Carlo Urbani: A 21st Century Hero and Martyr

Carlo Urbani was the first to recognize that the severe acute respiratory syndrome (SARS) epidemic of 2003 signified a new, not seen before, life-threatening, infectious disease. Sadly, Urbani succumbed to SARS while organizing the most effective containment response to a major epidemic in history. Several weeks afterward, the SARS agent was found to be a previously unknown coronavirus, and then aptly named the SARS coronavirus.

Carlo Urbani’s actions during the severe acute respiratory syndrome (SARS) epidemic of 2003 are remarkable on several counts and need to be much better known. But first, we begin with some relevant background

The first known reference to the SARS epidemic dates to February 2003, when the Chinese Ministry of Health announced the mysterious outbreak of an atypical pneumonia in the Guangdong Province of southern China. Chinese authorities reported a total of 305 cases, including five deaths, during the preceding three months. However, these figures were almost certainly an underestimate of the scope of the Chinese epidemic, as discussed below.

A Chinese doctor, who had been treating SARS patients in Guangdong, is believed to have brought the disease to Hong Kong that same February. He developed symptoms during his first day in Hong Kong, where he stayed at the Hotel Metropole. The next day he was transferred to a hospital, and succumbed the day after. However, during his brief stay at the Hotel Metropole, he somehow infected at least 10 other guests. Eight of those infected guests were on the same floor as the doctor, and the two others were two and five flights up from him. Those infected individuals subsequently boarded airplanes that took them to Singapore, Vietnam, Canada, and the United States, thereby spreading an epidemic that lasted more than 100 days.

The World Health Organization (WHO) estimated that there were 8,422 SARS cases worldwide during that 100-day period, resulting in 908 deaths. In all, 29 countries were affected. In the United States there were a total of eight confirmed SARS cases, none of which was fatal. Each of the infected individuals in the United States had shortly before traveled to an area where SARS transmission was occurring. Thus, the SARS outbreak of early 2003 was truly an epidemic of our modern global era, spread by air travel to at least three continents in a period of just a few weeks. Importantly, its consequences might well have been vastly more devastating and, perhaps, less so as well, as described below.

Our story of Carlo Urbani begins in Vietnam, where on February 28, 2003 (a still early time in the epidemic), the Vietnam French Hospital of Hanoi contacted the Hanoi office of the World Health Organization concerning a patient, an American businessman, who seemed to be showing signs of what the Vietnamese doctors feared might be an unusually severe case of the flu. Believing that they might be facing a potentially deadly avian influenza outbreak, hospital officials called on the WHO for help. Urbani, who was an infectious disease specialist, answered the call and quickly determined that the hospital was not facing influenza but, instead, something unusual; a new, previously unknown contagious respiratory disease.

Interestingly, Urbani might not seem to have been the obvious choice to consult on this case, since he was best known as an expert on parasitic infections. Nevertheless, the WHO staff still recommended him to the Vietnamese because of his reputation as a superb clinical diagnostician. Urbani lived up to his reputation, recognizing that SARS was a new and extremely dangerous infectious disease. Moreover, and crucially, he immediately notified the WHO of his findings, thereby without delay setting in motion the most effective global response to a major epidemic in history. His decisive and timely action may have saved millions of lives worldwide!

 urbani

Carlo Urbani, at the Vietnam French Hospital of Hanoi

Disregarding his own safety, Urbani spent the next several days continually at the Vietnam French Hospital of Hanoi, where he organized infection control procedures, while also taking patient samples for analysis. And, as it became clear that the infection was highly contagious and deadly, Urbani worked closely with the hospital staff to maintain morale. Moreover, Urbani, as well as others on the hospital staff, decided not to leave the hospital, so as not to place their families or the community at risk. In doing so, they knowingly placed themselves in jeopardy.

Acutely aware of the danger that the new disease posed to the Vietnamese, Urbani undertook the difficult task of arranging a meeting between WHO officials and the Vietnamese Vice Minister of Health. Urbani was able to bring these parties together largely because of the strong trust he had been building with Vietnamese authorities. At the meeting, Urbani explained the steps that needed to be taken to contain the Vietnamese outbreak. The Vietnamese government responded to Urbani’s recommendations by quarantining the Vietnam French Hospital of Hanoi, and establishing infection control procedures at other hospitals as well. Moreover, the Vietnamese government took the extraordinary step on its part of issuing a public international appeal for expert assistance, despite the possibility of hurting the Vietnamese economy or image by doing so. Specialists who answered the Vietnamese appeal came from the WHO, the CDC of the United States, and Médecins sans Frontières (Doctors without Borders). [Urbani was in fact president of the Italian chapter of Médecins Sans Frontières and was one of the individuals who accepted the 1999 Nobel Peace Prize on its behalf. 1 Speaking at the 1999 Nobel ceremony, Urbani stated that it was the doctors’ duty “to stay close to the victims.”]

Sadly, Urbani began to develop symptoms of SARS during a March 11 flight from Hanoi to Bangkok, where he had planned to attend a conference. He succumbed in a Bangkok hospital on 29 March 2003, not knowing that within several weeks’ time researchers working worldwide would isolate the SARS agent, sequence its genome, and identify it as a newly discovered coronavirus. 2 He was 49 years old. The following is from his obituary in the Guardian, written by Lorenzo Savioli: “His wife Giuliana told me that a few days before falling ill he had argued with her. She was concerned to see him working with patients with such a deadly disease. He said: ‘If I cannot work in such situations, what am I here for – answering emails, going to cocktail parties and pushing paper?’”

Here is another important aspect of the 2003 SARS epidemic to consider; the response of the Vietnamese authorities to the outbreak in their country, versus that of the Chinese authorities to the Chinese outbreak. The Vietnamese responded to their SARS outbreak by taking the unexpected step on their part of promptly issuing an international appeal for expert assistance, which it accepted from U.S. Centers for Disease Control, the WHO, and Médecins sans Frontières. And, by following Urbani’s recommendations, the Vietnamese quickly brought the outbreak in their country under control. In contrast, the Chinese initially tried to cover up their SARS outbreak, and then misrepresented the number of their cases. Indeed, there are reports that they had their SARS patients driven around in taxis to avoid being detected by WHO officials who came to visit their hospitals. News of the Chinese epidemic surfaced in the outside world largely because scientists, who were working in neighboring countries, become aware of what the Chinese authorities knew about, but tried to conceal.

Bearing in mind that the 2003 SARS epidemic may have initially emerged in China, if the Chinese authorities had been more forthcoming, and if they had taken appropriate containment measures at the start of their epidemic, many lives might have been saved worldwide. Moreover, the quarantines that needed to be instituted globally in response to the SARS epidemic, the disruption of international travel, and the worldwide economic consequences, all might have been much less severe. Reacting to international pressure, China finally established strong containment measures in April 2003. [In April 2004, the Chinese Ministry of Health reported several new SARS cases. And, in contrast to its actions of the preceding year, this time China responded aggressively, quickly isolating patients who developed SARS, identifying their nearly 1,000 recent contacts, and sharing information with outside groups such as the WHO.]

 On July 5, 2003, the WHO announced that the cycle of human-to-human transmission of the initial SARS outbreak was broken and that the epidemic had come to an end. The fact that containment of the 2003 outbreak was achieved within 4 months of the first global alert is a tribute to effective public health policy and, what’s more, to the united effort of the international community. As noted above, the global response to the SARS outbreak, first initiated by Urbani in Vietnam, was indeed the most effective response to a major epidemic in history. It also is noteworthy that containment was achieved without the benefit of a vaccine or critical diagnostic reagents; further evidence of the efficacy of good public health policy.

While the public health community well deserves praise for containing the SARS epidemic, the scientific community also merits praise for isolating and identifying the SARS agent within weeks of the initial 2003 outbreak. It happened as follows.

The symptoms of SARS did not suggest any one cause in particular. Thus, researchers tested patient specimens for a broad range of bacterial, chlamydial, rickettsial, and viral agents that were known to target the lower respiratory tract. Viral agents under suspicion included influenza viruses, paramyxoviruses, herpesviruses, and picornaviruses.

In order to amplify potential viral agents, patient samples were inoculated into cell cultures. Then, by means of electron microscopy, a virus, which originated in the respiratory secretions of a SARS patient, was seen which displayed characteristic coronavirus structural features. Then, using electron microscopy in some instances, and serological procedures in others, this virus was detected in additional SARS patients. Subsequent molecular biological and immunologic studies confirmed that the isolated agent was, in fact, a novel coronavirus. Next, the SARS virus isolates that had been grown in cell cultures were found to cause lower respiratory tract disease when inoculated into monkeys.

It is noteworthy, that in the modern genomics era of PCR primers and so forth; the SARS virus was first identified by means of classic tissue-culture amplification and electron microscopy. As noted by the authors, “…electron microscopy proved to be a rapid technique that did not require specific reagents for or prior knowledge of a particular agent but that could nevertheless categorize a pathogen on the basis of its appearance and morphogenesis.” 3

Although the SARS virus was identified using classic virological procedures, the SARS epidemic was the first infectious disease outbreak in which virus researchers took full advantage of the powerful new techniques of the genomics era to analyze the new pathogen. Using these techniques, the SARS virus genome was sequenced less than one month after the virus was first isolated. Within the next three months, genome sequences of 20 independent clinical isolates of the SARS virus were available in the GenBank database for comparison.

Interestingly, the SARS virus’ genealogy initially took researchers in the field by surprise. That was so because coronaviruses were previously known for the mild upper respiratory tract infections they cause in humans; infections which are similar clinically to the innocuous common colds caused by the human rhinoviruses.  In contrast, as many as 40% of individuals infected with the SARS coronavirus required mechanical breathing assistance, and the overall mortality rate for infected individuals was about 10%, rising to as high as 50% in the elderly.

Urbani succumbed to SARS just weeks before the SARS coronavirus was isolated and identified as the cause of the epidemic. So, Urbani never knew of the discovery. But, in tribute to the singular importance of Urbani’s deeds during the epidemic, and his personal sacrifice, the authors of the paper, which reported the identification of the SARS virus, dedicated the paper to Urbani. 3

Urbani also was not forgotten by the Vietnamese government, which conferred upon him two of their highest honorary titles: the medal of Friendship and the medal for People’s Health. What’s more, outside of Hanoi, a hospital has been built in his name. And, in Taiwan, a foundation has been named after him.

Footnotes:

1. The following is excerpted from the “Doctors Without Borders/Médecins Sans Frontières (MSF)” website:

“ Doctors Without Borders/Médecins Sans Frontières (MSF) is an international medical humanitarian organization created by doctors and journalists in France in 1971.Today, MSF provides independent, impartial assistance in more than 60 countries to people whose survival is threatened by violence, neglect, or catastrophe, primarily due to armed conflict, epidemics, malnutrition, exclusion from health care, or natural disasters. MSF provides independent, impartial assistance to those most in need…MSF medical teams often witness violence, atrocities, and neglect in the course of their work, much of which occurs in places that rarely receive international attention…. At times, MSF may speak out publicly in an effort to bring a forgotten crisis into view….For example, in 1985, MSF spoke out against the Ethiopian government’s forced displacement of hundreds of thousands of members of its own population. In 1994, the organization took the unprecedented step of calling for an international military response to the 1994 Rwandan genocide. The following year, MSF condemned the Serbian massacre of civilians at Srebrenica, and four years after that, denounced the Russian military bombardment of the Grozny, the capital of Chechnya. In 2004 and 2005, MSF called on the United Nations Security Council to pay greater attention to the crisis in Darfur. And in 2007, MSF denounced the targeting of civilians in conflict—something that was occurring with greater frequency in the Democratic Republic of Congo, Central African Republic, Chad, and Somalia—and the governments of Thailand and Laos, which were threatening to forcibly return nearly 8,000 Hmong refugees to Laos….”

2. Norkin, L. C., 2010. Virology: Molecular Biology and Pathogenesis, ASM Press, Washington, DC.

3. Ksiazek T. G., D Erdman, C. S. Goldsmith, S.R. Zaki, T. Peret, S. Emery, S. Tong, C. Urbani, J.A. Comer, W. Lim, P.E. Rollin, S. F. Dowell, A.E. Ling, C. D. Humphrey, W. J. Shieh, J. Guarner, C. D. Paddock, P. Rota, B. Fields, J. DeRisi, J. Y. Yang, N. Cox, J. M. Hughes, J. W. LeDuc, W. J. Bellini, L. J. Anderson; SARS Working Group. 2003. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 348:1953-1966.

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