Multisystem Infections PDF

Organisms Causing Multisystem Infections Prof. Jananie Kottahachchi Consultant Microbiologist Learning Outcomes Name and describe the pathogens that cause continued fever List the other main infections that each of these organisms cause Describe the pathogenes...

Organisms Causing Multisystem Infections Prof. Jananie Kottahachchi Consultant Microbiologist Learning Outcomes Name and describe the pathogens that cause continued fever List the other main infections that each of these organisms cause Describe the pathogenesis (source, mode of transmission, portal of entry and virulence factors) of these organisms Identify the pathology underlying the common infectious diseases Outline the laboratory diagnosis of these infections Outline the management of these infections Identify the important epidemiological features of these infections Describe the prevention and control of these infections including any currently available vaccines  Spirochetes Spirochetes are a group of microorganisms that morphologically resemble a spiral or a helix Motile Larger spirochaetes, Borrelia, are Gram negative Others do not stain at all or poorly stained They can be made visible by Dark ground microscopy Staining with heavy metals (eg. silver) Immunofluorescence microscopy using fluorescent labelled antibodies Spirochetes… There are 3 Genera Treponema Borrelia - has the largest spirals Leptospira - one or both ends are hooked Leptospira Obligate aerobes and optimum growth temp is 28-30 C About 20 species of Leptospira genus Pathogenic Opportunistic pathogens Non pathogenic Main pathogenic organism is Leptospira interrogans There are many serogroups under which many serovars in each serogroup Serovar icteroheamorrhagica Leptospirosis Zoonosis distributed globally First described in Sri Lanka in 1953 Maintained in nature by chronic renal infection of the wild mammals Infection of the carrier animals occur in infancy Human infection Direct contact with infected tissue or urine Indirect exposure to organism in damp soil or water Leptospirosis Most human infections – asymptomatic Spectrum of illness - undifferentiated febrile illness to severe multisystem disease Peak incidence - rainy season in tropical region - late summer to early fall in temperate regions It is a notifiable infection in Sri Lanka Most important reservoirs - rodents (eg: rats) and other small mammals Causative Organism Family – Spirochaetaceae Genus – Leptospira Species – 23 named species Some species contain both pathogenic and non pathogenic serovars whereas some contain entirely non pathogenic serovars Eg: Leptospira interogans – Contains pathogenic serovars Leptospira biflexa – Contains non pathogenic serovars  Genus Leptospira Interrogans Biflexa species >20 other species (Pathogenic) (saprophytic) serogroup Icterohaemorrhagieae Other serogroups serovars Icterohaemorrhagiae Other serovars 10 Sources of infection Many species of wild and domestic mammals Although rats are important primary hosts, a wide range of other mammals including dogs, fox, rabbits, cows and sheep also carry and transmit the disease as secondary hosts Bacteria are harboured in the kidneys of rats and are excreted in rat urine to the environment They survive in environments with stagnant water eg. paddy fields, streams ditches etc. Infection is acquire through recreational or occupational exposures Occupational Risk Factors Direct contact with animals in occupations Farmers Veterinarians & abattoir workers Meat inspectors Rodent control workers Indirect contact Sewer workers, miners, soldiers Septic tank cleaners, canal workers Fish farmers Rice field workers Banana farmers Sugar cane cutters Non Occupational Exposures Exposures that occur during the activities of daily life Walking in damp conditions in barefoot- many infections Gardening with bare hands Dogs - a significant reservoir for human infection Common during rainy season During floods  Bathing Water sports Floods 14 Pathogenesis Leptospires enter the body cuts and abrasions mucous membranes or conjunctivae aerosol inhalation of microscopic droplets Once entered- carried in the blood throughout the body Incubation period - 5 to 14 days Virulence factors – attachment toxin production immune mechanisms surface proteins Pathogenesis A systemic vasculitis occurs, which facilitates migration of leptospires into organs and tissues leading to a broad spectrum of clinical illness Sever vascular injury may result pulmonary haemorrhage, ischaemia of the renal cortex, renal tubular epithelial necrosis and destruction of the hepatic architecture leading to jaundice and liver cell injury Immunity to leptospirosis Serovar- specific antibodies are protective It will not protect against infection with other serovars Clinical Features Incubation period - 4-14 days Sub-clinical infection to clinically recognizable syndromes Self limited systemic illness - in 90% of infections A biphasic disease Septicaemic acute phase (1 week) Flu-like symptoms - chills, headache, myalgia, conjunctival suffusion, rarely a rash Death is rare in the acute phase of the illness Immune phase Antibody production and excretion of spirochaetes in urine Hepatic failure, renal failure etc can occur in severe disease Severe neurologic complications - coma, meningoencephalitis, transverse myelitis or Guillain- Barre-Syndrome Weil’s disease, characterized by hepatic and renal impairment Severe cases may also present with haemorrhagic pneumonitis, cardiac arrythmias or circulatory collapse Mortality is 5 to 40% in severe cases Laboratory diagnosis Direct demonstration of leptospires Blood - First 10 days of the illness Urine - From 2nd week onwards for 4-6 weeks or even longer By darkground/darkfield microscopy Immunofluorescence staining Immunoperoxidase staining To detect from tissues Silver staining PCR assays Isolation and identification Liquid or semisolid media are used for the isolation Serum or albumin is added to enhance the growth of leptospires Cultures are incubated at 300C for several weeks in a dark place Isolated leptospires are identified to the serovar level by traditional serological methods or by molecular methods Serological methods Microscopic agglutination test (MAT) Standard reference assay Live antigens representing different serogroups of leptospires are used Macroscopic slide agglutination test (Patoc slide test) Heat treated antigens are used IgM assays Complement fixation test Principle Ab +ve serum + live leptospira = look under dark ground microscope microscopic agglutination is seen 21 Treatment Severe disease – IV crystalline penicillin Mild cases - Oral doxycycline Antibiotics should be started as early in the course of infection Supportive care with strict attention to fluid and electrolyte balance is essential Dialysis is indicated in renal failure Prevention Health education Avoidance of high risk exposure Eg: Immersion in fresh water, avoidance of contact with infected animals and their body fluids. Adoption of protective measures Eg: Wearing boots, goggles and rubber gloves. Immunization of animals with killed vaccine is widely practiced in other countries But the immunity is short lived Needs annual boosters Use of prophylaxis Doxycycline 200mg weekly until the exposure is over  Enteric fever The classic syndrome of enteric fever is an acute systemic illness with typical manifestations of fever, headache, abdominal pain, relative bradycardia, and splenomegaly Caused by Salmonella enterica serotypes 25 Aetiology Caused by Salmonella enterica serotypes Genus Salmonella is included in the family Enterobacteriaceae Gram-negative bacilli Non-spore-forming Facultatively anaerobic 26 Salmonella …. O - Cell wall Ag H - Flagella Ag Vi - Capsular Ag These three antigens are important in the serodiagnosis of Salmonella 27 Salmonella …. Salmonellae are normal commensals in the gut of humans and animals (domesticated and wild mammals, reptiles, birds and insects) Two species in the genus: 1. Salmonella enterica – pathogenic (>2000 serotypes) 2. Salmonella bongori – non pathogenic 28 Salmonella enterica Typhoidal Non-typhoidal Enteric fever Gastroenteritis and (typhoid and paratyphoid) Food poisoning S. Typhi and S. Enteritidis Paratyphi A,B,C S. Typhimurium etc. Zoonotic disease Human pathogens Contaminated eggs, meat, milk and milk products 29 Causative Organisms of Enteric Fever The organism classically responsible for the enteric fever syndrome is S. enterica serotype Typhi Other salmonella serotypes, S. enterica serotype Paratyphi A Salmonella serotype Schottmuelleri (formerly S. Paratyphi B) Salmonella Hirschfeldii (formerly S. Paratyphi C) - growing in importance in South and South-East Asia 30  Pathogenesis of Enteric Fever Typhoidal serotypes of S. enterica grows intracellularly, primarily in reticuloendothelial cells in lymph nodes, spleen, liver, and bone marrow Virulence factors  Cell invasion (enteric epithelium, blood and organs)  Intracellular survival and multiplication  Avoid killing by macrophages and multiplication  Vi antigen (microcapsule)  Flagella Faeco-oral transmission 31  Pathogenesis…… Ingestion infective dose 106-9 Survive exposure to gastric acid Gain access to the small bowel Penetrate the intestinal epithelium possibly through microfold cells over Peyer’s patches via lymphatics Enter into intestinal lymphoid tissue (mesenteric LNs) Multiply Invade the blood stream (1ry bacteraemia - occult) 32 Pathogenesis…… Infection of liver, GB, spleen, BM, kidney (RES) Multiply Enter the blood stream (2ry bacteraemia) Onset of clinical features IP: 7-14 days Disseminate by the lymphatic or haematogenous route to multiple organs 33 Clinical features  An important cause of PUO 34 Fever pattern Step ladder – fever goes up a little each day Relative bradycardia 35 Rose spots Transient rash Indistinct in dark skinned patients Infectious 36  Diagnosis - Culture The definitive diagnosis of enteric fever is made by isolating Salmonella from blood Blood culture is the most important diagnostic tool Obtained before the initiation of antimicrobial therapy Multiple blood cultures increase sensitivity (73% - 97% ) 37 Diagnosis – Culture…. oBone marrow culture - may be positive when blood cultures are negative, even after antibiotics have been administered o Biopsy specimens of rose spots for culture - positive in ≈ 2/3 cases oStool cultures - positive in < 50% oUrine cultures - positive in < 50% 38 Diagnosis – Culture…. Specimen Ideal time of collection Blood culture From the 1st week of illness (throughout +ve) Feces 2nd / 3 rd week of illness Urine 3 rd week of illness The isolation of Salmonella from stool or urine may support the diagnosis, but could reflect past infection with carriage 39  Diagnosis – Culture…. Grow in routine culture media Identification of the species by Biochemical tests Serotyping (Latex agglutination test) 40 Diagnosis – serology Widal test /Standard Agglutination test (SAT) Detects antibodies to Salmonella Ags Role in the diagnosis of typhoid fever is limited  Very low sensitivity and specificity The significant titers differ for individual geographic areas – no appropriate cut off point Cross-reactions occur with other enterobacteria False positives occur with other diseases eg; RA  Paired sera (acute and convalescent samples) are needed 41  Treatment Effective antibiotics (choice based on the ABST) - Ampicillin/Amoxycllin Chloramphenicol Ciprofloxacin 3rd generation cephalosporins Oral agents for multi-drug resistant strains - azithromycin, cefixime In Sri Lanka, The commonest isolate is S. Paratyphi A which is resistant to ciprofloxacin The drug of choice is 3rd generation cephalosporins (ceftriaxone/cefotaxime) Treatment should be continued for 10 - 14 days 42  Prevention Clean water and food Proper disposal of human excreta Good sanitation and hygiene practices Notification of cases Carrier screening if indicated Vaccination 43  Melioidosis All infections caused by Burkholderia pseudomallei Burkholderia pseudomallei Gram negative, oxidase positive, non-fermenting bacterium (like Pseudomonas) Soil saprophyte Transmission Accidental pathogen Occupational /recreational / lifestyle exposure to surface water and mud Accidental pathogen Occupational /recreational / lifestyle exposure to surface water and mud Exposure to soil and water Inoculation Inhalation Ingestion Melioidosis… Variable incubation period Variable clinical features Chronic localized infection with abscess formation to acute fulminant septicaemia Tendency to relapse months to years later Potentially fatal infection Mortality varies from 9% (Australia) to 50% (Thailand) Reduced considerably by early diagnosis and effective therapy High risk co-morbidity Predisposing conditions Diabetes Renal disease Liver disease Alcoholism Lung disease Thalassaemia Morbidity and mortality Potentially fatal infection Mortality varies from 9% (Australia) to 50% (Thailand) Reduced considerably by early diagnosis and effective therapy Clinical diagnosis Variety of clinical manifestations Rare cause of each syndrome Involvement of almost any body site Lack of awareness among clinicians Requires microbiology laboratory support  Dengue A mosquito borne Arboviral infection Most infections are asymptomatic High fever, malaise, vomiting and a generalized erythematous macular papular rash characterizes primary dengue infection Complications Dengue haemorrhagic fever Dengue haemorrhagic shock syndrome Diagnosis Serology Treatment Supportive. No specific anti viral therapy  Rickettsial infections Type of disease organism Clinical features Epidemic typhus (louse R. prowazekii Usually a severe illness borne) Macular rash appear after 4-7 days of illness Has marked systemic features- Hepatosplenomagaly Endemic typhus R. typhi Symptoms –similar to epidemic typhus but disease is much milder Scrub typhus Orientia. Eschar is commonly seen at the site of tsutsugamushi mite bite. Generalized lymphadenopathy splenomegaly and a rash Rocky mountain R. rickettsii A maculo- papular rash first appears on spotted fever extremities within 3-4 days. ( palms and soles) Fever and lypmphadenopathy common