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1.
BMC Infect Dis ; 21(1): 332, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33832450

RESUMO

BACKGROUND: Malaria and helminths diseases are co-endemic in most parts of sub-Saharan Africa. Immune responses from each of these pathogens interact, and these interactions may have implications on vaccines. The GMZ2 malaria vaccine candidate is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP R0). GMZ2 has recently showed modest efficacy in a phase IIb multicenter trial. Here, we assessed the effect of hookworm (Necator americanus) infection and anthelmintic treatment on naturally acquired antibody responses against GMZ2 and constituent antigens. METHODS: This longitudinal cross-sectional study was conducted in the Kintampo North Municipality of Ghana. Blood and stool samples were taken from 158 individuals (4-88 years old) infected with either P. falciparum alone (n = 59) or both hookworm and P. falciparum (n = 63) and uninfected endemic controls (n = 36). Stool hookworm infection was detected by the Kato-Katz method and PCR. Malaria parasitaemia was detected by RDT, light microscopy and P. falciparum-specific 18S rRNA gene PCR. Serum samples were obtained prior to hookworm treatment with a single dose of albendazole (400 mg) and 3 weeks (21 days) after treatment. Levels of IgG1, IgG3 and IgM against GMZ2, MSP3 and GLURP R0 were measured by ELISA and compared among the groups, before and after treatment. RESULTS: Participants with P. falciparum and hookworm co-infection had significantly higher IgG3 levels to GMZ2 than those with only P. falciparum infection and negative control (p < 0.05) at baseline. Treatment with albendazole led to a significant reduction in IgG3 levels against both GMZ2 and GLURP R0. Similarly, IgM and IgG1 levels against MSP3 also decreased following deworming treatment. CONCLUSION: Individuals with co-infection had higher antibody responses to GMZ2 antigen. Treatment of hookworm/malaria co-infection resulted in a reduction in antibody responses against GMZ2 and constituent antigens after albendazole treatment. Thus, hookworm infection and treatment could have a potential implication on malaria vaccine efficacy.


Assuntos
Anti-Helmínticos/uso terapêutico , Anticorpos Antiprotozoários/imunologia , Infecções por Uncinaria/tratamento farmacológico , Vacinas Antimaláricas/imunologia , Malária Falciparum/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Albendazol/uso terapêutico , Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Feminino , Infecções por Uncinaria/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Estudos Longitudinais , Vacinas Antimaláricas/genética , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Parasitemia/parasitologia , Proteínas de Protozoários/imunologia , Adulto Jovem
2.
J Ethnopharmacol ; 266: 113424, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33010404

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is a life-threatening health problem worldwide and treatment remains a major challenge. Natural products from medicinal plants are credible sources for better anti-malarial drugs. AIM OF THE STUDY: This study aimed at assessing the in vitro and in vivo antiplasmodial activities of the hydroethanolic extract of Bridelia atroviridis bark. MATERIALS AND METHODS: The phytochemical characterization of Bridelia atroviridis extract was carried out by High-Performance Liquid Chromatography-Mass spectrometry (HPLC-MS). The cytotoxicity test on Vero cells was carried out using the resazurin-based assay while the in vitro antiplasmodial activity was determined on Plasmodium falciparum (Dd2 strain, chloroquine resistant) using the SYBR green I-based fluorescence assay. The in vivo assay was performed on Plasmodium berghei-infected rats daily treated for 5 days with distilled water (10 mL/kg) for malaria control, 25 mg/kg of chloroquine sulfate for positive control and 50, 100 and 200 mg/kg of B. atroviridis extract for the three test groups. Parasitaemia was daily monitored using 10% giemsa-staining thin blood smears. At the end of the treatment, animals were sacrificed, blood was collected for hematological and biochemical analysis while organs were removed for biochemical and histopathological analyses. RESULTS: The HPLC-MS analysis data of B. atroviridis revealed the presence of bridelionoside D, isomyricitrin, corilagin, myricetin and 5 others compounds not yet identified. Bridelia atroviridis exhibited good in vitro antiplasmodial activity with the IC50 evaluated at 8.08 µg/mL and low cytotoxicity with the median cytotoxic concentration (CC50) higher than 100 µg/mL. B. atroviridis extract significantly reduced the parasitemia (p < 0.05) with an effective dose-50 (ED-50) of 89 mg/kg. B. atroviridis also prevented anemia, leukocytosis and liver and kidneys impairment by decrease of transaminases, ALP, creatinine, uric acid, and triglycerides concentrations. As well, B. atroviridis extract decreased some pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) levels and significantly improved the anti-inflammatory status (P < 0.01) of infected animals marked by a decrease of IL-10 concentration. These results were further confirmed by the improved of antioxidant status and the quasi-normal microarchitecture of the liver, kidneys and spleen in test groups. Overall, the hydroethanolic bark extract of Bridelia atroviridis demonstrated antimalarial property and justified its use in traditional medicine to manage malaria disease.


Assuntos
Antimaláricos/farmacologia , Euphorbiaceae/química , Extratos Vegetais/farmacologia , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Animais , Antimaláricos/administração & dosagem , Antimaláricos/isolamento & purificação , Chlorocebus aethiops , Cloroquina/farmacologia , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Feminino , Concentração Inibidora 50 , Malária/tratamento farmacológico , Malária/parasitologia , Masculino , Espectrometria de Massas , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Ratos , Ratos Wistar , Células Vero
3.
J Ethnopharmacol ; 266: 113427, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33022339

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is caused by infection with some species of Plasmodium parasite which leads to adverse alterations in physical and hematological features of infected persons and ultimately results in death. Antrocaryon micraster is used to treat malaria in Ghanaian traditional medicine. However, there is no scientific validation of its anti-malaria properties. The plant does not also have any chemical fingerprint or standardization parameters. AIM OF THE STUDY: This study sought to evaluate the anti-malaria activity of standardized A. micraster stem bark extract (AMSBE) and its effect on mean survival time (MST) and body weight reduction of Plasmodiumberghei infested mice. And to study the effect of treatment of AMSBE on hematological indices of the P. berghei infested mice in order to partly elucidate its anti-malarial mechanism of action. MATERIALS AND METHODS: Malaria was induced in female ICR mice by infecting them with 0.2 mL of blood (i.p.) containing 1.0 × 107P. berghei-infested RBCs from a donor mouse and leaving them without treatment for 3 days. AMSBE or Lonart (standard control) was then orally administered at 50, 200 and 400 mg/kg or 10 mg/kg once daily for 4 consecutive days. The untreated control received sterile water. Malaria parasitemia reduction, anti-malarial activity, mean change in body weight and MST of the parasitized mice were evaluated. Furthermore, changes in white blood cells (WBCs), red blood cells (RBCs), platelets count, hemoglobin (HGB), hematocrit (HCT) and mean corpuscular volume (MCV) were also determined in the healthy animals before infection as baseline and on days 3, 5 and 8 after infection by employing complete blood count. Standardization of AMSBE was achieved by quantification of its constituents and chemical fingerprint analysis using UHPLC-MS. RESULTS: Administration of AMSBE, standardized to 41.51% saponins and 234.960 ± 0.026 mg/g of GAE phenolics, produced significant (P < 0.05) reduction of parasitemia development, maximum anti-malaria activity of 46.01% (comparable to 32.53% produced by Lonart) and significantly (P < 0.05) increased body weight and MST of P. berghei infected mice compared to the untreated control. Moreover, there were significant (P > 0.05) elevation in WBCs, RBCs, HGB, HCT and platelets in the parasitized-AMSBE (especially at 400 mg/kg p.o.) treated mice compared to their baseline values. Whereas, the non-treated parasitized control recorded significant reduction (P < 0.05) in all the above-mentioned parameters compared to its baseline values. The UHPLC-MS fingerprint of AMSBE revealed four compounds with their retention times, percentage composition in their chromatograms and m/z of the molecular ions and fragments in the spectra. CONCLUSIONS: These results show that A. micraster stem bark possessed significant anti-malaria effect and also has the ability to abolish body weight loss, leucopenia, anemia and thrombocytopenia in P. berghei infected mice leading to prolonged life span. The UHPLC-MS fingerprint developed for AMSBE can be used for rapid authentication and standardization of A. micraster specimens and herbal preparations produced from its hydroethanolic stem bark extract to ensure consistent biological activity. The results justify A. micraster's use as anti-malaria agent.


Assuntos
Anacardiaceae/química , Antimaláricos/farmacologia , Malária/tratamento farmacológico , Extratos Vegetais/farmacologia , Plasmodium berghei/efeitos dos fármacos , Animais , Antimaláricos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Gana , Malária/parasitologia , Medicina Tradicional Africana , Camundongos , Camundongos Endogâmicos ICR , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Casca de Planta , Extratos Vegetais/administração & dosagem
4.
Exp Parasitol ; 218: 108012, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33011239

RESUMO

Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in almost all countries of Latin America. In Brazil, oral infection is becoming the most important mechanism of transmission of the disease in several regions of the country. The gastrointestinal tract is the gateway for the parasite through this route of infection, however, little is known about the involvement of these organs related to oral route. In this sense, the present study evaluated the impact of oral infection on the digestive tract in mice infected by Berenice-78 (Be-78) T. cruzi strain, in comparison with the intraperitoneal route of infection. In this work, the intraperitoneal route group showed a peak of parasitemia similar to the oral route group, however the mortality rate among the orally infected animals was higher when compared to intraperitoneal route. By analyzing the frequency of blood cell populations, differences were mainly observed in CD4+ T lymphocytes, and not in CD8+, presenting an earlier reduction in the number of CD4+ T cells, which persisted for a longer period, in the animals of the oral group when compared with the intraperitoneal group. Animals infected by oral route presented a higher tissue parasitism and inflammatory infiltrate in stomach, duodenum and colon on the 28th day after infection. Therefore, these data suggest that oral infection has a different profile of parasitological and immune responses compared to intraperitoneal route, being the oral route more virulent and with greater tissue parasitism in organs of the gastrointestinal tract evaluated during the acute phase.


Assuntos
Doença de Chagas/patologia , Trato Gastrointestinal/patologia , Trato Gastrointestinal/parasitologia , Trypanosoma cruzi/patogenicidade , Administração Oral , Análise de Variância , Animais , Doença de Chagas/mortalidade , Doença de Chagas/parasitologia , Colo/parasitologia , Colo/patologia , Duodeno/parasitologia , Duodeno/patologia , Imunofenotipagem , Masculino , Camundongos , Monócitos/patologia , Parasitemia/mortalidade , Parasitemia/parasitologia , Estômago/parasitologia , Estômago/patologia , Taxa de Sobrevida
5.
Am J Trop Med Hyg ; 103(4): 1510-1516, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32783792

RESUMO

The prevalence of malaria in India is decreasing, but it remains a major concern for public health administration. The role of submicroscopic malaria and asymptomatic malaria parasitemia and their persistence is being explored. A cross-sectional survey was conducted in the Kandhamal district of Odisha (India) during May-June 2017. Blood samples were collected from 1897 individuals for screening of asymptomatic parasitemia. Samples were screened using rapid diagnostic tests (RDTs) and examined microscopically for Plasmodium species. Approximately 30% of randomly selected samples (n = 586) were analyzed using real-time PCR (qPCR), and the genetic diversity of Plasmodium falciparum was analyzed. The prevalence of Plasmodium species among asymptomatic individuals detected using qPCR was 18%, which was significantly higher than that detected by microscopy examination (5.5%) or RDT (7.3%). Of these, 37% had submicroscopic malaria. The species-specific prevalence among asymptomatic malaria-positive cases for P. falciparum, Plasmodium vivax, and mixed infection (P. falciparum and P. vivax) by qPCR was 57%, 29%, and 14%, respectively. The multiplicity of infection was 1.6 and 1.2 for the merozoite surface protein-1 gene (msp1) and (msp2), respectively. Expected heterozygosity was 0.64 and 0.47 for msp1 and msp2, respectively. A significant proportion of the study population, 105/586 (18%), was found to be a reservoir for malaria infection, and identification of this group will help in the development of elimination strategies.


Assuntos
Malária/epidemiologia , Parasitemia/epidemiologia , Plasmodium/isolamento & purificação , Adolescente , Adulto , Criança , Pré-Escolar , Coinfecção , Erradicação de Doenças , Feminino , Humanos , Índia/epidemiologia , Malária/parasitologia , Malária/prevenção & controle , Masculino , Parasitemia/parasitologia , Parasitemia/prevenção & controle , Plasmodium/genética , Reação em Cadeia da Polimerase em Tempo Real , Especificidade da Espécie , Adulto Jovem
6.
Am J Trop Med Hyg ; 103(5): 1893-1901, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32815499

RESUMO

Investigations of malaria infection are often conducted by studying rodent Plasmodium species in inbred laboratory mice, but the efficacy of vaccines or adjunctive therapies observed in these models often does not translate to protection in humans. This raises concerns that mouse malaria models do not recapitulate important features of human malaria infections. African woodland thicket rats (Grammomys surdaster) are the natural host for the rodent malaria parasite Plasmodium berghei and the suspected natural host for Plasmodium vinckei vinckei. Previously, we reported that thicket rats are highly susceptible to diverse rodent parasite species, including P. berghei, Plasmodium yoelii, and Plasmodium chabaudi chabaudi, and are a more stringent model to assess the efficacy of whole-sporozoite vaccines than laboratory mice. Here, we compare the course of infection and virulence with additional rodent Plasmodium species, including various strains of P. berghei, P. yoelii, P. chabaudi, and P. vinckei, in thicket rats versus laboratory mice. We present evidence that rodent malaria parasite growth typically differs between the natural versus nonnatural host; G. surdaster limit infection by multiple rodent malaria strains, delaying and reducing peak parasitemia compared with laboratory mice. The course of malaria infection in thicket rats varied depending on parasite species and strain, resulting in self-cure, chronic parasitemia, or rapidly lethal infection, thus offering a variety of rodent malaria models to study different clinical outcomes in the natural host.


Assuntos
Anopheles/parasitologia , Malária/parasitologia , Parasitemia/parasitologia , Plasmodium/imunologia , Vacinas/imunologia , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Murinae , Plasmodium berghei/imunologia , Plasmodium chabaudi/imunologia , Plasmodium yoelii/imunologia , Esporozoítos
7.
Parasitol Res ; 119(10): 3541-3548, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32803333

RESUMO

The aim of this study was to evaluate, through qPCR, the prevalence of parasitemia in sick kennel dogs naturally infected by canine leishmaniasis. An evaluation of daily changes of the parasitic load in peripheral blood was also performed. A comprehensive clinical examination and the collection of several samples (blood, lymph node, skin, and conjunctiva) were performed in 140 dogs living in an endemic area. Among these, only the dogs with clinically evident leishmaniasis were enrolled (39/140; 27.9%). Twelve (30.8%) out of 39 showed parasitemia, with a low load (median: 4 Leishmania/ml) despite a high lymph node parasite load (median: 4000 Leishmania/ml) and high IFAT titers (≥ 1:640). Seven sick dogs were sampled every 4 h for 6 times during a 24-h period, in order to obtain light- and dark-span samples. Only one (14.3%) out of the seven serial sampled dogs showed Leishmania DNA in the peripheral blood in two samples (2/42; 4.8%). Surprisingly, Leishmania DNA was also detected in the peripheral blood of asymptomatic dogs, negative to both serology and PCR performed on samples other than blood (6/101; 5.9%). The present study confirms that in canine leishmaniasis parasitemia is uncommon and even transitory. Even if recommended, microscopic examination is confirmed as a low sensitivity method with a lower diagnostic utility in canine leishmaniasis than qPCR. Moreover, circulating Leishmania DNA can be found even in healthy dogs. This finding is important in clinical practice because in endemic areas it suggests a transfusion risk and a possible transmission to the vector.


Assuntos
Doenças do Cão/parasitologia , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/veterinária , Parasitemia/veterinária , Animais , DNA de Protozoário/sangue , DNA de Protozoário/genética , Doenças do Cão/epidemiologia , Cães , Leishmania infantum/genética , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/parasitologia , Carga Parasitária/veterinária , Parasitemia/epidemiologia , Parasitemia/parasitologia , Prevalência , Reação em Cadeia da Polimerase em Tempo Real/veterinária
8.
PLoS Pathog ; 16(8): e1008230, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32797076

RESUMO

Neutrophil extracellular traps (NETs) evolved as a unique effector mechanism contributing to resistance against infection that can also promote tissue damage in inflammatory conditions. Malaria infection can trigger NET release, but the mechanisms and consequences of NET formation in this context remain poorly characterized. Here we show that patients suffering from severe malaria had increased amounts of circulating DNA and increased neutrophil elastase (NE) levels in plasma. We used cultured erythrocytes and isolated human neutrophils to show that Plasmodium-infected red blood cells release macrophage migration inhibitory factor (MIF), which in turn caused NET formation by neutrophils in a mechanism dependent on the C-X-C chemokine receptor type 4 (CXCR4). NET production was dependent on histone citrullination by peptidyl arginine deiminase-4 (PAD4) and independent of reactive oxygen species (ROS), myeloperoxidase (MPO) or NE. In vitro, NETs functioned to restrain parasite dissemination in a mechanism dependent on MPO and NE activities. Finally, C57/B6 mice infected with P. berghei ANKA, a well-established model of cerebral malaria, presented high amounts of circulating DNA, while treatment with DNAse increased parasitemia and accelerated mortality, indicating a role for NETs in resistance against Plasmodium infection.


Assuntos
Eritrócitos/imunologia , Armadilhas Extracelulares/imunologia , Fatores Inibidores da Migração de Macrófagos/metabolismo , Malária/imunologia , Neutrófilos/imunologia , Plasmodium/imunologia , Receptores CXCR4/metabolismo , Animais , Eritrócitos/metabolismo , Eritrócitos/parasitologia , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/parasitologia , Humanos , Malária/metabolismo , Malária/parasitologia , Malária/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Neutrófilos/parasitologia , Parasitemia/imunologia , Parasitemia/metabolismo , Parasitemia/parasitologia , Parasitemia/patologia
9.
Exp Parasitol ; 218: 107969, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32858043

RESUMO

Invasion of human red blood cells (RBCs) by Plasmodium parasites is a crucial yet poorly characterised phenotype. Two-color flow cytometry (2cFCM) promises to be a very sensitive and high throughput method for phenotyping parasite invasion. However, current protocols require high (~1.0%) parasitemia for assay set-up and need to be adapted for low parasitemia samples, which are becoming increasingly common in low transmission settings. Background fluorescence from nuclei-containing uninfected RBCs and high autologous reinvasion rates (merozoite invasion of donor uninfected RBCs present at 50% assay volume) are some of the limitations to the method's sensitivity to enumerate low parasitemia (<0.5%) with nucleic acid-based stains. Here, we describe modifications for plating unlabeled donor to labeled target RBCs per assay well and for gating parasitemia, that produces accurate quantifications of low reinvasion parasitemia. Plasmodium falciparum 3D7, Dd2 and field isolates at various low and high parasitemia (0.05%-2.0%) were used to set-up SyBr Green 1-based 2cFCM invasion assays. Target RBCs were labeled with CTFR proliferation dye. We show that this dye combination allowed for efficient parasite invasion into target RBCs and that a 1:3 ratio of unlabeled to labeled RBCs per assay greatly skewed autologous reinvasion (p < 0.001). Accuracy of quantifying reinvasion was limited to an assay parasitemia of 0.02% with minimal background interference. Invasion inhibition by enzymatic treatments increased averagely by 10% (p<0.05) across the entire parasitemia range. The effect was greater for samples with <0.5% parasitemia. Overall, a more sensitive method for phenotyping invasion of low P. falciparum parasitemia is described.


Assuntos
Citometria de Fluxo/métodos , Malária Falciparum/parasitologia , Parasitemia/parasitologia , Plasmodium falciparum/isolamento & purificação , Rastreamento de Células/métodos , Corantes , Eritrócitos/parasitologia , Humanos , Fenótipo , Plasmodium falciparum/classificação , Plasmodium falciparum/fisiologia , Recidiva , Sensibilidade e Especificidade , Coloração e Rotulagem/métodos
10.
Am J Trop Med Hyg ; 103(4): 1525-1533, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32700666

RESUMO

Tororo, a district in Uganda with historically high malaria transmission intensity, has recently scaled up control interventions, including universal long-lasting insecticidal net distribution in 2013 and 2017, and sustained indoor residual spraying (IRS) of insecticide since December 2014. We describe the burden of malaria in Tororo 5 years following the initiation of IRS. We followed a cohort of 531 participants from 80 randomly selected households in Nagongera subcounty, Tororo district, from October 2017 to October 2019. Mosquitoes were collected every 2 weeks using CDC light traps in all rooms where participants slept, symptomatic malaria was identified by passive surveillance, and microscopic and submicroscopic parasitemia were measured every 4 weeks using active surveillance. Over the 2 years of follow-up, 15,780 female anopheline mosquitos were collected, the majority (98.0%) of which were Anopheles arabiensis. The daily human biting rate was 2.07, and the annual entomological inoculation rate was 0.43 infective bites/person/year. Only 38 episodes of malaria were diagnosed (incidence 0.04 episodes/person/year), and there were no cases of severe malaria or malarial deaths. The prevalence of microscopic parasitemia was 1.9%, and the combined prevalence of microscopic and submicroscopic parasitemia was 10.4%, each highest in children aged 5-15 years (3.3% and 14.0%, respectively). After 5 years of intensive vector control measures in Tororo, the burden of malaria was reduced to very low transmission levels. However, a significant proportion of the population remained parasitemic, primarily school-aged children with submicroscopic parasitemia, providing a potential reservoir for malaria transmission.


Assuntos
Anopheles/parasitologia , Inseticidas/uso terapêutico , Malária/epidemiologia , Controle de Mosquitos , Mosquitos Vetores/parasitologia , Adolescente , Animais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Incidência , Malária/parasitologia , Malária/prevenção & controle , Malária/transmissão , Masculino , Parasitemia/epidemiologia , Parasitemia/parasitologia , Parasitemia/transmissão , Prevalência , Uganda/epidemiologia
11.
Sci Rep ; 10(1): 9398, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32523082

RESUMO

Incomplete non-sterile immunity to malaria is attained in endemic regions after recurrent infections by a large percentage of the adult population, who carry the malaria parasite asymptomatically. Although blood-stage Plasmodium falciparum rapidly elicits IgG responses, the target antigens of partially protective and non-protective IgG antibodies as well as the basis for the acquisition of these antibodies remain largely unknown. We performed IgG-immunomics to screen for P. falciparum antigens and to identify epitopes associated with exposure and clinical disease. Sera from malaria cases identified five prevalent antigens recognized by all analyzed patients' IgGs. Epitope mapping of them, using adult and children sera samples from an endemic malaria region in Ghana segregated into patients with positive or negative subclinical detection of P. falciparum, revealed binding specificity for two 20-mer immunodominant antigenic regions within the START-related lipid transfer protein and the protein disulfide isomerase PDI8. These 20-mer epitopes challenged with sera samples from children under 5 years old displayed specific IgG binding in those with detectable parasitemia, even at subclinical level. These results suggest that humoral response against START and PDI8 antigens may be triggered at submicroscopic parasitemia levels in children and may eventually be used to differentially diagnose subclinical malaria in children.


Assuntos
Epitopos/imunologia , Imunoglobulina G/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Adolescente , Adulto , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Criança , Mapeamento de Epitopos/métodos , Feminino , Gana , Humanos , Malária Falciparum/parasitologia , Masculino , Parasitemia/imunologia , Parasitemia/parasitologia , Proteínas de Protozoários/imunologia , Adulto Jovem
12.
Exp Parasitol ; 216: 107932, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32535113

RESUMO

Neglected tropical diseases, such as Chagas disease caused by the protozoa Trypanosoma cruzi, affect millions of people worldwide but lack effective treatments that are accessible to the entire population, especially patients with the debilitating chronic phase. The recognition of host cells, invasion and its intracellular replicative success are essential stages for progression of the parasite life cycle and the development of Chagas disease. It is predicted that programmed cell death pathways (apoptosis) would be activated in infected cells, either via autocrine secretion or mediated by cytotoxic immune cells. This process should play a key role in resolving infections by hindering the evolutionary success of the parasite. In this research, we performed assays to investigate the role of the lectin galectin-3 (Gal3) in parasite-host signaling pathways. Using cells with endogenous levels of Gal3 compared to Gal3-deficient cells (induced by RNA interference), we demonstrated that T. cruzi mediated the survival pathways and the subverted apoptosis through Gal3 promoting a pro-survival state in infected cells. Infected Gal3-depleted cells showed increased activation of caspase 3 and pro-apoptotic targets, such as poly (ADP-ribose) polymerase (PARP), and lower accumulation of anti-apoptotic proteins, such as c-IAP1, survivin and XIAP. During the early stages of infection, Gal3 translocates from the cytoplasm to the nucleus and must act in survival pathways. In a murine model of experimental infection, Gal3 knockout macrophages showed lower infectivity and viability. In vivo infection revealed a lower parasitemia and longer survival and an increased spleen cellularity in Gal3 knockout mice with consequences on the percentage of T lymphocytes (CD4+ CD11b+) and macrophages. In addition, cytokines such as IL-2, IL-4, IL-6 and TNF-α are increased in Gal3 knockout mice when compared to wild type genotype. These data demonstrate a Gal3-mediated complex interplay in the host cell, keeping infected cells alive long enough for infection and intracellular proliferation of new parasites. However, a continuous knowledge of these signaling pathways should contribute to a better understanding the mechanisms of cell death subversion that are promoted by protozoans in the pathophysiology of neglected diseases such as Chagas disease.


Assuntos
Apoptose/fisiologia , Doença de Chagas/parasitologia , Galectina 3/fisiologia , Trypanosoma cruzi/fisiologia , Análise de Variância , Animais , Western Blotting , Caspase 3/análise , Sobrevivência Celular , Doença de Chagas/mortalidade , Chlorocebus aethiops , Colorimetria , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Imunofluorescência , Galectina 3/análise , Galectina 3/genética , Células HeLa , Humanos , Imunofenotipagem , Macrófagos Peritoneais/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Parasitemia/mortalidade , Parasitemia/parasitologia , Fenótipo , Baço/patologia , Células Vero
13.
Rev Bras Parasitol Vet ; 29(2): e002420, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428179

RESUMO

Hepatozoon pyramidumi sp. n. is described from the blood of the Egyptian saw-scaled viper, Echis pyramidum, captured from Saudi Arabia. Five out of ten viper specimens examined (50%) were found infected with Hepatozoon pyramidumi sp. n. with parasitaemia level ranged from 20-30%. The infection was restricted only to the erythrocytes. Two morphologically different forms of intraerythrocytic stages were observed; small and mature gamonts. The small ganomt with average size of 10.7 × 3.5 µm. Mature gamont was sausage-shaped with recurved poles measuring 16.3 × 4.2 µm in average size. Infected erythrocytes were hypertrophied; their nuclei were deformed and sometimes displaced from their central position in the normal uninfected cell. Merogonic stages were observed in the lung endothelial cell and the liver parenchyma cells. Mature meront was 17.8 × 13.6 µm and contained banana-shaped merozoites with average size of ~15 × 2 µm. Phylogenetic analysis based on the SSU rDNA sequence clustered Hepatozoon pyramidumi sp. n with previously sequenced Hepatozoon spp., most of them infected reptilian hosts without geographic consideration. The morphological and molecular comparison with closely related species proved the taxonomic uniqueness and novelty of the present form.


Assuntos
Apicomplexa/genética , Apicomplexa/fisiologia , DNA de Protozoário/genética , Viperidae/parasitologia , Animais , Apicomplexa/classificação , DNA Ribossômico/genética , Eritrócitos/parasitologia , Eritrócitos/patologia , Fígado/parasitologia , Fígado/patologia , Pulmão/parasitologia , Pulmão/patologia , Parasitemia/parasitologia , Parasitemia/veterinária , Filogenia , Arábia Saudita , Análise de Sequência de DNA , Viperidae/sangue
14.
Am J Trop Med Hyg ; 103(3): 1329-1334, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32342841

RESUMO

Reductions in malaria morbidity have been reported following azithromycin mass drug administration (MDA) for trachoma. The recent Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) trial reported a reduction in child mortality following biannual azithromycin MDA. Here, we investigate the effects of azithromycin MDA on malaria at the MORDOR-Malawi study site. A cluster-randomized double-blind placebo-controlled trial, with 15 clusters per arm, was conducted. House-to-house census was updated biannually, and azithromycin or placebo syrup was distributed to children aged 1-59 months for a total of four biannual distributions. At baseline, 12-month, and 24-month follow-up visits, a random sample of 1,200 children was assessed for malaria with thick and thin blood smears and hemoglobin measurement. In the community-level analysis, there was no difference in the prevalence of parasitemia (1.0% lower in azithromycin-treated communities; 95% CI: -8.2 to 6.1), gametocytemia (0.7% lower in azithromycin-treated communities; 95% CI: -2.8 to 1.5), or anemia (1.7% lower in azithromycin-treated communities; 95% CI: -8.1 to 4.6) between placebo and azithromycin communities. Further interrogation of the data at the individual level, both per-protocol (including only those who received treatment 6 months previously) and by intention-to-treat, did not identify differences in parasitemia between treatment arms. In contrast to several previous reports, this study did not show an effect of azithromycin MDA on malaria parasitemia at the community or individual levels.


Assuntos
Anemia/epidemiologia , Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Malária/tratamento farmacológico , Parasitemia/tratamento farmacológico , Mortalidade da Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Lactente , Malária/epidemiologia , Malária/parasitologia , Masculino , Administração Massiva de Medicamentos , Parasitemia/epidemiologia , Parasitemia/parasitologia , Prevalência
15.
J Parasitol ; 106(2): 308-311, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32330279

RESUMO

Cytauxzoon felis is a pathogen responsible for cytauxzoonosis, a highly fatal disease in domestic cats. Although most studies of C. felis have focused on this parasite in domestic cats, bobcats are the reservoir host. In stark contrast, there is little information relative to the progression of C. felis infections in bobcats. We studied bobcats in southern Illinois during 2014-2017 to evaluate which environmental factors (i.e., ambient temperature; number of daylight hours; trapping year, month, and day) influenced C. felis parasitemia levels. Mean ambient temperature at 1 wk and 2 wk prior to sampling was associated with increased parasitemia levels. Vector activity intensifies with higher temperatures, suggesting that increased parasitemia levels are an adaptation to facilitate transmission.


Assuntos
Lynx/parasitologia , Parasitemia/veterinária , Piroplasmida/fisiologia , Infecções Protozoárias em Animais/parasitologia , Animais , Vetores Aracnídeos/parasitologia , Dermacentor/parasitologia , Reservatórios de Doenças/parasitologia , Reservatórios de Doenças/veterinária , Eritrócitos/parasitologia , Modelos Lineares , Meio-Oeste dos Estados Unidos/epidemiologia , Parasitemia/epidemiologia , Parasitemia/parasitologia , Infecções Protozoárias em Animais/epidemiologia , Infecções Protozoárias em Animais/transmissão , Estações do Ano
16.
Trends Parasitol ; 36(5): 413-426, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32298629

RESUMO

Antimalarial drugs are vital for treating malaria and controlling transmission. Measuring drug efficacy in the field requires large clinical trials and thus we have identified proxy measures of drug efficacy such as the parasite clearance curve. This is often assumed to measure the rate of drug activity against parasites and is used to predict optimal treatment regimens required to completely clear a blood-stage infection. We discuss evidence that the clearance curve is not measuring the rate of drug killing. This has major implications for how we assess optimal treatment regimens, as well as how we prioritise new drugs in the drug development pipeline.


Assuntos
Antimaláricos/uso terapêutico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Antimaláricos/farmacologia , Humanos , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/fisiologia , Resultado do Tratamento
17.
Malar J ; 19(1): 135, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228559

RESUMO

BACKGROUND: Owing to the large amount of host DNA in clinical samples, generation of high-quality Plasmodium falciparum whole genome sequencing (WGS) data requires enrichment for parasite DNA. Enrichment is often achieved by leukocyte depletion of infected blood prior to storage. However, leukocyte depletion is difficult in low-resource settings and limits analysis to prospectively-collected samples. As a result, approaches such as selective whole genome amplification (sWGA) are being used to enrich for parasite DNA. However, sWGA has had limited success in generating reliable sequencing data from low parasitaemia samples. In this study, enzymatic digestion with MspJI prior to sWGA and whole genome sequencing was evaluated to determine whether this approach improved genome coverage compared to sWGA alone. The potential of sWGA to cause amplification bias in polyclonal infections was also examined. METHODS: DNA extracted from laboratory-created dried blood spots was treated with a modification-dependent restriction endonuclease, MspJI, and filtered via vacuum filtration. Samples were then selectively amplified using a previously reported sWGA protocol and subjected to WGS. Genome coverage statistics were compared between the optimized sWGA approach and the previously reported sWGA approach performed in parallel. Differential amplification by sWGA was assessed by comparing WGS data generated from lab-created mixtures of parasite isolates, from the same geographical region, generated with or without sWGA. RESULTS: MspJI digestion did not enrich for parasite DNA. Samples that underwent vacuum filtration (without MspJI digestion) prior to sWGA had the highest parasite DNA concentration and displayed greater genome coverage compared to MspJI + sWGA and sWGA alone, particularly for low parasitaemia samples. The optimized sWGA (filtration + sWGA) approach was successfully used to generate WGS data from 218 non-leukocyte depleted field samples from Malawi. Sequences from lab-created mixtures of parasites did not show evidence of differential amplification of parasite strains compared to directly sequenced samples. CONCLUSION: This optimized sWGA approach is a reliable method to obtain WGS data from non-leukocyte depleted, low parasitaemia samples. The absence of amplification bias in data generated from mixtures of isolates from the same geographic region suggests that this approach can be appropriately used for molecular epidemiological studies.


Assuntos
DNA de Protozoário/análise , Plasmodium falciparum/genética , Sequenciamento Completo do Genoma/métodos , Malaui , Parasitemia/parasitologia , Sequenciamento Completo do Genoma/instrumentação
18.
Parasitol Res ; 119(4): 1301-1315, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32179986

RESUMO

Malaria and lymphatic filariasis (LF) are two leading and common mosquito-borne parasitic diseases worldwide. These two diseases are co-endemic in many tropical and sub-tropical regions and are known to share vectors. The interactions between malaria and filarial parasites are poorly understood. Thus, this study aimed at establishing the interactions that occur between Brugia pahangi and Plasmodium berghei ANKA (PbA) co-infection in gerbils. Briefly, the gerbils were matched according to age, sex, and weight and grouped into filarial-only infection, PbA-only infection, co-infection, and control group. The parasitemia, survival and clinical assessment of the gerbils were monitored for a period of 30 days post Plasmodium infection. The immune responses of gerbils to both mono and co-infection were monitored. Findings show that co-infected gerbils have higher survival rate than PbA-infected gerbils. Food and water consumption were significantly reduced in both PbA-infected and co-infected gerbils, although loss of body weight, hypothermia, and anemia were less severe in co-infected gerbils. Plasmodium-infected gerbils also suffered hypoglycemia, which was not observed in co-infected gerbils. Furthermore, gerbil cytokine responses to co-infection were significantly higher than PbA-only-infected gerbils, which is being suggested as a factor for their increased longevity. Co-infected gerbils had significantly elicited interleukin-4, interferon-gamma, and tumor necrotic factor at early stage of infection than PbA-infected gerbils. Findings from this study suggest that B. pahangi infection protect against severe anemia and hypoglycemia, which are manifestations of PbA infection.


Assuntos
Brugia pahangi/imunologia , Filariose/veterinária , Gerbillinae/parasitologia , Malária/veterinária , Plasmodium berghei/imunologia , Animais , Coinfecção/imunologia , Coinfecção/parasitologia , Citocinas/sangue , Feminino , Filariose/parasitologia , Interações Hospedeiro-Parasita/imunologia , Hipoglicemia/parasitologia , Malária/parasitologia , Masculino , Mosquitos Vetores/parasitologia , Parasitemia/parasitologia , Parasitemia/veterinária , Taxa de Sobrevida
19.
Infection ; 48(3): 367-373, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32077073

RESUMO

PURPOSE: When considering malaria disease severity, estimation of parasitemia in erythrocytes is important, but sometimes misleading, since the infected erythrocytes may be sequestered in peripheral capillaries. In African children and Asian adults with falciparum malaria, parasitemia as assessed by quantitative PCR (qPCR) in plasma seems to be a valuable indicator of disease severity, but data on African adults as well as the impact of co-infection with HIV is lacking. METHODS: In 131 patients with falciparum malaria in a public tertiary teaching hospital in Mozambique, plasma malaria parasitemia as assessed by qPCR, compared to qualitative malaria PCR in blood cell fraction, was related to malaria disease severity and HIV co-infection. RESULTS: Of the 131 patients with falciparum malaria, based on positive qualitative PCR in the blood cell fraction, 93 patients (72%) had positive malaria qPCR in plasma. Patients with severe malaria as defined by the WHO criteria had higher malaria quantitative plasma parasitemia (median 143 genomes/µL) compared to those with uncomplicated malaria (median 55 genomes/µL, p = 0.037) in univariate analysis, but this difference was attenuated after adjusting for age, sex and HIV co-infection (p = 0.055). A quarter of the patients with severe malaria had negative qPCR in plasma. CONCLUSIONS: This study of adult African in-patients with falciparum malaria with and without HIV co-infection, neither confirms nor rejects previous studies of malaria qPCR in plasma as an indicator of disease severity in patients with falciparum malaria. There is a need for further and larger studies to clarify if parasitemia as assessed malaria qPCR in plasma could be a surrogate marker of disease severity in falciparum malaria.


Assuntos
Infecções por HIV/virologia , Malária Falciparum/sangue , Parasitemia/parasitologia , Plasma/parasitologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Coinfecção/parasitologia , Coinfecção/virologia , Feminino , Humanos , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Moçambique , Parasitemia/sangue , Adulto Jovem
20.
Am J Trop Med Hyg ; 103(3): 1315-1318, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32067628

RESUMO

The relationship between malaria and malnutrition is complicated, and existence of one may predispose or exacerbate the other. We evaluated the relationship between malaria parasitemia and nutritional status in children living in communities participating in a cluster-randomized trial of biannual azithromycin compared with placebo for prevention of childhood mortality. Data were collected during the low malaria transmission and low food insecurity season. Parasitemia was not associated with weight-for-height Z-score (24 months: P = 0.11 azithromycin communities, P = 0.75 placebo communities), weight-for-age Z-score (24 months: P = 0.83 azithromycin, P = 0.78 placebo), height-for-age Z-score (24 months: P = 0.30 azithromycin, P = 0.87 placebo), or mid-upper arm circumference (24 months: P = 0.12 azithromycin, P = 0.56 placebo). There was no statistically significant evidence of a difference in the relationship in communities receiving azithromycin or placebo. During the low transmission season, there was no evidence that malaria parasitemia and impaired nutritional status co-occur in children.


Assuntos
Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Malária/epidemiologia , Administração Massiva de Medicamentos , Estado Nutricional , Parasitemia/epidemiologia , Pré-Escolar , Feminino , Humanos , Lactente , Malária/tratamento farmacológico , Malária/parasitologia , Malária/transmissão , Masculino , Níger/epidemiologia , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Parasitemia/transmissão , Estações do Ano
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