USTNotesGroup2009 • Sites: urethra, anal canal, conjunctivas, pharynx and endocervix

Micro Case 1-10 arrange by A. Abad Neisseria gonorrhea

Case 1-8 from Sec C, Case 9 from Sec A, Case 10 by Sec C/A1 Epidemiology
• Worldwide
Microbiology Case 1 • Transmitted by sexual contact often by women and men with
asymptomatic infection
A 14 year old male sought consult at the Out Patient Department
• Gonococcal pharyngitis results usually from orogenital contact
because of high fever and sore throat of 4 days duration.
Neisseria gonorrhea
Accompanying symptoms were headache, chills and nasal discharge,
• Risk factors: sexual behavior, illness behavior and accessibility to health
which was initially watery becoming mucopurulent. He is fond of
blowing his nose one nostril at a time. Two days after, he complained care
of pain on his right ear. • 20% of homosexual men or heterosexual women who engage in fellatio
with men who have urethral infection
PE showed an awake, alert, irritable patient. VS: T = 39°C, Incidence in:
RR=20/min CR=100/min, pink palpebral conjunctivae, non icteric • Heterosexual men: 0.2-1.4%
sclerae, throat congested, exudates on tonsillar areas. • Homosexual men: 5-25%
• Women: 5-18%
Otoscopy showed congested ear drum on the right ear. There was
tenderness on the area of the frontal and maxillary sinuses. Other Pathogenesis of N. gonorrhea
systems were unremarkable. • Attack mucous membranes of the genitourinary tract, eye, rectum and
throat
1. Diagnosis o Producing acute suppuration that might lead to tissue invasion
Viral Patient Bacterial • Followed by chronic inflammation and fibrosis
Anterior Fever Fever o In males – urethritis with yellow creamy pus and painful
stoma-titis Sore Throat Pharyngeal urination or may be asymptomatic
Conjunct- Chills erythema o In females – primary infection in the endocervix, urethra and
ivitis Nasal Discharge and swelling vagina; mucupurulent discharge
Coryza Exudates on Tonsillar
Cough tonsillar areas exudates Neisseria meningitidis
Hoarseness Pain on R ear Complication: Pathogenesis
Fatigue / Congested ear Otitis Media • Humans are the only hosts
malaise drum on R ear Palatal
• Nasopharynx is the portal of entry
Diarrhea Tenderness on petechiae
Absence of frontal and No rhinorrhea • Organisms may form part of the transient flora without producing
Fever maxillary sinuses No cough symptoms or may produce an exudative pharyngitis
No conjunct-
tivitis Moraxella catarrhalis
2. Common Etiologic Agents • Previously Branhamella catarrhalis
• Streptococcus pyogenes*
• Neisseria gonorrhea • Morphologically and biochemically resembles Neisseria
• Neisseria meningitidis • Aerobic coccobacilli and oxidase positive
• Moraxella catarrhalis • Fails to utilize carbohydrates in CTA reactions
• Epstein-Barr virus • DNase positive and produces beta-lactamases
• Normal member of the flora of the respiratory tract, particularly
Streptococcus pyogenes nasopharynx, and do not produce disease
• Gram (+) cocci • Causes bronchitis, pneumonia, pharyngitis, sinusitis, otitis media and
• Groups A streptococcus conjunctivitis
• Contains the groups A antigen • Infect immunocompromised individuals
• Beta hemolytic
Epstein Barr Virus
• Associated with local or systemic invasion and poststreptococcal
• Human herpesvirus 4
disorders
• PYR positive • Gammaherpesvirinae
• Streptococcus pyogenes • Ubiquitous
• Has 2 types: EBV-1 & EBV-2
Epidemiology • Targets B lymphocyte
• Members of the normal flora of the human body
• Produce disease only when they occur in parts where they are Epidemiology
not normally found • Common in all parts of the world
• Transmitted by contact with oropharnyngeal secretions
Pathogenesis of S. pyogenes • 90% of adults are seropositive
• Pyogenic inflammation • In developing countries, 90% of children are infected at age 6
• Locally at the site of the organism in the tissue • Industrialized nations, more than 50% are delayed until late adolescence
• Exotoxin production and young adulthood
• Widespread systemic symptoms • 100,000 cases of infectious mononucleosis annually in US
• Immunologic • Inapparent infections result to permanent immunity to infectious
• When antibody against a component of the organism cross- mononucleosis
reacts with normal tissue or forms immune complexes that • Immunocompromised people at highest risk for neoplastic disease
damage normal tissue
Pathogenesis of EBV
Diseases caused by S. pyogenes Primary Infection
• Pyogenic diseases • Transmitted by infected saliva
o Pharyngitis • Initiates infection through oropharynx
o Cellulitis and erysipelas • Viral replication through epithelial cells of the salivary glands and
o Impetigo pharynx
• Toxigenic diseases • Children - Subclinical
o Scarlet fever • Young adults -Acute infectious mononucleosis
o Toxic shock syndrome Reactivation from Latency
• Immunologic diseases • Increased levels of virus in saliva
o Rheumatic fever • Increased levels of virus in DNA blood cells
o Acute glomerulonephritis • Clinically silent
• Can be activated by immunosuppression
Neisseria gonorrhea
• Gram-negative diplococci Tumors of EBV
• Nonmotile and nonsporforming • Burkitt’s lymphoma
• Oxidase-positive • Nasopharyngeal carcinoma
• Humans are the only hosts o Elevated levels of virus-specific antigens

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 o Contains EBV DNA
o Express limited number of viral genes Disease Accompanying Radiologic
• Hodgkin’s disease Symptoms Findings
• B-cell lymphoma Chronic Mucopurulent sputum, Obvious bullae,
o Immunodeficient patients Bronchitis chronic paucity of
Exertional dyspnea parenchymal
3. Laboratory Procedures markings,
Gram stain Pneumonia Fevers and chills Infiltrates
• Gram-positive cocci often singly or in pairs rather than definite Pleuritic chest pain (localized
chains. Shrotness of breath opacification)
• May appear Gram-negative if bacteria are no longer viable.
Disease Accompanying Radiologic
• Rarely contributory to diagnosis since group A streptococci
Symptoms Findings
cannot be differentiated from viridans streptococci which are
normally present in the throat.
Lung Abscess Putrid smell of sputum Presence of cavity
Throat culture Weight loss with air-fluid level
• Most confirmatory diagnostic test for streptococcal pharyngitis Malaise, night sweats,
• Culture technique fever
o Inoculum from throat swab Clubbing of fingers if >3
o 5% blood agar weeks
Bronchiectasis Copious mucus Normal in mild
o Bacitracin disk (0.04 units)
production disease
o Incubated overnight at 35-37 C o
Dyspnea and wheezing Prominent cystic
• Results: spaces
o Beta-hemolysis around colonies
o Inhibited by bacitracin
• Additional test: PYR test
o Detects presence of the enzyme L-pyrroglutamyl- Pulmonary Dyspnea Normal to near-
aminopeptidase. Embolism Pleuritic chest pain normal
Low grade fever Weatermark’s sign
Antigen Detection Tests Syncope and cyanosis (if (focal oligemia)
• For rapid detection of group A streptococcal antigen from throat massive) Hampton’s hump
swabs (peripheral wedge-
shaped density
• EIA or agglutination to demonstrate presence of antigen
above the
• 60-90% sensitive and 98-99% specific compared to culture diaphragm)
methods Palla’s sign
(enlarged right
4. Possible Complications
• Suppurative Complications: Amoxicillin – penicillinase sensitive
o Acute otitis media Susceptible Organisms:
o Sinusitis
o Cervical lymphadenitis Common streptococci, menigococci, gram-positive bacilli, spirochetes
o Peritonsillar or retropharyngeal abscess Enterococci, Listeria monocytogenes, Escherichia coli, Proteus mirabilis,
o Bacteremia Haemophilus influenzae, Moraxella catarrhalis
o Necrotizing fasciitis
o Mastoiditis Probable Diagnosis:
o Meningitis Bacterial Pneumonia
• Nonsuppurative Complications:
o Rheumatic fever 2. What other laboratory exams would you request at this time to support
your diagnosis?
o Post-streptococcal glomerulonephritis
Additional tests that may be done include a complete blood count, gram
stain and culture of
5. Management
sputum, blood, pleural fluid
• Antibiotics
o  risk for Rheumatic fever Organism that Laboratory Exams
o  spread of infection esp. (overcrowding and close cause pneumonia
S. pneumoniae Gram stain and culture of
contact)
H. influenzae sputum, blood, pleural
o  symptomatic manifestation S. aureus fluid
o Oral penicillin - 50mg/kg/day PO bid for 10 days K. pneumoniae
o Amoxicillin - 45mg/kg/day PO bid or tid for 10 days E. coli
o Benzathine penicillin - 25,000 units/kg IM OD (for P. aeruginosa
those at risk for RF) M. catarrhalis
o Cephalexin - 50mg/kg/day PO qid for 10 days Legionella sp. PCR and culture of sputum
o Amoxicillin (90mg/kg/day) & Clavulanate M. pneumoniae
(6.4mg/kg/day) PO bid for 10 days C. pneumoniae Microimmunofluorescence
• Eat fruits and drink plenty of water or fluids with TWAR antigen and
• Oral hygiene PCR
o saline sol’n or antiseptic mouth wash Pneumocystis Methenamine silver,
jiroveci Giemsa, or DFA stains of
• REST
sputum or bronchoalveolar
lavage fluid
MICROBIOLOGY – CASE 2 by C5 Laboratory Tests:
• Sputum test
Salient Features • Blood test
• 45 years-old, M • Urine test
• Diabetic • Polymerase chain reaction (PCR)
1. What would be the probable diagnosis on the first time of
consultation? Imaging Techniques:
• Symptoms • X-Rays
– Fevers and chills of 1 week duration • Computed tomography (CT) scans
– Headache and body malaise • Magnetic resonance imaging (MRI) scans
– Cough with blood-tinged sputum
• Diagnostic Examination: Chest X-ray Invasive Diagnostic Procedures:
– Patches of infiltrates • Thoracentesis
• Treatment • Lung Biopsy
– Amoxicillin 500mg, 3x a day for 1 week • Lung Tap
4. What is your diagnosis during the second consultation?
Fever and Hemoptysis Salient features
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 • Low grade fever in the afternoon • For AIDS patients, no radiographic pattern can be considered
• Easy fatigability pathognomonic
• Anorexia
• weight loss PPD Skin testing
• Occasional chest pain • Mantoux test
• Poorly developed, poorly nourished, aesthenic • Diameter of induration is measured 48 hrs after injection
• BP: 130/80 (prehypertensive) • Interpretation depends on host status
• PR: 80/min (N)
• RR: 28 Nucleic Acid Amplification
• Temp: 37.9 C • To permit diagnosis in as little as several hours
• BMI: • High cost
• Decreased breath sounds on L LLF • Low sensitivity
• Moist rales on L ULF AFB smear <NA amplification <culture

Mycoplasma Klebsiella Haemophilus Drug Susceptibility

pneumoniae pneumoniae influenzae • Suspectibility to isoniazid, rifampicin and ethambutol
-Initial non-prod -Hemorrhagic -children • Directly- with clinical specimen
cough necrotizing -meningitis • Indirectly-with mycobacterial cultures
-Bloody sputum consolidation -Involves sinuses and • Liquid or solid media
-Chest pain -UTI middle ear • Results are obtained most rapidly by direct susceptibility on liquid
-Most common -Bacteremia w/ -in adults, bronchitis medium ( 3weeks)
(interstitial & focal lesions in or pneumonia • Indirect on solid ( 8 weeks or more)
peribronchial debilitated pxs
pneumonitis, Cytokine Release Assays
necrotizing
bronchiolitis) • QuantiFERON-TB test- commercially available whole-blood cytokine
Chlamidia Streptococcus Mycobacterium assay
pneumoniae pneumoniae tuberculosis • Night incubation of peripheral bood smear with PPD and control
- Pharyngitis is -sudden onset -Anorexia antigens followed by measurement if IFN-gamma released by
common -Fever -Fatigue sensitized lymphocytes in an ELISA
- Sinusitis and otitis -Chills -Weakness • Recommended for screening for latent TB infection in populations
media may occur w/ -Sharp pleural pain -Weight loss at low to moderate risk
lower airway - Bloody sputum -Fever 7. How will you manage your patient?
disease - Initially high fever -General malaise
-Pleuritic chest pain
-Low grade,
intermittent fever
Rales (Crackles)

RALES
• Abnormality of lungs (in pneumonia, fibrosis, early
congestive heart failure) or airways (bronchitis or
bronchiectasis)
• Discontinuous
BREATH SOUNDS
• Pneumothorax
• Liquefactive necrosis and cavity formation
5. Give the risk factors involved in this case.
Risk Factors for Bacterial Pneumonia Infection

• Extremes of age
• Chronic disease e.g. CHF, COPD, DM
• Congenital immune deficiencies
• Acquired immune deficiencies
• Impaired splenic function

Risk Factors for TB

• Elderly
• Poor
• DM
• Hodgkin’s Lymphoma
• Chronic lung disease esp. silicosis
• CRF
• Malnutrition
• Alcoholism
• Immunosuppression
6. What are the laboratory exams will you request at this time?
AFB microscopy
• Presumptive dx
• Kinyoun(cold) or Ziehl-Neelsen(hot) technique
• Collect sputum by “deep cough method” early in the Should patient be hospitalized?
morning for three consecutive days
• (+) red AFB bacilli Other factors to consider:

Culture • Availability of home support

• Use Lowenstein-Jensen or Middlebrook 7H10 (egg
or agar based medium)
• Incubate at 37°C under 5% carbon dioxide for 4-8 weeks
• Presumptively identified on basis of growth time, colony
pigmentation and morphology
• Identification by other biochemical tests
• liquid media for isolation and speciation by nucleic acid
probes or high-pressure liquid chromatography of mycolic
acids (2-3 weeks)
Radiographic Procedures
• In initial suspicion in high risk patients
• “classic” upper lobe infiltrates with cavitation
• Probability of compliance
• Availability of alternative settings for
supervised care.
Preferred antimicrobials for most patients (in no special order):
• Macrolide: erythromycin, clarithromycin, or azithromycin
• Fluoroquinolone: levofloxacin, sparfloxacin, grepafloxacin,
trovafloxacin, or another fluoroquinolone
with enhanced activity against S. pneumoniae.
• Doxycycline

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Further Care: – At least 2 (preferably 3) drugs that have never been used
and to which the bacilli are likely to be susceptible
• Adequate follow-up evaluations. – Isoniazid and Rifampicin may be continued together along
with
• Follow-up chest radiograph should be obtained in
about 6 weeks • Drug toxicity monitoring
 To ensure clearing of the infiltrate
 To assess persistent abnormality of the lung – Drug-induced Hepatitis (dark urine, loss of appetite)
parenchyma (eg, scarring, bronchiectasis • BASELINE ASSESSMENT OF LIVER FUNCTION
Further Care: – Serum levels of hepatic
aminotransferases and serum
• Pathogen-directed therapy based on: bilirubin
 laboratory data
 clinical response – Hypersensitivity reactions
• DISCONTINUE AND RECHALLENGE
• Unresponsive cases require:
 fiberoptic bronchoscopy or – Hyperuricemia and arthralgia (Pyrazinamide)
• ACETYLSALICYLIC ACID
 open lung biopsy for definitive diagnosis
• STOP IF THE PATIENT DEVELOPS GOUTY
ARTHRITIS
• Administer adequate respiratory support
(eg, as simple as low-flow oxygen or as complex as
– Autoimmune Thrombocytopenia (Rifampin)
assisted ventilation)
• DISCONTINUE
• Pulmonary toilet may include:
 active suction of secretions – Optic neuritis (Ethambutol)
 chest physiotherapy • DISCONTINUE
 positioning to promote dependent drainage
 incentive spirometry – Pruritus and GI upset
to enhance elimination of purulent sputum and to avoid atelectasis. • CAN BE MANAGED WITHOUT INTERRUPTION OF
• Systemic support may include: THERAPY
 proper hydration
 nutrition Case 3A
 mobilization to create a positive host milieu to A 2 year old child was brought to you because of diarrhea of 3 days
fight infection and speed recovery duration.
Stool were described to be blood-streaked occurring 3 – 4x per day.
• Early mobilization of patients, with encouragement Accompanying symptoms were moderate grade fever, tenesmus and
to sit, stand, and walk when tolerated, speeds abdominal pain.
recovery. PE showed a conscious child, slightly febrile. No signs of dehydration.
• Change occupation
DIAGNOSIS:
• Influenza vaccine which decreases the risk of - Acute infectious gastroenteritis
bacterial superinfection. - Shigellosis
Especially important in patients who are elderly and
in those with comorbidity (ie. DM). Acute infectious gastroenteritis
8. How long is the patient a source of infection to individual
around him?
Period of Communicability Signs & Viral Bacterial
• Theoretically, as long as living bacteria are being Symptoms Gastroenteritis Gastroenteritis
discharged in the sputum of a person with active
tuberculosis. Incubation Period 1-3 days 1-7 days
(few hours for toxin producing)
How does tuberculosis spread?
• Transmission of tuberculosis is by inhalation of droplet Common; non-bloody Prominent; frequently
nuclei produced when a person with active tuberculosis Diarrhea in almost all cases bloody
coughs, laughs, sneezes, sings, or talks.
• If another person breathes in these droplet nuclei, there is Fever Common Common
a chance that he/she may become infected with
tuberculosis. Tenesmus ------- Usually
• Usually a person has to be in close contact with someone
with infectious tuberculosis for a long period of time to Abdominal Pain Present / Absent ------

become infected.
• However, some people do become infected after short
periods, especially if the contact is in a closed or poorly
ventilated space.
Incubation Period
• 2 to 10 weeks for the primary TB
• If the immune system fails to stop the infection and it is
left untreated, the disease progresses to the secondary TB,
active disease.
• The risk for developing active disease is the highest in the
first 2 years after the primary infection.
9. How will you document response to adequate treatment?
BACTERIOLOGIC EVALUATION
1. Sputum examined monthly until cultures become negative
2rd mo >80% of the patients
3rd mo =all
>3 mos suspect tx failure/drug resistance
2. Sputum specimen should be collected at the end of tx to
document cure.
3. If mycobacterial cultures are not practical
– Monitor by AFB smear exam at 2, 5, 6 mos
– Tx failure: (+) smear after 5 mos
4. Current isolate should be tested for susceptibility to 1st
and 2nd line agents
!!! Always add more than 1 drug at a time to a failing regimen
Shigellosis
 Acute infectious inflammatory colitis
 “bacilliary dysentery”
 dysentery occurs commonly in patients in developing counties
PATHOGENESIS AND PATHOLOGY
 Enter the host via the mouth
 Survive low pH
 Incubation period 1-3 days
 Essential step in pathogenesis:
 Invasion of the colonic mucosa
 Cell-to-cell spread of infection
 Consequences
-mucosal ulcerations
-dysenteric, small-volume stools consisting of mucus, cellular debris,
neutrophil exudates, and blood
 The characteristic pathology of human bacillary dysentery
-extensive ulceration of the epithelial surface of the colonic mucosa
-exudate consisting of desquamated colonic cells, PMNs, and erythrocytes
-may resemble a pseudomembrane in severely affected areas
Two stages of infection:
First stage- watery diarrhea, lasts up to 3 days
Dysenteric phase - frequent passage of small-volume stools with blood,pus
and mucus
bacteria have invaded the intestinal epithelial lining causing severe
inflammation
accompanied by severe abdominal cramps and tenesmus
Etiologic Agent:

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  Shigellae are small, gram-negative, nonmotile bacilli  adonitol – negative
 dulcitol – negative
 Family: Enterobacteriaceae (related to Escherichia coli)
 D-mannose – positive
 Four Shigella species: S. dysenteriae, S. flexneri, S. boydii, 3. Slide agglutination by specific
and S. sonnei Shigella antisera
 S. sonnei – only species that exists as a single serotype.
 Acquired immunity is serotype-specific, an individual can Reaction Dysenteriae Flexneri Boydii Sonnei
be infected multiple times by different serotypes. Fermentation - - - +
 Lactose-negative of:Lactose - + + -
 Produce acid but not gas from glucose Mannitol - - - +
ODC - - - +
 Acid butt and alkaline slant in triple sugar iron agar without ONPG
H2S
EPIDEMIOLOGY
Management
 Worldwide
 Replacing lost fluids from diarrhea may be sufficient, particularly if
 At least 200 million clinical cases general health is good and shigella infection is mild.
 More then 650,000 deaths  Further treatments include:
 Occur annually, primarily in developing countries and  Antibiotics: sulfamethoxazole with trimethoprim
specially among children <5 year old (Children 6 mos - 10 (Bactrim, Septra, others), ofloxacin (Floxin) or
yrs) ciprofloxacin (Cipro). Antibiotics may also be necessary
 Shigellae are ubiquitous but no known animal hosts other for infants, older adults and people who have HIV
than higher primates infection, as well as in situations where there's high risk
 The infection is often symptomatic in children but of spreading the disease.
asymptomatic in adults
Transmission 5 f’s  Fluid and salt replacement: Children may benefit from
an oral rehydrating solution,
 -from feces to mouth (finger), generally via direct person-  Intravenous hydration provides the body with water and
to-person contact essential nutrients much more quickly than oral solutions
 -although intermediate vector such as water, food, flies do.
and fomites can be involved  mainstay of treatment is adequate rehydration
 Recreational water sports in poorly chlorinated pools or  World Health Organization recommends a solution
lakes fecally contaminated by infected infants and young containing 3.5 g sodium chloride, 2.5 g sodium
children bicarbonate, 1.5 g potassium chloride, and 20 g glucose
 Confined populations in close contact: (or 40 g sucrose) per liter of water.
 -Day-care centers  Oral rehydration solutions containing rice or cereal as the
 -Institutions for the mentally retarded carbohydrate source may be more effective than glucose-
 -Cruise ships based solutions.
 -Military bases  severely dehydrated or in whom vomiting precludes the
Probable Etiologic Agents use of oral therapy should receive intravenous solutions
 Shigella species such as Ringer's lactate.
CASE 3B
 EIEC (Enteroinvasive E. coli)
GENERAL DATA:
 Entamoeba histolytica 20 year old male, residing in the shoreline of Cavite
 all produce bloody diarrhea with vomiting, SYMPTOMS
abdominal pain and fever Diarrhea (1 day)
 Incubation pd: 8hrs – 12days Stool: watery, yellowish, non-foul (15-20x a day)
Vomiting
EIEC Dizziness
 Occurs in children in developing countries and travelers to No tenesmus
these countries on PE…
 Produce disease by invading intestinal mucosal epithelial Bed-ridden
cells BP: 60/40 (rapid pulse, compressible)
Entamoeba histolytica Skin: cold and dry on hands & feet: wrinkled
 Common parasite in the large intestines of humans Lips & mucous membrane: very dry
Shigella species RR: 40/min, deep
 Shigellae are small, gram-negative, nonmotile bacilli
Probable etiologic agents
 Family: Enterobacteriaceae (related to Escherichia coli)  Virbio cholerae
 Four Shigella species: S. dysenteriae, S. flexneri, S. boydii,  ETEC
and S. sonnei  EPEC
 Clostridium perfringens
 S. sonnei – only species that exists as a single serotype.
 Acquired immunity is serotype-specific, an individual can Vibrio cholerae ETEC
be infected multiple times by different serotypes. - 1-4 days incubation - 1-3 days incubation
 Lactose-negative - sudden onset of nausea and - Usually abrupt onset
 Produce acid but not gas from glucose vomiting - Vomiting rare
Laboratory Diagnosis of Shigella - watery diarrhea - watery diarrhea
 Specimen: - abdominal cramps - Usually self-limiting in 1–3 days
Culture Method : Fresh stool, Mucus flecks, - “rice water stools” - important cause of diarrhea in
Rectal swab - profound dehydration infant in developing countries
Serology: Serum - circulatory collapse - traveler’s diarrhea
- rapid loss of fluids and
1. Culture electrolytes
a.EMB or MacConkey – colorless colonies - anuria
b.Salmonella-Shigella agar – colorless colonies - spread by contact-to-contact or
without black centers by water and food
c. Hektoen Enteric agar – green colonies without EPEC Clostridium Perfringes
black centers - slow onset - 6-18 hrs
2. Biochemical tests - Insidious onset over 3 – 6 days - Abrupt onset
• TSIA – acid butt, alkaline slant, no gas, no H2S - Listlessness - usually NO vomiting and fever
• MR – positive - watery diarrhea - watery diarrhea
• Citrate – negative - Lasts 5 – 15 days - Recovery usually without
• ODC – negative - Dehydration can cause death treatment in 1 – 4 days.
• ADH – negative - important cause of diarrhea in - from warmed meat
• Deaminase (phenylalanine) – negative infant in developing countries - loss of fluids and electrolytes
• Urease – negative - Common cause of food poisoning
• Carbohydrate fermentation:
 sucrose – negative
 salicin – negative Diagnosis: CHOLERA

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CHOLERA  All ages, but children & elderly are more severely affected
 A disease that varies from mild, watery diarrhea to acute  Subjects with blood group “O” are more susceptible; Cause is
diarrhea with rice water stools. It can result in profound, unknown
rapidly progressive dehydration and death in a matter of  Subjects with reduced gastric acidity or malnutrition may have
hours. more severe forms
Vibrio cholerae Diagnostic Laboratory Tests
 Comma-shaped, curved or straight Gram-negative rods A. Specimens
 Motile with a single polar flagellum Mucus flecks from stool
 Habitat: plankton of fresh,brackish, and salt water B. Smears
 Typical zoonosis- coastal cholera outbreaks follow Dark-field or Phase contrast microscopy
zooplankton blooms Shows rapidly moving vibrios
 Regularly ferments glucose and mannose but not arabinose C. Culture
 Antigenic structure consists of Peptone Agar, Blood Agar with pH near 9.0, and TCBS Agar
 Flagellar H antigen Shows rapid growth (colonies in 18 h)
Taurocholate Peptone Broth
 Somatic O antigen
D. Specific Tests
 Responsible for pathogenic and
Biochemical Reaction Patterns
nonpathogenic strains
Slide Agglutination
• It is unable to survive in an acid medium. Therefore, any
Using Anti-O group O1 and O139 antiserum
condition that reduces gastric acid production increases the
Suitable Specimens
risk of acquisition.
1. Feces
watery stool samples should be inoculated fresh onto TCBS agar
The ff increases the risk of cholera
and incubated at 35 C.
Antacids
formed stools from asymptomatic individuals should be inoculated
Histamine-receptor blocker
into APW, and this medium subcultured onto TCBS after 6 and 18 hr.
Proton-pump inhibitor
2. Rectal Swabs
 Infectious dose varies with the source Alternative specimen for patients with profuse watery diarrhea
 Water – 103-106 organisms 3. Filter Paper
 Food – 102-104 organisms If prolonged transfer is anticipated
Identification
1) Presumptive Identification
Vibrio cholerae 01  Sucrose fermenting colonies on TCBS agar
 Responsible for Asiatic or epidemic cholera
 agglutinates with a single antisera against “serotype 0, 2) Definitive Identification
subgroup 1”
 Previous illness with V. cholera 01 does not confer immunity  Serotype O1 agglutinating antisera
and the disease is now endemic  Salt Substrate Utilization Tests
Cholera in the Philippines
2 Biotypes of V. cholera  80-90% of cases are mild to moderate
Classical El tor  Cases increase during rainy season
 Key indicator of social development
Hemolysis on sheep Non hemolytic Beta hemolytic In areas where access to safe drinking water and adequate sanitation cannot
blood agar be guaranteed
 According to a 2004 survey, 23.7 % of the Philippine population
Voges-Proskauer Negative Positive
have no access to safe water supply and 30.7% have no sanitary
toilets. In Autonomous region of Muslim Mindanao, 38.4% have no
Agglutination of Failure to Agglutinates
access to safe water and 57.2% have no toilets
chicken RBCs agglutinate chicken RBCs
 Most reported cases of cholera were from Regions V(48%), VII(29%),
Polymyxin B susceptible resistant
NCR(14%) and CARAGA(9%)
 Majority were males
 Most affected group ages 1-10
Pathogenesis Cholera worldwide
 Acquired through ingestion of contaminated food or fecally  Serious health problem in Africa, Asia and Latin America with as
contaminated water many as 200,000-500,000 cases per year and mortality rates
reaching 20-50%
 Disease spreads by poor sanitation, resulting in PREVENTION
contaminated water supplies
 An attack of cholera is followed by immunity to reinfection with
 Severe diarrheal disease due to production of potent
variable duration and degree
“Cholera enterotoxin” (choleragen)
 Vaccine can provide limited protection
Choleragen  WHO vaccination certificate – 6 mos
↓  Education
Attacks the bowel mucosa  Improved sanitation of food and water
↓  Patients should be isolated and their excreta disinfected
Adheres to villous absorptive cells via pili  Chemoprophylaxis with antimicrobials
↓ TREATMENT
Secretes cholera toxin (CT)  Water and electrolyte replacement
↓  to cerrect the severe dehydration and salt depletion
Increased adenylate cyclase activity  Antimicrobial therapy
↓  First choice
Inc CAMP synthesis  Tetracycline
↓
 Doxycycline
Inc fluid and electrolyte efflux
↓  Alternative (for resistant strains)
Rice water stool  Erythromycin
Clinical Findings  Co-trimoxazole (trimethoprim
 Typical incubation period: 24-72 hrs sulfamethoxazole)
 There is sudden onset of nausea, vomiting and profuse  Furazolidone
diarrhea  To reduce stool output in cholera
 Fever typically absent  Shortens the period of excretion of
 “Rice Water” stool vibrios
- Fluid stool with very little fecal material
- Appears within 24h from start of illness CASE 4
 In severe cases, diarrhea occurs as much as 20-30 L/d
leading to severe dehydration, shock or death if untreated PE showed stable vital signs, icteric sclera, with tender hepatomegaly.
 Death may result from dehydration, extreme loss of fluids Personal history revealed he underwent abdominal surgery 3 months
and electrolytes, hypovolemic shock and acidosis ago following a traumatic accident for which he received blood
 Infection may range from mild form, lasting 3-5 days, to a transfusion.
more serious form SALIENT FEATURES
Risk Groups  20 years old

6
 Male 3. Is there a need to isolate the patient?
Abdominal pain
Tea colored urine
Low grade fever one week ago No there is no need to isolate the patient as long as he does not :
Stable vital signs (PE) Give blood or donate his organs
Icteric sclera (PE) Does not share his razors/toothbrushes
Tender hepatomegaly (PE) Does not share needles
Abdominal surgery 3 months ago (traumatic accident) And he:
Blood transfusion Informs health professionals who care for him who may be exposed to
his blood about his condition
1. What is the diagnosis? Informs his sexual partners as well as his family about his condition so
as appropriate precautions could be undertaken.
DIAGNOSIS
VIRAL HEPATITIS
- inflammation of the liver But in the case that the patients condition has severely deteriorated and is
- characterized by: requiring hospitalization he should be isolated because of the risk of infecting
> malaise > vomiting 2-3x/day(first 5 days) patients who are
> joint aches > abdominal pain immunocompromised, or
> dark urine > hepatomegaly (enlarged liver) undergoing hemodialysis
> Fever > jaundice (icterus, yellowing of the wherein a significant association between dialytic age and anti-
eyes and skin) HCV positivity has been reported( Kuwait Medical Journal)
- usually caused by viral infections, toxic agents or drugs but may
also be an autoimmune response 4. What is the mode of infection in this case?

PARENTERAL
- most cases are caused by one of the ff agents: The most likely mode of infection in this case is through blood transfusion
viral hepatitis type A (infectious) which he received from an abdominal surgery he had 3 months ago.
viral hepatitis type B (serum)
viral hepatitis type C (post transfusion)
viral hepatitis type D (delta) 5. What steps should be done to avoid spread of the infection from any
viral hepatitis type E (enteric) family members?
Preventive measures
Vaccination (for HBV)
Acute Viral Hepatitis
Screening and testing blood, plasma, tissues, organs and semen donors
- newly acquired infection
Counseling of persons with high risk drug and sexual practices
- may or may not produce symptoms
- relatively long incubation period (1 to 6 months) Implementation of infection control practices in health care
Professional and public EDUCATION
Chronic Viral Hepatitis
- present for longer than six months
- Usually present for many years VACCINATION
- may or may not produce symptoms
HBV vaccine can confer lifelong immunity
2. What laboratory examinations are necessary to confirm our Unfortunately, there are NO vaccines for HCV
diagnosis?
Screening and testing blood, plasma, tissues, organs and semen donors
Laboratory Diagnosis Blood transfusion
Liver enzymes organ transplant
Bilirubin
Serologic markers clotting factor concentrates
ELISA
PCR/RT-PCR Counseling of persons with high risk drug and sexual practices
Multiple sex partners
Liver enzymes Adolescents and young adults, particularly those who use drugs
*Aminotransferases – rise to values of more than 200 - 500 IU/L
AST
ALT Implementation of infection control practices in health care
AST/ ALT ratio – close to 1 or favor ALT Avoid contact with an infected person’s blood or body fluids.
*LD – elevated to 300 – 500 IU/L
Avoid risky behavior when using needles and other sharp instruments
*ALP – elevated to 200 – 500 IU/L
Carefully dispose of sharp instruments in appropriate containers.
Wear protective equipment, including gloves and face shields
Bilirubin
*Total serum bilirubin – above 2 mg/dL
*Direct and indirect bilirubin - elevated Professional and public EDUCATION

Serologic Markers 6. How long will this patient serve as potential source of infection?
Hepatitis B Virus
Serology
HBsAg- represent viremic stage of HBV, occurs early, detectable in
2-6wks in advance of clinical evidence, persists throughout the
clinical course of the disease but disappears by the 6th month after
exposure
Anti-HBsAg – first detected after disappearance of HBsAg; indicates
past infection and immunity to HBV
IgM- specific anti-HBc- detected at the onset of clinical illness;
indicative of viral replication and recent infxn; (+) for 4-6mos after
infxn
Anti-HBe – (+) in serum of HBsAg carrier, suggesting low titer of
HBV
Person with hepatitis are generally infectious one or more weeks before
onset of symptoms
The hepatitis virus is usually detectable in the blood within one to three
weeks after infection and antibodies to the virus are generally detectable
within 3 to 12 weeks
All HBV and HCV positive persons are considered potentially infectious.
Contact with their blood can lead to HBV and HCV infections.
Some people carry the virus in their blood (carriers) and may remain
contagious for years

Hepatitis C Virus Hepatitis Virus

Hepatitis D Virus Hepatitis Virus
Differential diagnosis
Hepatitis B
ELISA – most useful method for viral antigen and antibodies Hepatitis C
detection Hepatitis D
Hepatitis B
PCR/RT-PCR – viral DNA detection EPIDEMIOLOGY

7
WORLDWIDE distribution 3rd hospital day: fever and chills
Transmission modes are vertical, contact, parenteral and sexual Post operative wound: clean
Infants and young children develop chronic infections CBC:leucocytosis, neutrophils
Adults subject to liver disease and high risk for hepatocellular CA urinalysis: pyuria

EPIDEMIOLOGY Diagnosis:
Detectable in saliva, semen, nasopharyngeal washings, menstrual Nosocomial UTI
fluid, vaginal secretions and blood
Nosocomial Infections
INCUBATION PERIOD – 50-180 days
Common among patients and staff of hemodialysis units • Infections that result from treatment in a hospital or hospital-like
50% of hemodialysis Px infected w/ HBV becomes chronic carrier of setting, secondary to the patient's original condition
HbsAg • Considered nosocomial :
Management -First appear 48 hours or more after admission
Treatment -Within 30 days after discharge
Supportive (Vitamin B complex) and directed at allowing
hepatocellular damage to resolve and repair itself Symptoms of UTI
Chronic HBV- recombinant IFN-alpha dysuria, urgency, frequency
Lamivudine- RTI, reduces HBV DNA levels fever, dysuria, urgency and frequency – usually present in upper UTI
Orthotopic liver transplantation for chronic HepaB end-stage Some patients with indwelling catheters may have bacteriuria but
liver disease remain asymptomatic.
Management
Prevention and Control Predisposing Factors to UTI Present in Patient
Vaccine Female
HBIG (Hepatitis B immune globulin) protective effect if given Pregnancy
after exposure; expensive Diabetes
Indwelling Catheter
Hepatitis C
Female:
Epidemiology
• Shorter urethra - easier for ascending infection
HCV infections are extensive throughout the world
Pregnancy:
The WHO estimated in 1997 that about 3% of the world has
• Immunocompromised state
been infected
High prevalence areas include: Africa, South America and Asia • Dilatation of the urinary collecting systems because of:
- Ureteral smooth muscle relaxation- action of progesterone
170 million chronic carriers worldwide
- Uterus compresses ureters- hydronephrosis
Hepatitis C
 In some cases there is stasis of urine during the pregnancy state,
Management
resulting in a breeding ground for bacteria.
Treatment of patients with hepatitis is supportive and directed
and allowing hepatocellular damage to resolve and repair itself
Diabetes Mellitus:
Recombinant interferon-α is currently the therapy of proved
• Altered immunity
benefit
• Diabetic neuropathy- once it affects the autonomic nerves causes
Combination therapy of interferon-α and ribavirin against
incomplete bladder emptying and stasis
chronic HCV infection gives a sustained response rate of up to
50%
Indwelling Catheter:
There is no vaccine for hepatitis C
• Creates entry points for bacteria
Control measures focus on prevention activities that reduce
the risks for contracting HCV • Most common source of gram-negative bacteremia in hospitalized
Hepatitis D (Delta hepatitis) patients
Caused by hepatitis D virus
Laboratory Tests
Enveloped ssRNA
• Urine culture
Replication defective
-Criterion standard for the diagnosis of UTI
Causes infection only in the presence of HBV (HBsAg)
-Bacterial count 105 organisms/mL and a single bacterial species indicate
2 settings: infection
Coinfection -Contamination usually does not occur when specimens are collected from
Superinfection catheters, nephrostomy tubes or by suprapubic aspiration directly from the
Hepatitis D bladder
Epidemiology • Leukocyte esterase
Worldwide -Dipstick test
Italy, Middle East, Central Asia, West Africa & South America -Rapidly screen for pyuria
All age groups -sensitivity: 57-96%
Multiple transfusions -specificity: 94-98%
Intravenous drug abusers • Gram Stain
Hepatitis D -sensitivity: 90%
2 epidemiologic patterns: -specificity: 88%
Mediterranean areas
•Endemic among persons with hepatitis B Probable Etiologic Agent
Escherichia Coli
•Transmission: intimate contact • Most common cause of nosocomial UTI
• Can also cause other nosocomial infections: GIT infections, meningitis,
US and N. Europe
peritonitis, septicemia, pneumonia
•Nonendemic areas • E. coli that colonize the urinary tract have fimbriae (pili)- enables
•Confined to persons exposed to blood and blood adherence to urethral and bladder epithelium
products (drug addicts and hemophiliacs) • Gram negative, rods, motile
Hepatitis D • EMB- green metallic sheen (lactose fermenter)
Management • MacConkey- pink colonies (lactose fermenter)
dependence of HDV on HBV could suggest that successful • Catalase (+)
treatment of HDV infection would follow successful treatment
• Indole (+)
of the supporting HBV infection
Interferon-α • Citrate (-)
• Ferments glucose and produce gas (methyl red positive)
38 y/o, G3P3, Diabetic, Caesarean section, Non-ambulatory
Case 5
first 24 hours post operation: Indwelling catheter
2rd H.D.: fever and chills
Salient Features:
post operative wound: clean
38 y/o
G3P3
CBC:leucocytosis, neutrophils Urinalysis: pyuria
diabetic
Caesarean section
non-ambulatory Nosocomial Infection Community-acquired
indwelling catheter (first 24 hours post operation) Infection

8
Setting - Acquired in the - Community
hospital but does not - the patient had not
become evident until recently been in a Escherichia Coli
after discharge health care facility or • 24% of catheter associated UTI
- infection in a been in contact with • Most common cause of nosocomial UTI
neonate that results someone who had • Causes: UTI, GIT infections, meningitis, peritonitis, septicemia,
from passage through been recently in a pneumonia
the birth canal health care facility • UTI associated serotypes: 01, 02, 04, 06, 07, 075
[CDC definition] • E. coli that colonize the urinary tract have fimbriae (pili)- enables
-. secondary disorder adherence to urethral and bladder epithelium
associated with being
treated in a hospital - Gram negative short rods
but unrelated to the - Motile
patient's primary - EMB- green metallic sheen
condition - MacConkey- lactose fermenters (pink colonies)
Onset of infection - 48 hours or more - prior to hospital - Catalase positve
after hospital admission and not - Indole positive
admission within 10 days of - Citrate negative
- infection present on hospital discharge - Ferments glucose to acid and produce gas (methyl red positive)
admission but patient
is within 10 days of Laboratory tests
previous in-patient • Urine culture
stay – Criterion standard for the diagnosis of UTI
– Bacterial count 105 organisms/mL and a single bacterial
Reasons why nosocomial infections are so common species indicate infection
• Weakened immune systems of patients
• Leukocyte esterase
• Lack of handwashing among hospital staff – Dipstick test
– Rapidly screen for pyuria
• Medical procedures bypass the body's protective barriers – Sensitivity: 57-96%; specificity: 94-98%

• Routine use of anti-microbial agents- emergence of • Gram Stain

resistant strains – Sensitivity: 90%; specificity: 88%
Catheter associated UTI
UTI Most common agents:
• the most common hospital-acquired infection in North E. coli, Proteus, Pseudomonas, Klebsiella, Serratia, Staphylococci,
America Enterococci, and Candida
Routes:
• the most frequent nosocomial infections in critically ill 1) Intraluminal Route- pathogens migrate through the column of urine in the
patients catheter lumen
2) Periurethral Route- pathogens move up the mucous sheath outside the
• 5% of patients admitted in acute care hospitals catheter

• PGH (1989), the prevalence was 16.3% Intraluminal

Hospital-acquired pathogens  Hands of hospital personnel,instruments 
• Philippine Renal Disease Registry of the Philippine Society Catheter-collecting tube junction or at the drainage bag portal  Ascend
of Nephrology (1998): UTI in over 40% of nosocomial intraluminally into the bladder
infections

• In tertiary centers in Manila, Cavite, Zamboanga (1998): 5-

17% of consultations
Periurethral
• is second to respiratory tract infections with a prevalence Patient’s own bowel flora  Perineal skin and periurethral area colonization
rate of 25.3%  Growth and attachment on the surfaces of the catheter  Ascend into
bladder
• 80% of nosocomial UTI are associated with the use of
urethral catheters Bacterial infection, microbial toxins  neutrophils, lymphocytes,
macrophages/monocyte, etc. proliferation and stimulation  IL-1, IL-6, IL-8,
• gram-negative bacteremia can develop in 30-40% of TNF, IFN  Hypothalamic endothelium PGE2 Cyclic AMP  Elevated
patients
thermoregulatory set point  Heat conservation, heat production  Fever
Symptoms of UTI
Treatment
• Lower UTI:
– Dysuria, Urgency, Frequency • Uncomplicated UTI: oral cotrimoxazole, daily or 3x/wk
• Pyelonephritis: administration of single dose of TMP-SMX or TMP alone or
– Fever + symptoms of lower UTI Nitrofurantoin
• However patients on indwelling catheters may be
asymptomatic • Complicated UTI: parenteral antibiotics (3rd generation
cephalosporin with or without aminoglycosides)
Predisposing factors
• UTI: penicillin – co-amoxiclav
• Female Shorter urethra - easier for ascending infection • Alternative: cephalosporin - cefixime
• Pregnancy • Severe UTi : fluoroquinolones – norfloxacin
Dilatation of the urinary collecting systems:
• Ureteral smooth muscle relaxation- Prevention
progesterone 1. Personnel: Only persons trained in correct aseptic techniques of
• Uterus compresses ureters- catheter insertion and care should handle urinary catheters , Hand
hydronephrosis washing should be done immediately before and after catheter
= Stasis of urine- creates an environment for bacterial insertion or care
colonization 2. Catheterization:
• Diabetes Avoid unnecessary catheter use
Altered immunity- contribute to asymptomatic bacteriuria Limit catheter use to carefully selected patients
Routine catheterization during labor or immediately post-partum for
Diabetic nephropathy- causes incomplete bladder emptying collection of urine sample is not recommended
and stasis Catheters should be inserted using aseptic technique and sterile
• Indwelling Catheter equipment
Creates entry points for bacteria Maintain a sterile, closed catheter system at all times. Open drainage is
Major predisposing factor for UTI unacceptable
Most common source of gram-negative bacteremia in Urine specimens should be obtained aseptically without opening the
hospitalized patients catheter-collection junction
• Sexual Activity Maintain unobstructed and adequate urine flow at all times

9
 Do not change catheters at arbitrary fixed intervals
Remove the urinary catheter ASAP!
Methods to prevent exogenous infection
- Irrigation of the bladder with antimicrobial agents is not
useful
- Instillation of disinfectants into the bag and the use of
antireflux valves and vents are not helpful
- Segregate infected from uninfected catheterized patients
Pathophysiology?Catheter-associated UTI
Routes:
1. Intraluminal- hospital-acquired pathogens (through the hands of
pers0nnel, intstruments) migrate through the column of urine in the
catheter lumen and ascend
intraluminally into the bladder
2. Periurethral route - patients own bowel flora
colonize perineal skin and periurethral area, attach
on the surfaces of the catheter and ascend into
bladder.
Fever,chills,pyuria,leukocytosis
Bacterial infxn,toxins--proliferati0n and stimulation
of neutrophils,lymphocytes,etc. release cytokines--
Cytokines enter systemic circulation and induce
hypothalamic endothelium to release PGE2-- release of
CAMP which elevates thermoregulatory set point in
hypothalamus-- increase in body temperature
Case 6
A 20 year old male worker was admitted to the USTH because of high
grade fever and severe headache. Five days PTA, he has severe “sore
throat” which he treated with a pain reliever only. Three days prior
to admission, he developed high grade fever accompanied by
headache.
A lumbar tap was done and revealed the following results:
gross description: slightly turbid, colorless
cell count: WBC = 100 x 106/L
neutrophils = 80%
lymphocytes = 20%
protein = 90 mgs/dl
sugar = 15 mg%
Working Diagnosis : Meningitis
 The diagnosis of meningitis requires a high degree of
suspicion when appropriate signs and symptoms are
observed plus lumbar puncture without delay followed by
examination of CSF.
Acute Bacterial Meningitis
 Bacterial meningitis is a life-threatening illness resulting
from bacterial infection of the meninges.
 Beyond the neonatal period, the 3 most common organisms causing
acute bacterial meningitis are Streptococcus pneumoniae,
Neisseria meningitidis, and Haemophilus influenzae type b (Hib).
 Neonates - Group B or D streptococci, nongroup B streptococci,
Escherichia coli, and L monocytogenes
 Infants and children - H influenzae (48%), S pneumoniae (13%),
and N meningitidis
 Adults - S pneumoniae, (30-50%), H influenzae (1-3%), N
meningitidis (10-35%), gram-negative bacilli (1-10%), staphylococci
(5-15%), streptococci (5%), and Listeria species (5%)
 Bacteria reach the subarachnoid space by a hematogenous route
and may reach the meninges directly in patients with a
parameningeal focus of infection.
 Once pathogens enter the subarachnoid space, an intense host
inflammatory response is triggered by lipoteichoic acid and other
bacterial cell wall products produced as a result of bacterial lysis.
 This response is mediated by the stimulation of macrophage-
equivalent brain cells that produce cytokines and other
inflammatory mediators.
 This resultant cytokine activation then initiates several processes,
which ultimately cause damage in the subarachnoid space
culminating in neuronal injury and apoptosis
 Morbidity and mortality depend on pathogen, patient's age and
condition, and severity of acute illness.
 Among bacterial pathogens, pneumococcal meningitis causes the
highest rates of mortality (21%) and morbidity (15%).
 Mortality rate is 50-90% and morbidity even higher if severe
neurologic impairment is evident at the time of presentation (or
with extremely rapid onset of illness), even with immediate
medical treatment.
 Race: Statistically, blacks are at greater risk than other races,
although race may not be an independent risk factor.
 Sex: In neonates, male-to-female ratio is 3:1. No sex preference
exists among adults.
 Age: Median age is 25 years. In 1986, it was 15 months.
 Excluding meningococcal meningitis, patients younger than 5 years
and older than 60 years are at increased risk.
 Newborns are at highest risk for acute bacterial meningitis. After
the first month of life, the peak incidence is in infants aged 3-8
months.
 In the US: The incidence of bacterial meningitis is 2-3 per 100,000.
Recent statistics show an increase among persons aged 60 years
and older independent of other factors. In 1995, incidence by
major pathogens (all ages per 100,000) was as follows:
 Streptococcus pneumoniae (1.1) in all except neonates
 Neisseria meningitidis (0.6), usually local outbreaks among young
adults, epidemics internationally, and increased incidence in late
winter or early spring
LABORATORY DIAGNOSIS
 All patients admitted to hospital with suspected meningitis should
have:
 A blood culture
 A throat swab
 A blood EDTA (ethylenediaminetetra-acetic acid)
specimen for PCR studies
 Baseline clotted blood for serology
 Full blood count, C reactive protein (CRP), clotting
studies, and urea and electrolytes should also be
routinely performed.
 Serum glucose level measurement
 Useful for interpreting CSF glucose levels and the
likelihood of meningitis.
 Spinal tap (lumbar puncture)
 Definitive diagnosis of meningitis
 Analyzing a sample of the cerebrospinal fluid (CSF)
 May also help the doctor identify the exact bacterium
that's causing the illness.
 CONTRAINDICATIONS: (for lumbar tap)
 Unstable patients with hypotension or respiratory distress
who may not be able to tolerate the procedure
 Brain abscess, brain tumors or other cause of raised
intracranial pressure
 Infection at the lumbar puncture site
If the condition became chronic and the laboratory finding is not in favor
of acute bacterial meningitis, what will be your considerations and
management?
10
Bacterial Viral TB Fungal  Outpatient care is sufficient for acquired disease in hosts
↑ WBC, ↑ WBC, ↑ WBC, ↑ WBC, who are immunocompetent and in persons with ocular
neutrophils lymphocytes lymphocytes lymphocytes toxoplasmosis.
and monocytes and monocytes  Inpatient care is appropriate initially for persons with
↑ CHON ↑ CHON ↑ CHON ↑ CHON CNS toxoplasmosis and for acute disease in hosts who are
↓ CHO Normal CHO ↓ CHO Normal – immunocompromised.
↓ CHO  Usually, no treatment is necessary in asymptomatic hosts,
↑ Lactate Normal Lactate ↑ Lactate ↑ Lactate except in children younger than 5 years.
↑ LD4 & LD5 ↑ LD2 & LD3 ↑ LD2 & LD3 ↑ LD2 & LD3  The current standard treatment for first stage disease is
intravenous pentamidine (for T.b. gambiense) or
Chronic Meningitis Intravenous suramin (for T.b. rhodesiense)
 The current standard treatment for second stage (late
Bacterial: stage) disease is intravenous melarsoprol 2.2 mg/kg daily
 Lyme disease (Bannwarth’s syndrome), Borrelia burgdorferi for 10 consecutive days.
 Traditional treatment of acute Lyme disease  Alternative first line therapies include intravenous
usually consists of a minimum two-week to one- melarsoprol 0.6 mg/kg on day 1, 1.2 mg/kg iv
month course of antibiotics. melarsoprol on day 2, and 1.2 mg/kg/day iv melarsoprol
 In later stages, the bacteria disseminate combined with oral 7.5 mg/kg nifurtimox twice a day on
throughout the body and may cross the blood- days 3 to 10, or itravenous eflornithine 50 mg/kd every
brain barrier, making the infection more six hours for 14 days.
difficult to treat.
 Late diagnosed Lyme is treated with oral or IV Why not Group B Streptococcus in our case?
antibiotics, frequently ceftriaxone, for a  Infection targets Infants (½ - 3 months) and Infants (½ - 3 months)
minimum of four weeks.  infection is often acquired from the mother during birth.

 Syphilis (secondary, tertiary), Treponema pallidum

 The first choice treatment for primary,
secondary, and early latent infection remains
penicillin, in the form of Benzathine penicillin
G, 2.4 MU IM in a single dose.
 Individuals who have severe allergic reactions to
penicillin may be effectively treated with oral
tetracyclines (100 mg orally twice a day for 14
days).
 Ceftriaxone may be considered as an alternative
therapy, although the optimal dose is not yet
defined and close clinical and serologic follow-up
is essential. If ceftriaxone is used for the
treatment of early syphilis, some experts
recommend 1 g daily, given intramuscularly or
intravenously, for 8 to 10 days
Fungal:
 Candida sp.
 Intravenous amphotericin B
 Amphotericin B + flucytosine= excellent rates of cure
 Fluconazole- maintenance, to prevent relapse.
Viral:
 Herpes Simplex Virus
 HSV-1 can cause pharyngotonsillitis and herpes
meningitis, among others.
 Antiviral drugs such as acyclovir, valacyclovir, and
vidarabine are used for HSV infections. All are
inhibitors of viral DNA synthesis.
 Enterovirus
 The associated clinical findings in enteroviral
infections include pharyngitis, pleurodynia, rash,
and pericarditis.
 Complications would include myocarditis, aseptic
meningitis, meningoencephalitis, and paralysis.
 Enteroviral infections heal spontaneously within
7-10 days; therefore, the main goal of treatment
is symptomatic relief.
 HIV
 Untreated AIDS patients are susceptible to
opportunistic infections. Among these
opportunistic organisms are those that can cause
meningitis (and sore throat) which are HSV and
Candida sp.
Protozoal:
 Toxoplasma gondii
 The vast majority of patients with a normal
immune system require no treatment.
 Patients with HIV/AIDS or patients who are
immunosuppressed should be given sulfadiazine
and pyrimethamine. Pregnant women who
become ill with acute toxoplasmosis should be
treated with spiramycin.
 Trypanosomiasis, Trypanosoma gambiense, T. rhodesiense
 Statistics: 4% of adult meningitis up to or > 60 y/o; low incidence
Listeria Monocytogenes
 Aerobic or facultatively anaerobic, nonsporulating gram-positive
bacilli that grow at 1 to 45˚C and typically have tumbling motility
when cultured at 20 to 25˚C
 Can be isolated from soil, vegetation and many animal reservoirs
 Human disease generally occurs in the setting of pregnancy or
immunosuppression caused by illness or medication
 Can cause invasive syndromes such as meningitis, sepsis,
chorioamnionitis and stillbirth
 Food-borne transmission as the common cause of epidemic and
sporadic disease
 Like contaminated coleslaw, pasteurized milk, soft cheese,
undercooked chicken and hotdogs
 Incubation period following consumption of contaminated food can
be 2 to 6 weeks
 Pregnancy-associated listeriosis
 Any stage of pregnancy, usually 3rd trimester
 Increased risk for pregnant women may be due to both
systemic and local immunologic changes associated with
pregnancy
 Neonatal listeriosis
 May be acquired during passage to the birth canal or
infections related to nosocomial transmission
 Listeriosis not associated with pregnancy
 Persons with immunosuppressive conditions
 Most common conditions associated with listeriosis are
chronic glucocorticoid therapy, solid or hematologic
malignancies, diabetes mellitus, renal and liver diseases
and AIDS.
H. Influenzae
 Found on the mucous membranes of the upper respiratory tract in
humans
 May be asymptomatic or causes respiratory tract infections and
meningitis in children
 most common cause of meningitis in children from 5 months to 5
years of age
 Many unimmunized children naturally acquire antibodies that
promote complement-dependent bactericidal killing and
phagocytosis
 The blood of many persons over age 3-5 years is bactericidal for H.
influenzae, and clinical infections are less frequent in such
individuals
N. Meningitidis
 Common to ages 5-29 years
 Preceded by throat soreness or upper respiratory symptoms
 Meningococcemia
 Fever, chills, nausea, vomiting, myalgias
 Most distinctive feature: rash (erythematous macules 
petechiae  purpura)may coalesce to become
hemorrhagic bullae or may become necrotic and
ulcerated
 If without meningitis: poor prognosticating factor
 Meningitis
 Patients with symptoms ≥ 24 hours before seeking
medical attention
 Nausea, vomiting, headache, neck stiffness, lethargy,
confusion

11
  Fulminant Meningococcemia • Serum should be collected as early as possible (within 7–10 days)
 With hemorrhagic skin lesions (petechiae, after onset of illness, and again 14–21 days (minimum of 7) days
pupura) and DIC later.
 Due to the endotoxin of N. Meningitidis ELISA
 CSF may be normal and culture negative • sensitive, widely available, and relatively easy to perform
• measures rise in IgG
 Other manifestations:
• can also be modified to measure IgM antibodies
 Arthritis (if within a few days of patient’s illness,
it is due to direct meningococcal invasion of
Hemagluttination Inhibition Test
joint; if occurs later, it’s due to immune complex
• was once the “standard” and most commonly used technique
deposition)
• Sensitive and simple to perform and allows for either screening or
 Pneumonia diagnosis (if paired acute- and convalescent-phase sera are tested)
 Endocarditis
 Conjunctivitis • fourfold rise or greater in HI-derived antibody titer in paired sera
 urethritis  diagnostic of recent infection
• modified to detect rubella-specific IgM antibody indicative of
S. Pneumoniae primary infection
 Common to ages 29 years and above Immunofluorescent antibody assay
 Usually presents with a preexisting respiratory condition • rapid and sensitive assay
that has distinctly deteriorated followed by pneumonia and • Commercial assays for both IgG and IgM are available in the United
high grade fever States.
• Care must be taken with the IgM assay to avoid false-positive
 “Classic” picture: sudden onset of fever, chills, sharp
results due to complexes with rheumatoid antibody.
pleural pain, blood-tinged sputum
 Bacteremia causes: meningitis, endocarditis, and septic Disease Rubeola Rubella Erythema
arthritis (Measles) infectiosum
 Patients who have undergone splenectomy: rapid (fifth disease)
progression (death occurs in as little as 24 hours) Etiology Family: Family: Human
Paramyxoviridae Togaviridae parvovirus
Genus: Genus: Rubivirus B19
Case 7 Morbillivirus
A 6 year old female was brought in for consultation because of Description of Macular-papular Pink macules and Begins as
generalized maculo-papular rashes. Five days before the appearance rash rash that may papules that classic bright-
of the rash, she developed low to moderate grade fever which lasted become develop on red facial rash
for 3 days. On physical examination, the patient was afebrile with confluent; begins forehead and ("slapped
palpable lymph nodes in the suboccipital area. Other findings were on face, neck and spread inferiorly cheek") and
unremarkable. shoulders and and to progresses to
spreads extremities lacy reticular
centrifugally and within one day; rash; may wax
Salient features inferiorly; fades in fading of macules and wane for
• 6 y/o female 4 to 6 days and papules in 6 to 8 weeks
• generalized maculo-papular rash reverse order by
• 3-day low to moderate grade fever five days prior to third day
appearance of rash Epidemiology Most common in Young adults, Children 3-12
• afebrile at PE children 5-9 y/o, nonimmune
• lymphadenopathy (suboccipital) nonimmune persons
persons
Rubella virus
Diagnostic Prodrome Prodrome Can present
• Respiratory transmission of virus clues consisting of uncommon, as rheumatic
• Replication in nasopharynx and regional lymph nodes symptoms of especially in syndrome in
• Viremia 5-7 days after exposure with spread to tissues upper respiratory children; adults;
• Placenta and fetus infected during viremia tract infection, petechiae on soft prodrome of
Clinical Features coryza, bark-like palate fever,
• Incubation period 14 days cough,malaise, (Forschheimer's anorexia; rash
photophobia and spots); in adults: typically
(range 12-23 days)
fever; Koplik's anorexia, beginning
• Prodrome of low-grade fever spots (prodromal malaise, after
• Maculopapular rash 14-17 days after exposure stage); conjunctivitis, resolution of
• Lymphadenopathy in second week development of headache and fever
CLINICAL CASE exanthem on symptoms of mild
1) acute onset of generalized maculopapular rash; fourth febrile day; upper respiratory
2) a temperature higher than 99°F (37.2°C), if measured; and infection
3) arthralgia or arthritis, lymphadenopathy, or conjunctivitis. Basis for Serology Serology Serology
diagnosis
Case classification
• suspected case is any generalized rash illness of acute
onset. Treatment
• probable case meets the clinical case definition, has • acetaminophen/paracetamol or ibuprofen to relieve fever and
noncontributory or no serologic or virologic test results, minor discomfort {avoid aspirin}
and is not epidemiologically linked to a laboratory- • anti-histamines for pruritus
confirmed case. Prevention
• confirmed case is laboratory confirmed or meets the Rubella Vaccine (MMR) Indications
clinical case definition and is epidemiologically linked to a • All infants >12 months of age
laboratory-confirmed case. • A second dose given at 4 to 6 years of age, but should be given no
later than 11 to 12 years of age.
CASE# 7B
Laboratory Diagnosis A five year old child consulted because of petichiae and fever at the OPD
 Isolation of rubella virus from clinical specimen (e.g.
nasopharynx, urine) Petechiae
 Positive serologic test for rubella IgM antibody • pinpoint-sized hemorrhages of small capillaries in the skin or
 Significant rise in rubella IgG by any standard serologic mucous membranes measuring >2 mm.
assay (e.g. enzyme immunoassay) • result from tiny areas of superficial bleeding into the skin
Isolation • appear as round, pinpoint-sized dots that are not raised
• nasal, blood, throat, urine and CSF • color varies from red to blue or purple as they age and gradually
• Virus may be isolated from the pharynx 1 week before and disappear
until 2 weeks after rash onset. • commonly appear on the lower legs, but may be distributed all
over the body.
• Viral culture  labor intensive  not done in many How to approach px
laboratories • Petechiae resolve completely without any treatment. However, a
• generally not used for routine diagnosis of rubella doctor should evaluate the child to determine that a serious
Serology disease process is not present.
• most common method • The child may need blood tests and x-rays to find the cause of the
• Acute rubella infection: significant rise in rubella antibody petechiae and fever.
titer in acute and convalescent-phase serum specimens by • Occasionally, a child also requires a lumbar puncture (spinal tap) to
the presence of serum rubella IgM. be sure meningitis is not the cause

12
 • Diagnosis of petechiae begins with the history and physical Immunity
exam. Blood tests are usually done, including: • Has 4 serotypes
- bleeding time • Infection confers lifelong protection
- tests that measure clotting abilities, such as a • Cross-protection: short duration
prothrombin time or partial • Reinfection w/ virus of different serotype tends to result in severe
thromboplastin time disease (DHF)
- complete blood count (CBC) Treatment
- platelet count  symptomatic and supporative, no specific anti-viral
Platelets are blood cells that aid in blood clotting. If a person has too treatment
few of them in the blood, the person may be more likely develop – Rehydration with IV fluids is often necessary to treat dehydration.
petechiae. A bone marrow biopsy may be done in some cases. – A transfusion of fresh blood or platelets can correct bleeding
problems.
Algorithm of Petechiae and Fever – Oxygen therapy may be needed to treat abnormally low blood
oxygen
Control Measures
• eradication of mosquitoes: elimination of breeding places, fogging
• eradication of mosquitoes: use insecticides
• screening of houses
• using tight fitting lids in water storage
• No vaccine yet
Neisseria meningitides (we were no longer asked to discuss this)

Haemophilus influenzae B
• small Gram (-) coccoid bacillus, occurring in pairs or chains which
can be grown on chocolate agar
• requires hemin (factor X) and nicotinamide adenine dinucleotide
(NAD+:factor V) for growth
• enhanced by high CO2 concentration (5%)
• polyribose-ribitol phosphate capsule
Clinical findings
Infectious diseases that manifest with petechiae • Naturally-acquired disease caused by H. influenzae seems to occur
• Dengue in humans only
• Meningococcal disease • In infants and young children (< 6 y.o.) - causes bacteremia and
• Haemopohilus influenzae type b acute bacterial meningitis
• Streptococcus pneumoniae • Suppurative respiratory infections (sinusitis, laryngotracheitis,
Dengue epiglottitis, otitis), cellulitis, osteomyelitis, and joint infections
Disease incidence
• Mode of transmission:
• remains a major cause of lower respiratory tract infections in
– day biting mosquitoes (Aedes aegypti)
infants and children in developing countries where vaccine is not
• Incubation period: widely used.
– 2-7 days (minimum 3 days, maximum 10 days) Pathogenesis
Prodromal symptoms include the following: • enters by way of respiratory tract (air droplets)
• Fever (may be sudden) • initial Sx: runny nose, low grade fever and headache (1-3 days)
• Headache • enters the circulation and crosses BBB, resulting in a rapidly
• Muscle aches progressing meningitis, convulsions, coma and death
• Joint aches • also establishes in joints
• Malaise & Chills • Resorvoir: Humans (asymptomatics) are the only known reservoir.
• Decreased appetite HiB does not survive in the environment on inanimate surfaces
• Vomiting Diagnosis
Clinical Findings  Culture and Gram staining
• Viremia: present at onset of fever, lasts for 3-5 days  a gram stain of the infected body fluid may demonstrate
• Characteristic: myalgia & deep bone pain small gram negative coccobacilli suggestive of invasive
• Rash: appear 3rd/4th day, lasts 1-5days Haemophilus disease
• Leukopenia with relative lymphocytosis, regular occurrence  CSF, blood, pleural fluid, joint fluid and middle ear
• Classic Dengue: self-limited aspirates should be cultured.
Acute phase symptoms include the following:  A positive culture for H. influenza establishes the
• Shock-like state diagnosis
– Sweaty (diaphoretic)  Serotyping
– Cold, clammy extremities  All isolates of H. influenza should be serotyped.
• Restlessness followed by:  This test determines whether an isolate is type b, which
– Worsening of earlier symptoms is the only type that is potentially preventable by vaccine
– Petechiae  Antigen Detection
– Ecchymosis  Latex agglutination—detects Hib capsular polysaccharide
Diagnosis: DHF antigen in CSF
fever-acute onset, high, contagious, lasting 2-7 days  Counterimmunoelectrophoresis
-hemorrhagic manifestations  Immunity:
-thrombocytopenia
-hemoconcentration: hematocrit increased by 20% or more,  The age incidence of H. influenzae meningitis is inversely
or objective evidence of capillary permeability proportional to the titer of bactericidal antibody in the
-Pathogen: may occur w/passive acquired Ab or preexisting blood, whether passively acquired from the mother or
dengue Ab from previous infection w/different serotype of actively formed
virus  Without artificial immunization, in children aged 2
-initial symptoms simulate normal dengue but conditions months to 3 years, antibody levels are minimal;
abruptly worsens thereafter antibody levels increase and the disease
Diagnosis :DSS becomes much less common
-all of the above criteria plus hypotension or narrow pulse  Immunity:
pressure  Artificial active immunization should begin at 2 months of
-characterized by: shock, hemoconcentration age, when nearly all passive immunity has waned, and
-more severe form the child enters a vulnerable non immune period of life
-Pathogen: preexisting dengue Ab  Prevention:
Lab Diagnosis  Conjugate Hib vaccines
• Viral isolation difficult
 The first dose of vaccine is normally given at 2
• PCR for rapid identification & subtyping
months of age
• Neutralizing & HI-AB appear within 7 days after onset of
 Control:
fever
• serologic tests (hemoagglutinin inhibition, CF tests,  Children with Hib infections should be excluded from
Neutralization tests, tests to detect type specific IgM, IgG child care/school until a course of appropriate antibiotic
and dengue antibodies is completed and a medical practitioner has confirmed
that the child may return.
13
 symptoms. One month ago, he complained of swelling of the (L) 2nd toe and
Indication Dosage Duration blisters on the palmar area that tend to excoriate and dry spontaneously
Ceftriaxone Meningitis 75-100 1-2 weeks
Epiglotitis mg/kg/d 2 Pertinent PE: Vital Signs normal
doses 12h Lower Extremities: erythema with thickening and cracks of the
apart interdigital areas of both feet. Left 2nd toenail shows tenderness and
50 mg/kg/d swelling of the base of the nail. The toenail is thickly cornified with scaling
3 doses 8h at the tip. Both hands were noted to have vesicular eruptions. Some have
apart dried up.
Cefotaxime Meningitis 200 1-2 weeks
Epiglotitis mg/kg/d 4 Salient Features
doses 6h • Male athlete
apart • 2 year hx of Interdigital itchiness and erythema
150 • relieved temporarily with foot creams and powder
mg/kg/d 3 • No systemic symptoms
doses 8h • swelling (L) 2nd toe and blisters on the palmar area that tend to
apart excoriate and dry spontaneously
Ampicillin + meningitis 200-300 1-2 weeks • both feet: erythema with thickening and cracks of the interdigital
Chloramphenicol mg/kg/d 4 areas of
doses • Left 2nd toenail: tenderness and swelling of the base of the nail
• Toenail: thickly cornified with scaling at the tip
75-100 • Both hands: vesicular eruptions. Some have dried up.
mg/kg/d 4
doses 1. Impression: Tinea Pedis + Tinea Ungium with Trichophytid Reaction
Dexamethasone meningitis 0.6 mg/kg/d 2 days
IV 4 doses TINEA PEDIS
• Initial manifestation is itching between the toes
Streptococcus pneumoniae • hyperkeratosis of the sole
• Gram (+) , lancet-shaped diplococci in chains • Development of vesicles that rupture and discharge a thin fluid
• Skin of the toe webs becomes macerated and peels
• α-hemolytic on blood agar, quellung reaction due to • Cracks and peeling appear due to chronicity
capsular polysaccharide, optochin sensitive
• enhanced by high CO2 concentration (5%) TINEA UNGIUM
Incidence • Brought about by Prolonged Tinea Pedis
• Males are more affected than females • Nail Infection with hyphal invasion
• decrease ability of children <2yr of age to produce antibody • Yellow, brittle, thickened, and crumbly nails
against polysaccharide antigens
Trichophytid Reaction
• spread from person-to-person through inhaling droplets • Hypersensitivity to constitiuents or products of the fungus
from the respiratory tract and through close personal • Allergic manifestations usually in the form of vesicles
contact. • Occurs elsewhere in the body, most commonly the hands
Pathogenesis
• in children, types 6, 14, 19 and 23 most frequent 2. What office procedure can be done to establish the diagnosis?
• production of disease through multiplication in tissues; no • The diagnosis of Tinea can be made from skin scrapings and nail
toxins of significance scrapings by culture or direct microscopic examination with
• Sudden onset of fever, chills, and sharp pleural pain; potassium hydroxide (KOH).
sputum similar to alveolar exudate (bloody or rusty) • In patients with suspected Trichophytid reaction, a skin test may be
• S. pneumoniae is normally found in the nasopharynx of 5- performed.
10% of healthy adults, and 20-40% of healthy children • Hair and nails from markedly inflamed skin may fail to show hyphae
• pneumonia occurs if the organisms are inhaled into the on direct examination so diagnosis is mostly based on the clinical
lungs and not cleared features.
• polysaccharide capsule makes it resistant to phagocytosis
• spreads to the blood stream and is carried to the meninges, 3. Are the lesions in the palm of the same nature as those in the feet?
joint spaces, bones, and peritoneal cavity No, the lesions on the palm of the hand are allergic manifestations due to the
• local complications: empyema, pericaditis, mastoiditis, constituents or products of the fungus. This hypersensitive reaction is also
epidural abscess or meningitis known as Trichophytid reactions. It is usually occur at sites distant to the
• rare complications can cause DIC & Hemolytic-uremic fungal infection When the lesions are examined in KOH, no fungal structures
syndrome will be observed.
Diagnosis
• Physical examination 4. What laboratory procedure will you perform to identify the organism?
• Chest x-ray A. Clinical Examination of the Infected area
• Phlegm test B. KOH Examination of skin scrapings
• Blood test C. Culture
• Urine test KOH Examination
• Blood drawn from culture, sputum • KOH is used to digest non-fungal cells so that the hyphae and
• Stained smears: RBCs with PMNs spores will be more visible
• Capsule swelling test: quellung reaction
• Culture: continuous monitoring at average time of
isolation; 14-15 hr
• Pneumococcal meningitis: prompt examination and culture Calcofluour / Cellufluour
of CSF - may be incorporated to facilitate detection of hyphae.
Immunity and Treatment - it binds to the chitin in the fungal cell wall and provides
• Type-specific vaccines due to transformation reactions excellent contrast in the preparation when examined with a
• Penicillins – DOC, but some already resistant fluorescent microscope.
• Oral Pen V for minor infections
• Intravenous Pen G for bacteremia, pneumonia, meningitis Culture
• For serious infections that are Pen-resistant; Vancomycin is • Most fungi grow optimally and more rapidly at an incubation at
used; Rifampin added in non-responsive cases 30oC. Room temperature, 25C, is acceptable if 30C is not
• Type-specific vaccines due to transformation reactions available.
• Penicillins – DOC, but some already resistant • Fungal cultures should be incubated for 2 to 4 weeks and examined
• Oral Pen V for minor infections periodically. Plates should be held for 4 weeks until reported
• Intravenous Pen G for bacteremia, pneumonia, meningitis “negative” for growth.
• For serious infections that are Pen-resistant; Vancomycin is
used; Rifampin added in non-responsive cases Culture Media for Isolation of Dermatophytes

a. Mycosel or Mycobiotic agar- Isolation of dermatophytes from hair, skin,

Case 8
and nail specimens; inhibitory agents are cycloheximide and
chloramphenicol; similar to DTM
A 23 year old male athlete has a 2 year history of interdigital
itchiness and erythema. He was prescribed creams and foot powder
b. Dermatophyte test medium (DTM)- Isolation of dermatophytes from hair,
which would temporarily relieve his condition. He had no systemic
skin, and nail specimens; dermatophytes produces alkaline metabolites ,

14
which raise the pH and change the color of the indicator from yellow appearance – clear; White cells – 150/mm3 predominantly
to red; antibiotics inhibit saprophytic fungi and bacteria lymphocytic; CSF glucose – 2.2 mmol/l; Blood glucose – 3.8 mmol/l;
Protein – 0.4 g/dl. India ink preparation was positive for budding
Differential Test Media yeast with thick capsule
a. Potato dextrose agar- Stimulation of conidia production of fungi;
demonstrates pigment production of T. rubrum CHIEF COMPLAINT :
Recurrent worsening headache
b. Trichophyton agars No1 – 7- Nutritional requirement tests for the
differentiation of Trichophyton. Seven media contains various growth SALIENT FEATURES
factor requirements for Trichophyton species. 24 years old
male
Tinea pedis: Tinea Unguium: (+) HIV (1997)
Trichophyton rubrum Trichophyton rubrum CD4 count 80/mm3 ( has been well)
Trichophyton mentagrophytes Trichophyton mentagrophytes (-) focal neurological signs
Epidermophyton floccosum Epidermophyton floccosum
normal fundoscopic findings
(+) curd like lesions
Morphology of Dermatophytes causing Tinea pedis
 tongue
Organism Colonial Microscopic Comments buccal mucosa
Characteristics Appearance normal CT scan
Epidermophyton White to tan Numerous Lumbar puncture results
floccosum colonies that club-shaped, CSF appearance – clear
become yellow, smooth- White cells (lymphocytic) – 150/mm3
mustard-yellow walled CSF glucose – 2.2 mmol/l
with age; flat, macroconidia Blood glucose – 3.8 mmol/l
suede-like with 2 to 4 Protein – 0.4 g/dl
texture with cells India ink preparation
folded center. occurring (+) budding yeast with thick capsule
Reverse side is singly or in
yellow-brown clusters of 3
or dark orange to 4;
with folds microconidia
is absent
Trichophyton Colonial types Microspores Urease
mentagrophytes may be velvety are positive in 48
and fluffly or numerous, hrs; grows on
granular and small, globose Trichophyton
flat. Color is and arranged agars nos
white or tan to in grapelike 1,2,3 and 4.
pink. Reverse clusters;
side is white, coiled, spiral
rose, or red- hyphae may
brown be observed;
macroconidia
are rare, thin
walled,
smooth and
cigar shaped
Trichophyton Fluffy or Tear-shaped Rarely
rubrum granular white microconidia hydrolyzes
to pink borne urea; requires
colonies. laterally from 7 days for
Reverse side is long strands observable
cherry-red or of hyphae; reaction;
wine-red when rare, thin- grow on
grown on walled Trichophyton
cornmeal agar smooth, agars 1, 2, 3
pencil-shaped and 4
macroconidia

Treatment
• topical or oral antifungals or a combination
• topical agents are used for 1-6 weeks
• recurrence of the infection is often
• chronic hyperkeratotic (moccasin) tinea pedis - apply PATHOGENESIS OF HIV DISEASE
medication to the bottoms and sides of the feet  HIV enters body and binds to Langerhans/ dendritic cells, which
• interdigital tinea pedis - apply the topical agent not only to carry the virus to CD4+ T cells. Infected CD4+ T cells home to
the interdigital areas but also to the soles lymphoid tissue, where the infection is established.
• steroids for the allergic reactions

 Virus replication accelerates, and massive viremia leads to wide

In addition:
• Keep your feet clean and dry, especially between your toes.
• Wash your feet thoroughly with soap and water and dry the
area very carefully and completely. Try to do this at least
twice a day.
• Wear clean, cotton socks and change your socks and shoes
as often as necessary to keep your feet dry.
Case 9
 A 24 year old man with HIV visits his doctor with six-week
history of recurrent worsening headaches. His CD4 count is
80/mm3 and he has been well since being diagnosed as HIV-
1 seropositive in 1997.
dissemination of virus throughout lymphoid tissue. HIV-specific
immune response occurs and virus is trapped on the follicular
dendritic cells of germinal centers in the lymphoid tissue. Chronic,
persistent infection is established despite an immunological
response to the virus.
 HIV-specific immune response occurs and virus is trapped on the
follicular dendritic cells of germinal centers in the lymphoid tissue.
Chronic, persistent infection is established despite an
immunological response to the virus.
 Lymphocyte depletion occurs, along with destruction of the
architecture of lymphoid tissue.


 On examination he has no focal neurological signs and

fundoscopy is normal. He has curd like lesions in the tongue
and buccal mucosa. A CT head scan was normal and a
lumbar puncture was performed. The results are : CSF

15
  Simultaneous blood glucose also considered
 Normally CSF glucose is 20-30 mg/dL lower than blood
glucose
 Patient blood glucose: 3.8 mmol/L or 69.09 mg/dL

Differentials- Fungal Meningitis

Cryptococcus neoformans

 Gradual onset of symptoms (headache)

 Onset may be : acute (esp. in AIDS patients)
 Signs and Symptoms:
 Headache
 Fever
 Nausea and vomiting
Time course and
 Stiff neck
stages of HIV disease
 Sensitivity to light
A long clinical latency  Hallucinations
period follows the  Occurs in:
initial mononucleosis-  AIDS patients
like symptoms.  Organ transplant recipients
The progressive  Idiopathic CD-4 lymphopenia
decrease in the  Hodgkin disease
number of CD4 T cells,  sarcoidosis
even during the Candida spp.
latency period, allows
opportunistic  The most common species :C albicans,
infections to occur.  Involvement of the CNS usually follows hematogenous
The stages in HIV dissemination.
disease are defined by  Most important predisposing risk for acquiring disseminated
the CD4 T-cell levels candidal infection:
and occurrence of  Iatrogenic in nature
opportunistic diseases.  Use of broad-spectrum antibiotics
 Use of indwelling devices such as urinary and
COMPLICATIONS OF HIV INFECTIONS vascular catheters
Opportunistic Infections  AIDS is also considered a predisposing risk factor.
1. Protozoal  May also follow neurosurgical procedures(e.g. placement
a. Toxoplasmosis of the brain of ventricular shunts)
b. Cryptosporidiosis w/ diarrhea
c. Isosporiasis w/ diarrhea DIAGNOSTIC TESTS
2. Fungal  Microscopic methods
a. Candidiasis of the esophagus, trachea and 1. CSF India ink preparation
lungs or Nigrosin stain
b. Pneumocystis carinii pneumonia  Identify capsule of
c. Cryptococcosis (extrapulmonary) Cryptococcus neoformans
d. Cryptococcal Meningitis (10% of HIV patients)  The test will be positive when about 103 to 104 CFU/ml
e. Histoplasmosis are present in a CSF sample
f. Coccidioidomycosis  AIDS patients have larger concentrations of yeast ranging
3. Viral between 105 to 107 CFU/ml
a. Cytomegalovirus disease 2. Hucker modification of Gram stain
b. Herpes simplex virus infection  Fungi are 2-3x the size of gram+ cocci, with hyphae often
c. Progressive multifocal leukoencephalopathy 2-3x wider than gram+ bacilli
d. Hairy leukoplakia caused by EBV  C. neoformans stain pale lavander with blue inclusions
 examine for pseudohyphae and budding yeast cells
4. Bacterial
a. Mycobacterium avium
 Culture
b. Any atypical mycobacterial disease
c. Extrapulmonary tuberculosis  Birdseed agar
d. Salmonella septicemia (recurrent)  C.neoformans
e. Pyogenic bacterial infections (multiple or recurrent)  Phenol oxidase(+)
5. Opportunistic neoplasias  agar turns brown-black colonies, 4-
a. Kaposi’s sarcoma 7days
b. Primary lymphoma of the brain  Cornmeal Tween 80 agar
c. Other non-Hodgkin’s lymphomas  Differentiation of candida and other yeasts
based on production of hyphae, pseudohyphae,
6. Others chlamydospores, arthroconidia
a. HIV wasting syndrome  Yeast assimilation media (carbon or nitrogen)
b. HIV encephalopathy  Detects CHO assimilation through utilization of
c. Lymphoid interstitial pneumonia carbon or nitrogen by yeast in presence of
oxygen
INITIAL DIAGNOSIS  Yeast fermentation broth
AIDS  Identification of yeasts by fermentation
reactions with various CHOs
 Rapid urease test for yeast
 Cryptococcus
 urease (+)
CSF VALUES INTERPRETATION  (+) yellow turns to pink in 4 hours

Diagnosis Cells CHON  Serology

(per uL) (mg/dL)  Cryptococcal Antigen Test
 Detection of Cryptococcus antigen in blood and CSF by
NORMAL 0-5 lympho 15-45 EIA method
Patient 150 (mostly 0.4 g/dL
Lympho) Or  Initial titer (in CSF) correlate with the yeast burden
400mg/dL
Granulomatous Meningitis 100-1000 (mostly High (>50)  Positive in over 90% of cases of Cryptococcal meningitis
(mycobacterial, fungal) Lympho) among HIV-positive patients
 In evaluating results of CSF glucose determinations  Latex Agglutination

16

 Simple and rapid latex agglutination test for the
qualitative and semi-quantitative detection of
the capsular polysaccharide antigens of
Cryptococcus neoformans in serum and
cerbrospinal fluid (CSF)
 Initial titer (in the CSF) correlate with the yeast
burden
 Consistently positive in over 90% of cases of
Cryptococcal meningitis among HIV-positive
patients
CSF ANALYSIS
 Reducing ICP by repeated LP and draining of CSF reduces
symptoms such as headache, nausea, vomiting, cranial
nerve palsy and visual changes.
CASE 10
This 19 year old student was in his usual state of health until the evening
prior to admission, when he went to bed with a headache. He told his
mother that he felt feverish, and on the following morning, his mother found
him in bed, moaning and lethargic. He was brought to the ER where he
appeared toxic and drowsy but oriented. His temp was 40°C, his HR was 126
bpm, and his BP was 100/60 mmHg. His neck was supple. He had an
impressive purpuric rash, not blanching, most prominent on the trunk, legs
and wrists. A gram stain of material taken from one of the patient’s skin
lesions show gram (-) diplococci. His WBC was 26,000/uL (25% band forms).
The platelet count was 80,000/uL.

Blood cultures were obtained, a lumbar puncture was performed, and the
patient was started on IV chloramphenicol. CSF glucose, protein and WBC
were normal, and CSF bacterial culture was negative. Blood cultures grew
the organism seen in patient’s skin lesions by gram staining.

Working Diagnosis: Meningococcal Disease (meningococcemia)

The most important tests for diagnosing meningitis are the gram stain and
culture. Suggestive findings: gram (-) diplococci in skin lesions, purpuric rash,
symptoms of meningitis
• however, CSF findings do not implicitly suggest bacterial meningitis
 probably in early stages of disease
Normal values Patient’s values CSF findings Bacterial Viral Fungal/tuberculous
 CSF adult wbc = 0-  Leukocytosis 150/mm3 meningitis meningitis meningitis
5/µL predominantly PMNs ↑↑
 CSF Protein level= lymphocytes Lymphocytes ↑ ↑
15-45 mg/dL  Elevated protein levels CHON Normal
↑↑ ↑
 CSF Glucose level= (400 mg/dL)
Glucose ↓ Normal ↓
2.8-3.9 mmol/L  Decreased glucose levels
(2.2 mmol/L)
Causative organisms:
Organism Peak age incidence Gram stain
COMMON ETIOLOGICAL AGENTS FOR MENINGITIS Escherichia coli Neonates Gram (-) rods
 Fungal – Cryptoccocus neoformans Haemophilus Infants and children Gram (-)
 Bacterial influenzae coccobacilli
 Neisseria meningitidis Neisseria Adolescents and Gram (-)
meningitides young adults diplococci
 Listeria Monocytogenes
Streptococcus Elderly Gram (+) cocci in
 Pseudomonas aeruginosa
pneumoniae chains
 Staphylococcus aureus
 Streptococcus agalactiae
 Haemophilus Influenzae Meningitis
 Mycobacterium tuberculosis  refers to inflammation the meninges of the brain or spinal cord.
 Viral Meningococcus /Meningococcal Meningitis  is reserved for the Gram-
 Herpesvirus type 1 and type 2 negative, bean-shaped diplococcus, Neisseria meningitidis.
 Rabies virus
Differential Diagnoses:
 Epstein-Barr Virus
- Tuberculous Meningitis
 Cytomegalovirus
- Viral Meningitis
 JC virus - Rocky Mountain Spotted Fever
 Protozoa – Toxoplasma gondii - Disseminated Gonococcemia
COMMON ETIOLOGICAL AGENTS FOR CURD LIKE LESIONS IN TONGUE
 Candida albicans QUESTIONS
1. What bacterium was causing this patient’s illness?  Neisseiria
PROGNOSIS meningitides
 Depends on management (patient’s response to antiviral 2. Is this organism ever part of the normal oropharyngeal flora?
and antifungal drugs) Neisseiria meningitides
 Can be dismal if no effective initial therapy is given upon o colonize the upper respiratory tract of about 10% or
diagnosis healthy individuals
 Management should address immune function and o infection occurs either by direct contact or by respiratory
nutritional status to improve outcome of disease droplets
 Poor indicators: Altered mental status, CN nerve o portal of entry: nasopharynx
involvement, Inc. ICP, Inc no. of organisms ( crypt, o found associated with or inside PMNs
antigen titers), < 20 WBC/mm3 o neisseria which are normal inhabitants of the human RT
rarely cause disease and occur extracellularly
MANAGEMENT
 Using higher doses of amphotericin B (w/ or w/o 3. Which immunologic abnormalities predispose individuals to
flucytosine) for induction infection with this organism?
- Host susceptibility
 amphotericin B (0.7 mg/kg/day) is given, with or
without oral flucytosine (5-FC, 25 mg/kg every - Absence of bactericidal antibody (IgM and IgG)
six hours) for two weeks.
 adding flucytosine to amphotericin B increases
- Inhibition of serum bactericidal action by a blocking
IgA antibody
the rate of clearance of CSF
 Using fluconazole rather than amphotericin B for - Complement component deficiency (C5, C6, C7, or
maintenance C8)
 fluconazole (400 mg/day for eight weeks, - Genetic component
followed by 200 mg/day) is preferred o Mannose-binding lectin variants
 Patients intolerant to fluconazole may benefit o Anti-inflammatory cytokine profile: low
from itraconazole maintenance at 400 mg/day. level of TNF and high level of IL-10
 Reducing intracranial pressure in patients presenting with o Factor V Leiden mutation
dangerously high opening pressures in their CSF o Polymorphism in PAI-1 gene
- Complement deficiency
o Antibody deficiency syndromes

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 o Deficiency of terminal components
(C5-9)

4. Which serogroups cause illness? The serogroup is based on

antigen from which part of the bacterium?
- At least 13 serogroups of N. meningititidis identified Age of Dose Duration Precaution
- Serogroups A, B, C, Y, and W-135 are associated w/ Infants/Child/Adult
Rifampicin 5mg/kg, 2 days May interfere
disease in humans
≤ 1 mo orally evry with efficacy
- The confirmed cases in Baguio in 2005 have been 12 hours of oral
identified as Serogroup A > 1 mo 2 days contraceptives
- 13 serologic groups are divided on the basis of the 10mg/kg and some
antigenicity of their capsular polysaccharides (max 600 seizure
o e.g The Group A polysaccharide is a polymer mg) every 12 prevention
hours and
of N-acetylmanosamine phosphate, and
anticoagulant
Group C of N-acetylneuraminic acid.
medications;
- These antigens are found in blood and CSF of patients
may stain soft
with active disease.
contact lens
5. Which prophylactic strategies are useful for large Ceftriaxone 125 mg IM Single dose To decrease
populations? ≤ 15 y/o the pain at
Organization or Community based outbreaks injection site,
-low risk: mostly are indirect contacts with high risk >15 y/o 250 mg IM Single dose dilute with 1%
individuals not index patient lidocaine
-mass vaccination Ciprofloxacin 500 mg IM Single dose Not
-however those with direct contacts should receive ≥ 18 y/o recommended
chemoprophylaxis also for people less
than 18 years
School or Institution based out breaks of age
High risk: direct contact with index patient - Rifampin and ciprofloxacin are commonly used for chemoprophylaxis.
-mass chemoprophylaxis Other agents include ceftriaxone and azithromycin
- Spiramycin is the primary prophylactic regimen used in many European
Meningococcal Polysaccharide Vaccine countries.
- Single administration of quadrivalent vaccine - Vaccination with monovalent A; monovalent C; bivalent A-C; or
(serogroups A, C, W-135 and Y) quadrivalent A, C, Y, and W-135 vaccine should be an adjunct to
- Immunizes 80 to 95% of immunocompetent adults antibiotic chemoprophylaxis of susceptible contacts in epidemics
- Children >3 y/o can be vaccinated to prevent - A single intramuscular dose of an oily suspension of chloramphenicol has
serogroup A, needs two doses with 2-3 months interval been shown to be as effective as 5 days of penicillin in persons with
- Ineffective for children <2 y/o meningococcal meningitis, and this may be useful in resource-poor
- Duration of vaccine induced immunity is <5 years countries.
- No vaccine for serogroup B since its polysaccharide is
a sialic acid polymer that is poorly immunogenic in 7. What is a purpuric rash, and which virulence factor plays a central role
humans responsible for its appearance?
Purpura
Age Dose Duration - dark (purple or red) non-blanching rash resulting from bleeding into the
skin from small blood vessels.
Rifampicin - Small spots- petechiae
< 1 mo 5mg/kg, orally every 12 hour 2 days - Large spots- ecchymoses
> 1 mo 10mg/kg (maximum 600mg), 2days - Endotoxin is the dominant proinflammatory molecule that mediates
orally every 12 hours meningococcal disease (esp. its lipid A moiety)
(need to know by A1)
Meningococcemia in the Philippines
- One of the 16 diseases targeted by the National Epidemic Sentinel
Surveillance System (NESSS)
Ceftriaxone - Average of 100 meningococcemia cases/year, without seasonal
< 15 y 125mg, intramuscularly Single dose variation
> 15 y 250mg, intramuscularly Single dose - Largest recorded outbreak - Sept 2004, CAR
o 150 cases, 40 deaths by February 2005
Ciprofloxacin o Serogroup A, sequence type 7
> 18 y 500mg, orally Single dose - Threshold levels for outbreak declaration
o Sporadic/Isolated Case - One case in a province/municipality
within a month
Drugs not used for chemoprophylaxis… o Geographic Cluster of Cases - 2 or 3 cases in a
Penicillin province/municipality within a month
-does not eradicate the carrier state o Outbreak - 4 or more cases, with at least one confirmed case,
Sulfonamides in a province/municipality within a month
-emergence of resistant strains - Geographic distribution
Minocycline o CAR – 28%; NCR – 15%
-can eradicate carrier state o City and province with highest number of reported cases
-produces dizziness and vertigo
– Baguio and Benguet
- Profile of Cases
6. Which prophylactic strategies are useful for exposed
o Age range: 2 months – 51 years (median 7 years)
individuals?
o Majority are males (57%)
High risk individuals:
- Persons living together and sharing sleeping
quarters (eg. People living in the same house, MENINGOCOCCAL DISEASE
dorm room, boarding houses, military barracks, - diseases caused by Neisseria meningitides (common name:
prison cells, evacuation camps), including meningococci)
overnight visitors in the week preceding the - includes:
onset of the case’s illness o Meningococcal meningitis
- Persons who have similar level of close contact o Meningococcemia
(eg. Barkadas, boyfriend/girlfriend kissing) - Pathogenesis
- Health care workers or care givers who have had Transmission (respiratory droplets)  acquisition  bacterial
intimate exposure to nasophrayngeal secretions colonization in NASOPHARYNX  either asymptomatic carriage OR
(eg. Mouth-to-mouth resuscitation, intubation bloodstream invasion
- Individuals with at least 7 hours of close contact
during the week before onset of illness have an BLOODSTREAM INVASION
increased risk of being infected. – 3 possibilities
55% - meningitis (most common)
30% - meningococcemia + meningitis

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 15% - fulminant meningococcemia  rapid multiplication in
bloodstream!
 HOST DEFENSE mechanisms: most important factor in
preventing bloodstream invasion by meningococci
o A, B, C, Y, W-135 are associated with human diseases
o Serogroups A, B and C account for over 90% of
meningococcal disease
o Most common cause of epidemics in Africa and Asia:
serogroup A and serogroup C

MENINGITIS (meningococcal cause) MENINGOCOCCEMIA

- classic triad: fever, headache, nuchal rigidity (stiff neck); - Etiologic agent: Neisseria meningitides
often altered mental status - Consequence of very rapid meningococcal multiplication in the
- CSF profile: ↑CHON, ↓neutrophils, ↓glucose bloodstream
- Gram stain of CSF: (+) gram negative diplococci - clinical features:
- CSF culture should grow meningococci on proper medium o purpuric skin lesions
 non-blanching
DIAGNOSIS: Meningococcemia WITHOUT Meningitis  trunk, extremities
 poor prognostic sign  most useful clinical finding
 means that bacteria multiplied rapidly in blood that meningeal o DIC
seeding has not yet occurred or has not yet elicited inflammation in o Shock
CNS o Sepsis
 why NOT Meningitis in our Px? - Complications
- Normal CSF profile o Depends on area of seeding
- (-) CSF culture  Meninges – meningitis (most common
- (-) nuchal rigidity complication)
- Still oriented; mental status not yet altered
 Joints – arthritis
 NO clinical evidence of meningitis!
 Pericardium – pericarditis
NEISSERIA MENINGITIDES - Definitive diagnosis: recovery of the bacteria (or its DNA/antigen)
- G(-) aerobic diplococci in CSF, blood, synovial fluid OR skin lesions
- Oxidase (+) - Other lab tests:
- (+) growth on chocolate blood agar, Mueller-Hinton o Gram staining: gram negative diplococci
agar o Culture: grow best on Mueller-Hinton agar, chocolate
- (+) glucose, (+) maltose utilization agar, blood agar – w/ CO2
- Virulence factors: o Oxidase test: (+) purple colonies
o Polysaccharide capsule: for bloodstream o CHO utilization: (+) glucose, (+) maltose
invasion; major virulence factor o Throat swab on Thayer-Martin agar  only confirms
o Lipooligosaccharide(LOS)/ endotoxin: carrier state, not disease
responsible for symptoms of Px o PCR – amplify DNA, sample: buffy coat or CSF
o Pili – adhesion to nasopharynx membrane o Latex agglutination test
 For meningococcal polysaccharides
- Epidemiology
o Humans – only natural reservoir (part of  Less sensitive than PCR
- Prevention & Control
upper resp tract flora)
o MOT: respiratory droplets, aerosols o Rifampin: 600 mg orally twice daily for 2 days
o Portal of entry: nasopharynx o Minocycline: 100 mg every 12 hours
- Serogroups:
o 12 serogroups identified

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