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Vaccine preventable waterborne diseases—Typhoid fever and Hepatitis A Professor Huma Arshad Cheema Pediatric Gastroenterologist Hepatologist Chairperson PPA GI group
Transmission of Hepatitis A and typhoid  Faeco-oral transmission Ever increasing burden due to declining standards of hygiene Diseases of both rich and poor due to contaminated food handling and poor hand washing
Ah the blessing of clean drinking water
Where do we stand? >1 billion people worldwide don’t have access to safe drinking water Labeled as “the Silent Global Emergency” by WHO & UNICEF in their report of Aug 26, 2004 Estimated that over two third of Pakistanis do not have access to clean drinking  water
Some facts  Ranking 135th on the United Nation’s Human Development Index, Pakistan has a population of approximately 148 million, ranking 7th in the world, of whom half are children.  Infant Mortality stands at 90 per 1,000 live births, and maternal Mortality at 340 per 100,000 live births (median estimates). In terms of health status, Pakistan faces a double burden: a rapidly increasing incidence of non-communicable diseases (NCDs) and injuries, superimposed on endemic communicable diseases (CDs).
Priorities
Forces we are up against
The heavy price of conflict
Price of natural and man made  disasters Natural disasters, conflict, economic crisis and political turmoil have increased the vulnerability of thousands of children. In 2008 and 2009, conflict displaced some 1.6 million children Ongoing conflict in the north-west has displaced some 2 million people since 2008, with most displaced since April 2009. About a tenth of those displaced live in camps for internally displaced people. 
Under-5 mortality rate (probability of dying by age 5 per 1000 live births)  
11 What has been the impact of vaccines on public health? The 2 things man has done to improve health the most: Clean Water Vaccines The impact of vaccines has been tremendous since they were first used in the 1700s.
12 Smallpox
13 Smallpox Vaccine Last case: 1979
14 Polio Last US case: 1979
15 Measles
16 Tetanus
And now this
Where are child death occurring? Eastern Mediterranean 14% Europe 2% Americas  4% Southeast Asia 30% Western Pacific 10% Africa  39% Developing countries: 99% Africa and Asia: 69%
Public Health Priorities
Hepatitis A
Difference between life and death
Some less understood facts about Hepatitis A  Among different parts of the world there is a notable difference in the predominant manifestation of hepatitis A. The clinical presentation of childhood hepatitis A is more severe with poverty and poor sanitation  In less developed regions, HAV is the main etiological agent for pediatric acute liver failure. Many affectedchildren are in the preschool age bracket.    
In Turkey, HAV was the most common identifiable cause of pediatric fulminant hepatic failure, accounting 26% of cases   In India, where the prevalence of HAV infection varies by geography and socio-economic class HAV infection was identified in 40–53% of cases of pediatric acute liver failure among cohorts from New Delhi, West Bengal and southern India
At Children's Hospital lahore 60  % of cases of fulminant hepatic failure were due to Hepatitis A with a mortality of 35%  Morbidity from other complications underestimated 	- prolonged cholestatic syndrome 	- Hemolytic anemia both viral induced and G6PD   	deficiency induced 	- precipitation of autoimmune liver disease  	- Bone marrow aplasia
Combined infections  Co infection with Hepatitis A and S typhi seen increasingly at Children's Co infection of Hepatitis A and E also seen producing more severe illness and prolonged cholestasis
Prevention is the Key Time to understand that the assumption that Hepatitis A is a harmless disease and vaccination is a luxury is false When the difference is between death and a thousand rupees the choice is obvious
Similarities between the epidemiology of Hep A and Polio virus suggesting  widespread vaccination of susceptible populations can substantially lower disease incidence  Eliminate virus transmission Ultimately eradicate HAV
Immunoprophylaxis Inactivated Hep A vaccine 	15 years of marketing experience Highly immunogenic Provides lasting protection in healthy individuals Generates protective levels of antibodies in patients with chronic liver disease or impaired immunity
Vaccine Timing of booster dose not critical to effectiveness but in routine now booster is recommended Effective in curbing outbreaks of hepatitis A After completion of primary dosage antibodies last longer than 10 years and immune memory may last even longer
Post exposure Effective postexposure due to rapid seroconversion and long incubation period Multiple studies show that contacts given vaccine within 14 days have equal or better protection than immunoglobulins Very young children  <  1 yrs may still need immunoglobulins
Where are the people dying from typhoid fever
Typhoid Global Burden Burden probably underestimated Many hospitals lack facilities for blood cultures Up to 90% of patients are treated as outpatients Sporadic disease in developed countries - mainly in returning travelers
Epidemiology of Typhoid Fever World wide Annual incidence of 12.5 M (WHO) Mortality rate: 600,000 deaths every year  more than 90% of morbidity and mortality occurs in Asia.  Incidence in developing countries 100-1000 per 100,000 per year Population-based studies indicate that, contrary to previous views, the age-specific incidence of typhoid may be highest in children <5 yr of age, with comparatively higher rates of complications and hospitalization
Typhoid in Pakistan  	As per a paper presented at the WHO 6th International Conference on Typhoid Fever and Other Salmonellas in 2004 Typhoid is the 4th most common cause of death in Pakistan 9 Source:  9. Richens J. Typhoid fever, Surgery in Africa – Monthly Review; 2006 (World     Health Organization. 6th International Conference on Typhoid Fever and     other Salmonellas. 2006. Geneva, WHO.)
Others (18.2%) S. typhi (42.8%) Strep. spp.  (8.3%%) Staph. epidermis (10.8%) S. paratyphi (8.3%) E.coli (2.7%) Study Results of AKUH Karachi 11 	Hospital-based and other studies have indicated that typhoid fever is a serious problem among children in Pakistan: 	S. typhi found to be most common cause on bacterium among children dying with diarrhea at AKUMC. Spectrum of Paediatric blood culture isolates from AKUMC emergency services
Causative Agent Salmonella typhi Flagellar antigen Capsular polysaccharideantigen (Vi) Somatic antigen
Some Important practical clinical information   Humans are the only natural reservoir of styphi Clinical presentation varies from mild disease to severe with high grade fever ,abdominal discomfort and complications Presentation more severe in infants and older patients  Infants may have diarrhea and abdominal distension along with fever as the main symptom
Some Important practical clinical information  Classic stepladder rise of fever is now rare Severe rigors unusual Hepatomegaly more frequent than splenomegaly Mild Hepatitis with altered liver enzymes very common but frank hepatitis with jaundice rare Bronchitis a frequent accompaniment
Deadly complications  Intestinal Bleed Intestinal perforation  Osteomyelitis
200 years old specimens of intestine from  Hunterian museum of RCSE
Typhoid Perforation and typhoid osteomyelitis
Diagnosis  First week --- and no previous antibiotic given the best yield is from a blood culture After 4 days the Typhidot test also becomes positive  Widal test has notoriously high percentage of false positive and negative---rising titres over the days more diagnostic
Treatment and the implications of Antibiotic ResistanceTHE SUPER BUGS Study of typhoid fever from 5 asian countries gives dismal news on antimicrobial resistance Nearly 60% of the isolates were resistant to chloramphenicol, ampicillin, TMP-SMX and nalidixic acid. In contrast, all isolates from sites in China and Indonesia were susceptible to all antimicrobial agents
THE SUPER BUGS Multidrug resistance (resistance to chloramphenicol, ampicillin and TMP-SMX) was observed in 65% isolates from the site in Pakistan Nalidixic acid resistance was found in 59% isolates from the site in Pakistan,
Disease Burden StudyAntibiotic resistance patterns No resistance against these antibiotics were found from China and Indonesia sites
Treatment of enteric fever Choosing the right empirical therapy is problematic and controversial Increasing incidence of multiresistance to chloramphenicol Ampicillin and TMP- SMX in 49-83% of salmonella typhi is being reported from India  Resistant strains are usually susceptible to third generation cephalosporins Quinolones are not to be used as first line
WHO POSITION PAPER-2008 In view of the continued high burden of typhoid fever and increasing antibiotic resistance, and given the safety, efficacy, feasibility and affordability of licensed vaccines , countries should consider the programmatic use of typhoid vaccines for controlling endemic disease.
WHO POSITION PAPER-2008 	All typhoid fever vaccination programmes should be implemented in the context of other efforts to control the disease, including  Health education, water quality Sanitation improvements,  Training of health professionals in diagnosis and treatment.
Current issues Very high incidence of this infectious and deadly disease in Pakistan Endemic all year round and incidence on the rise Multi drug resistant salmonella becoming a big health issue Significant cost of treatment and hospitalization.
Typhoid dragon can be slain by prevention
Prevention is the key
Public Health Measures Supply of clean, safe drinking water Effective and sanitary disposal of human feces and urine Careful attention to cleanliness and hygiene during food preparation Provision of adequate hand washing facilities wherever food is handled Education in personal hygiene procedures and public health measures Enforced regulations governing manufacture of food and drink
Vaccination …. Is the most effective and most reliable way of preventing typhoid fever.
The Vi polysaccharide vaccine First licensed in the United States in 1994. Elicits a T-cell independent IgG response that is not boosted by additional doses. The target value for each single human dose is about 25μg of the antigen. The Vi vaccine does not elicit adequate immune responses in children aged <2 years.
Schedule Only 1 dose is required, and the vaccine confers protection 7 days after injection.  To maintain protection, revaccination is recommended every 3 years Can be co administered with other childhood vaccines
Prevention is the need of the day
Vision of equal opportunities
Summary  	Ever increasing burden of infectious water borne diseases is a cause for alarm at all level Need to create public awareness about prevention through clean water , hand washing, better hygienic practices and vaccination  Professional body of doctors needs to push the government to clamp down on food vendors and public eating places for enforcing standards of hygiene
With availability of typhoid and hepatitis A vaccines at affordable prices there is no excuse for not vaccinating  Culture  of vaccination as a business should be discouraged in order to enroll and benefit more and more people

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Dr. Huma Arshad

  • 1. Vaccine preventable waterborne diseases—Typhoid fever and Hepatitis A Professor Huma Arshad Cheema Pediatric Gastroenterologist Hepatologist Chairperson PPA GI group
  • 2. Transmission of Hepatitis A and typhoid Faeco-oral transmission Ever increasing burden due to declining standards of hygiene Diseases of both rich and poor due to contaminated food handling and poor hand washing
  • 3. Ah the blessing of clean drinking water
  • 4. Where do we stand? >1 billion people worldwide don’t have access to safe drinking water Labeled as “the Silent Global Emergency” by WHO & UNICEF in their report of Aug 26, 2004 Estimated that over two third of Pakistanis do not have access to clean drinking water
  • 5. Some facts Ranking 135th on the United Nation’s Human Development Index, Pakistan has a population of approximately 148 million, ranking 7th in the world, of whom half are children. Infant Mortality stands at 90 per 1,000 live births, and maternal Mortality at 340 per 100,000 live births (median estimates). In terms of health status, Pakistan faces a double burden: a rapidly increasing incidence of non-communicable diseases (NCDs) and injuries, superimposed on endemic communicable diseases (CDs).
  • 7. Forces we are up against
  • 8. The heavy price of conflict
  • 9. Price of natural and man made disasters Natural disasters, conflict, economic crisis and political turmoil have increased the vulnerability of thousands of children. In 2008 and 2009, conflict displaced some 1.6 million children Ongoing conflict in the north-west has displaced some 2 million people since 2008, with most displaced since April 2009. About a tenth of those displaced live in camps for internally displaced people. 
  • 10. Under-5 mortality rate (probability of dying by age 5 per 1000 live births)  
  • 11. 11 What has been the impact of vaccines on public health? The 2 things man has done to improve health the most: Clean Water Vaccines The impact of vaccines has been tremendous since they were first used in the 1700s.
  • 13. 13 Smallpox Vaccine Last case: 1979
  • 14. 14 Polio Last US case: 1979
  • 18. Where are child death occurring? Eastern Mediterranean 14% Europe 2% Americas 4% Southeast Asia 30% Western Pacific 10% Africa 39% Developing countries: 99% Africa and Asia: 69%
  • 22. Some less understood facts about Hepatitis A Among different parts of the world there is a notable difference in the predominant manifestation of hepatitis A. The clinical presentation of childhood hepatitis A is more severe with poverty and poor sanitation  In less developed regions, HAV is the main etiological agent for pediatric acute liver failure. Many affectedchildren are in the preschool age bracket.    
  • 23. In Turkey, HAV was the most common identifiable cause of pediatric fulminant hepatic failure, accounting 26% of cases In India, where the prevalence of HAV infection varies by geography and socio-economic class HAV infection was identified in 40–53% of cases of pediatric acute liver failure among cohorts from New Delhi, West Bengal and southern India
  • 24.
  • 25. At Children's Hospital lahore 60 % of cases of fulminant hepatic failure were due to Hepatitis A with a mortality of 35% Morbidity from other complications underestimated - prolonged cholestatic syndrome - Hemolytic anemia both viral induced and G6PD deficiency induced - precipitation of autoimmune liver disease - Bone marrow aplasia
  • 26. Combined infections Co infection with Hepatitis A and S typhi seen increasingly at Children's Co infection of Hepatitis A and E also seen producing more severe illness and prolonged cholestasis
  • 27. Prevention is the Key Time to understand that the assumption that Hepatitis A is a harmless disease and vaccination is a luxury is false When the difference is between death and a thousand rupees the choice is obvious
  • 28. Similarities between the epidemiology of Hep A and Polio virus suggesting widespread vaccination of susceptible populations can substantially lower disease incidence Eliminate virus transmission Ultimately eradicate HAV
  • 29. Immunoprophylaxis Inactivated Hep A vaccine 15 years of marketing experience Highly immunogenic Provides lasting protection in healthy individuals Generates protective levels of antibodies in patients with chronic liver disease or impaired immunity
  • 30. Vaccine Timing of booster dose not critical to effectiveness but in routine now booster is recommended Effective in curbing outbreaks of hepatitis A After completion of primary dosage antibodies last longer than 10 years and immune memory may last even longer
  • 31. Post exposure Effective postexposure due to rapid seroconversion and long incubation period Multiple studies show that contacts given vaccine within 14 days have equal or better protection than immunoglobulins Very young children < 1 yrs may still need immunoglobulins
  • 32.
  • 33. Where are the people dying from typhoid fever
  • 34. Typhoid Global Burden Burden probably underestimated Many hospitals lack facilities for blood cultures Up to 90% of patients are treated as outpatients Sporadic disease in developed countries - mainly in returning travelers
  • 35. Epidemiology of Typhoid Fever World wide Annual incidence of 12.5 M (WHO) Mortality rate: 600,000 deaths every year more than 90% of morbidity and mortality occurs in Asia. Incidence in developing countries 100-1000 per 100,000 per year Population-based studies indicate that, contrary to previous views, the age-specific incidence of typhoid may be highest in children <5 yr of age, with comparatively higher rates of complications and hospitalization
  • 36. Typhoid in Pakistan As per a paper presented at the WHO 6th International Conference on Typhoid Fever and Other Salmonellas in 2004 Typhoid is the 4th most common cause of death in Pakistan 9 Source: 9. Richens J. Typhoid fever, Surgery in Africa – Monthly Review; 2006 (World Health Organization. 6th International Conference on Typhoid Fever and other Salmonellas. 2006. Geneva, WHO.)
  • 37. Others (18.2%) S. typhi (42.8%) Strep. spp. (8.3%%) Staph. epidermis (10.8%) S. paratyphi (8.3%) E.coli (2.7%) Study Results of AKUH Karachi 11 Hospital-based and other studies have indicated that typhoid fever is a serious problem among children in Pakistan: S. typhi found to be most common cause on bacterium among children dying with diarrhea at AKUMC. Spectrum of Paediatric blood culture isolates from AKUMC emergency services
  • 38. Causative Agent Salmonella typhi Flagellar antigen Capsular polysaccharideantigen (Vi) Somatic antigen
  • 39.
  • 40. Some Important practical clinical information Humans are the only natural reservoir of styphi Clinical presentation varies from mild disease to severe with high grade fever ,abdominal discomfort and complications Presentation more severe in infants and older patients Infants may have diarrhea and abdominal distension along with fever as the main symptom
  • 41. Some Important practical clinical information Classic stepladder rise of fever is now rare Severe rigors unusual Hepatomegaly more frequent than splenomegaly Mild Hepatitis with altered liver enzymes very common but frank hepatitis with jaundice rare Bronchitis a frequent accompaniment
  • 42. Deadly complications Intestinal Bleed Intestinal perforation Osteomyelitis
  • 43. 200 years old specimens of intestine from Hunterian museum of RCSE
  • 44. Typhoid Perforation and typhoid osteomyelitis
  • 45. Diagnosis First week --- and no previous antibiotic given the best yield is from a blood culture After 4 days the Typhidot test also becomes positive Widal test has notoriously high percentage of false positive and negative---rising titres over the days more diagnostic
  • 46. Treatment and the implications of Antibiotic ResistanceTHE SUPER BUGS Study of typhoid fever from 5 asian countries gives dismal news on antimicrobial resistance Nearly 60% of the isolates were resistant to chloramphenicol, ampicillin, TMP-SMX and nalidixic acid. In contrast, all isolates from sites in China and Indonesia were susceptible to all antimicrobial agents
  • 47. THE SUPER BUGS Multidrug resistance (resistance to chloramphenicol, ampicillin and TMP-SMX) was observed in 65% isolates from the site in Pakistan Nalidixic acid resistance was found in 59% isolates from the site in Pakistan,
  • 48. Disease Burden StudyAntibiotic resistance patterns No resistance against these antibiotics were found from China and Indonesia sites
  • 49.
  • 50. Treatment of enteric fever Choosing the right empirical therapy is problematic and controversial Increasing incidence of multiresistance to chloramphenicol Ampicillin and TMP- SMX in 49-83% of salmonella typhi is being reported from India Resistant strains are usually susceptible to third generation cephalosporins Quinolones are not to be used as first line
  • 51. WHO POSITION PAPER-2008 In view of the continued high burden of typhoid fever and increasing antibiotic resistance, and given the safety, efficacy, feasibility and affordability of licensed vaccines , countries should consider the programmatic use of typhoid vaccines for controlling endemic disease.
  • 52. WHO POSITION PAPER-2008 All typhoid fever vaccination programmes should be implemented in the context of other efforts to control the disease, including Health education, water quality Sanitation improvements, Training of health professionals in diagnosis and treatment.
  • 53. Current issues Very high incidence of this infectious and deadly disease in Pakistan Endemic all year round and incidence on the rise Multi drug resistant salmonella becoming a big health issue Significant cost of treatment and hospitalization.
  • 54. Typhoid dragon can be slain by prevention
  • 56. Public Health Measures Supply of clean, safe drinking water Effective and sanitary disposal of human feces and urine Careful attention to cleanliness and hygiene during food preparation Provision of adequate hand washing facilities wherever food is handled Education in personal hygiene procedures and public health measures Enforced regulations governing manufacture of food and drink
  • 57. Vaccination …. Is the most effective and most reliable way of preventing typhoid fever.
  • 58. The Vi polysaccharide vaccine First licensed in the United States in 1994. Elicits a T-cell independent IgG response that is not boosted by additional doses. The target value for each single human dose is about 25μg of the antigen. The Vi vaccine does not elicit adequate immune responses in children aged <2 years.
  • 59. Schedule Only 1 dose is required, and the vaccine confers protection 7 days after injection. To maintain protection, revaccination is recommended every 3 years Can be co administered with other childhood vaccines
  • 60. Prevention is the need of the day
  • 61.
  • 62. Vision of equal opportunities
  • 63. Summary Ever increasing burden of infectious water borne diseases is a cause for alarm at all level Need to create public awareness about prevention through clean water , hand washing, better hygienic practices and vaccination Professional body of doctors needs to push the government to clamp down on food vendors and public eating places for enforcing standards of hygiene
  • 64. With availability of typhoid and hepatitis A vaccines at affordable prices there is no excuse for not vaccinating Culture of vaccination as a business should be discouraged in order to enroll and benefit more and more people