Several Plasmodium vivax relapses after correct primaquine treatment in a patient with impaired cytochrome P450 2D6 function.

BACKGROUND: Plasmodium vivax malaria is characterized by the presence of dormant liver-stage parasites, called hypnozoites, which can cause malaria relapses after an initial attack. Primaquine, which targets liver hypnozoites, must be used in combination with a schizonticidal agent to get the radical cure. However, relapses can sometimes occur in spite of correct treatment, due to different factors such as a diminished metabolization of primaquine. CASE PRESENTATION: In January 2019, a 21 years old woman with residence in Madrid, returning from a trip to Venezuela with clinical symptoms compatible with malaria infection, was diagnosed with vivax malaria. Chloroquine for 3 days plus primaquine for 14 days was the elected treatment. Two months later and after a second trip to Venezuela, the patient presented a second P. vivax infection, which was treated as the previous one. A third P. vivax malaria episode was diagnosed 2 months later, after returning from a trip to Morocco, receiving chloroquine for 3 days but increasing to 28 days the primaquine regimen, and with no more relapses after 6 months of follow up. The genotyping of P. vivax in the three malaria episodes revealed that the same strain was present in the different relapses. Upon confirmation of correct adherence to the treatment, non-description of resistance in the infection area and the highly unlikely re-infection on subsequent trips or stays in Spain, a possible metabolic failure was considered. CYP2D6 encodes the human cytochrome P450 isoenzyme 2D6 (CYP2D6), responsible for primaquine activation. The patient was found to have a CYP2D6*4/*1 genotype, which turns out in an intermediate metabolizer phenotype, which has been related to P. vivax relapses. CONCLUSIONS: The impairment in CYP2D6 enzyme could be the most likely cause of P. vivax relapses in this patient. This highlights the importance of considering the analysis of CYP2D6 gene polymorphisms in cases of P. vivax relapses after a correct treatment and, especially, it should be considered in any study of dosage and duration of primaquine treatment.

Utilidad de la Beta2-transferrina y la proteína Beta-traza en el diagnóstico de fístula de líquido cefalorraquídeo / Beta2-transferrin and Beta-trace protein in the diagnosis of cerebrospinal fluid fistula

Introducción. El diagnóstico precoz de las fístulas de líquido cefalorraquídeo (LCR) minimiza el riesgo de que los pacientes desarrollen graves complicaciones. Una herramienta diagnóstica es demostrar la presencia de LCR en las secreciones nasales, óticas y heridas quirúrgicas mediante el uso de marcadores bioquímicos específicos. El objetivo del trabajo es evaluar la utilidad de la β2-transferrina (β2-Tr) y la proteína β-traza (p-βT) en el diagnóstico de la fístula de LCR. Material y métodos. Se realizó la detección de β2-Tr y la medición de p-βT en 68 muestras de secreciones nasales, óticas y heridas quirúrgicas, procedentes de 54 pacientes con sospecha de presentar una fístula de LCR. El diagnóstico fue confirmado por criterios clínicos y otras pruebas diagnósticas. Se calcularon la sensibilidad y la especificidad diagnóstica, el valor predictivo positivo (VPP) y negativo (VPN). Para la p-βT se obtuvo el punto de corte óptimo mediante un análisis de curva ROC. Resultados. Para la β2-Tr se obtuvo una sensibilidad del 83%, especificidad del 96%, VPP del 95% y VPN del 86%. Para la p-βT, se obtuvo un área bajo la curva de 0,981. Para un punto de corte óptimo de 1,14mg/L, se obtuvo una sensibilidad del 92%, especificidad del 95%, VPP del 96% y VPN del 91%. El punto de corte con un VPN del 100% fue de 0,64mg/L. Conclusiones. La β2-Tr y la p-βT pueden utilizarse como marcadores de la existencia de fístula de LCR por su elevada sensibilidad y especificidad diagnóstica. Se concluye que un valor de p-βT ≥ 1,14mg/L indica fístula de LCR y un valor ≤ 0,64mg/L la descarta. Valores entre 0,64 y 1,14mg/L no son concluyentes y sería necesario realizar la detección de β2-Tr (AU)

Introduction. Early diagnosis of cerebrospinal fluid (CSF) fistula minimizes the risk of severe complications for patients. A diagnostic approach consists in revealing the presence of CSF in nasal, ear, and surgical wound secretions. The aim of this work is to evaluate the usefulness of β2-transferrin (β2-Tr) and β-trace protein (p-βT) as markers for the diagnosis of a CSF fistula. Material and methods. A total of 68 samples of nasal, ear, and surgical wound secretions were taken and analysed from 54 patients with clinical suspicion of a CSF fistula. β2-Tr and p-βT were determined in all fluids. The CSF fistula was diagnosed by clinical criteria and other diagnostic procedures. Sensitivity and specificity, as well as positive (PPV) and negative (NPV) predictive values, were calculated. The optimal cut-off point for p-βT was obtained using a ROC curve analysis. Results. For β2-Tr, a sensitivity of 83%, a specificity of 96%, a PPV of 95% and a NPV of 86% were obtained. For the p-βT ROC curve analysis, the area under the curve was 0.981, with an optimal cut-off value of 1.14mg/L. For this cut-off point, a sensitivity of 92%, a specificity of 95%, a PPV of 96%, and a NPV of 91% were calculated. The p-βT cut-off point obtained for 100% NPV was 0.64mg/L. Conclusions. β2-Tr and p-βT can be used as CSF fistula markers, since both proteins have high sensitivity and specificity diagnostic values. It is concluded that, ≥ 1.14mg/L p-βT values are indicative of CSF fistula, and values ≤ 0.64mg/L rules it out. Values>0.64 and<1.14mg/L are not conclusive, and in these cases it would be necessary to determine β2-Tr (AU)

Infiltración meníngea de linfoma linfoplasmocítico: síndrome de Bing-Neel / Meningeal infiltration by lymphoplasmacytic lymphoma: Bing-Neel syndrome

La macroglobulinemia de Waldenström es un linfoma linfoplasmocítico caracterizado por una proliferación monoclonal de linfocitos B productores de inmunoglobulina M que infiltran la médula ósea. Las manifestaciones neurológicas asociadas a la macroglobulinemia de Waldenström suelen ser debidas al fenómeno de hiperviscosidad o a neuropatías desmielinizantes mediadas por inmunoglobulina M. Cuando la afectación neurológica es debida a la infiltración del sistema nervioso central por las células linfoplasmocitoides, se produce un síndrome denominado de Bing-Neel, con baja prevalencia y variedad de manifestaciones clínicas. Se presenta el caso clínico de una mujer de 76 años con antecedentes de macroglobulinemia de Waldenström, con un cuadro neurológico repentino de alteración del lenguaje y torpeza en la mano derecha. Cabe destacar la relevancia del laboratorio clínico en el diagnóstico del síndrome de Bing-Neel y en el seguimiento del tratamiento (AU)

Waldenström macroglobulinemia is a lymphoplasmacytic lymphoma defined by a monoclonal proliferation of bone marrow infiltrating immunoglobulin M producing B lymphocytes. Neurological simptoms of Waldenström macroglobulinemia are mainly dominated by signs of hyperviscosity and autoimmune neuropathies mediated by immunoglobulin M. Neurological involvement secondary to the infiltration of IgM producing B lymphocytes, is defined as a Bing-Neel syndrome. This syndrome has a low prevalence and the clinical manifestations are variable. The case described is about a 76 year-old female with a history of Waldenström macroglobulinemia, who presents sudden neurological signs such as alteration of spoken language and clumsiness of the right hand. The clinical laboratory has a primary role in the diagnosis of Bing-Neel syndrome and monitoring of the treatment (AU)