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Page 1: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 2: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 3: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 4: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 5: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 6: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

web.capetown.gov.za

Natural history and diversity of TB in children

H S Schaaf

Page 7: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Question

Children with pulmonary TB are not infectious

TRUE or FALSE

Page 8: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Question

Extrapulmonary TB occurs in about 30% of children with TB

TRUE or FALSE

Page 9: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Robert Koch (1843-1910) discovered M. tuberculosis 1882

Previously uncertainty if TB was an infectious disease or

merely due to poverty, poor diet or bad air.

Microscopy diagnosis still used today! It only detects large

numbers of bacilli in sputum (>5-10 000 bacilli/ml) therefore

children are rarely detected in this way (paucibacillary disease)

Page 10: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Transitions in TB

Susceptible

Exposed

InfectedDiseased

Infectious

SickAccessed care

Recognized

Diagnosed

Treated

Completed

CuredDon Enarson - IUATLD

Page 11: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 12: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 13: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

90%Info.med.yale.eduwww.info.gov.hk

10%

Active TB LTBI

Page 14: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Age-related risk

0

10

20

30

40

50

%

<1 1to2 2to5 5to10 10to15

Age in Years

PTB

Disseminated

Immune

compromised

Page 15: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Outpatient Case

• Baby-girl 14 weeks – cough >4 weeks. Was

seen at clinic several times. Amoxicillin given.

Mom told to stop smoking. Coughing bouts –

turns red says mom

• Fever for two weeks. Only had received her

6-week immunisations. No BCG given (out of

stock)

• Unbooked mom gravida 5 para 5: Baby born

at home. Breastfed since birth, but on clinic

card not thriving.

Page 16: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Outpatient Case

• A boarder at grandmother’s home has TB but

on effective treatment long before baby was

born – no-one else with TB at home

• Mom had TB 2009 – treated for 5 months?

Mom says she is coughing “on and off” –

describes it as a “normal cough”

• O/E (infant): Decreased air entry LUL;

hepatosplenomegaly

• Irritable baby, no neck stiffness or bulging

fontanelle, bilateral femoral hernias and low

grade fever

Page 17: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 18: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
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What next?

• FBC – HB 8.9 g/dl normocytic normochromic

• Platelets >500 x 109/L

• HIV-negative

• LP: CSF prot 0.7g/l, glucose 2.8 mmol/L,

polimorphs 10, lymphocytes 6, RBCs 2

• GAs sent for culture DST

• Boarder at grandmother’s house has TB, but

on TB Rx before baby was born

• Likely source?

• Remember to screen the caregivers!

Page 20: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 21: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 22: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Impact of HIV on TB in Africa

Notified cases per 100,000 pop

Percentage of global estimated HIV-positive TB cases

EMR

Cameroon

Thailand

Brazil

Democratic Republic of the Congo

China

Myanmar

EUR

Côte d'Ivoire

Malawi

United Republic of Tanzania

AMR

Zambia

WPR

Ethiopia

Mozambique

Kenya

Uganda

Zimbabwe

Nigeria

India

SEA

South Africa

AFR

1% 5% 10% 20% 50% 90%0

100

200

300

400

500

600

700

1980 1984 1988 1992 1996 2000 2004 2008

Botswana

Côte d'Ivoire

DR Congo

Gabon

Guinea

Kenya

Malawi

Mozambique

South Africa

UR Tanzania

Zimbabwe

79% of all estimated TB/HIV cases occur in Africa

South Africa

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2015 Data WHO

TB 834/100,000SA 14.4 new HIV infections/1000 uninfected

Page 24: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 25: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Increasing TB/HIV Burden

Lawn SD et al. CID 2006; 42: 1040-7

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TB - Age & Gender shift

Lawn SD et al. CID 2006; 42: 1040-7

3-4% 0-9y 25% 20-39y HIV prevalence in

general population:

Page 27: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Major transitions

Exposure

Infection

Disease

Understanding the

Natural History of Disease

Page 28: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Arvid Wallgren 1889-1973

Page 29: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Time-related risk

0 1 2 3 4 6 8 10 12 2 3

Infection Months Years

TimelinePhase of diseaseI Hypersensitivity

II Miliary TB and TBM

III Lymph node disease / Pleural effusion

IV Adult-type disease

HIV-infected - PERSISTENT RISK OF REACTIVATION DISEASE

I II III IV

Immune

compromised

Page 30: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Infection without disease

Page 31: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Progressive disease

Page 32: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Manifestations of

intra-thoracic TB

in children

DIVERSITY

OF

DISEASE

Page 33: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 34: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Pathophysiology

• From the primary focus bacilli may spread:

- locally and cause extension of primary focus

- lymphatically to the hilar/mediastinal lymph

nodes

- retrograde via lymphatics to abdominal

nodes or to cervical nodes

- haematogenously to any part of the body

- may break through to pleura or even chest

wall

• Rarely entry point may be the gut

(unpasteurised milk) or even the skin (injury

with local infection)

Page 35: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 36: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 37: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 38: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 39: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
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Cardiac Catheterization

Page 41: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 42: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 43: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 44: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 45: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Miliary or bronchopneumonic TB?

Page 46: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Miliary TB

Page 47: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes
Page 48: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Different age-related patterns

0 1 2 3 4 6 8 10 12 14

Age in years

Complicated Ghon focus

Miliary TB

Lymph node disease

Pleural effusion

Adult-type disease

Immune

compromised

Page 49: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Manifestations of

extra-thoracic TB

in children

DIVERSITY

OF

DISEASE

Page 50: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

TB cervical lymphadenitis• Most common form of extra-thoracic TB

• Diagnosis - persistent mass >2x2cm

no visible local cause or response to antibiotics

• In low-incidence countries – consider non-tuberculousmycobacteria as cause

Page 51: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

TB Meningitis (TBM)

History: Child <3yrs or immune compromised

Fever, lethargy (weight loss, recent TB contact)

LP – Cells <1000 / Lymphocyte predominance glucose low / protein high

Page 52: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

TB Abdomen• M. tuberculosis or M. bovis (latter from

unpasteurized milk)

• Through dissemination or swallowing

• Different types of

abdominal TB

- intestinal

involvement

- lymph nodes

- solid organ TB

- peritonitis

Page 53: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Osteo-articular TB

TB of vertebra (gibbus) – 50% of OA-TB

TB involving other bones - infants

TB of the joint – usually weight bearing

joints

Page 54: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Dermatological TB manifestations

Erythema nodosum

not TB but associated with TB

Sporotrichoid lesions + old TST

Page 55: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Erythema induratum

Papulonecrotic TB

Page 56: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

Other manifestations of EPTB• Ear/mastoiditis

• Pericardial

• Urogenital TB –

very rare in children

Page 57: PowerPoint Presentation filePreviously uncertainty if TB was an infectious disease or merely due to poverty, ... •LP: CSF prot 0.7g/l, glucose 2.8 mmol/L, polimorphs 10, lymphocytes

In summary

• Not all M.tuberculosis infection leads to disease

• The risk of developing disease is influenced

mainly by the age and immune status of the child

• There is a diverse spectrum of disease that

demonstrates clear age-related patterns

• Pulmonary/Intrathoracic TB most common, but

any organ/system can be affected by TB


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Gut microbiota determine insulin sensitivity · Fasting Insulin (mmol/L) MMT 80 (15-178) 85 (19-180) Cholesterol (mmol/L) 5.2 (3.5-8.8) 4.5 (3.5-7.2) TG (mmol/L) 2.0 (0.7-4.5) 1.1

A Simple and Mild Acylation of Alcohols, Phenols, Amines ...A mixture of alcohol, phenol, amine or thiol (1 mmol), toluene (1 mL), acetic anhydride (1.5 mmol) and WD catalyst (1 mmol

pH : 7,46 (air ambiant) PaCO 2 : 36 mm Hg CO 2 T : 23 mmol/l PaO 2 : 56 mm Hg Sat : 88 % Na + : 144 mmol/l K + : 4,2 mmol/l Cl - : 103 mmol/l CO 2 T :

Supplementary Materials for · THF (28 ml) were added phthalimide 2 (2.3g, 15.69 mmol) and PPh 3 (4.11g, 15.69 mmol). DEAD (2.73 g, 15.69 mmol) was then added dropwise to the stirred

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Supplementary Material - CSIRO PUBLISHING · To a 10 mL Schlenk tube, 1-butanol (0.74 g, 10 mmol), 1-bromobutane (0.69 g, 5 mmol), tetramethylguanidine (TMG, 5 mmol) and n-undecane

The Na+/Glucose Cotransporter Inhibitor Canagliflozin ... · (10 mmol/L), HEPES (20 mmol/L), sucrose (110 mmol/L), and fatty acid–free BSA (1 g/L). Primary hepatocytes from WT mice

Supporting Information · We thoroughly mixed PbO (3.348 g, 15 mmol), SrCO3 (1.476 g, 10 mmol), SiO 2 (0.601, 10 mmol), PbF 2 (1.225 g, 5 mmol), H 3 BO 3 (0.618 g, 10 mmol) and ground

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Electronic Supplementary Information · The mixture of commercial benzyl alcohol 1a (0.93 mL, 9 mmol), phenylacetone 6a (360.5 mg, 3 mmol), Cu(OAc)2.H2O (6 mg, 0.03 mmol, 1 mol%)

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69451 Weinheim, Germany - Wiley-VCH procedure for the reaction of alkenes with saccharin. In a glass tube, alkenes (1.2 mmol), saccharin (0.2 mmol), catalyst (0.02 mmol), Maleic anhydride

Exogenous-oxidant-free electrochemical oxidative C-H ...hydrazides (0.375 mmol), K 2 CO 3 (0.375 mmol), nBu 4 NBF 4 (0.1 mmol) were combined and added. The bottle was equipped with

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Conjugated Polymer for Fluorescent and Phosphorescent Light- … · 2015-07-06 · mmol), 1,10-phenanthroline (0.176 g, 0.970 mmol), CuCl (0.100 g, 0.950 mmol), and toluene (50 mL)

THE EFFECT OF PH CHANGES ON CRYSTALLIZATION ...One liter of this solution was given the following ion composition: 1.04 mmol calcium, 0.41 mmol magnesium, 4.17 mmol phosphate, 0.04

At GP surgery: BGL 25mmol/L – referred to ED In ED: Capillary blood gas: pH 7.18, bicarbonate (HCO3) 12 mmol/L, BGL 25 mmol/L, Na 136 mmol/L (corrected

Supplementary Information · 4.38 mmol), Palladium acetate (0.02 g, 0.1 mmol), tri-tert-butylphosphine (0.08 g, 0.42 mmol) and sodium tert-butoxide (0.6 g, 6.26 mmol) dissolved in

CDK4/6 Inhibitors Sensitize Rb-positive Sarcoma ... · 0.5 mmol/L phenylmethylsulfonyl fluoride, 50 mmol/L sodium fluoride, and 0.5 mmol/L sodium orthovanadate). The primary antibodies

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SUPPLEMENTARY INFORMATION Exercise and associated … · HDL (mmol/L) 1.44±0.04 1.2±0.4† 1.39±0.05 LDL (mmol/L) 3.07±0.1 2.94±0.1 2.73±0.2 Triglycerides (mmol/L) 0.86±0.05

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