Agents of infectious disease in developing countries

1. Agents of infectious disease in developing countries February 20, 2007

2. Infectious diseases in the developing world • Comprise 20% of all deaths worldwide • The burden of disease comes from a wide range of microbes • The take home message: The burden of infectious disease in the developing world is immense, and comes from many different sources

3. The study of individual diseases: why? • There are many, many infectious diseases that burden the developing world • They have unique biological characteristics • They cause unique kinds of damage • In order to defeat the enemy, you must first understand what it is • Understanding why these diseases survive and thrive is key to controlling them

4. Microbes: the unseen universe • Microbes are incredibly diverse and incredibly well adapted to their niches in the world • To know how to control microbes, we need to know how they live • Where do they live? • What are their life cycles: how do they ensure their own survival? • How do they survive both inside and outside humans?

5. Key concepts for understanding microbial life • There are three main classes of microbes • They differ in their biological complexity • Single celled • Multi-celled • No cells at all! • They differ in their ability to survive outside their human host • Some need us; some don’t • They differ in the complexity of their life cycles • Some live entirely in a human host • Some have complex cycles that go from us to the environment and back to us

6. 30-200 nm 1-2 microns 5 microns Microbial life: a hierarchy • There are three broad categories of microbes • The viruses • The bacteria • The parasites

7. TheViruses • The smallest microbes • Consist of nucleic acid (DNA or RNA) and protein • Sometimes surrounded by membrane (envelope) • Affects how well they survive in the environment • Taxonomy based on • Physical characteristics • Host range (not so much any more) • Nucleic acid similarity • Have family, genus, and species, somewhat like bacteria

8. The Viruses • Incapable of reproducing on their own • Totally dependent on a living host (human or animal) to produce more viruses • Hijack the machinery of living cells in order to reproduce themselves • Can survive free in the environment, but do not reproduce there • Survive in an inert state, waiting for contact with a host • Some remain infectious longer than others outside a host • Can survive in food, water, soil, on surfaces and objects

9. Control of viral diseases • Too small to be caught by size filtration • Filtration by charge interaction (stick to stuff) • Susceptible to chemical disinfectants • Can die off naturally in environment, but this is highly variable and influenced by many different factors (temperature, humidity, etc) • Vaccination can successfully control many serious viral diseases

10. The Bacteria • Single-celled organisms • Less complex internal structures than animal cells • Cell walls made of sugars/lipids • Replicate by binary fission

11. The Bacteria • Huge amount of diversity; many different cell types, habitats, survival strategies • Some live exclusively in association with living hosts; others can live free in the environment

12. Control of Bacteria • Can be removed by size filtration • Can be removed by coagulation and settling processes • Susceptible to chemical disinfectants • Can die off in the environment, but; • Some bacteria naturally live free in the environment • Some bacteria have very tough environmental forms capable of living for a long time

13. The Parasites • Very diverse group of microbes • Microscopic single celled organisms • More complex cellular structures than bacteria • Multicellular organisms: worms that can be seen with the naked eye

14. The Parasites • Have complex life cycles • Life cycles consist of several distinct stages • Some stages take place in living hosts • Some stages take place in the environment • Sexual and asexual stages of reproduction • Have forms that can live in the environment, but need living hosts for their complete life cycle and reproduction

15. Example: a parasite life cycle

16. Control of parasites • Can be removed by size filtration • Can be removed by coagulation and settling processes • Not susceptible to chemical disinfectants • Can die off in the environment, but; • Some have very tough environmental forms capable of living for a long time • Some live in insect vectors when they’re not living in the human body

17. Respiratory Diseases: the viruses • Adenovirus • Family Adenoviridae, genus adenovirus • Influenza • Family Orthomyxoviridae, genus influenzavirus • Parainfluenza • Family Paramyxoviridae, genus respirovirus • Respiratory syncytial virus • Family Paramyxoviridae, genus pneumovirus

18. Respiratory Diseases: the bacteria • Streptococcus pneumoniae • Haemophilus influenzae • Both causes of both pneumonia and meningitis • Often set in as secondary infections after viral respiratory infection weakens the host • Vaccine preventable

19. Respiratory disease • Bacterial and viral: both causes of pneumonia • The leading cause of infectious disease death among children (2 million/year) • Bacterial infections are more likely to cause death (often secondary infections) • At highest risk are newborns, children with malaria, and malnourished children

20. Human immunodeficiency virus • Second biggest killer after respiratory infections • Death is not from HIV, but from the opportunistic infections that devastate the human body once the immune defenses are eliminated by the virus • Those with HIV are vulnerable to every one of these infections

21. Rotavirus Family Reoviridae, genus rotavirus Norovirus Family Caliciviridae, genus norovirus and saprovirus Astrovirus Family Astroviridae, genus astrovirus Adenovirus Family Adenoviridae, genus adenovirus Hepatitis A virus Family Picornaviridae, genus hepatovirus Polio Family Picornaviridae, genus enterovirus Diarrheal Disease: the viruses

22. Diarrheal Disease: the bacteria • Cholera (Vibrio cholerae) • Shigella (S. dysenteriae, S. flexneri, S. sonnei, S. boydii • Escherichia coli • Salmonella (S. typhi, S. typhimurium) • Campylobacter (C. jejuni)

23. Diarrheal Disease • Can be both endemic and epidemic • Fecal-oral and person-to-person transmission • Can survive outside the human body in water, soil, feces • These are also vehicles for transmission • Death by dehydration, especially in children

24. Tuberculosis • Causative agent: Mycobacterium tuberculosis • Acid-fast rod-shaped bacterium • person-to-person transmission by aerosols • Does not live in the environment, but can live in some animals

25. Tuberculosis • Becomes chronic once it establishes itself • Fever, weight loss, night sweats • A disease that causes a slow decline • Half of untreated patients die within 5 years • Those who are already debilitated by other diseases are most susceptible • Lack of water and sanitation creates populations vulnerable to TB

26. The Childhood Diseases • Whooping cough • Bacteria: Bordatella pertussis • Measles • Virus: Family Paramyxoviridae, Genus Moribillivirus, measles virus • Tetanus • Bacteria: Clostridium tetani

27. Whooping cough • Person-to-person by contact and droplets • Paroxysmal coughing fits • Can cause vomiting • Characteristic “whoop” from the inability to get enough air through coughing fits • Most dangerous to very young infants • Vaccine preventable • In nonimmunized populations with malnutrition and underlying respiratory and enteric infection, it is one of the most lethal childhood diseases

28. Measles • Respiratory infection • Spread by droplet and contact • Cause of pneumonia and encephalitis • Fatality rates can read 10-30% in susceptible populations • Exacerbates complications of malnutrition • Vaccine preventable

29. Tetanus • Caused by the toxin produced by C. tetani • Muscle spasms (“lockjaw”) and respiratory failure • Lives in soil and feces • Introduced into the body through dirty wounds • Children: tetanus neonatorum • Vaccine preventable

30. Malaria • A single-celled parasite of the genus Plasmodium • Four species: falciparum, vivax, ovale, malariae • Vector: the Anopheles mosquito • Tropical and subtropical disease

31. Malaria • Not only is malaria a killer in and of itself, but it leaves people susceptible to many other diseases • Disease control requires vector control • Elimination of breeding sites of the vector • Improved sanitation can help achieve this

32. The parasitic diseases • Ascaris • Intestinal nematode (roundworm) • Ascaris lumbricoides • Infectious stages is the egg, which is excreted in feces and survives in warm, moist areas • Can cause stunting, migrate to other organs in the body • Hookworms • Intestinal nematodes (roundworms) • Ancylostoma duodenale and Necator americanus • Eggs are excreted in feces and grow in warm, moist areas • Become the infectious stage, the larvae • Infect by penetrating the skin • Attach in intestine and cause blood loss

33. The parasitic diseases • Schistosomiasis • Trematodes (flatworms) • Schistosoma haematobium, S. japonicum, and S. mansoni • Eggs are shed in feces • Life cycle takes place partly in water, requiring a snail as an intermediate host • People become infected by coming in contact with water • Worms migrate to organs • Cryptosporidium • C. parvum: coccidian single-celled parasite • Infectious form, the oocyst, is shed in feces • Infection acquired by ingesting contaminated water • Cause of chronic diarrhea

34. The parasitic diseases • Cysticeriosis • Caused by cestodes (tapeworms) • Taenia solium • Infectious stage, the egg, is shed in feces • Pigs ingest eggs from contact with human feces • People ingest eggs from fecal-oral transmission or ingestion of undercooked pork • Worms migrate to organs • Dracunculiasis • Nematode (roundworm) • Dracunculus medinensis • Transmitted through water • Humans ingest water with copepods (small crustaceans), which contain the larvae • Worms migrate though the body • Worms escape through the skin, leading to contamination of water when infected individuals come in contact with it

35. The parasitic diseases • Entamoeba • Single celled amoeba • Entamoeba histolytica • Mature cyst is the infectious form • Shed in feces • Spread through contaminated food, water, hands • Spread through the body • Giardia • Single celled protozoan • Giardia lamblia • Cyst is the infectious form • Shed in feces • Spread through contaminated food, water, hands • Diarrheal disease; can be chronic and cause malabsorption

36. Infectious diseases: the take home message • The burden of disease is an interplay among different kinds of diseases • Those who are already weak and unhealthy are vulnerable to infection • Those who are already debilitated by infection are prime hosts for even more microbes • Improvements in water and sanitation have ripple effects far beyond just the prevention of enteric disease