Here are some key points regarding the feasibility of bacteriological diagnosis in children with TB:
- Sputum induction or gastric lavage are generally required to obtain specimens from children, as they typically cannot produce sputum on demand. This requires specialized equipment and trained personnel.
- Even with induced sputum or gastric lavage, specimen quality and volume may be low, reducing the sensitivity of bacteriological tests.
- Young children especially may not be able to cooperate with procedures like sputum induction.
- Extrapulmonary TB is more common in children than adults, so specimens from sites like lymph nodes, cerebrospinal fluid, etc. need to be obtained invasively via procedures like biopsy or lumbar puncture
India has the largest burden of tuberculosis. The disease is gradually extending its storm into the paediatric age group, the manifest in which is severe and tortous. So a preventive approach is always better than a curative approach
This presentation was done by Dr. Julius P. Kessy,MD. An intern Doctor at Dodoma Regional Referral Hospital (DRRH) during pediatrics unit clinical meeting and supervised by Dr. Christina K. Galabawa,MD,Mmed2, Pediatrics and Child Health, University of Dodoma (UDOM) in November, 2017.
What is bronchiolitis and its definition, the age group, signs and symptoms and clinical presentation The clinical practice guidelines, how to diagnosis, clinical criteria, what are the severity degrees and How to assess the severity, what are the investigations that may be needed, Is there any diagnostic test, what is the prognosis
What is the management,
India has the largest burden of tuberculosis. The disease is gradually extending its storm into the paediatric age group, the manifest in which is severe and tortous. So a preventive approach is always better than a curative approach
This presentation was done by Dr. Julius P. Kessy,MD. An intern Doctor at Dodoma Regional Referral Hospital (DRRH) during pediatrics unit clinical meeting and supervised by Dr. Christina K. Galabawa,MD,Mmed2, Pediatrics and Child Health, University of Dodoma (UDOM) in November, 2017.
What is bronchiolitis and its definition, the age group, signs and symptoms and clinical presentation The clinical practice guidelines, how to diagnosis, clinical criteria, what are the severity degrees and How to assess the severity, what are the investigations that may be needed, Is there any diagnostic test, what is the prognosis
What is the management,
management of childhood tuberculosis in 2023.pptxPathKind Labs
diagnosis of childhood TB is a challange, but if we follow a system of screening and then appropriate diagnostic tests following contact tracing, we are likely to identify children with infection or disease and put them on appropriate treatment.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
2. • Most commonly child TB is pulmonary TB
• But the proportion of EPTB is higher as
compared to adults
3. Trend of Pediatric TB cases out of all New TB cases under RNTCP
64697
73430
79779
86532 85756 84064 81489
66469
6% 6% 6%
7% 7% 7% 7%
6%
0%
1%
2%
3%
4%
5%
6%
7%
8%
9%
10%
11%
0
10000
20000
30000
40000
50000
60000
70000
80000
90000
100000
2006 2007 2008 2009 2010 2011 2012 2013
No of Pediatric TB cases Proportion
6-7% consistently over the years
Revised National TB Control Programme
4. Source Case Contacts
No InfectionInfection
No DiseasePersistent “Latent”
Infection
Primary Disease
Late Reactivation Disease
70%30%
Risk
5-10%
lifetime
>50% in
infants & 25%
in 1-5 y
90-95%
Variable
Mycobacterial Virulence
Host Immunity
• Smear-positive: infectious
• Smear-negative: can also be
Infectious
• Extra-Pulmonary Disease:
Non- Infectious
4
5. Risk factors for TB infection and disease in children
For TB infection
• Increased exposure
– Living in high TB endemic
communities
– Children of families living with HIV
– Overcrowding
– Air pollution incl ETS
• Source case
– Cavitary disease /Smear positivity
– Cough frequency / Cough hygiene
– Delay in treatment of adult case
• Lack of contact screening
• Contact with source case
– Closeness of contact
– Duration of contact
For TB disease
• Young age
– Especially 0-2 years
• HIV infection
– Risk of infection and disease
• Other immunosuppression
– Malnutrition
– Post-measles
• Not BCG vaccinated
– Risk of disseminated disease
• Lack of prophylaxis
5
6. Three features common to primary infection are
(1) Patient may have non-specific mild symptoms which can go un-recognised,
(2) Primary lung foci are usually quite small relative to large hilar nodes, and
(3) Primary foci may resemble pneumonia & be located within any lobe
Caffey Pediatric Imaging
Radiological picture of a typical Ghon’s Complex
7. Primary Infection (LUNG)
Ghon’s Complex
Contained
Treated
Naturally Heal
Progress
Ghon complex = Ghon focus +
hilar lymph nodes
Progressive
Primary Ds
Reactivation disease
Risk much higher with natural healing as
compared to those treated
7
Is the reactivation
rates different
between naturally
healed versus
treated cases?
8. Reactivation or Post Primary tuberculosis
Disease of adolescence and adulthood
50- 90% of cases result from reactivation of a
previously dormant primary infection
Predilection for apical or posterior segment of upper
lobes or superior segment of lower lobes
Focal or patchy heterogeneous consolidation,
consolidation with cavitation, pleural extension
Tuberculomas are also seen but rare.
8
9. Who is a TB Suspect?
Symptom Characterization
Common Symptoms
• Fever for 2 weeks or more
• Unremitting cough for 2 weeks or more
• Loss of weight >5% of the weight in past 3
months
• Peripheral Painless swellings
• Meningitis of insidious onset
• Spine gibbus
• Any non specific symptoms in a contact of an
infectious TB case
When do
you suspect
TB in a
child?
10. Case
• Victor, 3 year old child
• h/o cough for 2 months
– Dry
– More for past 3 days
• Low grade fever for same
duration
• Not growing wel
• Fussy eater
• Father has chronic cough
– Has recd several sets of
antibiotics with no relief
• o/e
– Wt 10.7 kg
– Mild pallor
– No lymphadenopathy
– Chest:
• Bilateral crackles and
wheezes
– Rest NAD
10
11. Investigations
• Tuberculin Skin test (PPD
test)
14mm in transverse axis
• ESR 32mm
• TB Elisa positive IgG and
IgM
Diagnosis Pulmonary Koch’s
Started on ATT (for new case) along with bronchodilators
Has come for a review 11
12. TB like symptoms are common and non specific
Chronic cough – reported in up to 20% of children
from poor area
• Relatively a soft sign
• common with poor feeding habits or
• heavy worm infestation or
• food insecurity
• It could just be a perception and not real (objective measure)
• Always keep in mind the fallacies related to objective weight
measurement
• Machine errors or errors in method
• If weighed with clothes- a lot of error can happen, particularly
if layers of winter clothes are removed
Not growing well
12
13. Defining cough - duration and pattern
Intensity
of
Cough
1w 2w 3w 4w
Duration in weeks
1) Acute with
delayed recovery
2) Recurrent
3) Persistent,
non-remittent
• Prospective study - Cape Town, N= 151, 0-13 yrs; cough of 2 weeks or more;
• 21 (15.6%) reported symptoms with a persistent, non-remitting character.
• Tuberculosis diagnosed in 16 (10.5%) children,
TB like symptoms are common, but can be useful if well characterized
Arch Dis Child 2005;90:1162–1165
14. Symptom Characterization for TB suspect
• Definition: persistent (>2 week) and unexplained fever (>38C)
reported by a guardian or objectively recorded at least once.
Persistent unexplained fever
• Definition: persistent (>2 weeks), non-remitting cough
Persistent cough
• A definite weight loss (more than 5 % in past 3 months) with no
other apparent cause should prompt detailed history,
examination and investigation including investigation for TB
Definitive Weight Loss/ failure to thrive
14
15. Case
• Victor, 3 year old child
• h/o cough for 2 months
– Dry
– More for past 3 days
• Low grade fever
• Not growing well
• Fussy eater
• Father has chronic cough
• Has recd several sets of
antibiotics with no relief
O/e
• Wt 10.7 kg
• Mild pallor
• No lymphadenopathy
• Chest:
– Bilateral crackles and
wheezes
• Rest NAD
• Father has seasonal cough
and is a smoker
• Never treated for TB
16. History of Contact/ Exposure
• Unrecognized coexisting pulmonary involvement
In a symptomatic child, contact with a person with
any form of active tuberculosis within last two
years may be significant
• prompt detailed examination for likelihood of the disease, as
early as possible
Exposure to an infectious TB patient (any case
with laryngeal, airway or lung involvement) in
past 2 years
16
17. Victor’s Basis of ATT
• Victor has chronic cough and is not thriving well- TB like symptoms
• TST positive
• Father has chronic cough but unlike TB
• CXR suggestive - primary complex
• Basis for ATT justified
17
Please
comment
upon the
Chest X-ray
18. Radiological manifestations of TB
Highly Suggestive
• Patterns like
– Hilar Lymph nodes
– Chronic fibrocavitatory
disease
– Miliary pattern
• REMEMBER
– Specificity increased in a child
with TB symptoms and positive
TST
– These are still not diagnostic
and have differential diagnosis
Non Specific radiology
• Patterns like
– Consolidations
– Non homogenous opacity
– Ground glassing
– Thin walled cavities
• REMEMBER
– In such situations microbiology is very
important (GA/IS).
– If negative:
• Take specialist opinion
• Consider other investigations like CT
Chest, flexible bronchoscopy for
evaluation of persistent pneumonia
18
Please
comment on
radiological
manifestations
of TB
19. CXR – Remember PRIM
• P – Penetration
• R – Rotation
• I – Inspiration
• M - Motion
20. Consolidation
Cavity with in a
Consolidation
Parenchymal cavitation with
Consolidation
Cavity with in a
Consolidation
23. Summary
Reading of radiograph is important skill
Remember the TB suggestive and not suggestive shadows on chest x-ray
Adenitis, miliary and chronic fibro cavitary lesions are considered TB
suggestive radiological findings
Can be over and under read if the film is not properly projected (rotation,
expiratory, under- or over- penetrated, motion or other artefact and
cofounders like thymic shadow
Lateral views are useful
CECT and USG are contributory and recommended in select situations
23
24. Tests For Tubercular Hypersensitivity (Infection) -
Tuberculin Skin Test
Intra-dermal injection of PPD
Immunological test
Elicits Delayed-Type Hypersensitivity (DTH)
Indicates
Present or past infection with MTB
Not necessarily disease
Used as:
– Adjunct, to other tests, in the diagnosis of TB
– Screen children exposed to TB or at increased risk of M.
tuberculosis infection
• Contact with people with contagious TB
• HIV-infected children
25. Tuberculin Skin Test –
Which Tuberculin and What strength should be used?
• PPD-S is available in USA
• 5TU PPD-S had best discriminatory power between infected
and not- infected.
• Rest of the world uses PPD RT 23
• 5 TU PPD-S = 2 TU RT23 with Tween80.
• Current recommendation -use 2TU PPD RT23, given
intradermally
• Induration of 10 mm or more cutoff between infected and
not- infected.
26. Technique of administration
• Preparation of site
– 5–10 cm (2–4 inches) below elbow joint, on
ventral forearm
– Place forearm palm-up on a firm, well-lit surface
– The skin should not have barriers e.g. scars,
sores, veins
– Clean with alcohol
• Preparation of injection
– Check Expiry date and Tuberculin strength (2 TU
of PPD RT23)
– Use a single-dose syringe with a short (1/4 to ½
inches) 27-gauge needle with a short bevel
– Load with 0.1 ml tuberculin
• Injection of test drug
– Insert needle slowly, bevel up, at angle of 5–
15°
– Needle bevel should be visible just below skin
– Inject gently raising an Intradermal wheal of
at least 6 mm diameter
• If not, repeat at least 5 cm (2 inches) away
from the original site
• Record information
– Date and time of test
– Site location
– Lot number of tuberculin
– Tuberculin strength
• Tell the patient
– to avoid scratching the site,
– Keep it lean and dry, and avoid putting creams/
lotions
– Mention that getting the site wet with water is
not harmful, but the site should not be wiped or
scrubbed.
• Finally, return the tuberculin vial to the
refrigerator
27. Test Reading: When to read
• Ideally between 48 and 72 hours
• Patient misses appointment
– Comes beyond 72 hours up to 7 days
• Negative – repeat other forearm
• Still positive – interpret as positive
– Comes beyond 7 days - repeat test in other forearm
28. Test Reading: How to measure
• Measure only the induration (using a transparent ruler/scale)
• Place “0” of ruler line on left edge of the induration.
• Read ruler line on the right edge of the induration as identified (use lower
measurement if between two gradations on mm scale)
• Record measurement in millimeters (mm) usually across horizontal axis,
• Do not record as negative/positive. No induration = 0 mm
• In case there is huge erythema but no induration- it may be due to an inadvertent
subcutaneous leak. In such situations the test is repeated on the other arm
29. Causes of False positive/negative TST
• Incorrect technique of administration or
Interpretation
• Improper storage of tuberculin
• Immunodeficiency/suppression
– Primary
– Secondary
• HIV infection, SAM, etc
• Infections
– Viral(e.g. measles, varicella)
– Bacterial(e.g. Typhoid, leprosy, pertusis)
• Vaccinated with live viral vaccine (within 6
wk)
• Neonatal patients
• Severe TB
• False negative • False positive
• Incorrect technique of Interpretation
• BCG vaccination
• Infection with mycobacterium other
than TB
30. Tuberculin Skin Test (Mantoux’s Test)
• In HIV coinfected, 5mm may be taken as the cutoff
A positive Tuberculin skin test is defined as 10mm
or more induration after 48-72 hrs using no more
than 2TU RT23 tuberculin.
• 2TU dosage considered most appropriate for routine diagnostic
use
• If not available; no more than 5TU should be used but remember
that higher strengths give more false positives
• Non-availability of a standardized tuberculin in India: cause of
concern
Optimal strength of tuberculin to be used for
diagnosis in children
Summary
30
31. Frequently asked questions
Q1. My patient has a TST >20 mm. Should I start him on ATT?
– Any reaction more than the cut off JUST suggests infection.
– Strength of reaction does not discriminate between infection and disease
Q2. My patient has a TST which has got ulcerated. Should I start him on ATT?
– No. This also does not suggest disease
Q3. The patient did not come for reading at 72 h. What should I do?
– If there is a positive reaction, then it can be read upto 7 days
– If there is no reaction or <10 mm then repeat on the other forearm or a site away
from the previous test on the same arm
Q4. Should I use a two-step testing. Is it more sensitive?
– It has no added value for diagnosis in children in endemic situations.
31
32. Frequently asked questions
Q5. Should I repeat a TST after the completion of ATT?
– It does not help in guiding duration of treatment.
– Once the child is infected TST is likely to stay positive
Q6. In children with reactivation or re-infection what happens
to TST?
– It does not help in detecting a re-infection or reactivation
Q7. In my experience BCG test is very useful when TST is
negative? What do you suggest?
– Of No Use
– High false positivity and is not recommended due to lack of
standardisation
32
33. Interferon Assays [IGRAs]
• In vitro stimulation of whole blood with Mtb specific
antigens like ESAT-6, CFP-10 and Tb7.7
• Quantiferon Gold in tube test (TM) and Elispot-TB (TM)
are the 2 major commercially available tests.
• Both IGRAs and TST are tests to detect Latent TB infection.
– “Indirect tests' - do not detect actual TB bacilli but immune response
that suggests past or present exposure to TB bacilli.
• Both IGRA and TST tests cannot distinguish between latent
TB infection and active TB disease.
33
34. IGRA: Benefits
Requires a single patient visit to conduct the test
Results can be available within 24 hours
Does not boost responses measured by
subsequent tests
Prior BCG (bacille Calmette-Guérin) vaccination
does not cause a false-positive IGRA test result
34
35. Blood samples must be processed within 8-30 hours
after collection while WBC are still viable
Errors in collecting or transporting blood specimens
or in running and interpreting the assay can decrease
the accuracy of IGRAs
Limited data on the use of IGRAs to predict who will
progress to TB disease in the future.
• Children younger than 5 years of age;
• Persons recently exposed to M. tuberculosis;
• Immuno-compromised persons; and
• Serial testing.
Limited data on the use of IGRAs for:
Test is expensive
IGRA: Limitations
35
36. How feasible is Bacteriological Diagnosis?
Hurdle 1
• Access to specimen is hurdle
– Most children do not
expectorate
– Even if they have sputum, do
not cough violently enough to
bring it up
– Tend to swallow rather than
spit it out
– Unlike adults the specimen
needs retrieval in children
• Do we have a better (easy to
get and process) specimen?
Hurdle 2
• Low Sensitivity of Smear and
moderate sensitivity of culture
examination in Children
• Can we improve the yield of these
investigations?
37. Do we have a better sample?
GA/ gastric lavage
• Needs over night fasting
• Needs hospitalization
– Now can be done in
Ambulatory setting
• More invasive
• Needs better trained staff
Induced Sputum
• Fasting not needed
• Ambulatory setting
• Less invasive
• Can be learnt easily by
paramedics
• Risk of transmission to
provider higher as provokes
cough
Yield shall be an important deciding factor
38. Are there any other respiratory specimens which can be used?
Role of Bronchoscopy and BAL for Pulmonary TB
• Bronchoscopic findings of mucosal involvement is more likely
to yield AFB in BAL
• Findings like compression of airways or caseation or
bronchiectasis with mucosal ulcerations suggest TB pathology
• Add on test and stand alone does not give better yield than
GAs
39. What tests do we have to test respiratory
specimens effectively?
• ZN staining,
• Fluorescent microscopy
Smear for AFB
Cartridge Based Nucleic Acid Amplification Test (CBNAAT)
Liquid cultures (MGIT®)
Solid cultures (Lowenstein Jensen Media)
39
40. What is CBNAAT?
CBNAAT
• Currently available in country as Xpert MTB/RIF™ (aka Gene Xpert)
Cartridge
Based-
• Closed system, automated processing unlike earlier PCR based technologies
• Less prone to contamination
Real time
PCR
• amplified DNA is detected as the reaction progresses in "real time".
Nested
PCR
• involves two sets of primers (for Mtb and for Rif resistance), used in two
successive runs of polymerase chain reaction
• Detects M tb & RIF resistance in < 2 hours
42. To summarise, Available Diagnostic tests for TB
Direct
• Smear: positive in only 10-15%
of children
• Commonly performed on
sputum and gastric aspirates
• Culture : slow and cumbersome
requiring sequential procedures
for isolation and in-vitro drug
sensitivity testing
• CBNAAT: Rapid reliable WRD
which also tells abour Rif
resistance
Indirect
• Chest radiography: often
non specific findings, inter
and intra observer variation
• TST: is only a marker of
infection not disease
42
44. ESR
• Anemia
• Fasting
• Method
• Coagulant
• No specificity
Too many pretest variables
No role in diagnosis
44
45. Let us review our case finally
Victor’s Basis of ATT
• Victor’s has chronic cough and is not thriving well- TB like symptoms
• TST positive ?? 10 TU
• Father has chronic cough but unlike TB
• CXR suggestive - primary complex
• ESR 32mm ---- So What?
• TB Elisa positive IgG and IgM
• No attempt at microbiological diagnosis
• Basis for ATT justified
– NOooooo……
45
46. • Persistent Fever >2wk, without a known cause and/or
• Unremitting Cough for >2w and/or
• Wt loss of 5% in 3m or no wt gain in past 3 m
Sputum Smear (2 samples),
X-ray Chest (XRC), TST
Smear +ve
Bacteriological
confirmed TB Case
Smear –ve or
Sputum not available
XRC highly suggestive*
XRC NS shadows
TST –ve/+ve
XRC Normal
TST +ve
XRC Normal
TST -ve
Sputum/GA/IS for smear
and CB NAAT
+ve -ve
No other likely alternative diagnosis
Clinically Diagnosed TB case
Persistent shadow
and symptoms
Sputum/GA/IS for
smear and CB NAAT
+ve -ve
Refer to expert for
work up of persistent
pneumonia
Evaluate for EPTB
Refer to expert
Look for
alternate cause
Give course of
Antibiotics
Presumptive TB
46
47. Summary
• New diagnostic algorithm incorporating usage of new
technology like CBNAAT which is more sensitive than ZN
Smear or LED Fluorescent microscopy
– also far more costly and may be less easily be available.
• At the initial step, If self expectorated sputum is
available
– smear may be done
• All suspects with negative results and in all other
situations, CB NAAAT (where available) shall be
preferred to smear examination.
– Facilities for these test available under RNTCP labs (free of
cost) as well through a network of accredited private labs at
a subsidised price through Initiative for Promoting
Affordable Quality TB Tests (IPAQT).
47
48. Summary
• Algorithm is best suited for children who are new
cases (i.e. have not received ATT previously ever or
for <4 weeks) and likely to have drug sensitive
disease (no exposed to a known MDR source case)
• For Drug resistant TB Suspects (Treatment after
interruption, recurrent TB, failure and HIV
patients), bacteriological confirmation along with
first line drug sensitivity should be considered
upfront
– use any of the available WHO approved technologies
like MGIT culture sensitivity/ Line probe assay /
CBNAAT.
48
49. Lymph node Tuberculosis
• Lymph node TB is one of the most common forms of EPTB
• Cervical lymph nodes are most common site
– With or without associated disease of other lymphoid tissue
• Maximum prevalence was in 5-9 y.
50. Clinical features
• Enlarging masses over weeks to months
• Usual cervical: jugular, posterior triangle,
supraclavicular
• Others: axillary, inguinal
• Systemic symptoms commonly seen
– Local manifestation of a systemic disease
– Pulmonary route of entry of the pathogen hilar and
mediastinal LN
50
52. Other tests
• 5- 40% of patients may have pulmonary/ pleural abnormalities
• Hilar/ mediastinal lymph nodes
• Parenchymal lesions
• Pleural effusion
Chest Xray
TST positive in >70%
• Utility is in guiding for FNAC in non palpable or deep seated nodes
• Central hypoechogenecity where present is considered suggestive of
TB
Ultrasonography
52
53. Enlarged lymph node – Matted, cold abscess with or
without a discharging Sinus
Lymph node enlargement of >2 cm in one or
more sites
•Consider a course of antibiotics for 7 days (Do
not use Quinolones/Linezolid)
•Review after 2 weeks
Lymph Node Aspirate
•Smear examination for AFB by ZN staining on LN aspirate.
•CB NAAT for MTB in pus from discharging sinus/aspirate from lymph node/MGIT (if available)
•Aspirate for fine needle aspiration for cytology (FNAC), if the LN is non fluctuant
Algorithm for Lymph Node TB
Diagnosis confirmed in the pus/aspirate
from FNAC :
ZN stain +ve for AFB
CB NAAT Mtb positive
Caseation in granulomas
•If no granulomas /non casseating granulomas
and no AFB, consider alternative diagnosis;
•Lymph node biopsy.
•Isolated Mantoux test positivity without
suggestive findings on FNAC should not be
treated with ATT
Treat as Case 53
In case of non-response, suspect, TB as the cause
for lymphadenitis
54. • The three type of the populations are in constant dynamic relationship.
• Different drugs are effective in different metabolic populations, requiring a combination therapy for
treatment. (Modified from Grosset J, Clinics in Chest Medicine 1980;1:231-41)
105
Type A: Actively dividing
organisms 108 --
H>>S>>R>>E
Type B: Intracellular Slowly
multiplying organisms - PZA Type C: Extracellular Slowly
multiplying organisms and spurters
- RIF, INH.
Relapse due to persisters
Failure due to selection of
resistant organisms
2 6
Time in months
Basis of Chemotherapy of Tuberculosis
55. Bacillary characterisitics and Treatment Plan
TB Treatment needs multidrug therapy which can be biphasic
Initial part when more bugs, use more drugs
Drugs like PZA which work only in acidic environment useful only in IP when
there is inflammation and not later part of the disease
Possible to treat TB with intermittent therapy- due to lag period effect (bacilli
multiplication stops for hrs to days after exposure to drugs; it is dose
dependent for some drugs.
Shall need higher doses
– Field studies suggest that:
• The most efficacious intermittent therapy is thrice a week regimen
• Intermittent therapy is not safe without observation
• there is little margin for missing any doses.
56. Phases of Treatment
Early rapid Killing of Mtb, prevents
deterioration and death
Reduced infectivity
Sputum conversion in 80-90%
Addition of Z reduces duration to 6
months due to its sterilizing effect
Addition of E is useful if initial drug
resistance to INH is high
Eliminates most residual bacilli
Reduces failures and relapses
Small number of bacilli left:
fewer drugs are required
In presence of background
resistant to the companion
drugs; more drugs needed to
prevent amplification of drug
resistance
Intensive Phase (IP) Continuation Phase (CP)
57. Rationale of DOTS
• Right drugs
• Right doses
• Right intervals
• Complete course
Ensures treatment for entire course
• Adherence
• Completion of treatment
Ensures
The pitfalls & errors in prescription and completion of ATT in India were too many
and too hazardous to continue with the practice of unregulated treatment
Standardized drug regimens,
Reduced emergence of Drug resistance
58. Category of
treatment
Type of patient Regimens
New Cases
(erstwhile category
I and III*)
New sputum smear positive
New sputum smear negative
New extra-pulmonary
2HRZE+ 4HR
Re treatment Cases
(erstwhile category
II**)
Sputum smear positive relapse
Sputum smear positive failure
Sputum smear positive- treatment
after default
Others
2HRZES+ 1 HRZE+
5HRE
IAP -RNTCP guideline 2012
*New categories includes former Categories I & III
**Previously treated is former Category II
59. What Drug Doses do you use?
Thrice weekly Daily
Rifampicin R 15 (12-17) 10-12 mg/kg (max 600mg/day),
Isoniazid H 15 (12-17) mg/kg 10mg/kg (max 300mg/day)
Pyrazinamide Z 35 (30-40) mg/kg 20-25mg/kg (max 1500mg/day)
Ethambutol E 30 (25-30) mg/kg 30-35mg/kg (max 2000mg/day
Streptomycin S 15 mg/kg 15 mg/kg (max 1gm/day)
59
•Drug Doses have increased –
Please make a note
60. Available Drug Formulations may not be apt
• Almost all have 1:2 ratio of INH to Rif
instead of 1:1
• Available Triple combinations have much
poorer ratios of all three drugs
• Individual drugs increase pill burden
compared to combinations but allow
appropriate dosing
Commercial formulations
61. • Safety
• Simplified treatment
• No errors in missing one or more of the combination drugs
• Reduced risk of emergence of drug-resistant strains
• From programmatic view point it can simplify drug supply management, shipping and
distribution;
TB always requires multi-drug therapy and FDCs as a single
formulation ensures
WHO and IUATLD recommend the use of FDC formulations as
routine practice
FDC tablets of good quality and proven bioavailability of rifampicin
and in appropriate dosing combination should be used in the
treatment of TB.
None of the available FDCs in the country currently meet these
criteria
FDCs with appropriate dosing in pipeline (H 50, R 75, Z150)
(10:15:30)
Usage of FDCs
62. Writing TB prescription
• Diagnosis
• TB/ Koch’s not acceptable
• Details needed
• Basis of diagnosis
• Type of patient
• Past history of treatment
• Type of disease
• Treatment Plan
Essential components of your prescription
Editor's Notes
The slide shows the course of TB from the source which is a infectious TB case. TB is usually an airborne infection. It is also to be emphasized that children can be infectious as well.
Note the symbols of Mycobacterial virulence and Host immunity. The imbalance between these are detrimental to progression. The interaction of both these factors would decide whether the contacts would have a infection, whether the infection would remain latent or lead to a primary disease and reactivation of the latent infection.
Risk of progression of the TB infection to disease is about 5-10% over lifetime in a healthy individual but this is higher in young children, nearly >50% in infants & 25% in 1-5 y.
ETS – Environment Tobacco Smoke
Make a brief mention of the risk factors here
Most of these would be discussed in detail later in the module at some point of time.
This set of slides on Childhood TB tries to bring to fore the diagnostic and treatment issues using some case studies (based on real patients).
The Gold standard diagnosis of TB is demonstration of AFB on smear / Myc TB on culture of an appropriate specimen. However, the performance of this tool in primary TB and among children is poor. In the absence of an alternative fool proof, easy, patient friendly diagnostic tool, the diagnosis of TB in children is often based on the combination of indirect clues like suggestive symptamatology, suggestive radiology, history of contact, positive TST in combination. It is not uncommon that these indirect tools are used inappropriately and false positive diagnosis is made. Fateh’s case elaborates these issues and points to the imperfections or limitations of these indirect tools.
This 3 year old child has chronic suggestive symptoms and hence is investigated for TB and put on treatment. The family wants a review from an expert like you.
Show the CXR without any judgement or comment and it has been interpreted as bilateral prominence ? Primary TB
Highlight that the symptoms of TB are common even other wise and often non-specific.
Highlight that the caregiver often make a poor distinction between a persistent and not improving, slowly improving or recurrent pattern till specifically asked/probed. Emphasize the need for accurate symptom definition.
Not growing well ? Is it documented weight loss of more than 5% over last 3 months or no weight gain
13
These are the symptoms for the commonest form of TB- Pulmonary.
EP TB symptoms shall be discussed later.
Highlight the inaccuracies in Fateh’s symptoms/ history.
Inaccuracy in taking the History of Contact is the next focus point
History of exposure / contact is clarified.
Exposure to an infectious case should by itself prompt survey for disease in the child. The infectious contact is a patient with any form of lung or airway involvement due to TB. While the contacts of infectious smear positive case are at highest risk, the risk of spread remains with all pulmonary cases.
In symptomatic patient this threshold is lowered and contact with a person with any form of active tuberculosis within last two years may be considered significant as a significant proportion of these index cases may have unrecognized coexisting pulmonary involvement.
This index case will help us raise several issues relevant to pediatric TB diagnosis.
Link it with history of exposure.
Due Weightage to history of exposure is important and this cannot be used loosely e.g. contact with a patient with chronic cough like Victor’s father case.
The xrays shows areas of consolidation with a thick walled cavity inside. This in the indian set up is highly suggestive of TB if the history is long standing and the child is not sick.
In sick children with acute hisitory the foremost differential diagnosis would be a necrotizing pneumonia. In doubtful cases further investigations would clarify the diagnosis like gastric aspirates, bronchoscopy etc.
The bronchoscopy images show the extraneous compression of the trachea and the right main bronchus from the lymph node. This has still not lead to any radiological signs of obstruction like emphysema or collapse.
TB suspect with Miliary shadows is highly suggestive of TB in the Indian set up.
Remember: Milary shadows have other differential diagnosis like chronic aspiration, LCH, chronic interstial lung diseases, allergic bronchopulmonary aspergillosis etc.
Chest radiology has to be interpreted in the clinical context.
Emphasize it detects infection and not disease. It is an adjuvant to diagnosis and not a confirmatory test.
Induration not erythema
Palpate with fingertips or use ball point method to find margins horizontally
Induration may not always be visible, so always rely on palpation with fingertips to discover it.
The area is lightly touched with pads of fingertips. Using a light, gentle motion, fingertips are swept over surface of forearm in a 2-inch diameter around injection site in all four directions to locate the margins or edges of induration.
Mark the edges across the arm & perpendicular to this.
Highlight the fact that very variable and unsuitable strengths of PPD may be available.
The cutoff of 10mm is dependent on the strength of PPD used and there is no predictable linear relationship between the strength of PPD used and the induration produced. Higher strengths of PPD used lead to more non-specific false positives. Currently 2TU RT23 (equivalent of 5TU PPD-s ) is recommended. Other strengths are likely to lead to misinterpretation.
Ulceration: May be seen more often with use of higher strengths of Tuberculin (>2TU).
Two Step Testing:
Some people infected with M. tuberculosis may have a negative reaction to the TST if many years have passed since they became infected. They may have a positive reaction to a subsequent TST because initial test stimulates their ability to react to the test. This is commonly referred to as the “booster phenomenon” and may incorrectly be interpreted as a skin test conversion (going from negative to positive).
For this reason, the “two-step method” is recommended at the time of initial testing for individuals who may be tested periodically (e.g., health care workers). If the first TST result in the two-step baseline testing is positive, consider the person infected and evaluate and treat the person accordingly. If the first test result is negative, the TST should be repeated in 1–3 weeks. If the second test result is positive, consider the person infected and evaluate and treat the person accordingly; if both steps are negative, consider the person uninfected and classify the TST as negative at baseline testing.
IGRAs can be roughly translated as in vitro TST using specific antigens which do not cross react with BCG.
The information provided by a positive IGRA is that the patient is truly infected (no cross reaction with BCG). It makes no distinction between infection and disease (just as TST). It can also be falsely negative in a proportion of cases.
Being expensive and more resource demanding- it has little added value in the diagnostic algorithm. Like TST these also have potential for errors in conducting and interpreting the test.
Another test used for diagnosis of TB is Elisa for TB antibodies against antigen5/ LAM etc.
This test IS NOT PART OF THE ALGORITHM but is discussed to point out futility of its use.
These useless tests have been banned in our country and should NEVER be used.
ESR is another test often used as a supportive investigation but is of no value in ruling in or ruling out the diagnosis of TB due to its non-specificity, and possibility to be affected by many variables other than the disease.
Obviously it does not find its way into the algorithm!!
Victor looked quite like a TB case to start with but as we looked at each of the components of the diagnosis it pointed against the likelihood of TB.
CBNAAT is far more sensitive than ZN Smear or LED FM microscopy, but is also far more costly and less easily be available.
So it is not recommended at the initial step if there is a self expectorated sputum available which can be checked with smear for 2 reasons – easily available affordable technology and the smear positivity is higher in the older children where the self expectorated sputum is going to be available.
However, for all other situations, CB NAAAT where available shall be preferred to smear examination.
In addition, all DR TB suspects (contacts of a chronic patient or MDR case and All retreatment cases) MGIT culture sensitivity/ Line probe assay / CBNAAT must be used upfront for early detection of resistance and to appropriately treat the patient.
CBNAAT appears a useful test with yield better than Mtb culture and about 5x that of ZN staining on smear.
Always look for TB involvement at other sites, particularly the chest TB.
Trainers should also remind the group that the excised lymph node is to be sent appropriately (for Histopathology in formalin and Mtb culture or Xpert in saline).
I have a few changes in the slide and notes. Pl see if OK
Should we animate
Pharmacologic and microbiologic principles of TB treatment
The M TB population
Type A: Rapidly multiplying: in cavities (extra cellular environment), killed by INH, RIF, PZA, SM
Type B: Intracellular Slowly multiplying organisms: occasionally dividing, inside macrophages, killed by PZA
Type C: Extracellular Slowly multiplying organisms and spurters : Intermittently multiplying: in solid caseous material and killed by RiF
Drug resistant mutant: prevented by INH and PZA
Since there were 2 categories of treatment now, they were called New case regime and retreatment regime (5 drug biphasic intensive phase and 5 month 3 drug continuation phase)