Immune responses after controlled human malaria infections: acquisition, maintenance and association with protection

Contains fulltext : 134185.pdf (publisher's version ) (Closed access)Radboud Universiteit Nijmegen, 13 januari 2015Promotor : Sauerwein, R.W. Co-promotores : Scholzen, A., Luty, A.J.F

Plasmodium falciparum Infection of Human Volunteers Activates Monocytes and CD16+ Dendritic Cells and Induces Upregulation of CD16 and CD1c Expression.

Contains fulltext : 152586.pdf (publisher's version ) (Open Access

Mycobacterium tuberculosis induces IL-17A responses through TLR4 and dectin-1 and is critically dependent on endogenous IL-1.

Contains fulltext : 89445.pdf (publisher's version ) (Open Access)In the present study, we dissected the pathways that trigger the IL-17A responses by MTB. Dectin-1 and TLR4 were shown to be involved in MTB-induced IL-17A production, and blockade of the NOD2, TLR2, or MR had no effect on IL-17A. The MAPK Erk, known to mediate transcription of IL-1beta mRNA, was strongly involved in the IL-17A production induced by MTB. The intracellular enzymes caspase-1 and serine proteases, which process pro-IL-1beta into the active IL-1beta, were also crucial for the induction of IL-17A. Lastly, the MTB-induced IL-17A response was strongly dependent on signaling through the IL-1R but not the IL-6R pathway. In conclusion, the MTB-induced IL-17A response relies strongly on the endogenous IL-1 pathway and IL-1R signaling. TLR4 and dectin-1 are the main receptors responsible for mediating the signals responsible for IL-17A production by MTB. These findings contribute to a better understanding of the host response to mycobacteria and provide the opportunity to explore potential, novel, therapeutic strategies against TB.01 augustus 201

Two hospitals; two discourses Finnish missionaries and South African apartheid

This paper presents two hospitals in northern Namibia and discusses the architectural design as embedded in two different political discourses which generates entirely different forms. One is Onandjokwe hospital constructed by Finnish missionaries in 1911. The other, Oshakati hospital, inaugurated in 1966, was the first governmental hospital in this part of Namibia as a response to the international critic of apartheid neglect of black people’s health. There are major differences between the hospital design and construction management of the two hospitals. Discursive differences are visible in construction, building material and layout including spatial separation of patients as well as staff. The paper also frames the hospitals in the wider politico-geographical process in which South African warfare in the area from 1966 to 1989 is central. The two hospitals became associated to the two different antagonists in the conflict. Oshakati hospital became a part of the South African war machinery, while Onandjokwe became a “terrorist” hospital where wounded guerilla soldiers searched for care. The major South African army base was constructed just adjacent to the Oshakati hospital. Three other governmental hospitals were also constructed in the area during the conflict as a part of the strategy to “win the hearts and minds” of the local people

Estimating transmission parameters for respiratory syncytial virus and predicting the impact of maternal and pediatric vaccination.

Background Respiratory syncytial virus (RSV) is a leading cause of respiratory tract illness in young children and a major cause of hospital admissions globally. Methods Here we fit age-structured transmission models with immunity propagation to data from the Netherlands (2012–2017). Data included nationwide hospitalizations with confirmed RSV, general practitioner (GP) data on attendance for care from acute respiratory infection, and virological testing of acute respiratory infections at the GP. The transmission models, equipped with key parameter estimates, were used to predict the impact of maternal and pediatric vaccination. Results Estimates of the basic reproduction number were generally high (R0 > 10 in scenarios with high statistical support), while susceptibility was estimated to be low in nonelderly adults (<10% in persons 20–64 years) and was higher in older adults (≥65 years). Scenario analyses predicted that maternal vaccination reduces the incidence of infection in vulnerable infants (<1 year) and shifts the age of first infection from infants to young children. Conclusions Pediatric vaccination is expected to reduce the incidence of infection in infants and young children (0–5 years), slightly increase incidence in 5 to 9-year-old children, and have minor indirect benefits

Memory B-Cell and Antibody Responses Induced by Plasmodium falciparum Sporozoite Immunization

BACKGROUND: Immunization of healthy volunteers during receipt of chemoprophylaxis with Plasmodium falciparum sporozoites (CPS-immunization) induces sterile protection from malaria. Antibody responses have long been known to contribute to naturally acquired immunity against malaria, but their association with sterile protection after whole sporozoite immunization is not well established. We therefore studied the induction and kinetics of malaria parasite antigen-specific antibodies and memory B-cells (MBCs) during CPS-immunization and their correlation with protection from challenge infection. METHODS: We assessed humoral reactivity to 9 antigens representing different stages of the life cycle of P. falciparum by performing standardized MBC enzyme-linked immunospot and enzyme-linked immunosorbent assays on peripheral blood mononuclear cells and plasma samples from 38 Dutch volunteers enrolled in 2 randomized controlled clinical trials. RESULTS: MBCs and antibodies recognizing pre-erythrocytic and cross-stage antigens were gradually acquired during CPS-immunization. The magnitude of these humoral responses did not correlate with protection but directly reflected parasite exposure in CPS-immunization and challenge. CONCLUSIONS: Humoral responses to the malarial antigens circumsporozoite protein, liver-stage antigen-1, apical membrane antigen-1, and merozoite surface protein-1 do not to predict protection from challenge infection but can be used as sensitive marker of recent parasite exposure. CLINICAL TRIALS REGISTRATION: NCT01236612 and NCT01218893

Memory-like IFN-gamma response by NK cells following malaria infection reveals the crucial role of T cells in NK cell activation by P. falciparum.

NK cells are rapid IFN-gamma responders to Plasmodium falciparum-infected erythrocytes (PfRBC) in vitro and are involved in controlling early parasitaemia in murine models, yet little is known about their contribution to immune responses following malaria infection in humans. Here, we studied the dynamics of and requirements for in vitro NK responses to PfRBC in malaria-naive volunteers undergoing a single experimental malaria infection under highly controlled circumstances, and in naturally exposed individuals. NK-specific IFN-gamma responses to PfRBC following exposure resembled an immunological recall pattern and were tightly correlated with T-cell responses. However, although PBMC depleted of CD56(+) cells retained 20-55% of their total IFN-gamma response to PfRBC, depletion of CD3(+) cells completely abrogated the ability of remaining PBMC, including NK cells, to produce IFN-gamma. Although NK responses to PfRBC were partially dependent on endogenous IL-2 signaling and could be augmented by exogenous IL-2 in whole PBMC populations, this factor alone was insufficient to rescue NK responses in the absence of T cells. Thus, NK cells make a significant contribution to total IFN-gamma production in response to PfRBC as a consequence of their dependency on (memory) T-cell help, with likely positive implications for malaria vaccine development

Annual report Surveillance of COVID-19, influenza and other respiratory infections in the Netherlands: winter 2021/2022.

Abstract Each year, RIVM presents an overview of how many persons in the Netherlands got the flu and other respiratory infections. Since 2020, this report has also included an overview of how many people contracted the coronavirus. Coronavirus During the summer of 2021, from July through September, very few people tested positive for SARS-CoV-2. These numbers increased during the autumn and winter with the rise of the Delta and Omicron variants. Between May 2021 and May 2022, 6,448,170 persons tested positive for SARS-CoV-2, of whom 44,990 were admitted to the hospital and 5756 were admitted to intensive care. 3482 persons are known to have died as a result of COVID-19. Flu epidemic The flu epidemic during the 2021/2022 flu season started later than in previous seasons and lasted 13 weeks. During this season, about 127,378 people went to their general practitioner with flu-like illness. This was less than in previous seasons, as most people with flu-like illness were tested for coronavirus and did not go to their general practitioner. An estimated 795,000 persons have had the flu between October 2021 and May 2022. They mainly became ill with type A(H3N2) influenza virus. RS-virus Since the spring of 2021, hospitals have been reporting high numbers of infections with RS-virus, particularly in the summer of that year. These infections mainly occur in children under four years of age. Most have mild symptoms, but the infection can sometimes be so severe that hospitalization is necessary. After the summer of 2021, the number of infections decreased, though it remained high enough to speak of an epidemic. This epidemic has been going on for more than a year. In total, hospitals reported 4504 RS-virus infections between May 2021 and May 2022. Notifiable respiratory infections Some respiratory infections have to be reported to the Public Health Services. When necessary, they can then quickly take action to prevent their further spread. The number of reported legionella cases (658) has increased sharply in 2021. The number of tuberculosis cases was higher in 2021 (680) compared to 2020, but still lower than in previous years. The number of psittacosis (parrot fever, 55) cases was significantly lower in 2021 than in previous years and the number of Q fever cases (6) was comparable to 2020, but also lower than in previous years. Q fever, psittacosis and legionella generally manifest themselves in the form of pneumonia. Persons with pneumonia are often not tested, so the causative pathogen remains unknown. The actual numbers are therefore higher than the reported numbers

Australian Made: A multicultural reader. Front matter and table of contents.

BACKGROUND: Immunization of healthy volunteers by bites from Plasmodium falciparum-infected mosquitoes during chloroquine chemoprophylaxis (hereafter, chemoprophylaxis and sporozoites [CPS] immunization) induces sterile protection against malaria. CPS-induced protection is mediated by immunity against pre-erythrocytic stages, presumably at least partially by cytotoxic cellular responses. We therefore aimed to investigate the association of CPS-induced cytotoxic T-cell markers with protection. METHODS: In a double-blind randomized controlled trial, we performed dose titration of CPS immunization followed by homologous challenge infection in 29 subjects. Immune responses were assessed by in vitro restimulation of peripheral blood mononuclear cells and flow cytometry. RESULTS: Dose-dependent complete protection was obtained in 4 of 5 volunteers after immunization with bites from 45 P. falciparum-infected mosquitoes, in 8 of 9 volunteers with bites from 30, and in 5 of 10 volunteers with bites from 15 (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.5-17). Completely protected subjects had significantly higher proportions of CD4 T cells expressing the degranulation marker CD107a (OR, 8.4; 95% CI, 1.5-123; P = .011) and CD8 cells producing granzyme B (OR, 11; 95% CI, 1.9-212; P = .004) after P. falciparum restimulation. CONCLUSIONS: These data underline the efficiency of CPS immunization to induce sterile protection and support a possible role for cytotoxic CD4 and CD8 T-cell responses in pre-erythrocytic immunity. Clinical Trials Registration. NCT01218893