The Most Feared Pathogens: 9 Diseases that Could Cause a Major epidemic

These are the emerging pathogens of greatest concern to WHO, according to a list drawn up in 2016 and soon to be updated.

A pathogen priority list waiting to be updated

In 2016, following the Ebola epidemic in West Africa, the WHO compiled a list of emerging pathogens that are likely to cause the next pandemic. What did the 9 pathogens on the list have in common? They were all viruses for which relatively little was known and for which there was no vaccine or treatment at the time. They are emerging because, although they have been present in animal reservoirs for hundreds of years, they have only recently (in the last few decades) been identified as causing disease in humans. They are feared because of their high mortality rate and because, although the transmission rate may be low for some, certain hospital settings or genetic mutations could increase the ease with which they spread from person to person.

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The following year, the WHO added two pathogens to the list: Zika (which, although already known, caused a previously undescribed set of symptoms in the fetuses of pregnant women) and Disease X (recognising that there are many unknown viruses in animal reservoirs with the capacity to cause disease in humans).

In 2023, a consultation process was launched to update the list of priority pathogens with pandemic potential, the outcome of which should be known soon. In the meantime, the WHO has published a priority list of fungal pathogens (with global warming, mycoses are an increasing threat) and a list of antibiotic-resistant bacteria that pose the greatest threat to public health.

The emerging viruses that deserve the most attention, according to the original list, are:

1 & 2. Ebola and Marburg disease

The Ebola virus was first identified in 1976 and the Marburg virus in 1967. Both can jump from their natural reservoir (bats) to human and non-human primates. The virus can then spread to other humans through direct contact with blood and bodily fluids. Both diseases are characterized by fever, diarrhoea, vomiting and bleeding, and have a case fatality rate that varies between 25 and 90%. There are 5 species of Ebola virus, of which the Zaire species has caused the most outbreaks and deaths. The most lethal outbreak in recorded history has been the West African outbreak in 2014-2016, which caused more than 11,000 deaths.

Since the list was published in 2016, there have been two Ebola vaccines approved (both targeting the Zaire species) and two treatments based on monoclonal antibodies (also targeting the Zaire species).

The Marburg virus is also endemic to Africa and has caused outbreaks in Uganda, Democratic Republic of Congo, Kenya and South Africa. There are currently no approved treatments or vaccines against Marburg virus, although some are being tested in clinical trials.

3. Lassa fever

The Lassa fever virus was first identified in 1950 and its reservoir is the multimammate rat. It is transmitted to humans through the inhalation of aerosols or the ingestion of food contaminated by rat urine or droppings. Human to human transmission may also occur after exposure to blood or bodily fluids and it was estimated that up to 20% of Lassa fever cases may be due to this kind of transmission, with some individuals acting as “super spreaders”. Even though 80% of infected people do not develop symptoms, one out of five infections may be severe: 15 to 20% of patients hospitalized with Lassa fever die from the illness. There is no vaccine, although an antiviral treatment (ribavirin) has proved to be relatively effective. The disease is endemic in West Africa and has caused hundreds of deaths over the last years, particularly in Nigeria.

4. Crimean-Congo Haemorrhagic Fever (CCHF)

The CCHF virus, first identified in Crimea in 1944, is transmitted to humans by ticks on domestic animals such as cattle. Human to human transmission can also occur through exposure with bodily fluids. The virus causes a hemorragic fever with a case fatality rate of up to 50%.  The disease is endemic in countries below 5º north latitude, in Africa, the Balkans, Middle East and Asia. Cases have also been reported in Spain and other European countries.

5. Rift Valley Fever virus

The RVF virus was identified for the first time in Kenya in 1931 and, although it mainly affects animals, it can also infect humans. Its lethality rate is very low (1%) but the virus can occassionally cause a severe form of the disease characterized by ocular disorders, encephalitis and/or haemorrhagic fever, in which case the mortality is of 50%. The vast majority of human infections occur through the handling or ingestion of blood, organs or milk of infected animals.

Additionally, infections can also result from the bites of infected Aedes mosquitoes or flies. To date, no human to human transmission has been reported. A series of candidate vaccines against RVF are currently being tested. Outbreaks have been reported in Africa, Yemen and Saudi Arabia.

6. MERS

The coronavirus that causes Middle East Respiratory Syndrome was first identified in Saudi Arabia in 2012. Camels seem to be an important virus reservoir, although most cases reported are due to human to human transmission, almost exclusively in hospital settings. It is a mildly contagious virus that is transmitted upon close exposure to respiratory secretions, such as coughing. Its mortality rate is around 40% and it affects mainly older elderly people with underlying medical conditions. So far, all reported cases are linked to countries in the Arabian Peninsula, although an outbreak in South Korea in 2015, triggered by an imported case, confirms the pandemic potential pandemic of the virus.

7. SARS

The Severe Acute Respiratory Syndrome is caused by another coronavirus, similar to MERS and closely related to SARS-CoV-2. Its natural reservoir is not known with certainty but is probably bats and cat-like mammals called civets.  It was reported for the first time in 2003 in Asia, from where it rapidly spread to more than 12 countries in America, Europe and Asia causing 8,000 cases and more than 8,000 deaths. In contrast with MERS, SARS was transmitted outside hospital settings and affected mainly healthy, young people. Since 2004, no other SARS case has been reported.

8 & 9. Nipah and Hendra virus

Both viruses belong to the same family and share the same reservoir: bats. Nipah virus was first isolated in 1999 after an encephalitis outbreak among pig farmers in Malaysia and Singapur. Since then, periodic outbreaks have been reported in Bangladesh. It causes mild disease in pigs, but severe disease in humans, killing 40% of infected people.

Nipah causes mild disease in pigs, but severe disease in humans, killing 40% of infected people

It is transmitted to humans by direct exposure to pigs, bats and/or date palm sap contaminated by faeces from infected bats.  Transmission between humans, probably via saliva, has also been reported for the Bangladesh outbreaks. Concerning Hendra virus, one single outbreak of the disease was reported in Australia, in 1994, where horses and seven persons were affected, with a lethality rate of 60%.

Chikungunya and Zika

The chikungunya and zika viruses were not included in the list when it was established, but were classified as serious threats that require more R&D investment. In fact, due to the high association observed between foetal malformations and Zika infections in pregnant women, the WHO declared the Latin American Zika outbreak of 2016 a public health emergency of international concern and added the disease to the list.

Disease X

In February 2018, the WHO added Disease X to the list of priority pathogens, to draw attention to the fact that the next epidemic or pandemic could be caused by a yet unknown virus, and to highlight the need to develop tools (vaccines, treatments, diagnostics) that target whole classes of viruses rather than one specific pathogen. COVID-19, caused by a virus closely related to SARS (which was already on the list), is a perfect example of Disease X.

This priority list of “dangerous suspects” should provide the basis for accelerating research and development in diagnosis, vaccines and treatments against entire viral families

Other diseases with epidemic potential such as tuberculosis, HIV/AIDS, malaria, avian influenza and dengue were not included because there are major ongoing control and research networks for these pathogens, as well as approved or pipeline treatments.

This priority list of “dangerous suspects”, which will be updated soon, should provide the basis for accelerating research and development of diagnostics, vaccines and treatments not only against individual viruses but against broader viral families (e.g. vaccines that protect against all betacoronaviruses), and hopefully prevent another public health and humanitarian crisis like the COVID-19 pandemic.

[This article was originally published on February 2016 and it has been updated on September 6th, 2023]