BREAKTHROUGHS BLOG

January 25, 2016

Major R&D gaps exist for eight pathogens most likely to cause next epidemic

Senior Program Assistant
GHTC
Photo: PATH/Mike Wang
Photo: PATH/Mike Wang

Last month, the World Health Organization (WHO) convened experts to determine which emerging diseases could become “the next Ebola”—those pathogens most likely to cause the next major epidemic. The panel focused on diseases for which there are limited medical countermeasures, with the goal of galvanizing research and development (R&D) for the tools needed to prevent and control future outbreaks. Many have lauded the acceleration of Ebola R&D since the onset of the West Africa outbreak, with experimental treatments made available through emergency use authorizations, and stages of vaccine development and manufacturing progressing in months, rather than years. However, these last minute investments are costly and will not always be successful—underscoring the importance of having tools to prevent, detect, and treat these emerging pathogens before we need them.

The list of emerging diseases identified by the WHO includes Crimean Congo hemorrhagic fever (CCHF), Ebola and Marburg, Lassa fever, Rift Valley fever (RVF), Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS), and Nipah virus. There are some striking similarities between these eight pathogens: all eight are viral, zoonotic, and there are no approved vaccines, point-of-care diagnostics, or treatments for any of the eight diseases.

Below, GHTC provides an overview of the eight diseases and the state of R&D for diagnostics, drugs, vaccines and other technologies against them.

Crimean-Congo hemorrhagic fever

Why should we be concerned?

CCHF is tick-borne virus that is fatal in up to 40 percent of cases. First reported in Tajikistan in the 12th century, CCHF is now endemic in the Balkans, the Middle East, central and south Asia, and Africa. A hemorrhagic fever, CCHF affects many parts of the body and can weaken blood vessels. Initial symptoms are often nonspecific—fever, headache, muscle and back pain, vomiting, diarrhea—but as the disease progresses, patients may experience light sensitivity, redness of the face and throat, jaundice, depression, exhaustion, and mood swings.

CCHF can be found in a myriad of both wild and domestic animals, including cattle, sheep, goats, horses, hedgehogs, and even ostriches. While most human cases are attributable to either tick bites or interactions with livestock, it can be transmitted between humans through contact with body fluids.

Where does R&D stand?

There are several laboratory tests to diagnose CCHF, however, diagnosing the disease in low-resource settings presents challenges. Blood and tissue samples are contagious and should not be handled outside of “maximum biological containment conditions,” according to the WHO.

There are currently no vaccines or drugs approved to treat CCHF. Current treatment involves managing the symptoms, including the provision of fluids and electrolytes. Ribavirin, an antiviral hepatitis C medicine, is often used to treat CCHF, although clinical trials to demonstrate its efficacy have been inconclusive. There is a vaccine candidate in early-stage development which has proved effective in mice.

Ebola and Marburg virus disease

Why should we be concerned?

It is possible that Ebola could literally be the “next Ebola” outbreak. Marburg virus, a close relative of Ebola, is another leading contender. Both Ebola and Marburg viruses reside in monkeys and bats and can jump from animals to humans, however, most cases result from human-to-human transmission, through exposure to bodily fluids.

Ebola and Marburg are also hemorrhagic fevers, and the symptoms—fever, headache, malaise, diarrhea, abdominal pain, nausea, vomiting—are easily confused with malaria, typhoid fever, or meningitis, depending on the local disease burden. Cases of Marburg and Ebola can only be confirmed in laboratory settings, and similar to CCHF, patient samples are a major biosafety risk if handled inappropriately. In late 2014, the WHO Prequalification Program instated an emergency mechanism to allow for rapid review of Ebola diagnostics, resulting in the approval of six diagnostics for emergency use. The WHO, in partnership with Médecins Sans Frontières and FIND, also convened diagnostic companies to plan for the accelerated development of rapid, point-of-care diagnostics.

Where does R&D stand?

The recent West African outbreak galvanized US$165 million for Ebola R&D, and several Ebola vaccine and drug candidates in development are also intended to prevent and treat Marburg. However, to stymie the next outbreak, sustained investment in Ebola and Marburg R&D is needed for the advanced development, regulatory review, introduction, and roll-out of promising vaccines, drugs, and diagnostics.

Lassa fever

Why should we be concerned?

Lassa fever is primarily transmitted to humans through the bodily fluids of either rats or other humans. While 80 percent of those infected are asymptomatic, 20 percent experience the standard set of symptoms associated with hemorrhagic fevers, and in severe cases, swelling of the face and brain, shock and seizures, and deafness.

Where does R&D stand?

Cases can only be confirmed in the lab, and there are no vaccines or drugs approved to specifically treat or prevent Lassa. The aforementioned hepatitis C drug—ribavirin—is also used to treat Lassa fever, with again only limited data available on its efficacy. The primary method of Lassa prevention and control involves promoting hygiene and protecting homes and food from rodents.

Rift Valley Fever

Why should we be concerned?

RVF is found in sub-Saharan Africa and the Arabian Peninsula. Most cases are either asymptomatic or mild with nonspecific symptoms, including fever, muscle and joint pain, and headache. Eight percent of patients experience more severe symptoms which can include lesions in the eye and loss of vision; swelling of the brain (encephalitis); or a hemorrhagic fever.

Sheep, cattle, camels, and goats can all become infected with RVF and most human cases are attributable to contact with infected animal tissue, through slaughter, disposal, or veterinary care. It is believed that humans can also become infected through consumption of unpasteurized dairy products or mosquito bites. No cases of human-to-human transmission have been reported.

Where does R&D stand?

RVF can only be diagnosed in the lab, and the range of symptoms makes it difficult to detect. Treatment is supportive, and is tailored to the patients’ symptoms. The US Centers for Disease Control and Prevention have developed an experimental vaccine against RVF for use in animals. Initial studies have been encouraging, suggesting that the vaccine is safe, effective, and inexpensive.

Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome coronaviruses

Why should we be concerned?

MERS and SARS affect the upper respiratory and gastrointestinal systems, and the two coronaviruses have similar symptoms, including fever, cough, and shortness of breath. While MERS is less contagious than SARS, it is four times more deadly, killing up to 40 percent of those infected.

SARS was first identified in 2002, infecting 8,000 people, primarily in China, Hong Kong, and Taiwan. However, the outbreak lasted less than a year, and there have been no new cases since 2004. Since the 2012 emergence of MERS, more than 1,600 cases have been reported in 26 countries. Most cases, however, are found in the Arabian Peninsula, and all other cases are attributed to Middle East travel.

While both viruses are found in bats, most cases of these airborne diseases come from human-to-human transmission. MERS is also found in camels and camel-to-human transmission is believed to be a significant source of new cases. In the Arabian Peninsula, 12 percent of camels are infected with MERS at any given time, however, the virus merely causes an innocuous cold in camels.

Where does R&D stand?

There are no approved vaccines or drugs for either SARS or MERS, and both must be confirmed in the lab. Without effective antivirals against the coronaviruses, treatment involves addressing the symptoms. Convalescent blood plasma therapy—in which the blood plasma of survivors, containing antibodies against the virus, is provided to patients—has been used experimentally for both diseases, and decreased the SARS fatality rate by 23 percent. A number of treatments for MERS are in development, however, none have progressed to human trials. There are several MERS vaccine candidates, and human trials are planned for at least one. Additionally, a MERS vaccine for camels has undergone an initial, promising round of testing. GHTC member Sabin Vaccine Institute is also working on a vaccine for SARS.

Nipah

Why should we be concerned?

Nipah virus was first identified in 1999, during an outbreak of the illness in Malaysia and Singapore, in which nearly 300 cases and 100 deaths were recorded, primarily among pig farmers. To stop the spread of Nipah, more than 1 million pigs were slaughtered. Since then, regular outbreaks have occurred in Bangladesh and India.

Nipah impacts the nervous and respiratory systems, causing inflammation of the brain, sluggishness, disorientation, and encephalitis. Nipah kills 40 percent of those infected, and survivors often experience long-term effects, including convulsions and personality change.

Where does R&D stand?

Diagnosing Nipah virus requires multiple laboratory tests. As is the case with CCHF and Lassa fever, the drug ribavirin has been used to treat Nipah, however, its efficacy has not been confirmed. While there is no vaccine to prevent Nipah, human antibodies against it have been tested in ferrets, and results suggest that these antibodies could provide protection against the virus.

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