Kingdom of Bahrain Arabian Gulf University College of Medicine and Medical Sciences

1. Kingdom of BahrainArabian Gulf UniversityCollege of Medicine and Medical Sciences Infectious Diseases (Review) Year 5 – Internal Medicine Presented by: Dr. JameelaSalman Prepared by: Ali JassimAlhashli

2. Infectious Diseases Review • AIDS (Acquired Immune Deficiency Syndrome): • It is caused by Himan Immunodeficiency Virus (HIV). The primary mechanism of HIV is infection of a particular subset of lymphocytes called CD4 cells. • As a person’s CD4 count drops, he becomes at increasing risk of developing opportunistic infections and certain malignancies. • There is often 10-year lag between contracting HIV infection and developing the early symptoms. These are: • Fever, lethargy, sore throat, lymphadenopathy and maculopapular rash (similar to the clinical picture for infectious mononucleosis). These symptoms usually self-resolve in 2 weeks. Therefore you have to keep EBV infection, hepatitis and toxoplasmosis as your differential diagnosis. • How is HIV infection diagnosed? How many weeks after infection are antibodies formed? • ELISA followed by Western blot analysis. Antibodies are formed 3-4 weeks after infection. Nowadays ELISA alone is enough to check and diagnose infection with both HIV-1 and HIV-2. You must also check for the viral load (copies of viral RNA/mL of plasma) and CD4 count.

3. Infectious Diseases Review • AIDS (Acquired Immune Deficiency Syndrome): • Antiretroviral therapy: you have to start treatment with antiretroviral therapy immediately for any patient diagnosed with HIV (REGARDLESS OF CD4 COUNT). • What are the treatment guidelines? • Use 2 nucleosides combined with a protease inhibitor • Or use 2 nucleosides combined with NNRTI (non-nucleoside). • The first visit of your patient will be 6 weeks after starting therapy because during that time the viral load will drop by approximately 50%. Keep in mind that CD4 count will take a longer time to be corrected (months). • If a patient has hepatitis C and HIV, you should treat hepatitis C first and then start anti-retroviral therapy one the patient resolves from the infection. • If a patient has hepatitis B and HIV, start him on anti-retroviral medications which cover hepatitis B infection.

4. Infectious Diseases Review • AIDS (Acquired Immune Deficiency Syndrome): • Opportunistic Infections (OI) according to CD4 count: • > 500/µL: oral thrush, kaposi sarcoma, tuberculosis and zoster. • > 200/µL: pneumocysticcarinii pneumonia. • > 100/µL: toxoplasmosis, cryptococcus and cryptospordiasis. • > 50/µL: cytomegalovirus and Mycobacterium Avium Complex (MAC).

5. Infectious Diseases Review • Tuberculosis (TB): • It is an infection caused by: Mycobacterium tuberculosis. • Transmission: air-borne infection (which means that the organism can stay for hours in the surrounding air even if the patient leaves that area). Therefore, n95 mask is used in hospitals to prevent transmission of infection. • Patients with tuberculosis have prolonged presentation (complaining of their symptoms for weeks). Clinical presentation: fever, night sweats, weight loss, productive cough and hempotysis (although it is not very common). • Diagnosis: sputum or pleural fluid examination with specific staining for acid-fast bacilli (AFB) allows specific diagnosis in addition to chest x-ray. Nowadays, PCR provides results within 1 day in addition to sensitivity of the organism to isoniazid and rifampin.

6. Infectious Diseases Review • Tuberculosis (TB): • PPD is a screening (but not a diagnostic) test which is used to screen asymptomatic populations at risk of tuberculosis to see if they have been exposed and are at increased risk for re-activating the disease. PPD is considered positive based ob the amount of induration of the skin 48-72 hours after the intradermal injection of PPD. The cutoffs are as follows: • ≥ 5 mm: close contacts of active TB cases, HIV-positive persons and steroid use or organ transplantation recepients. • ≥ 10 mm: healthcare workers, prisoners, nursing home residents, recent immigrants from areas with a high prevalence and children > 4 years. • ≥ 15 mm: low-risk populations (those not mentioned above). • (+) PPD, abnormal CXR, (+) AFB smears → start tuberculosis treatment with isoniazid, rifampin, pyrazinamide and ethambutol for 2 months and then continue isoniazid and rifampin for another 4 months. • (+) PPD, normal or abnormal CXR, (-) AFB smears → this is latent TB and you have to treat it with isoniazid and vitamin B6 for 6-9 months.

7. Infectious Diseases Review • Tuberculosis (TB): • Side effects of tuberculosis treatment: • Isoniazid: preipheral neuropathy. Therefore, you must combine it with vitamin B6. • Rifampin: it is associated with causing a benign change in the color of all body fluids to orange/red. • Ethambutol: optic neuritis. • Pyrazinamide: benign hyperuricemia.

8. Infectious Diseases Review • Infectious mononucleosis: • Fact: 80-90% of the population are positive for either EBV or CMV. • EBV mononucleosis: • Transmission: respiratory droplets. • Clinical manifestations: EBV affects B-cells and causes a self-limiting syndrome of fever, pharyngitis, generalized lymphadenopathy and hepatosplenomegaly. • Other agents causing infectious mononucleosis-like disease: CMV, Human Herpes Virus-6, acute HIV, toxoplasmosis, viral hepatitis and syphilis. • Diagnosis (3 criteria): • Lymphocytosis (at least 10 atypical lymphocytes). • Heterophile test. • Positive serologic test for EBV. • EBV is associated with malignancy and lymphoproliferative disease in immunocompromised patients. • CMV mononucleosis: • Diagnosis: serology. • Treatment: • No treatment in immunocompetent patient. • IV ganciclovir in immunocompromised patients (e.g. HIV and those with transplantation). For resistant cases, foscarnet (a second-line agent) will be used.

9. Infectious Diseases Review • Infectious diarrhea/food poisoning: • Food poisoning: • Occurring within hours (1-6 hours) after eating food infected with toxins or spores and patients present predominantly with vomiting. Examples: • Bacillus cereus is associated with fried rice; the rice becomes contaminated with bacillus spores and as it is prepared for serving it is warmed only at a moderate temperature not hot enough to kill the spore. • S.aureus: foods at higher risk for transmitting S.aureus toxins are those that people handle and then do not cook. Examples are: sliced meat, puddings, pastries and sandwiches.

10. Infectious Diseases Review • Infectious diarrhea/food poisoning: • Infectious diarrhea: • Infectious causes of bloody diarrhea: Campylobacter, Shigella, Salmonella, enterohemorrhagic/enteroinvasiveE.coli, Clostridium difficile, Vibrioparahemolyticus and Entamebahistolytica. • Most commonly associated agent with contaminated poultry and eggs is salmonella (bloody diarrhea). • E.coli is the most common cause of traveler’s diarrhea. E.coli O157:H7 is associated with undercooked hamburger meat and can result in Hemolytic Uremic Syndrome (HUS: which is characterized by acute renal injury, microangiopathic hemolytic anemia and thrombocytopenia). • V.cholera causes water diarrhea (fluid replacement therapy is the most important aspect of management as with all other infectious agents causing diarrhea. Antibiotics are not always indicated). • Clostridium difficile is associated with previous antibiotic use. • Campylobacter is rarely associated with Guillain-Barre syndrome. • Viral infections: rotavirus or Norwalk which are most commonly associated with outbreaks in children.

11. Infectious Diseases Review • Infectious diarrhea/food poisoning: • Infectious diarrhea: • Diagnosis: CBC (looking for WBCs and differentials which might indicate the presence of an infection), Stool for leukocytes, stool for occult blood and stool culture (to determine the specific type). • Treatment: • Mild infections with the invasive pathogens and viruses require only fluid and electrolyte replacement. • Severe infections, such as those producing high fever, abdominal pain, tachycardia and hypotension require IV fluids and oral antibiotics (e.g. 3rd generation cephalosporins.

12. Infectious Diseases Review • Meningitis: • Etiology: • Most cases of meningitis are due to viruses! • Bacteria cause meningitis in > 10% of cases, according to age group: • Neonates: E.coli, S.agalactiae and Listeriamoncytogens. • Adolescents: S.pneumoniae, H.influenzae and N.meningitidis. • Adults: S.pneumoniae and N.meningitidis. • Elderly: S.pneumoniae and Listeriamonocytogens. • Treatment: empiric therapy of bacterial meningitis in adults is best achieved with vancomycin + 3rd generation cephalosporin + dexamethasone (lowering mortality and morbidity). Ampicillin is added to elderly and neonates to cover Listeria. • Clinical presentation: fever, photophobia, headache, meningeal signs (neck stiffness, positive Kernig and Brudzinski signs) and nausea/vomiting. • Diagnosis: first you have to do fundoscopy to check if patient has papilledema which indicates increased intracranial pressure (thus lumbar puncture will be contraindicated). CT-scan of the head is the best initial diagnostic test if the patient has papilledema. If none of the above is present, a lumbar puncture can be safely done.

13. Infectious Diseases Review • Meningitis:

14. Infectious Diseases Review • Malaria: • What are the 4 plasmodia which cause malaria and transmitted by the female Anopheles mosquito? • Plasmodium vivax. • Plasmodium ovale. • Plasmodium malariae. • Plasmodium falciparum. • P.vivax and P.ovale have hypnozoites(latent forms of plasmodia found in liver cells and can be reactivated). Therefore, these patients must be treated with primaquine. • P.vivax, P.ovale and Pfalciparum cause fever every 48 hours. • P.malariae causes fever every 72 hours. A complication of P.malariae is membranous glomerulonephritis. • Classic symptoms of malaria are: recurrent fevers associated with chills and sweats, patients may experience hemoglobinuria due to extensive hemolysis and kidney damage (the dark color of the urine gave rise to the name blackwaterfever.This occurs in infection with P.falciparum) • Diagnosis: presence of parasites in blood smears by thick and thin blood smears. Thick smears detect the presence of parasites while thin smears identify the species of malaria. • Treatment: • Drug of choice for non-resistant malaria: chloroquine. • Drugs for chloroquine-resistant malaria: mefloquine, malarone and quinine + doxycycline.

15. Infectious Diseases Review

16. Infectious Diseases Review • Typhoid fever: • Etiology: Salmonella typhi. • Clinical manifestations: high-grade fever, headache, abdominal pain and either constipation or diarrhea. There must be a history of traveling (maximum within 3 weeks). Rose spots might also appear. • Complications: • Intestinal bleeding or perforations. • Other less common complications are: meningitis or osteomyelitis. • Diagnosis: positive blood culture. • Treatment: 3rd generation cephalosporin (drug of choice) → if there is resistance → use ciprofloxacin → if still there is resistance → use macrolides.

17. Infectious Diseases Review • Infective endocarditis: • It is a colonization of heart valves with microbial organisms causing friable infected vegetations and valve injury (aortic and mitral valves are most commonly affected). • Predisposing factors to bacterial endocarditis: dental procedures that cause bleeding, prosthetic heart valves and IV drug use. • Pathogenesis: • Acute infective endocarditis: S.aureus is the most common cause; seeds previously normal valves; IV drug use is a major risk factor; patient will have fever, rapid valve destruction, large vegetations; embolic complications. • Subacute infective endocarditis: S.viridans is the most common cause; seeding previously abnormal valves; risk factors include VSD with shunt, stenosisod any valve, prosthetic valves and mitral valve prolapse; patient will have low-grade fever with flue-like symptoms and slow destruction of valves; small vegetations.

18. Infectious Diseases Review • Infective endocarditis:

19. Infectious Diseases Review • Infective endocarditis:

20. Infectious Diseases Review • Pneumonia: • Conditions predisposing to pneumonia: smoking, diabetes, alcoholism, malnutrition, obstruction of bronchi from tumors and immunosuppression. • The most common cause of community-ascquired pneumonia in all groups is: S. pneumoniae. • Viruses are the most common cause in children > 5 years of age. • Hospital-acquired or ventilator-associated pneumonia shows a predominance of gram-negative bacilli: E.coli, enterobacteriaceae, Pseudomonas and MRSA. • Infectious agents causing pnuemonia: • Typical: • S.pneumonia. • Hemophilusinfluenzae: in smokers and those with COPD. • Moraxellacatarrhalis. • Atypical: • Legionella: from infected water sources. • Mycoplasma: in young, otherwise healthy patients. • Chlamydia.

21. Infectious Diseases Review • Pneumonia: • Clinical presentation: fever, cough, sputum production and dyspnea. Pleuritic pain is associated with lobar pneumonia. • Bacterial infections such as S.pneumoniae, H.influenzae and Klebsiella have significant purulent sputum production because they are infectious of the alveolar air space. • The sputum in patient with S.pneumoniae has been clasically described as rusty. • Klebsiellapneumoniae has been associated with sputum described as being like currant jelly. • Interstitial infections such as those caused by Pneumocystis pneumonia, viruses, Mycoplasma and sometimes Legionella often give a non-productive or “dry” cough. • Physical examination: rales + signs of consolidation (with typical pneumonia): • Dullness to percussion. • Bronchial breath sounds. • Increased vocal fremitus. • Egophony (E changes to A).

22. Infectious Diseases Review • Pneumonia: • Diagnosis: • The most important initial test for any type of pneumonia is chest x-ray (CXR): • S.pneumoiae and other causes of typical pneumonia usually appear as a lobar pneumonia with parapneumonic pleural effusion. • Interstitial infiltrates are associated with PCP, viral, Mycoplasma, Chlamydia and sometimes Legionella pneumonia. • Sputum culture is the most specific diagnostic test for lobar pneumonia, such as with S.pneumoniae, Staphylococcus, Klebsiella and Hemophilus. • Treatment: • In most inpatient cases: 3rd generation cephalosporin (ceftriaxone) combined with a macrolide (azithromycin).

23. Good Luck!Wish You All The Best 