TB , PARASITIC ,

VIRAL & FUNGAL

LUNG DISEASES

Charles Y. Yu, MD ,MSc

DLSU Professor of Medicine
Vice-Chancellor, Mission & Linkages
 OUTLINE
• Definitions
• Clinical Symptoms: reliability
• Radiologic features
• Mycobacterial lung diseases
• Viral Lung Diseases
• Parasitic Lung Diseases
• Fungal Lung Diseases
 ILLUSTRATIVE CASE
• A 32 year old male Filipino presents with
a history of cough of more than 4 weeks
duration, on and off fever lasting 2 weeks,
weight loss of 10%. 1 day prior to
admission he complains of blood-streaked
phlegm which alarms him and he seeks
OPD consult.
• P.E. is unremarkable
 TB SITUATION
• One of the 20 high-burdened countries
( WHO TB Watchlist )

• 3rd in the Western Pacific - Case Notification

• 6th leading cause of deaths (1997)

• 6th leading cause of morbidity

• Prevalence of Smear (+) cases - 3.1 /1000

(240,000 cases)
THE URGENT NEED FOR NEW DRUGS
 TB SYMPTOMATIC
• Constitutional Symptoms
– Fever
– Weight Loss
– Anorexia
– Body Malaise
• Respiratory Symptoms
– Cough
– Hemoptysis
– Chest/Back Pains
 Natural History of TB
(in the absence of HIV infection)

50% 50%

10%

90%

Courtesy of Dr. Anne Ginsberg, Global TB Alliance

 The TB Life Cycle
Index Case

Exposure A TB patient infects Only active TB

N 10-15 persons / yr pts (specially
smear (+)) can
o In 90-95% 5-10% infect others
t of infected Infection lifetime
patients, M. risk
I tb remains 30% of un-
n dormant in treated TB
f
e
the body undergoes Disease Untreated, 70%
spont. re- will die in 5 yrs
c
mission > 90%
t
CURE RATE
e
d (w/ DOTS) Death
Healthy Subjects
 Model for the Epidemiology of
Tuberculosis
A Model for the Epidemiology of Tuberculosis

Risk Risk Risk Risk

factors factors factors factors

Infectious
tuberculosis
Subclinical
Exposure infection Death

Non-infectious
tuberculosis

Rieder HL. Infection 1995;23:1-4

Reider HL. Infection, 1995

 WHAT IS LATENT TB INFECTION?
• In latent infection, a person carries the bacteria but does
not have signs of active disease…LTBI is important
because it can be transmitted to others and or become
active infection--- Ringold S, Glass M JAMA 2005

• While the infection is latent, the person has no

symptoms or detectable signs of infection except for a
positive tuberculin skin test reaction

• LTBI is a clinical condition characterized by a positive

tuberculin skin test (TST) in the absence of clinical or
radiological signs of active tuberculosis disease—
Nuermberger et al Center for TB Research Johns
Hopkins Seminars in Resp & Crit Care Medicine 2004

• LTBI is a condition in which an individual is infected with

M.Tb but does not currently have active disease---
ATS/CDC/IDSA AJRCCM 2005
 RATIONALE FOR TREATMENT
OF LTBI
• Treatment of LTBI reduces an individual’s risk
and imparts public health benefit by reducing the
pool of latently infected individuals who could
develop active TB in the future
• TB is a suitable disease to target for screening
because of long and variable latent infection
• Acceptable treatment for LTBI that will reduce
the likelihood of disease by 75%

Chaulk, CP. JAMA 1998 (279) 943-949

Risk Factors For PTB Given That TB Infection Has Occurred
 Testing for
TB Disease and Infection
 Purpose of Targeted Testing

• Find persons with LTBI who would

benefit from treatment

• Find persons with TB disease who would

benefit from treatment

• Groups that are not high risk for TB

should not be tested routinely
 Administering the Tuberculin Skin Te

Inject intradermally 0.1 ml of 2

U PPD tuberculin

Produce wheal 6 mm to 10 mm
n diameter

Do not recap, bend, or break

eedles, or remove needles from syringes

Follow universal precautions for infection control

 Reading the Tuberculin Skin Test

•Read reaction 48-72 hours

after
injection
•Measure only induration

•Record reaction in
millimeters
 Limitations of the tuberculin skin
test (TST)
• Reader variability
• False-positive test results due to cross-
reactivity with environmental mycobacteria
and with previous BCG vaccination
• False-negative results due to anergy in
immuno-suppressed individuals,
malnutrition
 QuantiFERRON vs TST
IFN-gamma TST
Gp 1 No identifiable risk 4% 51%
Gp 2 Recent casual contacts 10% 60%
Gp 3 Recent close contacts 44% 71%
Gp 4 Bacterio/patho TB 81% 78%

Conclusions: the IFN-gamma assay is a better indicator of

Risk of M tuberculosis infection than TST in a BCG-vaccinated
population

Source: Kang, YA,(JAMA 2005) Discrepancy between the Tuberculin

Skin test and whole blood interferon (gamma) assay for
Diagnosis of LTBI in an intermediate TB-burden country
 DEFINITIONS:
• TB mimic has been classically defined as
diseases that manifest like TB but turn out
to be other diseases

• TB mimic may also mean the protean

picture of TB .i.e. the multiplicity of
manifestations from any organ in the body
that eventually turned out to be TB
 DEFINITIONS
• Symptomatic PTB
– At least 2 sp+ for AFB with or without x-ray
abnormalities
– 1 sp+ & with radio abnormalities consistent
with (active) PTB (as defined by a clinician*)
– All 3 sp- but w/ x-rays consistent with PTB, w
no hx of anti-TB treatment and with a previous
normal chest x-ray
2003 Comprehensive Unified Policy (CUP)
Philippines,ratified March 7,2003

*2003 WHO Guidelines for National Country Programs

 Can clinical signs and symptoms
discriminate between PTB and non-PTB
respiratory disease?
CONSENSUS STATEMENT:

Of the symptoms commonly associated with PTB,

only a chronic cough appears to consistently
differentiate between PTB and non-TB respiratory
disease.

Level of Evidence: 2
Recommendation Grade: B

2000 Philippine CPG on TB

 TB Symptomatic: A Differential
Diagnosis
Clinical Features Tuberc Parago Aspergillosis Crypto Silicosis Carcinoma Coccidio
ulosis nimiasis coccal diodes
lung Immitis
Cough 75% 83% 50-95% + + +++ +

Hemoptysis 25% 70% 50% - - ++ +

Fever/chills 50% 37% + ++

Fatigue 58% ++
Dyspnea 42% + + + ++
Wt.loss 75% +++
 Clinical Symptoms
• Correlation between Clinical symptomatology and chest
radiographic TB
• 6 variables correlated with radio. TB :
– age>45 (7 pts)
– male sex (5 pts)
– hemoptysis (6 pts)
– dyspnea (5 pts)
– weight loss>25%(6 pts)
– severity of cough (distressing 11 pts, non-distressing 8 pts)
• Logistic regression analysis
– Scores greater than 20 were associated with greater probability of
radiographic TB
– 88% radio TB provided sputum only 20% AFB+
– 70% of hemoptysis had radio TB (TB? Bronchiectasis?)
– Cavitary x-rays seen in 74/142 (52%) of which 33% were
described as far advanced
•De La Cruz, Roa et al. (PJIM Vol.29:187-203,1991)
 Tattevin Study (1999)
• Total : 211 patients
• Culture proven TB 22.3%
• Symptoms
Typical symptoms (cough,fever,drenching night sweats >3 weeks, hemoptysis)
• Compatible symptoms (cough,unxplained fever,nonpurulent sputum production,
anorexia, weight loss)
• X-rays
• Typical of PTB (presence of nodular, alveolar or interstitial
• Infiltrates in zones above clavicle or cavitations in upper zones or apical segment of
lower lobe)
• Compatible (enlarged hilar nodes, pneumonic lesion,atelectasis, mass
lesion,miliary,pleural exudate
• Atypical (any other pattern including normal CXR)
• Univariate analysis
– Predictive factors: Symptoms, CXR, age (40.8 TB vs 47.5 non-TB,absence of HIV, immigrant
status, BCG
• Multivariate analysis
– CXR (14 pts), aHIV (6 pts) and typical symptoms (12) independently predicted TB,compatible
symptoms (5)
• Immigrant status (2), BCG (2) homeless (2)
• Prediction Model 100% sensitive, 48.4% specificity and 25% PPV

Tattevin P.et al Chest 1999:115;248-53

The Validity of Medical History, Classic
Symptoms, and Chest Radiographs in
Predicting Pulmonary Tuberculosis
 Negative Predictors
• Cohen (1996) absence of ff:
– 2 weeks of cough/sputum
– Weight loss
– Absence of typical x-rays
• Strong negative predictors for PTB

• High TB prevalence setting (44%)

Cohen R Chest 1996: 109: 420-423
 TB Prediction Score (TPS)
among sputum negative TB
• Setting: UCSF affiliated public hospital 1993-1998
• Patients: 47 PTB patients, 141 controls
• Results:
• TPS < 0 low probability of PTB even in high prevalence
areas
• TPS >0 high probability (esp.in high prevalence areas)
Positive predictors:
– Positive tuberculin skin test (-1 pt) OR: 4.8 (2,11,9)
– HIV seropositivity + Positive mediastinal lymphadenopathy on x-
ray (+2 pts) OR:7.2 (1.4,36)
• Negative predictors:
– atypical x-ray (-1 pt) OR: 0.3 (0.1,0.7)
– expectoration with cough (-1 pt) OR : 0.3 (0.1,0.6)
• Range of outcomes (-2 to +3) (LRs 0.2-7.1)
Kanaya, AM et al. Chest 2001:120; 349-355
Identifying PTB in Patients with Smear- Results
 CLINICAL SUSPICION FOR TB
(CSTB MULTI-CENTER STUDY)
• NIH Funding (2004-2006)
• UCSD-Center for Pacific Rim Studies
• 5 sites:Philippines (DLSU,UST),Mexico, USA,UK
• Total of 3000 patients (1100 fm Philippines)
• CSTB
– Socio-economic/demo/hx & PE (clinical)
– AFB smear/culture
– Chest radiography
– Serology
Catanzaro, A. Natividad, P.,Dalay,V.
Can a patient with no symptoms have
PTB?
CONSENSUS STATEMENT:

PTB does not have to be symptomatic.

Even among culture-prove PTB patients, a
small percentage (5-6%) may have no
symptoms. Asymptomatic PTB is more
commonly observed in older age group.

Level of evidence: 6
Recommendation Grade: D
 Asymptomatic PTB
• Radio abnormalities consistent with PTB & at
least 1 sp+ for AFB OR
• Previous x-ray normal, current x-ray shows
abnormalities consistent with PTB, 3sp-
• Previous x-ray shows abnormality consistent
with PTB, current x-ray shows progression and
3 sp-
Note: If current x-ray shows abnormality & 3 sm-,
no previous x-rays & px do not fulfill the
criteria, ff-up sputum and x-ray should be done
at least 1 month after

2003 Comprehensive Unified Policy (CUP)

Philippines,ratified March 7,2003
 RADIOLOGIC FEATURES OF PTB
CONSENSUS STATEMENT

Most of the available evidence indicates that no radiologic feature

correlates well with PTB activity

One study ( evidence level 2 ) on hospitalized patients indicates

that hilar or mediastinal lymphadenopathy and diffuse
reticulonodular infiltration may individually correlated with the
presence of active PTB in the presence of a respiratory or
constitutional symptoms suggestive of respiratory disease.

Level of Evidence : 2
Recommendation Grade B
• MINIMAL
“ Slight lesions without demonstrable
cavitation confined to a small part of one or
noth lungs. The total extent ..shall not
exceed the equivalent of the volume of
lung tissue which lies above the second
chondrosternal junction and the spine of
the fourth or the body of the fifth vertebrae
on one side”
“equivalent of one-fifth of one lung)
 PTB Classification (Old)
• Minimal
1) The affected area is
less than the width of an
interspace (or rib).
2) No evidence of
cavitation is present.
3) May occur anywhere in
the lung, commonly in the
peripheral portion of the
1st and 2nd interspaces.
 PTB Classification (Old)
• Moderately advanced
1) The affected portions
of the lung comprise all or
the greater portion of a
lobe.
2) If a cavity is present
measuring up to 4 cm in
diameter.
3) If there are multiple
cavitations, the combined
sum of the diameters
totals 4 cm or less.
 PTB Classification (Old)
• Far Advanced
1) There is multilobar
involvement.
2) Cavities are larger
than 4cm in diameter
or the sum of the
diameters of the
multiple cavitations is
larger than 4cm.
• MODERATE
“Slight disseminated lesions which may extend
through not more thtan the volume of one lung
or the equivalent in both lungs”
“ Dense and confleunt lesions which may extend
through not more than the equivalent of one
third the volume of one lung”
“total diameter of cavities less than 4 cm”
• FAR ADVANCED
“ Lesions more extensive than
moderately advanced”
 NTP/WHO PTB CLASSIFICATION
TB Diagnostic TB Patients TB Treatment Regimens
Category Initial Phase Continuation Phase

I New smear-positive patients 2HRZE 4RH (6HE)

New smear-negative PTB with
extensive parenchymal involvement
Severe EPTB/HIV disease

II Previously treated sputum 2HRZES/1HRZE 5HRE

smear-positive PTB
-relapse
-treatment after interruption
-treatment failure
III New smear-negative PTB 2HRZE* 4RH (6HE)
(other than category i)

IV Chronic and MDR-TB Specially designed standardized

(still sputum-positive after or individualized regimens
supervised re-treatment) (Refer to DOTS Plus Facilities)
* May omit ethambutol if non-cavitary and smear-negative,non-HIV,known fully susceptible bacilli
Sources: DOH MOP 2004
WHO Treatment of TB Guidelines for National Programs, 2003
Microscopy is more objective and
reliable than X-ray
100 98%
Inter-observer
90
agreement
80
70%
70
60
50
40
30
20
10
0 AFB Microscopy X-ray
 Microscopy is a more specific
test than X-ray for TB diagnosis
100
98%
90
80 Specificity
70
60
50%
50
40
30
20
10
0
AFB Microscopy X-ray
Microscopy is more objective and
reliable than X-ray

100 Over-diagnosis
80
60

40
20

0
Diagnosed by Actual
X-ray alone Cases
 Highlights ….

• Radiographic differentiation between active

and inactive disease can only be reliably
made on the basis of temporal evolution.
- fibrosis and calcification are features found
in both healed and active disease; disease
status based on their presence is unreliable

• Radiologic manifestations of PTB are

dependent on several factors including prior
exposure to TB, age, and underlying
immune status. Leung, A. State-of-the-Art: Pulmonary TB
The Essentials. Radiology 1999:210:307-322
 Do radiologic features of PTB
correlate with disease activity?
• 2000 Consensus statement:
“Most of the available evidence indicates that no
radiologic feature correlates well with disease
activity”
…One hospital study indicated that
hilar/mediastinal lymphadenopathy and diffuse
reticulonodular infiltrates may individually
correlate with active PTB in the PRESENCE of
respiratory constitutional symptom of respiratory
disease. Grade B

2000 CPGs: Diagnosis , Treatment & Control of TB

PCCP,PSMID Task Force p.22
 THE

REVISED TUBERCULOSIS

CONTROL PROGRAM
 BACKGROUND
• 80 million population (2003)

• Department of Health sets policies, standards,

guidelines
TB Unit
Centers for Health Development

• Health program implementation is the mandate

of LGUs( Devolution )
Rural Health Units (RHUs) ; Health Centers
Barangay Health Stations (BHSs)
 WHAT HAD BEEN DONE?
1910 - PTS organized
1930 - TB Commission established
1954 - TB Law passed
1978 - Nationwide implementation of NTP
1987 - SCC in Blister-packs introduced
1992 - Local Government Code implemented
1994 - PhilCAT organized
1996 - D.O.T.S. strategy pilot-tested
2002 - D.O.T.S. nationwide (98% coverage)
2003 - GDF & GFATM grant approvals - PPM
 Directly-Observed Treatment
Shortcourse (D.O.T.S.)

• Political commitment
• Quality microscopy service
• Regular availability of drugs
• Standardized records & reports
• Supervised treatment
 PROGRAM
• Case-finding
• Case-Holding
• Recording & Reporting
• Monitoring & Supervision
 PROGRAM COMPONENTS
• CASEFINDING:
Objectives:
To identify TB symptomatics
To identify & diagnose TB cases early

Passive Casefinding - TB symptomatics

present themselves at the health facility.

Active Casefinding - purposive effort to find TB

cases among the symptomatics who don’t
seek consultation.
MAJOR POLICIES ON CASEFINDING
•Direct sputum smear microscopy shall be the
primary NTP diagnostic tool.

•All TB symptomatics must undergo sputum

examination, with or without X-ray results.
Only contraindication is massive hemoptysis.

•Three sputum specimens must be submitted -

1st spot, early morning, 2nd spot
Passive casefinding shall be implemented
in all health centers, health stations.

Sputum microscopy work shall be

performed only by adequately trained
health personnel.

Quality control of smear examination must

be observed. Validation system must be
established.
 CASEHOLDING
Objectives:
To render as many Smear (+) cases as non-
infectious & cured as early as possible.
To treat seriously-ill Smear (-) cases & other
potentially infectious cases.

Classification of TB Cases - based on location of

lesions:
Pulmonary Smear (+)
Smear (-)
Extra-pulmonary
 Definition of Pulmonary Case
• Smear (+):
- at least two AFB (+) smears on initial examination OR
- one AFB (+) plus radiographic abN as determined by
clinician OR
- one AFB (+) plus sputum culture positive for M. tb

• Smear (-):
- three sputum (-) for AFB AND
- radiographic abN for PTB AND
- no response to a course of antibiotics and/or
symptomatic meds AND
- decision by clinician to treat with a full course of anti-TB
meds
 Case Definition
• New: never tx or on anti-TB meds for less than a month

• Relapse: prev tx for TB with cure or complete outcome

and now bacteriologically positive

• Failure: while on tx, AFB (+) at 5 mos or later

• RAD: returns to tx with (+) bacteriology following

interruption for 2 mos or more

• Other: starting tx again after interruption for 2 mos but

smear (-)
- smear (-) then became smear (+)
- chronic case: sputum (+) at end of retreatment regimen
 NTP – WHO CATEGORIES
TB Patients to be Given
Treatment (ATS Class III)

Regimen I: New pulmonary

smear (+) cases;
severe smear (-)
cases
Regimen II: Treatment
failure, RAD,
relapse, others
Regimen III: New smear (-)
with
 TB Treatment Evolution
1950 1960 1970 1980 2005

1946 1952 1963 1970 1974 1998

Strepto- 1 regimen: BMRC Trials Rifapentine
st
Rifampin (R) BMRC
mycin 1st • Streptomycin discovered Trials add R & Z approved
used for TB • PAS 1961 add R
• Isoniazid Ethambutol (E)
Standard Therapy
1954 discovered
2 months: R, H, Z, E
Pyrazinamide (Z) +
discovered – but liver 4 months: R, H
toxicity

Standard Regimen by 1960s based on 1952 drugs

Rx shortened to 6 months

Rx shortened to 9 months

Rx lasts from 12-24 months

Figure 1: TB Drugs targeting distinct M. tuberculosis subpopulation
(adapted from Zhang, 2005)
 Current TB Drug Therapy
 Active, drug-sensitive TB
6 months of therapy (2HRZE/4HR)

 Resistant TB (MDR- and XDR-TB)

Individualized, prolonged therapy, few available drugs, poorly tolerated and
difficult to administer

 TB/HIV co-infection
Treatment as in active TB, but drug interactions with ARVs make
simultaneous therapy impractical in resource-limited settings

 Latent TB
9 months of INH therapy
 TREATMENT REGIMENS
TB Treatment TB Patients To Be DRUGS AND DURATION
Regimen Given Treatment
Initial Phase Continuation
Phase

I New smear-positive PTB; new smear- 2 HRZE 4 HR

negative PTB with extensive
parenchymal involvement; new cases of
severe forms of extra-pulmonary TB

II Previously treated smear-positive PTB; 2 HRZES/ 1 5 HRE

relapse; treatment failure; treatment after HRZE
interruption

III New smear-negative PTB (other than in 2 HRZ 4 HR

Category I); new less severe forms of
extra-pulmonary TB

IV Chronic case (still sputum-positive after Refer to specialized centers

supervised re-treatment) with access to second line
drugs
Table 1. Commonly used TB drugs and their targets (adapted from Zhang, 2005)
 Sites of Action of
TB Alliance Discovery Projects DNA Gyrase
Folic Acid Metabolism  Fluoroquinolones
 p-Aminosalicylic acid  GyrB inhibitors
RNA Polymerase
 Rifamycins
DHFA
Cell wall synthesis
 Isoniazid (prodrug) DNA
PABA
 Cycloserine Ribosome (50S)
 Ethambutol  Macrolides
 Novel InhA inhibitors (discontinued)
mRNA  Pleuromutilins
Energy Metabolism  Oxazolidinones
 ICL Inhibitors (Discontinued) H+ Reactive
ADP ATP Ribosome (30S)
 Malate synthase inhibitors Species
Peptide  Aminoglycosides
 E-transport inhibitors Reduction  Capreomycin/Viomycin
 Riminophenazines
 Pyrazinamide (prodrug)
 ATP Synthase: Diarylquinolines Multiple Targets Peptide Deformylase
 Nitroimidazoles  PDF inhibitors
 Bifunctional drugs
 SCHEDULE OF SPUTUM
FOLLOW-UP EXAMINATIONS

• CAT I : 2nd, (3rd), 4th, 6th

• CAT II : 3rd, (4th), 5th, 8th

• CAT III : 2nd

 Supervised Treatment
• a mechanism of ensuring treatment compliance
• TB patient is motivated to take his drugs
• Cured

* Treatment Partner *
• watches the patient take his drugs daily
• reports & traces the patient if he defaults
• provides health education regularly
• motivates the patient on sputum ff-ups
• Who will undergo supervised treatment ?
Priority are the Smear (+) TB cases
• Who could serve as Treatment Partner ?
Health Staff, Barangay Health Worker,
Community Volunteer, Family Member
• Where will D.O.T. take place ?
Health facility
Treatment Partner’s House
Patient’s House
• How long is treatment supervised ?
Daily drug intake is supervised during the
entire course of treatment.
RECORDS and REPORTS

NTP Laboratory Request Form

Laboratory Register

NTP Treatment Card

NTP Identification Card
TB Case Register

NTP Referral Form

 Reports

• Quarterly Report on Laboratory

• Quarterly Report on Casefinding

• Quarterly Report on Treatment Outcomes

CASEFINDING

• Proportion of Sputum (+) (60%)

= Total No. Sputum (+) cases discovered
Total No. of Pulmonary TB cases

• Proportion of 3 sputum examination (90%)

= No. TB symptomatics with 3 specimens
Total no. TB symptomatics examined
Casefinding
• (15-20%) Positivity
= No. Sputum (+)s discovered_________
Total no. TB Symptomatics examined

• Case Detection Rate (CDR=70%)

= No. of New Sputum (+) cases discovered
TP x 145/100,000 (Incidence)
 COHORT ANALYSIS
• A group of patients having the same
attributes at a certain period of time to
determine treatment outcome.

• Treatment Outcomes :
Cure R ate = 8 5 %
Completion Rate
Tx Failure Rate Defaulter Rate
Death Rate Trans-Out Rate
Cure Rate
= Total no. New Sputum (+)cases who got CURED
Total no. New Sputum (+) cases evaluated

General Attributes:
New, Pulmonary Sputum (+) case

Differentiating Attribute - CURED (Tx Outcome)

Cure - New Sputum (+) case, completed tx,

Sputum (-) at the end of treatment
RECORDING / REPORTING:
Objectives:
1. To know how best to assist clients / patients

2. To know how best to assist TB Program

implementors
RECORDS PERSON(s) IN-CHARGE
On Casefinding / Microscopy:
Symptomatic Masterlist Midwife
Lab Request Form Midwife, Nurse ( upper )
Medtech ( lower )
Lab. Register Medtech
On Caseholding:
Treatment Card Nurse ; Midwife
ID Card Nurse ; Tx Partner
TB Case Register Nurse
Referral Form Nurse ; Physician

REPORTS
- ALL are on quarterly basis.
• Casefinding for New Cases & Relapses
• Retrospective Cohort Report
• Drug Inventory
• Laboratory Report
 MAJOR POLICIES ON
RECORDING/REPORTING:
• Shall rely on all government health facilities,
including government hospitals.
• Shall include all cases of TB, classified according
to internationally accepted case definitions.
• Shall include private physicians & private clinics,
after agreement with parties concerned has been
made.
• Shall allow the calculation of the main indicators
for evaluation. (Cure Rate, Case Detection Rate)
 TB DIAGNOSTIC COMMITTEE
RATIONALE:
About 60% of the TOTAL reported
PTB Cases diagnosed by CXR (1996)
Dr. Pierre Chaulet’s study ( pilot
areas of C.R.U.S.H. TB Project)
No. of cases assessed = 101
36.5% Compatible
Doubtful
Doubtful

24.8%
No PTB
Compatible 38.6%
w/PTB NO PTB

(1)
VIRAL INFECTIONS OF THE
LUNG AND RESPIRATORY
TRACT
 RESP VIRAL INFXNS
Virus Clinical Syndrome
Group Common Cold Pharyngitis Croup Bronchiolitis Pneumonia

Adenovirus - + - + +
Coronavirus ++ - - - -
Herpesviruses
CMV - + - - +

EBV - ++ - - +
HSV - ++ - - +
VZV - - - - +
Orthomyxovirus
Influenza A,B,C + ++ + + ++
Paramyxoviruses
Measles - - - - +
Parainfluenza 1,2,3+ ++ +++ ++ -
Resp. Syncytial - + ++ +++ ++
Picornaviruses
Enteroviruses + - - - -
 COMMON COLD
• Self-limited acute coryzal illness
• Leading cause of MD consult in OPD, absence from
school & work
• 5 most common causes
– Orthomyxoviruses (influenza A & B)
– Paramyxoviruses (Parainfluenza, RSV)
– Adenoviruses
– Picornaviruses (Rhinovirus)
– Coronaviruses
• 25-30% remain undiagnosed
• Frequency of episodes relates to large number of
causative viruses & reinfections with certain types
(coronaviruses)
• Winter months, rainy season
• TRANSMISSION
– Contact with infected secretions
– Droplet nuclei in the air
– Hand to hand transmission possible (rhinoviruses)
– Large & small particle aerosol
• SYMPTOMS
– Start 1-3 days after infection
– Nasal discharge/obstruction, sneezing, sore throat
and cough
– Most cold symtpoms last 1 week up to 2 weeks
 TREATMENT
• Symptom relief
– Antibiotics not effective
– Decongestants/vasoconstrictors
– Anti-tussives
– Analgesics/antipyretics
 VIRAL PNEUMONIA
• Occurs in children & adults, both immunocompetent and
immunocompromised
• Causes resp. viruses particularly Influenza and RSV
• Immunocompromised hosts
– Herpesviruses , measles
– Tranplant cases (parainfluenza & RSV)
• Children
– RSV, parainfluenza viruses, influenza A & B
• Adults
– Influenza A & B,adenoviruses, parainfluenza viruses, RSV
 TREATMENT
• Mainly supportive
• Anti-virals
– Amantadine, rimantadine not systematically
tested vs influenza virus pneumonia
– Interferon alpha broad viral activity but not
very effective in releiving resp.viral disease
– Acyclovir/ganciclovir ineffective
 FUNGAL LUNG DISEASES
• Pulmonary Aspergillosis
• Mucormycosis
• Candidiasis
• Blastomycosis
• Coccidiomycosis
• Histoplasmosis
• Cryptococcosis
Coccidiomycosis, a systemic mycosis, in a 20 year old male initially suspected having

Hodgkin's disease. A small upper mediastinal mass was identified on a routine chest
X-ray. Coccidioides immitis is endemic in the southwest United States and parts of
Mexico, Central and South America. Inhalation of Coccidioides immitis arthroconidia,
carried by dust storms, causes pulmonary infection.
Photograph courtesy of Jack Saiki, M.D., University of New

Mexico Department of Medicine.

Chronic Coccidioides Immitis
Infection
Cryptococcal lung
 GUIDELINES FOR SELECTION OF
THERAPY FOR ENDEMIC MYCOSES

Infection Moderate-severe Mild Maintenance

Histoplasmosis Ampho B Itraconazole Itraconazole

Blastomycosis Ampho B Itraconazole Itraconazole
Coccidiomycosis Ampho B Fluconazole Fluconazole
or itraconazole or
itraconazole
IPA Ampho B Itraconazole
Mucormycosis Ampho B Ampho B
Pulmo Candidiasis Ampho B F luconazole
 PULMO PARASITIC PARENCHYMAL
& VASCULAR DISEASES
Manifestations INFECTION CAUSATIVE ORGANISM INFECTIVE PATHOGENIC STAGE
Loeffler-like syndrome* ASCARIASIS Ascaris Lumbricoides Embryonated eggs Migrating larva
in soil
HOOKWORMS Ancylostoma duodenale Larvae in soil Migrating larvae
Necator americanus larvae in soil
STRONGYLOIDES S. Stercoralis Larvae in soil

Pulmonary
Eosinophilia Lymphatic Filariasis Wuchereria bancrofti Larvae in mosquito Microfilariae

Space-occupying
Lesions Echinococcosis Echinococcus granulosus Eggs in soil Hydatid cysts

PARAGONOMIASIS P. westermani Metacercariae Adult worms

Schistosomiasis Schisostoma mansoni Cercariae in fresh water Eggs

S. japonicum
S. haematobium

•Persistent,irritating non-productive cough,substernal pain, hemoptysis & dyspnea

with eosinphilia,patchy or miliary infiltrates
 TREATMENT
• Mebendazole 100 mg/day for 3 days
– Ascaris & Hookworms
• Thiabendazole 25 mg/kg x 2 days
– Strongyloides
• Filariasis
– Diethylcarbamazine 5mg/kg divided doses for 2-3 weeks
• Scistosomiasis
– Praziquantel 40 mg/kg single dose & 20 mg/kg 3 doses for
japonicum
• Paragonomiasis
– Praziquantel 75 mg/kg per day for 2 days
Scattered areas of patchy pneumonia with "cotton wool"
opacities and ring shadows in adult Korean man with
pulmonary paragonimus
A 47-year-old Korean woman with pulmonary paragonimiasis showing cysts within an area of
consolidation (A) Chest radiograph shows relatively well-defined patchy opacity in upper lobe of
right lung that contains cystic cavities (arrows). (B) CT scan shows air-filled cysts (arrows) within
the mass-like consolidation, suggesting that fluid in the cysts has already been evacuated.

(Courtesy of Dr. J-G Im, et al and AJR 1992).

 RB, 51\M, truck driver from Nueva Ecija (last visit 15 years PTC), now
residing in Las Pinas, 5 months cough, productive of whitsh phlegm,
anorexia, afternoon fever. Positive for ova on sputum.. Paragonimus
10th HD
17th HD (+) resolution of the fever and the
other signs and symptoms
CXR:
Other xrays of early paragonimiasis
• TUBERCULOSIS
1.7 billion people

• PARAGONIMIASIS
20 million people
(WHO, 1994)
COUNTRIES WITH ENDEMIC
AREAS • Cameroon
• China
• Nigeria
• Korea
• Peru
• Laos
• Ecuador
• Philippines
• Thailand

(WHO, 1994)
AFFECTED AREAS IN THE
PHILIPPINES:

• Davao • Leyte
• Basilan • Sorsogon
• Cotobato • Mindoro
• Samar • Camarines
Sur

(Belizario et al, 1998)

EPIDIMIOLOGY:
Sorsogon “Kinagang”
 crab juice in grounded crab meat
 wrap in gabi leaves boiled till dry
Leyte “Kinilao”
 raw crabs mixed with citrus juice
Leyte “Sinugba”
 roasted until carapace
turns yellow
(Cabrera 1984)
• 87.5% of the municipalities of
Sorsogon
(+) Sundathelphusa p.
(Cabrera 1979)
• Infection rate of the snail
intermediate
host (Brotia asperata) .57-.7%
(Yogore, 1958A)
• Infection rate of the 2nd intermediate
host
Sundathelphusa p.
41- 98.5% (Yogore, 1957)
53% (Cabrera, 1973)
PREVALENCE:

• 1973-1975  (.57%) sputum

• 1974  (12.5%) sputum + feces
• 1975-1978  (.15%) sputum
CLINICAL MANIFESTATIONS:

• Constellation of symptoms mimic

PTB
• 50-70% initially diagnosed and
treated
for PTB
• Onset usually months to years after
the
the initial infection and can become
chronic
 CLINICAL MANIFESTATIONS OF PULMONARY
PARAGONIMIASIS (modified fom Kagawa, 1997)

Shim Chang Singh Johnson Im Belizario Total

(%) 1991 1958 1986 1983 1992 1996
Cough 66 100 62 92 62 76 83

Hemoptysis 61 74 95 64 61 25 70

Chest pain 41 94 62 38 22 65

Dypnea 42 53 5 54 ++ 42

Fever and 11 67 23 ++ 37
chills
No 8 0 8 2
Symptoms
 RADIOGRAPHIC MANIFESTATIONS OF
PARAGONIMISIS
(%) Shim Im Sing Johnso Total
1991 199 h n 1983
Consolidation 59 252 1986
62 68 58
Pleural Effusion* 66 54 10 48 51
Cysts or Cavities* 32 46 13 20 32
Linear streaking* 26 41 3 12 25
Nodules* 22 25 8 20 20
Pleural thickening 18 7 28 12 16
Ring shadows* (-) 23 3 8 9
Calcified lesions* (-) (-) 8 4 2
Adenopathy* (-) (-) 3 (-) .5
Normal* 5 (-) 13 8 5
 TUBERCULOSIS PARAGONIMU
S
SURROUNDING Evidence Of disorder Unaffected
LUNG present lung remains
• fibrosis normal
• contraction No nodulations
• nodulation
CAVITATION • ring shadows often “bubble
with definite walls of cavities”
variable thickness Smooth edged
• cavities may have transluscencie
craggy or smooth s within an
walls area of
• fluid levels may be consolidation.
seen No Fluid levels
 TUBERCULOSIS PARAGONIMU
S
PROGRESSION • Visible over long • Where linear
OF LESIONS periods (> 6 mo.) streaking has
• Progression not developed,
usually slow appearance
• Leaves scar and changeable
within
calcifications in
relatively short
lungs
intervals.
• Marked
changes may
occur within 3
months even
without
specific
treatment
 Stage Description Clinical features Radiographic
features

LARVAL 3-12 months hemoptysis Ill-defined

(77%) (100%) consolidation
cough (48) (63%)
chest pain (42) Pleural effusion
(53)
abdominal pain
(30) Pleural
thickening (9)
Normal (15)
ADULT can last for hemoptysis ring shadows
(18%) years (100%) (17%)
cough (55) nodular
densities (13)
cavities (11)
HEALING hemoptysis and Linear opacities
(4-5%) cough stable or
disappearing
ECTOPIC SITES; Clinical
Presentation
• Central headache, vomiting,
dizziness
abnormal vision, aphasia
speech disturbance, motor
and
sensory deficits
• Genital Infertility
Swelling of scrotum
• Cutaneous Skin cysts or lesions
Casiguran Sorsogon Cross Sectional
Survey
76%  chronic cough
25%  hemoptysis and cough
22%  chest or back pain
 dyspnea
 easy fatigability
 fever
 weight loss
 anorexia
 seizures
(Bellizario, 1996)
DIAGNOSTICS:
• CXR
• Sputum exam for ova
• Fecal exam for ova
• Pleural Fluid Examination
• Blood Tests
• Intradermal Test
• Serological Test
 Parasitological
Diagnosis
Pulmonary
paragonimiasis is
confirmed when eggs
are detected in the
sputum, stool,
bronchoscopic washing,
biopsy specimen or
pleural effusion.
Sputum
Examination
• Main diagnostic tool
• The observation of large
number of eosinophils
and/or Charcot-Leyden
crystals in the sputum
should raise the
suspicion of
Paragonimus infection
 Sputum
• Examination
Rusty sputum – pathognomonic
• Ova
– Confirmatory
– Most common
• Eggs are not always present in the sputum of
infected individuals
• Sensitivity: 30% - 40%
Kagawa 1997
The number of ova in the sputum is
proportional to the
– Severity of symptoms
• Blood streaked sputum
– Extent of radiological changes
• Diffuse infiltrates
• Cavitary lesions
 Sputum
Examination
• The egg excretion rates have been reported
to be low ( 28-39%).
• Im, Jung-Gi, AmJRad, 1992
• Johnson, AmRevResDse, 1983
• Shim, SemResMed, 1991

• Detection of eggs in the sputum is low

during the first 2 months or during the
• Multiple sputum examination chronic
increase the
stage.
yield to 54% – 89%
Kagawa 1997

• Concentration of the sputum increases the

positivity rate to 12%
Toscano, WHO, 1994
Sensitivity of Sputum Examination

# of test investigators n
sensitivity
1X Shim 1991 67
39%
Kim 1970 3518
37%
2X Kim 1970 607
48%
 Sputum
Examination
• Simple microscopy of a
wet sputum smear
– Typical yellowish –
brown, operculated
ova of the
paragonimus eggs
 Sputum
Examination
If eggs are not found by
direct sputum
examination, all sputum
produced during a 24
hour period should be
examined following
alkaline sodium
hypochlorite
(antiformin)
Stool Examination
• Swallowed by infected
patients
• Concomitant sputum
and fecal examinations
improve the overall rate
of detection of
infection.
Sensitivity of Stool Examination

# of test investigators n

sensitivity

1X Shim 1990 53

11%

Kim 1970 141

15%
 Pleural Fluid
Examination
Assist in diagnosis when
eggs are not found and
is useful in
distinguishing
paragonimiasis from
tuberculosis.
 Pleural Fluid
Examination
• Characteristically sterile
• Contains large number
of eosinophils and,
rarely, eggs can be
found in the sediment
Barrett-Connoer, AmRevResDse, 1990
Pleural Fluid
Examiantion
• Opaque exudate
• Glucose <10mg/dl 79%
• LDH >1,000 IU/L 84%
• Protein >3mg/dl 95%
• RBC >1000/m3 92%
• WBC >1000/ m3 97%
• Low pH
• Eosinophilia
 Blood Examination
• Eosinophilia suggests a parasitic infection
• Leukocytosis and eosinophilia are commonly
observed in paragonimiasis
• No quantitative correlation between eggs in
the sputum and eosinophilia has been
reported
• Eosinophilia is consistently present in the
acute stage
• Absolute count decreases in the chronic
stage
•
• Leukocytosis is highest
Increase serum in patients with
IgE levels
symptoms of <6 months
• Paragonimus-specific IgE estimated by
chromatography using immunoabsorbent
column
 Intradermal Tests
• Screening technique
– Crude Merthiolated saline extract of adult
Paragonimus westermani (Veronal
buffered saline [VBS] antigen)
• Highly specific & sensitive
• Detected within 2 weeks after infection
• Persists from 6-24 months after complete
disappearance of eggs from the sputum and
stool due to treatment
• Persists even up to 5 years after cure and
Cross-reaction
usually up to sinensis
– Clonorchis 20 years
• No cross-reactivity with tuberculosis or
histoplasmosis
• Simple & reliable screening test
Serological Tests
• Correlate with active
infection
• Great value in the
diagnosis, interpretation of
(+) intradermal reactions in
epidemiologic studies, ff-up
studies after treatment & in
the assessment of cure.
 Sensitivity & Specificity of
Serological Tests
Tests Investigators Sensitivity
Specificity

Complement Tsujii 1984 98%

Fixation

Immunoblot Semenda 1998 96% 99%

Indirect Tsujii 1984 90%

Hemagglutination
Parlyanonda 1990 88%
 Sensitivity & Specificity of
Serological Tests
Tests Investigators SensitivitySpecificity

Monoclonal
Zhang 1993 100% 99 + %
Antibody
IgG ELISA Knolbloch 1984 100%
Maleewong 1990 100% 96- 98%
Parlyanonda 1990 100% 97%
Immunoelectrophoresis
Tsujii 1984 100%
Immunodiffusion Tsujii 1984 100%
 TREATMENT
Kagawa 1997
Drugs Dossage
Duration
Cure Rate
Side Effects
Praziquantel 25mg/kg TID 1d 71-75%Dizziness
2d 85-100%HA, GI
3d 100%
Bithionol 30-50mg/kg BID
20 – 30 d 91 - 100%
GI, rash
Niclofolan 2mg/kg single dose
95% Neurotoxicity
Hepatotoxicity
Mebendazole50mg/kg 20d 60% Dizziness
Hypotension
Triclabendazole
10mg/kg single dose
80%
Follow – up examination
with multiple stool &
sputum specimens 3 –
4 mo after completion
of therapy is done to
determine if another
course is required.
Prognosis
• Fair to good
• Except when
– Worms become lodged in
critical foci
– Develops to generalized
fulminating condition
 WHO Diagnostic
Guidelines
If tuberculosis is suspected
in areas where
paragonimus infection is
prevalent, paragonimiasis
should be excluded by
parasitological
examination of the
sputum before
proceeding to further
examination.
 WHO Diagnostic
Guidelines
Conversely, particularly in
endemic areas where
suspicion of paragonimus
is high, tuberculosis
should always be
excluded by 3 direct
sputum smears, and if
available, culture of a
concentrated sputum
specimen.
 WHO Diagnostic
Guidelines
Tuberculosis laboratories
should have the capacity
and their staff the
necessary training to
undertake examination of
Paragonimus in the
sputum.
 WHO Diagnostic
Guidelines
• Paragonimus ova are
destroyed by Ziel-
Neelsen stain.
• Separate sputum
examinations for both
paragonimus & TB
bacilli are strongly
recommended.
• If not possible, sputum
should first be examined
 Methods of
Control
• Chemotherapy
• Disinfection of excreta
& sputum or its sanitary
disposal
• Anti – molluscan
campaigns
• Public education
 INVASIVE PULMONARY
ASPERGILLOSIS (IPA)
• Most common fungal pulmonary infection in severely
immuno-compromised patients
• Commonly isolated from soil, plant debris, indoor
environment, hospital
• Diagnosis is based on clinical, radiological,mycological data
• Clinical signs low specificity
• Typical radiologic findings: nodules with or without the halo
sign or air crescent sign
• Sensitivity of microscopy and culture of noninvasive collected
samples is low
• Galactomann/nucleic acid detection in serumor BAL
• Treatment: early initiation of antifungal therapy (Voriconazole,
Amphotericin B), Surgery (main indication is prevention of
severe hemoptysis when lesion is adjacent to a large vessel)
 Chest X-ray showing right upper zone volume loss with consolidation changes and a
large cavitating lesion with soft tissue mass, which contained the air crescent sign.

Computed tomography of the thorax showing a 6 x 6 x 6 cm non-calcified lesion

involving the lateral aspect of the right upper ribs with extra-thoracic extension. The
lesion was cavitary with a relatively smooth border and intraluminal roundish lesions that
gave rise to the crescent sign in keeping with aspergilloma
Mycetoma
 TARGET GROUPS FOR SPECIAL
INFLUENZA VACCINATION PROGRAMS
• Persons 65 >
• Residents of nursing homes or chronic care
facilities
• Adults & children with chronic pulmonary and
cardiovascular disorders including asthma
• Adults & children with required regular follow-up
or hospitalization during preceding year
(DM,renal diseases, immunocompromised
states)