Question

Discuss two different diesases, One disease example must be of microbial origin and the second disease example must be of non- microbial origin. For each disease, discuss the following:

-pathophysiology

-prevalence

-ethiology

-clinical manifestations

-diagnosis

-treatment (medication administration and dosage.)

Answer 1

Disease of microbial origin : Cholera

Cholera results from infection by Vibrio cholerae, a gram negative bacteria ,resulting in acute diarrheal illness . Cholera is endemic in middle East, Africa, central and South America, South Asia.

Pathophysiology:

· V cholerae is a comma shaped gram negative aerobic or facultatively anaerobic bacillus that varies in size from 1-3µm in length to 0.5-0.8 µm in diameter.

· Its antigenic structure consists of a flagellar H antigen and a somatic O antigen.

· Ingestion of V. cholera usually due to contaminated water enters the GI system and makes it resistant to gastric acid.

· There they colonize the small intestine and secrete enterotoxins.

· Enterotoxin binds to intestinal cells which activates the chloride channels

· Releasing large quantities of electrolytes & bicarbonates

· There is fluid hyper secretion manifested as diarrhea eventually leading to dehydration.

Prevalence :

· The incidence of Vibrio infection in the United States is low, with highest number documented in the age group older than 50 years, which has been around 0.50 cases per 100,000 population from 2003-2008.

· The frequency of cholera among international travelers returning to the United States has averaged 1 case per 500,000 population, with a range of 0.05-3.7 cases per 100,000 population

· There are roughly 1.3 to 4.0 million cases, and 21 000 to 143 000 deaths worldwide due to cholera

Etiology :

V cholerae result from human infection and poor sanitation with assistance from human migration and seasonal warming of coastal waters. Common sources include:

ü Municipal water supplies

ü Ice made from municipal water

ü Foods and drinks sold by street vendors

ü Vegetables grown with water containing human wastes

ü Raw or undercooked fish and seafood caught in waters polluted with sewage

· Transmission occurs almost exclusively via contaminated water or food

Clinical manifestations:

· Painless

· watery diarrhea (rice water diarrhea) , sometimes accompanied by vomiting.

· Severe fluid loss can be seen in more serious cases; thirst, oliguria, severe dehydration, acidosis, muscle cramps and shock may result.

· Most cases last approximately 2 to 7 days but death may occur within a few hours if the fluid loss is high.

Diagnosis :

· Cholera can be diagnosed by observing the organism’s characteristic motility during direct, bright–field or dark–field microscopic examination of the feces

· Bacteria can also be identified in the feces by immunofluorescence.

· Serologic tests include agglutination tests, complement fixation and tests to detect antitoxic antibodies. Enzyme –linked immunosorbent assays (ELISAs) and passive hemagglutination can also be used

· Hematological tests – hematocrit, serum specific gravity, serum proteins will be elevated in dehydrated patients

· Metabolic panel – changes in serum sodium, potassium levels , elevated BUN and creatinine levels

Treatment :

· A multifaceted approach which is a combination of surveillance, water, sanitation and hygiene, social mobilisation, treatment, and oral cholera vaccines are used.

· Fluid replacement and the restoration of electrolyte balance is the first line of treatment

· Rehydration is the first priority in the treatment of cholera. Rehydration is accomplished in 2 phases: rehydration and maintenance.

· Use lactated Ringer solution or, if that is not available, isotonic sodium chloride solution. If the patient can drink, begin giving oral rehydration salt solution (ORS) by mouth while the drip is being set up; ORS can provide the potassium, bicarbonate, and glucose that saline solution lacks.

· For patients older than 1 year, give 100 mL/kg IV in 3 hours—30 mL/kg as rapidly as possible (within 30 min) then 70 mL/kg in the next 2 hours. For patients younger than 1 year, administer 100 mL/kg IV in 6 hours—30 mL/kg in the first hour then 70 mL/kg in the next 5 hours.

· Administer ORS solution (about 5 mL/kg/h) as soon as the patient can drink, in addition to IV fluid.

· When a patient who has been rehydrated with IV fluid or ORS solution is reassessed and has no signs of dehydration, continue to administer ORS solution to maintain normal hydration.

· Antibiotics to diminish the duration of diarrhoea, reduce the volume of rehydration fluids needed, and shorten the amount and duration of V. cholerae excretion in their stool. Single-dose therapy with tetracycline, doxycycline, furazolidone, or ciprofloxacin can be administered for 3-5 days.

Antibiotic	Single Dose (PO)	Multiple Dose (PO)
Doxycycline†	7 mg/kg; not to exceed 300 mg/dose‡	2 mg/kg bid on day 1; then 2 mg/kg qd on days 2 and 3; not to exceed 100 mg/dose
Tetracycline†	25 mg/kg; not to exceed 1 g/dose‡	40 mg/kg/d divided qid for 3 d; not to exceed 2 g/d
Furazolidone	7 mg/kg; not to exceed 300 mg/dose	5 mg/kg/d divided qid for 3 d; not to exceed 400 mg/d
Trimethoprim and sulfamethoxazole	Not evaluated	< 2 months: Contraindicated ≥2 months: 5-10 mg/kg/d (based on trimethoprim component) divided bid for 3 d; not to exceed 320 mg/d trimethoprim and 1.6 g/d of sulfamethoxazole
Ciprofloxacin§	30 mg/kg; not to exceed 1 g/dose‡	30 mg/kg/d divided q12h for 3 d; not to exceed 2 g/d
Ampicillin	Not evaluated	50 mg/kg/d divided qid for 3 d; not to exceed 2 g/d
Erythromycin	Not evaluated	40 mg/kg/d erythromycin base divided tid for 3 d; not to exceed 1 g/d

· Resume feeding with a normal diet when vomiting has stopped. Breastfeeding should be continued for infants and young children.

· vaccine consists of a monovalent killed whole-cell V cholerae O1 with purified recombinant B-subunit of cholera toxoid 2 doses 1 week apart.

Rheumatoid arthritis

· Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease of unknown cause.

· It is characterized by persistent inflammation that primarily affects the peripheral joints.

Pathophysiology :

· RA is a systemic disease but the most characteristic lesions are seen in the synovium or within rheumatoid nodules

· There is proliferation of cells in the synovial layer of the joint

· There is vascular congestion with new blood vessel formation

· Infiltration of the sub synovial layers by polymorphs, lymphocytes and plasma cells

· There is thickening of the capsular structures , villous formation of the synovium and a cell rich effusion in the joints and tendon sheath

· There is joint and tendon destruction along with erosion of the cartilage, there is partial or complete rupture of the tendons all which leads to progressive instability and deformity of the joints

Prevalence :

· Prevalence varies from 0.5% to 1.5% of the population.

· RA affects more women than men (ratio 3:1).

· The age of onset is between 30 and 55 years.

Etiology :

The specific causes of RA are unknown, but some factors can increase the risk of developing the disease. There are a number of environmental and genetic factors wich increases ones risk of developing RA.

· Age – likelihood increases with age

· Sex – affects more women than men

· Genetics- HLA (human leukocyte antigen) class II genotypes increase probability of RA or worsens RA

· Smoking

· Women who have never given birth

· Obesity

Clinical manifestations:

· The onset is most often insidious but can be episodic or acute.

· Inflamed joints become swollen, painful, and stiff. Synovial fluid may accumulate, causing an effusion. Joint pain is usually more prominent and more persistent than in osteoarthritis

occurring at rest, at night, and on activity.

· Prolonged early morning stiffness is also a key diagnostic feature suggestive of inflammatory disease

· RA may also involve the cervical spine, causing pain in the neck and occipital headache

· Extra-articular features are common and may involve multiple organs, including the skin, eyes, lungs, and blood vessels.

Diagnosis :

The diagnosis of RA is usually based on criteria established by the American College of Rheumatology. To be diagnosed as having RA, a patient must meet four or more criteria, which include:

1. Morning stiffness in and around the joints lasting at least 1 hour

2. Soft-tissue swelling of three or more joints

3. Swelling of the proximal interphalangeal joints, metacarpophalangeal joints, or wrist joints

4. Symmetrical arthritis

5. Subcutaneous nodules

6. A positive test for rheumatoid factor

7. Radiographic evidence of erosions or periarticular osteopenia in the hand or wrist joints

· Check for Rheumatoid factor and Anti-citrullinated protein antibody

· C-reactive protein levels and erythrocyte sedimentation rate are often increased with active RA

· Baseline complete blood count with differential and assessment of renal and hepatic function are helpful because the results may influence treatment options

Treatment :

Early referral for a specialist’s opinion is recommended for any patient with RA or suspected synovitis of undetermined cause.

• Analgesics and nonsteroidal anti-inflammatory drugs can alleviate pain but do not affect disease progression.

· These are the main types of RA medications:

ü Disease-modifying anti- rheumatic drugs (DMARDs)

ü Biologic response modifiers (a type of DMARD)

ü Glucocorticoids

ü Nonsteroidal anti-inflammatory medications (NSAIDs)

ü Analgesics (painkillers)

· DMARDs- These RA drugs are often used along with NSAIDs or glucocorticoids. DMARDs can often slow or stop the progression of RA by interrupting the immune process that promotes inflammation . examples are methotrexate, injectable gold, penicillamine,azathioprine,chloroquine,hydroxychloroquine,sulfasalazine and oral gold.

· Biological response modifiers: these drugs directly modify the immune system by inhibiting proteins called cytokines which contribute to inflammation.Examples of tehse are abatacept, etanercept, infliximab,adalimumab and anakinra.

· glucocorticoids or prednislone : tehy are prescribed in small doses to slow joint damage caused by inflammation.

· NSAIDS & analgesics : morphine & acetoaminophen reduces pain, ibuprofen, indomethacin, COX-2 inhibitors like celecoxib, valdecoxib reduce inflammation and pain.

· Protein A immunoadsorption therapy –here there is filtration of blood to remove antibodies and immune complexes that promote inflammation.

· Surgery – synovectomy : to reduce the inflammatory tissue , osteotomy – done to increase stability by redistributing the weight on the joint, joint replacement surgery or arthroplasty

· Psychological therapy that incorporates coping strategies, relaxation therapy, education on disease and treatments, and stress management skills reduces pain and improves function.

· Physical therapy is effective in management of rheumatoid arthritis- support aerobic and strengthening exercises, transcutaneous electrical nerve stimulation, and ultrasound can be used.