INFECTIOUS DISEASES

1. INFECTIOUS DISEASES ABDI SOLOMON(MD)

2. Generally infectious diseases result from bacteria, viruses, fungi, and parasites. • Infectious diseases remain a major cause of death and are responsible for worsening the living conditions of many millions of people • Infectious diseases often do not occur in isolated cases • Many factors affect the likelihood of acquiring infections which include, host, environment and microbial factors.

3. Many factors affect the likelihood of acquiring infections which include • host • environment • Infectious agents.

4. Host factor • Many specific host factors influence the likelihood of acquiring an infectious disease. • Age, immunization history, prior illnesses, level of nutrition, pregnancy, coexisting illness, and perhaps emotional state all have some impact on the risk of infection after exposure to a potential pathogen. • Defense-immunity-innate/adaptive

5. Immune response: • Is a defense mechanism developed by the host for recognizing and responding to microorganisms. • two major classes. Innate and Acquired Immunity. Innate immunity (Natural Immunity) : • Is first line of defense and serves to protect the host with out prior exposure to the infectious agent. • is nonspecific and has no memory.eg phagocytosesby macrophages and nutrophils, complement system etc

6. Acquired (Adaptive) Immunity: specific immune mechanism developed against a particular organism.takes long time to develop It has two major arms: .Cellular immunity: comprising T- lymphocytes, NK cells .Humeral Immunity : comprises of B-Lymphocytes and antibodies produced by plasma cells.

7. Enviromental factors • Factors such as geography (e.g. altitude and malaria), environment (e.g. mosquito breeding site and malaria), disease vectors • Cleans of the environment • Over crowding

8. Infectious agent • Viruses • Viruses contain two types of macromolecule: proteins and nucleic acids, the latter of only one type (either DNA or RNA). • Bacteria • Long known as 'prokaryotes', bacteria share the following essential features: they contain both RNA and DNA, have facilities for protein metabolism and are generally free living. • Eukaryotes • These organisms exhibit subcellular compartmentalisation with intracellular functions being achieved by specific organelles, e.g. nucleus, chloroplasts, mitochondria and Golgi apparatus.Fungi,Protozoa,parasites

9. Incubation period: • The incubation period is the period between the invasion of the tissues by pathogens and the appearance of clinical features of infection. • The period of infectivity is the time that the patient is infectious to others

10. Typhoid (Enteric) Fever • Definition: Typhoid fever is a systemic infection caused by dissemination of Salmonella typhi and occasionally by S. paratyphi A and B and S.typhimarium • non capsulated, gram negative motile and rod shaped bacteria. • Antigens: • H-located in the cell capsule H (flagellar antigen). • O- (Somatic or cell wall antigen). • Vi -(polysaccharide virulence) “widel test”

11. A schematic diagram of a single Salmonella typhi cell showing the locations of the H (flagellar), 0 (somatic), and Vi (K envelope) antigens.

12. Epidemiology • Continues to be a global health problem • Areas with a high incidence include Asia, Africa and Latin America • Affects about 6000000 people with more than 600000 deaths a year. 80% in Asia

13. Transmission • fecal-oral route • close contact with patients or carriers • contaminated water and food • flies and cockroaches.

14. Ingested orally • Stomach barrier (some Eliminated) • enters the small intestine Penetrate the mucus layer  enter mononuclear phagocytes of ilealpeyer's patches and mesenteric lymph nodes  proliferate in mononuclear phagocytes spread to blood. initial bacteremia (Incubation period). Pathogenesis

15. Pathogenesis enter spleen, liver and bone marrow (reticulo-endothelial system) further proliferation occurs  A lot of bacteria enter blood again-(second bacteremia).  Recovery

16. Bac. In gall Bac. In feces S.Typhi eliminated convalvescence stage (4-5w) peyer's patches & mesenteric lymph nodes S.Typhi. liver、spleen、gall、 BM ,ect early stage&acme stage (1-3W） 2nd bacteremia stomach (mononuclear phagocytes) Lower ileum 1st bacteremia (Incubation stage) 10-14d LN Proliferate,swell necrosis defervescence stage （3-4w） thoracic duct Enterorrhagia,intestinal perforation

17. Clinical Manifestation • The incubation period varies from 3-60 days. • First week • Fever is high grade, with a daily increase in a step-ladder pattern for the 1st one week and then becomes persistent. • Headache , malaise , Abdominal pain • Initially diarrhea or loss stole followed by constipation in adults, diarrhea is dominate feature in children • Relative bradycardia • Splenomegally Hepatomegaly • “Rose spots”

18. Second week • Fever becomes continuous • The patient becomes very ill and withdrawn confused, delirious and sometimes may be even comatose Third Week • • The patient goes to a pattern of “typhoidal state" characterized by extreme toxemia, • disorientation, and “pea-soup” diarrhea and sometimes may be complicated by intestinal perforation and hemorrhage.

19. Fourth Week • Fever starts to decrease and the patient may deferveresce with resolution of symptoms. At this point patient may lose weight. • Relapse may occur in 10% of cases. • fatal complication • intestinal hemorrhage(serious blding 2-8%) • intestinal perforation (1-4%) • severe toxemia

20. Laboratory findings Routine examinations: • White blood cell count is normal or decreased. • Leukocytopenia

21. Bacteriological examinations: • Blood culture -mostly (up to 90%) patients have positive culture in the 1stweek, and only 50% by the 3rdweek. • The yield is much lower if patient has taken antibiotics prior to the test. • Stool culture is negative in the first week and becomes positive in 75%of patients in the 3rdweek. • Urine culture parallels stool culture.

22. Widal test • "O" agglutinin antibody titer ≥1:80 and "H" ≥1:160 or "O" 4 times higher supports a diagnosis of typhoid fever. • "O" rises alone, not "H", early of the disease. • Only "H" positive, but "O" negative, often nonspecifically elevated by immunization or previous infections • Antibody level maybe lower when have used antibiotics early.

23. Limitations of Widal test It is non specific and a positive test could be due to • Infection by other salmonellae (as the antigen used for the test is also shared by other salmonellae) • Recent vaccination for typhoid • Past typhoid (already treated)

24. Enteric (Typhoid) Fever: Treatment • Prompt administration of appropriate antibiotic therapy prevents severe complications of enteric fever and results in a case-fatality rate of <1%. • The initial choice of antibiotics depends on the susceptibility of the S.Typhi and S.Paratyphi strains in the area of residence or travel.

25. Rx…

26. 1st line • • Ciprofoxacin: 500mg PO BID for 5-7days • • Ceftriaxone 1-2 gm IM or IV for 10 -14 days • Alternative • • Azithromycine 1 gm PO daily for 5 days • • Chloramphenicol 500 mg Po QID for 14 days • • Norfloxacin 400mg twice daily for 10 days

27. 2.4 Rickettisial diseases: (Epidemic and Endemic Typhus) • Rickettisiae are small intracellular bacteria that are spread to man by arthropod vectors, namely human body lice, fleas, ticks & larval mites. • Epidemic Typhus (Louse born ): is caused by R.prowazekii and transmitted by human body louse (Pediculushumanuscorporis). • Endemic Typhus (Flea born) / Murine Typhus: is cause by R. thyphi which is transmitted by fleas.

28. Pathophysiology • In man rickettsia multiply in the endothelial cells of capillaries • causing lesions in the skin, brain, lung, heart, kidneys and skeletal muscles. • causes thromboses and small hemorrhages. • However, tissue and organ injury is commonly due to increased vascular permeability with resulting edema, hypovolemia and organ ischemia.

29. Clinical Features (epidemic typhus) • Incubation period of 1 week • Abrupt onset of illness with prostration, severe headache and rapidly rising fever of 38.8 to 40.0 °C • Cough s seen in 70 % of patients , myalgia may also occur which may be severe • Rash, begins on upper trunk around 5thday and then becomes generalized, involving the entire body except face, palms and soles; at first, rash is macular, becoming maculopapular, petechial and confluent without treatment, although in black people, rash may be absent (spotless epidemic typhus) • • Photophobia, with conjunctivalinfection and eye pain

30. signs of central nervous system involvement,may occur at the end of 1stweek (meningo-encephalitis)

31. Endemic typhus (Flea borne typhus) • Endemic typhus (also known as muri ne typhus) is a relatively milder. • The incubation period is 1 - 3 weeks and followed by sudden onset of fever, • rigors, frontal headache, pain in the back and limbs, constipation and cough (due to bronchitis). • The fever becomes constant after the third day and associated with conjunctivitis and orbital pain.

32. Laboratory investigations; • Serologic tests: • • Indirect fluorescent antibody test • • Weil-Felix agglutination test: nonspecific or sensitive • Isolation of the organism by inoculation into laboratory animals

33. Complications of Endemic and Epidemic Typhus • Skin necrosis, gangrene of digits, • Venous thrombosis • Interstitial pneumonia in severe cases • Myocarditis • Oliguric renal failure • Parotitis

34. Treatment of rickettsial diseases • Endemic Typhus • Doxycycline 100mg bid PO for 7-15 days • Chloramphenicol 500mg QID PO for7-15 days • Epidemic typhus • Doxycycline 200mg as single dose PO until the patient is afebrile for 24 hours. • Delousing louse borne typhus

35. Relapsing Fever • Definition • Relapsing fever is an acute febrile illness caused by Borrelia species, presenting with recurrence of characteristic febrile periods last ing for days alternating with afebrile periods. • Relapsing fever describes two distinct diseases: • • Louse borne (Endemic) relapsing fever (LBRF):- transmitted by body louse( Pediculushumanisvarcorporis) • • Tick borne (Epidemic) relapsing fever (TBRF)- transmitted by tick (Ornithodoros)

36. Etiology • Relapsing fever is caused by Borrelia species, which are spirochetal gram negative helical bacteria. • B. recurrentis is the only species that cause LBRF • B. duttoni is the commonest causes of TBRF in sub-Saharan Africa

37. PATHOGENESIS Portal of entry, infected lice crushed into abraded skin. Incubation period, 5-10 days. High level spirochetemia. Patients’ producing neutralizing antibodies, clearing of the circulating strain Borrelia in 3-5 days New ANTIGENIC VARIANTS appear Recurrence of clinical symptom/signs; up to 3-5 relapses may occur .

38. CLINICAL FEATURES Incubation period, 5-10 days, average 7 days. The range of clinical symptoms/ signs is wide. In a typical sever case there is abrupt onset of fever, 39-40. The following is the dominant clinical features:

39. CLINICAL FEATURES, contd. SIGNS • Temperature • Tachycardia • Hepatomegaly • Splenomegaly • Petichea/ Subconjunctival bleeding • Jaundice • Confusion/Meningism SYMPTOMS • Fever • Headaches • Arthralgia/myalgia • Dry cough • Epistaxis/gum bleeding

40. COMPLICATIONS Congestive heart failure Jaundice Bleeding diathesis Jarish- Herxheimer reaction: The first dose of appropriate antibiotic causes transient worsening of clinical symptoms/signs. Frequency, 35-100%, associated with increased mortality.

41. COMPLICATIONS contd. Physiologic change: chills phase, rise in BP, pulse,and respiratory rate; flush phase, BP falls dramatically . There is a marked, but transient rise in circulating level of : TNF, IL-6, and IL-8 at the peak of the reaction (figure 2). DIAGNOSIS Demonstration of the organism; blood film.

42. MANAGEMENT Aims of Management: Clinical cure Prevention of relapse Prevention/treatment of complications Antibiotic treatment: A number of antibiotics are effective: Anticipate the occurrence of Jarish- Herxheimer like reaction. In our setting we simply start with procaine penicillin 400,000IU IM and then observe for 12 hours and repeat blood film.

43. Management of complications Supportive treatment: IV fluids for hypotension, diuretics for pulmonary edema. Prevention and control Better housing, reliable water supply, good personal hygiene. Insecticides like DDT for killing lice.

44. Malaria

45. Defn: Is a protozoan disease transmitted by the bite of A. mosquito • Transmission in 107 countries • Affect 3 billion ppls worldwide

46. Etology • Four sp. Of the genus Plasmodium • Others – rare • P. falciparum – malignant malaria • P. vivax – tertian malaria • P. ovale – Tertian malaria • P. malariae – quartian malaria • NB: almost all deaths are caused by falciparum malaria

47. Epidemology • Is complex and varies considerably even within relatively small geographic area • Endemicity: defined interms of parasitemia rates or palpable spleen rates in childern 2 – 9 yrs of age as • Hypoendemic - < 10% • Mesoendemic – 11 – 50% • Hyperendemic – 51 – 75% • Holoendemic - > 75%

48. Epidemology • Stable transmission – is constant frequent round infection • Unstable transmission • transmission is low, erratic or focal • Full protective immunity is not acquired • Symptomatic disease occurs at all ages • Usually occurs in hypoendemic area

49. Epidemology • Principal determinants are • The density of the vector • Human biting habit • Life span of A. mosquito • Common in both low and highland and epidemics is commonly observed in highlands • Temprature – < 16 -18 oc sporogony is inhibted