254 A n t i b i o t i c E s s e n t i a l s

Parasites, Fungi, Unusual Organisms in Blood

Microfilaria in Blood

Subset	Pathogen	Preferred Therapy	Alternate Therapy
Filariasis	Brugia malayi	Doxycycline 100 mg (PO) of q12h × 6	Ivermectin 200 mcg/kg
		weeks plus	(PO) × 1 dose ± albendazole
		Diethylcarbamazine:	400 mg (PO) × 1 dose
		day 1: 50 mg (PO)
		day 2: 50 mg (PO) q8h
		day 3: 100 mg (PO) q8h
		days 4–14: 2 mg/kg (PO) q8h
	Wuchereria	Doxycycline 100 mg (PO) q12h ×6	Ivermectin 400 mcg/kg
	bancrofti	weeks plus	(PO) × 1 dose..
		Albendazole 400 mg (PO) × 1 dose
		plus
		Diethylcarbamazine:
		day 1: 50 mg (PO)
		day 2: 50 mg (PO) q8h
		day 3: 100 mg (PO) q8h
		days 4–14: 2 mg/kg (PO) q8h

Brugia malayi

Clinical Presentation:  May present as an obscure febrile illness, chronic lymphedema, lymphangitis, or cutaneous abscess.. “Filarial fevers” usually last 1 week and spontaneously remit..

Diagnostic Considerations:  Diagnosis by demonstrating microfilaria on Giemsa’s stained thick blood smear or by using the concentration method; yield is increased by passing blood through a Millipore filter before staining.. Several smears should be taken over 24 hours.. Adult worms may be detected in scrotal lymphatics by ultrasound. . Common infection in Southeast Asia (primarily China, Korea, India, Indonesia, Malaysia, Philippines, Sri Lanka).. Most species have nocturnal periodicity (microfilaria in blood at night).. Eosinophilia is most common during periods of acute inflammation..

Pitfalls:  Genital manifestations—scrotal edema, epididymitis, orchitis, hydrocele—are frequent with W.. bancrofti, but rare with B.. malayi..

Prognosis:  Related to state of health and extent of lymphatic obstruction.. No satisfactory treatment is available.. Single-dose ivermectin is effective treatment for microfilaremia, but does not kill the adult worm (although diethylcarbamazine kills some).. If no microfilaria in blood, full-dose diethyl­carbamazine (2 mg/kg q8h) can be started on day one.. Antihistamines or corticosteroids may decrease allergic reactions from disintegration of microfilaria..

Wuchereria bancrofti

Clinical Presentation:  May present as an obscure febrile illness, chronic lymphedema, lymphangitis, or cutaneous abscess.. Genital (scrotal) lymphatic edema, groin lesions, epididymitis, orchitis, hydroceles are characteristic.. Chyluria may occur..“Filarial fevers”usually last 1 week and spontaneously remit.. Lymphedema worsened by cellulitis associated with Tinea pedis infections..

Diagnostic Considerations:  Diagnosis by demonstrating microfilaria on Giemsa’s stained thick blood smear or by using the concentration method; yield is increased by passing blood through a Millipore filter before staining.. Several smears should to be taken over 24 hours.. W.. bancrofti is the most common

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human filarial infection, particularly in Asia (China, India, Indonesia, Japan, Malaysia, Philippines), Southeast Asia, Sri Lanka, Tropical Africa, Central/South America, and Pacific Islands.. Most species have nocturnal periodicity (microfilaria in blood at night).. Eosinophilia is common..

Pitfalls:  Differentiate from “hanging groins” of Loa Loa, which usually do not involve the scrotum.. Prognosis:  Related to state of health and extent of lymphatic obstruction. . No satisfactory treatment is available. . Single-dose ivermectin is effective treatment for microfilaremia, but does not kill the adult worm (although diethylcarbamazine kills some).. If no microfilaria in blood, full-dose diethyl­ carbamazine (2 mg/kg q8h) can be started on day one. . Antihistamines or corticosteroids decrease allergic reactions from disintegration of microfilaria. . Wolbachia bacteria are endosymbionts in W.. bancrofti filariasis.. Treatment with doxycycline effective against Wolbachia which are important in microfilarial reproduction..

Trypanosomes in Blood

Subset	Pathogen	Preferred Therapy	Alternate Therapy
Chagas’ disease	Trypanosoma	Nifurtimox	Benznidazole
(American	brucei cruzi	2–3 mg/kg/day (PO) q6h × 30–90	2..5–3..5 mg/kg (PO)
trypanosomiasis)		days	q12h × 60 days
Loa Loa (Loiasis)	L.. loa	Diethylcarbamazine 2 mg/kg (PO)	Albendazole 200 mg
		q8h × 3 weeks	(PO) q12h × 3 weeks
Sleeping sickness	Trypanosoma	Early disease
West African	brucei	Pentamidine 4 mg/kg (IM)
(Gambian)	gambiense	q24h × 7 days
trypanosomiasis
		Late disease
		Melarsoprol 2..2 mg/kg (IV)
		q24h × 10 days
		plus
		Nifurtimox 15 mg/kg (PO) q8h
		× 10 days
		or
		Eflornithine 100 mg/kg (PO) q6h ×
		10 days
East African	Trypanosoma	Early disease
(Rhodesian)	brucei	Suramin test dose of 4–5 mg/kg (IV)
trypanosomiasis	rhodesiense	day 1, then five injections of 20 mg/
		kg (IV) q 7 days (max.. dose 1 gm/
		injection day 3, 10, 17, 24, 31) max..
		dose 1 gm/injection
		Late disease
		Melarsoprol 3 series of 1..8, 2..16, 2..52
		mg/kg (IV) q24h; 3 series of 2..52,
		2..88, 3..25 mg/kg (IV) q24h; 3 series
		of 3..6, 3..6, 3..6 mg/kg (IV) q24h; the
		series given at intervals of 7 days

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Chagas’ Disease (Trypanosoma brucei cruzi) American Trypanosomiasis

Clinical Presentation:  Presents acutely after bite of infected reduviid bug with unilateral painless edema of the palpebrae/periocular tissues (Romaña’s sign), or as an indurated area of erythema and swelling with local lymph node involvement (chagoma).. Fever, malaise, and edema of the face and lower extremities may follow.. Generalized lymphadenopathy and hepatosplenomegaly occur.. Patients with chronic disease may develop cardiac involvement (cardiomyopathy with arrhythmias, heart block, heart failure, thromboembolism), GI involvement (megaesophagus, megaduodenum, megacolon) or CNS involvment in HIV/immunosuppressed..

Diagnostic Considerations:  Common in Central and South America.. Acquired from infected reduviid bug, which infests mud/clay parts of primitive dwellings.. Transmitted by blood transfusion (~10%), organ transplants, and congenitally.. Diagnosis in acute disease by detecting trypanosomes in wet prep of anticoagulated blood or stained buffy coat smears.. Amastigote forms present intracellularly in monocytes/ histiocytes in Giemsa-stained smears, bone marrow or lymph node aspirates, or by xenodiagnosis.. Screening test ELISA IFA; confirmatory test RIPA (radioimmuno precipitation assay)..

Pitfalls:  Do not overlook the diagnosis in patients from endemic areas with unexplained heart block ± apical ventricular aneurysms.. May be transmitted by blood transfusion/organ transplantation.. Prognosis:  Related to extent of cardiac GI, or CNS involvement..

Sleeping Sickness (T. brucei gambiense/rhodesiense) West African (Chronic)/East African (Acute) Trypanosomiasis

Clinical Presentation:  Sleeping sickness from T.. brucei gambiense is milder than sleeping sickness from T.. brucei rhodesiense, which is usually a fulminant infection.. A few days to weeks after bite of tsetse fly, patients progress through several clinical stages:

•Chancre stage:  Trypanosomal chancre occurs at bite site and lasts several weeks..

•Blood/lymphatic stage:  Blood parasitemia is associated with intermittent high fevers, headaches and insomnia, followed by generalized adenopathy. . Posterior cervical lymph node enlargement (Winterbottom’s sign) is particularly prominent with T.. brucei gambiense.. Hepatosplenomegaly and transient edema/pruritus/irregular circinate rash are common. . Myocarditis (tachycardia unrelated to fevers) occurs early (before CNS involvement) and is responsible for acute deaths from T.. brucei rhodesiense..

•CNS stage:  Occurs acutely with East African trypanosomiasis or chronically with West African trypanosomiasis after non-specific symptoms, and is characterized by increasing lethargy, somnolence (sleeping sickness), and many subtle CNS findings.. Coma and death ensue without treatment.. With melarsoprol, use prednisolone 1 mg/kg (PO) q24h (start steroid 1 day prior to first dose and continue to last dose).

Diagnostic Considerations:  Diagnosis by demonstrating trypanosomes in blood, chancre, or lymph nodes aspirates by Giemsa-stained thin and thick preparations, light microscopy, or buffy coat concentrates with acridine orange.. CSF determines early vs.. late stage disease (> 20 WBCs/mm3)..

Pitfalls:  Do not miss other causes of prominent bilateral posterior cervical lymph node enlargement, e..g.., lymphoma, EBV.. Serum arginase a biomarker for effective therapy..

Prognosis:  Related to extent of cardiac/CNS involvement.. Relapse may occur..

Loa Loa (Loiasis)

Clinical Presentation:  Cutaneous swellings (Calabar swellings) with pruritus. . Adults may be visible when migrations under the conjuctiva or under the skin.. Disappear in 3 days.. Calabar swellings are painless and appear on the extremeties.. Eosinophilia prominent..

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Diagnostic Considerations:  Demonstrates of microfilariae in blood (at noon) or by demonstration of L.. loa in skin/eye.. Immunodiagnosis unhelpful..

Pitfalls:  Calabar swellings occur one at time and may last for hours/days.. Prognosis:  Poorest with CNS involvement..

Spirochetes in Blood

Subset	Pathogen	Preferred Therapy	Alternate Therapy
Relapsing fever	Borrelia recurrentis	LBRF	TBRF with CNS
Louse-borne	> 15 Borrelia species	Erythromycin 500 mg	involvement
(LBRF)	(U..S.. B.. hermsi; Africa: B..	(IV or PO) q6h	Penicillin G 2 mu (IV)
Tick-borne (TBRF)	duttonii; Africa/Middle	× 7 days	q4h × 2 weeks
	East: B.. crocidurae)	TBRF	or
			Ceftriaxone 1 gm (IV)
		Doxycycline 200 mg (PO)
			q12h × 2 weeks
		× 3 days, then 100 mg (PO)
			or
		q12h
			Cefotaxime 3 gm (IV)
		× 7 days
			q6h × 2 weeks
Rat bite fever	Spirillum minus	Penicillin G 4 mu (IV) q4h ×	Amoxicillin 1 gm (PO)
		2 weeks	q8h × 2 weeks
		or	or
		Ceftriaxone 1 g (IV) q24h ×	Erythromycin 500 mg
		2 weeks	(IV or PO) q6h × 2 weeks
		or	or
		Doxycycline 200 mg (IV or	Chloramphenicol
		PO) q12h × 3 days, then 100	500 mg (IV) q6h ×
		mg (IV or PO) q12h	2 weeks
		× 11 days

Relapsing Fever, Louse-Borne (LBRF) / Tick-Borne (TBRF)

Clinical Presentation:  Abrupt onset of“flu-like” illness with high fever, rigors, headache, myalgias, arthralgias, tachycardia, dry cough, abdominal pain after exposure to infected louse or tick.. Truncal petechial rash and conjunctival suffusion are common.. Hepatosplenomegaly/DIC may occur.. Bleeding or rash at bite site.. Complications more common in LBRF.. Fevers last ~ 1 week, remit for a week, and usually relapse only once in LBRF, but several times in TBRF.. Relapses usually last 2–3 days.. Fevers are often higher in TBRF..

Diagnostic Considerations:  Borreliae seen in Wright/Giemsa-stained blood smears.. LBRF is endemic in South American Andes, Central and East Africa, and is associated with crowded, unhygienic conditions.. Soft ticks (Ornithodoros) TBRF main vector.. Bite at night, patients do not recall tick bite.. TBRF is seen throughout the world, and is endemic in Western U..S.., British Columbia, Mexico, Central/South America, Mediterranean, Central Asia, and Africa.. With TBRF, meningismus ± facial nerve palsy common with B.. duttoni rare with B.. hermsii..

Pitfalls:  Spirochetes are most likely to be seen during febrile periods.. Blood smears may be negative if not obtained during fever..

Prognosis:  Good if treated early.. Usually no permanent sequelae..

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Rat Bite Fever (Spirillum minus)

Clinical Presentation:  Infection develops 1–4 weeks following bite of a rat.. Healed rat bite becomes red, painful, swollen and ulcerated, with regional lymphangitis/adenopathy.. Recurrent fevers occurs in 2–4 day fever cycles.. Fevers are usually accompanied by chills, headache, ­photophobia, nausea, vomiting.. Rash on palms/soles develops in > 50%.. Arthritis, myalgias, and SBE are rare..

Diagnostic Considerations:  Spirochetes are seen in Wright/Giemsa-stained blood smears.. Differential diagnosis includes Borrelia, malaria, and lymphoma.. VDRL is positive..

Pitfalls:  May be confused with syphilis, due to rash on palms/soles and false-positive syphilis serology in 50%.. SBE occurs with Streptobacillus moniliformis, not S.. minus (unless there is preexisting valvular disease).. Bite wound ulcerates in S.. minus, not Streptobacillus moniliformis..

Prognosis:  Patients with arthritis have a protracted course..

Intracellular Inclusion Bodies in Blood

Subset	Pathogen	Preferred Therapy	Alternate Therapy
Babesiosis	Babesia microti	Azithromycin 500 mg	Clindamycin 600 mg (PO)
		(PO) × 1, then 250 mg	q8h × 7 days
		(PO) q24h × 7 days	plus
		plus	Quinine 650 mg (PO) q8h
		Atovaquone	× 7 days
		(suspension) 750 mg
		(PO) q12h × 7 days
Ehrlichiosis/		Doxycycline 200 mg (IV	Any once-daily quinolone (IV or
anaplasmosis		or PO) q12h × 3 days,	PO) × 1–2 weeks
Human	Ehrlichia	then 100 mg (IV or PO)	or
monocytic	chaffeensis,	q12h × 1–2 weeks total	Rifampin 300 mg (PO) q12h ×
ehrlichiosis	ewubguum		1–2 weeks*
(HME)			or
Human	Anaplasma		Chloramphenicol 500 mg
			(IV or PO) q6h × 1–2 weeks*
granulocytic	(Ehrlichia)
anaplasmosis	phagocytophilium
(HGA)
Severe Malaria	Quinidine gluconate plus either doxycycline or clindamycin 6..25 mg base/
(Usually P..	kg (= 10 mg salt/kg) loading dose (IV) over 1–2 h, then 0..0125 mg base/kg/min (=
falciparum)	0..02 mg salt/kg/min) continuous infusion for at least 24h.. An alternative regimen
	is 15 mg base/kg (= 24 mg salt/kg) loading dose infused over 4 hours, followed
	by 7..5 mg base/kg (= 12 mg salt/kg) infused over 4 hours every 8 hours, starting
	8 hours after the loading dose.. Once parasitemia <1%; and patient can take oral
	medications, complete therapy with oral quinine or an oral regimen.. (see below
	chloroquine-sensitive or resistant).. Quinidine/quinine course =7 days in
	Southeast Asia; =3 days in Africa or south America.

*May be used in pregnancy..

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Intracellular Inclusion Bodies in Blood (cont’d)

	Subset	Therapy
		or
		Quinine 20 mg (salt)/kg (IV) over 4 hours (in D5W), then 10 mg (salt)/kg (IV) over
		2 hours q8h until able to take oral meds; complete 7 days total therapy with
		doxycycline or oral regimen (see below chloroquine-sensitive or resistant)..
		or
		Artemether-lumefantrine 3..2 mg/kg (IM) × 1 dose, then 1..6 mg/kg (IM) q24h
		until able to take oral meds; complete 7 days total therapy with doxycycline or
		oral regimen (see below chloroquine-sensitive or resistant)..
		or
		Artesunate 2..4 mg/kg (IV) initially and at 12, 24, and 48 hours, then q24h until
		able to take oral meds; complete 7 days total therapy with doxycycline or oral
		regimen (see below chloroquine-sensitive or resistant)..
	Uncomplicated	Chloroquine-sensitive
	Malaria	Chloroquine phosphate 600 mg base (= 1000 mg salt) (PO) immediately,
	(P.. falciparum, P..	followed by 300 mg base (= 500 mg salt) (PO) at 6,24, and 48 hours..
	malariae,	Total dose = 1500 mg base (= 2500 mg salt)..
	P.. knowlesi or	or
	unidentified	Hydroxychloroquine 620 mg base (= 800 mg salt) (PO) loading dose, then 310
	species)
		mg base (= 400 mg salt) (PO) at 6, 24, and 48 hours..
	P.. vivax and	Plus primaquine phosphate 30 mg base (PO) q24h × 2 weeks..
	P.. ovale
		Chloroquine-resistant
		Quinine sulfate 625 mg base (= 625 mg salt) (PO) q8h × 7 days plus
		doxycycline 200 mg (PO) q12h × 3 days, then 100 mg (PO) q12h × 4 days..
		or
		Atovaquone/proguanil (250/100 gm PO tab) 4 tablets as single dose or
		4 tablets (PO) q12h × 3 days..
		or
		Artesunate 4 mg/kg (PO) × 3 days plus Mefloquine 684 mg base (= 750 mg
		salt) (PO) as initial dose followed by 456 mg base (= 500 mg salt) (PO) given 6–12
		hours after initial dose.. Total dose = 1250 mg salt..
		or
		Artemether/lumefantrine 4 tabs =1 dose (20/120 mg tablets) give initial dose,
		followed by second dose 8h later, then 1 dose (PO) q12h for the following 2 days..
		or
		Dihydroartemisinin 40 mg plus piperaquine 320 mg (PO) q24h × 3 days..

For CDC guidelines for malaria in US (see p.. 721)..

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Babesiosis (Babesia microti)

Clinical Presentation:  “Malarial-like illness” with malaise, fever, relative bradycardia, shaking chills, myalgias, arthralgias, headache, abdominal pain, and splenomegaly.. Laboratory abnormalities include anemia, atypical lymphocytes, relative lymphopenia, thrombocytopenia, mildly elevated LFTs, highly elevated ↑ ESR, ↑ ferritin, and ↑ LDH.. Transmitted by infected Ixodes ticks..

Diagnostic and Considerations:  Characteristic four merozoites (often pear shaped) arranged in “Maltese cross” formation (tetrads).. Serology diagnostic of acute infection.. Hyposplenic patients may have profound hemolytic anemia and life-threatening infection..

Pitfalls:  Co-infection with Lyme disease may occur.. No serological cross-reactivity between Babesia and Borrelia (Lyme disease).. Merozoites only may be confused with P.. falciparum malaria.. Extra-RBC forms and vacuolated RBCs distinguish babesiosis from malaria.. Travel history is important.. Doxycycline ineffective..

Prognosis:  May be more severe with Lyme disease co-infection.. Severe/fatal if ↓/absent splenic function.. Exchange transfusions may be life saving..

Ehrlichiosis (HME)/Anaplasmosis (HGA)

Clinical Presentation:  Acute febrile illness with chills, headache, malaise, myalgias, leukopenia, relative lymphopenia, atypical lymphocytes, thrombocytopenia, ↑LFTs, ↓ESR, ↑ferritin.. No vasculitis.. Resembles Rocky Mountain spotted fever (RMSF), but without rash..

Diagnostic Considerations:  Characteristic “morula” (spherical, basophilic, mulberry-shaped, cytoplasmic inclusion bodies) may be seen in peripheral blood neutrophils in HGA.. PCR from blood is 86% sensitive and highly specific for early diagnosis.. Obtain acute and convalescent IFA serology.. HGA vector is Ixodes ticks clinical co-infection with B.. burgdorferi (Lyme Disease) is rare, but may occur.. Main HME vector Ambylomma americanum (lone star tick)..

Pitfalls:  No morula with HME.. Rash uncommon in HME and rare in HGA.. E.. chaffeensis (HME) titers will not be elevated with A.. phagocytophilium (HGA) and vice versa.. PCR/blood smears positive early.. Seropositivity increases over time..

Prognosis:  Good if treated early.. Delayed response/more severe with Lyme co-infection disease..

Malaria (Plasmodium ovale/vivax/falciparum/malariae/knowlesi)

Clinical Presentation:  Presents acutely with fever/chills, severe headaches, cough, nausea/vomiting, diarrhea, abdominal/back pain.. Typical “malarial paroxysm” consists of chills, fever and profuse sweating, followed by extreme prostration.. There are a paucity of physical findings, but most have tender hepatomegaly/splenomegaly and relative bradycardia.. ↑ T.. bilirubin, thrombocytopenia, atypical lymphocytes, and ↑ LFTs are common..

Diagnostic Considerations:  Diagnosis by visualizing Plasmodium on thick/thin Giemsa or Wrightstained smears..

Pitfalls:  Be wary of diagnosing malaria without headache.. Dengue most closely resembles malaria.. On abdominal US, dengue patients have gallbladder wall thickening/splenomegaly but not hepatomegaly vs..malaria patients which have a normal gallbladder, splenomegaly/heptomegaly.. If no atypical lymphocytes on smear (auto cell counters are insensitive to atypical lymphocytes), question the diagnosis of malaria.. P.. knowlesi (monkey malaria emerging cause of human malaria.. Resembles P.. malariae (microscopically) but may be severe resembing P.. falciparum (clinically).. Treat P.. knowlesi as chloroquine sensitive (P.. vivax, P.. ovale, P.. malariae) malaria..

Prognosis:  Related to species degree of parasitemia P.. falciparum with high-grade parasitemia is most severe, and may be complicated by coma, hypoglycemia, renal failure, or non-cardiogenic pulmonary edema.. If parasitemia exceeds 15%, consider exchange transfusions..