Assessing the safety, impact and effectiveness of RTS,S/AS01E malaria vaccine following its introduction in three sub-Saharan African countries: methodological approaches and study set-up.

BACKGROUND: Following a 30-year development process, RTS,S/AS01E (GSK, Belgium) is the first malaria vaccine to reach Phase IV assessments. The World Health Organization-commissioned Malaria Vaccine Implementation Programme (MVIP) is coordinating the delivery of RTS,S/AS01E through routine national immunization programmes in areas of 3 countries in sub-Saharan Africa. The first doses were given in the participating MVIP areas in Malawi on 23 April, Ghana on 30 April, and Kenya on 13 September 2019. The countries participating in the MVIP have little or no baseline incidence data on rare diseases, some of which may be associated with immunization, a deficit that could compromise the interpretation of possible adverse events reported following the introduction of a new vaccine in the paediatric population. Further, effects of vaccination on malaria transmission, existing malaria control strategies, and possible vaccine-mediated selective pressure on Plasmodium falciparum variants, could also impact long-term malaria control. To address this data gap and as part of its post-approval commitments, GSK has developed a post-approval plan comprising of 4 complementary Phase IV studies that will evaluate safety, effectiveness and impact of RTS,S/AS01E through active participant follow-up in the context of its real-life implementation. METHODS: EPI-MAL-002 (NCT02374450) is a pre-implementation safety surveillance study that is establishing the background incidence rates of protocol-defined adverse events of special interest. EPI-MAL-003 (NCT03855995) is an identically designed post-implementation safety and vaccine impact study. EPI-MAL-005 (NCT02251704) is a cross-sectional pre- and post-implementation study to measure malaria transmission intensity and monitor the use of other malaria control interventions in the study areas, and EPI-MAL-010 (EUPAS42948) will evaluate the P. falciparum genetic diversity in the periods before and after vaccine implementation. CONCLUSION: GSK's post-approval plan has been designed to address important knowledge gaps in RTS,S/AS01E vaccine safety, effectiveness and impact. The studies are currently being conducted in the MVIP areas. Their implementation has provided opportunities and posed challenges linked to conducting large studies in regions where healthcare infrastructure is limited. The results from these studies will support ongoing evaluation of RTS,S/AS01E's benefit-risk and inform decision-making for its potential wider implementation across sub-Saharan Africa.

Human Taeniasis and Cysticercosis and Related Factors in Phu Tho Province, Northern Vietnam

Several factors presumed to facilitate the transmission of Taenia spp. were reported in Vietnam. We conducted a cross-sectional study taking questionnaires from 1,185 participants, and collecting 1,151 sera and 1,036 stool samples in northern Vietnam. Sera were examined for circulating antigens of Taenia solium cysticerci using ELISA, stools for Taenia eggs by Kato-Katz smear, and copro-antigens by ELISA. Ag-ELISA revealed 4.6% antigen positivity, indicating infection with viable cysticerci. Taenia eggs were detected in 1.5% of participants. Copro-antigens were found in 2.8% of participants. Eating raw meat and/or vegetables was significantly associated with the presence of copro-antigen (OR=8.6, 95% CI: 1.16-63.9, P=0.01). Considering the high taeniasis prevalence and the associated threat, public health attention should be given to treat the tapeworm carriers in the projected areas.

Human Taeniasis and Cysticercosis and Related Factors in Phu Tho Province, Northern Vietnam

Several factors presumed to facilitate the transmission of Taenia spp. were reported in Vietnam. We conducted a cross-sectional study taking questionnaires from 1,185 participants, and collecting 1,151 sera and 1,036 stool samples in northern Vietnam. Sera were examined for circulating antigens of Taenia solium cysticerci using ELISA, stools for Taenia eggs by Kato-Katz smear, and copro-antigens by ELISA. Ag-ELISA revealed 4.6% antigen positivity, indicating infection with viable cysticerci. Taenia eggs were detected in 1.5% of participants. Copro-antigens were found in 2.8% of participants. Eating raw meat and/or vegetables was significantly associated with the presence of copro-antigen (OR=8.6, 95% CI: 1.16-63.9, P=0.01). Considering the high taeniasis prevalence and the associated threat, public health attention should be given to treat the tapeworm carriers in the projected areas.

Using Discretely Integrated Condition Event Simulation To Construct Quantitative Benefit-Risk Models: The Example of Rotavirus Vaccination in France.

PURPOSE: Although quantitative benefit-risk models (qBRms) are indisputably valuable tools for gaining comprehensive assessments of health care interventions, they are not systematically used, probably because they lack an integrated framework that provides methodologic structure and harmonization. An alternative that allows all stakeholders to design operational models starting from a standardized framework was recently developed: the discretely integrated condition event (DICE) simulation. The aim of the present work was to assess the feasibility of implementing a qBRm in DICE, using the example of rotavirus vaccination. METHODS: A model of rotavirus vaccination was designed using DICE and implemented in spreadsheet software with 3 worksheets: Conditions, Events, and Outputs. Conditions held the information in the model; this information changed at Events, and Outputs were special Conditions that stored the results collected during the analysis. A hypothetical French birth cohort was simulated for the assessment of rotavirus vaccination over time. The benefits were estimated for up to 5 years, and the risks in the 7 days following rotavirus vaccination versus no vaccination were assessed, with the results expressed as benefit-risk ratios. FINDINGS: This qBRm model required 8 Events, 38 Conditions, and 9 Outputs. Two Events cyclically updated the rates of rotavirus gastroenteritis (RVGE) and intussusception (IS) according to age. Vaccination occurred at 2 additional Events, according to the vaccination scheme applied in France, and affected the occurrence of the other Events. Outputs were the numbers of hospitalizations related to RVGE and to IS, and related deaths. The entire model was specified in a small set of tables contained in a 445-KB electronic workbook. Analyses showed that for each IS-related hospitalization or death caused, 1613 (95% credible interval, 1001-2800) RVGE-related hospitalizations and 787 (95% credible interval, 246-2691) RVGE-related deaths would be prevented by vaccination. These results are consistent with those from a published French study using similar inputs but a very different modeling approach. IMPLICATIONS: A limitation of the DICE approach was the extended run time needed for completing the sensitivity analyses when implemented in the electronic worksheets. DICE provided a user-friendly integrated framework for developing qBRms and should be considered in the development of structured approaches to facilitate benefit-risk assessment.

Estimating Annual Fluctuations in Malaria Transmission Intensity and in the Use of Malaria Control Interventions in Five Sub-Saharan African Countries.

RTS,S/AS01E malaria vaccine safety, effectiveness, and impact will be assessed in pre- and post-vaccine introduction studies, comparing the occurrence of malaria cases and adverse events in vaccinated versus unvaccinated children. Because those comparisons may be confounded by potential year-to-year fluctuations in malaria transmission intensity and malaria control intervention usage, the latter should be carefully monitored to adequately adjust the analyses. This observational cross-sectional study is assessing Plasmodium falciparum parasite prevalence (PfPR) and malaria control intervention usage over nine annual surveys performed at peak parasite transmission. Plasmodium falciparum parasite prevalence was measured by microscopy and nucleic acid amplification test (quantitative PCR) in parallel in all participants, and defined as the proportion of infected participants among participants tested. Results of surveys 1 (S1) and 2 (S2), conducted in five sub-Saharan African countries, including some participating in the Malaria Vaccine Implementation Programme (MVIP), are reported herein; 4,208 and 4,199 children were, respectively, included in the analyses. Plasmodium falciparum parasite prevalence estimated using microscopy varied between study sites in both surveys, with the lowest prevalence in Senegalese sites and the highest in Burkina Faso. In sites located in the MVIP areas (Kintampo and Kombewa), PfPR in children aged 6 months to 4 years ranged from 24.8% to 27.3%, depending on the study site and the survey. Overall, 89.5% and 86.4% of children used a bednet in S1 and S2, of whom 68.7% and 77.9% used impregnated bednets. No major difference was observed between the two surveys in terms of PfPR or use of malaria control interventions.

Benefit-Risk Assessment of Vaccines. Part I: A Systematic Review to Identify and Describe Studies About Quantitative Benefit-Risk Models Applied to Vaccines.

INTRODUCTION: Understanding the balance between the benefits and risks of vaccination is essential to ensure informed and adequate public health decision making. Quantitative benefit-risk models (qBRm) represent useful tools to help decision makers with supporting benefit-risk assessment throughout the lifecycle of a medical product. However, few initiatives have been launched to harmonise qBRm approaches, specifically for vaccines. OBJECTIVES: The aim of this paper was to identify publications about qBRm applied to vaccines through a systematic literature review, and to describe their characteristics. METHODS: Medline, Scopus and Institute for Scientific Information Web of Knowledge databases were searched to identify articles in English, published from database inceptions up to December 2019. The search strategy included the combination of three key concepts: 'benefit-risk', 'modelling' and 'vaccines'. Data extracted included the modelling context and the methodological approaches used. RESULTS: Of 3172 publications screened, 48 original publications were included. Most of the selected studies were published over the past decade and focused on rotavirus (15), dengue (10) and influenza (6) vaccines. The majority (30) of studies reported analyses related to high-income countries. The methodology of the studies differed, particularly in modelling techniques, benefit-risk measures, and sensitivity analyses. The present work also pointed out a high level of variability in the quality of reporting across studies, with particular regard to input parameters and methodological approaches. CONCLUSIONS: This review provides an extensive list of qBRm applied to vaccines. Discrepancies across studies were identified during our review. While the number of published qBRm studies is increasing, no reporting guidance for qBRm applied to vaccines is currently available. This may affect decision makers' confidence in the results and their benefit-risk assessment(s); therefore, the development of such reporting guidance is highly needed.

Benefit-Risk Assessment of Vaccines. Part II: Proposal Towards Consolidated Standards of Reporting Quantitative Benefit-Risk Models Applied to Vaccines (BRIVAC).

INTRODUCTION: Quantitative benefit-risk models (qBRm) applied to vaccines are increasingly used by public health authorities and pharmaceutical companies as an important tool to help decision makers with supporting benefit-risk assessment (BRA). However, many publications on vaccine qBRm provide insufficient details on the methodological approaches used. Incomplete and/or inadequate qBRm reporting may affect result interpretation and confidence in BRA, highlighting a need for the development of standard reporting guidance. OBJECTIVES: Our objective was to provide an operational checklist for improved reporting of vaccine qBRm. METHODS: The consolidated standards of reporting quantitative Benefit-RIsk models applied to VACcines (BRIVAC) were designed as a checklist of key information to report in qBRm scientific publications regarding the assessed vaccines, the methodological considerations and the results and their interpretation. RESULTS: In total, 22 items and accompanying definitions, recommendations, explanations and examples were provided and divided into six main sections corresponding to the classic subdivisions of a scientific publication: title and abstract (items 1-2), introduction (items 3-4), methods (items 5-15), results (items 16-17), discussion (items 18-20) and other (items 21-22). CONCLUSIONS: The BRIVAC checklist is the first initiative providing an operational checklist for improved reporting of qBRm applied to vaccines in scientific articles. It is intended to assist authors, peer-reviewers, editors and readers in their critical appraisal. Future initiatives are needed to provide methodological guidance to perform qBRm while taking into account the vaccine specificities.

Quantitative Benefit-Risk Models Used for Rotavirus Vaccination: A Systematic Review.

BACKGROUND: Although rotavirus vaccines have proven to prevent the risk of rotavirus gastroenteritis (RVGE) in children under 5 years old, they are also associated with an increased transient risk of intussusception (IS). Several quantitative benefit-risk models (qBRm) are performed to measure this balance in hospitalizations and deaths prevented versus the ones induced. METHOD: In this study, our objective was to provide a complete overview of qBRm used for rotavirus vaccination. We systematically searched 3 medical literature databases to identify relevant articles, in English, that were published between 2006 and 2019. RESULTS: Of the 276 publications screened, 14 studies using qBRm for rotavirus vaccination were retained, based on preselected criteria. Four were performed in low- and middle-income countries. Almost all (13 of 14) displayed the following characteristics: force of infection assumed to be constant over time (static model), indirect effect of rotavirus vaccination (herd effect) not considered, closed model (individuals not allowed to enter and/or exit the model over time), and aggregated level (no tracking of individual's behavior). Most of the models were probabilistic (9 of 14) and reported sensitivity and/or scenario analyses (12 of 14). Input parameter values varied across studies. Selected studies suggest that, depending on the models used, for every IS hospitalization and death induced, vaccination would prevent, respectively, 190-1624 and 71-743 RVGE-related hospitalizations and deaths. CONCLUSIONS: The benefits of rotavirus vaccination were shown to largely exceed the increased risk of IS, across all studies. Future research aiming to harmonize qBRm for rotavirus vaccination should ensure the comparability of studies and provide additional information for regulatory authorities, physicians, and patients.

Introducing new vaccines in low- and middle-income countries: challenges and approaches.

INTRODUCTION: The number of new vaccine introductions (NVIs) in low and middle-income countries (LMICs) has markedly increased since 2010, raising challenges to often overstretched and underfunded health care systems. AREAS COVERED: We present an overview of some of these challenges, focusing on programmatic decisions, delivery strategy, information and communication, pharmacovigilance and post-licensure evaluation. We also highlight field-based initiatives that may facilitate NVI. EXPERT COMMENTARY: Some new vaccines targeting populations other than infants require alternative delivery strategies. NVIs impact upon existing supply chain management, in particular vaccines with novel characteristics. A lack of understanding about immunization and misconceptions may be detrimental to NVI, as well as insufficient or poorly trained health care workforce. Many barriers exist to achieving good vaccination coverage. Real-world evaluation of vaccine safety, effectiveness and impact in LMICs may be limited by lack of robust demographic and disease epidemiology data, as well as limited health care and surveillance infrastructure. A thorough planning phase is crucial to define the most suitable delivery strategy based on the vaccine's and country's specificities. A communication plan and social mobilization are essential. Implementation research and innovative approaches applied to logistics, delivery, communication and program evaluation can facilitate NVI.

Effectiveness of the Oral Human Attenuated Rotavirus Vaccine: A Systematic Review and Meta-analysis-2006-2016.

BACKGROUND: Gastroenteritis caused by rotavirus accounts for considerable morbidity in young children. We aimed to assess the vaccine effectiveness (VE) of the oral rotavirus vaccine Rotarix, as measured by laboratory-confirmed rotavirus infection after referral to hospital and/or emergency departments in children aged <5 years with gastroenteritis. METHODS: We performed a systematic search for peer-reviewed studies conducted in real-life settings published between 2006 and 2016 and a meta-analysis to calculate the overall Rotarix VE, which was further discriminated through stratified analyses. RESULTS: The overall VE estimate was 69% (95% confidence interval [CI], 62% to 75%); stratified analyses revealed a non-negligible impact of factors such as study design and socioeconomic status. Depending on the control group, VE ranged from 63% (95% CI, 52% to 72%) to 81% (95% CI, 69% to 88%) for unmatched and matched rotavirus test-negative controls. VE varied with socioeconomic status: 81% (95% CI, 74% to 86%) in high-income countries, 54% (95% CI, 39% to 65%) in upper-middle-income countries, and 63% (95% CI, 50% to 72%) in lower-middle-income countries. Age, rotavirus strain, and disease severity were also shown to impact VE, but to a lesser extent. CONCLUSIONS: This meta-analysis of real-world studies showed that Rotarix is effective in helping to prevent hospitalizations and/or emergency department visits due to rotavirus infection.

Assessment of the societal cost of Taenia solium in Angónia district, Mozambique.

BACKGROUND: The zoonotic parasite Taenia solium is endemic in Angónia district, Tete province, Mozambique, though the burden of the disease complex is unknown. METHODS: As part of two cross-sectional studies on human and porcine cysticercosis in the area, unique epidemiological and cost data were collected in Angónia district, Mozambique in 2007. These data provided the basis for the assessment of the societal cost of T. solium in the district, which estimates the impact of the disease on human and pig populations and includes both health and economic approaches in the analysis. RESULTS: Approximately 0.7% (95% Uncertainty Interval (UI), 0.4-0.9) and 0.4% (95% UI, 0.2-0.6) of the total population in the district was estimated to suffer from neurocysticercosis (NCC)-associated epilepsy and headache. The estimated average number of disability-adjusted life years (DALYs) due to NCC-associated epilepsy and headache was 6 (95% UI, 4-8) per thousand persons per year. The total annual costs due to T. solium cysticercosis were estimated at 90,000 USD (95% UI, 39,483-201,463) of which 72% (95% UI, 45-91) were costs linked to human cysticercosis and 28% (95% UI, 9.5-55) to pig production losses. The annual economic burden per NCC-associated epilepsy case in the district amounted to 33 USD (95% UI, 10-76). CONCLUSIONS: In this highly endemic area of Mozambique a large number of individuals suffer from symptoms associated with NCC. Healthy years of life are lost and people are left living with disabilities. Infected pork poses a serious risk to the community and affects the economy of smallholder farmers. Cost for treatment and hospitalization of patients with NCC-associated epilepsy, and lack of productivity and inability of suffering patients to work, further hinder socioeconomic development. Feasible solutions framed within a country specific algorithm and stepwise approaches are needed to control the parasite in the country.

Safety study of live, oral human rotavirus vaccine: A cohort study in United States health insurance plans.

As part of a regulatory commitment for post-licensure safety monitoring of live, oral human rotavirus vaccine (RV1), this study compared the incidence rates (IR) of intussusception, acute lower respiratory tract infection (LRTI) hospitalization, Kawasaki disease, convulsion, and mortality in RV1 recipients versus inactivated poliovirus vaccine (IPV) recipients in concurrent (cIPV) and recent historical (hIPV) comparison cohorts. Vaccine recipients were identified in 2 claims databases from August 2008 - June 2013 (RV1 and cIPV) and January 2004 - July 2008 (hIPV). Outcomes were identified in the 0-59 days following the first 2 vaccine doses. Intussusception, Kawasaki disease, and convulsion were confirmed via medical record review. Outcome IRs were estimated. Incidence rate ratios (IRRs) were obtained from Poisson regression models. A post-hoc self-controlled case series (SCCS) analysis compared convulsion IRs in a 0-7 day post-vaccination period to a 15-30 day post-vaccination period. We identified 57,931 RV1, 173,384 cIPV, and 159,344 hIPV recipients. No increased risks for intussusception, LRTI, Kawasaki disease, or mortality were observed. The convulsion IRRs were elevated following RV1 Dose 1 (cIPV: 2.07, 95% confidence interval [CI]: 1.27 - 3.38; hIPV: 2.05, 95% CI: 1.24 - 3.38), a finding which is inconclusive as it was observed in only one of the claims databases. The IRR following RV1 Dose 1 in the SCCS analysis lacked precision (2.40, 95% CI: 0.73 - 7.86). No increased convulsion risk was observed following RV1 Dose 2. Overall, this study supports the favorable safety profile of RV1. Continued monitoring for safety signals through routine surveillance is needed to ensure vaccine safety.

Benefit Versus Risk Assessment of Rotavirus Vaccination in France: A Simulation and Modeling Analysis.

INTRODUCTION: Two vaccines against rotavirus gastroenteritis (RVGE) in young children, Rotarix and RotaTeq, have been available in Europe since 2006. Vaccination against rotaviruses significantly reduces the burden of RVGE, but it is also associated with a very small increased risk of intussusception. In a benefit-risk analysis, the prevented RVGE burden is weighed against the possible excess of intussusception. PURPOSE: The aim was to compare the estimated benefits and risks of Rotarix vaccination in France. METHODS: We estimated the benefits (vaccine-preventable RVGE hospitalizations and deaths) and risks (vaccine-caused intussusception hospitalizations and deaths) following two doses of Rotarix in a birth cohort of 791,183 followed for 3-5 years in France. We used data from peer-reviewed clinical and epidemiological studies or publications, and government statistics. RESULTS: Within the total number of French children below 5 years of age, we estimate vaccination could prevent a median 11,132 [95% credible interval (CI) 7842-14,408] RVGE hospitalizations and 7.43 (95% CI 3.27-14.68) RVGE deaths. At the same time, vaccination could cause an average of 6.86 (95% CI 2.25-38.37) intussusception hospitalizations and 0.0099 (95% CI 0.0024-0.060) intussusception deaths in the entire French birth cohort of infants below 1 year of age. Therefore, for every intussusception hospitalization and every intussusception death caused by vaccination, 1624 (95% CI 240-5243) RVGE hospitalizations and 743 (95% CI 93-3723) RVGE deaths are prevented, respectively, by vaccination. CONCLUSIONS: The vaccine-prevented RVGE hospitalizations and deaths (benefit) greatly outweigh the excess potentially vaccination-related cases of intussusception (risk), indicating a favorable benefit-risk balance for Rotarix in France.

Methodology for computing the burden of disease of adverse events following immunization.

PURPOSE: Composite disease burden measures such as disability-adjusted life-years (DALY) have been widely used to quantify the population-level health impact of disease or injury, but application has been limited for the estimation of the burden of adverse events following immunization. Our objective was to assess the feasibility of adapting the DALY approach for estimating adverse event burden. METHODS: We developed a practical methodological framework, explicitly describing all steps involved: acquisition of relative or absolute risks and background event incidence rates, selection of disability weights and durations, and computation of the years lived with disability (YLD) measure, with appropriate estimation of uncertainty. We present a worked example, in which YLD is computed for 3 recognized adverse reactions following 3 childhood vaccination types, based on background incidence rates and relative/absolute risks retrieved from the literature. RESULTS: YLD provided extra insight into the health impact of an adverse event over presentation of incidence rates only, as severity and duration are additionally incorporated. As well as providing guidance for the deployment of DALY methodology in the context of adverse events associated with vaccination, we also identified where data limitations potentially occur. CONCLUSIONS: Burden of disease methodology can be applied to estimate the health burden of adverse events following vaccination in a systematic way. As with all burden of disease studies, interpretation of the estimates must consider the quality and accuracy of the data sources contributing to the DALY computation.

Cognitive impairment and quality of life of people with epilepsy and neurocysticercosis in Zambia.

Cognitive impairment and quality of life (Qol) are important to assess the burden of epilepsy and neurocysticercosis (NCC), which are common but neglected in Sub-Saharan Africa (SSA). The aims of this study were to assess cognitive performance and Qol of people with epilepsy (PWE) in Zambia and to explore differences in PWE with and without NCC. In this community based, cross-sectional case-control-study, 47 PWE and 50 healthy controls completed five neuropsychological tests (Mini Mental State Examination (MMSE), Digit Span, Selective Reminding Test (SRT), Spatial Recall Test (SPART), Test Battery of Attentional Performance (TAP)) and a World Health Organization (WHO) questionnaire of Qol. Comparisons were made between PWE (n=47) and healthy controls (n=50) and between PWE with NCC (n=28) and without NCC (n=19), respectively, using Analysis of Covariance (ANCOVA) and Linear Models (LMs) while correcting for confounders such as age, sex, and schooling years, and adjusting for multiplicity. Working memory, spatial memory, verbal memory, verbal learning, orientation, speech and language reception, visuoconstructive ability, and attentional performance were significantly reduced in PWE compared with healthy controls (ANCOVA and LM, p<0.05). Quality of life of PWE was significantly lower in three domains (psychological, social, environmental) and in overall Qol compared with healthy controls (ANCOVA, p<0.05). There were no significant differences between PWE with NCC and PWE without NCC detected by ANCOVA. Using LM, significant differences between the groups were detected in four tests, indicating worse performance of PWE without NCC in MMSE, Digit Span, SPART, and lower physical Qol. Epilepsy was found to be associated with cognitive impairment and reduced Qol. People with epilepsy due to NCC had similar cognitive impairment and Qol compared with PWE due to other causes. Further studies should investigate the role of different conditions of NCC and the role of seizures on cognition and Qol.

Pain caused by measles, mumps, and rubella vaccines: A systematic literature review.

PURPOSE: The risk of post-vaccination adverse events (AEs) is a primary public health concern. Among the AEs, pain is a significant source of anxiety for both children and their parents. This review describes and assesses the intensity of pain experienced by children post-vaccination with widely used Measles-Mumps-Rubella (MMR) vaccines. METHODS: A systematic literature search was conducted in Pubmed, Embase and Cochrane to identify publications describing immediate pain at injection site (primary objective) or pain within days (secondary objective) after 2 specific MMR vaccines. Immediate pain ('acute pain' according to the Brighton Collaboration case definition) was defined as pain occurring at the time or within 5min of injection. RESULTS: Four studies, which compared the intensity of immediate injection site pain experienced by children after MMR vaccination, were identified. Various pain assessment tools and methods were used to quantify the intensity of pain, including the median difference in Visual Analog Scale scores between vaccine groups. All four studies showed significantly less immediate pain caused by Priorix (GSK Vaccines) compared with M-M-R II (Merck & Co., Inc.). CONCLUSIONS: To our knowledge, this review summarizes for the first time the available scientific evidence on the intensity of pain following different MMR vaccines. It highlights that MMR vaccines can differ in terms of immediate pain. Further research may be needed to better understand the underlying reason for this observation. In this context, it is very important to understand which physicochemical properties are most relevant for the immediate pain profile of a vaccine to thereby support the development of vaccines with the best possible immediate pain profile.

High prevalence of bovine cysticercosis found during evaluation of different post-mortem detection techniques in Belgian slaughterhouses.

Bovine cysticercosis (BCC), caused by the helminth Taenia saginata, is currently diagnosed solely by official meat inspection (MI) based on macroscopic detection of viable cysticerci or typical lesions of degenerated larvae. MI has a known low sensitivity (<16%), leading to a large proportion of infected cattle carcasses entering the human food chain and posing a risk to public health. Prevalence in Belgium based on MI results is estimated at around 0.22%. Due to the low sensitivity of MI, alternative techniques to detect BCC should be considered. This study evaluates MI, MI with additional incisions in the heart, specific antibody detection against excretory/secretory (E/S) in the Ab-ELISA and circulating antigens in the B158/B60 Ag-ELISA on 715 (101 MI-positive and 614 MI-negative) samples collected from carcasses at slaughterhouses in Belgium. Full dissection of the predilection sites was considered the reference test. During the study, mostly carcasses with (very) light infections were detected containing predominantly degenerated or calcified cysticerci and only few viable cysticerci. Dissection of the predilection sites detected 144 (23%) additional infections in the 614 MI-negative carcasses. When sequentially performing first the dissection of the predilection sites, followed by the Ag-ELISA and the Ab-ELISA, an additional 36% of MI-negative carcasses were found positive for BCC, resulting in a prevalence very much higher than the above mentioned 0.22%. The B158/B60 Ag-ELISA showed a sensitivity of 40% for the detection of carcasses containing viable cysticerci and a specificity of 100%, and detected 70 positive carcasses of which only 14 had been identified as positive during MI. If Ag-ELISA were implemented as a detection technique for BCC in the slaughterhouses, many infected carcasses would still not be detected due to the sensitivity of 40%. But as sensitivity increases with increasing number of cysticerci in the carcass, the infected carcasses passing inspection will be the ones containing only a few viable cysticerci and thus posing a smaller food safety problem. Ag-ELISA is preferred over the ES Ab-ELISA in this study, which had a sensitivity of 13.3% and a specificity of 91.7% in a population with overall low infection burdens.

Epidemiology of polyparasitism with Taenia solium, schistosomes and soil-transmitted helminths in the co-endemic village of Malanga, Democratic Republic of Congo.

Helminth co-infections are common in sub-Saharan Africa. However, little is known about the distribution and determinants of co-infections with Taenia solium taeniasis/cysticercosis. Building on a previous community-based study on human cysticercosis in Malanga village, we investigated co-infections with Taenia solium, soil-transmitted helminths (STHs) and Schistosoma spp and associated risk factors in a random subsample of 330 participants. Real time PCR assays were used to detect DNA of soil-transmitted helminths (STHs), T. solium and Schistosoma in stool samples and Schistosoma DNA in urine samples. Serum samples were tested for T. solium cysticercosis using the B158/B60 monoclonal antibody-based antigen ELISA. Bivariate analysis and logistic regression were applied to assess associations of single and co-infections with common risk factors (age, sex, area, hygiene) as well as pair wise associations between helminth species. Overall, 240 (72.7%) participants were infected with at least one helminth species; 128 (38.8%) harbored at least two helminth species (16.1% with STHs-Schistosoma, 14.5% with STHs-T. solium taeniasis/cysticercosis and 8.2% with Schistosoma-T. solium taeniasis/cysticercosis co-infections). No significant associations were found between Schistosoma-T. solium taeniasis/cysticercosis co-infection and any of the risk factors studied. Males (OR=2 (95%CI=1.1-5), p=0.03) and open defecation behavior (OR=3.8 (95%CI=1.1-6.5), p=0.04) were associated with higher odds of STHs-T. solium taeniasis/cysticercosis co-infection. Village districts that were found at high risk of T. solium taeniasis/cysticercosis were also at high risk of co-infection with STHs and T. solium taeniasis/cysticercosis (OR=3.2 (95%CI=1.1-7.8), p=0.03). Significant pair-wise associations were found between T. solium cysticerci and Necator americanus (OR=2.2 (95%CI=1.2-3.8), p<0.01) as well as Strongyloides stercoralis (OR=2.7 (95%CI=1.1-6.5), p=0.02). These findings show that co-infections with T. solium are common in this polyparasitic community in DRC. Our results on risk factors of helminth co-infections and specific associations between helminths may contribute to a better integration of control within programmes that target more than one NTD.

Geospatial and age-related patterns of Taenia solium taeniasis in the rural health zone of Kimpese, Democratic Republic of Congo.

BACKGROUND: Taenia solium infections are mostly endemic in less developed countries where poor hygiene conditions and free-range pig management favor their transmission. Knowledge on patterns of infections in both human and pig is crucial to design effective control strategies. The aim of this study was to assess the prevalence, risk factors and spatial distribution of taeniasis in a rural area of the Democratic Republic of Congo (DRC), in the prospect of upcoming control activities. METHODS: A cross-sectional study was conducted in 24 villages of the health zone of Kimpese, Bas Congo Province. Individual and household characteristics, including geographical coordinates were recorded. Stool samples were collected from willing participants and analyzed using the copro-antigen enzyme-linked immunosorbent assay (copro-Ag ELISA) for the detection of taeniasis. Blood samples were collected from pigs and analyzed using the B158/B60 monoclonal antibody-based antigen ELISA (sero-Ag ELISA) to detect porcine cysticercosis. Logistic regression and multilevel analysis were applied to identify risk factors. Global clustering and spatial correlation of taeniasis and porcine cysticercosis were assessed using K functions. Local clusters of both infections were identified using the Kulldorff's scan statistic. RESULTS: A total of 4751 participants above 5 years of age (median: 23 years; IQR: 11-41) were included. The overall proportion of taeniasis positivity was 23.4% (95% CI: 22.2-24.6), ranging from 1 to 60% between villages, with a significant between-household variance of 2.43 (SE=0.29, p<0.05). Taeniasis was significantly associated with age (p<0.05) and the highest positivity was found in the 5-10 years age group (27.0% (95% CI: 24.4-29.7)). Overall, 45.6% (95% CI: 40.2-51) of sampled pigs were sero-positive. The K functions revealed a significant overall clustering of human and pig infections but no spatial dependence between them. Two significant clusters of taeniasis (p<0.001; n=276 and n=9) and one cluster of porcine cysticercosis (p<0.001; n=24) were found. CONCLUSION: This study confirms high endemicity and geographical dispersal of taeniasis in the study area. The role of age in taeniasis patterns and significant spatial clusters of both taeniasis and porcine cysticercosis were evidenced, though no spatial correlation was found between human and pig infections. Urgent control activities are needed for this endemic area.