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1.
N Engl J Med ; 385(9): 803-814, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34379916

RESUMO

BACKGROUND: Additional interventions are needed to reduce the morbidity and mortality caused by malaria. METHODS: We conducted a two-part, phase 1 clinical trial to assess the safety and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an extended half-life, and its efficacy against infection with Plasmodium falciparum. Part A of the trial assessed the safety, initial side-effect profile, and pharmacokinetics of CIS43LS in healthy adults who had never had malaria. Participants received CIS43LS subcutaneously or intravenously at one of three escalating dose levels. A subgroup of participants from Part A continued to Part B, and some received a second CIS43LS infusion. Additional participants were enrolled in Part B and received CIS43LS intravenously. To assess the protective efficacy of CIS43LS, some participants underwent controlled human malaria infection in which they were exposed to mosquitoes carrying P. falciparum sporozoites 4 to 36 weeks after administration of CIS43LS. RESULTS: A total of 25 participants received CIS43LS at a dose of 5 mg per kilogram of body weight, 20 mg per kilogram, or 40 mg per kilogram, and 4 of the 25 participants received a second dose (20 mg per kilogram regardless of initial dose). No safety concerns were identified. We observed dose-dependent increases in CIS43LS serum concentrations, with a half-life of 56 days. None of the 9 participants who received CIS43LS, as compared with 5 of 6 control participants who did not receive CIS43LS, had parasitemia according to polymerase-chain-reaction testing through 21 days after controlled human malaria infection. Two participants who received 40 mg per kilogram of CIS43LS and underwent controlled human malaria infection approximately 36 weeks later had no parasitemia, with serum concentrations of CIS43LS of 46 and 57 µg per milliliter at the time of controlled human malaria infection. CONCLUSIONS: Among adults who had never had malaria infection or vaccination, administration of the long-acting monoclonal antibody CIS43LS prevented malaria after controlled infection. (Funded by the National Institute of Allergy and Infectious Diseases; VRC 612 ClinicalTrials.gov number, NCT04206332.).


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antimaláricos/uso terapêutico , Malária Falciparum/prevenção & controle , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Anticorpos Antiprotozoários/sangue , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Antimaláricos/farmacocinética , Relação Dose-Resposta a Droga , Voluntários Saudáveis , Humanos , Infusões Intravenosas/efeitos adversos , Injeções Subcutâneas/efeitos adversos , Pessoa de Meia-Idade , Plasmodium falciparum/imunologia , Plasmodium falciparum/isolamento & purificação
2.
Ann Agric Environ Med ; 28(2): 237-242, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34184504

RESUMO

INTRODUCTION AND OBJECTIVE: Toxoplasmosis is an important zoonosis caused by a protozoan, Toxoplasma gondii. Raw or undercooked venison may be a source of infection in humans. The aim of the study was to determine the prevalence of T. gondii antibodies in wild boar from the Strzalowo Forest Division of the Warmia and Mazury Region of Poland. MATERIAL AND METHODS: A total of 90 samples were collected from 50 wild boar: 40 from both tongue and diaphragm muscles, 4 from diaphragm muscles and six from tongue muscles. Samples were analyzed using the commercial PrioCHECK® Toxoplasma Ab porcine ELISA, according to the manufacturer's instructions. RESULTS: T. gondii antibodies were detected in 24 of 50 (48%) tested animals. T. gondii antibodies were detected in 40 of 90 (44.4%) tested samples (21 of tongue muscles and 19 of diaphragm muscles). In the 40 wild boar that provided samples of meat juice from the tongue and diaphragm muscles, specific antibodies were more prevalent in the tongue (20 of 40 animals - 50%) than in the diaphragm muscles (17 of 40 animals - 42.5%). CONCLUSIONS: The study revealed a high percentage of wild boar seropositive to T. gondii. Muscle samples to obtain meat juice are easily available and simple to collect, even on the hunting grounds, which makes them suitable material for detecting T. gondii antibodies in wild boar. Wild boar are essential to T. gondii circulation in the environment, and raw or undercooked venison may be a source of human infections with this parasite.


Assuntos
Anticorpos Antiprotozoários/sangue , Doenças dos Suínos/sangue , Toxoplasma/isolamento & purificação , Toxoplasmose Animal/sangue , Animais , Florestas , Polônia/epidemiologia , Estudos Soroepidemiológicos , Sus scrofa , Suínos , Doenças dos Suínos/epidemiologia , Toxoplasma/genética , Toxoplasma/imunologia , Toxoplasmose Animal/epidemiologia , Toxoplasmose Animal/parasitologia
3.
Parasitol Res ; 120(7): 2681-2687, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34110503

RESUMO

Babesial parasites are some of the most ubiquitous blood pathogens and consequently have considerable worldwide veterinary impact. Dogs living in the tropics are highly exposed to babesial parasites, particularly to Babesia vogeli. Limited data on the seroprevalence and molecular prevalence of Babesia spp. in dogs are available in Latin America. We conducted a cross-sectional study combining serological and molecular tests to estimate the seroprevalence and molecular epidemiology of Babesia spp. infections in dogs in two hyperendemic foci in Brazil. A total of 630 privately owned dogs (417 from Goiana municipality, Pernambuco state, north-eastern Brazil, and 213 from São Joaquim de Bicas municipality, Minas Gerais state, south-eastern Brazil) were sampled and molecularly and serologically tested for Babesia spp. Overall, 519 dogs (82.4%) presented detectable IgG antibodies against Babesia spp., and seropositivity was significantly higher in dogs older than 1 year. Molecularly, 34 dogs (5.4%) were positive for a ~ 200 bp fragment of the 18S rRNA gene of Babesia spp. and 88 (14.0%) for a longer fragment (~ 450 bp) of the same gene of Babesia spp. and other protozoa. The 18S rRNA gene sequences generated herein corresponded to B. vogeli (n = 52) or Hepatozoon canis (n = 20). This study confirms a high level of exposure to B. vogeli in two areas of Brazil and highlights that most of the dogs living in these areas are infected during the course of their life, reflected by increased seroprevalence in older dogs. Increased awareness and prevention of tick-borne protozoa infections in dogs from Brazil and Latin America are urgently needed.


Assuntos
Babesiose/epidemiologia , Babesiose/parasitologia , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Fatores Etários , Animais , Anticorpos Antiprotozoários/sangue , Babesia/classificação , Babesia/genética , Babesia/imunologia , Brasil/epidemiologia , Estudos Transversais , DNA de Protozoário/química , DNA de Protozoário/isolamento & purificação , Cães , Doenças Endêmicas/veterinária , Feminino , Imunoglobulina G/sangue , Masculino , Epidemiologia Molecular , Filogenia , Prevalência , RNA Ribossômico 18S/genética , Estudos Soroepidemiológicos , Doenças Transmitidas por Carrapatos/epidemiologia
4.
Turkiye Parazitol Derg ; 45(2): 108-112, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34103286

RESUMO

Objective: This study aimed to investigate the seroprevalence of Neospora caninum and Besnoitia besnoiti in cattle in the Oguzlar district of Çorum province. Methods: Venous blood samples were collected from the vena jugularis of 100 cattle in the Oguzlar region and stored into anticoagulant-free tubes. Serum samples were examined with commercial c-ELISA kits for N. caninum (IDEXX, Switzerland) and B. besnoiti (ID.vet, France). Results: Two of serum samples were found to be N. caninum (2%) and five were B. besnoiti (5%) seropositive. No mixed infection was detected in any of serum samples. Conclusion: In this study, the presence of N. caninum and B. besnoiti was serologically determined in animals that are not imported in the Oguzlar region. This is the first study in the region to identify B. besnoiti in the seropositive cattle and is the third study in Turkey.


Assuntos
Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/parasitologia , Coccidiose/veterinária , Neospora/isolamento & purificação , Sarcocystidae/isolamento & purificação , Animais , Anticorpos Antiprotozoários/sangue , Bovinos , Coccidiose/epidemiologia , Coccidiose/parasitologia , Ensaio de Imunoadsorção Enzimática/veterinária , Neospora/imunologia , Sarcocystidae/imunologia , Estudos Soroepidemiológicos , Turquia/epidemiologia
5.
PLoS Negl Trop Dis ; 15(5): e0009389, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33979344

RESUMO

BACKGROUND: Interruption of domestic vector-borne transmission of Trypanosoma cruzi is still an unmet goal in several American countries. In 2007 we launched a long-term intervention program aimed to suppress house infestation with the main domestic vector in southern South America (Triatoma infestans) and domestic transmission in Pampa del Indio, a resource-constrained, hyperendemic municipality with 1446 rural houses inhabited by Creole and indigenous people, in the Argentine Chaco ecoregion. Here, we assessed whether the 10-year insecticide-based program combined with community mobilization blocked vector-borne domestic transmission of T. cruzi to humans and dogs. METHODS: We carried out two municipality-wide, cross-sectional serosurveys of humans and dogs (considered sentinel animals) during 2016-2017 to compare with baseline data. We used a risk-stratified random sampling design to select 273 study houses; 410 people from 180 households and 492 dogs from 151 houses were examined for antibodies to T. cruzi using at least two serological methods. RESULTS: The seroprevalence of T. cruzi in children aged <16 years was 2.5% in 2017 (i.e., 4- to 11-fold lower than before interventions). The mean annual force of child infection (λ) sharply decreased from 2.18 to 0.34 per 100 person-years in 2017. One of 102 children born after interventions was seropositive for T. cruzi; he had lifetime residence in an apparently uninfested house, no outside travel history, and his mother was T. cruzi-seropositive. No incident case was detected among 114 seronegative people of all ages re-examined serologically. Dog seroprevalence was 3.05%. Among native dogs, λ in 2016 (1.21 per 100 dog-years) was 5 times lower than at program onset. Six native adult dogs born after interventions and with stable lifetime residence were T. cruzi-seropositive: three had exposure to T. infestans at their houses and one was an incident case. CONCLUSIONS: These results support the interruption of vector-borne transmission of T. cruzi to humans in rural Pampa del Indio. Congenital transmission was the most likely source of the only seropositive child born after interventions. Residual transmission to dogs was likely related to transient infestations and other transmission routes. Sustained vector control supplemented with human chemotherapy can lead to a substantial reduction of Chagas disease transmission in the Argentine Chaco.


Assuntos
Doença de Chagas/prevenção & controle , Doenças do Cão/parasitologia , Trypanosoma cruzi/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Antiprotozoários/sangue , Argentina , Doença de Chagas/transmissão , Doença de Chagas/veterinária , Criança , Pré-Escolar , Estudos Transversais , Doenças do Cão/prevenção & controle , Cães , Feminino , Humanos , Lactente , Controle de Insetos , Insetos Vetores , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Triatoma
6.
Front Immunol ; 12: 610305, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968015

RESUMO

Sequestration of Plasmodium falciparum-infected erythrocytes expressing the VAR2CSA antigen in the placenta results in poor pregnancy outcomes, including low birth weight and maternal anemia. Antigen-specific antibody-mediated immunity is acquired during successive pregnancies. Thus, evaluating VAR2CSA-specific IgG profiles among pregnant women will increase knowledge on the immunological mechanisms associated with protection, and help in the development of VAR2CSA-based placental malaria vaccines. Using the PAMVAC candidate vaccine antigen, we assessed anti-VAR2CSA IgG subclass responses of a cohort of pregnant Beninese, and analyzed their relationships with pregnancy outcomes. Cytophilic IgG1 and IgG3 responses were the most frequent, with prevalences ranging from 28% (IgG3) up to 50% (IgG1). Elevated levels of VAR2CSA-specific total IgG and cytophilic IgG3 during pregnancy were consistently associated with higher birth weights, whilst high levels of IgG4 were associated with a reduced risk of placental infections. This suggests that protective anti-VAR2CSA IgG responses are coordinated between both cytophilic and non-cytophilic antibodies.


Assuntos
Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Imunoglobulina G/imunologia , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Plasmodium falciparum/imunologia , Adulto , Anticorpos Antiprotozoários/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Recém-Nascido de Baixo Peso , Malária Falciparum/transmissão , Gravidez , Complicações Parasitárias na Gravidez/imunologia , Complicações Parasitárias na Gravidez/parasitologia , Resultado da Gravidez , Fatores de Risco , Adulto Jovem
7.
Nat Immunol ; 22(5): 654-665, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33888898

RESUMO

Controlled human infections provide opportunities to study the interaction between the immune system and malaria parasites, which is essential for vaccine development. Here, we compared immune signatures of malaria-naive Europeans and of Africans with lifelong malaria exposure using mass cytometry, RNA sequencing and data integration, before and 5 and 11 days after venous inoculation with Plasmodium falciparum sporozoites. We observed differences in immune cell populations, antigen-specific responses and gene expression profiles between Europeans and Africans and among Africans with differing degrees of immunity. Before inoculation, an activated/differentiated state of both innate and adaptive cells, including elevated CD161+CD4+ T cells and interferon-γ production, predicted Africans capable of controlling parasitemia. After inoculation, the rapidity of the transcriptional response and clusters of CD4+ T cells, plasmacytoid dendritic cells and innate T cells were among the features distinguishing Africans capable of controlling parasitemia from susceptible individuals. These findings can guide the development of a vaccine effective in malaria-endemic regions.


Assuntos
Imunidade Adaptativa/imunologia , Suscetibilidade a Doenças/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Imunidade Adaptativa/genética , Adolescente , Adulto , Grupo com Ancestrais do Continente Africano/genética , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Células Dendríticas/imunologia , Suscetibilidade a Doenças/sangue , Suscetibilidade a Doenças/parasitologia , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Voluntários Saudáveis , Interações Hospedeiro-Parasita/genética , Interações Hospedeiro-Parasita/imunologia , Humanos , Imunidade Inata/genética , Imunidade Inata/imunologia , Interferon gama/metabolismo , Malária Falciparum/sangue , Malária Falciparum/parasitologia , Masculino , RNA-Seq , Análise de Sistemas , Linfócitos T/imunologia , Linfócitos T/metabolismo , Adulto Jovem
8.
Lancet Infect Dis ; 21(8): 1141-1150, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33836157

RESUMO

BACKGROUND: Assessment of therapeutic response with standard serological diagnostic assays in patients with chronic Chagas disease is a major challenge due to the long persistence of parasite-specific antibodies. The current consensus for parasitological cure is to monitor conversion from positive to negative Trypanosoma cruzi serology (seroreversion). However, because of robust humoral immune response, seroreversion by standard serological tests can take years to decades. Developing novel tests of parasitological cure or surrogates is thus a priority in the Chagas disease field. We aimed to evaluate the MultiCruzi assay as a predictive tool for parasitological cure in a cohort of treated infants and children with acute and chronic Chagas disease enrolled in a long-term retrospective longitudinal study with clinical, serological, and parasitological follow-up, and to explore whether MultiCruzi could predict parasitological cure more quickly than the current reference method. METHODS: Patients from two retrospective paediatric Chagas disease cohort studies with clinical, serological, and parasitological follow-up, diagnosed and treated at the parasitology service, Hospital de Niños Ricardo Gutierrez (Buenos Aires, Argentina) were included in this retrospective cohort study. Serum samples were collected every 6 months to 12 months between Oct 22, 1990, and June 3, 2019, for cohort 1 and 1 month after birth for cohort 2 and then every 3 months for a year between July 23, 2012, and April 19, 2016. We evaluated serological follow-up with the Chagatest ELISA (Wiener Lab, Rosario, Argentina) and used this as a clinical reference method for the evaluation of seroreversion. We compared Chagatest ELISA results with results of MultiCruzi (InfYnity Biomarkers, Lyon, France), a novel antibody profiling multiplex assay, investigating seroreversion events with both of the assays and prediction of seroreversion with MultiCruzi using an interpretation formula. FINDINGS: Combining experimental data from discrete analysis of 15 T cruzi antigens efficiently predicted seroreversion at an early stage, which was later confirmed by conventional T cruzi serology. In cohort 1 (n=69), which included children of three different age groups, we observed differences 2 years after therapy. In the 27 individuals from cohort 1 who were treated within the first 12 months of age, MultiCruzi predicted early seroreversion in 21 (78%) patients whereas nine (33%) patients showed seroreversion with Chagatest ELISA (seroreversion difference 0·44, 95% CI 0·26-0·63; p=0·0005). In the 12 patients from cohort 1 treated between 1 year and 2 years of age, MultiCruzi predicted early seroreversion in six (50%) patients, whereas only one (8%) patient was confirmed to be seronegative with Chagatest ELISA (seroreversion difference 0·42, 95% CI 0·14-0·70; p=0·0253). In the 30 patients from cohort 1 who were treated between 2 years and 19 years of age, MultiCruzi predicted early seroreversion in five (6%) patients, whereas no patients were found to be seronegative with Chagatest ELISA (seroreversion difference 0·17, 0·03-0·30; p=0·0253). In cohort 2 (n=27), which included only children younger than 1 year of age and had a shorter follow up (between 5 months and 32 months), the proportion of reported events was significantly different 180 days after treatment for the T cruzi-positive group (early seroreversion predicted in nine [90%] of ten patients with MultiCruzi and confirmed seroreversion in four [40%] of ten patients with Chagatest ELISA; seroreversion difference 0·50, 95% CI 0·19-0·81; p=0·0253) and for the T cruzi-negative group 90 days (early seroreversion predicted in five [29%] of 17 patients with MultiCruzi and confirmed seroreversion in one [6%] of 17 patients with Chagatest ELISA; seroreversion difference 0·24, 0·03-0·44; p=0·0455) and 180 days (early seroreversion predicted in 17 [100%] of 17 patients with MultiCruzi and confirmed seroreversion only in seven [41%] of 17 patients with Chagatest ELISA; seroreversion difference 0·59, 0·35-0·82; p=0·0016) after treatment. INTERPRETATION: The MultiCruzi assay can be used as a predictive monitoring tool to assess parasitological cure in children. This approach might be a solution to forecast forthcoming seroreversion in treated adults infected with T cruzi, but this requires further investigation. FUNDING: Drugs for Neglected Diseases initiative. TRANSLATIONS: For the Spanish, Portuguese and French translations of the abstract see Supplementary Materials section.


Assuntos
Anticorpos Antiprotozoários/sangue , Antiprotozoários/uso terapêutico , Doença de Chagas/tratamento farmacológico , Testes Sorológicos/métodos , Trypanosoma cruzi/imunologia , Adolescente , Formação de Anticorpos , Argentina , Criança , Pré-Escolar , Monitoramento de Medicamentos , Feminino , França , Humanos , Lactente , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Estudos Retrospectivos , Trypanosoma cruzi/genética , Trypanosoma cruzi/isolamento & purificação , Adulto Jovem
9.
Epidemiol Infect ; 149: e99, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33843523

RESUMO

Serology data are an increasingly important tool in malaria surveillance, especially in low transmission settings where the estimation of parasite-based indicators is often problematic. Existing methods rely on the use of thresholds to identify seropositive individuals and estimate transmission intensity, while making assumptions about the temporal dynamics of malaria transmission that are rarely questioned. Here, we present a novel threshold-free approach for the analysis of malaria serology data which avoids dichotomization of continuous antibody measurements and allows us to model changes in the antibody distribution across age in a more flexible way. The proposed unified mechanistic model combines the properties of reversible catalytic and antibody acquisition models, and allows for temporally varying boosting and seroconversion rates. Additionally, as an alternative to the unified mechanistic model, we also propose an empirical approach to analysis where modelling of the age-dependency is informed by the data rather than biological assumptions. Using serology data from Western Kenya, we demonstrate both the usefulness and limitations of the novel modelling framework.


Assuntos
Malária/epidemiologia , Modelos Teóricos , Adolescente , Anticorpos Antiprotozoários/sangue , Criança , Pré-Escolar , Humanos , Lactente , Quênia/epidemiologia , Malária/sangue , Malária/transmissão , Plasmodium/imunologia , Soroconversão , Testes Sorológicos
10.
J Wildl Dis ; 57(2): 393-398, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33822151

RESUMO

Serum samples of 11 Bengal tigers (Panthera tigris tigris) from Chitwan National Park in Nepal, collected between 2011-17, were evaluated for the presence of antibodies to eight diseases commonly investigated in large felids. This initial serologic survey was done to establish baseline information to understand the exposure of Nepal's free-ranging tiger population to these diseases. Tiger serum samples collected opportunistically during encounters such as translocation, human conflict, and injury were placed in cold storage for later use. Frozen serum samples were assessed for feline coronavirus (FCoV), feline immunodeficiency virus, feline leukemia virus, feline herpesvirus (FHV), canine distemper virus, canine parvovirus-2 (CPV-2), leptospirosis (LEP; seven serovars), and toxoplasmosis (TOX). Six tigers were found to be positive for LEP, eight for CPV-2, five for FHV, one for FCoV, and 10 for TOX. Tigers, like other wild felids, have been exposed to these common pathogens, but further research is needed to determine the significance of these pathogens to the Nepali population.


Assuntos
Doenças Transmissíveis/veterinária , Tigres , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antiprotozoários/sangue , Anticorpos Antivirais/sangue , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/imunologia , Feminino , Leptospirose/epidemiologia , Leptospirose/imunologia , Leptospirose/veterinária , Masculino , Nepal/epidemiologia , Toxoplasmose Animal/epidemiologia , Toxoplasmose Animal/imunologia , Viroses/epidemiologia , Viroses/imunologia , Viroses/veterinária
11.
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
12.
BMC Infect Dis ; 21(1): 369, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33874901

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) is severe and potentially fatal. Brazil is one of the countries with the greatest endemicity for the disease in the world. The reduction of CD4+ T lymphocytes, B cells activation and high levels of inflammatory cytokines (IL-6/IL-8/TNF/IL-1ß), plasma LPS, soluble CD14, anti-Leishmania IgG3 and low leptin levels are involved in the immunopathogenesis of VL, most associated with severe VL. Despite relapses occurring in about 4-5% of patients with VL not associated with HIV infection, the factors underlying relapses are little known. Our aim was to identify clinical, laboratory and immunological parameters that may be associated with recurrences in VL. METHODS: Fifteen VL patients recruited from Hospital Eduardo de Menezes (BH-MG) were grouped into relapsing (R-VL, n = 5) and non-relapsing (NR-VL, n = 10) and evaluated during active disease, immediately after treatment (post-treatment) and 6 months post-treatment (6mpt). Clinical and laboratory data obtained from medical records were correlated with CD4+ and CD8+ T cell counts and anti-Leishmania Igs and IL-6 plasma levels and compared to those parameters of ten healthy controls. RESULTS: During the active phase of VL, despite similarity in the clinical symptoms, the rates of thrombocytopenia, elevated transaminases (AST and ALT) and hyperbilirubinemia were higher in the NR-VL group compared to R-VL (p < 0.05), a profile reversed during the post-treatment phase. All patients had low CD4+ T counts in active phase, however, NR-VL patients had a higher gain of this cell type than R-VL in the post-treatment (p < 0.05). There was a significant reduction in IgG3 levels during the follow-up in the NR-VL group compared to the R-VL, especially at 6mpt (p < 0.05). In addition, IgG3 levels were negatively correlated with CD4+ T counts in the R-VL group (r = - 0.52). Elevated levels of IL-6 were observed in active VL and correlated with clinical markers of severity. CONCLUSIONS: During active phase of VL, the NR-VL patients presented more severe laboratorial abnormalities compared to R-VL, probably because the latter had already received previous treatment. On the other hand, R-VL exhibited greater impairment of immune reconstitution and a high degree of B lymphocyte activation, which must be a factor that favored relapses.


Assuntos
Anticorpos Antiprotozoários/sangue , Linfócitos T CD4-Positivos/citologia , Imunoglobulina G/sangue , Leishmania/imunologia , Leishmaniose Visceral/patologia , Adulto , Anfotericina B/uso terapêutico , Brasil , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Feminino , Infecções por HIV/complicações , Humanos , Interleucina-6/sangue , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/imunologia , Masculino , Pessoa de Meia-Idade , Recidiva
13.
Parasitol Res ; 120(5): 1771-1780, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33792813

RESUMO

Leishmaniasis is a vector-borne parasitic disease caused by protozoa of the genus Leishmania. Twenty different species are known to cause disease in humans with varying degrees of pathology. These diseases are transmitted throughout the geographic range of phlebotomine sandflies, found between the latitudes 50°N and 40°S. This study explores antibody dependent enhancement (ADE) as the cause of disease exacerbation in heterologous exposure of L. major primed mice to L. infantum challenge. BALB/c mice received serum from L. major infected or naive mice. All mice were challenged with L. infantum and tissue parasite burdens were recorded. Animals that received anti-L. major serum exhibited significantly higher parasite burdens. Surprisingly, these parasite burdens were higher than those of mice infected with L. major and challenged with L. infantum. In vitro phagocytosis assays were carried out to measure parasite uptake in the presence of naive vs. anti-L. major serum. J774A.1 murine monocytes were cultured with either L. major or L. infantum in the presence of anti-L. major serum, naive serum, or no serum. Significantly higher rates of L. major uptake by J774A.1 cells occurred in the presence of anti-L. major serum, but no measurable increase of L. infantum phagocytosis was seen. Our results suggest that increased disease severity observed in vivo in mice previously exposed to L. major and challenged with L infantum is not a result of extrinsic ADE. We speculate that intrinsic ADE, due to biased memory T cell responses caused by Fcγ signaling, could account for disease exacerbation seen in the animal model.


Assuntos
Leishmania infantum/imunologia , Leishmania major/imunologia , Leishmaniose/parasitologia , Animais , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Linhagem Celular , Modelos Animais de Doenças , Imunização Passiva , Memória Imunológica , Leishmaniose/imunologia , Leishmaniose Cutânea/complicações , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/parasitologia , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Psychodidae , Linfócitos T/imunologia
14.
Vet J ; 271: 105638, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33840483

RESUMO

Quantitative anti-Leishmania antibody titres are critical in the management of dogs with leishmaniosis, from diagnosis to treatment and follow-up, and there is a paucity of data relating changes in antibody titres to sand fly vector seasonality. This study aimed to evaluate seasonal variations in anti-Leishmania infantum antibody titres in dogs from a hyperendemic area for canine leishmaniosis (CanL). Leishmania infantum-seropositive and clinically healthy dogs (n=65) were sampled in June 2019 (sand fly season) and again in February-March 2020 (non-transmission season) to monitor clinical status and serological titres. There was a reduction in anti-L. infantum antibody titres during the non-transmission season in most dogs (n=36; 55.4%), and 44% of those dogs (n=16/36) became seronegative (i.e. below the cut-off value of 1:80). Given the relevance of serology to epidemiological, preventive and clinical studies related to CanL, seasonal variations in antibody titres are important in areas where phlebotomine vectors have seasonal patterns of activity. Sand fly seasonal period must be considered in the interpretation of annual anti-L. infantum antibody screening test results in asymptomatic dogs, to make clinical decisions about staging, treatment and prevention.


Assuntos
Anticorpos Antiprotozoários/sangue , Doenças do Cão/parasitologia , Leishmania infantum/imunologia , Leishmaniose Visceral/veterinária , Estações do Ano , Animais , Vetores de Doenças , Doenças do Cão/diagnóstico , Doenças do Cão/epidemiologia , Cães , Feminino , Itália/epidemiologia , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Masculino , Psychodidae/parasitologia
15.
J Parasitol ; 107(2): 309-319, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33886960

RESUMO

Toxoplasma gondii infections are common in humans and animals worldwide. The ingestion of food or water contaminated with oocysts excreted by infected cats or ingestion of uncooked or undercooked meat containing tissue cysts of T. gondii are the 2 major modes of transmission of T. gondii. Deer are a popular game. Recently, outbreaks of clinical toxoplasmosis were reported in humans in North America linked to ingestion of undercooked venison. Here, we review prevalence, persistence of infection, clinical disease, epidemiology, and public health risks of T. gondii infections in deer and other cervids for the past decade. Estimates of worldwide serological prevalence are summarized individually for each species of deer, elk, moose, and caribou. Genetic diversity of 112 viable isolates of T. gondii from cervids is discussed, including its public health significance. Prevalence of T. gondii in deer is very high. Any part of a deer, including liver, spleen, and muscles, should be cooked thoroughly before human consumption.


Assuntos
Cervos/parasitologia , Carne/parasitologia , Toxoplasma/isolamento & purificação , Toxoplasmose Animal/epidemiologia , Toxoplasmose Animal/transmissão , Toxoplasmose/etiologia , Aborto Animal/epidemiologia , Animais , Anticorpos Antiprotozoários/sangue , Culinária/métodos , Culinária/normas , DNA de Protozoário/análise , Genótipo , Humanos , Fígado/parasitologia , Músculos/parasitologia , Prevalência , Baço/parasitologia , Toxoplasma/classificação , Toxoplasma/genética , Toxoplasma/imunologia , Toxoplasmose/epidemiologia , Toxoplasmose/transmissão , Estados Unidos/epidemiologia
16.
Parasit Vectors ; 14(1): 154, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33722267

RESUMO

BACKGROUND: Besnoitia besnoiti is an Apicomplexan protozoa causative of bovine besnoitiosis, a chronic and debilitating disease of cattle, with a variety of pathological findings that could alter some laboratory parameters. A study was conducted in a bovine besnoitiosis endemically infected dairy herd located in Italy characterized by high intra-herd seroprevalence and cattle with clinical signs of the disease. In the study, alterations in laboratory parameters, i.e. hematological and biochemical parameters, enzyme activities and serum cortisol levels, in Besnoitia besnoiti naturally infected cows were investigated in depth. METHODS: Laboratory parameters in 107 cows, of which 61 were seronegative and 46 were seropositive to B. besnoiti, including 27 with clinical signs of bovine besnoitiosis, were compared. Generalized linear models were used to evaluate the effect of Besnoitia infection on the considered laboratory parameters. RESULTS: Hematological analyses revealed that B. besnoiti infection determined a significant alteration to the leukocyte differential, with a higher percentage of granulocytes and a lower percentage of lymphocytes in seropositive and clinically affected animals (Mann-Whitney U-test, P = 0.022); erythrocyte and platelet counts did not show any difference between the considered groups of cows. Biochemistry tests evidenced that the parasite infection influenced serum protein values in seropositive cows and glutamate dehydrogenase values in clinically affected animals. No or only slight differences were revealed for all of the other biochemical and enzyme activity parameters in B. besnoiti-infected animals. In addition, despite the lack of statistical significance, seropositive and clinically affected cows evidenced higher concentrations of serum cortisol values compared to seronegative animals. CONCLUSIONS: Although physiological, pathological and farm-related factors could have influenced the results in investigated animals, further studies involving more animals from different farms would be advisable to infer the role of B. besnoiti on these alterations, since laboratory parameters could help veterinarians in the diagnosis of bovine besnoitiosis in cattle.


Assuntos
Anticorpos Antiprotozoários/sangue , Doenças dos Bovinos/sangue , Doenças dos Bovinos/parasitologia , Coccidiose/sangue , Coccidiose/veterinária , Hidrocortisona/sangue , Sarcocystidae/imunologia , Animais , Bovinos , Doenças dos Bovinos/imunologia , Indústria de Laticínios , Feminino , Itália/epidemiologia , Estudos Soroepidemiológicos
17.
Mem Inst Oswaldo Cruz ; 116: e200428, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33729396

RESUMO

BACKGROUND: Dogs are the main peridomiciliary reservoir of Leishmania infantum thus the correct diagnosis of infection is essential for the control of the transmission and treatment as well. However, the diagnosis is based on serological assays that are not fully effective. OBJECTIVE: We aimed to establish an effective serological assay for the diagnosis of L. infantum infected dogs using Leishmania-derived recombinant antigens. METHODS: Leishmania derived rK39-, rK28-, rKR95-based enzyme-linked immunosorbent assay (ELISA) was standardized using symptomatic and asymptomatic L. infantum-infected dogs. Then 2,530 samples from inquiry in endemic areas for VL were evaluated and the results compared with recommended assays by the Brazilian Ministry of Health (MH algorithm). Further samples from a cohort of 30 dogs were searched. FINDINGS: For rK39-, rK28- and rKR95-ELISA the sensitivity was around 97% and specificity 100%. The positivity of these three ELISA in the inquiry samples was 27-28%, around 10% higher than the assays currently in use. When cohort samples were searched, we observed likely false-negative results (> 65%) with supposedly negative samples that turned positive six months later with the assays in use (MH algorithm). MAIN CONCLUSIONS: For the diagnosis of L. infantum-infected dogs, rK39-based ELISA showed better diagnostic performance than other assays in use in Brazil and worldwide.


Assuntos
Anticorpos Antiprotozoários/sangue , Doenças do Cão/diagnóstico , Ensaio de Imunoadsorção Enzimática/normas , Ensaio de Imunoadsorção Enzimática/veterinária , Leishmania infantum/imunologia , Leishmaniose Visceral/diagnóstico , Animais , Antígenos de Protozoários/biossíntese , Brasil , Cães , Ensaio de Imunoadsorção Enzimática/métodos , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/sangue , Leishmaniose Visceral/veterinária , Proteínas Recombinantes/imunologia , Sensibilidade e Especificidade , Testes Sorológicos
18.
Front Immunol ; 12: 610108, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717094

RESUMO

Pregnant women infected with Plasmodium falciparum often produce antibodies (Abs) to VAR2CSA, a ligand that binds to placental chondroitin sulfate A causing placental malaria (PM). Antibodies to VAR2CSA are associated with improved pregnancy outcomes. Antibody avidity is a surrogate marker for the extent of maturation of the humoral immune response. Little is known about high avidity Abs to VAR2CSA for women living in urban African cities. Therefore, this study sought to determine: i) if high avidity Abs to full-length VAR2CSA (FV2) increase with gravidity in women in Yaoundé, Cameroon exposed to ~ 0.3-1.1 infectious mosquito bites per month, ii) if high avidity Abs to FV2 are directed against a specific region of VAR2CSA, and iii) if having high avidity Abs to FV2 improve pregnancy outcomes. Plasma samples collected at delivery from 695 women who had Abs to FV2 were evaluated. Ab levels and the Avidity Index (AI), defined as the percent Abs remaining bound to FV2 after incubation with 3M NH4SCN, were determined. Similar Ab levels to FV2 were present in women of all gravidities (G1 through 6+; p=0.80), except significantly lower levels were detected in PM-negative (PM-) primigravidae (p <0.001). Median Ab avidities increased between gravidity 1 and 2 (p<0.001) and remained stable thereafter (G3-G6+: p=0.51). These results suggest that B cell clonal expansion began during the first pregnancy, with clonal selection primarily occurring during the second. However, the majority of women (84%) had AI <35, a level of high avidity Abs previously reported to be associated with improved pregnancy outcomes. When plasma from 107 Cameroonian women was tested against 8 different regions of FV2, high avidity Abs were predominately restricted to DBL5 with median AI of 50 compared to AI <25 for the other domains. The only significance influence of high avidity Abs on pregnancy outcome was that babies born to mothers with AI above the median were 104 g heavier than babies born to women with AI below the median (p=0.045). These results suggest that a vaccine that boosts maturation of the immune response to VAR2CSA may be beneficial for women residing in urban areas.


Assuntos
Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Complicações Parasitárias na Gravidez/epidemiologia , Complicações Parasitárias na Gravidez/imunologia , Anticorpos Antiprotozoários/sangue , Afinidade de Anticorpos/imunologia , Antígenos de Protozoários/sangue , Antígenos de Protozoários/química , Camarões/epidemiologia , Cidades , Feminino , Humanos , Malária Falciparum/sangue , Gravidez , Complicações Parasitárias na Gravidez/sangue , Resultado da Gravidez , Domínios e Motivos de Interação entre Proteínas/imunologia , Vigilância em Saúde Pública
19.
PLoS One ; 16(3): e0240874, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651845

RESUMO

Dried-leaf Artemisia annua L. (DLA) antimalarial therapy was shown effective in prior animal and human studies, but little is known about its mechanism of action. Here IC50s and ring-stage assays (RSAs) were used to compare extracts of A. annua (DLAe) to artemisinin (ART) and its derivatives in their ability to inhibit and kill Plasmodium falciparum strains 3D7, MRA1252, MRA1240, Cam3.11 and Cam3.11rev in vitro. Strains were sorbitol and Percoll synchronized to enrich for ring-stage parasites that were treated with hot water, methanol and dichloromethane extracts of DLA, artemisinin, CoArtem™, and dihydroartemisinin. Extracts of A. afra SEN were also tested. There was a correlation between ART concentration and inhibition of parasite growth. Although at 6 hr drug incubation, the RSAs for Cam3.11rev showed DLA and ART were less effective than high dose CoArtem™, 8 and 24 hr incubations yielded equivalent antiparasitic results. For Cam3.11, drug incubation time had no effect. DLAe was more effective on resistant MRA-1240 than on the sensitive MRA-1252 strain. Because results were not as robust as observed in animal and human studies, a host interaction was suspected, so sera collected from adult and pediatric Kenyan malaria patients was used in RSA inhibition experiments and compared to sera from adults naïve to the disease. The sera from both age groups of malaria patients inhibited parasite growth ≥ 70% after treatment with DLAe and compared to malaria naïve subjects suggesting some host interaction with DLA. The discrepancy between these data and in-vivo reports suggested that DLA's effects require an interaction with the host to unlock their potential as an antimalarial therapy. Although we showed there are serum-based host effects that can kill up to 95% of parasites in vitro, it remains unclear how or if they play a role in vivo. These results further our understanding of how DLAe works against the malaria parasite in vitro.


Assuntos
Antimaláricos/farmacologia , Artemisia annua/química , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Adulto , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Antimaláricos/química , Artemisia annua/metabolismo , Artemisininas/farmacologia , Criança , Humanos , Estágios do Ciclo de Vida/efeitos dos fármacos , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/imunologia
20.
PLoS One ; 16(3): e0247560, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33705437

RESUMO

In canine leishmaniosis caused by the protozoan Leishmania infantum, little is known about how co-infections with or co-seropositivities for other pathogens can influence aggravation of this disease. Therefore, the objectives of this study were to evaluate the frequency of co-infections with or co-seropositivities for certain pathogens in dogs seropositive for L. infantum and their relationship with clinical signs, histological changes and L. infantum load. Sixty-six L. infantum-seropositive dogs were submitted to clinical examination, collection of blood and bone marrow, culling, and necropsy. Antibodies against Anaplasma spp., Borrelia burgdorferi sensu lato, Ehrlichia spp. and Toxoplasma gondii and Dirofilaria immitis antigens were investigated in serum. Samples from different tissues were submitted to histopathology and immunohistochemistry for the detection of Leishmania spp. and T. gondii. Quantitative real-time PCR was used to assess the L. infantum load in spleen samples. For detection of Coxiella burnetii, conventional PCR and nested PCR were performed using bone marrow samples. All 66 dogs tested positive for L. infantum by qPCR and/or culture. Fifty dogs (76%) were co-seropositive for at least one pathogen: T. gondii (59%), Ehrlichia spp., (41%), and Anaplasma spp. (18%). Clinical signs were observed in 15 (94%) dogs monoinfected with L. infantum and in 45 (90%) dogs co-seropositive for certain pathogens. The L. infantum load in spleen and skin did not differ significantly between monoinfected and co-seropositive dogs. The number of inflammatory cells was higher in the spleen, lung and mammary gland of co-seropositive dogs and in the mitral valve of monoinfected dogs. These results suggest that dogs infected with L. infantum and co-seropositive for certain pathogens are common in the region studied. However, co-seropositivities for certain pathogens did not aggravate clinical signs or L. infantum load, although they were associated with a more intense inflammatory reaction in some organs.


Assuntos
Coinfecção/sangue , Coinfecção/veterinária , Doenças do Cão/sangue , Ehrlichia canis/imunologia , Ehrlichiose/sangue , Ehrlichiose/veterinária , Leishmania infantum/imunologia , Leishmaniose Visceral/sangue , Leishmaniose Visceral/veterinária , Carga Parasitária , Toxoplasma/imunologia , Toxoplasmose Animal/sangue , Animais , Anticorpos Antiprotozoários/sangue , Coinfecção/parasitologia , Coinfecção/patologia , Doenças do Cão/parasitologia , Doenças do Cão/patologia , Cães , Ehrlichiose/parasitologia , Ehrlichiose/patologia , Feminino , Imuno-Histoquímica/métodos , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/patologia , Leucócitos/imunologia , Masculino , Células Mieloides/imunologia , Toxoplasmose Animal/parasitologia , Toxoplasmose Animal/patologia
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