LETTERS agents cause limited damage. How- However, because of the immensity of trates how pathogens emerge and ever, more malignant forms of “auto- the threat, the Internet community spread in our increasingly small mutilating” hoaxes are likely to responded extremely rapidly. Within world. The speed of virtual pathogen emerge that could be as devastating to hours after its release, alerts to system evolution makes it possible to follow computers as some autoimmune dis- administrators on how to block the the process of mutation and selection eases are to humans. worm had effectively slowed its in real-time. With countless inter- The electronic monoculture that spread. Early surveillance and barrier linked computers, the risk for virtual improves communication also development averted disaster. As in contagion is so great that urgent steps increases the risk for contagion. Pre- contained epidemics of hemorrhagic are needed to avoid catastrophe. How dominant use of a single operating fevers, the immense threat of high many will it take before we system has improved communication contagion and lethality prompts effec- accept the risks and costs of computer and sharing of electronic data but has tive measures to rapidly recognize immunity? Similarly, to protect also facilitated ready amplification of outbreaks and prevent pandemics. against emerging pathogens, we must virulent programs. As with biological The types of measures to be used use all tools available, including vir- infection, transmission of computer against computer contagion can be tual pandemics. A task force to collect infection depends on susceptibility of learned from biology. Immune effec- data on the epidemiology of virtual the population. Virus producers saw tors of plants and animals protect infections as a model for infectious dis- an opportunity in the popular prefer- against a broad range of pathogens; eases might be an important first step. ence worldwide for PCs with however, in nature this system Microsoft Windows operating sys- evolved over millions of years. Engi- Trudy M. Wassenaar*† and tems. The enormous popularity of neering protective computer systems Martin J. Blaser‡ these systems, along with their long- with similar efficacy within a few recognized inadequate protection years is a great challenge. Current pro- *Molecular Microbiology and Genom- against misuse, made computer users tection programs mainly resemble ics Consultants, Zotzenheim, Ger- many; †Virtual Museum of Bacteria, susceptible. Virtual viruses able to innate immunity, but programs that www.bacteriamuseum.org; ‡New York learn from exposure (thus resembling infect multiple operating systems are University School of Medicine and rare (as are biological viruses with adaptive immunity) are under devel- New York Harbor VA Medical Center, broad host specificity), and even when opment. Vaccination with relatively New York, USA infected, computers that run on differ- harmless microbes primes the immune ent operating systems (e.g., Mac, system. Biological hosts also naturally Unix) or other-than-Outlook e-mail carry protective microflora that com- programs usually are dead-end hosts pete with pathogens. Could we pro- Emergence and for PC viruses. duce “virtual vaccines” that are Pathogens do not reinvent the beneficial to the computers carrying Rapid Spread of wheel. Virulence genes are constantly them (e.g., by blocking preferred sites - “stolen” and reused. Thus, new com- of entrance for viruses or repairing binations of virulence genes can result viral damage automatically) and let Resistant Vibrio in new pathogenic strategies, and such these “good” microbes circulate on the cholerae Strains, combinations frequently accumulate Internet just as malignant viruses do? Madagascar in pathogenicity islands. Reuse and Crude versions of such vaccines have combination of effective (and infec- already been developed. Recently, a tive) strategies are also common in worm by the name Fixing the Holes To the Editor: The Indian Ocean computer malware. A recent example was discovered that utilized known was free of for decades, until demonstrates the value of just the right security holes to spread to other hosts. January 1998, when an outbreak was amount of virulence. A highly danger- Using “good” microbes would have its detected in Comoros Islands (1). On ous worm called Nimda (Admin in costs: occupation of Internet capacity March 23, 1999, the Malagasy Epide- reverse) was released exactly 1 week and consequent slowdown of data miological Surveillance System after the September 11, 2001, terrorist transmission and presence of mali- reported the first case of cholera in attack in the United States. Nimda cious worms disguised as beneficial Mahajanga, a harbor on the northwest combined the most powerful strategies ones to elude detection. coast (2). In May 1999, the Malagasy of Code Red and SirCam and spread Knowledge of infectious diseases sanitary authorities set up sanitary bar- more rapidly than any previous worm. may help control computer contagion. ricades at the borders of the two prov- Clicking on the subject line of an Conversely, study of computer mal- inces—Mahajanga and Antananarivo infected e-mail (to delete it, for ware may help curb infectious disease —affected by the epidemic. Oral dox- instance) itself activated the worm. emergence. Internet contagion illus- ycycline was systematically given to

336 Emerging Infectious Diseases • Vol. 8, No. 3, March 2002 LETTERS all the travelers crossing the barri- restriction pattern similar to those of and nitrofurantoin, as well as to vibrio- cades. In addition, doctors in hospitals African and Comorian strains isolated static agent 0129. and dispensaries in these two prov- since 1994 and 1998, respectively (2,3). During the study period, we iso- inces gave to patients From July 1999 to March 2001, lated 351 (46.1%) V. cholerae strains with acute diarrhea. Despite these we monitored the tetracycline resis- from 761 stool samples analyzed. The measures, cholera had reached all six tance of V. cholerae isolated from the provinces of Antananarivo, Mahajanga, provinces of the island 10 months stool samples sent to the Institut Pas- and Toliary accounted for 85.9% of the later. In June 1999, a specific cholera teur de Madagascar in Antananarivo, stool samples sent to our laboratory. surveillance system was established in using the standard disk-diffusion From these provinces, we isolated 288 every Malagasy province with close method (4). Stool samples were col- strains; by contrast, from the three collaboration between the Malagasy lected in sterile containers, on What- other provinces (Antsiranana, Fian- Ministry of Health and the Institut man paper, or on rectal swabs. arantsoa, and Toamasina, located on Pasteur de Madagascar. Isolation of V. cholerae was carried the east coast), 63 strains were iso- The first strain isolated in out immediately after reception. Every lated. Rates of isolation, tested by a Mahajanga was sero- V. cholerae strain identified belonged chi-square test, did not differ signifi- group O1, serotype Ogawa, biotype El to serogroup O1, biotype El Tor. All the cantly between the six provinces Tor. Its antibiotype showed resistance tetracycline-resistant V. cholerae iso- (p=0.32). to trimethoprim-sulfamethoxazole, lated and 60 randomly selected tetracy- Fifty five (15.7%) of the 351 sulfonamides, trimethoprim, chloram- cline-susceptible strains were tested for strains isolated were found to be tetra- phenicol, streptomycin, and vibrio- sensitivity to the following drugs: cycline resistant (cross-resistance with static agent O129 (a molecule ampicillin, cephalotin, doxycycline, doxycycline) but had the same resis- naturally active against V. cholerae sulfonamide, trimethoprim, trimethop- tance pattern as the index strain iso- and used for identification). Suscepti- rim-sulfamethoxazole, chlorampheni- lated in Mahajanga for the other bility was conserved for tetracycline, col, streptomycin, spectinomycin, tested. During the first ampicillin, cephalotin, and pefloxacin neomycin, kanamycin, nalidixic acid, rainy season following the epidemic (2). This strain showed a rRNA gene pefloxacin, , rifampicin, (November 1999 to March 2000), a

International Conference on Emerging Infectious Diseases, 2002

The National Center for Infectious Diseases, Centers for Disease Control and Prevention, has scheduled the Third International Conference on Emerging Infectious Diseases for March 24-27, 2002, at the Hyatt Regency Hotel, Atlanta, Georgia, USA. More than 2,500 participants are expected, representing many nations and disciplines. They will dis- cuss the latest information on many aspects of new and reemerging pathogens, such as West Nile virus and issues concerning bioterrorism.

Conference information is available at http://www.cdc.gov/iceid

Contact person is Charles Schable, [email protected]

Emerging Infectious Diseases • Vol. 8, No. 3, March 2002 337 LETTERS unique tetracycline-resistant strain used in Madagascar, can be recom- References was isolated (in February 2000), in the mended any longer for treating severe 1. World Health Organization. Cholera in the capital Antananarivo; it was also resis- cases of cholera. This may represent a Comoros Islands. Wkly Epidemiol Rep tant to ampicillin, nalidixic acid, and critical public health problem in the 1998;5:32. 2. Duval P, Champetier de Ribes G, Ranjalahy nitrofurantoin. During the dry season country, especially as most of the pop- J, Quilici ML, Fournier JM. Cholera in (from April to October 2000), five ulation cannot afford more effective Madagascar. Lancet 1999;353:2068. (13.2%) of 38 V. cholerae new tetracy- but expensive antibiotics. 3. Germani Y, Quilici ML, Glaziou P, Mattera cline-resistant strains were found. Therefore, Malagasy medical D, Morvan J, Fournier JM. Emergence of However, during the last rainy season authorities should a) abandon any sys- cholera in the Central African Republic. Eur J Clin Microbiol Infect Dis (November 2000 to March 2001), 49 tematic chemoprophylaxis, b) advise 1998;17:888-990. (69 %) of 71 strains isolated were tet- only for mild- 4. National Committee for Clinical Labora- racycline resistant. They were mainly to-moderate cases, and c) reserve anti- tory Standards (NCCLS). Performance from the city and suburbs of Antanan- biotic therapy for severe illness (7). standards for antimicrobial disk suscepti- arivo (95.3%, 41/43 strains). The eight These measures against the cholera bility test: approved standard M2-A6. Wayne (PA): The Committee;1997. other resistant strains came from the epidemic should be accompanied by 5. Mhalu FS, Mmari PW, Ijumba J. Rapid provinces of Antananarivo, Toliary, general reinforcement of microbio- emergence of El Tor Vibrio cholerae resis- and Fianarantsoa. logic surveillance to monitor antibi- tant to antimicrobial agents during first six As observed in Tanzania (5), the otic resistance so that the island can months of fourth cholera epidemic in Tan- extensive prophylactic use of tetracy- respond effectively to any future bac- zania. Lancet 1979;1:345-7. 6. Materu SF, Lema OE, Mukunza HM, Adhi- cline may have triggered the rapid terial epidemics. ambo CG, Carter JY. resistance emergence and spread of tetracycline- pattern of Vibrio cholerae and Shigella resistant strains in Madagascar. The Jacques-Albert Dromigny, causing diarrhoea outbreaks in the eastern high rate of resistance in Antanan- Olivat Rakoto-Alson,* Africa region: 1994-1996. East Afr Med J arivo, where the major Malagasy hos- Davidra Rajaonatahina,† 1997;74:193-7. René Migliani,* 7. World Health Organization. Guidelines for pitals are located, could be due to cholera control. Geneva: World Health easier access to drugs in the capital Justin Ranjalahy,† Organization; 1993. than in the other provinces. and Philippe Mauclère* Of the 60 randomly selected tetra- cycline-susceptible strains, 56 had the *Institut Pasteur de Madagascar, original antibiotype; four became sus- Antananarivo, Republic of Madagas- car; and †Ministry of Health, Antanan- ceptible to vibriostatic agent O129 and arivo, Republic of Madagascar to all the antibiotics tested, except tri- methoprim. Four (3.5%) of the 115 strains tested (55 tetracycline-resis- tant and 60 tetracycline-susceptible strains) on a large panel of antibiotics were susceptible to trimethoprim-sul- famethoxazole. As usually observed in American Water Works Association other African cholera-endemic coun- Cascais, Portugal tries (6), only a small proportion of the strains were susceptible to trimetho- September 22–25, 2002 prim-sulfamethoxazole, one of the most frequently dispensed drugs. The American Water Works Association and the International Faced with this first emergence of cholera in Madagascar and its rapid Water Association are sponsoring the International Sympo- spread, medical authorities reacted sium on Waterborne Pathogens. immediately by using doxycycline as chemoprophylaxis (contrary to World For additional information, please contact Joe Bernosky at Health Organization recommendations the American Water Works Association (telephone: 303-347- [7]), probably because of its easy availability. 6209; e-mail: [email protected]) or visit the website at Our study demonstrates that 2 http://www.awwa.org/events//02iswp/call/ years after the epidemic began, neither trimethoprim-sulfamethoxazole nor tetracycline, the two first-line drugs

338 Emerging Infectious Diseases • Vol. 8, No. 3, March 2002