How the 'plates' of a health system can shift, change and adjust during economic recessions: A qualitative interview study of public and private health providers in Brazil's Sao Paulo and Maranhao states

Background: Economic recessions carry an impact on population health and access to care; less is known on how health systems adapt to the conditions brought by a downturn. This particularly matters now that the COVID-19 epidemic is putting health systems under stress. Brazil is one of the world’s most affected countries, and its health system was already experiencing the aftermath of the 2015 recession. Methods: Between 2018 and 2019 we conducted 46 semi-structured interviews with health practitioners, managers and policy-makers to explore the impact of the 2015 recession on public and private providers in prosperous (São Paulo) and impoverished (Maranhão) states in Brazil. Thematic analysis was employed to identify drivers and consequences of system adaptation and coping strategies. Nvivo software was used to aid data collection and analysis. We followed the Standards for Reporting Qualitative Research to provide an account of the findings. Results: We found the concept of ‘health sector crisis’ to be politically charged among healthcare providers in São Paulo and Maranhão. Contrary to expectations, the public sector was reported to have found ways to compensate for diminishing federal funding, having outsourced services and adopted flexible–if insecure–working arrangements. Following a drop in employment and health plans, private health insurance companies have streamlined their offer, at times at the expenses of coverage. Low-cost walk-in clinics were hit hard by the recession, but were also credited for having moved to cater for higher-income customers in Maranhão. Conclusions: The ‘plates’ of a health system may shift and adjust in unexpected ways in response to recessions, and some of these changes might outlast the crisis. As low-income countries enter post-COVID economic recessions, it will be important to monitor the adjustments taking place in health systems, to ensure that past gains in access to care and job security are not eroded

Cell-free antigens from precocious Paracoccidioides brasiliensis culture induce a typical delayed-type hypersensitivity reaction

Cell-free antigens (CFAg) derived from Paracoccidioides brasiliensis have typically been used in immunodiffusion reactions for serodiagnosis or therapeutic follow-up of paracoccidioidomycosis patients. Thus, we investigated the usefulness of CFAg obtained from cultures at different ages, to evaluate cellular immunity by the footpad test, in experimental murine paracoccidioidomycosis. Male mice infected with P. brasiliensis 265 strain were challenged in the footpad with CFAg obtained from four- (4d CFAg) or 11-day-old cultures (11d CFAg). The increase in footpad swelling provoked by 4d CFAg and 11d CFAg was similar and showed significant difference in relation to control groups. However, the infiltrate pattern was strikingly different: 4d CFAg induced a predominant mononuclear infiltrate whereas 11d CFAg provoked a predominant polymophonuclear infiltrate. These different inflammatory patterns were associated with distinct electrophoretic characteristics. By comparison with 11d CFAg, 4d CFAg showed more numerous and intense bands, including a strong one of 43 kDa (gp43). These results suggest that CFAg derived from Pb 265 isolate can be used as a reagent to evaluate cellular immunity; however, the culture's age is critical because only young cultures are able to induce a typical mononuclear infiltrate. The efficacy of this new paracoccidioidin to assay the cellular immunity in infections caused by other P. brasiliensis isolates is under investigation

Role of Paracoccidioides brasiliensis cell wall fraction containing beta-glucan in tumor necrosis factor-alpha production by human monocytes: correlation with fungicidal activity

The polysaccharide fraction of Paracoccidioides brasiliensis mycelial cell wall (F1 fraction), the active component of which is composed of beta-glucan, was investigated in regard to the activation of human monocytes for fungal killing. The cells were primed with interferon-gamma (IFN-gamma) or F1 (100 and 200 mug ml(-1)) or F1 (100 and 200 mug ml(-1)) plus IFN-gamma for 24 h and then evaluated for H2O2 release. In other experiments, the cells were pretreated with the same stimuli, challenged with a virulent strain of P. brasiliensis and evaluated for fungicidal activity and levels of tumor necrosis factor (TNF-alpha) in the supernatants. F1 increased the levels of H2O2 in a similar manner to IFN-gamma. However, a synergistic effect between these two activators was not detected. on the contrary, a significant fungicidal activity was only obtained after priming with IFN-gamma plus F1. This higher activity was associated with high levels of TNF-alpha in the supernatants of the cocultures. Overall, P. brasiliensis F1 fraction induced human monocytes to release relatively high levels of TNF-alpha, which, in combination with IFN-gamma, is responsible for the activation of human monocytes for effective killing of P. brasiliensis

Cytokines released from blood monocytes and expressed in mucocutaneous lesions of patients with paracoccidioidomycosis evaluated before and during trimethoprim-sulfamethoxazole treatment

Background Mucocutaneous lesions in paracoccidioidomycosis are granulomatous and result from tissue responses to Paracoccidioides brasiliensis, the aetiological agent.Objectives and methods In this study we investigate the expression of tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and transforming growth factor (TGF)-beta 1 by immunohistochemistry in skin and mucosa lesions from patients with the chronic form of paracoccidioidomycosis, evaluated before and at day 20 of trimethoprim-sulfamethoxazole treatment. Cytokine production by peripheral blood monocytes was also studied by enzyme immunoassay.Results Intense immunostaining for TNF-alpha was detected in mononuclear cells that infiltrated granulomas in all skin and mucosa lesions before treatment simultaneously with low IL-10 granular deposits in these cells. At day 20 of treatment, there was reduced TNF-alpha and IL-10 deposition. Immunoreactive TGF-beta 1 was observed diffusely in the dermis and generally in the cytoplasm of macrophages and giant cells, before treatment, and as increased TGF-beta 1 deposits in the fibrosis area at day 20 of treatment. Peripheral blood monocytes from patients with paracoccidioidomycosis, evaluated before treatment, produced high endogenous levels of TNF-alpha, TGF-beta 1 and IL-10 in relation to healthy controls. Lipopolysaccharide-stimulated monocytes from patients secreted lower levels of TNF-alpha in both periods of evaluation while no impairment in capacity of IL-10 and TGF-beta production was observed.Conclusions Trimethoprim-sulfamethoxazole therapy was effective in decreasing fungal load in the lesions, allowing patient immune response to control the infection leading to the healing of the lesions

Experimental paracoccidioidomycosis in high and low antibody responder mice of Selection IV-A

High (H) and low (L) responder mice were selected for their ability to produce antibodies against sheep and human erythrocytes (Selection IV-A). In this selection, the difference in antibody responsiveness between H and L lines (HIV-A and LIV-A mice, respectively) was shown to depend mainly on macrophage function. The more rapid catabolism of antigens by macrophages in L mice has been suggested as the main cause of the low antibody production. Due to this high macrophage activity, L animals have been described as more resistant than H animals to intracellular pathogens. These animals were utilized as an experimental model of paracoccidioidomycosis. HIV-A and LIV-A mice were infected with Paracoccidioides brasiliensis by the intravenous route. As expected, H mice were more susceptible to P. brasiliensis with a shorter survival time and higher levels of specific antibodies when compared to L mice. Contrasting with the survival time, the lungs, spleen and liver from H mice showed typical nodular granulomas containing epithelioid and giant cells and few fungi. on the other hand, in LN-A mice, the lesions of these organs were characterized by looser granulomas with irregular borders and the presence of a large number of fungi, However, the adrenal gland showed different lesion patterns. In H mice these lesions were extensive and characterized by loose granulomas with numerous fungi, while in LIV-A mice the lesions were small and limited to the cortex. Moreover the HIV-A mice presented higher levels of serum corticosterone when compared to LIV-A ones. The higher susceptibility of H mice could be attributed to the extensive lesions of the adrenal glands. These results suggest the use of the H line from the IV-A Selection as an experimental model for further studies of adrenal involvement in paracoccidioidomycosis

Effect of cytokines on the in vitro fungicidal activity of monocytes from paracoccidioidomycosis patients

Peripheral blood monocytes obtained from paracoccidioidomycosis patients and healthy individuals were preactivated with recombinant gamma interferon (IFN-gamma) in different concentrations (250, 500 and 1000 U/ml) and evaluated for fungicidal activity against Paracoccidiodes brasiliensis strain 18 (Pb 18, high-virulence strain) and strain 265 (Pb 265, low-virulence strain) by plating of cocultures and counting of colony-forming units, after 10 d. Monocytes from healthy individuals failed to present fungicidal activity against P. brasiliensis even after IFN-gamma activation at the three concentrations. However, patient, monocytes activated with IFN-gamma (1 000 U/ml) showed a significant fungicidal activity when compared to that obtained with non-activated or activated cells with other IFN-gamma concentrations (250 and 500 U/ml). Moreover,,patient monocytes presented higher fungicidal activity than the control, even before the activation process. These results may be explained by the activation state of patients' cells as a function of the in vivo contact with the fungus, which was confirmed by their higher capacity to release H2O2 in vitro. Unlike the results obtained with Ph 18, patient and control cells presented a significant fungicidal activity against Pb 265, after priming with IFN-gamma. These results are explained by the higher levels of TNF-alpha in supernatants of cultures challenged with Pb 265. Moreover, higher levels of the cytokine were obtained in patient cell supernatants. Taken together, our results suggest that for effective killing of P. brasiliensis by monocytes, an initial activation signal induced by IFN-gamma is necessary to stimulate the cells to produce TNF-alpha. This cytokine may be involved, through an autocrine pathway, in the final phase activation process. The effectiveness of this process seems to depend on the virulence of the fungal strain and the activation state of the challenged cells. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All fights reserved