The World Bank approaches malaria not only as a major public health issue but also as a broader development problem that costs Africa US12 billion a year and helps keep families and communities in ...poverty. In 2005, the World Bank reaffirmed its commitment to malaria control by launching the Booster Program for Malaria Control in Africa, a 10-year initiative that in its first three years committed over US470 million to malaria control on the continent. Focusing on a two-pronged approach of combining disease control interventions and health systems strengthening, the program has contributed significantly to the global effort to fight the disease.As Phase II (2008-2011) of the program begins, the World Bank will intensify its efforts to enable more countries in Africa to achieve and sustain large-scale impact on malaria. Major reductions in malaria deaths and illness are possible within the next five to seven years. Attacking the disease full-force with a front-loaded effort will have tremendous impact on health and economic outcomes. African nations and the global community are gearing up to meet this goal. As one of the top three funders of malaria control, the World Bank is called to play a lead role in this effort. Phase II of the Booster Program for Malaria Control in Africa is the Banks affirmative and emphatic response to this call.
Summary Background The RTS,S/AS01 malaria vaccine targets the circumsporozoite protein, inducing antibodies associated with the prevention of Plasmodium falciparum infection. We assessed the ...association between anti-circumsporozoite antibody titres and the magnitude and duration of vaccine efficacy using data from a phase 3 trial done between 2009 and 2014. Methods Using data from 8922 African children aged 5–17 months and 6537 African infants aged 6–12 weeks at first vaccination, we analysed the determinants of immunogenicity after RTS,S/AS01 vaccination with or without a booster dose. We assessed the association between the incidence of clinical malaria and anti-circumsporozoite antibody titres using a model of anti-circumsporozoite antibody dynamics and the natural acquisition of protective immunity over time. Findings RTS,S/AS01-induced anti-circumsporozoite antibody titres were greater in children aged 5–17 months than in those aged 6–12 weeks. Pre-vaccination anti-circumsporozoite titres were associated with lower immunogenicity in children aged 6–12 weeks and higher immunogenicity in those aged 5–17 months. The immunogenicity of the booster dose was strongly associated with immunogenicity after primary vaccination. Anti-circumsporozoite titres wane according to a biphasic exponential distribution. In participants aged 5–17 months, the half-life of the short-lived component of the antibody response was 45 days (95% credible interval 42–48) and that of the long-lived component was 591 days (557–632). After primary vaccination 12% (11–13) of the response was estimated to be long-lived, rising to 30% (28–32%) after a booster dose. An anti-circumsporozoite antibody titre of 121 EU/mL (98–153) was estimated to prevent 50% of infections. Waning anti-circumsporozoite antibody titres predict the duration of efficacy against clinical malaria across different age categories and transmission intensities, and efficacy wanes more rapidly at higher transmission intensity. Interpretation Anti-circumsporozoite antibody titres are a surrogate of protection for the magnitude and duration of RTS,S/AS01 efficacy, with or without a booster dose, providing a valuable surrogate of effectiveness for new RTS,S formulations in the age groups considered. Funding UK Medical Research Council.
Background.Plasmodium knowlesi is increasingly recognized as a cause of human malaria in Southeast Asia but there are no detailed prospective clinical studies of naturally acquired infections. ...Methods.In a systematic study of the presentation and course of patients with acute P. knowlesi infection, clinical and laboratory data were collected from previously untreated, nonpregnant adults admitted to the hospital with polymerase chain reaction-confirmed acute malaria at Kapit Hospital (Sarawak, Malaysia) from July 2006 through February 2008. Results.Of 152 patients recruited, 107 (70%) had P. knowlesi infection, 24 (16%) had Plasmodium falciparum infection, and 21 (14%) had Plasmodium vivax . Patients with P. knowlesi infection presented with a nonspecific febrile illness, had a baseline median parasitemia value at hospital admission of 1387 parasites/µL (interquartile range, 6-222,570 parasites/µL), and all were thrombocytopenic at hospital admission or on the following day. Most (93.5%) of the patients with P. knowlesi infection had uncomplicated malaria that responded to chloroquine and primaquine treatment. Based on World Health Organization criteria for falciparum malaria, 7 patients with P. knowlesi infection (6.5%) had severe infections at hospital admission. The most frequent complication was respiratory distress, which was present at hospital admission in 4 patients and developed after admission in an additional 3 patients. P. knowlesi parasitemia at hospital admission was an independent determinant of respiratory distress, as were serum creatinine level, serum bilirubin, and platelet count at admission (P<.002 for each). Two patients with knowlesi malaria died, representing a case fatality rate of 1.8% (95% confidence interval, 0.2%-6.6%). Conclusions.Knowlesi malaria causes a wide spectrum of disease. Most cases are uncomplicated and respond promptly to treatment, but approximately 1 in 10 patients develop potentially fatal complications.
Brazil currently contributes 42 % of all malaria cases reported in the Latin America and the Caribbean, a region where major progress towards malaria elimination has been achieved in recent years. In ...2014, malaria burden in Brazil (143,910 microscopically confirmed cases and 41 malaria-related deaths) has reached its lowest levels in 35 years, Plasmodium falciparum is highly focal, and the geographic boundary of transmission has considerably shrunk. Transmission in Brazil remains entrenched in the Amazon Basin, which accounts for 99.5 % of the country's malaria burden. This paper reviews major lessons learned from past and current malaria control policies in Brazil. A comprehensive discussion of the scientific and logistic challenges that may impact malaria elimination efforts in the country is presented in light of the launching of the Plan for Elimination of Malaria in Brazil in November 2015. Challenges for malaria elimination addressed include the high prevalence of symptomless and submicroscopic infections, emerging anti-malarial drug resistance in P. falciparum and Plasmodium vivax and the lack of safe anti-relapse drugs, the largely neglected burden of malaria in pregnancy, the need for better vector control strategies where Anopheles mosquitoes present a highly variable biting behaviour, human movement, the need for effective surveillance and tools to identify foci of infection in areas with low transmission, and the effects of environmental changes and climatic variability in transmission. Control actions launched in Brazil and results to come are likely to influence control programs in other countries in the Americas.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The development of highly effective and durable vaccines against the human malaria parasites Plasmodium falciparum and P. vivax remains a key priority. Decades of endeavor have taught that achieving ...this goal will be challenging; however, recent innovation in malaria vaccine research and a diverse pipeline of novel vaccine candidates for clinical assessment provides optimism. With first-generation pre-erythrocytic vaccines aiming for licensure in the coming years, it is important to reflect on how next-generation approaches can improve on their success. Here we review the latest vaccine approaches that seek to prevent malaria infection, disease, and transmission and highlight some of the major underlying immunological and molecular mechanisms of protection. The synthesis of rational antigen selection, immunogen design, and immunization strategies to induce quantitatively and qualitatively improved immune effector mechanisms offers promise for achieving sustained high-level protection.
Development of highly effective vaccines against human malaria remains a public health priority. In this Review, Draper et al. describe the latest vaccine approaches to prevent malaria alongside immunological and molecular mechanisms of protection. Rational antigen selection, immunogen design, and novel immunization strategies offer promise for achieving high-level protection.
New Insights into Malaria Pathogenesis Moxon, Christopher A; Gibbins, Matthew P; McGuinness, Dagmara ...
Annual review of pathology,
01/2020, Letnik:
15, Številka:
1
Journal Article
Recenzirano
Malaria remains a major public health threat in tropical and subtropical regions across the world. Even though less than 1% of malaria infections are fatal, this leads to about 430,000 deaths per ...year, predominantly in young children in sub-Saharan Africa. Therefore, it is imperative to understand why a subset of infected individuals develop severe syndromes and some of them die and what differentiates these cases from the majority that recovers. Here, we discuss progress made during the past decade in our understanding of malaria pathogenesis, focusing on the major human parasite
Plasmodium falciparum
.
Background. Plasmodium knowlesi commonly causes severe malaria in Malaysian Borneo, with high case-fatality rates reported. We compared risk, spectrum, and outcome of severe disease from P. knowlesi, ...Plasmodium falciparum, and Plasmodium vivax and outcomes following introduction of protocols for early referral and intravenous artesunate for all severe malaria. Methods. From September 2010 to October 2011 we prospectively assessed nonpregnant patients aged ≥12 years admitted to Queen Elizabeth Hospital (QEH), Sabah, with polymerase chain reaction—confirmed Plasmodium monoinfection. Standardized referral and prereferral intravenous artesunate were instituted at district hospitals. Results. Severe malaria occurred in 38 of 130 (29%) patients with P. knowlesi, 13 of 122 (11%) with P. falciparum, and 7 of 43 (16%) with P. vivax. The commonest severity criteria in knowlesi malaria included parasitemia >100 000/μL (n = 18), jaundice (n = 20), respiratory distress (n = 14), hypotension (n = 13), and acute kidney injury (n = 9). On multivariate analysis, P. knowlesi was associated with a 2.96-fold (95% confidence interval, 1.19–7.38-fold) greater risk of severity than P. falciparum (P = .020); only parasitemia and schizontemia >10% independently predicted knowlesi severity. Risk of severe knowlesi malaria increased 11-fold with parasitemia >20 000/μL, and 28-fold with parasitemia >100 000/μL. Nearly all (92%) knowlesi malaria patients received oral artemisinin therapy; 36 of 38 (95%) and 39 of 92 (42%) with severe and nonsevere disease, respectively, also received ≥1 dose of intravenous artesunate. No deaths occurred from any species. Conclusions. Plasmodium knowlesi is the commonest cause of severe malaria at QEH, with parasitemia the major risk factor for severity. Early referral and treatment with artesunate was highly effective for severe malaria from all species and associated with zero mortality.
Malaria-eliminating countries achieved remarkable success in reducing their malaria burdens between 2000 and 2010. As a result, the epidemiology of malaria in these settings has become more complex. ...Malaria is increasingly imported, caused by Plasmodium vivax in settings outside sub-Saharan Africa, and clustered in small geographical areas or clustered demographically into subpopulations, which are often predominantly adult men, with shared social, behavioural, and geographical risk characteristics. The shift in the populations most at risk of malaria raises important questions for malaria-eliminating countries, since traditional control interventions are likely to be less effective. Approaches to elimination need to be aligned with these changes through the development and adoption of novel strategies and methods. Knowledge of the changing epidemiological trends of malaria in the eliminating countries will ensure improved targeting of interventions to continue to shrink the malaria map.
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