An evaluation of the impact of the pneumococcal conjugate vaccine (PCV10) programme on invasive pneumococcal disease in Nigeria by using serial carriage studies and mathematical modelling

Principal Investigator: Ifedayo Adetifa
Institution: KEMRI Wellcome Trust Research Programme, Kilifi, Kenya (KWTRP; London School of Hygiene and Tropical Medicine (LSHTM)
Co-Investigators: Anthony Scott, John Ojal, Kofo Odeyemi, Victor Inem, Christy Okoromah, Aishatu Adamu, Musa Bello, Isa Abubakar

The World Health Organization (WHO) currently recommends that all countries introduce PCVs containing 10 (PCV10) or 13 (PCV13) serotypes in their immunisation programmes especially those with significant mortality in children aged <5 years.1 The first PCV, containing seven serotypes (PCV7), was licensed and introduced in the USA in 2000 and other developed countries followed suit.2 From 2009, PCV7 was replaced with formulations containing more serotypes – PCV10 and PCV13- in high income countries, because of an increase in IPD due to non-vaccine type (VT) pneumococci. This phenomenon also known as serotype replacement disease (SRD) was of such magnitude that it reduced the gains seen following PCV7 introduction.

Due to the high procurement costs, low and middle-income countries (LMICs) in Africa-South Africa and Gambia in April and August 2009 respectively- introduced PCVs almost a decade after the US. PCV is currently the most expensive vaccine in the routine immunisation schedule in Gavi-supported countries despite a preferential price of US$3.10 per dose. Consequently, there is a risk to sustainability of PCV programmes as these countries’ economies grow and they transition out of Gavi support. Although many African countries introduced PCVs over 5 years ago, only a minority - South Africa, Gambia, Rwanda and Kenya- have been able to report impact on pneumococcal disease endpoints. PCV introductions in these countries were also associated with complete or near complete replacement of VT serotypes in carriage and so far, a non-significant increase in SRD.

Nigeria has the largest birth cohort (~7 million) in Africa and therefore a potentially large burden of preventable invasive pneumococcal disease (IPD). It is one of the ten countries responsible for more than two-thirds of the global pneumonia deaths among children <5 years. With an estimated 6.7 million cases of pneumonia and IPD resulting in over 100,000 deaths, Nigeria is thought to have largest burden of pneumococcal disease in Africa. A phased PCV10 introduction commenced in 2014 and only just attained national coverage (in 36 states and Federal Capital) in 2016. Like other LMICs in Africa, this PCV10 programme is significantly subsidised by Gavi. The Nigerian Immunisation Programme anticipates the gap in immunisation financing will increase from $5.0 million in 2017 to $201 million by 2021, when current Gavi support terminates. In addition, Nigeria like most other African countries, does not have the mature surveillance systems required to generate evidence of vaccine impact on pneumococcal disease necessary for cost effectiveness analyses. Yet, local evidence of vaccine impact on pneumococcal disease will be required to make policy decisions in favour of continued investments in this expensive vaccination programme. At this point, setting up population-based surveillance for pneumococcal disease for the purpose of assessing vaccine impact is impractical and too late for Nigeria and many low-income countries who have already introduced PCVs.

In the absence of IPD surveillance, the use of changes in nasopharyngeal carriage complemented by mathematical models for predicting PCV impact on IPD is an attractive alternative. Carriage is more frequent and prevalent in populations compared to disease endpoints, carriage surveys are also less expensive and require less technical skills than clinical and laboratory disease surveillance. Methods for obtaining and transporting swabs; culturing and serotyping pneumococcal isolates have also been standardised to reduce study variability and to facilitate unbiased interpretations. Estimates of protection against carriage can provide measures of direct and indirect protection and this level of protection can be monitored in the long term via sequential carriage surveys. Mathematical models are attractive options for assessing vaccine impact because they can use minimal data to make predictions of vaccine impact. The following mathematical models have been used by us and others to predict the impact of PCV on carriage and IPD with reasonable accuracy. 

As an alternative to setting up IPD surveillance, we propose to demonstrate the utility of serial carriage data for estimating PCV10 impact in Nigeria-as an example of a setting with very high burden of IPD with no disease surveillance in place. We had previously reported very high pneumococcal carriage prevalence in Nigerian populations (>40% across all ages). Our overall aim is to use vaccine-induced changes in the prevalence of pneumococci in carriage to model the impact of PCV10 on IPD, to estimate cost effectiveness in Nigeria and link these to local vaccine policy.