Pneumonia accounts for 15% of deaths among children under-5 years of age globally. The burden of disease is especially high in South Asia, where one in four children suffer an episode of pneumonia every year. Streptococcus pneumoniae is one of the most significant causative pathogens of pneumonia and other serious invasive diseases.

Nepal research team Eric Montfort

One important strategy to help reduce under-five mortality to 25 per 1,000 live births by 2030 (Sustainable Development Goal 3) is the reduction in the burden of pneumococcal disease through the use of pneumococcal glycoconjugate vaccines (PCVs). These vaccines can reduce pneumococcal disease burden among vaccine recipients (i.e. direct protection) and in unimmunized community members (i.e. indirect effect). These effects are mediated in part, or entirely, by the ability of PCVs to reduce acquisition and density of vaccine serotype nasopharyngeal colonization, which is the biological precondition for progression to pneumococcal disease. The individual and community level impact of PCV on nasopharyngeal colonization is therefore an important endpoint in PCV impact assessments. Furthermore, the assessment of PCV on nasopharyngeal colonization provides critical data on the degree to which replacement carriage (i.e., increased carriage prevalence by non-vaccine serotypes) occurs, a key issue in determining overall impact on pneumococcal disease burden. 

Currently few data are available on the effectiveness of PCVs in South Asia. Although clinical trials have provided substantial evidence around the efficacy of PCV products, local and regional data on the impact of PCV in routine use are also important. Robust data are needed to document and quantify the scale and value of disease control provided by pneumococcal vaccines in order to underpin the financial commitments. 

PCV 10 was introduced in western Nepal in February 2015, but launch in Kathmandu and other eastern regions was delayed until July, perhaps in part due to the massive earthquakes that occurred near Kathmandu in April.  Currently PCV is given in a 2+1 schedule: one dose each at 6 and 10 weeks and a third at 9 months. This novel schedule was motivated by a desire to avoid more than two injections at any single visit; with the introduction of IPV in late 2014, which is given at 14 weeks, the second PCV dose was moved from 14 weeks to 10 and is given with pentavalent and OPV. Targeted Assessment study sites are at hospitals throughout the country, in rural and urban areas, including main study site at Patan Hospital in Kathmandu. Partner organizations include Patan Hospital, Nepal Ministry of Health, Patan Academy of Health Sciences Paediatric Faculty (PAHS), Nepal Pediatric Society (NEPAS), Oxford Vaccine Group (OVG), and the Bacterial Microarray Group at St. George’s (BuGS).

Gavi is supporting several assessments in Nepal, focusing on the effectiveness of PCV10, immunogenicity of PCV10 and economic impact of PCV10. The studies are important for Gavi and country to demonstrate the effectiveness of this vaccine (particularly given slower uptake of PCV in Asia) and to learn more of potential economic benefits. Studies began in 2014. 

Aims

  • Community Carriage study (pre/post-vaccine introduction):
    • NP Carriage
    • Prevalence
    • Density of colonization
    • Serotype distribution
  • Inpatient carriage & surveillance studies (pre/post-vaccine introduction):
    • Relative risk of VT vs. NVT carriage in pneumonia+ cases
    • Relative reduction in proportion of VT hospitalized pneumonia cases
    • Time trends in hospitalized pneumonia incidence & serotype distribution
  • Temporal association of PCV on hospitalized pneumonia and meningitis(pre/post vaccine introduction):
    • Pneumonia (all cause and severe) hospitalizations
    • Meningitis hospitalizations
  • Immunogenicity of PCV10 (RCT):
    • Proportion of kids in each group (second dose at 10 weeks or 14 weeks) considered immunogenic (IgG at or above 0.35 ug/ml) at 1 month following 2nd dose, 9 months, and 10 months
    • Overall mean IgG serum concentration for each group
  • Economic Impact of PCV:
    • Cost of illness (pre vs post)
    • Catastrophic payments?

Laboratory Research

Childhood pneumococcal pneumonia in Nepal: novel immunodiagnostic methods and transcriptomic investigation of aetiology (PANDIT):

This study aims to

  • Determine the potential of antibodies from lymphocyte supernatant (ALS) assay as a diagnostic test for pneumococcal infection in children with clinically diagnosed pneumonia.
  • Examine the utility of transcriptomic methods to diagnose and investigate pneumococcal disease in children with pneumonia.

 

Bacterial and Host Molecular Determinants of Pneumococcal Carriage in Nepalese Children:

This study aims to determine

  • The molecular epidemiology of pneumococcus carried by Nepalese children
  • The host genomic determinants of pneumococcal carriage. 

Our team