Opportunistic Infections

Dr. BALDEV S. PRAJAPATI, Associate Professor

Sheth L. G. General Hospital,
Smt. N. H. L. Municipal Medical College, Ahmedabad

Opportunistic Infection
An infection is referred to as opportunistic when
a microbial agent not commonly causing
diseases causes inflammation in an
immunocompromised or debilitated host

Opportunistic Infections (OIs)

Conditions associated with OIs
Newborn (Pre-terms)
Severe Malnutrition
Malignancies
Steroid & Immunosuppressive therapy
HIV & AIDS

Opportunistic Organisms
Pneumocystis jiroveci
(carinii)
Viral
Herpes simplex
Varicella zoster
Cytomegalo virus

Fungal

Candidiasis
Cryptococcus
Penicilliosis
Histoplasmosis
Blastomycosis
Co-ccidiodomycosis

Opportunistic Organisms

Toxoplasma gondii
Tuberculosis
Non-tuberculous Mycobacterial Infections (MAC)
Organisms causihg chronic diarrhea

Cryptosporidium
Microsporidium
Isospora belli & Cyclospora
E. Histolytica
G. Lamblia

Pneumocystis Jiroveci (Carinii)

Pneumonia (PCP)
Pneumocystis is an organism with biological characteristics similar
to that of fungi & protoza
Renamed as P. Jiroveci (Human strain) P. Carinii is now referred
to organism found in rats
A major cause of severe pneumonia & death
(30 to 50%) in HIV infected infants
Also called as AIDS Pneumonia
Highest incidence in first year of life, peak at 3 to 6 mon. of age

PCP - Clinical features

Age < 1 year
Tetrad of symptoms Fever, Cough, Tachypnoea
& Dyspnoea
Bilateral basal creps with respiratory distress &
hypoxia
Insidious onset of cough & dyspnoea may be
seen in older children

PCP- Investigations

X-Ray chest
ABG analysis
Serum LDH
Isolation of organisms by Gastric lavage /
Sputum / BAL
Bronchoscopy with transbronchial biopsy / open
lung biopsy

PCP - X-Ray Chest

Bil. diffuse paranchymal infiltrates with groundglass or reticulogranular appearance
Mild parenchymal infiltrates predominantly
perihilar & progressing peripherally to reach the
apical portion of the lung
Rarely, Lobar, cavitatory or milliary lesions,
pneumothorax or pneumomediastium

Diffuse bilateral interstitial infiltrates

In a child with Respiratory Distress,

Hypoxia & High LDH one may
suspect PCP

Treatment of PCP
Drugs
Dosage
TMP / SMX 15-20 mg / kg of TMP
IV / PO in 4 divided doses for 21 days
Primaquine / Primaquine base Clindamycin 0.3 mg /kg OD
Clindamycin PO (max. 30 mg/ day) + Clindamycin 10 mg /
kg IV or PO every 6 hours (max. 600 mg
IV, 300-450 mg PO) for 21 days

Treatment of PCP Contd..

Drugs
Dapsone / TMP

Dosage
Dapsone 2 mg / kg / day OD PO +
TMP 15 mg / kg / day in 3 divided
doses PO for 21 days

Steroids
Prednisolone
(Adjuvant Rx)
Pao2 < 70mm of Hg
at room air

Day 1 to 5 : 2 mg / kg / day PO BID

Day 6 to 10 : 1 mg / kg / day PO
Day 11 to 12 : 0.5 mg / kg / day PO OR
Dexamethasone IV / IM 0.3 to 0.5 mg
per kg 6 hourly for 5 days

Cotrimoxazole Prophylaxis For PCP Indications

All HIV exposed infants from 4 weeks of age (Infants
borne to HIV infected mothers) till proven to be
uninfected
All HIV infected asymptomatic infants till 1 year of age
All symptomatic HIV infected children
After initial treatment for PCP
All HIV infected children with CD4 count <15%
irrespective of symptoms
Dosage : 6 to 8 mg / kg of TMP per day daily PO

Cotrimoxazole Prophylaxis - How long

In HIV exposed infants till proved to be HIV

negative

In pts on ART, if there is evidence of rise in CD4

count > 15% on two occasions, at least 3 months
apart, consider stopping the prophylaxis

All HIV infected children who do not receive ART &

are symptomatic, prophylaxis for indefinite time

Candidiasis
The most common cause of fungal infection in
HIV infected children
Oral thrush is the commonest manifestation
Esophageal and systemic candidiasis may occur

Candidiasis - Clinical manifestations

Oropharyngeal (thrush)

Recurring or persistent thrush

in
non breast fed babies > 8
weeks of age

Esophageal
Seen in pts with low CD4 count
(< 100 / cu. mm.) high viral load
& neutropenia (< 500 / cu. mm.)
& those with oropharyngeal
thrush
AIDs defining condition

Pseudomembranous (creamy

Odynophagia (pain during

swallowing)

white curd like patches)

Dysphagia

Erythematous
Angular cheilitis

Retrosternal pain
Nausea & vomiting
Dribbling of saliva
Hoarse voice

Candidiasis - Clinical manifestations

Contd..
Systemic candidiasis may be seen in pts
especially on prolonged antibiotics
Endopthlamitis
Hepatic, splenic, renal & bone involvement
May present with shock & sepsis

Candidiasis - Diagnosis
Oropharyngeal
Characteristic clinical appearance & bleeding of
the mucosa on scraping
KOH preparation
Culture

Oesophageal
Barium swallow shows cobble stone appearance
Endoscopy
While raised plaques with extensive ulcerations
Scraping for histopathology & culture

Systemic
Blood culture

Candidiasis - Treatment
Oropharyngeal
Clotrimazole topical application qid for 7 to 14 days
Nystatin suspension qid for 7 to 14 days
For persistent infection, Fluconazole 3 to 6 mg / kg / day PO for 7 days
For resistant cases,
Itraconazole 2 to 5 mg /kg / day PO for 7 days
Amphotericin-B 0.3 mg / kg / day IV for 7 to 10 days.

Oesophageal
Fluconazole is the drug of choice, 3 to 6 mg / kg / day
Initially IV then, switch over to oral, when symptoms improve

Systemic
Amphotericin - B 0.5 to 1 mg / kg / day IV for 14 to 21 days

Candidiasis - Prophylaxis
Primary prophylaxis is not recommended
Secondary prophylaxis
Not recommended unless frequent recurrences in
severe form
May be stopped if CD4 suggests immune recovery
Risk of azole resistance
Fluconazole 3 to 6 mg / kg OD PO OR
Itraconazole 5 mg / kg OD PO

Cryptococcal Infections
Unusual in immunocompetent individuals
Less frequent among children
Leads to disseminated disease in HIV
infected children, involving brain, meninges,
skin, eyes etc.
Lower incidence with use of ART

Cryptococcosis - Clinical manifestations

Presents as acute, subacute meningitis,
encephalitis
Fever, headache, malaise & altered mental
status
Neck stiffness & focal deficit are rare

Crypotococcosis - Diagnosis
Based on high index of suspicion
Co-infection with TBM is reported
CSF
Protein, sugar & cell count may be normal
Elevated opening pressure is a diagnostic clue
India ink stain demonstrates the organism (low
sensitivity)
Cryptococcal antigen & fungal culture (more sensitivity)

Cryptococcosis - Treatment
Induction Phase
Amphotercicin-B 0.7 to 1.5 mg / kg / day IV for
2 weeks
Consolidation phase
Amphotericin-B 0.7 to 1.5 mg / kg / day IV for
8 to 10 weeks or until CSF is sterile or toxicity
develops, or Fluconazole 5 to 6 mg / kg / day IV or
PO for 8 to 10 weeks
Repeated CSF tap to offer clinical benefits
IV mannitol or oral Glycerol for cerebral oedema

Cryptococcosis - Prophylaxis

Primary, not recommended

Secondary
Fluconazole 3 to 6 mg / kg / day life long
or until CD4 % suggests immune recovery

Penicilliosis

Caused by penicillium marnafii, a dimorphic fungus

Endemic in NE part of India (Manipur)

Clinically presents with fever, papular rash with

central umbilication over face, ears and extremities
looking similar to molluscum

May be associated with lymphnode & hepatic

involvement

Penicilliosis - Diagnosis
Clinical suspicion
Wright staining of the skin scraping, bone marrow or
lymphnode biopsy demonstrates organism

Treatment
Amphotericin-B 0.6 mg / kg / day IV for 2 weeks
followed by oral Itraconazole 2 to 5 mg / kg / day for 8
to 10 weeks

Secondary Prophylaxis
Itraconazole 2 to 5 mg / kg / day PO until immune
recovery

Cytomegalovirus (CMV) - Epidemiology

CMV is a human herpes virus type 5
Infection is usually asymptomatic
Congenital or acquired CMV infection through
contact with saliva, urine or breast milk
Retinitis is common
Systemic infection is rare

CMV Retinitis
Commonest CMV disease
Asymptomatic & usually discovered on routine
ophthalmic evaluation
Children present with floaters & loss of vision
Fundoscopy: Retinal infilitrates & haemorrhages
Half yearly ophth. evaluation is a must in all children

CMV Retinitis - Treatment

Ganciclovir 5 mg / kg / dose IV BID for 14 to 21
days
Foscarnet in resistant cases
Intravitreal Ganciclovir given in a few referral
centres
Secondary Prophylaxis
Oral Ganciclovir 30 mg / kg / day until CD 4 %
suggests immune recovery

Herpes Simplex Virus

Two types : HSV-1 and HSV-2
Vertical & horizontal transmissions occur
Caesarean section lowers the risk of
transmission
Neonatal HSV infections caused by
HSV-2

Herpes Simplex Virus - Clinical

Manifestations
Neonatal HSV involves CNS, skin, eyes & mouth
Older infants & children develop ulcers in & around the
mouth (Gingivostomatitis)
Other soites such as oesophagus, CNS, genitals &
systemic disease may occur
HSV encephalitis is rare Diagnosis
Typical ulcers
Giemsa staining of scrapings of the lesions show
multinucleated giant cells & intranuclear inclusions which
are similar to varicella zoster

Herpes Simplex Virus - Treatment

Acyclovir is the drug of choice
Neonatal HSV & HSV encephalitis should receive IV
Acyclovir 10 mg / kg / dose tid for 7 to 14 days
Gingivostomatitis: Oral acyclovir 20 mg / kg / dose 5
times / day for 7 to 14 days
Valacyclovir & Foscarnet for resistant cases
Prophylaxis
Neither primary nor secondary prophylaxis is
recommended

Varicella
Varicella virus belongs to Herpes group
Can cause severe disease in HIV infected
children
Severe immune suppression results in,
Large extensive vesicles
Prolonged exanthematous phase
Complications like pneumonia, hepatitis, encephalitis
are common

Varicella
Diagnosis
Clinical Picture
Tzanck smear of scraping from the lesions
Treatment
In mild cases, acyclovir 20 mg / kg / dose qid PO x 7 days
In severe cases, acyclovir 10 mg / kg / dose tid IV x 7 days
Prophylaxis
HIV infected children without previous H/o chickenpox, who
have been exposed to varicella should receive VZIG within 96
hours of exposure, 1 vial / 10 kg (max. 5 vials)
Daily acyclovir for pts who have recurrent episodes

Herpes Zoster
Herpes Zoster usually occurs as reactivation of previous
varicella infection
Vesicles may occur in multiple dermatomes
May have associated retinitis, pneumonitis & encephalitis
May have prolonged clinical course
Healing is associated with extensive scarring
Treatment
In mild cases, acyclovir 20 mg / kg / dose gid PO for 7
days
In severe cases, acyclovir 10 mg / kg / dose tid IV for 7 to
14 days

Toxoplasmosis - Epidemiology
Caused by Toxoplasma gondii
Prevalent in the environment
Vertical transmission risk is 81% if
infection occurs in last few weeks of
pregnancy

CNS involvement is common

Toxoplasmosis - Clinical Manifestations

Asymptomatic at birth
During infancy:

lymphadenopathy,
microcephaly,

Older children:

rash, epatosplenomegaly,
jaundice, hydrocephalus,
intracranial
calcifications,
seizures

Fever, malaise, headache,

altered mental status, focal neurological deficits

Toxoplasmosis - Diagnosis
Detection of IgM antibodies in infants < 6 mon. of age
or persistence of IgG beyond 12 month of age is
diagnostic for congenital infection

Ring enhancing lesions in the basal ganglia and

corticomedullary junction on radio imaging study

Definitive diagnosis requires histologic or cytologic

confirmation by brain biopsy

Toxoplasmosis - Treatment
Congenital Toxoplasmosis
Pyrimethamine loading dose 2 mg / kg / day x 2
days, then 1 mg / kg / day x 2 to 6 month
followed by 1 mg / kg three times a week
+
Sulfadiazine 50 mg / kg / dose bid daily
+
Folinic acid 10 25 mg daily
Recommended duration of therapy is 12 mon.

Toxoplasmosis Treatment Contd..

HIV infected children with acquired CNS, ocular
or systemic toxoplasmosis
Pyrimethamine 2 mg / kg / day for 3 days, then 1 mg /
kg / day

+
Sulfadiazine 25-50 mg / kg / dose qid daily
+
Folinic acid 10 to 25 mg / day

Toxoplasmosis Treatment Contd..

HIV infected children with acquired CNS, ocular
or systemic toxoplasmosis
Therapy should be continued for 6 weeks
longer courses may be required with extensive
disease or poor response
Alternative treatment,
TMP 5 mg / SMX 25 mg IV / PO bid
(not studied in children)
Spiramycin 1.5 to 3 lacs units / kg / day in divided
doses

Toxoplasmosis - Prophylaxis
Secondary prophylaxis
Life long suppression is indicated to prevent
recurrences
Primary prophylaxis
TMP / SMX also provides prophylaxis against
toxoplasmosis

Chronic diarrhea - Organisms

Protozoa
E. Histolytica, G. Lamblia, Cryptosporidium Parvum,
Isospora belli, Microsporidia, Cyclospora etc
Bacteria
Salmonella, Campylobacter, Shigella, Cl. Diffiicile,
MAC
Viruses
CMV, Adenovirus, HIV, HSV, Rotavirus

Cryptosporidium

Cryptosporidium is a protozoa with three

different species: C. Hominis, C. Parvum, C.
Meleagridis

Mode of infection : Feco - oral contamination

Modified acid fast stain detects the oocysts

Immunoflouroscence & ELISA of stool are more

sensitive

Cryptosporidium - Treatment

No effective therapy

Use HAART to improve immune status

Nitazoxanide 100 mg bid x 3 days (age 1-3 yrs)

200 mg bid x 3 days ( age 3 to 10 yrs)

Azithromycin 10 mg / kg / on day 1 & then 5 mg / kg

PO OD from 2-10 days

Microsporidia
Spore forming protoza
Mode of infection : Feco - oral contamination
Stool exam or duodenal aspirate with modified
trichrome stain demonstrates the organisms

Treatment
No effective therapy
Nitazoxanide for 3 days
Albendazole 7.5 mg / kg / dose bid

Isospora belli & Cyclospora

Rare
Demonstrates oocyte with modified acid fast stain
Treatment
Isospora belli : TMP / SMX 20 mg / kg / day of TMP in 4
divided doses x 10 days and then twice a day x 3 days
Pyrimethamine with folic acid can be used in pts allergic to
sulfonamides
Cyclospora :

TMP / SMX 10 mg / kg / day of TMP in

two divided doses x 7 days

HIV & Tuberculosis

Look for an adult contact
HIV & TB coexist in 20% to 48% of children
Extra pulmonary & miliary TB are more common in young
children

Atypical features are common

MT generally negative due to immune suppression
If MT +ve in an asymptomatic child - latent infection - treatment is
required

Screen family members & test for drug resistance in the source,
if no response to treatment

HIV and Tuberculosis - Manifestations

May be non specific

Similar to those in non-HIV infected pts
Fever > 2 weeks
Cough > 2 weeks
Pneumonia not responding to antibiotics
Persistent lymphnode enlargement
Older children & adolescents may present with
cavitatory TB

Extra pulmonary Disseminated TB, CNS TB, Bone TB

and TB of Serosal surfaces

HIV & Tuberculosis - Diagnosis

MT > 5 mm

Gastric lavage / Induced sputum

Chest X-Ray

Radiometric (Bactec) cultures & drug sensitivity

BAL

Body fluid or Tissue diagnosis as needed

Serology & PCR are often not reliable

HIV & Tuberculosis - Management

Treatment for tuberculosis is priority
Start ART 2 to 8 weeks after Anti - TB treatment
Children already on ART, the regimen should
be reviewed

Modification of duration schedule and the

medications may be required

Duration of treatment as per the RNTCP

guidelines

HIV & Tuberculosis - Drug Resistant TB

Suspect MDR TB in children not responding to

standard anti - TB drugs

Confirm MDR TB by cultures & drug sensitivity

Use min. 3 drugs, 2 drugs bactericidal to which

the organism is susceptible

For INH Resistance,

Use RMP + PZA + EMB for 9 to 12 month

HIV & Tuberculosis - Drug Resistant TB

For RMP Resistance,

INH + PZA + EMB + SM for 2 months followed by
INH + PZA + EMB for 10 months
For older children, INH + EMB + Quinolone

For INH + RMP Resistance,

Capreomycin + Fluroquinolones for 12 to 24 months
Therapy may be individualized

HIV & Tuberculosis - Steroids

Use steroids cautiously in advanced severe

immunodeficiency

Indications same as in non-HIV pts

May be used in meningitis, miliary, endobronchial and

serosal forms

HIV & Tuberculosis

Monitoring
Clinical improvement, wt, symptoms
Monitoring LFT
Elevated enzyme levels 2 to 3 times may not require

stoppage of anti-TB drugs

Repeat X-Rays after 2 to 3 months
Lymphnodes may persist for 2 to 3 years after successful
therapy
Prophylaxis
HIV infected children in close contact with open cases of TB,
prophylaxis as per RNTCP guidelines
Secondary prophylaxis should not be given in a child who has
been successfully treated for TB

Mycobacterium Avium Complex (MAC)

MAC refers to various non-tuberculous

mycobacteria such as M. avium,
M. intracellulare, M. paratuberculosis

Occurs commonly at CD4 count as below

1 yr CD4 < 750 cells / l

6 to 12 yr CD4 < 50 cells / l

1 to 6 yr CD4 < 500 cells / l

MAC - Clinical features

Fever

Lymphadenopathy

Failure to thrive

Hepatosplenomegaly

Night sweats involvement

Bone marrow

Fatigue

Leucopenia

Chronic diarrhea

Neutropenia

Abd. Pain

Anemia

MAC - Diagnosis

Isolation from biopsy, bone marrow,

lymphnodes etc.

Multiple blood cultures (takes 2 weeks)

BACTEC

Raised alkaline phosphatase

MAC - Treatment

Minimum 2 to 3 drugs

Single drug Rx with macrolide causes

resistance

Clarithromycin 7.5 to 15 mg / kg PO BID

Azithromycin

10 to 20 mg / kg PO OD

Ethambutol

15 to 25 mg / kg PO OD

MAC - Treatment

Other drugs used,

Ciprofloxacin

20 to 30 mg / kg PO OD

Amikacin 15 to 30 mg / kg / day IV / IM (divided in two doses)

Streptomycin 20 to 40 mg / kg IM OD

Disseminated disease requires 3 to 4 drugs

If improvement is in 4 to 6 weeks, continue 2 drugs

MAC - Prophylaxis
Primary prophylaxis advocated for,
Any child in WHO stage IV
Based on CD4 counts as below
1 yr CD4 < 750 cells/l
1 to 6 yr CD4 < 500 cells /l
6 to 12 yr CD4 < 50 cells/l
Drugs recommended
Clarithromycin 7.5 mg / kg PO BID
Azithromycin 20 mg / kg once a week or 5 mg / kg OD
Secondary prophylaxis advocated for,
Those who have received Rx, to be given for life time
Clarithromycin or Azithromycin & ethamobutol & Ciprofloxacin

Bacterial Infections

Pneumonias are the most common

infections

Other infections include,

Meningitis

Otitis media

Sepsis

Osteomyelitis

Abscesses

Septic arthritis

Bacterial Infections - Etiological Agents

Strept. Pneumoniae

Pseudomonas

H. Influenza type B

B. Pertussis

Staph. aureus

Chlamydia

E. coli.

Catheter associated

Salmonella

staph, pseudomonas,
enterococcus etc

Bacterial Infections - Diagnosis

Depends on the site & system involved

Isolation of organism by culture from tissue
fluids or blood

In pneumonias, induced sputum after

nebulization with hypertonic saline

Relevant fluid examination and cultures with

sensitivity pattern

Bacterial Infections - Choice of Antibiotics

Empiric antibiotics as per suspected organisms
Pneumonias: S. pneumoniae, HIB, Staph. aureus,
klebsiella, Proteus Pseudomonas etc.

Meningitis : HIB, S. Pneumoniae, Staph

Osteomyelitis : Staph, Klebsiella, Salmonella,
Pseudomonal, Proteus etc.

Sepsis :

Gram neg. organisms, Staph, Anaerobes,

Enterobacter

Abscesses :

Staph, S. Pyogenes

Change of antibiotics based on culture & sensitivity

when available

Bacterial Infections - Prevention

TMP SMX

Immunization

HIB & Pneumococcal vaccines as

special ones

Thank you