2 \200\2235 d Undercooked have red blood cell [RBC] or WBC), abdominal pain, headache, myal- gias, fever Bloody diarr hea, tenesmus, pus in stools, abdominal pain, fever chicken, raw milk, non- chlorinated water Shigella spp. 12 \200\22350 h Any food (Continued) s e s a e s i d Table 14.16 (Continued) Causative agent Incubation period 12 \200\22372 h Predominant Clinical features Bloody diarrhea, hemolytic-ure- mic syndrome Diarrhea, cramps , low-grade fever Food associations Undercooked hamburger meat E. coli type 0157:H7 s u o i t c e f n I E. coli Contaminated water/food in developing countries Undercooked (enterotoxigenic) E. coli Watery or bloody (enteropathogenic) diarrhea, Meningoen- cephalitis, septicemia, often preceded by influenza- like symptoms, so metimes GI symptoms Diarrhea, may be bloody, fever, leuko- cytosis, may lead to toxic megac olon/ perforation meat Listeria monocytogenes Days to weeks Meats, cheese, p t s, raw milk Clostridium difficile Antibiotic exposure Cryptosporidium 4 \200\22312 d Diarrhea Contaminated water/food, manure Contaminated Giardia lamblia 1 1 \200\2234 wks Diarrhea, lactose intolerance Diarrhea, abdomi- water Balantidium coli Variable, often asymp- tomatic Contaminated nal pain water Characteristic Community acquired or recent Testing (stool) Salmonellosis, Shigellosis, E. coli travel Nosocomial >7 d of symptoms and/or immuno- 0157:H7 C. difficile Cryptosporidium , Giardia , 545 suppressed patients Cyclospora , Isospora , lactofer- rin, Salmonella , Shigella , E. coli 0157:H7. Add Microsp oridia and MAI, CMV, lymphoma in highly immunosuppressed. (Continued) Table 14.16 (Continued) Management is usually symptomatic. Maintain oral fluid intake ( oral rehydration solution ). For severe symptoms (but not in dysen- tery), give antiemetic (e.g., prochlorperazine 12 .5 mg/6 h IM) and an antidiarrheal (e.g., codeine 30 mg PO/IM or loperamide 4 mg initially then 2 mg after each loose stool). In general, routine antibiotics may cause more harm than good, and antimotility agents should be avoided in those with C. difficile infection. Anti biotics are generally recommended in travelers \200\231 diarrhea (often Enterotoxigenic E. coli ) and in patients who are systemically unwell, immunosuppressed, or elderly. Treat all typhi species of Salmonella and non-typhi in patients who are >50, or have prosthetic devi ces, severe atherosclerosis, valvular heart disease, cancer, uremia. Organism Vibrio choler a Treatment (when electing to treat) Doxycycline 300 mg PO \227 1, TMP/SMX DS/12 h PO \227 3 d, ciprofloxacin 1 g PO \227 1, Azithromycin 1 g PO \227 1 Salmonella TMP/SMX DS/12 h PO, Ciprofloxacin 500 mg/12 h PO, ceftriaxone 1 \200\2232 g/24 h IV X 5 \200\2237 d (lon- ger if immunocompromised or extraintestinal) TMP/SMX DS/12 h PO, ciproflo xacin 500 mg/12 h PO, azithromycin 500 mg \227 1, then 250 mg/12 h PO, ceftriaxone 1 \200 \2232 g/24 h \227 3 \200\2235 d (longer if immunocompromised) Shigella Campylobacter Erythromycin 500 mg/12 h PO \227 5 d (longer if immunocompromised) E. coli species (except enterohemorrhagic) TMP/SMX DS/12 h PO, ciprofloxacin 500 mg/12 h PO \227 3 d C. difficile: STOP Metronidazole 500 mg/8 h PO or oral vancomy- causative antibiotic if possible cin 125 \200\223250 mg/6 h \227 10 d or longer Cyclospora, Isospora TMP/SMX DS/12 h PO \227 7 \200\22310 d (consider q6h and longer in immunocompromised) Metronidazole 250 \200\223500 mg/8 h \227 7 \200\22310 d Metronidazole 750 mg/8 h \227 7 \200\22310 d + luminal Giardia E. histolytica agent (iodoquinol 650 mg/8 h \227 20 d or paro- momycin 500 mg/8 h \227 7 d) Balantidium coli Tetracycline 500 mg/6 h \227 10 d, iodoquinol 650 mg/8 h \227 20 d, metronidazole 750 mg/ 8 h \227 5 d 546 Bad Bug Book: Foodborne Pathogenic Microorganisms and Natural Toxins Handbook . Washington, DC: U.S. Food and Drug Administration, 2012. Evaluating the tropical traveler In every ill traveler, consider Malaria: Presentation : Fe ver, rigors, headaches, dizziness, flu-like symptoms, diarrhea, and thrombocytopenia. Compl ications: Anemia, parasite counts >5%, renal failure, pulmonary edema, cerebral edema. Diag nosis: Serial thick and thin blood films. Note : Mosquitoes may stowaway in luggage causing malaria in nontropical areas. Typhoid: Presents with fever, relative bradycardia, abdominal pain, dry cough, constipation , lymphadenopathy, headache, and splenomegaly rose spots (rare). Complications: GI perfo ration. Diagnosis: Blood or stool culture. Dengue fever: Presents with fever, headache, mya lgias, rash (flushing or petechial), thrombocytopenia, and leucopenia. Diagnosis: Serology. Amoebic liver abscess: Presents with fever, jaundice, right upper quadrant (RUQ) pain. Do serology and ultrasound. Blood cultures to rule out septicemia. See Table 14.17. A visit to the tropics does not preclude the mundane fevers (e.g., flu). Jaundice Think of viral hepa titis, cholangitis, liver abscess, leptospirosis, typhoid, malaria, dengue fever, yellow fe ver, and hemoglobinopathies. Hepatosplenomegaly leishmaniasis, schistosomiasis, toxoplasmos is. Gross splenomegaly Malaria, visceral leishmaniasis (kala-azar). Diarrhea and vomiting E nterotoxigenic E. coli (travelers \200\231 diarrhea) is most common. Consider Salmonella , Shigella , Campylobacter , Giardia lamblia, Vibrio cholerae, Yersinia, Cryptosporidium, Iso spora, E. coli 0157, Enteroinvasive E. coli, Aeromonas, Rotavirus, Noroviruses, etc. If dia rrhea prolonged, consider protozoal infection of small bowel or tropical sprue. In HIV: MAC , CMV, Cryptosporidium, Microsporidium , and Isospora belli . Respiratory symptoms Common r espiratory pathogens, typhoid, Legionella , TB, Q fever, histoplasmosis, L ffler \200 \231s syndrome. Arthritis Gonococcus; septicemia; viruses (Ross River, Chikungunya). Erythe ma nodosum Causes: Strep, TB, leprosy, fungi, Crohn \200\231s, ulcerative colitis, sarcoido sis, pregnancy, drugs (sulfonamides). Anemia Hookworm, malaria, kala-azar, hemolysis, and m alabsorption. Skin lesions Scabies (itchy allergic rash + burrows, e.g., in finger web- spa ces), bed bugs (grouped papules), myiasis (nodules \200\224larvae of various insects), orf (pustules), molluscum contagiosum (pearly, punctate, papules), leprosy (anesthetic, hypopig mented areas), Loa loa (calabar swellings), cercarial dermatitis (swimmer \200\231s itch), leishmaniasis (ulcers/nodules), rickettsial infections (African tick typhus, Mediterranean tick typhus, scrub typhus [painless eschar = scab]), drug reactions. Acute abdomen Perforat ion of a typhoid ulcer, toxic megacolon in amoebic or bacillary dysentery, sickle-cell cris is, ruptured spleen. Rarities to consider Use local emergency isolation policy. Rabies and other CNS viral infections (e.g., encephalitis). Yellow fever : Suspect in travelers from A frica. Lassa fever: Occurs in Nigeria, Sierra Leone, or Liberia. Signs: Fever; sore throat with exudates, face edema; shock. Marburg and Ebola virus: Seen in Sudan, Zaire, and Kenya. Signs: Fever, myalgias, diarrhea, nausea and vomiting (N&V), pleuritic pain, hepatitis, sh ock, and bleeding tendency. Maculopapular rash appears on day 5 \200\2237 and desquamates i n <5 d. Patients may bleed from all orifices and gums. Viruses that cause hemorrhage: Dengu e, Marburg, Lassa, Ebola, Crimea-Congo fever, hemorrhagic fever with renal syndrome, yellow fever. s e s a e s i d s u o i t c e f n I Viral hepatitis, malaria, Brucella , typhoid, 547 Table 14.17 Incubation times for fever in the tropical traveler The incubation times below are typical, but considerable variation occurs. <14 d Undifferen tiated fever Malaria Typhoid Leptospirosis Acute HIV infection Dengue fever Rickettsial 2 \200\2236 wks >6 wks Acute schistosomiasis Hepatitis E Hepatitis A Amoebic liver abscess Lymphatic filariasis Kala-azar Hepatitis B Fever with CNS signs <14 d East African trypanosomiasis Rabies Viral and bacte- rial mening itis/ encephalitis 2 \200\2236 wks >6 wks Poliomyelitis African trypanosomiasis Fever with chest signs <2 wks Q fever Histoplasmosis Coccidioidomycosis Influenza Legionell osis SARS 2 \200\2236 wks >6 wks 548 Tuberculosis Ryan ET. Illness after International Travel. N Engl J Med. 2002;347:505 . Malaria Clinical features and diagnosis Malaria is caused by plasmodium pro- tozoa injected by the nighttime biting female Anopheles mosquito. P . fal- ciparum and P. vivax are the m ost common. The organisms multiply in the liver and then infect RBCs causing hemolysis, RBC sequestration, and cytokine release. Malaria is one of the most common causes of fever and illness in the tropics. There are >200 million cases of malaria each year. The infection k ills nearly 800,000 people each year, mostly children in Africa. Partially protective immun ity develops over time, but wanes once a person leaves an endemic area. Thus, expatriates a nd travelers who normally live in nonendemic areas and enter malarious regions are at high risk for severe complications. P. falciparum malaria is the most deadly. Incubation: 12 d. Most travelers present within 2 months. Symptoms: Nonspecific flu-like prodrome: Headache, malaise, myalgias, and anorexia followed by fever and chills syncope. Classic periodic f ever (peaking every third day, i.e., tertian), headache and rigors are unusual initially. S igns: Anemia, jaundice, and hepatosplenomegaly. No rash or lymphadenopathy. Complications: Cerebral malaria: Seizures confusion then coma. Focal signs unusual. May have variable t one, extensor posturing; up going plantars, dysconjugate gaze. Mortality: 20%. Metabolic ( lactic) acidosis giving labored deep (Kussmaul \200\231s) breathing also major cause of dea th. Anemia is common due to hemolysis of parasitized RBCs. Elevated transaminases levels, h yperparasitemia (>5% of RBCs parasitized), and hypoglycemia can occur in severe malaria (8% of adults) or with quinine therapy. Acute renal failure from acute tubular necrosis, somet imes with hemoglobinuria ( blackwater fever ), and pulmonary edema are important causes of death in adults. Shock may develop in severe malaria ( algid malaria ) from bacterial septi cemia, dehydration or, rarely, splenic rupture. In pregnancy, the risk of miscarriage is up to 60% and death in the mother is up to 50%. Advise pregnant women to defer travel to mala rious regions. If that is not feasible, meticulous mosquito avoidance and chemoprophylaxis should be used. Relapse occurs as parasites lie dormant in the liver ( P. vivax and P. oval e ) or at low levels in the blood ( P. malariae ). Nephrotic syndrome (glomerulonephritis) may occur in chronic P. malariae infection. Diagnosis Serial thin and thick blood films (ne eds much skill, don \200\231t always believe negative reports or reports based on thin-movi e examination alone); if P. falciparum , use smears to determine level of parasitemia. Anti gen detection of P. falciparum and P. vivax using rapid diagnostic tests is emerging as an option in settings lacking timely access to high quality microscopy. Serology is not useful . Other tests: CBC (anemia, elevated transaminases, thrombocytopenia), clotting, glucose (h ypoglycemia), ABG/lactate (lactic acidosis), electrolytes (renal failure), urinalysis (hemo globinuria, proteinuria, casts), blood culture. See Table 14.18. Poor prognostic signs Seve re P. falciparum malaria, >5% parasitemia, hypotension, severe anemia, DIC, spontaneous ble eding, jaundice, seizures, impaired consciousness/ coma, repeated seizures, respiratory dis tress, acidemia, renal failure, hemo- globinuria. If 20% (or >10 4 /mcL) of parasites are m ature trophozoites or schizonts, the prognosis is poor, even if few parasites seen (reflect s critical mass of sequestered RBCs) s e s a e s i d s u o i t c e f n I 549 Table 14.18 Key points in diagnosis and management of malaria Think about malaria as a possible diagnosis! Take a full travel history, including stopover s in transit Before excluding the diagnosis, make sure enough blood smears (three sets) hav e been performed and check if the patient has already received treatment, which might make the blood smear negative. Don \200\231t delay therapy when there is a strong clinical suspi cion, severe dis- ease, or difficulty in getting timely laboratory confirmation of infectio n. Use IV quinidine as part of therapy in patients with severe disease. Make sure the drug gets to the patient promptly. Avoid potential delays due to inadequate communication betwee n medical, nursing and phar- macy staff. Do not delay therapy while trying to figure out if the patient should get artesunate or an exchange transfusion. Unless certain, assume patie nt has P. falciparum and that the infection is chloroquine resistant. Follow the patient cl osely for first few days. Remember that malaria is an important cause of coma, deep jaundic e, severe anemia, and renal failure in the tropics. Treatment If species unknown or mixed infection, treat as P. falciparum . Nearly all P. fal ciparum is now resistant to chloroquine and in many areas is also resistant to Fansidar ( pyrimethamine + sulfadoxine). If in doubt, consider as resistant. Chloroquine is the drug o f choice for nonfalciparum malarias in most parts of the world, but chloroquine-resistant P . vivax occurs in Papua New Guinea, Indonesia, and some areas of Brazil, Colombia, and Guya na. Never rely on chloroquine if used alone as prophylaxis. P. falciparum is still suscepti ble to chloroquine in Central America (West of the Panama Canal Zone), Haiti, Dominican Rep ublic, and most of the Middle East. See Table 14.19. If seriously ill, take to ICU and give quinidine IV with telemetry. Observe for QT prolongation, ventricular arrhythmias, hypoten sion and hypogly- cemia. Consider exchange transfusion if parasitemia is >10%, patient has altered mental status, ARDS or renal complications. Do not delay quinidine for exchange tra nsfusion . Artesunate can be obtained from CDC for severe malaria. CDC Malaria Hotline: 770 \200\223488 \200\2237788, 855 \200\223856 \200\2234713 (toll free), (770 \200\223488 \200 \2237100 (after hours) 550 s e s a e s i d Table 14.19 Malaria treatments Organism Uncomplicated P. falciparum (CQ susceptible), P. malariae , P. knowlesi, species n ot known Uncomplicated P. falciparum (CQ resistant or unknown) Modifying factor CQ 1,000 mg \227 1, then 500 mg at 6, 24, and Regimen 48 h s u o i t c e f n I Hydroxy-CQ 800 mg \227 1, then 400 mg at 6, 24, and 48 h Atovaquone (250 mg)/Proguanil (100 mg) 4 tabs/24 h \227 3 d Avoid in pregnancy Artemether (20 mg)/lumefantrine (120 mg) 4 tabs, Day 1 given at 0 and 8 h, d 2, 3 bid (total = 24 tabs) Avoid in pregnancy Quinine sulfate 650 mg/8 h \227 3 d (7 d if malaria acquired in SE Asia) and doxycycline 100 mg/12 h PO \227 7 d (or clindamycin 7 mg/kg/8 h P O \227 7 d) Avoid doxycycline in pregnancy Uncomplicated P. vivax, P. ovale CQ 1,000 mg \227 1, then 500 mg at 6,24 and 48 hours or Hydroxy-CQ 800 mg \227 1, then 400 mg at 6, 24, and 48 h and Primaquine 30 mg/24 h \227 14 d to treat liver stage and prevent relapse. Avoid in G6PD deficiency (screen before giving) and pregnancy Severe (typically P. Quinidine gluconate: 10 mg/kg loading dose IV over 1 \200\2232 h, then 0.02 mg/kg/min conti nuous infusion \227 24 h. After 24 h, if parasitemia is <1% and patient can tolerate orals , switch IV quinidine to PO quinine, otherwise continue IV. Total quinidine/quinine course generally 3 d (7 d if disease acquired in SE Asia) falciparum ) and Doxycycline 100 mg/12 h PO or IV \227 7 d (or clin- damycin 7 mg/kg/8 h PO. If giving IV: 10 mg/kg \227 1 then 5 mg/kg/8 h \227 7 d). Avoid doxycy- cline in pregnancy CQ, chlo roquine, all CQ, H-CQ, quinine and quinidine doses are for salt form of drug. 551 Other treatments Acetaminophen for fever. Transfuse if severe anemia. Consider exchange tra nsfusion if patient severely ill. Monitor bp, urine output, and blood glucose frequently. F ollow daily parasite count, platelets, LFT, and electrolytes. Antimalarial side effects \212 Artemether/lumefantrine: \212 Atovaquone/Proguanil: GI disturbances, dizziness, blurr ed \212 Chloroquine and hydroxychloroquine: vision, headache, insomnia, pruritus psychosis and retinopathy (chronic use) Doxycycline: esophagitis Headache, anorexia, and dizziness Abdominal pain, GI disturbances, headache \212 Phototoxicity, yeast vaginitis, GI disturbances, and pill \212 GI disturbances, headache, and neuropsychiatric symptoms Mefloquine: ranging from sleep dis turbances to psychosis. Avoid mefloquine if low risk of chloroquine-resistant malaria, past or family history of epilepsy, or need to perform complicated task (e.g., pilots). Give pa tient FDA meflo- quine medication guide. Primaquine: moglobinemia \212 Epigastric pain, hemolysis if G6PD-deficient, methe- Mycobacterium tuberculosis Basic terms Latent infection: Presence of M. tuberculosis in the body (detected by TST or IGRA) without disease. This person is not infectious. Active TB: Evidence of active infection (e.g., abnormal CXR) in a person with + TST or IGRA and/or sme ar, culture or polymerase chain reaction (PCR) evidence of M. tuberculosis. Clinical featur es Approximately one-third of the world \200\231s population is infected with TB. The vast majority (90%) will not develop active TB. The prevalence and mortal- ity of TB has decline d in recent years, but in 2010 there were about 9 million new active TB cases and 1.4 milli on deaths from TB. The rates of developing active infection are much higher in those with H IV. TB is the leading cause of death in people with HIV. In the United States, great stride s have been made in controlling TB. In 2009, there were about 11,000 new cases and 500 deat hs. About 3.3% of new TB cases are due to MDR-TB (resistant to isoniazid and rifampin). Mos t of those are from Eastern Europe, Asia, and parts of Africa. There are an estimated 25,00 0 cases/year of XDR-TB (resistant to isoniazid [INH], rifampin, quinolones, amikacin, capre omycin, and kanamycin). Primary TB Initial infection is usually pulmonary (by droplet sprea d). A lesion forms and its draining nodes are infected. There is early distant spread of th e bacilli, then an immune response suspends further multiplication at all sites. Primary TB is often asymptomatic or there is fever, anorexia, productive cough, or conjunctivitis (sm all, multiple, yellow-gray nodules near the limbus). Acid-fast bacilli (AFB) may be found i n sputum. CXR may be abnormal. The commonest nonpulmonary primary infection is GI, typicall y affecting the ileocecal junction and associated lymph nodes. Latent TB Rates of latent TB are highest in close contacts of those with active TB, homeless, foreign-born persons, pri soners, and injection drug users. Universal screening (with TST or IGRA) is not recommended . Many people with latent TB are at low risk for reactivation, and many false- positive tes ts are expected in low-risk groups. Screening is most useful (with an intention to treat po sitive results) in people with HIV, recipients of immunosuppressive medications, the homele ss, injection drug users, health care workers, and people whose test is newly positive (wit hin 2 yrs). 552 s e s a e s i d Table 14.20 Tests to diagnose latent tuberculosis (TB) Tuberculin skin test (aka Mantoux, TST, PPD) Read at 48 \200\22372 h Positive test Patient characteristic (induration diameter) \200\234 5 mm HIV+, TNF- \222 inhibitors, recent contact with per- son who has active TB, organ transpla nt recipi- ents, corticosteroids (e.g., prednisone >15 mg/d \227 >1 month), fibrotic chang es on CXR Recent immigrants from endemic regions, injec- tion drug users, lived or worked i n high-risk setting (e.g., homeless shelter, prison, health care facility, microbiology lab oratory), high-risk clinical condi- tions (e.g., chronic renal disease, silicosis, diabetes , heme malignancies, gastrectomy, chronic weight loss) No known risk factor for TB BCG vacc ine , may give a false positive skin test result, but results should be interpreted regardl ess of BCG history Interferon -release assays (IGRA) requires a blood sample, does not c ross-react with BCG, does not require a return visit to read skin reaction. Treatment of la tent TB: The goal is to eradicate the latent infections in patients at risk for reactivatio n. First step is to rule out active infection. In all cases, standard anti-TB therapy shoul d be initiated once any evidence of active disease (clinical or radiographic) is found to a void treatment failure and development of resistance. Regimen INH 300 mg/d \227 9 s u o i t c e f n I \200\234 10 mm \200\234 15 mm Comment \200\234Classic \200\235 regimen months INH 900 mg twice Use directly observed therapy weekly \227 9 months INH \227 6 months 9 months better, but 6 months will provide some protection Rifampin 600 mg/d \227 Lower risk of hepatotoxicity compared with INH, 4 months multiple drug interactions Use directly observed therapy INH 900 mg/rifapen- tine 900 mg/week \227 12 (doses based on weight \200\234 60 kg) 553 If there is a known contact with a person infected with INH-resistant TB, rifampin is an al ternative, but seek help. Reactivation >80% of active TB in the United States is due to rea ctivation from latent infection. Reactivation rates are particularly high in the first few years after TB exposure. Any form of immunocompromised may allow reactivation (e.g., HIV, m alignancy, poorly controlled diabetes, >2 wks of 15 mg/d prednisone, debilitation, treat ment with TNF- inhibitor, and chronic renal failure). Reactivation is significantly asso ciated with radiographic evidence of old healed (untreated) TB. The lung lesions, which usu ally are in the upper lobes, can progress and fibrose. Any other site may become the main c linical problem. Tuberculomas contain few AFB unless they erode into a bronchus, where the favorable environment ensures rapid multiplication, rendering the patient highly conta- gious. In the elderly or immunocompromised, dissemination of multiple tiny foci throughout the body (inc luding back to the lungs) results in miliary TB. Pulmonary TB This may be silent or present with cough, sputum, malaise, weight loss, night sweats, pleurisy, hemoptysis (may be massi ve), pleural effusion, or superimposed pulmonary infection. An aspergilloma/mycetoma may fo rm in the cavities. Miliary TB Occurs following hematogenous dissemination. Clinical featur es may be nonspecific. CXR shows characteristic reticulonodular shadowing. Look for retinal TB. Biopsy of lung, liver, lymph nodes, or marrow may yield AFB or granulomas. Meningeal T B Subacute onset of meningitis symptoms: Fever, headache, nausea, vomiting, neck stiffness, and photophobia. Genitourinary TB May cause frequency, dysuria, flank/back pain, hematuria , and, classically, sterile pyuria. Take three early-morning urine samples for AFB. Renal u ltrasound may help. Renal TB may spread to bladder, seminal vesicles, and epididymitis or f allopian tubes. Bone TB Look for vertebral collapse adjacent to a paravertebral abscess (Po tt \200\231s vertebra). Do biopsies for AFB stains and culture. Skin TB (lupus vulgaris) Je lly-like nodules; e.g., on face or neck. Peritoneal This causes abdominal pain. Look for AF B in ascites (send a large volume to lab); laparotomy may be needed. Acute TB pericarditis Think of this as a primary exudative lesion. Chronic pericardial effusion and constrictive pericarditis These reflect chronic granulomas. Fibrosis and calcification may be prominent with spread to myocardium. Additional points in all those with TB Advise HIV testing. Notif y local health department to arrange contact tracing and screening. Explain that prolonged treatment will be nec- essary. All patients should receive directly observed therapy (DOT). Monitoring of blood tests will be needed (LFTs). Explain the need for respiratory isolatio n procedures while infectious until three negative sputa for AFB. See Table 14.21. Tuberculosis diagnosis and treatment Diagnosis In all suspected cases, it is important to o btain the relevant clin- ical samples (sputum, pleural fluid, pleura, urine, pus, ascites, peritoneum, or CSF) for culture (or other testing) to establish the diagnosis. Get advice o n testing contacts from health department. Microbiology: AFB resist acid \200\223alcohol de colorization under auramine or Ziehl \200\223Neelsen (ZN) stain- ing. Sputum sample typical ly show few if any AFB. Send three expectorated sputum samples, preferably on different day s, for AFB stain and culture. Cultures require prolonged incubation (usually 2 \200\2236 wk s or longer). Sputum may be induced with aerosolized hypertonic saline. If no expectoration s, bronchoalveolar lavage (BAL) fluid can be tested. Smears of BAL fluid can be negative ev en when there is extensive disease. Many patients develop productive sputum after bronchosc opy. This sputum should be tested for AFB. Any suspicious lesions in liver, lymph nodes, or bone marrow can be biopsied. TB PCR: Can be applied to AFB + sputum specimen to facilitate rapid diagnosis of TB. A negative PCR does not rule out TB. In- terpretation of AFB negati ve smears with + PCR requires clinical judgment. PCR can also be used to test CSF, pleural and peritoneal fluid specimen. New PCR-based tests allow rapid identification of rifampicin (and likely multi-drug) resistance. Histology: The hallmark is the presence of case- 554 s e s a e s i d ating granulomas. Radiological features: CXR may show consolidation, cavitation, fibrosis , and calcification in pulmonary TB Phases of therapy Initial phase (8 wks on four drugs) is followed by continuation phase (4 months on two drugs) with rifampicin and INH at same dos es. Give pyridoxine throughout treatment. There are multiple dosing schedules: Phase 1 (8 w ks): INH/rifampin/PZA/ethambutol: 7 d/wk \227 8 wks, 5 d/wk \227 8 wks, 5 d or 7 d/wk \227 2 wks, then 2 \227 /wk \227 6 wks, 3 d/wk \227 8 wks. Phase 2 (18 wks): INH/rifampi n: There are multiple dosing schedules including: 7 d/wk \227 18 wks, 5 d/wk \227 18 wks, 3 d/wk \227 18 wks, 2 d/wk \227 18 wks s u o i t c e f n I Table 14.21 Tuberculosis and HIV/AIDS TB is a common, serious, but treatable complication of HIV infection. Worldwide, 10% of pat ients with new cases of TB also have HIV (40% in Africa). Screening tests may be negative w ith CD4 <200. After initiation of anti- viral therapy, retest those with negative TB test. Reactivation of latent TB can occur at any CD4 level Presentation may be atypical. Previous BCG vaccination does not prevent development of TB. Smears may be negative for AFB in pati ents with pulmonary TB with or without HIV. Smears that are positive tend to contain few AF B. This makes culture all the more important and is vital to characterize drug resistance. Atypical CXR: Lobar or bibasilar pneumonia, hilar lymphadenopathy. Extra pulmonary and diss eminated disease is much more common. More toxicity from highly active antiretroviral thera py and anti-TB ther- apy due to drug interactions with rifampin. Antiretroviral therapy rec onstitutes CD4 count and immune function, which may lead to a paradoxical worsening of TB s ymptoms. All persons with HIV who have evidence of latent TB should be treated. Respiratory isolation is essential when TB patients are near other patients, including those who are H IV positive. Nosocomial (hospital-acquired) and MDR-TB are now major problems worldwide. Mo rtality with MDR-TB is high. Test TB cultures against first- and second-line chemotherapeut ic agents; 5+ drugs may be needed in MDR-TB. Basic principles of treatment: 1. Adherence to therapy is crucial. It helps the patient, reduces develop- ment of resistance, and inhibit s further propagation of infection. 555 2. DOT is the preferred method of assuring adherence. 3. Treatment is long and should be co ordinated with the health department. 4. Monitor for toxicity (symptoms, CBC, liver, and renal function). A small rise in LFTs is common and acceptable and often resolves with- out change in therapy. Ethambutol may cause ocular toxicity, so test color vision (Ishihara chart) and acuity bef ore and during treatment if using ethambutol dose \200\234 25 mg/kg/d. 5. Seek help in patients with renal or hepatic failure, or pregnancy. 6. Steroids may be in dicated in meningeal and pericardial disease. (Continued) Table 14.21 (Coninued) Drug First-line antitubercular agents: All are PO. All doses given as daily. Intermittent d osing options should be given as DOT Isoniazid Dose (max) Potential side effects 5 mg/kg/d (300 mg), 15 mg/kg (900 mg) once, twice, or thrice weekly 10 mg/kg (600 mg) daily , twice or thrice weekly Hepatitis, neuropathy, pyri- doxine deficit, agranulocytosis Rifampin Hepatitis, orange discol- oration of urine and tears (contact lens staining), rash, many dr ug interactions (e.g., inactivation of birth control pills), flu-like syndrome with intermi ttent use. Heme toxicities, rash, GI intolerance, drug interac- tions often require dose ad justments Optic neuritis, color vision is first to deteriorate Rifabutin 5/mg/kg (300 mg) daily, twice or thrice weekly Ethambutol 15 mg \200\22320 mg/kg/d, 56 \200\22375 kg: 2 g thrice/wk, 2.8 g twice/wk 76 \200\22390kg: 2.4 g thrice/wk, 4 g twice/wk 20 \200\22325 mg/kg/d, 56 \200\22375 kg: 2.5 g thrice/ wk, 3 g twice/wk 76 \200\22390 kg: 3 g thrice/wk, 4 g twice/wk Hepatitis, non-gout polyar- thritis, arthralgias (gout is a contraindication) Pyrazinamide Second-line antitubercular agents : Associated with increased toxicity, some only available by injection Cycloserine 10 \200\22315 mg/kg/d (1,000 mg). Usually 500 \200\223750 mg/d in two doses Neuropsychiatric (includ- ing psychosis and seizures). Pyridoxine (100 \200\223200 mg/d) ma y help Severe GI, liver, endocrine, neuropathy Nephrotoxicity and ototoxicity Ethionamide 10 \200\22315 mg/kg/d (1,000 mg). Usually 500 \200\223750 mg/d 15 mg/kg/d (1 g) Streptomycin, amikacin, kanamycin, capreomycin (injected) p- Amino- salicylic acid Quinolon es 556 4 g/8 \200\22312 h/d Hypothyroid, GI, liver Levofloxacin: 500 \200\2231,000 mg/d Moxifloxacin: 400 mg/d GI, liver, neuropathy, tendinopathy (Continued) s e s a e s i d Table 14.21 (Coninued) Stopping the spread of MDR-TB Early identification and isolation and full treatment: Contro l depends upon early isolation of suspected patients. If there is a suspicious CXR or a pas t history of MDR-TB, don \200\231t wait to prove the diagnosis. Isolate. Isolate if cough > 2 wks and abnormal CXR. Provide negative air pressure in isolation rooms and N95 masks for staff. Obtain respiratory samples for microbiology testing in a timely fashion. Sputum indu ction/expectoration should be confined to isolation rooms. Only stop isolation after three sputum samples are AFB negative on culture for MDR-TB. Remove bar- riers for completion of therapy. Best achieved by directly observing and confirming that patients take all prescrib ed drugs. Frequent tuberculin skin surveillance tests for workers and contacts. Contact eva luation. s u o i t c e f n I Herpes infections Varicella zoster Chickenpox is the primary infection; after infection, vi - rus remains dormant in dorsal root ganglia. Reactivation causes shingles. Shingles affect s 20% at some time. High-risk groups: Elderly or immuno- suppressed. Clinical features: Pai n in a dermatomal distribution precedes malaise and fever by a few days. Some days later, m acules, papules, and vesicles develop in the same dermatome. Thoracic dermatomes and the op hthalmic division of trigeminal nerve are most vulnerable. If the sacral nerves are affecte d, urinary retention may occur. Motor nerves are rarely affected. Herpes zoster oticus (Ram sey Hunt syndrome II) involves the ear, mouth, and CN VII). Zoster recurrence suggests immu nosuppression. Investigations are rarely necessary; diagnosis can be confirmed by PCR, immu nohistochemical study, and culture of suspected lesion fluid. Indications for treatment (sy stemic antiviral therapy): All immunocompromised patients, otherwise: Age \200\234 50, mod erate or severe rash/pain, nontruncal involvement. Consider therapy in all patients to redu ce risk of postherpetic neuralgia. If possible, start therapy <72 h after onset. For immuno competent patients, use PO acyclovir 800 mg/4 \200\2235 h, famciclovir 500 mg/8 h, or valac yclovir 1 g/8 h for 7 \200\22310 d. If patient severely immunocompromised, start with IV ac yclovir 10 mg/kg/8 h until infection is controlled, then switch to oral therapy. For less i mmunosuppressed patients, try oral famciclovir or vala- cyclovir as initial therapy (with c areful monitoring). Control pain with oral analgesic gabapentin, tricyclics, carbamazepi ne, lidocaine patch and/or narcotics (underutilized). A course of corticosteroids tapered o ver 3 wks (prednisone 60 mg, 30 mg, 15 mg) can be considered in patients without contraindi cations. Care of herpes zoster ophthalmicus should involve an ophthalmologist. Use IV acycl ovir in cases of retinitis. Use topical anti- bacterial to protect ocular surface. Beware o f iritis. Measure visual acuity often. Advise patient to report any visual loss at once. SE of acyclovir: Renal impairment (check electrolytes) vomiting, urticaria, and encephalopath y. Complications: Postherpetic neuralgia in the affected dermatome can persist for years an d be very hard to treat. Try carbamazepine, phenytoin, amitrip- tyline, gabapentin, or caps aicin cream and narcotics. As a last resort, abla- tion of the appropriate ganglion may be tried. Refer to a pain clinic. 557