Clinical and epidemiological aspects of complicated malaria in Colombia, 2007–2013

Additional file 2. Annual percentage change (APC) for complicated malaria, stratified by age

Caracterización de la transmisión de Plasmodium malariae en cuatro regiones colombianas endémicas de malaria

The number of cases of Plasmodium malariae in Colombia shows a percent distribution concentrated in the Pacific Coast where it reaches 95% compared with 5% of casual cases in other areas of the country. Valle del Cauca region presents 85% of the cases, while 15% of the remaining cases correspond to Chocó and Cauca regions. Zacarias has 70% of the cases, followed by 30% in the areas of Citronela, Puerto Merizalde, Anchicayá, Meseta and Boca Dagua. An active search for malaria cases in Zacarias (Buenaventura) using thick smears demonstrated a prevalence of 9.1% of P malariae cases. Blood samples of gametocyte carriers were used to feed Anopheles albimanus mosquitoes and the reproduction of the sporogonic malaria cycle was successfully achieved. The presence of specific antibodies to P malariae was analyzed in 242 plasma samples obtained from individuals living in Zacarías and Punta Soldado (Valle), as well as in Pizarro (Chocó). It was found that 9.1% of the samples had specific antibodies as determined by an Elisa technique using a P malariae crude antigen preparation, whereas 42.1% of the samples showed specific antibodies when Elisa was performed using the (NAAG),synthetic peptide derived from the circumsporozoite (CS) protein. Samples from Bajo Guaviare region displayed a prevalence of 16% of anti-(NAAG), peptide antibodies. These results suggest that Zacarias on the Pacific Coast is the main focus of P malariae cases, but also that transmission of this parasite species coud occur in other regions of Colombia not yet reported.En Colombia, la detección del número de casos de infección por Plasmodium malariae muestra una distribución porcentual focalizada en la Costa Pacifica, donde alcanza un 95% en contraste con el 5% de casos más esporádicos que se presentan en otras regiones. El departamento del Valle del Cauca aporta el 85% y el 15% restante corresponde a los departamentos de Chocó y Cauca. La región de Zacarias aporta el 70% seguida por las regiones de Citronela, Puerto Merizalde, Anchicayá, Meseta y Boca Dagua, regiones que conjuntamente contribuyen con el 30%. En un estudio transversal, realizado en 1997 mediante gota gruesa en la población de Zacarías, se encontró una frecuencia de 9,1% de casos de P malariae. Se usaron muestras de donantes infectados con gametocitos de P malariae para alimentar mosquitos Anopheles albimanus y reproducir exitosamente el ciclo ex vivo. Se analizaron 242 plasmas obtenidos de individuos de Zacarias y Punta Soldado (Valle) y Pizarro (Chocó) para determinar la presencia de anticuerpos especificos para P malariae. Se encontró que el 9,1% contenía anticuerpos identificables por la técnica de Elisa contra una preparación cruda de antígeno y que el 42,1% presentaba anticuerpos contra el péptido sintético (NAAG), derivado de la proteína circumesporozoíto (CS). En 50 muestras analizadas de la región del Bajo Guaviare, se encontró presencia de anticuerpos contra (NAAG), en el 16%. Los resultados de este estudio muestran una gran delimitación de los casos de la Costa Pacífica, al área de Zacarias, indicando también la posible presencia de este parásito en otras regiones del paÍs

The Challenge of Assessing Microcephaly in the Context of the Zika Virus Epidemic

The present article examines the impact of the current limitations of the microcephaly definition in the context of the Zika virus outbreak. It highlights its dependence on the method used for determining gestational age and other anthropometric parameters, and includes original results of prevalence of microcephaly in four countries from two different continents (Mozambique, Brazil, Guatemala and Colombia). Alternative definitions of microcephaly are proposed to allow the identification of true cases of microcephaly in a more accurate manner

A Multi-Stage Plasmodium vivax Malaria Vaccine Candidate Able to Induce Long-Lived Antibody Responses Against Blood Stage Parasites and Robust Transmission-Blocking Activity

Malaria control and interventions including long-lasting insecticide-treated nets, indoor residual spraying, and intermittent preventative treatment in pregnancy have resulted in a significant reduction in the number of Plasmodium falciparum cases. Considerable efforts have been devoted to P. falciparum vaccines development with much less to P. vivax. Transmission-blocking vaccines, which can elicit antibodies targeting Plasmodium antigens expressed during sexual stage development and interrupt transmission, offer an alternative strategy to achieve malaria control. The post-fertilization antigen P25 mediates several functions essential to ookinete survival but is poorly immunogenic in humans. Previous clinical trials targeting this antigen have suggested that conjugation to a carrier protein could improve the immunogenicity of P25. Here we report the production, and characterization of a vaccine candidate composed of a chimeric P. vivax Merozoite Surface Protein 1 (cPvMSP1) genetically fused to P. vivax P25 (Pvs25) designed to enhance CD4+ T cell responses and its assessment in a murine model. We demonstrate that antibodies elicited by immunization with this chimeric protein recognize both the erythrocytic and sexual stages and are able to block the transmission of P. vivax field isolates in direct membrane-feeding assays. These findings provide support for the continued development of multi-stage transmission blocking vaccines targeting the life-cycle stage responsible for clinical disease and the sexual-stage development accountable for disease transmission simultaneously

Blood cytokine, chemokine and growth factor profiling in a cohort of pregnant women from tropical countries

The immune status of women changes during and after pregnancy, differs between blood compartments at delivery and is affected by environmental factors particularly in tropical areas endemic for multiple infections. We quantified the plasma concentration of a set of thirty-one TH1, TH2, TH17 and regulatory cytokines, pro-inflammatory and anti-inflammatory cytokines and chemokines, and growth factors (altogether biomarkers), in a cohort of 540 pregnant women from five malaria-endemic tropical countries. Samples were collected at recruitment (first antenatal visit), delivery (periphery, cord and placenta) and postpartum, allowing a longitudinal analysis. We found the lowest concentration of biomarkers at recruitment and the highest at postpartum, with few exceptions. Among them, IL-6, HGF and TGF-β had the highest levels at delivery, and even higher concentrations in the placenta compared to peripheral blood. Placental concentrations were generally higher than peripheral, except for eotaxin that was lower. We also compared plasma biomarker concentrations between the tropical cohort and a control group from Spain at delivery, presenting overall higher biomarker levels the tropical cohort, particularly pro-inflammatory cytokines and growth factors. Only IL-6 presented lower levels in the tropical group. Moreover, a principal component analysis of biomarker concentrations at delivery showed that women from Spain grouped more homogenously, and that IL-6 and IL-8 clustered together in the tropical cohort but not in the Spanish one. Plasma cytokine concentrations correlated with Plasmodium antibody levels at postpartum but not during pregnancy. This basal profiling of immune mediators over gestation and in different compartments at delivery is important to subsequently understand response to infections and clinical outcomes in mothers and infants in tropical areas

Microsatellite Genotyping of Plasmodium vivax Isolates from Pregnant Women in Four Malaria Endemic Countries

Plasmodium vivax is the most widely distributed human parasite and the main cause of human malaria outside the African continent. However, the knowledge about the genetic variability of P. vivax is limited when compared to the information available for P. falciparum. We present the results of a study aimed at characterizing the genetic structure of P. vivax populations obtained from pregnant women from different malaria endemic settings. Between June 2008 and October 2011 nearly 2000 pregnant women were recruited during routine antenatal care at each site and followed up until delivery. A capillary blood sample from the study participants was collected for genotyping at different time points. Seven P. vivax microsatellite markers were used for genotypic characterization on a total of 229 P. vivax isolates obtained from Brazil, Colombia, India and Papua New Guinea. In each population, the number of alleles per locus, the expected heterozygosity and the levels of multilocus linkage disequilibrium were assessed. The extent of genetic differentiation among populations was also estimated. Six microsatellite loci on 137 P. falciparum isolates from three countries were screened for comparison. The mean value of expected heterozygosity per country ranged from 0.839 to 0.874 for P. vivax and from 0.578 to 0.758 for P. falciparum. P. vivax populations were more diverse than those of P. falciparum. In some of the studied countries, the diversity of P. vivax population was very high compared to the respective level of endemicity. The level of inter-population differentiation was moderate to high in all P. vivax and P. falciparum populations studied

Naturally Acquired Binding-Inhibitory Antibodies to Plasmodium vivax Duffy Binding Protein in Pregnant Women Are Associated with Higher Birth Weight in a Multicenter Study

A vaccine to eliminate malaria would need a multi-stage and multi-species composition to achieve robust protection, but the lack of knowledge about antigen targets and mechanisms of protection precludes the development of fully efficacious malaria vaccines, especially for Plasmodium vivax (Pv). Pregnant women constitute a risk population who would greatly benefit from a vaccine preventing the adverse events of Plasmodium infection during gestation. We hypothesized that functional immune responses against putative targets of naturally acquired immunity to malaria and vaccine candidates will be associated with protection against malaria infection and/or poor outcomes during pregnancy. We measured (i) IgG responses to a large panel of Pv and Plasmodium falciparum (Pf) antigens, (ii) the capacity of anti-Pv ligand Duffy binding protein (PvDBP) antibodies to inhibit binding to Duffy antigen, and (iii) cellular immune responses to two Pv antigens, in a subset of 1,056 pregnant women from Brazil, Colombia, Guatemala, India, and Papua New Guinea (PNG). There were significant intraspecies and interspecies correlations for most antibody responses (e.g., PfMSP119 versus PfAMA1, Spearman's rho = 0.81). Women from PNG and Colombia had the highest levels of IgG overall. Submicroscopic infections seemed sufficient to boost antibody responses in Guatemala but not antigen-specific cellular responses in PNG. Brazil had the highest percentage of Duffy binding inhibition (p-values versus Colombia: 0.040; Guatemala: 0.047; India: 0.003, and PNG: 0.153) despite having low anti-PvDBP IgG levels. Almost all antibodies had a positive association with present infection, and coinfection with the other species increased this association. Anti-PvDBP, anti-PfMSP1, and anti-PfAMA1 IgG levels at recruitment were positively associated with infection at delivery (p-values: 0.010, 0.003, and 0.023, respectively), suggesting that they are markers of malaria exposure. Peripheral blood mononuclear cells from Pv-infected women presented fewer CD8+IFN-gamma+ T cells and secreted more G-CSF and IL-4 independently of the stimulus used in vitro. Functional anti-PvDBP levels at recruitment had a positive association with birth weight (difference per doubling antibody levels: 45 g, p-value: 0.046). Thus, naturally acquired binding-inhibitory antibodies to PvDBP might confer protection against poor outcomes of Pv malaria in pregnancy