-
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 -
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 -
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