Widespread flooding in Guyana led to conditions favorable for epidemic leptospirosis. Once clinical and pathological recognition raised concerns that early febrile illness cases and deaths were the result of leptospirosis, the Guyana MOH rapidly recognized the need to adapt emergency waterborne disease surveillance to detect and monitor an emerging leptospirosis outbreak. Because of this transition, standard case definitions were modified to accommodate the situation in this post-disaster environment. In collaboration with national, regional, and international organizations, the MOH quickly obtained diagnostic capacity in-country and launched a massive chemoprophylaxis campaign. These actions likely assured appropriate treatment for clinical cases and may have prevented additional cases from occurring.
The effectiveness of weekly chemoprophylaxis in the prevention of leptospirosis infection during outbreaks in endemic areas is questionable; however, weekly chemoprophylaxis has been shown to reduce severity of clinical illness and potentially to reduce mortality during seasonal outbreaks or following high levels of water exposure, even though serologic evidence of infection did not differ in those who received doxycycline versus those who received placebo 
. When used in United States soldiers in Panama, weekly doxycycline demonstrated a protective efficacy of 95% (p<0.001) for infection 
. Decision tree analysis of the cost effectiveness of empirical antimicrobial prophylaxis and treatment of leptospirosis showed that in regions with both high and low background incidence rates for leptospirosis, doxycycline prophylaxis, as compared to a no-prophylaxis strategy, provided cost savings, decreased severity of illness and mortality, and improved health outcomes 
In this outbreak, it is difficult to assess the efficacy of the prophylaxis campaign. As Figure S1
demonstrates, the number of cases decreased after the administration of prophylaxis to the community. However, during this same time period public awareness increased, flood waters began to recede, and the epidemic may have run its course. Additionally, this outbreak follows a similar time course and distribution pattern to other leptospirosis outbreaks where no chemoprophylaxis was delivered 
. Of the surveyed patients, a significant number who had received doxycycline chemoprophylaxis had positive DST testing, although the number was lower than those who had not. This could result from DST testing detecting serologic evidence of prior infection and not active infection and illness, administration of doxycycline after infection and illness were already present, or lack of effectiveness of the medication to prevent illness. A placebo-controlled trial would have been scientifically more rigorous, but was precluded by concerns based on studies published prior to this outbreak that had demonstrated benefit in providing prophylaxis 
and by the logistical and political complexities of implementing a research component into an emergency response when public distress was at its highest. The effectiveness of this chemoprophylaxis campaign could have been assessed via a serologic survey to determine the proportion of people who received doxycycline and had evidence of symptomatic or asymptomatic seroconversion; however, resource limitations did not permit this to occur.
With the lack of definitive data to guide decisions about initiating a chemoprophylaxis campaign, the Guyana experience does not suggest that chemoprophylaxis should be initiated without thorough consideration. Certainly the potential benefit of massive chemoprophylaxis has to be weighed against the potential for drug resistance. While there has been no documentation of Leptospira acquiring resistance of which the authors are aware, other bacteria may do so when exposed to antibiotics. Ideally prophylaxis is undertaken when point-source exposure is known and at-risk individuals can be targeted, such as in smaller outbreaks. In times of severe flooding and in developing countries, identifying and providing chemoprophylaxis only to those individuals who will develop leptospirosis is not feasible; therefore far larger numbers of patients will need to be treated in order to derive maximal individual and public health benefit. Should situations in the future warrant a chemoprophylaxis campaign such as was undertaken in Guyana because of the large number of at-risk individuals and the potential for widespread disease and fatalities, a case control study or other scientifically rigorous evaluation of its efficacy should be strongly considered. The logistics of a large-scale chemoprophylaxis campaign should not necessarily be considered insurmountable, as is highlighted by the successful delivery of medication to over 280,000 individuals in the immediate aftermath of severe flooding in Guyana.
Given the mode of transmissibility of leptospirosis through animal urine, it is not surprising that many patients reported exposure to animals. Those depending on their livestock for financial reasons disclosed bringing their animals into the home in order to prevent the animals’ death or loss. Rats in the home were a common complaint. Through public messaging, people were encouraged to try to eliminate rat entry by removing garbage, but due to the limited time and financial resources during the outbreak, no specific rodent control programs could be initiated. With the foresight afforded by this outbreak and response, future public health interventions, such as chemoprophylaxis campaign strategies, or implementation of disease prevention measures such as rodent control programs, can be evaluated for their efficacy at preventing exposure and illness.
Steps taken in response to the leptospirosis outbreak after the flood have yielded longer-term benefits. Clinicians and the general public in Guyana are now more aware of the disease and the means by which it is spread and can be prevented. This heightened awareness, and the availability of diagnostic testing in-country, will improve surveillance for sporadic cases of leptospirosis and help prevent, detect, and control future outbreaks. In the aftermath of this outbreak in 2005, these conditions were set in place in Guyana and allowed for prompt recognition and response to a similar leptospirosis outbreak occurring the following year 
The danger of the heightened sensitivity to a particular disease in an outbreak setting is the tendency to overlook other diseases that may have similar clinical presentations. In this outbreak, previous experience led to initial concerns about waterborne enteric disease, although the ecological conditions were favorable for a leptospirosis outbreak. Furthermore, the individual who was treated for presumed leptospirosis and ultimately succumbed to what was determined to be fulminant malaria based on post-mortem tissue examination, illustrates the need to keep the differential diagnosis open. In the aftermath of severe flooding, epidemics of febrile illnesses spread by mosquitoes, such as malaria and dengue, and by contaminated food and water, such as typhoid fever, may also occur 
. Distinguishing these diseases on clinical grounds alone can be challenging, and the appropriate treatment and public health interventions vary greatly 
. Providers were reminded through hospital alerts to evaluate for these diseases concurrently, but focus on the current outbreak did not always result in complete testing, and reliable and rapid results were not always available. Therefore, in order to recognize quickly, assess accurately, and respond appropriately to epidemics of infectious diseases in the post-disaster period, it is essential that rapid and accurate laboratory diagnostic services are available, that public health authorities and health care providers maintain a heightened index of suspicion, and that a timely, representative, and accurate disease surveillance system exists.
Commercially available diagnostic tests for leptospirosis that can be used in the field setting have been evaluated by the CDC 
. Although an antibody response may not be detected until 10 days or more after initial symptom onset, the use of such assays may help guide appropriate delivery of antimicrobial therapy, which has been shown to reduce the severity and duration of clinical illness, and reduce mortality 
. The performance of other clinical diagnostic tests which are commercially available or are research-only at this time, including the IgM-ELISA based on the rLipL32/1-LipL21-OmpL1/2 fusion protein 
, has not yet been evaluated in the outbreak setting.
Our investigation of this outbreak and the public health response had several limitations. In the emergency setting, information had to be gathered quickly and was therefore sometimes incomplete. Patient interviews and laboratory testing were not well coordinated, and linking the data later on proved difficult because a centralized identification scheme was not established early. No specific clinical, laboratory, or epidemiologic criteria were required for the case definition of suspected leptospirosis; instead, that determination was made entirely by individual healthcare providers. As awareness of the outbreak increased, the threshold for considering leptospirosis as a diagnosis was lowered and more individuals with suspected leptospirosis were reported than might have occurred had a standard case definition been applied. On the other hand, since leptospirosis often causes only mild or no symptoms, many more patients with leptospirosis were probably treated as outpatients or did not seek medical care. Limited resources precluded laboratory testing of all patients with suspected leptospirosis.
The laboratory tests also have inherent limitations. The DST test has high sensitivity (94.5%) and can detect antibodies as early as 3 days after onset of symptoms; however, the detection rate is generally low early in the disease and antibodies may remain detectable for up to one year 
. Those tested too early may have had false negative results. Similarly, low titers on MAT may be seen soon after onset, before titers have a chance to rise, or could represent previous exposure rather than new disease. In a well-publicized epidemic such as this, people may have sought medical care early in the course of disease before laboratory confirmation was possible. Culturing blood for leptospirosis would have assisted with confirmation of the outbreak but was not performed. This is a significant limitation to this outbreak investigation, as identification of the infecting serovar or serovars would have aided in identification of the animal reservoirs which contributed to the outbreak. However, with the recognition that leptospirosis cases and outbreaks can occur in Guyana with a greater frequency than previously recognized, preparatory steps can be taken to ensure in future investigations that cultures are obtained and infecting serovars identified in order to guide leptospirosis intervention and control programs.
Despite these limitations, valuable information has been gleaned from the response to this disaster. Natural disasters related to sudden geological and meteorological events are predicted to occur more often as a result of global warming 
. Human populations are increasingly concentrated in coastal areas that are at high risk for flooding and severe damage resulting from natural disasters. Consequently, the public health community must remain prepared for the sudden emergence of epidemics of infectious diseases like leptospirosis in the post-disaster period. The ability to rapidly detect, confirm, and respond to such infectious disease epidemics in this setting requires an alert, well-coordinated, and well-funded public health system at the local, national, regional and global levels, along with appropriate clinical diagnostic and investigation tools to identify specific etiologic causes. We should take encouragement from the response in Guyana and from other recent successes, but must not relax our efforts to build a strong and well-coordinated public health system worldwide and to improve the accuracy and availability of rapid diagnostic tests that function well under harsh field conditions. Prevention of illness and death in the post-disaster period anywhere in the world will depend on it