- Patient presentation
- History
- Differential Diagnosis
- Examination
- Investigations
- Discussion
- Final Outcome
- Evaluation - Questions & answers
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 | 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 |
Evaluation – Questions & answers
What is the Diagnosis at 25 months of age?
What is the definition of this disease?
How does drug-susceptible TB become drug-resistant TB?
What are the advantages of TB Diagnostic Algorithms?
• 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?
• 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?
What is the treatment for MDR TB?
• Pyrazinamide (PZA)
• Ethionamide
• Ofloxacin
• Ethambutol
• Amikacin
Would you change the ART regimen at this stage?
