The landscape of paediatric infectious disease exposure in a rural sub-Saharan Africa setting in Kilifi, Kenya: longitudinal serological analysis over two decades and priorities for future vaccine development

  1. Deirdre F Foley
  2. Timothy K Chege
  3. Joyce Kabagenyi
  4. Karen McCarthy
  5. Elijah T Gicheru
  6. Nelson Kibinge
  7. Angela W Maina
  8. Jacqueline M Waeni
  9. Ralf Clemens
  10. Sue-Ann Costa Clemens
  11. James Tuju
  12. Charles J Sande

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Abstract

Background

The paucity of data on the contemporary causes of serious infection among the world’s most vulnerable children means the landscape of emerging paediatric infectious disease remains largely undefined and out of focus on the global vaccine research and development agenda.

Methods

We aimed to partially define the paediatric infectious disease landscape in a typical low-income setting in sub-Saharan Africa in Kilifi, Kenya by simultaneously estimating antibody prevalence for 38 infectious diseases using a longitudinal birth cohort that was sampled between 2002 and 2008 and a paediatric inpatient cohort that was sampled between 2006 and 2017.

Findings

Among the infectious diseases with the highest antibody prevalence in the first year of life were vaccine-preventable diseases such as RSV (57.4%), mumps (31.5%) and influenza H3N2 (37.3%). Antibody prevalence for Plasmodium falciparum shifted substantially over time, from 47% in the mid 2000s to 13% approximately 10 years later corresponding to a documented decline in parasite transmission. A high prevalence of antibodies was also observed in the first year of life for infections for which no licenced vaccines are currently available, including norovirus (34.2%), cytomegalovirus (44.7%), EBV (29.3%) and coxsackie B virus (40.7%). The prevalence to antibodies to vaccine antigens in the local immunisation schedule was generally high but varied by antigen.

Interpretation

The data show a high and temporally stable infection burden of RSV, mumps and influenza, providing a compelling evidence base to support progress towards the introduction of these vaccines into the local immunization schedule. The high prevalence of norovirus, EBV, CMV and Coxsackie B provide rationale for increased vaccine research and development investment.

Funding

This research was funded by the Wellcome Trust (grant no. WT105882MA).

Article activity feed

  1. PREreview

    This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/13894074.

    Does the introduction explain the objective of the research presented in the preprint? Partly What justification explains the inclusion of only 38 infectious diseases ? Are these the only infectious diseases causing mortality in children within SSA?
    Are the methods well-suited for this research? Somewhat appropriate We think the authors didn't control for the confounding effects. The relationship between age and anti-body titre can be confounded by sex, socioeconomic status, nutritional status (malnutrition affects immune status), or even behavioral status. Second, authors could have regressed the anti-body levels against time while controlling for confounding effects, thus permitting the report of an adjusted p-trend. The difference between serological measures between the birth and in-patient cohorts could be interacted with time with probably repeated ANOVA. This could help visualize the sphericity in differences between the two groups in time; if that ever existed, then probably use cox-harzard model.
    Are the conclusions supported by the data? Somewhat supported We think the results are well discussed to suit the study objective (s) however, due to the limitation of not controlling or properly managing the confounding effect, we have some reservations about the conclusion being made.
    Are the data presentations, including visualizations, well-suited to represent the data? Highly appropriate and clear They present results appropriately, well captured and titled.
    How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research? Very clearly The authors explained it is the first study in this capacity in Africa, recommending the conduct of similar studies and vaccine developmentfor diseases that do not yet have one.
    Is the preprint likely to advance academic knowledge? Highly likely 1. The idea of comparing different cohorts of childbirth to advance knowledge in terms of preventing child mortality and development in medical research advancement(vaccine development). 2. It also helps in surveillance for available vaccine effectiveness
    Would it benefit from language editing? No The language is appropriate and can be understood by the target audience.
    Would you recommend this preprint to others? Yes, but it needs to be improved There is a need for minor revision or acknowledgment of confounding effects.
    Is it ready for attention from an editor, publisher or broader audience? Yes, after minor changes

    Competing interests

    The authors declare that they have no competing interests.

  2. PREreview

    This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/13118424.

    Foley et al's study titled "The landscape of paediatric infectious disease exposure in a rural sub-Saharan Africa setting in Kilifi, Kenya: longitudinal serological analysis over two decades and priorities for future vaccine development" presents significant public health implications, particularly in the context of introducing new vaccines and enhancing existing ones in the region under investigation. The research focused on addressing prevalent infectious diseases in Kilifi County, Kenya through the utilization of an indirect method involving antibody measurement. Despite the limitations associated with using antibody measurement for diagnosing infectious diseases, the study made efforts to minimize potential interference from maternal antibodies and antibodies resulting from previous infections.

    Major comment

    ·         The rationale for this study is based on the limited research conducted in the field. It is essential to thoroughly review previous studies on pediatric infectious diseases in specific regions and study area to identify gaps and to explain the preference for seroprevalence over other laboratory methods.

    ·         The term 'rural' needs to be clearly defined to provide context for the study. It is important to determine whether the entire Kilifi County in Kenya can be classified as rural or if there are specific criteria that need to be met.

    ·         Including information on the types of vaccines administered in Kilifi County, Kenya would be beneficial for the study. Understanding the vaccination practices in the region can provide valuable insights into the prevalence and prevention of pediatric infectious diseases.

    ·         The clarity of page 6 lines 141-146 is lacking. Within the method section, it is necessary to provide a clear definition of infection, as mentioned in the manuscript, where multiple blood samples were obtained from a single participant over a period of 3 months. It is important to specify which of these samples were utilized to define infection and temporally stable infection.

    ·         Antibodies can suggest exposure to a pathogen, vaccination, or passive acquisition from the mother. It is advisable to incorporate the vaccination status of participants. What is the rationale behind selecting 38 pathogens for consideration? Why were other pathogens like GBS, HIV, TB, Syphilis, Hib, etc. not included in the study?

    ·         The information regarding where the study took place, the group from which the participants were drawn, the individuals included in the study, how participants were chosen, and the requirements for inclusion were not adequately described.

    ·         Was consent obtained for this procedure, and what was the amount of blood collected (assuming it was a blood sample)? Additionally, could you provide details on how and from where the blood sample was obtained?

    ·         The results section lacks sufficient socio-demographic information about the participants, such as their sex, nutrition status, vaccination status..etc.

    ·         The manuscript lacks a clear definition of the term "pediatric," as it seems to overlap with the categories of infants and newborns. It is essential to provide a precise and distinct definition for each of these terms to avoid any confusion or ambiguity in the text.

    ·         Monitoring infants over time and tracking antibody levels may not provide a complete picture of the infection landscape, as existing antibodies can interfere with the results. It is important to take into account different infants at different time, as interference from existing and maternal antibodies can impact the accuracy of the findings. Additionally, there are various factors that may prevent infants from producing antibodies, potentially leading to false negative results.

    ·         On page 12, lines 307 to 311 of the discussion, it is possible that the interpretation may not be accurate, as a decrease in antibodies could indicate susceptibility to infection. It is important for vaccinations to maintain a sufficient level of antibodies in the bloodstream to protect against the specific pathogen targeted by the vaccine.

    ·         In cases where participants test positive for a certain condition or disease, it is crucial to provide appropriate support, counseling, and medical care.

    ·         Is it ethically justifiable to collect several blood samples from one participant?

    Minor comments

    ·         Page 5 line 116 was the PCR used? Line 118 what does pl stand for in 100/pl?

    ·         It is recommended to incorporate both frequency and percentage instead of just percentage in order to enhance clarity in the abstract and results section.

    ·         The placement of the table heading at the top would enhance the overall organization and clarity of the information presented.

    Competing interests

    The author declares that they have no competing interests.

  3. Version published to 10.1101/2024.01.10.24300883v1 on medRxiv