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Epidemiological characteristic and prevention of airborne infectious diseases General epidemiological characteristic. Actuality of airborne infections in the republic. Epidemiological and socialeconomical impact of airborne infections in the Republic of Moldova. Spreading Table 1 Incidence of airborne infections in the Republic of Moldova (2005) Nosologcal form Influenza and acute viral respiratory infections Tuberculosis Diphtheria Pertussis Measles Rubella Mumps Meningococcal infection Chicken-pox Scarlet fever Total Incidence Number of reported Cases per 100000 cases population 186821 5178,2 3674 14 5 13 283 62 8071 196 199139 101,8 0,4 0,1 0,4 7,8 1,74 233,7 5,4 5529,5 In the structure of morbidity caused by airborne infections in Moldova (2005), 93,8 % amount to flue and viral acute respiratory infections. The rate of morbidity caused by airborne infection in the structure of general morbidity caused by infectious diseases registered in Moldova in 2005 was 74,1 %, or those 9 of airborne infectious diseases out of total number of 34 infectious diseases registered in 2005 amount to 74,1% of all cases of registered infectious diseases. The social-economic impact - Level of incidence - Economical prejudice direct expenses for treatment expenses for realization of antiepidemic and preventing measures number of lost working days expenses from social fund - Severity chronicising complications disability lethality - attitude of the public administration bodies, population, mass-media to infections diseases - international importance of infectious diseases General epidemiological characteristic of airborne infections - aerogenic mechanism of spreading which is realized in 2 ways: with liquid aerosols. Liquid particles containing pathogenic agents are eliminated from the respiratory tract secret of ill persons (carriers of pathogenic agents) during speaking, coughing, sneezing) in the air and through it are spread and reaching the respiratory ways of healthy people with the inspired contaminated air. This way is typical for spreading of airborne infections whose pathogenic agents are not resistant in the environment (temperature, dryness) – measles, rubella, mumps, influenza, chicken-pox, pertussis. With solid aerosols. The liquid particles with pathogenic agents suspended in the air after a certain period of time depending on their size, temperature, humidity, and the speed of the air are dried and are transformed in solid particles that get into the airways of healthy people similarly with the liquid particles. This way is typical for spreading the airborne infections by pathogenic agents resistant in the environment – tuberculosis, diphtheria, smallpox. - Level of incidence of airborne infections (intensity of spreading) is determined by the protective level of population immunity. Circulation of the pathogenic agent in an immune population leads to reduction of their virulence and absence of cases of illness (states of carriers of pathogenic agents can be formed in some persons). On the contrary, circulation of pathogenic agents within a nonimmune (receptive) population leads to increasing of the pathogenic agent virulence and registration of multiple cases of manifested illness. - Ununiform receptivity of population (nonimmune) to different airborne infections. Receptivity of population to an infectious disease is determined by the index of receptivity (contagiousness) which represents theproportion between the number of ill persons and the number of receptive persons exposed to the risk of getting ill (had a contact with the source of infection). Depending on the index of receptivity (contagiousness) the airborne infections can be divided in 4 groups: – Infections with absolute receptivity, index of contagiousness is 100% (measles, chicken-pox, smallpox). The clinical manifestation of the disease is, as usual, pronounced. States of carriers are not registered. – Infections with high receptivity, index of contagiousness is 50-70% (flu, mumps, pertussis, rubella). Manifested, non-manifested clinical forms are registered, and can be states of carriers. 2 - Infections with moderate receptivity, index of contagiousness is 15-40% (diphtheria, scarlet fever). Manifested, non-manifested clinical forms are registered. The main role as the source of infection have the carriers of pathogenic agents. - Infections with very low receptivity, the index of contagiousness is smaller than 1%. More frequent non-manifested forms and states of carriers of pathogenic agents are registered (meningococcal infection). - Periodicity (cyclicity)of epidemic process – the multianual incidence by airborne infections has a cyclic character, caused by the characteristic of population susceptibility that is the regulating factor of epidemic process manifestation. Before implementing the immunization of population the periodicity of incidence in diphtheria, measles, pertussis, mumps, was 3-6 years. Now the cyclicity changed both in the level of incidence and the duration between cycles, and in regard with liquidation of the morbidity or registration of single cases of illness – this peculiarity in vaccine preventable diseases vaccination is not manifested. - Autumn-winter (diphtheria) or winter-spring (influenza) seasonality caused by decreasing the local resistance of the mucous membrane of the respiratory system organs, being indoors for a longer time and more intensive realization of transmission mechanism. - increased incidence through airborne infections in groups of population with high epidemiologic risk of contamination (in children medium). Contamination in the first months (years) of life of receptive childrenresulted in illness and forming of long term postinfectious immunity. In airborne infections preventable by vaccination this peculiarity has changed – cases of illness are registered also in adult population (diphtheria, measles, rubella), bat in nonpreventable diseasesthe peculiarity remained until now (chicken-pox, scarlet fever, meningococcal infection). - In combating the with airborne infection the main role belongs to immunoprophylaxis. Out of 10 infections included in NPI, 7 are airborne – TB, Diphtheria, Pertussis, Measles, Rubella, Mumps and Hib. Airborne infections controlled by immunoprophylaxis are called “Vaccine preventable infections”. - in the group of airborne infections there are emergent diseases (registered for the first time during the last 5 years) – severe acute respiratory syndrome, avian flu with flu virus A (H5N1) and re-emergent – TB, diphtheria epidemic outbreak of diphtheria in Moldova in 1994-1996 in Moldova and in the new independent states and increasing of incidence by TB in 2005 5 times in comparison with the level of incidence at the end of eighties of the last century. - according to the epidemiological classification depending on the source of pathogenic agents, the airborne infections are included into the group of anthroponoses. For this group of infections the medium of maintaining of pathogenic agents as a biological species is the human population. In the medium of human population the airborne infections are spread from one person to another, causing the appearance of epidemics, epidemic outbreaks, pandemies 3 Diphtheria An acute infectious disease caused by C.Difteriae, manifested by membranous inflammation (diphtheric membranes) of uppe respiratory tract (usually pharynx, but can affect palatine tonsils, nasal cavity, larynx, trachea), and affecting other organs including myocardium, nervous system, kidneys (by microbial exotoxins). Epidemiologic characteristic of pathogenic agent. Heterogenic population: - 3 biological types (depending on the morphological, cultural and fermentative properties) containing about 70 serovariants gravis mitis intermedius - depending on the capacity to produce the exotoxin all types of corinebacteria are divided in two groups toxicogenic: (all biotypes produce the same exotoxin. The toxicogenity is a genetically stabile property determined by the presence of the tox + genes integrated into the corinebacteriua genome). The exotoxin treated with 0,30,4% solution of formalin and maintained at a temperature of +38-400C during 14 days in a thermostat loses its toxic properties, but keeps its immunogenic properties. Thus a new preparation is obtained – toxoid (anatoxin), used for the immunoprophylaxis of diphtheria. atoxigenic microorganisms not containing tox+ genes don’t produce exotoxin and don’t cause a disease. - pathogenic agents of diphtheria are resistant to the action of different environmental factors: in milk, water – 20 days under sunrays resist several hours in the temperature of +600 resist 10 minutes are resistant to dryness (airborne mechanism of transmission can be realized both with liquid and solid aerosols) are sensitive to the action of disinfectant solutions in usual concentration. are sensitive to the action of antibiotics ( erythromycin, tetracycline used for treatment of patients and sanation of corinebacteria carriers). Mechanism of epidemic process developing - source of pathogenic agents diseased person – from the epidemiologic point of view, diseased persons with mild, atypical clinical forms presents a bigger risk for spreading the diphtheria. At this patients as a rule the diagnosis is establish with delay that leads to complications. The diseased person eliminates pathogenic agents in the last 2-3 days of the incubation periods and in the period of clinical manifestation. Carriers of corinebacteria 4 cases per 100000 population reconvalescent healthy (of toxicogenic corinebacteria) Duration of the state of carriers can up be to several months (90 days), in medium – 20-30days. - Mechanism of transmission. Clinico-epidemiological forms of diphtheria with liquid and solid aerosols (airborne, main) by food products (water, milk) very rarely by contact with objects contaminated with pathogenic agents (underwear, dishes, books, toys, etc.). Extrabuccal forms are developed; skin diphtheria, diphtheria of mucous membranes of eyes, genital organs. - Receptivity of population. In the natural conditions the index of receptivity (contagiousness) as a rule doesn’t exceed 40%. After disease long term antitoxic and antibacterial typospecific immunity is developed. - Manifestations of epidemic process (there are 2 forms – morbidity and cases of carrier) - Level of incidence of diphtheria correlates with the level of population immunity. Diphtheria is included in the Extended Global Program of Immunization and in NPI of over 200 countries of the world. In most of the countries the incidence has now a sporadic character. In the prevaccinal period diphtheria has a global spreading with a lethality of 10-15%, with increases of incidence once in 6-10 years. In the Republic of Moldova in prevaccinal period the average index of morbidity was 22 cases at 100 thousand of population (fig. 1 ). 45.00 40.00 35.00 30.00 25.00 20.00 15.00 10.00 5.00 2004 2001 1998 1995 1992 1989 1986 1983 1980 1977 1974 1971 1968 1965 1962 1959 1956 1953 1950 1947 1944 0.00 Fig.1. Incidence by diphtheria in the Republic of Moldova, 1994-2005 In the fifties of the last century in our republic the planned immunoprophylaxis started and the level of incidence began to degrease dramatically up to sporadic cases. After a favorable epidemiologic period of over 20 years (1968-1990) when on average 3 cases per year were registered, at the beginning of nineties the 5 incidence began to grow up, manifested in an epidemic spreading. Thus in 19941996 in the republic a epidemic of diphtheria was registered with 888 cases of illness, 46 patients (5,2%) died (fig. 2). cases per 100000 population 12.00 10.00 8.00 6.00 4.00 2.00 2003 2001 1999 1997 1995 1993 1991 1989 1987 1985 1983 1981 1979 0.00 Fig. 2 Epidemic outbreak of diphtheria in Moldova in 1994-1996 450 400 350 300 250 200 150 100 50 0 80 60 40 20 0 Nr. of cases of illness 100 19 90 19 91 19 92 19 93 19 94 19 95 19 96 19 97 19 98 19 99 20 00 20 01 20 02 20 03 20 04 20 05 coverage with vaccination The epidemics started as a result of deficiencies in immunoprophylaxis due to insufficient assurance with vaccines in the previous years (that caused the decrease of the index of coverage with vaccination in 1990-1993 up to 70%, Fig.3), DTP3 Diphtheria Fig. 3 Coverage with vaccination and morbidity by diphtheria in 1990-2005 implementation of imperfect schemes of vaccination, especially for children under one year – using for primary vaccination of children with some relative contraindications of DTP-M vaccine which in many cases doesn’t lead to forming a protective immunity but vice versa, leaded to accumulation of persons with non6 protective immunity. The epidemic spread of diphtheria in the republic was also conditioned by the influence of diphtheria outbreaks in Russia and Ukraine. Re-emergency of diphtheria in the republics of the former USSR and in some European countries, according to WHO conclusions, was conditioned by the unsatisfactory coverage with vaccination of children and other target groups of population. Factors that favoured the re-emergency: intensive migration of population delayed diagnosing (reduced attention of physicians and population) absence of reserves of antidiphtheric serum and antibiotics for treatment and sanitation of carriers of corinebacterria. Autumn-winter seasonality, a higher level of incidence in children age group and other peculiarities of incidence characteristic for epidemic spread are not registered now. State of carrier of toxicogenic corinebacteria at immune persons is another form of manifestation of epidemic process, being especially actual in the period of registering sporadic cases of disease. Incidence of states of immune carrier of toxicogenic corinebacteria correlates with morbidity by diphtheria (tab.2). With reducing the number of cases of disease, the frequency of registering of states of healthy carriers of toxicogenic corinebacteria is decreasing. Table 2 Correlation between the cases of illness and states of healthy carriers of diphtheric corinebacteria in the republic in 1990-2005 Period of time 1991-1993 1994-1996 1997-2000 2001-2005 Number of cases of diphtheria Number of cases of healthy carrier of toxicogenic corinebacteria Correlation of cases of illness/states of carriers 71 888 78 6 192 1319 88 3 1 : 2,7 1: 1,5 1:1,1 1: 0,5 This peculiarity contributes to maintaining of the favorable epidemiological situation and further reduction of the risk of diphtheria spreading. At the same time the existent measures of control of diphtheria don’t allow to put the task of eradication of diphtheria (maximal realization is liquidation of incidence). In spreading of diphtheria in the republic in 1991-2005 the following manifestations of epidemic process can be outlined: - aggravition of epidemic situation(1991-1993); - epidemic spread (1994-1996); - postepidemic decrease of incidence (1997-2000); 7 - stabilizing of incidence at the most reduced level – single annual cases or absence of cases (2001-2005). Antiepidemic measures. - Early detecting of cases of diphtheria and urgent information about each case of disease and state of carrier of toxicogenic corinebacteria. Early detecting and confirmation of cases by laboratory investigation with the purpose of: diagnosing (at persons with suspected diagnoses of diphtheria according to the definition of standard case). epidemiological indication (examination of persons who were in a contact with people with diphtheria or carriers of toxicogenic corinebacteria). preventing (some groups of population with high epidemiologic risk of spreading are examined – children before admitting to kindergartens, schools, orphanages, summer camps; patients of psychiatric hospitals, etc.). - Hospitalization of patients with suspicious diagnosis of diphtheria and carriers of toxicogenic corinebacteria is mandatory. Treatment with antitoxic serum and antibiotics as soon as possible after the beginning of the disease. - Dismissal of patient (carrier) after 3 negative bacteriological examinations. - Measures of liquidation of the focus of diphtheric infection: terminal disinfection with 1-2% solution of chloramine and disinfection in drying stove. medical supervision of people from the focus during 7 days including thermometry twice per day, consulting by ENT specialist once in three days. In case of an epidemic spread of diphtheria, an additional immunization of population is organized. Criteria of vaccination according to the epidemiological indications (companies of immunization) are: high rate of toxic forms at patients with diphtheria (15%) registering lethal cases among the vaccinated children insufficient level of coverage of population with vaccination (70%). Preventing the diphtheria includes: Immunization of target groups of population according to NPI (schedule of vaccination) coverage with vaccine of 95% minimum with 4 doses of DTP of children up to the age of 3 years coverage with vaccines of 95% minimum with diphthero-tetanic vaccines of target groups of children and adults. The main role in carrying out these activities belongs to the medical personnel of the primary health care system. 8 Measles Is an acute infectious disease characterized by fever, cough, conjunctivitis, rhinitis, maculo-papulous skin eruption and specific enanthema (Koplik spots) Complications of measles – are registered in 30% cases of illness more frequent in children under 5 years and adults (20 years and older). Diarrhea (8%) otitis media (7%) pneumonia (6%) encephalitis (0,1%) with a lethality of 15% and different residual neurological manifestations – 25% epileptic seizure (0,6-0,7% with or without fever) death (1-2 cases per 1000 patients with higher risk at children older than 5 years and adults. In 60% of cases the death is caused by pneumonia); subacute sclerosing panencephalitis (is a rare incurable complication of the CNS that is supposed to develop due to a long persistence of the measles virus in the brain on average after 7 years or more after the disease). Complications are more frequent registered in patients with chronic diseases, malnutrition. Epidemiological characteristic of pathogenic agent The measles virus is a paramyxovirus, gene Morbillvirus. It was isolated in the culture by J.Enders and T.Peebles in 1954 in the cell culture of monkey kidneys and human embryos. - stable antigenic structure (one serotype) - sensitive to the action of environmental factors dryness light (is inactivated in 8-10 minutes) temperature (resists at t0 370C up to 2 hours and at 560C – up to 30 minutes) acid medium (pH – 2,0-4,0) Mechanism of epidemic process development - source of pathogenic agents ill person – eliminates pathogenic agents in the last days of the period of incubation, prodrome (catarrhal) period and period of appearance of skin eruptions. Mechanism of transmission – with liquid aerosols Receptivity of population – absolute. Non-vaccinated persons and without immunity after a contact with a ill person are getting ill in 100% of cases independent of age. Manifestations of epidemic process 9 - Incidence. Despite the decrease of the level of incidence by measles in most countries of the world and even elimination of measles in USA, Canada, some countries of Western Europe, this disease remains at the global level one of the main causes of children death. In the European region in 2004 about 30 thousand cases of measles were registered, and in 2005 – 27 thousand. In the last 15 years in the European Region the number of registered cases of measles decreased considerably and its reporting was improved (tab.2). Table 2 Number of registered cases of measles and the reporting in different zones of European Region to WHO in 1991 and 2001 Zones Number of cases Western Europe 229447 Central and 31585 Eastern Europe New independent 43122 states (NIS) Total 304184 1991 2001 % of countries Number of % of countries that reported cases that reported 83 16575 96 100 30782 94 100 20402 100 92 67759 96 2004 2000 1996 1992 1988 1984 1980 1976 1972 1968 1964 1960 1956 1952 1948 1600 1400 1200 1000 800 600 400 200 0 1944 cases per 100000 population Incidence by measles in the Republic of Moldova in prevaccinal period was maintaining at a high level (560-1400 cases at 100 thousand population) with a periodicity of 2-3 years (fig. 4). Fig.4. Multiannual incidence by measles in the Republic of Moldova 1950-2005 10 After implementing the immunoprophylaxis of measles the character of incidence has changed: decreased the level of incidence beginning with the sixties and the duration of cycle increased, especially in the last years. A peculiarity of multianual incidence by measles is the higher level in the children medium, but in the year of epidemic increase of morbidity a slight increase of morbidity in the adult population is manifested too (fig.5). cases per 100000 population 1200.00 1000.00 800.00 600.00 400.00 200.00 2005 2003 2001 1999 1997 1995 1993 1991 1989 1987 1985 1983 1981 1979 0.00 Fig.5. Multiannual incidence by measles in children and adults in the Republic of Moldova 1979-2005 In 2002, when the last increase of incidence was registered, the adult population (including children older than 14 years) was more affected than in previous periodical increases. This peculiarity can be probably explained by the reduced level of incidence in 1996-2005 and accumulation of receptive population (children, adults) that favourised the epidemic spread of measles in 2002. Totally during the epidemics of measles in 2002 were registered 4928 cases of measles as epidemic outbreaks in schools, institutions of higher education, colleges and other collectives. From collectives the infection was spread in families that favourised the illness of over 160 children under 1 year who didn’t reach the eligible age of vaccination. In the period of increasing of the level of incidence was characteristic the winter-spring seasonality although deviations in May-June were registered. Nosocomial cases of measles were also registered. The results of analysis of incidence in the last years, WHO recommendations, were widely used for collaboration and implementation of new strategies for combating of measles in Moldova. 11 Antiepidemic measures - early diagnosing and hospitalization of patients; - urgent information of territorial CPM; - active detecting of ill persons in the focus; - evaluation of the state of immunization of population in localities where cases of illness were registered; - medical surveillance of people from the focus (who had a contact with the ill person) during 21 days: examining the airways mucous membranes conjunctiva teguments palpation of lymphatic ganglions focus visiting by the medical worker once in 3-4 days; administrating an additional dose of vaccine in 72 hours after detecting the patient to persons that had a direct contact with the patient (younger than 20 years, don’t have a measles history, or it is impossible to establish if they had measles , were not vaccinated or the dates of vaccination can’t be established, or received a single dose of vaccine more than 6 months ago) Vaccination of contacting persons in the focus is indicated beginning with the age of 10 months Administering normal human immunoglobulin in the first 5 days of contact to persons who have contraindications for vaccination (information about vaccination and administering the immunoglobulin should be written in the medical documents of vaccination evidence). - Establishing the borders of the focus and persons who had contacts with the ill person (will be done taking into consideration the difficulty of establishing preventive diagnosis of measles, airborne way of transmission by aerosols with a high degree of dispersing at a relatively big distance, high receptivity of non-immune persons. Thus the borders of the focus depending on the particular situation will comprise the family, block, house, institution, enterprise, and even some rural localities as a whole). - In collectives with a high degree of contact and risk of spreading of measles during 21 days after isolating the last patient, new persons who didn’t have measles or are not vaccinated against measles are not admitted. - In collectives with a high spreading risk of measles (institutions of education, sanatoriums, summer camps, army, etc.) persons younger than 35 years are not admitted without medical documents where information about vaccination against measles is included. - Antiepidemic measures in the measles focuses are done by the medical personnel of the primary health care institutions and the medical personnel of the respective collective. 12 Measles prevention In the Republic of Moldova the prevention of measles now is done in accordance with the Global Strategic Program of measles prevention approved by the WHO in 2001. The goal of the Global Strategic Program is liquidation of measles. In accordance with the Global Program, the European Bureau of the WHO defined the strategic goal of the measles prevention program in the countries members of WHO of the European region – Interrupting the epidemic transmission (spread) of measles in the European region (eliminating the measles from the European region) This activity in the Republic of Moldova is done according to the National Plan of eliminating the measles, combating the rubella and mumps, preventing the congenital rubella for 2002-2007 years. Carrying out the activities foreseen by the National plan has the goal creating of a immune protective layer among the whole population (not only children). Beginning with January 2002 in our republic the vaccine MMR is used and the vaccination against this infection is done with two doses (at 12 months and 6-7 years) according to the NPI for the years 2001-2005. (For a long time in the Republic of Moldova one dose of mono-vaccine was used for anti-measles vaccination in comparison with the European countries and NIS, where 2 doses were used). The company of immunization against measles (and rubella) started in November 2002 and was carried out in two steps: - The first step with the duration of 2 weeks foreseen the immunization of persons of the age of 7-22 with the vaccine MR. - The second step with the duration of 3 months immediately after the first step foreseen immunization of women of the age of 23-29 with a rubella vaccine. Objectives of the company: Assuring the coverage with the vaccine MR of persons of the age of 7-19 years at a 98% level. Assuring the coverage with the vaccine MR of persons of the age of 20-22 years at a 90% level. Assuring the coverage with the vaccine MR of persons of the age of 23-29 years at a 90% level. In general lines the strategy of eliminating the measles is based on: - vaccine coverage of children over 95% with two doses (at the age of 12 months and 6-7 years); - setting up and functioning of an efficient surveillance and control system (implementing the standard case definition for a complete detection of the infection) and strict antiepidemic measures in the focus (enumerated before). Indexes of qualitative epidemiologic surveillance of measles for carrying out the program of measles elimination. 13 Rate of incidence by measles beginning with 2009 1 confirmed case at 1000000 population. Rate of registration of suspected cases of measles 2 cases at 100000 population at the national level and 1 case at 100000 population at the level of administrative territory. Laboratory confirmation – carrying out laboratory examinations of adequate blood samples in 80% of suspected cases. (The adequate blood sample is the blood sample collected in the period of 4-28 days after appearing of eruptions, in the volume of 3-5 ml, with the serum collected separately (without hemolysis) stored and transported at a cool temperature, noncontaminated and accompanied by the approved statistical form. Transportation of 80% of samples for examination to the territorial CPM in the day of collecting. Transportation of 80% of samples for examination to the NSPCPM (reference laboratory) in the first 24 hours after their arrival to the CPM laboratory. Registration of 80% of samples registered at NSPCPM in 24 hours after the day f their arrival to the laboratory. Final classification of suspect cases of measles in the first 60 days after eruptions appearing (after 60 days this indicator should be zero). Determining the possible place of contamination in 80% of confirmed cases of measles (classification of case in: imported case, case epidemiologically linked with an imported case, case with local contamination, etc.). Presenting monthly reports to the NSPCPM in time 80% (before the date of 5 of the next month the CPM will present a month report – form nr.2). Presenting - before the date of 25 of the next month by the NSPCPM to the ERB WHO a month report 80% . Epidemiological investigation of the suspect cases of measles in the first 24 hours after registering the urgent information 80% of focuses. Investigation of epidemic outbreaks of measles (5 and more cases epidemiologically linked) with laboratory examination of not less than 5 patients 90% of outbreaks. 14