Fear of bioterrorism persists because of new reports of biological warfare, including the most recent attack that involved a Russian spy who was poisoned with polonium-210. However, vaccination against potential biological weapons, such as anthrax and smallpox, is controversial because of associated adverse effects.
Episodic, sometimes lurid, media coverage of new or newly recognized biological threats is now familiar. In this environment, it can be difficult to maintain a balance between solid preparedness and reasoned concern in proportion to the magnitude of potential threats. HIV/AIDS may be the clearest example in which a failure to appreciate the potential magnitude of an infectious disease may have resulted in early, rapid dissemination-with a devastating outcome. Resource allocation to new threats is also a challenge because existing medical problems compete for these same resources.
In this second article in a 2-part series, I will discuss bioterrorism, pandemic influenza, and emerging exotic infections. In a previous issue (CONSULTANT, October 2007), I addressed the emergence of antibiotic-resistant pathogens.
Whether it was the juxtaposition of the anthrax poisonings with the US terrorist attacks of September 2001 or just an outgrowth of fear of biological weapons, the public has heard more about bioterrorism in the past 6 years than at any previous time. Fear of bioterrorism persists because of new reports of biological warfare, including the most recent attack that involved a Russian spy who was poisoned with ionizing radiation (polonium-210). The fear also stems from the knowledge that biological weapons are inexpensive to produce and relatively easy to disseminate.
Salmonellosis. A less well-known example of a biological attack occurred in Oregon in 1984. A religious organization, the Rajneeshee group, "practiced" a mass attack by inoculating local salad bars with the Salmonella enterica serovar Typhimurium. A total of 751 cases of salmonellosis caused by this strain were reported in a county that usually reports 5 cases per year.1 Members of the group admitted to the salad bar attack as well as to an effort to disseminate the organism in the water supply.
In a suspected outbreak of salmonellosis, the information that ties together cases is obtained by laboratory testing of stool specimens. Given the long turnaround time for outbreak investigations, the spread of the disease has usually stopped by the time a definitive diagnosis is complete and the strain typing shows that an epidemic is under way. Regional or national public health authorities will assess whether there is a need for food testing or other precautionary measures.
Anthrax. Since the anthrax cases in 2001 that involved journalists, postal workers, and a few unlucky mail recipients, no further attacks have been documented in the United States. Patients who are concerned about anthrax can be reassured that the risk of contracting the disease is very low.
Figure 1 – This painless black eschar developed
on the arm of an importer of Asian rugs. Gram staining
and culture of the lesion confirmed the suspected diagnosis
of cutaneous anthrax.
The CDC Emergency Preparedness & Response Web site provides information on the clinical findings, diagnosis, and treatment of all 4 types of anthrax.2 The cases in 2001 involved persons who had cutaneous or inhalational anthrax. Erythema, such as that seen in cellulitis, followed by the development of a painless vesicle with a necrotic center is highly suggestive of cutaneous anthrax (Figure 1). The early stage of inhalational anthrax may be indistinguishable from pneumonia. Large hemorrhagic pleural effusions and mediastinitis with a widened mediastinum are suggestive findings.
A 60-day course of doxycycline or ciprofloxacin is currently recommended for those exposed to Bacillus anthracis. These persons should be advised of the adverse effects of postexposure prophylaxis-which are mild but common-and of the need to complete treatment.
The use of the anthrax vaccine remains somewhat controversial. The current anthrax vaccine is an improved version of a vaccine that was last tested in a randomized trial in humans in 1959. The relative efficacy then was 92%; however, the mill workers who were tested were at risk for cutaneous rather than inhalational anthrax.3 Although no severe side effects are associated with the anthrax vaccine, a substantial rate of local reactions (muscle soreness) and early fever after immunization has been reported. Fear of these side effects among persons in the military and National Guard has resulted in dismissal (or non-reenlistment).4
Smallpox. Despite the eradication of smallpox in 1977, some experts fear that strains kept in vitro may have been weaponized. In an effort to protect the US population in the event of a terrorist attack using the smallpox virus, select military personnel, civilian health care workers, and "first responders" were vaccinated in 2003. Because of the toxicity of this vaccine, careful selection criteria were applied to reduce morbidity. Nevertheless, cardiac toxicity was reported in both the large military population and smaller civilian population. The expanded program has led to a number of cases of myopericarditis (rarely fatal).5 The widespread use of vaccinia-based vaccination for smallpox could save countless lives (assuming the strains used by the terrorists are similar to those in circulation at the end of the era of naturally occurring smallpox).
Confirmation of even a single case of smallpox would constitute a major public health crisis. No one knows the degree to which previous immunization could confer immunity in older persons who received the vaccine when it was routinely administered. Few practicing clinicians have seen cases of smallpox; thus, a high index of suspicion would be required to make an expeditious diagnosis. If an otherwise healthy person presented with an acute febrile disease with deep, painful lesions and chickenpox or a rare entity such as monkeypox had been ruled out, an urgent laboratory evaluation for smallpox would be warranted. Regional and national public health resources should be mobilized quickly for any credible case of potential smallpox because delay is potentially very risky.
A pandemic influenza, possibly linked to the H5N1 avian influenza virus, is the most feared emerging infection. Of the 3 influenza pandemics in the 20th century (1918 to 1919, 1957 to 1958, and 1968 to 1969), the first was so devastating that it continues to hold a grip on the public imagination. In that long epidemic, the attack rate and case-fatality rate were unusually high.6
Figure 2 – This transmission electron micrograph
(magnification x108,000) reveals the ultrastructural
details of 2 avian influenza A (H5N1) virions.
Reconstruction of the 1918 viral genome from frozen human tissue buried nearly a century ago showed that the virus was an H1N1 strain that had initially been an avian strain with minor adaptive modifications, which enabled it to infect humans efficiently. These 2 minor modifications seem to alter the ability of the virus to interact with receptors, which vary slightly between birds and mammals. The question remains whether the current highly lethal H5N1 avian flu (Figure 2), which has a case-fatality rate of 50%,7 might be able to disseminate from person to person and set up a worldwide pandemic.
In the 1997 outbreak of H5N1 avian flu in humans in Hong Kong, the case-fatality rate was similar to that of the current avian flu (which has been infecting humans since late 2003) and was high despite the lack of person-to-person transmissibility. This outbreak seemed to settle down after a large-scale culling of birds (poultry and pet) in the territory.8 One of the worries about the current H5N1 infection is that it is now a major epizootic. If the virus maintains its ability to infect birds and becomes more infective in humans, multiple explosive outbreaks could theoretically occur that we would be unable to stop by reducing interpersonal interactions (so-called social distancing), which is central to the management of pandemic influenza.
Diligent notification of public health authorities about the possible importation of severe influenza is crucial. This might entail the administration of new vaccines or the submission of specimens from patients with significant respiratory illnesses. Ultimately, it may also trigger new isolation procedures, quarantine for contacts, and even major increases in social distancing (such as canceling athletic events or school).
Viral hemorrhagic fever. Infections that are localized by virtue of geography can sometimes be spread by panicked, infected people. In 2005, an outbreak of a viral hemorrhagic fever caused by the Marburg virus occurred in rural Angola near the border with Congo.9 Because Marburg infections, like Ebola virus infections, are highly lethal, can spread from person to person, and arise from an as yet unknown natural reservoir, the initial public health response is usually to quarantine. However, Angolans who were afraid to stay in their home province of Uige spread the virus to several other provinces (including the capital city of Luanda). The outbreak ended later the same year with the distinction of being the largest ever Marburg virus epidemic (with more than 300 deaths).
Severe acute respiratory syndrome (SARS). In November 2002, the first case of SARS occurred in East Asia. Over the next year and a half, about 8000 SARS cases (with about 800 deaths) were documented, mostly in Asia but also in Canada and Western Europe. The global spread of SARS was related to the ease of intercontinental travel and the transmission of the virus from unprotected health care providers to their coworkers and other patients.
SARS was found to be a new member of the coronavirus family. Suspicion of an animal source was strong because the first cases seemed to be in rural areas known for access to live animals in the so-called wet markets. Viral cultures showed that civets were infected by a related coronavirus. This led to a culling of civets and other exotic animals from some of these markets. However, later studies showed that the most likely culprit was the Chinese horseshoe bat, Rhinolophus sinicus.10
The CDC lists the following key clinical features of SARS-associated coronavirus (SARS-CoV) disease11:
• Incubation period of 2 to 10 days.
• Early systemic symptoms followed within 2 to 7 days by dry cough and/ or shortness of breath, often without upper respiratory tract symptoms.
• Development of radiographically confirmed pneumonia by day 7 to 10 of illness.
• Lymphopenia in most cases.
According to the CDC, in the absence of person-to-person transmission of SARS-CoV worldwide, the goal of domestic surveillance is to maximize early detection of cases of SARS while minimizing unnecessary laboratory testing, concerns about SARS-CoV, implementation of control measures, and social disruption.11
During the previous outbreaks, infants and children accounted for only a small percentage of SARS cases and had a much milder disease and better outcome than adults. Thus, screening for SARS should be limited to adults. A diagnosis should be considered only in adults who require hospitalization for radiographically confirmed pneumonia and who have an epidemiological history that raises the suspicion for SARS-CoV disease. This epidemiological history includes11:
• Travel to mainland China, Hong Kong, or Taiwan, or close contact with an ill person who has traveled to one of these areas.
• Employment in an occupation associated with a risk of SARS-CoV exposure (eg, health care worker or laboratory worker).
• Association with a cluster of cases of atypical pneumonia without an alternative diagnosis (eg, in 2 or more health care providers in the same facility).
Although it is impossible to tell where person-to-person transmission of SARS will recur, the above potential sources of recurrence should be considered. The CDC advises that testing for SARS-CoV be done judiciously in consultation with local or state health officials. Meticulous infection control, particularly of respiratory infection, is essential to prevent the spread of SARS.
Nipah virus encephalitis. The first Nipah virus epidemic started in 1998 with cases of a frightening febrile encephalitis in Malaysia and Southeast Asia that resulted in 105 human deaths and the destruction of more than a million pigs.12 Since then, a number of significant outbreaks have been reported from Australia to India. In all of these outbreaks, the case-fatality rate was about 50% or higher. In the 1998 outbreak, the Nipah virus was transmitted to humans and pigs via bats. The geographical distribution of the Nipah virus outbreaks overlap with one or another species of bats, including Pteropus, the flying fox.
POTENTIAL DISEASE VECTORS
Bats are important potential vectors of mammalian diseases because of their aerial lifestyle. They can release infectious secretions in their roost, at their destination, or on the route of flight. The best explanation of the recent emergence of SARS and Nipah virus epidemics is the encroachment of human activities on the habitat of bats.
Habitat alteration caused by global climate change is another concern. Global warming has already expanded the vertical (altitude) habitat of many important insect vectors, including malaria-bearing mosquitoes. Many large urban centers in Africa and Latin America are currently largely protected from malaria because their elevation above sea level precludes the breeding of these mosquitoes. We may find that previous influences of latitude change as air and water temperatures warm and new parts of the world become hospitable to pathogens and their animal vectors. Emerging infections include those that intrude on new geographical locations-we may be trading off the survival of the polar bear for the enhanced success of anopheline mosquitoes.
Torok TJ, Tauxe RV, Wise RP, et al. A large community outbreak of salmonellosis caused by intentional contamination of restaurant salad bars.
Centers for Disease Control and Prevention. Emergency Preparedness & Response. Fact Sheet: Anthrax Information for Health Care Providers.
Accessed October 9, 2007.
Brachman PS, Gold H, Plotkin SA, et al. Field evaluation of a human anthrax vaccine.
Am J Public Health.
Grier P. Officer resigns over anthrax vaccine.
. May 2000;83.
Accessed October 9, 2007.
Centers for Disease Control and Prevention. Update: adverse events following smallpox vaccination.
Taubenberger JK, Morens DM. 1918 influenza: the mother of all pandemics.
Emerg Infect Dis
. 2006; 12:15-22.
Oner AF, Bay A, Arslan S, et al. Avian Influenza A (H5N1) infection in Eastern Turkey in 2006.
N Engl J Med
Webster RG, Peiris M, Chen H, Guan Y. H5N1 outbreaks and enzootic influenza.
Emerg Infect Dis.
Ligon BL. Outbreak of Marburg hemorrhagic fever in Angola: a review of the history of the disease and its biological aspects.
Semin Pediatr Infect Dis.
Wang LF, Shi Z, Zhang S, et al. Review of bats and SARS.
Emerg Infect Dis.
Centers for Disease Control and Prevention. Severe Acute Respiratory Syndrome (SARS). In the Absence of SARS-CoV Transmission Worldwide: Guidance for Surveillance, Clinical and Laboratory Evaluation, and Reporting Version 2.
. Accessed October 9, 2007.
Eaton BT, Broder CC, Middleton D, Wang LF. Hendra and Nipah viruses: different and dangerous.
Nat Rev Microbiol.
• Centers for Disease Control and Prevention. Emergency Preparedness and Response. Fact Sheet: Anthrax Information for Health Care Providers. http://www.bt.cdc.gov/agent/anthrax/anthrax-hcp-factsheet.asp. Accessed October 9, 2007.
• Centers for Disease Control and Prevention. Severe Acute Respiratory Syndrome (SARS). In the Absence of SARS-CoV Transmission Worldwide: Guidance for Surveillance, Clinical and Laboratory Evaluation, and Reporting Version 2. http://www.cdc.gov/ncidod/sars/absenceofsars.htm. Accessed October 9, 2007.