Wasting Syndrome and Prolonged Fever in HIV-Infected Children HAIVN Harvard Medical School AIDS Initiative in Vietnam

Learning Objectives By the end of this session, participants should be able to: Define wasting syndrome and list common etiologies in HIV-infected children Review algorithmic approach to wasting syndrome Define prolonged fever and list common etiologies in HIV-infected children Review algorithmic approach to prolonged fever

Wasting syndrome http://www.siddhaquest.com/images/web_buttons/Wasting_Syndrome_1.jpg http://www1.lf1.cuni.cz/~hrozs/hiveng1.htm

Wasting In the absence of concurrent illness other than HIV Recognized AIDS-defining condition Can severely impact normal growth and development Associated with high risk for HIV disease progression and short-term mortality Tovo PA, de Martino M, Gabiano C, et al. Prognostic factors and survival in children with perinatal HIV-1 infection. The Italian Register for HIV Infections in Children. Lancet 1992; 339:1249.

HIV Wasting Syndrome: Clinical Diagnosis Weight loss of more than 10% of body weight or body mass index (BMI) <18.5 PLUS Prolonged & unexplained diarrhea (>2 loose stools /day for more than 1 month) OR Prolonged & unexplained fever (T> 37.5⁰C for more than 1 month)

HIV Wasting Syndrome – Definitive Diagnosis Documented weight loss (>10% of body weight) PLUS Two or more unformed stools negative for pathogens OR Documented T > 37.5⁰C with no other cause of disease -Temp: negative blood culture, negative malaria slide and normal or unchanged CXR

Clinical Staging -First box is definition of HIV wasting syndrome -Emphasize these children are in CS 3 or 4 so advanced disease

Common Etiologies - Wasting Malnutrition Inadequate intake due to factors such as drug side effects (e.g., taste disturbances) Infection(s) or illness, including recurrent / occult including resulting conditions such as malabsorption Oral or esophageal candidiasis (odynophagia) Opportunistic infections (OIs) Diarrhea HIV Depression

Medical History Severity of weight loss Symptoms/signs of occult infection Presence or history of diarrhea or vomiting Feeding practices Social or other factors affecting feeding/access to nutritious foods Medication history including any taste disturbances, reactions interfering with intake Review of nutritional intake

Physical Examination Record / trend weight and height Thorough exam of systems for any signs of overt or occult infection(s) Focus exam based on symptoms reported http://pediatrics.about.com/cs/growthcharts2/l/blboystwo.htm

Algorithmic approach to management of Wasting / failure to thrive

Management of Wasting Assessment: Take detailed history and perform thorough exam Initial support: Hydration and nutritional support. Begin evaluation for ARV if the child is eligible. History of inadequate caloric intake? History of thrush or oral ulcers? Child critically malnourished or dehydrated? History of fever or diarrhea? Give feeding trial for 7 days with increased caloric and vitamin supplementation Treat for candida or HSV (if ulcers) Hospitalize to give nutritional support, fluid replacement, vitamins and minerals If improved, continue treatment with close monitoring Perform complete blood count with differential WBC, albumin, blood cultures, CXR, rule out TB, stool studies for bacteria, ova and parasites. Evaluate as for patients with diarrhea, fever. Abdominal ultrasound may reveal enlarged liver and spleen. No improvement - Consider hospitalization for dietary support. - Re-evaluate for occult infection. - Consider ARV treatment if eligible Treat for causes No Causes found? Yes Adapted from Viet Nam MOH Guidelines

Prolonged fever

Prolonged Fever T > 37.5⁰C for more than 14 days Common etiologies Infectious: bacterial (salmonellosis, bacteremia, TB, MAC), fungal (cryptococcosis/meningitis, penicilliosis), viral (CMV, HSV/meningitis), malaria, etc. HIV related neoplasms (e.g. lymphoma) HIV itself Drug fever (hypersensitivity to drugs such as CTX or ARVs)

TB Pneumonia in a 2-year-old who presented with fever, cough, weight loss Source: www.Uptodate.com

Medical History Take a thorough history including: Was the onset acute or subacute? How long has the fever/ illness lasted? Is it associated with any signs/ symptoms (thorough review of symptoms by system, e.g., productive or dry cough, difficulty breathing, shortness of breath, skin or mucosal lesions, night sweats, chills, weight loss, mental status changes, joint pains)? Has anyone in patient’s family or close contacts been diagnosed with / is currently being treated for TB or other infectious diseases? Medication history including ARVs, CTX, allergies History of OIs or other HIV-related conditions?

Physical Examination Perform detailed physical exam looking for signs of: General conditions: weight loss, skin or mucosal lesions, lymphadenopathy Respiratory complications: dyspnea, cyanosis, crackles, fremitus, digital clubbing Other: mental-physical underdevelopment, immunodeficiency (e.g. oral thrush, cachexia) Focus exam from history taking/ symptoms

8-year-old boy presenting with prolonged fever and skin lesions Source: www.med.cmu.ac.th

Algorithmic approach to management of prolonged fever

Give antipyretics, rehydration, good nutrition Prolonged fever Give antipyretics, rehydration, good nutrition Take history Examine physically Routine and cause-guiding investigations: CBC, CD4 (if available) Respiratory findings: CXR, sputum for AFB Neurologic findings: PL Septicemia, penicilliosis: blood culture Lymphadenopathy: aspiration Abdomen ultrasound, etc... Suggestive causes of fever: Lymphadenopathy: TB, MAC, fungal septicemia Respiratory findings: TB, PCP, bacterial pneumonia Diarrhea: Salmonellosis, TB enteritis, MAC Neurologic findings: Bacterial, TB, cryptococcal meningitis, Toxoplasma encephalitis, malaria Anemia: TB, MAC, fungal septicemia History with medication: allergy Skin lesions: Penicilliosis, Cryptococcosis Etc.... Empirical treatment: Bacterial or cryptococcal meningitis: proper antimicrobials Septicemia: appropriate antimicrobials Toxoplasma encephalitis: co-trimoxazole Penicilliosis: itraconazole PCP: co-trimoxazole Etc... TB: Anti-TB drugs Diagnosis confirmed by investigations, and/or the child responds to empirical therapy Diagnosis not confirmed by investigations, the child does not respond to empirical treatment Continue and complete treatment. Maintenance treatment if indicated Re-evaluate clinically, consider other causes, especially TB, MAC or fever due to HIV itself Do corresponding lab tests and investigations; consider lymphnode biopsy, bone marrow analysis and biopsy... Treat presumptively for TB; MAC Consider ARV treatment Adapted from Viet Nam MOH Guidelines

Key points HIV wasting syndrome is defined either clinically by patient/ caregiver report or definitively through documentation of weight loss and prolonged diarrhea or fever A thorough medical history and physical examination should be performed to rule out and / or address any treatable causes of wasting Prolonged fever is diagnosed when the child has T>37.5⁰C for >14 days A thorough medical history and physical examination should be performed to diagnose and address any treatable causes of prolonged fever Health care providers can refer to the algorithms adapted from the Viet Nam Ministry of Health for further guidance on how to manage wasting syndrome and/ or prolonged fever

Thank you! Questions?