INTERNAL MEDICINE POSTING

INFECTIOUS DISEASE
1.0 CHOLERA
Etiological agent Diagnosis
Vibrio cholera (curved, flagellated Gram- negative bacillus) -examination of freshly passed stool: can isolate rapidly
-only type O1 & O139 cause disease,eg explosive outbreaks motile organism
or pandemics that affect whole country -rapid dipstick test
-stool and rectal swab
Transmission
-fecal oral route (by contaminated carriers, foodstuff, contact Management
carriers) 1. Oral rehydration salt
-glucose (and other CHO) enhance Na & water reabsorption
Pathogenesis in the small intestine, even in the presence of secretory loss
-cholera toxin: d/t toxin
produce massive secretion of isotonic fluid into the -cereal based electrolyte solution: not only can rehydrate but
intestinal lumen also reduce stool volume
release serotonin from enterochromaffin cell in the gut,
which activate a neural secretory reflex in the enteric nervous 2. Antibiotic
system -oral erythromycin and ciprofloxacin 1g PO stat

Clinical feature 3. Zinc supplement

-incubation period: few hrs to 6 days -can shorten the illness
-profuse painless diarrhea + vomiting
-rice water stool Prevention
-massive fluid losshypovolaemic shock 1. Lived attenuated and killed vaccine
(hypotension, tachycardia, cold & -advailable but neither protect against O139 strain
clammy hand, peripheral cyanosis)
dehydration (sunken eyeball, hollow 2. Good hygiene and sanitation
cheeks, ↓ urine output)

2.0 TYPHOID FEVER

-one of the typical form of enteric fever
Etiological agent
Salmonella typhi (rod- shaped, flagellated, aerobic gram –ve
organism)
Transmission
Fecal oral (acid suppression from PPI ↑ risk)
Pathogenesis
Bacterial invade the small bowel wall via Peyer’s patches,
then spread to regional LN and blood
Clinical feature
-incubation period: 10-14 days
-abdominal tenderness, hepatomegaly lymphadenopathy and
scanty maculopapular rash (rose spot)
-without treatment, will have serious complication usually in
3rd week: meningitis, lobar pneumonia, osteomyelitis,
intestinal perforation and intestinal haemorrhage
-patient will gradually improved on 4th week, although in
developing country, up to 30% of the infected will die and
10% of untreated survivors will relapse
-after clinical recovery 5-10% will become convalescent
carriers (continue to excrete S. typhi for several month) and 1-
4% will become chronic carriage (carry the organism for >
1yr) with usual site of carriage is gallbladder a/w the present
of gallstone.
Diagnosis
-blood culture: +ve in most cases within first 2 weeks
-culture of intestinal secretion, faeces and urine
-bone marrow culture: more sensitive than blood culture, but
rarely required (exp in pt who have already receive
antibiotics)
Management
1. Fluid replacement and good nutrition
2. Ciprofloxacin 500mg bd for 10d
Alternative to ciprofloxacin resistance: ceftriazone 2g IV
daily for 14d OR azithromycin 1g PO on 1d then 500mg on
d2-6
if severe: IV ciprofloxacin or cefotaxime for 10-14d
if encephalopathy+ shock:IV dexamethasone 3mg/kg stat
before any antibiotics
Prevention
-improved sanitation and clean water
-vaccination with either injectable inactivated or oral live
attenuated vaccines give partial protection
3.0 DENGUE FEVER
Etiological agent: Dengue virus (Flaviviridae group, genus Flavivirus)
consist of 4 closely related but antigenically distinct serotype: DEN-1, DEN-2, DEN-3, DEN-4.

Vector: Aedes mosquitoes (arbovirus)

aedes aegypti: more effective than other because it can stand long period of dessication
: invasion during warm period, not survived the winter
aedes albopictus: rural areal areas

Epidemiology: affects tropical and subtropical areas, predominant in urban and semiurban

Incubation period: 2-7 days

Clinical course of dengue

1. Febrile phase -2 to 7 days

differentiate dengue with other illness
2. Critical phase
differentiate DF and DHF
crucial to be recognised as clinical
deterioration at this phase
-early marker: ↑ HCT
-late marker: fluid accumulation at
extravascular space
3. Recovery phase
-high grade fever, skin flush, generalised body ache, myalgia, arthralgia,
headache, sorethroat, anorexia, nausea and vomiting
-+ve hemorrhagic manifestation: +ve tourniquet test, petechiae, mucosal bleeding
-lab test: leukopenia
-toward late febrile (after 3rd day of fever)/ around deferversence (3rd-5th of
illness)
-↓ body temperature coincide with ↑ capillaries permeability
-duration: 24-48 hrs
-condition depend on plasma leak
better if no/↓plasma leak
worse if a critical volume of plasma leak
-less severe: minimal, transient, recover spontaneously
-more severe: restlessness, cold extremities, ↑capillaries refill time
: ↑PR, ↑DBP, ↓pulse pressure
: abdominal pain, restlessness, altered conscious level, clinical fluid
accumulation, tender hepatomegaly
-lab ix: thrombocytopenia, ↑ HCT, leukopenia, hypoproteinemia,
hypoalbuminaemia, ↑ AST
-plasma leakage is stop and is followed by reabsorption of extravascular fluid
-general well being is improved
-classical rash (islet of white in the seas of red)
-pruritus
-bradycardia and ECG changes
-lab ix: HCT↓ d/t hemodilution (reabsorption of extravascular fluid), recovery of
plt count and WCC
Dengue Haemorrhagic Fever/ Dengue Shock Syndrome
Pathophysiology
-acute ↑ in vascular permeabilityleakage of plasma into the extravascular compartment↑HCT, hypovolaemia, shock↑
sympathetic outputreflex tachycardia, generalised vasoconstriction
-underlying pathological mechanism is unknown, however
upon post- mortem, perivascular edema and lost of integrity endothelial junction can be seen
abnormal immune response (production of cytokine, chemokine, T lymphocyte) and disturbances haemostatic system

Clinical manifestation

g. Others: lactic acidosis (↑ anaerobic glycolysis), massive bleeding, DIVC, multi organ failure

Note:
Secondary infection with heterotypic dengue virus is a/w ↑ risk of developing DHF?

CONCEPT: ANTIBODY DEPENDENT ENHANCEMENT PHENOMENON

Infection with 1 serotype of DENV provide immunity to that serotype for life but no long term immunity to other serotype.
Subsequent infection (2nd infection) by different serotype ↑ the risk of developing severe dengue/ DHF
sub neutralising concentration of the cross- reacting antibody from the previous infection may opsonise the virus and
enhance it uptake and replication in the macrophages or mononuclear cells
enhance T cell activation suppress or delay viral elimination, leading o higher viral load and increase immunopathology

WHO Classification of dengue

Grade I, II: mild
Grade I: fever+/- positive torniquet test+/- easy bruising
Grade II: presence of spontaneous bleeding

Grade III, IV: severe (DSS)

Grade III: circulatory failure
Grade IV: profound shock with undetectable blood pressure or pulse
Lab investigation
(I) Disease monitoring lab test
1. WBC: normal in early febrile phase, decrease rapidly as disease progress
2. HCT: differentiate btw DF and DHF
3. Thrombocytopenia: early febrile-normal
: late febrile- decrease and continue to remain low after several day of recovery
4. LFT: greater elevation of AST>ALT (more prominent in DHF than DF)

(II) Dengue diagnostic test

1. Virus culture + immunofluorescent
-cell culture: vero, LLC-MK2, mosquito cells C6/36 Aedes albopictus
-syncytium formation
-identify by neutralisation test, EIA, haemagglutination inhibition or indirect immunofluorescence

2. Serology
-Immunochromatography (ICT)-rapid diagnosis
-EIA: Dengue IgM & IgG
Dengue IgM usually +ve after d5-7 of illness. Therefore, -ve IgM before d5-7 do not exclude dengue infection
If IgM –ve before d7, repeated sample must be taken in recovery phase
If IgM –ve after day d7 and IgG –ve less than day 7, dengue IgG is recommended for diagnostic confirmation
-NS1 Ag (for all flavivirus)
-Dengue IgA
-Haemagglutination inhibition: differentiate primary and secondary infection
: gold standarc but required paired sera

3. Genome detection/ PCR

useful for diagnosis of dengue infection in early phase (<5d)
able to determine dengue serotype
↓advailability and ↑ cost

Treatment
1. Supportive: fluid replacement, fresh blood transfusion, plt transfusion
2. Isolate pt, g. mosquitoes net

Control
1. Vector control: chemical, biological, environmental, education, law
2. Notify to Ministry of Health/ Local authority/ fogging
4.0 MALARIA
Etiological agent: Plasmodium sp.
Plasmodium falciparum Trophic and subtrophic (severest)
Plasmodium vivax Worldwide
Plasmodium malariae Trophic and subtrophic
Plasmodium ovale West Africa, south America, asia
Plasmodium knowlesi Zoonotic infection (Macaque monkey)-Sabah and Sarawak

Vector: anopheles mosquitoes

Mode of transmission:
1. Inoculation of sporozoites from anopheles
2. Blood transfusion, contaminated syringe, across placenta: trophozoites and schizonts

Classification of malaria
By sp By epidemiology
1. Single infection 1. Indigenous: origin in which the case is diagnosed is at a
-1 sp in pt blood known malarious area outside the country
2. Mixed infection 2. Imported: any case contracted locally without strong
->1 sp in pt blood evidence of direct link to an imported case
3. Multiple infection 3. Introduced: any case contracted locally with strong
->1 parasite in 1 RBC evidence of direct link to an imported case
4. Induced: through blood transfusion and other form of
parenteral inovulation

Life cycle
1. Human cycle
-mosquitoes anopheles feeds on blood after piercing the skin, sporozoites frm salivary gland injected to blood capillaries
(a)pre erythrocytic stage
-sporozoite enter hepatocyte, undergo repeated nuclear division to form pre-erythrocytic schizont which then ruptured
releasing merozoites
-no pigment released
(I) plasmodium vivax and ovale: 2 type of sporozoite, some multiply to form schizont while some remain dormant
(hynopzoite) and reactivate from time to time to form schizont (relapse)

(II)plasmodium falciparum and malariae: no hynopzoite present but small amount of erythrocytic stage persist (dormant) in the
blood stream

(b)erythrocytic stage
-merozoite invade RBC then loss its organelle, appear as a rounded body with vacuole at the centre, cytoplasm pushed at
periphery, nucleus to 1 pole to form ring shaped trophozoite releasing malaria pigment
-trophozoite underfo nuclear division to form erythrocytis schizont then ruptured releasing merozoite (process repeating)

*plasmodium falciparum: erythrocytic schizogony take place @ capillaries and vascular bed of internal organ
: schizont and merozoites not seen in peripheral blood

(c)Gametocyte
-some merozoite develop into sexually diff form, gametocyte (round, exp P. falciparum which is crescent shaped)
-a person with gametocyte is called carrier/ reservoir
-gametocyte is not for clinical illness but transmission

2. Mosquitoes cycle
-fertilization btw male and female gametocyte to form zygoteoocystsporozoite (infective form)

Pathogenesis
Term:
1. Prepatent period: the min time btw entry of sporozoite and the frst appearance of parasite in the peripheral blood film
2. Incubation period: the interval btw the entry of sporozoites and the first manifestation of clinical symprom
: erythrocytic cycle + preerythrocytic cycle
P. ovale & P. vivax: 8-27d
P. falciparum: 8-25d
P. malariae: 15-30d
3. Preerythrocytic cycle
-no significant pathology
-few liver parenchymal is being invaded by the sporozoite to form schizont
-P. vivax and P. ovale: hynopzoiterelapse\

4. Erythrocytic cycle
-complex pathology
-RBC lysis
-recrudescent: all sp (2nd attack of fever d/t leftover erythrocytic schizont)

**Pathological stage: schizont

**Pathology: lysis and necrosis of RBC d/t multiplication of plasmodium

Clinical feature
Fever Pathogenesis
Direct lysis of infected RBC release RBC fragment, malarial fragmentphagocytosis of the product by
macrophages and PMN will release endogenous pyrogene +(cytokine and IL-1)elevation of temperature

Paroxysm/ periodicity of fever

-regular periodicity usually seen after few days of continuous, remittent fever
-atypical fever: diff brood do not become synchronised (P. falciparum)
-fever pattern varies with erythrocytic cycle
P. falciparum Malignant tertian malaria Fever recur at 2d interval
P. vivax & P. ovale Benign tertian malaria Fever recur at 2d interval
P. malariae Benign quartan malaria Feer recur at 3d interval

Stage
-Cold stage (chill and rigor for 1hr)
-Hot stage (fever +HNV for 2-6 hrs)
-Sweating stage (profuse sweating, decreased temperature)
-apyrexia stage (btw paroxysm pt feel well)

Anaemia Pathogenesis
-direct lysis of RBC
-removal of infected or non- infected RBC by the spleen
-autoimmune lysis of coated infected/ non- infected RBC
-decreased incorporation of iron into heme
-increased fragility of RBC
-decreased RBC production from BM suppression

Type: NCNC

Other haematological changes: monocytosis and thrombocytopenia

Splenomegaly Pathogenesis
-massive proliferation of macropahgesdiffused cellular hyperplasia and hypertrophy of
reticuloendothelium cells and dilated sinusoidscongestion and enargement of spleenlater become dark
d/t malaria pigmentchronic: hard (fibrosis)

1. Relapse: reactivation of hynopzoite

: eg. P.ovale & P. vivax
: can be prevented by giving primaquine to eradicate hynopzoite
2. Recrudescent: reactivation of erythrocytic schizogony (d/t development of partial immunity or resistant sppersistence of
parasite at subclinical level)
3. Drug resistance: ability of malarial parasies to multiply or survive at a therapeutic dose of antimalarial drug
(a) RI: parasitaemia clears but recrudescence occurs
(b) RII: reduction but not clearance of parasitaemia
(c) RIII: no reduction of parasitaemia

Outcome
1. Self limiting
2. Complication
(a) Parasite: virulent strain-P. falciparum :infect both young and old RBC (↑RBC affected)
**P. malariae: old RBC; P. ovale, P.vivax: reticulocyte
: can cause multiple infection
 : ↑ parasitaemia
: sequestration of RBC into internal organ to form a knob which block blood flow
(stasis) AKI and cerebral malaria
: resistant sp
(b) Host immunity: non immune individual
(c) Host resistant: extreme age, pregnancy, poor health and nutritional status

Complication
1. Acute
Severe anaemia -HCT</= 20%
-result in CF, shock, hypoxia, confusion
Hypoglycemia -Blood glucose</=2.2mmol/l
-seen in children, pregnant women, IV quinine
Cerebral malaria -d/t sequestration of RBC inside capillaries of RBC
-in pt with depressed consciousness
-resemble bac/ viral meningitis
Renal complocation -creatinine >/=2.5umol/l; UO</=400ml/day
-d/t hypovolaemia, sequestration of RBC, IV haemolysis, haemoglobinuria
Circulatory collapse -systolic BP</=80mmHg
Metabolic acidosis -indicator of severe malaria
ARDS -d/t inravenous fluid overload or pneumonia
Hepatic dysfunction -raised AST (X3 normal) and jaundice
DIVC
Secondary infection -aspiration pneumonia, UTI (catheterization), nosocomial infection
Hyperparasitaemia >/=5% of parasitaemia count
Malaria haemoglobinuria -seen in pt with G6PD treated with primaquine

2. Chronic
(a) Tropical splenomegaly syndrome
(b) Complex immune nephrosis

Lab ix
Blood film -gold standard (can monitor parasitaemia count and severity)
-both qualitative and quantitative
-Giemsa stain

1. Thin smear
-confirm mixed infection
-determining the sp.

2. Thick smear
-lyse RBC to see parasite
-chances tod detect ↑
-sp determination is difficult

Quantitative buffy -small amount of blood is spun in QBC centrifuged at 1200 rpm for 5min
coat -RBC with malaria less dense than normal RBC is isolated
-coat with acridine dye induced fluorescent of parasite which can be readily visualised under oil
immersion
nucleus of parasite detected as green-yello against red blackground
Serology -IGA, IFA, ELISA
-not differentiate btw active and past infection
PCR -to detect sp and drug resistant

Treatment

Term:
1. Radical cure: eliminate all form of Plasmodium sp.
-to prevent the occurrence of clinical symptom (clinical cure-BS)
-to prevent recrudescent and relapse (BS, TS)
-to prevent transmission of infection (Ga)

2. Chemoprophylaxis
-pure: destroy sporozoite
-causal: eliminate tissue schizont (hynopzoite)
-suppressive: eliminate blood asexual form
Quinine -rapid acting BS, Ga (non falciparum)
-used in both uncomplicated and severe malaria
-minor S/E: cinchonism
-major S/E: cardiotoxicity, hypersensitivity, hypoglycaemia
-safe for pregnant women
-quinine resistamt are rare
Chloroquine -rapid acting BS, Ga (non falciparum)
-used in uncomplicated non- falciparum
-highly effective for PO and OM
-S/E: dermatitis, psoriasis, headache, retinopathy
-high level resistant: chloroquine resistant falciparum
Sulphadoxine- -rapid acting BS
pyrimethamine -used in uncomplicated falciparum
-uncomplicated falciparum
-S/E: skin eruption, Steven Johnson syndrome, agranulocytosis
-C/I: preterm, newborn, sensitive to sulphonamide
Mefloquine -rapid acting BS
-used in uncomplicated falciparum
-S/E: psychiatric
-C/I: pregnant
Halofantrine -rapid acting BS
-used in uncomplicated falciparum malaria
-C/I: pregnant and lactating women
ACT -rapid BS
-best current treatment: uncomplicated falciparum malaria, complicated and multi-drug
-as recrudescent is common if montherapy <7d, so used in combination with an longer acting
antimalarial
-S/E: sleep disturbances, type I hypersensitivity
Antibiotic -slow acting BS
-never used as monotherapy
Primaquine -TS and Ga
-S/E: haemolysis in G6PD deficiency pt
-C/I: pregnancy, G6PD

5.0 CLINICAL APPROACH TO PT WITH PROLONGED FEVER

HT -normal HOPI +
(a) travel history
(b) food and water history
(c) occupational history
(d) animal contact
(e) sexual activity
(f) IVDU
(g) leisure activities
PE -skin rashes, lymphadenopathy
-rectal, vaginal, penile examination (STD)
-fever pattern
Ix 1. General ix
(a) Blood test-routine blood test, ESR, CRP, biochemical profile, U&E
(b) Imaging: XRay, Echocardiography, CT, MRI
(c) Radionuclide scanning: injection of indium or technetium labelled leukocyte may occasionally help to
localised infection

2. Microbiological ix
(a) Direct test
-Direct examination of tissue specimen (eg. blood, CSF, urine)
-microscopy and electron microscope

(b) Nucleic acid detection

-identify pathogen specific nucleic acid in body fluid and tissue
-technique: PCR
 (c) Culture: blood, urine, CSF, sputum, biopsy, faecal culture

(d) Immunodiagnostic test:

-tests that detect microbial component
-test that detect an antibody response to infection

Tx -supportive therapy: antipyrexia

-antibiotics, antiviral, antifungal
6.0 AIDS AND HIV
Etiological agent: Human Immunodeficiency Virus
consist of 2 type: HIV- 1 (global) and HIV- 2 (west Africa, france and protugal)
belong to lentivirus group of retrovirus family
retrovirus: characterised by the presence of reverse transcriptase: allow viral RNA to be transcribed into DNA and thence
incorporated into host cell genome
: error prone process lead to genetic variation and diversity
of viral subtype (M, N, O, P)

Route of transmission
Sexual intercourse -vaginal and anal
-heterosexual intercourse account for vast majority on
infection and co- existent STI, especially those with genital
ulcer enhance transmission
-passage of HIV more efficient from men to women and to
receptive partner in anal intercourse
Mother to child (vertical transmission) -transplacental, perianal (majority), breastfeeding
-↑vertical transmission a/w advanced disease in mother,
maternal viral load, prolonged and premature rupture of
membrane and chorioamnionitis
Contaminated blood, blood products and organ donation -in some part of the world where blood may not be screened
and in area where new HIV infection is very high, transfusion
associated infection continues to occur
Contaminated needles -sharing needle and syringe for IVDU
-health care workerneedle stick injury

Pathogenesis
1. Virus transported by dendritic cell from mucosal surface to regional LN where permanent infection is establish
2. The interaction btw host cellular receptor CD4 and HIV surface glycoprotein gp120, together with host chemokine CCR5
co-receptor, is responsible for HIV entry into the cell
3. Virus production by the cell last for 2 day d/t limitation by cell death owing to direct HIV effect, linking HIV replication
to the process of CD4 destruction and depletion. Loss of CD4 is key factor for immunopathogenesis of HIV.
4. Resulting CMI leaves the host open to infections with intracellular pathogen, while coexisting antibody abnormality
predispose to infection with encapsulated bacteria
5. T- cell activation is observed from the earliest stages of infection which in turn lead to ↑ no of CD4 bearing target cell that
can become infected and destroyed

Replication
Clinical feature
Classification- CDC ( based on CD4 count)
Stages
Incubation, seroconversion,
primary illness
Clinical latency
Symptomatic HIV infection
-primary infection: first 6 mth period following HIV acquisition
2-4 weeks following infection may be silent both clinically and serologically
3-6 weeks: self limiting non specific illness, eg fever, arthralgia, myalgia, lymphadenopathy,
sore throat, mucosal ulcer, transient faint pink maculopapular rash, neurological symptom (eg.
headache, photophobia, myelopathy, neuropathy, encephalopathy)
-lab: lymphopenia, thrombocytopenia, ↑ AST
: depleted CD4 lymphocytes
: antibody to HIV absent, viral HIV and p24 core protein ↑
-the majority of ppl with HIV infection may be asymptomatic for a substantial but variable
length of time. However, the virus continue to replicate and person is infectious
-a subgroup of patient with asymptomatic infection have persistent generalised
lymphadenopathy
lymphadenopathy (> 1cm) at 2 or more extrainguinal site for more than 3 mth in the absent
of cause other than HIV infection: symmetrical, firm, mobile, non- tender
-as HIV viral load rises, the CD4 count falls and pt developed an array of sign and symptom.
 -as a result of direct HIV effect and the assoc immunosupression
-the clinical consequences of HIV related immune dysfunction depend on 3 factor
microbial exposure of the pt throughout life
pathogenicity of the organism encounterd
*high grade pathogen: mild immunosupression
*less virulent organism: later stage of immunodeficiency
degree of immunosupression of the host: in severely immunocompromised individual
(CD4<100/mm3) disseminated infection with organism of very low virulence can infected

Systemic based effect of HIV infection

Neurological -infection of the nervous system occur at early stage but clinical neurological involvement
increased as HIV advances
-pathogenesis: release of neurotoxic product by HIV and cytokine abnormality secondary to
immune dysregulation
(a) AIDS dementia complex: have varying degree of severity, ranging from mild memory
impairment and poor concentration to sever cognitive deficit, personality change and
psychomotor slowing
(b)Sensory plyneuropathy: mainly in feet and leg, causing severe pain, which disrupt sleep,
impair mobility and generally reduces the quality of life
(c) Autonomic neuropathy: a/w postural hyotensiona nd diarrhoea
Eye -cytomegalovirus retinitis
-anterior uveitis: acute red eye a/w rifabutin therapy for mycobacterial infection in HIV
Mucocutaneous -common site d/t function of dendritic and langerhand cell, both target cell of HIV, is
disrupted
-pruritus, generalise dry,itchy, flaky skin, recurrent apthous ulcer, common site for
opportunistic infection
Haematological -lymphopenia: as ↓CD4
-anaemia: NCNC
-neutropenia
-isolated thrombocytopenia: circulating ntiplt antibiotics lead to peripheral destruction
-pancytopenia: d/t underlying opportunistic infection or malignancies
GIT -weight loss, diarrhoea, wasting
-GIT infection is common
-HIV enteropathy with varying degree of villous atrophy hhas been described with chronic
diarrhoea when no other pathogen has found
-hypochlorhydia is reported in advanced HIV disease and may have consequences for drug
absorption and bacterial overgrowth in the gut
Renal -HIV associated nephropathy
-nephrotic syndrome
-many nephrotoxic drugs: management of HIV associated pathology
Respiratory -the upper airway and lungs serve as a physical barrier to airborne pathogen and any damage
will decreased the efficiency of protection, leading to increase in upper and lower respiratory
tract infection
-lymphoid interstitial pneumonitis: more commonly in paediatric d/t infiltration of
lymphocyte, plasma cell, lymphoblast in alveolar tissue
Endocrine -reduced level of testosterone and abnormal adrenal function
Cardiac -cardiomyopathy
-lymphocytic and necrotic myocarditis

Opportunistic infection
*refer to table in UM espress
-disease caused by organism that are not usually considered pathogenic, unusual presentation of known pathogen and the
occurrence of tumor that may have oncogenic viral aetiology
-CD4 T lymphocyte used as a marker to predict the risk of infection(CD4>200: low risk)
-Diagnosis in immunosuppressed pt may be complicated by the lack of typical sign, as the inflammatory response is impaired
-specimen should be obtained from the appropiae site for examination and culture in order to make a diagnosis

Etiological agent Feature

1. Fungal
(a) Pneumocystis jiroveci -cause pneumocytic pneumonia and disseminated infection
-seen when pt are severely immunocompromised with CD4 count below 200
Clinical feature
-insidious onset
-SOB, non productive cough, fever, malaise

(b) Cryptococcus neoformans
(c) Candida albicans
(d) Aspergillus
(e) Histoplasmosis,
blastomycosis,
coccidiodomycosis,
penicillium marneffei
2. Protozoa
(a) Toxoplasmosis
(b) Cryptococcocis
3. Virus
(a) Hepatitis B
(b) Hepatitis C
(c) Cytomegalovirus
-PE: tachypnoea, tachycardia, cyanosis, hypoxia, fine crackles
-Lab ix: CT- ground glass appearance
: isolation of organism from bronchoalveolar lavage (silver staining or
immunofluorescent technique)
: PCR amplification of fungal DNA
Treatment: IV co-trimoxazole 120mg/kg daily in divided dose for 21 days
: continuous positive airway pressure (CPAP) or mechanical ventilation
: HAART
: secondary prophylaxis in pt whose CD4 count remain below 200
-cause meningitis, pulmonary, disseminated infection
-source: bird dropping
-mode of infection: inhalation
Clinical feature
-non specific fever, nausea, headache, impaired consciouss level
Diagnosis
-CSF examination (indian ink staining)
-CSF and blood culture
Treatment
-IV liposomal amphotericinB (4.0mg/kg per day) +/- flucytosine
-mucosal infection, particularly oral, vulvovaginal, esophageal, disseminated (uncommon)
Oral
pseudomembranous candidiasis: creamy plague in the mouth and pharynx
erythematous candidiasis: creamy plague in the mouth and pharynx
-rare in HIV, unless there is co- existing factors
-following inhalation, lung infection proceeds to hematogenous spread to other organ
-Treatment: voriconzole
-pneumonia
-caused encephalitis and cerebral abscess
Clinical presentation
-focal neurological lesion with convulsion, fever, headache and possible confusion, eye
involvement (retinitis)
Diagnosis: characteristic radiological finding in CT and MRI ( multiple ring enhancing
lesion)
Treatment: pyrimethamine for at least 6 weeks (loading dose 200mg, then 50mg daily)
combined with sulfadiazine and folinic acid
: HAART is initiated as soon as the pt is clinically stable
-severe and progressive watery diarrhoea +/-anorexia, abdominal pain, nausea, vomiting
-cysts attach to the epithelium of the small bowel wall, causing ssecretion of fluid into the
gut lumen and failure of fluid absorption
-Treatment: supportive (main)
: Nitazoxanide
: HAART
-does not appear to influence the natural history of HIV
-there is significant ↓ HbE Ag clearance, ↑ chronic infection development, HBV
reactivation and reinfection
-more rapid progression of HIV infection and blunted CD4 response to HAART
-More rapid Hepatitis C progression and elevated viral load
-worsening drug related toxicity
Treatment
-similar to just Hepatitis C alone (depend on stage of disease and HCV genotype)
-treat HCV first if HIV infection is stable
1. CMV retinitis
-usually unilateral to begin with then only involve both eye
-clinical feature: loss of vision, floaters, loss of visual acuity, field loss, scotomata, orbital
pain and headache
-Fundoscopy: haemorrhage, exudates follow vasculature of the retina (pizza pie appearance)
-Treatment: oral valganciclovir (900mg twice a day), IV gancyclovir (5mg/kg twice daily)
or foscarnet (90mg/kg twice daily) for at least 3 weeks or until retinitis is
quiescent
 : HAART

2. CMV gastrointestinal condition

-abdominal pain, often generalised or in the lt iliac fossa, bloody diarrhea, generalised
abdominal tenderness, low grade fever
-other: ulceration of oesophagus, hepatitis
-Lab ix: sigmoidoscopy- friable and ulcerated mucosa
: histology- owl eye cytoplasmic inclusion
-Tx: IV ganciclovir (5mg/kg twice daily)
: HAART

3. CMV neurological condition

-CMV encephalopathy
-Treatment: ganciclovir, HAART
(d) Herpesviruses -varicella zoster virus, human herpes virus-8
(e) EBV -primary cerebral lymphoma, non- Hodgkin lymphoma
-oral hairy leukoplakia (leukoplakia at the lateral border of the tongue or the buccal mucosal
as a pale ridge lesion which unsightly and occasionally painful)
(f) HPV -genital, plantar an oral warts
-a/w rapid development of cervical and anal intraepithelial neoplasia
(g) Polyomavirus JC virus
-cause progressive multifocal leucoencephalopathy
infect oligodendrocyte
demyelination within the white matter of the brain
clinical feature: progressive neurological and intellectual impairment, hemiparesis and
aphasia

4. Bacteria
(a) MTB -Pattern of disease differ with immunosuppression
well preserved CD4 count have a clinical picture similar to that seen in HIV negative
patient with pulmonary infection
in advance HIV disease: prominent hilar lymphadenopathy, extrapulmonary TB
(affecting LN, BM, liver), bacteremia
-Treatment: usual regime (extended duration) with long term isoniazid prophylaxis
drug- drug interaction: btw antiviral and antiTB medication
paradoxical inflammatory reaction: new or worsening clinical sign d/t improvement in
immune fuction seen in HIV infected patient starting HAART in the face of MTB

(b) Mycobacterium Avium -occur at late stage of HIV infection when pt are profoundly immunosuppresed
Intracellulare -major clinical feature: fever, malaise, weight loss, anorexia, sweat
: GIT symptom- diarrhoea and malabsorption
-treatment: typically resistant to standard antiTB, although ethambutol may be useful
5. Others 1. Influenza A
2. Salmonella-oral or disseminated
3. Skin condition: folliculitis, abscess, cellulitis (etiological agent: Staphl. Aureus),
necrotizing periodontal disease
4. Strongyloides: hyperinfection syndrome
5. Scabies: widely disseminated atypical, crusted popular lesion known as Norwegian
scabies
6. Neoplasm
(a) Kaposi sarcoma -etiological agent: HHV-8
-Gross: pigmented, well circumscribed and occur at multiple sites
-Histology: multicentric tumor consist of spindle cell and vascular endothelial cells, which
tgt form slit like space in which RBC become trapped
-Treatment: HAART, local radiotherapy, systemic chemotherapy
(b) Lymphoma Non Hodgkin Lymphoma
-Etiological agent EBV
-very aggressive, progress rapidly despite chemotherapy, poor prognosis
(f) Cervical carcinoma -Etiological agent: HPV

Lab investigation
Diagnostic test
1. Detection of IgG antibody to envelope component
-ELISA
-no protective function and persist for life
-can cross the placenta
-not a reliable marker of active infection

2. IgG antibody to p24

-detected from the earliest weeks of infectionand through the asymptomatic phase
-frequently loss as the disease progresses

3. Genome detection assay

4. Viral p24 antigen
-detectable shortly after infection and usually disappear by 8-10 weeks after exposure

5. Isolation of virus in the culture

Monitoring
1. Immunological monitoring
-by CD4 lymphocytes
-bear relationship to the risk of the occurrence of HIV- related pathology
>200: ↑ risk
-performed at approximately 3 mth interval unless value are approaching critical level for intervention, then only performed
more frequently

2. Virological monitoring
-by viral RNA levels
branched chain DNA
RT- PCR
nucleic acid sequence based amplification
-abt 6 mth after seroconversion to HIV, the viral set point for an individual is estalblished and there is corelationbtw HIV RNA
levels and long term prognosis
in pt viral load consistently >100000 copies/ml have 10 times higher risk of progression to AIDS over the ensuing 5 yrs

3. Genotype determination
-result is used to guide the selection of HAART

Treatment
Nucleoside and nucleotide
reverse transcriptase
analogue
Non nucleoside RTI
Protease inhibitor
Integrase inhibitor
Co- receptor
Fusion inhibitor
-tenofovir, abacavir, -Nucleoside RTI: inhibit the synthesis of DNA by reverse
zidovudin, stavudin, transcriptase
lamivudin : need 3 time intracellular phosphorylation
-Nucleotide RTI: same MOA as NRTI
: need 2 time intracellular phosphorylation
Efavirenz, nevirapine -MOA: interfere with RT by direct binding to the enzyme
Fosamprenavir, atazanavir -MOA: act competitively on HIV aspartyl protease enzyme which
is involved in the production of functional viral proteinviral
maturation is impaired and immature dysfunctional viral particles
are produced
Raltegravir -MOA: selective inhibitor of HIV integrase which block viral
replication by preventing insertion of HIIV DNA into human DNA
genome
Maraviroc -MOA: chemokine receptor antagonist which block the cellular
CCR5 receptor entry by CCR5 strains of HIV
Enfurvitide -MOA: inhibit gp-41 mediated fusion of HIV with the target cell
7.0 SEXUALLY TRANSMITTED DISEASE
Disease Feature
Gonorrhea Etiological agent: Neisseria gonorrhoea (gram –ve intracellular diplococcus)
Mode of transmission: horizontal- sexual; vertical- childbirth
Pathogenesis:
1. Virulence factor

2. Gonococci invade non ciliated epithelial cell and multiple in intracellular vacuole protected from
phagocytes and intracellular ab
3. Intracellular vacuole fuse with basement membrane, releasing multiplied bac into subepithelial
CT
4. LPS and cell wall component induce inflammatory response- chronic inflammation
5. Occasionally invade bloodstream- disseminated infection

Clinical feature
-incubation period: 2-14d
-men: ant urethritis (dysuria +/- urethral discharge)
: complication-ascending infection (epididymis or prostate)
: MSM- rectal infection (proctitis)
-women: altered vaginal discharge, pelvic pain d/t ascending infection, dysuria, intermenstrual
bleeding
: complication-bartholin’s abscess
-neonates: opthalmia neonatorum

Diagnosis
1. Culture on Thayer Martin agar/ VCNT agar-small, translucent, convex xolonies
 2. Gram stain- gram –ve intracellular diplococcic
3. Nucleic acid amplification test

Treatment
-single dose ceftriazone IM 500mg (UK)
-single dose oral amoxicillin 3g + probenecid 1g, ciprofloxacin 500mg, ofloxacin (400mg) in low
prevalence of antibiotic resistant
-follow up and culture test repeated 72hrs after tx is completed
-sexual contact notified, examined, treated

Chlamydial infection Etiological agent: Chlamydia trachomatis (obligate intracellular organism)

serotype A,B,C: Trachoma
serotype D-K: urogenital tract infection,pneumonia in newborn, neonatal conjunctivitis, adult
inclusion conjunctivitis

Pathogenesis
1. Exist as 2 form:
elementary body: metabolically inactive but infectious
reticulate body: metabolically active but not infectious
2. EB bind to specific receptor on host cell and enter cell by endocytosis forming EB- containing
vesicle
3. Lysosome cannot fuse with EB- containing vesicle
4. EB differentiate to RB which divide by primary inclusion with host’s cytoplasm, forming
inclusion body
5. After 48 hrs, binary fision stop and RB condense forming EB
6. Cell rupture and release new EB to infect neighbouring cell
7. Host release proinflammatory cytokine which induce progressive chronic inflammatory process

Clinical feature
-men: ant urethritis (dysuria +/- urethral discharge)
: complication-ascending infection (epididymis or prostate)
: MSM- rectal infection (proctitis)
-women: common site of infection- endocervix
: vaginal discharge, post- coital, intermenstrual bleeding, lower abdominal pain
: ascending infection- acute salpingitis
-neonatal: mucopurulent conjunctivitis and pneumonia

Diagnosis
1. Nucleic acid amplification assay
2. Elementary detection using immunofluorescent stain
3. Culture in Mac Coy Cell pretreated with cyclohexamide for detection of cytoplasmic inclusion
body
men: first voided urine, urethral swab
women: endocervical swab

Treatment
-tetracycline or macrolide antibiotic
azithromycin 1g single dose/ doxycycline 100mg 12hrly for 7d for uncomplicated infection
-erythromycin 500mg 4 times daily
-sexual contact notified, examined, treated

Urethritis -2 type: gonococcal or non- gonococcal urethritis

Clinical feature
-characterised in men by discharge from urethra, dysuria, varying degree of discomfort within the
penis
-urethral discharge usually mucoid and worse in the morning
-crusting at meatus and stain in the underwear

Diagnosis
-NAAT
-smear from urethra when pt has not voided urine for at least 4 hr: gram stain and observed under high
power oil immersion lamp>/= 5 PMN per high power field

Treatment
 -azithromycin 1g orally single dose or doxycycline 100mg 12 hrly for 7d
-avoid sexual intercourse
-sexual contact notified, examined, treated

Lymphogranuloma Etiological agent: Chlamydia trachomatis serotype L1,2,3

venereum
Clinical feature
-painless genital ulcer
-painful genital bulboes with sinus formation d/t spread to inguinal lymph node

Diagnosis
1. Detection of nucleic acid
2. Isolation of C. trachomatis from clinical lesions in tissue culture remains the most specific test
3. C. trachoatis serology

Treatment
-doxycycline (100mg twice daily for 21 d) or erythromycin (500mg four times daily for 21d)
-surgical drainage or reconstructive surgery
-sexual contact notified, examined, treated

Syphilis Etiological agent: Treponema pallidum

Mode of transmission: Horizontal- minute abrasion on skin or mucous membrane and sexual contact
: Vertical- transplacental

Clinical feature and pathogenesis

Primary -primary chancre -multiplication of treponema
punched out lesion, raised border, smooth base confined to site of entry
found at contact site -spread by lymphatic and
single and highly infectious blood
-painless regional lymphadenopathy
Secondary -disseminated disease -systemic spread to LN, liver,
-flu like symptom joint, muscle, skin, mucous
-generalised mucocutaneous rash membrane
-condylomata lata (raised, flat, moist, grey) -remain dormant in liver and
-snail tract ulcer (serpenginous ulcer at mouth spleen
and other mucosal surface)
Tertiary -gummas in bone, skin, other tissue -reawakening, multiplication
-neurosyphilis: tabes dorsalis and further dissemination of
-cardiovascular syphilis: aortic lesion, HF treponema

Investigation
1. Histology
exudate
-dark field microscopy to visualised motile spirochetes
-UV microscopy: fluorescent- stained with anti- treponemal antibodies)
biopsy
-silver stained

2. Serologic test
specific: Treponemal IgM and IgG (ELISA)
: TP haemagglutination assay
: TP particle agglutination assay
: fluorescent treponemal antibodies absorption
non- specific: VDRL
:RPR

Treatment
-IM benzathine and procaine penicillin
if allergic: treat with doxycycline

Chancroid Etiological agent: Haemophilus ducreyi

Clinical feature
 -incubation period: 3-10d
-erythematous popular lesion form which then break down into ulcer
necrotic base, ragged edge, bleed easily and painful
several ulcers merge to form giant serpenginous lesion
men: prepuce and frenulum
women: vaginal entrance and perineum
-inguinal lymphadenopathy

Diagnosis
-isolation of H. ducreyi from culture in chocolate agar
-gram stain: gram –ve coccobacilli in rail road or school of fish appearance

Treatment
-single dose regimen include azithromycin 1g orally or ceftriazone 250mg IM
-patient follow up 307 days
--sexual contact notified, examined, treated
Donovaniosis -as known as granuloma inguinale
-Etiological agent: Kelsiella granulomatis

Clinical feature
-heaped up ulcerating lesion with prolific red granulation tissue appears on the external genitalia,
perianal skin or the inguinal region
-pseudo-bubo: extension of the primary lesion from external genitalia to inguinal region

Diagnosis
-ulcer smear and biopsy
-perform Giemsa stain to visualise Donovan bodies in monocyte

Treatment
-3 week treatment: doxycycline 100mg twice daily, trimoxazole 960mg twice daily, azithromycin
500mg daily or 1g weekly, ceftriazone 1g daily
-sexual partner notified, examined and treated
Herpes Simplex -Etiological agent: Enveloped double stranded DNA virus
HSV-1: common inchildhood, increased with age
HSV-2: increased with sexual activity

-Transmisson: oral- oral, oral- genital, sexual

Pathogenesis
• Infects and replicates in skin cells – lysis of infected cells (cytolytic virus) = PrimaryInfection
(vesicles , cold sores, ulcers)
• Spread locally via cell-to-cell invasion
• Spread to distance sites via sensory nerves to sensory ganglia – can remain in latency
HSV-1 : trigeminal ganglia
HSV- 2: sacral ganglia
• Reactivation = post primary infection

Clinical feature
• Primary Infection:
Gingivostomatitis, Herpetic whitlow, Keratoconjunctivitis, Encephalitis, Herpes genitalis

• Post primary infection (recurrences):

Herpes labialis (cold sores), keratitis, encephalitis

Diagnosis
-Clinical diagnosis: typical presentation
-Lab investigation:
(a) virus culture: vescicular specimen ( MRC5/ fibroblast cell line)
(b) serology: detect antibody in serum
(c) PCR: HSV-DNA

Treatment
-primary: saltwater bathing or sitting in a warm bath
: acyclovir 200mg 5 times daily, famciclovir 250mg 3 times daily, valaciclovir 500mg twice
daily (all for 5d)
 : rest, analgesia, antipyretics
-recurrent: less severe and can be manages with simple measure eg. Saltwater bathing
: initially course of acyclovir 400mg twice daily or valaciclovir 250mg twice daily for 6-12
6-12 month
HPV -Non-enveloped double-stranded DNA virus
->150 types oncogenic types
HPV 16 and HPV 18 types account for the majority of worldwide cervical cancers.
nononcogenic types
HPV 6 and 11 types are most often associated with external anogenital warts.

Mode of transmission
-close contact with infected genital skin, mucous membranes, or bodily fluids
-sexual activity
-vagina delivery

Pathogenesis
Infect cells in basal layers of skin and mucosa, divide, squamified, keratinised and protruding layers
become a wart (filiform, flat, plantar, cauliflower-like, dysplasia)

Clinical feature
-Warts - Condyloma acuminata, genital - HPV-6, 11
-Juvenile laryngeal papilloma - HPV-6, 11
-Plantar warts - HPV 1, 4
-CIN & cancer cervix - HPV-16, 18
-Oropharyngeal cancer
-Cancer of anus, vulva, vagina, penis
Diagnosis
-Clinical: typical presentation
-Laboratory investigation: cannot be cultured
: serology not useful
: PCR=HPV-DNA

Treatment
-warts: karyolitic agent like podophyllin, cryotherapy, surgery
-cancer: surgery, radiotherapy, chemotherapy

Prevention
-Vaccination
Gardasil: effective against HPV type 6,11, 16 and 18
Cevarix: effective against HPV type 16, 18
-Condoms

Trichomoniasis Mode of transmission

-horizontal: sexual
-vertical: perinatal

Clinical feature
-women: offensive vaginal discharge, pruritus, dyspareunia, dysuria, frequency, low abdominal pain
: profuse yellow or green diacharge, inflamed vulva and vagina, strawberry cervix
-men: asymptomatic, may have uethral discharge, irritation or urinary frequency

Diagnosis
-direct microscopy examination: motile, flagellated trophozoites

Treatment
-metronidazole 2g orally as a single dose or 400mg twice daily for 7d
-topical therapy: intravaginal tinidazole
Candidiasis Etiological agent: Candida albicans

Risk factor: hormonal changes-OCP & pregnancy

: broad spectrum antibiotic
: tight and nylon clothing-↑moisture and temperature

Clinical feature
-women: vaginal discharge- non offensive, creamy white and curdy
 : pruritus vulva
-men: balanoposthitis
: burning penile irritation immediately after sexual intercourse

Diagnosis
-gram stain: pus cell and yeast cell
-blood agar: star shaped colonies

Treatment
-clotrimazole pessary 500mg weekly for 6 month
-if topical therapy failed: fluconazole 150mg single dose or itraconazole 200mg twice in 1d