Ebola Outbreak Response in the DRC with rVSV-ZEBOV-GP Ring Vaccination.

Background: At the beginning of the 2018-2020 outbreak of Ebola virus disease (EVD) in eastern Democratic Republic of Congo (DRC), no vaccine had been licensed. However, cluster-randomized evidence from Guinea in 2015 had indicated that ring vaccination around new cases (targeting contacts and contacts-of-contacts) with the use of single-dose live-replicating rVSV-ZEBOV-GP vaccine reduced EVD rates starting 10 days after vaccination. Thus, ring vaccination was added to the standard control measures for that outbreak.

Zinc as an adjunct therapy in the management of severe pneumonia among Gambian children: randomized controlled trial.

Background: The benefit of zinc as an adjunct therapy for severe pneumonia is not established. We assessed the benefit of adjunct zinc therapy for severe pneumonia in children and determined whether the study children were zinc deficient.

Methods: This was a randomized, parallel group, double-blind, placebo-controlled trial with an allocation ratio of 1:1 conducted in children with severe pneumonia to evaluate the efficacy of daily zinc as an adjunct treatment in preventing 'treatment failure' (presence of any sign of severe pneumonia) on day-5 and day-10 and in reducing the time to resolution of signs of severe pneumonia.

Ring vaccination with rVSV-ZEBOV under expanded access in response to an outbreak of Ebola virus disease in Guinea, 2016: an operational and vaccine safety report.

Background: In March, 2016, a flare-up of Ebola virus disease was reported in Guinea, and in response ring vaccination with the unlicensed rVSV-ZEBOV vaccine was introduced under expanded access, the first time that an Ebola vaccine has been used in an outbreak setting outside a clinical trial. Here we describe the safety of rVSV-ZEBOV candidate vaccine and operational feasibility of ring vaccination as a reactive strategy in a resource-limited rural setting.

Methods: Approval for expanded access and compassionate use was rapidly sought and obtained from relevant authorities.

Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!).

Background: rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa.

Methods: We did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone.

Meningococcal disease in the Asia-Pacific region: Findings and recommendations from the Global Meningococcal Initiative.

The Global Meningococcal Initiative (GMI) is a global expert group that includes scientists, clinicians, and public health officials with a wide range of specialties. The purpose of the Initiative is to promote the global prevention of meningococcal disease (MD) through education, research, and cooperation. The first Asia-Pacific regional meeting was held in November 2014.

Immunogenicity of Yellow Fever Vaccine Coadministered With MenAfriVac in Healthy Infants in Ghana and Mali.

Background: Yellow fever (YF) is still a major public health problem in endemic regions of Africa and South America. In Africa, one of the main control strategies is routine vaccination within the Expanded Programme on Immunization (EPI). A new meningococcal A conjugate vaccine (PsA-TT) is about to be introduced in the EPI of countries in the African meningitis belt, and this study reports on the immunogenicity of the YF-17D vaccines in infants when administered concomitantly with measles vaccine and PsA-TT.

Human Complement Bactericidal Responses to a Group A Meningococcal Conjugate Vaccine in Africans and Comparison to Responses Measured by 2 Other Group A Immunoassays.

Background: PsA-TT (MenAfriVac) is a conjugated polysaccharide vaccine developed to eliminate group A meningococcal disease in Africa. Vaccination of African study participants with 1 dose of PsA-TT led to the production of anti-A polysaccharide antibodies and increased serum bactericidal activity measured using rabbit complement (rSBA). Bactericidal responses measured with human complement (hSBA) are presented here.

Antibody Persistence at 1 and 4 Years Following a Single Dose of MenAfriVac or Quadrivalent Polysaccharide Vaccine in Healthy Subjects Aged 2-29 Years.

Background: Mass vaccination campaigns of the population aged 1-29 years with 1 dose of group A meningococcal (MenA) conjugate vaccine (PsA-TT, MenAfriVac) in African meningitis belt countries has resulted in the near-disappearance of MenA. The vaccine was tested in clinical trials in Africa and in India and found to be safe and highly immunogenic compared with the group A component of the licensed quadrivalent polysaccharide vaccine (PsACWY). Antibody persistence in Africa and in India was investigated.

Antibody Persistence 1-5 Years Following Vaccination With MenAfriVac in African Children Vaccinated at 12-23 Months of Age.

Background: Following mass vaccination campaigns in the African meningitis belt with group A meningococcal conjugate vaccine, MenAfriVac (PsA-TT), disease due to group A meningococci has nearly disappeared. Antibody persistence in healthy African toddlers was investigated.

Methods: African children vaccinated at 12-23 months of age with PsA-TT were followed for evaluation of antibody persistence up to 5 years after primary vaccination.

A Phase 3, Double-Blind, Randomized, Active Controlled Study to Evaluate the Safety of MenAfriVac in Healthy Malians.

Background: A safe, affordable, and highly immunogenic meningococcal A conjugate vaccine (PsA-TT, MenAfriVac) was developed to control epidemic group A meningitis in Africa. Documentation of the safety specifications of the PsA-TT vaccine was warranted, with sufficient exposure to detect potential rare vaccine-related adverse reactions.

Methods: This phase 3, double-blind, randomized, active controlled clinical study was designed to evaluate the safety--primarily vaccine-related serious adverse events (SAEs)--up to 3 months after administration of a single dose of the PsA-TT vaccine to subjects aged 1-29 years in Mali.

Safety Monitoring in Group A Meningococcal Conjugate Vaccine Trials: Description, Challenges, and Lessons.

Background: The determination of the safety profile of any vaccine is critical to its widespread use in any population. In addition, the application of international guidelines to fit local context could be a challenging but important step toward obtaining quality safety data.

Methods: In clinical studies of PsA-TT (MenAfriVac), safety was monitored immediately after vaccination, at 4-7 days for postimmunization local and systemic reactions, within 28 days for adverse events, and throughout the duration of study for serious adverse events.

Ethical Challenges and Lessons Learned During the Clinical Development of a Group A Meningococcal Conjugate Vaccine.

Background: The group A meningococcal vaccine (PsA-TT) clinical development plan included clinical trials in India and in the West African region between 2005 and 2013. During this period, the Meningitis Vaccine Project (MVP) accumulated substantial experience in the ethical conduct of research to the highest standards.

Methods: Because of the public-private nature of the sponsorship of these trials and the extensive international collaboration with partners from a diverse setting of countries, the ethical review process was complex and required strategic, timely, and attentive communication to ensure the smooth review and approval for the clinical studies.

Community Perspectives Associated With the African PsA-TT (MenAfriVac) Vaccine Trials.

Background: The Meningitis Vaccine Project (MVP) was established to address epidemic meningitis as a public health problem in sub-Saharan Africa and, to that end, worked to develop a group A meningococcal conjugate vaccine, PsA-TT.

Methods: Experiences in 4 clinical trial sites are described. Culturally sensitive collaborative strategies were adopted to manage acceptable communication methods, peculiarities with the consent process, participant medical issues, community care, and death.

Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial.

Background: A recombinant, replication-competent vesicular stomatitis virus-based vaccine expressing a surface glycoprotein of Zaire Ebolavirus (rVSV-ZEBOV) is a promising Ebola vaccine candidate. We report the results of an interim analysis of a trial of rVSV-ZEBOV in Guinea, west Africa.

Methods: For this open-label, cluster-randomised ring vaccination trial, suspected cases of Ebola virus disease in Basse-Guinée (Guinea, west Africa) were independently ascertained by Ebola response teams as part of a national surveillance system.

Evolving meningococcal immunization strategies.

Meningococcal disease is a major public health problem and immunization is considered the best strategy for prevention. The introduction of meningococcal C conjugate immunization schedules that targeted adolescents, with catch-up programs in several European countries, Australia and Canada proved to be highly effective, with dramatic reduction in the incidence of serogroup C disease, not only in vaccinated, but also in unvaccinated individuals. Meningococcal quadrivalent (A, C, W, Y) conjugate vaccines are now licensed and are being used in adolescent programs in North America and to control serogroup W disease in South America.

Effectiveness of an oral cholera vaccine in Zanzibar: findings from a mass vaccination campaign and observational cohort study.

Background: Zanzibar, in east Africa, has been severely and repeatedly affected by cholera since 1978. We assessed the effectiveness of oral cholera vaccination in high-risk populations in the archipelago to estimate the indirect (herd) protection conferred by the vaccine and direct vaccine effectiveness.

Methods: We offered two doses of a killed whole-cell B-subunit cholera vaccine to individuals aged 2 years and older in six rural and urban sites.

Safety of the recombinant cholera toxin B subunit, killed whole-cell (rBS-WC) oral cholera vaccine in pregnancy.

Introduction: Mass vaccinations are a main strategy in the deployment of oral cholera vaccines. Campaigns avoid giving vaccine to pregnant women because of the absence of safety data of the killed whole-cell oral cholera (rBS-WC) vaccine. Balancing this concern is the known higher risk of cholera and of complications of pregnancy should cholera occur in these women, as well as the lack of expected adverse events from a killed oral bacterial vaccine.

Evaluation of a rapid dipstick (Crystal VC) for the diagnosis of cholera in Zanzibar and a comparison with previous studies.

Background: The gold standard for the diagnosis of cholera is stool culture, but this requires laboratory facilities and takes at least 24 hours. A rapid diagnostic test (RDT) that can be used by minimally trained staff at treatment centers could potentially improve the reporting and management of cholera outbreaks.

Methods: We evaluated the Crystal VC™ RDT under field conditions in Zanzibar in 2009.

Pneumococcal antibody concentrations and carriage of pneumococci more than 3 years after infant immunization with a pneumococcal conjugate vaccine.

Background: A 9-valent pneumococcal conjugate vaccine (PCV-9), given in a 3-dose schedule, protected Gambian children against pneumococcal disease and reduced nasopharyngeal carriage of pneumococci of vaccine serotypes. We have studied the effect of a booster or delayed primary dose of 7-valent conjugate vaccine (PCV-7) on antibody and nasopharyngeal carriage of pneumococci 3-4 years after primary vaccination.

Methodology/principal Findings: We recruited a subsample of children who had received 3 doses of either PCV-9 or placebo (controls) into this follow-up study.

The immunogenicity and impact on nasopharyngeal carriage of fewer doses of conjugate pneumococcal vaccine immunization schedule.

The immunogenicity and impact on carriage of fewer doses of pneumococcal conjugate vaccine (PCV7) followed by booster with pneumococcal polysaccharide vaccine (PPV) were investigated. 684 infants were assigned randomly to one of the three groups that received one (A), two (B) or three (C) doses of PCV7 between 2 and 4 months of age, plus PPV at 10 months. Following primary vaccination protective antibody titers of >0.

Paperless registration during survey enumerations and large oral cholera mass vaccination in Zanzibar, the United Republic of Tanzania.

Problem: Field trials require extensive data preparation and complex logistics. The use of personal digital assistants (PDAs) can bypass many of the traditional steps that are necessary in a paper-based data entry system.

Approach: We programmed, designed and supervised the use of PDAs for a large survey enumeration and mass vaccination campaign.

A decline in the incidence of invasive non-typhoidal Salmonella infection in The Gambia temporally associated with a decline in malaria infection.

Background: Malaria is a risk factor for invasive non-typhoidal Salmonella (NTS) infection in children. In the last 10 years, indices of malaria infection in The Gambia have fallen substantially.

Methods: We compared temporal trends of childhood malaria and NTS infection in two Gambian locations.

Seasonality and outbreak of a predominant Streptococcus pneumoniae serotype 1 clone from The Gambia: expansion of ST217 hypervirulent clonal complex in West Africa.

Background: Streptococcus pneumoniae serotype 1 causes > 20% of invasive disease, among all age groups combined, in The Gambia. In contrast, it is rarely detected in carriage studies. This study compares the molecular epidemiology of S.

Molecular epidemiology of pneumococci obtained from Gambian children aged 2-29 months with invasive pneumococcal disease during a trial of a 9-valent pneumococcal conjugate vaccine.

Background: The study describes the molecular epidemiology of Streptococcus pneumoniae causing invasive disease in Gambian children

Methods: One hundred and thirty-two S. pneumoniae isolates were recovered from children aged 2-29 months during the course of a pneumococcal conjugate vaccine trial conducted in The Gambia of which 131 were characterized by serotyping, antibiotic susceptibility, BOX-PCR and MLST.

Results: Twenty-nine different serotypes were identified; serotypes 14, 19A, 12F, 5, 23F, and 1 were common and accounted for 58.