1 Respiratory Diseases in HIV-infected Children - Part 1- Upper Respiratory Infection and Pneumonia HAIVN Harvard Medical School AIDS Initiative in Vietnam

2 Learning Objectives By the end of this session, participants should be able to: Identify the most common causes of respiratory disease in HIV patients Describe how to manage ear infections Explain how to clinically diagnose and treat: Bacterial pneumonia Viral pneumonia Fungal pneumonia

What are Common Respiratory Syndromes in HIV infected Children? Upper respiratory infections:  Ear infections  Sinusitis Lower respiratory infections:  Pneumocystis jiroveci pneumonia (PCP)  Bacterial pneumonia  Pulmonary tuberculosis  Viral pneumonia  Fungal pneumonia Infectious causes  Upper respiratory infections: Ear infections Sinusitis  Lower respiratory infections: Pneumocystis jiroveci pneumonia (PCP) Bacterial pneumonia Pulmonary tuberculosis Viral pneumonia Fungal pneumonia Non-infectious causes  Lymphocytic interstitial pneumonitis (LIP)

Bệnh cảnh nhập viện ở BV Nhi Đồng 1 – khảo sát năm % trẻ nhập viện vì bệnh cảnh hô hấp n = 134 Bs. Trương Hữu Khanh NĐ1

5 Upper Respiratory Infections

Ear Infections SymptomsTreatment Otitis media Usually begins at age 6-9 months Fever, pain, irritability Tends to be recurrent Complications: perforated tympanic membranes common, chronic otitis media Acute pain, often severe Edema, erythema of the canal Thick, clumpy otorrhea Otitis externa Amoxicillin: 80-90mg/kg/day for days Cipro or ofloxacin otic drops

Sinusitis (1) Pathology: Viral upper respiratory tract infection Viral rhinosinusitis Acute bacterial sinusitis

8 Sinusitis (2) Symptoms: Fevers, poor feeding Nasal congestion, purulent nasal discharge Cough for >10-14 days, or high fever to 39 o C and purulent discharge for 3-4 days, indicate bacterial sinusitis Treatment: Mild casesAmoxicillin 45mg/kg/day More severe casesAmoxicillin-clavulanate (80-90mg/kg/day) AlternativesAzithromycin, cotrim, cefuroxime, ceftriaxone, levofloxacin

9 Pharyngitis Usually caused by virus or Bacteria: Group A streptococcus Symptoms: Fever With/without rash Sore throat Large tonsils and lymph node on the neck

10 Pharyngitis Acute pharyngitis caused by Strep.

11 Lower Respiratory Infections

12 Lower Respiratory Infections Pneumonia is the number one cause of deaths in children worldwide: Responsible for nearly 1 in 5 deaths, for an estimated 1.8 million deaths annually Most cases are in Africa and South East Asia Incidence may be higher where there is high prevalence of HIV Occurs more often and more severe, with higher mortality rates, in HIV- infected children

Pneumonia – Etiology by Age AgeEtiologies <2 months Gram-negative organisms Anaerobes and PCP <1 year PCP <2 years Viral (RSV), mixed with bacteria <5 years Bacterial:  Streptococcus pneumoniae  Haemophilus influenzae  and Staphylococcus aureus >5 years Mycoplasma pneumoniae or Chlamydophila pneumoniae TB? LIP?

Pneumonia – Diagnosis Non-severe pneumonia (can be managed as outpatient) Diagnosis based on clinical presentation Moderate to severe pneumonia (especially in inpatient setting) Indicate: Pulse oximetry Microbiology: Obtaining sputum when possible Blood culture Acute phase reactant (CRP, ESR) Complete blood count Viral specific testing CXR

15 Bacterial Pneumonia

16 Bacterial Respiratory Infections Bacterial pneumonias were more common in HIV-infected children than HIV-uninfected: S. pneumoniae43x H. Influenzae B21x S. aureus49x E. coli98x M. tuberculosis23x * Madhi SA et al, Clin Infect Dis 2000;31:170.

17 Bacterial Pneumonia in HIV-infected Patients Compared to non-HIV infected: More frequent, more severe, more likely to be fatal Caused by a wider variety of organisms, including resistant ones More likely to be polymicrobial More often accompanied by bacteremia

18 Bacterial Pneumonia – Clinical Presentation Onset usually acute High fevers, rigors, chills Cough productive of sputum Tachypnea, dyspnea Chest pain May have poor feeding, nausea/vomiting Rales often present on lung exam

19 Bacterial Pneumonia – CXR (1) Often seen: Lobar infiltrate Bronchoalveolar infiltrate Parapneumonic effusions Pleural effusions

Bacterial Pneumonia – CXR (2)

Bacterial Pneumonia – CXR (3)

Bacterial Pneumonia – CXR (4)

Bacterial Pneumonia – CXR (5)

Bacterial Pneumonia – Treatment Inpatient (moderate to severe pneumonia) Outpatient (mild to moderate pneumonia) Ampicillin + gentamycin (WHO) or Ceftriaxone or cefotaxime  Azithromycin (also for atypical pneumonia)  Amoxicillin/clavulanate  Use Cotrimoxazole for PCP for all infants ≤ 1 year  Vancomycin, clindamycin if suspect MRSA  Levofloxacin or ciprofloxacin if suspect resistant S. pneumoniae and TB has been ruled out

25 Viral Respiratory Infections

26 Viral Respiratory Infections (1) Most viral infections manifest no differently in HIV-negative children than in HIV- positive children until HIV disease is advanced RSV, influenza, parainfluenza, coronaviruses, rhinovirus, are similar except: Virus is excreted for longer For RSV, influenza and parainfluenza, wheezing is less frequent Bacterial co-infections are more frequent Hospitalization and mortality rates are higher

27 Viral Respiratory Infections (2) Outcomes are worse with certain infections: Measles, varicella, CMV, adenovirus CMV pneumonia is present in advanced HIV infection, usually as a co-pathogen, especially in infants and young children

28 Viral Respiratory Infections (3) Diagnosis: RSV: bronchiolitis Influenza: seasonal, with local circulation CMV: severe pneumonia. CXR with bilateral infiltrates, CMV IgM+, PCR+ with high titer Treatment: mostly supportive Influenza: oseltamivir (Tamiflu), zanamivir (Relenza), peramivir (IV), amantadine, rimantadine CMV: gancyclovir IV

29 Fungal Pneumonia

30 Fungal Pneumonia Difficult to diagnose clinically Diagnosis requires microbiology, specific testing Sputum or bronchoalveolar stain and culture, biopsy Fungal pneumonia in the immunocompromosed patients is often part of a systemic, multi-organ infection Cryptococcosis with meningitis Penicillium marneffei with skin lesions, splenomegaly CXR reveals no typical findings Treatment according to etiology

Pneumonia – IMCI Severity of Pneumonia Definitions Mild  Cough or difficulty breathing with age-adjusted tachypnea:  Age 0-2 months: ≥60/min  Age 2-11 months: ≥50/min  Age 1-5 years: ≥40/min  Age > 5 years: ≥20/min Severe  Cough or difficulty breathing plus one of the following:  Lower chest indrawing  Nasal flaring  Or grunting Very severe  Cough or difficulty breathing plus one of the following:  Cyanosis  Severe respiratory distress  Inability to drink or vomiting everything  Lethargy  Loss of consciousness/convulsions

32 Pneumonia – Criteria for Admission Moderate to severe pneumonia, with respiratory distress and hypoxemia (SpO2 <90%) 8 signs of respiratory distress 1.Tachypnea, respiratory rate, breaths/min Age 0–2 months:.60 Age 2–12 months:.50 2.Dyspnea 3.Retractions (suprasternal, intercostals, or subcostal) 4.Grunting 5.Nasal flaring 6.Apnea 7.Altered mental status 8.Pulse oximetry measurement,90% on room air  Age 1–5 Years:.40  Age.5 Years:.20

33 Case Study

34 Linh, Girl (1) A 17 month old girl with fever and dyspnea is transferred to your clinic PM: 10 days prior to the admission, patient presented fever (38), productive cough, dyspnea. The fever and dyspnea went worse with time. The child had no vomiting or convulsion. The patient had been treated at provincial hospital for 4 days without improvement.

35 Linh, Girl (2) Both parent are HIV positive, not yet on ART The child was not on PMCTC; TB vaccination at 1 months PE: alert, no fever, non-productive cough Blue lips while crying, subcostal withdrawing, BR: 70 per min, Sp0 2 : 82% no oxygen Lung: moist rales, sound breath decreased on the left lung Heart: HR: 155 per min, regular Oral thrush Abdomen: soft, hepatomegaly, 4cm subcostal HIV ELISA: Positive

36 Linh, Girl (3) What do you see on CRX? Opaque entire left lung, mediasternal shift What is your clinical diagnosis: Bacterial pneumonia Pleural effusion Tuberculosis PCP At admission

37 Linh, Girl (4) What possible diagnostic tests are necessary? WBC: 15 G/l Thoracentesis: pus fluid Pleural fluid culture: Staphyloccocus aureus, TB PCR neagative PCR for TB from gastric lavage: negative What is the diagnosis? Pneumonia and empyema What is the best treatment plan? Pleural drainage Antibiotics: Vancomycin, Ceftriaxone, Amikacin

Linh, Girl (5) The patient got better after 7 days treatment (no fever, no dyspnea) and after two weeks patient was discharged HIV + confirmed, initiated ARV After 7 days treatmentAt the timing of discharge

39 Key Points Otitis media is common in children with HIV and should be treated with a long course of antibiotics to prevent complications Recurrent bacterial pneumonia is common in HIV infected children

40 Thank you! Questions?