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5.
Clin Infect Dis ; 68(10): 1763-1768, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30239602

RESUMO

During the late phase of the large West-African Ebola virus disease (EVD) outbreak, the majority of patients were cared for in designated treatment centers. However, the preexisting healthcare infrastructure was already overwhelmed by the outbreak. This had a huge impact on other, non-EVD-related diseases, causing an unprecedented increase in morbidity and mortality, which most likely exceeded the toll due to EVD directly. Consequently, a crucial question is how to provide appropriate healthcare and safeguard functionality of a healthcare system that also serves patients not suspected or diagnosed to have EVD. Here, we report on the Lion Heart Medical Center's experience in Sierra Leone and note that a case definition of Ebola that is broader than those commonly applied may be better suited when it is necessary to identify atypically presenting, pauci-symptomatic cases.

11.
Travel Med Infect Dis ; 24: 23-24, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29715560

RESUMO

In scientific discourse, few would consider the widely used term resistance as ambiguous. The definition and usage of the term antimicrobial resistance revolves around the concept that microorganisms change in ways that render antimicrobial medications clinically ineffective. Because artemisinins have become the cornerstone for antimalarial therapy, the widely used term artemisinin resistance in scientific literature is highly alarming. Naturally, many people will assume that artemisinin resistance must essentially be the same as antimicrobial resistance, which means it is clinically ineffective. However, this is incorrect, and the WHO defines artemisinin resistance differently to antimicrobial resistance as "partial/relative resistance". This means that parasite clearance times are increased but does not automatically mean that artemisinins have become clinically inefficacious. Is the ambiguous use of the term resistance justified and appropriate, although it might be misleading biomedical researchers, the media, policy makers and possibly attending physicians? Science is also about clear and unambiguous use of terminology, so that a message is accurately communicated and understood. Ambiguity can lead to misunderstandings, and misunderstandings can cause wrong actions; unnecessarily so.


Assuntos
Antimaláricos/farmacologia , Artemisininas/efeitos adversos , Artemisininas/farmacologia , Resistência a Medicamentos , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Humanos , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Organização Mundial da Saúde
12.
Travel Med Infect Dis ; 21: 3-20, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29242073

RESUMO

BACKGROUND: We evaluated existing data on the prophylactic efficacy of atovaquone-proguanil (AP) in order to determine whether prophylaxis in travellers can be discontinued on the day of return from a malaria-endemic area instead of seven days after return as per currently recommended post-travel schedule. METHODS: PubMed and Embase databases were searched to identify relevant studies. This PROSPERO-registered systematic review followed PRISMA guidelines. The search strategy included terms or synonyms relevant to AP combined with terms to identify articles relating to prophylactic use of AP and inhibitory and half-life properties of AP. Studies considered for inclusion were: randomized controlled trials, cohort studies, quasi-experimental studies, open-label trials, patient-control studies, cross-sectional studies; as well as case-series and non-clinical studies. Data on study design, characteristics of participants, interventions, and outcomes were extracted. Primary outcomes considered relevant were prophylactic efficacy and prolonged inhibitory activity and half-life properties of AP. RESULTS: The initial search identified 1,482 publications, of which 40 were selected based on screening. Following full text review, 32 studies were included and categorized into two groups, namely studies in support of the current post-travel regimen (with a total of 2,866 subjects) and studies in support of an alternative regimen (with a total of 533 subjects). CONCLUSION: There is limited direct and indirect evidence to suggest that an abbreviated post-travel regimen for AP may be effective. Proguanil, however, has a short half-life and is essential for the synergistic effect of the combination. Stopping AP early may result in mono-prophylaxis with atovaquone and possibly select for atovaquone-resistant parasites. Furthermore, the quality of the studies in support of the current post-travel regimen outweighs the quality of the studies in support of an alternative short, post-travel regimen, and the total sample size of the studies to support stopping AP early comprises a small percentage of the total sample size of the studies performed to establish the efficacy of the current AP regimen. Additional research is required - especially from studies evaluating impact on malaria parasitaemia and clinical illness and conducted among travellers in high malaria risk settings - before an abbreviated regimen can be recommended in current practice. PROSPERO REGISTRATION NUMBER: CRD42017055244.


Assuntos
Antimaláricos/administração & dosagem , Atovaquona/administração & dosagem , Malária/tratamento farmacológico , Profilaxia Pós-Exposição , Proguanil/administração & dosagem , Viagem , Esquema de Medicação , Combinação de Medicamentos , Sinergismo Farmacológico , Doenças Endêmicas/prevenção & controle , Humanos , Malária/prevenção & controle , Doença Relacionada a Viagens
14.
Am J Trop Med Hyg ; 96(5): 1205-1214, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28500816

RESUMO

AbstractThe serum lipid profile in malaria patients has been found to differ from that of healthy controls. We investigated serum lipid profile changes in malaria patients over time compared with patients with other febrile diseases. In total, 217 patients were included in the study (111 malaria patients and 106 symptomatic controls, defined as malaria-negative febrile patients). Serum lipid levels (mmol/L) were significantly lower in malaria patients compared with those with other febrile diseases (total cholesterol [TC] = 3.26 [standard deviation = 0.94] versus 3.97 [1.22; P < 0.001]; high-density lipoprotein cholesterol [HDL-C] = 0.43 [0.47] versus 1.05 [0.67; P < 0.001], low-density lipoprotein cholesterol [LDL-C] = 2.05 [0.76] versus 2.42 [0.90; P < 0.001]. Triglycerides (TGs) levels were higher in malaria patients (1.81 [1.02] versus 1.11 [0.82; P < 0.001]). No significant differences were found for apolipoprotein A1, apolipoprotein B, and lipoprotein(a). Cholesterol levels increased toward reference values on day 28 (TC = 3.26-3.98, P < 0.001; HDL-C = 0.43-0.96, P < 0.001; LDL-C = 2.05-2.60, P < 0.001). TG levels decreased from 1.81 on admission to 1.76 (day 3) and 0.88 (day 28; P = 0.130). Lipid profile changes were not correlated with parasitemia or Plasmodium falciparum histidine-rich protein 2 levels. This study confirms characteristic temporary lipid profile changes in malaria. Lipid profile changes demonstrated a good accuracy to discriminate between malaria and other febrile diseases (area under the curve = 0.80 (95% confidence interval = 0.742-0.863, P < 0.001). Several plausible hypotheses exist regarding the pathophysiology of lipid profile changes in malaria. Further studies to elucidate the precise pathways may lead to improved understanding of the underlying pathophysiology.


Assuntos
Febre/diagnóstico , Malária Falciparum/diagnóstico , Parasitemia/diagnóstico , Adulto , Antígenos de Protozoários/sangue , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Febre/sangue , Gabão , Humanos , Metabolismo dos Lipídeos , Lipoproteína(a)/sangue , Malária Falciparum/sangue , Malária Falciparum/parasitologia , Masculino , Parasitemia/sangue , Parasitemia/parasitologia , Plasmodium falciparum/crescimento & desenvolvimento , Proteínas de Protozoários/sangue , Curva ROC , Triglicerídeos/sangue
18.
Trends Parasitol ; 32(2): 94-96, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26704075

RESUMO

New malaria diagnostic methods based on hemozoin (Hz) detection have been reported recently and were investigated in rodent models. These models are likely to produce unduly favorable results compared to the reality of Plasmodium falciparum malaria. Thus, for malaria diagnostics, results from rodent malaria experiments must be interpreted with caution.


Assuntos
Hemeproteínas/análise , Malária Falciparum/diagnóstico , Animais , Técnicas e Procedimentos Diagnósticos/normas , Modelos Animais de Doenças , Humanos , Malária Falciparum/sangue , Plasmodium falciparum , Reprodutibilidade dos Testes
19.
Malar J ; 14: 403, 2015 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-26458401

RESUMO

BACKGROUND: The haem-haemozoin biocrystallization pathway is an attractive target where several efficacious and safe anti-malarial drugs act. Consequently, in vitro haemozoin (Hz) inhibition assays have been developed to identify novel compounds. However, results may differ between assays and often require complex methods or sophisticated infrastructure. The recently reported growth of haemozoin-like crystals (HLC) appears to be a simple alternative although the endproduct is structurally different to Hz. This study set out to characterize this assay in depth, optimize it, and assess its performance. METHODS: The HLC assay was used as previously described but a range of different growth conditions were examined. Obtained HLCs were investigated and compared to synthetic (sHz) and natural haemozoin (nHz) using scanning electron microscopy, powder X-ray diffraction (PXRD), Fourier Transform Infrared spectroscopy (FTIR) and Raman spectroscopy (RS). Interactions of HLC with quinolines was analysed using RS. Inhibitory effects of currently used anti-malarial drugs under four final growth conditions were established. RESULTS: HLC growth requires Mycoplasma Broth Base, Tween 80, pancreatin, and lysed blood or haemin. HLCs are similar to nHz and sHz in terms of solubility, macroscopic and microscopic appearance although PXRD, FTIR and RS confirm that the haem aggregates of HLCs are structurally different. RS reveals that CQ seems to interact with HLCs in similar ways as with Hz. Inhibition of quinoline drugs ranged from 62.5 µM (chloroquine, amodiaquine, piperaquine) to 500 µM in mefloquine. CONCLUSIONS: The HLC assay provides data on inhibiting properties of compounds. Even if the end-product is not structurally identical to Hz, the inhibitory effects appear consistent with those obtained with sHz assays, as illustrated by the results obtained for quinolines. The assay is simple, inexpensive, robust, reproducible and can be performed under basic laboratory conditions with a simple visual positive/negative read-out.


Assuntos
Antimaláricos/metabolismo , Hemeproteínas/antagonistas & inibidores , Hemeproteínas/metabolismo , Quinolinas/metabolismo , Hemeproteínas/química , Hemeproteínas/ultraestrutura , Humanos , Microscopia Eletrônica de Varredura , Ligação Proteica , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Difração de Raios X
20.
PLoS Negl Trop Dis ; 9(5): e0003769, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25993501

RESUMO

BACKGROUND: Foci of the HIV epidemic and helminthic infections largely overlap geographically. Treatment options for helminth infections are limited, and there is a paucity of drug-development research in this area. Limited evidence suggests that antiretroviral therapy (ART) reduces prevalence of helminth infections in HIV-infected individuals. We investigated whether ART exposure and cotrimoxazole preventive therapy (CTX-P) is associated with a reduced prevalence of helminth infections. METHODOLOGY AND PRINCIPAL FINDINGS: This cross-sectional study was conducted at a primary HIV-clinic in Lambaréné, Gabon. HIV-infected adults who were ART-naïve or exposed to ART for at least 3 months submitted one blood sample and stool and urine samples on 3 consecutive days. Outcome was helminth infection with intestinal helminths, Schistosoma haematobium, Loa loa or Mansonella perstans. Multivariable logistic regression was used to assess associations between ART or CTX-P and helminth infection. In total, 408 patients were enrolled. Helminth infection was common (77/252 [30.5%]). Filarial infections were most prevalent (55/310 [17.7%]), followed by infection with intestinal helminths (35/296 [11.8%]) and S. haematobium (19/323 [5.9%]). Patients on CTX-P had a reduced risk of Loa loa microfilaremia (adjusted odds ratio (aOR) 0.47, 95% CI 0.23-0.97, P = 0.04), also in the subgroup of patients on ART (aOR 0.36, 95% CI 0.13-0.96, P = 0.04). There was no effect of ART exposure on helminth infection prevalence. CONCLUSIONS/SIGNIFICANCE: CTX-P use was associated with a decreased risk of Loa loa infection, suggesting an anthelminthic effect of antifolate drugs. No relation between ART use and helminth infections was established.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/complicações , Helmintíase/prevenção & controle , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adolescente , Adulto , Animais , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Gabão/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Helmintíase/epidemiologia , Humanos , Modelos Logísticos , Loíase/epidemiologia , Loíase/prevenção & controle , Masculino , Pessoa de Meia-Idade
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