Progress for child survival: Infectious diseases

ANDREW PRENDERGAST: So one of the most remarkable achievements I think in global child health has been the huge reduction in child mortality over the last 50 years. If we were having this interview in the 1960s, around 30 million children a year were dying, predominantly from infections, and now that number is just over 5 million, so remarkable gains in child survival. Clearly, still too many children each year around the world die. That’s around 15,000 children a day. But there have been incredible achievements, particularly in reducing infections by prevention measures, like vaccination, but also in better case management of common infections, like diarrhoea, through things like use of oral rehydration solution.

So vaccination has clearly been an enormous success over the last 50 years. Diseases like measles, rotavirus, diarrhoea, pneumonia, sepsis, meningitis, all now have effective interventions with high coverage globally, and there’s exciting new prospects on the horizon with malaria vaccination, dengue vaccination, now becoming available, although each come with its own challenges. One of the big success stories has been the development of oral vaccines. The advantage of those is that they can be given at scale very readily without the need for needles, for example. And they provide really long term protection, particularly for diseases like enteric infection, where they act in the gut, where the infection is going to be met. However, there are challenges.

So for example, rotavirus vaccination, which is incredibly effective in high income settings, is much less effective in low middle income countries. So for rotavirus for example, in studies in Europe and the US, over 90% of children respond well and make a good immune response to the vaccine, whereas in studies in sub-Saharan Africa, that number is more like 20% to 30%. So there is a vaccine gap, an efficacy gap, which we need to really understand better, and a lot of research at the moment is trying to figure out why the vaccine works less well, where it’s actually most needed. If we could understand that, then we could actually improve the performance of those vaccines and get even greater gains.

So there are interventions that we know are really effective to prevent infections, but they don’t necessarily get implemented at the coverage we would like. So a good example is a really simple intervention, like optimal breastfeeding. So there’s really three components to breastfeeding. One is early initiation, that children should start breastfeeding within the first hour of life, and that’s clearly associated with improved child survival. The second is exclusive breastfeeding, and that means that a child only takes breast milk, they take no water, food, or other non breast milk substitutes. And actually optimal exclusive breastfeeding probably averts about 10% of under five mortality, yet it’s pretty poorly taken up.

And so there is an area where actually we could improve early and exclusive breastfeeding. The third component is prolonged breastfeeding through to 12 to 24 months of age. And again, together these three interventions are clearly incredibly effective, scalable, low cost, and yet we need more work to figure out how to improve coverage of that simple intervention. So I think one of our biggest challenges is still neonatal mortality. Increasingly, neonatal mortality is a larger fraction of all child deaths, and so now, more than half of child deaths are in the first month of life, the neonatal period. And we really don’t yet have very effective interventions to reduce mortality from infections during that period.

One of the challenges is that the most vulnerable children are those who are born with low birth weight, and there’s two key factors that cause low birth weight. One is a child born too small for their gestational age, and one is a child who is born too early. And so it’s really these sick, vulnerable, newborn babies who are at particular risk of infection, and that’s an area where we really need to understand more. It’s probably harder to intervene with vaccination, although we do have some vaccines that are highly effective in that very early life period.

We really need to understand what interventions we could implement, maybe even before birth, firstly to improve infant size, but also to prevent infection from the moment they’re born. And so that’s an area of really active research. By 2030, one in three children will be born in Africa, and there has been much less progress in reducing neonatal mortality, compared to post neonatal mortality. So it’s really an area where we need to focus efforts from now on. So I think newborn babies are an example of a particularly vulnerable group to infections who really need to be targeted for prevention approaches. But there are other groups who are highly vulnerable as well. So one is children who are undernourished.

So undernutrition is still a huge problem globally, and actually, some of the most common forms of undernutrition are really invisible. So stunting, where a child is too short for their height, affects almost one in four children globally and is really a hidden problem. Children appear healthy. They’re just a little short for their age. But we know those children have more infections. They have more morbidity. They have higher mortality for reasons we don’t fully understand. But they’re clearly a group who are in need of probably targeted interventions. Another group would be children who have been hospitalised.

So we know that hospitalisation marks children out as being of particularly high risk over the subsequent months, and it’s probably because children come into hospital with vulnerabilities. They leave before they fully recuperated from all of the effects of an infection in hospital, and they go back to the same home environment, which may be an impoverished environment. And so there are increasing realisations that we need to target that group in particular. One trial at the moment, for example, is giving antibiotics routinely to children as they leave hospital with the aim of keeping them protected over the subsequent weeks and months. Probably, it requires even more than that. It may require packages of interventions that really targets the vulnerabilities children have.

So for example, nutritional status, full restoration of health and physiological processes, as well as preventing infection over the coming weeks. One of the most interesting approaches in the last couple of years has been actually evaluating giving mass antibiotics at scale as a way of reducing child mortality. So this followed interesting observations in East Africa, where trachoma programmes, which were giving out single doses of an antibiotic called azithromycin to prevent the common eye infection, trachoma, that they discovered a side benefit was that it halved child mortality. So specific trials were designed to actually evaluate across three countries whether that strategy would improve child survival even if we weren’t treating trachoma.

And actually, there was a significant reduction in mortality by going into communities and giving a single dose of azithromycin to under five children every six months. Now, the question that arises, of course, is whether that’s a sensible strategy to be employing at scale, because quite rightly, people worry about resistance to antibiotics, about them becoming less effective over time, and that’s an interesting tension, because we have an intervention that clearly works, is very scalable, it reduces child mortality, and yet we also need to be mindful of the potential long term consequences.

So there’s a lot of global dialogue at the moment about whether this is a scalable approach that really should be used in a public health approach in high mortality countries. Two other really exciting areas in the last few years in adult infectious diseases have been advances in treatment for TB, for hepatitis C. So in TB now, there is evaluation of much shorter and more simplified treatment approaches, and that’s potentially a real game changer for TB. It’s still a very common infection. One in three people in the world are infected with TB, even if it’s not yet causing disease.

And what we need is better prevention approaches for children– those are being evaluated at the moment– and also these shorter regimens to be translated into paediatric care, because keeping a child on treatment for six to nine months of treatment is really difficult. So anything we can do to simplify that is going to be an enormous advantage. Hepatitis C is another area where there’s been enormous strides in adults with hepatitis C over the last few years. It’s now possible to cure hepatitis C with a completely oral regimen of drugs over 8 to 12 weeks. So this is not just controlling infection. This is eliminating hepatitis C. Again, children lag behind. There’s been less evaluation of these new regimens in children.

And actually, we know remarkably little about how to prevent hepatitis C transmission to children during pregnancy. So there’s a lot of work to be done, but an exciting time for hep C, because we now have really good tools available that are much simpler and shorter and now need to get into children as well. So as we have these enormous gains in child survival, we’re really shifting the global agenda to go beyond just survival to really making sure children thrive, develop well, grow properly and lead productive lives.

And so really this shift from pure child survival to what we might call thrival has really been one of the big changes in the last few years during this epidemiological transition that we’re seeing as we move away from infectious disease burden towards non-communicable disease. And although people often think of that as being something that only affects adults and people later in the life course, in fact, the origins of that occur very early in life, in foetal life or even preconception. So increasingly, we’re thinking as we implement interventions, not just about the short term effects in keeping children alive, but actually in trying to improve their growth, their development, and their long term metabolic health.

And so this is the way we’ve really sort of shifted in thinking in the last few years.