RESUMEN

Cerebral malaria in young African children is associated with high mortality, and persisting neurological deficits often remain in survivors. Sequestered Plasmodium-infected red blood cells lead to cerebrovascular inflammation and subsequent neuroinflammation. Brain inflammation can play a role in the pathogenesis of neurologic sequelae. Therefore, we assessed a select set of proinflammatory analytes (IP10, IL23, MIP3α, GRO, MCP-1, and osteopontin in both the plasma and cerebrospinal fluid(CSF) of Zambian children with cerebral malaria and compared this with children with neurological symptoms that were negative for Plasmodium falciparum (non-cerebral malaria). Several similarities in plasma and CSF levels were found, as were some striking differences. We confirmed that IP10 levels were higher in the plasma of cerebral malaria patients, but this was not found in CSF. Levels of osteopontin were elevated in both the plasma and CSF of CM patients compared to the non-CM patients. These results show again a highly inflammatory environment in both groups but a different profile for CM when compared to non-cerebral malaria. Osteopontin may play an important role in neurological inflammation in CM and the resulting sequelae. Therefore, osteopontin could be a valid target for further biomarker research and potentially for therapeutic interventions in neuroinflammatory infections.

Asunto(s)

Biomarcadores , Malaria Cerebral , Osteopontina , Humanos , Malaria Cerebral/líquido cefalorraquídeo , Malaria Cerebral/sangre , Malaria Cerebral/parasitología , Osteopontina/líquido cefalorraquídeo , Osteopontina/sangre , Masculino , Femenino , Preescolar , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/sangre , Inflamación/líquido cefalorraquídeo , Inflamación/sangre , Niño , Plasmodium falciparum/patogenicidad , Lactante , Malaria Falciparum/líquido cefalorraquídeo , Malaria Falciparum/sangre , Malaria Falciparum/parasitología

RESUMEN

Plasmodium parasites cause Malaria disease, which remains a significant threat to global health, affecting 200 million people and causing 400,000 deaths yearly. Plasmodium falciparum and Plasmodium vivax remain the two main malaria species affecting humans. Identifying the malaria disease in blood smears requires years of expertise, even for highly trained specialists. Literature studies have been coping with the automatic identification and classification of malaria. However, several points must be addressed and investigated so these automatic methods can be used clinically in a Computer-aided Diagnosis (CAD) scenario. In this work, we assess the transfer learning approach by using well-known pre-trained deep learning architectures. We considered a database with 6222 Region of Interest (ROI), of which 6002 are from the Broad Bioimage Benchmark Collection (BBBC), and 220 were acquired locally by us at Fundação Oswaldo Cruz (FIOCRUZ) in Porto Velho Velho, Rondônia-Brazil, which is part of the legal Amazon. We exhaustively cross-validated the dataset using 100 distinct partitions with 80% train and 20% test for each considering circular ROIs (rough segmentation). Our experimental results show that DenseNet201 has a potential to identify Plasmodium parasites in ROIs (infected or uninfected) of microscopic images, achieving 99.41% AUC with a fast processing time. We further validated our results, showing that DenseNet201 was significantly better (99% confidence interval) than the other networks considered in the experiment. Our results support claiming that transfer learning with texture features potentially differentiates subjects with malaria, spotting those with Plasmodium even in Leukocytes images, which is a challenge. In Future work, we intend scale our approach by adding more data and developing a friendly user interface for CAD use. We aim at aiding the worldwide population and our local natives living nearby the legal Amazon's rivers.

Asunto(s)

Microscopía , Humanos , Microscopía/métodos , Plasmodium falciparum/patogenicidad , Plasmodium vivax , Biología Computacional/métodos , Malaria/parasitología , Plasmodium , Aprendizaje Profundo , Bases de Datos Factuales , Procesamiento de Imagen Asistido por Computador/métodos , Malaria Falciparum/parasitología , Diagnóstico por Computador/métodos

RESUMEN

Asymptomatic malaria can impact existing malaria control and elimination efforts around the world, particularly in Africa, where the majority of malaria cases and death occurs. This is a cross-sectional study aimed to determine the prevalence and predictors of asymptomatic malaria among migrant farmworkers from June to July 2020 in the Upper Awash Agro-industry, East Shewa zone, Oromia Regional State, Ethiopia. A total of 254 migrant farmworkers without signs and symptoms of malaria were enrolled. Data on socio-demographic characteristics and malaria prevention practices were obtained through a structured questionnaire. Venous blood samples were collected and diagnosed using microscopy, rapid diagnostic tests, and polymerase chain reaction (PCR). Data were coded, entered, and analyzed using SPSS version-21 statistical software. Multivariable logistic regression was used to assess associated factors. A p < 0.05 was considered statistically significant. The overall prevalence of asymptomatic malaria among farmworkers in this study was 5.1% [95% CI 1.6, 6.7]. The proportions of Plasmodium falciparum was 90.0% (9/10) while it was 10.0% (1/10) for Plasmodium vivax. Out of the microscopy and/or RDT-confirmed malaria cases, (n = 9; 100%) were confirmed to be P. falciparum by nested PCR, while (n = 3/122; 2.46%) were found to be P. falciparum among 50% negative cases with the microscopy and/or RDT. The gametocyte stage was detected in 40% of microscopically positive cases out of which 44.4% belongs to P. falciparum. Home area/origin of migrant laborers [AOR = 6.08, (95% CI 1.08, 34.66)], family history of malaria [AOR = 8.15, (95% CI 1.43, 46.44)], and outdoor sleeping [AOR = 10.14, (95% CI 1.15, 89.14)] were significantly associated with asymptomatic malaria. In conclusion, asymptomatic malaria was detected among farmworkers in the study area and it was significantly associated with outdoor sleeping, home area, and family history of malaria. Prevention tools and control strategies, particularly focusing on migrant farmworkers, should be considered to support the ongoing malaria control and elimination effort in Ethiopia.

Asunto(s)

Agricultores , Migrantes , Humanos , Etiopía/epidemiología , Migrantes/estadística & datos numéricos , Femenino , Masculino , Adulto , Estudios Transversales , Prevalencia , Adulto Joven , Adolescente , Malaria/epidemiología , Malaria/parasitología , Persona de Mediana Edad , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Malaria Falciparum/diagnóstico , Plasmodium falciparum/aislamiento & purificación , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidad , Infecciones Asintomáticas/epidemiología , Plasmodium vivax/aislamiento & purificación , Factores de Riesgo , Malaria Vivax/epidemiología , Malaria Vivax/parasitología

RESUMEN

Among the factors affecting the effectiveness of malaria control is poor knowledge of the entomologic drivers of the disease. We investigated anopheline populations as part of a baseline study to implement house screening of windows and doors as a supplementary malaria control tool towards elimination in Jabi Tehnan district, Amhara Regional State of Ethiopia. The samples were surveyed monthly using CDC light traps between June 2020 and May 2021. Mosquito trap density (< 3 mosquitoes/trap) was low, however, with a high overall Plasmodium sporozoite rate (9%; indoor = 4.3%, outdoor = 13.1%) comprising P. falciparum (88.9%) and P. vivax (11.1%). Anopheles gambiae s.l., mostly An. arabiensis, comprised > 80% of total anopheline captures and contributed ~ 42% of Plasmodium-infected mosquitoes. On the other hand, morphologically scored Anopheles funestus s.l., constituting about 6% of anopheline collections, accounted for 50% of sporozoite-infected mosquitoes. Most of the infected An. funestus s.l. specimens (86.7%) were grouped with previously unknown or undescribed Anopheles species previously implicated as a cryptic malaria vector in the western Kenyan highlands, confirming its wider geographic distribution in eastern Africa. Other species with Plasmodium infection included An. longipalpis C, An. theileri, An. demillioni, and An. nili. Cumulatively, 77.8% of the infected mosquitoes occurred outdoors. These results suggest efficient malaria parasite transmission despite the low vector densities, which has implications for effective endpoint indicators to monitor malaria control progress. Additionally, the largely outdoor infection and discovery of previously unknown and cryptic vectors suggest an increased risk of residual malaria transmission and, thus, a constraint on effective malaria prevention and control.

Asunto(s)

Anopheles , Mosquitos Vectores , Etiopía/epidemiología , Animales , Anopheles/parasitología , Mosquitos Vectores/parasitología , Humanos , Malaria/transmisión , Malaria/epidemiología , Plasmodium falciparum/aislamiento & purificación , Plasmodium falciparum/patogenicidad , Plasmodium vivax/fisiología , Esporozoítos , Control de Mosquitos/métodos , Malaria Vivax/transmisión , Malaria Vivax/epidemiología , Malaria Vivax/parasitología , Malaria Falciparum/transmisión , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Femenino

RESUMEN

While often undetected and untreated, persistent seasonal asymptomatic malaria infections remain a global public health problem. Despite the presence of parasites in the peripheral blood, no symptoms develop. Disease severity is correlated with the levels of infected red blood cells (iRBCs) adhering within blood vessels. Changes in iRBC adhesion capacity have been linked to seasonal asymptomatic malaria infections, however how this is occurring is still unknown. Here, we present evidence that RNA polymerase III (RNA Pol III) transcription in Plasmodium falciparum is downregulated in field isolates obtained from asymptomatic individuals during the dry season. Through experiments with in vitro cultured parasites, we have uncovered an RNA Pol III-dependent mechanism that controls pathogen proliferation and expression of a major virulence factor in response to external stimuli. Our findings establish a connection between P. falciparum cytoadhesion and a non-coding RNA family transcribed by Pol III. Additionally, we have identified P. falciparum Maf1 as a pivotal regulator of Pol III transcription, both for maintaining cellular homeostasis and for responding adaptively to external signals. These results introduce a novel perspective that contributes to our understanding of P. falciparum virulence. Furthermore, they establish a connection between this regulatory process and the occurrence of seasonal asymptomatic malaria infections.

Asunto(s)

Malaria Falciparum , Plasmodium falciparum , ARN Polimerasa III , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidad , Plasmodium falciparum/enzimología , Virulencia , ARN Polimerasa III/metabolismo , ARN Polimerasa III/genética , Humanos , Malaria Falciparum/parasitología , Eritrocitos/parasitología , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/genética , Factores de Virulencia/metabolismo , Factores de Virulencia/genética , Adhesión Celular , Regulación de la Expresión Génica

RESUMEN

Malaria is a disease that affects millions of people worldwide, particularly in developing countries. The development of accurate and efficient methods for the detection of malaria-infected cells is crucial for effective disease management and control. This paper presents the electrical impedance spectroscopy (EIS) of normal and malaria-infected red blood cells. An EIS microfluidic device, comprising a microchannel and a pair of coplanar electrodes, was fabricated for single-cell measurements in a continuous manner. Based on the EIS results, the aim of this work is to discriminate Plasmodium falciparum-infected red blood cells from the normal ones. Different from typical impedance spectroscopy, our measurement was performed for the cells in a low-conductivity medium in a frequency range between 50 kHz and 800 kHz. Numerical simulation was utilized to study the suitability parameters of the microchannel and electrodes for the EIS experiment over the measurement frequencies. The measurement results have shown that by using the low-conductivity medium, we could focus on the change in the conductance caused by the presence of a cell in the sensing electrode gap. The results indicated a distinct frequency spectrum of the conductance between the normal and infected red blood cells, which can be further used for the detection of the disease.

Asunto(s)

Espectroscopía Dieléctrica , Eritrocitos , Plasmodium falciparum , Eritrocitos/parasitología , Espectroscopía Dieléctrica/métodos , Espectroscopía Dieléctrica/instrumentación , Humanos , Plasmodium falciparum/fisiología , Plasmodium falciparum/patogenicidad , Electrodos , Dispositivos Laboratorio en un Chip , Malaria Falciparum/diagnóstico , Malaria Falciparum/parasitología , Impedancia Eléctrica , Malaria/diagnóstico , Malaria/parasitología

RESUMEN

Leukocyte telomere length (LTL) varies significantly across human populations, with individuals of African ancestry having longer LTL than non-Africans. However, the genetic and environmental drivers of LTL variation in Africans remain largely unknown. We report here on the relationship between LTL, genetics, and a variety of environmental and climatic factors in ethnically diverse African adults (n = 1,818) originating from Botswana, Tanzania, Ethiopia, and Cameroon. We observe significant variation in LTL among populations, finding that the San hunter-gatherers from Botswana have the longest leukocyte telomeres and that the Fulani pastoralists from Cameroon have the shortest telomeres. Genetic factors explain ∼50% of LTL variation among individuals. Moreover, we observe a significant negative association between Plasmodium falciparum malaria endemicity and LTL while adjusting for age, sex, and genetics. Within Africa, adults from populations indigenous to areas with high malaria exposure have shorter LTL than those in populations indigenous to areas with low malaria exposure. Finally, we explore to what degree the genetic architecture underlying LTL in Africa covaries with malaria exposure.

Asunto(s)

Malaria Falciparum , Telómero , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , África del Sur del Sahara/epidemiología , Población Negra/etnología , Población Negra/genética , Enfermedades Endémicas , Leucocitos/metabolismo , Malaria Falciparum/genética , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidad , Pueblo Africano Subsahariano , Telómero/genética , Homeostasis del Telómero/genética , Botswana , Tanzanía , Camerún , Pueblo del Sur de África

RESUMEN

The symptoms of malaria occur during the blood stage of infection, when parasites invade and replicate within human erythrocytes. The PfPCRCR complex1, containing PfRH5 (refs. 2,3), PfCyRPA, PfRIPR, PfCSS and PfPTRAMP, is essential for erythrocyte invasion by the deadliest human malaria parasite, Plasmodium falciparum. Invasion can be prevented by antibodies3-6 or nanobodies1 against each of these conserved proteins, making them the leading blood-stage malaria vaccine candidates. However, little is known about how PfPCRCR functions during invasion. Here we present the structure of the PfRCR complex7,8, containing PfRH5, PfCyRPA and PfRIPR, determined by cryogenic-electron microscopy. We test the hypothesis that PfRH5 opens to insert into the membrane9, instead showing that a rigid, disulfide-locked PfRH5 can mediate efficient erythrocyte invasion. We show, through modelling and an erythrocyte-binding assay, that PfCyRPA-binding antibodies5 neutralize invasion through a steric mechanism. We determine the structure of PfRIPR, showing that it consists of an ordered, multidomain core flexibly linked to an elongated tail. We also show that the elongated tail of PfRIPR, which is the target of growth-neutralizing antibodies6, binds to the PfCSS-PfPTRAMP complex on the parasite membrane. A modular PfRIPR is therefore linked to the merozoite membrane through an elongated tail, and its structured core presents PfCyRPA and PfRH5 to interact with erythrocyte receptors. This provides fresh insight into the molecular mechanism of erythrocyte invasion and opens the way to new approaches in rational vaccine design.

Asunto(s)

Eritrocitos , Malaria Falciparum , Complejos Multiproteicos , Parásitos , Plasmodium falciparum , Proteínas Protozoarias , Animales , Humanos , Anticuerpos Neutralizantes/inmunología , Antígenos de Protozoos/química , Antígenos de Protozoos/inmunología , Microscopía por Crioelectrón , Disulfuros/química , Disulfuros/metabolismo , Eritrocitos/metabolismo , Eritrocitos/parasitología , Vacunas contra la Malaria/inmunología , Malaria Falciparum/inmunología , Malaria Falciparum/metabolismo , Malaria Falciparum/parasitología , Malaria Falciparum/patología , Merozoítos/metabolismo , Complejos Multiproteicos/química , Complejos Multiproteicos/inmunología , Complejos Multiproteicos/metabolismo , Complejos Multiproteicos/ultraestructura , Parásitos/metabolismo , Parásitos/patogenicidad , Plasmodium falciparum/metabolismo , Plasmodium falciparum/patogenicidad , Proteínas Protozoarias/química , Proteínas Protozoarias/inmunología , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/ultraestructura

RESUMEN

Upon infection by the malaria parasite Plasmodium falciparum, the glycolytic rate of a red blood cell increases up to 100-fold, possibly contributing to lactic acidosis and hypoglycemia in patients with severe malaria. This dramatic increase in glucose uptake and metabolism was correctly predicted by a newly constructed detailed enzyme kinetic model of glucose metabolism in the trophozoite-infected red blood cell. Subsequently, we expanded the model to simulate an infected red blood cell culture, including the different asexual blood-stage forms of the malaria parasite. The model simulations were in good agreement with experimental data, for which the measured parasitic volume was an important parameter. Upon further analysis of the model, we identified glucose transport as a drug target that would specifically affect infected red blood cells, which was confirmed experimentally with inhibitor titrations. This model can be a first step in constructing a whole-body model for glucose metabolism in malaria patients to evaluate the contribution of the parasite's metabolism to the disease state.

Asunto(s)

Antimaláricos , Eritrocitos , Glucólisis , Malaria Falciparum , Modelos Biológicos , Terapia Molecular Dirigida , Plasmodium falciparum , Humanos , Acidosis Láctica , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Antimaláricos/metabolismo , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Eritrocitos/parasitología , Glucosa/metabolismo , Glucólisis/efectos de los fármacos , Hipoglucemia , Cinética , Malaria Falciparum/metabolismo , Malaria Falciparum/parasitología , Plasmodium falciparum/metabolismo , Plasmodium falciparum/patogenicidad , Plasmodium falciparum/fisiología , Trofozoítos/patogenicidad , Trofozoítos/fisiología , Terapia Molecular Dirigida/métodos , Carga de Parásitos

RESUMEN

Plasmodium falciparum expresses clonally variant proteins on the surface of infected erythrocytes to evade the host immune system. The clonally variant multigene families include var, rifin, and stevor, which express Erythrocyte Membrane Protein 1 (EMP1), Repetitive Interspersed Families of polypeptides (RIFINs), and Sub-telomeric Variable Open Reading frame (STEVOR) proteins, respectively. The rifins are the largest multigene family and are essentially involved in the RBC rosetting, the hallmark of severe malaria. The molecular regulators that control the RIFINs expression in Plasmodium spp. have not been reported so far. This study reports a chromodomain-containing protein (PfCDP) that binds to H3K9me3 modification on P. falciparum chromatin. Conditional deletion of the chromodomain (CD) gene in P. falciparum using an inducible DiCre-LoxP system leads to selective up-regulation of a subset of virulence genes, including rifins, a few var, and stevor genes. Further, we show that PfCDP conditional knockout (PfΔCDP) promotes RBC rosette formation. This study provides the first evidence of an epigenetic regulator mediated control on a subset of RIFINs expression and RBC rosetting by P. falciparum.

Asunto(s)

Epigénesis Genética , Eritrocitos , Histonas , Malaria Falciparum , Plasmodium falciparum , Proteínas Protozoarias , Formación de Roseta , Animales , Eritrocitos/inmunología , Eritrocitos/parasitología , Eliminación de Gen , Histonas/metabolismo , Malaria Falciparum/parasitología , Familia de Multigenes , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidad , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Virulencia/genética

RESUMEN

Spatial arrangement of chromosomes is responsible for gene expression in Plasmodium parasites. However, methods for rearranging chromosomes have not been established, which makes it difficult to investigate its role in detail. Here, we report a method for splitting chromosome in rodent malaria parasite by CRISPR/Cas9 system using fragments in which a telomere and a centromere were incorporated. The resultant split chromosomes segregated accurately into daughter parasites by the centromere. In addition, elongation of de novo telomeres were observed, indicating its proper function. Furthermore, chromosome splitting had no effect on development of parasites. Splitting of the chromosome is expected to alter its spatial arrangement, and our method will thus be useful for investigating its biological role related with gene expression.

Asunto(s)

Sistemas CRISPR-Cas/genética , Cromosomas/genética , Malaria/genética , Plasmodium berghei/genética , Animales , Centrómero/genética , Regulación de la Expresión Génica/genética , Malaria/parasitología , Plasmodium berghei/patogenicidad , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidad , Roedores/parasitología , Telómero/genética

RESUMEN

Sequencing large numbers of individual samples is often needed for countrywide antimalarial drug resistance surveillance. Pooling DNA from several individual samples is an alternative cost and time saving approach for providing allele frequency (AF) estimates at a population level. Using 100 individual patient DNA samples of dried blood spots from a 2017 nationwide drug resistance surveillance study in Haiti, we compared codon coverage of drug resistance-conferring mutations in four Plasmodium falciparum genes (crt, dhps, dhfr, and mdr1), for the same deep sequenced samples run individually and pooled. Samples with similar real-time PCR cycle threshold (Ct) values (+/- 1.0 Ct value) were combined with ten samples per pool. The sequencing success for samples in pools were higher at a lower parasite density than the individual samples sequence method. The median codon coverage for drug resistance-associated mutations in all four genes were greater than 3-fold higher in the pooled samples than in individual samples. The overall codon coverage distribution for pooled samples was wider than the individual samples. The sample pools with < 40 parasites/µL blood showed more discordance in AF calls for dhfr and mdr1 between the individual and pooled samples. This discordance in AF estimation may be due to low amounts of parasite DNA, which could lead to variable PCR amplification efficiencies. Grouping samples with an estimated ≥ 40 parasites/µL blood prior to pooling and deep sequencing yielded the expected population level AF. Pooling DNA samples based on estimates of > 40 parasites/µL prior to deep sequencing can be used for rapid genotyping of a large number of samples for these four genes and possibly other drug resistant markers in population-based studies. As Haiti is a low malaria transmission country with very few mixed infections and continued chloroquine sensitivity, the pooled sequencing approach can be used for routine national molecular surveillance of resistant parasites.

Asunto(s)

Resistencia a Medicamentos/genética , Ensayos Analíticos de Alto Rendimiento/métodos , Plasmodium falciparum/genética , Animales , Antimaláricos/farmacología , Pruebas con Sangre Seca/métodos , Monitoreo Epidemiológico , Haití , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Malaria/epidemiología , Malaria Falciparum/parasitología , Técnicas de Amplificación de Ácido Nucleico/métodos , Parásitos/genética , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/patogenicidad , Reacción en Cadena de la Polimerasa/métodos , Análisis de Secuencia de ADN

RESUMEN

Globally, malaria is the major public health disease caused by plasmodium species and transmitted by the bite of the female anopheles mosquito. Assessment of the trend of malaria prevalence is important in the control and prevention of the disease. Therefore, the objective of this study was to assess the six year trend of malaria prevalence at the University of Gondar Comprehensive Specialized Hospital, northwest Ethiopia, from 2014 to 2019. A retrospective laboratory registration logbook review study was conducted on the malaria blood film examination results at the University of Gondar Comprehensive Specialized Hospital. The data was collected by using a data extraction tool and entered into SPSS version 20 for analysis. Descriptive statistics were used to summarize the socio-demographic characteristics of study participants and presented by graphs, tables and texts. The binary logistic regression was also used to test the association the trend of malaria prevalence and different factors like sex, age, year, and season. From a total of 17,500 malaria blood film examinations, 1341 (7.7%) were confirmed for malaria parasites. Of the confirmed malaria cases, 47.2%, 45.6% and 7.2% were P. vivax, P. falciparum and mixed infection, respectively. The proportion of P. vivax was the predominant species in the first three study years (2014-2016) and P. falciparum became the predominant species in the last three study years (2017-2019). The odds of malaria prevalence was lower by 68%, 60% and 69% in the year 2017, 2018 and 2019 compared to 2014, respectively. It was also 1.41 times higher in males than in females. Moreover, the odds of malaria prevalence were 1.60, 1.64, 2.45 and 1.82 times higher in the age group of < 5, 5-14, 15-24 and 25-54 years old compared to the older age groups (> 54 years old), respectively. Even there was a significant declining in prevalence trend; malaria is still a major public health problem. The study showed that there was high seasonal fluctuation from year to year. Moreover, males and the younger age groups were more affected than females and old age groups, respectively. Therefore, malaria prevention and control activities should be strengthened and require extra efforts by considering these variability.

Asunto(s)

Coinfección/epidemiología , Malaria Falciparum/epidemiología , Malaria Vivax/epidemiología , Plasmodium falciparum/patogenicidad , Plasmodium vivax/patogenicidad , Adolescente , Adulto , Anciano , Animales , Anopheles/parasitología , Niño , Preescolar , Coinfección/parasitología , Coinfección/transmisión , Etiopía/epidemiología , Femenino , Humanos , Lactante , Modelos Logísticos , Malaria Falciparum/parasitología , Malaria Falciparum/transmisión , Malaria Vivax/parasitología , Malaria Vivax/transmisión , Masculino , Persona de Mediana Edad , Mosquitos Vectores/parasitología , Plasmodium falciparum/crecimiento & desarrollo , Plasmodium vivax/crecimiento & desarrollo , Prevalencia , Estudios Retrospectivos , Estaciones del Año , Factores Sexuales

RESUMEN

BACKGROUND: Malaria is one of the leading causes of morbidity and mortality especially in pregnant women and under-five-year-old children. However, data on the prevalence among delivering mothers, potential fetal transmission, and associated birth outcomes is lacking in Ethiopia. OBJECTIVE: To assess the prevalence of Plasmodium infection from peripheral, placental, and cord blood samples among delivering mothers in Kuch health center, Northwest Ethiopia. METHODS: An institution-based cross-sectional study was conducted among 218 delivering mothers from February to May 2021 in Kuch health center. Data on sociodemographic characteristics and clinical and obstetric history of mothers were collected using a structured questionnaire. Giemsa stained blood films from maternal capillary and placental and umbilical cord blood were examined for plasmodium infection. Data were analyzed using Statistical Package for the Social Sciences version 23 software package. RESULTS: The prevalence of maternal, placental, and umbilical cord malaria was 6.4% (14/218), 2.3% (5/218), and 0.5% (1/218), respectively. Plasmodium falciparum and Plasmodium vivax accounted 3.7% (8/218) and 2.8% (6/218), respectively, in maternal peripheral blood but only Plasmodium falciparum was detected in placental and umbilical cord blood samples. Maternal malaria had significant association with primigravida (χ 2 = 12.611, p = 0.002) and low birth weight (χ 2 = 8.381, p = 0.004). Placental malaria was also significantly associated with low birth weight (χ 2 = 32.255, p ≤ 0.001). CONCLUSION: The prevalence of malaria among delivering mothers was considerable. Maternal peripheral malaria had a significant association with gravidity and birth weight. Placental and umbilical cord malaria also had a significant association with birth weight. Pregnant mothers should be examined for malaria and receive appropriate treatment to prevent adverse birth outcomes.

Asunto(s)

Malaria/epidemiología , Madres/estadística & datos numéricos , Adulto , Peso al Nacer/fisiología , Estudios Transversales , Etiopía/epidemiología , Femenino , Sangre Fetal/parasitología , Feto/parasitología , Número de Embarazos/fisiología , Instituciones de Salud/estadística & datos numéricos , Humanos , Placenta/parasitología , Plasmodium falciparum/patogenicidad , Plasmodium vivax/patogenicidad , Embarazo , Complicaciones del Embarazo/parasitología , Atención Prenatal/estadística & datos numéricos , Prevalencia , Cordón Umbilical/parasitología , Adulto Joven

RESUMEN

Measuring gene flow between malaria parasite populations in different geographic locations can provide strategic information for malaria control interventions. Multiple important questions pertaining to the design of such studies remain unanswered, limiting efforts to operationalize genomic surveillance tools for routine public health use. This report examines the use of population-level summaries of genetic divergence (FST) and relatedness (identity-by-descent) to distinguish levels of gene flow between malaria populations, focused on field-relevant questions about data size, sampling, and interpretability of observations from genomic surveillance studies. To do this, we use P. falciparum whole genome sequence data and simulated sequence data approximating malaria populations evolving under different current and historical epidemiological conditions. We employ mobile-phone associated mobility data to estimate parasite migration rates over different spatial scales and use this to inform our analysis. This analysis underscores the complementary nature of divergence- and relatedness-based metrics for distinguishing gene flow over different temporal and spatial scales and characterizes the data requirements for using these metrics in different contexts. Our results have implications for the design and implementation of malaria genomic surveillance studies.

Asunto(s)

Flujo Génico/genética , Genética de Población , Malaria Falciparum/genética , Plasmodium falciparum/genética , Animales , Variación Genética/genética , Genoma/genética , Geografía , Humanos , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Plasmodium falciparum/patogenicidad , Secuenciación Completa del Genoma

RESUMEN

Anopheline mosquitoes are the sole vectors for the Plasmodium pathogens responsible for malaria, which is among the oldest and most devastating of human diseases. The continuing global impact of malaria reflects the evolutionary success of a complex vector-pathogen relationship that accordingly has been the long-term focus of both debate and study. An open question in the biology of malaria transmission is the impact of naturally occurring low-level Plasmodium infections of the vector on the mosquito's health and longevity as well as critical behaviors such as host-preference/seeking. To begin to answer this, we have completed a comparative RNAseq-based transcriptome profile study examining the effect of biologically salient, salivary gland transmission-stage Plasmodium infection on the molecular physiology of Anopheles gambiae s.s. head, sensory appendages, and salivary glands. When compared with their uninfected counterparts, Plasmodium infected mosquitoes exhibit increased transcript abundance of genes associated with olfactory acuity as well as a range of synergistic processes that align with increased fitness based on both anti-aging and reproductive advantages. Taken together, these data argue against the long-held paradigm that malaria infection is pathogenic for anophelines and, instead suggests there are biological and evolutionary advantages for the mosquito that drive the preservation of its high vectorial capacity.

Asunto(s)

Anopheles/genética , Perfilación de la Expresión Génica , Malaria Falciparum/genética , Mosquitos Vectores/genética , Plasmodium falciparum/patogenicidad , Transcriptoma , Envejecimiento/genética , Envejecimiento/metabolismo , Animales , Anopheles/metabolismo , Anopheles/parasitología , Evolución Molecular , Aptitud Genética , Interacciones Huésped-Parásitos , Malaria Falciparum/parasitología , Mosquitos Vectores/metabolismo , Mosquitos Vectores/parasitología , Odorantes , RNA-Seq , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Olfato/genética

RESUMEN

Malaria eradication is still a major global health problem in developing countries, which has been of more concern ever since the malaria parasite has developed resistance against frontline antimalarial drugs. Historical evidence proves that the plants possess a major resource for the development of novel anti-malarial drugs. In the present study, the bioactivity guided fractionation of the oleogum-resin of Boswellia serrata Roxb. yielded the optimum activity in the ethyl acetate fraction with an IC50 of 22 ± 3.9 µg/mL and 26.5 ± 4.5 µg/mL against chloroquine sensitive (NF54) and resistant (K1) strains of Plasmodium falciparum respectively. Further, upon fractionation, the ethyl acetate fraction yielded four major compounds, of which 3-Hydroxy-11-keto-ß-boswellic acid (KBA) was found to be the most potent with IC50 values 4.5 ± 0.60 µg/mL and 6.25 ± 1.02 µg/mL against sensitive and resistant strains respectively. KBA was found to inhibit heme detoxification pathways, one of the most common therapeutic targets, which probably lead to an increase in reactive oxygen species (ROS) and nitric oxide (NO) detrimental to P. falciparum. Further, the induced intracellular oxidative stress affected the macromolecules in terms of DNA damage, increased lipid peroxidation, protein carbonylation as well as loss of mitochondrial membrane potential. However, it did not exhibit any cytotoxic effect in VERO cells. Under in vivo conditions, KBA exhibited a significant reduction in parasitemia, retarding the development of anaemia, resulting in an enhancement of the mean survival time in Plasmodium yoelii nigeriensis (chloroquine-resistant) infected mice. Further, KBA did not exhibit any abnormality in serum biochemistry of animals that underwent acute oral toxicity studies at 2000 mg/kg body weight.

Asunto(s)

Antimaláricos/farmacología , Boswellia , Hemo/metabolismo , Malaria/tratamiento farmacológico , Extractos Vegetales/farmacología , Plasmodium falciparum/efectos de los fármacos , Plasmodium yoelii/efectos de los fármacos , Triterpenos/farmacología , Animales , Antimaláricos/aislamiento & purificación , Antimaláricos/toxicidad , Boswellia/química , Chlorocebus aethiops , Modelos Animales de Enfermedad , Peroxidación de Lípido/efectos de los fármacos , Malaria/sangre , Malaria/parasitología , Ratones , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Plasmodium falciparum/metabolismo , Plasmodium falciparum/patogenicidad , Plasmodium yoelii/metabolismo , Plasmodium yoelii/patogenicidad , Carbonilación Proteica/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Resinas de Plantas , Triterpenos/aislamiento & purificación , Triterpenos/toxicidad , Células Vero

RESUMEN

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family members mediate receptor- and tissue-specific sequestration of infected erythrocytes (IEs) in malaria. Antibody responses are a central component of naturally acquired malaria immunity. PfEMP1-specific IgG likely protects by inhibiting IE sequestration and through IgG-Fc Receptor (FcγR) mediated phagocytosis and killing of antibody-opsonized IEs. The affinity of afucosylated IgG to FcγRIIIa is up to 40-fold higher than fucosylated IgG, resulting in enhanced antibody-dependent cellular cytotoxicity. Most IgG in plasma is fully fucosylated, but afucosylated IgG is elicited in response to enveloped viruses and to paternal alloantigens during pregnancy. Here we show that naturally acquired PfEMP1-specific IgG is strongly afucosylated in a stable and exposure-dependent manner, and efficiently induces FcγRIIIa-dependent natural killer (NK) cell degranulation. In contrast, immunization with a subunit PfEMP1 (VAR2CSA) vaccine results in fully fucosylated specific IgG. These results have implications for understanding protective natural- and vaccine-induced immunity to malaria.

Asunto(s)

Antígenos de Protozoos/metabolismo , Plasmodium falciparum/metabolismo , Plasmodium falciparum/patogenicidad , Anticuerpos Antiprotozoarios/metabolismo , Antígenos de Protozoos/inmunología , Femenino , Humanos , Inmunoglobulina G/metabolismo , Malaria Falciparum/inmunología , Malaria Falciparum/prevención & control , Embarazo , Vacunación

RESUMEN

The pathology associated with malaria infection is largely due to the ability of infected human RBCs to adhere to a number of receptors on endothelial cells within tissues and organs. This phenomenon is driven by the export of parasite-encoded proteins to the host cell, the exact function of many of which is still unknown. Here we inactivate the function of one of these exported proteins, PFA66, a member of the J-domain protein family. Although parasites lacking this protein were still able to grow in cell culture, we observed severe defects in normal host cell modification, including aberrant morphology of surface knobs, disrupted presentation of the cytoadherence molecule PfEMP1, and a total lack of cytoadherence, despite the presence of the knob associated protein KAHRP. Complementation assays demonstrate that an intact J-domain is required for recovery to a wild-type phenotype and suggest that PFA66 functions in concert with a HSP70 to carry out host cell modification. Strikingly, this HSP70 is likely to be of host origin. ATPase assays on recombinant protein verify a functional interaction between PFA66 and residual host cell HSP70. Taken together, our data reveal a role for PFA66 in host cell modification, strongly implicate human HSP70s as being essential in this process and uncover a new KAHRP-independent molecular factor required for correct knob biogenesis.

Asunto(s)

Proteínas HSP70 de Choque Térmico/metabolismo , Interacciones Huésped-Parásitos/fisiología , Malaria Falciparum/metabolismo , Plasmodium falciparum/patogenicidad , Proteínas Protozoarias/metabolismo , Humanos , Malaria Falciparum/parasitología , Malaria Falciparum/patología , Plasmodium falciparum/metabolismo , Virulencia

RESUMEN

BACKGROUND: Irrigation schemes may result in subsequent changes in malaria disease dynamics. Understanding the mechanisms and effects of irrigation on malaria vector bionomics and transmission intensity is essential to develop new or alternative surveillance and control strategies to reduce or control malaria risk. This study was designed to assess the effect of rice irrigation on malaria vector bionomics and transmission intensity in the Gambella Region, Ethiopia. METHODS: Comparative cross-sectional study was conducted in Abobo District of the Gambella Region, Ethiopia. Accordingly, clusters (kebeles) were classified into nearby and faraway clusters depending on their proximity to the irrigation scheme. Adult mosquito survey was conducted in February, August and November 2018 from three nearby and three faraway clusters using Centers for Disease Control and Prevention (CDC) light traps (LTs). During the November survey, human landing catch (HLC) and pyrethrum spray catch (PSC) were also conducted. The collected mosquitoes were morphologically identified to species and tested for Plasmodium infection using circumsporozoite protein enzyme-linked immunosorbent assay (CSP-ELISA). Furthermore, species-specific polymerase chain reaction (PCR) was performed to identify member species of the Anopheles gambiae complex. Chi-square and t-tests were used to analyze the data using the SPSS version 20 software package. RESULTS: A total of 4319 female anopheline mosquitoes comprising An. gambiae sensu lato, An. funestus group, An. pharoensis, An. coustani complex and An. squamosus were collected. Overall, 84.5% and 15.5% of the anopheline mosquitoes were collected from the nearby and faraway clusters, respectively. Anopheles gambiae s.l. was the predominant (56.2%) anopheline species in the area followed by An. pharoensis (15.7%). The density of anopheline mosquitoes was significantly higher in the nearby clusters in both HLCs [t(3) = 5.14, P = 0.0143] and CDC LT catches [t(271.97) = 7.446, P < 0.0001). The overall sporozoite rate of anopheline species from the nearby clusters was 10-fold higher compared to the faraway clusters. CONCLUSIONS: Significantly higher mosquito population density was observed in areas close to the irrigation sites. Sporozoite infection rate in the mosquito population was also markedly higher from the nearby clusters. Therefore, the irrigation scheme could increase the risk of malaria in the area.

Asunto(s)

Riego Agrícola , Anopheles/fisiología , Malaria/prevención & control , Malaria/transmisión , Mosquitos Vectores/fisiología , Animales , Anopheles/clasificación , Anopheles/parasitología , Estudios Transversales , Ecología , Etiopía , Conducta Alimentaria , Femenino , Humanos , Oryza , Plasmodium falciparum/patogenicidad , Densidad de Población , Esporozoítos/fisiología