Antifúngicos/economia , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Análise Custo-Benefício , Árvores de Decisões , Farmacorresistência Fúngica , Equinocandinas/administração & dosagem , Equinocandinas/economia , Fluconazol/administração & dosagem , Fluconazol/economia , Humanos , Unidades de Terapia Intensiva , Peritonite/tratamento farmacológico , Peritonite/microbiologia , Reação em Cadeia da Polimerase/economia , Anos de Vida Ajustados por Qualidade de Vida
12.
Malar J ; 15(1): 572, 2016 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-27887614

RESUMO

BACKGROUND: The spread of Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia is a major source of concern and the emergence of resistance in Africa would have dramatic consequences, by increasing malaria mortality and morbidity. It is therefore urgent to implement regular monitoring in sentinel sites in sub-Saharan Africa using robust and easy-to-implement tools. The prevalence of k13-propeller mutations and the phenotypic profiles are poorly known in sub-Saharan Africa. Here, the k13-propeller polymorphism was compared to both ex vivo susceptibility to DHA and early parasitological and clinical responses to artemisinin combination therapy (ACT). METHODS: Plasmodium falciparum isolates were collected in 2015 in Yaoundé (Cameroon) from patients treated with dihydroartemisinin-piperaquine combination. Samples were analysed for their susceptibility to artemisinin using the k13-propeller sequencing, the ex vivo ring-stage survival assay, the in vivo parasite positive rate and the clinical statute at day 2. RESULTS: None of the collected isolates revealed the presence of resistance mutations in the k13-propeller sequence. The median ring-stage survival rate for all the 64 interpretable isolates after a 6-hour pulse of 700 nM dihydroartemisinin was low, 0.49% (IQR: 0-1.3). Total parasite clearance was observed for 87.5% of patients and the remaining parasitaemic isolates (12.5%) showed a high reduction of parasite load, ranging from 97.5 to 99.9%. Clinical symptoms disappeared in 92.8% of cases. CONCLUSION: This study demonstrated the absence of k13-resistant genotypes in P. falciparum isolates from Cameroon. Only synonymous mutations were found with a low prevalence (4.3%). A good association between k13 genotypes and the ex vivo ring-stage survival assay or parasitological and clinical data was obtained. These results give a baseline for the long-term monitoring of artemisinin derivative efficacy in Africa.


Assuntos
Antimaláricos/farmacologia , Artemisininas/farmacologia , Resistência a Medicamentos , Malária Falciparum/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Polimorfismo Genético , Proteínas de Protozoários/genética , Adolescente , Adulto , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Camarões , Criança , Feminino , Humanos , Malária Falciparum/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Testes de Sensibilidade Parasitária , Plasmodium falciparum/genética , Plasmodium falciparum/isolamento & purificação , Mutação Puntual , Estudos Prospectivos , Quinolinas/uso terapêutico , Resultado do Tratamento , Voluntários , Adulto Jovem
13.
Proc Natl Acad Sci U S A ; 110(20): 8123-8, 2013 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-23637341

RESUMO

Plasmodium vivax is considered to be absent from Central and West Africa because of the protective effect of Duffy negativity. However, there are reports of persons returning from these areas infected with this parasite and observations suggesting the existence of transmission. Among the possible explanations for this apparent paradox, the existence of a zoonotic reservoir has been proposed. May great apes be this reservoir? We analyze the mitochondrial and nuclear genetic diversity of P. vivax parasites isolated from great apes in Africa and compare it to parasites isolated from travelers returning from these regions of Africa, as well as to human isolates distributed all over the world. We show that the P. vivax sequences from parasites of great apes form a clade genetically distinct from the parasites circulating in humans. We show that this clade's parasites can be infectious to humans by describing the case of a traveler returning from the Central African Republic infected with one of them. The relationship between this P. vivax clade in great apes and the human isolates is discussed.


Assuntos
Evolução Molecular , Especificidade de Hospedeiro , Malária/parasitologia , Plasmodium vivax/genética , Adulto , Animais , República Centro-Africana , Culicidae/parasitologia , DNA Mitocondrial/genética , Variação Genética , Genoma , Haplótipos , Hominidae/parasitologia , Humanos , Masculino , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase , Fatores de Tempo
14.
Euro Surveill ; 21(1)2016.
Artigo em Inglês | MEDLINE | ID: mdl-26767427

RESUMO

We present a case of acute schistosomiasis acquired in Corsica after bathing in the Cavu River during the summer of 2015. The diagnosis was made following epidemiological, laboratory and serological assessments. After a previous outbreak of urogenital schistosomiasis during the summer of 2013, when more than 120 infections were diagnosed, this further case indicates transmission was still effective in 2015, thus suggesting a permanent presence of schistosomiasis in Corsica.


Assuntos
Schistosoma haematobium/isolamento & purificação , Esquistossomose Urinária/diagnóstico , Adulto , Animais , Anti-Helmínticos/uso terapêutico , Western Blotting , Ensaio de Imunoadsorção Enzimática , França , Humanos , Masculino , Praziquantel/uso terapêutico , Esquistossomose Urinária/tratamento farmacológico , Resultado do Tratamento
16.
Emerg Infect Dis ; 21(10): 1733-41, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26401601

RESUMO

Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia threatens global malaria control strategies. Whether delayed parasite clearance, which exposes larger parasite numbers to artemisinins for longer times, selects higher-grade resistance remains unexplored. We investigated whether long-lasting artemisinin pressure selects a novel multidrug-tolerance profile. Although 50% inhibitory concentrations for 10 antimalarial drugs tested were unchanged, drug-tolerant parasites showed higher recrudescence rates for endoperoxides, quinolones, and an antifolate, including partner drugs of recommended combination therapies, but remained susceptible to atovaquone. Moreover, the age range of intraerythrocytic stages able to resist artemisinin was extended to older ring forms and trophozoites. Multidrug tolerance results from drug-induced quiescence, which enables parasites to survive exposure to unrelated antimalarial drugs that inhibit a variety of metabolic pathways. This novel resistance pattern should be urgently monitored in the field because this pattern is not detected by current assays and represents a major threat to antimalarial drug policy.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Tolerância a Medicamentos/imunologia , Malária Falciparum/parasitologia , Malária/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Sudeste Asiático , Humanos , Malária Falciparum/tratamento farmacológico
17.
J Antimicrob Chemother ; 70(9): 2566-71, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26080363

RESUMO

OBJECTIVES: To determine, 6 years after the adoption of intermittent preventive treatment of pregnant women with sulfadoxine/pyrimethamine (IPTp-SP) in Cameroon, (i) the polymorphism and prevalence of Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) gene mutations associated with sulfadoxine/pyrimethamine resistance and (ii) the consequences of sulfadoxine/pyrimethamine use in the selection of pfdhfr/pfdhps alleles. METHODS: pfdhfr and pfdhps genes from P. falciparum isolates collected in Yaoundé (Cameroon) from pregnant women with symptomatic malaria before taking IPTp-SP [SP- group (control) (n = 51)] or afterwards [SP+ group (n = 49)] were sequenced. RESULTS: The pfdhfr N51I, C59R, S108N triple mutant had a prevalence close to 100% (96/100) and no mutations at codons 50 and 164 were detected in either of the groups. The most frequent pfdhps mutation was A437G with a prevalence of 76.5% (39/51) in the SP- group, which was significantly higher in pregnant women who took sulfadoxine/pyrimethamine [95.9% (47/49)] (P = 0.012). Our study confirmed the presence of the pfdhps K540E mutation in Cameroon, but it remained rare. The prevalence of pfdhps A581G and A613S mutations had increased [5.9% (3/51) and 11.8% (6/51) in the control group, respectively] since the last studies in 2005. Surprisingly, the new pfdhps I431V mutation was detected, at a prevalence of 9.8% (5/51), and was found to be associated with other pfdhfr/pfdhps alleles to form an octuple N51I, C59R, S108N/I431V, S436A, A437G, A581G, A613S mutant. CONCLUSIONS: Significant changes were found in pfdhps polymorphism. In particular, we observed several parasites carrying eight mutations in pfdhfr/pfdhps genes, which are very susceptible to having a high level of resistance to sulfadoxine/pyrimethamine.


Assuntos
Antimaláricos/farmacologia , Resistência a Medicamentos , Frequência do Gene , Malária Falciparum/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Complicações Infecciosas na Gravidez/parasitologia , Pirimetamina/farmacologia , Sulfadoxina/farmacologia , Adulto , Camarões/epidemiologia , Di-Hidropteroato Sintase/genética , Combinação de Medicamentos , Feminino , Humanos , Malária Falciparum/epidemiologia , Mutação , Plasmodium falciparum/isolamento & purificação , Polimorfismo Genético , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Prevalência , Análise de Sequência de DNA , Tetra-Hidrofolato Desidrogenase/genética , Adulto Jovem
18.
Parasitology ; 142(4): 543-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25374302

RESUMO

Piroplasms, including Babesia, Cytauxzoon and Theileria species, frequently infect domestic and wild mammals. At present, there is no information on the occurrence and molecular identity of these tick-borne blood parasites in the meerkat, one of South Africa's most endearing wildlife celebrities. Meerkats live in territorial groups, which may occur on ranchland in close proximity to humans, pets and livestock. Blood collected from 46 healthy meerkats living in the South-African Kalahari desert was screened by microscopy and molecular methods, using PCR and DNA sequencing of 18S rRNA and ITS1 genes. We found that meerkats were infected by 2 species: one species related to Babesia sp. and one species related to Cytauxzoon sp. Ninety one percent of the meerkats were infected by the Cytauxzoon and/or the Babesia species. Co-infection occurred in 46% of meerkats. The pathogenicity and vectors of these two piroplasm species remains to be determined.


Assuntos
Carnívoros/parasitologia , Piroplasmida/genética , Infecções Protozoárias em Animais/parasitologia , Animais , Animais Selvagens , Babesia/classificação , Babesia/genética , Babesiose/parasitologia , DNA de Protozoário/química , DNA de Protozoário/genética , DNA de Protozoário/isolamento & purificação , DNA Espaçador Ribossômico/química , Filogenia , Piroplasmida/classificação , RNA Ribossômico 18S/genética , África do Sul
19.
Parasitol Res ; 114(11): 4127-33, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26268566

RESUMO

This study concerns the first urinary schistosomiasis case observed in Corsica (France, Europe) occurring in a 12-year-old German boy. The aim was to identify the relationship between this Schistosoma haematobium infection and other schistosomes of the Schistosoma group with terminal-spined ova. Morphological and molecular analyses were conducted on the ova. The results showed that the schistosome responsible for the emergence of schistosomiasis in Corsica was due to S. haematobium introgressed by genes from S. bovis.


Assuntos
Schistosoma haematobium/isolamento & purificação , Schistosoma/isolamento & purificação , Esquistossomose Urinária/parasitologia , Animais , Criança , França , Humanos , Masculino , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Filogenia , Schistosoma/classificação , Schistosoma/genética , Schistosoma haematobium/classificação , Schistosoma haematobium/genética
20.
Emerg Infect Dis ; 20(9): 1490-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25148074

RESUMO

Pneumocystis jirovecii pneumonia (PCP) in patients without AIDS is increasingly common. We conducted a prospective cohort study of consecutive patients with proven PCP; of 544 patients, 223 (41%) had AIDS (AIDS patients) and 321 (59%) had other immunosuppressive disorders (non-AIDS patients). Fewer AIDS than non-AIDS patients required intensive care or ventilation, and the rate of hospital deaths--17.4% overall--was significantly lower for AIDS versus non-AIDS patients (4% vs. 27%; p<0.0001). Multivariable analysis showed the odds of hospital death increased with older age, receipt of allogeneic bone marrow transplant, immediate use of oxygen, need for mechanical ventilation, and longer time to treatment; HIV-positive status or receipt of a solid organ transplant decreased odds for death. PCP is more often fatal in non-AIDS patients, but time to diagnosis affects survival and is longer for non-AIDS patients. Clinicians must maintain a high index of suspicion for PCP in immunocompromised patients who do not have AIDS.


Assuntos
Pneumocystis carinii , Pneumonia por Pneumocystis/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/epidemiologia , Adulto , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Razão de Chances , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/tratamento farmacológico , Estudos Prospectivos , Fatores de Risco
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