INTERNAL-MEDICINE.pptx

MARCH 12, 2023
8:00AM-10:00AM IDS/COMMUNICABLE
DISEASES
10:00AM-10:30AM BREAK
10:30AM-12:00PM PULMONOLOGY
12:00PM-1:00PM LUNCH BREAK
1:00PM-1:30PM PULMO CONTINUATION
1:30PM-3:00 PM GASTROENTEROLOGY
3:00PM-3:30PM BREAK
3:30PM-4:00PM GASTRO CONTINUATION
4:00PM – 5:00 PM RHEUMATOLOGY

Leptospirosis
Typhoid
Tetanus
Malaria
Schistosomiasis
HIV/AIDS
Dengue
Rabies
STD’s

Which of the following regarding leptospirosis is/are TRUE?
A.Vasculitis is responsible for most of the manifestations of the disease.
B.Severe hepatocellular necrosis is a feature of leptospirosis.
C.More than 90% of symptomatic patients have the anicteric form of the
disease without meningitis.
D.In the immune leptospiremic phase, the most common finding is fever
with conjunctival suffusion
ANSWER:
A

 Spirochetes belonging to the order Spirochaetales and the family Leptospiraceae
 Can be seen microscopically by dark-field examination and after silver
impregnation staining
 Require special media and conditions for growth
 Take weeks for cultures to become positive
•Coiled, thin, highly motile organisms with hooked ends
•2 periplasmic flagella (permit burrowing into tissue)

 Important zoonosis with a worldwide distribution
 Affects at least 160 mammalian species
 Rodents (rats): most important reservoir
 Other wild mammals as well as domestic and farm animals may harbor
leptospires
 Establish a symbiotic relationship with their host and can persist in the renal
tubules for years
OCCUPATIONAL GROUPS AT HIGH RISK:
Veterinarians
Agricultural workers
Sewage workers
Slaughterhouse employees
Workers in the fishing industry
** Acquire leptospirosis through direct exposure to or contact with contaminated water and
soil

Direct contact : urine, blood tissue
from an infected animal
Exposure to a contaminated
environment
Human-to-human transmission is
RARE
** Leptospires are excreted in the
urine
** Can survive in water for many
months
** Water : important vehicle of

All forms of leptospires : damage the wall of small blood vessels 
vasculitis with leakage  extravasation of cells  hemorrhages
Most important known pathogenic properties:
1. Adhesion to cell surfaces
2. Cellular toxicity

Vasculitis : most important manifestations of the disease
Mainly infect the kidneys and liver
Severe leptospirosis  vasculitis  impair the
microcirculation  increase capillary permeability 
fluid leakage  hypovolemia

 KIDNEY  leptospires 
interstitium, renal tubules,
tubular lumen  interstitial
nephritis  tubular necrosis
** Hypovolemia (dehydration or
altered capillary permeability ) 
renal failure
 LIVER
Centrilobular necrosis
Proliferation of Kupffer cells
Hepatocellular necrosis NOT a
feature of leptospirosis
 PULMONARY
result of hemorrhage and not
of inflammation
 SKELETAL MUSCLE
Swelling
vacuolation of the myofibrils
focal necrosis

Antibodies formed  eliminated from all sites in the host (EXCEPT
: eye, proximal renal tubules, brain)  persist for weeks or months
Persistence of leptospires in the aqueous humor  chronic or
recurrent uveitis
Systemic immune response
effective in eliminating the organism
produce symptomatic inflammatory reactions
rise in antibody titer coincides with the development of meningitis

 Many Leptospira-infected persons remain asymptomatic
 Serologic evidence of past inapparent infection is frequently found in persons
who have been exposed to leptospires but have not become ill
 Symptomatic cases: mild to serious or even fatal
 > 90% of symptomatic persons : mild and usually anicteric form of
leptospirosis, with or without meningitis
 Severe leptospirosis with profound jaundice (Weil's syndrome) : develops in
5–10% of infected individuals
 (Weil's syndrome): jaundice, renal dysfunction, and hemorrhagic diathesis

ANICTERIC LEPTOSPIROSIS
 Most common PE finding: fever with
conjunctival suffusion

Asymptomatic within 1 week
 1-3 days interval: illness recurs in a number of
cases
 Start of 2nd (immune) phase coincides with the
development of antibodies
Symptoms are variable : leptospiremic phase
An important event during the immune phase is
the development of ASEPTIC MENINGITIS

SEVERE LEPTOSPIROSIS
(WEIL'S SYNDROME)
 Renal dysfunction, hemorrhagic diathesis
 Profound jaundice : orange cast to the
skin, not associated with severe hepatic
necrosis
 Mortality rate : 5–15%
 Onset of illness : no different from less
severe leptospirosis
 After 4–9 days  jaundice + renal and
vascular dysfunction
 (+) Hepatomegaly and RUQ tenderness
 Splenomegaly : 20% of cases

SEVERE LEPTOSPIROSIS
(WEIL'S SYNDROME
 2nd week of illness  Renal failure
 Hypovolemia + decreased renal perfusion 
acute tubular necrosis  oliguria or anuria
 Pulmonary involvement occurs frequently :
cough, dyspnea, chest pain, and blood-
stained sputum, hemoptysis, respiratory
failure
 Hemorrhagic manifestations: epistaxis,
petechiae, purpura, and ecchymoses
 Rhabdomyolysis, hemolysis, myocarditis,
pericarditis, congestive heart failure,
cardiogenic shock, adult respiratory distress
syndrome, necrotizing pancreatitis,
multiorgan failure

LABORATORY AND
RADIOLOGIC FINDINGS
 Urinary sediment changes (leukocytes, erythrocytes, and hyaline or
granular casts)
 Mild proteinuria: anicteric leptospirosis
 Renal failure and azotemia: severe disease
 Erythrocyte sedimentation rate: elevated
 Anicteric leptospirosis: peripheral leukocyte count (3000 to 26,000/L)
 Weil's syndrome: marked leukocytosis
 Mild thrombocytopenia occurs in up to 50% of patients and is associated
with renal failure

LABORATORY AND
RADIOLOGIC FINDINGS
 Elevated serum levels of bilirubin and alkaline phosphatase
 Mild increases (up to 200 U/L) in serum levels of aminotransferases
 Weil's syndrome: prothrombin time prolonged; corrected with vitamin K
 Creatine phosphokinase elevated in 50% of patients during the 1st week
of illness (differentiate from viral hepatitis)
 (+) Meningitis : initially polymorphonuclear leukocytes  mononuclear
cells
CSF protein: elevated
CSF glucose: normal

 Severe leptospirosis : pulmonary radiographic abnormalities
common
 Develop 3–9 days after the onset of illness
 Most common radiographic finding: patchy alveolar pattern
(scattered alveolar hemorrhage)
** lower lobes in the periphery of the lung fields

 DEFINITE DIAGNOSIS
1. Isolation of the organism from the patient
2. Seroconversion
3. Rise in antibody titer in the microscopic agglutination test (MAT)

 Single antibody titer of 1:200–1:800 in the MAT
 Fourfold or greater rise in titer is detected between acute- and convalescent-phase
serum specimens
 Antibodies do not reach detectable levels until the second week of illness
 The antibody response can be affected by early treatment

 Blood and/or CSF: first 10 days of illness
 Urine: several weeks beginning at ~1 week
 (+) Culture: after 2–4 weeks (1 week to 6 months)
 Urine cultures remain positive for months or years after the start of illness
** Isolation of leptospires is important since it is the only way the infecting
serovar can be correctly identified
** Dark-field examination of blood or urine frequently results in
misdiagnosis and should not be used

Treatment and Chemoprophylaxis of Leptospirosis
Purpose of Drug
Administration
Regimen
Treatment
Mild leptospirosis Doxycycline, 100 mg orally bid or
Ampicillin, 500–750 mg orally qid
or
Amoxicillin, 500 mg orally qid
Moderate/severe
leptospirosis
Penicillin G, 1.5 million units IV qid
or
Ampicillin, 1 g IV qid or
Amoxicillin, 1 g IV qid or
Ceftriaxone, 1 g IV once daily or
Cefotaxime, 1 g IV qid or
Erythromycin, 500 mg IV qid
Chemoprophylaxis Doxycycline, 200 mg orally once a week

 Avoidance of exposure to urine and tissues from infected animals
 Vaccination of animals
The animal vaccine used in a given area should contain the serovars
known to be present in that area
 Rodent control
 Chemoprophylaxis with doxycycline (200 mg once a week): efficacious to
some extent; indicated only in rare instances of sustained short-term
exposure

Which of the following is the most frequent manifestation of typhoid fever?
A. Rose-spots
B. pulse-fever disproportion
C. prolonged persistent fever
D. splenomegaly
ANSWER:
C

ENTERIC (TYPHOID) FEVER
 Systemic disease
 Fever and abdominal pain
 Dissemination of S. Typhi or S. Paratyphi
 Enlarged Peyer's patches and mesenteric lymph nodes

Ingestion of organisms in
contaminated food or water
(103–106 colony-forming units)
Decrease stomach acidity or
intestinal integrity
Penetrate the mucous layer of the
gut; Traverse the intestinal layer
through phagocytic microfold (M)
cells {Peyer's patches}
bacteria-mediated
endocytosis (BME)
S. Typhi & S. Paratyphi,
phagocytosed by
macrophages
Small
intestine
Formation of
membrane
ruffles
disseminate via the
lymphatics; colonize
reticuloendothelial tissues
(liver, spleen, lymph nodes,
bone marrow)

TYPHOID FEVER:
EPIDEMIOLOGY
 S. typhi and S. paratyphi serotypes A, B, C
 No known hosts other than humans
 Food-borne or waterborne transmission
 From fecal contamination by ill or asymptomatic chronic carriers
 Sexual transmission between male partners has been described
 Health care workers occasionally acquire enteric fever after exposure to
infected patients or during processing of clinical specimens and cultures

contaminated : water or ice
Flooding
Food and drinks purchased from street vendors
Raw fruits and vegetables grown in fields fertilized with sewage
Ill household contact
Lack of hand washing and toilet access
Evidence of prior Helicobacter pylori infection (an association probably
related to chronically reduced gastric acidity)
TYPHOID FEVER: RISK
FACTORS

Hallmark features : fever and abdominal pain (variable)
Fever : >75% of cases
Abdominal pain: 30–40%
High index of suspicion : when a person presents with
fever and a history of recent travel to a developing country

 Incubation period : 10–14 days (ranges from 3 to 21 days)
 Duration reflecting the inoculum size and the host's health and immune status
 Most prominent symptom : prolonged fever (38.8°–40.5°C)
can continue for up to 4 weeks if untreated
 headache (80%) chills (35–45%)
 cough (30%) sweating (20–25%)
 myalgias (20%), malaise (10%)
 arthralgia (2–4%) anorexia (55%)
 abdominal pain (30–40%) nausea (18–24%)
 vomiting (18%) diarrhea (22–28%)
 constipation (13–16)

 EARLY PHYSICAL FINDINGS:
Rash ("rose spots"): faint, salmon-colored,
blanching, maculopapular rash located
primarily on the trunk and chest
- evident in ~30% of patients at the end of the
first week
- resolves without a trace after 2–5 days
- two or three crops of lesions
- cultured from punch biopsies of these lesions
- faintness of the rash makes it difficult to detect
in highly pigmented patients
Hepatosplenomegaly (3–6%)
 Epistaxis
Relative bradycardia at the peak of high fever

 Severe disease : occurs in ~10–15% of patients
 Depends on host factors: immunosuppression,
antacid therapy, previous exposure,
vaccination, strain virulence and inoculum,
choice of antibiotic therapy
 Gastrointestinal bleeding (10–20%)
 Intestinal perforation (1–3%) : 3rd – 4th weeks
of illness
hyperplasia, ulceration, and necrosis of the
ileocecal Peyer's patches at the initial site of
Salmonella infiltration
 Neurologic manifestations : 2–40% of patients
Meningitis, Guillain-Barré syndrome,
neuritis, neuropsychiatric symptoms
("muttering delirium" or "coma vigil")

Considered in any febrile traveler returning from a
developing country
Other than a positive culture ; no specific laboratory test is
diagnostic for enteric fever
15–25%: leukopenia and neutropenia are detectable
Leukocytosis : more common among children, during the
first 10 days of illness, and in cases complicated by
intestinal perforation or secondary infection

 Definitive diagnosis of enteric fever: isolation of S. Typhi or S. Paratyphi
from blood, bone marrow, other sterile sites, rose spots, stool, or
intestinal secretions
 Sensitivity: 90% during the 1st week; decreases to 50% 3rdweek
** Low yield in infected patients is related to low numbers of salmonella (<15
organisms/mL) and/or to recent antibiotic treatment

 Bone marrow culture remains highly (90%) sensitive despite 5 days of antibiotic therapy
 Culture of intestinal secretions (best obtained by a noninvasive duodenal string test)
can be positive despite a negative bone marrow culture
 If blood, bone marrow, and intestinal secretions are all cultured, the yield is >90%
 Stool cultures, while negative in 60–70% of cases during the first week, can become
positive during the third week of infection in untreated patients
 Widal test for "febrile agglutinins“: not sufficiently sensitive or specific to replace
culture-based methods for the diagnosis of enteric fever in developed countries.

EMPIRICAL TREATMENT
Ceftriaxone 1–2 g/d (IV) 7–14
Azithromycin 1 g/d (PO) 5
FULLY SUSCEPTIBLE
Ciprofloxacin (first line) 500 mg bid (PO) or
400 mg q12h (IV)
5-7
Amoxicillin (second
line)
1 g tid (PO) or 2 g q6h
(IV)
14
Chloramphenicol 25 mg/kg tid (PO or
IV)
14-21
Trimethoprim-
sulfamethoxazole
160/800 mg bid (PO) 14

MULTIDRUG-RESISTANT
Ciprofloxacin 500 mg bid
(PO) or 400
mg q12h (IV)
5-7
Ceftriaxone 2–3 g/d (IV) 7-14
Azithromycin 1 g/d (PO) 5

Which of the following is a sign of severe (stage III) tetanus?
A.spasms lasting for less than 10 seconds
B.lock jaw
C.risus sardonicus
D.localized muscle stiffness
ANSWER:
C

Neurologic disorder
Increased muscle tone and spasms
Caused by a toxin – tetanospasmin
Clostridium tetani
Generalized
Neonatal
Localized disease

 Occurs sporadically
 Affects : unimmunized persons
partially immunized persons
fully immunized individuals (fail to
maintain adequate immunity with
booster doses of vaccine)
 Entirely preventable by immunization
 Notifiable disease in many countries

 Clostridium tetani
anaerobic, motile, gram-positive rod
forms an oval, colorless, terminal spore
resembling a tennis racket or drumstick
Found : in soil, in the inanimate environment, in animal feces, and occasionally in
human feces
Spores may survive for years
Resistant to various disinfectants and to boiling for 20 min
Vegetative cells are easily inactivated and are susceptible to several antibiotics
(Metronidazole and Penicillin)

• Contamination
of wounds with
spores of C.
tetani
• Wound with low
oxidation-
reduction
potential
(Germination and
toxin production)
- devitalized tissue,
foreign bodies, or
active infection
• Enters the axon
• Transported to
the nerve-cell
body
brainstem
and spinal cord
Retrograde
intraneuronal
transport
• blocks release of
GABA from
vesicles
• Tetanospasmin
resting firing rate of
the motor neuron
increases
TOXIN
synapse to
presynaptic
terminals
RIGIDITY

 Toxin : preganglionic sympathetic neurons in the lateral gray matter
of the spinal cord and parasympathetic centers
Loss of inhibition of preganglionic sympathetic neurons 
sympathetic hyperactivity and high circulating catecholamine levels
 Tetanospasmin block neurotransmitter release at the
neuromuscular junction  weakness or paralysis
 Recovery requires sprouting of new nerve terminals

Nerves supplying the affected muscles
Generalized tetanus occurs when toxin released in the
wound enters the lymphatics and bloodstream and spread
widely to distant nerve terminals
Blood-brain barrier blocks direct entry into the central
nervous system

GENERALIZED TETANUS
most common form of the disease
increased muscle tone
generalized spasms
7 days: median time of onset after injury
15% : within 3 days
10%: after 14 days

 Increased tone in the masseter muscles (trismus, or lockjaw)
 Dysphagia
 Stiffness or pain in the neck, shoulder, and back muscles
 Rigid abdomen
 Stiff proximal limb muscles
 Hands and feet are relatively spared
 Sustained contraction of the facial muscles (risus
sardonicus)
 Contraction of the back muscles (opisthotonos)
 Paroxysmal, violent, painful, generalized muscle spasms
 Cyanosis
 Threaten ventilation
GENERALIZED TETANUS

 Occur repetitively
 Spontaneous or provoked
 Even the slightest stimulation
 Reduced ventilation or apnea or laryngospasm
 May be febrile
 Unimpaired mentation
 DTRs may be increased
 Severity of illness:
1. MILD : muscle rigidity and few or no spasms
2. MODERATE: trismus, dysphagia, rigidity, and spasms
3. SEVERE: frequent explosive paroxysms; risus sardonicus
GENERALIZED TETANUS

 Uncommon form
 Manifestations are restricted to muscles near the wound
 Prognosis is excellent
*** CEPHALIC TETANUS
Rare form of local tetanus
Follows head injury or ear infection
One or more facial cranial nerves
 Incubation period: few days
Mortality : high
LOCAL TETANUS

 Based entirely on clinical findings
 Markedly increased tone in central muscles (face, neck, chest, back, and abdomen), with
superimposed generalized spasms and relative sparing of the hands and feet, strongly suggests
tetanus
 unlikely if completion of a primary vaccination series and the receipt of appropriate booster doses
 Wounds should be cultured in suspected cases
 C. tetani can be isolated from wounds of patients without tetanus and frequently cannot be recovered
from wounds of those with tetanus
 Serum antitoxin levels of 0.1 IU/mL (as measured by enzyme-linked immunosorbent assay) are
considered protective and make tetanus unlikely

 Leukocyte count : may be elevated
 CSF examination : normal
 EMG: continuous discharge of motor units and shortening
absence of the silent interval normally seen after an
action potential
 ECG: Nonspecific changes
 Muscle enzyme levels: may be raised

TETANUS: TREATMENT
Goals:
Eliminate the source of toxin
Neutralize unbound toxin
Prevent muscle spasms
Monitor patient's condition
Provide support (respiratory support)
Admit to a quiet room (intensive care unit)
- where observation and cardiopulmonary monitoring can be maintained continuously ;
stimulation can be minimized
Wounds should be explored, carefully cleansed, and thoroughly debrided

 ANTIBIOTIC THERAPY
Eradicate vegetative cells (source of toxin)
Penicillin (10–12 million units IV, given daily for 10 days)
Metronidazole (500 mg every 6 h or 1 g every 12 h) : excellent
antimicrobial activity and the absence of the GABA-
antagonistic activity seen with penicillin
Alternative: Clindamycin and Erythromycin
TETANUS: TREATMENT

 ANTITOXIN
Neutralize circulating toxin and unbound toxin
Effectively lowers mortality
Toxin already bound to neural tissue is unaffected
Human tetanus immune globulin (TIG)
Preparation of choice
Given promptly
Dose : 3000–6000 units IM, in divided doses
Optimal dose is not known
TETANUS: TREATMENT

RESPIRATORY CARE
Intubation or tracheostomy (with or without mechanical ventilation)
Hypoventilation due to oversedation or laryngospasm
Avoidance of aspiration by patients with trismus, disordered
swallowing, or dysphagia
** Should be anticipated and undertaken electively and early
TETANUS: TREATMENT

 ALL partially immunized and unimmunized adults should receive vaccine, as should those
recovering from tetanus
 Primary series for adults :
 First and second doses : given 4–8 weeks apart
 Third dose : 6–12 months after the second
 Booster dose : every 10 years
 Combined tetanus and diphtheria toxoid, adsorbed (Td, for adult use)—rather than single-antigen
tetanus toxoid—is preferred for persons >7 years of age
 Adsorbed vaccine is preferred because it produces more persistent antibody titers than fluid vaccine

Two combined tetanus/diphtheria/attenuated pertussis
vaccines have recently been approved:
1. ADACEL: for adults 19–64 years
2. BOOSTRIX: for adolescents 11–18 years
The Advisory Committee on Immunization Practices has
recommended a single dose of Tdap (ADACEL) for adults
19–64 years old who have not received Tdap

L.E., a 29 years old female presented at the ER with a 4-day history of fever (T40C) and
myalgia. She had come from a beach outing in Palawan 2 weeks ago. After an hour, she
started to be lethargic and had seizures. Capillary blood glucose was low (<40 mg/dL) and
arterial blood gas showed metabolic acidosis (pH 7.2, HCO3 15). What is the BEST diagnostic
test that can be done for this patient?
ANSWER:
D
A. blood culture
B. cranial CT scan
C. CSF analysis
D. thick and thin blood smear

 Protozoan disease
 Bite of infected Anopheles mosquitoes
 Four species of the genus Plasmodium
P. falciparum,
P. vivax,
P. ovale
P. malariae
 Almost all deaths are caused by falciparum malaria

Characteristic P. falciparum P. vivax P. ovale P. malariae
Duration of intrahepatic phase (days) 5.5 8 9 15
Number of merozoites released per
infected hepatocyte
30,000 10,000 15,000 15,000
Duration of erythrocytic cycle (hours) 48 48 50 72
Red cell preference Younger cells
(but can
invade cells of
all ages)
Reticulocytes
and cells up to
2 weeks old
Reticulocytes Older cells
Morphology Usually only
ring formsa;
banana-
shaped
gametocytes
Irregularly
shaped large
rings and
trophozoites;
enlarged
erythrocytes;
Schüffner's
dots
Infected
erythrocytes,
enlarged and
oval with
tufted ends;
Schüffner's
dots
Band or
rectangular
forms of
trophozoites
common
Pigment color Black Yellow brown Dark brown Brown black
Ability to cause relapses No Yes Yes No

 Principal determinants of the epidemiology of malaria
- Number (density)
- Human-biting habits
- Longevity of the anopheline mosquito vectors
 Mosquito longevity is important, because the portion of the
parasite's life cycle that takes place within the mosquito—from
gametocyte ingestion to subsequent inoculation (sporogony)—lasts
8–30 days → thus, to transmit malaria, the mosquito must survive
for >7 days

 P. falciparum infections: membrane protuberances (Knobs) appear on
the erythrocyte's surface (12–15 h after the cell's invasion)
 Mediates attachment to receptors on venular and capillary
endothelium (cytoadherence)
 P. falciparum–infected RBCs : adhere to uninfected RBCs (to form
rosettes) and to other parasitized erythrocytes (agglutination)
 The processes of cytoadherence, rosetting, and agglutination: central
to the pathogenesis of falciparum malaria

 P.vivax/ ovale/ malariae : sequestration does not occur
- All stages of the parasite's development are evident on peripheral
blood smears
 P. vivax, P. ovale, and P. malariae : marked predilection for either
young RBCs (P. vivax, P. ovale) or old cells (P. malariae)
 P. falciparum : invade erythrocytes of all ages
- associated with very high levels of parasitemia.

 Very common cause of fever in tropical countries
 First symptoms: nonspecific (lack of a sense of well-being, headache, fatigue,
abdominal discomfort, muscle aches followed by fever)
 Malarial paroxysms: fever spikes, chills, and rigors
 Generalized seizures = falciparum malaria → development of cerebral
disease
 Anemia: young children living in areas with stable transmission

Features Indicating a Poor Prognosis in Severe Falciparum Malaria
CLINICAL
Marked agitation
Hyperventilation (respiratory distress)
Hypothermia (<36.5°C)
Bleeding Deep coma
Repeated convulsions
Anuria
Shock
LABORATORY
Biochemistry
Hypoglycemia (<2.2 mmol/L)
Hyperlactatemia (>5 mmol/L)
Acidosis (arterial pH <7.3, serum HCO3 <15 mmol/L)
Elevated serum creatinine (>265 mol/L)
Elevated total bilirubin (>50 mol/L)
Elevated liver enzymes (AST/ALT 3 times upper limit of normal, 5-nucleotidase )
Elevated muscle enzymes (CPK , myoglobin )
Elevated urate (>600 mol/L)

 Demonstration of asexual forms of the parasite in
stained peripheral-blood smears
 Negative blood smear--> repeat smears should be made
if there is a high degree of suspicion
 Both thin and thick blood smears should be examined

 UNCOMPLICATED MALARIA: electrolytes, BUN, and
creatinine
= normal
 SEVERE MALARIA: metabolic acidosis, low plasma
concentrations of glucose, sodium, bicarbonate, calcium,
phosphate, and albumin together with elevations in lactate,
BUN, creatinine, urate, muscle and liver enzymes, and
conjugated and unconjugated bilirubin
 ADULTS AND CHILDREN WITH CEREBRAL MALARIA:
mean opening pressure at lumbar puncture = ~160 mm of
cerebrospinal fluid (CSF); usually the CSF is normal or has a
slightly elevated total protein level [<1.0 g/L (<100 mg/dL)] and
cell count (<20/L)

Known chloroquine-sensitive strains of
Plasmodium vivax, P. malariae, P. ovale, P.
falciparuma
Chloroquine (10 mg of base/kg stat followed by 5 mg/kg at 12, 24, and 36 h or
by 10 mg/kg at 24 h and 5 mg/kg at 48 h)
or
Amodiaquine (10–12 mg of base/kg qd for 3 days)
Radical treatment for P. vivax or P. ovale
infection
In addition to chloroquine or amodiaquine as detailed above, primaquine (0.25
mg of base/kg qd; 0.375–0.5 mg of base/kg qd in Southeast Asia and Oceania)
should be given for 14 days to prevent relapse. In mild G6PD deficiency, 0.75
mg of base/kg should be given once weekly for 6 weeks. Primaquine should
not be given in severe G6PD deficiency.
Sensitive P. falciparum malariab Artesunatec (4 mg/kg qd for 3 days) plus sulfadoxine (25 mg/kg)/pyrimethamine
(1.25 mg/kg) as a single dose
or
Artesunatec (4 mg/kg qd for 3 days) plus amodiaquine (10 mg of base/kg qd for
3 days)d
Multidrug-resistant P. falciparum malaria Either artemether-lumefantrinec (1.5/9 mg/kg bid for 3 days with food) or
artesunatec (4 mg/kg qd for 3 days)
plus
Mefloquine (25 mg of base/kg—either 8 mg/kg qd for 3 days or 15 mg/kg on
day 2 and then 10 mg/kg on day 3)d
Second-line treatment/treatment of imported
malaria
Either artesunatec (2 mg/kg qd for 7 days) or quinine (10 mg of salt/kg tid for 7
days)
plus 1 of the following 3:
1. Tetracyclinee (4 mg/kg qid for 7 days)
2. Doxycyclinee (3 mg/kg qd for 7 days)
3. Clindamycin (10 mg/kg bid for 7 days)
or
Atovaquone-proguanil (20/8 mg/kg qd for 3 days with food)

Artesunatec (2.4 mg/kg stat IV followed by 2.4 mg/kg
at 12 and 24 h and then daily if necessary)g
or
Artemetherc (3.2 mg/kg stat IM followed by 1.6 mg/kg
qd)
or
Quinine dihydrochloride (20 mg of salt/kgh infused
over 4 h, followed by 10 mg of salt/kg infused over 2–8
h q8hi)
or
Quinidine (10 mg of base/kgh infused over 1–2 h,
followed by 1.2 mg of base/kg per houri with
electrocardiographic monitoring)

Atovaquone/proguanil
(Malarone)
Prophylaxis in areas with
chloroquine- or mefloquine-
resistant Plasmodium
falciparum
1 adult tablet
PO
5–8 kg: 1/2 pediatric
tabletb daily
Begin 1–2 days before travel to
malarious areas. Take daily at the
same time each day while in the
malarious area and for 7 days after
leaving such areas. Atovaquone-
proguanil is contraindicated in
persons with severe renal
impairment (creatinine clearance
rate <30 mL/min). It is not
recommended for children weighing
<5 kg, pregnant women, or women
breast-feeding infants weighing <5
kg. Atovaquone/proguanil should be
taken with food or a milky drink.
8–10 kg: 3/4 pediatric
tablet daily
10–20 kg: 1 pediatric
tablet daily
tablets daily
tablets daily
40 kg: 1 adult tablet
daily
Chloroquine phosphate
(Aralen and generic)
Prophylaxis only in areas
with chloroquine-sensitive
P. falciparumc
300 mg of base
(500 mg of salt)
PO once weekly
5 mg/kg of base (8.3 mg
of salt/kg) PO once
weekly, up to a
maximum adult dose of
300 mg of base
Begin 1–2 weeks before travel to
malarious areas. Take weekly on
the same day of the week while in
the malarious areas and for 4
weeks after leaving such areas.
Chloroquine phosphate may
exacerbate psoriasis.

Hydroxychloroquine sulfate
(Plaquenil)
An alternative
to chloroquine
for primary
prophylaxis only
in areas with
chloroquine-
sensitive P.
falciparumc
310 mg of base (400
mg of salt) PO once
weekly
5 mg of base/kg (6.5 mg of salt/kg)
PO once weekly, up to maximum
adult dose of 310 mg of base
malarious areas. Take weekly
on the same day of the week
while in the malarious areas
and for 4 weeks after leaving
such areas. Hydroxychloroquine
may exacerbate psoriasis.
Mefloquine (Lariam and
generic)
Prophylaxis in
areas with
chloroquine-
resistant P.
falciparum
228 mg of base (250
mg of salt) PO once
weekly
9 kg: 4.6 mg of base/kg (5 mg of
salt/kg) PO once weekly
malarious areas. Take weekly
on the same day of the week
while in the malarious areas
and for 4 weeks after leaving
such areas. Mefloquine is
contraindicated in persons
allergic to this drug or related
compounds (e.g., quinine and
quinidine) and in persons with
active or recent depression,
generalized anxiety disorder,
psychosis, schizophrenia, other
major psychiatric disorders, or
seizures. Use with caution in
persons with psychiatric
disturbances or a history of
depression. Mefloquine is not
recommended for persons with
cardiac conduction
abnormalities.
10–19 kg: 1/4 tablet once weekly
46 kg: 1 tablet once weekly

Primaquine Used for presumptive
antirelapse therapy
(terminal prophylaxis) to
decrease risk of relapses
of P. vivax and P. ovale.
30 mg of base (52.6
mg of salt) PO qd for
14 days after
departure from the
malarious area
0.5 mg of base/kg
(0.8 mg of salt/kg),
up to adult dose,
PO qd for 14 days
after departure
from the malarious
area
This therapy is
indicated for persons
who have had prolonged
exposure to P. vivax
and/or P. ovale. It is
contraindicated in
persons with G6PD1
deficiency as well as
during pregnancy and
in lactation unless the
infant being breast-fed
has a documented
normal G6PD level.

Which of the following causes of portal circulatory obstruction is presinusoidal in
location?
A.Cirrhosis
B.Schistosomiasis
C. Budd Chiari
D.Inferior Venal caval obstruction.
ANSWER:
B

 Human schistosomiasis: five
species of the parasitic trematode
genus Schistosoma
INTESTINAL SPECIES : S.
mansoni, S. japonicum,
S. mekongi, and S. intercalatum
URINARY SPECIES:
S. haematobium

ETIOLOGY
 Human infection  penetration of intact skin
with infective cercariae
 CERCARIAE  released from infected snails
in freshwater bodies (~2 mm in length;
anterior and a ventral sucker that attach to
the skin and facilitate penetration) 
subcutaneous tissue  cercariae 
schistosomula (morphologic, membrane, and
immunologic changes)
 Cercarial outer membrane  changes from a
trilaminar -> heptalaminar (maintained
throughout the organism's life span in humans
)  schistosome's main adaptive mechanism
for survival in humans
 Schistosomula  migration within 2–4 days
 venous or lymphatic vessels  lungs 
Liver parenchyma

 Sexually mature worms  descend into the venous
system at specific anatomic locations
 INTESTINAL VEINS (S. mansoni, S. japonicum, S.
mekongi, and S. intercalatum)
 VESICAL VEINS (S. haematobium)
 After mating  adult gravid females  travel
against venous blood flow  small tributaries 
deposit their ova intravascularly
 50% of ova: retained in host tissues locally
(intestines or urinary tract)
 50% : carried by venous blood flow to the liver and
other organs
 Schistosome ova that reach freshwater bodies hatch,
releasing free-living miracidia that seek the snail
intermediate host  asexual multiplication cycles
 Infective cercariae are shed from snails

PATHOGENESIS AND
IMMUNITY
 Cercarial invasion : associated with
dermatitis arising from dermal and
subdermal inflammatory responses
 Sexual maturity  commencement of
oviposition  acute schistosomiasis or
Katayama fever
 Antigen excess  formation of soluble
immune complexes  deposited in several
tissues  MULTIPLE PATHOLOGIC
EVENTS

PATHOGENESIS AND
IMMUNITY
 CHRONIC SCHISTOSOMIASIS: most disease manifestations are due to eggs retained in
host tissues
 CELL MEDIATED GRANULOMATOUS RESPONSE: regulated both positively and
negatively by a cascade of cytokine, cellular, and humoral responses
 GRANULOMA FORMATION :
Recruitment of a host of inflammatory cells in response to antigens secreted by the living
organism within the ova
Cells recruited : phagocytes, antigen-specific T cells, and eosinophils
Fibroblasts, giant cells, and B lymphocytes predominate later
** Granulomatous response  fibrosis  permanent disease sequelae

PATHOGENESIS AND
IMMUNITY
 Ova  carried by portal blood  embolize to the liver 
lodge at presinusoidal sites  formation of granulomas
 hepatomegaly
 Presinusoidal portal blockage  portal hypertension 
portosystemic collaterals (esophagogastric junction and
other sites)  Esophageal varices
 Compensatory arterialization of the blood flow through
the liver is established  retention of hepatocyte
perfusion permits maintenance of normal liver function
for several years
 Schistosomal liver enlargement : associated with certain
class I and class II human leukocyte antigen (HLA)
haplotypes and markers; its genetic basis appears to be
multigenic.

PATHOGENESIS AND
IMMUNITY
 LIVER FIBROSIS
Periportal (Symmers' clay pipe–
stem fibrosis)
May be diffuse = areas of egg
deposition and granuloma formation
(portal tracts)
Pure fibrotic lesions in the liver
Cirrhosis occurs when other
nutritional factors or infectious
agents (e.g., hepatitis B or C virus)
are involved

PATHOGENESIS AND
IMMUNITY
Similar processes occur in urinary schistosomiasis
Granuloma formation at the lower end of the ureters obstructs
urinary flow  hydroureter and hydronephrosis
Urinary bladder  protrusion of papillomatous structures into its
cavity  ulcerate and/or bleed
** Chronic stage of infection: scarring and deposition of calcium in bladder
wall

CLINICAL FEATURES
 CERCARIAL INVASION:
Swimmers' itch: S. mansoni and S. japonicum
2 or 3 days after invasion
Itchy maculopapular rash on the affected areas of the skin
Self-limiting
 ACUTE SCHISTOSOMIASIS OR KATAYAMA FEVER
During worm maturation
Beginning of oviposition (4–8 weeks after skin invasion)
Serum sickness–like syndrome: fever, generalized lymphadenopathy,
and hepatosplenomegaly
High degree of peripheral blood eosinophilia
Generally benign
Mortality: heavy exposure to schistosomes

CLINICAL FEATURES
 HEPATOSPLENIC PHASE
 manifests early (during the first year of infection, particularly in children)
 liver enlargement: parasite-induced granulomatous lesions
 Hepatomegaly (~15–20% )
 right-upper-quadrant ("dragging" pain )
 Splenomegaly
 Bleeding from esophageal varices
** Late-stage disease : fibrotic changes occur along with liver function deterioration; onset of ascites,
hypoalbuminemia; defects in coagulation
** Intercurrent viral infections of the liver (especially hepatitis B and C) or nutritional deficiencies accelerate the
deterioration of hepatic function
Intestinal species (S. mansoni, S. japonicum, S. mekongi, and S.
intercalatum): intestinal and hepatosplenic disease (manifestations
associated with portal hypertension)

CLINICAL FEATURES
 S. haematobium
occur relatively early
80% of children: terminal dysuria, frequency, and hematuria
Urine examination: (+) blood and albumin
(+) bacterial urinary tract infection and urinary sediment cellular metaplasia
Obstruction of the lower end of the ureters  hydroureter and hydronephrosis
Bladder granulomas  fibrosis  typical sandy patches visible on cystoscopy
** In many endemic areas, an association between squamous cell carcinoma of the bladder
and S. haematobium infection has been observed
-- younger age group
-- S. haematobium: human carcinogen

CLINICAL FEATURES
 PULMONARY SCHISTOSOMIASIS
embolized eggs  lodge in small arterioles  necrotizing arteriolitis  granuloma
formation  fibrous tissue deposition  endarteritis obliterans  pulmonary
hypertension  cor pulmonale
S. mansoni and S. japonicum: schistosome eggs reach the lungs after the
development of portosystemic collateral circulation
S. haematobium: ova may reach the lungs directly via connections between the
vesical and systemic circulation
Cough, fever, and dyspnea

CLINICAL FEATURES
CNS SCHISTOSOMIASIS
Due to S. japonicum infection
Migratory worms deposit eggs in the brain and induce a
granulomatous response
 Jacksonian epilepsy (S. japonicum)
 Transverse myelitis (S. mansoni and S. haematobium)
eggs traveling to the venous plexus around the spinal cord

DIAGNOSIS
Geographic history
Clinical presentation
Presence of schistosome ova in excreta
Diagnosis may also be established with the serologic assays
- applied either to blood or to other body fluids (e.g., cerebrospinal fluid)
Examination of tissue samples: rectal biopsies
Other biopsy procedures (e.g., liver biopsy) are not needed, except in rare circumstances

TREATMENT
S. mansoni,
S.
intercalatum,
S.
haematobium
Praziquantel 20 mg/kg, 2 doses in 1
day
S. japonicum,
S. mekongi
Praziquantel 20 mg/kg, 3 doses in 1
day

In patients with suspected dengue hemorrhagic fever, the following
should be done:
A. Infusion of crystalloid or colloid to prevent hemoconcentration
B. Administer steroid to prevent hypotension
C. Blood transfusion if the hematocrit goes below 36%
D. Prophylactic platelet transfusion if platelet count goes below
100,000
ANSWER:
A

VIRUS
 Dengue virus (DEN) : small single-stranded RNA virus
 4 distinct serotypes: DEN-1 to -4
 Belong to the genus Flavivirus, family Flaviviridae
VECTORS
 Through the bites of infected Aedes mosquitoes
(Ae. Aegypti)
 Immature stages  found in water-filled habitats
(artificial containers)
 Most female Ae. aegypti may spend their lifetime
in or around the houses where they emerge as
adults

HOST
 After an incubation period of 4--10 days  wide spectrum of illness
 Primary infection: induce lifelong protective immunity to the infecting
serotype
 Individuals suffering an infection are protected from clinical illness with
a different serotype within 2--3 months of the primary infection
 No long-term cross-protective immunity

 Dengue virus -> via the skin (infected mosquito is taking a bloodmeal)
 Acute phase of illness : the virus is present in the blood
- clearance from this compartment generally coincides with defervescence
 Humoral and cellular immune responses : contribute to virus clearance  generation of
neutralizing antibodies
 activation of CD4+ and CD8+ T lymphocytes
 Innate host defense
 After the infection: Serotype specific and cross-reactive antibodies and CD4+ and CD8+ T
cells remain measurable for years

Plasma leakage
Hemoconcentration
Abnormalities in homeostasis
The mechanisms leading to severe illness not well defined
** Immune response, the genetic background of the
individual and the virus characteristics may all contribute
to severe dengue
SEVERE
DENGUE

Febrile, critical and recovery phases in dengue
1. Febrile Phase Dehydration; high fever may
cause neurological
disturbances and febrile
seizures in young children
2. Critical phase Shock from plasma leakage;
severe hemorrhage; organ
impairment
3. Recovery phase Hypervolemia (only if IV fluid
therapy has been excessive
and/or has extended into this
period)

Warning Signs
Clinical Abdominal pain or
tenderness
Persistent vomiting
Clinical fluid
accumulation
Mucosal bleed
Lethargy, restlessness
Liver enlargement >2cm
Laboratory Increase in HCT
concurrent with rapid
decrease in platelet
count

Mild hemorrhagic manifestations (petechiae and mucosal
membrane bleeding (e.g. nose and gums)
Massive vaginal bleeding and gastrointestinal bleeding
may occur during this phase but is not common
Liver is often enlarged and tender after a few days of fever
Earliest abnormality : progressive decrease in total white
cell count

 Time of defervescence (T: drops to 37.5–38oC or less): 3–7 of illness
 Increase in capillary permeability in parallel with increasing hematocrit
levels
**Marks the beginning of the critical phase
** Period of clinically significant plasma leakage
**Usually 24–48 hours

Plasma leakage: preceded by progressive leukopenia followed by
rapid decrease in platelet count
Without increase in capillary permeability: improve
With increased capillary permeability: worsen (lost of plasma
volume
 Pleural effusion and ascites: clinically detectable; depending on the degree of
plasma leakage and the volume of fluid therapy
Chest x-ray and abdominal ultrasound :useful tools for diagnosis
 The degree of increase above the baseline hematocrit : reflects the severity of
plasma leakage

Shock : critical volume of plasma is lost through leakage
Warning signs  prolonged shock  hypoperfusion  progressive
organ impairment  metabolic acidosis  disseminated
intravascular coagulation  severe hemorrhage hematocrit
decrease  severe shock
** Instead of the leukopenia, total white cell count increase in
patients with severe bleeding

 Gradual reabsorption of extravascular compartment fluid: 48–72 hours
 General well-being improves
 Appetite returns
 Gastrointestinal symptoms abate
 Hemodynamic status stabilizes
 Rash of “isles of white in the sea of red” : Herman’s rash
 Generalized pruritus
 Bradycardia and electrocardiographic changes
 Hematocrit stabilizes (may be lower due to the dilutional effect)
 WBC count: starts to rise soon after defervescence
 Recovery of platelet count: later than that of white blood cell count
 During the critical and/or recovery phases, excessive fluid therapy is associated with pulmonary
edema or congestive heart failure

One or more of the following:
(i) Plasma leakage that may lead to shock (dengue shock)
and/or fluid accumulation, with or without respiratory
distress
(ii) Severe bleeding
(iii)Severe organ impairment

• There is evidence of plasma leakage, such as:
– high or progressively rising haematocrit;
– pleural effusions or ascites;
– circulatory compromise or shock (tachycardia, cold and clammy extremities,
- capillary refill time greater than three seconds, weak or undetectable pulse,
- narrow pulse pressure or, in late shock, unrecordable blood pressure)
• There is significant bleeding
• There is an altered level of consciousness (lethargy or restlessness, coma, convulsions)
• There is severe gastrointestinal involvement (persistent vomiting, increasing or intense
abdominal pain, jaundice)
• There is severe organ impairment (acute liver failure, acute renal failure, encephalopathy or
encephalitis, or other unusual manifestations, cardiomyopathy) or other unusual manifestations

GROUP B
(Referred for in-hospital care)
Group criteria
Patients with any of the following features:
• Coexisting conditions such as pregnancy,
infancy, old age, diabetes mellitus, renal
failure
•Social circumstances such as living alone,
living far from hospital
Laboratory Tests
• Full blood count (FBC)
•Haematocrit (HCT)
Treatment
• Encouragement for oral fluids. If not
tolerated, start intravenous fluid therapy
0.9% saline or Ringer’s Lactate at
maintenance rate.
Monitoring
Monitor:
• temperature pattern
•Volume of fluid intake and losses
•Urine output (volume and frequency)
•Warning signs
•HCT, WBC and Platelet

GROUP B
(Referred for in-hospital care)
OR: Existing warning signs
Laboratory tests
• full blood count (FBC)
•Haematocrit (HCT)
Treatment
Obtain reference HCT before fluid therapy.
Give isotonic solutions such as 0.9% saline,
Ringer’s Lactate. Start with 5-7 ml/kg/hr for 1-2
hrs, then reduce to 3-5 ml/kg/hr for 2-4 hr, and
then reduce to 2-3 ml/kg/hr or less according to
clinical response.
Reassess clinical status and repeat HCT:
• if HCT remains the same or rises only minimally
-> continue with 2-3 ml/kg/hr for another 2-4 hrs;
•If worsening of vital signs and rapidly rising HCT
-> increase rate 5-10 ml/kg/hr for 1-2 hrs.
Reassess clinical status, repeat HCT and
review fluid Infusion rates accordingly:
• reduce intravenous fluids gradually when
the rate of plasma leakage decreases towards
the end of the critical phase.

SEVERE DENGUE
GROUP C
(Require emergency treatment)
Group Criteria
Patients with any of the following features:
• severe plasma leakage with shock and/or fluid accumulation with respiratory distress
•Severe bleeding
•Severe organ impairment
Laboratory tests
• full blood count
•Heamatocrit
•Other organ function tests as indicated
Treatment of compensated shock
Start IV fluid resuscitation with isotonic crystalloid solutions at 5-10ml/kg/hr over 1 hour.
Reassess patient’s condition.

If patient improves:
• IV fluids should be reduced gradually to 5-7 ml/kg/hr for 1-
2 hrs, then 3-5ml/kg/hr for 2-4 hrs, then to 2-3 ml/kg/hr for
2-4 hrs and then reduced further depending on hemolytic
status;
•IV fluids can be maintained for up to 24-48 hrs.
If patient is still unstable:
•Check hematocrit after first bolus;
•If HCT increases/still high (>50%), repeat a second bolus of
crystalloid solution at 10-20 ml/kg/hr for 1 hour.
•If there is improvement after second bolus, reduce rate to 7-
10 ml/kg/hr for 1-2 hrs and continue to reduce as above;
•If HCT decreases, this indicates bleeding and need to cross
match and transfuse blood as soon as possible,

Treatment of hypotensive shock
Treatment of hypotensive shock
Initiate IV fluid resuscitation with crystalloid or
colloid solution at 20 ml/kg as a bolus for 15 min.
If patient improves:
•Give a crystalloid/colloid solution of 10 ml/kg/hr for
1 hr, then reduce gradually as above.
If patient is still unstable:
• review the HCT taken before the first bolus;
•If HCT was low (<40% in children and adult
females, <45% in adult males) this indicates
bleeding. The need to cross-match and transfuse (see
above)
• If HCT was high compared to baseline value,
change to IV colloids at 10-20 ml/kg as a second
bolus over 30 min to 1 hr; reassess after second
bolus.
•If patient is improving reduce the rate to 7-10
ml/kg/hr for 1-2 hrs, then back to IV crystalloids and
reduce as rates as above;
•If patient’s condition is still unstable, repeat HCT
after second bolus.
•If HCT decreases, this indicates bleeding (see above)
•If HCT increases/remains high (>50%) continue
colloid infusion at 10-20 ml/kg as a third bolus over 1
hr, then reduce to 7-10 ml/kg/hr 1-2 hrs, then change
back to crystalloid solution and reduce rate as above.
Treatment of hemorrhagic complications
Give 5-10 ml/kg of fresh packed red cells or 10-20
ml/kg of fresh whole blood.

Discharge criteria
(all of the following conditions must be present)
Clinical No fever for 48 hrs.
Improvement in clinical
status (general well-being,
appetite, hemodynamic
status, urine output, no
respiratory distress).
Laboratory Increasing trend of platelet
count
Stable hematocrit without IV
fluids.

These are cytoplasmic inclusion bodies found in certain neurons in the
brain, and are diagnostic of rabies:
A. Negri bodies
B. Schuffner’s dots
C. Owl’s eye bodies
D. James stipplings
ANSWER:
A

 Acute viral disease of the CNS
 Transmitted to humans by infected animals
 Encephalitis
 Paralytic form of the disease
 Progresses to coma and death

 Member of the genus
Lyssavirus
 Family Rhabdoviridae
 Rhabdos : "rodlike“
distinctive elongated shape
of these viruses
 Enveloped virions
 Single-strand, nonsegmented,
negative-sense RNA
 Genome
- 11,932 nucleotides
- Encodes five proteins:
1. nucleocapsid
2.matrix
3.phosphoprotein
4.glycoprotein
5. RNA polymerase

 Transmitted to humans by the bite of a rabid animal
 Dogs : primary reservoir and vector for rabies
- Major source of transmission to humans in Asia and Africa
 Bats, raccoons, skunks, foxes
 Non bite exposures only rarely transmit rabies virus infection
 Exposures to aerosols in the laboratory or in caves containing
millions of bats have resulted in human rabies
 Transplanted corneal tissue , solid organs

Virus
inoculation
(Administration
of rabies PEP )
Viral
replication in
the muscle
Virus binds to
nicotinic acetylcholine
receptors at
neuromuscular
junction
Virus travels within
axons in peripheral
nerves via retrograde
fast axonal transport
Replication in motor
neurons of the spinal
cord and local dorsal
root ganglia and rapid
ascent to brain
Infection of brain
neurons with
neuronal dysfunction
Centrifugal spread
along nerves to
salivary glands, skin,
cornea and other
organs

 NEGRI BODIES
Eosinophilic cytoplasmic inclusions in brain neurons
Randomly oriented rabies virus nucleocapsids embedded
in an amorphous substance or matrix
Most commonly present in Purkinje cells of the cerebellum
and in pyramidal cells in the hippocampus
Negri bodies are rarely produced in infections caused by
laboratory variants of rabies virus
~80% of cases : wild, or "street," rabies infection
(+) Negri bodies
*** Absence of Negri bodies does not exclude the diagnosis

Phase Duration Signs/Symptoms
Incubation period 1–3 months None
Prodrome 1–7 days Fever, malaise, headache, nausea, vomiting,
agitation, focal paresthesias, pain
Acute neurologic phase
Encephalitic (80%) 1–7 days Fever, confusion, hallucinations, hyperactivity,
pharyngeal spasms (hydrophobia/aerophobia),
seizures
Paralytic (20%) 2–10 days Ascending flaccid paralysis
Coma/death 1–14 days . . .

 Fever, confusion, hallucinations, combativeness, muscle spasms,
hyperactivity, and seizures
 Autonomic dysfunction : hypersalivation, excessive perspiration,
gooseflesh, pupillary dilation, and/or priapism
 Episodes of hyperexcitability are typically followed by periods of
complete lucidity that become shorter as the disease progresses
 Brainstem involvement: hydrophobia and aerophobia

 Early and prominent muscle weakness
 Beginning in the bitten extremity - spreading to produce
quadriparesis and facial weakness

 Rabies-specific tests
 Diagnostically useful specimens: serum, CSF, fresh saliva, brain tissue
(when available), and skin biopsy samples from the neck
- Demonstration of rabies virus in cutaneous nerves at the base of hair
follicles
- Samples from the neck should include at least 10 hair follicles
 Multiple testing modalities are required to ensure a high negative
predictive values
 Serum antibodies often do not develop until very late in the disease

 Rabies Virus–Specific Antibodies
- suggests rabies regardless of immunization status
 Reverse Transcription Polymerase Chain Reaction (RT-PCR)
- highly sensitive and specific
- detect virus in fresh saliva samples, CSF, and tissue
- distinguish between rabies virus variants
 Direct Fluorescent Antibody (DFA) Testing
- highly sensitive and specific
- brain tissue or skin biopsies from the nape of the neck
- rabies virus can be detected in cutaneous nerves at the base of hair follicles

 No established treatment for rabies
 Fatal disease
 Almost always preventable with appropriate post exposure therapy
during the incubation period
 Most patients die within several days even with aggressive care in a
critical care unit

CATEGORY I
Petting, feeding ,licking of healthy skin with no open wound, no mucous membrane
contact (reliable Hx)
Unknown, escaped, sick, proven rabid or healthy animal
NO TREATMENT
except consider preexposure prophylaxis in a patient who is
concerned about or
is likely to have repeat exposure

CATEGORY II
superficial scratch/abrasion without break in skin or bleeding, nibbling of uncovered
skin, licking over broken skin or healing wounds.
Cat I w/ unreliable Hx
unknown, escaped,
sick, proven rabid animal
Healthy animal
VACCINE (FULL
COURSE)
Animal gets sick/dies
Sacrifice animal
VACCINE
OBSERVE FOR 10
DAYS
Animal remains
healthy
May opt to d/c
vaccine

Sacrifice animal
send head for laboratory exam
(FAT)*
negative
May
discontinue
treatment
positive
Complete
course

CATEGORY III
All head/neck exposures, single or multiple transdermal bites,
licking of mucous membrane unknown,
unknown, escaped,
sick, proven rabid animal
Healthy animal
RIG + VACCINE
(full course)
Remains healthy
May opt to d/c
vaccine
RIG + VACCINE
OBSERVE FOR 10
DAYS
Dies
CONTINUE
VACCINE

 Occupational or recreational risk of rabies exposures
 Travelers to rabies-endemic areas
 Primary schedule: days 0, 7, and 21 or 28
 When a previously immunized individual is exposed to rabies: two
booster doses of vaccine should be administered on days 0 and 3
 Wound care remains critical
 RIG should not be administered to previously vaccinated persons

SEXUALLY
TRANSMITTED
INFECTIONS

Which of the following is the etiologic agent of chancroid?
A.Treponema pallidum
B.Haemophilus ducreyi
C.Calymmatobacterium granulomatis
D.Neisseria gonorrhea
ANSWER:
B

MAJOR STD SYNDROMES AND SEXUALLY TRANSMITTED
MICROBIAL ETIOLOGIES
Syndrome ST Microbial Etiologies
AIDS HIV types 1 and 2
Urethritis: males Neisseria gonorrhoeae, Chlamydia trachomatis,
Mycoplasma genitalium, Ureaplasma urealyticum
(?subspecies urealyticum), Trichomonas vaginalis,
HSV
Epididymitis C. trachomatis, N. gonorrhoeae
Lower genital tract infections: females
Cystitis/urethritis C. trachomatis, N. gonorrhoeae, HSV
Mucopurulent cervicitis C. trachomatis, N. gonorrhoeae, M. genitalium
Vulvitis Candida albicans, HSV
Vulvovaginitis C. albicans, T. vaginalis
Acute pelvic inflammatory disease N. gonorrhoeae, C. trachomatis, BV-associated bacteria, M.
genitalium, group B streptococc
Ulcerative lesions of the genitalia HSV-1, HSV-2, Treponema pallidum, Haemophilus ducreyi,
C. trachomatis (LGV strains), Calymmatobacterium
granulomatis

URETHRITIS IN MEN
 Urethral discharge, dysuria, usually without frequency of urination
Neisseria gonorrhoeae
C. trachomatis
Mycoplasma genitalium
Ureaplasma urealyticum
Trichomonas vaginalis
HSV
adenovirus

INITIAL TREATMENT FOR PATIENT
AND PARTNERS
 Treat gonorrhea
(unless excluded):
Ceftriaxone, 125 mg IM; or
Cefpodoxime, 400 mg PO; or
Cefixime, 400 mg POa
 Treat chlamydial infection:
Azithromycin, 1 g PO; or
Doxycycline, 100 mg bid for 7
days
PLUS

URETHRITIS AND THE URETHRAL
SYNDROME IN WOMEN
 C. trachomatis, N. gonorrhoeae, HSV : urethral syndrome
"internal" dysuria (usually without urinary urgency or frequency)
Pyuria
absence of Escherichia coli and other uropathogens in urine at counts of 102/mL
• VULVAR HERPES OR VULVOVAGINAL CANDIDIASIS :
External dysuria : painful contact of urine with the inflamed or ulcerated labia or
introitus
• BACTERIAL CYSTITIS
Acute onset, urinary urgency or frequency, hematuria, or suprapubic bladder
tenderness

VULVOVAGINAL
INFECTIONS
Feature Normal Vaginal
Examination
Vulvovaginal
Candidiasis
Etiology Uninfected; lactobacilli
predominant
Candida albicans
Typical symptoms None Vulvar itching and/or
irritation
Discharge
Amount Variable; usually scant Scant
Color Clear or slightly white White
Consistency Nonhomogeneous,
floccular
Clumped; adherent
plaques

Feature Normal Vaginal
Examination
Vulvovaginal Candidiasis
Inflammation of vulvar or
vaginal epithelium
None Erythema of vaginal epithelium,
introitus; vulvar dermatitis, fissures
common
pH of vaginal fluidb Usually 4.5 Usually 4.5
Amine ("fishy") odor with
10% KOH
None None
Microscopyc Normal epithelial cells;
lactobacilli predominant
Leukocytes, epithelial cells; mycelia or
pseudomycelia in up to 80% of C. albicans
culture-positive persons with typical
symptoms
Usual treatment None Azole cream, tablet, or suppository—e.g.,
miconazole 100-mg vaginal suppository or
clotrimazole 100-mg vaginal tablet, once daily for 7
days
Fluconazole, 150 mg orally (single dose)
Usual management of
sexual partner
None None; topical treatment if candidal
dermatitis of penis is detected

Feature Trichomonal Vaginitis
Etiology Trichomonas vaginalis
Typical symptoms Profuse purulent discharge;
vulvar itching
Discharge
Amount Often profuse
Color White or yellow
Consistency Homogeneous

Feature Trichomonal Vaginitis
Inflammation of vulvar or vaginal
epithelium
Erythema of vaginal and vulvar epithelium;
colpitis macularis
pH of vaginal fluidb Usually 5.0
Amine ("fishy") odor with 10% KOH May be present
Microscopyc Leukocytes; motile trichomonads seen in 80–90% of
symptomatic patients, less often in the absence of
symptoms
Usual treatment Metronidazole or tinidazole, 2 g orally (single dose)
Metronidazole, 500 mg PO bid for 7 days
Usual management of sexual
partner
Examination for STD; treatment with
metronidazole, 2 g PO (single dose)

Feature Bacterial Vaginosis
Etiology Associated with Gardnerella vaginalis, various
anaerobic and/or noncultured bacteria, and
mycoplasmas
Typical symptoms Malodorous, slightly increased discharge
Discharge
Amount Moderate
Color White or gray
Consistency Homogeneous, low viscosity; uniformly
coats vaginal walls

Feature Bacterial Vaginosis
Inflammation of vulvar or
vaginal epithelium
None
pH of vaginal fluidb Usually >4.5
Amine ("fishy") odor with
10% KOH
Present
Microscopyc Clue cells; few leukocytes; no lactobacilli or only a
few outnumbered by profuse mixed flora, nearly
always including G. vaginalis plus anaerobic
species on Gram's stain (Nugent's score 7
Usual treatment Metronidazole, 500 mg PO bid for 7 days
Clindamycin, 2% cream, one full applicator
vaginally each night for 7 days
Usual management of
sexual partner
Examination for STD; no treatment if
normal

CLINICAL FEATURES OF GENITAL
ULCERS
Feature Syphilis Herpes Chancroid Lympho-granuloma
Venereum
Donovanosis
Etiologic agent Treponema pallidum HSV 1 and HSV 2 Haemophilus dcruyi Chlamydia
trachomatis
Klebsiella
granulomatis
(formerly
Calymmatobacteriu
m granulomatis)
Incubation period 9–90 days 2–7 days 1–14 days 3 days–6 weeks 1–4 weeks (up to 6
months)
Early primary
lesions
Papule Vesicle Pustule Papule, pustule, or
vesicle
Papule
No. of lesions Usually one Multiple Usually multiple,
may coalesce
Usually one; often
not detected, despite
lymph
adenopathy
Variable
Diameter 5–15 mm 1–2 mm Variable 2–10 mm Variable
Edges Sharply demarcated,
elevated, round, or
oval
Erythematous Undermined, ragged,
irregular
Elevated, round, or
oval
Elevated, irregular

Feature Syphilis Herpes Chancroid Lympho
granuloma
Venereum
Donovanosis
Depth Superficial or
deep
Superficial Excavated Superficial or
deep
Elevated
Base Smooth,
nonpurulent,
relatively
nonvascular
Serous,
erythematous
, nonvascular
Purulent,
bleeds easily
Variable,
nonvascular
Red and
velvety,
bleeds readily
Induration Firm None Soft Occasionally
firm
Firm
Pain Uncommon Frequently
tender
Usually very
tender
Variable Uncommon
Lymph
adenopathy
Firm,
nontender,
bilateral
Firm, tender,
often bilateral
with initial
episode
Tender, may
suppurate,
loculated,
usually
unilateral
Tender, may
suppurate,
loculated,
usually
unilateral
None;
pseudobuboes

INITIAL MANAGEMENT OF GENITAL
OR PERIANAL ULCER
 INITIAL TREATMENT
 Herpes confirmed or suspected (history or sign of vesicles):
Treat for genital herpes with acyclovir, valacyclovir, or famciclovir
• Syphilis confirmed (dark-field, FA, or PCR showing T. pallidum, or RPR reactive):
Benzathine penicillin 2.4 million units IM once to patient, recent (e.g., within 3 months)
seronegative partner(s), and all seropositive partners
• Chancroid confirmed or suspected (diagnostic test positive, or HSV and syphilis excluded,
and lesion persists):
Ciprofloxacin 500 mg PO as single dose or Ceftriaxone 250 mg IM as single dose or
Azithromycin 1 g PO as single dose

HUMAN
IMMUNODEFICIENCY
VIRUS (HIV)

Which of the following is the generally accepted indicator of immunologic
competence in patients with HIV infection?
ANSWER:
B
A. level of plasma viremia
B. CD4
+ T lymphocyte count
C. immunoglobulin level
D. PPD

 HIV infection/AIDS is a global pandemic
 Cases reported from virtually every country
 2007: 33.2 million individuals (range: 30.6–36.1 million) HIV/AIDS
 95% of people living with HIV/AIDS reside in low- and middle-income countries
 ~50% are female
 2.5 million: children <15 years

REVISED CLASSIFICATION SYSTEM FOR HIV INFECTION AND
EXPANDED AIDS SURVEILLANCE CASE DEFINITION FOR
ADOLESCENTS AND ADULTS
CD4+ T Cell
Categories
A
Asymptomatic,
Acute
(Primary) HIV
or PGL
B
Symptomatic,
Not A or C
Conditions
C
AIDS-Indicator
Conditions
>500/uL A1 B1 C1
200–499/uL A2 B2 C2
<200/uL A3 B3 C3

CATEGORY A:
Consists of one or more of the conditions listed
below in an adolescent or adult (>13 years)
with documented HIV infection
Conditions listed in categories B and C must
not have occurred.
Asymptomatic HIV infection
Persistent generalized lymphadenopathy
Acute (primary) HIV infection with
accompanying illness or history of acute HIV
infection
Clinical Categories of HIV Infection

 CATEGORY B: Consists of symptomatic conditions in an HIV-infected
adolescent or adult that are not included among conditions listed in clinical
category C and that meet at least one of the following criteria:
(1) The conditions are attributed to HIV infection or are indicative of a defect in
cell-mediated immunity
(2) the conditions are considered by physicians to have a clinical course or to
require management that is complicated by HIV infection. Examples include,
but are not limited to, the following: Bacillary angiomatosis Candidiasis,
oropharyngeal (thrush) Candidiasis, vulvovaginal; persistent, frequent, or
poorly responsive to therapy Cervical dysplasia (moderate or severe)/cervical
carcinoma in situ Constitutional symptoms, such as fever (38.5°C) or diarrhea
lasting >1 month Hairy leukoplakia, oral Herpes zoster (shingles), involving
at least two distinct episodes or more than one dermatome Idiopathic
thrombocytopenic purpura Listeriosis Pelvic inflammatory disease,
particularly if complicated by tuboovarian abscess Peripheral neuropathy

 CATEGORY C: Conditions listed in the AIDS surveillance case definition.
Candidiasis of bronchi, trachea, or lungs Candidiasis, esophageal Cervical
cancer, invasivea Coccidioidomycosis, disseminated or extrapulmonary
Cryptococcosis, extrapulmonary Cryptosporidiosis, chronic intestinal (>1
month's duration) Cytomegalovirus disease (other than liver, spleen, or
nodes) Cytomegalovirus retinitis (with loss of vision) Encephalopathy,
HIV-related Herpes simplex: chronic ulcer(s) (>1 month's duration); or
bronchitis, pneumonia, or esophagitis Histoplasmosis, disseminated or
extrapulmonary Isosporiasis, chronic intestinal (>1 month's duration)
Kaposi's sarcoma Lymphoma, Burkitt's (or equivalent term) Lymphoma,
primary, of brain Mycobacterium avium complex or M. kansasii,
disseminated or extrapulmonary Mycobacterium tuberculosis, any site
(pulmonarya or extrapulmonary) Mycobacterium, other species or
unidentified species, disseminated or extrapulmonary Pneumocystis
jiroveci pneumonia Pneumonia, recurrenta Progressive multifocal
leukoencephalopathy Salmonella septicemia, recurrent Toxoplasmosis of
brain Wasting syndrome due to HIV

ETIOLOGIC AGENT
 Lentivirus (a class of retrovirus)
- slow virus (take a long time to cause overt disease)
- target cells of the immune system  immunodeficiency
- 5 serogroups : primates, sheep and goats, horses, cats, and cattle.
 Two types of HIV:
1. HIV-1
2. HIV-2
*** These cause clinically indistinguishable disease, although the time to disease onset is longer
for HIV-2.
***The worldwide epidemic of HIV and AIDS is caused by HIV-1 while HIV-2 is mostly restricted
to west Africa.

HIV-1 binds to its target cell via the CD4
molecule, leading to a conformational change in
the gp120 molecule that allows it to bind to the co-
receptor CCR5 (for R5-using viruses).
The virus then firmly attaches to the host cell
membrane in a coiled-spring fashion via the newly
exposed gp41 molecule.

TRANSMISSION
 HIV is transmitted by:
homosexual and heterosexual contact
by blood and blood products
by infected mothers to infants either intrapartum, perinatally, or via
breast milk

PATHOPHYSIOLOGY AND
PATHOGENESIS
 Progressive quantitative and qualitative deficiency of the subset of T lymphocytes (helper T
cells)  profound immunodeficiency
 T cell (CD4 molecule): primary cellular receptor for HIV
 Co-receptor must be present together with CD4 for efficient fusion and entry of HIV-1 into
its target cells : CCR5 and CXCR4
- primary receptors for certain chemoattractive cytokines
 Mechanisms responsible for cellular depletion and/or immune dysfunction of CD4+ T cells :
direct infection and destruction by HIV
immune clearance of infected cells
immune exhaustion due to aberrant cellular activation and activation-induced cell death

Patients with CD4+ T cell levels below certain thresholds
are at high risk of developing a variety of opportunistic
diseases, particularly the infections and neoplasms that
are AIDS-defining illnesses

ACUTE INFECTION
(ACUTE
RETROVIRAL
SYNDROME)
 Lasts for 6 to 12 weeks after initial infection
until anti-HIV antibodies are detectable
 If acquired by sexual activity, the virus enters
the body in infected macrophages in semen or
vaginal secretions
 Dendritic cells in the mucosal linings bind the
virus shed by macrophages and carry it to the
lymph nodes where CD4+ T4 cells become
infected
 During the course of the disease, the virus
migrates to other cell types
 HIV infection produces a mild disease that is
self-limiting
 This is not seen in all patients and about 30%
remain asymptomatic during the initial period
of infection

LATENT
RESERVOIR
 As a result of the strong immune defense, the
number of viral particles in the blood stream
declines and the patient enters clinical latency
 Little virus can now be found in the bloodstream
or in peripheral blood lymphocytes
 The virus persists elsewhere (lymph nodes ) 
viral replication continues as follicular dendritic
cells interact with more CD4+ cells that become
infected
 Virus is detectable
 Latency period : > 10 years

LOSS OF CD4+ CELLS AND COLLAPSE OF
THE IMMUNE RESPONSE
 During the course of infection, there is a profound loss of the specific
immune response to HIV because:
responding CD4+ cells become infected. Thus, there is clonal deletion
leading to tolerance. The cells that proliferate to respond to the virus are
infected and killed by it
epitope variation can lead to escape of HIV from the immune response
activated CD4+ T cells are susceptible to apoptosis. Spontaneous apoptosis
of uninfected CD4+ and CD8+ T cells occurs in HIV-infected patients. Also
there appears to be selective apoptosis of HIV-specific CD8+ cells
the number of follicular dendritic cells falls over time, resulting in
diminished capacity to stimulate CD4+ cells

ONSET OF DISEASE - AIDS
Rare in less than 3 years except in children
Virus can no longer be controlled as helper CD4+ (T4) cells
are destroyed
As the CD4+ cells fall below 200/cubic mm, virus titers
rise rapidly and immune activity drops precipitously
It is the loss of immune competence that enables normally
benign opportunistic parasites such as viruses, fungi or
protozoa to cause infections

AIDS DEFINING
DISEASE
 Candidiasis of the esophagus, trachea, bronchi, or lungs
 Cryptococcosis, extrapulmonary
 Cryptosporidosis with diarrhea persisting more than 1 month
 Cytomegalovirus disease of an organ other than liver, spleen, or lymph nodes in a patient of more than
one month of age
 Herpes simplex virus infection causing a mucocutaneous ulcer that persists longer than 1 month; or
bronchitis, pneumonitis, or esophagitis for any duration affecting a patient of more than one month of age
 Kaposi's sarcoma affecting a patient less than 60 years of age
 Lymphoma of the brain (primary) affecting a patient less than 60 years of age
 Lymphoid interstitial pneumonia and/or pulmonary lymphoid hyperplasia (LIP/PLH complex) affecting a
child less than 13 years of age
 Mycobacterium avium complex or M. kansasii disease, disseminated (at a site other than or in addition to
lungs, skin, or cervical or hilar lymph nodes)
 Pneumocystis carinii pneumonia
 Progressive multifocal leukoencephalopathy
 Toxoplasmosis of the brain affecting a patient more than one month of age

CELLS THAT ARE INFECTED
BY HIV
CD4+ T4 helper cells
Natural Killer cells
CD8+ Killer T cells
Macrophages
Cells of the nervous system
Dendritic cells

DIAGNOSIS OF HIV INFECTION
 demonstration of antibodies to HIV and/or the direct detection of HIV or
one of its components
 antibodies to HIV generally appear in the circulation 2–12 weeks
following infection
 standard blood screening test: ELISA (EIA)
 Most commonly used confirmatory test : Western blot

LABORATORY
MONITORING
CD4+ T Cell Counts: best indicator of the immediate state
of immunologic competence of the patient with HIV
infection
HIV RNA Determinations
HIV Resistance Testing
Co-Receptor Tropism Assays

ANTIRETROVIRAL DRUGS USED IN THE
TREATMENT OF HIV INFECTION
Reverse Transcriptase Inhibitors
 Zidovudine (AZT, azidothymidine, Retrovir, 3'azido-3'-deoxythymidine
 Didanosine (Videx, Videx EC, ddI, dideoxyinosine, 2',3'-dideoxyinosine)
 Stavudine (d4T, Zerit, 2'3'-didehydro-3'-dideoxythymidine)
 Lamivudine (Epivir, 2'3'-dideoxy-3'-thiacytidine, 3TC)
 Emtricitabine (FTC, Emtriva)
 Abacavir (Ziagen)
 Tenofovir (Viread)
 Delavirdine (Rescriptor)
 Nevirapine (Viramune)
 Efavirenz (Sustiva)

Protease Inhibitors
Saquinavir mesylate (Invirase—hard gel capsule)
Ritonavir (Norvir)
Indinavir sulfate (Crixivan
Nelfinavir mesylate (Viracept)
Amprenavir (Agenerase)
Fosamprenavir (Lexiva)
Lopinavir/ritonavir (Kaletra
Atazanavir (Reyataz)
Tipranavir (Aptivus)
Darunavir (Prezista)

Entry Inhibitors
Enfuvirtide (Fuzeon)
Maraviroc (Selzentry)
Integrase Inhibitor
Raltegravir (Isentress)

INDICATIONS FOR CHANGING
ANTIRETROVIRAL THERAPY IN
PATIENTS WITH HIV INFECTION
 Less than a 1-log drop in plasma HIV RNA by 4 weeks
following the initiation of therapy
 A reproducible significant increase (defined as 3-fold or
greater) from the nadir of plasma HIV RNA level not
attributable to intercurrent infection, vaccination, or
test methodology
 Persistently declining CD4+ T cell numbers
 Clinical deterioration
 Side effects

Pneumonia
TB
Asthma
COPD
Pleural Effusion

According to the Philippine Clinical Practice Guidelines on CAP, the basis for
the diagnosis of pneumonia is established by:
A.when cough has been present for two weeks
B.clinical findings alone
C.radiologic diagnosis to confirm the diagnosis
D.by sputum G/S and C/S done routinely
ANSWER:
C

 Infection of the pulmonary parenchyma caused by various bacterial
species, virus, fungi and parasites
• Not a single disease, but a group of specific infection, each having
different epidemiology, pathogenesis, clinical manifestations and clinical
course.

TRANSMISSION
Aspiration
Inhalation
Hematogenous

Aspiration
Most common mechanism
50% of healthy adults aspirate oropharyngeal secretions during
sleep
Common pathogens in the nasopharynx: S. pneumoniae, S.
pyogenes, M. pneumoniae, H. influenzae, Moraxella catarrhalis
Source of anaerobic pulmonary pathogen: gingival crevice and
dental plaque (contain > 10 11 cfu/gm)
Aerobic Gm (-) bacillary colonization increases with
hospitalization, worsening debility, severe underlying illness,
alcoholism, DM, advanced age
 Due to increased salivary proteolytic activity w/c destroys fibronectin (receptor for
normal Gm (+) flora of oropharynx)

Factors that increase risks for aspiration:
 Alcoholics
 Stroke patients
 Seizure
 Drug abusers
 General anesthesia

Inhalation of infectious aerosols
 Size factor:
 >10 um diameter = nose and upper airway
 <5 um diameter (airborne) =deposited in small bronchiole and alveoli
Etiologies acquired by inhalation:
 TB
 Influenza
 Legionella
 Psittacosis
 Histoplasma
 Q fever
Inhalation

 Dissemination from an extrapulmonaty site
 Eg: staph aureus- IV drug user, abscess
 Fusobacterium – from retrophangeal tissue
 Direct inoculation and contiguous spread
 Eg: stab wound, tracheal intubation
 Contiguous spread from adjacent site of infection
Hematogenous

ETIOLOGY
Factors that determine the etiologic agent
1. Setting from which infection is acquired
 Community
 Hospital
2. Age
3. Comorbid condition

Community acquired infection:
 Streptococcus pneumonia
 Haemophilus influenza
 Chlamydia pneumonia
 Mycoplasma pneumonia
Hospital Acquired Pneumonia (HAP)
 Staphyloccocus aureus- < 10% of HAP
 Enteric Gm (-) bacilli & Pseudomonas aeruginosa- >50% of HAP
Water storage system with warm temp, stagnation and
sediment accumulation:
 Legionella species

Age Factor:
Infants < 6 months:
RSV
Chlamydia trachomatis
6 months to 5 years:
H. influenza
Young adults:
M. pneumonia
C. pneumonia
Hantavirus
Elderly
H. influenza
M. catarhallis
Co-morbidities
HIV
Pneumocystis carinii
M. tuberculosis

PATHOLOGY
Site of inflammation:
Interstitium
Alveoli
Lobar pneumonia- involves the entire lobe
Bronchopneumonia- alveoli continuous to bronchi
Necrotizing pneumonia- multiple cavities < 2 cm in diameter
Lung abscess- one or more cavities > 2 cm in diameter

CLINICAL MANIFESTATION
Community Acquired Pneumonia
 Atypical
 Typical
Nosocomial Pneumonia
Aspiration Pneumonia

Atypical Pneumonia
Syndrome
Typical Pneumonia Syndrome
Etiology M. pneumonia, Legionella
sp, C. pneumonia, viruses
S. pneumonia, H. influenza,
Klebsiella sp, mixed aerobic &
anaerobic oral flora
Onset gradual Abrupt
Cough Dry cough Productive cough
Sputum scanty Purulent
Pulmonary signs
and symptom
Shortness of breath Shortness of breath, pleuritic
chest pain, sign of pulmonary
consolidation, rales
Extrapulmonary
symptoms
Prominent (headache,
myalgia, fatigue, nausea,
vomiting, diarrhea)
Not prominent

Nosocomial Pneumonia
Occurrence of the following findings >48 hrs after
hospital admission:
New or progressive pulmonary infiltrate
Purulent tracheobronchial secretion
Fever
Leukocytosis

Aspiration Pneumonia
Sudden onset of dyspnea, wheezing, hypoxemia
CXR: Infiltrate in the right lower lobe
Result in putrid sputum, tissue necrosis & pulmonary cavities
Etiology:
Oropharygeal pathogen
 Anaerobes
Chemical Pneumonitis

LABORATORY
EXAMINATION
A. Chest X ray (PA-Lateral views)
 New parenchymal infiltrate
 Confirms the diagnosis
 Assess the severity / prognostication
 May suggest the etiology
DIAGNOSIS
History and Physical examination
 60% accuracy

B. Sputum Examination
 Gram stain
 Good specimen: >25 PMN; <10 epith cell per LPF
 Sensitivity: 60-80%
 Specificity: 85% in identifying pneumococcus
 Culture
 40-60% specificity
 BAL, TTA, PSB, LA
 not routinely done
 Better specificity
C. Serologic Test
 Urinary antigen test
 Legionella pneumophila
 Indirect immunoflourescence
 IgM>1:20, IgG>1:128 – diagnostic for Chlamydia pneumoniae
 IgM>1:16, IgG>1:128 - diagnostic of Mycoplasma peumoniae
D. Blood Culture- Gold standard in Dx of Pneumonia
E. Other tests
 CBC, electrolytes, liver function, creatinine
 Arterial Blood Gas

PATIENT RISK
STRATIFICATION
Different Guidelines
ATS 2001
IDSA 2003
Diagnosis, Empiric Management and Prevention
of Community-Acquired Pneumonia in
Immunocompetent Adults 2016 Update
Treatment

Diagnosis, Empiric Management and Prevention of
Community-Acquired Pneumonia in Immunocompetent
Adults 2016 Update Treatment

EMPIRIC TREATMENT
 LOW RISK CAP
Previously healthy: amoxicillin or extended macrolide, alternative: cotrimoxazole
with stable co morbid illness: co-amoxiclav or sultamicillin or 2nd gen
cephalosporin + extended macrolide
MODERATE RISK CAP
- IV non antipseudomonal B lactams (BLIC, cephalosphorin) + extended macrolide OR
respiratory fluoroquinolone
HIGH RISK CAP
No risk for P. aeruginosa: IV non-antipseudomonal B lactam (BLIC,
cephalosphorin, carbapenem) + IV extended macrolide OR IV respiratory
fluoroquinolone
W/ risk of P. aeruginosa: IV antipneumococcal antipseudomonal B lactam (BLIC,
cephalosphorin, carbapenem) + IV extended macrolide + aminoglycoside OR IV
antipeumoccocal, antipseudomonal B lactam (BLIC, cephalosphorin or carbapenem) +
IV ciprofloxacin or high dose IV levofloxacin

Which antimycobacterial agent should be stopped if the patient
develops gouty arthritis?
ANSWER:
D
A. Rifampicin
B. Isoniazid
C. Ethambutol
D. Pyrazinamide

FROM EXPOSURE TO
INFECTION
 MOT: inhalation of droplet nuclei
 Droplet nuclei
 Aerosolized by coughing, sneezing, speaking.
 Tiny droplets dry rapidly
 Smallest droplets (<5um) is more effective in transmitting infection.
 Cavitary, endobronchial, laryngeal or AFB (+)
 Other routes (skin, placenta) are uncommon & of no epidemiologic significance
 Crowding in poorly ventilated rooms is important in transmission (increases intensity of
contact)
 Transmission is largely dependent on exogenous or environmental factors

RISK FACTORS FOR DEVELOPING
TUBERCULOSIS
 HIV/AIDS
 CD4 count
 Silicosis
 Lymphoma
 Leukemia
 Malignancy
 Hemophilia
 malnutrition
 CRF & hemodialysis
 Diabetes mellitus
 Immunosuppressive therapy
 Organ transplantation
 Old, self-healed fibrotic TB
lesions

PATHOPHYSIOLOGY
Cell-mediated Immunity:
 Alveolar macrophages secrete:
 Interleukin (IL)4- contributes fever
 IL-6: contributes to
hyperglobulinemia
 Tumor necrosis factor α (TNF- α)
 Killing of MTb
 Granuloma formation
 Fever, weight loss
 CD4 lymphocytes
 Lymphokines
Delayed-type hypersensitivity
 Basis of PPD test (the only
reliable test that detects
asymptomatic infection
 PPD reactivity: mainly related to
previously sensitized CD4+
lymphocytes attracted to the skin-
test site

Day Pathogenetic Events in Tuberculosis
0 M. Tb deposits in alveoli or terminal airways.
This usually occurs in the lower lobes since
inhaled air is preferentially delivered to the
lower lobes.
< 5 Macrophage (MC) phagocytize M. Tb but unable
to kill it (needs sensitization from past infection).
5-10 Infected MCs bring M. Tb to the regional nodes.
Chest xray at this may show the Ranke’s
complex (peripheral pnuemonitis (Ghon’s focus),
lymphangitis and hilar adenopahthy).
Minimal if any symptoms are experienced at this
time, hence, this stage of the disease usually
goes on undetected
11-20 M. Tb reaches the circulation from the
lymphatics. This bacteremia seeds all organs
including the lungs again. Hence, primary TB is
a bacteremic disease!
Infected
Droplet
1- 5
5 -10
R
(Day 0)

Day Pathogenetic Events in Tuberculosis
3-6 wks Cell mediated immunity develops (PPD now (+)
). M. Tb bacilli killed but a few managed to
survive in semi-dormancy inside granulomas
(latent TB) at seeded sites
Re-
activation
day
Sometime in the future: immune system falters.
Surviving M. Tb in the seeded sites undergo
rapid multiplication (secondary TB). High O2
tension areas favored: upper lungs and superior
segments of lower lobes. Other sites also
reactivate if immune system becomes severely
compromised.
Infected
Droplet
1- 5
5 -10
R
(Day 0)

CLINICAL
MANIFESTATION
2. Post primary TB
 Adult-type, reactivation, or secondary
 Reactivation of latent infection
 Late adolescent, early adulthood, &
elderly
 Chest X-ray
 Apical & posterior segments UL
 Superior segment LL
 Infiltrates, cavitations
 Tuberculous pneumonia
 Fibrotic lesions, calcifications

SIGNS & SYMPTOMS
Symptoms
 Non-specific, insidious
 Fever
 night sweats
 Anorexia
 weight loss
 Malaise & weakness
 Cough, dry to productive
 Hemoptysis
 Rasmussen’s aneurysm
(rupture of dilated vessel in a
cavity)
 Aspergilloma
Signs
 Normal
 Crackles or rales
 Rhonchi
 Atelectasis
 Effusion
 Mild anemia,
leukocytosis
 Hyponatremia,
SIADH
 Mimics other
diseases

EXTRA-PULMONARY TUBERCULOSIS
50% - NO EVIDENCE OF LUNG PARENCHYMAL LESION ON CHEST X-
RAY
 Pleura
 Penetration of TB bacilli
 Effusion is common
 PF AFB-low yield
 PF Culture(+)-1/3
 Pleural biopsy/culture-70%
 CNS
 Lymphatic system
 Cervical & supraclavicular
 AFB(+) 50%
 Culture (+) 70-80%
 GIT
Genitourinary systems
Bones and joints
Spine (thoraco-lumbar), hips, knee
Pott’s dse/TB spondylitis
Upper thoracic-children
Lower thoracic & upper lumbar-adults
Disseminated (miliary TB)
Millet seeds (CXR)
AFB(-) 80%
PPD (-) 50%
Choroidal tubercles-
pathognomonic for miliary TB

 Presumptive TB – A patient who presents with symptoms or signs (radiologic
findings) suggestive of TB (replaces the term TB suspect or TB symptomatic).
 Bacteriologically confirmed case of TB – A patient from whom a biological
specimen is positive by smear microscopy, culture or WHO-approved rapid
diagnostic test (such as Xpert® MTB/RIF). All such cases should be notified,
regardless of whether TB treatment is started.
 Clinically diagnosed case of TB – A patient who does not fulfill the criteria for
bacteriologically confirmed TB but has been diagnosed with active TB by a
clinician or other medical practitioner who has decided to give the patient a full
course of TB treatment (based on imaging studies, suggestive histology and extra-
pulmonary cases without laboratory confirmation). Clinically diagnosed cases
subsequently found to be bacteriologically positive (before or after starting
treatment) should be reclassified as bacteriologically confirmed
CPG Diagnosis, Treatment, Prevention and Control of TB in
Adult Filipinos 2016 Update

 Case of pulmonary TB – Any bacteriologically confirmed or clinically diagnosed
case of TB involving the lung parenchyma or the tracheobronchial tree. A patient
with both pulmonary and extra-pulmonary TB should be classified as a case of
pulmonary TB.
 Case of extra-pulmonary TB – Any bacteriologically confirmed or clinically
diagnosed case of TB involving organs other than the lungs, e.g. abdomen,
genitourinary tract, joints and bones, lymph nodes, meninges, pleura, skin.

 TB culture remains the gold standard for TB diagnosis.

For the diagnostic evaluation of PTB, two (2) sputum specimens should be obtained for DSSM.
(Strong recommendation, moderate quality evidence)
Same day (spot-spot) strategy using 2 consecutive specimens collected 1-hour apart is
recommended for direct Ziehl-Neelsen microscopy (Strong recommendation, moderate quality
evidence)
How many sputum specimens should be collected? What should be the
timing of sputum collection?
The NTP MOP requires at least 1 teaspoonful (5-10mL) for DSSM.
 Direct Sputum Smear Microscopy (DSSM)

• As initial diagnostic test in adults with presumptive TB
• As follow-on test to smear-negative patients with chest x-ray findings suggestive
of active PTB
• As initial diagnostic test for presumptive drug-resistant TB
• In comparison with smear microscopy, Xpert® MTB/Rif increased TB detection
among culture-confirmed cases by 23%
When should Xpert® MTB/Rif be requested? How accurate is Xpert® MTB/Rif
in confirming PTB?
 Xpert® MTB/Rif

• There are no radiographic findings considered specific for active TB. Clinical
correlation, together with bacteriologic confirmation, is required to assess activity
BEFORE initiation of full course of appropriate treatment
• Together with a good clinical history, a good quality chest x-ray flm is needed to
initially guide the clinician in the identifcation of presumptive PTB for further
bacteriologic confrmation
 Chest Xray

 New Case – patient who has never been treated for TB or has taken antiTB drugs for less
than 1 month.
 Retreatment Case – patient who has received 1 month or more of anti-TB drugs in the past
(excluding prophylaxis or treatment for latent TB infection), further classified by the
outcome of most recent course of treatment, as follows:
• Relapse – patient has previously been treated for TB, declared cured or treatment
completed at the end of most recent course of treatment, and is now
diagnosed with a recurrent episode of TB (either a true relapse or a new
episode of TB caused by reinfection

 Treatment after failure – patient has previously been treated for TB and declared
treatment failed at the end of most recent course of treatment
 • Treatment after lost to follow-up (TALF) – patient has previously been treated for TB,
declared lost to follow-up at the end of most recent course of treatment (previously known
as Return After Default)
 • Previous Treatment Outcome Unknown (PTOU) – patient has previously been treated for
TB but outcome after their most recent course of treatment is unknown or undocumented

TREATMENT
 Short-course regimen
1. Initial, intensive or bactericidal phase (2m)
 Majority of bacilli are killed
 Symptoms resolve
 Patient becomes noninfectious
2. Maintenance, continuation or sterilizing phase
(4m)
 Eliminate semi-dormant “persisters”

 FIRST LINE ESSENTIAL DRUGS
Isoniazid – bactericidal, extra-cellular
Rifampicin – bactericidal, extra/intra-cellular
 FIRST LINE SUPPLEMENTAL DRUGS
Pyrazinamide – weakly bactericidal, w/in
macrophages, acute inflammation
Ethambutol – bacteriostatic/cidal at higher doses;
extra/intra cellular
Streptomycin - bactericidal

 SECOND-LINE DRUGS
PAS (para-amino salicylic acid)
Ethionamide
Cycloserine
Kanamycin
Capreomycin
 ALTERNATIVE DRUGS
Quinolones
Macrolides
Rifamycin
Clofazimine
TREATMENT

ADVERSE REACTIONS TO
FIRST LINE DRUGS
Isoniazid
 Hepatitis, peripheral neuritis, neuropathy, hypersensitivity
Rifampicin
 Orange discoloration of body fluids, N/V, hepatitis, rash
Pyrazinamide
 Hepatotoxicity, hyperuricemia
Ethambutol
 Optic neuritis, dec red-green color discrimination, dec visual acuity, rash
Streptomycin
 Ototoxicity, nephrotoxicity

ADVERSE REACTION TO
SECOND-LINE DRUGS
 Capreomycin
 Auditory, vestibular & renal toxicity
 Kanamycin
 Auditory & renal toxicity
 Ethionamide
 Hepatoxicity, hypersensitivity, GI disturbance
 PAS
 GI disturbance, hypersensitivity, hepatoxicity
 Cycloserine
 Psychosis, personality changes, convulsions, rash

Which of the following statements is TRUE regarding asthma?
ANSWER:
D
A. Heterogeneous disease characterized by chronic airway
inflammation
B. Symptoms are often worse at night
C. Positive Bronchodilator Reversibility Test
D. All of the above

 Heterogeneous disease characterized by chronic airway inflammation.
 History of respiratory symptoms such as wheeze, shortness of breath, chest
tightness and cough that vary over time and in intensity, together with variable
expiratory airflow limitation
 Asthma phenotypes: recognizable clusters of demographic, clinical and or
pathophysiological characteristics
 Usually associated with airway hyperresponsiveness and airway inflammation,
but these are not necessary to make the diagnosis

 What is ASTHMA CONTROL?
 Extent to which the manifestations of asthma can be observed in the patient or
have been reduced or removed by treatment.
 Two domains: Symptom control and future risk of adverse outcomes
 Retrospectively assessed, after 2-3 months of treatment
 Distinguish between severe asthma and uncontrolled asthma, e.g. incorrect
inhaler technique

 MILD ASTHMA
controlled with low dose ICS or as needed ICS-formoterol
 MODERATE ASTHMA
controlled with low or medium dose ICS-LABA
 SEVERE ASTHMA
uncontrolled despite optimized treatment with high dose ICS-LABA

 To achieve good control of symptoms and maintain normal activity levels
 To minimize the risk of asthma related death, exacerbations, persistent airflow
limitation and side effect
 The patient’s own goals regarding their asthma and its treatment should also be
identified.

 CONTROLLER MEDICATIONS:
Inhaled corticosteroids (ICS)
Reduce airway inflammation, control symptoms
Reduce future risk of exacerbations and decline in lung function
Dose and regimen are optimized minimize the risk of medication side effects
 RELIEVER MEDICATIONS:
For as needed relief of breakthrough symptoms (worsening asthma or exacerbations)
As needed ICS-formoterol or SABA*
 ADD-ON THERAPIES FOR PATIENTS WITH SEVERE ASTHMA
Patients with persistent symptoms and or exacerbations despite optimized treatment
with
high dose controller medications.

CHRONIC
OBSTRUCTIVE
PULMONARY DISEASE

A 60-year old male, 30-pack year smoker came in due to chronic cough and
mild exertional dyspnea for 3 years. He self medicated with mucolytic but afforded
no relief. On PE occasional wheezes and rhonchi were noted. What is the diagnosis?
ANSWER:
B
A. Pulmonary Tuberculosis
B. Chronic Obstructive Pulmonary Disease
C. Bronchial Asthma
D. Pneumonia

 disease state characterized by airflow limitation that is not fully
reversible
 Emphysema: an anatomically defined condition characterized by
destruction and enlargement of the lung alveoli.
 Chronic bronchitis: a clinically defined condition with chronic cough
and phlegm;
 Small airways disease: a condition in which small bronchioles are
narrowed

 Airflow limitation
 the major physiologic change in COPD
 also known as airflow obstruction is typically determined by spirometry
 chronically reduced ratio of FEV/FVC
In contrast to asthma， the reduced FEV， in COPD seldom shows large responses to inhaled
bronchodilators
 Hyperinflation
 in COPD there is often “air trapping” (increased residual volume and increased ratio of
residual volume to total lung capacity) and progressive hyperinflation (increased total
lung capacity) late in the disease.
 Gas Exchange
 Nonuniform ventilation and ventilation-perfusion mismatching are characteristic of
COPD

 Cigarette smoking – major environmental factor for COPD
 Airway responsiveness
 Occupational exposure
 Respiratory Infections
 Ambient Air pollution
 Passive, or second hand smoking
 Genetic consideration: alpha 1 anti trypsin deficiency

Which of the following diseases can present as an
exudative pleural effusion?
ANSWER:
D
A. Congestive Heart
Failure
B. Cirrhosis
C. Nephrotic Syndrome
D. Chylothorax

A pleural effusion is present when there is an excess quantity of
f1uid in the pleural space.
Transudative pleural effusion occurs when systemic factors that
inf1uence the formation and absorption of pleural f1uid are
altered.
Exudative pleural effusion occurs when local factors inf1uence
the formation and absorption of pleural f1uid are altered.

 1. Pleural f1uid protein/serum protein >0.5
 2. Pleural f1uid LDH/serum LDH >0.6
 3. Pleural f1uid LDH more than two-thirds the normal upper limit for
serum
Exudative pleural effusions meet at least one of the following criteria，
whereas transudative pleural effusions meet none

GI bleeding
Peptic Ulcer Disease
Inflammatory Bowel Disease vs. Irritable Bowel Syndrome
Viral Hepatitis

Which of the following is the best parameter used to initially
assess a patient with GI bleeding?
ANSWER:
A
A.Heart and blood pressure
B.Oxygen saturation
C.Hgb and Hct
D.None of the above

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