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Preventive Veterinary Medicine Nov 2014Canine leishmaniosis (CanL) is an important zoonotic disease; however, the efficacy of available vaccines for the prevention of naturally-occurring Leishmania infantum... (Review)
Review
Canine leishmaniosis (CanL) is an important zoonotic disease; however, the efficacy of available vaccines for the prevention of naturally-occurring Leishmania infantum (L. infantum) infection in dogs remains unclear. The objective of this review was to determine the efficacy of currently available vaccines to prevent naturally-occurring L. infantum infection in dogs. Four bibliographic databases (CAB Direct 2011, Web of Science 2011, U.S. National Library of Medicine 2011 and Literatura Latino Americana e do Caribe em Ciências da Saúde) were searched along with eight sets of conference proceedings and the International Veterinary Information Service (IVIS) database, from 1980 to November 2012. Randomised controlled trials (RCTs), non-randomised clinical trials (NRCTs), cohort studies and case-control studies that investigated vaccine efficacy for natural L. infantum infection in dogs were eligible for inclusion. Two review authors independently assessed each study against the inclusion criteria, independently extracted relevant data from all included studies and assessed the risk of methodological shortcomings in each individual study. The odds ratio (OR) and absolute risk reduction (ARR) for dichotomous outcomes and mean difference for continuous outcomes were calculated. Meta-analysis was not performed due to heterogeneity of the studies identified. The search was conducted for all mitigations for CanL and yielded the title and abstract of 937 articles, from which 84 articles were screened based on full text. Twelve studies on vaccinations (five RCTs, seven NRCTs) were identified. Ten studies were at a high risk of methodological shortcomings, whilst two were at an unclear risk. The use of 200 μg ALM protein, Leishmune(®), CaniLeish(®), LiESAp with MDP, and ALM with BCG tended to significantly reduce the proportion of dogs infected with L. infantum based on either parasitological or serological evidence. The use of lyophilized protein vaccine significantly increased the proportion of dogs infected with L. infantum based on either parasitological or serological evidence. There is peer-reviewed evidence that control measures are effective in preventing CanL with the results suggesting that between 6 and 54% of infections could be prevented with vaccination. However, this evidence is based on a small number of RCTs, all of which are either at high or unclear risk of methodological shortcomings. Well-designed, adequately powered and properly reported randomised clinical trials are needed to clearly establish efficacy of vaccines as CanL control measures.
Topics: Animals; Dog Diseases; Dogs; Leishmaniasis; Leishmaniasis Vaccines
PubMed: 25074635
DOI: 10.1016/j.prevetmed.2014.06.015 -
Journal of Veterinary Internal Medicine 2013This review assesses the efficacy of whole cell Tritrichomonas foetus vaccine to prevent and treat trichomoniasis in beef cattle. Three databases were searched in June... (Meta-Analysis)
Meta-Analysis Review
This review assesses the efficacy of whole cell Tritrichomonas foetus vaccine to prevent and treat trichomoniasis in beef cattle. Three databases were searched in June 2012. Eligible studies compared infection risk, open risk, and abortion risk in heifers or infection risk in bulls that received vaccine compared with no vaccine. Study results were extracted, summary effect measures were calculated, and the quality of the evidence was assessed. From 334 citations identified, 10 were relevant to the review. For heifers, there was limited evidence of moderate quality to assess the impact of vaccination on infection risk (RR, 0.89; P = .16; 95% CI, 0.76-1.05; 6 randomized and 4 nonrandomized studies; 251 animals) and open risk (RR, 0.80; P = .06; 95% CI, 0.63-1.01; 6 randomized and 5 nonrandomized studies; 570 animals). The quality of the body of work describing the impact of vaccination on abortion risk was low (summary RR, 0.57; P = .0003; 95% CI, 0.42-0.78; 3 randomized and 2 nonrandomized studies; 176 animals). The quality of evidence was very low for duration of infection (mean difference, -23.42; P = .003; 95% CI, -38.36 to -7.85; 2 randomized and 3 nonrandomized studies; 163 animals). Although the summary effect measures suggest a benefit to vaccination, due to publication bias the effect reported here is likely an over estimate of efficacy. For bull-associated outcomes, the evidence base was low or very low quality.
Topics: Animals; Cattle; Cattle Diseases; Protozoan Infections, Animal; Protozoan Vaccines; Tritrichomonas
PubMed: 23701212
DOI: 10.1111/jvim.12112 -
Microbial Pathogenesis Jan 2019At present, there is not any available accepted vaccine for prevention of Toxoplasma gondii (T. gondii) in human and animals. We conducted literature search through...
At present, there is not any available accepted vaccine for prevention of Toxoplasma gondii (T. gondii) in human and animals. We conducted literature search through English (Google Scholar, PubMed, Science Direct, Scopus, EBSCO, ISI Web of Science) scientific paper databases to find the best vaccine candidates against toxoplasmosis among T. gondii antigens. Articles with information on infective stage, pathogenicity, immunogenicity and characterization of antigens were selected. We considered that the ideal and significant vaccines should include different antigens and been expressed in all infective stages of the parasite with a high pathogenicity and immunogenicity. Evaluation within this systematic review indicates that MIC 3, 4, 13, ROP 2, RON 5, GRA 1, 6, 8, 14 are expressed in all three infective stages and have pathogenicity and immunogenicity. MIC 5, ROM 4, GRA 2, 4, 15, ROP 5, 16, 17, 38, RON 4, MIC 1, GRA 10, 12, 16, SAG 3 are expressed in only tachyzoites and bradyzoites stages of T. gondii with pathogenicity/immunogenicity. Some antigens appeared to be expressed in a single stage (tachyzoites) but have high pathogenicity and induce immune response. They include enolase2 (ENO2), SAG 1, SAG5D, HSP 70, ROM 1, ROM 5, AMA 1, ROP 18, RON2 and GRA 24. In conclusion, current vaccination against T. gondii infection is not satisfactory, and with the increasing number of high-risk individuals, the development of an effective and safe specific vaccine is greatly valuable for toxoplasmosis prevention. This systematic review reveals prepare candidates for immunization studies.
Topics: Animals; Antigens, Protozoan; Databases, Factual; Humans; Immunization; Microbial Sensitivity Tests; Protozoan Proteins; Protozoan Vaccines; Toxoplasma; Toxoplasmosis; Vaccination; Vaccines, DNA; Virulence
PubMed: 30399440
DOI: 10.1016/j.micpath.2018.11.003 -
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 -
Journal of the American Academy of... Aug 2010Cutaneous leishmaniasis (CL) has traditionally been underrecognized and underreported. Improved awareness is warranted as the number of cases has increased as a result... (Review)
Review
BACKGROUND
Cutaneous leishmaniasis (CL) has traditionally been underrecognized and underreported. Improved awareness is warranted as the number of cases has increased as a result of increased travel to endemic countries, the HIV/AIDS pandemic, and the larger number of military and contract workers deployed overseas.
OBJECTIVE
We sought to present a systematic review of evidence from a gamut of research trials on the treatment efficacy of different regimens and aggregate this knowledge for use as a guide for clinical practice decisions.
METHODS
We performed a comprehensive search of print and electronic sources to identify the accumulated research information on New World CL.
RESULTS
Topical treatment of New World CL lesions is generally not recommended. Findings support the systemic administration of pentavalent antimonials as first-line treatment. Exception to this is infection with L guyanensis in French Guiana where systemic pentamidine is suggested as first-line treatment.
LIMITATIONS
The reliability of the findings of this review of research evidence is dependent on the individual quality and potential bias in its component principal trials. There was a conscious attempt to only include evidence derived from randomized controlled studies, with adequate randomization, adequate patient numbers, and complete follow-up information. However, because of the relatively small number of such studies on New World CL, evidence from nonrandomized studies and case series studies was also considered.
CONCLUSIONS
The pentavalent antimony compounds remain the first-line treatment choice for the treatment of New World CL. Concerns with cost, availability, poor compliance, and systemic toxicity, however, may compel clinicians to opt for alternative treatment modalities. Some advances in the development of an antileishmanial vaccine have been made but none is yet available for clinic use. The increase, over recent years, in the incidence of CL warrants an enhanced effort to increase awareness of the disease, assure timely diagnosis, and implement effective management and treatment strategies.
Topics: Amebicides; Antifungal Agents; Antiprotozoal Agents; Humans; Leishmaniasis Vaccines; Leishmaniasis, Cutaneous
PubMed: 20303613
DOI: 10.1016/j.jaad.2009.06.088 -
European Journal of Clinical... Apr 2019Toxoplasma gondii is an intracellular parasite infecting almost all warm-blooded animals. Many studies on vaccination have been performed previously, and micronemal...
Toxoplasma gondii is an intracellular parasite infecting almost all warm-blooded animals. Many studies on vaccination have been performed previously, and micronemal proteins (MICs) have crucial importance in this regard. The current review aims to reveal the efficiency of MICs as target antigen, adjuvants, animal models (species/strain), T. gondii strains for challenge infection, and routes of vaccine to prevent Toxoplasma infection. A comprehensive literature search was performed on April 18, 2018, in several known databases. Studies were included when evaluating vaccines based on MIC against T. gondii compared to that of a control group. Two independent researchers done the search process, study choice, and data extraction. A total of 28 articles published were selected for further analysis. Among them, 57.03% of the studies focused on MIC3 and its epitopes. SAG1 was further used in cocktail vaccines compared to other antigens. GM-CSF and Freund's complete were the predominant adjuvants used. BALB/c mice have been introduced as a proper model for lethal challenge. Virulent T. gondii (RH) was utilized more than other strains for challenge. Among MICs, the results of vaccination with MIC1-4, MIC6, and PLP1 demonstrated significantly strong humoral and cellular immunity, increased survival time, and reduced cyst burden in the mice. This review summarizes the latest results on MIC-based vaccines and presents that the most effective vaccination procedure is the administration of the cocktail vaccines. Our survey can serve as a basis for further studies to develop more efficient novel vaccines against T. gondii for animals and humans.
Topics: Animals; Antibodies, Protozoan; Antigens, Protozoan; Disease Models, Animal; Freund's Adjuvant; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunity, Cellular; Immunity, Humoral; Mice, Inbred BALB C; Protozoan Proteins; Toxoplasma; Toxoplasmosis; Vaccination; Vaccines, DNA; Vaccines, Synthetic
PubMed: 30680553
DOI: 10.1007/s10096-018-03442-6 -
Immunotherapy Jun 2021Current treatments for leishmaniases are not satisfactory, thus alternatives are needed. We searched for clinical trials with immunotherapeutic approaches for patients... (Meta-Analysis)
Meta-Analysis
Current treatments for leishmaniases are not satisfactory, thus alternatives are needed. We searched for clinical trials with immunotherapeutic approaches for patients with leishmaniasis. Out of 205 articles, 24 clinical trials were selected, and eight submitted to meta-analysis. A reduction in healing time was observed in patients with tegumentary leishmaniasis treated with pentavalent antimony plus granulocyte-macrophage colony-stimulating factor, and therapeutic vaccines. Overall meta-analysis indicated that immunotherapy associated with the standard chemotherapy generated a significantly reduced risk of treatment failure than the pentavalent antimony alone (p = 0.03). Our review confirmed the efficacy of immunotherapies for the treatment of cutaneous and visceral leishmaniasis and highlighted the importance of clinical trials using immunotherapies for leishmaniases.
Topics: Antiprotozoal Agents; Humans; Immunotherapy; Leishmaniasis; Leishmaniasis Vaccines
PubMed: 33853344
DOI: 10.2217/imt-2020-0184 -
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 -
Comparative Immunology, Microbiology... Apr 2020Toxoplasma gondii is an intracellular parasite that infects a broad range of animal species and humans. As the main surface antigen of the tachyzoite, SAG1 is involved... (Meta-Analysis)
Meta-Analysis
Toxoplasma gondii is an intracellular parasite that infects a broad range of animal species and humans. As the main surface antigen of the tachyzoite, SAG1 is involved in the process of recognition, adhesion and invasion of host cells. The aim of the current systematic review study is to clarify the latest status of studies in the literature regarding SAG1-associated recombinant proteins or SAG1-associated recombinant DNAs as potential vaccines against toxoplasmosis. Data were systematically collected from six databases including PubMed, Science Direct, Web of Science, Google Scholar, EBSCO and Scopus, up to 1st of January 2019. A total of 87 articles were eligible for inclusion criteria in the current systematic review. The most common antigens used for experimental cocktail vaccines together with SAG1 were ROP2 and SAG2. In addition, the most parasite strains used were RH and ME49. Freund's adjuvant and cholera toxin have been predominantly utilized. Furthermore, regarding the animal models, route and dose of vaccination, challenge methods, measurement of immune responses and cyst burden have been discussed in the text. Most of these experimental vaccines induce immune responses and have a high degree of protection against parasite infections, increase survival rates and duration and reduce cyst burdens. The data demonstrated that SAG1 antigen has a high potential for use as a vaccine and provided a promising approach for protecting humans and animals against toxoplasmosis.
Topics: Adjuvants, Immunologic; Animals; Antigens, Protozoan; Disease Models, Animal; Humans; Immunization; Mice; Protozoan Proteins; Protozoan Vaccines; Toxoplasma; Toxoplasmosis; Vaccines, DNA
PubMed: 31958746
DOI: 10.1016/j.cimid.2020.101414 -
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