Drugs for Malaria: Need to Overcome Resistance to Artemisinins and Eliminate All Stages of Parasites in a Wide Range of Transmission and Disease Settings

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.


Targeting the parasite: a malarial sporozoite in an infected epithelial cell. Image credit: Frevert et al. 10.1371/journal.pbio.0030192

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.
Continue reading »

Category: Collections, General | Tagged , , , , , , | 1 Comment

Malaria: Targets and Drugs for All Stages

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.
Continue reading »

Category: Collections, General | 4 Comments

Cancer Genomics: Data, Data and more Data

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

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.
Continue reading »

Category: Cancer, Global Health | 1 Comment

Child Cancer Care and Hospital Hygiene – Can We Have One without the Other?

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.

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.
Continue reading »

Category: Cancer, Global Health, Maternal Newborn and Child Health | 2 Comments

Training the Next Generation of Scientists from Disease Endemic Countries Should be a High Priority in Disease Elimination Efforts

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

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.

Continue reading »

Category: Global Health, Neglected Diseases | 1 Comment

Ready or Not: Here Come the Data

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.

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.

Continue reading »

Category: Global Health | 1 Comment

Time for a jumpstart: accelerating access to new and promising DR-TB drugs

On World TB day, Grania Brigden (@TBbrigden) of Médecins Sans Frontières (@MSF) calls for improved global access to MDR-TB drugs.

Image credit: Matthias Steinbach

Image credit: Matthias Steinbach

World TB Day is an opportunity to reflect on the progress that has been made in beating this ancient disease. At first glance, the news looks good: two new drugs – the first in decades – have been registered for hard-to-treat multidrug-resistant tuberculosis (MDR-TB) and the global rate of new cases of MDR-TB has remained stable at 3.5%.

However, appearances can be deceptive. While the global rate of MDR-TB is stable, on closer examination the data are not complete; many parts of the world are dealing with a serious and growing MDR-TB crisis. In some countries, including Belarus, Kyrgyzstan and Kazakhstan, up to 35% of people diagnosed with TB for the first time already have MDR-TB, and more than 70% of patients previously treated for TB now have MDR-TB.

These countries are facing a potential future where MDR-TB is the ‘normal’ TB diagnosis. Both MDR and the even-more-severe extensively drug-resistant TB (XDR-TB), carry huge human and financial costs. And the cure rates are abysmally low: around 50% for MDR and 20% for XDR-TB.

Continue reading »

Category: General, Global Health, Tuberculosis | 1 Comment

The Oral Microbiota Affects More Than Just the Mouth

For World Oral Health Day, Lily Berrin, daughter of a periodontist and dental hygienist, highlights recent PLOS Pathogens content to remind us that oral pathogens do more than just cause cavities.

There is more going on behind that smile than you know; brushing, flossing, and seeing the dentists regularly are only the beginning to a healthy mouth and a healthy body. Bacteria, fungi, and even protozoa can inhabit the mouth, leading to more than just bad breath and cavities. If not treated, these pathogens can cause more severe ailments, from inflammatory diseases, such as cardiovascular disease and rheumatoid arthritis, to cancer. In addition to being partly responsible for causing and exacerbating these diseases, and the critters in your mouth can also help inform scientists about the health in other parts of the body.

Coronation Dental Specialty Group, Wikimedia Commons

Image credit: Coronation Dental Specialty Group, Wikimedia Commons

Continue reading »

Category: General | Tagged , , , | 7 Comments

Engaging the Public on Global Health

In the wake of Ebola, Sara Gorman (@saragorm) discusses the need to keep the general public engaged and informed on global health issues.

Image credit: Михаил Чуркин, Flickr.

Image credit: Михаил Чуркин, Flickr.

A simple Google AdWords search of Ebola keyword searches in the past twelve months in the U.S. shows a general disinterest in Ebola all through the summer when cases were raging in West Africa and a sudden spike to 24 million searches in October 2014 just when cases were coming to the U.S. Similarly, average search volumes of “Ebola in Africa” are around 8,100 per month, while “Ebola in the U.S.” gets about 74,000 searches per month. Clearly, something is not right.

Yet the problem may not be exactly what we think it is. It is certainly not the case that people simply don’t care about global health and only become concerned when a disease encroaches on their own borders. In a Kaiser Family Foundation survey from 2012, 52% of people said that the media pays too little attention to health issues in developing countries. 50% of people said they paid at least some attention to global health issues in the news, 18% said they paid a lot of attention, and only 6% said they paid no attention at all. Lest we think people are merely self-interested, when asked why the U.S. should spend money on global health, 51% of people said it was because “it is the right thing to do”. Charitable giving statistics lend a bit more meat to this argument. In 2013, individual donation to health organizations in the U.S. amounted to a total of $31.86 billion, up 6% from 2012. Naturally, many of these health organizations have domestic missions. However, it does show concern about health in particular.

From these surveys and statistics, it would be difficult to argue that the American public has absolutely no interest in global health and international development. But there does seem to be a barrier to getting more involved in these issues: the way the information is presented. But the American public seems interested in knowing more about global health outside of these crises.

Continue reading »

Category: Ebola, Global Health, Policy, Public | 4 Comments

Reflecting on the Maternal Health Collections

In celebration of the MHTF-PLOS Maternal Health collaboration we take a look back through the collections and highlight some of the most influential and interesting articles included in the collections.

In November 2011, the Maternal Health Task Force (MHTF) and PLOS Medicine embarked on a 3 year partnership culminating in the launches of 3 collections focussed on improving maternal and infant health globally. Today we take a look back through the achievements of these collections and using article level metrics gather a picture of the diverse issues and solutions for women and their offspring.

Jack Zalium at flickr.com

Jack Zalium at flickr.com

Year 1: Quality of Maternal Health 

Announced in PLOS Medicine, the theme was chosen to highlight the continued need for attention and action to improve the overall quality of maternal health.

Following the call for papers and rigorous editorial and peer review, 18 articles were published from a wide range of authors and settings, including 14 original research articles and 4 policy and health in action papers.

One of those Health in Action articles, The Midwives Service Scheme in Nigeria, focussed on a project to balance the level of care through Nigeria – so both urban and rural-based mothers received a similar level of care at births. The outcome of this project indicated an uneven improvement in the quality of care received, with the availability and retention of trained midwives noted as a particularly major challenge faced.

Year 2: Maternal Health is Women’s Health

In November 2012, we called for papers for the second year of the collection. The theme recognized the importance of considering maternal health in the context of women’s health throughout their lifespans.

A celebratory event was held in December 2013, featuring authors of the collection sharing their insights and lessons learned.

A prominent topic of this discussion was addressed by Dr. Agampodi through his PLOS ONE paper, Antenatal Depression in Anuradhapura, Sri Lanka and the Factor Structure of the Sinhalese Version of Edinburgh Post Partum Depression Scale among Pregnant Women’. The conversation focused on working towards a coordinated consensus in order to treat ‘minor aliments’, such as nausea, vomiting and lower back ache, during pregnancy, primarily concentrating on best-practice treatment for Sri Lankan women.

Year 3: Integrating Health Care to Meet the Needs of the Mother–Infant Pair

Moving into the final year, we chose the theme of integration with the aim of strengthening the evidence for approaches to providing combined care for both mothers and infants.

The culmination of this collection highlighted the pressing need to consider treatment and prevention simultaneously to form a clearer understanding of the importance for the integration of care.

The MHTF followed up with one of the collection authors, Yaliso Yaya, whose paper, Maternal and Neonatal Mortality in South-West Ethiopia: Estimates and Socio-Economic Inequality, highlighted the importance of strengthening obstetric inventions in rural Ethiopia. Dr. Yaya concluded with advice to include the results of all pregnancies and not just the pregnancy outcomes to ensure proper antenatal controls and referrals to institutions when required.

Three Very Global Collections

From Argentina to Zimbabwe, the articles in the collections were submitted from over 400 institutions around the world.

Representing work from low- and middle-income countries including Burundi, China, DRC, Ghana, India, Indonesia, Kenya, Lesotho, Nepal, Nigeria, New Guinea, the Philippines, Sri Lanka, Vietnam, and Zambia, as well as high income countries, the collections were distinctly diverse, setting them apart from other collections in the field.

Map of MHTF authors

Image Credit: PLOS

The 100+ articles in the collections have represented hugely varied and topical issues that have now been brought to the attention of the global community through the collections in a concise and contained format.

We wish to thank all authors, editors & reviewers who assisted in the creation and development of the collection articles and hope that the work published will continue to nurture opportunities to improve maternal, newborn and children’s health worldwide.

To view the collections, please visit: www.ploscollections.org/maternalhealth

To view the Article Level Metrics Reporting data for the collections, please click here.

Category: Maternal Newborn and Child Health | 2 Comments