Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 39
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Pediatr Infect Dis J ; 38(11): e295-e300, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31626041

RESUMO

BACKGROUND: Intravenous artesunate (ivA) is the standard treatment for severe malaria. Data systematically evaluating the use of ivA in pediatric patients outside malaria-endemic regions are limited. The aim of this case series was to summarize efficacy and safety of ivA for imported severe malaria in children in Germany. METHODS: Our retrospective case series included pediatric patients with imported severe malaria treated with at least 1 dose of ivA (Artesun, Guilin Pharmaceutical; Shanghai, China) at 4 German tertiary care centers. Severe malaria was defined according to World Health Organization criteria. RESULTS: Between 2010 and 2018, 14 children with a median [interquartile range (IQR)] age of 6 (1;9.5) years were included. All children were of African descent. All but 2 patients had Plasmodium falciparum malaria; 1 child had P. vivax malaria and 1 child had P. falciparum and P. vivax co-infection. Median (IQR) parasitemia at admission in patients with P. falciparum was 9.5% (3;16.5). Patients were treated with 1-10 [median (IQR) 3 (3;4)] doses ivA. All but one patient received a full course of oral antimalarial treatment. Parasite clearance was achieved within 2-4 days, with the exception of 1 patient with prolonged clearance of peripheral parasitemia. Three patients experienced posttreatment hemolysis but none needed blood transfusion. Otherwise ivA was safe and well tolerated. CONCLUSIONS: ivA was highly efficacious in this pediatric cohort. We observed episodes of mild to moderate posttreatment hemolysis in approximately one-third of patients. The legal status and usage of potentially lifesaving ivA should be evaluated in Europe.

2.
Infection ; 47(5): 847-852, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31190299

RESUMO

PURPOSE: Due to early antenatal screening and treatment, HIV mother-to-child transmission (MTCT) rarely occurs in Germany. The study aimed to investigate the impact on prevalence of HIV infection in the antenatal population and the incidence of late-presenting HIV-infected mothers attributable to increased numbers of refugees. METHODS: Retrospective analysis and comparison were performed for all deliveries in HIV-infected pregnant women presenting to medical care in Munich (southern Germany) and Hamburg (northern Germany) covering two time periods, A (2010-2012) and B (2013-2015). RESULTS: In Munich, deliveries in HIV-infected pregnant women increased 1.6-fold from period A (n = 50) to B (n = 79) with late-presenting cases rising significantly from 2% (1/50) in period A to 13% (10/79) in B. In contrast, late-presenting cases in Hamburg decreased from 14% (14/100) in period A to 7% (7/107) in B, while the total number of HIV-infected women giving birth remained stable. From 2010 to 2015, one late-presenting pregnant woman transmitted HIV in Munich by presumed in utero mode of infection (case reviewed here), while no MTCT occurred in Hamburg. CONCLUSIONS: HIV infections diagnosed late in pregnancy and leading to delayed ART initiation are rising in Munich compared to Hamburg. Antenatal care of HIV-infected pregnant women in Munich appears to have been more affected by the recent refugee influx than Hamburg. Our study highlights the importance of screening all pregnant women for HIV early in pregnancy and providing timely health care access for pregnant refugees and asylum seekers to effectively prevent MTCT in Germany.

3.
Front Immunol ; 10: 297, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30941118

RESUMO

Non-canonical NF-κB-pathway signaling is integral in immunoregulation. Heterozygous mutations in NFKB2 have recently been established as a molecular cause of common variable immunodeficiency (CVID) and DAVID-syndrome, a rare condition combining deficiency of anterior pituitary hormone with CVID. Here, we investigate 15 previously unreported patients with primary immunodeficiency (PID) from eleven unrelated families with heterozygous NFKB2-mutations including eight patients with the common p.Arg853* nonsense mutation and five patients harboring unique novel C-terminal truncating mutations. In addition, we describe the clinical phenotype of two patients with proximal truncating mutations. Cohort analysis extended to all 35 previously published NFKB2-cases revealed occurrence of early-onset PID in 46/50 patients (mean age of onset 5.9 years, median 4.0 years). ACTH-deficiency occurred in 44%. Three mutation carriers have deceased, four developed malignancies. Only two mutation carriers were clinically asymptomatic. In contrast to typical CVID, most patients suffered from early-onset and severe disease manifestations, including clinical signs of T cell dysfunction e.g., chronic-viral or opportunistic infections. In addition, 80% of patients suffered from (predominately T cell mediated) autoimmune (AI) phenomena (alopecia > various lymphocytic organ-infiltration > diarrhea > arthritis > AI-cytopenia). Unlike in other forms of CVID, auto-antibodies or lymphoproliferation were not common hallmarks of disease. Immunophenotyping showed largely normal or even increased quantities of naïve and memory CD4+ or CD8+ T-cells and normal T-cell proliferation. NK-cell number and function were also normal. In contrast, impaired B-cell differentiation and hypogammaglobinemia were consistent features of NFKB2-associated disease. In addition, an array of lymphocyte subpopulations, such as regulatory T cell, Th17-, cTFH-, NKT-, and MAIT-cell numbers were decreased. We conclude that heterozygous damaging mutations in NFKB2 represent a distinct PID entity exceeding the usual clinical spectrum of CVID. Impairment of the non-canonical NF-κB pathways affects function and differentiation of numerous lymphocyte-subpopulations and thus causes a heterogeneous, more severe form of PID phenotype with early-onset. Further characteristic features are multifaceted, primarily T cell-mediated autoimmunity, such as alopecia, lymphocytic organ infiltration, and in addition frequently ACTH-deficiency.

4.
Pediatr Infect Dis J ; 38(7): 727-730, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31033907

RESUMO

Using retrospectively collected data from 383 infants born to HIV-1-infected mothers receiving antiretroviral therapy, we compared transmission rates and hematologic toxicity between infants receiving 2-week (short course) versus longer duration zidovudine postexposure prophylaxis. Short course resulted in lower hematologic toxicity without evidence of increased vertical transmission risk.

5.
Brain ; 2018 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-29985992

RESUMO

The transcription factor BCL11B is essential for development of the nervous and the immune system, and Bcl11b deficiency results in structural brain defects, reduced learning capacity, and impaired immune cell development in mice. However, the precise role of BCL11B in humans is largely unexplored, except for a single patient with a BCL11B missense mutation, affected by multisystem anomalies and profound immune deficiency. Using massively parallel sequencing we identified 13 patients bearing heterozygous germline alterations in BCL11B. Notably, all of them are affected by global developmental delay with speech impairment and intellectual disability; however, none displayed overt clinical signs of immune deficiency. Six frameshift mutations, two nonsense mutations, one missense mutation, and two chromosomal rearrangements resulting in diminished BCL11B expression, arose de novo. A further frameshift mutation was transmitted from a similarly affected mother. Interestingly, the most severely affected patient harbours a missense mutation within a zinc-finger domain of BCL11B, probably affecting the DNA-binding structural interface, similar to the recently published patient. Furthermore, the most C-terminally located premature termination codon mutation fails to rescue the progenitor cell proliferation defect in hippocampal slice cultures from Bcl11b-deficient mice. Concerning the role of BCL11B in the immune system, extensive immune phenotyping of our patients revealed alterations in the T cell compartment and lack of peripheral type 2 innate lymphoid cells (ILC2s), consistent with the findings described in Bcl11b-deficient mice. Unsupervised analysis of 102 T lymphocyte subpopulations showed that the patients clearly cluster apart from healthy children, further supporting the common aetiology of the disorder. Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay. In addition, we suggest that missense mutations affecting specific sites within zinc-finger domains might result in distinct and more severe clinical outcomes.

6.
Euro Surveill ; 23(12)2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29589578

RESUMO

BackgroundIn Germany, the incidence of tuberculosis (TB) in children has been on the rise since 2009. High numbers of foreign-born asylum seekers have contributed considerably to the disease burden. Therefore, effective screening strategies for latent TB infection (LTBI) and active TB in asylum seeking children are needed. Aim: Our aim was to investigate the prevalence of LTBI and active TB in asylum seeking children up to 15 years of age in two geographic regions in Germany. Methods: Screening for TB was performed in children in asylum seeker reception centres by tuberculin skin test (TST) or interferon gamma release assay (IGRA). Children with positive results were evaluated for active TB. Additionally, country of origin, sex, travel time, TB symptoms, TB contact and Bacille Calmette-Guérin (BCG) vaccination status were registered. Results: Of 968 screened children 66 (6.8%) had TB infection (58 LTBI, 8 active TB). LTBI prevalence was similar in children from high (Afghanistan) and low (Syria) incidence countries (8.7% vs 6.4%). There were no differences regarding sex, age or travel time between infected and non-infected children. Children under the age of 6 years were at higher risk of progression to active TB (19% vs 2% respectively, p=0,07). Most children (7/8) with active TB were asymptomatic at the time of diagnosis. None of the children had been knowingly exposed to TB. Conclusions: Asylum seeking children from high and low incidence countries are both at risk of developing LTBI or active TB. Universal TB screening for all asylum seeking children should be considered.

7.
J Allergy Clin Immunol ; 141(4): 1427-1438, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28782633

RESUMO

BACKGROUND: Primary antibody deficiencies (PADs) are the most frequent primary immunodeficiencies in human subjects. The genetic causes of PADs are largely unknown. Sec61 translocon alpha 1 subunit (SEC61A1) is the major subunit of the Sec61 complex, which is the main polypeptide-conducting channel in the endoplasmic reticulum membrane. SEC61A1 is a target gene of spliced X-box binding protein 1 and strongly induced during plasma cell (PC) differentiation. OBJECTIVE: We identified a novel genetic defect and studied its pathologic mechanism in 11 patients from 2 unrelated families with PADs. METHODS: Whole-exome and targeted sequencing were conducted to identify novel genetic mutations. Functional studies were carried out ex vivo in primary cells of patients and in vitro in different cell lines to assess the effect of SEC61A1 mutations on B-cell differentiation and survival. RESULTS: We investigated 2 families with patients with hypogammaglobulinemia, severe recurrent respiratory tract infections, and normal peripheral B- and T-cell subpopulations. On in vitro stimulation, B cells showed an intrinsic deficiency to develop into PCs. Genetic analysis and targeted sequencing identified novel heterozygous missense (c.254T>A, p.V85D) and nonsense (c.1325G>T, p.E381*) mutations in SEC61A1, segregating with the disease phenotype. SEC61A1-V85D was deficient in cotranslational protein translocation, and it disturbed the cellular calcium homeostasis in HeLa cells. Moreover, SEC61A1-V85D triggered the terminal unfolded protein response in multiple myeloma cell lines. CONCLUSION: We describe a monogenic defect leading to a specific PC deficiency in human subjects, expanding our knowledge about the pathogenesis of antibody deficiencies.

8.
Inflamm Bowel Dis ; 23(12): 2109-2120, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28930861

RESUMO

BACKGROUND: In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients. METHODS: We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients. RESULTS: Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients. CONCLUSIONS: Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers.


Assuntos
Diarreia/etiologia , Predisposição Genética para Doença , Doenças Inflamatórias Intestinais/genética , Idade de Início , Criança , Pré-Escolar , Doença Crônica , Feminino , Estudo de Associação Genômica Ampla , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Sequenciamento Completo do Exoma
9.
Transplantation ; 101(5): e166-e169, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28263223

RESUMO

Persistently elevated eosinophil granulocytes in the peripheral blood in children is challenging because of a complex diagnosis especially after solid organ transplantation and can lead to difficulties in finding an underlying causative factor.We report a 12-year-old boy who developed severe hypereosinophilia 11 years after liver transplantation due to biliary atresia. Accompanying symptoms were recurrent fever, fatigue, elevated liver enzymes, abdominal pain, and significant weight loss. After exclusion of secondary causes of eosinophilia, an idiopathic hypereosinophilic syndrome (I-HES) was diagnosed. Treatment with prednisolone resulted in an immediate response with rapid reduction of eosinophils, normalization of liver enzymes, and amelioration of any clinical symptoms. A hypereosinophilic syndrome in patients after liver transplantation is rare, and a broad differential diagnosis has to be considered. Prednisolone may lead to a prompt amelioration of eosinophilia and associated symptoms.


Assuntos
Síndrome Hipereosinofílica/etiologia , Transplante de Fígado , Complicações Pós-Operatórias , Criança , Humanos , Síndrome Hipereosinofílica/diagnóstico , Masculino , Complicações Pós-Operatórias/diagnóstico
10.
BMC Nephrol ; 18(1): 96, 2017 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-28320387

RESUMO

BACKGROUND: Influenza A infections have been described to cause secondary hemolytic uremic syndrome and to trigger atypical hemolytic uremic syndrome (aHUS) in individuals with an underlying genetic complement dysregulation. To date, influenza B has not been reported to trigger aHUS. CASE PRESENTATION: A 6-month-old boy presented with hemolytic uremic syndrome triggered by influenza B infection. Initially the child recovered spontaneously. When he relapsed Eculizumab treatment was initiated, resulting in complete and sustained remission. A pathogenic mutation in membrane cofactor protein (MCP) was detected. CONCLUSION: Influenza B is a trigger for aHUS and might be underreported as such. Influenza vaccination may protect patients at risk.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/etiologia , Vírus da Influenza B/isolamento & purificação , Influenza Humana/complicações , Influenza Humana/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/terapia , Diagnóstico Diferencial , Humanos , Lactente , Vírus da Influenza B/classificação , Influenza Humana/terapia , Masculino , Resultado do Tratamento
11.
Haematologica ; 102(2): e52-e56, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27789675
13.
Blood ; 128(2): 227-38, 2016 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-27099149

RESUMO

Autoimmune lymphoproliferative syndrome (ALPS) is a human disorder characterized by defective Fas signaling, resulting in chronic benign lymphoproliferation and accumulation of TCRαß(+) CD4(-) CD8(-) double-negative T (DNT) cells. Although their phenotype resembles that of terminally differentiated or exhausted T cells, lack of KLRG1, high eomesodermin, and marginal T-bet expression point instead to a long-lived memory state with potent proliferative capacity. Here we show that despite their terminally differentiated phenotype, human ALPS DNT cells exhibit substantial mitotic activity in vivo. Notably, hyperproliferation of ALPS DNT cells is associated with increased basal and activation-induced phosphorylation of serine-threonine kinases Akt and mechanistic target of rapamycin (mTOR). The mTOR inhibitor rapamycin abrogated survival and proliferation of ALPS DNT cells, but not of CD4(+) or CD8(+) T cells in vitro. In vivo, mTOR inhibition reduced proliferation and abnormal differentiation by DNT cells. Importantly, increased mitotic activity and hyperactive mTOR signaling was also observed in recently defined CD4(+) or CD8(+) precursor DNT cells, and mTOR inhibition specifically reduced these cells in vivo, indicating abnormal programming of Fas-deficient T cells before the DNT stage. Thus, our results identify the mTOR pathway as a major regulator of lymphoproliferation and aberrant differentiation in ALPS.


Assuntos
Síndrome Linfoproliferativa Autoimune/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular/imunologia , Transdução de Sinais/imunologia , Serina-Treonina Quinases TOR/imunologia , Adolescente , Adulto , Síndrome Linfoproliferativa Autoimune/patologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lectinas Tipo C/imunologia , Antígenos Comuns de Leucócito/imunologia , Masculino , Proteínas Proto-Oncogênicas c-akt/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Transativadores/imunologia
14.
Gene ; 586(2): 234-8, 2016 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-27063510

RESUMO

Recently, gain-of-function (GOF) mutations in the gene encoding signal transducer and activator of transcription 1 (STAT1) have been associated with chronic mucocutaneous candidiasis (CMC). This case report describes a 10-year-old boy presenting with signs of common variable immunodeficiency (CVID), failure to thrive, impaired neurological development, and a history of recurrent mucocutaneous Candida infections. Sequencing of the STAT1 gene identified a heterozygous missense mutation in exon 7 encoding the STAT1 coiled-coil domain (c.514T>C, p.Phe172Leu). In addition to hypogammaglobulinemia with B-cell deficiency, and a low percentage of Th17 cells, immunological analysis of the patient revealed a marked depletion of forkhead-box P3(+)-expressing regulatory T cells (Tregs). In vitro stimulation of T cells from the patient with interferon-α (IFNα) and/or IFNÉ£ resulted in a significantly increased expression of STAT1-regulated target genes such as MIG1, IRF1, MX1, MCP1/CCL2, IFI-56K, and CXCL10 as compared to IFN-treated cells from a healthy control, while no IFNα/É£-mediated up-regulation of the FOXP3 gene was found. These data demonstrate that the STAT1 GOF mutation F172L, which results in impaired stability of the antiparallel STAT1 dimer conformation, is associated with inhibited Treg cell development and neurological symptoms.


Assuntos
Imunodeficiência de Variável Comum/genética , Mutação de Sentido Incorreto , Fator de Transcrição STAT1/genética , Linfócitos T Reguladores/imunologia , Candidíase Mucocutânea Crônica/complicações , Candidíase Mucocutânea Crônica/diagnóstico , Criança , Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/imunologia , Expressão Gênica , Humanos , Masculino , Transtornos do Neurodesenvolvimento/complicações , Transtornos do Neurodesenvolvimento/diagnóstico , Fenótipo
15.
J Clin Immunol ; 36(1): 73-84, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26604104

RESUMO

PURPOSE: Gain-of-function (GOF) mutations in the signal transducer and activator of transcription 1 (STAT1) result in unbalanced STAT signaling and cause immune dysregulation and immunodeficiency. The latter is often characterized by the susceptibility to recurrent Candida infections, resulting in the clinical picture of chronic mucocutaneous candidiasis (CMC). This study aims to assess the frequency of GOF STAT1 mutations in a large international cohort of CMC patients. METHODS: STAT1 was sequenced in genomic DNA from 57 CMC patients and 35 healthy family members. The functional relevance of nine different STAT1 variants was shown by flow cytometric analysis of STAT1 phosphorylation in patients' peripheral blood cells (PBMC) after stimulation with interferon (IFN)-α, IFN-γ or interleukin-27 respectively. Extended clinical data sets were collected and summarized for 26 patients. RESULTS: Heterozygous mutations within STAT1 were identified in 35 of 57 CMC patients (61%). Out of 39 familial cases from 11 families, 26 patients (67%) from 9 families and out of 18 sporadic cases, 9 patients (50%) were shown to have heterozygous mutations within STAT1. Thirteen distinct STAT1 mutations are reported in this paper. Eight of these mutations are known to cause CMC (p.M202V, p.A267V, p.R274W, p.R274Q, p.T385M, p.K388E, p.N397D, and p.F404Y). However, five STAT1 variants (p.F172L, p.Y287D, p.P293S, p.T385K and p.S466R) have not been reported before in CMC patients. CONCLUSION: STAT1 mutations are frequently observed in patients suffering from CMC. Thus, sequence analysis of STAT1 in CMC patients is advised. Measurement of IFN- or IL-induced STAT1 phosphorylation in PBMC provides a fast and reliable diagnostic tool and should be carried out in addition to genetic testing.


Assuntos
Candidíase Mucocutânea Crônica/diagnóstico , Síndromes de Imunodeficiência/diagnóstico , Leucócitos Mononucleares/imunologia , Mutação/genética , Fator de Transcrição STAT1/metabolismo , Adulto , Candidíase Mucocutânea Crônica/genética , Células Cultivadas , Citocinas/metabolismo , Análise Mutacional de DNA , Feminino , Humanos , Síndromes de Imunodeficiência/genética , Masculino , Linhagem , Fenótipo , Estrutura Terciária de Proteína/genética , Fator de Transcrição STAT1/genética
16.
Vaccine ; 33(49): 6967-9, 2015 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-26386163

RESUMO

During this year's 33rd annual meeting in Leipzig, Germany, the European Society of Paediatric Infectious Diseases (ESPID) jointly together with the European Scientific Working group on Influenza (ESWI), organized a staged debate on the motion of universal annual immunization of children against influenza as a cost-effective health intervention in Europe. Six invited speakers, all experts in the field of influenza vaccination, who were not necessary confident with their given position of pro or contra, battled each other with short oral presentations to convince the audience to vote for or against the motion.


Assuntos
Influenza Humana/prevenção & controle , Pediatria , Vacinação/economia , Criança , Congressos como Assunto , Análise Custo-Benefício , Europa (Continente) , Alemanha , Humanos , Influenza Humana/economia , Sociedades
18.
Int J Health Geogr ; 13: 35, 2014 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-25270342

RESUMO

BACKGROUND: Malaria is a mosquito-borne parasitic disease that causes severe mortality and morbidity, particularly in Sub-Saharan Africa. As the vectors predominantly bite between dusk and dawn, risk of infection is determined by the abundance of P. falciparum infected mosquitoes in the surroundings of the households. Remote sensing is commonly employed to detect associations between land use/land cover (LULC) and mosquito-borne diseases. Due to challenges in LULC identification and the fact that LULC merely functions as a proxy for mosquito abundance, assuming spatially homogenous relationships may lead to overgeneralized conclusions. METHODS: Data on incidence of P. falciparum parasitaemia were recorded by active and passive follow-up over two years. Nine LULC types were identified through remote sensing and ground-truthing. Spatial associations of LULC and P. falciparum parasitaemia rate were described in a semi-parametric geographically weighted Poisson regression model. RESULTS: Complete data were available for 878 individuals, with an annual P. falciparum rate of 3.2 infections per person-year at risk. The influences of built-up areas (median incidence rate ratio (IRR): 0.94, IQR: 0.46), forest (median IRR: 0.9, IQR: 0.51), swampy areas (median IRR: 1.15, IQR: 0.88), as well as banana (median IRR: 1.02, IQR: 0.25), cacao (median IRR: 1.33, IQR: 0.97) and orange plantations (median IRR: 1.11, IQR: 0.68) on P. falciparum rate show strong spatial variations within the study area. Incorporating spatial variability of LULC variables increased model performance compared to the spatially homogenous model. CONCLUSIONS: The observed spatial variability of LULC influence in parasitaemia would have been masked by traditional Poisson regression analysis assuming a spatially constant influence of all variables. We conclude that the spatially varying effects of LULC on P. falciparum parasitaemia may in fact be associated with co-factors not captured by remote sensing, and suggest that future studies assess small-scale spatial variation of vegetation to circumvent generalised assumptions on ecological associations that may in fact be artificial.


Assuntos
Mapeamento Geográfico , Malária Falciparum/etnologia , Malária Falciparum/transmissão , Plasmodium falciparum/isolamento & purificação , População Rural , Seguimentos , Gana/etnologia , Humanos , Lactente
19.
N Engl J Med ; 365(8): 718-24, 2011 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-21793736

RESUMO

An outbreak caused by Shiga-toxin­producing Escherichia coli O104:H4 occurred in Germany in May and June of 2011, with more than 3000 persons infected. Here, we report a cluster of cases associated with a single family and describe an open-source genomic analysis of an isolate from one member of the family. This analysis involved the use of rapid, bench-top DNA sequencing technology, open-source data release, and prompt crowd-sourced analyses. In less than a week, these studies revealed that the outbreak strain belonged to an enteroaggregative E. coli lineage that had acquired genes for Shiga toxin 2 and for antibiotic resistance.


Assuntos
Infecções por Escherichia coli/microbiologia , Genoma Bacteriano , Síndrome Hemolítico-Urêmica/microbiologia , Escherichia coli Shiga Toxigênica/genética , Adolescente , Técnicas de Tipagem Bacteriana , Criança , Diarreia/epidemiologia , Diarreia/microbiologia , Fezes/microbiologia , Feminino , Alemanha , Síndrome Hemolítico-Urêmica/epidemiologia , Humanos , Masculino , Dados de Sequência Molecular , Filogenia , Plasmídeos/genética , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Escherichia coli Shiga Toxigênica/classificação , Escherichia coli Shiga Toxigênica/isolamento & purificação
20.
Hum Mol Genet ; 20(6): 1173-81, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21224257

RESUMO

Using segregation analyses, control of malaria parasites has previously been linked to a major gene within the chromosomal region 5q31-33, but also to complex genetic factors in which effects are under substantial age-dependent influence. However, the responsible gene variants have not yet been identified for this chromosomal region. In order to perform association analyses of 5q31-33 locus candidate single nucleotide polymorphisms (SNPs), 1015 children were recruited at the age of 3 months and followed monthly until the age of 2 years in an area holoendemic for Plasmodium falciparum malaria in Ghana. Quantitative (incidence rates of malaria episodes) and qualitative phenotypes (i.e. 'more than one malaria episode' or 'not more than one malaria episode') were used in population- and family-based analyses. The strongest signal was observed for the interleukin 3 gene (IL3) SNP rs40401 (P = 3.4 × 10(-7), P(c)= 1.4 × 10(-4)). The IL3 genotypes rs40401(CT) and rs40401(TT) were found to exert a protective effect of 25% [incidence rate ratio (IRR) 0.75, P = 4.1 × 10(-5)] and 33% (IRR 0.67, P = 3.2 × 10(-8)), respectively, against malaria attacks. The association was confirmed in transmission disequilibrium tests (TDT, qTDT). The results could argue for a role of IL3 in the pathophysiology of falciparum malaria.


Assuntos
Cromossomos Humanos Par 5/genética , Variação Genética , Interleucina-3/genética , Malária Falciparum/genética , Pré-Escolar , Feminino , Gana/epidemiologia , Humanos , Imunidade Inata , Lactente , Interleucina-3/imunologia , Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Malária Falciparum/prevenção & controle , Masculino , Plasmodium falciparum/fisiologia , Polimorfismo de Nucleotídeo Único , Recidiva
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA