Enteric Fever

Enteric Fever includes Typhoid and Paratyphoid fever.

Organism: ● Typhoid fever: Salmonella typhi ● Paratyphoid fever: S. paratyphi A, B, C
Mode of transmission: Humans are the only natural host and reservoir. The infection is transmitted by ingestion of
food or water contaminated with feces.
Incubation period: 7-14 days
First Week:
Acute febrile illness: Fever shows a step-ladder pattern — i.e., the temperature rises over the course of each day and
drops by the subsequent morning. The peaks and troughs rise progressively over time. BUT rarely fever shows this
pattern. ++
≥ 1 of the followings
Anorexia
Bodyache (Malaise)
Body weight loss
Chill (+/- rigor)
Abdominal pain and tenderness; sometimes, fierce coliky pain in RUQ.
Relative Bradycardia- temp elevation not accompanied by a physiological increase in the pulse rate
Constipation (Monocytic infiltration in Peyer’s patches, causing inflammation and narrowing)
Diarrhoea: Sometimes, foul smelling green-yellow, liquid diarrhoea (“pea-soup diarrhea”)
Dull frontal headache
Energy lack (Malaise)
Encephalopathy: Altered sensorium/ Behavioural disturbance/Cofusion/Coma/ Carphology: picking or grasping at
own clothes or bed linens as well as imaginary objects/Delirium
This encephalopathic stage is called Typhoid state/ Muttering delirium/ Coma vigil
Second week
Already existing signs and symptoms continue + followings:
Abdominal distension
Cutaneous: Rose spots- Salmon-colored, blanching, maculopapular rash on the chest, abdomen, and back, may not be
visible in dark-skinned individuals- resolve within 2-5 days. Represent bacterial emboli to the dermis.
Enlarged organs: Soft Hepato and/or splenomegaly
Normally with each degree Farenheit rise of temp Pulse
Third week: “week of complications” rate rises by ≥ 10/min.
Already existing signs and symptoms continue + followings: Relative bradycardia= Rate of rise of Pulse <than 10/min.
Abdominal distension increases
Bowel perforation and peritonitis due to necrosis in Peyer’s patches
Investigations:
1. Hematological tests
1. CBC: Hb: Mild anemia TLC: Low to normal Platelets: Low to normal
2. LFT: Mildly abnormal Serum transaminase levels 2 to 3 times the upper limit of normal

2. Tests to confirm diagnosis:

a. Blood culture: The specificity of a blood culture is 100%.
b. Typhidot: Typhidot is an enzyme immunoassay (EIA) that rapidly detects IgG and IgM antibodies to a specific 50
kD outer membrane protein (OMP) antigen of S. typhi. Detection of IgM signifies acute enteric in the early phase of
infection while detection of both IgG and IgM indicates acute enteric in the middle phase of infection. The test
becomes positive right in the first week of fever and the results are available within one hour.
Typhidot M: A modified and improved version of Typhidot, obtained by inactivating total IgG in the serum sample,
which allows access of the antigen to the specific IgM, thereby enhancing diagnostic accuracy. If specific IgM is
detected it points towards acute typhoid infection.

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c. Widal test: Should not be done before one week of the onset of fever (rather should not be done at all!!). With the
availability of other highly reliable tests, the importance of Widal has declined. A single Widal has no value
The test is based on the demonstration of a rising titer of antibodies in paired samples 10-14 days apart. It uses O and
H antigens of S. typhi, S. paratyphi A, S. paratyphi B and S. paratyphi C to detect antibodies in blood.
Pitfalls of Widal:
Negative in 30% of culture proven cases of enteric fever.
Prior antimicrobial treatment may adversely affect the antibody response.
False positive results may occur in other clinical conditions, such as Malaria, Typhus, Bacteremia

Treatment: 7-14 DAYS DEPENDING ON THE DRUG USED AND CINICAL RESPONSE
A. Cephalosporins: Ceftriaxone/Cefotaxime/ Cefixime
B. Chloramphenicol
C. Fluoroquinolones: Ciprofloxacin or Ofloxacin
D. Azithromycin
General Principles of blood culture
 At least 25-30 ml of blood should be collected for a good yield.
 The ideal time of obtaining a sample is when the patient is having chills or when the fever spikes
 Ideally should be taken before giving the first dose of antibiotics. However, in clinical practice OFTEN
antibiotic is initiated based on the presumptive diagnosis, and a blood culture is advised.
 A single culture should not be encouraged.

Leishmaniasis
Causative agent: Leishmania donovani
Mode of transmission: Bite of female Phlebotomine sandfly- P.argentipes
Incubation period: 1- 4 months
C/F:
1. Visceral Leishmaniasis ( Kala- azar)
Acute febrile illness: high grade spikes of intermittent fever+ absence of any significant localizing symptoms
++
≥ 1 of the followings
Anorexia
Anaemia
Bodyache (Malaise)
Body weight loss
Chill (+/- rigor)
Cough
Diarrhoea
Dermal: Hyperpigmentation of face/hands/feet/abdomen
Post kala-azar dermal leishmaniasis (PKDL): Hypopigmented nodules/macules (simulating Leprosy) but
no hypoesthesia: May appear several years after complete recovery from kala-azar
Enlarged organ: Hepatomegaly/Splenomegaly
Endemic area: resident of/travel to
Fever- Often diagnosis is not thought of in the beginning and remains undiagnosed for a considerable period of time,
so many patients come with “PUO”
Fatigue
2. Cutaneous Leishmanisis: Systemic symptoms typically absent. Small papules/non-ulcerated plaques/encrusted
ulcers over the parts exposed to sandfly bite
3. Mucocutaneous Leishmaniasis:
Cutaneous leishmaniasis: Systemic symptoms typically absent. Small papules/non-ulcerated plaques/encrusted
ulcers over the parts exposed to sandfly bite

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Mucosal involvement: Ulcers of nasal mucosa/septum/face +/- secondary bacterial infection. Mutilation of face
may occur
Investigation:
1. Light Microscopy: demonstration of amastigote forms of the protozoa by light microscopy using Geimsa stain.
Samples
 Peripheral blood film (easy to obtain but have low detection rates)
 Bone marrow aspirate
 Lymph node aspiration
 splenic aspirate (highest yield but carries the risk of splenic rupture)
2. Culture of the organism from any of the tissue samples is also a sensitive method but requires special culture
techniques. Also, culture facilities are not routinely available.
3. Serologic diagnosis: It is the most widely used indirect method of diagnosis.
Direct Agglutination Test (DAT) and Immunochromatographic Test (ICT) using rK-39 antigen are most widely
accepted because of their high sensitivity
4. Molecular diagnosis: PCR-based nucleic acid amplification techniques have the advantage of higher sensitivity
and also require peripheral blood as test specimen rather than invasive tissue sampling such as bone marrow
aspirate or lymph node biopsy for light microscopy; however the facility is available only in referral centers and not
suitable for field diagnosis as it requires specialized equipment.
5. Hematological tests: Hb: Anaemia WBC: Leukopenia with Monocytosis; Increased Globulin

Treatment:
1. Pentavalent Antimonial compounds: Sodium Stibogluconate: Once a first-line treatment for visceral
leishmaniasis, these drugs are now almost obsolete in India because of rising incidence of drug resistance,
particularly the northern states like Bihar.
2. Amphotericin B: Liposomal Amphotericin B- a potential advantage of liposomal amphotericin B is short course
treatment- ranging from single dose infusion to total dose administered over 4-5 days.
3. Miltefosine: This phospholipid-derivative anti-leishmania drug has cure rates comparable to amphotericin B and
has the added advantage of ease of oral administration.
4. Paramomycin
5. Pentamidine Isothianate
6. Sitamaquine: This is another oral drug undergoing evaluation in clinical trials.
It has been advocated to administer these drugs in various combinations. It has added benefit of reducing drug
toxicity and treatment duration in addition to improving patient compliance and reducing treatment cost.

Leprosy
Organism- Mycobacterium leprae
Incubation period- Months to years
Mode of transmission- probably transmitted by droplets from the nose and mouth when people are in close and
frequent contact with an infectious person.
Spectrum of the disease- clinical course depends on pt’s immune status-
a. If the immune response is ineffective Lepromatous disease develops (dominated by histiocytes full of bacilli but
few lymphocytes)
b. If the immune response is vigorous Tuberculoid disease develops( granulomatous inflammation containing
epithelloid cells and lymphocytes but few or no bacilli)
Between these two poles lie those with borderline disease.

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 Tuberculoid (TT),
1 or >1 hypopigmented skin macules or anaesthetic patches (because of
Paucibacillary Borderline damaged peripheral nerves that has been attacked by host’s immune cells)
tuberculoid (BT)
Skin lesions resemble tuberculoid leprosy but are more numerous and
irregular; large patches may affect a whole limb
midborderline or Peripheral nerve involvement with weakness and loss of sensation is
Multibacillary borderline (BB) common. This type is unstable and may become more like lepromatous
leprosy or may undergo a reversal reaction becoming more like the
tuberculoid form.
Borderline Symmetric skin lesions/ nodules/ plaques
Multibacillary lepromatous (BL),and frequent involvement of the nasal mucosa resulting in nasal
Lepromatous (LL) congestion and epistaxis but nerve damage is a late feature.
Clinical features
1. Cutaneous-
1. Hypopigmented anaesthetic macules/papules/annular lesion with raised erythematous rims
2. Eryhthema Nodouosum- in Lepromatous disease
2. CNS: Nerve lesions- Peripheral neuropathy due to involvement of major sensory nerves usually
3. Lepra Reaction- ….(important: Short note)
During the course of leprosy, immunologically mediated episodes of acute or subacute inflammation known as Lepra
reactions may occur in up to 25% of patients with paucibacillary leprosy and as much as 40% in multibacillary
leprosy.
These reactions may rapidly cause severe and irreversible nerve damage and must always be treated promptly.
During a lepra reaction, do not interrupt leprosy multidrug therapy. Treatment with multidrug therapy reduces the
frequency and severity of lepra reactions.
There are two types of reactions – Reversal Reaction (or Type 1) Erythema Nodosum Leprosum (ENL or Type 2)
Both the types of reactions can occur before the start of treatment, during treatment, or after the treatment has been
completed. Both types can be divided into mild or severe.
Type 1 (Reversal Reaction) Type II (ENL)
1. Delayed hypersensitivity 1. Antigen antibody reaction
2. Occurs in PB and MB type of cases (Borderline group) 2. Seen in MB cases only (BL & LL type)
3. Skin lesions suddenly become reddish, swollen, warm, 3. Red, painful, tender, sub cutaneous nodules on face,
painful, and tender. New lesions may appear. arms, legs usually bilateral symmetrically.
4. Nerves close to skin may be enlarged, tender and 4. Nerves may be affected but not as common or severe
painful (neuritis) with loss of nerve function (loss of as in Type 1
sensation and muscle weakness) and may appear
suddenly or rapidly
If any of the following sign is found, the reaction should If any of the following signs is found, the reaction
be treated as severe: should be treated as severe:
a. Loss of nerve function i.e. loss of sensation or muscle a. Pain or tenderness in one or more nerves, with or
weakness. without loss of nerve function
b. Pain or tenderness in one or more nerves. b.Ulceration of ENL nodules
c. Marked swelling & redness in skin patches. c. Pain and/or redness of the eyes, with or without loss
d. A red, swollen patch on the face, or overlying another of visual acuity
major nerve trunk. d.Painful swelling of testis or of the fingers
e. A skin lesion anywhere that remains ulcerated. e.Marked arthritis or lymphadenitis
f. Marked oedema of the hands, feet or face.
5. Other organs - Not affected 5. Organs like eyes, testis, and kidneys may be affected
6. General symptoms - Not common 6. Fever, joints pain, red eyes with watering
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Investigations
1. Skin smear examination-Look for the presence of acid-fast bacilli under oil immersion Lens
Bacteriological Index (BI)
0= No bacilli seen in 100 fields 1+= 1 to 10 bacilli in 100 fields 2+= 1 to 10 bacilli in 10 fields
3+= 1 to 10 bacilli, in each field 4+= 10 to 100 bacilli in each field 5+= 100 to 1000 bacilli, in each field
6+= >1000 bacilli, in each field
2. Histopathology of skin or nerve biopsy
A. Punch (5 mm) biopsy or incision biopsy for histopathological examination may help.
B. Specimen can be taken from just inside the edge of the lesion/cutaneous branch of peripheral nerve- the common
nerve for biopsy includes the index branch of Radial cutaneous nerve and Sural nerve unless any other superficial
sensory nerve is affected.
C. Presence of lepra bacilli in or around the nerve is diagnostic, but only granuloma or infiltration without support
of clinical signs may mislead.
D. FNAC/Biopsy from the lymph gland is usually helpful in suspected lepra reaction type 2.
3. Radiological examinations
a. X-rays- osteoporosis/ fractures of small bones/ absorption of bones/ sequestra
b. USG of nerve trunks or internal organs e.g. testes, reticulo-endothelial organs may help in judging the diagnosis
and prognosis of complicated cases.
Treatment-….important
Standard Rx regimen for MB leprosy- Standard Rx regimen for PB leprosy-
Rifampicin..................600 mg once a month Rifampicin..................600 mg once a month
Clofazimine................300 mg once a month Dapsone.....................100 mg daily
+ 50 mg daily
Dapsone.....................100 mg daily Duration: 6 months
Duration: 12 months

Treatment of Lepra reaction-

Type 1
1. Corticosteroid – Oral Prednisolone- reaction is generally controlled within a few days and the dose is then
gradually reduced weekly or fortnightly and eventually stopped. Most reversal reactions and neuritis can be treated
successfully with a standard 12 week course
Type 2 (erythema nodosum leprosum)
1. Analgesics- Paracetamol
2. Corticosteroids- oral Prednisolone
3. Clofazimine/Thalidomide- patients with severe type 2 reactions, who do not respond to corticosteroids or in
whom corticosteroids are contraindicated, Clofazimine at high doses or thalidomide may be used under close
medical supervision. Clofazimine often requires 4-6 weeks before an effect is seen, and therefore must never be used
as monotherapy for treatment of severe type 2 reactions. However, it may be useful for reducing or withdrawing
corticosteroids from patients who have become dependent on corticosteroids.

Syphilis
Systemic sexually transmitted disease (STD) caused by the spirochete-Treponema pallidum.
Mode of transmission-
1. STD
Vaginal, anal, or oral sex through direct contact with a syphilis chancre
Person to person during foreplay, even when there is no penetrative sex (less common)
2. Pregnant mother with syphilis to fetus

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Clinical stages/types
Primary Stage (highly infectious)
1. One or more chancres appear- usually firm, round, small, and painless at the site of infection (most often the
genital area) 10 to 90 days after infection.
2. The chancres heal on their own in 3-6 weeks
3. Patient is highly infectious in the primary stage
Secondary Stage (highly infectious)
1. Rashes occur as the chancres fade or a few weeks after the they heal
2. Rashes typically appear on the palms of the hands, the soles of the feet, or on the face, but also may appear on
other areas of the body.
3. Sometimes wart-like “growths” may appear the genital area.
4. Rashes and syphilitic warts tends to clear up on their own within 2-6 weeks, but may take upto 12 weeks.
Late (Tertiary) stage (not infectious)…….3C…(important)
● Cutaneous- Lesions in the skin and bones (gummas)
Gummatous syphilis usually occurs years after the initial infection, with an average of 15 years.
Characterized by the formation of chronic gummas which are soft, tumor-like balls of inflammation of variable size
typically affecting skin, bone, and liver
● Central nervous system (Neurosyphilis) - Infection involving the central nervous system- typically occurs 4 to 25
years after the initial infection
Asymptomatic
Syphilitic meningitis
General paresis- dementia/personality disturbance
Tabes dorsalis-
1. Dorsal column lesion leading to loss of deep sensations (position and vibration sense)
2. Electric shock like pain in the extremities
Argyll Robertson pupils (ARP) - Bilateral small pupils with loss of light reflex but Accommodation Reaction
preserved.
● Cardiovascular- Usually occurs 10–30 years after the initial infection. Syphilitic aortitis which may result in Aortic
aneurysm formation and AR
Congenital Syphilis Severity ranges from asymptomatic to fatal.
1. Early manifestations - spontaneous abortion, stillbirth, encephalitis, generalized skin rash, rhinitis
(“snuffles”), hepatic dysfunction, consumption coagulopathy, multiorgan failure
2. Late manifestations – usually not apparent at birth include osteitis of long bones, maxillofacial and dental
malformations, keratitis, hearing loss, and chronic neuropsychological deficit
Diagnosis-
1. Dark-field examinations or direct fluorescent antibody tests of chancre tissue are the definitive methods for
diagnosing primary and secondary syphilis
2. A presumptive diagnosis is possible with sequential serologic tests (e.g. VDRL, RPR), using the same method
each time. A 4 fold change in titer (e.g. from 1:8 to 1:32) is usually considered to be clinically significant
Treatment-
Primary/ Secondary/ or Early Latent <1 year- IM of Benzathine Penicillin G single dose
Latent >1 year or Latent of Unknown Duration- IM of Benzathine Penicillin G in 3 doses each at 1 week intervals
Neurosyphilis- IV of Crystalline Penicillin G 10-14 days
Congenital Syphilis-IV Crystalline Penicillin G during approx. first 3 weeks of life

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 Malaria
Agent: P. falciparum and P. vivax - In India mainly these 2
P. ovale, P. malariae
Incubation period: Vivax 8-17 days; Falciparum 9- 14 days
Mode of transn: Bite of infected female Anopheline mosquito (female bites are responsible for Loveria as well!!)
C/F-
1. Uncomplicated malaria (both Falciparum and Vivax)
Acute febrile illness- With a periodicity of 48 or 72 hours can be seen in Non falciparum malaria
or
Continuous fever
A febrile episode often passes through 3 stages-
1. Cold stage- ½ - 1 hour- feels very cold+ chill+ rigor
2. Hot stage- 2-upto 6 hours-feels intensely hot
3. Sweating stage- fever comes down with drenching sweat (with or without Paracetamol)
++
≥ 1 of the followings
Anorexia
Bodyache/body weakness
Chill (+/- Rigor)
Decresed energy level (malaise)
Eye- Mild icterus
Enlarged Spleen +/- Liver

2. Complicated Malaria/Cerebral Malaria- usually occurs in some Falciparum patients*important-LQ/SN

F/O uncomplicated disease + ≥ 1 Following pathophysiological events can occur
ARDS- SOB/Tachypnoea/Low O2 saturation/bilateral crepts
AKI- Low urine output/Uremic encephalopathy/Acidotic breathing
Anaemia- severe hemolytic anaemia (Intravascular hemolysis)
Bilirubin ↑↑ - Icterus (hyperbilirubinemia is due to hemolysis)
Black water fever/hemoglobinuria (due to Intravascular hemolysis)
CNS- Encephalopathy…its “ABCDE”!!
Circulatory collapse - shock- Hypotension/feeble pulse/tachycardia
CBG- Hypoglycemic spells
DIC- spontaneous bleeding
Eventually some patients develop multi-organ failure
Investigations-
To diagnose Malaria
a. MP detection in peripheral smear-
Thick and thin film- thick reliable for searching/thin- for identification of species
b. Rapid Diagnostic Test- Detection of Vivax and Falciparum antigen (Malarial dual antigen)
Some of the Ag detection kits may show positive result up to 3 weeks after parasite clearance. In these cases, results
should be correlated with microscopic diagnosis.
To diagnose/monitor complications- In a suspected complicated case following tests are indicated
a. FBC e. ABG
b. Urea/Cr/Na/K f. FDP
c. CBG monitoring- tendency of hypoglycemia g. CxR
d. LFT

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Treatment (Imp) Ans. Model 1 (particularly if Q.- Rx of severe/complicated/Cerebral Malraia)Imp
Treatment - a. Antimalarials b. Supportive Rx
a. Antimalarials
Day 1- 10mg/kg
1. P. vivax cases after 24 hours
a.Chloroquine- 25 mg/kg over 3 days Day 2- 10mg/kg
after 24 hours
Day 3- 5mg/kg
b. To prevent quick relapse- Primaquine should be given at a dose of 0.25 mg/kg body weight daily for 14
days with pretreatment estimation of G 6 PD level.

2. P.falciparum cases- Complicated or Uncomplicated Day 1: Artesunate + Sulfadoxine-Pyrimethamine

a. Artemesinin Combination Therapy (ACT)- 1st line: total 3 days Day 2: Artesunate + single dose of Primaquine

if not feasible/ available Day 3: Atresunate

b. Quinine + (Doxycycline OR Clindamycin)- 2nd line: total 7 days Rx

ACT regimens
Artesunate + Sulfadoxine-Pyrimethamine (recommended in the National Programme for all India except NE states)
Artemether + Lumefantrine (NE states)
Artesunate+ Amodiaquine
Artesunate + Mefloquine
b.Supportive- Especially for complicated Malaria- Rx depends on specific complications
ARDS- Intubate and Ventilate
AKI- Dialysis
Anaemia- Packed cell transfusion
Circulatory collapse- IV fluid resuscitation + Maintenance fluid therapy+/- Vasopressor
DIC- FFP
Drugs- supportive drugs
a. Antipyretic- Paracetamol
b. Antiemetic- Ondansetron
c. Anticonvulsant- Levetiracetam/Phenytoin
Ans. Model 2 (particularly if Q.- Rx of severe/complicated/Cerebral Malraia)Imp
A-Admit
A-Airway- to be protected if Comatose/ARDS suspected
B-Breathing- Ventilate if ARDS
B-Blood biochemistry monitoring during critical stage- Electrolytes/Ur/Cr/ABG/FBC/CBG
B-Bladder and bowel care B- Bed sore prevention
C-Circulation- IV fluid resuscitation + Maintenance fluid therapy+/- Vasopressor if in shock
C-Catheterize to monitor urine output
D-Drugs- Antimalarials
Antipyretic
Antiemetic AS ABOVE
Anticonvulsant
D-Dialysis for AKI
D-Diet- Nutritious diet- Orally or through R/T if comatose
D- DVT prevention
DIC- FFP
(if above fails, D- death certificate!!)
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 Complicated Malaria pathogenesis/pathophysiology (Short notes)
The following are some of the factors known to play a role in the clinical manifestations of severe/complicated
malaria infection.
 Species of parasite: Only P. falciparum causes severe/complicated malaria
 Host Immunity
 The degree of parasite drug resistance that prevails locally
Processes Contributing To Specific Complications
AKI-Acute tubular necrosis due to tubular damage by endogenous ‘tubulotoxin’- free Hb
ARDS-Pulmonary oedema (non-cardiogenic) possibly through release of cytokines which is a direct effect of
parasites sequestered in the lungs
Anaemia- Intravascular haemolysis due to the destruction of red cells that contain parasites.
Bilirubin↑ (Jaundice)- due to haemolysis and partly to liver dysfunction
Black water fever/ Haemoglobinuria- massive intravascular haemolysis leading to release of free Hb in circulation
Cerebral Malaria- sequestration of infected RBCs in the brain
Circulatory collapse (Shock) inadequate cardiac output +/- poor tissue perfusion
CBG fall (Hypoglycaemic tendency)- Impaired Neoglucogenesis & release of glucose by the liver + increased
utilization in the tissues + Quinine s/e (stimulates release of insulin)
DIC- release of procoagulant cytokines

HIV
2 types: HIV1 and HIV2. HIV1- more virulent, more infective & causes majority of infections globally.
Clinical stage 1
Asymptomatic Persistent generalized lymphadenopathy
Clinical stage 2
Angular cheilitis
Body wt. loss- Moderate (≤10% of presumed or measured body weight)
Buccal ulceration recurrent
C ××
Dermal- Papular pruritic eruptions/Dermatitis (Seborrhoeic)
ENT infection- Recurrent sinusitis/tonsillitis/otitis media/pharyngitis
Fungal nail infections
G ××
Herpes zoster
Clinical stage 3
Acute necrotizing ulcerative stomatitis/gingivitis/periodontitis
Body wt. loss- severe (= >10% of presumed or measured body weight)
Bacterial infections-Pneumonia/Empyema/Bone or Joint /Meningitis/Bacteraemia
Candidiasis- Persistent oral
Cytopenias
Chest- Pulmonary TB (active)
Diarrhoea for longer than one month
E ××
Fever of unknown origin (> 99.6 F intermittent or constant, for longer than one month)
Stage 4 (Clinically AIDS defining illness)
Any disseminated mycosis- coccidiomycosis/ histoplasmosis
Bacterial pneumonia- Recurrent severe
Chronic herpes simplex infection- more than 1 month- oro-labial/genital/anorectal/visceral at any site
Candidiasis Oesophageal/tracheal/bronchial/lungs
CNS toxoplasmosis
Cryptosporidiosis Cryptococcosis-meningitis CMV- retinitis or infection of other organs Cystoisosporiasis
Disseminated non-tuberculous mycobacterial infection
Extrapulmonary tuberculosis

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F ×× G××
AIDS is defined as presence of any one of the following in a
HIV wasting syndrome person with confirmed HIV infection
HIV-associated nephropathy ● Clinical diagnosis (presumptive or definitive) of any stage 4
HIV-associated cardiomyopathy condition
HIV encephalopathy ● Immunological diagnosis first-ever documented CD4 count
Invasive cervical carcinoma less than 200 per mm3 or %CD4+ <15%
Jiroveci- Pneumocystis jiroveci pneumonia
Kaposi’s sarcoma
Leishmaniasis- Atypical disseminated Leishmaniasis
Lymphoma
Leukoencephalopathy-Progressive multifocal leukoencephalopathy
Investigation
For symptomatic persons: sample should be reactive with 2 different kits. (kit= ELISA test kit for Anti HIV)
For asymptomatic persons: the sample should be reactive with 3 different kits
Blood
Anti HIV
A1

A1 +ve A1 -ve
Report: Non-Reactive
A2
Anti HIV

A1+ve, A2+ve A1+ve, A2-ve

Report Reactive

Tiebreaker A3
Anti HIV

A1+ve, A2-ve, A3+ve A1+ve, A2-ve, A3-ve

Report: Reactive Report: Non-Reactive
Essential tests Additional tests
FBC For all patients to be started on ART (as
Urine R/E and M/E per the physician’s decision depending
FBG/PPBG on clinical presentation)
Urea, Creatinine USG abdomen
SGPT Sputum for AFB
VDRL CSF analysis
CD4 count
CxR
Pregnancy test (if required)
Symptoms and signs directed investigations for ruling out Ols
Tests for Special Situation Tests for monitoring purpose
HBsAg: for all patients if facility is available CD4, Hb, TC, DC, SGPT
Anti - HCV antibody
Treatment- Principles
1. ART if indicated
2. Rx of opportunistic infection
3. Rx of specific clinical situation(s)
4. Contact tracing and monitoring them +/- Rx if indicated
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1. ART…(short notes)
Drugs
Nucleoside reverse transcriptase inhibitors (NRTI)- Zidovudine/ Lamivudine/ Didanosine/ Emtricitabine
Nucleotide reverse transcriptase inhibitors (NtRT)- Tenofovir
Non-nucleoside reverse transcriptase inhibitors (NNRTI)- Nevirapine/ Efavirenz
Protease inhibitors (PI)- Saquinavir/Ritonavir/Indinavir

Initiation of ART based on CD4 count and WHO clinical staging

1. Clinical Stage I and II - Start ART if CD4 ≤ 500 cells/mm3
2. Clinical Stage III and IV- Start ART irrespective of CD4 count
3. HIV and TB co-infection (Pulmonary/ Extra-Pulmonary)-Start ART irrespective of CD4 count and type of TB
4. HIV and HBV / HCV co-infection
[

 with significant evidence of chronic Liver disease - Start ART irrespective of CD4 count
 without significant evidence of chronic Liver disease - Start ART if CD4 ≤ 500 cells/mm3
5. All pregnant and breast feeding patient: All clinical stages- Start ART irrespective of CD4 count

Regimes
Zidovudine/Tenofovir + Lamivudine + Nevirapine- 1st line for who are not on concomitant ATDs
Zidovudine/Tenofovir + Lamivudine + Efavirenz- 1st line for who are on concomitant ATDs
Tenofovir + Lamivudine + Efavirenz- 1st line for all with Hepatitis B and/or Hepatitis C co-infection

Prophylaxis of opportunistic Infections (OIs)

Co-trimoxazole is effective against several organisms- Toxoplasma/PJ and several others causing diarrhoea in HIV.
Dapsone is an alternative for pts with Sulpha drug allergy.
Co-trimoxazole prophylaxis recommendations
1. Any WHO clinical stage with CD4 < 250
2. Symptomatic patients with any clinical stage with CD4 < 350
3. WHO stage 3 or 4 irrespective of CD4 count

Stopping prophylaxis- If CD4 count >250 for at least 6 months and If patient is on ART for at least 6 months & is
asymptomatic and well

Immune reconstitution inflammatory syndrome (IRIS)

It is a paradoxical worsening of an existing infection or disease process or appearance of a new infection/disease
process soon after initiation ART in HIV-infected patients.
ART initiation in HIV-infected patients leads to recovery of CD4+T cell numbers and restoration of protective
immune responses against a wide variety of pathogens, resulting in reduction in the frequency of opportunistic
infections and prolonged survival. However, in a subset of patients, dysregulated immune response after initiation of
ART leads to IRIS.
The immunopathogenesis of the syndrome is unclear but it appears to be result of unbalanced reconstitution of
effector and regulatory T-cells, leading to exuberant inflammatory response in patients receiving ART.
C/F Majority of patients with IRIS have a self-limiting disease course. Common manifestations are due to infection
with followings-

Mycobacteria: Myco. TB; Myco. avium complex; Mycobacterium leprae

Protozoa: Toxoplasma; Microsporidia; Leishmania; Cryptosporidia
Fungal infections: Cryptococcus; Pneumocystis jiroveci; Histoplasma; Candida
Bacteria: Bartonella
Viruses: Herpes simplex; Herpes zoster; CMV; Parvovirus B19; Molluscum contagiosum
Helminth: Schistosoma; Strongyloides.
Treatment: ART is usually continued and treatment for the associated condition optimized.

11
 Pneumocystis jiroveci/Pneumocystis carini
Pneumocystis jiroveci is one of the most common opportunistic infection in persons with HIV infection.
Pneumocystis is a genus of unicellular fungi found in the respiratory tracts of many mammals and humans.
Groups are at risk
Persons with HIV infection whose CD4 + below 200/µL and who are not receiving PJP prophylaxis
Persons with primary immune deficiencies
Long-term immunosuppressive regimens
Hematologic and nonhematologic malignancies
C/F-Typically causes Pneumocystis jiroveci/carini Pneumonia (PJP or PCP) - an interstitial Pneumonitis
Progressive exertional dyspnea Tachypnea
Fever Fever
Nonproductive cough Tachycardia
Chest discomfort Pulmonary: mild crackles and rhonchi but normal in
Weight loss many pts
Hemoptysis
Investigation
1.LDH level- usually elevated in PJP who are infected with HIV- high sensitivity but not a specific marker because
other disease processes can result in an elevated LDH level. LDH levels appear to reflect the degree of lung injury.
(BUT high LDH is NOT a diagnostic feature/criteria!!)
2. CxR- often surprisingly normal
3. HRCT
4. Sputum induction- Pneumocystis organisms are found in sputum induced by inhalation of a hypertonic saline
solution. Expectorated sputum has a very low yield.
5.ABG- Hypoxia

Treatment
1. TMP-SMX
2. 2nd line agents- Pentamidine OR (Dapsone + Pyrimethamine) OR Atovaquone
3. Corticosteroids-as adjunctive therapy in patients with HIV infection who have severe PJP as defined by a room air
PaO2 < 70 mm Hg

Skin manifestations of HIV

Conditions in Patients with CD4+ Counts Below 200/µL who are not on ART
Photodermatitis
Prurigo Nodularis
Molluscum
Diseases that do not go away even with ART
Eczema
Xerosis
Kaposi’s sarcoma
Human papilloma virus-associated warts
Conditions emerging with Immune Reconstitution under ART
Acne
Staph infections- frequently MRSA
Erythema nodosum

Opportunistic infection in AIDS

Bacterial Infections- Strep.pneumoniae, Staph.aureus, H. influenzae, Pseudomonas
Candida Infections- Orpharyngeal/ Oesophageal/Invasive or disseminated
Coccidioidomycosis-Pneumonia/CNS
Cryptococcosis-Meningoencephalitis
Cryptosporidiosis-relapsing/chronic diarrhoea or cholera-like diarrhoea
Cytomegalovirus-chorioretinitis/ pneumonia/Colitis
12
Giardiasis-chronic diarrhoea
Herpes Simplex Virus perioral vesicles/ Genital infection/ keratitis/ encephalitis
Histoplasmosis Meningitis/ Progressive disseminated histoplasmosis (PDH)
Human Herpesvirus 8 Disease- Kaposi sarcoma (KS)
Human Papillomavirus
Influenza
Isosporiasis (Cystoisosporiasis)
Malaria
Microsporidiosis
Mycobacterium avium Complex Disease
Mycobacterium tuberculosis
Pneumocystis jirovecii Pneumonia
Progressive Multifocal Leukoencephalopathy
Syphilis
Toxoplasmosis
Varicella-Zoster Virus
Diarrhoea in HIV
The most common of the opportunistic infections that cause diarrhoea in patients with AIDS are-
CMV infection
Cryptosporidiosis Microsporidiosis
Giardiasis MAC infection (Myco. avium & Myco. intracellulare)
CMV-colitis associated with fever, crampy abdominal pain, and frequent often bloody stools.
Cryptosporidium-causes diarrhoea which can be transient or may last for months in patients with AIDS, causing
malabsorption, gradual debilitation through dehydration, and metabolic abnormalities
Microsporidia- Enterocytozoon bieneusi and Encephalitozoon intestinalis are the 2 microsporidia found in patients
with AIDS.
MAC- Symptoms caused by MAC infection are usually evidence of severe immunodeficiency. Systemic MAC
infection can cause spiking fever and lethargy. Diarrhoeal illness caused by MAC can cause these as well.
Investigations
1. 3 stool specimens- ova, parasites, C difficile, common enteric bacteria, Cryptosporidium, and Microsporida. 2.
Blood cultures-for febrile patients
2. Colonoscopy when other tests do not result in a diagnosis
Treatment-
CMV-colitis- Ganciclovir or Foscarnet. Effective HAART will often reduce the need for prolonged maintenance
therapy.
Cryptosporidium- No effective therapy- Paromomycin sometimes offers slight symptomatic relief.
Microsporidia: Albendazole
MAC: prolonged therapy with ≥ 2 1st line ATDs + ART

AIDS
AIDS is defined as presence of any one of the following in a person with confirmed HIV infection
 Clinical diagnosis (presumptive or definitive) of any stage 4 condition
 Immunological diagnosis first-ever documented CD4 count less than 200 per mm3 or %CD4+ <15%
Stage 4 (Clinically AIDS defining illness)
Any disseminated mycosis- coccidiomycosis/ histoplasmosis
Bacterial pneumonia- Recurrent severe
Chronic herpes simplex infection- more than 1 month- orolabial/genital/anorectal/visceral at any site
Candidiasis Oesophageal/tracheal/bronchial/lungs
CNS toxoplasmosis
Cryptosporidiosis
Cryptococcosis-meningitis
CMV- retinitis or infection of other organs
Cystoisosporiasis
13
Disseminated non-tuberculous mycobacterial infection
Extrapulmonary tuberculosis
F ×× G××
HIV wasting syndrome
HIV-associated nephropathy
HIV-associated cardiomyopathy
HIV encephalopathy
Invasive cervical carcinoma
Jiroveci- Pneumocystis pneumonia
Kaposi’s sarcoma
Leishmaniasis
Lymphoma
Leukoencephalopathy-Progressive multifocal leukoencephalopathy
Investigation
1. Symptomatic persons: sample should be reactive with 2 different kits. (kits= ELISA test kit for Anti HIV)
2. Asymptomatic persons: the sample should be reactive with 3 different kits
3. Other relevant tests to diagnose underlying opportunistic infection/problems
Treatment- Principles
1. ART 3. Rx of specific clinical situation(s)
2. Prevention/Prophylaxis against of 4. Contact tracing and monitoring them +/- Rx if
opportunistic infection indicated
ART Regimes
Zidovudine/Tenofovir + Lamivudine + Nevirapine- 1st line for who are not on concomitant ATDs
Zidovudine/Tenofovir + Lamivudine + Efavirenz- 1st line for who are not on concomitant ATDs
Tenofovir + Lamivudine + Efavirenz- 1st line for all with Hepatitis B and/or Hepatitis C co-infection
Prophylaxis of opportunistic Infections (OIs)
Co-trimoxazole is effective against: Toxoplasma
PJ
Several organisms causing diarrhoea in HIV.
Dapsone is an alternative for pts with Sulpha drug allergy.

Dengue
Causative agent: Dengue virus Vector: Aedes aegypti Reservoir of infection: Man & mosquito
Incubation period: 7- 10 days
C/F
1. Febrile phase:Acute febrile illness
++
≥ 1 of the followings
Bodyache: may be severe (“break bone fever”): Arthralgia+ Myalgia + headache+ retro-orbital pain
Chill
Cutaneous: initially flushed but on day 2-3 day of fever maculopapaular rash may appear which usually spares
palm/sole
Complications: Usually appear (if at all) between day 3 to day 7 of illness however may appear earlier.
Early warning signs are
 Abdominal pain/tenderness  Drowsiness
 Bleeding manifestations  Dehydration
 Blood parameters: ↑↑Hct/ Falling Platelet  Enalrged liver: more than 2 cm
 Clinical evidence of fluid accumulation
Decreased energy level
Eye: conjunctival congestion
Enlarged organ: Hepato and/or Splenomagaly (clinical or radiological)

14
2. Critical phase: Complications if at all classically start between day 3 to day 7 of illness

A. Hypovolemia: DSS loss of plasma volume Volume depletion

Increased capillary permeability leads to Plasma leakage
Accumulation of fluid in serous cavities
1. Loss may be mild/moderate /severe: depending on the degree of volume loss patient may develop manifestations
of different degrees of dehydration
Asymptomatic Dry throat
BP: normal or low or Pulse pressure < 20 mm of Hg Drowsiness/Delirium
CRT: Normal or prolonged (more than 2 seconds) Excessive thirst
Decreased urine output & Dark urine Extremity: cold/clammy
Dry skin & mucous membrane Pulse: rapid +/- weak volume

2. Accumulation of Fluid in serous cavities: Fluid: Ascites/Pleural effusion

(may be clinically obvious or radiologically seen)
B. Hemorrhage: DHF: Due to Thrombocytopenia
Asymptomatic
Bleeding manifestations: Spontaneous bleeding:
 Superficial: Purpura/Ecchymosis/Epistaxis/gum bleeding
 Deep seated bleeding: GI bleed/GU bleed /ICH/Intra-abdominal bleeding
Circulatory: Shock due to severe blood loss
C. Refractory shock and/or Cytokine release may lead to following consequences in some patients of DHF/DSS:
ARDS Dysfunction of Organs (Multiorgan
Acidosis dysfunction/failure)
Bleeding (severe)  Acute Kidney Injury
Circulatory failure  Acute Liver Injury
DIC
A+B+C= answer for “Complications of Dengue”

For Short Notes Lovers!!

Risk factors for DHF
Virus factors: Host factor:
Virulence of strain Pre-existing anti-dengue antibody due to previous infection
or
DHF risk is greatest when DEN-2 follows DEN-1 maternal antibodies in the
infants
Hyperendemic transmission: locations with ≥ 2 serotypes circulating simultaneously

Under NVBDCP the case definitions recommended by WHO are being followed………(short notes)

Dengue Fever: Clinical description

An acute febrile illness of 2-7 days duration with two or more of the following manifestations:
 Headache  Arthralgia
 Retro-orbital pain  Rash
 Myalgia  Haemorrhagic manifestations

Criteria for Dengue Haemorrhagic Fever and Dengue Shock Syndrome

Tourniquet test: performed by inflating a BP cuff to a
Dengue Haemorrhagic Fever: (….short notes)
midpoint between the SBP & DBP for 5 minutes. The
a).A probable or confirmed case of dengue
test is considered positive when ≥10 petechiae/2.5 cm2
Plus
are observed. In DHF, the test usually gives a definite
b). Haemorrhagic tendencies evidenced by ≥1 of the following
positive test with ≥20 petechiae.
15
1. Positive tourniquet test
2. Superficial bleed: Petechiae, ecchymoses or purpura
3. Mucosal bleed: GI bleed/GU bleed
Plus
c). Thrombocytopenia
Plus
Evidence of plasma leakage due to increased vascular permeability, manifested by one or more of the following:
1. A > 20% rise in average haematocrit for age and sex
2. A > 20% drop in haematocrit following volume replacement treatment compared to baseline
3. Signs of plasma leakage: pleural effusion, ascites
Dengue Shock Syndrome:…..(short notes)
All the above criteria for DHF
Plus 1. BP: hypotension narrow pulse pressure
Evidence of circulatory failure manifested by ≥ 1 of these: 2. rapid and weak pulse
3. cold and clammy skin
4. restlessness
Grading of DHF (….short notes)
Grade Symptoms/signs Laboratory findings
DHF Grade DF + Platelet count less than
1 Positive tourniquet test 100,000/cu.mm
Evidence of Plasma leakage Haematocrit rise 20% or more

DHF Grade Above signs and symptoms + Platelet count less than
2 Evidence of spontaneous bleeding: Superficial and/or 100,000/cu.mm
deep Haematocrit rise 20% or more
Abdominal pain
DHF Grade Above signs and symptoms + Platelet count less than
3 Circulatory failure: 1 of the followings 100,000/cu.mm
 Weak, rapid pulse Haematocrit rise 20% or more
 Pulse pressure < 20 mm of Hg
 Hypotension
 cold clammy skin
 restlessness
DHF Grade Above signs and symptoms + Platelet count less than
4 Profound shock with undetectable blood pressure or 100,000/cu.mm
pulse Haematocrit rise 20% or more

Investigations:
1. To confirm diagnosis:
Days Post onset of symptoms Tests recommended

1 to 5 Detection of Viral protein: NS1 antigen

Day 5 onwards NS1 antigen
Dengue IgM +/-IgG

2. To look for complications: these tests help to monitor activity of the disease
CBC:
 Hb: if bleeding significant
 TC: common in viral fever
 Platelet : often monitoring required on a regular basis- frequency depends on the trend of platelet count
 Hct:↑ indicates hemoconcentration (due to dehydration from plasma leakage)

16
 can be due to
 Correction of dehydration with fluid
 Bleeding
Hct: often monitoring required on a regular basis- frequency depends on the trend
Biochemistry: Required in selected patients if complications arise
 Urea/Cr: Impaired due to dehydration
 Na/K: dyselectrolytemia due to dehydration
 LFT: abnormal in complicated cases(nonspecific hepatitis)
 ABG: Metabolic acidosis in complicated cases
CxR: effusion
USG abdomen: Ascites

Treatment:
A: Admit if
A: Airway- Intubate if needs to be ventilated
B: Bed rest till symptomatic recovery occurs
B: Blood parameter montoring: Hct, platelet- frequency depends on the trend
B: Breathing: Ventilate if ARDS
B: Bed sore prevention for patients who are comatose
C: Circulation: Adequate Fluid/Hydration is the cornerstone of management
Oral fluid only for patients without any symptoms/signs of fluid deficit
IV fluid: for Hypovolemic patients: Amount/rate of administration/duration depends on clinical status
C: Catheterise if urine output monitoring becomes essential
C: Complication: monitor closely and treat if develops
 ARDS: Intubate & Ventilate
 Acidosis: IV NaHCO3 in severe acidosis (pH < 7.1)
 Bleeding: Blood transfusion +/- Platelet transfusion
 Coagulopathy: Thrombocytopenia: Platelet transfusion only if bleeding or platelet count <10,000/cmm
 DIC: FFP transfusion
 Dysfunction of Organs: AKI: Dialysis(if required) ALI: supportive Rx
D: Diet: Nutritious diet
D: Drugs: ● Antipyretic: Paracetamol ● Analgesic: NSAIDS for severe pain ● Antiemetic:
Domperidone/Ondensetron
D: DVT prophylaxis for immobile/bedbound patients
E: Eligible for Discharge when
 Afebrile for at least 24 hours without antipyretic
 Appetite returning
 Atleast 2- 3 days after recovery from shock
 Blood: Platelet count > 50,000/ cumm and trend is upwards
 Clinical improvement obvious

F: Fluid therapy: Start with Crystalloid- Isotonic Saline/Ringer Lactate

17
DHF Grades I & II DHF Grades III & IV
Initiate IV NaCl 6 ml/kg/hr for 1-2 hrs

Improvement No Improvement

3 ml/kg/hr for next 12- 24 hours 10 ml/kg/h for 2 hrs No Improvement IV NaCl 10- 20 ml/kg/hr for 1-2 hrs

Improvement Improvement Improvement No Improvement

discontinue IV after 24 hrs 6 ml/kg/ hr then 10 ml/kg/hr 1.Colloid or plasma 10ml/kg/hr

3 ml/kg/hr then 6 ml/kg/hr 2.Blood transfusion if bleeding
then 3 ml/kg/hr
discontinue after 24-48 hrs discontinue after 24-48 hrs Improvement

10 ml/kg/hr then
6 ml/kg/hr then
3 ml/kg/hr

discontinue after 24-48 hrs

Improvement = Haematocrit falls, pulse rate and blood pressure stable, urine output rises
No Improvement = Haematocrit or pulse rate rises, pulse pressure < 20 mmHg, Urine output falls

Fluid therapy: Model 2!!...if you don’t want to tax your brain toooo much!!

Princicple: Rate+ amount+ duration of fluid therapy depends on pt’s clinical status

Fluid of choice: Isotonic Saline/ Ringer Lactate

Rate: Depending on hemodynamic status+ Urine output + periodic Hct results there are 4 standard regimes:
20 ml/kg/hr
10 ml/kg/hr switch between different regimes on the basis regular monitoring
6 ml/kg/hr of above parameters
3 ml/kg/hr
Additionally: Some patients may need:
 Colloid in case of refractory shock not responding to Crystalloid
 Blood transfusion in case of significant bleeding respectively

18
 TB
Causative organism: Mycobacterium tuberculosis
Mode of transmission: Transmission occurs when a person inhales droplet nuclei containing M. tuberculosis, and the
droplet nuclei traverse the mouth or nasal passages, upper respiratory tract, and bronchi to reach lungs
Pathogenesis
Infected person
droplets
Susceptible host

Lungs: primary infection

Subpleural focus bacilli Regional spread: lymph nodes

(Ghon focus)

Dead Dormant (Live) Multiplication (progressive primary disease)

Lungs
Latent infection (LTBI) Extrapulmonary
Disseminated disease
Reactivation or reinfection (secondary/post primary TB)
Lungs
Extrapulmonary
Disseminated disease
Clinical features: 1. Systemic 2. Focal
Systemic: ≥ 1 of the followings
 Appetite loss  Chill (+/- Rigor)
 Acute febrile illness  Decreased
 Appetite loss  Energy loss
 Body weight loss
Focal: depends on the site of Infection
Active Pulmonary TB: severity of symptoms and signs depend on extent/degree of lung damage/involvement
Symptoms: Signs:
 Asymptomatic Signs of Consolidation
 Breathlessness Signs of Cavity
 Cough
 Chest pain
 Hemoptysis
Extrapulmonary TB: FEATURES VARY ACCORDING TO SITE/FOCUS
Pleural: 1. f/o Pl. effusion GU
Pericardial: 1.f/o Pericarditis 2. f/o Pericardial effusion 1.f/o Pelvic Inflammatory disease
Neurological: 1. f/o Meningitis 2. f/o Tuberculoma 2.f/o Urethritis/Epidymitis
3.Renal TB: Sterile Pyuria (Urinary WBCs++ but
Adrenal: 1. f/o Adrenocortical insufficiency
\

Culture negative)
Lymph Nodes: Lymphadenopathy
Skeletal: Bone/Joint TB
1.Superficial: typically palpable +/- tender node(s)
1.f/o Osteomyeltis
2.Deep lymph nodes: Mediastinal/hilar/intra-abdominal
2.Vertbral TB: may lead to compressive Myelopathy
enlarged node(s): mostly radiologically evident
Abdominal Active3.Peritoneal:
pulmonaryAscites
disease is NOT a prerequisite for any
1.f/o Colitis Extrapulmonary TB
2.f/o Intestinal obstruction (due to fibrotic stensosis)

19
Investigations
1. Microbiological diagnosis: Confirmation of the disease-
 Demonstration of AFB
 Mycobacterial Culture (preferably BACTEC MGIT)
 XpertTB/RIF assay: detects M. TB DNA + Rifampicin resistance( which is a predictor of INH resistance)
Samples for these tests are taken from the affected site/organ-
Pulmonary TB- Extrapulmonary-
Sputum: spontaneous/induced Pleural- Pleural fluid/ Pleural biopsy
Bronchoscopic washing/lavage Meningeal TB- CSF
Lung biopsy Pericardial- Pericardial fluid
Lymph nodes- Biopsy
Peritoneal- Ascitic fluid/Peritoneal Biopsy
GU- urine/Vaginal swab
2. Supportive tests- they suggest TB when backed by proper clinical context
1. Radiological- Xray/CT findings 3. Biochemical marker- High ADA (Pleural fluid/Pericardial fluid/CSF)
2. Histopathological- Biopsy sample showing caseating granulomatous inflammatory changes
4. Mantoux test- DOES NOT confirm TB, SUGGESTS exposure to TB bacilli

Active pulmonary disease is NOT a prerequisite for an extrapulmonary TB

Treatment: daily regime

Pulmonary TB (Non- drug resitant/Drug sensitive cases)

Type of cases Intensive phase(IP) Continuation phase(CP)
New cases: 2 months: HRZE 4 months: HRE H: Isoniazid
R: Rifampicin
Previously treated cases: 2 months: HRZES E: Ethambutol
followed by 5 months: HRE Z: Pyrazinamide
1 month: HRZE S: Streptomycin (IM

Extrapulmonary TB: ALL extrapulmonary same as Pulmonary TB EXCEPT

CNS TB
Skeletal TB IP same; CP: is extended by ANOTHER 3-6 months depending on clinical response
Disseminated TB So IP 2 months; CP 7-10 months
Total duration of Treatment
Pulmonary TB & ALL extrapulmonary TB EXCEPT CNS TB / Skeletal TB/ Disseminated TB: 6 months
CNS TB / Skeletal TB/ Disseminated TB: 9-12 months

Additional drugs:
1. Vitamin B6: throughout the ENTIRE duration of ATD therapy to prevent INH induced Peripheral neuropathy
resulting from B6 depletion
2. Corticosteroid for 6- 8 weeks depending on clinical response in cases of
 CNS TB
 Pericardial TB
Monitoring:
LFT: Pretreatment and thereafter periodically if hepatitis develops
Microbiological: 1 sputum specimen at the completion of IP and 1 at the end of the treatment
Body weight: monthly
Chest x ray: if required (as per clinical scenario)
Extrapulmonary TB: Treatment response is best assessed clinically, help of radiological or any other relevant
investigations can be taken based on clinical judgement.

20
 Classification and side effects of ATDs
WHO grouping
Group 1: First Line Oral Agents -RHEZ
Rifampicin: (R) INH: (H)
Hepatotoxicity Peripheral neuropathy
Immunological reactions: Hepatitis
 Agranulocytosis Lupus like syndrome
 Thrombocytopenia Pyrazinamide: (Z)
 Leukopenia Hepatotoxicity
 Acute interstitial nephritis Hyperuricemia +/- Acute gouty arthritis
Exanthem Exanthem
Orange urine Ethambutol: (E) Retro bulbar neuritis

For Drug resistance cases only- traditionally following are called 2nd line ATDs
Group 2: Injectables: Kanamycin/Amikacin/Capreomycin/Streptomycin (S) - Ototoxity and Nephrotoxicity
Group 3: FQs: Levofloxacin; Moxifloxacin; Ofloxacin
Group 4: Para-Aminosalicylic Acid; Cycloserine; Ethionamide
Group 5 TB drugs: limited data on efficacy and/or long term safety
Clofazimine/Linezolid/ (Amoxicillin+ Clavulanate)/Thioacetazone/ (Imipenem+Cilastatin)/(Meropenem+
Clvulanate)/High Dose Isoniazid/ Clarithromycin/ Bedaquiline
Ongoing Clinical trial Pretomanid; Delamanid

Bedaquiline
The only new medicine/molecule discovered in more than forty years for TB.
It is a Diarylquinoline anti mycobacterial drug indicated as part of combination therapy in adults with MDR-TB
when an effective treatment regimen cannot otherwise be provided. It should be administered by DOTS.
The WHO Expert Groups recommendation,
It may be added to a WHO-recommended regimen in adult MDR-TB patients in following circumstances:
• When an effective treatment regimen containing four second-line drugs in addition to Pyrazinamide
according to WHO recommendations cannot be designed
• When there is documented evidence of resistance to any FQ in addition to multidrug resistance.
MOA: Bedaquiline affects the proton pump for ATP synthase.
S/E
Nausea
Joint
Chest pain
Headache
Arrhythmias may induced by prolonged QT
MDR TB
MDR-TB is defined as TB bacilli resistance to INH and Rifampicin with or without resistance to other ATDs.
(Based on DST results from an RNTCP accredited laboratory.)
MDR-TB Suspect can be any of the following:
• Any TB patient who fails an RNTCP Category I or III treatment regimen
• Any RNTCP Category II patient who is sputum smear positive at the end of the fourth month of treatment or later
• Close contacts of MDR-TB patients who are found to have smear positive pulmonary TB (PTB) disease

C/F- depends on site of TB

21
Clinical features: 1. Systemic 2. Focal
Systemic: ≥ 1 of the followings
 Appetite loss
 Acute febrile illness
 Body weight loss
 Cachexia
 Decreased energy level
Focal: depends on the site of Infection
Active Pulmonary TB: severity of symptoms and signs depend on extent/degree of lung damage/involvement
Symptoms: Signs:
 Asymptomatic Signs of Consolidation
 Breathlessness Signs of Cavity
 Cough
 Chest pain
 Hemoptyis
Extrapulmonary TB: FEATURES VARY ACCORDING TO SITE/FOCUS
Pleural f/o Pl. effusion
Pericardial:
1. f/o Pericarditis
2. f/o pericardial effusion -
Neurological
1. f/o TB Meningitis
2. f/o Tubeculoma
Lymph Nodes TB Lymphadenotahy
1. Superficial: typically palpable (+/- tender) cervical node(s)
2. Deep lymph nodes: Mediastinal/hilar/intra-abdominal enlarged node(s): mostly radiologically evident
Abdominal
1. f/o Colitis
2. Intestinal obstruction
3. Peritoneal: Acites
GU
1. f/o PID
2. f/o urethritis/epidymitis/prosititis
3. Renal: Sterile pyuria( WBCs++ but no organism/culture negative)
Skeletal- Bone TB:
1. f/o Osteomyelitis
2. If vertebral: f/o compressive myelopathy
Adrenal: f/o Adrenocorical insuffiency
Active pulmonary disease is NOT a prerequisite for an extrapulmonary TB
Investigations:

1.Microbiological diagnosis-
 AFB
 Mycobacterial Culture (preferably BACTEC MGIT)
 XpertTB/RIF assay: detects Myco. tb DNA+ Rifampicin resistance( which is a predictor of INH
resistance)

22
Samples for these tests are taken from the affected site/organ-
Extrapulmonary-
Pulmonary TB- Pleural- Pleural fluid/ Pleural biopsy
Sputum Meningeal TB- CSF
Bronchoscopic washing/lavage Pericardial- Pericardial fluid
Lung biopsy Lymph nodes- Biopsy
Peritoneal- Ascitic fluid/Peritoneal Biopsy
GU- urine/Vaginal swab

2. Supportive tests- they suggest TB when backed by proper clinical context

1. Radiological- Xray/CT
2. Histopathological- Biopsy sample showing caseating granulomatous inflammatory changes
3. Biochemical marker- ADA
4. Mantoux test- DOES NOT confirm TB, SUGGESTS exposure to TB bacilli
Treatment- called Cat IV regimen
6 drugs for 6 - 9 months (Intensive phase)
Kanamycin + Ofloxacin/Levofloxacin + Ethionamide + Pyrazinamide + Ethambutol + Cycloserine
4 drugs for atleast 18 months (Continuation phase)
Ofloxacin/Levofloxacin + Ethionamide + Ethambutol + Cycloserine
Extensively Drug resistance TBXDR-TB
XDR-TB = resistance to Isoniazid and Rifampicin (i.e MDR) + resistance to any of the FQs and to at least one of
injectable second-line drugs (Amikacin/Capreomycin/Kanamycin)

• Use Pyrazinamide and any other Group 1 agent that may be effective.
• Use an injectable agent to which the strain is susceptible and consider an extended duration of use (12 months or
possibly the whole treatment).
• Use a higher-generation fluoroquinolone such as Moxifloxacin/Gatifloxacin.
• Use all Group 4 agents that have not been used extensively in a previous regimen or any that are likely to be
effective.
• Add two or more Group 5 drugs (consider adding Bedaquiline or Delamanid)
• Consider adding a new investigational drug eligible for use under the compassionate use scheme if policy of the
WHO endorses its use for XDR-TB.
• Consider high-dose isoniazid treatment if low-level resistance or absence of the katG gene is documented.

X-DR Regimen design- at least six drugs were used in the intensive phase and four in the continuation phase
IP: 6-12 months:
Capreomycin+ Para-Aminosalicyclic acid+ Moxifloxacin+ High dose INH+ Clofazimine+ Linezolid+ Co-amoxiclav

CP: 18 months: Para-Aminosalicyclic acid+ Moxifloxacin+ High dose INH+ Clofazimine+ Linezolid+ Co-amoxiclav
“Options are limited and there is no expert consensus on a specific regimen that would be best for X-DR
patients”- WHO

23
 Manotux test
It’s a test which is indicative of the presence of cell mediated immunity (CMI) against Mycobacterium- technically
meaning that the person has had prior sensitization with mycobacterial antigen, either of M. tuberculosis or of
another cross reacting mycobacterium.
Method:
0.1 ml of PPD is injected strictly intradermally on the volar aspect of the forearm

Area observed for any INDURATION after 48 to 72 hours

Redness (but no induration) Induration

Size: diameter perpendicular to the long axis

Negative
Interpretation to be done keeping patient profile in mind
Interpretation: Induraton is indicative of the presence of cell mediated immunity (CMI) of the delayed
hypersensitivity type. Technically, this means that the person has had prior sensitization with mycobacterial antigen,
either of M. tuberculosis or of another cross reacting mycobacterium. In other words a result of 5 mm and above of
induration is positive for CMI, strictly from immunological view point.
The Mantoux test does not measure immunity to TB but the degree of hypersensitivity to tuberculin. There is no
correlation between the size of induration and likelihood of current active TB disease.The test has a poor positive
predictive value for current active disease.
The results of this test must be interpreted carefully. The person's medical risk factors determine the size of
induration considered to be positive
≥5 mm is considered to be positive in
HIV-positive person
Recent contacts of active TB cases
Persons with nodular or fibrotic changes on Chest X-ray consistent with old healed TB
Severely immunocompromised persons: eg. a. Organ transplant recipients b. Pts. on cytotoxic/immunosuppressives
≥10 mm is considered to be positive in
Recent arrivals from high-prevalence countries
Persons with lots of medical comorbidities
Children less than four years of age
Health care professionals
≥15 mm is positive in
Persons with no known risk factors for TB. Reactions larger than 15 mm are unlikely to be due to previous BCG
vaccination or exposure to environmental mycobacteria.
False-positive result: Some persons may react to the TST even though they are not infected with M. tuberculosis. The
causes of these false-positive reactions may include, but are not limited to, the following:
1. Infection with non tuberculous mycobacteria
2. Previous BCG vaccination
False-negative result: A negative Mantoux result usually signifies that the individual has never been exposed to M.
tuberculosis. However, there are factors that may cause a false-negative result or diminished ability to respond to
tuberculin.
1. Cutaneous anergy ( inability to react to skin tests because of a weakened immune system)
2. Very young age (less than six months old)
3. Recent live-virus vaccination (e.g., measles vaccine)
4. Overwhelming TB disease
5. Incorrect method of TST administration/Incorrect interpretation/insufficient dose

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