OPPORTUNISTIC INFECTIONS. IAP UG Teaching slides

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1 OPPORTUNISTIC INFECTIONS 1

2 OPPORTUNISTIC INFECTIONS An infection is referred to as opportunistic when a microbial agent not commonly causing diseases causes inflammation in an immunocompromised or debilitated host IAP UG Teaching slide G Teaching 2 2

3 OPPORTUNISTIC INFECTIONS (OIS) Conditions associated with OIs Newborn (Pre terms) Severe Malnutrition Malignancies Steroid & Immunosuppressive therapy HIV & AIDS 3 3

4 OPPORTUNISTIC ORGANISMS Pneumocystis jiroveci (carinii) Viral Herpes simplex Varicella zoster Cytomegalovirus Fungal Candidiasis Cryptococcus Penicilliosis Histoplasmosis Blastomycosis Coccidiodomycosis slides IAP UG Teaching 4

5 OPPORTUNISTIC ORGANISMS Toxoplasma gondii Tuberculosis Non tuberculous Mycobacterial Infections (MAC) Organisms causing chronic diarrhea Cryptosporidium Microsporidium Isospora belli & Cyclospora E. Histolytica G. Lamblia 5

6 PNEUMOCYSTIS JIROVECI (CARINII) PNEUMONIA (PCP) Pneumocystis is an organism with biological characteristics similar to that of fungi & protozoa 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 6

7 PCP CLINICAL FEATURES Age < 1 year Tetrad of symptoms Fever, Cough, Tachypnoea & Dyspnoea Bilateral basal crepts with respiratory distress & hypoxia Insidious onset of cough & dyspnea may be seen in older children 7

8 PCP INVESTIGATIONS X Ray chest ABG analysis Serum LDH Isolation of organisms by Gastric lavage / Sputum / BAL Bronchoscopy with transbronchial biopsy / open lung biopsy 8

9 PCP X RAY CHEST Bilateral diffuse paranchymal infiltrates with ground glass or reticulogranular appearance Mild parenchymal infiltrates predominantly perihilar & progressing peripherally to reach the apical portion of the lung Rarely, Lobar, cavitatory or miliary lesions, pneumothorax or pneumomediastium 9

10 DIFFUSE BILATERAL INTERSTITIAL INFILTRATES 10

11 IN A CHILD WITH RESPIRATORY DISTRESS, HYPOXIA & HIGH LDH ONE MAY SUSPECT PCP 11

12 TRE ATM ENT OF Drugs PCP TMP / SMX Primaquine Clindamycin Dosage mg / kg of TMP IV / PO in 4 divided doses for 21 days Primaquine base Clindamycin 0.3 mg /kg OD PO (max. 30 mg/ day) + Clindamycin 10 mg / kg IV or PO every 6 hours (max. 600 mg IV, mg PO) for 21 days 12

13 TREATMENT OF PCP CONTD.. Drugs Dosage Dapsone / TMP Dapsone 2 mg / kg / day OD PO + TMP 15 mg / kg / day in 3 divided doses PO for 21 days Steroids Day 1 to 5 : 2 mg / kg / day PO Prednisolone BID (Adjuvant Rx) Day 6 to 10 : 1 mg / kg / day PO Pao2 < 70mm of Day 11 to 12 : 0.5 mg / kg / day Hg at room air PO OR Dexamethasone IV / IM 0.3 to 0.5 mg per kg 6 hourly for 5 days 13

14 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 14

15 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 CD 4 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 15

16 CANDIDIASIS The most common cause of fungal infection in HIV infected children Oral thrush is the commonest manifestation Esophageal and systemic candidiasis may occur 16

17 CANDIDIASIS CLINICAL MANIFESTATIONS Oropharyngeal (thrush) Esophageal Recurring or persistent thrush in non breast fed babies > 8 weeks of age Pseudomembranous (creamy white curd like patches) Erythematous Angular cheilitis Seen in pts with low CD 4 count (< 100 / cu. mm.) high viral load & neutropenia (< 500 / cu. mm.) & those with oropharyngeal thrush AIDs defining condition Odynophagia (pain during swallowing) Dysphagia Retrosternal pain Nausea & vomiting Dribbling of saliva Hoarse voice 17

18 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 18

19 CANDIDIASIS DIAGNOSIS Oropharyngeal Characteristic clinical appearance & bleeding of the mucosa on scraping KOH preparation Culture Esophageal Barium swallow shows cobble stone appearance Endoscopy While raised plaques with extensive ulcerations Scraping for histopathology & culture Systemic Blood culture 19

20 Oropharyngeal CANDIDIASIS TREATMENT 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. Esophageal 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 20

21 CANDIDIASIS PROPHYLAXIS Primary prophylaxis is not recommended Secondary prophylaxis Not recommended unless frequent recurrences in severe form May be stopped if CD 4 suggests immune recovery Risk of azole resistance Fluconazole 3 to 6 mg / kg OD PO OR Itraconazole 5 mg / kg OD PO 21

22 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 22

23 CRYPTOCOCCOSIS CLINICAL MANIFESTATIONS Presents as acute, subacute meningitis, encephalitis Fever, headache, malaise & altered mental status Neck stiffness & focal deficit are rare 23

24 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) IAP UG IAP Teaching UG Teaching slides slides

25 Induction Phase CRYPTOCOCCOSIS TREATMENT Amphotericin 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 edema 25

26 CRYPTOCOCCOSIS PROPHYLAXIS Primary, not recommended Secondary Fluconazole 3 to 6 mg / kg / day life long or until CD 4 % suggests immune recovery 26

27 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 lymph node & hepatic involvement 27

28 Clinical suspicion PENICILLIOSIS DIAGNOSIS Wright staining of the skin scraping, bone marrow or lymph node 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 28

29 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 29

30 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 30

31 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 31

32 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 32

33 HERPES SIMPLEX VIRUS CLINICAL MANIFESTATIONS Neonatal HSV involves CNS, skin, eyes & mouth Older infants & children develop ulcers in & around the mouth (Gingivostomatitis) Other sites such as esophagus, 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 33

34 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 34

35 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 35

36 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 36

37 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 qid PO for 7 days In severe cases, acyclovir 10 mg / kg / dose tid IV for 7 to 14 days 37

38 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 38

39 TOXOPLASMOSIS CLINICAL MANIFESTATIONS Asymptomatic at birth During infancy: Older children: rash, hepatosplenomegaly, lymphadenopathy, jaundice, hydrocephalus, microcephaly, intracranial calcifications, seizures Fever, malaise, headache, altered mental status, focal neurological deficits 39

40 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 40

41 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 mg daily Recommended duration of therapy is 12 mon. 41

42 R H E I A V T i M n E f N e T c t C e O d N c T h D. i. l d 42

43 R E A T M E N T C O N T D.. 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 43

44 TOXOPLASMOSIS PROPHYLAXIS Secondary prophylaxis Life long suppression is indicated to prevent recurrences Primary prophylaxis TMP / SMX also provides prophylaxis against toxoplasmosis 44

45 CHRONIC DIARRHEA ORGANISMS Protozoa E. Histolytica, G. Lamblia, Cryptosporidium Parvum, Isospora belli, Microsporidia, Cyclospora etc Bacteria Salmonella, Campylobacter, Shigella, Cl. Difficle, MAC Viruses CMV, Adenovirus, HIV, HSV, Rotavirus 45

46 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 46

47 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 47

48 MICROSPORIDIA Spore forming protozoa 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 48

49 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 allergic to sulfonamides be used in pts Cyclospora :TMP / SMX 10 mg / kg / day of TMP in two divided doses x 7 days 49

50 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 50

51 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 lymph node enlargement Older children & adolescents may present with cavitatory TB Extra pulmonary Disseminated TB, CNS TB, Bone TB and TB of Serosal surfaces 51

52 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 IAP UG are Teaching often slides not reliable 52

53 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 53

54 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 54

55 For RMP Resistance, HIV & TUBERCULOSIS DRUG RESISTANT TB 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 + Fluoroquinolones for 12 to 24 months Therapy may be individualized 55

56 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 56

57 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 Lymph nodes 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 57

58 MYCOBACTERIUM AVIUM COMPLEX (MAC) MAC refers to various non tuberculous mycobacteria such as M. avium, M. intracellulare, M. paratuberculosis Occurs commonly at CD 4 count as below 1 yr CD4 < 750 cells / µl 1 to 6 yr CD 4 < 500 cells / µl 6 to 12 yr CD 4 < 50 cells / µl 58

59 CLIN ICAL FEAT URE Fever S Failure to thrive Lymphadenopathy Hepatosplenomegaly Night sweats Bone marrow involvement Leucopenia Fatigue Neutropenia Chronic diarrhea Anemia Abd. Pain 59

60 MAC DIAGNOSIS Isolation from biopsy, bone marrow, lymphnodes etc. Multiple blood cultures (takes 2 weeks) BACTEC Raised alkaline phosphatase 60

61 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 61

62 Other drugs used, Ciprofloxacin Amikacin MAC TREATMENT 20 to 30 mg / kg PO OD 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 62

63 MAC PROPHYLAXIS Primary prophylaxis advocated for, Any child in WHO stage IV Based on CD 4 counts as below 1 yr CD4 < 750 cells/µl 1 to 6 yr CD 4 < 500 cells /µl 6 to 12 yr CD 4 < 50 cells/µl Drugs recommended Clarithromycin7.5 mg / kg PO BID Azithromycin 20 mg / kg once a week or 5mg / kg OD Secondary prophylaxis advocated for, Those who have received Rx, to be given for life time Clarithromycin or Azithromycin & ethambutol & Ciprofloxacin 63

64 BACTERIAL INFECTIONS Pneumonias are the most common infections Other infections include, Meningitis Sepsis Abscesses Otitis media Osteomyelitis Septic arthritis 64

65 BACTERIAL INFECTIONS ETIOLOGICAL AGENTS Strept. Pneumoniae H. Influenza type B Staph. aureus E. coli. Salmonella Pseudomonas B. Pertussis Chlamydia Catheter associated staph, pseudomonas, enterococcus etc 65

66 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 66

67 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, Pseudomonas, Proteus etc. Sepsis : Gram neg. organisms, Staph, Anaerobes, Enterobacter Abscesses : Staph, S. Pyogenes Change of antibiotics based on culture & sensitivity when available 67

68 BACTERIAL INFECTIONS PREVENTION TMP SMX Immunization HIB & Pneumococcal vaccines as special ones 68

69 Thank you 69

Cerebral Toxoplasmosis in HIV-Infected Patients. Ahmed Saad,MD,FACP

Cerebral Toxoplasmosis in HIV-Infected Patients Ahmed Saad,MD,FACP Introduction Toxoplasmosis: Caused by the intracellular protozoan, Toxoplasma gondii. Immunocompetent persons with primary infection