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1.
Trends Parasitol ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34857495

RESUMO

Last month, the World Health Organization (WHO) recommended widespread use of RTS,S/AS01 vaccine to prevent malaria in young African children, noting its 30% reduction in deadly severe malaria. In a recent report, Das et al. describe antibody effector functions that may contribute to RTS,S efficacy and thereby guide vaccine improvements.

2.
Lancet Infect Dis ; 21(12): 1634, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34838227
3.
Can J Public Health ; 112(6): 967-969, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34846704
4.
BMJ ; 375: n2455, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620612
5.
Science ; 374(6565): 245-246, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34648307

RESUMO

[Figure: see text].

6.
N Engl J Med ; 385(11): 1005-1017, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34432975

RESUMO

BACKGROUND: Malaria control remains a challenge in many parts of the Sahel and sub-Sahel regions of Africa. METHODS: We conducted an individually randomized, controlled trial to assess whether seasonal vaccination with RTS,S/AS01E was noninferior to chemoprevention in preventing uncomplicated malaria and whether the two interventions combined were superior to either one alone in preventing uncomplicated malaria and severe malaria-related outcomes. RESULTS: We randomly assigned 6861 children 5 to 17 months of age to receive sulfadoxine-pyrimethamine and amodiaquine (2287 children [chemoprevention-alone group]), RTS,S/AS01E (2288 children [vaccine-alone group]), or chemoprevention and RTS,S/AS01E (2286 children [combination group]). Of these, 1965, 1988, and 1967 children in the three groups, respectively, received the first dose of the assigned intervention and were followed for 3 years. Febrile seizure developed in 5 children the day after receipt of the vaccine, but the children recovered and had no sequelae. There were 305 events of uncomplicated clinical malaria per 1000 person-years at risk in the chemoprevention-alone group, 278 events per 1000 person-years in the vaccine-alone group, and 113 events per 1000 person-years in the combination group. The hazard ratio for the protective efficacy of RTS,S/AS01E as compared with chemoprevention was 0.92 (95% confidence interval [CI], 0.84 to 1.01), which excluded the prespecified noninferiority margin of 1.20. The protective efficacy of the combination as compared with chemoprevention alone was 62.8% (95% CI, 58.4 to 66.8) against clinical malaria, 70.5% (95% CI, 41.9 to 85.0) against hospital admission with severe malaria according to the World Health Organization definition, and 72.9% (95% CI, 2.9 to 92.4) against death from malaria. The protective efficacy of the combination as compared with the vaccine alone against these outcomes was 59.6% (95% CI, 54.7 to 64.0), 70.6% (95% CI, 42.3 to 85.0), and 75.3% (95% CI, 12.5 to 93.0), respectively. CONCLUSIONS: Administration of RTS,S/AS01E was noninferior to chemoprevention in preventing uncomplicated malaria. The combination of these interventions resulted in a substantially lower incidence of uncomplicated malaria, severe malaria, and death from malaria than either intervention alone. (Funded by the Joint Global Health Trials and PATH; ClinicalTrials.gov number, NCT03143218.).


Assuntos
Amodiaquina/uso terapêutico , Antimaláricos/uso terapêutico , Vacinas Antimaláricas , Malária Falciparum/prevenção & controle , Pirimetamina/uso terapêutico , Sulfadoxina/uso terapêutico , Antimaláricos/efeitos adversos , Burkina Faso/epidemiologia , Quimioprevenção , Terapia Combinada , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/efeitos adversos , Malária Falciparum/epidemiologia , Malária Falciparum/mortalidade , Masculino , Mali/epidemiologia , Estações do Ano , Convulsões Febris/etiologia
7.
Malar J ; 20(1): 325, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315489

RESUMO

BACKGROUND: Malaria continues to be a major disease of public health concern affecting several million people worldwide. The World Health Organization (WHO) started a pilot study on a malaria vaccine (RTS,S) in Ghana and two other countries in 2019. This study aimed at assessing the factors associated with uptake of the vaccine in the Sunyani Municipality of Ghana. METHODS: The study was a cross-sectional study employing a quantitative approach. Stratified sampling technique was used to select respondents. A structured questionnaire was administered to parents/caregivers with children eligible to have taken the first three doses of the malaria vaccine by December 2019. The Child Welfare Clinic (CWC) cards of the eligible children were also inspected. Ordinal logistic regression analysis was done to determine the association between the independent variables and full vaccine uptake. RESULTS: Uptake of RTS,S 1 was 94.1%. However, this figure reduced to 90.6% for RTS,S 2, and 78.1% for RTS,S 3. Children with a parent who had been educated up to the tertiary level had 4.72 (AOR: 4.72, 95% CI 1.27-17.55) increased odds of full uptake as compared to those who completed secondary education. Parents whose children had experienced fever as an adverse reaction were more likely to send their children for the malaria vaccine as compared to those whose children had ever suffered abscess as an adverse reaction (AOR: 2.27, 95% CI 1.13-5.10). Children with parents who thought vaccines were becoming too many for children had 71% (AOR: 0.29, 95% CI 0.14-0.61) reduced odds of full uptake as compared to those who thought otherwise. CONCLUSION: Uptake of RTS,S 1 and RTS,S 2 in Sunyani Municipality meets the WHO's target coverage for vaccines, however, RTS,S 3 uptake does not. Furthermore, there is a growing perception amongst parents/caregivers that vaccines are becoming too many for children which negatively affects uptake.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Vacinas Antimaláricas/uso terapêutico , Cobertura Vacinal/estatística & dados numéricos , Adolescente , Adulto , Feminino , Gana , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Vaccine ; 39(22): 2907-2916, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33931251

RESUMO

Considerable progress has been made in malaria control in the last two decades, but progress has stalled in the last few years. New tools are needed to achieve public health goals in malaria control and elimination. A first generation vaccine, RTS,S/AS01, is currently being evaluated as it undergoes pilot implementation through routine health systems in parts of three African countries. The development of this vaccine took over 30 years and has been full of uncertainties. Even now, important unknowns remain as to its future role in public health. Lessons need to be learnt for second generation and future vaccines, including how to facilitate early planning of investments, streamlining of development, regulatory and policy pathways. A number of candidate vaccines populate the current development pipeline, some of which have the potential to contribute to burden reduction if efficacy is confirmed in conditions of natural exposure, and if they are amenable to affordable supply and programmatic implementation. New, innovative technologies will be needed if future malaria vaccines are to overcome important scientific hurdles and induce durable, high level protection. WHO convened a stakeholder consultation on the status of malaria vaccine research and development to inform the recently reconstituted Malaria Vaccine Advisory Committee (MALVAC) which will assist WHO in updating its current guidance and recommendations about priorities and product preferences for malaria vaccines.


Assuntos
Vacinas Antimaláricas , Malária Falciparum , Malária , África , Humanos , Malária/prevenção & controle , Encaminhamento e Consulta , Organização Mundial da Saúde
10.
Risk Manag Healthc Policy ; 14: 1033-1039, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33737844

RESUMO

Background: Recent advances in mosquito eradication and antimalarial treatments have reduced the malaria burden only modestly. An effective malaria vaccine remains a high priority, but its development has several challenges. Among many potential candidates, the RTS,S/AS01 vaccine (MosquirixTM) remains the leading candidate. Objective and Method: This review aims to understand the advances in the RTS,S/AS01 vaccine, and future comments regarding the vaccine's effectiveness in malaria eradication. Literature review for the past five decades was performed searching PubMed, EMBASE Ovid, and Cochrane Library, with using the following search items: ("malaria" OR "WHO's malaria" OR "Plasmodium falciparum" OR "RTS,S" OR "RTS,S/AS01" OR "RTS,S/AS02" OR "pre-erythrocytic malaria" OR "circumsporozoite" OR "Mosquirix") AND ("vaccine" OR "vaccination"). Results: RTS,S/AS01, a recombinant pre-erythrocytic vaccine containing Plasmodium falciparum surface-protein (circumsporozoite) antigen, is safe, well-tolerated, and immunogenic in children. Three doses, along with a booster, have a modest efficacy of about 36% in children (age 5-17 months) and about 26% in infants (age 6-12 weeks) against clinical malaria during a 48-month follow-up. However, the efficacy varies among population subgroups and with the parasite strain, it reduces without a booster and offers protection for a limited duration. Because of its potential cost-effectiveness and positive public health effect, the vaccine is being investigated in a pilot program for mortality benefits and broader deployment. Conclusion: The RTS,S/AS01 vaccine prevents malaria; however, it should be considered another addition to the malaria-control program and not as an eradication tool because of its relatively low to modest efficacy.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33533814

RESUMO

Malaria represents a serious public health problem, presenting with high rates of incidence, morbidity and mortality in tropical and subtropical regions of the world. According to the World Health Organization, in 2018 there were 228 million cases and 405 thousand deaths caused by this disease in the world, affecting mainly children and pregnant women in Africa. Despite the programs carried out to control this disease, drug resistance and invertebrate vector resistance to insecticides have generated difficulties. An efficient vaccine against malaria would be a strategy with a high impact on the eradication and control of this disease. Researches aimed at developing vaccines have focused on antigens of high importance for the survival of the parasite such as the Circumsporozoite Surface Protein, involved in the pre-erythrocytic cycle during parasites invasion in hepatocytes. Currently, RTS'S is the most promising vaccine for malaria and was constructed using CSP; its performance was evaluated using two types of adjuvants: AS01 and AS02. The purpose of this review was to provide a bibliographic survey of historical researches that led to the development of RTS'S and its performance analysis over the decade. The search for new adjuvants to be associated with this antigen seems to be a way to obtain higher percentages of protection for a future malaria vaccine.


Assuntos
Vacinas Antimaláricas/uso terapêutico , Malária/prevenção & controle , Plasmodium falciparum/genética , Plasmodium falciparum/metabolismo , Proteínas de Protozoários , Humanos , Malária/parasitologia , Vacinas Antimaláricas/administração & dosagem , Proteínas de Membrana
12.
PLoS One ; 16(1): e0244995, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33428635

RESUMO

BACKGROUND: The RTS,S/ASO1E malaria vaccine is being piloted in three countries-Ghana, Kenya, and Malawi-as part of a coordinated evaluation led by the World Health Organization, with support from global partners. This study estimates the costs of continuing malaria vaccination upon completion of the pilot evaluation to inform decision-making and planning around potential further use of the vaccine in pilot areas. METHODS: We used an activity-based costing approach to estimate the incremental costs of continuing to deliver four doses of RTS,S/ASO1E through the existing Expanded Program on Immunization platform, from each government's perspective. The RTS,S/ASO1E pilot introduction plans were reviewed and adapted to identify activities for costing. Key informant interviews with representatives from Ministries of Health (MOH) were conducted to inform the activities, resource requirements, and assumptions that, in turn, inform the analysis. Both financial and economic costs per dose, cost of delivery per dose, and cost per fully vaccinated child (FVC) are estimated and reported in 2017 USD units. RESULTS: At a vaccine price of $5 per dose and assuming the vaccine is donor-funded, our estimated incremental financial costs range from $1.70 (Kenya) to $2.44 (Malawi) per dose, $0.23 (Malawi) to $0.71 (Kenya) per dose delivered (excluding procurement add-on costs), and $11.50 (Ghana) to $13.69 (Malawi) per FVC. Estimates of economic costs per dose are between three and five times higher than financial costs. Variations in activities used for costing, procurement add-on costs, unit costs of per diems, and allowances contributed to differences in cost estimates across countries. CONCLUSION: Cost estimates in this analysis are meant to inform country decision-makers as they face the question of whether to continue malaria vaccination, should the intervention receive a positive recommendation for broader use. Additionally, important cost drivers for vaccine delivery are highlighted, some of which might be influenced by global and country-specific financing and existing procurement mechanisms. This analysis also adds to the evidence available on vaccine delivery costs for products delivered outside the standard immunization schedule.


Assuntos
Custos de Cuidados de Saúde , Programas de Imunização/economia , Vacinas Antimaláricas/economia , Malária/prevenção & controle , Vacinação/economia , Análise Custo-Benefício , Gana , Humanos , Quênia , Malaui , Organização Mundial da Saúde
13.
Biochimie ; 181: 176-190, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33346039

RESUMO

The malaria parasite has an extraordinary ability to evade the immune system due to which the development of a malaria vaccine is a challenging task. Extensive research on malarial infection in the human host particularly during the liver stage has resulted in the discovery of potential candidate vaccines including RTS,S/AS01 and R21. However, complete elimination of malaria would require a holistic multi-component approach. In line with this, under the World Health Organization's PATH Malaria Vaccine Initiative (MVI), the research focus has shifted towards the sexual stages of malaria in the mosquito host. Last two decades of scientific research obtained seminal information regarding the sexual/mosquito stages of the malaria. This updated and comprehensive review would provide the basis for consolidated understanding of cellular, biochemical, molecular and immunological aspects of parasite transmission right from the sexual stage commitment in the human host to the sporozoite delivery back into subsequent vertebrate host by the female Anopheles mosquito.


Assuntos
Anopheles/parasitologia , Vacinas Antimaláricas/uso terapêutico , Malária Falciparum , Plasmodium falciparum/metabolismo , Animais , Feminino , Humanos , Malária Falciparum/metabolismo , Malária Falciparum/prevenção & controle , Masculino
14.
PLoS Med ; 17(11): e1003377, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33253211

RESUMO

BACKGROUND: The RTS,S/AS01 vaccine against Plasmodium falciparum malaria infection completed phase III trials in 2014 and demonstrated efficacy against clinical malaria of approximately 36% over 4 years for a 4-dose schedule in children aged 5-17 months. Pilot vaccine implementation has recently begun in 3 African countries. If the pilots demonstrate both a positive health impact and resolve remaining safety concerns, wider roll-out could be recommended from 2021 onwards. Vaccine demand may, however, outstrip initial supply. We sought to identify where vaccine introduction should be prioritised to maximise public health impact under a range of supply constraints using mathematical modelling. METHODS AND FINDINGS: Using a mathematical model of P. falciparum malaria transmission and RTS,S vaccine impact, we estimated the clinical cases and deaths averted in children aged 0-5 years in sub-Saharan Africa under 2 scenarios for vaccine coverage (100% and realistic) and 2 scenarios for other interventions (current coverage and World Health Organization [WHO] Global Technical Strategy targets). We used a prioritisation algorithm to identify potential allocative efficiency gains from prioritising vaccine allocation among countries or administrative units to maximise cases or deaths averted. If malaria burden at introduction is similar to current levels-assuming realistic vaccine coverage and country-level prioritisation in areas with parasite prevalence >10%-we estimate that 4.3 million malaria cases (95% credible interval [CrI] 2.8-6.8 million) and 22,000 deaths (95% CrI 11,000-35,000) in children younger than 5 years could be averted annually at a dose constraint of 30 million. This decreases to 3.0 million cases (95% CrI 2.0-4.7 million) and 14,000 deaths (95% CrI 7,000-23,000) at a dose constraint of 20 million, and increases to 6.6 million cases (95% CrI 4.2-10.8 million) and 38,000 deaths (95% CrI 18,000-61,000) at a dose constraint of 60 million. At 100% vaccine coverage, these impact estimates increase to 5.2 million cases (95% CrI 3.5-8.2 million) and 27,000 deaths (95% CrI 14,000-43,000), 3.9 million cases (95% CrI 2.7-6.0 million) and 19,000 deaths (95% CrI 10,000-30,000), and 10.0 million cases (95% CrI 6.7-15.7 million) and 51,000 deaths (95% CrI 25,000-82,000), respectively. Under realistic vaccine coverage, if the vaccine is prioritised sub-nationally, 5.3 million cases (95% CrI 3.5-8.2 million) and 24,000 deaths (95% CrI 12,000-38,000) could be averted at a dose constraint of 30 million. Furthermore, sub-national prioritisation would allow introduction in almost double the number of countries compared to national prioritisation (21 versus 11). If vaccine introduction is prioritised in the 3 pilot countries (Ghana, Kenya, and Malawi), health impact would be reduced, but this effect becomes less substantial (change of <5%) if 50 million or more doses are available. We did not account for within-country variation in vaccine coverage, and the optimisation was based on a single outcome measure, therefore this study should be used to understand overall trends rather than guide country-specific allocation. CONCLUSIONS: These results suggest that the impact of constraints in vaccine supply on the public health impact of the RTS,S malaria vaccine could be reduced by introducing the vaccine at the sub-national level and prioritising countries with the highest malaria incidence.


Assuntos
Vacinas Antimaláricas , Malária Falciparum/prevenção & controle , Malária/prevenção & controle , Modelos Teóricos , Criança , Pré-Escolar , Feminino , Gana , Humanos , Incidência , Lactente , Recém-Nascido , Quênia , Malária/epidemiologia , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/farmacologia , Malária Falciparum/epidemiologia , Malaui , Masculino , Saúde Pública/estatística & dados numéricos
15.
16.
Malar J ; 19(1): 79, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075635

RESUMO

BACKGROUND: According to the World Health Organization reports, billions of people around the world are at risk for malaria disease and it is important to consider the preventive strategies for protecting the people that are living in high risk areas. One of the main reasons of disease survival is diversity of vectors and parasites in different malaria regions that have their specific features, behaviour and biology. Therefore, specific regional strategies are necessary for successful control of malaria. One of the tools that needs to be developed for elimination and prevention of reintroduction of malaria is a vaccine that interrupt malaria transmission (VIMTs). VIMT is a broad concept that should be adjusted to the biological characteristics of the disease in each region. One type of VIMT is a vector-based vaccine that affects the sexual stage of Plasmodium life cycle. According to recent studies, the aminopeptidase N-1 of Anopheles gambiae (AgAPN-1) is as a potent vector-based VIMT with considerable inhibition activity against the sexual stage of Plasmodium parasite. METHODS: Systems for rapid amplification of cDNA ends (3'-RACE) and genome walking methods were used for sequence determination of apn-1 gene from Anopheles stephensi and distinct bioinformatics software were used for structural analysis. AsAPN-1 was expressed in Spodoptera frugiperda (Sf9) insect cell line using the baculovirus expression system. Recombinant AsAPN-1 was purified under the hybrid condition and its biological activity was assayed. RESULTS: Asapn-1 gene and its coded protein from An. stephensi were characterized for the first time in this study. Subsequently, the structural features and immunological properties of its coded protein were evaluated by in silico approaches. Enzymatic activity of the recombinant AsAPN-1, which was expressed in Sf9 insect cell line, was equal to 6 unit/µl. CONCLUSIONS: Results of this study revealed that AsAPN-1 is very similar to its counterpart in An. gambiae. In silico evaluation and fundamental data which are necessary for its evaluation as a VIMT-based vaccine in the next steps were acquired in this study and those could be useful for research groups that study on malaria vaccine for countries that An. stephensi is the main malaria vector there.


Assuntos
Anopheles/genética , Antígenos CD13/farmacologia , Proteínas de Insetos/genética , Malária/prevenção & controle , Plasmodium falciparum/imunologia , Animais , Anopheles/enzimologia , Proteínas de Insetos/farmacologia , Vacinas Antimaláricas/imunologia , Células Sf9 , Spodoptera
18.
Artigo em Alemão | MEDLINE | ID: mdl-31828371

RESUMO

Globally, 3.1 billion people live in areas endemic for malaria (the tropics and subtropics). Annually, around 200 million fall ill, and around 500,000 persons die as a result of this infection. Mainly children are the victims. In order to control and eventually prevent any new infection, the development of effective vaccines is pivotal. In this review, background information about the history of vaccine development and malaria disease as well as possibilities for therapy and control is given. In the main part of the article, an update on the development of vaccines against Plasmodium falciparum is provided followed by an extensive discussion.Malaria is a parasitic infectious disease caused by the single cell organism Plasmodium. Five different Plasmodium species can induce disease in humans with P. falciparum being the origin for more than 99% of infections in Africa. The vector is the Anopheles mosquito. The life cycle of Plasmodium offers several approaches for vaccines to have an impact. Out of around 70 candidates, pre-erythrocytic vaccine candidates interfering with the liver phase of the parasite are the most developed. However, a vaccine with more than 75% efficacy, as required by the World Health Organization (WHO), is not yet in sight.Currently, for the first time, a moderately efficacious vaccine (RTS,S/AS01) is being applied in large-scale operations. But it is obvious that malaria can only be controlled in combination with concurring measures. For example, the use of impregnated mosquito nets, indoor residual spraying, elimination of vector breeding sites, rapid diagnosis, and therapy of the infection as well as a functioning health system are important elements, which can hardly be guaranteed in areas characterized by poverty.


Assuntos
Vacinas Antimaláricas , Malária Falciparum , Malária , Animais , Criança , Alemanha , Humanos , Plasmodium falciparum
19.
Rev. Investig. Salud. Univ. Boyacá ; 7(1): 137-160, 2020. tab, ilust
Artigo em Espanhol | LILACS | ID: biblio-1178380

RESUMO

Introducción. La malaria por Plasmodium falciparum es una enfermedad causante de altas tasas de morbimortalidad a nivel mundial. Diferentes candidatos a vacuna se han evaluado experimentalmente en humanos; sin embargo, no se dispone de ninguna vacuna que reduzca o elimine esta devastadora enfermedad. Objetivo. Describir en términos de diseño, respuesta inmune, eficacia protectiva y perspectivas, los principales candidatos vigentes a vacuna contra la malaria por Plasmodium falciparum, dirigidos a las fases pre-eritrocítica y eritrocítica. Metodología. Se realizó una revisión descriptiva de trabajos publicados en bases de datos PubMed, Science Direct, Embase y MedLine. Los criterios de inclusión fueron: trabajos publicados en una ventana de tiempo entre 2000 y 2019, candidatos a vacuna contra Plasmodium falciparum en estadíos pre y eritrocíticos y vigencia según la Organización Mundial de la Salud. En total, se revisaron 90 artículos originales, encontrando que 63 cumplieron con todos los criterios establecidos, mientras que 27, no cumplieron por lo menos con un criterio. Resultados. Los candidatos a vacunas vigentes incluyen diseños basados en parásitos atenuados, proteínas recombinantes, vectores virales y síntesis química. Las formulaciones contienen un número mínimo de antígenos con secuencias de aminoácidos altamente polimórficas, que inducen un aceptable perfil de inmunogenicidad, aunque una limitada eficacia protectora contra la malaria, debido a que tales regiones polimórficas son inmunodominantes, confiriendo únicamente inmunidad específica de cepa. Conclusiones. El desarrollo de una vacuna efectiva contra la malaria por Plasmodium falciparum posiblemente requiera incluir múltiples epítopes funcionalmente relevantes, del estadío pre y eritrocítico, que contengan regiones conservadas entre cepas, para lograr inducir respuestas inmunes duraderas que bloqueen la invasión del parásito a células hepáticas y eritrocitos.


Introduction. Plasmodium falciparum malaria is a disease that causes high rates of morbidity and mortality worldwide. Different vaccine candidates have been evaluated experimentally in humans; however, there is no vaccine available that reduces or eliminates this devastating disease. Objective. Describe in terms of design, immune response, protective efficacy and perspectives, the main current candidates for Plasmodium falciparum malaria vaccine aimed at the pre-erythrocytic and erythrocyte phases. Methodology. A descriptive review of works published in PubMed, Science Direct, Embase and MedLine databases was carried out. The inclusion criteria were: papers published in a time window between 2000 and 2019, candidates for vaccine against Plasmodium falciparum in pre and erythrocyte stages and validity according to the World Health Organization. In total, 90 original articles were reviewed, finding that 63 met all the established criteria, while Introduction. Plasmodium falciparum malaria is a disease that causes high rates of morbidity and mortality worldwide. Different vaccine candidates have been evaluated experimentally in humans; however, there is no vaccine available that reduces or eliminates this devastating disease. Objective. Describe in terms of design, immune response, protective efficacy and perspectives, the main current candidates for Plasmodium falciparum malaria vaccine aimed at the pre-erythrocytic and erythrocyte phases. Methodology. A descriptive review of works published in PubMed, Science Direct, Embase and MedLine databases was carried out. The inclusion criteria were: papers published in a time window between 2000 and 2019, candidates for vaccine against Plasmodium falciparum in pre and erythrocyte stages and validity according to the World Health Organization. In total, 90 original articles were reviewed, finding that 63 met all the established criteria, while 27 did not meet at least one criterion. Results. Applicants for current vaccines include designs based on attenuated parasites, recombinant proteins, viral vectors and chemical synthesis. The formulations include a minimum number of an- tigens with highly polymorphic amino acid sequences, which induce an acceptable immunogenicity profile, although a limited protective efficacy against malaria. Conclusion. The development of an effective vaccine against malaria by Plasmodium falciparum may require the inclusion of multiple functionally relevant epitopes, from the pre and erythrocyte stage, which do not contain polymorphic regions, in order to induce lasting immune responses that block the invasion of the parasite to hepatic and erythrocyte target cells.27 did not meet at least one criterion. Results. Applicants for current vaccines include designs based on attenuated parasites, recombinant proteins, viral vectors and chemical synthesis. The formulations include a minimum number of an- tigens with highly polymorphic amino acid sequences, which induce an acceptable immunogenicity profile, although a limited protective efficacy against malaria. Conclusion. The development of an effective vaccine against malaria by Plasmodium falciparum may require the inclusion of multiple functionally relevant epitopes, from the pre and erythrocyte stage, which do not contain polymorphic regions, in order to induce lasting immune responses that block the invasion of the parasite to hepatic and erythrocyte target cells.


Introdução. A malária por Plasmodium falciparum é uma doença que causa altas taxas de morbimortalidade em todo o mundo. Diferentes candidatos à vacina foram avaliados experimentalmente em humanos; no entanto, nenhuma vacina está disponível para reduzir ou eliminar esta doença devastadora. Objetivo. Descrever em termos de projeção, resposta imune, eficácia protetora e perspectivas, os principais candidatos atuais à vacina contra a malária por Plasmodium falciparum, visando às fases pré-eritrocítica e eritrocítica. Metodologia. Foi realizada uma revisão descritiva dos trabalhos publicados nas bases de dados PubMed, Science Direct, Embase e MedLine. Os critérios de inclusão foram: trabalhos publicados em uma janela temporal entre 2000 e 2019, candidatos à vacina contra Plasmodium falciparum nos estágios pré e eritrocitários e validade de acordo com a Organização Mundial da Saúde. No total, foram revisados 90 artigos originais, constatando que 63 atendiam a todos os critérios estabelecidos, enquanto 27 não atendiam pelo menos um critério. Resultados. Os candidatos atuais à vacina incluem projeções baseadas em parasitas atenuados, pro- teínas recombinantes, vetores virais e síntese química. As formulações contêm um número mínimo de antígenos com sequências de aminoácidos altamente polimórficas, que induzem um perfil de imu- nogenicidade aceitável, embora com eficácia protetora limitada contra a malária, uma vez que essas regiões polimórficas são imunodominantes, conferindo apenas imunidade específica à cepa. Conclusão. O desenvolvimento de uma vacina eficaz contra a malária por Plasmodium falciparum pode exigir a inclusão de vários epítopos funcionalmente relevantes, do estágio pré e eritrocítico, contendo regiões conservadas entre as cepas, a fim de induzir respostas imunes duradouras que permitam bloquear a invasão do parasita nas células hepáticas e eritrócitos.


Assuntos
Malária , Plasmodium falciparum , Vacinas , Proteção , Imunogenicidade da Vacina
20.
MDM Policy Pract ; 4(2): 2381468319896280, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31903424

RESUMO

Background. The World Health Organization has recommended pilot implementation of a candidate vaccine against malaria (RTS,S/AS01) in selected sub-Saharan African countries. This exploratory study aimed to estimate the costs of implementing RTS,S in Burkina Faso, Ghana, Kenya, Mozambique, and Tanzania. Methods. Key informants of the expanded program on immunization at all levels in each country were interviewed on the resources required for implementing RTS,S for routine vaccination. Unit prices were derived from the same sources or from international price lists. Incremental costs in 2015 US dollars were aggregated per fully vaccinated child (FVC). It was assumed the four vaccine doses were either all delivered at health facilities or the fourth dose was delivered in an outreach setting. Results. The costs per FVC ranged from US$25 (Burkina Faso) to US$37 (Kenya) assuming a vaccine price of US$5 per dose. Across countries, recurrent costs represented the largest share dominated by vaccines (including wastage) and supply costs. Non-recurrent costs varied substantially across countries, mainly because of differences in needs for hiring personnel, in wages, in cold-room space, and equipment. Recent vaccine introductions in the countries may have had an impact on resource availability for a new vaccine implementation. Delivering the fourth dose in outreach settings raised the costs, mostly fuel, per FVC by less than US$1 regardless of the country. Conclusions. This study provides relevant information for donors and decision makers about the cost of implementing RTS,S. Variations within and across countries are important and the unknown future price per dose and wastage rate for this candidate vaccine adds substantially to the uncertainty about the actual costs of implementation.

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