Pneumonia is one of the greatest threats to children worldwide, with over 2 million children dying each year from the disease. The Gambia in West Africa is no exception. There, pneumonia is one of the leading causes of death among children under the age of five. 

The disease is often caused by the bacterium Streptococcus pneumoniae, which varies in virulence, depending on its form. Fortunately the bacteria can be targeted by a widely available vaccine called Pneumococcal Conjugate Vaccine-7, or PCV-7. Its name denotes its effectiveness against 7 forms, or serotypes, of the bacteria. Pneumococcus has over 90 serotypes and the vaccine is directed against its most dangerous regions.

The Genome Institute is collaborating with researchers in the Gambia to understand why these pneumococcus bacteria are so deadly and how the vaccine affects the microbial populations that colonize infants. This global collaboration has turned out to be a key part of the research.

“Genomics has an important role to play in global health research, but it’s under-developed because of access,” says Dr. George Weinstock, Associate Director of The Genome Institute. “Many laboratories don’t have access to state-of-the-art DNA sequencing and its associated computational and analysis methods. We wanted to collaborate and help export sequencing and computational technologies for use in public health problems.” 

The project began by sequencing the genome of a single pneumococcus bacterium that was causing pediatric infections in the Gambia. Over time it has expanded to include over 20 different strains representing a range of infections. Most of the African bacteria were more virulent than those in the US.

Tiffany Williams, a recent graduate from Dr. Weinstock’s lab, has played a large part in the pneumococcus sequencing project. She has been looking at the difference in pneumococcus and its disease severity in the Gambia as compared to the US and the UK. In African countries, like the Gambia, one form of pneumococcus - called serotype 1 - is responsible for a great deal of morbidity and mortality. In the US and the UK, though, serotype 1 has little to no effect on the population.

By culturing children’s bacteria from clinical cases in the US, UK and the Gambia, Tiffany and colleagues sequenced the samples to compare them at the genomic level. Using next generation sequencing technology, they compared the genes and single letters of the DNA in the bacteria from the US and UK samples with the African samples. They found that the US and UK samples differed vastly from the Gambian ones, providing insight into which genes cause increased virulence. Before drawing any final conclusions, they still need to sequence more samples from additional locations to rule out natural variation. But the preliminary results give them the starting material for solving this puzzle.

The researchers are also considering certain theories as to why there are differences in pneumococcus across the different continents. Looking at older bacterial samples, they found that prior to the 1950s the US had pneumococcus infections that seemed more closely related to the current African serotype 1. “At that time in the US pneumococcal deaths were one of the most common infectious disease-related deaths. Then around the 1950s the disease disappeared and no one knows why,” says Tiffany. Perhaps some event – such as improved housing, public health efforts, etc. - could have caused the virulent US bacteria to disappear, while the less virulent bacteria became more prevalent. The African countries may not have experienced such an event, which may be why they continue to harbor the virulent serotype 1 version of the bacteria.

Much of this work has been done in collaboration with the Medical Research Council (MRC), a UK-based program that has long been involved with tropical medicine research in the Gambia and many other developing countries. Brenda Kwambana is a graduate student with the MRC who works closely with Dr. Martin Antonio, an MRC molecular biologist who leads the pneumococcus work. Originally from Zimbabwe, she has spent part of her research time in the Gambia looking at the impact of the PCV-7 vaccine on the bacterial composition of an area deep within the nose (between nostrils and respiratory passage) called the nasopharynx.

There are myriad bacterial species that reside in the nasopharynx, all of which make up what’s called the ‘microbiome’ of that region. “Compared to other parts of the human body, the nasopharyngeal microbiome has huge gaps that still need to be closed. It’s a very important ecological reservoir that’s clinically significant,” says Brenda. Using the PCV-7 vaccine to eliminate certain pneumococcus serotypes from this region may alter that microbiome and allow other forms of pneumococcus or deadly bacterial species to grow in its place, something Brenda hopes to understand better with this research.

After collecting over 1500 samples from more than 100 children from the nasopharyngeal regions of vaccinated and unvaccinated Gambian infants, Brenda came to The Genome Institute to sequence the samples on next generation sequencers. With the help of the institute’s high throughput sequencing and analysis skills, Brenda and colleagues were able to characterize what types of bacteria colonize the nasopharyngeal regions and the effects of vaccination on the make-up of those bacteria.

This work will have important implications for pneumococcus vaccine research by providing new targets and determining the long-term effects of vaccination. The research is also providing valuable skills to young researchers like Tiffany and Brenda who hope to continue clinical research in countries such as the Gambia. “Part of this project is to train other scientists and help them figure out how to bring what they’ve learned back to their country so they can apply it at a local level,” says Dr. Weinstock. Over time, he hopes this kind of research will help implement genomic-based tools for use by clinicians and public health officials around the world.