Public Health Emergency of International Concern (PHEIC) is defined in the International Health Regulations (IHR, 2005) as an extraordinary event that is determined to “constitute a public health risk to other states through the international spread of disease and to potentially require a coordinated international response” [1].

This definition implies that a situation that is serious, unusual or expected; carries implications for public health beyond the affected states national borders and might require immediate international action (2,3). 

To decide that whether an event is a PHEIC or not, the WHO-Director general requires the convening of a committee of experts–the IHR Emergency Committee (EC). WHO member states have 24 hours timeline to report the supposedly or potential PHEIC events to WHO (4). This committee advises the Director- General as to what should be the recommended measures to be taken on emergency basis, called as temporary recommendations. These recommendations are specifically for the country experiencing the PHEIC and by others to prevent the spread of disease internationally. For ensuring rapid detection, verification and response to public health risks the WHO develops and provides the tools, guidance and training. Since 2009 there have been following declarations:

 

• H₁N₁Pandemic (swine flu) in 2009

• Polio declaration in 2014

• Outbreak of Ebola in western Africa in 2014

• Zika virus outbreak in 2015-16

• Kivu Ebola virus outbreak in 2018-20

• Recent ongoing COVID-19 Epidemic

IHR algorithm helps and assists WHO member states to arrive at a conclusion that whether a PHEIC exists or not and thereafter the WHO is notified. If any two out of the four questions mentioned below are confirmed then WHO must be notified [2]:

• Q1. Is the public health impact of the event serious?

• Q2. Is the event unusual or unexpected?

• Q3. Is there a significant risk for international spread?

• Q4. Is there a significant risk for international travel or trade restrictions?

Besides these there are list of diseases that are always notifiable as PHEIC. Smallpox, SARS, Poliomyelitis and any new type of human influenza are always a PHEIC and do not require an IHR decision to declare them as PHEIC [2]. These four diseases have been well established as being unusual or unexpected and are expected to have serious public health impact thereafter even a single case of these four disease entities (as defined by the WHO case definitions) must be notified to WHO, irrespective of the context in which they occur. 

Review of all the PHEIC’s

We present various PHEIC’s individually with respect to the timelines and various scientific facts associated with them.

H₁N₁ Infuenza 2009

H₁N_1, a novel influenza virus began spreading in 2009 and CDC labeled it as the first global flu pandemic in 40 yrs. H₁N_1, is a type of influenza virus, a RNA virus. The incubation period of H₁N₁ is 1-7 days. It causes an acute febrile respiratory illness. The R₀ of H₁N₁ (2009) was 1.46 -1.48 [5].

The timelines of this pandemic are:

April 2009: On 15th April, the first human infection with novel H₁N₁virus was detected in California in a 10-year-old boy, who had developed symptoms in the month of March 2009. Subsequently, on 17th April 2009, the second case was detected who was an eight-year-old boy, around 130 miles away from the first case and this child also had symptoms since March 2009 [6]. CDC reported to WHO through IHR, the first novel H₁N₁infections on 18th April 2009 [7].

CDC declared 2 cases of novel H₁N₁virus on 21^st April 2009and conveyed that the efforts to develop a vaccine were initiated. In Texas, 2 more cases were reported on 23^rd April 2009. The gene sequence of novel H₁N₁ were uploaded by CDC on influenza databases on 24^th April 2009 [7]. On 25^th April 2009, under the rules of International Health Regulations (IHR), the Director General of WHO declared H₁N₁ as a PHEIC [8].

WHO declared H₁N₁ as a PHEIC in April 2009 and subsequently a pandemic in June 2009, after the virus reached more than seventy countries. In response to this some countries implemented travel restrictions for travel to North America. China imposed mandatory quarantines for patients and their close contacts [7]. The CDC estimated that between 151,700 and 575,400 people died worldwide and around 12,500 in the United States in the first year after the virus was discovered. Around 80 percent of those who died were younger than sixty-five. ⁽⁷⁾

The EC, established in compliance with the IHR (2005), held its second meeting on 27 April 2009 [9]. The Committee considered available data and based on their advice, the WHO Director-General raised the level of influenza pandemic alert from phase 3 to phase 4. It was recommended not to restrict international travel. 

People, who were sick, were advised to delay international travel and those who developed symptoms following international travel were asked to seek medical attention [9]. 

WHO decided to facilitate the process needed to develop a vaccine effective against (H₁N₁) virus [9].

June 2009: The WHO Director-General convened a third meeting of the IHR EC on 5 June 2009 [11]. In discussion with the committee, the Director-General noted that the pandemic was continuing and reaffirmed that WHO will continue to monitor the situation closely in all countries reporting cases of new influenza A (H₁N₁) [10].

The EC held its fourth meeting on 11th June 2009 [11].

September 2009: As of 20^th September, there were more than 3,18,925 laboratory confirmed cases of pandemic influenza H₁N₁, 3917 deaths, in 191 countries and territories reported to WHO [12]. The ECEC held its fifth meeting (online meeting) on 23 September 2009. ⁽¹³⁾ The committee considered a proposal from the WHO Director-General regarding the continuation of three temporary recommendations issued under the IHR and there was a consensus on continuing these [13].

A vaccine for H₁N₁ was expected in November 2009, with production of three billion doses per year [14]. The FDA gave approval to four H₁N₁ (2009) influenza vaccines [15].

October 2009: Worldwide there were more than 414,000 laboratory confirmed cases of influenza H₁N₁ 2009 and over 5000 deaths reported to WHO [16]. First doses of H₁N₁ vaccine were given in the U.S [15].

November 2009: On 22nd November 2009, more than 207 countries and overseas territories or communities reported 622482 laboratory confirmed cases of pandemic influenza H₁N₁ (2009), including 7826 deaths [17]. The EC held its sixth meeting, by teleconference on 26 November 2009. ⁽²⁴⁾ After considering the views of the EC, the Director-General conveyed that it was appropriate to continue all the temporary recommendations [18].

February 2010: Worldwide more than 213 countries and overseas territories or communities had reported laboratory confirmed cases of pandemic influenza H₁N₁ 2009, including at least 16226 deaths [19]. The EC held its seventh meeting by teleconference on 23 February 2010. ⁽²⁰⁾ Having considered the views of the EC and the ongoing pandemic situation, the Director-General suggested to continue the three temporary recommendations [20]. 

June 2010: The EC held its eighth meeting by teleconference on 1^st June 2010 [28]. A global update was provided to the Committee on the pandemic situation. The most active areas of pandemic transmission were in tropical areas, primarily in parts of the Caribbean and Southeast Asia. Following the advice of the EC, the Director-General conveyed that while the period of most intense pandemic activity had passed, pandemic disease was expected to continue, therefore another meeting of the EC would be done to reassess the epidemiological situation [21].

August 2010: The EC held its ninth meeting by teleconference on 10^th August 2010 [22]. The EC was given an epidemiological overview and update of the global H₁N₁ (2009) pandemic influenza situation by the secretariat. The WHO announced the pandemic’s end in August 2010, though the strain continues to circulate seasonally [22]. 

POLIO 2014

Polio virus belongs to human enterovirus of Picornaviridae family. It is a non enveloped RNA type of virus. It consists of intranuclear cowdry 3 inclusion bodies. Wild Poliovirus (WPV) has 3 serotypes, Type 1, 2 and 3. Type 1 is the most common type which is responsible for epidemics whereas type 2 causes endemic infections and type 3 is the most common cause for Vaccine Associated Paralytic Polio (VAPP), associated with Sabin OPV. Poliomyelitis predominantly affects children and leads to acute flaccid paralysis and sometimes death by paralysis of respiratory muscles.

There were approximately 3, 50,000 annual cases reported in 125 countries in 1988 which decreased to 143 cases in two countries in 2019 [23]. 

The WHO region of Americas was certified to be polio free in 1994, followed by the Western Pacific region in year 2000 and WHO European region in 2002. In March 2014, WHO South –East Asia region was also declared polio free and the transmission of wild poliovirus was interrupted in 11 countries extending from Indonesia to India [24].

2012 to 2013: Lowest number of new polio cases were reported worldwide in 2012, when 293 confirmed cases were reported from nine countries, of which 223 were caused by WPV [34]. The number of polio cases caused by WPV increased to 417 in 2013.There were outbreaks reported from Somalia and Syria. Circulation of WPV was confirmed in Israel through environmental and human surveillance, but no symptomatic cases were reported [25]. 

2014: From 1^st January to 31^st April 2014, 68 confirmed WPV cases were notified worldwide, 54 of which were reported from Pakistan [25]. On 5^th May 2014, the Director-General of the World Health Organization (WHO), on the recommendation of the EC under the IHR declared that the spread of WPV in 2014 constituted a PHEIC, in accordance with the IHR [26]. This was the second PHEIC declared under IHR 2005 after the pandemic of influenza A (H₁N₁) in 2009. The temporary recommendations to reduce the spread of WPV were issued and it was decided to reassess the situation every three months by the EC [26]. 

On 31^st July 2014, the IHR EC met again for the situational analysis of PHEIC status of polio and for future action. Based on the conclusions of this meeting, the WHO Director General declared that the international spread of WPV in 2014 continues to be PHEIC. The temporary recommendations issued on 5 May 2014 remained valid. ⁽²⁷⁾ The international spread of WPV happened in central Asia from Pakistan to Afghanistan from May till July 2014. Meanwhile in June 2014 the WPV which had originated in Equatorial Guinea in central Africa was detected in America [27].

The WPV was actively transmitted within at least ten countries with a risk of exportation and infection to others. Eastern Mediterranean Region had maximum cases because of the “Pakistan to Afghanistan” and “Syria to Iraq” exportations. The “Cameroon to Equatorial Guinea” and “Equatorial Guinea to Brazil” were some documented exportations in the rest of world during 2014 [28]. 

2015 to 2017: There were a total of 74 cases of WPV type-1(WPV1) and all the cases were reported from two endemic countries Pakistan (54 cases) and Afghanistan (20 cases) [38]. In 2016, Pakistan reported 20 cases, Afghanistan reported 13 cases and Nigeria reported 4 cases, so a total of 37 cases were reported globally. ⁽³⁸⁾ In 2017, there were 22 cases reported from Pakistan and Afghanistan. Pakistan reported lesser cases (8 cases) as compared to previous years. Afghanistan had reported 14 cases [29,30]. 

2018: The number of cases of WPV1 in Pakistan, were same as in 2017, but in Afghanistan the number of polio cases increased from 14 in year 2017 to 21 in 2018. Total cases of WPV1 were 33 [29,30]. 

From January 2018 to June 2019, outbreaks of circulating vaccine derived polio virus (cVDPV) Type 1 and 2 were detected in 25 countries across 4 WHO regions (African, Eastern Mediterranean, South–East Asian and western pacific regions) [31]. 

2019: There was a significant rise in number of cases of WPV1. A total of 143 cases were reported. Pakistan had maximum number of cases (117 cases) and Afghanistan reported 26 cases [38]. The EC, which met in December 2019, expressed concern over “the significant increase” in cases of WPV1, the last of three strains to be eliminated [41]. 

Members said progress “appears to have reversed”, as international spread of WPV1 was at the highest point since the declaration of a PHEIC, in 2014. Transmission remained widespread in Pakistan, where challenges include continued refusal to accept vaccination by individuals and communities. There was also evidence of further spread to neighboring Afghanistan [32].

Regarding circulating vaccine derived polioviruses (cVDPV), the EC recalled that outbreaks hadoccurred in Africa, the Eastern Mediterranean, South-East Asia and the Western Pacific regions, while seven countries had reported outbreaks since its last meeting. Additionally, spread of cVDPV2 was recorded in West Africa and the Lake Chad area, reaching Cote d’Ivoire, Togo and Chad, while cVDPV1 moved from Philippines to Malaysia [33].

Besides this, there was outbreak of vaccine derived poliovirus cases in 16 countries, with 249 vaccine derived cases in 2019. Pakistan had 12 cases; Angola reported 86 cases and the Democratic Republic of the Congo had 63 cases of vaccine derived poliovirus. Nigeria reported 18 cases of vaccine-derived poliovirus, although no case of WPVtype-1 had been reported since August 2016. WPV has been eradicated in all the continents except Asia and in year 2020, Pakistan and Afghanistan were the only two countries where the disease was endemic.

2020: The number of cases of WPV cases in Pakistan decreased to 84 and the number of cases in Afghanistan increased to 56. 

2021: On 1^st Feb 2021, the 27^th meeting of the EC under the IHR (2005) was held. The EC reviewed the data on WPV1 and cVDPV and noted that based on results from sequencing of WPV1 since the last committee meeting in October 2020; there were further instances of international spread of viruses from Pakistan to Afghanistan. The ongoing frequency of WPV1 international spread between the two countries and the increased vulnerability in other countries where routine immunization and polio prevention activities have both been adversely affected by the COVID-19 pandemic are two major factors that suggest the risk of international spread may be at the highest level since 2014 [34]. 

The number of cVDPV2 cases in 2020 was 1009, 254% higher than the total for 2019. In all the years following 2016 when OPV2 was withdrawn, the number of cVDPV2 cases globally had been greater than the number of WPV1 cases. Based on the situation regarding WPV1 and cVDPV and the reports provided by affected countries, the Director-General accepted the Committee’s assessment and on 19 February 2021 determined that the situation relating to poliovirus continues to be a PHEIC, with respect to WPV1 and cVDPV [34]. The twenty-eighth meeting of the EC under the IHR (2005) was convened by the WHO Director-General on 4 May 2021 via video conference, supported by the WHO Secretariat. The EC reviewed the data on WPV1cVDPV. ⁽³⁵⁾

The Committee unanimously agreed that the risk of international spread of poliovirus remains a PHEIC and recommended the extension of temporary recommendations for a further three months. The Committee recognized the concerns regarding the lengthy duration of the polio PHEIC, but concluded that the situation is extraordinary, with clear ongoing substantial risk of international spread and utmost need for coordinated international response [35]. 

The twenty-ninth meeting of the EC under the IHR (2005) was convened by the WHO Director-General on 4^th August 2021 via video conference. The EC reviewed the data on WPV1 and cVDPV. The Committee unanimously agreed that the risk of international spread of poliovirus remains a PHEIC and recommended the extension of temporary recommendations for a further three months. The committee expressed the concerns regarding the lengthy duration of the polio PHEIC, but concluded that the situation remains risky, with ongoing risk of international spread and ongoing need for coordinated international responses [36].

EBOLA 2014

Ebola virus belongs to the family Filoviridae, it has 5 species and the Zaire, Bundibugyo, Sudan strains are the deadliest while the other two Reston and Tai Forest are not. All the species have caused disease in humans except Reston virus. The outbreak in 2014-16 in Africa was caused by Zaire species. The transmission of the disease in animals like monkeys, apes and porcupines etc. are by fruit bats who are the natural hosts of the disease. Human beings become infected only when there is a close contact with the body secretions or blood of the infected animal.

The 2014 event has been the largest documented outbreak of Ebola thus far. Nearly 14,100 cases were reported worldwide, killing almost 5,200 people-an overall mortality of 37% [37]. In August 2014 hemorrhagic Ebola Virus Disease (EVD) in West Africa was declared as a PHEIC due to potentiality of further international spread. Ebola was particularly serious in terms of rapid communicability and disastrous outcomes [38]. Furthermore, EVD had showed devastating attacks to health care providers and emergency management teams [39]. The statistically estimated basic reproductive number (R0) of EVD is 2 (95% CI, 1.44 to2.01) [40].

EVD in 2014 started and propagated in western Africa. Guinea was the index country which exported the infection to Sierra Leone and Liberia initially and later to Nigeria, Senegal and Mali in addition to Spain and United States of America [41].

The timelines of the EVD (2014-2016) are:

December 2013: The index case was reported; the case was an eighteen months old boy from a village in Guinea. The child was thought to be infected with bats [42]. 

January 2014: On 24^th January 2014, an official alert was sent to the district health officials as there were reports of 5 more cases of severe and fatal diarrhea in the area. Subsequently, many similar cases were reported from Conakry, the capital city of Guinea [42].

March 2014: On March 13^th 2014, the Ministry of Health in Guinea issued an alert for an unidentified illness. The Pasteur Institute in France inveterate that this unidentified illness is EVD. The cases kept on increasing and with 49 confirmed cases and 29 deaths, WHO officially declared an outbreak of EVD [42].

The outbreak spread very fast to the neighboring countries, Liberia and Sierra Leone. 

On March 23, 2014, the WHO was notified of an outbreak of EVD in Guinea. On August 8, the WHO declared the epidemic to be a “Public health emergency of international concern [40,42].

May 2014: On May 26 WHO reports the first deaths in Sierra Leone [43].

July 2014: The Ebola outbreak spread to the capital cities of Guinea, Liberia and Siberia. The number of EVD cases in Sierra Leone exceeded those of Liberia and Guinea. The distribution and classification of the cases was: Sierra Leone, 533 cases (473 confirmed, 38 probable and 22 suspected) including 233 deaths; Guinea, 460 cases (336 confirmed, 109 probable and 15 suspected) including 339 deaths; Liberia, 329 cases (100 confirmed, 128 probable and 101 suspected) including 156 deaths [44].

August 2014: On 6^th August 2014 the above mentioned three countries reported 1779 cases and 961 deaths. This was one of the biggest Ebola disease outbreaks. The Director-General of WHO on 8^th August 2014 declared the EVD outbreak in West Africa a PHEIC under the IHR 2005 [45,46]. 

September 2014: On 30^th September 2014, CDC confirmed the first travel-associated case of EVD diagnosed in the United States in a man who traveled from West Africa to Dallas, Texas [47].

October 2014: The index case died on 8^th October, 2014. Two healthcare workers who cared for him in Dallas tested positive for EVD but they both recovered. On 23^rd October, 2014, a medical aid worker who had volunteered in Guinea was hospitalized in New York City with suspected EVD. The diagnosis was confirmed by the CDC the next day. The patient recovered [48].

The third meeting of the EC convened by the WHO Director-General under the IHR 2005 regarding the 2014 EVD outbreak in West Africa was conducted on 22nd October 2014. As of 22nd October 2014, the total number of cases was 9936, with 4877 deaths. It was the unanimous view of the Committee that the event continues to constitute a PHEIC [48].

January 2015: The 4^th meeting of the EC under (IHR) 2005 regarding the EVD outbreak was conducted on 20^th January 2015to review, whether it continues to be a PHEIC and, if so, whether this warranted an extension or revision of the temporary recommendations, which were first issued on 8^th August 2014 and extended on 22 September 2014 and 23 October 2014. It was recommended by the committee for the 3 most affected countries (Guinea, Liberia and Sierra Leone) to maintain proactive exit screening until the Ebola transmission stops in these countries. The countries who shared the borders with Guinea, Liberia and Sierra Leone were advised to conduct active surveillance and remain vigilant for new cases. The Committee concluded that the primary emphasis should be on ‘getting to zero’ Ebola cases, by stopping the transmission within the three most affected countries. It was the unanimous view of the Committee that the event continues to constitute a PHEIC. The Committee reviewed the temporary recommendations previously issued and stated that all previous temporary recommendations should remain in effect [49].

April 2015: The 5^th meeting of the EC convened by the WHO Director-General under the IHR 2005 was conducted on 9^th April 2015.The Director-General endorsed the Committee’s advice and declared that the Ebola outbreak in Guinea, Liberia and Sierra Leone continues to constitute a PHEIC. The existing temporary recommendation were extended and the additional advice was issued as the new temporary recommendations under IHR (2005). On 19^th April 2014, there were a total of 26044 reported confirmed, probable and suspected cases of EVD in Guinea, Liberia and Sierra Leone, with 10808 reported deaths [50].

May 2015: Liberia was first declared EVD-free in May 2015. Again, there were some cases reported and subsequently the country was declared free of the EVD in September 2015 [41].

July 2015: The 6th meeting of the EC under the IHR (2005) was held by teleconference on 2^nd July 2015 and by electronic correspondence from 2-6 July 2015. The Director-General declared that the Ebola outbreak in Guinea, Liberia and Sierra Leone continues to constitute a PHEIC. Previously issued temporary recommendations were extended and it was advised by the committee that the affected countries must ensure to retain and retrain the health workers, engage as well as support the communities in all aspects of response. The committee emphasized on surveillance, collaboration across borders, efficient alert system and contact tracing for the countries sharing the borders with Guinea, Liberia and Sierra Leone [51].

September 2015: Liberia was declared free of the EDV in September 2015 [52].

October 2015: The 7th meeting of the EC convened by the WHO Director-General under the IHR (2005) took place by teleconference on 1^st October 2015 and by electronic correspondence from 1^st-3^rd October 2015. The Committee noted the enhanced Ebola control measures being implemented in each country and reaffirmed the importance of the community outreach, social mobilization and other best practices. The Committee advised that the EVD outbreak continues to constitute a PHEIC. They suggested that there should be no general ban on international travel or trade; there should be no restrictions on the travel of EVD survivors; states should provide travelers to areas of active Ebola transmission with relevant information on risks, measures to minimize those risks and advice for managing a potential exposure. Also, if active Ebola transmission is confirmed to be occurring in the state, the full recommendations for states with Ebola transmission should be implemented, on either a national or sub national level, depending on the epidemiologic and risk context [53].

November 2015: More cases emerged in Liberia. Sierra Leone was declared EVD-free [54].

December 2015: In Guinea, the first declaration of end of EVD was in December 2015 [55].

January 2016: Liberia was again labeled as EVD free. Sierra Leone again reported a case of EVD [42].

March 2016: EVD cases started occurring again in Liberia as well as in Guinea. On March 17, 2016 Sierra Leone was declared EVD free and also the WHO lifted the PHEIC status on West Africa’s Ebola situation. The impact this epidemic had on the world and particularly West Africa, is significant [53]. 

A total of 28,616 cases of EVD and 11,310 deaths were reported in Guinea, Liberia and Sierra Leone. There were an additional 36 cases and 15 deaths that occurred when the outbreak spread outside of these three countries [42]. 

Zika Virus 2015-16

Zika virus is an icosahedral, enveloped, single stranded RNA arbovirus of Flavivirus genus primarily transmitted through the Aedes aegypti mosquito [56]. Zika virus was first isolated in 1947 in the zika forest in Uganda where transmission of the ancestral African lineage of zika virus was limited to enzootic circulation between nonhuman primates and sylvatic aedes mosquitoes, with sporadic spillover infection to humans [56]. As zika virus migrated to Asia, the Asian lineage of the virus emerged, which was capable of being transmitted by human-adapted aedes mosquitoes (e.g., Aedes aegypti) [57]. The various routes of transmission of virus are from pregnant mother to fetus, blood transfusions, sexual route and organ transplantation. The incubation period of the disease is 3 days to 14 days. Majority of people (80%) affected by zika virus do not develop any symptoms and those who develop symptoms include rashes, conjunctivitis, muscle and joint pains, malaise and headache [58]. 

The biggest Zika virus outbreak happened in 2015-2016 and affected more than 33 countries and there were around 1.4 million cases in Brazil.

Following are the timelines of Zika virus outbreak:

February 2015: The authorities of Brazil confirmed cluster of cases of rash in the state of Maranhao, in the northeast of Brazil. The cases reported fever, muscle and joint pain, rash and headache, but no severe cases or deaths were reported. Samples from 25 patients were tested, 14 samples resulted positive for dengue and all samples were negative for chikungunya, rubella or measles [59].

April 2015: On 29^th April 2015, authorities of Brazil shared a preliminary report from the Bahia state laboratory that samples tested positive for Zika virus but confirmatory tests from the National reference laboratory were still pending [59].

May 2015: On 7^th May 2015, PAHO issued an epidemiological alert, titled zika virus infection, describing the infection and giving Member States recommendations for influencing the existing surveillance systems for dengue and chikungunya to increase their sensitivity to detect possible cases of zika virus infection. The alert also included details on laboratory testing, case management and prevention and control measures including recommendations to travelers. On 14^th May 2015, the Evandro Chagas Institute, a national reference laboratory, confirmed a positive result for Zika virus in samples taken from the States of Rio Grande do Norte and Bahia in Brazil. On 31 May 2015, the authorities of Brazil reported that five states were reporting circulation of Zika virus-Alagoas, Bahia, Para, Rio Grande do Norte and Sao Paulo [60].

June 2015: The number of states with Zika circulation had increased to eight [59].

July 2015: The authorities of Brazil reported that 58 cases of neurological complications temporally associated with rash illness were identified in the state of Bahia until 4^th July 2015. Of these 58 cases, 29 cases were confirmed as Guillain-Barre Syndrome (GBS) by clinical criteria. Among the 29 confirmed cases, 19 cases had a previous history of Zika virus infection and 2 cases presented serology reactive for dengue. On 17^thJuly 2015, Brazil reported 101 cases of neurological complications. Of these, 49 were confirmed as GBS by clinical criteria, 47 of which had prior history of chikungunya, dengue or zika virus infections [59].

October 2015: The authorities of Colombia confirmed to PAHO/WHO the first cases of zika virus in Bolivar Department. PAHO/WHO received information from the Brazil IHR national focal point regarding an unusual increase in the number of cases of microcephaly since August 2015.The newborns presented with microcephaly, below the 5^th percentile of the head circumferences as per the WHO standard [59].

November 2015: On 11^th November 2015, the authorities of Brazil officially declared a national public health emergency due to a detected increase in cases of microcephaly in the state of Pernambuco, Paraiba and Rio Grande do Norte in the northeast of the country [61].

December 2015: On 1^st December 2015, PAHO published an epidemiological alert titled, "Neurological syndrome, congenital malformations and zika virus infection: implications for public health in the Americas.” highlighting the increased detection of congenital anomalies and neurological syndromes in Brazil. The alert also made a series of recommendations for enhanced surveillance of neurological syndromes and congenital malformations and included recommendations for the monitoring of pregnant women and newborns with congenital malformations in the context of zika virus circulation [60].

January 2016: On 15^th January 2016, the CDC issued a travel alert advising pregnant women to postpone travel to Brazil and other countries due to reports of microcephaly and poor pregnancy outcomes. Till the end of January 2016, local transmission of Zika infection was reported from more than 20 countries and territories in the Americas, as well as there were reports of an outbreak affecting thousands of cases in Cabo Verde, western Africa. Zika virus infections were spread worldwide possibly by international travel [62].

February 2016: On 1^st February 2016, WHO declared zika infection associated with microcephaly and other neurological disorders as a PHEIC. Temporary recommendations as suggested by the committee members were issued by the Director-General of WHO under IHR (2005) [63]. 

On 5^th February 2016 USA reported the laboratory confirmation of one case of sexually transmitted Zika virus [64].

March 2016: The 2^nd EC was convened by the Director General under the IHR (2005) on 8^th March 2016. The Committee advised that the clusters of microcephaly cases and other neurological disorders in areas affected by zika virus continue to constitute a PHEIC and there was increasing evidence of a causal relationship with zika virus. The zika virus transmission was reported from 33 countries, 12 countries or territories had reported an increased incidence of GBS and/or laboratory confirmation of a zika virus infection among GBS cases [65].

June 2016: The 3^rd EC convened by the Director-General under the IHR (2005) was held by teleconference on 14^th June 2016. In addition to providing views to the Director-General on whether the event continued to constitute a PHEIC, the Committee was asked to consider the potential risks of zika transmission for mass gatherings, including the olympic and paralympic games scheduled for August and September 2016, in Rio de Janeiro and Brazil respectively. Based on this advice the Director-General declared the continuation of the PHEIC [66].

July 2016: The virus was present in 63 countries, of which 13 had reported microcephaly cases whereas 15 had cases of GBS [67].

September 2016: The 4^th meeting of the EC on zika and microcephaly convened by the Director-General under the IHR (2005) was held by teleconference on 1^st September 2016 and it was decided to continue it as a PHEIC [68].

November 2016: The 5^th meeting of the EC on zika and microcephaly convened by the Director-General under the IHR 2005 was held by teleconference on 18^th November 2016. The Committee was updated on the latest developments on zika virus geographic spread, natural history, epidemiology, microcephaly and other neonatal complications associated with zika virus, GBS and knowledge on sexual transmission of zika virus [69].

The EC reviewed the recommendations made at its previous meetings and agreed to the WHO zika transition plan for establishing the long term response mechanism which delivers the strategic objectives already identified in the zika strategic response plan. Based on this advice, the Director-General declared the end of the PHEIC. By November 2016, when the WHO declared an end to the zika emergency, there had been 2,300 confirmed cases worldwide of babies born with microcephaly [69].

Kivu Ebola Declaration 2018–20

There was an outbreak of Ebola Virus Disease (EVD) in Democratic Republic of Congo (DRC) from 2018 to 2020. The previous Ebola outbreak from 2014-2016 in Guinea, Liberia and Sierra Leona and the total number of cases were more than 28000 and nearly 11000 deaths [70]. 

May 2018: The 1^st meeting of EC convened by the Director General under the IHR 2005 was held on 18^th May 2018. The committee’s conclusion was that the conditions for a PHEIC were not met [71].

August 2018: On 1^st August 2018, WHO was notified by the Ministry of Health in North Kivu province that there were 26 cases including 20 deaths due to a hemorrhagic fever [72]. Some of the samples were reported to be positive for Ebola by the National Institute of Biological Research in Kinshasa. It all started with the burial of an old lady in month of July 2018. Her burial was probably unsafe (as per the burial process followed for EVD deaths) and it was followed by the death of 7 family members who had participated in the burial ceremony [73]. Later, there were reports of cases from Ituri province as well. 

October 2018: The second EC meeting under IHR (2005) was held on 17th October, based on the committee’s suggestion the outbreak was not declared as an outbreak. Till the last week of October 2018, there were 274 cases of EVD, including 174 deaths. The Case Fatality Ratio (CFR) was 63.5% [74,75].

November 2018: A total of 421 EVD cases were reported from 14 health zones in the two neighboring provinces of North Kivu and Ituri. Of the 421 cases, 241 had died [76].

December 2018: 585 EVD cases were reported from 16 health zones in the two neighboring provinces of North Kivu and Ituri. Overall, there were 356 deaths, CFR was 61 % [77].

January 2019: There were 689 cases of EVD and a total of 407 deaths among confirmed cases. The CFR was 59% [78].

February 2019: From the beginning of the outbreak till February end, a total of 872 EVD cases, including 807 confirmed and 65 probable cases were reported from 19 health zones in the North Kivu and Ituri provinces. A total of 548 deaths were reported and overall CFR was 63% [79].

March 2019: Till March 2019, a total of 1016 EVD cases, including 951 confirmed and 65 probable cases, were reported. This includes 634 deaths and overall CFR was 62% [80].

April 2019: On 12^th April 2019, 3^rd WHO EC was held and it was decided that the EVD outbreak did not qualify to be a PHEIC [81].

June 2019: The meeting of the EC convened by the WHO Director-General under the IHR (2005) regarding Ebola virus disease in the Democratic Republic of the Congo (DRC) was held on 14^th June 2019, a review of the confirmed cases in Uganda was done but it wasn’t declared a PHEIC as all three criteria to label the outbreak as a PHEIC were not met [82].

July 2019: On 14^th July, doctors in Goma confirmed that a person who travelled to the city by bus from the city of Butembo, a hotspot of the outbreak, had contracted Ebola. He died two days later. And on 17 July, the DRC health ministry and the WHO reported that a woman who was diagnosed with Ebola in the DRC had travelled to Uganda through an illegal border to sell fish; she died there after bouts of profuse vomiting. On 15^th July 2019, fourth review was done and WHO declared EVD as a PHEIC on 17^th July 2019 [83].

September 2019: There was decreasing trend in the number of cases in DRC [84].

October 2019: The number of cases further decreased and it was confined to the Mandima region. Initially there were nearly 207 health zones affected but in this month decreased to 27 health zones. 5^th EC meeting under IHR (2005) was held in mid October and it was recommended by the committee to continue the status of PHEIC [85].

February 2020: On 10 February, there were a total of 3431 cases, of which 3308 were confirmed and 123 were probable. 2253 persons had died (66%). On 12^th February, the 6^th EC meeting under IHR (2005) was held and it was decided that the status of EVD outbreak as a PHEIC continues. The number of new cases of EVD reduced to zero in this month [86].

April 2020: The 7^th EC meeting under IHR (2005) was held on 14^th April 2020 and it was decided that EVD outbreak remains a PHEIC. Three new cases of Ebola were reported in Beni health zone [87].

June 2020: On 25^th June 2020, in the 8^th EC meeting under IHR (2005) it was decided that the outbreak had ended and was no longer a PHEIC. A total of 3470 EVD cases were reported from 29 health zones, including 3317 confirmed and 153 probable cases, of which 2287 cases died (CFR 66%). Since the last reported case was on 27 April 2020, no new confirmed or probable cases of EVD were reported. The DRC Ministry of Health declared that human-to-human transmission of Ebola virus had ended in Ituri, North Kivu and South Kivu provinces [88].

SARS-COV-2(COVID-19)

A new corona virus originated from Wuhan in China in December 2019. This corona virus was initially named novel corona virus and later SARS-COV-2. The corona virus derived their name from the latin word ‘corona’ meaning the crown. The virus has a unique appearance under electron microscope as round particles with a rim of projections. They are enveloped; positive sense single stranded RNA viruses. The timelines for SARS-COV-2 pandemic are.

31 Dec 2019: On 31 December 2019, the WHO China Country Office was informed of cases of pneumonia of unknown etiology (unknown cause) detected in Wuhan City, Hubei Province of China [89].

1 January 2020: The Incident Management Support Team (IMST) was set up by WHO at the headquarters, regional headquarters and country level [90]. 

5 January 2020: WHO had published the first disease outbreak news on this novel virus [90].

10 January 2020: Technical guidance was issued by WHO regarding the detection, testing and management of the potential cases, according to the knowledge about the virus at that point of time. On the basis of the previous experiences with SARS and MERS, the infection and prevention guidelines were issued for protecting the health workers and it was suggested to ensure the precautionary measures while caring for patients and airborne precautions for aerosol generating procedures conducted by health workers [90].

12 January 2020: The genetic sequence ofCOVID-19 was shared publicly by China [90]. 

13 January 2020: The first case outside China was reported in Thailand [90]. 

20-22 January 2020: WHO experts from China and Western Pacific regional offices conducted a brief field visit to Wuhan. The experts were of the view that there was evidence of human-to-human transmission in Wuhan but more investigations were required to understand the modes of transmission [90]. 

22-23 January 2020: WHO Director General convened an EC under the IHR 2005 for assessment that whether the outbreak was a public health emergency or not. There was no consensus on this issue and the members suggested calling for a meeting after 10 days to review the situation [90,91]. 

30 January 2020: The WHO Director-General called the EC meeting, earlier than the 10-day period; two days after the first reports of limited human-to-human transmission were reported outside China. On 30^th January 2020, there were 7818 confirmed cases worldwide, with majority of cases in China and 82 cases in 18 countries outside China. The EC had consensus that the outbreak constituted a PHEIC and the Director-General accepted the recommendation and declared the novel corona virus outbreak (2019-nCoV) a PHEIC. This was the 6^th PHEIC, declared by WHO under the IHR 2005.The EC provided advice to WHO and to all countries, on measures to control this outbreak viz; early detection, isolation and treatment of cases, social distancing and contact tracing [90,92].

February 2020: The first death was reported outside of China, in the Philippines. The patient was a close contact of the first patient confirmed in the Philippines. Globally there were 20630 confirmed cases. China had 20471 confirmed cases and 425 deaths. Outside of China there were 159 confirmed cases in 23 countries with one death [93]. 

WHO developed the global strategic preparedness and response plan, which described the public health measures to be implemented by various countries for responding to the 2019‑nCoV outbreak [94]. WHO also published the document on the rational use of personal protective equipment which provided the details as to which type of personal protective equipment should be used depending on the setting, personnel and type of work [94,95].

Also, there was a publication by WHO describing the details regarding the quarantine of individuals in the context of COVID-19. There was a second case confirmed in WHO African region, in Algeria. The Regional Director for Africa called for countries to step up their readiness [95]. 

March 2020: WHO appealed to the industries and governments to increase manufacturing of personal protective equipment for the health workers worldwide. Global research roadmap was published by the working groups of the research forum which had outlined the priorities of research in key areas, mainly the natural history of the virus, epidemiology, diagnostics, clinical management, ethical considerations and social sciences, as well as longer-term goals for therapeutics and vaccines.

On 7 March 2020, the number of confirmed COVID-19 cases surpassed one lakh globally, therefore, WHO released a statement for action to stop, contain, control, delay and reduce the impact of the virus at every opportunity. On 11^th March 2020, WHO declared COVID-19 a pandemic because of the alarming levels of spread and severity. Europe had become the epicentre of the pandemic with several cases and deaths.

WHO also released the laboratory testing strategy and a manual on how to setup a severe respiratory infection treatment centre and also a screening facility in for COVID-19 in March 2020 [95].

April 2020: WHO suggested that there is evidence of transmission from symptomatic, pre-symptomatic and asymptomatic people infected with COVID-19. On 4^th April 2020 there were over a million cases of COVID-19, globally. On 6^th April 2020, there were 1,272,900 cases globally and 69,426 deaths. On 30^th April, 210 countries were affected and the total number of cases crossed 3 million and there were 228194 deaths globally. The Director-General convened the IHR EC on COVID-19 for a third time on 30^th April 2020. It was decided that the outbreak of COVID-19 continued to constitute a PHEIC. Among other commitments, it was mentioned that WHO would “continue to call on countries to implement a comprehensive package of measures to find, isolate, test and treat every case and trace every contact”, as it had “done clearly from the beginning” [95,96].

May 2020: On 18th-19th May 2020, the 73^rd World Health Assembly was held virtually and a resolution was taken to intensify the efforts to bring the world together to fight this pandemic. The resolution called for the intensification of efforts to control the pandemic and also advocated the extensive immunization against COVID-19. On 31^st May, the total number of cases had crossed 6 million and there were 370,893 deaths, globally” [95,97].

June 2020: WHO appreciated the funding commitments made at the Global vaccine summit which was hosted virtually by the UK government, Gavi, the vaccine alliance’s, third pledging conference. These commitments would be to help the lower-income countries, mitigating the impact of the COVID-19 pandemic. The summit also highlighted how important a safe, effective and equitably accessible vaccine will be in controlling COVID-19” [98]. On 30^th June 2020, there were 10 million cases and over 5 lakh deaths [98]. 

July 2020: On 31^st July, the 4^th meeting of EC under IHR (2005) was held. The Director-General declared that the outbreak of COVID-19 continues to constitute a PHEIC. He accepted the advice of the committee to WHO and issued the committee’s advice to states parties as temporary recommendations under the IHR (2005). The Committee put forward a number of recommendations for countries to continue to implement to bring the virus under control [99]. 

August 2020: On 31^st August there were 25,378,371 cases and 850163 deaths globally [100]. 

September 2020: WHO joined with partners to make 120 million affordable, quality COVID-19 rapid tests available for low- and middle-income countries. On 30^th September the total number of cases was more than 33 million with over 1 million deaths worldwide [95]. 

October 2020: The Director-General convened the IHR EC on COVID-19 for a fifth time on 29^th October and issued its statement on 30th October .The Director-General declared that the outbreak of COVID-19 continues to be a PHEIC and mentioned that the focus should be on breaking the chains of transmission and WHO and governments must work closely to develop rollout strategies, train health workers and ensure clear communications with the general public about vaccination” [101]. 

On 31^st October the total number of cases was 45.8 million and deaths nearly 1.2 million, globally [102]. 

November 2020: The 73^rd WHA held from 9^th-13^th November, adopted a resolution to strengthen preparedness for health emergencies. Recognizing the dedication and sacrifice of the millions of health care workers at the forefront of the Covid-19 pandemic, the Member states unanimously designated 2021 as the ‘International year of Health care workers [103]. 

An important observation was that the pandemic had “demonstrated the consequences of chronic under-investment in public health”, therefore, the Director-General announced a council on the Economics of Health for all. The Council’s main focus had to be on investments in health and achieving sustainable, inclusive and innovation-led economic growth [104].

On 30^th November 2020, the total number of cases was ~63 million and total number of deaths was ~1.46 million worldwide [105]. 

December 2020: On 14^th December, UK authorities reported SARS-COV-2 variant to WHO. On 31st December, the total number of cases was 83 million and 1.81 million deaths, globally [106].

January 2021: On 5^th January 2021, WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) met to review the vaccine data for the Pfizer/BioNTech vaccine and formulate policy recommendations on how best to use it. This vaccine was the first to receive an emergency use validation from WHO for efficacy against COVID-19 [107]. 

On 14^th January 2021, the sixth EC meeting under IHR (2005) was held to review the situation of COVID-19 and it was decided that it continues to be a PHEIC. On 25^th January 2021, the total number of cases crossed 100 million, with more than 2 million deaths [108]. 

February 2021: On 28^th February the total number of cases was 114,365,469 with 2.5million deaths [105]. 

March 2021: On 31^st March total number of cases was 128,788,382 with 2.8million deaths [105].

April 2021: The 7^th meeting of the EC convened by the WHO Director-General under the IHR (2005) regarding the Coronavirus Disease (COVID-19) took place on Thursday, 15 April 2021 by video conferencing. The Director-General determined that the COVID-19 pandemic continues to constitute a PHEIC. He accepted the advice of the Committee to WHO and issued the Committee’s advice to States Parties as Temporary Recommendations under the IHR [109]. By the end of this month there were a total of 151,113,012 cases and 3,178,655 deaths [105]. 

May 2021: On 31^st May 2021, total number of cases was 171,038,250 and 3,556,889 deaths [105]. 

July 2021: The 8^th meeting of the EC under the IHR (2005) regarding the COVID-19 took place on 4^th July 2021. The IHR Committee noted that, despite national, regional and global efforts, the pandemic continues. The pandemic continues to evolve with five variants of concern dominating global epidemiology. The Committee recognized the strong likelihood for the emergence and global spread of new and possibly more dangerous variants of concern that may be even more challenging to control [110].

The Director-General determined that the COVID-19 pandemic continues to constitute a PHEIC. He accepted the advice of the Committee to WHO and issued the Committee’s advice to States Parties as Temporary Recommendations under the IHR which included continuing the advocacy for equitable vaccine access and distribution ; to expedite the work to establish updated means for documenting COVID-19 status of travelers, including vaccination, history of SARS-CoV-2 infection and SARS-CoV-2 test results; to continue strengthening the global monitoring and assessment framework for SARS CoV-2 variants and strengthening the communication strategies at national, regional and global levels [110].

August 2021: On 31^st August 2021, there were total 217,913,843 cases and 4,523,984 deaths [111].

October 2021: The ninth meeting of the Emergency Committee convened by the WHO Director-General under the International Health Regulations (2005) (IHR) was held on 22^nd October 2021. The Committee discussed key issues including: SARS-CoV-2 surveillance efforts and challenges:

• immunity acquired through natural infection or vaccination and protection offered by both

• the value of intra-action reviews for States Parties to inform and enhance response efforts; and the importance of maintaining risk-informed and multi-faceted PHSM [112]

On 30^th October 2021 there were 247,136,432 cases and 5,010,533 deaths [113].

November 2021: On 30^th November 2021 there were 262,381,452 cases and 5,224,682 deaths [113].

December 2021: On 31^st December 2021 there were 284,909,138 cases 5,438,627 deaths [113].

Table 1: Overview of all the PHEIC’s                                                

There has been a total of six diseases which have been declared as PHEIC under IHR (2005). H₁N₁ influenza was the first PHEIC, declared in 2009 and the last one is COVID 19 declared in year 2020. (Table 1) Total nine EC meetings under IHR (2005) were conducted for H₁N₁, twenty-nine for polio (2014) till August 2021, nine for EVD (2014), five for Zika virus (2016), eight for EVD (2018-2020) and nine meetings till October 2021 for COVID-19.

The incubation period of these six diseases ranges from one day to twenty-one days (Table 2).

The R₀ of the disease signifies how many people can get affected by one infected person in the community, if the exposed person does not have protection from this disease by vaccination or by prior infection. The R₀ of various PHEIC is mentioned in Table 3, amongst these the highest R₀ is of polio, 5–7. The current PHEIC of COVID-19 has R₀ of 1.4 to 3.9. 

After the notification to WHO, the decision is taken by the committee of expert members of IHR EC that whether a particular event is a PHEIC or not. Within one week of notification of cases of H₁N₁ to the WHO, the first EC under IHR (2005) was conducted and it was declared as a PHEIC. In case of polio, it took nearly 4 months after notification to WHO whereas in case of EDV (2014) it took 4^1/2 months, for Zika (2016) it took 2 months and in EDV (2018) it took 11^1/2 months. The current COVID-19 was declared a PHEIC, after one month of notification of cases to WHO. (Table 1).

The H1N1 remained a PHEIC for 1 year and 4 months; EDV (2014) for nearly 20 months; Zika (2016) for 9 and a half months and EDV (2018) for nearly 11 months. Polio was declared a PHEIC in 2014 and for last seven and a half years it continues to be a PHEIC. COVID-19 is also an ongoing PHEIC from January 2020 till now.

The total number of countries affected during H₁N₁ PHEIC was 214; 17 countries in Polio PHEIC; 10 countries affected during EVD (2014) PHEIC and 87 countries were affected in Zika PHEIC (2016). Two countries were affected during EVD (2018-20) and almost all the countries of the world were affected in COVID-19 PHEIC (2020).

The CFR (case fatality ratio) of H₁N₁ PHEIC (2009) was 1.2% whereas it was 0.025% to 0.05% for Polio and 62.9% for EDV (2014). The CFR for the fetus borne to Zika mothers was 8.3% to 10.5%. The CFR of EDV (2018) was highest among all the PHEIC, it was reported to be 67%. In the current PHEIC of COVID-19, the reported CFR varies from less than 0.1% to more than 25% in different countries of the world [114].

One of the most important components in limiting the spread of these PHEIC’s during as well as after the outbreaks has been the development and usage of vaccines.

Table 2: Incubation period of all the PHEIC’s

Table 3: R0 of all the PHEIC’s

Any unusual event which can have serious public health impact and/or has a risk for spreading across international boundaries and result in restrictions on travel and trade is declared as a PHEIC.

The travel and trade restrictions usually have major economic repercussions. These were evident during the current COVID-19 PHEIC. 

Further, the main purpose of declaring any events as PHEIC is to draw international attention for channelizing the support and resources for timely action and restricting the damaging effects of these health events on human lives and society. This was quite evident during the current PHEIC of COVID-19, wherein internationally on one hand the resources were mobilized to save human lives and on the other hand the trade as well as travel restrictions were stringently implemented so as to limit the spread of the infections.

1. World Health Organization. Poliomyelitis – International Health Regulations (IHR) Emergency Committee Statement. WHO, 2014. Available at: https://www.who.int/news/item/05-05-2014-statement-on-the-meeting-of-the-international-health-regulations-emergency-committee-concerning-the-international-spread-of-wild-poliovirus.

2. World Health Organization. Statement on the Second Meeting of the IHR Emergency Committee Concerning the Outbreak of Novel Coronavirus (2019-nCoV). WHO, 2020. Available at: https://www.who.int/news/item/30-01-2020-statement-on-the-second-meeting-of-the-international-health-regulations.

3. World Health Organization. Zika Virus and Complications: 2016 Public Health Emergency of International Concern. WHO, 2016. Available at: https://www.who.int/emergencies/zika-virus.

4. World Health Organization. Ebola Virus Disease – Democratic Republic of the Congo. WHO, 2018. Available at: https://www.who.int/emergencies/disease-outbreak-news/item/2018-DON212.

5. World Health Organization. H1N1 in Post-Pandemic Period. WHO, 2010. Available at: https://www.who.int/mediacentre/news/statements/2010/h1n1_vpc_20100810/en/.

6. Biggerstaff, M., et al. "Estimates of the Reproduction Number for Seasonal, Pandemic, and Zoonotic Influenza: A Systematic Review of the Literature." BMC Infectious Diseases, vol. 14, 2014, p. 480, https://doi.org/10.1186/1471-2334-14-480.

7. Lipsitch, M., et al. "Transmission Dynamics and Control of Severe Acute Respiratory Syndrome." Science, vol. 300, no. 5627, 2003, pp. 1966–70, https://doi.org/10.1126/science.1086616.

8. Petersen, L.R., D.J. Jamieson, and M.A. Honein. "Zika Virus." New England Journal of Medicine, vol. 375, 2016, pp. 294–95, https://doi.org/10.1056/NEJMp1605367.

9. WHO Ebola Response Team. "Ebola Virus Disease in West Africa—The First 9 Months of the Epidemic and Forward Projections." New England Journal of Medicine, vol. 371, 2014, pp. 1481–95, https://doi.org/10.1056/NEJMoa1411100.

10. Baud, D., et al. "Real Estimates of Mortality Following COVID-19 Infection." The Lancet Infectious Diseases, vol. 20, no. 7, 2020, p. 773, https://doi.org/10.1016/S1473-3099(20)30195-X.