Middle East Respiratory Syndrome

What is it?

Middle East Respiratory Syndrome (MERS) is a respiratory illness caused by a coronavirus called Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This virus belongs to the same family of viruses that causes the common cold, severe acute respiratory syndrome (SARS), and COVID-19.

MERS is a zoonotic disease, meaning it passes from animals to humans. Dromedary camels have been shown to also carry the virus, and are thought to be the main source of infections in humans. Direct or indirect contact with infected dromedary camels, including animal husbandry, care, and slaughter, increases the risk of infection with MERS-CoV. Other risk factors include consumption of raw or undercooked dromedary meat, milk or urine. Human-to-human transmission is possible, but only a few such transmissions have been found among family members living in the same household. In health care settings, however, human-to-human transmission appears to be more frequent.

The origins of the virus are not fully understood but, according to the analysis of different virus genomes, it is believed that it may have originated in bats and was transmitted to camels sometime in the distant past.

Where does it occur?

The first documented cases of MERS-CoV were identified in 2012 in Jordan and Saudi Arabia. Since then, most cases have been reported from the Arabian Peninsula, with Saudi Arabia reporting about 80% of global total cases. From 2012 to 2020, 27 countries have reported cases of MERS to the WHO, of which 12 are in the Eastern Mediterranean WHO region. All reported cases of MERS to date have been linked to the Arabian Peninsula.

In 2015, the Republic of Korea suffered the largest MERS outbreak outside of the Middle East, with 185 laboratory-confirmed cases and 38 deaths reported. The outbreak was caused by the importation of a single case returning from the Arabian Peninsula.

Who does it affect?

MERS-CoV can infect people of any age, however middle-aged adults are at highest risk of infection. The age group 50-59 years has been the most affected by primary infections (i.e. from dromedary camels). The age group 30-39 years is the most affected among secondary cases (acquired from other persons through human-to-human transmission).

The symptoms of disease may vary from case to case, with a clinical spectrum ranging from infection with no symptoms, mild respiratory illness to severe respiratory disease and death. MERS-CoV infection typically causes respiratory symptoms including cough, shortness of breath and pneumonia. Other symptoms include fever, headache, and diarrhoea.

The virus appears to cause more severe disease in older people, people with weakened immune systems, and those with chronic diseases such as renal disease, cancer, chronic lung disease, and diabetes.

Approximately 35% of people with confirmed MERS-CoV infection have died. However, this may be an overestimate of the true case fatality risk (CFR), as mild cases of MERS may be missed by existing surveillance systems.

How do we currently prevent infections?

MERS-CoV, like other coronaviruses, is thought to spread from an infected person’s respiratory secretions, such as through coughing. However, the precise ways the virus spreads are not currently well understood. MERS-CoV has spread from ill people to others through close contact, such as caring for or living with an infected person. Infected people have spread MERS-CoV to others in healthcare settings, such as hospitals.

Adherence to strict infection prevention protocols in health care settings is essential. Preventive measures in the community including hand hygiene, coughing away from others and into elbows, and avoiding social contacts when symptomatic.

When handling camels, practicing good hygiene measures is important, and protective equipment may be advised in some instances.

When handling camel products, raw materials should be handled according to safe food hygiene practices, and consumption of raw and undercooked meat and milk should be avoided.

No vaccine or specific treatment is currently available, however several MERS-CoV specific vaccines and treatments are in development. Treatment is supportive and based on the patient’s clinical condition.

How is CEPI supporting MERS vaccine R&D?

CEPI has invested in the development of four MERS vaccine candidates, three of which are in active development. Three of these vaccines have entered clinical trials.

With partnerships initiated to advance development of MERS vaccine candidates, CEPI was able to use this knowledge of another coronavirus and act quickly in response to the COVID-19 pandemic.

In October 2020, the first WHO International Standard for MERS-CoV antibodies was established by the WHO Expert Committee on Biological Standardization. This standard was developed by the International Vaccine Institute (IVI) and the National Institute for Biological Standards and Control (NIBSC), funded and facilitated by CEPI. Antibody standards act as a comparator to assess the antibody (immune) response elicited by candidate vaccines. It is also a useful tool for research on MERS-CoV immunity.

Nipah virus

What is it?

Nipah virus belongs to the Paramyxoviridae family of viruses, genus Henipavirus, alongside Hendra virus. Nipah is a zoonotic disease, meaning it passes from animals to humans.

The natural hosts of the virus are fruit bats (also known as flying foxes) of the genus Pteropus. Nipah virus can be spread to people from infected bats, infected pigs, or infected people.

Where does it occur?

Nipah virus was first identified in 1999 during an outbreak of illness affecting pig farmers and others having close contact with pigs in Malaysia and Singapore. Over 100 human deaths were reported, and over a million pigs were killed in the effort to stop the outbreak. No cases of person-to-person spread were reported. In 2001, there was an outbreak of Nipah virus in people in Bangladesh, and a separate outbreak in a hospital in India. In both countries, person-to-person transmission occurred. Since then, Bangladesh has suffered outbreaks nearly every year – with over 300 confirmed cases occurring there from 2001 to 2015.

India has also occasionally reported cases and experienced an outbreak in the southern State of Kerala earlier in 2018. A total of 19 Nipah virus cases, including 17 deaths, were reported from Kerala State. Those who died included a nurse who had been caring for a patient ill with Nipah virus disease. More than 2500 contacts of Nipah patients were monitored by the state surveillance system and a 24-hour helpline took queries from the community. By mid-June, the Kerala government and the Union Health Ministry announced that the outbreak had been contained.

In June 2019, the Indian Government confirmed a new case of Nipah virus infection in a 23-year-old man in Kerala, India – the same state that experienced a deadly outbreak of the disease last year. The patient was hospitalised and was discharged after 2 months. In total, 355 case contacts were monitored and 7 were kept in the isolation ward of a government hospital.

So far, Nipah outbreaks have been confined to South and Southeast Asia, but Pteropus bats are found in a large geographical area across the globe covering a population of more than 2 billion people.

What are the symptoms?

Nipah virus infection can cause severe, rapidly progressive illness that affects the respiratory system and the central nervous system, including inflammation of the brain (encephalitis). Symptoms begin between 5 and 14 days after infection, and include fever, altered mental state, cough and respiratory problems.

Through a 14-year study in Bangladesh, another country prone to Nipah outbreaks, research published in May 2019 identified that increasing age and respiratory problems were key indicators in the infectivity of the virus.

How do we currently prevent infections?

People are advised to avoid contact with ill pigs and bats in countries where Nipah virus is known to occur. They are also advised to avoid drinking raw date palm sap, which can be infected with bodily fluids from bats.

The experimental antiviral drug, Remdesivir, which is being tested against the Ebola virus in the ongoing outbreak in the DRC, has also shown promise in protecting against infection with Nipah virus in preclinical trials.

How is CEPI supporting Nipah vaccine R&D?

There are currently no vaccines or specific therapeutics against Nipah virus approved for use in humans.

CEPI has invested in the development of four Nipah vaccine candidates, one of which is the first ever Nipah vaccine to enter clinical trials.

In 2019, CEPI co-hosted the first ever international Nipah virus conference with Duke NUS Medical School in Singapore.

Rift Valley fever

What is it?

Rift Valley fever (RVF) is an acute viral haemorrhagic disease caused by the RVF virus (RVFV), an RNA virus belonging to the Phlebovirus genus and Phenuiviridae family. RVFV is transmitted by mosquitoes (Aedes, Culex, Anopheles, and Mansonia spp.) and blood feeding flies and most commonly affects domesticated animals (such as cattle, sheep, goats, and camels) but can also cause illness in people.

Most human infections occur due to direct contact with; 1) blood, body fluids, or tissue of infected animals during slaughter or butchering; 2) during veterinary procedures like assisting an animal while giving birth, 3) when consuming raw or undercooked animal products, and 4) through bites from infected mosquitoes.

Because of its potential to cause a public health emergency and the absence of an efficacious vaccine, RVF is a WHO priority disease for which accelerated vaccine research and development is urgently required.

RVF disease affects trade resulting in significant economic losses due to mortality and abortion among RVF-infected livestock in the regions where outbreaks occur (e.g. ~$60M loss in East Africa during the 2006-2007 outbreak, ~$17.8M loss in South Africa, during the 2010 outbreak).

Where does it occur?

RVF was first identified in 1930, during an outbreak of sudden deaths and abortions among sheep along the shores of Lake Naivasha in the greater in Rift Valley, Kenya. Since then, multiple outbreaks have been reported across the African continent and the Arabian Peninsula. To date, RVF has been found in over 30 countries.

The most serious outbreaks recorded occurred in Egypt in 1977 during which 20,000 to 40,000 people were infected and 600 people died. In 1997, another major outbreak occurred in East Africa, during which 90,000 people were infected and 500 people died. Recent confirmed outbreaks have occurred in Sudan in 2020, the island of Mayotte, a French overseas territory in the Indian Ocean in 2019 and in Kenya in 2018.

There is a RVF endemic cycle and periods of climate-driven epidemics, particularly seen in East Africa. Past outbreaks in this region have been closely associated with cycles of abnormally heavy rainfall that occur during the warm phase of the El Niño/Southern Oscillation (ENSO) phenomenon. This results to floods and increased vegetation cover favoring high vector density and species diversity.

What are the symptoms?

People with RVF usually show no symptoms or develop a mild illness. Sign of illness include fever, weakness, myalgia (muscle pain), back ace, dizziness liver abnormalities, and weight loss. In some patients, the illness can progress to haemorrhagic fever, encephalitis (inflammation of the brain), or ocular disease (inflammation of the eye, blindness). Severe complications develop in 8-10% of cases though most people recover within four to seven days. Approximately one per cent (1%) of humans infected with RVF dies of the disease. In people who develop the haemorrhagic form of the disease, the fatality is around 50%.

RVF causes severe disease in animals that is characterized by fever, weakness, abortions, and a high rate of severe illness and death, particularly among young animals. RVFV infection causes abortion in nearly 100% of livestock pregnancies and most young animals that are infected will die, whereas fatality among adult animals is significantly lower.

How do we currently prevent infections?

People are advised to 1) avoid contact with blood, body fluids, or tissues of infected animals, 2) avoid unsafe animal products, and 3) avoid exposure to mosquitoes When handling specimens from patients, healthcare workers caring for patients with suspected or confirmed RVF should implement Standard Precautions.

Because most cases of RVF are mild and self-limiting, a specific treatment for RVF has not been established. Treatment for more serious cases may require hospitalization and are generally limited to supportive care.

RVF vaccines have been used successfully to protect livestock. However, there are no vaccines currently approved for human use.

How is CEPI supporting Rift Valley fever vaccine R&D?

CEPI has invested in the development of two RVF vaccine candidates. One of these vaccines is amongst the first in the world to enter clinical trials.

Our Rift Valley fever vaccine projects and Chikungunya vaccine projects receive support from the European Union’s Horizon 2020 programme.

CEPI is also funding a RVF systematic literature review and meta-analysis to consolidate the understanding of the RVF epidemiology to determine the feasibility of a vaccine efficacy trial.

What is it?

Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, is a severe, often fatal illness which affects humans and other primates (such as monkeys, gorillas, and chimpanzees). It is caused by an infection with a group of viruses within the genus Ebolavirus.

Ebola is a zoonotic disease, meaning it passes from animals to humans. Outbreaks are thought to occur when Ebola is transmitted to people from wild animals, following which it can spread in the human population. Infection may occur through direct contact with blood or other body fluids of sick people, through direct contact with a symptomatic person (social, or caregiving) or through contact with surfaces (such as bedding or clothing) contaminated with body fluids of a sick person. The virus can also be transmitted through sexual contact or when handling the body of a person who has died from Ebola virus disease.

It is thought that fruit bats of the Pteropodidae family act as a reservoir for Ebola virus.

Where does it occur?

The first documented Ebola outbreaks occurred in remote villages in Central Africa, near tropical rainforests. The risk of Ebola outbreaks exists primarily on the African continent. Since the virus and associated disease were identified in 1976, outbreaks have been reported from 8 African countries. The most recent outbreaks have occurred in the Democratic Republic of Congo (DRC), in North Kivu and Ituri provinces from August 2018 to June 2020 and in Equateur province from June 2020 to November 2020.

From 2014 to 2016, West Africa suffered the largest and most complex Ebola epidemic since the virus was first discovered in 1976. Sierra Leone, Liberia, and Guinea were the most affected countries. This multi-country and region outbreak resulted in over 28,000 cases and 11,000 lives lost to the disease.  The epidemic spread across borders to other countries in the region (Mali, Senegal, Nigeria) as well as Europe and the United States.  It is estimated that the epidemic resulted in a socioeconomic loss of over US $53 billion.

The world’s response to this crisis fell tragically short. While Ebola vaccines had been in development for more than a decade, no system existed to facilitate and speed up the development of vaccines to respond to this type of outbreak. As a result, it was nearly a year into the epidemic before clinical trials were deployed to try to develop vaccines.

CEPI was set up in response to this devastating outbreak, as an international, intergovernmental alliance to develop vaccines to better prepare for emerging disease threats.

What are the symptoms?

The Ebola incubation period is typically from 2 to 21 days. A person infected with Ebola virus cannot spread the disease until they develop symptoms.

Symptoms of EVD can be sudden and include fever, fatigue, muscle pain, headache and sore throat. This can be followed by vomiting, diarrhoea, rash, symptoms of impaired kidney and liver function and haemorrhaging. The average case fatality rate is around 50%, although case fatality rates have varied from 25% to 90% in different outbreaks.

Ebola survivors may experience long term impacts of the disease following recovery from acute illness, including vision problems, tiredness, muscle aches, and stomach pain.

How do we currently prevent and manage infections?

Effective control of an outbreak of Ebola relies on coordination and implementation of several interventions including case management, infection prevention and control, surveillance and contact tracing, laboratory and diagnostics, and safe and dignified burials. Community engagement is critical to successfully controlling outbreaks.

Several vaccines to protect against Ebola are in development and have been used to help control the spread of Ebola during outbreaks. In 2019, the European Commission granted a conditional marketing authorisation to the Ervebo vaccine, produced by Merck, and the WHO prequalified this vaccine allowing UN agencies and Gavi to procure the vaccine for distribution. In December 2019, Ervebo was approved for use in the USA. In 2020, a second Ebola vaccine developed by Janssen, the vaccine arm of Johnson & Johnson, received regulatory approval from the European Commission.

Ebola-specific treatments are also being evaluated and have been deployed in outbreaks. Supportive care, including rehydration with oral or intravenous fluids, and treatment of specific symptoms can significantly improve survival. Two drugs, REGN-EB3 and mAb114, have been found to improve survival, in a multi-drug randomised control trial, conducted in the DRC in 2019.

How is CEPI supporting Ebola vaccine R&D?

To date, two Ebola vaccines have achieved licensure and WHO prequalification. CEPI has supported the generation of clinical trial data for both of these vaccines, and is contributing to expanding access to Ebola vaccines to additional at-risk groups and subpopulations by funding trials in people living with HIV, pregnant women and infants.

In 2019, CEPI was part of a global consortium supporting the Government of the DRC to conduct a large-scale clinical trial with a second investigational Ebola vaccine, manufactured by Janssen, the vaccine arm of Johnson & Johnson, as part of ongoing efforts to control the outbreak in North Kivu and Ituri provinces. The consortium was led by the DRC Ministry of Health and Institut National de Recherche Biomédicale and included London School of Hygiene and Tropical Medicine, CEPI, Médecins Sans Frontières, and Epicentre; with the Wellcome Trust contributing critical strategic guidance. Janssen Vaccines & Prevention B.V. donated the experimental vaccine regimen for the study undertaken by the consortium.

In addition, CEPI is:

– Part of a collaboration which launched a two-year clinical trial of the Janssen vaccine among healthcare and frontline workers in Uganda.

– Supporting a clinical trial to assess the safety and immunogenicity of the Janssen vaccine in pregnant women in Rwanda.

– An associated partner of EBOVAC 3, an IMI-funded project to assess the safety and immunogenicity of the Janssen vaccine in infants in Guinea and Sierra Leone and healthcare workers in DRC.

– Supporting PREVAC-UP, an EDCTP-funded project to assess long-term immunogenicity of both the Janssen and Merck vaccines in Guinea, Liberia and Sierra Leone.