Submitted by: Luisa Marie Andrea G.

Roma

DIPHTHERIA
Diphtheria (Greek upper respiratory tract illness (diphthera) caused "pair of leather scrolls") is an

byCorynebacterium

diphtheriae,

a facultative

anaerobic, Gram-positive bacterium. It is characterized by sore throat, lowfever, and an adherent membrane (a pseudomembrane) on the tonsils, pharynx, and/or nasal cavity.[3] A milder form of diphtheria can be restricted to the skin. Less common consequences include myocarditis (about 20% of cases) [4] andperipheral neuropathy (about 10% of cases). Diphtheria is a contagious disease spread by direct physical contact or breathing the aerosolized secretions of infected individuals. Historically quite common, diphtheria has largely been eradicated in industrialized nations through widespreadvaccination. In the United States, for example, there were 52 reported cases of diphtheria between 1980 and 2000; between 2000 and 2007, there were only three cases as the diphtheriapertussistetanus (DPT) vaccine is recommended for all school-age children. Boosters of the vaccine are recommended for adults, since the benefits of the vaccine decrease with age without constant re-exposure; they are particularly recommended for those traveling to areas where the disease has not been eradicated.

Signs and symptoms

The symptoms of diphtheria usually begin two to seven days after infection. Symptoms of diphtheria include fever of 38C (100.4F) or above, chills, fatigue, bluish skin coloration, sore throat, hoarseness, cough, headache, difficulty swallowing, painful swallowing, difficulty breathing, rapid breathing, foul-smelling bloodstained nasal discharge and lymphadenopathy. Symptoms can also include cardiac arrhythmias, myocarditis, and cranial and peripheral nerve palsies.

Diphtheria toxin mechanism

Diphtheria Diphtheria toxin is produced a single, by C. diphtheriae only when it is infected with of a bacteriophage that integrates the toxin-encoding genetic elements into the bacteria. toxin is 60,000 molecular weight protein composed two peptide chains, fragment A and fragment B, held together by a disulfide bond. Fragment B is a recognition subunit that gains the toxin entry into the host cell by binding to the EGF-like domain of heparin-binding EGF-like growth factor (HB-EGF) on the cell surface. This signals the cell to internalize the toxin within an endosome via receptor-mediated endocytosis. Inside the endosome, the toxin is split by a trypsin-like proteaseinto its individual A and B fragments. The acidity of the endosome causes fragment B to create pores in the endosome membrane, thereby catalyzing the release of fragment A into the cell's cytoplasm.

Fragment A inhibits the synthesis of new proteins in the affected cell. It does this by catalyzing ADP-ribosylation of elongation factor EF-2a protein that is essential to the translation step of protein synthesis. This ADP-ribosylation involves the transfer of an ADP-ribose from NAD+ to a diphthamide (a modified histidine) residue within the EF-2 protein. Since EF-2 is needed for the moving of tRNA from the A-site to the P-site of the ribosome during protein translation, ADPribosylation of EF-2 prevents protein synthesis. ADP-ribosylation of EF-2 is reversed by giving high doses of nicotinamide (a form of vitamin B3), since this is one of the reaction's end-products, and high amounts will drive the reaction in the opposite direction.

Diagnosis
The current definition of diphtheria used by the Centers for Disease Control and Prevention (CDC) is based on both laboratory and clinical criteria.

Laboratory criteria
Isolation of Corynebacterium diphtheriae from a gram stain or throat culture from a clinical specimen , or Histopathologic diagnosis of diphtheria

Clinical criteria
Upper respiratory tract illness with sore throat Low-grade fever (>102F is rare) An adherent pseudomembrane of the tonsil(s), pharynx, and/or nose.

Case classification
Probable: a clinically compatible case that is not laboratory-confirmed and is not epidemiologically linked to a laboratory-confirmed case Confirmed: a clinically compatible case that is either laboratory-confirmed or epidemiologically linked to a laboratory-confirmed case

Empirical treatment should generally be started in a patient in whom suspicion of diphtheria is high.

Treatment
The disease may remain manageable, but in more severe cases, lymph nodes in the neck may swell, and breathing and swallowing will be more difficult. People in this stage should seek immediate medical attention, as obstruction in the throat may require intubation or a tracheotomy. Abnormal cardiac rhythms can occur early in the course of the illness or weeks later, and can lead to heart failure. Diphtheria can also cause paralysis in the eye, neck, throat,

or respiratory muscles. Patients with severe cases will be put in a hospital intensive care unit and be given a diphtheria antitoxin. Since antitoxin does not neutralize toxin that is already bound to tissues, delaying its administration is associated with an increase in mortality risk. Therefore, the decision to administer diphtheria antitoxin is based on clinical diagnosis, and should not await laboratory confirmation. Antibiotics have not been demonstrated to affect healing of local infection in diphtheria patients treated with antitoxin. Antibiotics are used in patients or carriers to eradicate C. diphtheriae and prevent its transmission to others. The CDC recommends either: Metronidazole Erythromycin (orally or by injection) for 14 days (40 mg/kg per day with a maximum of 2 g/d), or Procaine penicillin G given intramuscularly for 14 days (300,000 U/d for patients weighing <10 kg and 600,000 U/d for those weighing >10 kg). Patients with allergies to penicillin G or erythromycin can use rifampin or clindamycin. In cases that progress beyond a throat infection, diphtheria toxin spreads through the bloodstream and can lead to potentially life-threatening complications that affect other organs of the body, such as the heart and kidneys. The toxin can cause damage to the heart that affects its ability to pump blood or the kidneys' ability to clear wastes. It can also cause nerve damage, eventually leading to paralysis. About 40% to 50% of those left untreated can die.

Epidemiology
Diphtheria is a serious disease, with fatality rates between 5% and 10%. In children under five years and adults over 40 years, the fatality rate may be as much as 20%.Outbreaks, though very rare, still occur worldwide, even in developed nations, such as Germany and Canada. After the breakup of the former Soviet Union in the late 1980s, vaccination rates in its constituent countries fell so low that there was an explosion of diphtheria cases. In 1991, there were 2,000 cases of diphtheria in the USSR. By 1998, according to Red Cross estimates, there were as many as 200,000 cases in the Commonwealth of Independent States, with 5,000 deaths. This was so great an increase that diphtheria was cited in the Guinness Book of World Recordsas "most resurgent disease".

History
The disease was named by French doctor Pierre Bretonneau in 1855 (substituted for his earlier term diphthrite). In 1878, Queen Victoria's daughter Princess Alice and her family became infected with it, causing two deaths, Princess Marie of Hesse and by Rhine and Princess Alice herself. In the 1920s, there were an estimated 100,000 to 200,000 cases of diphtheria per year in the United States, causing 13,000 to 15,000 deaths per year. Children represented a large majority of these cases and fatalities. One of the most famous outbreaks of diphtheria was in Nome, Alaska;

the "Great Race of Mercy" to deliver diphtheria antitoxin is now celebrated by theIditarod Trail Sled Dog Race. One of the first effective treatments for diphtheria was discovered in the 1880s by U.S. physician Joseph O'Dwyer (18411898). O'Dwyer developed tubes that were inserted into the throat, and prevented victims from suffocating due to the membrane sheath that grows over and obstructs airways. In 1884, Friedrich Loeffler discovered the causative organism (Corynebacterium diphtheriae). In the 1890s, the German physician Emil von Behring developed an antitoxin that did not kill the bacterium, but neutralized the toxic poisons the bacterium releases into the body. Von Behring discovered that animal blood has antitoxins in it, so he took the blood, removed the clotting agents and injected it into human patients. Von Behring was awarded the first Nobel Prize in Medicine for his role in the discovery, and development of a serum therapy for diphtheria. (Americans William H. Parkand Anna Wessels Williams, and Pasteur Institute scientists Emile Roux and Auguste Chaillou also independently developed diphtheria antitoxin in the 1890s.) The first successful vaccine for diphtheria was developed in 1913 by Behring. However, antibiotics against diphtheria were not available until the discovery and development of sulfa drugs. The Schick test, invented between 1910 and 1911, is a test used to determine whether or not a person is susceptible to diphtheria. It was named after its inventor, Bla Schick (18771967), a Hungarian-born American pediatrician. A massive five-year campaign was coordinated by Dr. Schick. As a part of the campaign, 85 million pieces of literature were distributed by theMetropolitan Life Insurance Company with an appeal to parents to "Save your child from diphtheria." A vaccine was developed in the next decade, and deaths began declining in earnest in 1924. In early May 2010, a case of diphtheria was diagnosed in Port-au-Prince, Haiti after the devastating 2010 Haiti earthquake. The 15-year-old male patient died while workers searched for antitoxin.

ENCEPHALITIS
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue. More advanced and serious symptoms include seizures orconvulsions, tremors, hallucinations, and memory problems.

Cause
Viral

Viral encephalitis can occur either as a direct effect of an acute infection, or as one of the sequelae of a latent infection. The most common causes of acute viral encephalitis are rabies virus, Herpes simplex, poliovirus, measles virus, and JC virus.[1]Other causes include infection by flaviviruses such as Japanese encephalitis virus, St. Louis encephalitis virus or West Nile virus, or by Togaviridae such as Eastern equine encephalitis virus (EEE virus), Western equine encephalitis virus (WEE virus) or Venezuelan equine encephalitis virus (VEE virus).

Bacterial and other

It can be caused by a bacterial infection, such as bacterial meningitis, spreading directly to the brain (primary encephalitis), or may be a complication of a current infectious disease syphilis (secondary as toxoplasmosis, malaria, encephalitis). or primary Certain parasitic or protozoal infestations, meningoencephalitis, can also such cause amoebic

encephalitis in people with compromised immune systems. Lyme disease and/or Bartonella henselae may also cause encephalitis. Cryptococcus neoformans is notorious for causing fungal encephalitis in the immunocompromised. Streptococci, Pneumococci, Staphylococci and certain gram negative bacilli cause ceribritis prior to the formation of a brain abscess. Another cause is granulomatous amoebic encephalitis.

Diagnosis
Adult patients with encephalitis present with acute onset of fever, headache, confusion, and sometimes seizures. Younger children or infants may present irritability, poor appetite and fever. Neurological examinations usually reveal a drowsy or confused patient. Stiff neck, due to the irritation of the meninges covering the brain, indicates that the patient has either meningitis or meningoencephalitis. Examination of the cerebrospinal fluid obtained by a lumbar puncture procedure usually reveals increased amounts of protein and white blood cells with normal glucose, though in a significant percentage of patients, the cerebrospinal fluid may be normal. CT scan often is not helpful, as cerebral abscess is uncommon. Cerebral abscess is more common in patients with meningitis than encephalitis. Bleeding is also uncommon except in patients with herpes simplex type 1encephalitis. Magnetic resonance imaging offers better resolution. In patients with herpes simplex encephalitis, electroencephalograph may show sharp waves in one or both of the temporal lobes. Lumbar puncture procedure is performed only after the possibility of prominent brain swelling is excluded by a CT scan examination. Diagnosis is often made with detection of antibodies in the cerebrospinal fluid against a specific viral agent (such as herpes simplex virus) or by polymerase chain reaction that amplifies theRNA or DNA of the virus responsible (such as varicella zoster virus). Serological tests may show high antibody titre against the causative antigen.

Treatment
Treatment is usually symptomatic. Reliably tested specific antiviral agents are few in number (e.g. acyclovir for herpes simplex virus) and are used with limited success in treatment of viral infection, with the exception of herpes simplex encephalitis. In patients who are very sick, supportive treatment, such as mechanical ventilation, is equally important. Corticosteroids (e.g., methylprednisolone) are used to reduce brain swelling and inflammation. Sedatives may be needed for irritability or restlessness. ForMycoplasma infection, parentral tetracycline is given. Encephalitis due to Toxoplasma is treated by giving a combination of pyrimethamine and sulphadimidine.

Prevention
Post-infectious encephalomyelitis complicating small pox vaccination is totally avoidable now as small pox is now eradicated. Contraindication to Pertussis immunisation should be observed in patients with encephalitis. An immunodeficient patient who have had contact with chicken pox virus should be given prophylaxis with hyperimmune zoster immunoglobulin.

Encephalitis lethargica
Encephalitis lethargica is an atypical form of encephalitis which caused an epidemic from 1918 to 1930. Those who survived sank into a semi-conscious state that lasted for decades until the Parkinson's drug L-DOPA was used to revive those still alive in the late 1960s by Oliver Sacks. There have been only a small number of isolated cases in the years since, though in recent years a few patients have shown very similar symptoms. The cause is now thought to be either a bacterial agent or an autoimmune response following infection.

Limbic system encephalitis

In a large number of cases, called limbic encephalitis, the pathogens responsible for encephalitis attack primarily the limbic system (a collection of structures at the base of the brain responsible for emotions and many other basic functions).