Influenza & Diphtheria Epidemiology PDF

## EPIDEMIOLOGY OF COMMUNICABLE DISEASES ### INFLUENZA **Hospital Care** * Requires early supplemental oxygen therapy. * Careful fluid replacement * Antimicrobials for co-infections * Proactive observation for progression of illness **Antiviral Therapy** * Oseltamivir * Zanamivir * Amantadine o...

## EPIDEMIOLOGY OF COMMUNICABLE DISEASES ### INFLUENZA **Hospital Care** * Requires early supplemental oxygen therapy. * Careful fluid replacement * Antimicrobials for co-infections * Proactive observation for progression of illness **Antiviral Therapy** * Oseltamivir * Zanamivir * Amantadine or rimantadine **Treatment Recommendations** * Patients who have severe or progressive clinical illness should be treated with oseltamivir. * This recommendation applies to all patient groups including pregnant women and young children < 2 years. * Do not deliver via nebulization due to the presence of lactose, which may compromise ventilator function. **Standard Antiviral Treatment Regimens** **Oseltamivir** * Adults: 75 mg twice daily for 5 days * Infants < 1 year: * **>3 months to 12 months:** 3 mg/kg twice daily for 5 days * **>1 month to 3 months:** 2.5 mg/kg twice daily for 5 days * **0 to 1 month:** 2 mg/kg twice daily for 5 days * Children > 1 year to 12 years: * **15 kg or less:** 30 mg twice a day for 5 days * **15-23 kg:** 45 mg twice a day for 5 days * **24-40 kg:** 60 mg twice a day for 5 days * **>40 kg:** 75 mg twice a day for 5 days **Zanamivir** * Adults and children (>5 years): 2 inhalations (2 x 5 mg) twice daily for 5 days. **Chemoprophylaxis** * Oseltamivir is the drug of choice. * Given until 10 days after last exposure. * Dosage by body weight: * **Weight less than 15 kg:** *> 3 months: 30 mg OD * 3-5 months: 20mg OD * 6-11 months: 25mg OD * **15-23 kg:** 45 mg OD * **24-40 kg:** 60 mg OD * **> 40 kg:** 75 mg OD **Influenza Surveillance** * Monitors the prevalence of circulating strains and to detect new strains necessary for vaccine information. * Estimates influenza related impact on morbidity, mortality, and economic loss. * Rapidly detect outbreaks and disease control through rapid action. ## DIPHTHERIA * An acute bacterial infectious disease caused by toxigenic strains of Corynebacterium diphtheriae. * Three major clinical types have been described - anterior nasal, faucial and laryngeal; however, the skin, conjunctiva, vulva and other parts of the body may be affected. * The bacilli multiply locally, usually in the throat, and elaborate a powerful exotoxin which is responsible for: * The formation of a greyish or yellowish membrane ("false membrane") over the tonsils, pharynx, or larynx, with well-defined edges. The membrane cannot be wiped away. * Marked congestion, oedema, or local tissue destruction. * Enlargement of the regional lymph nodes. * Signs and symptoms of toxaemia. * Fatality rate is about 5-10% on average. * In children under 5 years of age and adults over 40 years of age, one out of 5 people with diphtheria dies. **Problem Statement:** **WORLD:** * Diphtheria is a rare disease in most developed countries owing to routine children vaccination. * Vaccination schemes have been instituted in some countries and the disease has so declined that it is no longer regarded as a public health problem. * The disease is occasionally seen among non-immunized children in developed countries. * Improved socio-economic conditions are changing the epidemiology of diphtheria. * Epidemics are largely due to decreasing immunization coverage among infants and children, waning immunity to diphtheria in adults, movement of large groups of population in the last few years, and an irregular supply of vaccine. * These outbreaks highlight the need for booster vaccinations. * Disease continues to be endemic in developing countries due to lack of adequate widespread immunization. * The true numbers of diphtheria cases and deaths are unknown because of incomplete reporting from most countries where the disease occurs. * During 2021, about 8,639 diphtheria cases were reported globally. **INDIA:** * Diphtheria is an endemic disease. * Retrospective data indicate a declining trend in the country due to increasing coverage of child population by immunization. * During 2020, about 1,991 cases of diphtheria were reported in India with about 28 deaths. * Most cases were from West Bengal, Telangana, Andhra Pradesh, Rajasthan, and Delhi. **Epidemiological Determinants:** **Agent Factors:** * **The causative agent:** C. diphtheriae is a gram-positive, non-motile organism. * It has no invasive power *but* produces a powerful exotoxin. * Four types of diphtheria bacilli are differentiated - gravis, mitis, belfanti, and intermedius, all pathogenic to man. * Gravis infections tend to be more severe than mitis infections. * Not all strains of the organism are toxigenic. * There is evidence that a non-toxigenic strain may become toxigenic when exposed to a particular bacteriophage - the beta phage - carrying the gene for toxin production. **Portal of Entry** * **Respiratory Route:** This is the most common portal of entry. * **Non-Respiratory Routes:** * The portal of entry sometimes may be the skin where cuts, wounds, and ulcers not properly attended to, may get infected with diphtheria bacilli. * The umbilicus in newborns may also be a portal of entry. * The site of implantation may be the eye, genitalia, or middle ear. * Non-respiratory routes of infection are less common in developed countries where spread by droplet infection is more common. **Incubation Period** * 2 to 6 days; occasionally longer. **Clinical Features** * **Respiratory Tract Forms of Diphtheria:** * Pharyngotonsillar,laryngotracheal, nasal, and combinations thereof. * Patients with pharyngotonsillar diphtheria usually have a sore throat, difficulty in swallowing, and low-grade fever at presentation. * Examination of the throat my show only mild erythema, localized exudate, or a pseudo-membrane. * The membrane may be localized or a patch of the posterior pharynx or tonsil, may cover the entire tonsil, or less frequently, may spread to cover the soft and hard palates and the posterior portion of the pharynx. * In the early stage, the pseudo-membrane may be whitish and may wipe off easily. * The membrane may extend to become thick, blue-white to grey-black, and adherent. * Attempts to remove the membrane result in bleeding. * A minimal area of mucosal erythema surrounds the membrane. * Patients with severe disease may have marked oedema of the submandibular area and the anterior portion of the neck, along with lymphadenopathy, giving a characteristic "bull-necked" appearance (1). * **Laryngotracheal Diphtheria:** * Most often preceded by pharyngotonsillar disease. * Usually associated with fever, hoarseness, and croupy cough at presentation. * If the infection extends into bronchial tree, it is the most severe form of disease. * It may be clinically indistinguishable from viral croup or epiglottitis. * Prostration and dyspnoea soon follow because of the obstruction caused by the membrane. * Obstruction may even cause suffocation if not promptly relieved by intubation or tracheostomy. * The diphtheria bacilli within the membrane continue to produce toxin actively. * This is absorbed and results in distant toxic damage. * Irregularities of cardiac rhythm indicate damage to the heart. * Later, there may be difficulties with vision, speech, swallowing, or movement of the arms or legs. * **Nasal Diphtheria:** * The mildest form of respiratory diphtheria. * Usually localized to the septum or turbinates of one side of the nose. * A membrane may extend into the pharynx. * **Non-Respiratory Mucosal Surface:** * The conjunctiva and genitals may also be sites of infection. * **Cutaneous Diphtheria:** * Common in tropical areas. * Often appears as a secondary infection of a previous skin abrasion or infection. * The presenting lesion, often an ulcer, may be surrounded by erythema and covered with a membrane. * Patients generally seek treatment because of the chronicity of the lesion. **Control of Diphtheria** 1. **Cases and Carriers** * **Early Detection:** An active search for cases and carriers should start immediately amongst family and school contacts. Carriers can be detected only by culture method. Swabs should be taken from both the nose and throat and examined by culture methods for diphtheria bacilli. Tests should be made for the virulence of the organism. * **Isolation:** All cases, suspected cases, and carriers should be promptly isolated, preferably in a hospital, for at least 14 days or until proved free of infection. At least 2 consecutive nose and throat swabs, taken 24 hours apart, should be negative before terminating isolation. * **Treatment:** * **Cases:** When diphtheria is suspected, diphtheria antitoxin should be given without delay, IM or IV, in doses ranging from 20,000 to 100,000 units or more, depending upon the severity of the case, after a preliminary test dose of 0.2 ml subcutaneously to detect sensitization to horse serum. For mild early pharyngeal or laryngeal disease, the dose is 20,000-40,000 units; for moderate nasopharyngeal disease, 40,000-60,000 units; for severe, extensive or late (3 days or more) disease, 80,000-100,000 units (10). In addition to antitoxin, every case should be treated with penicillin or erythromycin for 5 to 6 days to clear the throat of C. diptheriae and thereby decrease toxin production. * **Carriers:** The carriers should be treated with 10 days course of oral erythromycin, which is the most effective drug for the treatment of carriers. The immunity status should be upgraded as discussed below. 2. **Contacts** * Contacts merit special attention. They should be throat swabbed and their immunity status determined. Different situations pose different options: * Where primary immunization or booster dose was received within the previous 5 years, no further action would be needed. * Where primary course or booster dose of diphtheria toxoid was received more than 5 years before, only a booster dose of diphtheria toxoid need be given. * Non-immunized close contact should receive prophylactic penicillin or erythromycin. They should be given 1000-2000 units of diphtheria antitoxin and actively immunized against diphtheria. Contacts should be placed under medical surveillance and examined daily for evidence of diphtheria for at least a week after exposure. The bacteriological surveillance of close contacts should be continued for several weeks by repeated swabbing. 3. **Community** * The only effective control is by active immunization with diphtheria toxoid of all infants as early in life as possible, as scheduled, with subsequent booster doses every 10 years thereafter. The aim should be to immunize before the infant loses his maternally derived immunity so that there will be continuous protection from birth without any gap in immunity to natural disease. The vaccine being a toxoid is not directed against organisms. Therefore immunization does not prevent the carrier state; consequently, the non-immune individuals are not protected by a high level of population immunity (11). This implies that immunization rate must be maintained at a high level. **Diphtheria Immunization** **Current Prophylactics** * **Combined or Mixed Vaccines:** * DPT * DTPw * DTPa * DT * dT * Pentavalent (Diphtheria, tetanus, pertussis, hepatitis B, and Hib) * **Single Vaccines:** * FT (formal-toxoid) * APT (alum-precipitated toxoid) * PTAP (purified toxoid, aluminum phosphate) * PTAH (purified toxoid aluminum hydroxide) * TAF (toxoid-antitoxin flocculus) * **Antisera:** * Diphtheria antitoxin **Combined Vaccines** 1. **DPT Vaccine** * For immunizing infants, the preparation of choice is DPT. * Firstly because, the infant can be immunized simultaneously against three diseases, viz., diphtheria, pertussis, and tetanus which is a great gain administratively. Secondly the pertussis component in DPT vaccine enhances the potency of the diphtheria toxoid. * There are two types of DPT vaccines- plain and adsorbed. Adsorption is usually carried out on a mineral carrier like aluminium phosphate or hydroxide. Studies have shown that adsorption increases the immunological effectiveness of the vaccine. The WHO recommends that only adjuvant DPT preparations be utilized in immunization programmes (12). * **Storage:** DPT/DT vaccines should not be frozen. They should be stored in a refrigerator between 2 to 8 deg. C. * **Optimum age:** It has been found that young infants respond well to immunization with potent vaccines and toxoids even in the presence of low to moderate levels of maternal antibodies. Accordingly, the Global Advisory Group of the Expanded Programme on Immunization (EPI), has recommended that DPT vaccine can be safely and effectively administered as early as 6 weeks after birth. * **Number of Doses:** Three doses of DPT each of which is usually 0.5 ml, should be considered optimal for primary immunization. It is associated with higher and more sustained levels of diphtheria and tetanus antitoxin and acceptable level of pertussis protection, i.e., vaccine efficiency 95 percent (13). * **Interval between doses:** The current recommendation is to allow an interval of 4 weeks between the 3 doses, with a booster injection at 16-24 months, followed by another booster at the age of 5 to 6 years. * **Mode of Administration:** DPT should be administered intramuscularly in antero (lateral aspect) of the thigh. * **Reactions:** Fever and mild local reactions following DPT immunization are common. It is estimated that 2 to 6 per cent of vaccinees develop fever of 39 deg. C or higher, and that 5 to 10 per cent experience swelling and induration or pain lasting more than 48 hours. * **The most severe complications following DPT immunization are neurological (encephalitis/encephalopathy, prolonged convulsions, infantile spasms and Reye's syndrome) and are thought to be due primarily to the pertussis component of the vaccine the estimated risk is 1:170,000 doses administered.** * **Contraindications:** Minor illnesses such as cough, cold, mild fever are not considered contraindications to vaccination, only such children who are seriously ill or need hospitalization are not vaccinated. DPT should not be repeated if a severe reaction occurred after a previous dose. Such reactions include collapse or shock-like state, persistent screaming episodes, temperature above 40 deg.C, convulsions, other neurological symptoms and anaphylactic reactions. In the case of DPT, subsequent immunization with DT only is recommended, without the pertussis component. Local reactions at the site of injection or mild fever do not by themselves preclude the further use of DPT. * **Since the severity of pertussis infection decreases with age, the pertussis component in DPT vaccine is not usually recommended after the age of 6 years (1). Therefore, children over the age of 5 years who have not received DPT, need only 2 doses of DT vaccine, 4 weeks apart, with a booster dose 6 months to 1 year later. Those children who received the primary course of DPT earlier, should receive only DT as booster at 5-6 years or at school entry.** 2. **Pentavalent Vaccine** * Pentavalent vaccine provides protection to a child from 5 life threatening diseases - diphtheria, pertussis, tetanus, hepatitis B and haemophilus influenzae type b (Hib). * Giving pentavalent vaccine reduces the number of pricks to a child. * When used, it replaces Hepatitis B and DPT primary vaccination schedule at 6, 10 and 14 weeks in the immunization programme, except that the birth dose of hepatitis B and booster doses of DPT are continued. * The UIP pentavalent vaccine comes in liquid form in a vial. * Each dose (0.5 ml) is given by intramuscular injection in anterolateral aspect of the mid-thigh, using auto-disabled syringe. * Pentavalent vaccine is a freeze sensitive vaccine and should be stored and transported at 2-8°C temperature. * Pentavalent vaccine is very safe. * As with all medicines, a few side effects are possible. * Pain, redness and swelling at the site of injection, fever, vomiting, loss of appetite, abnormal crying, irritability are the common side effects. * The rare side effects are high fever (more than 39.5°C) and fits or seizures, and very rarely severe allergic reaction can occur. 3. **Single Vaccines** * Single vaccines (e.g., FT, PTAP, APT, PTAH) are less frequently used. * They are all good immunizing agents. * APT is hardly used because it is prone to give rise to serious reactions. Each dose of these antigens generally contains 25 Loeffler (Lf) units of diphtheria toxoid. 4. **Antisera** * Diphtheria antitoxin prepared in horse serum is still the mainstay of passive prophylaxis and also for treatment of diphtheria. * It has been shown, protection against diphtheria toxin is a quantitative phenomenon, so that a serum antitoxin titre that protects against a small dose of toxin may not protect against a large dose; for this reason, failures of diphtheria immunization may take place (14).