Earlier last week, the findings from two critically important studies on the use of the Rotarix vaccine (produced by GSK-biologicals) to combat rotavirus related diarrhea in the developing world. After prenatal causes and pneumonia, diarrhea is the most important cause of child deaths in the world – accounting for an estimated 16% of under five mortality. Most of the tools to combat the disease – oral re-hydration therapy and clean water and sanitation – have not been adequate to reduce the burden of this seemingly simple condition, perhaps because the needed behavioral response is not so easy after all. The study results overall were very positive, which is really great news, but it also raised a few important caveats which may limits its overall impact in the long run.
Rotavirus is considered to be the single largest cause of diarrhea globally and alone thought to be responsible for upwards of half a million child deaths a year. Six of the seven countries with the highest mortality due to rotavirus are in Africa (can anyone guess the other one?). Vaccines against rotavirus have been introduced in the past – and one has even been withdrawn – but their use has become increasingly common in many middle and high income countries in recent years. The world had been waiting for the results from the studies released last week.
One study, conducted in South Africa, and Malawi demonstrate that when the vaccine is given properly, it reduces all forms of reported diarrhea by about 30% and reduced the incidence of rotavirus induced diarrhea by 60% although the results were much higher in South Africa. There were not major differences in severe events, suggesting that the vaccine was also safe.
But why was there such much lower efficacy in Malawi? The results from this African study suggest that the vaccine is less efficacious in Africa than in other settings where the vaccine has been tested. There is some evidence that live oral vaccine in general tend to be less effective in low income countries, perhaps because they require an in tact and effective immune system to generate a sufficient immune response to provide protective benefits. It is also possible that children in these settings are also already exposed by the time they get the vaccine, making the vaccine seem less effective when studied in trial settings.
Also, the study findings point to a story where the timing of when this vaccine appears to matter quite a bit – not just or the sake of protecting children earlier, but or the sake of avoiding age-dependent risk of developing intussusception, a rare but dangerous side effect which was part of the reason that earlier forms of the vaccines were not expanded to the developing world. There are frequently delays in vaccine timing in many developing countries, so this might represent a real challenge precisely in the countries where it is needed most.
Plus, since this is a live oral vaccine, the cold chain considerations for this vaccine are likely to be much more important than for other forms of vaccines.
The second study, conducted in Mexico, assessed the impact of rotavirus vaccine introduction in Mexico on child mortality rates. Mexico is obviously a much richer country than Malawi and South Africa, but rather sizable declines in mortality were observed. Rates of diarrhea related deaths reduced from 61.5 to 36.0 deaths per 100,000. While not all of this can be directly related to the vaccine, it is notable and incredibly good news as I would see this as a lower bound of what might be expected in poorer countries.
So overall, really promising news on the rotavirus front – there should be no reason to hold back plans to roll this vaccine out in the poorest countries as soon as possible. But lots more attention needs to be given to the additional challenges of delivery this particular vaccine. Good thing Bill Gates has doubled his commitments to childhood immunizations…I know how I would spend some of that big chunk of change.Share on Facebook