RESUMEN
Malaria is increasingly diagnosed in urban centers across the Amazon Basin. In this study, we combined repeated prevalence surveys over a 4-year period of a household-based random sample of 2,774 persons with parasite genotyping to investigate the epidemiology of malaria in Mâncio Lima, the main urban transmission hotspot in Amazonian Brazil. We found that most malarial infections were asymptomatic and undetected by point-of-care microscopy. Our findings indicate that as malaria transmission decreases, the detection threshold of microscopy rises, resulting in more missed infections despite similar parasite densities estimated by molecular methods. We identified genetically highly diverse populations of Plasmodium vivax and P. falciparum in the region; occasional shared lineages between urban and rural residents suggest cross-boundary propagation. The prevalence of low-density and asymptomatic infections poses a significant challenge for routine surveillance and the effectiveness of malaria control and elimination strategies in urbanized areas with readily accessible laboratory facilities.
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Microscopía , Brasil/epidemiología , Humanos , Prevalencia , Microscopía/métodos , Femenino , Masculino , Adulto , Adolescente , Malaria Vivax/epidemiología , Malaria Vivax/parasitología , Niño , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Malaria Falciparum/prevención & control , Malaria/epidemiología , Malaria/transmisión , Malaria/prevención & control , Malaria/parasitología , Plasmodium vivax/genética , Población Urbana , Preescolar , Plasmodium falciparum/genética , Persona de Mediana Edad , Adulto Joven , Lactante , Historia del Siglo XXIRESUMEN
BACKGROUND: Plasmodium falciparum malaria is a public health issue mostly seen in tropical countries. Until now, there is no effective malaria vaccine against antigens specific to the blood-stage of P. falciparum infection. Because the pathogenesis of malarial disease results from blood-stage infection, it is essential to identify the most promising blood-stage vaccine candidate antigens under natural exposure to malaria infection. METHODS: A cohort of 400 pregnant women and their infants was implemented in South Benin. An active and passive protocol of malaria surveillance was established during pregnancy and infancy to precisely ascertain malaria infections during the follow-up. Twenty-eight antibody (Ab) responses specific to seven malaria candidate vaccine antigens were repeatedly quantified during pregnancy (3 time points) and infancy (6 time points) in order to study the Ab kinetics and their protective role. Abs were quantified by ELISA and logistic, linear and cox-proportional hazard model were performed to analyse the associations between Ab responses and protection against malaria in mothers and infants, taking into account socio-economic factors and for infants an environmental risk of exposure. RESULTS: The levels of IgM against MSP1, MSP2 and MSP3 showed an early protective response against the onset of symptomatic malaria infections starting from the 18th month of life, whereas no association was found for IgG responses during infancy. In women, some IgG responses tend to be associated with a protection against malaria risk along pregnancy and at delivery, among them IgG3 against GLURP-R0 and IgG2 against MSP1. CONCLUSION: The main finding suggests that IgM should be considered in vaccine designs during infanthood. Investigation of the functional role played by IgM in malaria protection needs further attention.
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Anticuerpos Antiprotozoarios , Antígenos de Protozoos , Inmunoglobulina G , Inmunoglobulina M , Malaria Falciparum , Plasmodium falciparum , Humanos , Femenino , Plasmodium falciparum/inmunología , Malaria Falciparum/prevención & control , Malaria Falciparum/inmunología , Embarazo , Lactante , Inmunoglobulina M/sangre , Inmunoglobulina G/sangre , Anticuerpos Antiprotozoarios/sangre , Benin , Antígenos de Protozoos/inmunología , Adulto , Adulto Joven , Ensayo de Inmunoadsorción Enzimática , Recién Nacido , Complicaciones Parasitarias del Embarazo/prevención & control , Complicaciones Parasitarias del Embarazo/inmunología , Estudios de CohortesAsunto(s)
Antimaláricos , Malaria Falciparum , Malaria , Piperazinas , Quinolinas , Humanos , Malaria/tratamiento farmacológico , Malaria/epidemiología , Malaria/prevención & control , Quinolinas/uso terapéutico , América del Sur/epidemiología , Antimaláricos/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/epidemiología , Malaria Falciparum/prevención & controlRESUMEN
Mozambique is one of the four African countries which account for over half of all malaria deaths worldwide, yet little is known about the parasite genetic structure in that country. We performed P. falciparum amplicon and whole genome sequencing on 2251 malaria-infected blood samples collected in 2015 and 2018 in seven provinces of Mozambique to genotype antimalarial resistance markers and interrogate parasite population structure using genome-wide microhaplotyes. Here we show that the only resistance-associated markers observed at frequencies above 5% were pfmdr1-184F (59%), pfdhfr-51I/59 R/108 N (99%) and pfdhps-437G/540E (89%). The frequency of pfdhfr/pfdhps quintuple mutants associated with sulfadoxine-pyrimethamine resistance increased from 80% in 2015 to 89% in 2018 (p < 0.001), with a lower expected heterozygosity and higher relatedness of microhaplotypes surrounding pfdhps mutants than wild-type parasites suggestive of recent selection. pfdhfr/pfdhps quintuple mutants also increased from 72% in the north to 95% in the south (2018; p < 0.001). This resistance gradient was accompanied by a concentration of mutations at pfdhps-436 (17%) in the north, a south-to-north increase in the genetic complexity of P. falciparum infections (p = 0.001) and a microhaplotype signature of regional differentiation. The parasite population structure identified here offers insights to guide antimalarial interventions and epidemiological surveys.
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Humanos , Malaria Falciparum/prevención & control , Malaria/patología , Antimaláricos/farmacología , Humanos , Resistencia a Medicamentos/genética , Malaria Falciparum/terapiaRESUMEN
(1) Background: Malaria, a vector-borne infectious disease, is caused by parasites of the Plasmodium genus, responsible for increased extreme morbidity and mortality rates. Despite advances in approved vaccines, full protection has not yet been achieved upon vaccination, thus the development of more potent and safe immuno-stimulating agents for malaria prevention is a goal to be urgently accomplished. We have focused our research on a strategy to identify Plasmodium spp. epitopes by naturally acquired human antibodies and rodent malaria infection models immunized with site-directed non-natural antigens. (2) Methods: Some predictive algorithms and bioinformatics tools resembling different biological environments, such as phagosome-lysosome proteolytic degradation, affinity, and the high frequency of malaria-resistant and -sensitive HLA-II alleles were regarded for the proper selection of epitopes and potential testing. Each epitope's binding profile to both host cells and HLA-II molecules was considered for such initial screening. (3) Results: Once selected, we define each epitope-peptide to be synthesized in terms of size and hydrophobicity, and introduced peptide-bond surrogates and non-natural amino acids in a site-directed fashion, and then they were produced by solid-phase peptide synthesis. Molecules were then tested by their antigenic and immunogenic properties compared to human sera from Colombian malaria-endemic areas. The antigenicity and protective capacity of each epitope-peptide in a rodent infection model were examined. The ability of vaccinated mice after being challenged with P. berghei ANKA and P. yoelii 17XL to control malaria led to the determination of an immune stimulation involving Th1 and Th1/Th2 mechanisms. In silico molecular dynamics and modeling provided some interactions insights, leading to possible explanations for protection due to immunization. (4) Conclusions: We have found evidence for proposing MSP1-modified epitopes to be considered as neutralizing antibody stimulators that are useful as probes for the detection of Plasmodium parasites, as well as for sub-unit components of a site-directed designed malaria vaccine candidate.
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Malaria Falciparum , Malaria , Parásitos , Peptidomiméticos , Humanos , Animales , Ratones , Epítopos , Proteína 1 de Superficie de Merozoito , Plasmodium falciparum , Antígenos de Protozoos , Proteínas Protozoarias/química , Malaria Falciparum/prevención & control , Malaria/prevención & control , Vacunación , Inmunoglobulinas , PéptidosRESUMEN
INTRODUCTION: Serological methods provide useful metrics to estimate age-specific period prevalence in settings of low malaria transmission; however, evidence on the use of seropositivity as an endpoint remains scarce in studies to evaluate combinations of malaria control measures, especially in children. This study aims to evaluate the immediate effects of a targeted mass drug administration campaign (tMDA) in Haiti by using serological markers. METHODS: The tMDA was implemented in September-October 2018 using sulfadoxine-pyrimethamine and single low-dose primaquine. A natural quasi-experimental study was designed, using a pretest and posttest in a cohort of 754 randomly selected school children, among which 23% reported having received tMDA. Five antigens were selected as outcomes (MSP1-19, AMA-1, Etramp5 antigen 1, HSP40, and GLURP-R0). Posttest was conducted 2-6 weeks after the intervention. RESULTS: At baseline, there was no statistical difference in seroprevalence between the groups of children that were or were not exposed during the posttest. A lower seroprevalence was observed for markers informative of recent exposure (Etramp5 antigen 1, HSP40, and GLURP-R0). Exposure to tMDA was significantly associated with a 50% reduction in the odds of seropositivity for Etramp5 antigen 1 and a 21% reduction in the odds of seropositivity for MSP119. CONCLUSION: Serological markers can be used to evaluate the effects of interventions against malaria on the risk of infection in settings of low transmission. Antibody responses against Etramp5 antigen 1 in Haitian children were reduced in the 2-6 weeks following a tMDA campaign, confirming its usefulness as a short-term marker in child populations.
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Malaria Falciparum , Malaria , Anticuerpos Antiprotozoarios , Niño , Combinación de Medicamentos , Haití/epidemiología , Humanos , Malaria/tratamiento farmacológico , Malaria/epidemiología , Malaria/prevención & control , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/epidemiología , Malaria Falciparum/prevención & control , Preparaciones Farmacéuticas , Plasmodium falciparum , Estudios SeroepidemiológicosRESUMEN
Understanding local epidemiology is essential to reduce the burden of malaria in complex contexts, such as Brazilian municipalities that share borders with endemic countries. A descriptive study of malaria in the period 2003 to 2020 was conducted using data from the Malaria Epidemiological Surveillance Information System related to a remote municipality with an extensive border with Peru to understand the disease transmission, focusing on the obstacles to its elimination. The transmission increases at the end of the rainy season. During the period of 18 years, 53,575 malaria cases were reported (Mean of API 224.7 cases/1,000), of which 11% were imported from Peru. Thirteen outbreaks of malaria were observed during the studied period, the last one in 2018. The highest burden of cases was caused by P. vivax (73.2%), but P. falciparum was also prevalent at the beginning of the study period (50% in 2006). Several changes in the epidemiological risk were observed: (1) the proportion of international imported cases of malaria changed from 30.7% in 2003 to 3.5% in 2020 (p<0.05); (2) indigenous people affected increased from 24.3% in 2003 to 89.5% in 2020 (p<0.0001); (3) infected children and adolescents < 15 years old increased from 50.2% in 2003 to 67.4% in 2020 (p<0.01); (4) the proportion of men decreased from 56.7% in 2003 to 50.4% in 2020 (p<0.01); (5) the likelihood of P. falciparum malaria has significantly declined (p<0.01). The number of cases and the incidence of malaria in 2019 and 2020 were the lowest in the period of 18 years. The burden of malaria in indigenous areas and its determinants, seasonality, geographical access and the long international border are obstacles for the elimination of malaria that must be overcome.
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Malaria Falciparum , Malaria Vivax , Malaria , Adolescente , Brasil/epidemiología , Niño , Humanos , Incidencia , Malaria/epidemiología , Malaria/prevención & control , Malaria Falciparum/epidemiología , Malaria Falciparum/prevención & control , Malaria Vivax/epidemiología , Malaria Vivax/prevención & control , Masculino , PerúRESUMEN
BACKGROUND: Malaria incidence in Brazil reversed its decreasing trend when cases from recent years, as recent as 2015, exhibited an increase in the Brazilian Amazon basin, the area with the highest transmission of Plasmodium vivax and Plasmodium falciparum. In fact, an increase of more than 20% in the years 2016 and 2017 revealed possible vulnerabilities in the national malaria-control programme. METHODS: Factors potentially associated with this reversal, including migration, economic activities, and deforestation, were studied. Past incidences of malaria cases due to P. vivax and P. falciparum were analysed with a spatio-temporal Bayesian model using more than 5 million individual records of malaria cases from January of 2003 to December of 2018 in the Brazilian Amazon to establish the municipalities with unexpected increases in cases. RESULTS: Plasmodium vivax incidence surpassed the past trends in Amazonas (AM), Amapá (AP), Acre (AC), Pará (PA), Roraima (RR), and Rondônia (RO), implying a rebound of these states between 2015 and 2018. On the other hand, P. falciparum also surpassed the past trends in AM, AC, AP, and RR with less severity than P. vivax incidence. Outdoor activities, agricultural activities, accumulated deforestation, and travelling might explain the rebound in malaria cases in RR, AM, PA, and RO, mainly in P. vivax cases. These variables, however, did not explain the rebound of either P. vivax and P. falciparum cases in AC and AP states or P. falciparum cases in RR and RO states. CONCLUSION: The Amazon basin has experienced an unexpected increase in malaria cases, mainly in P. vivax cases, in some regions of the states of Amazonas, Acre, Pará, Amapá, Roraima, and Rondônia from 2015 to 2018 and agricultural activities, outdoor activities, travelling activities, and accumulated deforestation appear linked to this rebound of cases in particular regions with different impact. This shows the multifactorial effects and the heterogeneity of the Amazon basin, boosting the necessity of focusing the malaria control programme on particular social, economic, and environmental conditions.
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Malaria Falciparum , Malaria Vivax , Malaria , Teorema de Bayes , Brasil/epidemiología , Humanos , Malaria/epidemiología , Malaria Falciparum/epidemiología , Malaria Falciparum/prevención & control , Malaria Vivax/epidemiología , Malaria Vivax/prevención & control , Plasmodium falciparum , Plasmodium vivax , Análisis Espacio-TemporalRESUMEN
Human malaria continues to be a public health problem and an important cause of morbidity and mortality in the world. Malaria control is achieved through both individual protection against mosquito bites and drug treatment, which is hampered by the spread of Plasmodium falciparum resistance to most antimalarials, including artemisinin derivatives. One of the key pharmacological strategies for controlling malaria is to block transmission of the parasites to their mosquito vectors. Following this rational, MEFAS, a synthetic hybrid salt derived from artesunate (AS) and mefloquine has been previously reported for its activity against asexual P. falciparum parasites in vitro, in addition to a pronounced reduction in the viability of mature gametocytes. Herein, MEFAS was tested against asexual forms of Plasmodium vivax and for its ability to block malaria transmission in Anopheles darlingi mosquitoes in a membrane feeding assay using P. vivax field isolates. MEFAS demonstrated high potency, with a IC50 of 6.5â¯nM against asexual forms of P. vivax. At 50⯵M, MEFAS completely blocked oocyst formation in mosquitoes, regardless of the oocyst number in the control group. At lower doses, MEFAS reduced oocyst prevalence by greater than 20%. At equivalent doses, AS irregularly reduced oocyst formation and caused only slight inhibition of mosquito infections. These results highlight the potential of MEFAS as a novel transmission-blocking molecule, as well as its high blood schizonticidal activity against P. vivax and P. falciparum field isolates, representing a starting point for further development of a new drug with dual antimalarial activity.
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Antimaláricos , Malaria Falciparum , Malaria Vivax , Malaria , Animales , Antimaláricos/farmacología , Artesunato , Humanos , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/prevención & control , Malaria Vivax/tratamiento farmacológico , Malaria Vivax/prevención & control , Mefloquina/farmacología , Plasmodium falciparum , Plasmodium vivaxRESUMEN
As malaria elimination becomes a possibility the focus of interventions changes from vector control to disease control. It is important that treatment occurs early during an infection in order for it to be efficacious, especially at the population level. The time between the onset of symptoms and treatment seeking is, therefore, crucial. Following a census and an oral autopsy survey of the inhabitants of Furvela, a village in southern Mozambique, a malaria post (MP) where malaria was diagnosed and treated was established in 2001. The time between the onset of symptoms and attendance at the MP was determined and compared to the severity of disease. A cross-sectional survey was also conducted, in 2007, to determine prevalence amongst 235 children aged between 6 months and 15 years of age. Malaria was hyperendemic in the village and was responsible for most deaths reported from the two years prior to the start of the project. In the prevalence survey 74% of two-to-four-year-old children had malaria parasites. The likelihood of being parasite positive was significantly higher in children living in houses with roofs made of traditional materials compared to those living in houses with tin roofs. At the start of the project only 12% of residents owned or used a mosquito net, most of which were not treated with insecticide. However, even before any formal intervention, malaria declined in the village between 2001 and 2007, but there was a rebound in later years. Nevertheless, the relative proportion of patients who had to be referred to the hospital declined significantly in the latter years of the project, and the incidence of both Plasmodium ovale and P. malariae also decreased significantly. Overall 16698 patients, the majority of which were under one year of age, attended the MP between 2001 and 2010. The proportion of patients with a positive slide for P. falciparum remained relatively constant throughout the study (mean 0.66 std. dev. 0.3) Most of the patients came from the village of Furvela, or its environs, but some came from the nearby town, ostensibly because of the good treatment they received. Infection rates increased up to the first three years of life to a peak incidence of 92% at 31 months. Children with fever had higher parasite densities than those without fever. Mothers generally bought their children to the MP on the second day of symptoms but on the first day if they had fever. Older patients, with lower density infections, delayed in coming for treatment. These patients may harbour sub-microscopic gametocytes which would help maintain transmission in the village. Mothers acted appropriately in their treatment seeking behaviour. The establishment of village-based MPs are an effective way of providing adequate diagnosis and treatment in villages such as Furvela.
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Humanos , Preescolar , Niño , Adolescente , Aceptación de la Atención de Salud , Malaria Falciparum/prevención & control , Plasmodium falciparum , Prevalencia , Estudios Transversales , Malaria Falciparum/epidemiología , Cuidadores , Mozambique/epidemiologíaRESUMEN
BACKGROUND: In French Guiana, gold miners working illegally represents a major reservoir of malaria. This mobile population, mainly of Brazilian descent, enters the French Guianese forest from neighbouring countries, Suriname and Brazil. A complex and innovative intervention was piloted as a cooperation with the three involved countries involved to control malaria in this specific population. The principle was that health workers called "facilitators" provide the participants with a self-diagnosis and self-treatment kit along with adequate training and material to rapidly manage an episode of malaria symptoms on their own, when they find themselves isolated from health care services. METHODS: This paper describes the design, development, content of the intervention and players' organization of this multi-country project, the opportunities and constraints encountered, and the lessons learnt at this stage. RESULTS: The choice not to implement the usual "Test and Treat" approach within the community is mainly driven by regulatory reasons. The content of medical messages tends to balance the tension between thoroughness, accuracy and efficacy. The wide range of tools developed through a participatory approach was intended to cope with the challenges of the literacy level of the target population. Despite the difficulties encountered due to language, regulation differences and distance between partners, cooperation was fruitful, due to the complementary of stakeholders, their involvement at all important stages and regular face-to-face meetings. DISCUSSION AND CONCLUSION: This experience shows the feasibility of an ambitious project of action-research in a border malaria context, involving several countries and with a mobile and undocumented population. It reveals some factors of success which may be transferable in analogous settings.
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Control de Enfermedades Transmisibles/métodos , Malaria Falciparum/prevención & control , Malaria Vivax/prevención & control , Adulto , Brasil , Femenino , Guyana Francesa , Investigación sobre Servicios de Salud , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , SurinameRESUMEN
BACKGROUND: As malaria endemic countries strive towards elimination, intensified spatial heterogeneities of local transmission could undermine the effectiveness of traditional intervention policy. METHODS: The dynamic nature of large-scale and long-term malaria heterogeneity across Brazilian Amazon basin were explored by (1) exploratory analysis of Brazil's rich clinical malaria reporting database from 2004 to 2018, and (2) adapting Gini coefficient to study the distribution of malaria cases in the region. RESULTS: As transmission declined, heterogeneity increased with cases clustering into smaller subpopulations across the territory. In 2004, the 1% of health units with the greatest number of cases accounted for 46% of all reported Plasmodium vivax cases, whereas in 2018 52% of P. vivax cases occurred in the top 1% of health units. Plasmodium falciparum had lower levels of transmission than P. vivax, and also had greater levels of heterogeneity with 75% of cases occurring in the top 1% of health units. Age and gender stratification of cases revealed peri-domestic and occupational exposure settings that remained relatively stable. CONCLUSION: The pathway to decreasing incidence is characterized by higher proportions of cases in males, in adults, due to importation, and caused by P. vivax. Characterization of spatio-temporal heterogeneity and risk groups can aid stratification for improved malaria control towards elimination with increased heterogeneity potentially allowing for more efficient and cost-effective targeting. Although distinct epidemiological phenomena were clearly observed as malaria transmission declines, the authors argue that there is no canonical path to malaria elimination and a more targeted and dynamic surveillance will be needed if Brazil decides to adopt the elimination target.
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Malaria Falciparum/epidemiología , Malaria Vivax/epidemiología , Plasmodium falciparum/fisiología , Plasmodium vivax/fisiología , Factores de Edad , Brasil/epidemiología , Femenino , Humanos , Incidencia , Malaria Falciparum/parasitología , Malaria Falciparum/prevención & control , Malaria Vivax/parasitología , Malaria Vivax/prevención & control , Masculino , Factores SexualesRESUMEN
This work describes a methodology for developing a minimal, subunit-based, multi-epitope, multi-stage, chemically-synthesised, anti-Plasmodium falciparum malaria vaccine. Some modified high activity binding peptides (mHABPs) derived from functionally relevant P. falciparum MSP, RH5 and AMA-1 conserved amino acid regions (cHABPs) for parasite binding to and invasion of red blood cells (RBC) were selected. They were highly immunogenic as assessed by indirect immunofluorescence (IFA) and Western blot (WB) assays and protective immune response-inducers against malarial challenge in the Aotus monkey experimental model. NetMHCIIpan 4.0 was used for predicting peptide-Aotus/human major histocompatibility class II (MHCII) binding affinity in silico due to the similarity between Aotus and human immune system molecules; â¼50% of Aotus MHCII allele molecules have a counterpart in the human immune system, being Aotus-specific, whilst others enabled recognition of their human counterparts. Some peptides' 1H-NMR-assessed structural conformation was determined to explain residue modifications in mHABPs inducing secondary structure changes. These directly influenced immunological behaviour, thereby highlighting the relationship with MHCII antigen presentation. The data obtained in such functional, immunological, structural and predictive approach suggested that some of these peptides could be excellent components of a fully-protective antimalarial vaccine.
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Eritrocitos/parasitología , Vacunas contra la Malaria/farmacología , Plasmodium falciparum/patogenicidad , Animales , Antígenos de Protozoos/química , Aotidae , Proteínas Portadoras/química , Epítopos , Eritrocitos/efectos de los fármacos , Antígenos de Histocompatibilidad Clase II/metabolismo , Interacciones Huésped-Parásitos/efectos de los fármacos , Humanos , Espectroscopía de Resonancia Magnética , Vacunas contra la Malaria/inmunología , Vacunas contra la Malaria/metabolismo , Malaria Falciparum/inmunología , Malaria Falciparum/prevención & control , Péptidos/inmunología , Péptidos/metabolismo , Proteínas Protozoarias/química , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/farmacologíaRESUMEN
After a centenary fight against malaria, Brazil has seen an opportunity for change with the proposal of the malaria elimination policy set by the Brazilian government, in line with malaria elimination policies in other Latin American countries. Brazilian malaria experts regard eliminating malaria by 2030 to be within reach. Herein we evaluated the likelihood that malaria elimination can be accomplished in Brazil through systematic review of the literature on malaria elimination in Brazil and epidemiological analysis. Fifty-two articles referring to malaria eradication/elimination in Brazil were analyzed to identify challenges and technological breakthroughs for controlling malaria. Monthly deaths (1979-2016) and monthly severe malaria cases (1998-2018) were analyzed according to age groups, geographic region and parasite species. As a result, we observed that the declining malaria burden was mostly attributable to a decline in Plasmodium falciparum-malaria. At the same time, the proportional increase of Plasmodium vivax-malaria in comparison with P. falciparum-malaria was notable. This niche replacement mechanism was discussed in the reviewed literature. In addition, the challenges to P. vivax-malaria elimination outnumbered the available technological breakthroughs. Although accumulated and basic information exists on mosquito vector biology, the lack of specific knowledge about mosquito vector taxonomy and ecology may hamper current attempts at stopping malaria in the country. An impressive reduction in malaria hospitalizations and mortality was seen in Brazil in the past 3 decades. Eliminating malaria deaths in children less than 5 years and P. falciparum severe cases may be achievable goals under the current malaria policy until 2030. However, eliminating P. vivax malaria transmission and morbidity seems unattainable with the available tools. Therefore, complete malaria elimination in Brazil in the near future is unlikely.
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Antimaláricos/uso terapéutico , Malaria Falciparum/epidemiología , Malaria Vivax/epidemiología , Malaria/epidemiología , Brasil/epidemiología , Erradicación de la Enfermedad , Humanos , Malaria/parasitología , Malaria/prevención & control , Malaria Falciparum/parasitología , Malaria Falciparum/prevención & control , Malaria Vivax/parasitología , Malaria Vivax/prevención & control , PolíticasRESUMEN
Introducción: El paludismo es una enfermedad febril aguda potencialmente mortal causada por parásitos que se transmiten al ser humano por la picadura de mosquitos del género Anopheles. Cuba logró eliminar la transmisión de esta enfermedad gracias a grandes esfuerzos encaminados a conseguirlo, por lo que es necesario adoptar una serie de medidas para evitar su reaparición, mediante la vigilancia y el Programa de Control Sanitario Internacional. Objetivo: Caracterizar clínicamente un grupo de pacientes con paludismo importado. Métodos: Se realizó un estudio descriptivo de corte transversal de 46 pacientes adultos con paludismo importado, ingresados en el Instituto de Medicina Tropical Pedro Kourí desde enero 2015 a diciembre 2016. Los datos fueron tomados de las historias clínicas. El análisis de las variables cualitativas fue expresado en tablas de frecuencias absolutas y relativas. Resultados: Predominaron los pacientes del sexo masculino, con una edad media de 37,4 años. Entre los pacientes, 38 (82,6 por ciento) arribaron del continente africano, la mayoría de ellos de Angola (26,1 por ciento del total de casos). Fue significativa la relación existente entre el supuesto estado no inmune de los pacientes con la severidad del cuadro clínico y presencia de comorbilidades; así como la severidad del cuadro clínico con mayor parasitemia y la especie Plasmodium falciparum. La respuesta al tratamiento resultó excelente con los esquemas combinados utilizados a base de quinina y cloroquina según la especie. Conclusiones: La demora desde el arribo al ingreso hospitalario de los pacientes constituye un riesgo extraordinario para la reintroducción del paludismo en Cuba y para la vida de estos(AU)
Introduction: Malaria is an acute potentially fatal febrile disease caused by parasites transmitted to humans through the bite of mosquitoes from the genus Anopheles. Cuba succeeded in eliminating transmission of this disease thanks to great efforts geared to such an end. It is therefore necessary to take a number of measures aimed at preventing its re-emergence via surveillance and the International Health Control Program. Objective: Clinically characterize a group of patients with imported malaria. Methods: A descriptive cross-sectional study was conducted of 46 adult patients with imported malaria admitted to Pedro Kourí Tropical Medicine Institute from January 2015 to December 2016. The data were collected from the patients' medical records. Results of the analysis of qualitative variables were transferred onto absolute and relative frequency tables. Results: Male patients prevailed, with a mean age of 37.4 years. Of the patients studied, 38 (82.6 percent) were from the African continent, most of them from Angola (26.1 percent of the total cases). A significant relationship was found between the supposed non-immune status of patients and the severity of the clinical status and the presence of comorbidities, as well as between the severity of the clinical status and greater parasitemia and the presence of the species Plasmodium falciparum. An excellent response was obtained to treatment with combined schemes based on quinine and chloroquine, depending on the species. Conclusions: Delay between arrival and hospital admittance of patients is an extraordinary risk for the reintroduction of malaria in Cuba and to the patients' lives(AU)
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Humanos , Medicina Tropical , Politica Nacional de Vigilancia Sanitaria , Cloroquina/uso terapéutico , Epidemiología Descriptiva , Estudios Transversales , Malaria Falciparum/prevención & control , CubaRESUMEN
BACKGROUND: The present study provides a countrywide perspective of the malaria situation in Panamá over a long-term framework, with the purpose of identifying historical malaria resurgence events and their potential causes. METHODS: A descriptive-ecological study was conducted by analysing demographic and epidemiological annual malaria time series data in Panamá (1884-2019) using several data sources. Malaria intensity indicators were calculated during the study period. The effects of El Niño Southern Oscillation on malaria transmission were also analysed using a retrospective analysis of malaria cases between 1957 and 2019. RESULTS: Several factors were identified responsible for malaria resurgence in Panamá, mostly related with Malaria Control Programme weakening. During the past 20 years (2000-2019) malaria has progressively increased in prevalence within indigenous settlements, with a predominance of male cases and a high proportion (15% of total cases) in children less than 5 years old. During this period, a significant and increasing proportion of the Plasmodium falciparum cases were imported. Retrospective analysis (1957-2019) evidenced that ENSO had a significant impact on malaria transmission dynamics in Panamá. CONCLUSIONS: Data analysis confirmed that although authorities have been successful in focalizing malaria transmission in the country, there are still neglected issues to be solved and important intercultural barriers that need to be addressed in order to achieve elimination of the disease by 2022. This information will be useful for targeting strategies by the National Malaria Elimination Programme.
Asunto(s)
El Niño Oscilación del Sur , Política de Salud/legislación & jurisprudencia , Malaria Falciparum , Malaria Vivax , Salud Pública/legislación & jurisprudencia , Humanos , Malaria Falciparum/prevención & control , Malaria Falciparum/transmisión , Malaria Vivax/prevención & control , Malaria Vivax/transmisión , Panamá , Plasmodium falciparum/fisiología , Plasmodium vivax/fisiología , Estudios RetrospectivosRESUMEN
The Mediterranean diet (MedDiet) consists of consumption of vegetables and healthy oils and have beneficial effects on metabolic and inflammatory diseases. Our goal here is to discuss the role of fatty acid content in MedDiet, mostly omega-3, omega-6, and omega-9 on malaria. Malaria affects millions of people around the globe. The parasite Plasmodium causes the disease. The metabolic and inflammatory alterations in the severe forms have damaging consequences to the host. The lipid content in the MedDiet holds anti-inflammatory and pro-resolutive features in the host and have detrimental effects on the Plasmodium. The lipids from the diet impact the balance of pro- and anti-inflammation, thus, lipids intake from the diet is critical to parasite elimination and host tissue damage caused by an immune response. Herein, we go into the cellular and molecular mechanisms and targets of the MedDiet fatty acids in the host and the parasite, reviewing potential benefits of the MedDiet, on inflammation, malaria infection progression, and clinical outcome.
Asunto(s)
Antiinflamatorios/administración & dosificación , Dieta Mediterránea , Inflamación/dietoterapia , Lípidos/análisis , Malaria Falciparum/prevención & control , Plasmodium falciparum/aislamiento & purificación , Humanos , Inflamación/patología , Malaria Falciparum/parasitologíaRESUMEN
Malaria remains a large-scale public health problem, killing more than 400,000 people and infecting up to 230 million worldwide, every year. Unfortunately, despite numerous efforts and research concerning vaccine development, results to date have been low and/or strain-specific. This work describes a strategy involving Plasmodium falciparum Duffy binding-like (DBL) and reticulocyte-binding protein homologue (RH) family-derived minimum functional peptides, netMHCIIpan3.2 parental and modified peptides' in silico binding prediction and modeling some Aotus major histocompatibility class II (MHCII) molecules based on known human molecules' structure to understand their differences. These are used to explain peptides' immunological behaviour when used as vaccine components in the Aotus model. Despite the great similarity between human and Aotus immune system molecules, around 50% of Aotus allele molecules lack a counterpart in the human immune system which could lead to an Aotus-specific vaccine. It was also confirmed that functional Plasmodium falciparum' conserved proteins are immunologically silent (in both the animal model and in-silico prediction); they must therefore be modified to elicit an appropriate immune response. Some peptides studied here had the desired behaviour and can thus be considered components of a fully-protective antimalarial vaccine.
Asunto(s)
Vacunas contra la Malaria/inmunología , Malaria Falciparum/prevención & control , Plasmodium falciparum/inmunología , Proteínas Protozoarias/inmunología , Vacunas de Subunidad/inmunología , Secuencia de Aminoácidos , Animales , Aotidae , Control de Enfermedades Transmisibles , Enfermedades Transmisibles/inmunología , Modelos Animales de Enfermedad , Antígenos de Histocompatibilidad Clase II/inmunología , Humanos , Vacunas contra la Malaria/química , Vacunas contra la Malaria/uso terapéutico , Malaria Falciparum/inmunología , Modelos Moleculares , Plasmodium falciparum/química , Proteínas Protozoarias/química , Proteínas Protozoarias/uso terapéutico , Vacunas de Subunidad/química , Vacunas de Subunidad/uso terapéuticoRESUMEN
BACKGROUND: Case management is one of the principal strategies for malaria control. This study aimed to estimate the economic costs of uncomplicated malaria case management and explore the influence of health-seeking behaviours on those costs. METHODS: A knowledge, attitudes and practices (KAP) survey was applied to 680 households of fifteen communities in Mazan-Loreto in March 2017, then a socio-economic survey was conducted in September 2017 among 161 individuals with confirmed uncomplicated malaria in the past 3 months. Total costs per episode were estimated from both provider (Ministry of Health, MoH) and patient perspectives. Direct costs were estimated using a standard costing estimation procedure, while the indirect costs considered the loss of incomes among patients, substitute labourers and companions due to illness in terms of the monthly minimum wage. Sensitivity analysis evaluated the uncertainty of the average cost per episode. RESULTS: The KAP survey showed that most individuals (79.3%) that had malaria went to a health facility for a diagnosis and treatment, 2.7% received those services from community health workers, and 8% went to a drugstore or were self-treated at home. The average total cost per episode in the Mazan district was US$ 161. The cost from the provider's perspective was US$ 30.85 per episode while from the patient's perspective the estimated cost was US$ 131 per episode. The average costs per Plasmodium falciparum episode (US$ 180) were higher than those per Plasmodium vivax episode (US$ 156) due to longer time lost from work by patients with P. falciparum infections (22.2 days) than by patients with P. vivax infections (17.0 days). The delayed malaria diagnosis (after 48 h of the onset of symptoms) was associated with the time lost from work due to illness (adjusted mean ratio 1.8; 95% CI 1.3, 2.6). The average cost per malaria episode was most sensitive to the uncertainty around the lost productivity cost due to malaria. CONCLUSIONS: Despite the provision of free malaria case management by MoH, there is delay in seeking care and the costs of uncomplicated malaria are mainly borne by the families. These costs are not well perceived by the society and the substantial financial impact of the disease can be frequently undervalued in public policy planning.
Asunto(s)
Manejo de Caso/economía , Conocimientos, Actitudes y Práctica en Salud , Malaria Falciparum/prevención & control , Malaria Vivax/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Perú , Adulto JovenRESUMEN
Although viruses and bacteria have been known as agents of diseases since 1546, 250 years went by until the first vaccines against these pathogens were developed (1796 and 1800s). In contrast, Malaria, which is a protozoan-neglected disease, has been known since the 5th century BCE and, despite 2,500 years having passed since then, no human vaccine has yet been licensed for Malaria. Additionally, no modern human vaccine is currently licensed against Visceral or Cutaneous leishmaniasis. Vaccination against Malaria evolved from the inoculation of irradiated sporozoites through the bite of Anopheles mosquitoes in 1930's, which failed to give protection, to the use of controlled human Malaria infection (CHMI) provoked by live sporozoites of Plasmodium falciparum and curtailed with specific chemotherapy since 1940's. Although the use of CHMI for vaccination was relatively efficacious, it has some ethical limitations and was substituted by the use of injected recombinant vaccines expressing the main antigens of the parasite cycle, starting in 1980. Pre-erythrocytic (PEV), Blood stage (BSV), transmission-blocking (TBV), antitoxic (AT), and pregnancy-associated Malaria vaccines are under development. Currently, the RTS,S-PEV vaccine, based on the circumsporozoite protein, is the only one that has arrived at the Phase III trial stage. The "R" stands for the central repeat region of Plasmodium (P.) falciparum circumsporozoite protein (CSP); the "T" for the T-cell epitopes of the CSP; and the "S" for hepatitis B surface antigen (HBsAg). In Africa, this latter vaccine achieved only 36.7% vaccine efficacy (VE) in 5-7 years old children and was associated with an increase in clinical cases in one assay. Therefore, in spite of 35 years of research, there is no currently licensed vaccine against Malaria. In contrast, more progress has been achieved regarding prevention of leishmaniasis by vaccine, which also started with the use of live vaccines. For ethical reasons, these were substituted by second-generation subunit or recombinant DNA and protein vaccines. Currently, there is one live vaccine for humans licensed in Uzbekistan, and four licensed veterinary vaccines against visceral leishmaniasis: Leishmune® (76-80% VE) and CaniLeish® (68.4% VE), which give protection against strong endpoints (severe disease and deaths under natural conditions), and, under less severe endpoints (parasitologically and PCR-positive cases), Leishtec® developed 71.4% VE in a low infective pressure area but only 35.7% VE and transient protection in a high infective pressure area, while Letifend® promoted 72% VE. A human recombinant vaccine based on the Nucleoside hydrolase NH36 of Leishmania (L.) donovani, the main antigen of the Leishmune® vaccine, and the sterol 24-c-methyltransferase (SMT) from L. (L.) infantum has reached the Phase I clinical trial phase but has not yet been licensed against the disease. This review describes the history of vaccine development and is focused on licensed formulations that have been used in preventive medicine. Special attention has been given to the delay in the development and licensing of human vaccines against Protozoan infections, which show high incidence worldwide and still remain severe threats to Public Health.