Open access to anti-Trypanosomatid compounds selected from whole-cell high throughput screenings

Ana Rodriguez, Deputy Editor of PLOS NTDs, and Julio Alonso Padilla, former visiting fellow at GlaxoSmithKline, announce the disclosure of a large collection of antiparasitic compounds to facilitate research and drug development for Chagas Disease, Human African Trypanosomiasis (HAT) and Leishmaniasis.

trypanasome

Trypanosoma cruzi trypomastigote Image Credit: Carlos Bautista Ojeda http://www.carlosbautista.es

High throughput screening (HTS) against a particular microbe or target protein is a powerful tool for drug development against infectious diseases that Pharma companies frequently use. Three of the main Tropical Neglected Diseases –Chagas, HAT and Leishmaniasis– are in great need of new drugs with improved efficacy and lower toxicity, but the parasites causing these diseases are not frequently targeted outside academic labs. Recently, a Pharma company with the required facilities and experience in HTS, GlaxoSmithKline (GSK) merged forces with academic labs (New York University, University of Dundee and Instituto Lopez-Neyra of Granada) that were doing research in the parasites causing these diseases and screened a 1.8 million compound library against whole-cell Trypanosoma cruzi, Trypanosoma brucei and Leishmania donovani. As expected, these three large HTS have identified numerous compounds with activity against each of the parasites.

This valuable information has been processed at GSK to release 200 structures of compounds with activity against each parasite and is reported here. These compounds were selected with bioinformatics methodologies to include structures from different chemical families that are likely to be active against a wide variety of targets. The analysis suggests that most of the compounds are new chemical entities with potential novel mechanisms of actions that have not been previously clinically exploited against these parasites. Importantly, all the data have been made publicly available and the compound sets –called chemical boxes– will be provided on request as an open resource for researchers (contact julio.j.martin@gsk.com or albane.2.kessler@gsk.com).

Researchers in the field of drug development for trypanosomatid diseases have also an additional resource for testing more advanced candidate compounds. A service center which offers in vitro and mouse screening services for Trypanosoma cruzi, Trypanosoma brucei, Leishmania and Plasmodium is available to academic and pharma scientists. These resources should facilitate the early stages of development of new, improved medicines for trypanosomatid diseases.

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Chagas Disease: The New Numbers

Peter Hotez (@PeterHotez), Co-Editor in Chief of PLOS NTDs, comments on new WHO estimates of the burden of Chagas disease in Latin America.

Image Credit: Nicolas Raymond

Image Credit: Nicolas Raymond

The World Health Organization (WHO) has just released new estimates on the number of people living with Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi) in Latin America by country (for the year 2010), together with estimates on new cases due to vectorial, maternal-to-child, and blood transfusion transmission (pdf available here). Shown in Tables 1 and 2 is my summary and ranking of some of these data.

Today the largest numbers of people living with Chagas disease live in Argentina, Brazil, and Mexico, followed by Bolivia and Colombia (Table1).  Similarly, Argentina and Brazil lead in the number of cases of Chagasic cardiomyopathy, although more cases are found in Colombia and Bolivia than in Mexico.


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Category: General | 1 Comment

“Vaccine Hesitancy”: The PLOS Currents Collection

Peter Hotez (@peterhotez), President of the Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, announces the launch of PLOS Currents Outbreaks collection on Vaccine Hesitancy.

needle-vials_squared(Dawn Huczek, Flickr)

Image Credit: Dawn Huczek, Flickr

Measles was eliminated from the United States in 2000 – with elimination defined as “the absence of continuous disease transmission for 12 months or more in a specific geographic area”.  But in 2014 things began to unravel when the US experienced its largest number of measles cases since elimination was declared, and later at the beginning of 2015 when a measles outbreak began in Disneyland and subsequently spread to multiple states.  The primary cause of the California measles outbreak was parents who chose not to vaccinate their children because of unwarranted fears that vaccines were linked to autism, despite the fact that such connections have been disproven in the scientific literature.  As both a parent of a child who is severely disabled by autism and other mental disabilities and a vaccine researcher and head of a non-profit vaccine product development partnership, I like to also point out the absence of any scientific plausibility for connecting autism to vaccines  (Thoughts on World Autism Awareness Day).


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Chlamydia trachomatis –Urgent need for an effective T cell vaccine to combat the silent epidemic of a stealth bacterial pathogen

Toni Darville from the University of North Carolina considers the potential for a successful T cell vaccine to combat the silent epidemic of Chlamydia trachomatis.

Human pap smear showing clamydia in the vacuoles at 500x and stained with H&E.

Human pap smear showing chlamydia in the vacuoles at 500x and stained with H&E. Image credit: Wikimedia Commons

Chlamydia trachomatis accounts for ~100 million genital tract infections in industrialized nations annually, and continues to be the most frequently reported bacterial sexually transmitted infection in the United States. The majority of genital infections in men and women are asymptomatic, and thus go undetected and untreated, likely contributing to its high prevalence.
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What Kills Little Kids?

Peter Hotez (@PeterHotez), co-Editor in Chief of PLOS NTDs and Jennifer Herricks (@JenHerricks) of the National School of Tropical Medicine, Baylor College of Medicine comment on the recently released global mortality numbers, specifically those for children under five.

Image Credit: Marcie Casas

Image Credit: Marcie Casas

The Global Burden of Disease Study 2013 (GBD 2013) based at the Institute of Health Metrics and Evaluation at the University of Washington recently released its global mortality numbers for the year 2013.

We find the under-five childhood deaths particularly instructive.  Of the almost four million children between the ages of one and 59 months who tragically died before their time, almost one-half of them died from infectious diseases, led by lower respiratory infections (708,600), malaria (570,000), or diarrheal disease (474,900).

More interesting is when the respiratory and diarrheal diseases are broken down by specific infections with known etiological agents.  This information is shown in the Table.

Today, malaria, most caused by Plasmodium falciparum, is the leading killer of children under the age of five – most of these deaths occurred in sub-Saharan Africa.  Although great progress has been made in reducing these deaths through mass interventions such as insecticide-treated bednets and anti-malarial drugs we still urgently need a malaria vaccine, especially as resistance to current interventions increases.


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Category: General | 4 Comments

Book Review: What Cancer Teaches Us About Ourselves

Seth M. Holmes from University of California Berkeley and Molly Hales from University of California San Francisco and Berkeley review Malignant: How Cancer Becomes Us by S. Lochlann Jain.

Image credit: Kenny Louie, Flickr

Image credit: Kenny Louie, Flickr

Much as we might want to render cancer an external threat to be battled, it just is not so. Cancer is our history. Cancer has become us. Manifest within individual bodies—many, many bodies—it is also embedded within this country’s key industries, medicine not least among them.  (p.8)

Cancer is widespread and devastating.  It affects bodies, but it also affects economies, neighborhoods, populations, families, and loved ones. Cancer affects us all.

Author S. Lochlann Jain is not only an award-winning medical and cultural anthropologist, she is also a cancer survivor. Her book Malignant: How Cancer Becomes Us is therefore doubly relevant to practitioners of medicine and public health. Jain’s analysis unveils how cancer relates to institutions and industries, from agriculture to cosmetics to medical research. At the same time, her analysis of her own illness and treatment experiences illustrate the impact that cancer can have on an individual.

Jain begins the book with a simple premise: That the situation could be otherwise. It is not the biological disease itself that has made cancer so difficult to prevent, treat, and come to terms with.  Rather, the way that we have approached cancer is the problem. The way that cancer circulates as a concept in society makes some aspects ubiquitous – and thus quotidian – while obscuring other crucial facts.


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Category: Book Review, Cancer | 1 Comment

Translating Research into Practice Series: From Inaction to Advocacy: Placing Women and Children at the Center of Sustainable Development

Originally featured on the Maternal Health Task Force (MHTF) Blog site, this post is part of the Translating Research into Practice Series which features guest posts from authors of the MHTF-PLOS Maternal Health Collections describing the impact of their research since publication.

Post written by: By Alicia Ely Yamin, Lecturer on Global Health and Policy & Director of the François-Xavier Bagnoud (FXB) Center for Health and Human Rights, Harvard University

 

The sudden loss of a woman’s life during pregnancy or childbirth is both a terrible tragedy and a preventable injustice. With affordable access to a set of basic interventions, nearly all maternal deaths could be avoided. Of the 289,000 global maternal deaths estimated in 2013, the overwhelming majority occurred in developing countries, and sub-Sarahan Africa has the highest regional maternal mortality ratio, accounting for 62% of the global burden. While a maternal death is devastating in its own right, a mother’s death is not an isolated event; when a mother dies there are immediate and lasting repercussions for her children, her family, and the broader community.

Image Credit: Jack Zalium, flickr.com

Image Credit: Jack Zalium, flickr.com

Recently, the FXB Center for Health and Human Rights at the Harvard School of Public Health conducted a mixed-methods research study, the Impacts of Maternal Deaths on Living Children Studyin four countries in sub-Saharan Africa—Tanzania, Ethiopia, Malawi, and South Africa—in order to quantify the previously largely undocumented intergenerational health effects of maternal mortality and detail the mechanisms through which a mother’s death impacts child health, development, and well-being. Preliminary findings show not only greatly elevated rates of infant mortality, but increased risk of nutritional deficiency, poor educational outcomes, early marriage, and early pregnancy for the surviving children.
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Translating Research into Practice Series: Emergency Obstetric Referral and Transport in Low- and Middle-Income Countries: the Direction of Travel

Originally featured on the Maternal Health Task Force (MHTF) Blog site, this post is part of the Translating Research into Practice Series which features guest posts from authors of the MHTF-PLOS Maternal Health Collections describing the impact of their research since publication.

Post written by: Dr Julia Hussein, Scientific Director, Immpact, University of Aberdeen

In low- and middle-income countries, adequate plans to seek care in case of an emergency are important especially if women live far away from where lifesaving care is available. Decisions to seek care can be deferred or hindered. Even if decisions are rapidly made to seek care, transport may be unavailable or slow.

Image Credit: Jack Zalium, flickr.com

Image Credit: Jack Zalium, flickr.com

Mechanisms to improve referral and transportation of mothers and babies are crucial to reduce maternal and newborn mortality, as they enable women to reach care when complications unexpectedly occur. Various forms of transport for obstetric emergencies have been put forward, from stretchers carried by volunteers to bicycles, boats, motorcycles and other forms of motorised vehicles. The type of vehicle will obviously affect the time for transportation, with geography, terrain and affordability influencing the choice.
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Category: Collections, Maternal Newborn and Child Health | 1 Comment

Translating Research into Practice Series: Improving Birth and Pregnancy Outcomes through Registries in Southern Ethiopia

Originally featured on the Maternal Health Task Force (MHTF) Blog site, this post is part of the Translating Research into Practice Series which features guest posts from authors of the MHTF-PLOS Maternal Health Collections describing the impact of their research since publication.

Post written byBy Yaliso Yaya, PhD candidate, Centre for International Health, University of Bergen, Norway and teaching staff, Arba Minch College of Health Science, Ethiopia

 

Unfortunately, there is still limited information to oversee maternal and newborn mortality interventions in low-income countries. Developing countries lack vital registrations that are present in high-income countries. Because of the shortage of such essential information, translating policy into action and monitoring programmes to reduce maternal and neonatal deaths is difficult.

Image credit: Jack Zalium, Flickr

Image credit: Jack Zalium, Flickr

The new Sustainable Development Goals divide countries into three groups where the maternal mortality ratio (MMR) is greater than 400, between 100 and 400, and less than 100 based on the ratio in 2010. Such a grouping is necessary because different ratios may determine different intervention strategies. Unfortunately, for many countries there is a controversy over the level of the MMR. If we use Ethiopia as an example, a UN estimate of MMR in 2010 is 350 per 100,000 live births, whereas the DHS estimated it to be 676 for the same year.
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Translating Research into Practice Series: Using Research Findings to Influence Maternal Health Action: An Example from Nigeria

Originally featured on the Maternal Health Task Force (MHTF) Blog site, this post is part of the Translating Research into Practice Series which features guest posts from authors of the MHTF-PLOS Maternal Health Collections describing the impact of their research since publication.

Post Written By: Bolaji Fapohunda, Senior Advisor & Nosakhare Orobaton, Chief of Party, TSHIP

 

Image Credit: Jack Zalium, flickr.com

Image Credit: Jack Zalium, flickr.com

Our paper—When Women Deliver with No One Present in Nigeria: Who, what, where and so what, published in the MHTF-PLOS Year 2 Collection—revealed that over one in five births in Nigeria was delivered with no one present (NOP) and 94% of those deliveries occurred in northern Nigeria. A woman’s age, increasing number of pregnancies, Muslim religion, and residence in northern Nigeria increased her risk of delivering alone. However, with greater economic status, decision-making power, and education women were less likely to deliver alone.
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Category: Collections, General, Maternal Newborn and Child Health | 1 Comment