Failure to thrive despite appropriate treatment

Patient presentation

A two year 1 month old boy who has been on TB treatment and antiretroviral therapy for the past 9 months presents with failure to thrive despite adherence and nutritional counseling.

Acknowledgement
This case study was kindly provided by Dr Claire Egbers from the Wits Paeds HIV Clinics.

History

At 13 months:

  • Patient admitted for Kwashiorkor. At this time he was also diagnosed with HIV infection.

At 14 months:

  • 6.6 kg, height 64 cm (below 5th centile for height and weight)
  • He showed signs of HIV infection which included generalised lymphadenopathy, 2cm hepatomegaly and less then 60% estimated weight for age (Marasmic Kwashiorkor). He was classified as WHO stage IV due to severe failure to thrive (FTT)
  • Child exhibited a chronic cough
  • Monocytosis on full blood count
  • Chest X-Ray (CXR) showed right lung multilobar consolidation
  • Night sweats, family or contact history of TB, fever, lethargy and anorexia were all nil of note.
  • Gastric washings for acid fast bacilli (AFB) were negative
  • Patient was diagnosed empirically with TB based on the above criteria
  • TB treatment of Rimcure (rifampicin, isoniazid and pyrazinamide) was started

At 16 months:

  • 6.6 kg, height 70 cm (below 5th centile for height and weight)
  • HAART was started, calculated using weight specific doses and body surface area (BSA):

Stavudine(d4T) = 7mls
Lamivudine(3TC) = 2.3mls
Kaletra = 1.3 mls

Ritonavir boost dose = Kaletra dose * 0.75
= 1.3 * 0.75
= 1ml

 At 19 months (3 months after starting HAART):

  • 7 kg, height 72 cm (below 5th centile for height and weight)
  • Clinically stable, no admissions for acute illnesses at this time.
  • However weight gain was still inadequate despite treatment adherence and nutritional counseling.

At 22 months (6 months after starting HAART):

  • 8 kg, height 76 cm (below 5th centile for height and weight)
  • Intensive adherence counseling was given to the mother, but no adherence problems were found. Another sibling in the mothers care was fully suppressed on ART
  • CXR changes had not resolved
  • TB treatment was continued for a further 3 months
  • Induced sputum and TB Bactec done, which were negative

 Currently at 25 months (9 months after starting HAART):

  • Weight gain has remained inadequate

Diagnosis

  • Non compliance to medication
  • Poverty, inadequate nutrition
  • Multi drug resistant (MDR) TB

Examination

Initial visit, 14 months – TB treatment initiated 16 months, HAART started 19 months 22 months
Age 14 months 16 months 19 months 22 months
Weight 6.6 6.6 7 8
Height 64 70 72 76
CD 4% 3.95 4.58 3.15
CD4 count 160 261 176
Viral load 660 000 46 000 58 000

Investigations

Age Investigation Result
13 months Elisa test for HIV Positive
14 months FBC Monocytosis
CXR Right lung multilobar cons
Mantoux test (PPD) Negative
Gastric washings and AFB culture Negative
CD4% 3.95
CD4 count 160
Viral load 660 000
16 months HAART was started, no further investigations done at this time
19 months (3 months after starting HAART) CD4% 4.58
CD4 count 261
Viral load 46 000
22 months (6 months after starting HAART) CXR No change. Right lung multilobar consolidation
Gastric washings and Bactec Negative
CD4% 3.15
CD4 count 176
Viral load 58 000
25 months (9 months after starting HAART) Sputum cultures Positive TB
Sensitivity Rifampicin, ethionamide and isoniazid resistant

Discussion

Elisa or PCR

When performing an HIV test on an infant it is important to know the patient’s age as it will determine whether to use PCR or ELISA:
• < 18 months old use PCR testing as this will detect actual virus
• > 18 months use Elisa as the maternal antibodies have now cleared

The guidelines for diagnosis of TB in Children:
It is difficult to obtain bacteriological confirmation therefore we need to rely on a cluster of suggestive factors:

HISTORY of positive contact
• Mantoux skin test (PPD)
• Chest X-ray
• Sputum microscopy and culture
• Culture of other body fluids
• Biopsy specimens

ALGORITHMS for guiding decision to treat:

Feature: 0 1 2 3 4 Score
General
Weeks of illness <2 41731 >4
Nutrition (% weight for age) 0.8 60-80% 0.6
Family history of TB None Reported by Family Proved sputum positive
Mantoux Test Positive
Malnutrition Not improved after 1 month Rx
Unexplained Fever No response to Rx

Feature: 0 1 2 3 4 Score
Local
Lymph nodes
Joint or bone swelling
Abdominal mass or ascities
CNS signs, CSF abnormal
X-Rays Broad mediastinum due to enlarged hilar glands Gibbus

Total = score for general features + score for local features (any score ≥7 is suggestive of TB

This patient scored 12

Mantoux test
Utilises the fact that the body’s Cell Mediated Immunity (CMI) reacts against foreign protein

  • 2TU of Purified Protein Derivative (PPD)  injected intradermally on left forearm (mid-third)
  • Read 48 to 72 hr later
  • Area of transverse induration measured (in millimetres)

Many factors influence body’s response to PPD

The following can give rise to a negative result:

  • Acute viral infection e.g. measles
  • Overwhelming bacterial infection
  • Overwhelming TB
  • HIV infection
  • Immunosuppressive therapies
  • Malnutrition
  • Recent live viral vaccine
  • Incorrect PPD administration technique

The following can give rise to a false positive test:

  • Previous BCG vaccination
  • Previously treated TB
  • Exposure to environmental mycobacteria

Interpretation

  • Skin test  ≥ 5 mm denotes TB infection in HIV positive children
  • A positive skin test means TB Infection, not necessarily TB Disease
Previous BCG No previous BCG HIV Positive
Mantoux >15 mm >10 mm >5 mm

At the patients 12 month visit (28 months old), he had been on MDR TB treatment  for 3 months and had gained over a kilo in weight and was clinically well. These were his results:

Age 28 months
Weight 9.5kg
Height 79cm
CD4% 8.39
CD4 count 607
Viral load <25

Evaluation – Questions & answers

What is the Diagnosis at 25 months of age?

Multi drug-resistant tuberculosis (MDR TB)

What is the definition of this disease?

MDR TB is a form of tuberculosis that is resistant to two or more of the primary drugs, isoniazid and rifampicin used for the treatment of tuberculosis.

How does drug-susceptible TB become drug-resistant TB?

Drug resistance arises due to the improper use of antibiotics in chemotherapy of drug-susceptible TB patients. This improper use is a result of a number of actions, including administration of improper treatment regimens by health care workers and failure to ensure that patients complete the whole course of treatment. Essentially, drug-resistance arises in areas with poor TB control programmes.

What are the advantages of TB Diagnostic Algorithms?

• Relies on History, Examination and Mantoux test
• X-ray is not considered to be an important part of the diagnostic workup
• Highlights fact that sputum AFB determination is not necessary to diagnose Childhood TB

What are the disadvantages of TB Diagnostic Algorithms?

• Their usefulness has not been tested in controlled clinical trials
• They tend to detect cases with longstanding disease whereas most childhood TB is an acute presentation of recent infection.

Why should TB ideally be excluded or treatment started before starting HAART?

This is done to reduce the chance of Immune Reconstitution Inflammatory Syndrome (IRIS) which is a paradoxical clinical deterioration after starting HAART.

What is the treatment for MDR TB?

Choice of drugs will depend on the results from sensitivity testing. The following drugs are amongst those used to treat MDR TB:
• Pyrazinamide (PZA)
• Ethionamide
• Ofloxacin
• Ethambutol
• Amikacin

Would you change the ART regimen at this stage?

Yes, the Ritonivir boost can be stopped because the patient is no longer on a rifampicin containing regimen.