Efectos de la malaria gestacional por Plasmodium vivax sobre el estado clínico e inmune en gestantes del Noroccidente de Colombia.

Objetive: The study explored the effects of Plasmodium vivax infection on the balance of pro- versus anti- inflammatory cytokines and chemokines and their relationship with some clinical and epidemiology outcomes. Methods: Thirty-five pregnant women were recruited. Of these, 15 subjects had malaria at delivery (GM+), and 20 had no exposition to infection throughout the pregnancy (GM-) and at delivery. Epidemiological and clinical data were recorded after reviewing the clinical records. At delivery, whole blood from the mother as well as placental tissue was collected. Diagnosis of infection was performed by thick smear and a polymerase chain reaction (PCR). Expression of pro-inflammatory and anti-inflammatory cytokines and chemokines was measured by a real time PCR. Results: The clinical and epidemiological variables explored were similar in both groups, with the exception of gestational age. When comparing the GM+ group with the GM- group, it is clear that although the differences generally are not significant, pro- inflammatory cytokines are elevated in both maternal blood and placental; anti-inflammatory ones are elevated in the mother and reduced in the placenta, and the chemokines are reduced in both compartments, except for MCP-1 which is elevated in all. Conclusion: The results appear to be strongly affected by the small number of women with GM by P. vivax at childbirth. Additional studies are needed with larger groups in this and other regions of the country

Malaria placentaria submicroscópica por Plasmodium vivax o Plasmodium falciparum : histopatología, células inmunitarias y expresión de genes asociados a hipoxia, apoptosis e inflamación

RESUMEN: El efecto de la malaria durante el embarazo ha sido explorado durante varias décadas en África y en los últimos años en América. En Colombia, la condición a menudo no se detecta y la infección submicroscópica se ha confirmado en alrededor del 50% de las mujeres residentes en zonas de malaria endémica, pero aún es desconocido el efecto que tienen la infección plasmodial placentaria sobre la regulación de la respuesta inmune y el daño placentario

The Economics of Vivax Malaria Treatment

The control and eventual elimination of malaria will require widescale adoption of strategies to ensure early diagnosis and highly effective treatment of infected individuals. In Plasmodium vivax, multiple relapse episodes can only be averted by treating the dormant liver stage of the parasite life cycle - a strategy known as radical cure. This thesis aims to investigate key factors determining treatment-seeking behaviour and costs associated with vivax malaria, how these influence healthcare decisions, the cost-effectiveness of screening tests and treatments for radical cure, and the cost-benefit implications of their global implementation. Treatment-seeking behaviour, assessed in Papua, Indonesia, demonstrated that household costs per person seeking treatment for vivax malaria were similar to those for falciparum malaria. Switching from ineffective to effective malaria treatment in the public sector improved the behaviour of patients and both public and private healthcare providers. Diagnostic strategies were investigated on the Thai-Myanmar border, where screening for glucose-6-phosphate-dehydrogenase (G6PD) deficiency prior to radical cure reduced the disease burden while being a cost-effective option for healthcare providers that do not use radical cure and a potentially cost-saving alternative where primaquine is prescribed without screening. The costs of implementing G6PD screening were collected in three countries, and highlighted that RDTs consistently reduced costs as compared to the widely-used fluorescent spot test. Across four countries, the indirect cost due to lost productivity was the largest cost component for households of patients with vivax malaria. After combining provider and patient costs with case estimates, the global economic burden of vivax malaria was estimated to be US$330 million per year. Adopting a policy of screening for G6PD deficiency with delivery of highly effective radical cure was projected to save US$45 million. P. vivax malaria causes a large economic burden that can be reduced substantially by delivering safe and effective radical cure

Inmunomodulación en malaria asociada al embarazo y su efecto en la respuesta materno-neonatal a antígenos vacunales

RESUMEN: Introducción: la malaria asociada al embarazo (MAE) es común en regiones endémicas, en especial las infecciones submicroscópicas, que por ser asintomáticas no son tratadas. Es importante entender el impacto de estas infecciones con bajas cargas parasitarias en las poblaciones afectadas. Las infecciones asintomáticas crónicas favorecen la persistencia del parásito, especialmente en áreas donde las condiciones ecoepidemiológicas óptimas para para la transmisión del parásito fluctúan. En infecciones crónicas, la persistencia del estímulo antigénico cambia los perfiles transcripcionales de mediadores inmunes y promueve la constante regulación inmune, incluyendo el aumento de células T reguladoras. Estas alteraciones del sistema inmune pueden comprometer la respuesta a la vacunación de rutina. Objetivo: evaluar el efecto de la MAE sobre la respuesta inmune materna y neonatal frente a vacunas incluidas en el Plan Ampliado de Inmunización (PAI) colombiano. Metodología: en gestantes con 1) infección plasmodial submicroscópica en el parto, 2) historia de malaria durante el embarazo y 3) sin infección plasmodial, así como en sus lactantes de 6 meses, fue cuantificada la expresión de diferentes mediadores inmunes en sangre periférica materna, tejido placentario y sangre periférica del lactante. Los niveles de anticuerpos contra toxoide tetánico (TT) y rotavirus (RV) fueron cuantificados en sangre periférica materna, de cordón y de lactantes; mientras que los niveles de anticuerpos contra hepatitis B (HB), tres polisacáridos (PSC) de neumococo y BCG, así como la respuesta inmune celular frente a BCG, fueron cuantificados en sangre periférica de lactantes. Resultados: la MAE se asoció con disminución en los niveles de anticuerpos antiTT en madres, así como con disminución en los niveles de anticuerpos antiTT, antiRV, antiBCG, antiPSC y en la respuesta inmune celular frente a BCG en los lactantes, asociadas a la vacunación. Además, la MAE se asoció con defectos en la inmunidad pasiva transplacentaria encontrándose una disminución en las concentraciones de IgG especìficas frente a TT. Se observaron alteraciones en la expresión transcripcional de genes como Foxp3, TNF-RII, IL-10, IL-13, CD-163, CD-40 e IFN-γ, asociados con regulación, activación y función de poblaciones de células T reguladoras, macrófagos M2 y células Th1 y Th2 en sangre periférica materna y del lactante y en tejido placentario. Conclusión: la MAE modifica el perfil transcripcional de mediadores inmunes en sangre periférica materna y del lactante, así como en el tejido placentario; además, la MAE se asocia con la alteración de la respuesta inmune frente algunas vacunas aplicadas a gestantes y lactantes colombianos, así como con la transferencia transplacentaria de anticuerpos (inmunidad pasiva).ABSTRACT: Introduction: Pregnancy-associated malaria (PAM) is common in endemic areas, in particular submicroscopic infections that are asymptomatic, and as result, are not treated. Therefore, it is important to understand the impact of these low-level infections in the affected populations. The asymptomatic chronic infections are advantageous for parasite persistence, particularly in areas where the optimal eco-epidemiological conditions for parasite transmission fluctuate. In chronic infections, the persistence of the antigenic stimulus changes the expression of immune mediators and promotes constant immune regulation, including increases in regulatory T cell populations. These alterations of the immune system could compromise the response to routine vaccination. Objective: To evaluate the effects of PAM on the maternal and neonatal immune response to the vaccines included in the in Colombian national immunization plan. Methodology: The expression of different immune mediators in maternal and infant peripheral blood and in placental tissue was quantified in pregnant women with 1) submicroscopic plasmodial infection at delivery, 2) history of malaria during pregnancy, and 3) without plasmodial infection, as well as their infants aged 6 months. Levels of antibodies against tetanus toxoid (TT) and rotavirus (RV) were quantified in maternal, cord and infant peripheral bloods; meanwhile the levels of antibodies against hepatitis B (HB), three polysaccharides (PSC) of pneumococcus, and BCG, as well as the cellular immune response against BCG were quantified in infant peripheral blood.Results: PAM was associated with decreased levels of antiTT in mothers, as well as decreased levels of antiTT, antiRV, antiBCG, antiPSC, and cellular immune response against BCG in infants. In addition, PAM was associated with decreased transplacental passive immunity against TT. Transcriptional alterations of immune mediators associated with regulation, activation and function of T regulator cells, macrophages M2 and Th1 and Th2 cells such as Foxp3, TNF-RII, IL-10, IL-13, CD-163, CD-40 and IFN-γ were observed in maternal and infant peripheral bloods as well as in placental tissue. Conclusion: PAM modified the transcriptional profile of immune mediators in both maternal and infant peripheral blood, as well as in placental tissue. These changes interfered with the development of an adequate immune response against some vaccines applied to Colombian pregnant women and infants, as well as with the transplacental transference of antibodies (neonatal passive immunity)

The burden of malaria in pregnancy in Madhya Pradesh, India

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Ultrasensitive detection of toxocara canis excretory-secretory antigens by a nanobody electrochemical magnetosensor assay.

peer reviewedHuman Toxocariasis (HT) is a zoonotic disease caused by the migration of the larval stage of the roundworm Toxocara canis in the human host. Despite of being the most cosmopolitan helminthiasis worldwide, its diagnosis is elusive. Currently, the detection of specific immunoglobulins IgG against the Toxocara Excretory-Secretory Antigens (TES), combined with clinical and epidemiological criteria is the only strategy to diagnose HT. Cross-reactivity with other parasites and the inability to distinguish between past and active infections are the main limitations of this approach. Here, we present a sensitive and specific novel strategy to detect and quantify TES, aiming to identify active cases of HT. High specificity is achieved by making use of nanobodies (Nbs), recombinant single variable domain antibodies obtained from camelids, that due to their small molecular size (15kDa) can recognize hidden epitopes not accessible to conventional antibodies. High sensitivity is attained by the design of an electrochemical magnetosensor with an amperometric readout with all components of the assay mixed in one single step. Through this strategy, 10-fold higher sensitivity than a conventional sandwich ELISA was achieved. The assay reached a limit of detection of 2 and15 pg/ml in PBST20 0.05% or serum, spiked with TES, respectively. These limits of detection are sufficient to detect clinically relevant toxocaral infections. Furthermore, our nanobodies showed no cross-reactivity with antigens from Ascaris lumbricoides or Ascaris suum. This is to our knowledge, the most sensitive method to detect and quantify TES so far, and has great potential to significantly improve diagnosis of HT. Moreover, the characteristics of our electrochemical assay are promising for the development of point of care diagnostic systems using nanobodies as a versatile and innovative alternative to antibodies. The next step will be the validation of the assay in clinical and epidemiological contexts