Prospective study of malaria in pregnancy, placental and congenital malaria in Northwest Colombia.

BACKGROUND: Pregnancy Associated Malaria (PAM) include malaria in pregnancy (MiP), placental malaria (PM), and congenital malaria (CM). The evidence available in Colombia on PAM focuses on one of the presentations (MiP, PM or CM), and no study longitudinally analyses the infection from the pregnant woman, passing through the placenta, until culminating in the newborn. This study determined the frequency of MiP, PM, and CM caused by Plasmodium vivax, Plasmodium falciparum, or mixed infections, according to Thick Blood Smear (TBS) and quantitative Polymerase Chain Reaction (qPCR). Identifying associated factors of PAM and clinical-epidemiological outcomes in northwestern Colombia. METHODS: Prospective study of 431 pregnant women, their placenta, and newborns registered in the data bank of the research Group "Salud y Comunidad César Uribe Piedrahíta" which collected information between 2014 and 2020 in endemic municipalities of the departments of Córdoba and Antioquia. The frequency of infection was determined with 95% confidence intervals. Comparisons were made with the Chi-square test, Student t-test, prevalence ratios, and control for confounding variables by log-binomial regression. RESULTS: The frequency of MiP was 22.3% (4.6% using TBS), PM 24.8% (1.4% using TBS), and CM 11.8% (0% using TBS). Using TBS predominated P. vivax. Using qPCR the proportions of P. vivax and P. falciparum were similar for MiP and PM, but P. falciparum predominated in CM. The frequency was higher in nulliparous, and women with previous malaria. The main clinical effects of PAM were anaemia, low birth weight, and abnormal APGAR score. CONCLUSIONS: The magnitude of infections was not detected with TBS because most cases were submicroscopic (TBS-negative, qPCR-positive). This confirmed the importance of improving the molecular detection of cases. PAM continue being underestimated in the country due to that in Colombia the control programme is based on TBS, despite its outcomes on maternal, and congenital health.

Social determination of malaria in pregnancy in Colombia: a critical ethnographic study.

BACKGROUND: The meanings and experiences related to malaria in pregnancy (MiP) and its processes of social determination of health (PSDH) have not been reported in the world scientific literature. The objective was to understand the meanings and experiences of MiP, and to explain their PSDH in an endemic area from Colombia, 2022. METHODS: Critical ethnography with 46 pregnant women and 31 healthcare workers. In-depth and semi-structured interviews, focus group discussions, participant and non-participant observations, and field diaries were applied. A phenomenological-hermeneutic analysis, saturation and triangulation was carried out. The methodological rigor criteria were reflexivity, credibility, auditability, and transferability. RESULTS: At the singular level, participants indicated different problems in antenatal care and malaria control programmes, pregnant women were lacking knowledge about MiP, and malaria care was restricted to cases with high obstetric risk. Three additional levels that explain the PSDH of MiP were identified: (i) limitations of malaria control policies, and health-system, geographic, cultural and economic barriers by MiP diagnosis and treatment; (ii) problems of public health programmes and antenatal care; (iii) structural problems such as monetary poverty, scarcity of resources for public health and inefficiency in their use, lacking community commitment to preventive actions, and breach of institutional responsibilities of health promoter entity, municipalities and health services provider institutions. CONCLUSION: Initiatives for MiP control are concentrated at the singular level, PDSH identified in this research show the need to broaden the field of action, increase health resources, and improve public health programmes and antenatal care. It is also necessary to impact the reciprocal relationships of MiP with economic and cultural dimensions, although these aspects are increasingly diminished with the predominance and naturalization of neoliberal logic in health.

Clinical and Parasitological Profiles of Gestational, Placental and Congenital Malaria in Northwestern Colombia.

This study compared the clinical-parasitological profiles of gestational (GM), placental (PM), and congenital (CM) malaria in northwestern Colombia. A cross-sectional study with 829 pregnant women, 549 placentas, and 547 newborns was conducted. The frequency of GM was 35.8%, PM 20.9%, and CM 8.5%. P. vivax predominated in GM; in PM, the proportion of P. vivax and P. falciparum was similar; in CM, P. falciparum predominated. The main clinical findings were headache (49%), anemia (32%), fever (24%), and musculoskeletal pain (13%). The clinical manifestations were statistically higher in P. vivax infections. In submicroscopic GM (positive with qPCR and negative with thick blood smear), the frequency of anemia, sore throat, and a headache was statistically higher compared with pregnant women without malaria. GM, PM, and CM reduce birth weight and head circumference. In Colombia, this is the first research on the clinical characteristics of GM, PM, and CM; contrary to evidence from other countries, P. vivax and submicroscopic infections are associated with clinical outcomes.

A systematic review of mixed studies on malaria in Colombia 1980-2022: what the "bifocal vision" discovers.

Mixed methods are essential in public health research and malaria control, because they allow grasping part of the complexity and diversity of the factors that determine health-disease. This study analyzes the mixed studies on malaria in Colombia, 1980-2022, through a systematic review in 15 databases and institutional repositories. The methodological quality was assessed with Mixed Methods Appraisal Tool (MMAT), STrengthening the Reporting of OBservational studies in Epidemiology (STROBE), and Standards for Reporting Qualitative Research (SRQR). The qualitative and quantitative findings were grouped into a four-level hierarchical matrix. The epidemiological profile of malaria morbidity, from traditional epidemiology, has been sustained by environmental problems, armed conflict, individual risk behaviors, and low adherence to recommendations from health institutions. However, the qualitative component reveals deeper causes that are less studied, of greater theoretical complexity, and that reflect challenges to design and implement health interventions, such as socioeconomic and political crises, poverty, and the neoliberal orientation in the malaria control policy; the latter reflected in the change in the role of the State, the fragmentation of control actions, the predominance of insurance over social assistance, the privatization of the provision of health services, the individualistic and economistic predominance of health, and low connection with popular tradition and community initiatives. The above confirms the importance of expanding mixed studies as a source of evidence to improve malaria research and control models in Colombia, and to identify the underlying causes of the epidemiological profile.

Diagnostic Accuracy of a Thick Blood Smear Compared to qPCR for Malaria Associated with Pregnancy in Colombia.

This study aimed to evaluate the accuracy of the thick blood smear (TBS) versus quantitative polymerase chain reaction (qPCR) for the diagnosis of malaria associated with pregnancy (MAP) caused by P. falciparum or P. vivax in Colombia in its gestational malaria (GM), placental malaria (PM), and congenital malaria (CM) forms as well as to compare its accuracy in different subgroups of pregnant women according to the presence of fever, anemia and a history of malaria. This was a diagnostic evaluation of 829 pregnant women, 579 placentas, 381 umbilical cord samples, and 221 neonatal peripheral blood samples. Accuracy was evaluated based on the parameters of sensitivity, specificity, predictive values, likelihood ratios, and validity index, with their 95% confidence intervals. The frequency of GM was 36% (n = 297/829), PM 27% (n = 159/579), and CM 16.5% (n = 63/381) in umbilical cord samples and 2% (n = 5/221) in neonatal peripheral blood samples. For GM, the sensitivity was 55%, with higher rates in those infected with P. vivax (68%), with a history of malaria (69%), and with fever (96%). These three subgroups presented the best results in terms of the negative likelihood ratio and validity index. For PM, sensitivity was 8%; in subgroup analyses in terms of species, symptomatology (anemia and fever), and history of malaria, it was 1-18%, and the negative likelihood ratio was >0.80 in all subgroups. No false positives were recorded in any of the subgroups. The TBS did not detect any cases of CM. This study found the TBS yielded satisfactory results in terms of diagnosing GM for P. vivax, pregnant women with previous malaria and febrile. It also showed that the TBS is not useful for diagnosing PM and CM. It is necessary to conduct surveillance of MAP with molecular methods in in groups where TBS is deficient (asymptomatic GM, P. falciparum, and pregnant women without history of malaria) to optimize the timely treatment of PM and CM, avoid the deleterious effects of MAP and achieve the malaria elimination goals in Colombia.

Systematic review of the diagnostic accuracy of thick smear compared to polymerase chain reaction for pregnancy-associated malaria, 2010-2022. / Revisión sistemática de la exactitud diagnóstica de la gota gruesa en comparación con la reacción en cadena de la polimerasa para malaria asociada al embarazo, 2010-2022.

OBJECTIVE.: To evaluate the accuracy of thick smear (TS) versus quantitative polymerase chain reaction (PCR) for pregnancy-associated malaria (PAM). MATERIALS AND METHODS.: We carried out a systematic review of diagnostic tests in nine databases. Methodological quality was evaluated with QUADAS. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the ROC curve were estimated. Heterogeneity was determined with the Der Simonian-Laird Q method and uncertainty with the weighted percentage of each study on the overall result. RESULTS.: We included 10 studies with 5691 pregnant women, 1415 placentas and 84 neonates. In the studies with nested PCR (nPCR) and quantitative PCR (qPCR) as the standard, the diagnostic accuracy results were statistically similar, with very low sensitivity (50 and 54%, respectively), high specificity (99% in both cases), high PLR and poor NLR. When nPCR was used, the DOR was 162 (95%CI=66-401) and the area under the ROC curve was 95%, while with qPCR it was 231 (95%CI=27-1951) and 78%, respectively. CONCLUSIONS.: We demonstrated that research on the diagnostic accuracy of TS in PAM is limited. Microscopy showed poor performance in the diagnosis of asymptomatic or low parasitemia infections, which reinforces the importance of implementing other types of techniques for the follow-up and control of malaria infections in pregnant women, in order to achieve the control and possible elimination of PAM.

OBJETIVOS.: Evaluar la exactitud de gota gruesa (GG) frente a la reacción en cadena de la polimerasa (PCR) cuantitativa para la malaria asociada al embarazo (MAE). MATERIALES Y MÉTODOS.: Se realizó una revisión sistemática de pruebas diagnósticas en nueve bases de datos. Se evaluó la calidad metodológica con QUADAS. Se estimó sensibilidad, especificidad, cociente de probabilidad positivo (CPP) y negativo (CPN), razón de odds diagnóstica (ORD) y área bajo la curva ROC. Se determinó la heterogeneidad con el estadístico Q de Der Simonian-Laird y la incertidumbre con el porcentaje de peso de cada estudio sobre el resultado global. RESULTADOS.: Se incluyeron diez estudios con 5691 gestantes, 1415 placentas y 84 neonatos. En los estudios con nPCR (PCR anidada) y qPCR (PCR cuantitativa) como estándar, los resultados de exactitud diagnóstica fueron estadísticamente similares, con sensibilidad muy baja (50 y 54%, respectivamente), alta especificidad (99% en ambos casos), alto CPP y deficiente CPN. Usando nPCR la OR diagnóstica fue 162 (IC95%=66-401) y el área bajo la curva ROC fue 95%, mientras que con qPCR fueron 231 (IC95%=27-1951) y 78%, respectivamente. CONCLUSIONES.: Mediante un protocolo exhaustivo se demostró el bajo desarrollo de investigaciones sobre la exactitud diagnóstica de la GG en MAE. Se demostró que la microscopía tiene un desempeño deficiente para el diagnóstico de infecciones asintomáticas o de baja parasitemia, lo que afianza la importancia de implementar otro tipo de técnicas en el seguimiento y control de las infecciones por malaria en las gestantes, con el fin de lograr el control y posible eliminación de la MAE.

Effect of Plasmodium Infection during Pregnancy on Passive Neonatal Immunity against Tetanus Toxoid and Rotavirus.

Passive immunity acquired through transplacental IgG transport is essential to protect infants against pathogens as childhood vaccination programs begins. Diarrhea caused by rotavirus and neonatal tetanus are common and potentially fatal childhood infections that can be prevented by transplacental IgG. However, it is not known whether maternal infections in pregnancy can reduce the transfer of these antibodies to the fetus. This study evaluated the effect of submicroscopic Plasmodium infection during pregnancy on the transfer of maternal IgG antibodies against rotavirus (anti-RV) and tetanus toxoid (anti-TT) to newborns of pregnant women residing in Puerto Libertador and Tierralta, Colombia. Expression of different immune mediators and levels of IgG against rotavirus and tetanus toxoid were quantified in pregnant women with and without Plasmodium infection during pregnancy. Submicroscopic infection at the time of delivery was associated with a cord-to-maternal ratio (CMR) > 1 for anti-RV and < 1 for anti-TT IgG, as well as with an increase in the expression of immune mediators of inflammation (IFN-γ), anti-inflammation (IL-10, TGF-ß), and regulation (FoxP3, CTLA-4). When compared by species, these findings (CMR > 1 for anti-RV and < 1 for anti-TT IgG) were conserved in submicroscopic Plasmodium vivax infections at delivery. The impact of Plasmodium infections on neonatal susceptibility to other infections warrants further exploration.

Revisión sistemática de la exactitud diagnóstica de la gota gruesa en comparación con la reacción en cadena de la polimerasa para malaria asociada al embarazo, 2010-2022 / Systematic review of the diagnostic accuracy of thick smear compared to polymerase chain reaction for pregnancy-associated malaria, 2010-2022

RESUMEN Objetivos. Evaluar la exactitud de gota gruesa (GG) frente a la reacción en cadena de la polimerasa (PCR) cuantitativa para la malaria asociada al embarazo (MAE). Materiales y métodos. Se realizó una revisión sistemática de pruebas diagnósticas en nueve bases de datos. Se evaluó la calidad metodológica con QUADAS. Se estimó sensibilidad, especificidad, cociente de probabilidad positivo (CPP) y negativo (CPN), razón de odds diagnóstica (ORD) y área bajo la curva ROC. Se determinó la heterogeneidad con el estadístico Q de Der Simonian-Laird y la incertidumbre con el porcentaje de peso de cada estudio sobre el resultado global. Resultados. Se incluyeron diez estudios con 5691 gestantes, 1415 placentas y 84 neonatos. En los estudios con nPCR (PCR anidada) y qPCR (PCR cuantitativa) como estándar, los resultados de exactitud diagnóstica fueron estadísticamente similares, con sensibilidad muy baja (50 y 54%, respectivamente), alta especificidad (99% en ambos casos), alto CPP y deficiente CPN. Usando nPCR la OR diagnóstica fue 162 (IC95%=66-401) y el área bajo la curva ROC fue 95%, mientras que con qPCR fueron 231 (IC95%=27-1951) y 78%, respectivamente. Conclusiones. Mediante un protocolo exhaustivo se demostró el bajo desarrollo de investigaciones sobre la exactitud diagnóstica de la GG en MAE. Se demostró que la microscopía tiene un desempeño deficiente para el diagnóstico de infecciones asintomáticas o de baja parasitemia, lo que afianza la importancia de implementar otro tipo de técnicas en el seguimiento y control de las infecciones por malaria en las gestantes, con el fin de lograr el control y posible eliminación de la MAE.

ABSTRACT Objective. To evaluate the accuracy of thick smear (TS) versus quantitative polymerase chain reaction (PCR) for pregnancy-associated malaria (PAM). Materials and methods. We carried out a systematic review of diagnostic tests in nine databases. Methodological quality was evaluated with QUADAS. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the ROC curve were estimated. Heterogeneity was determined with the Der Simonian-Laird Q method and uncertainty with the weighted percentage of each study on the overall result. Results. We included 10 studies with 5691 pregnant women, 1415 placentas and 84 neonates. In the studies with nested PCR (nPCR) and quantitative PCR (qPCR) as the standard, the diagnostic accuracy results were statistically similar, with very low sensitivity (50 and 54%, respectively), high specificity (99% in both cases), high PLR and poor NLR. When nPCR was used, the DOR was 162 (95%CI=66-401) and the area under the ROC curve was 95%, while with qPCR it was 231 (95%CI=27-1951) and 78%, respectively. Conclusions. We demonstrated that research on the diagnostic accuracy of TS in PAM is limited. Microscopy showed poor performance in the diagnosis of asymptomatic or low parasitemia infections, which reinforces the importance of implementing other types of techniques for the follow-up and control of malaria infections in pregnant women, in order to achieve the control and possible elimination of PAM.

A Retrospective Review on Severe Malaria in Colombia, 2007-2020.

BACKGROUND: Knowledge of severe malaria (SM) or complicated malaria is insufficient in all its components. The least known type is the one associated with Plasmodium vivax, compared to that caused by P. falciparum. The aim of this study was to provide a general overview of epidemiological information about the burden of SM, obtained from the National Public Health Surveillance System (SIVIGILA) for the period 2007-2020 in Colombia. METHODS: A descriptive, retrospective, and cross-sectional study of secondary information was performed via SIVIGILA. RESULTS: There were 9881 SM cases among 1,060,950 total malaria cases in Colombia in 2007-2020: 9.31 SM cases per 1000 malaria cases. During this period, there were 7145 SM cases due to the following species: Plasmodium vivax, 57.6%; P. falciparum, 38.6%; severe mixed malaria, 3.2%; and P. malariae, 0.6%. The most compromised organ systems are the hematological system (54.9%), the liver (9.1%), the kidneys (4.2%), the lungs (1.9%) and the brain (1.6%). CONCLUSIONS: There has been a reduction in malaria incidence in Colombia in the last 10-15 years, but there has also been a strong increase in SM incidence. We suggest emphasizing the prevention of the onset of severe malaria, with the early and accurate diagnosis of plasmodial infection.

Frequency of gestational malaria and maternal-neonatal outcomes, in Northwestern Colombia 2009-2020.

Research on Gestational Malaria (GM) is scarce in America's. In the few available studies in Colombia, the analysis of immunological or parasitological aspects predominates, with few analyzes of epidemiological aspects. The objectives were to determine the frequency of GM and submicroscopic infections (positive with PCR and negative with thick blood smears), to identify obstetric and malaria history associated with GM, and to describe maternal and neonatal outcomes associated with GM, in northwestern Colombia. A retrospective study with records of 825 pregnant women was conducted. qPCR and thick blood smear were performed. Frequencies were determined with 95% confidence intervals. Comparisons were made with the Chi-square test, Mann-Whitney U test, and prevalence ratios adjusted in a log-binomial model. The frequency of GM was 35.8% (95% CI 32.4-39.1) of submicroscopic infection was 16.2% (95% CI 13.7-18.8). According to the multivariable model, the subgroups with the highest frequency of GM were pregnant women without healthcare coverage (32.3%), in the third trimester of pregnancy (30.5%), nulliparous (35.6%), and with a previous diagnosis of malaria in the current pregnancy (64.0%). GM was associated with more frequency of gestational anemia, infection in neonates, and lower birth weight. The results indicate in a precise and direct way that malaria control in this northwestern region of Colombia is far from adequate, which is even more serious considering the affectations for the mother and the neonate.

Frequency of placental malaria and its associated factors in northwestern Colombia, pooled analysis 2009-2020.

Knowledge about placental malaria (PM) is insufficient in the world, and incipient in Colombia where studies are few and recent. In this country, PM has been reported by Plasmodium vivax, Plasmodium falciparum, and mixed infection. The objective was to determine the frequency of PM and its associated clinical-epidemiological factors in mothers and neonates in northwestern Colombia, 2009-2020. A Retrospective pooled analysis with 602 placentas captured in five investigations. The diagnosis of PM was made with thick blood smear (TBS) and qPCR. The groups with and without PM were compared using the Chi-square test, Mann-Whitney test, and crude and adjusted prevalence ratios in a log-binomial model. The prevalence of PM was 27.7% with 92% (155/167) of submicroscopic cases; 41.3% by P. vivax, 44,3% by P. falciparum, and 14.4% by mixed infections. In the multivariate adjustment, PM was associated with the diagnosis of congenital malaria, low neonatal weight, gestational malaria, maternal anemia, previous malaria during pregnancy, and age between 25-43 years. This research is the investigation with the largest number of subjects for studying PM in Colombia, in the ecoepidemiological zone that produces more cases of malaria per year, finding a high prevalence of submicroscopic PM that caused serious maternal (anemia) and neonatal (congenital malaria and low neonatal weight) effects. The results show limitations in the timely diagnosis and treatment, given that the epidemiological surveillance program in Colombia is based on thick blood smear, which generates a substantial underestimation of the magnitude of PM, with serious effects and clinical risks. It is urgent to demand that the health authorities adopt measures such as prenatal control visits as soon as the pregnancy begins, monthly implementation of TBS, and active search for infected pregnant women in their homes and workplaces.

Congenital malaria: Frequency and epidemiology in Colombia, 2009-2020.

Congenital Malaria (CM) is an underestimated and under-researched problem in Colombia, despite its severe clinical, epidemiological, economic, and public health consequences. The objective was to determine the general frequency of CM, the specific frequency of CM by diagnostic test and plasmodial species, and identify its associated factors. A retrospective study was carried out using the records of 567 newborns. qPCR and Thick Blood Smear (TBS) were performed. The frequency of infection was determined with a 95% confidence interval. Associated factors were identified by non-parametric tests and odds ratios; the confusion was controlled with a logistic regression model. All cases corresponded to submicroscopic CM (negative with TBS and positive with PCR), and the frequency was 12.2% (95%CI = 9.4-14.9). The detection was statistically higher in the umbilical cord with 16,2% (95%CI = 12.4-19.9) versus peripheral blood of the newborn with 2.2% (95%CI = 0.7-4.9). CM was statistically higher in newborn whose mothers had malaria in the last year, gestational and placental malaria. The median birth weight in newborn infected with CM was lower compared to the one of healthy neonates. Because the control program in Colombia is based on TBS, it must be improved with the inclusion of other tests that allow the detection of submicroscopic CM. In addition, the program has other limitations such as do not have specific actions for pregnant women and have a passive surveillance system. These difficulties do not allow to show the magnitude of CM, its consequences on neonatal and infant health, constituting a serious problem of health injustice.

Placental malaria caused by Plasmodium vivax or P. falciparum in Colombia: Histopathology and mediators in placental processes.

Knowledge about the relation of histopathological characteristics and mediators of physiological processes in the placenta malaria (PM) is poor, and that PM caused by Plasmodium vivax is almost null. The objective was to compare histopathological characteristics, cytokines and mediators of physiological processes in PM depending on the parasitic species, through a cross-sectional study in three groups: negative-PM, vivax-PM, falciparum-PM from Northwestern Colombia. The diagnosis of PM was made with thick blood smear, qPCR, and histopathology. Immuno-histochemical was made with EnVision system (Dako) and Zeiss Axio Imager M2 with light microscope. Cells in apoptosis were studied with the TUNEL technique. To measure the expression level of cytokines and mediators qRT-PCR was used. We included 179 placentas without PM and 87 with PM (53% P. vivax and 47% P. falciparum). At delivery, anemia was 25% in negative-PM, 60% in vivax-PM, and 44% in falciparum-PM group. The neonatal weight had an intense difference between groups with 3292±394g in negative-PM, 2,841±239 in vivax-PM, and 2,957±352 in falciparum-PM. The histopathological characteristics and CD+ cells in placenta with statistical differences (Dunn´s test) between negative-PM vs vivax-PM (P. falciparum was similar to P. vivax) were infarction, fibrinoid deposits, calcification, cells in apoptosis, immune infiltrates in decidua and intervillous space, CD4+, CD8+, CD14+, CD56+, CD68+. The expression levels of mediators in the placenta with statistical differences (Dunn´s test) between negative-PM vs vivax-PM (P. falciparum was similar to P. vivax) were Fas, FasL, HIF1α, Cox1, Cox2, VEGF, IL4, IL10, IFNγ, TNF, TGFß, FOXP3, and CTLA4. PM with P. falciparum and P. vivax, damages this organ and causes significant alteration of various physiological processes, which cause maternal anemia and a reduction in neonatal weight in degrees that are statistically and clinically significant. It is necessary that the search for plasmodial infection in pregnant and placenta goes from passive to active surveillance with adequate diagnostic capacity.

Interaction of histological events and physiological mediators in healthy placentas from malaria-endemic area in Colombia: An approach with a factorial model.

The biological study of the placenta is fragmented and focused on morbid events. The interaction of histological events and mediators of physiological processes in healthy placentas in malaria-endemic areas is unknown. This study aimed to build a factorial model for the convergence of events and mediators in healthy placentas of women living in northwestern Colombia through a study of 44 placentas. Linear correlations and exploratory factor analysis were carried out with histological events and expression of genes related to mediators. The factor analysis allowed us the identification of three components. The first compound by the following histological variables: number of capillaries and villus, immune cells in villus, atherosis, and CD8+ lymphocytes. The second with articulation of histological variables (syncytyal nodes, fibrinoid deposits, thrombi and immune cells) and physiological mediators of apoptosis and regulation. The thirth included physiological mediators of hypoxia, angiogenesis, pro-inflammation and anti-inflammation. All components presented excellent predictive and construct validity, and excellent goodness of fit parameters. In healthy placentas, the factorial structure of histological events and physiological mediators in three underlying components that support their interactions was demonstrated. These findings are significant because they help improve the study of healthy placental biology in malaria endemic areas and evaluate mechanisms that alter its morphology and function, with their subsequent risk for pregnancy and maternal-fetal health.

Meta-analysis of the prevalence of malaria associated with pregnancy in Colombia 2000-2020.

Knowledge about malaria associated with pregnancy is scarce in Latin America, and in Colombia, little is known about the magnitude of this infection. A systematic review was conducted to determine the prevalence of malaria associated with pregnancy (MAP) and each of its three forms: gestational (GM), placental (PM), and congenital (CM) tested using thick blood smear (TBS) and PCR. Also to compare the proportion of cases due to Plasmodium falciparum and Plasmodium vivax in Colombia from the year 2000-2020. We searched in Pubmed, Science Direct, EMBASE, EMCare, Cochrane Library, Scielo, Lilacs, Google Scholar, libraries, and repositories of Colombian universities, to obtain data on prevalence of GM, PM and CM with their respective testing method. We performed a meta-analysis with a random-effects model to obtain pooled prevalence of MAP and its three forms categorized by testing methods (TBS and PCR). We used data from 14 studies (out of 258 screened) contributing 7932, 2506 women for GM and PM respectively, also data on 1143 umbilical cord blood samples, and 899 peripheral blood of neonates. We found prevalence by TBS as, MAP 4.5% (95%CI = 2.9-6.9), GM 5.8% (95%CI = 3.8-8.7), PM 3.4% (95%CI = 1.7-6.7) and CM 1.3% (95%CI = 0.6-3.0). With PCR the prevalence was, MAP 14.4% (95%CI = 7.6-25.5), GM 16.7% (95%CI = 9.0-28.8), PM 11.0% (95%CI = 4.1-26.3) and CM 16.2% (95%CI = 8.2-29.5). The prevalence of submicroscopic infection was 8.5% (95%CI = 3.4-19.7) in GM, 10.1% (95%CI = 3.5-25.5) in PM and 22.0% (95%CI = 13.2-34.3) in CM. Infections by P. vivax was dominant over P. falciparum when tested with TBS, the PCR test gave similar proportions of P. falciparum and P. vivax. This meta-analysis has demonstrated high prevalence of MAP in Colombia, and highlights the urgent need to increase attention of researchers, research funding institutions, government agencies, and health authorities to study and intervene MAP, that has currently been under investigated.

Antigen Discovery in Circulating Extracellular Vesicles From Plasmodium vivax Patients.

Plasmodium vivax is the most widely distributed human malaria parasite with 7 million annual clinical cases and 2.5 billion people living under risk of infection. There is an urgent need to discover new antigens for vaccination as only two vaccine candidates are currently in clinical trials. Extracellular vesicles (EVs) are small membrane-bound vesicles involved in intercellular communication and initially described in reticulocytes, the host cell of P. vivax, as a selective disposal mechanism of the transferrin receptor (CD71) in the maturation of reticulocytes to erythrocytes. We have recently reported the proteomics identification of P. vivax proteins associated to circulating EVs in P. vivax patients using size exclusion chromatography followed by mass spectrometry (MS). Parasite proteins were detected in only two out of ten patients. To increase the MS signal, we have implemented the direct immuno-affinity capture (DIC) technique to enrich in EVs derived from CD71-expressing cells. Remarkably, we identified parasite proteins in all patients totaling 48 proteins and including several previously identified P. vivax vaccine candidate antigens (MSP1, MSP3, MSP7, MSP9, Serine-repeat antigen 1, and HSP70) as well as membrane, cytosolic and exported proteins. Notably, a member of the Plasmodium helical interspersed sub-telomeric (PHIST-c) family and a member of the Plasmodium exported proteins, were detected in five out of six analyzed patients. Humoral immune response analysis using sera from vivax patients confirmed the antigenicity of the PHIST-c protein. Collectively, we showed that enrichment of EVs by CD71-DIC from plasma of patients, allows a robust identification of P. vivax immunogenic proteins. This study represents a significant advance in identifying new antigens for vaccination against this human malaria parasite.

Perfil de investigaciones en malaria asociada al embarazo: revisión sistemática 1925-2018 / Research profile in pregnancy-associated malaria: systematic review 1925-2018 / Perfil das pesquisas sobre malária associada à gravidez: Revisão sistemática 1925-2018

Resumen Objetivo: Describir el perfil de publicaciones en malaria asociada al embarazo en el ámbito mundial, con base en los países, tipos y años de estudio, 1925-2018. Metodología: Revisión sistemática de la literatura, mediante el seguimiento de la guía prisma y garantizando la reproducibilidad del protocolo de selección y extracción de variables. Se aplicaron doce estrategias de búsqueda en PubMed, Science Direct, SciELO y Google Scholar. Se realizó síntesis cualitativa mediante frecuencias para el país, año de estudio y tipología de investigación. Resultados: Se tamizaron 3362 publicaciones, de las cuales 617 cumplieron el protocolo. El 81,5 % fueron de África, 9,9 % de Asia y 5,3 % de América. La mayor proporción de publicaciones fue posterior al 2009. El 65,8 % fueron estudios observacionales; el 22,0 %, ensayos clínicos, y los estudios cualitativos, de evaluación económica o evaluación de programas y políticas, fueron menores al 5 %. No se hallaron estudios de pruebas diagnósticas, evaluación de programas o investigaciones cualitativas en América. Conclusión: El perfil de publicaciones evidencia el predominio de la investigación epidemiológica tradicional-positivista y su concentración en África, lo que implica retos para las agendas sanitarias y de investigación en salud pública, pero con mayor necesidad en América.

Abstract Objective: To describe the profile of publications on pregnancy-associated malaria worldwide, based on countries, types and years of study, 1925-2018. Methodology: Systematic review of the literature, by monitoring the PRISMA guide and guaranteeing the reproducibility of the variable selection and extraction protocol. Twelve search strategies were applied in PubMed, Science Direct, SciELO and Google Scholar. Qualitative synthesis was performed using frequencies for the country, year of study and type of research. Results: 3362 publications were screened, of which 617 complied with the protocol. 81.5% were from Africa, 9.9% from Asia and 5.3% from America. The highest proportion of publications was after 2009. 65.8% were observational studies; 22.0%, clinical trials, while qualitative studies, economic evaluation studies or evaluation studies of programs and policies accounted for less than 5%. No studies of diagnostic tests, evaluation of programs or qualitative research were found in America. Conclusion: The profile of publications shows the predominance of traditional-positivist epidemiological research and its concentration in Africa, which implies challenges for health and research agendas in public health, but with greater need in America.

Resumo Objetivo: Descrever o perfil das publicações sobre malária associada à gravidez no âmbito mundial, com base nos países, tipos e anos de estudo, 1925-2018. Metodologia: Revisão sistemática da literatura através do seguimento da recomendação PRISMA e garantindo a reprodutibilidade do protocolo de seleção e extração de variáveis. Foram aplicadas doce estratégias de busca em PubMed, Science Direct, SciELO e Google Scholar. Foi realizada síntese qualitativa através de frequências para o país, ano do estudo e tipologia de pesquisa. Resultados: Foram escolhidas 3362 publicações, das quais 617 cumpriram o protocolo. Um total de 81,5% foi da África, 9,9% da Ásia e 5,3% da América. O maior número proporcional de publicações foi posterior a 2009. Os estudos observacionais registraram 65,8%; os ensaios clínicos 22,0% e os estudos qualitativos, de avaliação econômica ou avaliação de programas e políticas registrados foram menores a 5%. Não foram encontrados estudos de testes diagnósticos, avaliação de programas ou pesquisas qualitativas na América. Conclusão: O perfil das publicações evidencia a predominância da pesquisa epidemiológica positivista tradicional e sua concentração na África, o que representa desafios para as agendas de saúde e de pesquisa em saúde pública, mas com uma necessidade maior na América.

Cost-effectiveness of rapid diagnostic tests, compared to microscopic tests, for the diagnosis and treatment of gestational malaria in Colombia from an institutional perspective.

BACKGROUND: Gestational malaria is associated with negative outcomes in maternal and gestational health; timely diagnosis is crucial to avoid complications. However, the limited infrastructure, equipment, test reagents, and trained staff make it difficult to use thick blood smear tests in rural areas, where rapid testing could be a viable alternative. The purpose of this study was to estimate the cost-effectiveness of rapid tests type III (Plasmodium falciparum/Plasmodium spp P.f/pan) versus microscopic tests for the diagnosis and treatment of gestational malaria in Colombia. METHODS: Cost-effectiveness analyses of gestational malaria diagnosis from an institutional perspective using a decision tree. Standard costing was performed for the identification, measurement and assessment phases, with data from Colombian tariff manuals. The data was collected from Health Situation Analysis, SIVIGILA and meta-analysis. Average and incremental cost-effectiveness ratio were estimated. The uncertainty was assessed through probabilistic sensitivity analysis. RESULTS: The cost of rapid diagnostic tests in 3,000 pregnant women with malaria was US$66,936 and 1,182 disability adjusted life years (DALYs) were estimated. The cost using thick blood smear tests was US$50,838 and 1,023 DALYs, for an incremental cost-effectiveness of US$ 101.2. The probabilistic sensitivity analysis of rapid diagnostic tests determined that they are highly cost-effective in 70% of the cases, even below the US$1,200 threshold; also, they showed an incremental net monetary benefit of $150,000 when payer's willingness is US$1,000. CONCLUSION: The use of rapid diagnostic tests for timely diagnosis and treatment of gestational malaria is a highly cost-effective strategy in Colombia, with uncertainty analyses supporting the robustness of this conclusion and the increased net monetary benefit that the health system would obtain. This strategy may help in preventing the negative effects on maternal health and the neonate at a low cost.

Submicroscopic placental malaria: histopathology and expression of physiological process mediators. / Malaria placentaria submicroscópica: histopatología y expresión de mediadores de procesos fisiológicos.

OBJETIVES: To relate histopathological events of placental malaria (PM), immune cell behavior and gene expression associated with cytokines, hypoxia, inflammation and angiogenesis in placentas with or without plasmodial infection. MATERIALS AND METHODS: Transversal design, with three independent groups. Women were recruited, and their placentas were collected in 2009-2016, in the hospitals of Puerto Libertador and Tierralta, northwestern Colombia. The sample size was defined by convenience. The malaria diagnosis was based on real-time quantitative PCR. RESULTS: We studied 20 cases of PM by P. vivax (PM-V), 20 cases of PM by P. falciparum (PM-F) and 19 without PM; 95% of the cases of PM are submicroscopic placental plasmodial infection (SPPI). The three groups differ in frequency and number of histopathological events. Physiological process mediators showed significant difference between groups, except IL-2, VEGF, VEGFR-1 and C5a. CONCLUSIONS: Infected placentas are clearly different from uninfected ones. P. vivax behaves as pathogenic as P. falciparum. The approximation to the integral approach of the problem of PM is underlined. Submicroscopic placental plasmodial infection causes tissue and physiological mediator alterations as does microscopic infection, although probably to a lesser degree.

OBJETIVOS: Relacionar entre sí los eventos histopatológicos de malaria placentaria (MP), el comportamiento de células inmunitarias y la expresión de genes asociados a citoquinas, hipoxia, inflamación y angiogénesis en placentas con o sin infección plasmodial. MATERIALES Y MÉTODOS: Diseño transversal, con tres grupos independientes. Las mujeres y sus placentas fueron captadas en 2009-2016, en los hospitales de Puerto Libertador y Tierralta, noroccidente de Colombia. El tamaño muestral se definió por conveniencia. El diagnóstico malárico se basó en PCR cuantitativa en tiempo real. RESULTADOS: Se estudiaron 20 casos con MP por P. vivax (MP-V), 20 casos de MP por P. falciparum (MP-F) y 19 sin MP; 95% de los casos de MP son infección plasmodial placentaria submicroscópica (IPPS). Los tres grupos difieren en frecuencia y cantidad de eventos histopatológicos. Los mediadores de procesos fisiológicos presentaron diferencia significativa entre grupos, excepto IL-2, VEGF, VEGFR-1 y C5a. CONCLUSIONES: Las placentas con infección difieren claramente de las no infectadas. P. vivax se comporta tan patógeno como P. falciparum. Se resalta la aproximación al abordaje integral del problema de MP. La infección plasmodial placentaria submicroscópica causa alteraciones tisulares y en mediadores fisiológicos como lo hace la infección microscópica, aunque probablemente en menor grado.