586 skin paucibacillary disease is treated with a rifampin 600 mg, ofloxacin 400 mg, and minocy cline 100 mg as a one-time treatment. Beware of inflammatory reactions with therapy caused by infection and/or dying bacilli. Erythema nodosum leprosum , which may present as sudden nerve inflammation ( orchitis, lymphadenitis, nephritis, periostitis, irido- cyclitis) ma y be seen with treatment of widespread infection. Treat with steroids and referral to ophth almologist for ocular disease. Thalidomide or clofazimine may be useful. The latter causes skin pigmentation. Edema and erythema of preexisting lesions (reversal reactions) may even cause skin ulceration and neuritis. Treat with corticosteroids. Neuritis can occur in the a bsence of a reactive episode and may respond to steroids. s e s a e s i d s u o i t c e f n I Spirochetes Lyme disease is a tick-borne infection caused by Borrelia burgdorferi . Al- tho ugh originally described in Lyme (Connecticut) it is now widespread. Not all will remember being bitten by a tick. Presentation: Erythema migrans malaise, cognitive impairment, ly mphadenopathy, arthralgias, myocarditis, heart block, meningitis, ataxia, amnesia, cranial nerve palsies (Bell \200\231s pal- sy), neuropathy, lymphocytic meningoradiculitis (Bannwar th \200\231s syndrome). Diagnosis: If erythema migrans is present at evaluation, then serol ogy is not needed. Otherwise, diagnose using clinical features + serology at 4 \200\2236 wk s. Serology is a two-step process with a screening ELISA followed by confirmatory IgG and I gM immunoblot if ELISA is positive. If symptoms are present >4 months, IgG must be present to be considered positive. Treatment: Skin rash, isolated cranial nerve palsy: Doxycycline 100 mg/12 h PO (amoxicillin, cefuroxime also active) for 14 \200\22321 d, arthritis (21 d). CNS, peripheral nerve disease, carditis, or recurrent arthritis: Ceftriaxone 2 g/d IV (cef otaxime, PCN G also good). Prevention: Keep limbs covered; use insect repellent; tick colla rs for pets; check skin often when in risky areas. Vaccination is no longer available. A si ngle dose of doxycycline 200 mg PO given within 72 h of a bite is effective prophylaxis; in highly endemic areas, this may be worthwhile (e.g., if risk is >1%). Removing ticks: Using fine- tipped tweezers, gently remove tick by grasping it as close to skin surface as possi ble, then pull up with steady, even pressure. Endemic treponematoses Yaws is caused by T. p ertenue , which is serologically indistinguishable from T. pallidum . It is a chronic granu lomatous disease prevalent in children in the rural tropics. Spread is by direct contact, v ia skin abrasions, and is promoted by poor hygiene. The primary lesion (an ulcerating papul e) appears 4 wks after exposure. Scattered secondary lesions then appear (e.g., in moist s kin, but can be anywhere). These may become exuberant. Tertiary lesions are subcutaneous gu mmatous ulcerating granulomata, affecting skin and bone. Cardiovascular and CNS complicatio ns do not occur. Pinta ( T. carateum ) affects only skin; seen in Central and S America. En demic nonvenereal syphilis (bejel ; T. pallidum ) is seen in third-world children, when it resembles yaws. In the developed world, T. pallidum causes syphilis. Diagnosis: Clinical. T reatment: Procaine penicillin. Leptospirosis Caused by bacteria in the genus Leptospira . S pread is by contact with soil or water contaminated by urine or body fluids of infected ani mals (e.g., rodents, livestock, and dogs). Typical exposures involve swimming/rafting/kayak ing in fresh water, especially in tropical regions (e.g., Hawaii, Caribbean) and exposure t o surface water in endemic regions. Presentation: Fever, jaundice, headache, red conjunctiv ae, tender legs (myositis), purpura, hemoptysis, hematemesis, or any bleeding. Meningitis, myocarditis, and renal failure may develop. AST rise may be small. Diagnosis: Rapid serolog ical assays are replacing the old microscopic 587 agglutination test. Also take blood, urine, and CSF culture (for 4 \200\2236 wks). Treat sy mptomatically; give doxycycline 100 mg/12 h or, in serious disease, IV benzylpenicillin 600 mg/6 h for 7 d. Prophylaxis (e.g., doxycycline 200 mg/ wk PO) may be useful for those at h igh risk for short periods. Canicola fever is aseptic meningitis caused by Leptospira canic ola . Relapsing fever Tick-borne relapsing fever (TBRF) is usually caused by Borrelia herms ii. Transmission is via a soft tick. In the United States, most cases are in western mounta inous regions. Louse-borne relapsing fever (LBRF) is caused by B. recurrentis transmitted p erson to person by the body louse. It typically occurs in epidemics following war or disast er. Illness may be severe (30 \200\22370% mortality) with enormous death tolls in outbreak settings. Incubation: 4 \200\22318 d. Presentation: Abrupt onset of fever, rigors, and head ache. A petechial rash (which may be faint or absent), jaundice, and tender hepatosplenomeg aly may develop. Serious complications include myocarditis, hepatic failure, and DIC. Crise s of very high fever and tachycardia occur. When the fever abates, hypotension due to vasod ilatation may occur and be fatal. Relapses occur, but are milder. Tests: Organisms are seen on Leishman-stained thin or thick films. Treatment: TBRF: Erythromycin 500 mg/6 h PO or IV , tetracycline 500 mg/6 h PO or 250 mg/6 h IV, or doxycycline 100 mg/12 h PO or IV \227 7 d. LBRF can be treated with a single dose of ABX. Monitor for Jarisch \200\223Herxheimer re action (fevers chills, hypotension with lysis of organisms) in first few hours after ABX. D elouse the patient and his or her clothes. Doxycycline is useful prophylaxis in high-risk g roups. Viral hemorrhagic fevers Yellow fever An epidemic arbovirus disease spread by Aedes mosquit oes (Brazil, Bolivia, Peru, and Central and West Africa). Incubation: 2 \200\22314 d. Clini - cal presentation: In mild forms, fever, headache, nausea, albuminuria, myal- gias, and re lative bradycardia. If severe: 3 d of headache, myalgias, anorexia nausea, followed by a brupt fever, a brief remission, then prostration, jaundice ( fatty liver), hematemesis an d other bleeding, oliguria. Mortality: <10% (day 5 \200\22310). Diagnosis: ELISA. Treatment : Symptomatic. Lassa fever, Ebola virus, Marburg virus, and dengue hemorrhag- ic fever (DHF ) These diseases may start with sudden-onset headache, pleuritic pain, backache, myalgias, conjunctivitis, prostration, dehydration, facial flushing (dengue), and fever. Bleeding soo n supervenes. There may be spontaneous resolution or renal failure, encephalitis, coma, and death. Treatment: Primarily symptomatic; ribavirin is useful in Lassa fever if given early in disease. Use special infection control measures (Lassa, Ebola, and Marburg); get expert help at once. Dengue is the most prevalent arbovirus disease. There is a global pandemic o f this RNA flavivirus, related to poor vector control ( Aedes mosquitoes), urbanization, an d rapid migrations bringing new strains (DEN \200\2232), which become more virulent in thos e who have had mild dengue. About 50 million cases of dengue infection occur each year and 500,000 are hospitalized each year with DHF. Infants typically have a simple febrile illnes s with a maculopapular rash. Older children/adults have flushing of face, neck, and chest o r a centrifugal maculopapular rash from day 3, or a late confluent petechiae with round pal e areas of normal skin. Also, patients may have headache, arthralgias, jaundice, hepatosple nomegaly, and anuria. Hemorrhagic signs: (Unlikely if AST normal), petechiae, GI, gum or no sebleeds, hematuria, hypermenorrhea. Monitor: BP, urine flow, WBC, HCT, PLT. A positive tou rniquet test (>20 petechiae inch 2 ) + rise in HCT by 20% are telling signs (rapid endothel ial plasma leak is the key pathophysiology of DHF). Differential diagnosis: Chikungunya, me asles, 588 leptospirosis, typhoid, malaria. Exclusion: If symptoms start >2 wks after leaving a dengue -endemic area, or if fever lasts >2 wks, dengue can be ruled out. Treatment: With more seve re disease (e.g., DHF or dengue shock syndrome) fluid and electrolyte resuscitation/managem ent is critical. Blood transfusions may be required as well. If in shock mortality is high, fluid resuscitation should be aggressive: Give a bolus of 15 mL/kg; repeat as necessary un til BP rises and urine flow is >30 mL/h. s e s a e s i d s u o i t c e f n I Rickettsia and arthropod-borne bacteria Rickettsial infections are carried by host arthropo ds and invade human mononuclear cells, neutrophils, or blood vessel endothelium (vasculotro - pic). All the cataclysmic events of the last century (war, revolution, flood, famine, gen ocide, and overcrowding) have favored lice infestation. As a result, these infections (in p articular typhus) have killed untold millions. Q fever is caused by Coxiella burnetii . It is so named because it was first labeled \200\234query fever \200\235 in workers in an Aus tralian abattoir. Epidemiology: Occurs worldwide and is usually rural, with its reservoir i n cattle and sheep. The organism is very resistant to drying and is usually inhaled from in fected dust. It can be contracted from unpasteurized milk, directly from carcasses in abatt oirs, sometimes by droplet spread, and occasionally from tick bites. Clinical features: Q f ever should be suspected in patients with FUO or atypical pneumonia. It may present with fe ver, myalgias, sweats, headache, cough, and hepatitis. In chronic cases, suspect endocardit is (typically \200\234culture-negative \200\235). This usually affects the aortic valve, b ut clinical signs may be absent. It also causes miscarriages and CNS infection. Investigati ons: CXR may show consolidation (e.g., multilobar or slowly resolving). Liver function test s may be hepatitic, and biopsy may show granulomata. Platelets may be low. Diagnosis is ser ologically, but may be negative in first 7 \200\22310 d of infection. Phase I antigens indi cate chronic infection; phase II antigens indicate acute infection. A fourfold rise antibod y titer is diagnostic. PCR may be used on serum and tissue samples. CSF tests may be needed . Treatment: Get expert microbiological help. Acute: Doxycycline 100 mg/12 h for 2 \200\223 3 wks. Chronic: Doxycycline 100 mg/12 h + Chloroquine 200 mg/8 h \227 18 months. Valve rep lacement may be needed in cases of endocarditis. Bartonellosis is caused by Bartonella baci lliformis , a gram-negative, motile, bacillus-like organism that infects red blood cells. S pread is by sandflies in the Andes regions of Peru, Ecuador, and Colombia. The disease has two phases, an acute hemolytic febrile illness called Oroya fever and an eruptive phase wit h red to purple angioproliferative nodular skin lesions (verruga peruana). Clinical feature s of acute infection include fever, myalgias, headache, hepatosplenomegaly, lymphadenopathy , and anemia. Complications include end organ damage (e.g., CNS, liver, GI, pulmonary) due to microvascular thrombosis. Diagnosis is by observation of the organism on Giemsa-stained blood films or by culture. A similar acute syndrome has been described due to B. rochalimae , a newly described organism. With recovery from acute infection, patients are at transien t risk for opportunistic infection with toxoplasmosis and salmonellosis. Treatment: Acute i nfection: Ciprofloxacin, doxycycline, ampicillin, TMP/SMX \227 7 \200\22314 d. Eruptive ph ase: Rifampin 10 mg/kg/d (max 600 mg) \227 10 \200\22314 d or streptomycin 15 \200\22320 m g/kg/d \227 10 d. Steroids may be indicated if there is severe neurological involvement. C at scratch disease is caused by Bartonella henselae . Bacillary angiomatosis/ peliosis: May occur in immunocompromised patients (e.g., those with AIDS) and is manifested by neovascul ar proliferation that may involve skin, lymph nodes, liver, spleen, bone, brain, cervix, lu ng and bowel, caused by B. henselae or B. quintana . Treatment is with doxycycline for seve ral months. 589 Trench fever is caused by Bartonella quintana inoculated from infected louse feces, not onl y in soldiers, but also in the homeless and in alcoholics. Clinical features: Fever, headac he, myalgias, dizziness, back pain, macular rash, eye pain, leg pain, splenomegaly, and rar ely, endocarditis. In HIV- infected patients, the skin lesions may resemble Kaposi \200\231 s sarcoma. May cause culture negative endocarditis; may relapse after clinical improvement. Investigations: Blood culture, serology, PCR. Treatment: Doxycycline 100 mg/12 h PO for 15 d. Endocarditis requires long therapy. Ehrlichiosis is caused by organisms related to Rick ettsia that target macrophages ( Ehrlichia chaffeensis ) and granulocytes ( E. ewingii and Anaplasma phagocytophilum ). Ticks spread ehrlichiosis. Symptoms: Fever, headache, anorexia , malaise, abdominal pain, epigastric pain, conjunctivitis, lymphadenopathy, jaundice, rash , confusion, and cervical lymphadenopathy. Investigations: Leucopenia, thrombocytopenia, AS T elevation. Serology and PCR are used for diagnosis. Intracellular inclusions may rarely b e observed on buffy coat preparation of blood smear. Treatment: Doxycycline 100 mg/12 h PO for 7 \200\22314 d. General comments about rickettsial infections \212 The archetypal disease. Organisms are transmitted between hosts Typhus: by arthropods. The incubation period is 2 \200\22323 d. Do not delay therapy while waiting for laboratory conf irmation. Pathology: any organ, and thrombotic occlusion may lead to gangrene. Infection ma y be mild and asymptomatic or severe and Clinical features: systemic. There may be sudden o nset of fever, frontal headache, confu- sion, and jaundice. With some species, an eschar (b lack scar at the site of the initial inoculation) may be present. A rickettsial rash may be macular, papular, petechial, or hemorrhagic. may show hemolysis, neutrophilia, thrombocyto penia, clot- Investigations ting abnormalities, hepatitis, and renal impairment. Patients d ie of shock, renal failure, DIC, or stroke. Tick-borne and endemic in the Rocky Mountain sp otted fever (R. rickettsii): Rocky Mountains and the southeastern states of the United Stat es. The rash begins as macules on the hands and feet, then spreads becoming petechial or he morrhagic. Endemic in Africa, the Arabian Gulf, and the Tick typhus (R. conorii): Mediterra nean. A black eschar may be visible at the site of the infecting bite. The rash starts in t he axillae, becoming purpuric as it spreads. Other features: impairment. Carried by human l ice ( Pediculus humanus ) Epidemic typhus (R. prowazekii): whose feces are inhaled or pass through skin. Typhus may become latent, only to recrudesce later (Brill \200\223Zinsser dis ease). Murine (endemic) typhus (R. typhi): humans. It is more prevalent in warm, coastal po rts. Rickettsialpox (R. akari): or vesicular. Scrub typhus (Orienta tsutsugamushi): \212 Widespread vasculitis and endothelial proliferation may affect \212 \212 \212 \212 \212 Conjunctival suffusion; jaundice, deranged clotting, renal \212 590 \212 Transmitted by fleas from rats to \212 Mite-borne infection. Rash is macular, papular, \212 Diagnosis: This is difficult as often the picture is nonspecific, the organisms are d ifficult to grow, and the traditional heterophil antibody Weil \200\223Felix test has low s ensitivity and specificity. A rise in antibody titer in paired sera is diagnostic. Latex ag glutination, indirect immunofluorescence, and ELISAs are available. An accurate, rapid dot blot immunoassay is available for scrub typhus. Skin biopsy may be diagnostic in Rocky Moun tain spotted fever. Treatment: Doxycycline 100 mg/12 h for at least 7 d or longer (2 d afte r fever resolves). Most common in Southeast Asia. Giardiasis Giardia lamblia is a flagellate protozoon that lives in the duodenum and je- jun um. It is spread by the fecal \200\223oral route. Risk factors for transmission are travel, immunosuppression, MSM, achlorhydria, playgroups, and swimming. Drinking water may become contaminated. Presentation: Often asymp- tomatic. Lassitude, bloating, flatulence, abdomina l discomfort, loose stools explosive diarrhea are typical. Malabsorption, weight loss, a nd lactose in- tolerance may occur. Diagnosis: Organisms are excreted intermittently and ev en repeated stool microscopy for cysts or trophozoites may be negative. Fecal immunoassays are more sensitive and specific. Finally, a trial of therapy may be needed. Differential di agnosis: Any cause of diarrhea, tropical sprue, celiac disease. Treatment: Scrupulous hygie ne. Metronidazole 250 mg/8 h \227 5 d, tinidazole 2 g PO once, nitazoxanide 500 mg/12 h \227 3 d. If treatment with metronidazole fails, treat longer or try nitazoxanide. For furt her recur- rences, consider treating the whole family. If diarrhea persists, avoid milk, as lactose intolerance may persist for 6 wks. Other GI protozoa Cryptosporidium, Microsporidi um and Isospora occur in AIDS, Balantidium coli , and Sarcocystis . s e s a e s i d s u o i t c e f n I Amebiasis Entamoeba histolytica occurs worldwide. Spread: Fecal \200\223oral. Boil water an d infected food to destroy cysts. Trophozoites may remain in the bowel or invade extraintes tinal tissues, leaving \200\234flask-shaped \200\235 GI ulcers. Presen- tation may be asym ptomatic, with mild diarrhea or with severe amoebic dysentery. Amoebic dysentery may occur yrs after the initial infection. Diarrhea begins slowly, but becomes profuse and bloody. An acute febrile prostrating illness does occur but high fever, colic, and tenesmus are rare. May remit and relapse. Diagnosis: Stool microscopy shows trophozoites, red and white blood cells. Distinguish from E. dispar , which looks identical, is more common, and doesn \200 \231t cause disease. Fecal antigen detection makes this distinction and is a preferred test . Serology indicates previous or current infection and may be unhelpful in acute infection. Differential diagnosis: Bacillary dysentery often has a sudden onset and may cause dehydra tion. Stools are more watery initially, then bloody. E. coli 0157 is a common cause of acut e bloody diarrhea without fever. Acute ulcerative colitis has a more gradual onset and the stools are very bloody. Amoebic colonic abscess may perforate causing peritonitis. Amoeboma is an inflammatory mass most often found at the cecum, where it must be distinguished from other RLQ masses. Amoebic liver abscess is usually a single mass in the right lobe and con tains \200\234anchovy-sauce \200\235 pus. There is usually a high swinging fever, sweats, RUQ pain, and tenderness. WBC elevation, LFT may be normal or elevated (cholestasis). 50% h ave no history of amoebic dysentery. Diagnosis: Ultrasound/CT aspiration; positive serol ogy in almost all patients. Treatment: Asymptomatic colonization : Paromomycin 10 mg/kg/8 h \227 5 \200\2237 d. Colitis: Metronidazole 750 mg/8 h PO for 5 \200\22310 d, then paromom ycin to destroy gut cysts. Liver abscess: Metronidazole for 10 d or longer. Aspirate if no improvement within a few days of starting metronidazole and in lesions at high risk for rup ture (cavity >5 cm, left lobe of liver). 591 Trypanosomiasis African trypanosomiasis (sleeping sickness) In West and Central Africa, Try panosoma brucei gambiense causes a slow, wasting illness with a long latent period. In East Africa, T. brucei rhodesiense causes a more rapidly progressive illness. Spread by tsetse flies, entering skin following an insect bite. It spreads via the blood to the lymph nodes, spleen, heart, and brain. Prevalence: 30,000 cases in 2009. Nearly all cases are due to T. b. gambiense. Infections to international travelers or imported cases to the United Stat es in immigrants are rare. Presentation: A tender, subcutaneous nodule ( T. chancre ) devel ops at the site of infection. Two stages follow: Stage I (hemolymphatic): Nonspecific sympt oms including fever, rash, rigors, headaches, hepatosplenomegaly, lymphadenopathy, and join t pains. Win- terbottom \200\231s sign (enlargement of posterior cervical nodes) is a relia ble sign, particularly in T. b. gambiense infections. In T. b. rhodesiense infections, this stage may be particularly severe, with potentially fatal myocarditis. Stage II (meningoenc ephalitic): Occurs weeks (in T. b. rhodesiense ) or months (in T. b. gambiense ) after init ial infection. Patients exhibit CNS features; e.g., convulsions, agitation, and confusion, with later apathy, depression, ataxia, dyskinesias, dementia, hypersomnolence, and coma. Di agnosis: T. b. rhod- esiense trypomastigotes can be seen in blood films or from fluid expre ssed from lymph nodes or chancres. T. b. gambiense is more difficult to see in blood films. Repeated tests and concentration techniques (analysis of buffy coat and use of miniature a nion exchange centrifugation) can improve yield. Analysis of fluid from lymph nodes may be positive in 40 \200\22380% of cases. Se- rology is only reliable in T. b. gambiense infecti ons. Staging: Hemolymphatic phase (fevers, headaches, arthralgias, and pruritus) and neurol ogical phase ( change of behavior, confusion, ataxia, sensory abnormalities). CSF should be evaluated in all patients for disease staging. Presence of trypanosomes or 6 WBC in CSF indicate neurological phase. Treatment: Seek expert help. Suramin, melarsoprol, and eflorn ithine are available through Division of Parasitic Diseases at CDC, 410 \200\223718 \200 \2234745, and E-mail parasites@cdc.gov Treat anemia and other infections first. Hemolymphat ic phase: T. b. rhodesiense: Suramin 1 g on days 1, 3, 5, 14, 21. T. b. gambiense: Pentamid ine 4 mg/kg/d IV or IM \227 7 \200\22310 d. Neurological phase: T. b. rhodesiense: Melarso prol \200\2343 by 3 \200\235 regimen. 2 \200\2233.6 mg/kg/d \227 3 d, 7 d later repeat se ries at 3.6 mg/kg/d \227 3 d, 7 d later repeat series again at 3.6 mg/kg/d \227 3 d. Mela rsoprol is associated with lethal encephalopathy in up to 10% (abnormal behavior, seizures, and coma). This is partly preventable with prednisolone (1 mg/kg/24 h, max 40 mg/24 h), st arting the day before the first injection. T. b. gambiense: Eflornithine 100 mg/kg/6 h \227 14 d. American trypanosomiasis (Chagas disease) is caused by T. cruzi . It occurs in L atin America and is spread by triatomine bugs. Presentation: Acute disease predominantly af fects children. An erythematous, indurated nodule (chagoma) forms at the site of infection, which may then scar. Signs: Fever, myalgias, rash, lymphadenopathy, hepatosplenomegaly. If the eye is infected, unilateral conjunctivitis and periorbital edema may occur (Roma a \200\231s sign). Occasionally death is from myocarditis or meningoencephalitis. In up to 30 % of cases, progression to chronic disease occurs after a latency of about 20 yrs. Multiorg an invasion may cause megaesophagus (dysphagia, aspiration), megacolon (abdominal distensio n, constipation), or dilated cardiomyopathy (chest pain, heart failure, arrhythmias, syncop e, thromboembolism). CNS lesions may occur in HIV-positive patients. Diagnosis: Acute disea se: Trypomastigotes may be seen in or grown from blood, CSF, or lymph node aspirate. Chroni c disease: Serology (Chagas \200\231 IgG ELISA). Treatment: Nifurtimox 2 mg/kg/6 h PO after food \227 90 d, or, alternatively, benznidazole 3.7 mg/kg/12 h PO for 60 d. Both are toxi c and only available from CDC . Decisions regarding treatment need to be individualized. In fected children, 592 patients with acute infections or reactivated disease, and those aged 19 \200\22350 without advanced heart disease should be offered treatment. s e s a e s i d Leishmaniasis Leishmania protozoa are intracellular organisms that cause granulomata. They are spread by sandflies and occur in Africa, India, Latin America, the Middle East, and the Mediterranean. Clinical effects reflect the ability of each species to induce or suppress the immune response, to metastasize, and to invade cartilage, and the speed and efficiency of the patient \200\231s immune response. L. major , for example, is the most immunogenic a nd allergenic of cutaneous Old World Leishmania and causes necrosis. L. tropica is less imm unogenic and causes less inflamed, slow healing sores with relapsing lesions having tubercu loid histology. Cutaneous leishmaniasis (CL) Almost all cases occur in parts of Afghanistan , Algeria, Syria, Iran, Saudi Arabia ( L. tropica and L. major ) and parts of South America ( L. mexicana, L. panamensis, and L. braziliensis ). Lesions develop at the site of the bi te, beginning as an itchy papule, from which the crust may fall off to leave an ulcer. Most heal spontaneously, typically within 3 \200\22318 months, with scarring (disfiguring if ex tensive). L. mexicana may cause destruction of the pinna. L. braziliensis and L. panamensis can cause mucocutaneous disease months to years after spontaneous healing of primary cutan eous lesion. Typically, this involves mucosa of the nose, pharynx, palate, and larynx. Naso pharyngeal lesions are called espundia. Diagnosis: Microscopy, culture, and PCR of skin scr aping from the edge of the ulcer. Punch biopsy can be helpful if skin scrapings are unrevea ling. Treatment: Get help. Not all cutaneous lesions need to be treated, but scarring will likely happen without treatment. Standard therapy is with Pentostam (sodium stibogluconate, a pentavalent antimonial) 20 mg/ kg/d \227 20 d. This is available through CDC. L. major can be treated with fluconazole 200 mg/d PO for 6 wks. L. major, L. mexicana, and L. paname nsis can be treated with ketoconazole 600 mg/d \227 28 \200\22330 d. Treatment is unsatisf actory once mucosae are involved, so treat all cutaneous lesions due to L. brasiliensis and L. panamensis early. Data on alternative therapies are limited. These include liposomal am photericin B, topical paromomycin, intralesional pentavalent antimonial injections, thermot herapy, and oral miltefosine. Visceral leishmaniasis (kala-azar) Kala-azar means \200\234b lack sickness \200\235 and is characterized by dry, warty, hyperpigmented skin lesions. Alm ost all cases are in the Asian subcontinent, Sudan, and Brazil. It is usually caused by L. donovani and L. infantum (also called L. chagasi ). Incubation: Usually 2 \200\2236 months, but may be 2 wks \200\2232 yrs. The organisms spread via lymphatics from minor skin lesion s and multiply in macrophages of the reticuloendothelial system (Leishman \200\223Donovan b odies). There are 30 subclinical cases for every clinical case. Increased risk in HIV infec tion. Presentation: Insidious onset of fevers, malaise, wasting, splenomegaly, hepatomegaly , cytopenias, decreased albumin, hypergammaglobulinemia, immunosuppression with bacterial s uperinfection. Complications: Over months to years, emaciation and exhaustion occur, with a protuberant abdomen. Intercurrent infections are common, especially pneumococcal otitis, p neumonia and septicemia, tuberculosis, measles. Untreated mortality: >80%; with treatment 10%. Poorer outcomes are seen in those with HIV, jaundice, and wasting, and severe anemia. Diagnosis: Leishman \200\223Donovan bodies in bone marrow (80%), lymph node, or splenic as pirates (95%).Serology is useful, but may be negative in those with HIV. Treatment: Seek ex pert help. First line: Liposomal amphotericin B 3 mg/kg IV on days 1 \200\2235, 14, and 21. Use higher doses for longer in HIV (and post-treatment prophylaxis recommended). s u o i t c e f n I 593 Pentostam 20 mg/kg/24 h IV or IM, for 28 \200\22330 d is a widely used alternative (availab le from CDC). Other therapies include miltefosine, deoxycholate, amphotericin B, and parent eral paromomycin. Post kala-azar dermal leishmaniasis may occur months or years following s uccessful treatment; lesions resemble leprosy. Fungal infections Fungi may cause disease by acting as airborne allergens, by producing tox ins, or by direct infection. Fungal infection may be superficial or deep, and both are much more common in the immunocompromised. Corticosteroids increase risk dramatically. ( Tricho phyton, Dermatophytes Superficial mycoses Microsporum, and Epidermophyton ) causes tinea (r ingworm). Diagnosis Skin scraping microscopy. Treatment: Topical clotrimazole 1%. Continue for 14 d after healing. If intractable, try itraconazole (100 \200\223200 mg/24 h PO for 7 d), terbinafine (250 mg/24 h PO for 4 wks), or griseofulvin 0.5 \200\2231 g/24 h ( SE : Agr anulocytosis; SLE). Candida albicans causes skin infection in moist macerated skin regions (e.g., under breasts, oral and vulvovaginal infections). Malassezia furfur causes pityriasi s versicolor; a macular rash that appears brown on pale skin and pale on tanned skin. Diagn osis: Microscopy of skin scrapings under Wood \200\231s light. Treatment: Ketoconazole 200 mg/24 h PO with food for 7 d (also available as a cream); alternatively selenium sulfide lo tion. Some superficial mycoses penetrate the epidermis and cause chronic subcu- taneous inf ections such as Madura foot or sporotrichosis . Treatment is complex and may require amputa tion of the affected limb. Systemic mycoses Aspergillus fumigatus may precipitate asthma, a llergic bronchopulmonary aspergillosis (ABPA), or cause aspergilloma. Pneumonia and invasiv e aspergillosis occur in the immunosuppressed, particularly with defects in neutrophil numb er and/or function. Diagnosis: Culture of organism from affected area, galactomannan (serum or BAL); CT scan with \200\234halo sign \200\235 in neutropenic patient is suggestive of invasive aspergillosis. Successful treatment of invasive infection depends on host factors (immune reconstitution) and appropriate antifungal therapy. Voriconazole is first- line the rapy. Amphotericin B preparations are an alternative. Echinocandins (e.g., caspofungin, mic afungin, and anidulafungin) are probably less effective. Combination therapy with voriconaz ole and an echinocandin may have a role in selected patients. Invasive candidiasis is a maj or cause of bloodstream infections in hospi- talized patients. Risk factors include central venous catheters (especially with parenteral nutrition and hemodialysis), abdominal surger y, and cytotoxic chemotherapy with mucositis, neutropenia, and stay in ICU. Other sites of infection can include peritoneal cavity, post sternotomy wounds, and, rarely, heart valves. Candidemia may be complicated by endophthalmitis. Treatment is with echinocandins, flucona zole (unless C. krusei or many C. glabrata isolates). Alternatives are amphotericin B and v oriconazole. Candiduria often responds to removal of urinary catheter and does not usually require antifungal therapy. Empiric therapy in high-risk ICU patients targeting Candida spe cies may be considered. Empiric therapy in patients with neutropenia and persistent fever s hould target Candida spp. and fila- mentous fungi (e.g., with amphotericin B or an echinoca ndin). infection 594 Cryptococcus neoformans causes pneumonia and/or disseminated disease with fungemia and meni ngitis, or pneumonia. Risk factors are advanced HIV, solid organ transplantation, and other chronic immunosuppressing conditions (e.g., long-term corticosteroid use). Presentation: T he history may be subacute and there may be features suggesting elevated intracranial press ure (e.g., confusion, papilledema, cranial nerve palsies). Diagnosis: Serum and CSF cryptoc occal antigen; India ink CSF staining; and blood, sputum, and CSF culture. All immunocompro mised patients require evaluation of CSF that includes pressure measurement. Treatment: Amp hotericin B deoxycholate 0.7 \200\2231.0/kg/d (or liposomal 3 \200\2234 mg/kg/d) IV + flucy tosine 25 mg/kg/6 h PO \227 14 d or longer, then fluconazole 400 \200\223800 mg/d \227 8 wks or longer, then 200 mg/d until CD4 >200 \227 6 months (AIDS patients). If CSF opening pressure (OP) is >250 mm H 2 O, drain CSF until OP decreases 50%. Repeat drainage daily unt il OP is <200. Failure to do this is an important cause of morbidity and mortality due to c ryptococcal meningitis. Fluconazole at 400 mg/d for 6 \200\22312 months can be used in pati ents with mild to moderate pulmonary disease only (CSF evaluation required). Other fungi ca using deep infection Histoplasma capsulatum, Coccidioides immitis, Paracoccidioides brasili ensis , and Blastomyces dermatitidis may cause asymptomatic infections, acute or chronic lu ng disease, or disseminated infection. Acute histoplasma pneu- monitis is associated with a rthralgias, erythema nodosum, and erythema multiforme. Chronic disease may cause upper-zone fibrosis or radiographic \200\234coin lesions. \200\235 Diagnosis: CXR, serology, culture , and biopsy. When severe (usually in immunocompromised patients), treatment is with an amp hot- ericin B formulation. After stabilization or when mild to moderate, these diseases are treated with itraconazole, except coccidioidomycosis, which may be treated with fluconazol e (especially with cocci meningitis). s e s a e s i d s u o i t c e f n I Preventing fungal infections This is a goal in the immunocompromised. Fluconazole, posacona zole, voriconazole, and topical nystatin have roles in prevention of infection depending on risk factors (e.g., cytotoxic chemotherapy, solid organ trans- plantation, bone marrow tra nsplant, and as secondary prophylaxis after cryptococcal meningitis in HIV patients). Decis ions regarding prophylaxis depend on knowledge of risk factors. 595 Table 14.31 Fungal prophylaxis Infection Candidiasis Patient type Oropharyngeal: HIV, radiation therapy, cytotoxic chemotherapy, poor-fitting dentures Vulvovaginal: Antibiotics, DM, otherwise healthy women Disseminated: Central venous catheters, cytotoxic chemotherapy, neutropenia, abdominal surg ery, burns, parenteral nutrition Aspergillosis Invasive disease in those with neutropenia, trans- plant, corticosteroids, chronic granulom atous disease (CGD). Cryptococcosis Mucormycosis HIV, transplant, corticosteroids, lymphoma Neutropenia, transplant, uncontrolled DM, deferoxamine Histoplasmosis Exposure in endemic areas (e.g., Ohio River Valley), usually a self limited disease. Disseminated disease in those with risks similar t o cryptococcosis Coccidioidomycosis Exposure in endemic area (e.g., Southwestern United States, California \200\231s Central Va lley), usually a self limited disease (valley fever). Disseminated disease in those with ri sks similar to cryptococcosis Rare filamentous fungal infections Fusarium, Scedosporium, Ochroconis, and many others: Risk for invasive disease similar to a spergillosis Table 14.32 Treatment of fungal infections Antifungal Typical use Typical dose (normal GFR) Loading dose: 800 mg \227 1 then 400- mg/d (IV or PO). Lower dos es oral candidi- asis, 150 mg \227 1 for vulvovaginal disease Renal adjust- ment required Toxicity Fluconazole Liver, drug Candida, interactions, Cryptococcosis, Coccidioides 596 (Continued) s e s a e s i d Table 14.32 (Continued) Antifungal Typical use Typical dose (normal GFR) IV: Loading Toxicity Voriconazole Aspergillus, can- Liver, CNS, skin, QT, multiple drug interactions s u o i t c e f n I dida , other fila- mentous fungal infections (not mucormycosis) dose of 6 mg/ kg/12 h \227 2 then 4 mg/ kg/d Caution with IV solution with GFR <50; cyclo- dextrin vehicle may cause renal accumulate an d exacerbate renal damage PO: Loading dose: 400 mg/12 h \227 2, then 200 mg/12 h. Decrease doses by 50% for patients <40 kg Posaconazole Aspergillus, Candida , mucormycosis (not first line) Histoplasmosis, blastomycosis 200 mg/8 h PO Liver, QT, multiple drug interactions Itraconazole 200 mg/12 h PO. Oral solution bet- ter absorbed than tabs Anidulafungin: 200 mg \227 1, th en 100 mg/d IV Liver, GI upset, negative ino- trope, QT, drug interactions Echinocandins Candida, Histamine release, Aspergillus (not first line) liver Caspofungin: 70 mg \227 1, then 50 mg/d IV Micafungin 100 mg/d IV Deoxycholate Amphotericin B (AmB) Candida, Infusion reac- Aspergillus , mucormycosis, Cryptococcus, Histoplasma, Coccidioides AmB: 0.7 \200\2231.0 mg/kg/d IV tion, renal and electrolyte Liposomal 597 AmB: 3 \200\2236 mg/kg/d IV (less toxic than deoxycholate) Flucytosine (5-FC) Used as part of combina- tion therapy with AmB for cryptococcosis 25 mg/kg/6 h Renal adjust- ment required Myelo suppression colitis, hepatitis