RESUMO
BACKGROUND: Infections with soil-transmitted helminths (STH) and schistosomiasis (SCH) result in a significant global health burden, particularly in rural communities in low and middle-income countries. While microscopy remains the primary diagnostic method for STH and SCH in resource-limited settings, nucleic acid amplification tests (NAATs) are gaining prominence as tools for evaluation of public health control programs in endemic countries, and individual diagnosis in high-income countries. Despite the high sensitivity and specificity of NAATs, previous research has highlighted inter-laboratory variations, both in technical and clinical performance, justifying the need for continuous proficiency testing. METHODOLOGY: Results from 5 rounds over a 5-year period of the so far only longitudinal international Helminth External Molecular Quality Assessment Scheme (HEMQAS), coordinated by the Dutch Foundation for Quality Assessment in Medical Laboratories (SKML), were examined in order to (i) assess the diagnostic proficiency of laboratories in detecting helminths in stool and (ii) identify potential factors contributing to variations in performance. OUTCOME AND CONCLUSIONS: Thirty-six laboratories, from 18 countries and 5 continents, participated in HEMQAS. The overall diagnostic performances were satisfying, with remarkably low numbers (<2%) of false-positive results. False-negative results were more often reported for stool (15%) than for DNA (5%) samples. False-negative results varied largely between targets (the highest number (29%) for Trichuris trichiura). Twenty-five laboratories provided a sufficient number of results for a robust comparison between participating laboratories, which confirmed substantial inter-laboratory variability in quantitative NAAT results (Cq-values). This variability likely arises from differences in pre-treatment, DNA isolation and DNA-target amplification procedures. This study emphasizes the complexity of molecular diagnosis for STH and SCH, highlighting the critical role of proper stool preparation and DNA isolation methods. The results underscore the necessity for laboratory professionals and public health decision-makers to recognize these complexities and continuously undertake external quality assessment schemes to ensure accurate and reliable performance in molecular diagnosis.
Assuntos
Fezes , Helmintíase , Helmintos , Técnicas de Amplificação de Ácido Nucleico , Schistosoma , Esquistossomose , Solo , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Amplificação de Ácido Nucleico/normas , Humanos , Animais , Helmintíase/diagnóstico , Helmintíase/parasitologia , Fezes/parasitologia , Solo/parasitologia , Esquistossomose/diagnóstico , Schistosoma/genética , Schistosoma/isolamento & purificação , Helmintos/isolamento & purificação , Helmintos/genética , Helmintos/classificação , Sensibilidade e Especificidade , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normasRESUMO
BACKGROUND: For fully automated detection and quantification of Plasmodium parasites, Sysmex developed the XN-31 hemocytometer. This study investigated whether the XN-31 can also detect and quantify bloodstream form trypanosomes (trypomastigotes). METHODS: Axenic cultures of Trypanosoma brucei brucei were used to prepare two dilution series of trypomastigotes in the whole blood of a healthy donor, which were subsequently examined by the XN-31 as well as by microscopic examination of thin and thick blood films. Trypomastigote intactness during the procedures was evaluated by microscopy. RESULTS: The XN-31 hemocytometer detected trypomastigotes with a detection limit of 26 trypomastigotes/µL. Scattergram patterns of Trypanosoma and Plasmodium parasites were clearly distinct, but current interpretation settings do not allow the identification of trypomastigotes yet, and therefore, need future refinement. CONCLUSION: Proof of concept was provided for an automated fluorescent flow cytometry method that can detect and quantify Plasmodium spp., as well as Trypanosoma brucei trypomastigotes.
Assuntos
Hematologia , Trypanosoma brucei brucei , Humanos , Hematologia/métodos , Reprodutibilidade dos Testes , MicroscopiaRESUMO
PURPOSE: The purpose of this study was to assess the variation in methods and to determine whether an External Quality Assessment Scheme (EQAS) for polymerase chain reaction (PCR) detection of Acanthamoeba keratitis is valuable for the diagnostic process. METHODS: A multicenter EQAS was introduced, covering 16 diagnostic laboratories. Using Acanthamoeba castellanii ATCC strain 30010, 3 sets of samples were prepared, containing different amounts of DNA, cysts, or trophozoites. Samples were masked and sent to the participants with instructions for use and a questionnaire concerning the applied methodologies. Special attention in this questionnaire was given to the used pretreatment methods to assess existing variations in these procedures. RESULTS: A large variation in the methodologies and substantial differences in the diagnostic performance were found between participants. In contrast to the DNA samples where all participants had a perfect score, several false negative results were reported for the samples containing cysts or trophozoites. Only 9 participants had an optimal score, whereas one participant reported all samples as negative, one participant reported failures due to inhibition, and the other 5 reported in total 7 false negative results. A clear correlation was noticed between the PCR detection rate and the number of cysts or trophozoites in the sample. CONCLUSIONS: The results indicate that a pretreatment procedure can be a risky step in PCR-based detections of Acanthamoeba , but it improves the sensitivity and reliability, especially of samples containing cysts. Therefore, participation in an EQAS is informative for routine diagnostic laboratories and can assist in improving the laboratory procedures used for the diagnosis of Acanthamoeba keratitis.
Assuntos
Ceratite por Acanthamoeba , Acanthamoeba castellanii , Cistos , Animais , Humanos , Ceratite por Acanthamoeba/diagnóstico , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase/métodos , TrofozoítosAssuntos
Infecções , Malária Falciparum , Parasitos , Animais , Humanos , Plasmodium falciparum , Reação de Fase Aguda , ColesterolRESUMO
BACKGROUND: Due to increased travel from endemic countries, malaria occurs more frequently in non-endemic regions. It is a challenge for diagnostic laboratories in non-endemic countries to provide reliable results, as experience of staff is often limited to only a few cases per year. This study evaluated the diagnostic accuracy of the fully automated Sysmex XN-31 malaria analyzer in a routine diagnostic setting in a non-endemic region was evaluated. METHODS: Samples from 112 patients suspected for malaria were examined by the Sysmex XN-31 analyzer to determine the absolute count of malaria-infected red blood cells count (MI-RBC/µL). Microscopic examination of both Quantitative Buffy Coat capillary tubes and thick and thin blood films were used as reference methods. Limits of blank (LoB), detection (LoD) and quantification (LoQ) were investigated using an in vitro Plasmodium falciparum culture. Nine hundred twenty samples of patients with RBC abnormalities were included to determine which RBC abnormalities trigger indeterminate or false positive results. RESULTS: No false positive nor false negative results were obtained for the examined patient samples suspected for malaria. For 3% of samples an indeterminate result by the XN-31 was obtained. The Passing-Bablok regression line for diagnostic accuracy of the parasitaemia was y = 39.75 + 0.7892 × showing a positive bias of about 21% when comparing the MI-RBC results to microscopy. The LoB, LoD and LoQ were calculated to be 4.7, 5.9, and 19.0 infected RBC/µL, respectively. From the 920 abnormal RBC samples collected, 4.6% resulted in a false positive MI-RBC result and almost half of the samples produced indeterminate results. These results were related to increases in nucleated red blood cells, reticulocytes and other abnormal RBC morphologies such as sickle cells. CONCLUSIONS: Based on the results, the XN-31 is a fast and reliable screening method in the detection and quantification of Plasmodium species in patients However, if an abnormal red blood cell morphology is present, the results of the XN-31 should be interpreted with caution as false positive results can be caused by interfering abnormal erythrocytes.
Assuntos
Malária , Plasmodium , Eritrócitos , Humanos , Malária/diagnóstico , Parasitemia/diagnóstico , Plasmodium falciparumRESUMO
BACKGROUND: Microscopic examination of thick and thin blood films is the gold standard in current guidelines for the diagnosis of malaria, but guidelines do not uniformly agree on which combination of other methods should be used and when. METHODS: Three questionnaires were sent between March 2018 and September 2019 to laboratories subscribing to the external quality assessment scheme for the diagnosis of blood and intestinal parasites of the Dutch Foundation for Quality Assessment in Medical Laboratories in order to investigate how much variation in the laboratory diagnosis of malaria between different clinical laboratories is present in the Netherlands. RESULTS: The questionnaires were partially or fully completed by 67 of 77 (87%) laboratories. Only 9 laboratories reported 10 or more malaria positive patients per year. Most laboratories use a different diagnostic strategy, within office versus outside office hours depending on the screening assay result. Within office hours, 62.5% (35/56) of the responding laboratories perform an immunochromatographic test (ICT) in combination with microscopic examination of thick and thin blood films without additional examinations, such as Quantitative Buffy Coat and/or rtPCR analysis. Outside office hours 85.7% (48/56) of laboratories use an ICT as single screening assay and positive results are immediately confirmed by thick and thin blood films without additional examinations (89.6%, 43/48). In case of a negative ICT result outside office hours, 70.8% (34/48) of the laboratories perform microscopic examination of the thick film the next morning and 22.9% (11/48) confirm the negative ICT result immediately. Furthermore, substantial differences were found in the microscopic examinations of thick and thin blood films; the staining, theoretical sensitivity of the thick film and determination of parasitaemia. CONCLUSIONS: This study demonstrated a remarkably high variation between laboratories in both their diagnostic strategy as well as their methods for microscopic examination for the diagnosis of malaria in a clinical setting, despite existing national and international guidelines. While the impact of these variations on the accuracy of the diagnosis of malaria is yet unknown, these findings should stimulate clinical laboratories to critically review their own diagnostic strategy.
Assuntos
Laboratórios/normas , Malária/diagnóstico , Corantes Azur/normas , Corantes/normas , Humanos , Laboratórios/estatística & dados numéricos , Limite de Detecção , Países Baixos , Parasitemia/diagnóstico , Sensibilidade e Especificidade , Coloração e Rotulagem/métodos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: In falciparum malaria the total parasite biomass can be estimated by blood levels of histidine-rich protein 2 (PfHRP2), a Plasmodium falciparum-specific protein, which has been widely studied in malaria-endemic regions. This study investigates the usefulness of PfHRP2 as marker for disease severity in imported falciparum malaria. METHODS: A retrospective cohort analysis was done in 145 patients with imported falciparum malaria. Associations between PfHRP2, malaria disease severity and classic parameters of disease severity were examined by statistical analyses. Patients with different travel purposes were examined in two groups: visiting friends and relatives (VFRs) and other travel purposes (mainly tourists). RESULTS: High PfHRP2 levels were clearly associated with disease severity. VFRs status showed to be an independent determinant protecting against severe malaria. At similar PfHRP2 levels VFRs patients had significantly lower levels of peripheral blood parasitemia compared to other patients. CONCLUSION: Our study confirms the association between PfHRP2 and disease severity in patients with imported falciparum malaria, but for proper interpretation of PfHRP2 levels as disease severity marker in travellers, the possible presence of pre-existing acquired anti-malarial immunity should be taken into account as the correlation between PfHRP2 levels and disease severity differed significantly between VFRs patients and patients with other travel purposes.
Assuntos
Malária Falciparum , Malária , Histidina , Humanos , Parasitemia , Plasmodium falciparum , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Nucleic acid amplification tests (NAATs) are increasingly being used as diagnostic tools for soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, Necator americanus, Ancylostoma duodenale and A. ceylanicum), Strongyloides stercoralis and Schistosoma in human stool. Currently, there is a large diversity of NAATs being applied, but an external quality assessment scheme (EQAS) for these diagnostics is lacking. An EQAS involves a blinded process where test results reported by a laboratory are compared to those reported by reference or expert laboratories, allowing for an objective assessment of the diagnostic performance of a laboratory. In the current study, we piloted an international EQAS for these helminths (i) to investigate the feasibility of designing and delivering an EQAS; (ii) to assess the diagnostic performance of laboratories; and (iii) to gain insights into the different NAAT protocols used. METHODS AND PRINCIPAL FINDINGS: A panel of twelve stool samples and eight DNA samples was validated by six expert laboratories for the presence of six helminths (Ascaris, Trichuris, N. americanus, Ancylostoma, Strongyloides and Schistosoma). Subsequently this panel was sent to 15 globally dispersed laboratories. We found a high degree of diversity among the different DNA extraction and NAAT protocols. Although most laboratories performed well, we could clearly identify the laboratories that were poorly performing. CONCLUSIONS/SIGNIFICANCE: We showed the technical feasibility of an international EQAS for the NAAT of STHs, Strongyloides and Schistosoma. In addition, we documented that there are clear benefits for participating laboratories, as they can confirm and/or improve the diagnostic performance of their NAATs. Further research should aim to identify factors that explain poor performance of NAATs.
Assuntos
Helmintíase/diagnóstico , Ensaio de Proficiência Laboratorial/organização & administração , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Adolescente , Animais , Criança , Fezes/parasitologia , Feminino , Helmintos/classificação , Helmintos/genética , Helmintos/isolamento & purificação , Humanos , Masculino , Técnicas de Diagnóstico Molecular/normas , Técnicas de Amplificação de Ácido Nucleico/normas , Projetos PilotoRESUMO
For some diseases, successful vaccines have been developed using a nonpathogenic counterpart of the causative microorganism of choice. The nonpathogenicity of the rodent Plasmodium berghei (Pb) parasite in humans prompted us to evaluate its potential as a platform for vaccination against human infection by Plasmodium falciparum (Pf), a causative agent of malaria. We hypothesized that the genetic insertion of a leading protein target for clinical development of a malaria vaccine, Pf circumsporozoite protein (CSP), in its natural pre-erythrocytic environment, would enhance Pb's capacity to induce protective immunity against Pf infection. Hence, we recently generated a transgenic Pb sporozoite immunization platform expressing PfCSP (PbVac), and we now report the clinical evaluation of its biological activity against controlled human malaria infection (CHMI). This first-in-human trial shows that PbVac is safe and well tolerated, when administered by a total of ~300 PbVac-infected mosquitoes per volunteer. Although protective efficacy evaluated by CHMI showed no sterile protection at the tested dose, significant delays in patency (2.2 days, P = 0.03) and decreased parasite density were observed after immunization, corresponding to an estimated 95% reduction in Pf liver parasite burden (confidence interval, 56 to 99%; P = 0.010). PbVac elicits dose-dependent cross-species cellular immune responses and functional PfCSP-dependent antibody responses that efficiently block Pf sporozoite invasion of liver cells in vitro. This study demonstrates that PbVac immunization elicits a marked biological effect, inhibiting a subsequent infection by the human Pf parasite, and establishes the clinical validation of a new paradigm in malaria vaccination.
Assuntos
Vacinas Antimaláricas , Malária Falciparum , Malária , Parasitos , Animais , Anticorpos Antiprotozoários , Imunização , Malária Falciparum/prevenção & controle , Plasmodium falciparum , Proteínas de Protozoários/genética , Roedores , VacinaçãoRESUMO
BACKGROUND: After a controlled human malaria infection (CHMI), presentation of clinical signs and symptoms and host responses is heterogeneous. Transforming growth factor-beta (TGF-ß) is the first serum cytokine that changes in malaria-naïve volunteers after CHMI. We studied a possible relation between TGF-ß changes, pro-inflammatory cytokines, activation of haemostasis and endothelial cells and clinical symptoms. METHODS: A panel of cytokines including TGF-ß, and markers of activation of haemostasis and endothelial cells were measured in blood samples of 15 volunteers at baseline before CHMI and during CHMI at day of treatment. The change of the parameters on the day of treatment was examined for a significant alteration during infection. RESULTS: Nine of 15 volunteers showed a significant decrease in TGF-ß compared to baseline, with concomitant increased concentrations of D-dimer (pâ¯=â¯0.012), Von Willebrand factor (pâ¯=â¯0.017), IL-6 (pâ¯=â¯0.012) and IFN-γ (0.028) and a significantly decreased platelet count (pâ¯=â¯0.011). In contrast, 6 of 15 volunteers showed sustained or increased TGF-ß concentrations without change in the aforementioned parameters. The sustained responders presented with less moderate and severe clinical symptoms than the negative responders (pâ¯=â¯0.036) and had a higher baseline lymphocyte count (pâ¯=â¯0.026). TGF-ß concentrations did not correlate with the parasitaemia on day of treatment. CONCLUSION: Early decreases of serum TGF-ß might function a marker for a pro-inflammatory host response and downstream clinical symptoms and pathology during CHMI.
Assuntos
Células Endoteliais/metabolismo , Hemostasia , Malária/sangue , Parasitemia/sangue , Fator de Crescimento Transformador beta/sangue , Adulto , Plaquetas/metabolismo , Correlação de Dados , Regulação para Baixo , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/parasitologia , Interferon gama/sangue , Interferons , Interleucina-6/sangue , Linfócitos/metabolismo , Malária/parasitologia , Malária/fisiopatologia , Masculino , Contagem de Plaquetas , Regulação para Cima , Fator de von Willebrand/metabolismoAssuntos
Antimaláricos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Malária Falciparum/tratamento farmacológico , Adulto , Antimaláricos/uso terapêutico , Citocinas , Feminino , Humanos , Inflamação , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estresse OxidativoRESUMO
Controlled human malaria infections (CHMIs) with Plasmodium falciparum (Pf) parasites are well established. Exposure to five Pf (NF54)-infected Anopheles mosquitoes results in 100% infection rates in malaria-naïve volunteers. Recently Pf clones NF135.C10 and NF166.C8 were generated for application in CHMIs. Here, we tested the clinical infection rates of these clones, using graded numbers of Pf-infected mosquitoes. In a double-blind randomized trial, we exposed 24 malaria-naïve volunteers to bites from one, two, or five mosquitoes infected with NF135.C10 or NF166.C8. The primary endpoint was parasitemia by quantitative polymerase chain reaction. For both strains, bites by five infected mosquitoes resulted in parasitemia in 4/4 volunteers; 3/4 volunteers developed parasitemia after exposure to one or two infected mosquitoes infected with either clone. The prepatent period was 7.25 ± 4.0 days (median ± range). There were no serious adverse events and comparable clinical symptoms between all groups. These data confirm the eligibility of NF135.C10 and NF166.C8 for use in CHMI studies.
Assuntos
Anopheles/parasitologia , Malária Falciparum/parasitologia , Mosquitos Vetores/parasitologia , Plasmodium falciparum/fisiologia , Adolescente , Adulto , Animais , Método Duplo-Cego , Feminino , Humanos , Malária Falciparum/transmissão , Masculino , Voluntários , Adulto JovemAssuntos
DNA de Protozoário/metabolismo , Fezes/parasitologia , Parasitos/genética , Reação em Cadeia da Polimerase/métodos , Animais , Cryptosporidium/genética , Cryptosporidium/isolamento & purificação , DNA de Protozoário/genética , DNA de Protozoário/normas , Entamoeba histolytica/genética , Entamoeba histolytica/isolamento & purificação , Trato Gastrointestinal/parasitologia , Giardia lamblia/genética , Giardia lamblia/isolamento & purificação , Humanos , Laboratórios Hospitalares/normas , Países Baixos , Parasitos/isolamento & purificação , Doenças Parasitárias/diagnóstico , Reação em Cadeia da Polimerase/normas , Controle de Qualidade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Both in endemic countries and in imported malaria, changes in total and differential leukocyte count during Plasmodium falciparum infection have been described. To study the exact dynamics of differential leukocyte counts and their ratios, they were monitored in a group of healthy non-immune volunteers in two separate Controlled Human Malaria Infection (CHMI) studies. METHODS: In two CHMI trials, CHMI-a and CHMI-b, 15 and 24 healthy malaria-naïve volunteers, respectively, were exposed to bites of infected mosquitoes, using the P. falciparum research strain NF54 and the novel clones NF135.C10 and NF166.C8. After mosquito bite exposure, twice-daily blood draws were taken to detect parasitaemia and to monitor the total and differential leukocyte counts. All subjects received a course of atovaquone-proguanil when meeting the treatment criteria. RESULTS: A total of 39 volunteers participated in the two trials. Thirty-five participants, all 15 participants in CHMI-a and 20 of the 24 volunteers in CHMI-b, developed parasitaemia. During liver stage development of the parasite, the median total leukocyte count increased from 5.5 to 6.1 × 109 leukocytes/L (p = 0.005), the median lymphocyte count from 1.9 to 2.2 (p = 0.001) and the monocyte count from 0.50 to 0.54 (p = 0.038). During the subsequent blood stage infection, significant changes in total and differential leukocyte counts lead to a leukocytopenia (nadir median 3.3 × 109 leukocytes/L, p = 0.0001), lymphocytopenia (nadir median 0.7 × 109 lymphocytes/L, p = 0.0001) and a borderline neutropenia (nadir median 1.5 × 109 neutrophils/L, p = 0.0001). The neutrophil to lymphocyte count ratio (NLCR) reached a maximum of 4.0. Significant correlations were found between parasite load and absolute lymphocyte count (p < 0.001, correlation coefficient - 0.46) and between parasite load and NLCR (p < 0.001, correlation coefficient 0.50). All parameters normalized after parasite clearance. CONCLUSIONS: During the clinically silent liver phase of malaria, an increase of peripheral total leukocyte count and differential lymphocytes and monocytes occurs. This finding has not been described previously. This increase is followed by the appearance of parasites in the peripheral blood after 2-3 days, accompanied by a marked decrease in total leukocyte count, lymphocyte count and the neutrophil count and a rise of the NLCR.
Assuntos
Contagem de Leucócitos , Malária Falciparum/parasitologia , Parasitemia/parasitologia , Plasmodium falciparum/fisiologia , Antimaláricos/administração & dosagem , Infecções Assintomáticas , Atovaquona/administração & dosagem , Combinação de Medicamentos , Voluntários Saudáveis , Humanos , Fígado/parasitologia , Malária Falciparum/sangue , Parasitemia/sangue , Proguanil/administração & dosagemRESUMO
Background: Treatment of blood samples from hemorrhagic fever virus (HFV)-infected patients with 0.1% detergents has been recommended for virus inactivation and subsequent safe laboratory testing. However, data on virus inactivation by this procedure are lacking. Here we show the effect of this procedure on diagnostic test results and infectious Ebola virus (EBOV) titers. Methods: Serum and whole-blood samples were treated with 0.1% or 1% sodium dodecyl sulfate (SDS) or 0.1% Triton X-100 and assayed for clinical chemistry and malaria antigen detection. Infectious EBOV titers were determined in SDS-treated plasma and whole blood from EBOV-infected nonhuman primates (NHPs). Infectious titers of EBOV or herpes simplex virus type 1 (HSV-1) in detergents-treated cell culture medium containing various serum concentrations were determined. Results: Laboratory test results were not affected by 0.1% detergent treatment of blood samples, in contrast with 1% SDS treatment. However, 0.1% detergent treatment did not inactivate EBOV in blood samples from infected NHPs. Experiments with cell culture medium showed that virus inactivation by detergents is annulled at physiological serum concentrations. Conclusions: Treatment of blood samples with 0.1% SDS or Triton X-100 does not inactivate EBOV. Inactivation protocols for HFV should be validated with serum and whole blood.
Assuntos
Detergentes/farmacologia , Ebolavirus/efeitos dos fármacos , Soro , Dodecilsulfato de Sódio/farmacologia , Inativação de Vírus/efeitos dos fármacos , Animais , Herpes Simples , Humanos , Laboratórios , Macaca mulatta , OctoxinolRESUMO
Malaria sporozoites must first undergo intrahepatic development before a pathogenic blood-stage infection is established. The success of infection depends on host and parasite factors. In healthy human volunteers undergoing controlled human malaria infection (CHMI), we directly compared three clinical Plasmodium falciparum isolates for their ability to infect primary human hepatocytes in vitro and to drive the production of blood-stage parasites in vivo. Our data show a correlation between the efficiency of strain-specific sporozoite invasion of human hepatocytes and the dynamics of patent parasitemia in study subjects, highlighting intrinsic differences in infectivity among P. falciparum isolates from distinct geographical locales. The observed heterogeneity in infectivity among strains underscores the value of assessing the protective efficacy of candidate malaria vaccines against heterologous strains in the CHMI model.
Assuntos
Malária Falciparum/parasitologia , Parasitemia/parasitologia , Esporozoítos/patogenicidade , Feminino , Hepatócitos/parasitologia , Humanos , Malária Falciparum/sangue , Parasitemia/sangue , Plasmodium falciparum/patogenicidade , Estudos Retrospectivos , VoluntáriosRESUMO
BACKGROUND: Acute kidney injury (AKI) is a frequently encountered complication of imported Plasmodium falciparum infection. Markers of structural kidney damage have been found to detect AKI earlier than serum creatinine-based prediction models but have not yet been evaluated in imported malaria. This pilot study aims to explore the predictive performance of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for AKI in travellers with imported P. falciparum infection. METHODS: Thirty-nine patients with imported falciparum malaria from the Rotterdam Malaria Cohort with available serum and urine samples at presentation were included. Ten of these patients met the criteria for severe malaria. The predictive performance of NGAL and KIM-1 as markers for AKI was compared with that of serum creatinine. RESULTS: Six of the 39 patients (15 %) developed AKI. Serum and urine NGAL and urine KIM-1 were all found to have large areas under the receiver operating characteristics curves (AUROC) for predicting AKI. Urine NGAL was found to have an excellent performance with positive predictive value (PPV) of 1.00 (95 % CI 0.54-1.00), a negative predictive value (NPV) of 1.00 (95 % CI 0.89-1.00) and an AUROC of 1.00 (95 % CI 1.00-1.00). CONCLUSION: A good diagnostic performance of NGAL and KIM-1 for AKI was found. Particularly, urine NGAL was found to have an excellent predictive performance. Larger studies are needed to demonstrate whether these biomarkers are superior to serum creatinine as predictors for AKI in P. falciparum malaria.
Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Receptor Celular 1 do Vírus da Hepatite A/análise , Receptor Celular 1 do Vírus da Hepatite A/sangue , Lipocalina-2/sangue , Lipocalina-2/urina , Malária Falciparum/complicações , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico , ViagemRESUMO
BACKGROUND: Acute kidney injury (AKI) is a known complication of malaria, and is reported to occur in up to 40% of adult patients with a severe Plasmodium falciparum infection in endemic regions. To gain insight in the incidence and risk factors of AKI in imported P. falciparum malaria, a retrospective analysis was performed on a large cohort of mostly non-immune patients with imported P. falciparum malaria. Aiming to include not only severe but also milder forms of renal failure, the KDIGO criteria were used to define AKI. METHODS: Clinical and laboratory data from 485 consecutive cases of imported P. falciparum malaria were extracted from the Rotterdam Malaria Cohort database. Acute kidney injury (AKI) was defined using the KDIGO criteria. Univariate and multivariate logistic regression analyses were used to identify risk factors for AKI. RESULTS: AKI was seen in 39 (8%) of all patients and in 23 (38%) of the 61 patients with severe malaria. Eight patients eventually needed renal replacement therapy (RRT); seven of them already had AKI at presentation. Higher age, higher leucocyte count and thrombocytopaenia were independently-associated with AKI but their positive predictive values were relatively poor. CONCLUSION: AKI was found to be a common complication in adults with imported P. falciparum necessitating RRT in only a small minority of patients. The use of the KDIGO staging allows early recognition of a decline in renal function.