-
Molecular Biotechnology Jul 2023Emerging infectious diseases have vigorously devastated the global economy and health sector; cost-effective plant-based vaccines (PBV) can be the potential solution to... (Review)
Review
Emerging infectious diseases have vigorously devastated the global economy and health sector; cost-effective plant-based vaccines (PBV) can be the potential solution to withstand the current health economic crisis. The prominent role of tobacco as an efficient expression system for PBV has been well-established for decades, through this review we highlight the importance of tobacco-based vaccines (TBV) against evolving infectious diseases in humans. Studies focusing on the use of TBV for human infectious diseases were searched in PubMed, Google Scholar, and science direct from 1995 to 2021 using the keywords Tobacco-based vaccines OR transgenic tobacco OR Nicotiana benthamiana vaccines AND Infectious diseases or communicable diseases. We carried out a critical review of the articles and studies that fulfilled the eligibility criteria and were included in this review. Of 976 studies identified, only 63 studies fulfilling the eligibility criteria were included, which focused on either the in vitro, in vivo, or clinical studies on TBV for human infectious diseases. Around 43 in vitro studies of 23 different infectious pathogens expressed in tobacco-based systems were identified and 23 in vivo analysis studies were recognized to check the immunogenicity of vaccine candidates while only 10 of these were subjected to clinical trials. Viral infectious pathogens were studied more than bacterial pathogens. From our review, it was evident that TBV can be an effective health strategy to combat the emerging viral infectious diseases which are very difficult to manage with the current health facilities. The timely administration of cost-effective TBV can prevent the outburst of viral infections, thereby can protect the global healthcare system to a greater extent.
Topics: Humans; Nicotiana; Vaccines; Vaccines, Virus-Like Particle; Malaria Vaccines; Virus Diseases
PubMed: 36528727
DOI: 10.1007/s12033-022-00627-5 -
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 -
PloS One 2022Malaria is the second leading cause of death in children after diarrheal disease, with low- and middle-income countries (LMICs) accounting for over 9 in 10 incidence and... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis of the prevalence of caregiver acceptance of malaria vaccine for under-five children in low-income and middle-income countries (LMICs).
INTRODUCTION
Malaria is the second leading cause of death in children after diarrheal disease, with low- and middle-income countries (LMICs) accounting for over 9 in 10 incidence and deaths. Widespread acceptance and uptake of the RTS,S vaccine, recently approved by the world health organization (WHO), is projected to significantly reduce malaria incidence and deaths. Therefore, we conducted this systematic review and meta-analysis with the aim to determine the malaria vaccine acceptance rate and the factors associated with acceptance.
METHODS
We searched six databases including Google Scholar, PubMed, Cochrane, African Index Medicus, The Regional Office for Africa Library, and WHO Institutional Repository for Information Sharing (IRIS) to identify studies evaluating the malaria vaccine acceptance rate. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Studies were included if they were original articles published in the English language in peer-reviewed journals and assessed the prevalence of willingness to accept a free malaria vaccine, and not qualitative. The risk of publication bias was checked using both Beggar's funnel plot and Egger's test, while the I2 statistic was used to assess the heterogeneity of the included studies. Study quality was determined using the Newcastle-Ottawa scale. A meta-analysis was performed using a random effects model to evaluate the pooled prevalence of malaria vaccine acceptance. The protocol for this article was registered prospectively on the International Prospective Register for Systematic Reviews (PROSPERO), with ID number CRD42022334282).
RESULTS
Our analysis included 11 studies with a total sample size of 14, 666 participants. The aggregate malaria vaccine acceptance rate was 95.3% (95% CI:93.0%-97.2%). Among the general population, the acceptance rate was 96.3% (95% CI:92.0%-99.0%) and among mothers, it was 94.4% (95% CI:90.8%-97.2%). By country, Nigeria had the highest acceptance rate (97.6%, 95% CI:96.0%-98.8%), followed by Ghana (94.6%, 95% CI:93.8%-95.3%) and Tanzania (92.5%, 95% CI:84.4%-97.8%). Sociodemographic determinants of vaccine acceptance included place of residence, tribe, age, sex, occupation, and religion. Reasons for low acceptance included safety concerns, efficacy profile, vaccine's requirement for multiple injections, and poor level of awareness.
CONCLUSION
Future efforts should be focused on identifying factors that may improve the actual uptake of the RTS,S vaccine in malaria-endemic communities.
Topics: Child; Humans; Malaria Vaccines; Prevalence; Caregivers; Developing Countries; Ghana
PubMed: 36455209
DOI: 10.1371/journal.pone.0278224 -
BMC Infectious Diseases Dec 2021The development of novel malaria vaccines and antimalarial drugs is limited partly by emerging challenges to conduct field trials in malaria endemic areas, including...
BACKGROUND
The development of novel malaria vaccines and antimalarial drugs is limited partly by emerging challenges to conduct field trials in malaria endemic areas, including unknown effects of existing immunity and a reported fall in malaria incidence. As a result, Controlled Human Malaria Infection (CHMI) has become an important approach for accelerated development of malarial vaccines and drugs. We conducted a systematic review of the literature to establish aggregate evidence on the reproducibility of a malaria sporozoite challenge model.
METHODS
A systematic review of research articles published between 1990 and 2018 on efficacy testing of malaria vaccines and drugs using sporozoite challenge and sporozoite infectivity studies was conducted using Pubmed, Scopus, Embase and Cochrane Library, ClinicalTrials.gov and Trialtrove. The inclusion criteria were randomized and non-randomized, controlled or open-label trials using P. falciparum or P. vivax sporozoite challenges. The data were extracted from articles using standardized data extraction forms and descriptive analysis was performed for evidence synthesis. The endpoints considered were infectivity, prepatent period, parasitemia and safety of sporozoite challenge.
RESULTS
Seventy CHMI trials conducted with a total of 2329 adult healthy volunteers were used for analysis. CHMI was induced by bites of mosquitoes infected with P. falciparum or P. vivax in 52 trials and by direct venous inoculation of P. falciparum sporozoites (PfSPZ challenge) in 18 trials. Inoculation with P. falciparum-infected mosquitoes produced 100% infectivity in 40 studies and the mean/median prepatent period assessed by thick blood smear (TBS) microscopy was ≤ 12 days in 24 studies. On the other hand, out of 12 infectivity studies conducted using PfSPZ challenge, 100% infection rate was reproduced in 9 studies with a mean or median prepatent period of 11 to 15.3 days as assessed by TBS and 6.8 to 12.6 days by PCR. The safety profile of P. falciparum and P.vivax CHMI was characterized by consistent features of malaria infection.
CONCLUSION
There is ample evidence on consistency of P. falciparum CHMI models in terms of infectivity and safety endpoints, which supports applicability of CHMI in vaccine and drug development. PfSPZ challenge appears more feasible for African trials based on current evidence of safety and efficacy.
Topics: Adult; Animals; Humans; Malaria Vaccines; Malaria, Falciparum; Pharmaceutical Preparations; Reproducibility of Results; Sporozoites
PubMed: 34930178
DOI: 10.1186/s12879-021-06953-4 -
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 -
Revista Da Sociedade Brasileira de... 2020Trypanosoma rangeli is a protozoan that infects several domestic and wild mammals and shows significant distribution in Latin American countries. T. rangeli infection is... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Trypanosoma rangeli is a protozoan that infects several domestic and wild mammals and shows significant distribution in Latin American countries. T. rangeli infection is similar to Chagas disease, both in diagnostic and prophylactic terms. Thus, the objective of this work was to review the diagnostic aspects and use of T. rangeli as an immunogen for Trypanosoma cruzi infection.
METHODS
For this elaboration, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adopted with descriptors derived from the Medical Subject Headings (MeSH) platform in the PubMed/MEDLINE and SciELO databases. The inclusion criteria were defined as original articles on "Trypanosoma rangeli" and diagnostic aspects of T. rangeli infection in humans and/or research on the possible vaccines developed using T. rangeli strains for T. cruzi infection.
RESULTS
After applying the inclusion and exclusion criteria, 18 articles were procured, of which 4 addressed research on the possible vaccines developed using T. rangeli for T. cruzi infection in vertebrates and the remaining 14 predominantly dealt with the diagnostic aspects of T. rangeli infection in humans.
CONCLUSIONS
In this study, we formulated a compilation of the essential literature on this subject, emphasizing the need for more accurate and accessible techniques for the differential diagnosis of infections caused by both protozoa, and underscored several prospects in the search for a vaccine for Chagas disease.
Topics: Animals; Humans; Trypanosoma; Trypanosoma cruzi; Trypanosoma rangeli
PubMed: 32935777
DOI: 10.1590/0037-8682-0608-2019 -
The Cochrane Database of Systematic... Aug 2020On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites. Pentavalent antimonials remain the first-choice treatment. There are alternative interventions, but reviewing their effectiveness and safety is important as availability is limited. This is an update of a Cochrane Review first published in 2009.
OBJECTIVES
To assess the effects of interventions for all immuno-competent people who have American cutaneous and mucocutaneous leishmaniasis (ACML).
SEARCH METHODS
We updated our database searches of the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and CINAHL to August 2019. We searched five trials registers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing either single or combination treatments for ACML in immuno-competent people, diagnosed by clinical presentation and Leishmania infection confirmed by smear, culture, histology, or polymerase chain reaction on a biopsy specimen. The comparators were either no treatment, placebo only, or another active compound.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our key outcomes were the percentage of participants 'cured' at least three months after the end of treatment, adverse effects, and recurrence. We used GRADE to assess evidence certainty for each outcome.
MAIN RESULTS
We included 75 studies (37 were new), totalling 6533 randomised participants with ATL. The studies were mainly conducted in Central and South America at regional hospitals, local healthcare clinics, and research centres. More male participants were included (mean age: roughly 28.9 years (SD: 7.0)). The most common confirmed species were L. braziliensis, L. panamensis, and L. mexicana. The most assessed interventions and comparators were non-antimonial systemics (particularly oral miltefosine) and antimonials (particularly meglumine antimoniate (MA), which was also a common intervention), respectively. Three studies included moderate-to-severe cases of mucosal leishmaniasis but none included cases with diffuse cutaneous or disseminated CL, considered the severe cutaneous form. Lesions were mainly ulcerative and located in the extremities and limbs. The follow-up (FU) period ranged from 28 days to 7 years. All studies had high or unclear risk of bias in at least one domain (especially performance bias). None of the studies reported the degree of functional or aesthetic impairment, scarring, or quality of life. Compared to placebo, at one-year FU, intramuscular (IM) MA given for 20 days to treat L. braziliensis and L. panamensis infections in ACML may increase the likelihood of complete cure (risk ratio (RR) 4.23, 95% confidence interval (CI) 0.84 to 21.38; 2 RCTs, 157 participants; moderate-certainty evidence), but may also make little to no difference, since the 95% CI includes the possibility of both increased and reduced healing (cure rates), and IMMA probably increases severe adverse effects such as myalgias and arthralgias (RR 1.51, 95% CI 1.17 to 1.96; 1 RCT, 134 participants; moderate-certainty evidence). IMMA may make little to no difference to the recurrence risk, but the 95% CI includes the possibility of both increased and reduced risk (RR 1.79, 95% CI 0.17 to 19.26; 1 RCT, 127 participants; low-certainty evidence). Compared to placebo, at six-month FU, oral miltefosine given for 28 days to treat L. mexicana, L. panamensis and L. braziliensis infections in American cutaneous leishmaniasis (ACL) probably improves the likelihood of complete cure (RR 2.25, 95% CI 1.42 to 3.38), and probably increases nausea rates (RR 3.96, 95% CI 1.49 to 10.48) and vomiting (RR 6.92, 95% CI 2.68 to 17.86) (moderate-certainty evidence). Oral miltefosine may make little to no difference to the recurrence risk (RR 2.97, 95% CI 0.37 to 23.89; low-certainty evidence), but the 95% CI includes the possibility of both increased and reduced risk (all based on 1 RCT, 133 participants). Compared to IMMA, at 6 to 12 months FU, oral miltefosine given for 28 days to treat L. braziliensis, L. panamensis, L. guyanensis and L. amazonensis infections in ACML may make little to no difference to the likelihood of complete cure (RR 1.05, 95% CI 0.90 to 1.23; 7 RCTs, 676 participants; low-certainty evidence). Based on moderate-certainty evidence (3 RCTs, 464 participants), miltefosine probably increases nausea rates (RR 2.45, 95% CI 1.72 to 3.49) and vomiting (RR 4.76, 95% CI 1.82 to 12.46) compared to IMMA. Recurrence risk was not reported. For the rest of the key comparisons, recurrence risk was not reported, and risk of adverse events could not be estimated. Compared to IMMA, at 6 to 12 months FU, oral azithromycin given for 20 to 28 days to treat L. braziliensis infections in ACML probably reduces the likelihood of complete cure (RR 0.51, 95% CI 0.34 to 0.76; 2 RCTs, 93 participants; moderate-certainty evidence). Compared to intravenous MA (IVMA) and placebo, at 12 month FU, adding topical imiquimod to IVMA, given for 20 days to treat L. braziliensis, L. guyanensis and L. peruviana infections in ACL probably makes little to no difference to the likelihood of complete cure (RR 1.30, 95% CI 0.95 to 1.80; 1 RCT, 80 participants; moderate-certainty evidence). Compared to MA, at 6 months FU, one session of local thermotherapy to treat L. panamensis and L. braziliensis infections in ACL reduces the likelihood of complete cure (RR 0.80, 95% CI 0.68 to 0.95; 1 RCT, 292 participants; high-certainty evidence). Compared to IMMA and placebo, at 26 weeks FU, adding oral pentoxifylline to IMMA to treat CL (species not stated) probably makes little to no difference to the likelihood of complete cure (RR 0.86, 95% CI 0.63 to 1.18; 1 RCT, 70 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Evidence certainty was mostly moderate or low, due to methodological shortcomings, which precluded conclusive results. Overall, both IMMA and oral miltefosine probably result in an increase in cure rates, and nausea and vomiting are probably more common with miltefosine than with IMMA. Future trials should investigate interventions for mucosal leishmaniasis and evaluate recurrence rates of cutaneous leishmaniasis and its progression to mucosal disease.
Topics: Administration, Oral; Adult; Antiprotozoal Agents; Azithromycin; BCG Vaccine; Female; Humans; Hyperthermia, Induced; Immunocompetence; Injections, Intramuscular; Injections, Intravenous; Interferon-gamma; Leishmaniasis Vaccines; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Male; Meglumine Antimoniate; Pentoxifylline; Phosphorylcholine; Randomized Controlled Trials as Topic
PubMed: 32853410
DOI: 10.1002/14651858.CD004834.pub3 -
Frontiers in Immunology 2019Malaria elimination remains a priority research agenda with the need for interventions that reduce and/or block malaria transmission from humans to mosquitoes.... (Meta-Analysis)
Meta-Analysis
Malaria elimination remains a priority research agenda with the need for interventions that reduce and/or block malaria transmission from humans to mosquitoes. Transmission-blocking vaccines (TBVs) are in development, most of which target the transmission stage (i.e., gametocyte) antigens Pfs230 and Pfs48/45. For these interventions to be implemented, there is a need to understand the naturally acquired immunity to gametocytes. Several studies have measured the prevalence of immune responses to Pfs230 and Pfs48/45 in populations in malaria-endemic areas. We conducted a systematic review of studies carried out in African populations that measured the prevalence of immune responses to the gametocyte antigens Pfs230 and Pfs48/45. We assessed seroprevalence of antibody responses to the two antigens and investigated the effects of covariates such as age, transmission intensity/endemicity, season, and parasite prevalence on the prevalence of these antibody responses by meta-regression. We identified 12 studies covering 23 sites for inclusion in the analysis. We found that the range of reported seroprevalence to Pfs230 and Pfs48/45 varied widely across studies, from 0 to 64% for Pfs48/45 and from 6 to 72% for Pfs230. We also found a modest association between increased age and increased seroprevalence to Pfs230: adults were associated with higher seroprevalence estimates in comparison to children (β coefficient 0.21, 95% CI: 0.05-0.38, = 0.042). Methodological factors were the most significant contributors to heterogeneity between studies which prevented calculation of pooled prevalence estimates. Naturally acquired sexual stage immunity, as detected by antibodies to Pfs230 and Pfs48/45, was present in most studies analyzed. Significant between-study heterogeneity was seen, and methodological factors were a major contributor to this, and prevented further analysis of epidemiological and biological factors. This demonstrates a need for standardized protocols for conducting and reporting seroepidemiological analyses.
Topics: Africa; Antibodies, Protozoan; Antigens, Protozoan; Female; Humans; Life Cycle Stages; Malaria Vaccines; Malaria, Falciparum; Male; Plasmodium falciparum
PubMed: 31695697
DOI: 10.3389/fimmu.2019.02480 -
PloS One 2018The Malaria Vaccine Implementation Program, coordinated by the World Health Organization, intended to initiate the roll-out of the RTS, S/AS01 malaria vaccine in 3...
BACKGROUND
The Malaria Vaccine Implementation Program, coordinated by the World Health Organization, intended to initiate the roll-out of the RTS, S/AS01 malaria vaccine in 3 sub-Saharan African countries in 2018. With sub-optimal implementation, the effectiveness of this vaccine in routine clinical use could be significantly lower than its measured efficacy in randomized trials. This study had as objectives to systematically review and summarize published studies addressing the challenges faced during the implementation phase of malaria vaccination programs and randomized trials conducted in sub-Saharan Africa. The review also sought to report proposed solutions to the challenges identified.
METHOD
This was a systematic review of studies published between 1947 and 2017. Medline, Embase and the Cochrane library databases were searched. Of the 365 studies retrieved, 8 eligible studies reported on challenges of implementing a malaria vaccine in sub-Saharan Africa and possible solutions to these challenges. Data were abstracted from the eligible studies and a qualitative synthesis was done.
RESULTS
The 8 studies included in the review had a total of 6189 participants and used a variety of methodologies (3 qualitative, 1 quantitative, 3 mixed method studies and 1 clinical trial review). There was an overall positive acceptance towards the new malaria vaccine (n = 6/8 studies), with a mean acceptance rate of 86.1% (95% CI: 62.0-110.2, n = 2). The main challenges to vaccine receptivity were: inadequate community engagement due to lack of information about the vaccine (n = 6), fear of the vaccine's side effects (n = 5), inefficient delivery of vaccination services to children (n = 4), and sub-optimal quality of the health services (n = 3). Main themes identified from the proposed solutions consisted of the following: using dynamic communication models and trusted sources for delivering vaccine-related health information to the communities (n = 6), community engagement at both national and district level (n = 6), implementing the new vaccine services alongside the existing health services already delivered (n = 6).
CONCLUSION/RECOMMENDATIONS
Effective implementation of the malaria vaccine program requires careful consideration of the socio-cultural context of each community. The RTS, S/AS01 malaria vaccine acceptance and uptake may be significantly enhanced if caregivers' perceptions about vaccines and their importance are adequately fine-tuned. In order to achieve these, community participation and the provision of adequate information in an acceptable form via reliable communication channels seem to be imperative.
Topics: Africa South of the Sahara; Humans; Immunization Programs; Immunization Schedule; Malaria; Malaria Vaccines
PubMed: 30596732
DOI: 10.1371/journal.pone.0209744