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1.
Eur J Immunol ; 54(4): e2350784, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38308504

RESUMO

Fever is common among individuals seeking healthcare after traveling to tropical regions. Despite the association with potentially severe disease, the etiology is often not determined. Plasma protein patterns can be informative to understand the host response to infection and can potentially indicate the pathogen causing the disease. In this study, we measured 49 proteins in the plasma of 124 patients with fever after travel to tropical or subtropical regions. The patients had confirmed diagnoses of either malaria, dengue fever, influenza, bacterial respiratory tract infection, or bacterial gastroenteritis, representing the most common etiologies. We used multivariate and machine learning methods to identify combinations of proteins that contributed to distinguishing infected patients from healthy controls, and each other. Malaria displayed the most unique protein signature, indicating a strong immunoregulatory response with high levels of IL10, sTNFRI and II, and sCD25 but low levels of sCD40L. In contrast, bacterial gastroenteritis had high levels of sCD40L, APRIL, and IFN-γ, while dengue was the only infection with elevated IFN-α2. These results suggest that characterization of the inflammatory profile of individuals with fever can help to identify disease-specific host responses, which in turn can be used to guide future research on diagnostic strategies and therapeutic interventions.


Assuntos
Infecções Bacterianas , Dengue , Gastroenterite , Malária , Infecções Respiratórias , Humanos , Dengue/diagnóstico , Infecções Respiratórias/complicações , Gastroenterite/complicações , Viagem , Febre/complicações
2.
Emerg Med J ; 41(4): 242-248, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38355290

RESUMO

BACKGROUND: Fever is a common symptom among travellers returning from tropical/subtropical areas to Europe, and promptly distinguishing severe illnesses from self-limiting febrile syndromes is important but can be challenging due to non-specific clinical presentation. METHODS: A cross-sectional study enrolled adults and children who sought care during 2015-2020 at Karolinska University Hospital, Stockholm, Sweden with fever within 2 months after returning from travel to a tropical/subtropical area. Data on symptoms and laboratory parameters were prospectively and retrospectively collected. Two separate scoring systems for malaria and dengue were developed based on backward elimination regressions. RESULTS: In total, 2113 adults (18-94 years) and 202 children (1-17 years) were included, with 112 (4.8%) confirmed malaria by blood thick smear and 90 (3.9%) PCR/serology dengue-positive cases. Malaria was more likely in a patient who had visited sub-Saharan Africa and presented with combination of thrombocytopenia, anaemia and fever ≥39.5°C. Leucopenia, muscle pain and rash after travelling to Asia or South/Latin America indicated high probability of dengue. Two scoring systems with points between 0 and 7 for prediction of malaria or dengue were created based on the above predictors. Scores ≥3 indicated >80% sensitivity and specificity for malaria and >90% specificity for dengue in children and adults (area under the curve (AUC) for dengue: 0.92 in adults (95% CI 0.90 to 0.95) and 0.95 in children (95% CI 0.88 to 1.0); AUC for malaria: 0.93 in adults (95% CI 0.91 to 0.96) and 0.88 in children (95% CI 0.78 to 0.99)). Internal validation of optimism and overfitting was managed with bootstrap. CONCLUSION: The presented scoring systems provide novel tools for structured assessment of patients with tropical fever in a non-endemic area and highlight clinical signs associated with a potential severe aetiology to direct the need for microbial investigation.


Assuntos
Dengue , Malária , Adulto , Criança , Humanos , Estudos Retrospectivos , Estudos Transversais , Dengue/diagnóstico , Dengue/epidemiologia , Malária/diagnóstico , Malária/epidemiologia , Malária/complicações , Febre/etiologia , Febre/complicações , Viagem
3.
Emerg Infect Dis ; 29(6): 1220-1222, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37069700

RESUMO

We compared cycle thresholds from mpox skin lesions with other specimen sites and over time from onset of clinical signs among 104 patients in Sweden. Cycle thresholds differed by anatomic site. We identified 2 early mpox cases from anorectal swab specimens after skin samples were negative, indicating necessity of sampling multiple sites.


Assuntos
Mpox , Humanos , Suécia/epidemiologia , Reação em Cadeia da Polimerase , Monkeypox virus
4.
Emerg Infect Dis ; 29(6): 1240-1243, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37141616

RESUMO

We performed 2 surveys during 2022 to estimate point prevalences of SARS-CoV-2 infection compared with overall seroprevalence in Sweden. Point prevalence was 1.4% in March and 1.5% in September. Estimated seroprevalence was >80%, including among unvaccinated children. Continued SARS-CoV-2 surveillance is necessary for detecting emerging, possibly more pathogenic variants.


Assuntos
COVID-19 , Criança , Humanos , COVID-19/epidemiologia , Prevalência , SARS-CoV-2 , Suécia/epidemiologia , Estudos Soroepidemiológicos
5.
Clin Infect Dis ; 74(7): 1199-1207, 2022 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-34216464

RESUMO

BACKGROUND: The effect of primaquine in preventing Plasmodium vivax relapses from dormant stages is well established. For Plasmodium ovale, the relapse characteristics and the use of primaquine is not as well studied. We set to evaluate the relapsing properties of these 2 species, in relation to primaquine use among imported malaria cases in a nonendemic setting. METHODS: We performed a nationwide retrospective study of malaria diagnosed in Sweden 1995-2019, by reviewing medical records of 3254 cases. All episodes of P. vivax (n = 972) and P. ovale (n = 251) were selected for analysis. RESULTS: First time relapses were reported in 80/857 (9.3%) P. vivax and 9/220 (4.1%) P. ovale episodes, respectively (P < .01). Without primaquine, the risk for relapse was higher in P. vivax, 20/60 (33.3%), compared to 3/30 (10.0%) in P. ovale (hazard ratio [HR] 3.5, 95% confidence interval [CI] 1.0-12.0). In P. vivax, patients prescribed primaquine had a reduced risk of relapse compared to episodes without relapse preventing treatment, 7.1% vs 33.3% (HR 0.2, 95% CI .1-.3). In P. ovale, the effect of primaquine on the risk of relapse did not reach statistical significance, with relapses seen in 2.8% of the episodes compared to 10.0% in patients not receiving relapse preventing treatment (HR 0.3, 95% CI .1-1.1). CONCLUSIONS: The risk of relapse was considerably lower in P. ovale than in P. vivax infections indicating different relapsing features between the two species. Primaquine was effective in preventing P. vivax relapse. In P. ovale, relapse episodes were few, and the supportive evidence for primaquine remains limited.


Assuntos
Antimaláricos , Malária Vivax , Malária , Plasmodium ovale , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Doença Crônica , Humanos , Malária/tratamento farmacológico , Malária/epidemiologia , Malária Vivax/tratamento farmacológico , Malária Vivax/epidemiologia , Plasmodium vivax , Primaquina/efeitos adversos , Recidiva , Estudos Retrospectivos
6.
Emerg Infect Dis ; 28(10): 2074-2077, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36148930

RESUMO

A previously healthy male patient had detectable monkeypox virus DNA in saliva 76 days after laboratory confirmation of infection. A comprehensive characterization of viral kinetics and a detailed follow-up indicated a declining risk for transmission during the weeks after monkeypox symptoms appeared.


Assuntos
Mpox , DNA Viral , Surtos de Doenças , Seguimentos , Humanos , Masculino , Mpox/diagnóstico , Mpox/epidemiologia , Monkeypox virus/genética , Suécia/epidemiologia
7.
J Infect Dis ; 221(5): 775-785, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-31585009

RESUMO

BACKGROUND: The malaria parasite Plasmodium falciparum holds an extensive genetic polymorphism. In this pooled analysis, we investigate how the multiplicity in asymptomatic P. falciparum infections-that is, the number of coinfecting clones-affects the subsequent risk of clinical malaria in populations living under different levels of transmission. METHODS: A systematic search of the literature was performed to identify studies in which P. falciparum infections were genotyped in asymptomatic individuals who were followed up prospectively regarding the incidence of clinical malaria. Individual participant data were pooled from 15 studies (n = 3736 individuals). RESULTS: Multiclonal asymptomatic infections were associated with a somewhat increased subsequent risk of clinical malaria in the youngest children, followed by an initial declining risk with age irrespective of transmission intensity. At approximately 5 years of age, the risk continued the gradual decline with age in high-transmission settings. However, in older children in moderate-, low-, and seasonal-transmission settings, multiclonal infections were either not significantly associated with the risk of subsequent febrile malaria or were associated with an increased risk. CONCLUSIONS: The number of clones in asymptomatic P. falciparum infections is associated with different risks of subsequent clinical malaria depending on age and transmission intensity.


Assuntos
Infecções Assintomáticas/epidemiologia , Genótipo , Malária Falciparum/epidemiologia , Plasmodium falciparum/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Protozoários/genética , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Masculino , Proteína 1 de Superfície de Merozoito/genética , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas de Protozoários/genética , Risco , Adulto Jovem
8.
BMC Med ; 17(1): 22, 2019 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-30696449

RESUMO

BACKGROUND: Antibodies against merozoite antigens are key components of malaria immunity. The naturally acquired antibody response to these antigens is generally considered short-lived; however, the underlying mechanisms remain unclear. Prospective studies of travellers with different levels of prior exposure, returning to malaria-free countries with Plasmodium infection, offer a unique opportunity to investigate the kinetics and composition of the antibody response after natural infection. METHODS: Adults diagnosed with P. falciparum malaria in Stockholm, Sweden (20 likely malaria naïve and 41 with repeated previous exposure during residency in sub-Saharan Africa) were sampled at diagnosis and 10 days and 1, 3, 6, and 12 months after treatment. Total and subclass-specific IgG responses to P. falciparum merozoite antigens (AMA-1, MSP-119, MSP-2, MSP-3, and RH5) and tetanus toxoid were measured by multiplex bead-based immunoassays and ELISA. Mathematical modelling was used to estimate the exposure-dependent longevity of antibodies and antibody-secreting cells (ASCs). RESULTS: A majority of individuals mounted detectable antibody responses towards P. falciparum merozoite antigens at diagnosis; however, the magnitude and breadth were greater in individuals with prior exposure. In both exposure groups, antibody levels increased rapidly for 2 weeks and decayed thereafter. Previously exposed individuals maintained two- to ninefold greater antibody levels throughout the 1-year follow-up. The half-lives of malaria-specific long-lived ASCs, responsible for maintaining circulating antibodies, ranged from 1.8 to 3.7 years for merozoite antigens and were considerably short compared to tetanus-specific ASCs. Primary infected individuals did acquire a long-lived component of the antibody response; however, the total proportion of long-lived ASCs generated in response to infection was estimated not to exceed 10%. In contrast, previously exposed individuals maintained substantially larger numbers of long-lived ASCs (10-56% of total ASCs). CONCLUSION: The short-lived nature of the naturally acquired antibody response, to all tested merozoite antigens, following primary malaria infection can be attributed to a combination of a poor acquisition and short half-life of long-lived ASCs. Greater longevity is acquired with repeated infections and can be explained by the maintenance of larger numbers of long-lived ASCs. These insights advance our understanding of naturally acquired malaria immunity and will guide strategies for further development of both vaccines and serological tools to monitor exposure.


Assuntos
Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Memória Imunológica/imunologia , Malária Falciparum/imunologia , Imunidade Adaptativa/imunologia , Adulto , Animais , Feminino , Humanos , Merozoítos/imunologia , Plasmodium falciparum/imunologia , Estudos Prospectivos , Suécia
9.
Euro Surveill ; 24(5)2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30722809

RESUMO

Global migration has resulted in a large number of asylum applications in Europe. In 2014, clusters of Plasmodium vivax cases were reported among newly arrived Eritreans. This study aimed to assess malaria among Eritrean migrants in Europe from 2011 to 2016. We reviewed European migration numbers and malaria surveillance data for seven countries (Denmark, Germany, Netherlands, Norway, Sweden, Switzerland and the United Kingdom) which received 44,050 (94.3%) of 46,730 Eritreans seeking asylum in Europe in 2014. The overall number of malaria cases, predominantly P. vivax, increased significantly in 2014 compared to previous years, with the largest increases in Germany (44 P. vivax cases in 2013 vs 294 in 2014, p < 0.001) and Sweden (18 in 2013 vs 205 in 2014, p < 0.001). Overall, malaria incidence in Eritreans increased from 1-5 to 25 cases per 1,000, and was highest in male teenagers (50 cases/1,000). In conclusion, an exceptional increase of malaria cases occurred in Europe in 2014 and 2015, due to rising numbers of Eritreans with high incidence of P. vivax arriving in Europe. Our results demonstrate potential for rapid changes in imported malaria patterns, highlighting the need for improved awareness, surveillance efforts and timely healthcare in migrants.


Assuntos
Malária Vivax/diagnóstico , Malária Vivax/etnologia , Plasmodium vivax/isolamento & purificação , Migrantes/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Eritreia/etnologia , Europa (Continente)/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Refugiados , Vigilância de Evento Sentinela , Viagem , Adulto Jovem
10.
Clin Infect Dis ; 64(2): 199-206, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27986683

RESUMO

BACKGROUND: Artemisinin-based combination therapy (ACT) is the first-line treatment of Plasmodium falciparum malaria. Since the introduction of artemether-lumefantrine (AL) for treatment of uncomplicated malaria in Sweden, treatment failures have been reported in adults. METHODS: A retrospective comparative analysis of treatment regimen for P. falciparum malaria in adults in Stockholm during 2000-2015 was performed to evaluate the effectiveness of AL. Parasite genotyping and drug concentrations were investigated in the AL treatment failures. RESULTS: Among the total 397 P. falciparum episodes, 310 were treated with oral regimen only (95 AL, 162 mefloquine, 36 atovaquone-proguanil [AP], and 17 others), and 87 were administered initial intravenous therapy (38 artesunate and 49 quinine) followed by oral treatments. Five late treatment failures were detected after AL and one slow response to AP. The effectiveness of AL alone was 94.7% (95% confidence interval [CI], 88.1%-98.3%), compared with 99.5% for other oral regimens (P = .003). All AL failures occurred in European men and the effectiveness in this group was only 73.7% (95% CI, 48.8%-90.0%). Genotyping confirmed recrudescence of the initial parasite populations and drug resistance markers revealed no clinically significant resistance patterns. Lumefantrine concentrations suggested subtherapeutic concentrations in at least 2 cases. CONCLUSIONS: Our findings indicate a high rate of symptomatic late treatment failures after 6-dose AL regime in nonimmune adults, especially in men. Our report warrants the need to establish optimal dosing of AL in adults and to alert clinicians about the importance of informing patients regarding the risk of parasites reappearing weeks after AL treatment.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Etanolaminas/uso terapêutico , Fluorenos/uso terapêutico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/imunologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/imunologia , Viagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimaláricos/administração & dosagem , Combinação Arteméter e Lumefantrina , Artemisininas/administração & dosagem , Combinação de Medicamentos , Resistência a Medicamentos , Etanolaminas/administração & dosagem , Feminino , Fluorenos/administração & dosagem , Genótipo , Humanos , Malária Falciparum/diagnóstico , Malária Falciparum/epidemiologia , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum/genética , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Suécia/epidemiologia , Falha de Tratamento , Resultado do Tratamento , Adulto Jovem
11.
Infect Immun ; 84(4): 950-963, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26787721

RESUMO

Severe malaria (SM) is a life-threatening complication of infection with Plasmodium falciparum Epidemiological observations have long indicated that immunity against SM is acquired relatively rapidly, but prospective studies to investigate its immunological basis are logistically challenging and have rarely been undertaken. We investigated the merozoite targets and antibody-mediated mechanisms associated with protection against SM in Kenyan children aged 0 to 2 years. We designed a unique prospective matched case-control study of well-characterized SM clinical phenotypes nested within a longitudinal birth cohort of children (n= 5,949) monitored over the first 2 years of life. We quantified immunological parameters in sera collected before the SM event in cases and their individually matched controls to evaluate the prospective odds of developing SM in the first 2 years of life. Anti-AMA1 antibodies were associated with a significant reduction in the odds of developing SM (odds ratio [OR] = 0.37; 95% confidence interval [CI] = 0.15 to 0.90; P= 0.029) after adjustment for responses to all other merozoite antigens tested, while those against MSP-2, MSP-3, Plasmodium falciparum Rh2 [PfRh2], MSP-119, and the infected red blood cell surface antigens were not. The combined ability of total IgG to inhibit parasite growth and mediate the release of reactive oxygen species from neutrophils was associated with a marked reduction in the odds of developing SM (OR = 0.07; 95% CI = 0.006 to 0.82;P= 0.03). Assays of these two functional mechanisms were poorly correlated (Spearman rank correlation coefficient [rs] = 0.12;P= 0.07). Our data provide epidemiological evidence that multiple antibody-dependent mechanisms contribute to protective immunity via distinct targets whose identification could accelerate the development of vaccines to protect against SM.


Assuntos
Anticorpos Antiprotozoários/fisiologia , Malária Falciparum/imunologia , Plasmodium falciparum/fisiologia , Envelhecimento , Antígenos de Protozoários/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Inibidores do Crescimento/metabolismo , Humanos , Lactente , Quênia/epidemiologia , Merozoítos/imunologia , Razão de Chances , Explosão Respiratória/fisiologia
12.
J Infect Dis ; 212(4): 608-16, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25712968

RESUMO

BACKGROUND: Immunity to the antigenically diverse parasite Plasmodium falciparum is acquired gradually after repeated exposure. Studies in areas of high malaria transmission have shown that asymptomatic individuals infected with multiclonal infections are at reduced risk of febrile malaria during follow-up. METHODS: We assessed the relationship between the genetic diversity of clones in P. falciparum infections that persist through the dry season and the subsequent risk of febrile malaria in 225 individuals aged 2-25 years in Mali, where the 6-month malaria and dry seasons are sharply demarcated. Polymerase chain reaction-based genotyping of the highly polymorphic merozoite surface protein 2 gene was performed on blood samples collected at 5 cross-sectional surveys. RESULTS: In an age-adjusted analysis, individuals with multiclonal P. falciparum infections before the rainy season were at reduced risk of febrile malaria, compared with individuals who were uninfected (hazard ratio [HR], 0.28; 95% confidence interval [CI], .11-.69). In contrast, there was no significant association between risk of malaria and having 1 clone at baseline (HR, 0.71; 95% CI, .36-1.40). CONCLUSIONS: The results suggest that persistent multiclonal infections carried through the dry season contribute to protection against subsequent febrile malaria, possibly by maintaining protective immune responses that depend on ongoing parasite infection.


Assuntos
Malária Falciparum/imunologia , Plasmodium falciparum/genética , Estações do Ano , Adolescente , Adulto , Envelhecimento , Antígenos de Protozoários/genética , Antígenos de Protozoários/metabolismo , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Genótipo , Humanos , Malária Falciparum/diagnóstico , Malária Falciparum/prevenção & controle , Masculino , Plasmodium falciparum/imunologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Chuva , Fatores de Tempo , Adulto Jovem
13.
Lakartidningen ; 1202023 06 19.
Artigo em Sueco | MEDLINE | ID: mdl-37334572

RESUMO

Mpox (monkeypox) is an infection caused by the monkeypox virus, which belongs to the same family as the smallpox virus. Sporadic infections in humans have been known since the 1970s. Since spring 2022 there has been a global epidemic. The large majority of the mpox cases in the ongoing epidemic have been reported in adult men, the number of infected children is small.  The typical manifestation of mpox includes a rash that initially presents as maculopapular lesions and then develops into vesicles and eventually crusts. Transmission of the virus primarily occurs through close contact with infected individuals, particularly through contact with unhealed blisters or wounds, as well as through sexual contacts and exposure to body fluids.  In cases of documented close contact with an infected individual, post-exposure prophylaxis is recommended and may also be administered to children whose guardians have contracted mpox.


Assuntos
Exantema , Mpox , Adulto , Masculino , Humanos , Criança , Suécia/epidemiologia , Estações do Ano
14.
Elife ; 122023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-36752598

RESUMO

During respiratory viral infections, the precise roles of monocytes and dendritic cells (DCs) in the nasopharynx in limiting infection and influencing disease severity are incompletely described. We studied circulating and nasopharyngeal monocytes and DCs in healthy controls (HCs) and in patients with mild to moderate infections (primarily influenza A virus [IAV]). As compared to HCs, patients with acute IAV infection displayed reduced DC but increased intermediate monocytes frequencies in blood, and an accumulation of most monocyte and DC subsets in the nasopharynx. IAV patients had more mature monocytes and DCs in the nasopharynx, and higher levels of TNFα, IL-6, and IFNα in plasma and the nasopharynx than HCs. In blood, monocytes were the most frequent cellular source of TNFα during IAV infection and remained responsive to additional stimulation with TLR7/8L. Immune responses in older patients skewed towards increased monocyte frequencies rather than DCs, suggesting a contributory role for monocytes in disease severity. In patients with other respiratory virus infections, we observed changes in monocyte and DC frequencies in the nasopharynx distinct from IAV patients, while differences in blood were more similar across infection groups. Using SomaScan, a high-throughput aptamer-based assay to study proteomic changes between patients and HCs, we found differential expression of innate immunity-related proteins in plasma and nasopharyngeal secretions of IAV and SARS-CoV-2 patients. Together, our findings demonstrate tissue-specific and pathogen-specific patterns of monocyte and DC function during human respiratory viral infections and highlight the importance of comparative investigations in blood and the nasopharynx.


Assuntos
COVID-19 , Doenças Transmissíveis , Vírus da Influenza A , Influenza Humana , Infecções por Orthomyxoviridae , Humanos , Idoso , Monócitos , Fator de Necrose Tumoral alfa/metabolismo , Proteômica , COVID-19/metabolismo , SARS-CoV-2 , Células Dendríticas
15.
Cell Rep ; 39(3): 110709, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35443186

RESUMO

Natural immunity to malaria develops over time with repeated malaria episodes, but protection against severe malaria and immune regulation limiting immunopathology, called tolerance, develops more rapidly. Here, we comprehensively profile the blood immune system in patients, with or without prior malaria exposure, over 1 year after acute symptomatic Plasmodium falciparum malaria. Using a data-driven analysis approach to describe the immune landscape over time, we show that a dampened inflammatory response is associated with reduced γδ T cell expansion, early expansion of CD16+ monocytes, and parasite-specific antibodies of IgG1 and IgG3 isotypes. This also coincided with reduced parasitemia and duration of hospitalization. Our data indicate that antibody-mediated phagocytosis during the blood stage infection leads to lower parasitemia and less inflammatory response with reduced γδ T cell expansion. This enhanced control and reduced inflammation points to a potential mechanism on how tolerance is established following repeated malaria exposure.


Assuntos
Malária Falciparum , Malária , Humanos , Imunoglobulina G , Parasitemia , Plasmodium falciparum , Análise de Sistemas
16.
Nat Commun ; 13(1): 331, 2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-35039519

RESUMO

Strengthening malaria surveillance is a key intervention needed to reduce the global disease burden. Reliable serological markers of recent malaria exposure could improve current surveillance methods by allowing for accurate estimates of infection incidence from limited data. We studied the IgG antibody response to 111 Plasmodium falciparum proteins in 65 adult travellers followed longitudinally after a natural malaria infection in complete absence of re-exposure. We identified a combination of five serological markers that detect exposure within the previous three months with >80% sensitivity and specificity. Using mathematical modelling, we examined the antibody kinetics and determined that responses informative of recent exposure display several distinct characteristics: rapid initial boosting and decay, less inter-individual variation in response kinetics, and minimal persistence over time. Such serological exposure markers could be incorporated into routine malaria surveillance to guide efforts for malaria control and elimination.


Assuntos
Anticorpos Antiprotozoários/imunologia , Biomarcadores/metabolismo , Malária/epidemiologia , Malária/imunologia , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Adulto , Formação de Anticorpos/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Epitopos/imunologia , Feminino , Fluorescência , Humanos , Lactente , Quênia/epidemiologia , Cinética , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Curva ROC , Adulto Jovem
17.
J Immunol Methods ; 478: 112715, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31809709

RESUMO

Analysis of B-cell specificities at the single cell level provides important information on how the B-cell compartment responds when challenged by infection or vaccination. We recently developed a reversed B-cell FluoroSpot assay and showed that it could be used to detect B cells specific for different antigens simultaneously in a mouse model. The aim of this study was to further develop the method to detect and quantify antigen-specific memory B cells (MBCs) in humans where circulating antigen-specific cells are less frequent. We show that MBCs specific for three antigens, tetanus toxoid, hepatitis B surface antigen and cytomegalovirus pp65, could be detected simultaneously in one well. In addition to enumerating antigen-specific MBCs, we also assessed the spot volume to estimate the intensity of the response in individual cells and found this to be a new and sensitive approach to study MBC responses after vaccination. This unique B-cell FluoroSpot approach provides a simple and sensitive multiplex analysis of MBCs and can be adapted to most antigens and host species.


Assuntos
Antígenos Virais/imunologia , Linfócitos B/imunologia , Separação Celular/métodos , Imunofluorescência/métodos , Ensaios de Triagem em Larga Escala/métodos , Memória Imunológica , Animais , Buffy Coat/citologia , Separação Celular/instrumentação , Citomegalovirus/imunologia , Estudos de Viabilidade , Imunofluorescência/instrumentação , Corantes Fluorescentes/química , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Ensaios de Triagem em Larga Escala/instrumentação , Humanos , Hibridomas , Imunogenicidade da Vacina , Camundongos , Proteínas Recombinantes/imunologia , Reprodutibilidade dos Testes , Coloração e Rotulagem , Toxoide Tetânico/imunologia , Vacinação , Fluxo de Trabalho
18.
Front Immunol ; 11: 619398, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33679707

RESUMO

Memory B cells (MBCs) are believed to be important for the maintenance of immunity to malaria, and these cells need to be explored in the context of different parasite antigens and their breadth and kinetics after natural infections. However, frequencies of antigen-specific MBCs are low in peripheral blood, limiting the number of antigens that can be studied, especially when small blood volumes are available. Here, we developed a multiplexed reversed B-cell FluoroSpot assay capable of simultaneously detecting MBCs specific for the four Plasmodium falciparum blood-stage antigens, MSP-119, MSP-2, MSP-3 and AMA-1. We used the assay to study the kinetics of the MBC response after an acute episode of malaria and up to one year following treatment in travelers returning to Sweden from sub-Saharan Africa. We show that the FluoroSpot assay can detect MBCs to all four merozoite antigens in the same well, and that the breadth and kinetics varied between individuals. We further found that individuals experiencing a primary infection could mount and maintain parasite-specific MBCs to a similar extent as previously exposed adults, already after a single infection. We conclude that the multiplexed B-cell FluoroSpot is a powerful tool for assessing antigen-specific MBC responses to several antigens simultaneously, and that the kinetics of MBC responses against merozoite surface antigens differ over the course of one year. These findings contribute to the understanding of acquisition and maintenance of immune responses to malaria.


Assuntos
Anticorpos Antiprotozoários/análise , Linfócitos B/imunologia , ELISPOT/métodos , Memória Imunológica/imunologia , Malária Falciparum/imunologia , Adulto , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Feminino , Humanos , Masculino , Merozoítos
19.
JCI Insight ; 52019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30939125

RESUMO

Humoral immunity is important in limiting clinical disease in malaria, yet the longitudinal B cell response to infection remains unclear. We performed a 1-year prospective study in patients treated for acute P. falciparum malaria for the first time, or with previous exposure to the disease. Using an unbiased exploratory approach with mass cytometry, followed by targeted flow cytometry, we found that ~80% of mature B cells that proliferated in response to acute infection expressed CD11c. Only ~40% of CD11c+ B cells displayed an atypical B cell phenotype, with the remaining cells primarily made up of activated- and resting memory B cells. The CD11c+ B cells expanded rapidly following infection, with previous exposure to malaria resulting in a significantly larger increase compared to individuals with primary infection. This was attributed to an expansion of switched CD11c+ B cells that was absent in primary infected individuals. The rate of contraction of the CD11c+ B cell compartment was independent of previous exposure to malaria and displayed a slow decay with a half-life of ~300 days. Collectively, these results identify CD11c as a marker of B cells responding to malaria and further highlight differences in primary- and secondary B cell responses during infection.


Assuntos
Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Antígeno CD11c/imunologia , Malária/imunologia , Adulto , Idoso , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Feminino , Citometria de Fluxo/métodos , Humanos , Imunoglobulina G/sangue , Memória Imunológica/imunologia , Malária Falciparum/imunologia , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum , Estudos Prospectivos , Suécia , Adulto Jovem
20.
Front Immunol ; 10: 1116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31156653

RESUMO

NK cells in the human lung respond to influenza A virus- (IAV-) infected target cells. However, the detailed functional capacity of human lung and peripheral blood NK cells remains to be determined in IAV and other respiratory viral infections. Here, we investigated the effects of IAV infection on human lung and peripheral blood NK cells in vitro and ex vivo following clinical infection. IAV infection of lung- and peripheral blood-derived mononuclear cells in vitro induced NK cell hyperresponsiveness to K562 target cells, including increased degranulation and cytokine production particularly in the CD56brightCD16- subset of NK cells. Furthermore, lung CD16- NK cells showed increased IAV-mediated but target cell-independent activation compared to CD16+ lung NK cells or total NK cells in peripheral blood. IAV infection rendered peripheral blood NK cells responsive toward the normally NK cell-resistant lung epithelial cell line A549, indicating that NK cell activation during IAV infection could contribute to killing of surrounding non-infected epithelial cells. In vivo, peripheral blood CD56dimCD16+ and CD56brightCD16- NK cells were primed during acute IAV infection, and a small subset of CD16-CD49a+CXCR3+ NK cells could be identified, with CD49a and CXCR3 potentially promoting homing to and tissue-retention in the lung during acute infection. Together, we show that IAV respiratory viral infections prime otherwise hyporesponsive lung NK cells, indicating that both CD16+ and CD16- NK cells including CD16-CD49a+ tissue-resident NK cells could contribute to host immunity but possibly also tissue damage in clinical IAV infection.


Assuntos
Vírus da Influenza A/fisiologia , Influenza Humana/imunologia , Pulmão/fisiologia , Apresentação de Antígeno , Circulação Sanguínea , Hiper-Reatividade Brônquica/metabolismo , Citotoxicidade Imunológica , Humanos , Células K562 , Células Matadoras Naturais/imunologia , Ativação Linfocitária
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