In the wake of the recent devastating earthquakes, PLOS Medicine Consulting Editor Lorenz von Seidlein visited Nepal to assess outbreak risks. Lorenz travelled with Anuj Bhattachan, International Vaccine Institute, Seoul, Korea and guidance from Deepak C. Bajracharya and Shyam Raj Upreti from the Group for Technical Assistance, Kathmandu, Nepal. The assessment was requested by the epidemiology and disease control division of the Ministry of Health of Nepal and facilitated by Stop Cholera. Here he reports on the damage he witnessed and considers the choice of administering vaccines pre-emptively versus reactively in response to an outbreak.
Image credit: Lorenz von Seidlein
The two earthquakes in April and May 2015 seem to have selectively erased much of northern Nepal’s architecture and history. Many buildings in urban Kathmandu were constructed during the last 20 years. These buildings, in many cases multi-storey or high-rise, did not collapse during the recent earthquakes. The older buildings in urban Kathmandu are brick and mortar constructions without a frame. These vintage structures give Kathmandu its characteristic charm but they fell like dominoes during the first earthquake on 25th April. In rural districts the buildings are mostly stone and clay; they are perfectly adapted for the high altitude climate of the Himalayas but offer very little resistance against an earthquake. Most of the stone houses completely crumbled or have large enough cracks to suggest imminent collapse. According to government figures, 488,579 houses were destroyed and 260,026 damaged. The probability of a quick reconstruction is small because of the widespread damage. Furthermore, majority of men of working age are employed abroad, leaving a denuded local labour force.1
Current estimates suggest that 8,151 people died and some 17,866 people were injured in the two quakes. Currently most health care is required for acute trauma but trauma will be replaced by other presentations during the coming months. Water resources of the 660,000 to 1.3 million people were affected and between 850,000 to 1.7 million need sanitation support. Concurrently 945 health facilities, mostly village health posts, are partially or totally damaged. Health services have been severely compromised. Routine childhood vaccinations had to be suspended in some districts. The makeshift temporary living conditions, disruptions to water supply and sanitation, and strained health services foreshadow an aftershock of a different variety: enteric diseases may seize this opportunity to spread through an already devastated country.
A recent study in PLOS Pathogens investigates how Epstein-Barr virus and malaria co-infection may create a lethal combination if the timing is right.
Spleen section for mock infected, MHV68 infected, P. yoelii XNL infected and MHV68 and P. yoelii XNL co-infected animals. Image credit: Matar et al. (2015)
Epstein-Barr virus and malaria are two infections that can each be controlled on their own, but a new study in PLOS Pathogens shows that co-infection can perhaps become more lethal than each infection alone, providing one possible explanation for why young children are so much more vulnerable to severe malaria.
The study, led by Samuel H. Speck and Tracey J. Lamb of the Emory University School of Medicine finds that Epstein-Barr virus (EBV) may contribute to the development of severe malaria and malaria-related deaths in sub-Saharan African children. Almost all African children will be infected with both Epstein-Barr virus and malaria by the age of 6-12 months. Because both of these infections occur around the same time in these children, many are at a high risk for co-infection before the age of 1.
Sarah Venis, Research Coordinator at Médecins Sans Frontières, highlights the topics at the 2015 MSF Scientific Day, May 7th and 8th in London and New Delhi.
At the time of writing, the West Africa Ebola epidemic at last appears to be under control, and as the response is scaled down there is more capacity within Médecins Sans Frontières (MSF) to begin to appraise the evidence collected, technological approaches trialed, and lessons learned. Much of the analysis is yet to come – the work that will be presented at the 2015 MSF Scientific Day on May 7th and 8th is an early snapshot across some of the most important areas of uncertainty in the response.
MSF staff member in personal protective equipment, Liberia.
Image credit: Yann Libessart/MSF
The MSF Scientific Day, now in its 12th year, aims to connect audiences – across countries, organisations, specialties, and disciplines – to promote debate on the state of the evidence underpinning medical humanitarian operations. Anyone with access to the internet or a smart phone can watch online and ask questions via the MSF Scientific Day website or Twitter using #MSFsci. The posters are also available at a permanent MSF Scientific Day archive hosted by f1000 and this year we are running a poster competition – please view and vote for your favourite.
This year, the conference is taking place over two days (May 7th, 8th) and is hosted in New Delhi as well as London. In addition to the auditorium delegates, we hope that our virtual audience (in 2014 over 2200 people in over 100 countries) will once again join us. The intention behind both the new event in India and the online version of the conference is to engage MSF field staff, partner organisations, and other relevant medical and policy audiences to help guide field operations, influence policy, and increase the benefit for the populations in which the research was conducted.
On World Malaria Day 2015, Allan Schapira and Lorenz von Seidlein discussed the accomplishments and challenges of the fight against malaria.
Image Credit: James Gathany, Wikimedia Commons
Lorenz: Is there much to celebrate on World Malaria Day 2015?
Allan: Well, in 2000 we estimated there were roughly 801,000 malaria related deaths in Africa. In 2014 we estimate that this number had dropped to 528,000 malaria deaths.
Lorenz: 528,000 malaria deaths are really nothing to celebrate. That is a lot of misery.
Allan: Indeed, but the malaria mortality rate in Africa has decreased by more than 50% ¹ over less than 15 years – that’s an epic achievement, but certainly not enough. I find it striking that the number of ACT courses procured in the world in 2013 was as high as 392 million courses, while the estimated proportion of all children with malaria who received ACTs was estimated at only 9 to 26%.
Lorenz: 74 to 91% of children with malaria are not treated. Again there is not much to celebrate.
Allan: The first problem to deal with is the unsatisfactory and slowing decline in malaria mortality in Africa. While there is room for improvement of ITN coverage, the priority should be to scale up access to early effective treatment including improved care-seeking. There is always scope for cost-effectiveness studies and comparisons of private and public approaches, the surest and most rapid way to reduce malaria mortality is a massive scale-up of community case management of childhood illness (CCM), which will also help reduce pneumonia and gastroenteritis mortality. It will also strengthen health systems, which is now better understood as a priority, as the international community is trying to deal with Ebola. CCM is still conducted as a pilot activity. Why has it not been mainstreamed?
In their second post honoring World Malaria Day, Kasturi Haldar, Editor-in-Chief of PLOS Pathogens, and Margaret Phillips comment on the challenges for drug development and the path to malaria control, elimination and eradication.
For additional analysis, see their first linked post here.
The second decade of the 21st century has been infused with optimism for malaria eradication. Although deadlines have been breached, it appears that the cumulative and long haul fight against malaria is yielding impactful results: reduction of malaria deaths from a staggering 1.2 million to ~ 600,000 from 2000 to 2013 provides a realistic context for elimination and eradication agendas. But the path forward is not just details. Major discoveries in basic, translational and capacity building research supported by commensurate funding are urgently needed to navigate challenges posed by dynamic and heterogeneous disease frontiers.
Drugs have been the mainstay of reducing the malaria burden through treatment of patients. Drug research in malaria started with blood stages of Plasmodium falciparum, the most dangerous and prevalent of human malarias. But it has expanded to other stages as well as to Plasmodium vivax a second parasite species that causes widespread disease but is not as virulent as P.falciparum. Treatment to cure the patient remains a primary goal. However, malaria elimination and eradication also require reducing transmission to the mosquito stages and clearance of latent infection in the liver. Severe disease like cerebral malaria and severe malarial anemia are frequently fatal and need renewed attention since they are impacted by natural immunity to malaria, which is changing in context of control measures. This is reflected in the Malaria: Targets and Drugs for All Stages Collection, which was originally assembled in April 2013 and now includes a new Appendix of papers published after the collection’s launch through April 25, 2015. Over the last two years there has been a marked increase of papers in host (human and mosquito) response to infection, liver stage infection, transmission and severe malaria and coincident infections, how to measure their burden and treat them, both in human disease and animal models. The collection also includes studies on mechanisms of drug resistance and the spread of resistant parasites in human populations including (but not limited to) resistance to frontline artemisinins and their combination therapies. The selected papers represent significant research at the highest levels: they are only a portion of the literature but well reflect the tools being developed in the larger malaria drug discovery endeavor to overcome major hurdles for malaria elimination.
This is the updated Malaria: Targets and Drugs for All Stages Collection, which was originally published on April 25, 2013. Articles published by an expanded number of PLOS journals after the collection’s launch through April 25, 2015 are now included in the Appendix.
For additional analysis from Katsuri Haldar and Margaret Phillips, see their second linked post here.
More drugs for malaria: time to expand the antimalarial portfolio
Malaria is an ancient enemy. Its treatments predate modern drug discovery, most notably the use of the Qinghao plant in ancient China (2nd century BC to 340 CE) and Peruvian bark in the early 17th century, the medicines from which are now known to be artemisinin and quinine respectively. Calls for the eradication of malaria have brought renewed focus on tools to control malaria. Yet, although disease burdens have been lowered in the last five years, malaria remains endemic in over 100 countries and, with an estimated seven hundred thousand deaths in 2010, is still a leading cause of mortality and morbidity worldwide.
Drug research in malaria often focuses on blood stage parasites because they are responsible for the symptoms of the disease and are easier to manipulate in the laboratory. The assembled PLOS Collection describes multiple parasite and host processes engaged in infection in blood, the blocking of which could stop human illness. However, control and eradication of malaria will also require the development of drugs against stages responsible for mosquito transmission and those that remain latent in the liver, also summarized in the collection. Although these selected papers represent significant research at the highest levels, they are only a fraction of the malaria drug discovery literature.
Despite research, a significant historical hurdle was the market failure of the pharmaceutical industry to invest in the discovery and development of new antimalarials. Thus new partnerships have arisen that bring together academic and pharmaceutical work. For example, the not-for-profit product development partnership Medicines for Malaria Venture (MMV) was established in 1999 to discover, develop and deliver new antimalarials in collaboration with both the public and private sector. They are joined by the Bill and Melinda Gates Foundation , multiple agencies including the National Institutes of Health , the Wellcome Trust, Medical Research Council and others. Never before have philanthropic, public and large Pharma resources been better integrated for antimalarials, progressing research in early stages to testing drugs in humans, subsequent registration and delivery to patients.
PLOS Medicine’s Senior Research Editor, Clare Garvey, recently caught up with Francis Ouellette, the Associate Director of Informatics and Biocomputing at the Ontario Institute for Cancer Research (OICR) to find out about progress in cancer genomics, the issues surrounding the tsunami of data that has been generated by The Cancer Genome Atlas Project (TCGA) and the International Cancer Genome Consortium (ICGC), and how developments may impact clinical care for cancer patients.
This interview accompanies the editorial appearing in this week’s PLOS Medicine.
Image credit: National Cancer Institute, Wikimedia Commons
Francis, can you tell us what the goals of the TCGA and ICGC projects were and how they are overlapping or complementary?
The TCGA pilot was started 2006 and precedes the inaugural ICGC planning working group meeting in 2007 – the ICGC per se started in 2008. Since the beginning, the TCGA has been part of the ICGC. The overall goals of the two projects are similar – to capture the genomic information on tumour types in many different ways: with exome or whole genome sequencing to determine the simple somatic mutations; copy number variations; structural variations and effects on transcriptional regulation that happen in cancer. For this, genomic, mRNA, miRNA, and epigenomic data is collected. The goal of the ICGC has been to capture the genomic, transcriptomic, epigenomic and clinical information on 50 different tumour types and for each of these projects, collect 500 tumours and their matched normal DNA sample (commonly from blood, except for leukemias) for each tumour type and so that’s an ambitious goal of 25,000 donors, i.e. 50,000 genomes (tumour and a ‘normal’ wild type match). Approximately half of the ICGC genomes are from the TCGA projects. If you go to the ICGC data portal you will see a list of all of the cancer genome projects that have submitted data to date.
Since the initial plan to obtain data for 50 tumours, additional projects have been added, taking the number to 85 projects. ICGC Cancer Genome Projects support the characterization of 500 unique cases of one cancer type or subtype. Some of the additional projects focus on rare cancers, such as childhood leukemias, and for these rare tumor types we may only get 100 or 200 donors.
Jocalyn Clark (@JocalynClark) describes the challenge of achieving and maintaining basic cleanliness and sanitation in a children’s cancer ward in Dhaka, Bangladesh.
Image credit: gosheshe, Flickr.
A couple of years ago I wrote about a talk Wendy Graham gave at the Maternal Health conference in Arusha, where PLOS Medicine was launching its Maternal Health Collection. I found the talk startling. She raised troubling questions about the global push for institutional births when facilities in many regions are ill-equipped, unclean, under-staffed, and otherwise inadequate to meeting women’s needs. Why focus so much on facility interventions to reduce maternal deaths when the settings (hospitals or clinics) themselves lack the basic hygiene and sanitary conditions necessary to achieve intended health outcomes?
The notion of hygiene as such a basic determinant of health hadn’t quite hit home for me until her talk. Since then there has been slowly growing recognition of how essential cleanliness and sanitation are to healthcare, including a recent call to action in PLOS Medicine to join up the WASH (water, sanitation, hygiene) and maternal health sectors in the new post-2015 development agenda.
I was reminded of this hygiene-healthcare link this past year when I began volunteering at a children’s cancer ward in Dhaka. To put it bluntly the ward was filthy. During a bi-monthly volunteer clean-up day, it literally felt repulsive. Feces on the walls. Cockroaches and discarded syringes on the floors, dirt and stains on beds and sheets. Toilets barely approachable. In fact, a big focus of Dhaka Kids With Cancer, the charity helping improve care for the children on the ward, has necessarily been on cleanliness and hygiene. When the charity first launched here in Dhaka, they recognised massive needs around training of medical staff to ensure best clinical practice and of purchasing medicines and chemotherapy – they’ve recently received funds from World Child Cancer to help do so. But the charity also recognised early on that they wouldn’t get the desired improvements in health outcomes without immediate improvements in hygiene.
Serap Aksoy, co-Editor in Chief of PLOS NTDs, comments on the importance of training young scientists in the Tropical Infectious Disease community.
Image Credit: Serap Aksoy
There is a lot of excitement in the NTD community around the “E” words. After the many investments made by many, Elimination or Eradication is anticipated for several of the devastating Neglected Tropical Diseases (NTDs). The WHO roadmap includes 17 NTDs, which have transmission characteristics or treatment possibilities that make them good candidates to be effectively controlled and, in many cases, eliminated. The most promising diseases targeted for elimination by 2020 include Leprosy, Chagas Disease, Leishmaniasis, Onchocerciasis, Soil-transmitted Helminthiasis, Trachoma, Human African Trypanosomiasis, Dranculiasis, Lymphatic Filariasis and Schistosomiasis. While this progress is most welcoming, the sustainability of such elimination efforts will no doubt pose the next major challenge for the NTD community. An essential tenant for their sustainability requires presence of local capacity in disease endemic countries both in terms of infrastructure that can continue surveillance and treatment efforts when needed and the availability of scientists and clinicians trained in these diseases. Now is the time to invest in the next generation of scientists who will ensure the sustainability of the progress made on these diseases. An essential tenant of this effort also includes the development of enhanced capacity for local journals, including publication and peer-review ethics.
Michael W. Painter of the Robert Wood Johnson Foundation asks if you are ready for the data explosion in health care, and announces the release of the Foundation’s Data for Health Advisory Committee report.
Image caption: Bob Mical, Flickr.
You are aware that your devices are tracking, recording and collecting the interesting and mundane about nearly every aspect of your life, right?
Your smartphone, for instance, can do that because it has an incredible array of sensors—including accelerometer, gyroscope, GPS, thermometer, barometer, light and proximity sensors. Plus, wearable devices with their own range of sensors are coming to us fast. Did you hear about that Apple Watch arriving at a store near you very soon?
Let’s not forget our health professionals: most of our health care teams now have “electronic health records” and there are or should be sharable data coming from them as well.
Are you ready for all that data?
We already have enormous amounts of data about almost every aspect of our lives, but we’re really just at the beginning. We’re also on a Moore’s Law escalation adventure with it. The sheer amount of data is increasing rapidly, probably exponentially, as computing power increases and our devices grow smaller and more ever-present in our lives. We’ll soon be carrying, wearing, driving, living with and implanting more and more powerful computers that will help us in unimaginable ways—assuming we can get to the data, turn it into useful information and then be able to act on it to improve our health and our lives.