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1. Guidelines for Prevention and
Treatment of Opportunistic Infections
among HIV-Infected Children
Parasitic Infections
Recommendations from Centers for Disease Control and Prevention,
the National Institutes of Health, the HIV Medicine Association of
the Infectious Diseases Society of America, the Pediatric Infectious
Diseases Society, and the American Academy of Pediatrics

2. July 2009
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These slides were developed using the April 2008
Guidelines. The intended audience is clinicians
involved in the care of patients with HIV.
Users are cautioned that, because of the rapidly
changing field of HIV care, this information could
become out of date quickly. Finally, it is intended that
these slides be used as prepared, without changes
in either content or attribution. Users are asked to
honor this intent. Expert opinion should be sought
for complex treatment regimens.
– AETC NRC
About This Presentation

3. July 2009
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Cryptosporidiosis/Microsporidiosis:
Epidemiology
 Protozoal parasites that cause enteric illness in humans
and animals
 Human infection primarily caused by C hominis,
C parvum, C meleagridis
 Microsporida include E bieneusi and E intestinalis
 Infection results from ingestion of oocysts excreted in
feces of humans or animals
 Invade intestinal tract mucosa causing watery,
nonbloody diarrhea, dehydration, malnutrition

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Cryptosporidiosis/Microsporidiosis:
Epidemiology (2)
 Person-to-person transmission in child care
centers
 Oocysts can contaminate water supplies
 Outbreaks associated with contaminated
drinking water and swimming pools
 Incidence declined since advent of ART

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Cryptosporidiosis/Microsporidiosis:
Clinical Manifestations
 Frequent watery, nonbloody diarrhea
 Abdominal cramps, fatigue, vomiting, anorexia, weight
loss, poor weight gain
 Fever and vomiting more common in children
 Liver involvement causes abdominal pain and elevated
alkaline phosphatase
 Less common: myositis, cholangitis, sinusitis, hepatitis,
CNS disease
 Different species may cause different clinical
syndromes (eg, Encephalitozoon hellem associated
with keratoconjunctivitis, sinusitis, prostatic abscess)

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Cryptosporidiosis/Microsporidiosis:
Diagnosis
Cryptosporidiosis
 Concentrated stool samples demonstrating
oocysts
 Evaluate at least 3 separate stool samples
 Monoclonal antibody fluorescein stain and EIA
for antigen have enhanced specificity and
sensitivity

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Cryptosporidiosis/Microsporidiosis:
Diagnosis (2)
Microsporidia
 Use thin smears of unconcentrated stool-
formalin suspension or duodenal aspirates
stained with trichrome or chemofluorescent
agents
 Consider endoscopy in all patients with diarrhea
>2 months duration
 PCR techniques still in research

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Cryptosporidiosis/Microsporidiosis:
Prevention
 Avoid direct contact with fecal material from adults,
diaper-age children, and infected animals
 Carefully investigate sources of drinking water and
recreational activities involving water
 HIV-infected children should not be allowed to drink
water directly from lakes or rivers
 Outbreaks of cryptosporidiosis occasionally have been
linked to municipal water contamination
 Some experts recommend that severely
immunocompromised HIV-infected patients should not
share a room with patients who have cryptosporidiosis

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Cryptosporidiosis/Microsporidiosis:
Treatment
 Immune restoration following antiretroviral
treatment frequently results in clearing
 Supportive care, hydration, electrolyte
replenishment, nutritional supplements
 Available treatment inconsistently effective

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Cryptosporidiosis: Treatment
 No agents have been consistently effective
 Nitazoxanide: effective for Cryptosporidium and
Giardia lamblia (B I for children and C III for HIV-
infected children)
 Nitazoxanide dosage: 100 mg orally BID for
children 1-3 years; 200 mg BID for children 4-11
years
 Limited data: paromomycin, azithromycin

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Microsporidiosis: Treatment
 Albendazole: 7.5 mg/kg orally BID; maximum
dosage 400 mg orally BID (A II)
 Fumagillin: limited data for adults, no data for
HIV-infected children

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Malaria: Epidemiology
 Malaria is caused by the obligate intracellular
protozoa Plasmodium
 4 species account for most human infections: P
falciparum (60%), P vivax (25-30%), P ovale and
P malariae
 In the United States, 1,200 to 1,400 cases are
reported annually
 Most cases of malaria infection in U.S. citizens
are a result of not taking appropriate malaria
chemoprophylaxis
 Over 30% of malaria cases in children are
found in newly arrived immigrants

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Malaria: Clinical Manifestations
 Clinical studies of malaria present differing conclusions
on whether parasitemia, frequency of malaria,
recurrence, and severity of infection differ in HIV-infected
vs HIV-uninfected children
 Fever is the most common symptom of malaria,
accompanied by chills, sweating, headache, myalgias,
malaise, nausea, vomiting, diarrhea, and cough
 Chronic symptoms include splenomegaly, fever,
thrombocytopenia, and anemia
 Congenital malaria is rare
 Malaria may be misdiagnosed as a viral infection or HIV
(HIV also may be misdiagnosed as malaria)

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Malaria: Diagnosis
 Thick blood smears are the most sensitive
technique for detecting infection but are not
helpful in determining the infectious species
 Giemsa-stained thin blood smear gives the
malaria parasite’s distinctive appearance
 Blood smear examination taken at 12-24 hour
intervals may be needed to rule out a diagnosis
 A rapid malaria antigen capture assay (Binax
Now) has been approved by the FDA
 The test is less sensitive for asymptomatic
individuals

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Malaria: Prevention
 HIV-infected children who travel to regions of
endemic malaria should use clothing impregnated
with permethrin
 DEET mosquito repellent (30-50% concentration)
is practical and effective
 Insecticide-treated bed nets should be provided
 Recommendations for chemoprophylaxis are the
same for HIV-infected children and HIV-
uninfected children

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Malaria: Prevention (2)
 Prevention includes mefloquine (Lariam) and
Malarone
 Mefloquine chemoprophylaxis is less expensive
and more convenient (once a week) but may be
associated with central nervous system effects
 Doxycycline is an alternative chemoprophylaxis
agent
 Emerging evidence suggests that TMP-SMX
may protect against new or recurrent cases of
malaria

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Malaria: Treatment
 HIV infection status should not determine the
choice of treatment (A II)
 Chloroquine-sensitive P falciparum should be
treated with chloroquine
 In the United States, resistant P falciparum
treatment choices include atovaquone-
proguanil, quinine with clindamycin, or
doxycycline or mefloquine

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Malaria: Treatment (2)
 Severe P falciparum should be treated with IV
quinidine gluconate (or IV quinine when
available)
 Ritonavir inhibits quinidine metabolism and is
contraindicated
 Artemisinin, artesunate and other derivatives
combined with additional antimalarial drugs
have not been approved in the United States
but may be available through the CDC

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Malaria: Treatment (3)
P vivax, P ovale, P malariae
 The drug of choice for non-P falciparum is
chloroquine
 The drug is well tolerated and side effects
are usually limited to itching
 Resistance to chloroquine may exist,
warranting treatment with quinine plus
clindamycin or doxycycline, atovaquone-
proguanil, or mefloquine

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Malaria: Adverse Events
 Severe malaria commonly induces
hypoglycemia in children, especially when
treated with IV quinine/quinidine
 Cardiac monitoring and intensive care
monitoring are recommended when using
quinine/quinidine

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Toxoplasmosis: Epidemiology
 Primarily perinatal transmission from primary
infection of mothers during pregnancy
 Older children acquire toxoplasmosis from poorly
cooked food and from ingestion of sporulated
oocysts in soil, water, or food

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Toxoplasmosis: Epidemiology (2)
 Risk of transmission in HIV-uninfected
mothers with primary infection during
pregnancy = 29% (lower if maternal
infection in 1st trimester)
 Perinatal toxoplasmosis infection may
occur in HIV-positive women with chronic
infection
 <1% of AIDS-defining illnesses in
children

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Toxoplasmosis: Clinical Manifestations
 Non-immunocompromised infants are usually
asymptomatic at birth but majority develop late
manifestations: retinitis, neurologic impairment
 Newborn symptoms can include:
 Rash, lymphadenopathy, jaundice, hematologic
abnormalities, seizures, microcephaly, chorioretinitis,
hydrocephalus

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Toxoplasmosis: Clinical Manifestations (2)
 Toxoplasmosis acquired after birth is initially
asymptomatic, followed by infectious
mononucleosis-like syndrome
 Chronic toxoplasmosis can reactivate in HIV-
infected children
 Isolated ocular toxoplasmosis is rare is usually
associate with CNS disease
 Less frequently observed presentations
include pneumonitis, hepatitis, myocarditis

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Toxoplasmosis: Diagnosis
 Test all HIV-infected pregnant women for
toxoplasmosis
 If positive, evaluate infant for congenital
toxoplasmosis
 Use antibody assay to detect IgM-, IgA-, or
IgE-specific antibody in first 6 months or
persistence of IgG antibody after 12 months

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Toxoplasmosis: Diagnosis (2)
 Additional methods include isolation of
toxoplasmosis from body fluids or blood
 Negative antibody does not exclude
toxoplasmosis – may require CT, MRI, or
brain biopsy in case of encephalitis
 In the United States, routine screening for
Toxoplasma is not recommended in HIV-
infected children when the mother does not
have Toxoplasma infection

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Toxoplasmosis: Prevention
 Council all HIV-infected children and their caregivers
regarding sources of Toxoplasma gondii infection
 Advise not to eat raw or undercooked meat
 Hands should be washed after contact with raw meat or
when gardening or in contact with soil
 Vegetables should be washed well and never eaten raw
 Stray cats should not be handled or adopted
 Toxoplasma-seropositive adolescents and adult
patients with CD4 counts of <100 cells/µL and
Toxoplasma-seropositive children with CD4 percentage
<15% should be administered prophylaxis with TMP-
SMX

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Toxoplasmosis: Treatment
 If HIV-infected mother has symptomatic toxoplasmosis
during pregnancy, infant should be treated (B III)
 Preferred treatment – congenital toxoplasmosis:
 Pyrimethamine loading dose of 2 mg/kg orally once
daily for 2 days; then 1 mg/kg orally once daily for
2-6 months; then 1 mg/kg orally 3 times/week with
sulfadiazine 50 gm/kg/dose BID and with leucovorin
(folinic acid) 10 mg orally with each dose of
sulfadiazine (A II)
 Optimal duration of treatment: 12 months

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Toxoplasmosis: Treatment (2)
 Pyrimethamine: 2 mg/kg/day (maximum 50 mg/kg) orally
for 3 days; then 1 mg/kg/day orally and leucovorin 10-25
mg/day plus sulfadiazine 25-50 mg/kg/dose orally, given
4 times daily
 Continue acute therapy for 6 weeks
 Lifelong therapy should be provided
 Alternative to pyrimethamine and leucovorin in sulfa-
sensitive individuals is clindamycin
Treatment of HIV-infected children with acquired
CNS, ocular, or systemic toxoplasmosis

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Toxoplasmosis: Alternative Treatment
 Azithromycin: 900-1,200 mg/kg/day with
pyrimethamine and leucovorin (B II), but not
evaluated in children
 Clindamycin with pyrimethamine leucovorin
 Adults – atovaquone: 1,500 mg orally BID
plus pyrimethamine and leucovorin (C III), but
not evaluated in children
 Limited use of corticosteroids as adjuvant
therapy with CNS disease

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Toxoplasmosis: Adverse Events
 Pyrimethamine: rash, Stevens-Johnson
syndrome, nausea, reversible bone marrow
toxicity
 Sulfadiazine: rash, fever, leukopenia, hepatitis,
nausea, vomiting, diarrhea, crystalluria
 IRIS rare in patients with HIV in toxoplasmosis

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 This presentation was prepared by Arthur Ammann,
MD, Clinical Professor of Pediatrics University of
California and President of Global Strategies for HIV
Prevention for the AETC National Resource Center, in
July 2009
 See the AETC NRC website for the most current
version of this presentation:
http://www.aidsetc.org
About This Slide Set