̽��ֱ�� of Cambridge - Gianni Lo Iacono

New model could help improve prediction of outbreaks of Ebola and Lassa fever

cjb250 — Fri, 02 Sep 2016 18:00:41 +0000

Many of the major new outbreaks of disease, particularly in Africa, are so-called zoonotic infections, diseases that are transmitted to humans from animals. ̽��ֱ��Ebola virus, for example, which recently killed over 11,000 people across Africa, was most likely transmitted to humans from fruit bats.

Modelling how outbreaks arise and whether they will take hold or quickly die out has proved challenging, with two factors in particular being difficult to quantify. ̽��ֱ��first is ‘spillover’, where the pathogen – a virus or parasite, for example – passes from an animal to a person. This can be through direct transmission, for example by being bitten or by eating ‘bush meat’ (wild animals such as fruit bats or monkeys that are caught and consumed), or indirectly, such as through contact with faeces or disease-carrying mosquitoes.

In many cases, a spillover will go no further. When a human is bitten by a rabid dog, they may become infected, but as the disease cannot transmit from human-to-human, the disease hits a dead end.

However, in some cases the infected person goes on to infect other humans. This is the case for diseases such as Ebola, Lassa fever (spread from rodents) and Crimean Congo haemorrhagic fever (spread from ticks). But in many cases, unless there are additional spillover events, the disease eventually fades out. This is referred to as a ‘stuttering chain’, and even though the disease is transmitted from human-to-human, they are still considered to be zoonotic infections.

Diseases such as HIV, however, which almost certainly began as a spillover from chimpanzees, are no longer considered to be zoonotic as the chain of transmission from humans to other humans is continuous and no longer relies on spillover to sustain transmission.

“Modelling spillovers is a real challenge,” says Dr Gianni Lo Iacono from the Department of Veterinary Medicine at the ̽��ֱ�� of Cambridge. “We don’t have particularly good data on wildlife numbers, such as fruit bats in Sierra Leone, and only a crude idea of their geographic distribution and how many are infected. Even in the UK, we don't really know how many deer we have, which would be really useful to estimate the risk of Lyme disease.”

In addition, measuring the likelihood of contact with the infected animals is also extremely difficult as it involves understanding human and animal behaviour.

Stuttering transmission, too, can be difficult to model, says Dr Lo Iacono. “In the case of Lassa fever, people who catch the disease from animals show the same symptoms as those who get it from humans. So is this case a spillover or part of a human-to-human chain of transmission? And if members of the same family get the disease, have they caught it from a family member or from the same pot of contaminated rice?

“Sometimes you can be lucky and work this out, as we did in a previous study, but this was possible because information of outbreaks that were known to be pure human-to-human chains was, unusually, available. But we need more general methods.”

Dr Lo Iacono and colleagues have developed the most coherent and potentially most accurate mathematical model to date for zoonotic diseases, which incorporates spillover and stuttering transmission.

“ ̽��ֱ��pathogen does not care if it jumped from an animal or from another human; the only difference is that in a stuttering transmission an infected person can trigger other chains of human infections. A general, realistic model should capture this mechanism,” adds Dr Lo Iacono.

Details of the model, including a demonstration applying the framework to Lassa fever, are published today in the open access journal PLOS Neglected Tropical Diseases.

“By modelling potential outbreaks more accurately, we can help inform public health messages,” explains Professor James Wood, Head of the Department of Veterinary Medicine, and senior author. “If you know that most cases of an outbreak of Lassa fever come from spillovers, then the message might be ‘kill the rats’, but if it is now mainly spreading between humans, the messages will be around washing your hands or avoiding contact with bodily fluids.”

̽��ֱ��beauty of the model, say the researchers, is that it is simple to implement, so public health officials and non-mathematicians could easily use it. It also allows for the incorporation of data from different disciplines, factoring in socioeconomic, ecological and environmental factors, for example.

“It’s important to understand if and how these other important factors can increase the impact of stuttering chains,” says Professor Wood. “Ebola has always been a very severe disease but previously confined to small, remote regions. Then suddenly, in the last two years it exploded in West Africa. Why? Was it because social patterns changed? Our model could be used to address such questions better.”

̽��ֱ��research informing the paper was carried out as part of the Dynamic Drivers of Disease in Africa Consortium, which was funded by Ecosystem Services for Poverty Alleviation (ESPA).

Reference
Lo Iacono, G et al. A unified framework for the infection dynamics of zoonotic spillover and spread. PLOS NTD; 2 Sept 2016; DOI: 10.1371/journal.pntd.0004957

Potential outbreaks of diseases such as Ebola and Lassa fever may be more accurately predicted thanks to a new mathematical model developed by researchers at the ̽��ֱ�� of Cambridge. This could in turn help inform public health messages to prevent outbreaks spreading more widely.

If you know that most cases of an outbreak of Lassa fever come from spillovers, then the message might be ‘kill the rats’, but if it is now mainly spreading between humans, the messages will be around washing your hands or avoiding contact with bodily fluids

James Wood

Global Panorama

Ebola in West Africa

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Lassa fever controls need to consider human to human transmission and the role of ‘super spreaders’, say researchers

Anonymous — Thu, 15 Jan 2015 00:00:00 +0000

Lassa fever is an acute viral haemorrhagic illness caused by Lassa virus. First identified in the village of Lassa, Nigeria, in 1969, the disease is thought to be transmitted to humans from contact with food or household items contaminated with rat urine or faeces. There have also been recorded cases of human-to-human transmission within hospital settings, but until now the risk – or mode – of transmission has not been clear. Understanding the different modes of transmission and how they are affected by factors such as people’s interaction with their environment is crucial for understanding the link between Lassa and changes in the ecosystem, and has important implications for public health strategies.

“Given the many competing health priorities in West Africa – exacerbated by the current Ebola epidemic – it is essential that we know the relative risk of human-to-human transmission of other potentially deadly diseases, such as Lassa fever,” says first author Dr Gianni Lo Iacono from the Department of Veterinary Medicine at the ̽��ֱ�� of Cambridge. “That way, public health officials can decide where to focus their public health campaigns and how to prevent or respond to potential outbreaks.”

̽��ֱ��researchers, part of the Dynamic Drivers of Disease in Africa Consortium, used mathematical modelling to analyse data from outbreaks known to be due to human-to-human chains of transmission, and calculated the ‘effective reproductive number’. This number represents the number of secondary infections from a typical infected individual – for an outbreak to take hold, this number needs to be greater than one. They compared data from hundreds of Lassa infected patients from Kenema Government Hospital, in Sierra Leone, who could have been infected either by rodents or humans, with the data from human-to-human chains. By considering the effective reproductive numbers, they inferred the proportion of patients infected by humans rather than rodents.

̽��ֱ��researchers estimated that around one in five cases (20%) of infection is caused by human-to-human transmission. However, the study also highlighted the disproportionate number of infections that could be traced back to a small number of people, whom the researchers describe as ‘super-spreaders’ – rather than passing their infection on to just one other person (if at all), these individuals infected multiple others. It is not clear what makes them a super-spreader – their physiology, the environment in which they live, their social interactions or probably a combination of these factors.

Dr Donald Grant, chief physician at the Lassa ward in Kenema Government Hospital and co-author of the research, said: "Simple messages to the local people could change their perceptions of risk and hopefully make the difference. For example, making people aware that the virus can remain in urine for several weeks during the recovery period, could promote improved hygienic practices.

“What’s more, measures to target human-to-human spread of Lassa virus can be bundled in with prevention interventions for diseases with similar transmission routes, such as Ebola and even Hepatitis B.”

Professor James Wood, Head of the Department of Veterinary Medicine and senior author on the study, says: “ ̽��ֱ��idea of super-spreaders in infectious diseases is not new. We’ve known about them since the notorious case of ‘Typhoid Mary’ in the early twentieth century and they’ve been documented for other diseases including TB, measles and SARS.

“Although we don’t understand what makes someone a ‘super-spreader’, it highlights the importance of strict hygiene measures in preventing infection. In the case of Lassa fever, we now know that whilst the chance of transmission between humans is much lower than it is from rodents, it is still a very real risk.”

Further progress has been hampered by the Ebola outbreak, which has resulted in the death of key collaborators in Kenema Government Hospital, which was used to nurse Ebola patients, in particular Dr Sheik Humarr Khan, who played such a key role in establishing and furthering the Lassa fever research programme.

̽��ֱ��Dynamic Drivers of Disease in Africa Consortium, a multidisciplinary research project considering the linkages between zoonoses, ecosystems, health and wellbeing, is supported the UK Government through the Ecosystem for Poverty Alleviation (ESPA) research programme.

Reference
G. Lo Iacono, A. A. Cunningham, E. Fichet-Calvet, R. F. Garry, D. S. Grant, S. H. Khan, M. Leach, L. M. Moses, J. S. Schieffelin, J. G. Shaffer, C. T. Webb, J. L. N. Wood. Using modelling to disentangle the relative contributions of zoonotic and anthroponotic transmission: the case of Lassa fever. PLOS NTD; January 2015.

One in five cases of Lassa fever – a disease that kills around 5,000 people a year in West Africa – could be due to human-to-human transmission, with a large proportion of these cases caused by ‘super-spreaders’, according to research published today in the journal PLOS Neglected Tropical Diseases.

Given the many competing health priorities in West Africa – exacerbated by the current Ebola epidemic – it is essential that we know the relative risk of human-to-human transmission of other potentially deadly diseases, such as Lassa fever.

Dr Gianni Lo Iacono

Catherine Grant

Housing in Kenema, Sierra Leone

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