Infeksi Gastrointestinal non diare

Dian Widiyanti, SSi., MSi, Ph.DBagian Mikrobiologi

Fakultas Kedokteran Universitas YARSI

Helicobacter pylori

HistoryBarry Marshal & Robyn

Warren in 1982 Campylobacter pyloridis from dyspepsia patient now known as Helicobacter pylori

In 2005 nobel prize in physiology or medicine

MorphologySpiral with 1-3 turns, 0.5 ×5 μm in

length, with 5 to 7 polar sheathed flagella

Motile with corkscrew motilitySlow growth (3-6 days) at 37o CpH optimum 6-7Microaerophilic organismOxidase positive, catalase positive,

produce ureaseCause acute or chronic gastritis,

predisposing factor in peptic ulcer, gastric carcinoma, MALT lymphoma

Transmission

Risk factor

Virulence Factor Effect

Colonizing

Flagella Active movement through mucin

Urease Neutralization acid

Adhesin Anchoring to epithelium

Tissue damaging

Proteolytic enzymes Glucosulfatase degrades mucin

120-kDa cytotoxin (Gac A) Related to ulcer and severe gastritis

Vacuolating cytotoxin (Vac A) Damage of the epithelium

Urease Toxic effect on epithelial cell, disrupting tight junction

Phospholipase A Digest phospholipid in cell membrane

Alcohol dehydrogenase Gastric mucosal injury

Survival

Intracellular surveillance Prevent killing in phagocytes

Superoxide dismutase, catalase Prevent phagocytosis and killing

Coccoid forms Dormant form

Heat shock protein

Urease Sheathing antigen

Other

Lipopolysaccharide Low biological activity

Lewis X/Y blood group homology Autoimmunity

Pathogenesis

Clinical sign and symptoms

Upper abdominal painNausea and vomitingFrequent burpingBloatingLoss appetite, Fast satiationWeight lossBleeding from stomach lining (severe case)

Stages in Helicobacter infection

H. pylori induce autoimmune

Diagnosis Non invasive test

Urea breath test Stool antigen Serology (ELISA)

• Endoscopic based test

Rapid urease test Histology Culture (Br+5%

horse blood or BHI+ 7% horse blood) 5-10% O2, 5-12% CO2 5-7 days at 37o C

Treatment

Kombinasi beberapa antibiotik + inhibtor pompa proton

Contoh amoksilin, metronidazol, omeprazol

Leptopirosis

Occupational hazard of rice harvesting (China), autumn fever (Japan)

Adolf Weil in 1886 the first modern clinical description of leptospirosis which characterized by splenomegaly, jaundice, nephritis Weil’s disease

Inada et.al in 1916 • isolated leptospires, • identified the organism as the causal agent of leptospirosis • determined that rats are reservoir for transmission to human

Classification Order: SpirochaetalesFamily : Leptospiraceae

L. interrogans sensu lato (>240 serovar, 24 serogroups)L. biflexa sensu lato (>60 serovars)

Genotypic classification 20 genomospecies

Morphology• Spiral-shaped bacterium• Size 0.1 x 6-20 m• Highly motile• Has two axial filament (endoflagella) at its ends• Obligate aerobes • Slow growth with optimal temperature 30o C• Has Gram-negative bacterial cell wall

Reference: Albert I. Ko, et.al., 2009, Nature Reviews Microbiology, 7:736-747

(Reference: Jurg Utzinger, et.al., 2012, Swiss Medical Weekly 142:w13727)

Reservoir host

Cattle Dog Sheep and Goat

Horses Pig

Leptospira serovars

PomonaHardjo

Canicola PomonaHardjo

BratislavaPomona

BratislavaAustralisPomona

Symptoms and syndromes

Reproductive failureAbortionStill-birthsFetal mummificationWeak calvesMilk drop syndrome

IctericHemorrhagicUremic (Stuttgart disease)Abortion and premature or weak pups

SepticemiaRedwaterAbortionMilk drop syndrome

AbortionRedwater in foalsMoon blindness

AbortionStill-birthWeak piglets

Leptospirosis in Animals

Mice (Mus musculus) and rats (Rattus norvegicus and Rattus rattus) don’t show sign but harbor leptospires in kidney Hamsters and guinea pigs are highly susceptible and can be used as animals models of human leptospirosis

Leptospirosis in humans

Reference: Feigin RD, Anderson DC: Human leptospirosis. CRC Crit Rev Clin Lab Sci 1975;5: 413-67. Copyright CRC Press, Inc., Boca Raton, FL

PathogenesisThe clinical manifestations are caused by damage to the

endothelial lining of small blood vessels by mechanisms that are still poorly understood. Infection multisystem. Some virulence factors hemolysin, Lig A and Lig B, LPS

TreatmentPenicillin i.v., amoxicillin, ampicillin, doxycycline, eritromicinJarisch-Herxheimer reaction may appear following penicillin treatment

Prevention Prevention and control should be targeted at :

(a) the infection source; (b) the route of transmission between the infection

source and the human host(c) infection or disease in the human host.

(Reference: Pappas G., P. Papadimitriou, V. Siozopoulou, L. Christou, and N. Akriditis. 2008. Int. J. Infect. Dis. 12: 351-357

The Caribbean and Latin America, the Indian subcontinent, Southeast Asia, Oceania, and to a lesser extent Eastern Europe, are the most significant foci of the disease

Clinical sample for leptospirosis diagnosis

1. BloodBlood is used for culture, collected with heparin to

prevent clotting on the first 10 days. Ten days after the onset, leptospires mostly dissappeared from blood.

2. SerumSerum is used for serologic test, collected two

times at interval several days. To detect rise in titres between two samples or seroconversion and confirm the diagnosis

3. UrineMidstream urine is collected and cultured as soon as possible (2 hours after sampling) because leptospires

die quickly in urine.4. Postmortem

Collected from many organs soon after the death and transported to laboratorium in 4o C to prevent autolysis.

5. CSF

Diagnosis of leptospirosis

Detection of host responseMicroscopic Agglutination Test (MAT)

one of the gold standard in diagnosis of leptospirosis. Serum of suspected patient is reacted to culture of leptospira strain. The agglutinated of leptospires will form clumps. MAT result is

determined positive if the proportion of free leptospires is less than 50%. Enzyme-Linked Immunosorbent Assay (ELISA)

using wide variety of leptospiral sonicates to recombinant protein (i.e. LipL32, LigA, OmpL1). IgM dipstick

detect the IgM which appeared during acute phase and often use for initial screening.

Microcapsule Agglutination Test (MCAT)

Detection of causative agentCulture

growth in EMJH or Korthof medium. Definitive diagnosis, but need long incubation due to slow growth of Leptospira strains

Polymerase Chain Reaction (PCR) has high sensitivity

Loop-mediated isothermal amplification (LAMP) amplification of DNA under isothermal condition and the result can be seen with naked eye. It has high sensitivity and specificity, no need sophisticated equipment.

Latex agglutination, immunofluorescence, immunoprecipitation lack of sensitivity and specificity

WHO References1. The culture of sample from normally sterile organ, showed

sufficient growth2. Clear amplified DNA in PCR from organ or body fluid3. Four-fold increase of titers between acute and convalescent sera in

MAT