PROBLEM 3Caryn Miranda SaptariGROUP 14

LO 1 : Salmonellosis

Salmonella MicrobiologyEtiology

Small gram-negative rods (2-4 X 0.5 microns)Most motile with flagella .Shigella and Klebsiella are non motile.facultative anaerobes.Reduce nitrate.Many genera:Escherichia, Salmonella, Shigella, Klebsiella, Proteus, Enterobacter, Yersinia, etc.Some strains are opportunistic pathogens.Some strains are true pathogens Salmonella, Shigella, Yersinia, some strains of E. coli.Enterobacteriaceae Etiology

Etiology

LPS on SurfaceLipopolysaccharideProtective outer layer of most strainsMemory immune response and antibodies directed against LPSPolymorphic nature of side chains is advantageous for bacteriaSince Typhi has outer capsule, this infection is worse.Etiology

Antigenic components of S. TyphiThe O antigen (endotoksin, somatic antigen)Represent side chain of repeating oligosaccharide units projecting outwards from the LPS layer of the cell wallThe H antigen (flagellar antigen)Occur in phase 1 and phase 2The Vi antigenLocated in outermost layer of S.typhiOuter membrane proteins (OMPs)Almost half of the mass of the outer membrane is protein (porin and non-porin proteins)Etiology

Etiology

Overview Typhoid fever, Salmonellosis, TyphusEnteric FeverOther Diarrhoeal diseasesParatyphoid FeverNon Typhoid Salmonella (NTS)S. Paratyphi AS. Paratyphi B / S. SchotsmuelleriS. Paratyphi C / S. HirschfeldiiFlea & Louse Borne TyphusEndemic Murine TyphusEpidemic TyphusScrub TyphusQ FeverRickettsia typhiRickettsia prowazekiiOrientia tsutsugamushiTyphoid FeverSalmonella typhiSalmonellosisRickettsial DiseasesEhrlichioses & AnasplasmosisTick & Mite Borne Fever

Modes of Transmission Person to person transmition Rarely (bactery 10 - 10 6)Contamination of food products Salmonella live in the chicken intestineContamination of food processing contamination of process equipment food presentation

Affecting FactorMicroorganisms Factor -The number of ingested microorganisms -Serotypes and virulence strains Host factors -Gastric acidity -Gastrointestinal motility -Normal flora -Humoral and cellular immunization system -Malnutrition-Metabolic and Nutritional Factors -Age -Other diseases -Use of antibiotics -Vaccinations -Duration of illness Environmental Factors -Tropical and sub tropical -Urbanization -Standards of hygiene and sanitation

SALMONELLOSIS

DefinitionSalmonellosis is a common and widely distributed food-borne disease that is a global major public health problem affecting millions of individuals with significant mortality.Salmonellae live in the intestinal tracts of warm- and cold-blooded animals

NonTyphoidal SalmonellosisETIOLOGY : Salmonellae are motile, nonsporulating, nonencapsulated, gram-negative rods that grow aerobically and are capable of facultative anaerobic growth.They are resistant to many physical agents but can be killed by heating to 130F (54.4C) for 1 hr or 140F (60C) for 15 min.They remain viable at ambient or reduced temperatures for days and may survive for weeks in sewage, dried foodstuffs, pharmaceutical agents, and fecal material. Like other members of the family Enterobacteriaceae, Salmonella possesses somatic O antigens and flagellar H antigens.With the exception of a few serotypes that affect only 1 or a few animal species, such as S. dublin in cattle and S. choleraesuis in pigs, most serotypes have a broad host spectrum. Typically, such strains cause gastroenteritis that is often uncomplicated and does not need treatment, but can be severe in the young, the elderly, and patients with weakened immunity.The causes are typically S. Enteritidis (S. enterica serotype Enteritidis) and S. Typhimurium (S. enterica serotype Typhimurium), the 2 most important serotypes for salmonellosis transmitted from animals to humans

Host Factors and Conditions Predisposing to the Development of Systemic Disease with Non-typhoidal Salmonella StrainsNeonates and young infants (3 mo of age)HIV/AIDSOther immune deficiencies and chronic granulomatous diseaseImmunosuppressive and corticosteroid therapyMalignancies, especially leukemia and lymphomaHemolytic anemia, including sickle cell disease, malaria, and bartonellosisCollagen vascular diseaseInflammatory bowel diseaseAchlorhydria or antacid medication useImpaired intestinal motilitySchistosomiasis, malariaMalnutrition

Clinical Manifestation Acute Enteritis. The most common clinical presentation of salmonellosis is with acute enteritis. After an incubation period of 672 hr (mean, 24 hr), there is an abrupt onset of nausea, vomiting, and crampy abdominal pain, primarily in the periumbilical area and right lower quadrant, followed by mild to severe watery diarrhea and sometimes by diarrhea containing blood and mucus. A large proportion of children are febrile, although younger infants may exhibit a normal or subnormal temperature. Symptoms usually subside within 27 days in healthy children and fatalities are rare. However, some children develop severe disease with a septicemia-like picture (high fever, headache, drowsiness, confusion, meningismus, seizures, abdominal distention). The stool typically contains a moderate number of polymorphonuclear leukocytes and occult blood. Mild leukocytosis may be detected.

Bacteremia. While bacteremia can occur with minimal associated symptoms in newborns and very young infants, in older infants it typically follows gastroenteritis and can be associated with fever, chills, and septic shock. In patients with AIDS, recurrent septicemia appears despite antibiotic therapy, often with a negative stool culture for Salmonella and sometimes with no identifiable focus of infection.Nontyphoidal Salmonella gastrointestinal infections commonly cause bacteremia in developing countries. High rates of invasive disease with S. Typhimurium and S. Enteritides reported from Africa (3870% of isolates) suggest an association with HIV infections and malaria.Extraintestinal Focal Infections. Following bacteremia, salmonellae have the propensity to seed and cause focal suppurative infection of many organs. The most common focal infections involve the skeletal system, meninges, and intravascular sites and sites of pre-existing abnormalities; areas of bone infarction as in sickle cell disease; or bone prostheses.

ComplicationSalmonella gastroenteritis can be associated with acute dehydration and complications resulting from delayed presentation and inadequate treatment. Bacteremia in younger infants and immunocompromised individuals can have serious consequences and potentially fatal outcomes. Salmonella organisms can seed many organ systems, leading to intracranial infections (meningitis, focal brain abscesses) as well as osteomyelitis in children with sickle cell disease. Reactive arthritis may follow Salmonella gastroenteritis, usually in adolescents with HLA-B27 antigen.In certain high-risk groups, especially those with impaired immunity, the course of Salmonella gastroenteritis may be more complicated. Neonates, infants

In children with AIDS, the infection frequently becomes widespread and overwhelming, causing multisystem involvement, septic shock, and death. In patients with inflammatory bowel disease, especially active ulcerative colitis, Salmonella gastroenteritis may be potentially fatal, with rapid development of toxic megacolon, bacterial translocation, and sepsis. In children with schistosomiasis, the Salmonella may persist and multiply within schistosomes, leading to chronic infection unless the schistosomiasis is effectively treated.Prolonged or intermittent bacteremia is associated with low-grade fever, anorexia, weight loss, diaphoresis, and myalgias, and may occur in children with underlying problems and reticulo-endothelial system dysfunction such as hemolytic anemia or malaria.

DiagnosisDefinitive diagnosis of Salmonella infection is based on clinical correlation of the presentation and culturing and subsequent identification of Salmonella organisms from feces or other body fluids. In children with gastroenteritis, cultures of stools have higher yields than rectal swabs.In children with nontyphoidal Salmonella gastroenteritis, prolonged fever lasting 5 days or more and young age should be recognized as risk factors closely associated with development of bacteremia. In patients with sites of local suppuration, aspirated specimens should be Gram stained and cultured. Salmonella organisms grow well on nonselective or enriched media, such as blood agar, chocolate agar, or nutrient broth, but stool specimens containing mixed bacterial flora require selective media such as MacConkey, xylose-lysine-deoxycholate (XLD), bismuth sulfite (BBL), or Salmonella-Shigella (SS) agar for isolation.Although other rapid diagnostic methods, such as latex agglutination and immunofluorescence, have been developed for rapid diagnosis of Salmonella in cultures, there are few comparable tests for rapid serologic detection. Polymerase chain reaction (PCR) techniques may offer a rapid alternative to classic cultures but are as yet not in widespread use in clinical settings

Identification of salmonella sp.

TABLE 195-3 --Treatment of Salmonella Gastroenteritis

ORGANISM AND INDICATIONDOSE AND DURATION OF TREATMENTSalmonella infections in infants

PrognosisMost healthy children with Salmonella gastroenteritis recover fully. However, malnourished children and those who do not receive optimal supportive treatment (are at risk for developing prolonged diarrhea and complications. Young infants and immunocompromised patients often have systemic involvement, a prolonged course, and extraintestinal foci. In particular, children with HIV infection and Salmonella infections can have a florid course.After infection, nontyphoidal salmonellae are excreted in feces for a median of 5 wk. However, after clinical recovery from Salmonella gastroenteritis, asymptomatic fecal excretion of the organism may occur for several months, particularly in younger children or those treated with antibiotics. A prolonged carrier state after nontyphoidal salmonellosis is rare (

Typhoid Fever

Definition of Typhoid FeverAcute enteric infectious diseasecaused by Salmonella typhi (S.Typhi).prolonged fever, Relative bradycardia, apathetic facial expressions, roseola, splenomegaly, hepatomegaly, leukopenia.intestinal perforation, intestinal hemorrhage

ETIOLOGYSalmonella typhiSalmonella Paratyphi ASalmonella paratyphi BSalmonella chloreasuis

ephidemiologyTyphoid fever as an endemic disease in IndonesiaIn 1990 9,2 per 10,000 citizenIn 1994 became 15,4 per 10,000 citizen1981-1986 improved 35,8% : 19.596 26.606cases

Epidemiology Fig. 1. The typhoid fever surveillance study siteshttp://www.who.int/bulletin/volumes/86/4/06-039818/en/Incidence of typhoid fever Strongly endemic Endemic Sporadic cases

Characteristic Typhoid fever

PREVALENCE TYPOID FEVER

Sign and symptomsTyphoid fever is characterized by a slowly progressive fever as high as 40 C (104 F), profuse sweating, gastroenteritis, and nonbloody diarrhea. Less commonly, a rash of flat, rose- colored spots may appear. In the first week :a slowly rising temperature with relative bradycardiaMalaiseheadache and coughA bloody nose ( epistaxis) is seen in a quarter of cases abdominal pain is also possibleleukopenia, with eosinopenia and relative lymphocytosisblood cultures are positive for Salmonella typhi or paratyphiThe classic Widal test is negative in the first week.

Sign and symptomsIn the second week of the infection :the patient lies prostrate with high fever in plateau around 40 C (104 F) bradycardia (sphygmothermic dissociation), classically with a dicrotic pulse waveDelirium is frequent, frequently calm, but sometimes agitated. This delirium gives to typhoid the nickname of "nervous feverRose spots appear on the lower chest and abdomen in around a third of patientsThe abdomen is distended and painful in the right lower quadrant

There are rhonchi in lung basesDiarrhea can occur in this stage: six to eight stools in a day, green with a characteristic smell, comparable to pea soupconstipation is also frequentThe spleen and liver are enlarged (hepatosplenomegaly) and tenderThe Widal reaction is strongly positive with anti O and anti H antibodiesBlood cultures are sometimes still positive at this stage. (The major symptom of this fever is the feve r usually rises in the afternoon up to the first and second week.)

Sign and symptomsIn the third week of typhoid fever, a number of complications can occur: Intestinal hemorrhage due to bleeding in congested Peyer's patches; this can be very serious but is usually not fatal. Intestinal perforation in the distal ileum, this is a very serious complication and is frequently fatal. It may occur without alarming symptoms until septicemia or diffuse peritonitis sets in. Encephalitis Metastatic abscessesCholecystitisEndocarditisosteitis

Sign and symptomsThe fourth week :The fever has started reducing (defervescence stage)Fever come down, gradual improvement in all symptoms and signs, but still danger

The fifth week :convalescence stagedisappearance of all symptoms, but can relapse

Pathophysiology patogene

Contaminated Food Stomach destroyed by HClpass into the intestinereproductionPenetrate to epithelial cells (M cell)IgA

Multiply in the extracellular organ/sinusoidblood circulationBakterimia 2 (simptomatik)Hepar gall bladderintestinal lumenFaeces activatedmacrophagesHyperactive hyperplasia reaction plaque peyeriprocess continueserosion of blood vesselsNecrotic hyperplasiapenetrate the mucosa and muscle layerPerforation Release cytocin & infl rxpenetrate the gut againdelayed type hypersensitivity reaction

Clinical formsMild infection: very common seen recently symptom and signs mild good general condition temperature is 380C short period of diseases recovery expected in 1~3 weeks young children mild more

Clinical formsPersistent infection:diseases continue than 5 weeksAmbulatory infection:mild symptoms,early intestinal bleeding or perforation.

Clinical formsFulminate infection:rapid onsetsevere toxemiaSepticemiaHigh feverChillcirculation failure

ShockDeliriumComaMyocarditisbleeding

Major findings in lower ileumHyperplasia stage(1st week):swelling lymphoid tissue and proliferation of macrophages.Necrosis stage(2nd week):necrosis of swelling lymph nodes or solitary follicles.Ulceration stage(3rd week):shedding of necrosis tissue and formation of ulcer ----- intestinal hemorrhage, perforation .Stage of healing (from 4th week):healing of ulcer, no cicatrices and no contraction

NegatifPositif 60 90%NegatifPos / NegNegatifPositif 80 %Pos 50 %NegatifPositif 20 %Pos 50 %Pos 80 %MANIFESTASI KLINIK

InkMg IMg IIMg IIIMg IV

Biakan DarahBiakan FesesTes Widal

Diagnose

LAB diagnoseRutine check-SGOT and SGPT increase-leukositosis (aneusinofilia and limfopenia)- LED increaseWIDAL TESTAglutination reaction between S. Typhii (antigen) with antibody (aglutinin)TUBEX test Detect antibody anti S.Typhi 09 in the serum of patientTyphidot TESTAntibody IGM and IG G in the outer membran of salmonela typhiIGM dipstick testAntibody IGM specific S.Typhii in the whole blood serumBlood culture Positive if typhoid fever but can be negative too

Therapy Non farmacoRest and therapyDiet farmaco

DOSISESkloramfenikol4x500 mg /Hari (oral/IV)Anemia aplastiktiamfenikol4x500 mg/HariAnemia aplastikklotrimoksazole2x 2 tablet (sulfametoksazole 400 mg dan 80 mg trimetroprim) ampisilim50-150 mg/KgBBsefalosporin3-4 gram dalam dekstrosa 100 cc diberikan jam infus

Complication

Complication IntestinalBleeding intestinalPerforationNon intestinalHepatitis tifosaPankreatitis tifosaComplication hematologyMiokarditisneuropsikiatrik

PREVENTIONChoose food processed for safetyPrepare food carefullyKeep food contact surfaces cleanEat cooked food as soon as possibleMaintain clean handsSteam or boil shellfish at least 10 minutesAll milk and dairy products should be pasteurizedControl fly populations

Prevention of typhoid feverAvoid risky foods and drinks. Get vaccinated against typhoid fever. Remember that you will need to complete your vaccination at least 1 week before you travel so that the vaccine has time to take effect!!Taking antibiotics will not prevent typhoid fever; they only help treat it.

VACCINESRoutine typhoid vaccination is indicated for:travelers to endemic areas, persons with intimate exposure to a documented S typhi carrier (e.g, household contact), and microbiology laboratory personnel who frequently work with S typhi

Vaccines are not approved for use children younger than 2 years.

Typhoid Vaccines Available in the United States

Vaccine NameHow GivenDoses Total Time Needed to Set Aside For VaccinationDosing intervalMinimum AgeBooster Needed Every...Ty21a1 capsule per oral42 weeks2 days6 years5 yearsViCPS0.50 mLIntramuscular Injection12 weeksNot applicable2 years2 years

Treatment of complicationToxic myocarditis:bed restcardiac muscle protection drugs, dexamethasone, digoxin.

Viral infectionSuch as upper respiratory tract infection. Abrupt onset with fever, headache, leucopenia, sore throat, cough, coryza.No rose spots, no enlargement of liver & spleen. The course of illness no more than 2 weeks.Differential diagnosis depends on typical manifestations and blood culture.

Malaria History of exposure to malaria.Paroxysms(often periodic) of sequential chill,high fever and sweating.Headache, anorexia, splenomegaly, anemia, leukopeniaCharacteristic parasites in erythrocytes,identified in thick or thin blood smears.

Dengue FeverSudden high fever day 1-3 (above 38,5o C), in day 3 or day 4-5 increase but not very high (below 38,5o C)

Typhoid feverenteritisMalariaDengue feverCaused:Infection byBacteria: Salmonella typhi,Salmonella paratyphiS. enteritidis bioserotypes (e.g., S. typhimurium)Parasite: Plasmodium falciparum, P. vivax,P.ovale, and P.malariae1 of the 4 serotypes of dengue virus, family Flaviviridae, genus Flavivirusincubation period 10-14 days6-48hours10 -15 days4-7dayssymptompsProlonged fever, headache, malaise and anorexia, constipation, bloody diarrheaNausea, vomiting, nonbloody diarrhea, fever, cramps, myalgia and headacheflu-like illness with fever, chills, muscle aches, andheadache, nausea, vomiting,cough, anddiarrhea. high fever, headaches, joint and muscle pain, vomiting and a rash,pain behind the eyes

DIFFERENTIAL DIAGNOSISParatyphoids A, B & C The laboratory is usually required as the final authority. The paratyphoids tend to run a milder course with profuse rose spots. Salmonella infection and gastroenteritis Salmonellae, the dysentery group, and staphylococci may occasionally cause an invasive illness resembling typhoid fever with bacteremia. Usually, however, the gastrointestinal symptoms are more acute than the general manifestations, and the pyrexia much lower and of shorter duration.

DIFFERENTIAL DIAGNOSISOther diseases in differential diagnosisMalaria This may be mistaken for typhoid in countries where both are endemic. A history of previous attacks, the more rapid onset in malaria, the shivering and sweating, the high early pyrexia, the relative infrequency of abdominal symptoms and signs, and a positive blood slide all point to a diagnosis of malaria.

b. Influenza Influenza may also be confused with typhoid, but is usually of much more rapid onset with high temperature, severe sore throat, cough, and the absence of a palpable spleen and rose spots.

DIFFERENTIAL DIAGNOSISc. Bacillary dysentery This disease seldom causes much difficulty in diagnosis. The onset is usually acute, with severe blood diarrhoea, although in mild cases the blood may be absent. Diarrhoea with blood is rare in early typhoid. The signs and symptoms in dysentery are usually abdominal and remain so, the mental state and chest being clear.

d. Typhus and other rickettsial infections These conditions should be considered important when considering the differential diagnosis. This is because both typhus and typhoid can cause a febrile illness with delirium, chest signs, and abdominal discomfort. In typhus, however, the onset is acute, and the temperature high at an early stage. Shivering attacks are common at the onset, and prostration is rapid. The rash is quite different (brownish red in colour, and much more profuse). It does not fade on pressure, as does the rose spot in typhoid. There is a leucocytosis and the Weil-Felix test becomes significantly positive at about the tenth day.

Dengue FeverDengue fever is virus based disease spread by mosquitoes.Most commonly the mosquito Aedes Aegypti.

Sign and symptomp

Criteria suspect of dengue fever

Danger signs

Character Dengue Fever

Differential Diagnose

CauseDengue fever is caused by any one of four dengue viruses spread by the Aedes aegypti mosquito.DENGUE FEVER

SymptomsHigh fever, up to 105 F (40.6 C)A rash over most of your body, which may subside after a couple of days and then reappearSevere headache, backache or bothPain behind your eyes Severe joint and muscle pain Nausea and vomiting DD - dengue fever

Risk factorsYoung children and infantsTravelers coming from areas with no malariaPregnant women and their unborn children

MALARIA

SymptomsModerate to severe shaking chillsHigh feverProfuse sweating as body temperature fallsHeadacheNauseaVomitingDiarrheaDD malaria

SymptomsFatigueNausea and vomitingAbdominal pain or discomfort, especially in the area of your liver on your right side beneath your lower ribsLoss of appetiteLow-grade feverDark urineMuscle painItchingYellowing of the skin and eyes (jaundice)HEPATITIS ADifferential diagnose

SymptomsAbdominal painDark urineJoint painLoss of appetiteNausea and vomitingWeakness and fatigueYellowing of your skin and the whites of your eyes (jaundice)

HEPATITIS BDifferential diagnose

SymptomsFatigueFeverNausea or poor appetiteMuscle and joint painsTenderness in the area of your liver

HEPATITIS CDifferential diagnose

Caused by Salmonella paratyphoid A,B,C respectively.in no way different from typhoid fever in epidemiology, pathogenesis, pathology, clinical manifestations, diagnosis, treatment and Prophylaxis

PARATYPHOID FEVER A, B, CDifferential diagnose

Buku Ajar Infeksi & Pediatri Tropis ed.2, IDAI 2010Harrisons Manual of Medicine 17th ed, McGraw Hill Companies Inc.

DiseaseDifferenceHepatitisLow grade fever, dark urine, jaundice. Dx: AST & ALT level Dengue FeverPalatal vesicles, maculopapular rash, epistaxis, petechiae. Dx: blood - ELISA / PCRBrucellosisFebrile illness similar but less severe / fever & acute monarthritis @ hip or knee (septic arthritis) / long lasting fever & low back pain (vertebral osteomyelitis). Dx: Agglutination assays for IgM. Difficult to distinguish from TF & early symptom of TBTBMostly confined in lung(s) with cough & purulent sputum production. GI TB peritonitis. Dx: peritoneal biopsyMalariaFebrile paroxysm at regular interval, (falcip) multiorgan dysfx.Dx: asexual form of parasites on peripheral blood smearInfluenzaAbrupt onset of systemic symptoms. Dx: tissue culture of virus from throat swab, nasopharyngeal wash, or sputumTularemia (oropharyng & GI)Pharyngitis, cervical & mesenteric adenopathy, intestinal ulceration. Dx: microagglutination / tube agglutination test, PCRGastroenteritisDiarrhea with stools containing blood, mucus, leukocytes. Dx: blood/stool culturesBronchitisBronchopneumoniaShigellosisw/o th/ most cases resolve in 1 week. Dx: stool cultureSystemic fungal infections

Incidence and Timing of Various Manifestations of Untreated Typhoid Fever

prognosisSymptoms usually improve in 2 to 4 weeks with treatment. The outcome is likely to be good with early treatment, but becomes poor if complications develop.Symptoms may return if the treatment has not completely cured the infection.

*A general picture of a salmonella bacterium. Notice the flagellaS. Typhi has an outer-capsule, while most other serovars have the lipopolysaccharide coat.*This is a membrane of S. typhi. Other serovars do not have the outer capsule.Notice parts of LPS. Lipid A (conserved). Polysaccharide part is variable, especially O polysaccharide (what antibodies bind to)*******************************P. falciparum: 8 15 hari, Malaria P. vivax: 10 15 hari, Malaria P. malariae: 30 40 hari

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