I hope you're doing well. I also hope that you'll find the following article about Pontiac Fever by Dr. Joseph Manfrida both interesting and useful.

With best wishes,
Dave Gallup

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Legionnaires' Disease is a frequently discussed and extensively studied illness linked to infection caused by the Legionella bacterium. However, Legionnaires' Disease is just one of the two potential illnesses that can be caused by legionellosis (a Legionella infection). The second illness, Pontiac Fever, is far more widespread than Legionnaires' Disease.

Pontiac Fever is not a potentially life threatening illness, and therefore has not been subject to the same level of scientific investigation as Legionnaires' Disease. However, a deeper understanding of Pontiac Fever can be revealing of the full extent of Legionella contamination in our environment, as well as providing useful clues into how the infection functions and what needs to be done to reduce the overall number of legionellosis cases, for both the dangerous Legionnaires' Disease and the more innocuous Pontiac Fever pathologies.

One of the greatest challenges facing clinicians and researchers seeking to study Pontiac Fever is identifying patients who have contracted the illness. Unlike Legionnaires' Disease, which results in a severe and potentially fatal pneumonia that invariably drives infected individuals to seek medical attention, Pontiac Fever's symptoms and signs are fairly benign and not life-threatening. The fever, chills and muscle pain resulting from Pontiac Fever are easily mistaken for a mild flu. Individuals suffering from the Pontiac Fever pathology of legionellosis are unlikely to seek medical attention, thereby hiding outbreaks of the illness from all but the most thorough medical surveillance.

Current estimates of legionellosis put the number of annual cases in the United States between 8,000 and 18,000 infections per year, however because of the difficult to diagnose nature of the Pontiac Disease pathology, the true numbers are likely to be significantly higher¹. Legionellosis infections can be identified either through the detection of antibodies against Legionella in the blood or urine or by detection of specific antigens or DNA of the Legionella bacterium in sputum samples from the lungs². (The first method indirectly detects the infection by quantitatively isolating the antibodies produced by an individual's immune system in response to the invading bacterium, while the second method directly detects the presence of the bacterium by quantitatively identifying components of the Legionella bacterium in an individual's fluids.)

In this case of infection identification, the Pontiac Fever pathology poses a problem when compared to the Legionnaires' Disease pathology for legionellosis. The onset of Pontiac Fever is very quick when compared to that of Legionnaires' Disease, 24 to 48 hours as opposed to 2 to 14 days. It has also proven to be impossible to isolate the causative bacterium from patients with Pontiac Fever due to the lack of associated pneumonia³. As a result, doctors and scientists have a very small window of opportunity to identify Pontiac Fever victims to study, and when they do, they are limited to studies using only antibody detection from patients' fluids, since there is no isolatable organism on which to perform direct antigen, culture or DNA testing.

There has also been research suggesting that the reason why researchers and doctors have been unable to isolate Legionella bacteria from patients with Pontiac Fever is because the organism is not causing a direct infection, but rather a toxic or allergic reaction to a component of the bacterium. It is well established that Legionnaires' Disease occurs when Legionella bacteria invade a host's tissues and begin reproducing within them⁴. This was thought to be the case for Pontiac Fever as well until a paper published in 2001 found an outbreak traced to a whirlpool spa in a Wisconsin hotel which indicated another possibility.

During the investigation of this outbreak of Pontiac Fever, it was found that the water in the hotel's whirlpool spa contained no culturable live Legionella, but that the water did contain elevated levels of endotoxin presumably derived from a viable Legionella contamination detected in a sand and water filter attached upstream of the spa⁵. This led the study's authors to hypothesize that it was not live Legionella bacteria infecting the tissues of the Pontiac Fever victims that caused the disease, but rather endotoxins given off by the bacterium in the filter that may have been responsible for the pathology. In this model of Pontiac Fever, the symptoms are generated as an immune response from exposure to biological chemicals given off by the upstream bacterial contamination.

The implications of this hypothesis are significant if it is eventually proven to be true. Current protocols for the prevention of Legionella disease are based on the concept that it is sufficient to kill the bacterium to render the organism harmless. If Pontiac Fever is actually caused by an allergic response to a cellular component of the bacterium, then simply killing the contaminating bacteria may not be sufficient to eliminate the threat it poses to human health.

For example, treating a contaminated whirlpool spa with chlorine at sufficient concentrations to kill the contaminating Legionella bactera will prevent those bacteria from infecting anyone, however dead bacteria will lyse (rupture) and release their internal components into the surrounding water. If these components, such as endotoxins, are not removed from the treated water source, then it is possible that a person exposed to those components could have an allergic reaction to them and suffer symptoms of Pontiac Fever.

At this time, the hypothesis that Pontiac Fever is an allergic reaction or toxic effect generated by Legionella bacteria, rather than an infection, is still not verified. The 2001 study demonstrates correlation, but not causation. Additional in vivo and epidemiological work will need to be completed to either verify or refute this hypothesis.

The study of legionellosis outbreaks requires large scale data collection and real-time analysis that is not available in the United States. Currently Legionella outbreaks are tracked and recorded by the CDC with the help of local state boards of health. This method has proven to be largely inadequate to track patients experiencing the symptoms of Pontiac Fever due to its very short incubation time and the likelihood that many cases are not reported to clinicians.

The current system which requires data to be transferred from the local clinician, to the state board of health, then eventually to the CDC (frequently in hard copy format rather than electronically) simply takes too long for the CDC to organize a meaningful response either for treatment or data collection. Europe has developed a solution to this problem through the deployment of the European Legionnaire's Disease Surveillance Network (ELDSNet). Originally deployed in 1987 to monitor the spread of Legionnaire's Disease through travelers, ELDSNet is a computerized system for monitoring medical records in near real-time that has become a very powerful tool for studying Legionella disease outbreaks⁶.

One of the more impressive research papers published as a result of Europe's vigilance against Legionella disease tracked a legionellosis outbreak across Pas-de-Calais, France between November 2003 and January 2004⁷. In this case, 86 individuals in Pas-de-Calais were confirmed to have Legionnaires' Disease by means of urine antigen tests. Clinical isolates were obtained from lung fluid samples of 23 separate patients and were found to be genetically identical. The genetic information was compared to over 1100 environmental samples taken from around the area of the outbreak. Of the environmental samples, 104 of them were positive for Legionella, but only 4 of them had genetic tests matching the clinical samples. Examination of the 4 locations with the genetic match revealed that only one of them was centrally located to the outbreak and had high concentrations of the bacterium.

This centrally located source of the genetically identical Legionella was a cooling tower. Computer modeling of the aerosols generated by the cooling tower indicated that it could have easily spread Legionella bacteria over a 6 kilometer radius area where the outbreak was centralized. This level of detection and isolation of the original source of a major outbreak from an environmental sample was possible only because the French medical authorities were able to become aware of the outbreak rapidly enough to sample patients and environmental sources at the same time while the outbreak was in progress. This rapid response would not have been possible if the information had to pass through multiple layers of bureaucracy prior to being collated and presented to the centralized medical authority for analysis.

The European ELDSnet model for disease monitoring could be applied to outbreaks of both Legionnaires' Disease and Pontiac Fever in the United States. Knowledge of Pontiac Fever outbreaks obtained in near real-time could be used to pinpoint contamination sources and mount consistent and rapid responses to the threats posed by Legionella. This would allow for the reduction of outbreak occurrence and recurrence by identifying and eliminating the sources of widespread environmental contamination.

However, a European style system is not without drawbacks. ELDSnet requires that medical information be immediately uploaded to a centralized computer by doctors as they collect data from their patients. This level of surveillance represents a potential source for violation of the Health Information Privacy Act of 1999 which seeks to keep medical information confidential. Furthermore, rapid response would require a significant investment of resources which could be used elsewhere. Finally, in order to carry out rapid testing for contamination and remediation of an identified source requires that local and state medial authorities surrender a significant amount of their power to a centralized national organization. Historically, the centralization of power in the federal government has been politically divisive. There is a potential for Pontiac Fever to serve as a tool for the control and elimination of Legionella outbreaks, but only if the cost in resources and political will can be mustered to do so.

References:
1. Benin, Andrea L., Benson, Robert F., Arnold, Kathryn E., Fiore, Anthony E., Cook, Patricia G., Williams, L. Keoki, Fields, Barry, and Richard E. Besser. 2002. An Outbreak of Travel-Associated Legionnaires' Disease and Pontiac Fever: The Need for Enhanced Surveillance of Travel-Associated Legionellosis in the United States. The Journal of Infectious Diseases 185:237-243.

2. CDC Position Statement: Strengthening surveillance for travel-associated legionellosis and revised case definitions for legionellosis. Accessed on 5/21/2012.

3. CDC: Top 10 Things Every Clinician Needs to Know About Legionellosis. Accessed on 5/21/2012.

4. Mayo Clinic: Legionnaires' Disease. Accessed on 5/21/2012.

5. Fields, Barry S., Haupt, Thomas, Davis, Jeffery P., Arduino, Matthew J., Miller, Phyllis H., and Jay C. Butler. 2001. Pontiac Fever Due to Legionella micdadei from a Whirlpool Spa: Possible Role of Bacterial Endotoxin. The Journal of Infectious Disease 184:1289-1292.

6. Cowgill, Karen D., Lucas, Claressa E., Benson, Robert F., Chamany, Shadi, Brown, Ellen W., Fields, Barry S., and Daniel R. Feikin. 2005. Recurrence of Legionnaires' Disease at a Hotel in the United States Virgin Islands over a 20-Year Period. Clinical Infectious Diseases 40:1205-1207.

7. Nguyen, Tran Minh Nhu, Ilef, Daniele, Jarraud, Sophie, Rouil, Laurence, Campese, Chrisitine, Che, Didier, Haeghebaert, Sylvie, Ganiayre, Francois, Marcel, Frederic, Etienne, Jerome, and Jean-Claude Desenclos. 2006. A Community-Wide Outbreak of Legionnaires' Disease Linked to Industrial Cooling Towers - How Far Can Contaminated Aerosols Spread? The Journal of Infectious Diseases 193:102-111.

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