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Transactions of the Royal Society of... Nov 2016The advancement in any antimalarial medicinal product including vaccines, drugs and diagnostics will have a vital influence on malaria elimination in China and on the... (Review)
Review
BACKGROUND
The advancement in any antimalarial medicinal product including vaccines, drugs and diagnostics will have a vital influence on malaria elimination in China and on the global malaria control framework. This study aimed to identify research progress and challenges in China, hoping to better facilitate domestic elimination and for China to be more effectively involved in global malaria research and development.
METHODS
A systematic search was conducted for research articles published from 2005 to 2014 in PubMed, CNKI and Wanfang using terms including malaria, diagnosis, drugs and vaccines. In total, 4259 articles from PubMed and 561 references from Chinese databases were included and categorized by topic.
RESULTS
The literature from PubMed was clustered and seven antimalarial medicinal product research hotspots were identified; including drug resistance, diagnostic tests and vaccine antigen screening. The reports related to drugs accounted for the largest proportion in PubMed (57%) and Chinese studies (51%) while references associated with diagnostics accounted for the lowest proportion, 10% in PubMed and 14% in Chinese studies.
CONCLUSIONS
Despite continuous effort in malaria research and development, there exist gaps in progressive discoveries on malaria diagnostics and drugs in China. Successive focus on antimalarial medicinal products is essential to facilitate malaria control in China and worldwide.
Topics: Animals; Antimalarials; Bibliometrics; China; Drug Resistance; Humans; Malaria
PubMed: 28158859
DOI: 10.1093/trstmh/trw083 -
Human Vaccines & Immunotherapeutics Jan 2017Although vaccines would be the ideal tool for control, prevention, elimination, and eradication of many infectious diseases, developing of parasites vaccines such as...
Although vaccines would be the ideal tool for control, prevention, elimination, and eradication of many infectious diseases, developing of parasites vaccines such as malaria vaccine is very complex. The most advanced malaria vaccine candidate is RTS,S, a pre-erythrocytic vaccine for which pivotal phase III trial design is underway. Few recent malaria vaccine review articles have attempted to outline of all clinical trials that have occurred globally and no meta-analysis was performed on efficacy of Phase 3 Trial of RTS, S/AS01 Malaria vaccine up to now in infants. Therefore, a systematic review and meta-analysis was carried out to review new and existing data on efficacy of Phase 3 Trial of RTS, S/AS01 Malaria Vaccine in infants. The electronic databases searched were Pubmed (1965-present) and Web of Science (1970-present) (Search date: May, 2016). After full-text review of the papers evaluating clinical/severe malaria in several well-designed phase III field efficacy trials, 5 were determined to meet the eligibility criteria for inclusion in the systematic review. Four out of the 5 publications dealing with efficacy of Phase 3 Trial of RTS, S/AS01 malaria vaccine were included in the qualitative analysis. Pooled estimate of vaccine efficacy in clinical and severe malaria in children aged 5-17 mo was 29% (95% CL: 19%-46%) and 39% (95% CI 20%-74%), while this estimate vaccine in clinical and severe malaria in children aged 6-12 mo was 19% (95% CI 14%-24%) and 21 (95% CI 19%-37%), respectively. On the other hand, higher VE was seen in both per- protocol and intention-to-treat population in children aged 5-17 than the children aged 6-12 mo. The results of this meta-analysis suggest that this candidate malaria vaccine has relatively little efficacy, and the vaccine apparently will not meet the goal of malaria eradication by itself.
PubMed: 28059665
DOI: 10.1080/21645515.2016.1271686 -
PLoS Neglected Tropical Diseases Jan 2017This study systematically reviews the literature on the occurrence, incidence and case fatality rate (CFR) of invasive nontyphoidal Salmonella (iNTS) disease in Africa... (Review)
Review
This study systematically reviews the literature on the occurrence, incidence and case fatality rate (CFR) of invasive nontyphoidal Salmonella (iNTS) disease in Africa from 1966 to 2014. Data on the burden of iNTS disease in Africa are sparse and generally have not been aggregated, making it difficult to describe the epidemiology that is needed to inform the development and implementation of effective prevention and control policies. This study involved a comprehensive search of PubMed and Embase databases. It documents the geographical spread of iNTS disease over time in Africa, and describes its reported incidence, risk factors and CFR. We found that Nontyphoidal Salmonella (NTS) have been reported as a cause of bacteraemia in 33 out of 54 African countries, spanning the five geographical regions of Africa, and especially in sub-Saharan Africa since 1966. Our review indicates that NTS have been responsible for up to 39% of community acquired blood stream infections in sub-Saharan Africa with an average CFR of 19%. Salmonella Typhimurium and Enteritidis are the major serovars implicated and together have been responsible for 91%% of the cases of iNTS disease, (where serotype was determined), reported in Africa. The study confirms that iNTS disease is more prevalent amongst Human Immunodeficiency Virus (HIV)-infected individuals, infants, and young children with malaria, anaemia and malnutrition. In conclusion, iNTS disease is a substantial cause of community-acquired bacteraemia in Africa. Given the high morbidity and mortality of iNTS disease in Africa, it is important to develop effective prevention and control strategies including vaccination.
Topics: Africa South of the Sahara; Bacteremia; Humans; Incidence; Risk Factors; Salmonella Infections; Salmonella enterica
PubMed: 28056035
DOI: 10.1371/journal.pntd.0005118 -
Vaccine Nov 2016Shifting the malaria priorities from a paradigm of control and elimination to a goal of global eradication calls for renewed attention to the interruption of malaria... (Review)
Review
Shifting the malaria priorities from a paradigm of control and elimination to a goal of global eradication calls for renewed attention to the interruption of malaria transmission. Sustained progress toward eradication will require both improved understanding of infectious reservoirs and efficient development of novel transmission-blocking interventions, such as rapidly acting and highly efficacious therapeutics and vaccines. Here, we review the direct skin feeding assay (DSF), which has been proposed as a valuable tool for measuring the in natura transmission of malaria parasites from human hosts to mosquito vectors across heterogeneous populations. To capture the methodological breadth of this assay's use, we first systematically review and qualitatively synthesize previously published investigations using DSFs to study malaria transmission in humans. Then, using a recent Phase 1 trial in Mali of the Pfs25H-EPA/Alhydrogel® vaccine candidate (NCT01867463) designed to interrupt Plasmodium falciparum transmission as a case study, we describe the potential opportunities and current limitations of utilizing the endpoints measured by DSF in making early clinical decisions for individually randomized transmission-interrupting intervention candidates. Using simulations based on the data collected in the clinical trial, we demonstrate that the capacity of the DSF to serve as an evaluative tool is limited by the statistical power constraints of the "effective sample size" (i.e. the number of subjects that are capable of transmitting at the time of feeding). Altogether, our findings suggest DSFs have great potential utility for assessing the public health impacts of emerging antimalarial tools, but additional research is needed to address issues of scalability and to establish correlation with community-wide clinical endpoints as well as complementary in vitro measures, such as standard membrane feeding assays.
Topics: Adult; Animals; Anopheles; Clinical Trials as Topic; Feeding Behavior; Female; Humans; Malaria Vaccines; Malaria, Falciparum; Male; Middle Aged; Mosquito Vectors; Protozoan Proteins; Skin; Young Adult
PubMed: 27789147
DOI: 10.1016/j.vaccine.2016.10.027 -
The Cochrane Database of Systematic... Jul 2016Immunisation is a powerful public health strategy for improving child survival, not only by directly combating key diseases that kill children but also by providing a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immunisation is a powerful public health strategy for improving child survival, not only by directly combating key diseases that kill children but also by providing a platform for other health services. However, each year millions of children worldwide, mostly from low- and middle-income countries (LMICs), do not receive the full series of vaccines on their national routine immunisation schedule. This is an update of the Cochrane review published in 2011 and focuses on interventions for improving childhood immunisation coverage in LMICs.
OBJECTIVES
To evaluate the effectiveness of intervention strategies to boost and sustain high childhood immunisation coverage in LMICs.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2016, Issue 4, part of The Cochrane Library. www.cochranelibrary.com, including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register (searched 12 May 2016); MEDLINE In-Process and Other Non-Indexed Citations, MEDLINE Daily and MEDLINE 1946 to Present, OvidSP (searched 12 May 2016); CINAHL 1981 to present, EbscoHost (searched 12 May 2016); Embase 1980 to 2014 Week 34, OvidSP (searched 2 September 2014); LILACS, VHL (searched 2 September 2014); Sociological Abstracts 1952 - current, ProQuest (searched 2 September 2014). We did a citation search for all included studies in Science Citation Index and Social Sciences Citation Index, 1975 to present; Emerging Sources Citation Index 2015 to present, ISI Web of Science (searched 2 July 2016). We also searched the two Trials Registries: ICTRP and ClinicalTrials.gov (searched 5 July 2016) SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCT), non-RCTs, controlled before-after studies, and interrupted time series conducted in LMICs involving children aged from birth to four years, caregivers, and healthcare providers.
DATA COLLECTION AND ANALYSIS
We independently screened the search output, reviewed full texts of potentially eligible articles, assessed risk of bias, and extracted data in duplicate; resolving discrepancies by consensus. We then conducted random-effects meta-analyses and used GRADE to assess the certainty of evidence.
MAIN RESULTS
Fourteen studies (10 cluster RCTs and four individual RCTs) met our inclusion criteria. These were conducted in Georgia (one study), Ghana (one study), Honduras (one study), India (two studies), Mali (one study), Mexico (one study), Nicaragua (one study), Nepal (one study), Pakistan (four studies), and Zimbabwe (one study). One study had an unclear risk of bias, and 13 had high risk of bias. The interventions evaluated in the studies included community-based health education (three studies), facility-based health education (three studies), household incentives (three studies), regular immunisation outreach sessions (one study), home visits (one study), supportive supervision (one study), information campaigns (one study), and integration of immunisation services with intermittent preventive treatment of malaria (one study).We found moderate-certainty evidence that health education at village meetings or at home probably improves coverage with three doses of diphtheria-tetanus-pertussis vaccines (DTP3: risk ratio (RR) 1.68, 95% confidence interval (CI) 1.09 to 2.59). We also found low-certainty evidence that facility-based health education plus redesigned vaccination reminder cards may improve DTP3 coverage (RR 1.50, 95% CI 1.21 to 1.87). Household monetary incentives may have little or no effect on full immunisation coverage (RR 1.05, 95% CI 0.90 to 1.23, low-certainty evidence). Regular immunisation outreach may improve full immunisation coverage (RR 3.09, 95% CI 1.69 to 5.67, low-certainty evidence) which may substantially improve if combined with household incentives (RR 6.66, 95% CI 3.93 to 11.28, low-certainty evidence). Home visits to identify non-vaccinated children and refer them to health clinics may improve uptake of three doses of oral polio vaccine (RR 1.22, 95% CI 1.07 to 1.39, low-certainty evidence). There was low-certainty evidence that integration of immunisation with other services may improve DTP3 coverage (RR 1.92, 95% CI 1.42 to 2.59).
AUTHORS' CONCLUSIONS
Providing parents and other community members with information on immunisation, health education at facilities in combination with redesigned immunisation reminder cards, regular immunisation outreach with and without household incentives, home visits, and integration of immunisation with other services may improve childhood immunisation coverage in LMIC. Most of the evidence was of low certainty, which implies a high likelihood that the true effect of the interventions will be substantially different. There is thus a need for further well-conducted RCTs to assess the effects of interventions for improving childhood immunisation coverage in LMICs.
Topics: Developing Countries; Health Education; Humans; Immunization; Infant; Infant, Newborn; Motivation; Randomized Controlled Trials as Topic; Reward
PubMed: 27394698
DOI: 10.1002/14651858.CD008145.pub3 -
Vaccine Feb 2016New adjuvants such as the AS- or the MF59-adjuvants improve vaccine efficacy and facilitate dose-sparing. Their use in influenza and malaria vaccines has resulted in a... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
New adjuvants such as the AS- or the MF59-adjuvants improve vaccine efficacy and facilitate dose-sparing. Their use in influenza and malaria vaccines has resulted in a large body of evidence on their clinical safety in children.
METHODS
We carried out a systematic search for safety data from published clinical trials on newly adjuvanted vaccines in children ≤10 years of age. Serious adverse events (SAEs), solicited AEs, unsolicited AEs and AEs of special interest were evaluated for four new adjuvants: the immuno-stimulants containing adjuvant systems AS01 and AS02, and the squalene containing oil-in-water emulsions AS03 and MF59. Relative risks (RR) were calculated, comparing children receiving newly adjuvanted vaccines to children receiving other vaccines with a variety of antigens, both adjuvanted and unadjuvanted.
RESULTS
Twenty-nine trials were included in the meta-analysis, encompassing 25,056 children who received at least one dose of the newly adjuvanted vaccines. SAEs did not occur more frequently in adjuvanted groups (RR 0.85, 95%CI 0.75-0.96). Our meta-analyses showed higher reactogenicity following administration of newly adjuvanted vaccines, however, no consistent pattern of solicited AEs was observed across adjuvant systems. Pain was the most prevalent AE, but often mild and of short duration. No increased risks were found for unsolicited AEs, febrile convulsions, potential immune mediated diseases and new onset of chronic diseases.
CONCLUSIONS
Our meta-analysis did not show any safety concerns in clinical trials of the newly adjuvanted vaccines in children ≤10 years of age. An unexplained increase of meningitis in one Phase III AS01-adjuvanted malaria trial and the link between narcolepsy and the AS03-adjuvanted pandemic vaccine illustrate that continued safety monitoring is warranted.
Topics: Adjuvants, Immunologic; Adolescent; Child; Child, Preschool; Clinical Trials as Topic; Drug Combinations; Humans; Infant; Likelihood Functions; Lipid A; Polysorbates; Risk; Saponins; Squalene; Vaccines; alpha-Tocopherol
PubMed: 26740250
DOI: 10.1016/j.vaccine.2015.12.024 -
Future Microbiology 2015The first clinical Phase III trial evaluating a malaria vaccine was completed in December 2013 at 11 sites from seven sub-Saharan African countries. This systematic... (Review)
Review
The first clinical Phase III trial evaluating a malaria vaccine was completed in December 2013 at 11 sites from seven sub-Saharan African countries. This systematic review assesses data of Phase I-III trials including malaria-naive adults and adults, children and infants from malaria endemic settings in sub-Saharan Africa. The main endpoint of this systematic review was an analysis of the consistency of efficacy and immunogenicity data from respective Phase I-III trials. In addition, safety data from a pooled analysis of RTS/AS Phase II trials and RTS,S/AS01 Phase III trial were reviewed. The RTS,S/AS01 malaria vaccine may become available on the market in the coming year. If so, further strategies should address challenges on how to optimize vaccine efficacy and implementation of RTS,S/AS01 vaccine within the framework of established malaria control measures.
Topics: Adult; Africa South of the Sahara; Child; Child, Preschool; Humans; Infant; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Vaccination
PubMed: 26437872
DOI: 10.2217/fmb.15.90 -
BMC Medicine Sep 2014Identifying Plasmodium vivax antigen-specific antibodies associated with P. vivax infection and protective immunity is key to the development of serosurveillance tools... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Identifying Plasmodium vivax antigen-specific antibodies associated with P. vivax infection and protective immunity is key to the development of serosurveillance tools and vaccines for malaria. Antibody targets of P. vivax can be identified by seroepidemiological studies of individuals living in P. vivax-endemic areas, and is an important strategy given the limited ability to culture P. vivax in vitro. There have been numerous studies investigating the association between P. vivax antibody responses and P. vivax infection, but there has been no standardization of results to enable comparisons across populations.
METHODS
We performed a systematic review with meta-analysis of population-based, cross-sectional, case-control, and cohort studies of individuals living in P. vivax-endemic areas. We searched 6 databases and identified 18 studies that met predefined inclusion and quality criteria, and examined the association between antibody responses to P. vivax antigens and P. vivax malaria.
RESULTS
The majority of studies were published in South America (all from Brazil) and the rest from geographically diverse areas in the Asia-Pacific region. Considerable heterogeneity in estimates was observed, but IgG responses to PvCSP, PvMSP-119, PvMSP-9RIRII, and PvAMA1 were associated with increased odds of P. vivax infection in geographically diverse populations. Potential sources of heterogeneity included study design, different transmission intensities and transmigrant populations. Protective associations were observed for antibodies to PvMSP-119, PvMSP-1NT, PvMSP-3α and PvMSP-9NT antigens, but only in single geographical locations.
CONCLUSIONS
This systematic review revealed several antigen-specific antibodies that were associated with active infection and protective immunity, which may be useful biomarkers. However, more studies are needed on additional antigens, particularly cohort studies to increase the body of evidence for protective immunity. More studies representing diverse geographical regions encompassing varying P. vivax endemicities are needed to validate the generalizability of the findings and to provide a solid evidence base for the use of P. vivax antigens in vaccines and serosurveillance tools.
Topics: Antibodies, Protozoan; Antigens, Protozoan; Biomarkers; Female; Humans; Malaria, Vivax; Male; Plasmodium vivax; Protozoan Proteins; Seroepidemiologic Studies
PubMed: 25199532
DOI: 10.1186/s12916-014-0150-1