The Impact of Pneumococcal and Malaria Vaccines on Bacterial Resistance, Febrile Illness and Antibiotic Usage in Young Children in Malawi
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 13,200
- 试验地点
- 1
- 主要终点
- The antibiotic resistance profile of S. pneumoniae carriage isolates from children <3 years following a PCV13 schedule that extends protection (2+1 vs. 3+0) or the introduction of malaria vaccine (RTS,S/AS01)
研究概览
简要总结
Vaccination is a potentially critical component of efforts to arrest development and dissemination of antimicrobial resistance (AMR), though little is known about vaccination impact within low-income and middle-income countries. This study will evaluate the impact of vaccination on reducing carriage prevalence of resistant Streptococcus pneumoniae and extended spectrum beta-lactamase-producing Escherichia coli and Klebsiella species. We will leverage two large ongoing cluster-randomised vaccine evaluations in Malawi assessing; first, adding a booster dose to the 13-valent pneumococcal conjugate vaccine (PCV13) schedule, and second, introduction of the RTS,S/AS01 malaria vaccine.
Six cross-sectional surveys will be implemented within primary healthcare centres (n=3000 users of outpatient facilities per survey) and their local communities (n=700 healthy children per survey): three surveys in Blantyre district (PCV13 component) and three surveys in Mangochi district (RTS,S/AS01 component). We will evaluate antibiotic prescription practices and AMR carriage in children ≤3 years. For the PCV13 component, surveys will be conducted 9, 18 and 33 months following a 3+0 to 2+1 schedule change. For the RTS,S/AS01 component, surveys will be conducted 32, 44 and 56 months post-RTS,S/AS01 introduction. Six health centres in each study component will be randomly selected for study inclusion. Between intervention arms, the primary outcome will be the difference in penicillin non-susceptibility prevalence among S. pneumoniae nasopharyngeal carriage isolates in healthy children. The study is powered to detect an absolute change of 13 percentage points (ie, 35% vs 22% penicillin non-susceptibility).
This study has been approved by the Kamuzu University of Health Sciences (Ref: P01-21-3249), University College London (Ref: 18331/002) and University of Liverpool (Ref: 9908) Research Ethics Committees. Parental/caregiver verbal or written informed consent will be obtained prior to inclusion or recruitment in the health centre-based and community-based activities, respectively. Results will be disseminated via the Malawi Ministry of Health, WHO, peer-reviewed publications and conference presentations.
详细描述
Type of research study: A series of community and health centre based cross-sectional surveys
Problem: Pneumonia is a leading cause of child mortality globally and Streptococcus pneumoniae a leading cause of lower respiratory tract infections (LRTI) in under-fives. Malaria remains endemic in much of sub- Saharan Africa, commonly causing febrile illness in children and despite substantial progress with control programmes, Malaria continues to be a leading cause of child mortality. Vaccination is therefore an attractive solution.
Vaccines are thought to be crucial to Anti-Microbial Resistance (AMR) control but their impact on AMR may be more complex than originally thought. Both the direct and indirect impacts of vaccine on AMR require a systematic evaluation. In collaboration with the Malawi Ministry of Health, we are commencing two funded, regulatory approved, cluster-randomised evaluations of vaccines that target two of the commonest causes of febrile illness and life-threatening disease in children under 5 years in Africa: pneumococcal invasive infection, and malaria. This study will leverage two large funded cluster- randomised vaccine evaluations (13-valent Pneumococcal Conjugate Vaccine (PCV13) schedule change of 3+0 to 2+1 and RTS,S/AS01 (trade name Mosquirix) malaria vaccine introduction). We will assess the selective effects of pneumococcal and malaria vaccines on antibiotic resistance, febrile illness and antibiotic usage in children <3 years.
Hypothesis: Extending vaccine-mediated protection against Streptococcus pneumoniae through a 3+0 to 2+1 schedule change will be associated with a reduction in the prevalence of S. pneumoniae carriage isolates with increased AMR in children <3 years. The introduction of the malaria vaccine will reduce the frequency of healthcare attendances resulting in antibiotic prescription, reduce the prevalence of Extended spectrum beta-lactamases (ESBL) Escheriquia coli or Klebsiellae in the stool of children <3 years, and change the upper respiratory tract resistome profile in children <3years.
Aim: To establish the direct and indirect selective effects of pneumococcal and malaria vaccines on antibiotic resistance, febrile illness, and antibiotic usage in young children in Malawi.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 5 Months 至 3 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Permanent residence in Blantyre (PCV cohort) or Mangochi (RTS,S/AS01 cohort)
- •Parent/legal guardian consent
- •Evidence of having received an initial 2 or 3 doses of the PCV13 vaccine (survey 1) or the full PCV13 schedule (surveys 2 and 3: Either 2+1 or 3+0 depending on cluster) or full initial (+/- booster) course of the RTS,S/SA01 vaccine (in Mangochi intervention cluster).
排除标准
- •Current tuberculosis (TB) treatment
- •Terminal illness (Defined as a condition that cannot be cured and it is likely to lead to the individual's death)
- •Having received antibiotic treatment <14 days before study enrolment
- •Hospitalisation for pneumonia <14 days before study enrolment
- •Presence of gross respiratory tract pathology
- •For the HC audits, we will request to review the health information from attendees that comply with the following characteristics:
- •<3 years of age
- •HC attendance for investigation and/or treatment of ill health
结局指标
主要结局
The antibiotic resistance profile of S. pneumoniae carriage isolates from children <3 years following a PCV13 schedule that extends protection (2+1 vs. 3+0) or the introduction of malaria vaccine (RTS,S/AS01)
时间窗: less than 3 years
This outcome measure focused on assessing the antibiotic resistance profile of Streptococcus pneumoniae isolates obtained from nasal or throat swabs of children under the age of 3. We compared two different vaccination schedules for the pneumococcal conjugate vaccine (PCV13) through a 3+0 dosing schedule and through a 2+1 dosing schedule (two primary doses followed by a booster). Additionally, the impact of the introduction of the malaria vaccine (RTS,S/AS01) on the antibiotic resistance profile of S. pneumoniae isolates was evaluated. This outcome measure aimed to determine whether different vaccination schedules or the introduction of the malaria vaccine influenced the prevalence or patterns of antibiotic resistance in S. pneumoniae, a common bacterial pathogen associated with respiratory infections in young children.
次要结局
- The frequency of febrile illness and antibiotic use in children <3 years after PCV13 schedule change or malaria vaccine introduction.(less than 3 years)
- The stool carriage of ESBL E. coli or Klebsiella in children <3 years after PCV13 schedule change or malaria vaccine introduction.(less than 3 years)
- The change in the upper respiratory tract resistome in children <3 years after PCV13 schedule change or malaria vaccine introduction.(less than 3 years)
研究者
Thoko Kapalamula
Local Principal Investigator
Malawi Liverpool Wellcome Programme