Working Together to Address Human Health and Food Safety Concerns

1. Working Together to Address Human Health and Food Safety Concerns Miguel A. Escobedo, MD, MPH Medical Officer El Paso CDC Quarantine Station

2. Presentation Overview Review examples of Infectious diseases related to environmental health in the US Mexico Border region Discuss relevance to security issues Economic impact Human health and potential for bioterrorism What actions can public health/CDC take o address food safety Research, information sharing Discuss public health impact and economic impact

3. Border Infectious Diseases related to the environment Food borne Hepatitis A, Hepatitis E Salmonella Listeria, Brucellois Mycobacterium bovis Vector borne Dengue and West Nile Virus Zoonotic Pandemic & Avian Influenza Rabies Parasitic Cystocircosis Giardiasis and Amebiasis

4. Cross-Border Infectious Disease Principles Disease agents do not respect borders US-MX border is one community for Public Health Purposes Extensive economic, family, socio-cultural ties Approximately 1.2 million daily border crossings in to U.S. Certain foods can only be acquired in Mexico US and MX have unique food safety systems in place We never point the finger at the other side

5. Pandemic / Avian Influenza Three players Seasonal influenza, yearly world wide outbreaks Avian Influenza due to HP H5N1 is global concern with a huge economic impact Pandemic Human Influenza is a global threat with enormous human health and security concerns. The Security and Prosperity Partnership Agreement for North America has focuses on joint pandemic influenza preparedness.

6. Very importantly, preparedness and understanding of each is needed to enhance preparedness and understanding of all forms of influenza. A recurring theme in this training will be that a strong seasonal influenza surveillance and response system will serve the purposes of pandemic preparedness, and vice-versa.Very importantly, preparedness and understanding of each is needed to enhance preparedness and understanding of all forms of influenza. A recurring theme in this training will be that a strong seasonal influenza surveillance and response system will serve the purposes of pandemic preparedness, and vice-versa.

7. Avian Influenza Type A influenza Endemic in birds H5, H7 subtypes can cause serious disease or death in wild birds; often cause death in poultry Virus in saliva and feces of wild birds and poultry can be directly transmitted to humans and other animals Can contaminate clothing, equipment, water, feed Currently, scientists believe that a pandemic strain of influenza is most likely to develop from an avian Influenza type A virus, such as the H5N1 strain that is currently circulating in birds through much of the world. Avian Influenza A viruses differ from human Influenza A viruses in several respects. All type A viruses can infect birds and many do infect birds without causing any disease. However, certain subtypes (H5 and H7) are deadly to many species of birds�especially domestic poultry. Infected birds excrete large amounts of virus in respiratory secretions, saliva, and feces. Avian viruses may be transmitted to humans and other animals through contact with respiratory secretions and feces. These viruses may survive at low temperatures, at low humidity, and in water for days to weeks. Other modes of transmission including contamination of clothing, farm equipment, water, and feed are possible. Currently, scientists believe that a pandemic strain of influenza is most likely to develop from an avian Influenza type A virus, such as the H5N1 strain that is currently circulating in birds through much of the world. Avian Influenza A viruses differ from human Influenza A viruses in several respects. All type A viruses can infect birds and many do infect birds without causing any disease. However, certain subtypes (H5 and H7) are deadly to many species of birds�especially domestic poultry. Infected birds excrete large amounts of virus in respiratory secretions, saliva, and feces. Avian viruses may be transmitted to humans and other animals through contact with respiratory secretions and feces. These viruses may survive at low temperatures, at low humidity, and in water for days to weeks. Other modes of transmission including contamination of clothing, farm equipment, water, and feed are possible.

8. H5N1 Possible Travel Routes Legal poultry business Illegal bird trade Untreated fertilizer Migrating birds Humans (contaminated objects) There are many suggested theories for how the avian influenza H5N1 virus can spread throughout the world. Both the legal and the illegal poultry trade may contribute to the spread by the movement of poultry and other birds sick with avian influenza H5N1 across borders. The widespread use of untreated poultry feces as a fertilizer is another possible risk factor. Migrating birds also appear to be a means of virus spread since ducks and other migratory fowl can be infected without illness. Humans may also play a direct role in the movement of avian influenza H5N1 virus through contamination on clothes or farm equipment. There are many suggested theories for how the avian influenza H5N1 virus can spread throughout the world. Both the legal and the illegal poultry trade may contribute to the spread by the movement of poultry and other birds sick with avian influenza H5N1 across borders. The widespread use of untreated poultry feces as a fertilizer is another possible risk factor. Migrating birds also appear to be a means of virus spread since ducks and other migratory fowl can be infected without illness. Humans may also play a direct role in the movement of avian influenza H5N1 virus through contamination on clothes or farm equipment.

9. Cause for Concern Avian influenza can have a large impact on poultry Can cause high mortality Significant economic impact Rarely, avian influenza can cause illness in humans Avian influenza viruses can serve as source of next pandemic strain In the past few years, increased attention has been paid by public health officials and the media to avian influenza. Avian influenza can have a large impact on poultry and can cause high mortality in poultry flocks producing significant economic impact and loss of a valuable food source. Rarely, avian influenza can cause illness in humans and because of this, avian influenza viruses could serve as a source of next pandemic influenza strain. In the past few years, increased attention has been paid by public health officials and the media to avian influenza. Avian influenza can have a large impact on poultry and can cause high mortality in poultry flocks producing significant economic impact and loss of a valuable food source. Rarely, avian influenza can cause illness in humans and because of this, avian influenza viruses could serve as a source of next pandemic influenza strain.

10. H5N1 Avian Influenza Currently spreading through Asia, Africa, Europe, Middle East Can be highly lethal to domestic poultry and other animal species Virus of greatest concern for pandemic potential, but other viruses in animals also of concern\ Humans can become infected with avian influenza viruses Usually through exposure to infected domestic poultry that have become infected with wild bird avian viruses Avian influenza A (H5N1) is currently spreading through Asia, Africa, Europe, Middle East. More will be discussed on the nomenclature �H5N1� later in this module. Avian influenza A (H5N1) can be highly lethal to domestic poultry and other animal species and produces occasional human cases but no efficient human to human transmission. While this is the virus that is of greatest concern for pandemic potential, there are other viruses in animals that are also of concern. Avian influenza A (H5N1) is currently spreading through Asia, Africa, Europe, Middle East. More will be discussed on the nomenclature �H5N1� later in this module. Avian influenza A (H5N1) can be highly lethal to domestic poultry and other animal species and produces occasional human cases but no efficient human to human transmission. While this is the virus that is of greatest concern for pandemic potential, there are other viruses in animals that are also of concern.

11. Clinical illness with H5N1 compared with typical human influenza illness More severe illness in younger persons Primary viral pneumonia appears to be more common and with rapid onset Incubation period may be longer Duration of infectious period likely longer, particularly among adults In comparison with seasonal influenza, human infection with avian influenza A (H5N1) results in more severe illness in younger persons. Primary viral pneumonia appears to be more common and with rapid onset. The incubation period may be longer and the duration of the infectious period likely longer, particularly among adults. In comparison with seasonal influenza, human infection with avian influenza A (H5N1) results in more severe illness in younger persons. Primary viral pneumonia appears to be more common and with rapid onset. The incubation period may be longer and the duration of the infectious period likely longer, particularly among adults.

12. Queso Fresco and Salmonella on the California/Mexico Border I�ll present two binational outbreak investigations which conformed reasonably closely to the US Mexico Guidelines. The first is an outbreak of Salmonella typhimurium associated with queso fresco in Imperial County and Mexicali. Good morning. I�ll be speaking about queso fresco, which translates fresh cheese in Spanish, that is Mexican style cheese which is frequently consumed unpasteurized, and its associated infectious disease health risks focusing on two recent Salmonella outbreaks in the California border Latino population. I�ll present two binational outbreak investigations which conformed reasonably closely to the US Mexico Guidelines. The first is an outbreak of Salmonella typhimurium associated with queso fresco in Imperial County and Mexicali. Good morning. I�ll be speaking about queso fresco, which translates fresh cheese in Spanish, that is Mexican style cheese which is frequently consumed unpasteurized, and its associated infectious disease health risks focusing on two recent Salmonella outbreaks in the California border Latino population.

13. �Queso Fresco� Associated Diseases Salmonella S. Typhimurium DT 104 Yakima, Washington, 1999 S. Typhimurium San Diego 2004 S. Typhimurium Imperial County 2005 Brucellosis Highest rates in Hispanics US Mexico border counties relative risk > 8 Listeria Los Angeles 1985 North Carolina 2000 Texas 2003 Emerging Infections Food Net surveillance � higher rates in Hispanic infants M. bovis New York City outbreak 2001-2004 San Diego County A series of outbreaks cause by a variety of organisms associated with consumption of raw Mexican style cheese or queso fresco have been reported. All of these organisms, salmonella, brucellosis, listeria, and Mycobacterium bovis are associated with cattle or goats. I�ll speak later on the outbreak of salmonella in Imperial County. Brucellosis is another sometimes difficult to diagnose serious systemic infection often causing hospitalizations. Listeria monocytogenes infections are associated with high rates of hospitalization and death. Perinatal listeria infection can cause spontaneous abortion, premature delivery and neonatal infection. New York City detected 35 cases (97% Hispanic) of M. bovis between 2001 and 2004 including a fatal case in a 15 month old. 10% of Mexican born TB cases in NYC are due to M. bovis, and a similar proportion of San Diego County�s TB cases are due to M. bovis. I�d like to start my presentation by giving an overview of queso fresco cheese associated disease morbidity among Latinos not only on the US Mexico border but also among Latino immigrants throughout the US. Raw Mexican cheese has been connected to outbreaks and sporadic infections among Latinos in the US from a number of etiologic agents in recent years. In addition to the two outbreaks I�ll be presenting, a Salmonella typhimurium outbreak with a virulent strain was documented in Washington state in 1999. In a review of national notifiable disease surveillance data in the 1990�s, brucellosis rates in US border counties were over 8 times higher than rates in non-border states. (The Mexican state of Baja California experienced in 1995 an outbreak involving about 500 cases of Brucella melitensis infections associated with consumption unpasteurized goat milk and cheese.) A notorious outbreak of perinatal listeria took place in Los Angeles in 1985. This outbreak raised awareness in the US of listeria as a foodborne disease associated with Mexican style cheese. The vehicle in Los Angeles was a contaminated commercial product made in Los Angeles County. An outbreak of listeria among Latinos in North Carolina in 2000 was traced to local production of queso fresco from unpasteurized milk. A smaller similar outbreak was picked up by Pulsenet molecular epidemiology testing in Texas in 2003. While the incidence of perinatal listeriosis declined from 104 to 29 per 100,000 from 1996-2003, higher rates of listeria persist among Hispanic infants in CDC Emerging Infection Program surveillance data. San Diego County has consistently found that about 7% of its TB cases (roughly 20 cases/year) are due to M. bovis and not M. TB. M. bovis in Latinos in the US is ultimately related to imperfect control of M. bovis in Mexican cattle populationsA series of outbreaks cause by a variety of organisms associated with consumption of raw Mexican style cheese or queso fresco have been reported. All of these organisms, salmonella, brucellosis, listeria, and Mycobacterium bovis are associated with cattle or goats. I�ll speak later on the outbreak of salmonella in Imperial County. Brucellosis is another sometimes difficult to diagnose serious systemic infection often causing hospitalizations. Listeria monocytogenes infections are associated with high rates of hospitalization and death. Perinatal listeria infection can cause spontaneous abortion, premature delivery and neonatal infection. New York City detected 35 cases (97% Hispanic) of M. bovis between 2001 and 2004 including a fatal case in a 15 month old. 10% of Mexican born TB cases in NYC are due to M. bovis, and a similar proportion of San Diego County�s TB cases are due to M. bovis. I�d like to start my presentation by giving an overview of queso fresco cheese associated disease morbidity among Latinos not only on the US Mexico border but also among Latino immigrants throughout the US. Raw Mexican cheese has been connected to outbreaks and sporadic infections among Latinos in the US from a number of etiologic agents in recent years. In addition to the two outbreaks I�ll be presenting, a Salmonella typhimurium outbreak with a virulent strain was documented in Washington state in 1999. In a review of national notifiable disease surveillance data in the 1990�s, brucellosis rates in US border counties were over 8 times higher than rates in non-border states. (The Mexican state of Baja California experienced in 1995 an outbreak involving about 500 cases of Brucella melitensis infections associated with consumption unpasteurized goat milk and cheese.) A notorious outbreak of perinatal listeria took place in Los Angeles in 1985. This outbreak raised awareness in the US of listeria as a foodborne disease associated with Mexican style cheese. The vehicle in Los Angeles was a contaminated commercial product made in Los Angeles County. An outbreak of listeria among Latinos in North Carolina in 2000 was traced to local production of queso fresco from unpasteurized milk. A smaller similar outbreak was picked up by Pulsenet molecular epidemiology testing in Texas in 2003. While the incidence of perinatal listeriosis declined from 104 to 29 per 100,000 from 1996-2003, higher rates of listeria persist among Hispanic infants in CDC Emerging Infection Program surveillance data. San Diego County has consistently found that about 7% of its TB cases (roughly 20 cases/year) are due to M. bovis and not M. TB. M. bovis in Latinos in the US is ultimately related to imperfect control of M. bovis in Mexican cattle populations

14. Epidemiologic Investigation Imperial County 43 cases of gastrointestinal illness identified with onset dates during August 12--October 19, 2005. 21 Imperial County residents met confirmed case definition. 22 met the suspect case definition (epidemiologically linked). Imperial County, the CA county bordering Mexico immediately to the east of San Diego, identified an outbreak of gastrointestinal illness with 21 positive cultures for Salmonella typhi in late summer 2005. The culture confirmed cases had a new characteristic Pulse Field Gel Electrophoresis (PFGE) pattern. An additional 22 suspect cases had gastrointestinal illness during Aug-October and were epidemiologically linked to the culture positive cases. Confirmed case = person with culture-confirmed ST with a pulsed field gel electrophoresis (PFGE) pattern matching outbreak pattern by at least one enzyme, and GI onset between Aug-Oct 2005, and hx or QF consumption prior to illness. Suspect case = person with GI with onset between Aug 12 and Oct 19, 2005, and hx of QF consumption one week prior to illness onset. Imperial County, the CA county bordering Mexico immediately to the east of San Diego, identified an outbreak of gastrointestinal illness with 21 positive cultures for Salmonella typhi in late summer 2005. The culture confirmed cases had a new characteristic Pulse Field Gel Electrophoresis (PFGE) pattern. An additional 22 suspect cases had gastrointestinal illness during Aug-October and were epidemiologically linked to the culture positive cases. Confirmed case = person with culture-confirmed ST with a pulsed field gel electrophoresis (PFGE) pattern matching outbreak pattern by at least one enzyme, and GI onset between Aug-Oct 2005, and hx or QF consumption prior to illness. Suspect case = person with GI with onset between Aug 12 and Oct 19, 2005, and hx of QF consumption one week prior to illness onset.

15. Imperial County Outbreak: Summary Imperial County cases ranged from 3 � 79 years of age. All were Latino. 14% of cases were hospitalized. The majority of the cases had consumed queso fresco. A case control study was not performed. Imperial County cases ranged from 3 � 79 years of age. All were Latino. 14% of cases were hospitalized. The majority of the cases had consumed queso fresco. A case control study was not performed.

16. Epidemiologic InvestigationImperial County & Mexicali Imperial County became aware that its sister jurisdiction across the border in Mexicali, Baja California�s capital city, was experiencing simultaneously a large outbreak of gastroenteritis associated with purchase of queso fresco from a supermarket. The two jurisdictions worked together to combine their data into this single epidemiologic curve. Imperial County became aware that its sister jurisdiction across the border in Mexicali, Baja California�s capital city, was experiencing simultaneously a large outbreak of gastroenteritis associated with purchase of queso fresco from a supermarket. The two jurisdictions worked together to combine their data into this single epidemiologic curve.

17. This slide is from a simlar outbreak investigation one year before in San Diego County showing street vendors who sold non-commercially packaged cheese often stored inadequately. This slide is from a simlar outbreak investigation one year before in San Diego County showing street vendors who sold non-commercially packaged cheese often stored inadequately.

18. This is a small cheese producing unit which makes pasteured queso fresco in Mexico taken by a California Department of Food and Agriculture veterinarian who works collaboratively with agricultural officials in Mexico. This is a small cheese producing unit which makes pasteured queso fresco in Mexico taken by a California Department of Food and Agriculture veterinarian who works collaboratively with agricultural officials in Mexico.

19. Port of Entry Results 94% (n=203) samples alk phos pos 13% pos for Salmonella species PFGE pattern indistinguishable from San Diego outbreak strain Q2 4% Listeria sp. M. bovis in one sample The next three slides are not part of the Imperial County/Mexicali salmonella typhymurium investigation, but demonstrate the type of work that could be made even more powerful with binational collaboration. A special survey of cheese done at the San Ysidro port of entry revealed that that 95% of the samples were determined to be unpasteurized by alkaline phosphatase testing. 13% were positive for various species of Salmonella including an isolate with the San Diego Q2 PFGE outbreak strain. 4% of samples were positive for Listeria species and one sample was positive for Mycobacterium bovis at FDA�s laboratory. The next three slides are not part of the Imperial County/Mexicali salmonella typhymurium investigation, but demonstrate the type of work that could be made even more powerful with binational collaboration. A special survey of cheese done at the San Ysidro port of entry revealed that that 95% of the samples were determined to be unpasteurized by alkaline phosphatase testing. 13% were positive for various species of Salmonella including an isolate with the San Diego Q2 PFGE outbreak strain. 4% of samples were positive for Listeria species and one sample was positive for Mycobacterium bovis at FDA�s laboratory.

20. 99% received prenatal care for current or most recent pregnancy Only 1 pregnant woman reported that she was told during a prenatal care visit not to eat queso fresco Women Infant Children (WIC) Survey in Los Angeles A survey in Los Angeles federal Woman, Infant, and Children clinics confirmed that queso fresco is a highly popular food item among Latinos, consumed in this survey by 83% of the women. However, most did not know whether the cheese they eat is pasteurized or unpasteurized, and only 1 pregnant woman reported she was told during her prenatal care not to eat queso fresco. A survey in Los Angeles federal Woman, Infant, and Children clinics confirmed that queso fresco is a highly popular food item among Latinos, consumed in this survey by 83% of the women. However, most did not know whether the cheese they eat is pasteurized or unpasteurized, and only 1 pregnant woman reported she was told during her prenatal care not to eat queso fresco.

21. Brochure Provides detailed information Risks of eating queso fresco How to choose safe queso fresco Safe alternatives to queso fresco during pregnancy Spanish/English The California Department of Health Services developed a Spanish brochure based on the feedback from these Latina women to provide information on the risks of queso fresco and how to avoid unsafe unpasteurized cheese. The California Department of Health Services developed a Spanish brochure based on the feedback from these Latina women to provide information on the risks of queso fresco and how to avoid unsafe unpasteurized cheese.

22. Dengue Fever on the Mexico-U.S. Border The second example of a binational outbreak investigation is the dengue fever investigation done in Laredo and Nuevo Laredo in 1999. In 2005, a more serious outbreak of dengue hemorrhagic fever outbreak occurred in the sister cities of Brownsville and Matamoros, also in South Texas. The second example of a binational outbreak investigation is the dengue fever investigation done in Laredo and Nuevo Laredo in 1999. In 2005, a more serious outbreak of dengue hemorrhagic fever outbreak occurred in the sister cities of Brownsville and Matamoros, also in South Texas.

23. Aedes aegypti Primarily a daytime feeder Lives around human habitation Lays eggs and produces larvae in artificial containers Dengue is transmitted by Aedes aegypti mosquitoes. Dengue is transmitted by Aedes aegypti mosquitoes.

24. Aedes aegypti distribution has increased dramatically since the breakdown of once successful mosquito control programs in the Americas. Aedes aegypti distribution has increased dramatically since the breakdown of once successful mosquito control programs in the Americas.

25. Household Survey 622 household surveys 313 in Nuevo Laredo 309 in Laredo 516 blood samples 288 from Nuevo Laredo residents 228 from Laredo residents 622 houses were surveyed over a 2-week period in early September, 313 in Nuevo Laredo and 309 in Laredo, by binational teams. 516 blood samples were obtained, 288 from Nuevo Laredo residents and 228 from Laredo residents.622 houses were surveyed over a 2-week period in early September, 313 in Nuevo Laredo and 309 in Laredo, by binational teams. 516 blood samples were obtained, 288 from Nuevo Laredo residents and 228 from Laredo residents.

26. Seroprevalence Estimates Antibody Mexico(%) U.S.(%) IgM 16.0 1.3 95% CI (0.90-22.2) (0-2.8) IgG 47.8 22.5 95% CI (41.0-54.5) (17.0-28.0) The results of the laboratory analysis reveal the difference in dengue transmission between the two cities. IgM antibodies, indicating exposure to dengue sometime during the last 3 months, were found in 16% of Mexican residents tested, compared to 1.3% of U.S. residents. IgG antibodies, indicating dengue exposure sometime in the past, were found in almost 48% of Mexican residents, compared to 23% of U.S. residents.The results of the laboratory analysis reveal the difference in dengue transmission between the two cities. IgM antibodies, indicating exposure to dengue sometime during the last 3 months, were found in 16% of Mexican residents tested, compared to 1.3% of U.S. residents. IgG antibodies, indicating dengue exposure sometime in the past, were found in almost 48% of Mexican residents, compared to 23% of U.S. residents.

27. Mosquito Larvae Results Mexico U.S. House Index 25% 37% Breteau Index 38 91 Surveying yards and patios for the presence of mosquito larvae revealed that Aedes aegypti larvae were prevalent in both cities. The house index, the percentage of houses examined which had larvae present, was higher in the U.S. than in Mexico. Likewise, the Breteau index, which is the number of containers with larvae in them per 100 houses examined, was also higher in the U.S. than in Mexico. These differences are believed to be due to an intensive clean-up campaign by the Tamaulipas Secretariat of Health in Mexico during the dengue outbreak.Surveying yards and patios for the presence of mosquito larvae revealed that Aedes aegypti larvae were prevalent in both cities. The house index, the percentage of houses examined which had larvae present, was higher in the U.S. than in Mexico. Likewise, the Breteau index, which is the number of containers with larvae in them per 100 houses examined, was also higher in the U.S. than in Mexico. These differences are believed to be due to an intensive clean-up campaign by the Tamaulipas Secretariat of Health in Mexico during the dengue outbreak.

28. WNV Human Cases, US and Mexico 2006

29. Distribution of Coccidioides spp. in U.S. and Mexico

31. Acute Hepatitis A Cases*, by Country and Year, BIDS Project 2000 - 2006

32. Number of Hepatitis A, by age and year in El Paso, TX, 1990-2006

33. Hepatitis A risk factors*, U.S. and Mexico U.S. risk factors Border crossing,** frequency and duration of crossing Contact with a suspected hepatitis case Mexico risk factors Municipal water vs bottled*** *Univariate analysis ** Rel. risk 3.6 (95% C.I., 1.8, 7.2) *** Rel. risk 1.8 (95% C.I., 1.5, 2.3) We compared BIDS patients with positive tests for Hep A IgM with patients that were negative for all serologic viral hepatitis testing. The number of negative controls obtained in this way were 215, 114 from Mexico and 111 from the U.S. Some of these negative controls had other non viral hepatitis diagnoses and some were of unknown etiology. It is possible that a small proportion of the controls were misclassified as viral serologic testing is not 100% sensitive and the timing of the sample can affect results. While this analysis is ongoing we did identify border crossing as a statistically significant risk factor for hepatitis A infection among U.S. patients. This finding was also apparent as a trend when looking at frequency and duration of border crossing. Contact with a suspected hepatitis case was a strong risk factor on the U.S. side but contact was not a statistically significant risk factor for Mexican patients. For Mexican patients, using municipal drinking water compared to bottled water as a main water source was a significant risk factor. Use of municipal water is probably correlated with lower socioeconomic status and so this other risk factor findings need to be corroborated with controlled multivariate analysis. We compared BIDS patients with positive tests for Hep A IgM with patients that were negative for all serologic viral hepatitis testing. The number of negative controls obtained in this way were 215, 114 from Mexico and 111 from the U.S. Some of these negative controls had other non viral hepatitis diagnoses and some were of unknown etiology. It is possible that a small proportion of the controls were misclassified as viral serologic testing is not 100% sensitive and the timing of the sample can affect results. While this analysis is ongoing we did identify border crossing as a statistically significant risk factor for hepatitis A infection among U.S. patients. This finding was also apparent as a trend when looking at frequency and duration of border crossing. Contact with a suspected hepatitis case was a strong risk factor on the U.S. side but contact was not a statistically significant risk factor for Mexican patients. For Mexican patients, using municipal drinking water compared to bottled water as a main water source was a significant risk factor. Use of municipal water is probably correlated with lower socioeconomic status and so this other risk factor findings need to be corroborated with controlled multivariate analysis.

35. Thank you y muchas graciasQuestions?