Vaccines and antibiotic resistance: A conversation with Dr. Keith Klugman

Written by
Longitude team
Dr. Keith Klugman

Dr. Keith Klugman is Director for Pneumonia at the Bill & Melinda Gates Foundation, where he leads the foundation’s work to combat the leading cause of child mortality worldwide. 

One of the world’s foremost experts on antibiotic resistance in pneumonia pathogens, Dr. Klugman helped develop the pneumococcal conjugate vaccine (PCV) that’s now part of the immunisation programme in the US and is being rolled out globally.

Today, six years into the 'Decade of Vaccines', (a global action plan to deliver universal access to immunisation by 2020), the PCV-10 and PCV-13 vaccines have reached more than 70 million of the world’s most vulnerable children in 54 Gavi-eligible countries (nations that qualify for support from the global vaccine alliance). 

For World Immunisation Week, we spoke to Dr. Klugman about his work to combat pneumonia, and the potential for new and existing vaccines to tackle antibiotic resistance. 

1. How did you become interested and involved in vaccinations, and in combatting pneumonia specifically?

Pneumonia is the leading infectious cause of death in both adults and children, and the pneumococcus bacterium is the leading cause of those deaths.

Since prevention is better than cure, once the proof of concept to make a pneumococcal vaccine was discovered, I was passionate about getting a vaccine into the developing world (where factors such as malnutrition have a huge impact on survival rates and the majority of deaths from pneumonia occur). 

2. How is drug resistance affecting pneumonia and how can vaccines – and PCV specifically – help tackle antibiotic resistance?

Drug resistance affects nearly all infectious diseases; in pneumonia it has its biggest impact in newborns.  

PCV was proven in a large trial, which we conducted in Soweto, South Africa, to reduce drug-resistant infections (most of the strains that have shown resistance are the same strains that are targeted by the PCV-10 and PCV-13 vaccines). 

However, in addition to preventing drug-resistant infections, prevention of drug-susceptible infections also means less infection overall and therefore less antibiotic use. In fact, as use drives resistance, even vaccines for viral infections such as influenza can help reduce resistance for bacterial infections, as fewer antibiotics are used if there are fewer influenza infections (clinicians don’t usually know if the infection is bacterial or viral, so many viral infections are treated with antibiotics).

3. Last year’s report from the AMR Review called for wider use of vaccines to tackle AMR, noting that universal global coverage of PCV specifically could prevent 11.4 million days of antibiotic use per year in children younger than five. How are you working to improve access and uptake of PCV in developing countries? 

PCV access was transformed by the Advance Market Commitment, (a financial commitment from Italy, the UK, Canada, Russia, Norway and the Bill & Melinda Gates Foundation, to the tune of US$1.5bn) which allowed Gavi to promote the introduction of PCV into developing countries.

Thanks to these partnerships, low-income countries have made great strides in preventing pneumonia-related deaths in recent years. Today, the burden of pneumonia continues to shift to middle-income countries, which collectively will soon bear the majority of the world’s unvaccinated children.

To make PCV more affordable for middle income countries, we are also supporting developing country manufacturers to make PCV locally. 

4. The AMR Review found there were no licensed vaccines for any of the bacteria considered by US CDC to represent the most urgent drug-resistance threats (two of which were also featured on WHO’s list of priority pathogens), and few in the pipeline. What are the biggest roadblocks preventing progress in this area and where is there greatest scope for new vaccines to make a difference?

Most of the WHO target pathogens cause hospital infections; it’s difficult to predict who will get hospitalised and therefore who are the target group to get immunised – many hospitalised patients are also immune compromised so they respond poorly to vaccines.

Another group who get these infections though are newborns, so we at the foundation are looking to see if there are vaccines against these pathogens we can develop to give to their mothers, so that their mothers’ antibodies can protect their newborns, or to develop monoclonal antibodies that can be given to newborns to protect them from the multi-resistant pathogens.