MyD88 signaling is directly involved in the development of murine placental malaria.

Malaria is a widespread infectious disease caused by the parasite Plasmodium. During pregnancy, malaria infection leads to a range of complications that can affect both the mother and fetus, including stillbirth, infant mortality, and low birth weight. In this study, we utilized a mouse model of placental malaria (PM) infection to determine the importance of the protein MyD88 in the host immune response to Plasmodium during pregnancy. Initially, we demonstrated that Plasmodium berghei NK65GFP adhered to placental tissue via chondroitin sulfate A and induced PM in mice with a C57BL/6 genetic background. To evaluate the involvement of MyD88 in the pathology of PM, we performed a histopathological analysis of placentas obtained from MyD88(-/-) and wild-type (WT) mice following infection on the 19th gestational day. Our data demonstrated that the detrimental placental alterations observed in the infected mice were correlated with the expression of MyD88. Moreover, in the absence of this protein, production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) was significantly reduced in the infected mice. More importantly, in contrast to fetuses from infected WT mice, which exhibited a reduction in body weight, the fetuses from infected MyD88(-/-) mice did not display significant weight loss compared to their noninfected littermates. In addition, we observed a decrement of maternal care associated with malaria infection, which was attenuated in the MyD88-deficient mice. Collectively, the results of this study illustrate the pivotal importance of the MyD88 signaling pathway in the pathogenesis of placental malaria, thus presenting new possibilities for targeting MyD88 in therapeutic interventions.

Ultrastructure of the lung in a murine model of malaria-associated acute lung injury/acute respiratory distress syndrome.

BACKGROUND: The mechanisms through which infection with Plasmodium spp. result in lung disease are largely unknown. Recently a number of mouse models have been developed to research malaria-associated lung injury but no detailed ultrastructure studies of the disease in its terminal stages in a murine model have yet been published. The goal was to perform an ultrastructural analysis of the lungs of mice that died with malaria-associated acute lung injury/acute respiratory distress syndrome to better determine the relevancy of the murine models and investigate the mechanism of disease. METHODS: DBA/2 mice were infected with Plasmodium berghei strain ANKA. Mice had their lungs removed immediately after death, processed using standard methods and viewed by transmission electron microscopy (TEM). RESULTS: Infected red blood cell:endothelium contact, swollen endothelium with distended cytoplasmic extensions and thickening of endothelium basement membrane were observed. Septa were thick and filled with congested capillaries and leukocytes and the alveolar spaces contained blood cells, oedema and cell debris. CONCLUSION: Results show that the lung ultrastructure of P. berghei ANKA-infected mice has similar features to what has been described in post-mortem TEM studies of lungs from individuals infected with Plasmodium falciparum. These data support the use of murine models to study malaria-associated acute lung injury.

TRPV1 antagonism by capsazepine modulates innate immune response in mice infected with Plasmodium berghei ANKA.

Thousands of people suffer from severe malaria every year. The innate immune response plays a determinant role in host's defence to malaria. Transient receptor potential vanilloid 1 (TRPV1) modulates macrophage-mediated responses in sepsis, but its role in other pathogenic diseases has never been addressed. We investigated the effects of capsazepine, a TRPV1 antagonist, in malaria. C57BL/6 mice received 10(5) red blood cells infected with Plasmodium berghei ANKA intraperitoneally. Noninfected mice were used as controls. Capsazepine or vehicle was given intraperitoneally for 6 days. Mice were culled on day 7 after infection and blood and spleen cell phenotype and activation were evaluated. Capsazepine decreased circulating but not spleen F4/80(+)Ly6G(+) cell numbers as well as activation of both F4/80(+)and F4/80(+)Ly6G(+) cells in infected animals. In addition, capsazepine increased circulating but not spleen GR1(+) and natural killer (NK) population, without interfering with natural killer T (NKT) cell numbers and blood NK and NKT activation. However, capsazepine diminished CD69 expression in spleen NKT but not NK cells. Infection increased lipid peroxidation and the release of TNFα and IFNγ, although capsazepine-treated group exhibited lower levels of lipid peroxidation and TNFα. Capsazepine treatment did not affect parasitaemia. Overall, TRPV1 antagonism modulates the innate immune response to malaria.

Predictive criteria to study the pathogenesis of malaria-associated ALI/ARDS in mice.

Malaria-associated acute lung injury/acute respiratory distress syndrome (ALI/ARDS) often results in morbidity and mortality. Murine models to study malaria-associated ALI/ARDS have been described; we still lack a method of distinguishing which mice will develop ALI/ARDS before death. This work aimed to characterize malaria-associated ALI/ARDS in a murine model and to demonstrate the first method to predict whether mice are suffering from ALI/ARDS before death. DBA/2 mice infected with Plasmodium berghei ANKA developing ALI/ARDS or hyperparasitemia (HP) were compared using histopathology, PaO2 measurement, pulmonary X-ray, breathing capacity, lung permeability, and serum vascular endothelial growth factor (VEGF) levels according to either the day of death or the suggested predictive criteria. We proposed a model to predict malaria-associated ALI/ARDS using breathing patterns (enhanced pause and frequency respiration) and parasitemia as predictive criteria from mice whose cause of death was known to retrospectively diagnose the sacrificed mice as likely to die of ALI/ARDS as early as 7 days after infection. Using this method, we showed increased VEGF levels and increased lung permeability in mice predicted to die of ALI/ARDS. This proposed method for accurately identifying mice suffering from ALI/ARDS before death will enable the use of this model to study the pathogenesis of this disease.

Distinct placental malaria pathology caused by different Plasmodium berghei lines that fail to induce cerebral malaria in the C57BL/6 mouse.

BACKGROUND: Placental malaria (PM) is one major feature of malaria during pregnancy. A murine model of experimental PM using BALB/c mice infected with Plasmodium berghei ANKA was recently established, but there is need for additional PM models with different parasite/host combinations that allow to interrogate the involvement of specific host genetic factors in the placental inflammatory response to Plasmodium infection. METHODS: A mid-term infection protocol was used to test PM induction by three P. berghei parasite lines, derived from the K173, NK65 and ANKA strains of P. berghei that fail to induce experimental cerebral malaria (ECM) in the susceptible C57BL/6 mice. Parasitaemia course, pregnancy outcome and placenta pathology induced by the three parasite lines were compared. RESULTS: The three P. berghei lines were able to evoke severe PM pathology and poor pregnancy outcome features. The results indicate that parasite components required to induce PM are distinct from ECM. Nevertheless, infection with parasites of the ANKAΔpm4 line, which lack expression of plasmepsin 4, displayed milder disease phenotypes associated with a strong innate immune response as compared to infections with NK65 and K173 parasites. CONCLUSIONS: Infection of pregnant C57BL/6 females with K173, NK65 and ANKAΔpm4 P. berghei parasites provide experimental systems to identify host molecular components involved in PM pathogenesis mechanisms.

IFN-γ-mediated efficacy of allergen-free immunotherapy using mycobacterial antigens and CpG-ODN.

Epidemiological and experimental evidence supports the notion that microbial infections that are known to induce Th1-type immune responses can suppress Th2 immune responses, which are characteristics of allergic disorders. However, live microbial immunization might not be feasible for human immunotherapy. Here, we evaluated whether induction of Th1 immunity by the immunostimulatory sequences of CpG-oligodeoxynucleotides (CpG-ODN), with or without culture filtrate proteins (CFP), from Mycobacterium tuberculosis would suppress ongoing allergic lung disease. Presensitized and ovalbumin (OVA)-challenged mice were treated subcutaneously with CpG, or CpG in combination with CFP (CpG/CFP). After 15 days of treatment, airway inflammation and specific T- and B-cell responses were determined. Cell transfer experiments were also performed. CpG treatment attenuated airway allergic disease; however, the combination CpG/CFP treatment was significantly more effective in decreasing airway hyperresponsiveness, eosinophilia and Th2 response. When an additional intranasal dose of CFP was given, allergy was even more attenuated. The CpG/CFP therapy also reduced allergen-specific IgG1 and IgE antibodies and increased IgG2a. Transfer of spleen cells from mice immunized with CpG/CFP also reduced allergic lung inflammation. CpG/CFP treatment induced CFP-specific production of IFN-γ and IL-10 by spleen cells and increased production of IFN-γ in response to OVA. The essential role of IFN-γ for the therapeutic effect of CpG/CFP was evidenced in IFN-γ knockout mice. These results show that CpG/CFP treatment reverses established Th2 allergic responses by an IFN-γ-dependent mechanism that seems to act both locally in the lung and systemically to decrease allergen-specific Th2 responses.

Respiratory allergy to Blomia tropicalis: immune response in four syngeneic mouse strains and assessment of a low allergen-dose, short-term experimental model.

BACKGROUND: The dust mite Blomia tropicalis is an important source of aeroallergens in tropical areas. Although a mouse model for B. tropicalis extract (BtE)-induced asthma has been described, no study comparing different mouse strains in this asthma model has been reported. The relevance and reproducibility of experimental animal models of allergy depends on the genetic background of the animal, the molecular composition of the allergen and the experimental protocol. OBJECTIVES: This work had two objectives. The first was to study the anti-B. tropicalis allergic responses in different mouse strains using a short-term model of respiratory allergy to BtE. This study included the comparison of the allergic responses elicited by BtE with those elicited by ovalbumin in mice of the strain that responded better to BtE sensitization. The second objective was to investigate whether the best responder mouse strain could be used in an experimental model of allergy employing relatively low BtE doses. METHODS: Groups of mice of four different syngeneic strains were sensitized subcutaneously with 100 microg of BtE on days 0 and 7 and challenged four times intranasally, at days 8, 10, 12, and 14, with 10 microg of BtE. A/J mice, that were the best responders to BtE sensitization, were used to compare the B. tropicalis-specific asthma experimental model with the conventional experimental model of ovalbumin (OVA)-specific asthma. A/J mice were also sensitized with a lower dose of BtE. RESULTS: Mice of all strains had lung inflammatory-cell infiltration and increased levels of anti-BtE IgE antibodies, but these responses were significantly more intense in A/J mice than in CBA/J, BALB/c or C57BL/6J mice. Immunization of A/J mice with BtE induced a more intense airway eosinophil influx, higher levels of total IgE, similar airway hyperreactivity to methacholine but less intense mucous production, and lower levels of specific IgE, IgG1 and IgG2 antibodies than sensitization with OVA. Finally, immunization with a relatively low BtE dose (10 microg per subcutaneous injection per mouse) was able to sensitize A/J mice, which were the best responders to high-dose BtE immunization, for the development of allergy-associated immune and lung inflammatory responses. CONCLUSIONS: The described short-term model of BtE-induced allergic lung disease is reproducible in different syngeneic mouse strains, and mice of the A/J strain was the most responsive to it. In addition, it was shown that OVA and BtE induce quantitatively different immune responses in A/J mice and that the experimental model can be set up with low amounts of BtE.

Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes.

Placental malaria (PM) is associated with severe inflammation leading to abortion, preterm delivery, and intrauterine growth restriction. Innate immunity responses play critical roles, but the mechanisms underlying placental immunopathology are still unclear. Here, we investigated the role of inflammasome activation in PM by scrutinizing human placenta samples from an endemic area and ablating inflammasome components in a PM mouse model. The reduction in birth weight in babies from infected mothers is paralleled by increased placental expression of AIM2 and NLRP3 inflammasomes. Using genetic dissection, we reveal that inflammasome activation pathways are involved in the production and detrimental action of interleukin-1ß (IL-1ß) in the infected placenta. The IL-1R pharmacological antagonist Anakinra improved pregnancy outcomes by restoring fetal growth and reducing resorption in an experimental model. These findings unveil that IL-1ß-mediated signaling is a determinant of PM pathogenesis, suggesting that IL-1R antagonists can improve clinical outcomes of malaria infection in pregnancy.

Fetal-Derived MyD88 Signaling Contributes to Poor Pregnancy Outcomes During Gestational Malaria.

Placental malaria (PM) remains a severe public health problem in areas of high malaria transmission. Despite the efforts to prevent infection poor outcomes in Plasmodium endemic areas, there is still a considerable number of preterm births and newborns with low birth weight resulting from PM. Although local inflammation triggered in response to malaria is considered crucial in inducing placental damage, little is known about the differential influence of maternal and fetal immune responses to the disease progression. Therefore, using a PM mouse model, we sought to determine the contribution of maternal and fetal innate immune responses to PM development. For this, we conducted a series of cross-breeding experiments between mice that had differential expression of the MyD88 adaptor protein to obtain mother and correspondent fetuses with distinct genetic backgrounds. By evaluating fetal weight and placental vascular spaces, we have shown that the expression of MyD88 in fetal tissue has a significant impact on PM outcomes. Our results highlighted the existence of a distinct contribution of maternal and fetal immune responses to PM onset. Thus, contributing to the understanding of how inflammatory processes lead to the dysregulation of placental homeostasis ultimately impairing fetal development.

O censo da população em situação de rua da cidade de São Paulo: perfil das pessoas LGBTQIA+ e os desafios das políticas públicas de saúde / The census of the homeless population in the city of São Paulo: profile of LGBTQIA+ people and the challenges of public health policies

O último censo da população em situação de rua da cidade de São Paulo, em 2021, recenseou 31.884 pessoas. O quesito identidade de gênero foi autodeclarado por 68,58%, contra 31,42% dos que não responderam. Majoritariamente, 54,91% são homens cisgêneros e 11,58% mulheres cisgêneros. Na pesquisa censitária, 668 pessoas (3,05%) autodeclararam outras identidades não cisgênero e representam o universo LGBTQIA+ analisado. Considerando-se as vulnerabilidades individuais, sociais e programáticas das pessoas LGBTQIA+, examina-se, na perspectiva interseccional, o perfil dessa população, quanto à caracterização da situação de rua, o tempo de vivência na rua, a faixa etária, as especificidades da identidade de gênero e a raça/cor/etnia, bem como as dificuldades metodológicas na coleta dos dados. Predominantemente, 58,08% se concentram em três das 31 subprefeituras; a maioria é do sexo masculino; um terço se identifica como agênero; 63,03% se autodeclaram como pretos e pardos; 45,21% têm entre 31 e 49 anos de idade; mais da metade vive nas ruas há mais de dois anos; 71,41% se encontravam em situação de rua e menos de um terço foi acolhido pelos serviços municipais. A pandemia da covid-19, intensificou as vulnerabilidades da população LGBTQIA+ em situação de rua na cidade mais rica do País e sua mitigação exige maior proatividade das políticas públicas de saúde em interface com outros setores.

Publisher Correction: TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Role of endogenous IFN-gamma in macrophage programming induced by IL-12 and IL-18.

Besides the established role of interleukin-12 (IL-12) and IL-18 on interferon-gamma (IFN-gamma) production by natural killer (NK), T, and B cells, the effects of these cytokines on macrophages are largely unknown. Here, we investigated the role of IL-12/IL-18 on nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production by CD11b(+) adherent peritoneal cells, focusing on the involvement of endogenously produced IFN-gamma. C57BL/6 cells released substantial amounts of NO when stimulated with IFN-gamma or lipopolysaccharide (LPS), but failed to respond to IL-12 or IL-18 or both. However, IL-12/IL-18 pretreatment was able to program these cells to release 6-8-fold more NO and TNF-alpha in response to LPS or Trypanosoma cruzi stimulation, with NO levels directly correlating with macrophage resistance to intracellular parasite growth. Analysis of IL-12/IL-18-primed cells from mice deficient in IFN-gamma, IFNGR, and IFN regulatory factor-1 (IRF-1) revealed that these molecules were essential for LPS-induced NO release, but TNF-alpha production was IFN-gamma independent. Conversely, the myeloid differentiation factor 88 (MyD88)-dependent pathway was indispensable for IL-12/IL-18-programmed LPS-induced TNF-alpha production, but not for NO release. Contaminant T and NK cells largely modulated the IL-12/IL-18 programming of LPS-induced NO response through IFN-gamma secretion. Nevertheless, a small population of IFN-gamma(+) cells with a macrophage phenotype was also identified, particularly in the peritoneum of chronically T. cruzi-infected mice, reinforcing the notion that macrophages can be an alternative source of IFN-gamma. Taken together, our data contribute to elucidate the molecular basis of the IL-12/IL-18 autocrine pathway of macrophage activation, showing that endogenous IFN-gamma plays an important role in programming the NO response, whereas the TNF-alpha response occurs through an IFN-gamma-independent pathway.

[Governance and regulation in health: challenges for health management in Greater Metropolitan São Paulo, Brazil]. / Governança e regulação na saúde: desafios para a gestão na Região Metropolitana de São Paulo, Brasil.

This paper discusses the relationship between the public and private sectors in the Unified National Health System (SUS), based on research whose objective was to identify governance strategies and mechanisms for public/private relations in the health sector, considering the search for equity in Greater Metropolitan Sao Paulo, Brazil. Governance was used as an analytical category, with health system regulation as the issue. Municipal and State health secretaries, members of health councils, and SUS staff were interviewed, and the empirical material was classified as: (a) regulatory mechanisms and instruments; (b) power loci; and (c) actors' positions concerning the SUS and its relationship to the private sector. Mechanisms and instruments have been created and used in the municipalities for regulation of their own services. Regulatory measures for the complementary and supplementary healthcare sector are practically nonexistent. There are numerous institutional power loci, seen more as places for submitting demands than as forums for negotiation. Despite some progress, governance appears to be more of a formal issue. Discussion is needed on the relationship between the public and private sectors and its regulation by municipalities in order to improve the health system.

Os grupos de pesquisa LGBT+ no Brasil: perfil dos pesquisadores e as contribuições do campo da Saúde Coletiva / LGBT+ research groups in Brazil: researcher's profile and the contributions from the Collective Health field

Analisou-se a distribuição dos grupos de pesquisa do Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq) quanto ao perfil dos pesquisadores e das linhas de pesquisa sobre a população LGBT+ no Brasil e a atuação destes no campo da Saúde Coletiva. Realizou-se um estudo exploratório, descritivo, de abordagem quantitativa, baseado no inventário de 75 grupos de pesquisa, cadastrados no CNPq até 28 de setembro de 2018. Majoritariamente, 81,3% tem até uma década de atuação e 73,3% são formados por até dez pesquisadores. Foram identificados 632 pesquisadores, sendo 76,3% doutores e 23,7%, mestres. Constatou-se o predomínio de grupos vinculados às instituições publicas, perfazendo 82,7%, contra 17,3% de instituições privadas, evidenciando a hegemonia da pesquisa publica sobre a temática LGBT+ no país. 57,3% dos grupos possuem até três linhas de pesquisa e são oriundos das Ciências Humanas. Na Saúde Coletiva, foram encontrados sete grupos, majoritariamente oriundos de universidades publicas e com até dez anos de existência. Quanto ao foco das linhas de pesquisa, destaca-se a ancoragem na determinação social do processo saúde-doença e nas vulnerabilidades associadas as infecções sexualmente transmissíveis e ao HIV/aids, especialmente entre homens que fazem sexo com homens, travestis e transexuais.

A Copa do Mundo FIFA 2022 e o flagelo da homofobia / The 2022 FIFA World Cup and the scourge of homophobia

A homofobia é um instrumental de dominação psicopolítica que priva sujeitos de sua condição humana por meio da injúria e da violação da dignidade. Causa dor e sofrimento, aliena a pessoa da capacidade de agir e de se perceber como capaz de existir em todas as esferas da vida. Em tempos de Copa do Mundo FIFA 2022 no Qatar, emergem muitas questões que atingem sujeitos e instituições no tocante a garantias de direitos e da dignidade humana, sobretudo, em um país que criminaliza com prisão ou mesmo apedrejamento o amor entre iguais. A homofobia mata. Ela tem vitimado pessoas no mundo e a cultura do futebol tem contribuído para essa triste realidade. Esse ensaio tece reflexões sobre como uma instituição da envergadura da FIFA tem pautado essa questão e como as nações que celebram esse megaevento têm encarado o flagelo da homofobia no mundo do futebol.

TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria.

Malaria-associate pregnancy has a significant impact on infant morbidity and mortality. The detrimental effects of malaria infection during pregnancy have been shown to correlate with immune activation in the placental tissue. Herein we sought to evaluate the effect of Toll-like receptors (TLRs) activation on placental malaria (PM) development by using the Plasmodium berghei NK65GFP infection model. We observed that activation of the innate immune system by parasites leads to PM due to local inflammation. We identified TLR4 activation as the main pathway involved in the inflammatory process in the placental tissue since the absence of functional TLR4 in mice leads to a decrease in the pro-inflammatory responses, which resulted in an improved pregnancy outcome. Additionally, a similar result was obtained when infected pregnant mice were treated with IAXO-101, a TLR4/CD14 blocker. Together, this study illustrates the importance of TLR4 signalling for the generation of the severe inflammatory response involved in PM pathogenesis. Therefore, our results implicate that TLR4 blockage could be a potential candidate for therapeutic interventions to reduce malaria-induced pathology both in the mother and the fetus.

[The right to prevention and the challenges of reducing vulnerability to HIV in Brazil]. / O direito à prevenção e os desafios da redução da vulnerabilidade ao HIV no Brasil.

The study evaluates the Brazilian response to the targets established by UNGASS for the prevention of HIV/AIDS. The analysis was based on national research, documents and information from the National Program STD/AIDS and on state-level action plans and targets. Brazil relies on various prevention policies to attain the UNGASS targets proposed for 2005. These include: addressing discrimination issues, promotion of HIV testing, distribution of condoms, needle exchange programs, discussion of sexuality in schools, prevention initiatives for sex workers and homosexuals and prevention in the workplace. These have resulted in increases in testing and condom use. Various challenges are discussed, including: overcoming discontinuity in action plans (particularly with more vulnerable groups), training prevention teams, increasing monitoring of quantity and quality of preventative actions and overcoming regional, racial and gender inequalities. It is concluded that the right to prevention is not a public priority, nor is it on the social movement agendas. This contrasts with the right to better HIV treatment. In order to increase the efficacy of these programs, it is suggested that they be understood and incorporated based on the promotion and guarantee of human rights, thereby advancing the ethical/political debate at local and national levels.

Acordos de empréstimo para AIDS e a Política de Incentivo no Sistema Único de Saúde: avanços e lacunas / Loan agreements for AIDS and the National Health System Incentive Policy: advances and gaps

Resumo Introdução No Brasil, os acordos de empréstimo e a Política de Incentivo foram fundamentais para a gestão descentralizada da política de aids, entretanto poucos estudos avaliaram os seus efeitos no âmbito do Sistema Único de Saúde (SUS). Objetivo Analisar a implementação das ações programáticas em DST/Aids no país e no estado de São Paulo quanto aos avanços e lacunas dos acordos de empréstimo com o Banco Mundial e a implantação da Política de Incentivo vigente no SUS. Método Estudo de caso, retrospectivo-descritivo, baseado em análise documental e entrevistas em profundidade com seis coordenadores das três esferas governamentais e dois presidentes do Fórum Estadual de ONG/AIDS de São Paulo. Resultados Identificaram-se diferentes graus e distintas formas de operacionalização da política de aids, demarcadas por períodos de centralização das decisões e do financiamento no "Projeto AIDS I", seguida pela desconcentração administrativa no final do "Projeto AIDS II" e, finalmente a descentralização com a Política de Incentivo, transferindo responsabilidades e recursos em consonância aos princípios do SUS. Conclusão Não obstante os avanços da gestão descentralizada, fragilidades constatadas no processo de monitoramento e avaliação das ações podem comprometer a sustentabilidade técnico-financeira da Política de Incentivo no SUS.

Abstract Background In Brazil, loan agreements and the Incentive Policy were fundamental to decentralize the management of the AIDS policy; however, few studies have evaluated their effects within the scope of the National Health System (NHS). Objective To analyze the implementation of programmatic actions related to STD/AIDS in the country and in the state of São Paulo regarding the advances and gaps of the loan agreements with the World Bank and the implementation of the NHS Incentive Policy currently in force. Method A retrospective descriptive case study based on documentary analysis and in-depth interviews with six coordinators from three governmental levels and two presidents of the State Forum for NGO/AIDS in São Paulo. Results Different degrees and forms of operationalization of the AIDS policy were identified; they are marked by periods of centralization of decisions and funding in the "AIDS Project I", followed by administrative decentralization at the end of the "AIDS Project II" and, finally, decentralization brought about by the Incentive Policy, which transfers responsibilities and resources in line with NHS' principles. Conclusion Despite the progress of decentralized management, weaknesses along the process of monitoring and evaluation of actions may compromise the technical and financial sustainability of the NHS Incentive Policy.

O "Terceiro Setor na Saúde": temas de investigação, atores, avanços e lacunas na gestão do Sistema Único de Saúde no prisma das Ciências Sociais e Humanas em Saúde / The "Third Sector in Health": research themes, actors, advances and gaps in the management of the National Health System from the perspective of Social and Human Sciences in Health

Analisou-se a produção científica sobre o "Terceiro Setor na Saúde", a partir dos congressos promovidos pela Associação Brasileira de Pós Graduação em Saúde Coletiva (ABRASCO), entre 1995 e 2011, quanto à contribuição para o desenvolvimento do subcampo das Ciências Sociais e Humanas em Saúde, vinculado ao campo interdisciplinar da Saúde Coletiva. Realizou-se um estudo exploratório, descritivo, retrospectivo de abordagem quantitativa, baseado nos Anais dos cinco congressos da ABRASCO. Identificaram-se 126 resumos, classificados em 12 temas de investigação. Quase um terço dos trabalhos evidenciaram a atuação dos movimentos sociais e das ações conduzidas por Organizações Não Governamentais no setor Saúde, ao passo que os temas que abordaram o exercício do controle social nos conselhos de saúde, o mix público-privado na saúde, a gestão/gerência das Organizações Sociais da Saúde, o voluntariado e o direito constitucional à saúde foram exíguos. Recomenda-se assim, a incorporação e manutenção desses temas com baixa visibilidade na produção científica, nas agendas de pesquisa em curso nos subcampos das Ciências Sociais e Humanas em Saúde e das Políticas, Planejamento e Gestão em Saúde, considerando a sua relevância para a gestão do Sistema Único de Saúde.

Liposomes loaded with P. falciparum merozoite-derived proteins are highly immunogenic and produce invasion-inhibiting and anti-toxin antibodies.

The formulation of an effective vaccine against malaria is still a significant challenge and the induction of high anti-parasite antibody titers plus a sustained T cell response is mandatory for the success of such a vaccine. We have developed a nanoliposome-based structure which contains plasma membrane-associated proteins (PfMNP) of Plasmodium falciparum merozoites on its surface. Incorporation of parasite-derived proteins led to a significant increase in the size and dispersity of particles. Immunization of particles in BalbC and C57BL/6 mice led to high anti-MSP119 IgG titers (10(4)) after the first dose and reached a plateau (>10(6)) after the third dose. While very high titers were observed against the C-terminal domain of the vaccine candidate MSP1, only modest titers (≤10(3)) were detected against MSP2. The induced antibodies showed also a strong growth-inhibiting effect in reinvasion assays. In addition, PfMNP immunization generated antibodies which partially blocked the inflammatory response, probably by blocking TLR-induced activation of macrophages by malarial toxins such as GPI anchors. The results underline the potential of nanoliposome-based formulations as anti-malarial vaccines.