Featured Event - DxMc launches Special Supplement in journal Nature

2 December 2015

New Nature supplement published by Diagnostics Modelling Consortium calls for greater investment in new diagnostic tools to aid the control of outbreaks and elimination efforts for malaria and other infectious diseases affecting global health

A new collection of 8 peer reviewed papers spanning major infectious diseases launches today in a special Nature supplement, coordinated by the Diagnostics Modelling Consortium, Imperial College London and the Bill and Melinda Gates Foundation.

Infectious disease control and elimination - Modelling the impact of improved diagnostics

This supplement entitled responds to an earlier diagnostics compendium, also published by the Nature Publishing Group and the Gates Foundation  in 2006, Improved Diagnostic Technologies for the Developing World, which utilised modelling techniques to define the value of new diagnostic tools for resource poor settings.

The authors argue that new diagnostic tools in resource poor settings are as vital in reducing the burden of infectious diseases as the drugs and vaccines that are more often referred to in the media and call for enhanced international investment . It is important to capture data about the infectiousness of an individual and tranmission patterns at the population level to be able to translate this into provision of adequate treatment pathways and move towards elimination of diseases in the field. However understanding the role of diagnostics and prognostics is complex. Performance and use and/or interpretation of tests by health workers is crucial as is realising appriopriate and timely care.

Simple tools could have a very big impact

Researchers focusing on pneumonia suggest that a simple device that clips onto the finger to measure oxygen in the blood could prevent one in six child pneumonia deaths in countries where the disease is most prominent, a study has found.

Pulse Oximeter. Courtesy of Lifebox.org 2015

Routinely used in hospitals, pulse oximetry is a non-invasive technology that measures oxygen in the blood, and can help doctors diagnose conditions such as pneumonia which trigger low oxygen levels.  The pulse oximeter device - which is around the size of a large mobile phone and can be battery-operated- is not routinely available in community settings. Instead, healthcare workers diagnose pneumonia by techniques such as counting the number of breaths per minute, and observing whether a child is sucking their chest under the rib cage, which suggests they are struggling to breathe.

The authors argue that if pulse oximetry was made more widely available in the community, it could allow children to be diagnosed quicker and sent to hospital for life-saving oxygen and antibiotics. However the authors caution their results depend on a child having reasonable access to a nearby hospital or medical facilities.

Researchers also call for investment in diagnostic tools to detect those that are infected but may not show any symptoms of disease 

Current diagnostic tests for malaria involve just a blood finger-prick and can therefore be used in surveys to identify those carrying the malaria parasite. The researchers show, however, that they currently only identify around half of those that are infected and may go on to infect others.  A relatively simple improvement in these tests to detect a 10-fold lower density of parasites in the blood could increase this to over 80%. This would increase the chance that the disease could be eliminated and also reduce the number of years that it takes to eliminate malaria.

Rapid disposable diagnostic malaria test, Cambodia, courtesy of Bill & Melinda Gates Foundation, 2014

“Increasing the sensitivity of these tests could improve the prospect of malaria elimination”, says Dr Hannah Slater, lead author of one of the malaria papers based at Imperial College London.

Malaria disease currently kills 438,000 children each year, but with recent investment from the UK government and the Bill and Melinda Gates Foundation it is hoped that it could be eradicated in the next 30 years.

A third paper from Imperial authors calls for the use and further development of rapid diagnostic tests for Ebola. Testing a patient for ebola took between two days and a week in the recent outbreak. But in this time the patient had to remain in a 'holding area' - where infected and uninfected patients stayed together until their results were confirmed. This increased their risk of contracting Ebola, as well as taking up limited bed capacity. The authors calculate that if rapid tests had been available and used from the start of the recent outbreak, it could have reduced its scale by a third.

Three Ebola healthcare unit diagnostic testing and patient triage strategies. Courtesy of Nouvellet et al, Nature 528, S109-S116 (2015)

“The availability of a rapid diagnostic test could have had a dramatic impact on the epidemic and is therefore a priority for future investment “, says Dr Pierre Nouvellet, lead author of the paper based at Imperial College London. “Our study also emphasizes the usefulness of rapid tests with limited sensitivity and specificity when employed in a thoughtful manner, and is therefore relevant to the control of any future outbreak of a novel pathogen”.

HIV, TB and NTD's

The supplement also explores similar issues for HIV, TB and neglected tropical diseases - namely visceral leishmaniasis, and involves authors from the University of Warwick, Liverpool School of Tropical Medicine, the University of Washington and UCL, London.

In their analysis of the role of the diagnostic for visceral leishmaniasis (VL) Medley et al take a similar approach to detecting asymptomatic infections. Concentrating on the potential to eliminate VL in the Indian sub-continent they conclude that shortening the delay in seeking care to receiving a diagnosis could substanially reduce incidence of the disease, especially if a test is produced which can accurately detect infectious individuals prior to the onset of kala-azar (or clinical disease).

In their paper on viral load measurement the Working Group on Modelling of Antiretroviral Therapy Monitoring Stategies in sub-Saharan Africa continue the theme of patient flow through the health system to explore the impact and cost-effectiveness of using the measurement to differentiate levels of care to ensure fewer clinic visits for those in lesser need. Thereby freeing up already limited health care capacity to those in greater need. Similarly Sharma et al focus on a review of the methods of improving coverage of testing, concluding that community based testing and counselling, compared to facility-based testing, successfully identifies HIV-infected individuals at an earlier stage of infection, opening up potentially more timely treatment pathways, especially for higher risk groups. Similarly Pathy et al consider this issue more broadly for tuberculosis, proposing that the impact of new diagnostic test on patient behaviour and care seeking rather than sensitivity and specificity alone must be evaluated.

Timely outputs

The outputs of the work of the Diagnostics Modelling Consortium presented in this supplement clearly demonstrate the impact and cost effectiveness of new diagnostic approaches for multiple diseases of global health significance. Yet their impact remains overlooked. These findings therefore could not come at a better time for improving diagnostics. As the shift in the epidemiology of infectious diseases moves towards high reductions in burden stimulated by the Millennium Goals, the recent London Declaration on NTDs and the Gates Foundation's push towards eradication within the lifetimes of Bill and Melinda Gates, global health funding has steadily increased. This has been accompanied by a switch to prevention strategies and early treatment of diseases away from centralised facilities.

The launch of the Ross Fund, recently announced by the UK Government and the Bill and Melinda Gates Foundation, supports the urgency of investing in diagnostic development which will ultimately benefit those populations that are affected by the burden of infectious diseases but also developed countries by nsuring that drugs such as antibiotics remain available.

Read the full supplement online here.