37 research outputs found
An evaluation of generic medicines availability in pharmacies and drugstores in Maringá (PR) and comparison of their prices in relation with the similars and the references
O debate sobre a implementação de genéricos vem sendo realizado no Brasil desde 1976. Entretanto, somente em 1991, foi elaborado um projeto, visando à implantação dos medicamentos genéricos. A lei nº 9787 ("Lei dos genéricos") só foi publicada no Diário Oficial da União em 11 de fevereiro de 1999. Os objetivos deste trabalho foram verificar a disponibilidade de medicamentos genéricos em farmácias e drogarias, bem como comparar os preços destes medicamentos em relação aos similares e aos de referência. Verificou-se a disponibilidade dos medicamentos genéricos em 22 farmácias e drogarias do municÃpio de Maringá, estado do Paraná, de 30 de outubro a 22 de novembro de 2002. Dos 222 princÃpios ativos disponibilizados no Brasil como genéricos, foram encontrados 71 (32%). Os medicamentos genéricos não sujeitos a controle especial são em média 42% mais baratos do que os de referência e 15% mais baratos que os similares. Os medicamentos genéricos de venda controlada com tarja vermelha são, em média, 36% mais baratos que os de referência e 12% mais baratos que os similares. Os medicamentos genéricos com tarja preta são, em média, 37% mais baratos que os de referência e 14% mais baratos que os similares.The discussion about the implementation of generics has being carried trough since 1976 in Brazil. However, just in 1991 a project which proposes the implantation of generic medicines has been elaborated. The Law 9787 (called Law of the Generic medicines) has been only published in Diário Oficial da União in February 11th, 1999. The objectives of this work had been to verify generic medicine availability in pharmacies and drugstores, as well as comparing their prices in relation with the similars and the references. The generic availability was verified in 22 pharmacies and drugstores in Maringá city, state of Paraná, from October, 30th to November, 20th ,2002. In a total of 222 active principles available in Brazil as generic, 71 (32%) had been found. Those generic medicines sold not under special control are in average 42% cheaper than the reference and 15% cheaper than the similar ones. Those generic medicines with red label, sold under special control, are in average 36% cheaper than the reference and 12% cheaper than the similar ones. The generic medicines with black label are 37% cheaper than the reference and 14% cheaper than the similars ones
Clinical complications of G6PD deficiency in Latin American and Caribbean populations : systematic review and implications for malaria elimination programmes
Background: Although G6PDd individuals are generally asymptomatic throughout their life, the clinical burden of this genetic condition includes a range of haematological conditions, including acute haemolytic anaemia (AHA), neonatal jaundice (NNJ) and chronic non-sphaerocytic anaemia (CNSA). In Latin America (LA), the huge knowledge gap regarding G6PDd is related to the scarce understanding of the burden of clinical manifestation underlying G6PDd carriage. The aim of this work was to study the clinical significance of G6PDd in LA and the Caribbean region through a systematic review. Methods: A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Only original research was included. All study designs were included, as long as any clinical information was present. Studies were eligible for inclusion if they reported clinical information from populations living in LA or Caribbean countries or about migrants from these countries living in countries outside this continent. Results: The Medline search generated 487 papers, and the LILACS search identified 140 papers. After applying the inclusion criteria, 100 original papers with any clinical information on G6PDd in LA were retrieved. Additionally, 16 articles were included after reading the references from these papers. These 116 articles reported data from 18 LA and Caribbean countries. The major clinical manifestations reported from LA countries were those related to AHA, namely drug-induced haemolysis. Most of the published works regarding drug-induced haemolysis in LA referred to haemolytic crises in P. vivax malaria patients during the course of the treatment with primaquine (PQ). Favism, infection-induced haemolysis, NNJ and CNSA appear to play only a minor public health role in this continent. Conclusion: Haemolysis in patients using PQ seems to be the major clinical manifestation of G6PDd in LA and contributes to the morbidity of P. vivax infection in this continent, although the low number of reported cases, which could be linked to under-reporting of complications. These results support the need for better strategies to diagnose and manage G6PDd in malaria field conditions. Additionally, Malaria Control Programmes in LA should not overlook this condition in their national guidelines
Declining malaria transmission in rural Amazon: changing epidemiology and challenges to achieve elimination
BACKGROUND: In recent years, considerable success in reducing
its incidence has been achieved in Brazil, leading to a relative
increase in the proportion of cases caused by Plasmodium vivax,
considered a harder-to-eliminate parasite. This study aim is to
describe the transmission dynamics and associated risk factors
in a rural settlement area in the Western Brazilian Amazon.
METHODS: A prospective cohort was established in a rural
settlement area for 3 years. Follow-up included continuous
passive case detection and monthly active case detection for a
period of 6 months. Demographic, clinical and transmission
control practices data were collected. Malaria diagnosis was
performed through thick blood smear. Univariable and
multivariable analyses of factors associated with malaria
incidence were performed using negative binomial regression
models. Factors associated with recurrence of P. vivax and
Plasmodium falciparum malaria within 90 days of a previous
episode were analysed using univariable and multivariable
Cox-Proportional Hazard models. RESULTS: Malaria prevalence
decreased from 7 % at the study beginning to 0.6 % at month 24,
with P. vivax predominating and P. falciparum disappearing after
1 year of follow-up. Malaria incidence was significantly higher
in the dry season [IRR (95 % CI) 1.4 (1.1-1.6); p < 0.001)].
Use of ITN was associated to malaria protection in the
localities [IRR (95 % CI) 0.7 (0.6-0.8); p = 0.001)]. A
recurrent P. vivax episode within 90 days was observed in 29.4 %
of individuals after an initial diagnosis. A previous P. vivax
[IRR (95 % CI) 2.3 (1.3-4.0); p = 0.006)] or mixed P. vivax + P.
falciparum [IRR (95 % CI) 2.9 (1.5-5.7); p = 0.002)] infections
were significantly associated to a vivax malaria episode within
90 days of follow-up. CONCLUSIONS: In an area of P. falciparum
and P. vivax co-endemicity, a virtual disappearance of P.
falciparum was observed with P. vivax increasing its relative
contribution, with a large proportion of recurring episodes.
This finding reinforces the perception of P. falciparum being
more responsive to early diagnosis and treatment and ITN use and
the contribution of relapsing P. vivax to maintain this species'
transmission. In areas of P. vivax endemicity, antihypnozoite
treatment effectiveness assessment in different transmission
intensity may be a fundamental activity for malaria control and
elimination
Spleen rupture in a case of untreated Plasmodium vivax infection
We report the unique case of a 19-yearold nonimmune patient with Plasmodium vivax monoinfection, confirmed by PCR in the peripheral blood and in the spleen section, who was splenectomized due to spleen rupture two days prior to the diagnosis and treatment of the malarial infection. Microscopic analyses evidenced white pulp expansion and a diffuse hypercellularity in the splenic red pulp, with intense proliferating plasmablasts in the subcapsular and perivascular compartments as well as large numbers of intact P. vivax-infected reticulocytes in the cords, in the absence of other concomitant infectious diseases. To our knowledge, this is the first full detailed immunohistopathological characterization of a nontreated P. vivax-infected spleen
Do climate changes alter the distribution and transmission of malaria? Evidence assessment and recommendations for future studies
Malaria, a mosquito-borne infectious disease, is considered a significant global health burden. Climate changes or different weather conditions may impact infectious diseases, specifically those transmitted by insect vectors and contaminated water. Based on the current predictions for climate change associated with the increase in carbon dioxide concentrations in the atmosphere and the increase in atmospheric temperature, the Intergovernmental Panel on Climate Change predicts that in 2050, malaria may threaten some previously unexposed areas worldwide and cause a 50% higher probability of malaria cases. Climatebased distribution models of malaria depict an increase in the geographic distribution of the disease as global environmental temperatures and conditions worsen. Researchers have studied the influence of changes in climate on the prevalence of malaria using different mathematical models that consider different variables and predict the conditions for malaria distribution. In this context, we conducted a mini-review to elucidate the important aspects described in the literature on the influence of climate change in the distribution and transmission of malaria. It is important to develop possible risk management strategies and enhance the surveillance system enhanced even in currently malaria-free areas predicted to experience malaria in the future. © 2019, Sociedade Brasileira de Medicina Tropical. All rights reserved
Fixed-Dose Artesunate-Amodiaquine Combination vs Chloroquine for Treatment of Uncomplicated Blood Stage P. vivax Infection in the Brazilian Amazon: An Open-Label Randomized, Controlled Trial
BACKGROUND: Despite increasing evidence of the development of
Plasmodium vivax chloroquine (CQ) resistance, there have been no
trials comparing its efficacy with that of artemisinin-based
combination therapies (ACTs) in Latin America. METHODS: This
randomized controlled trial compared the antischizontocidal
efficacy and safety of a 3-day supervised treatment of the
fixed-dose combination artesunate-amodiaquine Winthrop(R) (ASAQ)
versus CQ for treatment of uncomplicated P. vivax infection in
Manaus, Brazil. Patients were followed for 42 days. Primary
endpoints were adequate clinical and parasitological responses
(ACPR) rates at day 28. Genotype-adjustment was performed.
RESULTS: From 2012 to 2013, 380 patients were enrolled. In the
per-protocol (PP) analysis, adjusted-ACPR was achieved in 100%
(165/165) and 93.6% (161/172) of patients in the ASAQ and CQ arm
(difference 6.4%, 95% CI 2.7%; 10.1%) at day 28 and in 97.4%
(151/155) and 77.7% (129/166), respectively (difference 19.7%,
95% CI 12.9%; 26.5%), at day 42. Apart from ITT D28 assessment,
superiority of ASAQ on ACPR was demonstrated. ASAQ presented
faster clearance of parasitaemia and fever. Based on CQ blood
level measurements, CQ resistance prevalence was estimated at
11.5% (95% CI: 7.5-17.3) up to day 42. At least one emergent
adverse event (AE) was recorded for 79/190 (41x6%) in the ASAQ
group and for 85/190 (44x7%) in the CQ group. Both treatments
had similar safety profiles. CONCLUSIONS: ASAQ exhibited high efficacy against CQ resistant P. vivax and is an adequate alternative in the study area. Studies
with an efficacious comparator, longer follow-up and genotype-adjustment can improve CQR characterization
Utility of ultra-sensitive qPCR to detect Plasmodium falciparum and Plasmodium vivax infections under different transmission intensities
Background: The use of molecular diagnostics has revealed an unexpectedly large number of asymptomatic
low-density malaria infections in many malaria endemic areas. This study compared the gains in parasite prevalence
obtained by the use of ultra-sensitive (us)-qPCR as compared to standard qPCR in cross-sectional surveys conducted
in Thailand, Brazil and Papua New Guinea (PNG). The compared assays differed in the copy number of qPCR targets in
the parasite genome.
Methods: Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) parasites were quantified by qPCR amplifying the
low-copy Pf_ and Pv_18S rRNA genes or the multi-copy targets Pf_varATS and Pv_mtCOX1. Cross-sectional surveys at
the three study sites included 2252 participants of all ages and represented different transmission intensities.
Results: In the two low-transmission areas, P. falciparum positivity was 1.3% (10/773) (Thailand) and 0.8% (5/651) (Bra-
zil) using standard Pf_18S rRNA qPCR. In these two countries, P. falciparum positivity by Pf_varATS us-qPCR increased
to 1.9% (15/773) and 1.7% (11/651). In PNG, an area with moderate transmission intensity, P. falciparum positivity
significantly increased from 8.6% (71/828) by standard qPCR to 12.2% (101/828) by us-qPCR. The proportions of P.
falciparum infections not detected by standard qPCR were 33%, 55% and 30% in Thailand, Brazil and PNG. Plasmodium
vivax was the predominating species in Thailand and Brazil, with 3.9% (30/773) and 4.9% (32/651) positivity by Pv_18S
rRNA qPCR. In PNG, P. vivax positivity was similar to P. falciparum, at 8.0% (66/828). Use of Pv_mtCOX1 us-qPCR led to
a significant increase in positivity to 5.1% (39/773), 6.4% (42/651) and 11.5% (95/828) in Thailand, Brazil, and PNG. The
proportions of P. vivax infections missed by standard qPCR were similar at all three sites, with 23%, 24% and 31% in
Thailand, Brazil and PNG.
Conclusion: The proportional gains in the detection of P. falciparum and P. vivax infections by ultra-sensitive diag-
nostic assays were substantial at all three study sites. Thus, us-qPCR yields more precise prevalence estimates for
both P. falciparum and P. vivax at all studied levels of endemicity and represents a significant diagnostic improvement
Association of TLR variants with susceptibility to Plasmodium vivax malaria and parasitemia in the Amazon region of Brazil
BACKGROUND: Plasmodium vivax malaria (Pv-malaria) is still
considered a neglected disease despite an alarming number of
individuals being infected annually. Malaria pathogenesis occurs
with the onset of the vector-parasite-host interaction through
the binding of pathogen-associated molecular patterns (PAMPs)
and receptors of innate immunity, such as toll-like receptors
(TLRs). The triggering of the signaling cascade produces an
elevated inflammatory response. Genetic polymorphisms in TLRs
are involved in susceptibility or resistance to infection, and
the identification of genes involved with Pv-malaria response is
important to elucidate the pathogenesis of the disease and may
contribute to the formulation of control and elimination tools.
METHODOLOGY/PRINCIPAL FINDINGS: A retrospective case-control
study was conducted in an intense transmission area of
Pv-malaria in the state of Amazonas, Brazil. Genetic
polymorphisms (SNPs) in different TLRs, TIRAP, and CD14 were
genotyped by polymerase chain reaction-restriction fragment
length polymorphism (PCR-RFLP) analysis in 325 patients infected
with P. vivax and 274 healthy individuals without malaria
history in the prior 12 months from the same endemic area.
Parasite load was determined by qPCR. Simple and multiple
logistic/linear regressions were performed to investigate
association between the polymorphisms and the occurrence of
Pv-malaria and parasitemia. The C/T (TLR5 R392StopCodon) and T/T
(TLR9 -1486C/T) genotypes appear to be risk factors for
infection by P. vivax (TLR5: C/C vs. C/T [OR: 2.116, 95% CI:
1.054-4.452, p = 0.031]; TLR9: C/C vs. T/T [OR: 1.919, 95% CI:
1.159-3.177, p = 0.010]; respectively). Fever (COEF = 7599.46,
95% CI = 3063.80-12135.12, p = 0.001) and the C/C genotype of
TLR9 -1237C/T (COEF = 17006.63, 95% CI = 3472.83-30540.44, p =
0.014) were independently associated with increased parasitemia
in patients with Pv-malaria. CONCLUSIONS: Variants of TLRs may
predispose individuals to infection by P. vivax. The TLR5
R392StopCodon and TLR9 -1486C/T variants are associated with
susceptibility to Pv-malaria. Furthermore, the TLR9 variant
-1237C/C correlates with high parasitemia
Temporal patterns of cytokine and injury biomarkers in hospitalized COVID-19 patients treated with methylprednisolone
BackgroundThe novel coronavirus disease 2019 (COVID-19) presents with complex pathophysiological effects in various organ systems. Following the COVID-19, there are shifts in biomarker and cytokine equilibrium associated with altered physiological processes arising from viral damage or aggressive immunological response. We hypothesized that high daily dose methylprednisolone improved the injury biomarkers and serum cytokine profiles in COVID-19 patients.MethodsInjury biomarker and cytokine analysis was performed on 50 SARS-Cov-2 negative controls and 101 hospitalized severe COVID-19 patients: 49 methylprednisolone-treated (MP group) and 52 placebo-treated serum samples. Samples from the treated groups collected on days D1 (pre-treatment) all the groups, D7 (2 days after ending therapy) and D14 were analyzed. Luminex assay quantified the biomarkers HMGB1, FABP3, myoglobin, troponin I and NTproBNP. Immune mediators (CXCL8, CCL2, CXCL9, CXCL10, TNF, IFN-γ, IL-17A, IL-12p70, IL-10, IL-6, IL-4, IL-2, and IL-1β) were quantified using cytometric bead array.ResultsAt pretreatment, the two treatment groups were comparable demographically. At pre-treatment (D1), injury biomarkers (HMGB1, TnI, myoglobin and FABP3) were distinctly elevated. At D7, HMGB1 was significantly higher in the MP group (p=0.0448) compared to the placebo group, while HMGB1 in the placebo group diminished significantly by D14 (p=0.0115). Compared to healthy control samples, several immune mediators (IL-17A, IL-6, IL-10, MIG, MCP-1, and IP-10) were considerably elevated at baseline (all p≤0.05). At D7, MIG and IP-10 of the MP-group were significantly lower than in the placebo-group (p=0.0431, p=0.0069, respectively). Longitudinally, IL-2 (MP-group) and IL-17A (placebo-group) had increased significantly by D14. In placebo group, IL-2 and IL-17A continuously increased, as IL-12p70, IL-10 and IP-10 steadily decreased during follow-up. The MP treated group had IL-2, IFN-γ, IL-17A and IL-12p70 progressively increase while IL-1β and IL-10 gradually decreased towards D14. Moderate to strong positive correlations between chemokines and cytokines were observed on D7 and D14.ConclusionThese findings suggest MP treatment could ameliorate levels of myoglobin and FABP3, but appeared to have no impact on HMGB1, TnI and NTproBNP. In addition, methylprednisolone relieves the COVID-19 induced inflammatory response by diminishing MIG and IP-10 levels. Overall, corticosteroid (methylprednisolone) use in COVID-19 management influences the immunological molecule and injury biomarker profile in COVID-19 patients