INFECTION

Dr. Mehrunnisa Umar Assistant Professor Department of Medicine

An Observation
In developed countries infection continues to be one of the most common causes of disease and death, particularly in children. Infections like pneumonia, diarrhoea, malaria, tuberculosis, and conditions like malnutrition etc. have bad effects on health and growth of nation.

Vaccination and control of vectors transmitting diseases has significant effect but diseases tend to reappear.

Microbiology
Microbiology is the science of studying the microbes Variety in the genes of microbes explain behavior as well as how microbes are helpful and/or problematic to us.

These teeny, tiny dots that we may not even be able to see with the highest power of our microscopes, are sometimes able to kill us.
Keep in mind that humankind has also been able to harness the power of the microbial world for our benefit using their versatility and success at adaptation.

Microbiology
Given that pathogenic microbes are ubiquitous, why aren't we sick all the time? This is because;

Species and individual defense mechanisms

Artificial immunity through immunizations and herd immunity.

Public health measures enacted to interrupt natural transmission cycles.

A complex interaction b/w bacteria & host

Bacteria must overcome obstacles before disease occurs They must enter the host successfully and colonize tissue and then damage host tissue, and grow in that location.

Microorganisms enter the body, for example, through respiratory tract, cuts or wounds, insect bites and consumption of contaminated food. Additionally, hospital procedures involving catheters, intravenous therapy or transplantation increase the chances of microorganisms entering a patients body.

Effects of Infection on Human Body

Acute Effects

Fever, lethargy, weakness, catabolism, WBC, anaemia, Inflammation (five signs) Mental disorientation Shock Septicaemia, bleeding Organ Failure

Effects of Infection on Human Body

Chronic Effects

Weight loss, wasting Physical retardation in children Malnutrition Chronic damage to organs Post infection syndrome - fatigue

Effects of Infection on Human Body

Immune mediated

Skin rashes and nodulation Arthritis e.g. RA, RF, Serositis Neuropathy herpes Haematological immune damages Nephritis strep

Effects of Infection on Human Body

Toxic (Toxin Mediated)

Erythematous strep rashes STSS Toxic diarrhoeas Toxic membrane diphtheria Bacterial toxins clostridia (tetanus, botulism), diphtheria

Pathogenecity - Pathology
Pathogenicity is the ability to destroy tissue and cause a physiological or anatomical change and, eventually disease. MECHANISMS OF PATHOGENESIS Microorganisms cause disease by certain basic mechanisms: Invasion of tissue Production of toxins Virulence

Defense Mechanism Of The Human Body

The body resists infection and disease in a number of ways through nonspecific responses and specific responses. Four nonspecific defenses in the body Skin Mucous membranes Phagocytosis

Inflammation

Defense Mechanism Of The Human Body

HUMORAL IMMUNITY Antibodies are highly specific protein molecule Antibody mediated defenses include: Antitoxins, Bacteriolytic antibodies, Antibodies plus complement, Opsonizing antibodies

Defense Mechanism Of The Human Body

CELL MEDIATED IMMUNITY Specific immune response provided by Tlymphocytes Cell-mediated defenses include:

Cytotoxic T-lymphocytes, K & NK cells, Activated macrophages

Host Microbe Interaction

Host: Any organism that harbors a microbe is a host. Mutualism: A relationship between a host and microbe where they both benefit each other.

Commensalisms: a relationship between host and microbe where one benefits and the other is neither harmed nor helped. Parasitism: a relationship between host and microbe where one benefits and the other is harmed.

 Disease: When an organism can't carry out normal cell function, results in a disturbance in state of health. Not just microbes that cause these malfunctions, but when microbes are the cause, it's called infectious disease. Infection means the multiplication of a pathogenic microbe in a host.

Bacterial Diseases
Infection: During this stage the bacteria are introduced into the body tissues Incubation: During this stage the bacteria multiply in numbers, at times even before the body defense mechanism could come into action. Prodromal Phase: During prodrome the symptoms of disease begin to appear.

 Clinical Phase: Characteristic clinical features of a given disease

Resolution Phase: When diagnosed and appropriate treatment with antibiotic is instituted, resolution is expected. At times the disease complicates and the patient may be killed by the disease like in severe pneumonia

Fever
FEVER is a Diagnostic Clue It is an essential host defense mechanism Associated with or without localizing signs It can be due to Infection, inflammation or neoplasm

Behavioral changes

Fever
PGE2 and other Arachidonic Acid metabolites

CORTEX

THERMOREGULATORY NEURONS Elevated Thermostat

Vasomotor center

HYPOTHALAMIC ENDOTHELIUM

Peripheral efferents

Sympathetic chain

ENDOGENOUS PYROGENS PG

Muscle contraction

casoconstriction

Heat production MACROPHAGES ENDOTHELIUM PG

Heat conservation

+
MONOKINES LYMPHOKINES CYTOKINES

FEVER

Macrophages Endothelium Lymphocytes Other cells

Infections Toxins Inflammation Immunologic responses

Fever
Range 36.8 + 0.4o C (98.2 + 0.7o F) Lowest at 6 A.M. Peak at 4 - 6 P.M. 37.2o C (98.9o F) 37.7o C (998.9o F)

Fever Development
It is controlled increase in body temperature over normal values It is regulated in the same manner as normal temperature but the thermostat is set at a different (higher) level Factors that are responsible for setting of the thermostat at a higher level are called `Pyrogens`.

Fever Development
PYROGENS: Substances (chemicals, toxins or drugs) that can cause fever are called pyrogens

May be exogenous (outside the host) or endogenous (produced by the host)

Fever Development
PYROGENS: Exogenous pyrogens Llipopolysacchride found in the outer membrane of Gram -ve organisms. Lipteichoic acid Peptidoglycans

Act primarily by inducing formation of endogenous pyrogens or sometimes acting directly on the endothelial cells in the brain.

Fever Development
PYROGENS: Endogenous pyrogens are polypeptides produced by a variety of host cells, usually monocytes and macrophages. They include:

Interleukin-1 Interleukin - 1 Tumour necrosis factor (TNF ) Interferon (IFN) Interleukin 6

Fever Development
PYROGENS: Endogenous pyrogens are polypeptides produced by a variety of host cells, usually monocytes and macrophages. They include:

Interleukin-1 Interleukin - 1 Tumour necrosis factor (TNF ) Interferon (IFN) Interleukin 6

Fever
EFFECTS OF FEVER ON THE BODY: BENEFITS: Improves survival in animals Improves inflammatory responses to illness in humans

Fever
EFFECTS OF FEVER ON THE BODY: COSTS: Each one degree Celsius rise in temperature increases oxygen consumption by 13%. Increase in caloric and fluid requirement as more heat and fluid is lost from the body in febrile condition. Pyrogens accelerate muscle breakdown. Mental acuity and concentration is reduced. There may be state of delirium to coma. In children, fits may be present.

Fever- Patterns
o Intermittent type temp return to normal once during most days o Remittent type temp do not return to normal each day o Sustained/Continuous
degree F /day
temp do not vary more than 1

o Relapsing - recurrent over days to weeks

Classical PUO
1. FEVER MORE THAN 101 F 2. MORE THAN 3 WEEKS 3. CAUSE NOT DIAGNOSED AFTER ONE WEEK OF INTENSIVE HOSP INVESTIGN
TYPES OF PUO ACUTE, NOSOCOMIAL, HIV ASSOCIATED NEUTROPENIC PUO

PUO causes
INFECTIONS 30% MALIGNANCY 20% CONNECTIVE TISSUE D- 15 % OTHERS 20 % UNDIAGNOSED 15 %

FEVER - Common Clues

RESPIRATORY SYMPTOMS URTI ,LRTI,TB, URINARY SYMPTOMS UTI,APN,CYSTITIS ABDOMINAL SYMPTOMS ABSCESS,ACUTE
ABDOMEN

ARTHRITIS SYMPTOMS RA,SLE,AS TRAVEL HISTORY DIETARY HISTORY OCCUPATIONAL HISTORY

TRAVEL History
MALARIA ENDEMIC AREAS DENGUE FEVER - Eg )SINGAPORE VIRAL FEVERS TYPHOID TUBERCULOSIS SCHISTOSOMIASIS

Dietary & Occupational History

BIRDS PSITTACOSIS ANIMALS CONTACT- TOXOPLASMOSIS (CAT), BRUCELLOSIS,LEPTOSPIROSIS (RAT) UNCOOKED MEAT/SEA FOOD/ HEPATITIS A & E,SALMONELLA UNPASTEURIZED MILK SALMONELLA,TB,BRUCELLOSIS

Drug fever
All drugs can produce Drug INDUCED fever except DIGOXIN Bradycardia, hypotension, Skin rash, pruritus +, Eosinophilia eg) pencillin, sulpha, ATT

THERE IS NO SUBSTITUTE FOR OBSERVING THE PATIENT, TALKING TO HIM AND THINKING ABOUT HIM.

FEVER & MYALGIA

VIRAL FEVERS LEUCOPENIA & THROMBOCYTOPENIA INFLUENZA URTI SYMPTOMS

POLYMYOSITIS PROXIMAL M WEAKNESS, MUSCLE PAIN & TENDERNESS, CPK HIGH MENINGOCOCCAL INFECTION -Rash

SEPSIS

Fever & Night Sweats

TUBERCULOSIS LYMPHOMA ABSCESS BRUCELLOSIS INFECTIVE ENDOCARDITIS ALCOHOL WITHDRAWAL SYNDROME

FEVER Brady, Tachycardia

RELATIVE BRADYCARDIA TYPHOID FEVER MALARIA MENINGITIS LEPTOSPIROSIS VIRAL DRUG FEVER

 RELATIVE TACHYCARDIA TOXINS

Fever & Eyes

EYE PAIN TEMPORAL ARTERITIS WATERY EYES- PAN DRY EYES SLE,RA

SC Hemorrhages SBE CONJUNCTIVITIS TB,SLE CONJUNCTIVAL SUFFUSION- LEPTOSPIROSIS UVEITIS- TB,SLE,SARCOIDOSIS

FEVER WITH JAUNDICE

LEPTOSPIROSIS RENAL FAILURE + HEPATITIS- DRUGS (ATT) ,VIRAL ALCOHOLIC HEPATITIS CIRRHOSIS OF LIVER HEPATOMA VIRAL FEVERS MALARIA

GENERALIZED LYMPHADENOPATHY
LEUKEMIA ALL , CLL LYMPHOMA MEDIASTINAL INVOLVEMENT HIV INFECTION ORAL CANDIDIASIS,THIN BUILT, TOXOPLASMOSIS- WITH LIVER,SPLEEN DISSEMINATED TUBERCULOSIS WITH LIVER ,SPLEEN BRUCELLOSIS- WITH LIVER,SPLEEN

FEVER WITH HEPATOSPLENOMEGALY

MALARIA TYPHOID LYMPHOMA LEUKEMIA DISSEMINATED TB INFECTIVE ENDOCARDITIS BRUCELLOSIS KALA AZAR

FEVER WITH MENTAL CONFUSION

MENINGITIS MENINGISM- TYPHOID HIV BRUCELLOSIS CNS NEOPLASMS

LOCAL TENDERNESS
TONGUE- RELAPSING FEVER TRAPEZIUS SUB DIAPHRAGMATIC ABSCESS STERNAL METASTASIS, PRE LEUKEMIA SPINAL BRUCELLOSIS,TYPHOID,SBE,OM THIGH- POLYMYOSITIS,BRUCELLOSIS CALF POLYMYOSITIS, RMSF

FEVER - ARDS

SARS INFECTION CEREBRAL MALARIA (P FALCIPARUM ) HANTA VIRUS INFECTION SEPSIS

HIGH ESR
TB TEMPORAL ARTERITIS CARCINOMA LYMPHOMAS ABSCESS MYELOPROLIFERATIVE DISORDER

FEVER & LOW PLATELETS

DENGUE FEVER VIRAL FEVERS LEUKEMIA LYMPHOMA MYELOPROLIFERATIVE DISORDER DRUG FEVER SLE HIV INFECTION

CHEST X-RAY DIAGNOSIS

TB- ANY FORM LYMPHOMAS- MEDIASTINAL INVOLVEMENT SARCOIDOSIS BHL PNEUMONIAS AUTOIMMUNE DISEASES

DIAGNOSTIC TESTS
ANA,ANTI DS DNA SLE BONE SCAN- OSTEOMYELITIS,METASTASIS ECHO HEART ATRIAL MYXOMA,IE,PCITIS SMEAR TEST + VE MALARIA, ELISA IGM AB - LEPTOSPIRA VIRAL CULTURE + IN EBV,CMV INFECTIONS BLOOD CULTURE + IN IE,SEPSIS, AGGLUTININ TEST + IN SALMONELLA , BRUCELLOSIS

ULTRA SOUND
HEPATOMA ABSCESS HYPERNEPHROMA (PHYSICIAN S TUMOUR) LYMPHOMA PELVIC TUMORS

Cultures:
Blood cultures for aerobic and anaerobic pathogens. maximum 6 sets of blood cultures are required. Urine culture Cultures of sputum Stool Cultures Perform cultures for - Bacteria, - Mycobacteria, and - Fungi

Serologies
Serologies are most helpful if paired samples show a significant, usually 4-fold, increase of antibodies specific to an infectious microorganism. Brucellosis, CMV, infectious mononucleosis, HIV, amebiasis, toxoplasmosis, and chlamydial diseases are diagnosed by serology. These diagnostic tests are of limited value in most patients with FUO, but they are appropriate for evaluation of the above illnesses in the correct clinical and epidemiological setting.

THANK YOU
ALL WE KNOW IS STILL INFINITELY LESS THAN ALL THAT REMAINS UNKNOWN -WILLIAM HARVEY -