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Emerging Infections in Latin America

OVERVIEW

Economic globalization, demographic change, and the rapidly rising costs of health care in all countries are converging factors that transcend national borders. In Latin America, economic globalization has meant the increased movement of people and goods and changes in environmental and occupational health hazards—often occurring in the context of political instability. It has also meant that health risks are being transferred. For example, an epidemiologic transition, marked by a gradual increase in the rate of noncommunicable diseases, is now under way in the region. In the next 25 years it is expected that the dominant diseases in Latin America will increasingly become like those of the United States and other more industrialized nations, where depression, heart disease, and cancer are the primary health problems. The infectious etiologies of chronic conditions will be of increasing importance and will require action. Thus, the opportunities for the transmission of emerging and reemerging infectious diseases remain and in some instances have increased. As the region's needs change, the responses of national and international health agencies are evolving. Cooperative actions and solutions for infectious disease surveillance and response among government health agencies and between countries are key elements needed to address the common problems of emerging infections in Latin America.



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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections 2 Emerging Infections in Latin America OVERVIEW Economic globalization, demographic change, and the rapidly rising costs of health care in all countries are converging factors that transcend national borders. In Latin America, economic globalization has meant the increased movement of people and goods and changes in environmental and occupational health hazards—often occurring in the context of political instability. It has also meant that health risks are being transferred. For example, an epidemiologic transition, marked by a gradual increase in the rate of noncommunicable diseases, is now under way in the region. In the next 25 years it is expected that the dominant diseases in Latin America will increasingly become like those of the United States and other more industrialized nations, where depression, heart disease, and cancer are the primary health problems. The infectious etiologies of chronic conditions will be of increasing importance and will require action. Thus, the opportunities for the transmission of emerging and reemerging infectious diseases remain and in some instances have increased. As the region's needs change, the responses of national and international health agencies are evolving. Cooperative actions and solutions for infectious disease surveillance and response among government health agencies and between countries are key elements needed to address the common problems of emerging infections in Latin America.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections EMERGING INFECTIONS IN COLOMBIA: A NATIONAL PERSPECTIVE Jorge Boshell-Samper, M.D. Director General, Instituto Nacional de SaludBogotá, Colombia Several key elements are responsible for the resurgence of infectious diseases in Colombia, including: environmental changes; human demographics, mosquito behavior, and deforestation; emerging antimicrobial resistance; political decentralization and complacency; and natural disasters. Although tuberculosis (TB) is considered a major emerging disease in the developed world, it has always been prevalent in Colombia and does not fit the criteria and concepts of an emerging infection. It has been a continuous threat. Environmental Changes Unpredictable and unusually heavy rainfalls have resulted in the emergence of Venezuelan equine encephalomyelitis (VEE) virus outbreaks that afflicted thousands of horses and humans in Colombia and Venezuela. Although the disease had been silent for more than 20 years, outbreaks occurred in 1992, 1995, and 1998. The immediate response involved vaccination of horses with the TC83 vaccine. An international research project that involved a collaboration between the University of Texas Medical Branch at Galveston, the Instituto Nacional de Higiene of Venezuela, and the Instituto Nacional de Salud (INS) of Colombia was launched to understand the epidemiology of enzootic sylvatic disease cycles and their mechanisms of emergence as epizootic strains that killed horses. In addition, increased surveillance of VEE virus-infected horses was conducted through a national laboratory-based network system. Seasonal rainfall changes were also associated with the reemergence of influenza epidemics that afflicted hundreds of individuals throughout the country: influenza A/Wuhan/H3N2 in 1996, influenza B/Beijing and influenza A/ Sydney/H3N2 in 1997, influenza A/Sydney/H3N2 in 1998, and influenza A/ pending/H3N2 in 1999. The Colombian response was the implementation of a regular sentinel surveillance system sponsored by INS for influenza and other respiratory viruses. This surveillance system will be for prediction of and planning for the next influenza pandemic in the region. The information obtained from the surveillance system underscores the importance of research. Human Demographics, Mosquito Behavior, and Deforestation Dengue was a forgotten disease in Colombia by the 1950s and 1960s because of the eradication of Aedes aegypti, the mosquito vector. After reinvasion, of the country by Ae. aegypti the country experienced multiple epidemics. In the

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections 1970s the four serotypes of dengue virus were documented and in the 1980s dengue virus serotypes 1, 2, and 4 infected thousands of patients. Because Ae. aegypti spread horizontally throughout lowland areas of the country and also spread vertically up the populated cordilleras, a series of parallel mountain ranges, dengue fever is now endemic and causes frequent epidemic peaks. Moreover, dengue hemorrhagic fever (DHF) has emerged as an epidemic illness, with 39 registered cases in 1990, followed by 100 cases in 1991 and 359 cases in 1992. The incidence of DHF per 100,000 population in Colombia rose from 0.11 in 1990 to 9.82 in 1997. Colombia has responded with an aggressive medical and public health education program in medical schools and with local and regional symposia with public health providers and local and foreign scientists as speakers (sponsored by the Pan American Health Organization (PAHO) or the Colombian Ministry of Health). In addition, the country adopted community-based education programs, educated the public through national television programs, and adopted municipality-based biological control programs. It also made sporadic attempts at mosquito control. The real goal is to implement a strategy to develop a dengue vaccine through cooperation between INS and the Instituto de Immunologia, Universidad Nacional de Colombia. In the American region enzootic for yellow fever, Colombia is the only country that has escaped jungle yellow fever (JYF) outbreaks for more than 10 years, despite serious and constant civil unrest and intense illegal activities in the jungles of Colombia. However, the emergence of urban yellow fever remains a Sword of Damocles for the country, because most isolated cases of JYF, among patients still in the viremic phase of their infection, are found in hospitals located in urban centers full of Ae. aegypti, the urban vector of yellow fever virus (Breteau indexes [see the glossary in Appendix A], over 60 percent). The response has been to update the 17D yellow fever vaccine manufacturing plant to implement good manufacturing practices and implement a stringent program for the detection and diagnosis of febrile cases of yellow fever among individuals in the jungle of the Amazon and Orinoco regions. An outbreak of acute Chagas disease myocarditis was diagnosed for the first time in Colombia during April and May 1999 in a rural municipality on the Caribbean coast. The best hypothesis to explain this epidemic implicates ecological changes brought about when the palm trees in the neighborhood were cut down. An increased surveillance program has been initiated. Emerging Antimicrobial Resistance Clones of Streptococcus pneumoniae with diminished susceptibility to penicillin (DSP) or with multidrug resistance are emerging in Colombia, as documented by the PAHO/SIREVA project. From 1994 to 1996 the rate of DSP was low (12 percent), but the rate of resistance increased yearly and by 1997 it

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections had reached 39 percent, along with the emergence of multidrug-resistant (clones 23F and 14B). Furthermore, 42.4 percent of the DSP population studied was found to be multidrug resistant. The Colombian response has been to continue the national surveillance program with the Colombian Pneumococcal Study Group and public health programs to detect changes in the susceptibility pattern. The annual parasitic index (API which is the number of parasitologically confirmed cases per 1,000 population per year) for malaria has continuously increased in Colombia from 1970 (API = 1) through the end of the 1990s (API = 6). This increase is due to a variety of factors, including resistance to antimalarials (resistance to chloroquine in Plasmodium falciparum was first reported in 1961), vector resistance to pesticides, and the breakdown of public health measures. There has been major support for the development and improvement of a synthetic antimalarial vaccine (SPf66), primarily by Manuel E. Patarroyo at the Instituto de Immunologia, Universidad Nacional de Colombia. Furthermore, multicenter studies have been conducted in areas of malaria endemicity to develop community-based programs for vector control. Complacency and Natural Disasters Despite the elimination of poliomyelitis in the Americas, there is a risk of the reemergence of this disease through importation, decreasing levels of vaccine coverage, and breakdown of intensified surveillance, as currently seen in Haiti and the Dominican Republic. Although the last confirmed case of wild-type derived poliomyelitis on the North American continent was reported in June 1991, the risk of importation and spread of wild-type poliovirus strains into the Americas has been documented on two occasions in Canada (1992 and 1996). This type of episode is especially problematic because of breakdowns in active surveillance and decreased vaccine coverage. Colombia and the rest of Latin America are in the final phases of measles eradication. After measles was on the verge of control in 1996, outbreaks in Brazil, Argentina, and Bolivia are reminders of the reality of the reestablishment of transmission. Decentralization of health services in the process of health reform requires that national surveillance and control be conducted through INS, a step being implemented by the Colombia Ministry of Health. Public health authorities are very much aware of potential disease outbreaks after natural disasters. Active surveillance after the earthquakes in Armenia and the coffee-growing region of Colombia brought attention to the fact that an apparent outbreak of hepatitis A had been endemic and undiscovered for more than 3 months before the disaster. In addition, an urban malaria outbreak was diagnosed for the first time in more than 30 years.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections Conclusion The constantly changing and unpredictable factors that contribute to the resurgence of infectious diseases in Colombia require increased and sustained surveillance. A NATIONAL STRATEGY FOR EMERGING INFECTIOUS DISEASES: THE ARGENTINE CASE OF 1999 Elsa L. Segura, Ph.D. Director, Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS MALBRAN), Ministry of Health Buenos Aires, Argentina Emerging infectious diseases have increasingly been detected in Argentina, starting with epidemic outbreaks of Argentine hemorrhagic fever (AHF) in the 1950s, human immunodeficiency virus infection (HIV)/AIDS and leishmaniasis in the 1980s, and cholera, antimicrobial resistance (e.g., resistance of meningococcus type B and Mycobacterium tuberculosis), hantavirus, and dengue in the 1990s. Argentina has a population of 36 million and comprises a federal organization of 23 provincial states and the city of Buenos Aires. The national health system is coordinated at the political and technical levels by the Federal Health Council (COFESA), which meets at least six times a year. At the central level, the Directorate of Epidemiology is in charge of national epidemiological surveillance. Laboratory responsibilities are led by the Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS MALBRAN), a decentralized national administration that coordinates 11 health institutes and centers and a network of 650 laboratories distributed throughout the country, with a presence in each one of the provincial states. Networked activities include research and development, training, production of biologicals, and quality control for the diagnosis of diseases affecting public health. In recent years there has been enhanced cooperation of these networks with the epidemiological efforts of the Argentine Ministry of Health. External quality control was enacted in 78 percent of the network laboratories in 1999. As a direct result of these efforts, the laboratories cooperated in writing national guidelines for diseases subject to mandatory notification. The objectives of the strategic plan of ANLIS MALBRAN for emerging and reemerging infectious diseases are research and analysis of the results obtained by the diagnostic laboratories and application of these analyses to surveillance and policy development. Since 1960 the Argentine National Epidemiological Surveillance System (enacted by law) each week has collected information on 60 infectious diseases for which notification by provincial public hospitals is mandatory, making its findings available to the public. Since 1992—after a cholera

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections outbreak—the public health laboratory network for cholera has confirmed the results obtained through the mandatory notification process. At present, the surveillance system in Argentina includes three components: (1) physicians at the first health care level (sentinels), (2) public health laboratories distributed throughout the country, and (3) provincial epidemiology units that analyze the collected data. Applied research and quality assurance processes—directed to increasing the specificity of epidemiological surveillance— occupy a central role in the organization of the 650 laboratories in the Argentine network. Argentine Hemorrhagic Fever Argentine hemorrhagic fever (AHF) has been a major public health concern since 1955. It is an acute viral disease caused by the Junin virus, an arenavirus, and it is endemic to the Argentine humid pampa. An increased incidence of AHF has been observed among adult rural workers, reflecting occupational exposure to the virus. The focal incidence of AHF correlates well with the distribution of the rodent reservoirs. The affected area has gradually been extending and now covers approximately 150,000 square kilometers (58,000 square miles), including densely populated areas in the Department Rosario in the province of Santa Fe. The population at risk is approximately 5 million. AHF has shown 5-year cycles, likely related to fluctuations in the densities of rodent populations. Because the control of rodent reservoirs of the Junin virus is not feasible in such an extended geographical area, most preventive efforts have been directed to vaccine development. The development of a vaccine against AHF has a long history. In a first stage (1968–1969), a live, attenuated, cloned virus vaccine, XJ Clon 3, was developed in the Faculty of Medicine at the University of Buenos Aires (Weissenbacher et al., 1969) and was tested successfully in 300 volunteers. In a second stage, a clone from the Junin virus formed the Candid 1 vaccine, developed as a result of an international cooperative project between the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), PAHO, and the Argentine Ministry of Health. Between 1985 and 1990 a vaccine trial involving more than 7,000 volunteers in Argentina established the immunogenicity, inoculability, and efficacy (95.5 percent) of the Candid 1vaccine. The vaccine was readily accepted by the population, which was significant considering that vaccination was voluntary, experimental, restricted geographically, required an informed consent as well as a pregnancy blood test for women of reproductive age, and required travel to designated vaccination posts, which were open only on certain fixed days at fixed times (Enria et al., 1998). The Candid 1 vaccine is highly effective; it elicits high levels of protective antibodies for 9 years after vaccination in approximately 90 percent of people vaccinated with a single dose. However, AHF is not an eradicable disease, and despite good vaccine coverage rates, isolated cases and limited outbreaks will likely occur

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections in the future. Therefore surveillance aimed at detection and prompt treatment of people with AHF and research on the activity of the Junin virus in the rodent reservoirs must remain active. Research on AHF and development of an effective vaccine demonstrated that a developing country can solve its own infectious disease problems and enhance an initiative through international cooperation. HIV/AIDS The cumulative number of HIV/AIDS cases in Argentina was 15,166 as of July 31, 1999. Because of a delay in the notification process, however, approximately 17,000 cases may have occurred up to that date (Ministry of Health and Social Welfare of Argentina, 1999). Surveillance is carried out through mandatory notification, and only laboratory-confirmed cases are reported. The system uses the reporting criteria of the Centers for Disease Control and Prevention except for the determination of CD4/CD8 cell counts. Leishmaniasis An epidemic of cutaneous-mucocutaneous leishmaniasis occurred in the province of Salta in northwestern Argentina between 1984 and 1987. The etiologic agent was identified as Leishmania (Viannia) braziliensis. The local incidence rate rose from 6.4 cases per 100,000 in 1984 to 28.7 cases per 100,000 in 1985 (Sosa Estani et al., 1998). Since October 1997 there has been an increase in the number of cases in the departments of Orán and San Martín (Salta), close to the site of the upsurge from 1984 to 1987, whereas other outbreaks were detected in the northeastern province of Misiones. The rising incidence rate was likely associated with traditional deforestation activities in Salta and climatic phenomena in Misiones. Cholera Epidemic The first case of cholera was reported in Argentina in the summer of 1992 and was caused by Vibrio cholerae O1 biotype El Tor, serotype Ogawa, producer of the cholera enterotoxin (CT). The epidemic started in the northwestern province of Salta, and spread to neighboring areas in the provinces of Formosa and Jujuy. Sporadic cases occurred later in other areas after the movement of the population from the affected areas (Varela, 1994). By June 1995, four epidemic outbreaks had occurred, mainly during the summer months. National health authorities determined that only bacteriologically confirmed cases of cholera would be reported in the country. As a consequence, hospital laboratories performed an essential role in diagnosing cases of cholera. Contrary to the serotype prevalent in the rest of the Latin American region, Ogawa was the most prevalent serotype (91.8 percent) in Argentina, and 99.2 percent of the isolates pro-

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections duced CT, as determined by enzyme-linked immunosorbent assay (ELISA). During the second and third outbreaks, only 24 (1.7 percent) isolates presented with resistance to antibiotics. Among these isolates, seven were resistant to tetracycline. In addition, five isolates presented with unusual multidrug resistance, accompanied by ß-lactamase activity against broad-spectrum (third-generation) cephalosporins. Hemolytic-Uremic Syndrome Hemolytic-uremic syndrome (HUS) is an endemic disease that affects children younger than 5 years but that most frequently affects children between the ages of 6 and 36 months. Cases mainly occur during the warm season and include eutrophic children, children with good nutrition, and those living under good hygienic conditions. In many of the affected infants, the diarrhea that occurs during the prodromal period is the first diarrhea of their lifetimes. Reporting of HUS was made mandatory in 1999. Age- and gender-specific incidence and prevalence rates are estimated according to data reported by hospital-based centers of nephrology to the Nephrology Commission of the Argentine Pediatric Society. In 1998, the total number of reported cases was 227. The incidence rate was 6.8 per 100,000 children younger than 5 years, with a 2 percent mortality rate. More than 6,000 cases have been reported in Argentina since 1963. The central and southern provinces have the highest incidence rates. The mortality rate decreased from 15 percent in 1965 to 2 percent in 1998 as a consequence of early specific diagnosis, knowledge of disease physiopathology, and therapeutic measures, such as the implementation of peritoneal dialysis for severe forms of HUS with oliguria and anuria (Rivas et al., 1994). Bacterial Antibiotic Resistance In Argentina the rate of penicillin resistance of respiratory system pathogens, such as Streptococcus pneumoniae (24 percent) and Haemophilus influenzae (15 percent), is, on average, similar to that observed in Europe and other countries in the Americas. However, for some enteropathogens, like Salmonella or Shigella, an alarming proportion of isolates are resistant to first-line drugs. This phenomenon has not been observed in other regions. Outbreaks of nosocomial infections of multidrug-resistant Salmonella have been reported for more than 7 years, particularly in hospitals located along the northeastern rivers in the provinces of Buenos Aires, Entre Rios, Corrientes, Santa Fe, and Misiones. All isolates produce an extended spectrum ß-lactamase and the CTX-M2, as well as aminoglycoside acetyltransferase AAC(3)II and AAC(6)I enzymes which inactivate aminoglycosides. The corresponding genes are located in a conjugate plasmid of high molecular weight. These resistant

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections genes were also detected in Vibrio cholerae isolates during the second and sixth cholera outbreaks. In general, in Argentina the proportions of gram-negative bacilli resistant to ß-lactam antibiotics (40 to 60 percent), aminoglycosides (4 to 32 percent), or trimethoprim-sulfamethoxazole (45 to 62 percent) are three times higher than those observed in developed countries (Rossi et al., 1999). The new cephalosporins and aminoglycosides are first-line drugs for the treatment of severe infections. The most efficient resistance mechanism involves the production of extended-spectrum ß-lactamase-inactivating enzymes and enzymes that modify aminoglycosides. In Argentina a national reference laboratory (Rossi et al., 1999) is in charge of coordinating the network of 200 countrywide laboratories and is part of the World Health Organization (WHO) international program of antimicrobial resistance surveillance (WHONET). It is necessary, therefore, to provide training on standardized methods for sensitivity studies, design quality control programs for microbiological diagnosis, and to develop national reference laboratories to verify, characterize, and be alert to the development of new resistance mechanisms. Multidrug Tuberculosis Resistance The Argentine National Tuberculosis Control Program reported 12,205 cases of TB in 1998 (400 cases fewer than in 1997). The decrease in the number of reported cases reflected a 5 percent reduction in the morbidity rate, from 35.5 per 100,000 population in 1997 to 33.8 per 100,000 population in 1998. The incidence of TB decreased by 18 percent relative to that in 1993. In 1998, the program was notified by 1,700 fewer cases than the number in 1993. The case notification rate in Argentina was 33.9 per 100,000 in 1998. All 650 laboratories of the TB diagnostic network use bacilloscopy. Isolation through culture is performed in approximately 100 laboratories; 18 perform sensitivity tests and identification by biochemical tests. Two national laboratories characterize isolates by biochemical procedures and hybridization. The National Tuberculosis Control Program surveys the magnitude and characteristics of Mycobacterium tuberculosis resistance to antibiotics; the last trial was conducted in 1994. Initial resistance trends for TB unrelated to AIDS have not changed since 1968. However, acquired resistance trends have increased, especially in recent years, because of multidrug resistance (simultaneous resistance to at least isoniazid and rifampcin). Nevertheless, resistance levels are not yet alarming. Furthermore, to improve cure rates and block the transmission chain, the rate of directly observed therapy (short course) was 95 percent in 1999, whereas it was 74 percent in 1996. In Argentina, a close relationship has been observed between multidrug-resistant TB outbreaks, HIV infection, and hospitalization in infectious disease hospitals located in big cities (e.g., Buenos Aires and Rosario). However, a seri-

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections ous increase in the rate of multidrug-resistant TB was also observed in patients without evidence of HIV infection who had a history of TB treatment. Hantavirus Pulmonary Syndrome Hemorrhagic fever with renal distress (HFRS), geographically restricted to Asia and Europe, was until 1993 the only disease known to be caused by hantaviruses. In 1993, a new clinical entity emerged in the United States—hantavirus pulmonary syndrome (HPS)—characterized by severe acute respiratory distress. Its etiologic agent was identified as a new hantavirus, Sin Nombre virus. HPS is a viral zoonosis transmitted to humans by inhalation of the excreta of infected rodents. In Argentina, infection of wild and laboratory rodents as well as subclinical human infections were reported between 1983 and 1985. Clinical cases presenting as both HFRS and HPS were retrospectively diagnosed between 1987 and 1996. In March 1995, the first case of a familial outbreak of HPS was reported in El Bolsón, in southern Argentina. As of December 15, 1996, a total of 77 cases of HPS has been reported (with a 48 percent fatality rate) in the southern, northern, and central regions of Argentina. During this outbreak, data suggested for the first time the possibility of person-to-person transmission (Enria et al., 1996, Wells et al., 1997). A retrospective case-control study carried out to identify risk factors associated with HPS showed that people who have had physical contact with an HPS patient or his or her bodily fluids and who shared a room with a patient with HPS were at increased risk of acquiring the disease. Person-to-person transmission was evaluated by comparing the viral sequence homologies of viruses from 16 epidemiologically linked patients with HPS (nosocomial or household contacts) (Padula et al., 1998). As of November 1999, 255 accumulated cases of HPS had occurred in Argentina. Dengue Several cases of dengue were reported in northern Argentina between 1905 and 1911. In 1916, an outbreak of 15,000 clinically diagnosed cases was reported in eastern Argentina. In 1955, the vector mosquito Aedes aegypti covered 15 million square kilometers (5.8 million square miles), reaching the city of Buenos Aires. By 1963, Ae. aegypti was considered eradicated, but 12 cases of dengue were confirmed between April and October 1997, the first occurrence since 1916. At present, Ae. aegypti occupies the same distribution range as it did in 1955—including the city of Buenos Aires—according to data collected by the

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections Table 2-1 Health Component of Bilateral Trade Agreements, Argentina, 1980–1999 Health Agreement Argentine Law Number, Date Subject Protocol Bolivia-Argentina (ARBOL) 22.253, July 16,1980 Transmissible diseases in border zone, epidemic outbreaks Cholera, malaria, Chagas' disease, dengue, hemorrhagic fever Paraguay-Argentina 23.435, July 28, 1986 Transmissible diseases in border zone Same as ARBOL plus health control of migrant population Uruguay-Argentina 24.116, August 5, 1992 Transmissible diseases in border zone, medical technology Same as ARBOL, plus HIV/AIDS, emerging infectious diseases, joint epidemiological surveillance Paraguay-Argentina 24.836, July 27, 1996 Transmissible diseases in border zone, nutrition, environmental engineering, local development Joint surveillance in border zone, emerging infections, Chagas' disease Chile-Argentina 25.130, August 4, 1999 Promotion, protection, exchange of technology, health in border zone Information about emerging infections in border zones, network of scientific and technical information SOURCE: Oscar González Carrizo, Dirección de Relaciones Internacionales, MSAS, Argentine Ministry of Health. In preparation for the future, the Ministry of Health is strengthening entomological actions through community-based control programs. Laboratories are building a network for the diagnosis of dengue infections by MAC ELISA. In 1998, a dengue outbreak occurred in the province of Salta (Aviles et al., 1999). In total, 644 cases of dengue (58 percent, affecting 10 localities between January 3 and May 31, 1998) were detected by laboratory-based diagnostic methods. Dengue serotype 2 virus was isolated and was implicated in the outbreak. Clinically, all cases corresponded to classical dengue. This is the first time that a dengue outbreak was diagnosed by laboratory-based means in Argentina and also the first time that dengue virus was isolated in the country.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections Bilateral and Multilateral Agreements Bilateral and multilateral (Mercosur) trade agreements signed between Argentina and neighboring countries (Bolivia, Brazil, Chile, Paraguay, and Uruguay) have included a health protection component (Table 2-1). Since the 1970s, emphasis has been given to health in the borders zones and internationally agreed upon quality and safety standards. The goal is to promote the participation of the health sector in international trade agreements that may affect human, animal, or plant health from an early stage of the negotiation process. Current objectives are: (1) improve the three components of the surveillance system, especially the efficacy of surveillance at sites distant from the most populated districts, including the border zones; (2) upgrade the infrastructure and qualification of human resources; and (3) permit rapid intra- and inter-country communications on health issues, including outbreaks. DIAGNOSIS, EPIDEMIOLOGICAL SURVEILLANCE, AND CONTROL PROGRAMS FOR EMERGING AND RE-EMERGING INFECTIOUS DISEASES IN MEXICO Ana Flisser, D.Sc.* Director, Instituto Nacional de Diagnóstico y Referencia Epidemiológicos (INDRE) Secretaria de Salud (SSA), Colonia Santo Tomas, Mexico Transitions in disease epidemiology are the result of the social transformation of a developing country such as Mexico and the forces that give rise to new health risks. These risks include both nontransmissible diseases and transmissible diseases. However, it is the spectrum of transmissible diseases that is changing rapidly in conjunction with changes in society and the environment. These diseases are considered either emerging or reemerging infections, and epidemiological and laboratory surveillance for these types of infections are at the center of Mexico's disease control efforts. For this purpose, the Secretary of Health (SSA) in Mexico has established a Coordination of Epidemiological Surveillance activity through the National Institute of Epidemiological Diagnosis and Reference (INDRE), the National Public Health Laboratory, the Directorate of Epidemiology, and several disease control programs. This section presents the *The author gratefully acknowledges the personnel from the National Institute of Epidemiological Diagnosis and Reference, the National Network of Public Health Laboratories, the Coordination of Epidemiological Surveillance, the Directorate of Epidemiology, and the AIDS National Council for the information provided in preparing the manuscript. Special thanks are given to Alejandro Escobar for critical comments on the manuscript.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections current state of surveillance for the most important emerging and reemerging infectious diseases in Mexico. Dengue Dengue has become an epidemiological priority in Mexico, and the etiological detection of dengue virus is mandatory. Figure 2-1 shows the number of samples that INDRE has analyzed for dengue in the last 4 years. The rate of positivity for dengue virus-specific antibody has been approximately 40 percent in all years, suggesting that clinicians have an adequate case definition of dengue, especially since dengue symptomatology can be pleomorphic. As shown in Figure 2-1, the number of samples analyzed by INDRE has decreased because samples are increasingly also processed by the National Network of Public Health Laboratories (NNPHL). However, reference procedures for dengue virus serotype identification performed by cell culture or polymerase chain reaction (PCR) are performed only at INDRE. These specialized assays have detected an important increase in serotype 3 dengue virus (Figure 2-2), suggesting that the Mexican population is susceptible to this virus serotype. PCR is performed preferentially for hemorrhagic cases to provide the result in less than 48 hours. Many samples submitted for viral identification from patients with suspected dengue virus infection are negative. These may be false-negative results because of the short period of time during which virions can be detected in serum and also the presence of other, not considered, etiologies of the disease. During 1996 and 1997, analysis by PCR gave higher rates of positivity than the rates obtained by cell culture, whereas during 1997 and 1998 the two assays had similar rates of positivity. Early on, only samples from patients with well-characterized hemorrhagic cases of dengue virus infection were subjected to PCR to ensure adequate performance of the technique. Later on, samples from patients with a less stringent definition of dengue virus infection were accepted for stronger support of the infectious epidemiology. Leptospirosis Leptospirosis has been documented in Mexico for more than 20 years, according to serological studies. Evaluation for leptospirosis is the first option in the differential diagnosis of dengue. In 1998, 8 percent of samples negative for dengue virus had antibodies to Leptospira. Different serological variants (serovars) are associated with exposure to different animals. For example, abattoir workers who handle pigs are more likely to have antibodies to the pomona serovar, whereas dog owners have antibodies to the canicol serovar.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections Tuberculosis In contrast to dengue, the incidence of TB in Mexico is stable, although multidrug-resistant Mycobacterium tuberculosis strains are emerging. Laboratory studies for the diagnosis of TB are performed in 637 laboratories belonging to the NNPHL. An evaluation of these laboratories revealed that the microscopes in one-third of the laboratories were in need of repair, one-quarter of the laboratories did not have sufficient reagents, and across the laboratories half the personnel needed training. Of the 32 states that make up the Republic of Mexico, 7 do not have the proper facilites and equipment (e.g., safety cabinets or centrifuges with aerosol containment lids) to culture mycobacteria. In response to the laboratory inspection, microscopes were repaired and more than 350 microscopists attended INDRE for a 3-day update course. In addition, laboratories acquired the needed reagents and, in collaboration with the Centers for Disease Control and Prevention (CDC), conducted proficiency tests for external quality control. Also in collaboration with CDC, a M. tuberculosis drug resistance study conducted in three states shows that the proportion of isolates with acquired resistance to isoniazid and rifampin is within the expected limits (22.4 percent), but the proportion of isolates with primary resistance is very high (2.4 percent for both drugs). After improved laboratory quality control and surveillance, it was found that 61 percent of TB cases are located in 160 municipalities. A directly observed supervised therapy program has recently been organized in these municipalities. HIV/AIDS Since 1996, the number of new cases of HIV/AIDS has peaked at about 4,000 per year in Mexico. The prevalence is highest among homosexual and bisexual men, male sex workers, and intravenous drug users. The prevalence has decreased remarkably among those who receive blood transfusions. Coordinated efforts have been made in recent years to distribute reliable screening kits for antibody detection to blood banks and NNPHL. In addition, intensive information and education campaigns are under way, including a recently published edition for clinicians that contains guidelines on the diagnosis, management, and treatment of patients with HIV/AIDS. Specialized medical services for patient management were recently established in most Mexican states. An independent component of the SSA, called FONSIDA, has been established to provide antiretroviral treatment for infected persons who cannot afford it through specialized medical services. FONSIDA began by treating children and pregnant women and has recently included other groups of adults. INDRE and the National Institute of Nutrition are responsible for performing tests to determine viral load and have standardized the assays for viral load determination.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections Other Emerging and Reemerging Diseases Cholera reemerged in Mexico in 1991 and was characterized by a steep increase in the number of cases, reaching 16,430 cases in 1995. The incidence of cholera has markedly declined since then, and few cases are now reported. This may be a consequence of the intensive control measures that have been implemented, but the precise reason for the impressive reduction in the number of cases of cholera is not known. Rotavirus infection has been detected more frequently in children younger than 3 years, mainly in the winter. The most common serotypes circulating are G1, G2 and G3, P1, and P2, with mixtures of serotypes being found. Chagas' disease (the causative agent for which is Trypanosoma cruzi), previously considered rare in Mexico, has been associated with blood transfusion, with rates of occurrence above 1.4 percent in some states. It is now mandatory for blood banks throughout Mexico to search for antibodies to T. cruzi, in addition to antibodies to HIV and hepatitis viruses, in blood from donors. Studies performed in Mexico and elsewhere have shown that an individual infected with the intestinal adult tapeworm (Taenia solium) is the main risk factor for neurocysticercosis among household occupants. This disease has been a public health problem for many years in developing countries and is now considered an emerging infectious disease in some developed countries such as the United States. With the aid of modern diagnostic assays and by asking patients if tapeworm segments are seen in feces or if there are cases of late-onset epilepsy in the family, it is possible to identify tapeworm carriers and provide them with successful treatment. This approach is being tested in two political jurisdictions of two Mexican states (a population of more than one million) by educating all physicians who provide primary care in health centers through social service activities. Surveillance in Response to Natural Disasters Mexico has instituted a special surveillance program in response to natural disasters. In recent years, earthquakes and extreme climate events, such as heavy rainfalls, hurricanes, and flooding in several states, have created the need to establish field laboratory facilities in affected communities for the diagnosis of dengue, leptospirosis, enterobacterial infection, and cholera. The program also provides reagents, training, and quality control activities. In 1998 this surveillance program analyzed more than 38,000 blood, fecal and environmental samples from seven states for leptospirosis, dengue, malaria, cholera, and entero-bacteria. The prevalences of the first three diseases by laboratory diagnosis were 14, 5, and 3 percent, respectively. Among the 6,859 fecal samples collected, 87 were positive, 3 contained Vibrio cholerae O1, 24 contained V. cholerae non-O1, 5 contained Salmonella, 1 contained Shigella, and 54 harbored Escherichia coli. Of 8,642 environmental samples assayed, 380 contained V. cholerae non-O1.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections After natural disasters, large-scale entomological studies on the malaria and dengue vectors are performed before and after chemical control efforts. These studies help define the impact that the control measures have on the mosquito populations and disease transmission. The results from those studies are used to support disease control decision making by field health brigades that remain in the disaster areas as long as they are needed. Seven thousand localities with approximately 850,000 homes were surveyed in 1999, and more than 600,000 medical appointments were provided. In summary, SSA has made an intensive effort to diagnose, survey, and control emerging and reemerging diseases in Mexico. It is hoped that other countries can learn from the Mexican experience with combating the threats from emerging and reemerging infections in their efforts to help better understand these diseases and to prevent and mitigate their impacts. RESPONSE OF THE PAN AMERICAN HEALTH ORGANIZATION TO COMBATING EMERGING INFECTIOUS DISEASES IN LATIN AMERICA AND THE CARIBBEAN Francisco Pinheiro, M.D. Advisor on Viral Diseases, Program for Communicable Diseases Pan American Health Organization, Washington, D.C. In the Americas, a complex array of factors has contributed to the recognition of an increasing number of emerging, and reemerging infectious diseases. The problem is marked by the appearance of new pathogens causing disease of marked severity, such as HIV, arenaviruses, and hantaviruses. Simultaneously, old pathogens—such as those that cause cholera, plague, dengue hemorrhagic fever, and yellow fever—have reemerged and are having a considerable impact in the Americas. Microorganism mutations that lead to drug-resistant and multidrug-resistant strains of Mycobacterium tuberculosis, enterobacteria, staphylococci, pneumococci, malarial parasites, and other agents have been occurring and are becoming major obstacles to the control of these infections. In response to this alarming trend, in June 1995 PAHO convened a meeting of international experts to discuss strategies for the prevention and control of emerging infectious diseases. As a result of this meeting, a regional plan of action was prepared to develop regional and subregional approaches and to guide member states in addressing specific problems. The regional plan has four goals: (1) strengthening regional surveillance networks for infectious diseases in the Americas; (2) establishing national and regional infrastructures to provide an early warning of and a rapid response to infectious disease threats through multidisciplinary training programs and laboratory enhancement; (3) promoting the further development of applied research in the areas of diagnosis, epidemiology,

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections prevention, and clinical studies; and (4) strengthening the regional capacity for effective implementation of prevention and control strategies. Subsequently, PAHO has implemented activities in accordance with the regional plan, taking into consideration priorities that have been reviewed since 1996 on an annual basis by PAHO's Task Force on Surveillance for Emerging and Reemerging Diseases. Efforts are under way to establish networks for the surveillance of emerging infectious diseases in nine countries of the Amazon Region and the Southern Cone Region. A plan of action was developed for each region in collaboration with international reference centers, including CDC, the University of Texas Medical Branch at Galveston, and the U.S. Army Medical Research Institute of Infectious Diseases. The network should be able to perform active surveillance on the basis of a syndromic approach. Five disease syndromes were selected for both regions, and two additional ones were recommended for the Southern Cone Region. The five syndromes are undifferentiated febrile syndrome, hemorrhagic fever, febrile icteric syndrome, acute respiratory distress syndrome, and sudden unexplained death. In view of growing evidence of an alarming increase in the rate of antimicrobial drug resistance in the Americas and other parts of the world, strengthening of surveillance of the antimicrobial resistance of selected enteropathogens, mainly to monitor the patterns of resistance of salmonellae, shigellae, and Vibrio cholerae, has been implemented for the past 3 years in 15 countries of Latin America and the Caribbean in collaboration with the Laboratory Centers for Disease Control in Canada. The goals of this project include strengthening diarrheal disease surveillance, improving national laboratory capabilities, standardizing methodologies for diagnosis, establishing a network of national reference laboratories, and creating databases of emerging antibiotic-resistant organisms. Since 1996, five workshops have been conducted on subjects such as laboratory and epidemiology relationships, diagnostic methods, antiserum production, data analysis, proficiency testing, and external quality assurance. In addition, a project addressing the basis for the prevention and control of antibiotic resistance in the Americas has been proposed by PAHO. The objectives of this project are (1) to decrease the incidence and spread of antimicrobial resistance and, consequently, improve the treatment of infectious diseases, and (2) to provide for more effective delivery of interventions for the control and prevention of antimicrobial resistance. A project to strengthen a regional system for epidemiological surveillance is under way. The PAHO strategy used to achieve this has been to focus on (1) improved national surveillance, (2) the development of a regional electronic platform to collect and communicate surveillance data, (3) training in outbreak detection and response, and (4) surveillance of antimicrobial resistance. Several activities are being implemented, including training workshops to improve the system.