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Wednesday’s Child

“The Long Journey Home”

Summary of Events
• 10 years old female from Payatas,Q.C.
• Fever 5 days PTA and 32 days in the hospital
• Mother had intermittent fever at 3 months AOG. A
sibling has “bronchial asthma”
• Bipedal edema with abdominal enlargement
• Irritable
• Severely wasted/stunted
• (+) cervical lymphadenopathies
• Fine crackles
• Hepatomegaly
• Global developmental delay
Summary of Events

• In the ward: Pneumonia with mild pleural

effusion; hematochezia and melena; passage
of ascaris; DIC; became dyspneic
• Eventual bleeding and death
Summary of Events
• Admitted: Kwashiorkor vs. Nephrotic
• Lab: Initial CBC-anemia; proteinuria, pyuria;
electrolyte imbalance; abnormal A/G ratio;
normal Serum Cholesterol, abnormal serum
transaminases, abnormal total bilirubin (B1 &
B2), normal ASO titre
• Subsequent lab results: leucocytosis,
Typhidot (-); Blood culture (-); Abdominal UTZ:
liver parenchymal inflammation, ascites; (-)
Malarial smear, (+) E.histolytica cysts &
Summary of Events
• Managed with IVF, low salt diet, diuretic,special
milk formula, Vit C, K & multivitamins, antacids
and whole blood & plasma transfusions
• Penicillin V, Cotrimoxazole, Cefuroxime,
Ceftriaxone, Cloxacillin, Piperacillin-Tazobactam,
Amikacin, Ciprofloxacin, Amphotericin B,
Salient Features
• Prolonged fever
• Bipedal edema with abdominal enlargement
• Global developmental delay
• Energy and Protein Undernutrition
– Weight loss/anorexia
– Abnormal albumin/globulin ratio
• Irritability
• Cough and dyspnea
• Nonresponse to multiple antibiotics
• Hepatomegaly with abnormal liver studies
• Hematochezia and Melena
• Pyuria and proteinuria
Kwashiorkor Vs. Nephrotic Syndrome
• Presenting manifestation: Edema
– Mechanism is well understood
– Renal disorder – water and salt retention
– Hypoalbuminemia – kwashiorkor
– Passive congestion – CHF
– Angioneurotic edema - allergy
Renal Disorders presenting
with Edema in Childhood
• Nephrotic Syndrome
– Periorbital edema esp on waking
– Scrotal, leg and ankle edema
– Ascites
– Breathlessness due to pleural effusions and
abdominal distension
– Age between 1 – 10 yrs
– No macroscopic hematuria
– Normal BP
– Normal complement levels
– Normal renal function
Renal Disorders presenting
with Edema in Childhood
• Acute PS Glomerulonephritis
– Usually follows strep sore throat or skin
– Raised ASO titre, low complement levels
 glomerular cellularity restrict GFR
UO and volume overload
• Hypertension & seizures
• Edema esp. periorbital
• Hematuria and proteinuria
• Marasmus: weight loss <60% mean for age
and wasted, apathetic, wizened mien; (-)
• Kwashiorkor: body weight 60-80% of
expected; edema present
– “flaky-paint” skin rash with hyperkeratosis and
– Distended abdomen and enlarged liver
– Angular stomatitis
– Sparse depigmented hair (+ flag sign)
– Diarrhea, hypothermia, bradycardia and
– Low plasma albumin, potassium, glucose and
Unexplained data
• Prolonged fever
• Cough and dyspnea
• Nonresponse to multiple antibiotics
• Hematochezia and melena
• Hepatomegaly and weight loss not a feature of
renal diseases
• Pyuria not a feature of kwashiorkor
• Normal ASO titer r/o PS Glomerulonephritis
• Normal Cholesterol r/o Nephrotic syndrome
• Abnormal serum transaminases
• Abnormal UTZ findings
Prolonged Fever

• Typhoid Fever
• Miliary/Disseminated Tuberculosis
• Urinary Tract Infection
• Malaria
• Septicemia
• Hidden/”Cryptic” abscesses
Hidden Abscess
Differential diagnosis
Abscess •Fever with no obvious focus of infection
(deep abscesses)
•Tender or fluctuant mass
•Local tenderness or pain
•Specific signs depend on site –
subphrenic, psoas,lung, renal
•Follows surgical operations or
manipulation/cumbilical catheterization
Urinary Tract
Differential Diagnosis
Urinary tract •CVA or suprapubic tenderness
Infection •Crying on passing urine
•Passing urine more frequently
than usual
•Incontinence in previously
continent child
•White blood cells and/or
bacteria in urine on
Signs and Symptoms of UTI in
Different Age Groups
Neonate Hypothermia, hyperthermia,
and failure to thrive, vomiting,
infant diarrhea, sepsis, irritability,
lethargy, jaundice, malodorous
urine, crying on urination

Abdominal pain, vomiting,

Toddler diarrhea, constipation, abnormal
voiding pattern, malodorous urine,
fever, poor growth
Signs and Symptoms of UTI in
Different Age Groups
School age Dysuria, frequency, urgency,
abdominal pain, abnormal voiding
pattern (including incontinence or
secondary enuresis), constipation,
malodorous urine, fever

Adolescent Dysuria, frequency, urgency,

abdominal discomfort,
malodorous urine, fever
Some Antimicrobials for
Oral Treatment of UTI
Antimicrobial Daily Dosage

Amoxicillin 20-40 mg/kg/day in 3

Co-trimoxazole 6-12 mg TMP, 30-60
mg SMX / kg/day in 2
Sulfisoxazole 120-150 mg/kg/day in 4
Some Antimicrobials for
Parenteral Treatment of UTI
Antimicrobial Daily Dosage
Ampicillin 100mg/kg/d divided q 6h
Cefazolin 50mg/kg/d divided q 8h
Cefuroxime 50-75 mg/kg/d q 8h
Ceftriaxone 75mg/kg q 24h
Cefotaxime 150mg/kg/d divided q 6h
Ceftazidime 150mg/kg/d divided q 6h

Gentamicin 7.5mg/kg/d divided q 8h

Tobramycin 5mg/kg/d divided q 8h

Ticarcillin 300mg/kg/d divided q 6h

Differential diagnosis
Septicemia • Seriously and obviously ill,
highly febrile child with no
focus of infection
•Purpura, petechiae
•Shock or hypothermia in a
young infant
•(+) blood cultures


Malaria •Residence in an endemic area

•Blood films positive
•Severe anemia
•Enlarged spleen
Clinical Features
• Visit to a malaria area in preceding year
• Splenomegaly, anemia and jaundice
• Syndrome of high fever, shaking chills and
drenching sweats with accompanying headache,
muscle and abdominal pains, cough, diarrhea
and vomiting
• Clinical manifestations basis: destruction of RBC
by parasite and resultant disruption in
Clinical Features &
• First attack lasts 2 weeks in falciparum
• Continuous/intermittent fever more
common in children
• Synchronization of parasite cycle
established only after several days
• Detection of the ring forms of the parasite in
thick and thin smears of peripheral blood
• Lethal form associated with P. falciparum
• Algid malaria from circulatory collapse
• Cerebral malaria: encephalopathy from cerebral
anoxia and edema
• Renal insufficiency from cortical ischemia
• Pulmonary insufficiency
• Hematologic
– Anemia
– Depletion of platelets and coagulation abnormalities

Early “ring” form Mature trophozoite

trophozoite of P.falciparum of P. malariae
Gametocyte, P. falciparum Multiple ring forms, P. falciparum
Differential diagnosis
Salmonella •Seriously and obviously ill with
infection no apparent cause
(Typhoid fever) •Abdominal tenderness
•Child with sickle cell disease
•Osteomyelitis or arthritis in
•Anemia associated with malaria
Salmonella Infections are
Categorized as
1. Asymptomatic carriage
2. Gastroenteritidis - the most common

recognized illness
3. Enteric fever
– Typhoid fever (S.typhi)
– Paratyphoid fever (S.paratyphi)
4. Bacteremia without focality and
focal infections such as meningitis,
Symptoms of Typhoid Fever
• Fever - more than 5 days, stepladder
• Headache
• Nausea
• Vomiting
• Abdominal pain and distention
• Diarrhea or Constipation
• Cough,
• Chills
• Myalgia
Signs of Typhoid Fever
• Rose spots: 5-10% of cases
• Abdominal tenderness
• Hepatomegaly or splenomegaly
• Relative bradycardia
• Coated tongue
• Rales or rhonchi
• Epistaxis
• Meningismus
Medical Complications
• Lobar pneumonia - 2nd or 3rd week
• Venous thrombosis
• Hemolytic anemia
• Nephrosis/nephritis
• Meningitis- less than 1 %
• Neuropsychiatric sx e.g. psychosis
• Peripheral neuropathy
• Pharyngitis/parotitis/orchitis
• Myocarditis
• Secondary to Toxemia:
– Myocarditis
– Hepatic damage
– Bone marrow damage
– Encephalopathy
• Secondary to Local Gastrointestinal
– 0.5 % of cases
– Intestinal hemorrhage
– Intestinal perforation

1. Blood - anemia,leucopenia,
2. Liver function tests- elevated bilirubin,
3. Urinalysis- proteinuria, hematuria
4. Microbiologic studies:
Microbiologic Studies
• Blood culture: 75% positive during 1st
week in patients with no previous
antibiotic intake
• Urine: Positive during first 2 weeks
• Stool culture: 75% positive during 3rd-
4th week
• Bone marrow: positive in >90%, not
influenced by prior antibiotic intake
• Others: Rose spot aspirate or biopsy,
Duodenal String Culture
Approach to Management
First-Line Treatment
Chloramphenicol 3-4 g/d in adults and
50-75 mg/kg/d in children
Cotrimoxazole 320- 480 mg or 8 mg/kg/d
(Trimethoprim) in 2
divided doses
Amoxicillin 4-6 g/d TID in adults and
100 mg/kg/d in children
*Given for 14 days. Defervescence in 3-5
Differential Diagnosis
Miliary Tuberculosis •Weight loss
•Anorexia, night sweats
•Systemic upset
•Enlarged liver and/or spleen
•Tuberculin test positive or
•Sterile pyuria
– Epidemiological
– Clinical grounds
– Cultures rarely available
– Tubercle bacilli few in number
– Sputum not obtained in < 6 years
– < 50% (+) in samples
TB in children
• Given
– Unlike adults, the diagnosis of TB in
children is difficult and often based on
epidemiological and/or clinical grounds
and cultures are rarely available
• TB Exposure (Class I)
• TB Infection (Class II)
• TB Disease (Class III)
• TB Inactive (Class IV)

– National Consensus on Childhood

Tuberculosis, 1997
TB Exposure
• Exposed to adult/adolescent with
active TB disease
• No signs or symptoms of TB
• Negative Mantoux tuberculin test
• Negative chest x-ray
TB Exposure
• 3 months:
– Delayed hypersensitivity to tuberculin
– Before clinical signs and symptoms develop
– Before chest x-rays become positive
• MD must identify source case
– Complete history and PE
– Hx of previous drug intake, duration and compliance
– Do CXR, Sputum culture, drug sensitivity studies
TB Infection
• With/without history of exposure
• Positive Mantoux tuberculin test
• No signs or symptoms of TB
• Negative Chest x-ray
TB Infection
• Preclinical state
• Risk of developing disease
– 5-15% during first 10 yrs.after primary
– Highest risk (50%) in infants 3-9 mos
– 25% in 1-5 yrs., 15% in adolescents
– Dependent on age, nutritional state,
bacteriological status of source case and
intensity of contact
TB Disease
3 or more of the following:
2. Exposure to adult/adolescent with active
3. Positive Mantoux
4. Suggestive Signs/symptoms
5. Abnormal CXR suggestive of TB
6. Lab findings suggestive of TB
(histological, cytological, biochemical,
immunological and/or molecular)
TB Disease
• Most TB infections in children are
asymptomatic even if TST is positive
• Early clinical manifestations occurring 1-6 mo
after Primary infection:
– Fever, weight loss, cough, night sweats,
chills. PE extensive cervical or other nodal
– CXR findings: hilar, mediastinal
lymphadenopathies, atelectasis or pleural
effusion, cavitary lesions, miliary disease
TB Disease
• Common signs/symptoms
– Cough/wheezing > 2 weeks
– Fever > 2 weeks
– Painless cervical &/or other lymphadenopathy
– Poor weight gain
– Failure to make quick return to normal health after
an infection (e.g. measles, pertussis)
– Failure to respond to appropropriate antibiotic tx
(e.g. pneumonia, ome)
TB Disease
• Patient should be referred to hospital:
– Sinus in neck
– Large painless lymphadenopathies (neck,
axilla, groin)
– Angle deformity of bone
– Joint or bone swelling or sinuses
– Unexplained abdominal mass or ascites
– Change in temperament, fits or convulsions
Clinical Presentations of
Pulmonary Childhood TB
• Asymptomatic PTB:
• + TST, normal CXR and no clinical
manifestations. Diagnosed on routine
skin testing and investigation of the
adult contact
Clinical Presentations of
Pulmonary Childhood TB
• Endothoracic Lymphadenopathy and
Endobronchial Disease:
– earliest symptoms from compression
obstruction of blood vessels and airways
– Persistent cough
– Signs of bronchial obstruction from hilar
– “Collapse-consolidation” CXR
Clinical Presentations of
Pulmonary Childhood TB
• Chronic Pulmonary TB:
– Adult TB or reactivation TB
– Develops through endogenous reinfection
from prior established foci of TB reinfection
from Simon’s foci (apical or posterior
pulmonary segment)
Clinical Presentations of
Pulmonary Childhood TB
• Progressive Primary PTB:
– Primary pulmonary focus fails resolve or
calcify and progresses locally to form large
caseous mass
– Ill-appearing, progressive weight loss,
malaise, cachexia and productive cough.
On PE: dullness, diminished breath sounds
and egophony
– CXR cavitation
Extrapulmonary Tuberculosis
• TB meningitis
• Pleural TB
• Miliary/Disseminated TB
• TB of the Peripheral lymph nodes
• Abdominal TB (GI,Hepatic, Ascitic TB)
• TB of the bones and joints
• Genitourinary TB
• Cardiovascular TB
• Otologic TB
• Ocular TB
• Cutaneous TB
Miliary TB
• Most severe form of hematogenous TB
• Results from erosion of caseous focus into blood
vessel with widespread dissemination
• Clinical manifestations: insidious onset with low
grade fever, malaise and weight loss or acute
onset with high fever, lethargy, anorexia and
generalized weakness. PE acutely ill with
hepatosplenomegaly and generalized
Miliary TB
• Early – absent respiratory symptoms to tachypnea,
cough, cyanosis and diffuse rales
• Choroid tubercles on ophthalmologic examination
• 1/3 to ½ have meningitis
• Chest x-ray: diffuse bilateral miliary lesions, with
equal distribution of tubercles over the entire lung
Miliary Tuberculosis
• Snowflake
appearance of the
lung fields. Note the
marked mediastinal
shift to the right and
emphysema due to
obstruction and
valve action by the
Evidence based CPG on the
Diagnosis of Childhood
CLINICAL QUESTION 1: What is the value
of a history of contact in the diagnosis
of tuberculosis?

• In the evaluation of a child suspected of having
tuberculosis, a search for a history of exposure to an
adult &/or adolescent who has tuberculosis disease
should be done. (Grade A Level II)
• A negative history of exposure does not rule out
tuberculosis (Grade A Level II)
Evidence-Based CPG on the Diagnosis of
Childhood Tuberculosis

CLINICAL QUESTION 2: What are the clinical

manifestations most suggestive of childhood
tuberculosis disease?

The following clinical manifestations, when taken
together, are most suggestive of childhood tuberculosis
disease: history of recent weight loss or failure to
gain weight, cough &/or wheezing for > 2 weeks,
and prolonged unexplained fever (> 2 weeks).
(Grade A Level II)
Evidence-Based CPG on the Diagnosis of
Childhood Tuberculosis

In addition to the signs and symptoms
enumerated above, failure to respond to
appropriate medications and failure to
regain previous state of health 2 wks after
an infection are also suggestive of
tuberculosis disease.
In the presence of any 3 of the 5 signs
and symptoms, work up for TB disease is
Evidence based DRAFT on
Tuberculosis in children
CLINICAL QUESTION 4: What is the optimal drug regimen for
newly diagnosed pulmonary tuberculosis in children?
1. For primary pulmonary tuberculosis, the optimal drug regimen is
a 6-month regimen consisting of 3 drugs (HRZ) for 2 months
followed by 2 drugs (HR) for 4 months. If primary drug
resistance is suspected, 4 drugs (HRZS or HRZE) should be
used during the intensive phase. (Grade A, Level 2c)
2. For children with extensive pulmonary disease, including those
with extensive parenchymal lesions, endobronchial tuberculosis,
upper lobe infiltrates, consolidation, cavitation, or extensive
pleural effusion; and for patients > 15 years old, the optimal drug
regimen is a 6-month regimen consisting of 4 drugs (HRZS or
HRZE) for 2 months followed by 2 drugs (HR) for 4 months.
(Grade A, Level 1)
Evidence based DRAFT on
Tuberculosis in children
CLINICAL QUESTION 4: What is the optimal drug regimen for
newly diagnosed pulmonary tuberculosis in children?

3. Drugs may be administered by any of the following methods: (a)
daily during the intensive and continuation phase (b)
intermittent twice- or thrice- weekly during the intensive and
continuation phase; or (c) daily during the intensive phase of
treatment followed by intermittent twice- or thrice-weekly
administration during the continuation phase. (Grade A, Level
4. Antituberculosis drugs given daily may be administered by
family-supervised or health-worker supervised directly observed
therapy (DOT) while drugs administered by intermittent therapy
must be given by health worker-supervised DOT. (Grade A,
Level 2c)
Basis for the Clinical
• Chronicity of the infection negates more acute
• Clinical signs and symptoms fulfill the criteria
• Questionable history of exposure
• Cervical lymphadenopathies
• Hepatomegaly
• Involvement of multiple organ systems
• Non response to appropriate antibiotics
• Failure to regain health after a history of
• Partial autopsy (w/o head) showed multiple
areas of inflammation and ulcerations in both
small and large intestines. The entire right
ureter was obstructed with caseous material
with both kidneys showing areas of caseation
and inflammation. Likewise, the right adrenal
gland manifested areas of caseation necrosis. 3
granulomatous sites with some caseated foci
were seen in the right hepatic lobe. The lungs
were necrotic with inflammatory exudates and
the pleural cavities with some cheesy materials
and effusion