Measles virus

MEASLES VIRUS

Table of contents :

Epidemiology

Genomics

Laboratory examinations

Prevention

Web resources

Epidemiology : epidemics every 2-3 yrs. at late Winter; usually within age 15; 2002 incidence : 30 millions. Deaths :

2002 : 800,000 deaths, predominantly African infants (at least 500,000 could be saved by vaccination). It kills 2,000 children every day around the world because of a lack of immunization against the disease.
2003 : 530,000 deaths

Africa : 252,000 (48%)
Southeast Asia : 182,000 (34%)
Eastern Mediterranean : 69,000 (13%)
Western Pacific : 22,000 (4%)
Europe : 5,000 (1%)
Americas : 0 (0%)

Deaths from the contagious disease which can be prevented by vaccination have already fallen by 39% since 1999 (873,000 deaths) to 2003 (530,000 deaths), though 2004 figures are not in yet. The world is "on target" to halve global deaths from measles by the end of 2005. Only a decade ago, measles killed millions of children each year, and left many with life-long disabilities such as blindness and brain damage. Africa remains the hardest-hit continent, but even there, the number of cases has fallen 46% due to mass vaccinations. WHO and UN campaign is targeting 45 countries, mostly in sub-Saharan African and south Asia, where measles immunisation coverage averages only 60%. The focus now is to increase support to the large priority countries -- Nigeria, India and Pakistan. About 50% of all measles deaths last year occurred in the 3 countries. Nigeria, India and Pakistan -- where the crippling polio virus is also taking a toll despite a global eradication campaign -- lack strong health care systems and routine vaccine coverage. The likely next goal would be to reduce mortality by 90% by 2010, compared with 1999. It costs around 25 cents to immunize a youngster. Because this is beyond the budget of many poor countries, they have been helped by the U.N. campaign. The campaign aims to ensure 90% of children are immunized before they are 9 months old, with booster vaccinations every three or four years until age 14. The program has reached >150 million children since it was launched in 2001. Late in 2004, > 95% of children in the African nation of Togo received vaccines to prevent measles and polio, mosquito nets to stop the spread of malaria, and tablets against worms. Despite the advances, millions of children remain at risk from measles. Malnourished and unimmunized children under age 5, especially babies, are particularly vulnerable. The number of measles deaths worldwide fell from an
estimated 873 000 (uncertainty bounds 634 000 to 1 140 000) in 1999 to 345 000 (247 000 to 458 000) in 2005 (60% fall)^ref. This figure surpasses the target set by the UN in 2002 to reduce deaths due to measles by half in this period. The Measles Initiative, launched in 2001, is focusing on 4 key strategies:

providing one dose of measles vaccine to all infants via routine health services;
a second opportunity for measles immunisation for all children, generally through mass vaccination campaigns;
effective surveillance for measles; and
enhanced care, including the provision of supplemental vitamin A.

As a result of these measures, measles immunisation coverage with the 1st routine dose increased from 71 to 77% globally between 1999 and 2005, and over 360 million children aged between 9 months and 15 years received measles vaccines through immunisation campaigns. The largest percentage reduction in estimated measles mortality between 1999 and 2005 was in the western Pacific region (81%), followed by Africa (75%) and the eastern Mediterranean region (62%). Africa achieved the largest total reduction; 72% of the global reduction in measles mortality. Nearly 7.5 million deaths from measles were prevented through immunisation in this period, with the Measles Initiative's activities and improved routine immunisation accounting for 2.3 million of these prevented deaths^ref. The Measles Initiative has now set a new target: to cut measles deaths to 90% of the level they were in 2000 by 2010, primarily through ensuring children receive a second dose of measles vaccine shortly after the first. The WHO Regional Office for Europe has targeted measles for elimination from the 52 member states of the WHO European Region by 2010. Over 29 000 measles cases from the region were reported to the WHO in 2004, and the WHO has estimated that 4850 measles deaths may have occurred in the region in 2003^ref. The Measles Initiative will now target India, Indonesia, Pakistan and other large countries who have yet to increase routine coverage and address susceptible adults through mass vaccination campaigns more aggressively, in the hope of making further progress in the worldwide target of mortality reduction^ref.

Africa contains 95% of the victims : In 1999, of approximately 871,000 deaths from measles worldwide, 61% occurred in sub-Saharan Africa^ref. In 2001, countries in the WHO African Region began an accelerated measles-control program to reduce by half by 2005 the number of deaths that were caused by measles in 1999^ref. According to these estimates, coverage with 1 dose of measles vaccine in the African Region among children aged 12-23 months increased from 52% in 1999 to 67% in 2004. In 2004, 37 of the region's 46 countries were estimated to have coverage rates >60%, and 17 countries were estimated to have coverage rates >80%^ref. By 2000, 7 countries in the African Region had completed national catch-up SIAs, and during the period December 2001 to December 2004, 25 additional countries completed national catch-up SIAs. Ten of these 32 completed national follow-up SIAs. Measles vaccination coverage rates during these SIAs were >90%, except for the catch-up SIAs in Republic of the Congo (78%), Eritrea (82%), Ethiopia (87%), and Gabon (80%) and the follow-up SIAs in Lesotho (75%), Swaziland (81%), and Zimbabwe (85%). By December 2004, a total of 207.9 million children in 32 countries had been targeted by catch-up SIAs, which is 69% of the population of children aged <15 years in the African Region. During the same period, 16.1 million children aged 9 to 59 months in 10 countries were targeted by follow-up SIAs, which represents 14 percent of the population of children aged <5 years in the African Region. The quality indicators used for the case-based surveillance system include the proportion of reported cases with a blood specimen (goal: 80 percent of cases not confirmed by epidemiologic linkage) and the proportion of districts reporting at least one suspected case with a blood specimen per year (goal: 80 percent). For Niger and Tanzania, the total number of cases with a blood specimen was <80% of the aggregate case total, so aggregate case totals were used for analysis. For all other countries, blood specimens were obtained for >90% of reported cases. The increase from 2988 cases in 1999 to 3626 cases in 2005 from countries in Group A is largely a result of the increase in cases reported from South Africa. For example, in 2000, South Africa reported 117 confirmed measles cases^ref, compared with 609 in 2005. During the period 2003 to 2005, South Africa experienced a large, nationwide measles outbreak involving 1676 confirmed cases, the result of measles importation from Mozambique and failure to vaccinate enough of the population to prevent endemic measles transmission. By December 2005, approximately 87% of the population aged <15 years (267.2 million children) in the countries in the African Region had been targeted by catch-up SIAs. In 2006, nationwide catch-up SIAs are focusing on the areas that have not yet been covered, including 29 million children in southern Nigeria and 7 million children in the Democratic Republic of the Congo. Successful control of measles in the African Region will depend on conducting high-quality campaigns (i.e., campaigns that achieve >95 percent coverage) in these areas. At the same time, countries should continue to improve their routine immunization services, maintain high coverage with follow-up SIAs every 4-5 years, improve measles case management, and monitor their success by using case-based surveillance with laboratory confirmation to control measles and reach the global goal of reducing measles mortality^ref.

Chad : an epidemic in 2005 caused 115 deaths with > 6000 reported cases nationwide -- of which > 3400 are in N'Djamena. From January until April 2005, the capital city reported as many cases as for the entire year 2004. Moreover, the total number of individuals now infected is likely to be 2-3 times higher than the reported figure. In the paediatric ward of some hospitals, 50% of the death toll is due to measles in April.
Democratic Republic of Congo^ref: up to 800 cases (including 3 deaths) of measles have been reported in Basankusu, 210 km north east of Mbandaka, the main town in the province of Equateur : < 80% of Basankusu's 100 000 residents were vaccinated against measles

Year / Vaccine coverage in infants < 1 year old / Cases reported
1974 / na / 57 774
1975 / na / 51 040
1977 / na / 43 451
1978 / na / 37 142
1979 / na / 29 497
1980 / 18% / 32 596
1981 / 23% / 38 142
1982 / 25% / 30 775
1983 / 30% / 21 057
1984 / 30% / 11 385
1985 / 40% / 19 508
1986 / 39% / 19 430
1987 / 41% / 14 666
1988 / 44% / 13 214
1989 / 41% / 11 178
1990 / 38% / 4564
1991 / 17% / na
1992 / 25% / na
1993 / 33% / 2749
1994 / 39% / 12 573
1995 / 27% / 5443
1996 / 21% / 9546
1997 / 20% / 5766
1998 / 20% / 15 271
1999 / 15% / 12 135
2000 / 46% / 8282
2001 / 37% / 8072
2002 / 45% / 30 466

Comoros Islands : some 1040 cases of measles have been reported on the 3 semi-autonomous islands since the epidemic was declared on 31 Jul 2005, 770 cases on the island of Anjouan alone. Comoros is formed by 3 of the 4 main islands in the Comoros Archipelago, which is situated in the Indian Ocean, between the African coast and Madagascar. The Union of the Comoros (until 2002 the Islamic Federal Republic of the Comoros) is a country in the Indian Ocean, situated at the northern end of the Mozambique Channel between northern Madagascar and northern Mozambique. The country consists principally of 3 volcanic islands: Grande Comore, Moheli and Anjouan, while the nearby island of Mayotte is claimed by Comoros but declined independence from France, the former colonial power in the region. Political turmoil, the neglect of health care services, and geography have left the Comoros vulnerable to the ravages of a disease successfully contained by vaccination elsewhere. The situation is reminiscent of the outbreak of measles in the Faroe Islands observed by Panum in 1846, which enabled him for the 1st time to deduce the length of the incubation period of the disease and to establish that those who recovered from the infection enjoyed life long immunity (see: Katz, M. In: Measles virus. Eds V ter Meulen and MA Billeter. Springer Verlag, 1995). The incidence in the current outbreak is extraordinarily high: 1651 per 100 000. The experts from WHO and UNICEF have been sent to the Islands for carrying out nationwide vaccinations against measles.
Kuwait : reported measles cases between 1990 and 2005^ref

1990 / 71
1991 / 165
1992 / 383
1993 / 260
1994 / 432
1995 / 12
1996 / 15
1997 / 26
1998 / 90
1999 / 13
2000 / 6
2001 / NA
2002 / NA
2003 / NA
2004 / 23
2005 / 10

Asia :

North Korea : according to the WHO website, there were no cases of measles reported in 1990, nor were there any cases reported during the period 2001 through 2005^ref; about 345 000 people, most of them children, died from measles in 2005. Vaccination coverages during this period were high (1990 / 98%; 2000 / 92%; 2001/ 92%; 2002 / 98%; 2003 / 95%; 2004 / 95%; and 2005/ 96%). These reported coverages are for single doses of measles vaccine and not for 2nd doses (most countries have adopted a 2-dose schedule for measles vaccination). Of note, when one reviews the full time series for estimated vaccination coverages, one can see years with extremely low reported coverages (less than 40 percent in 1997, 1998, and 1980 through 1984^ref)
Taiwan : the numbers of clinical cases of measles reported annually in Taiwan were: 1386 in 1988; 44 in 1990; 303 in 1992; 71 in 1993; 101 in 1994; 40 in 1995; 49 in 1996; 63 in 1997; 49 in 1998; 23 in 1999; 48 in 2000; 59 in 2003; 36 in 2004; 39 in 2005; 24 in 2006. Taiwan has undertaken the goal of measles elimination by 2010. The vaccination coverage of the cohort born in 2002 of 95% with MMR 1st dose. No information was available on 2nd dose coverages.
Japan : outbreak due to D5 strain in 2007^ref associated with documented measles in Japanese tourists visiting Canada and US tourists returnig from Japan^ref. During the period 1 Jan 2007 through 27 May 2007, there were a total of 1508 cases of measles reported through 2 sentinel reporting systems (pediatric sentinels and adult hospital sentinels). Of these, 1121 were < 15 years of age (74%). Overall, 426 (28%) were in the less than 5 year old population, the group that was most often involved in measles outbreaks in the pre-vaccine era. Of note is that overall, 387 cases (26%) were in the over 15 year old population, a group that does not routinely present to the health sector for "childhood" vaccinations. The observation that 91% of the adult cases (defined as over 15 years of age) were in those < 35 years of age, suggests that the susceptible population in Japan includes those individuals born later than 1972. (the musings of a former EPI -- Expanded Programme on Immunizations -- epidemiologist who enjoys the occasional number crunching). The D5 strain of measles virus had been endemic in Japan in the past. According to Riddell MA and colleagues^ref genotype D5 is endemic in Cambodia and has been associated with measles cases detected in the Americas, the UK, Germany and Australia. Epidemiological investigations have identified Japan and Thailand as the main sources for these importations. Until recently both genotype D3, and genotype D5 were endemic in Japan. However, recent evidence suggests that these genotypes may no longer be predominant in Japan. Of note in the above summary is the spread of the measles activity to northern parts of the country, with Hokkaido being the most northerly of the prefectures in Japan. Because there has been significant circulation of measles virus in schools (including universities), as the summer season approaches and school vacations begin, the risk of further geographic expansion (both within Japan as well as internationally) related to travelling infected students exists (as seen by the recent imported cases among a school group travelling to Canada). A 26-year-old Chinese woman living in Banciao, Taiwan, who has not been vaccinated against measles visited Japan with her Taiwanese husband in mid-May when she probably contracted the disease^ref

Americas : the ongoing effort to interrupt measles transmission began in late 1989 and was adopted as a regional goal in 1994. Beginning in 2003, all reported outbreaks of measles in the Americas have been importation related, including a major outbreak in Mexico that began in 2003 and continued through 2004^ref. (The major outbreak of measles in Venezuela in 2006 that has continued into 2007 was an importation related outbreak^ref). According to the Pan American Health Organization Measles and Rubella Bulletin, as of week 21 in the Americas region there have been a total of 43 cases of measles confirmed in the Americas region^ref. Of these 43 cases, 23 were in Venezuela, 7 were in Canada and 13 were in the USA. Of the cases where information on origin of the case was known, in the USA, 8 were classified as imported cases and 4 were classified as importation related cases; of the Canadian cases 4 were classified as imported cases and 2 were classified as unknown origin. Given the high amount of travel between Japan and the Americas region, one would not be surprised to learn of other instances of importations of measles into countries in the region now that

^ref

USA : before the measles vaccine was introduced in the 1960s, there were about 450 000 measles cases and an average of 450 measles deaths annually in the USA^ref1,
ref2. During 2001, an outbreak among children adopted internationally resulted in 14 US measles cases, 10 among adopted children and 4 among caregivers and siblings aged 28 months to 47 years. In March 2004 2 children were adopted from 2 orphanages in Hunan Province, China, and traveled to 5 US states (8 traveled to Washington, and one each traveled to Alaska, Florida, Maryland, and New York) : all 4 confirmed and 5 suspected cases of measles have been in children aged >12 months, for whom vaccination with measles-containing vaccine is recommended in both the US and China. Vaccination of internationally adopted children is not required before their immigration into the US, but should occur within 30 days of entry. Since 1994, rapid progress has been made in the elimination of measles from the Americas : the number of measles cases has declined >99%, from about 250 000 in 1990 to 105 confirmed cases reported in 6 countries in 2003. During 2003, only Mexico and the United States reported outbreaks. In 1999, autochthonous transmission in Mexico was interrupted after 3 consecutive years without virus transmission. The 3 chains of transmission in Mexico and 2 US outbreaks were import-related; a 3rd US outbreak was of unknown source. Since November 2002, no transmission of the D6 and D9 genotypes has been reported; these genotypes were responsible for several large outbreaks in the region during the period 1997-2002^ref. Because the region is under constant threat of measles importation from regions where the disease is endemic, countries will have to maintain high population immunity to measles and sensitive surveillance to ensure the timely detection of imported cases and allow for rapid implementation of control measures. The outbreak in the orphanage in China -- with importations of cases of measles to the USA, Spain, and Norway -- serves as a reminder of the presence of measles internationally and the need to adhere to vaccination schedules. In 2006 there were 60 cases in Iowa : of them at least 66% had had the recommended 2-shot vaccination, while 14% had received one dose. A mumps vaccine was introduced in 1967. Iowa law requires schoolchildren to be vaccinated. People born before 1957 are believed to have been exposed to mumps during childhood and therefore should be immune, according to the CDC. The last mumps outbreak in Iowa was in 1987, when 467 cases were recorded. Since then, < 60 cases have been reported annually, with only one to 3 cases reported in the past 5 years^ref. A measles outbreak in 2006 in Indiana in which 34 people became ill (the largest in the USA since 1996) was spread by an unvaccinated 17-year-old U.S. girl who visited Romania for less than 2 weeks, where she did missionary work at an orphanage. There were 66 confirmed cases of measles in the USA in 2005, with no deaths : 50 were unvaccinated and 17 were infected while traveling abroad. A smaller outbreak was traced to a 6-year-old visitor from Nigeria who was hospitalized in Ohio, and another limited outbreak occurred among people who had returned to Texas after a family reunion in Mexico. The 37 cases of measles in 2004 were the fewest ever recorded in the USA^ref1,
ref2.
Mexico : from January 1 to of 17 May 2004 the Mexican Secretariat of Health reported 64 cases of measles, all linked to an imported strain with origins in Asia. The cases have occurred in 5 areas: the Federal District and the states of Mexico, Hidalgo, Campeche, and Coahuila. Mexico reported only 44 cases of measles in 2003, no cases in 1997 and 1999, and few cases during intervening years. Most of the persons affected have been older than 15 years of age. The Mexican government has launched a vaccination campaign and enhanced surveillance in response to the situation. On 14 May 2004, the Mexican Secretariat of Health reported 2 cases of measles in Coahuila state across the border from Del Rio, Texas. In response to the 2 border cases, Texas Department of Health (TDH) issued a notice asking Texas doctors and others to be alert for possible cases of measles along the state's border with Mexico. The TDH notice recommends that persons visiting Mexico follow the standard ACIP recommendations for international travelers. Persons who travel or live abroad and who do not have acceptable evidence of immunity should be vaccinated with MMR (measles, mumps, and rubella vaccine). In general, people can be considered immune to measles if they have documentation of physician-diagnosed measles, laboratory evidence of measles immunity, or proof of receipt of 2 doses of live measles vaccine on or after their 1st birthday. Most people born before 1957 are likely to have had measles disease and generally are not considered susceptible. However, measles or MMR vaccine may be given to this group of people if there is reason to believe they might be susceptible. Children who travel or live abroad should be vaccinated at an earlier age than recommended for children remaining in the United States. Before their departure from the United States, children aged > 12 months should have received 2 doses of MMR vaccine separated by at least 28 days, with the 1st dose administered on or after the 1st birthday. Children aged 6-11 months should receive a dose of measles vaccine before departure. These children should be revaccinated with 2 doses of MMR, the 1st of which should be administered when the child is aged >12 months and the second at least 28 days later. Although vaccination against measles, mumps, or rubella is not a requirement for entry into any country (including the USA), U.S. residents traveling internationally to any destination or living abroad should ensure that they are immune to all 3 diseases. Measles is still common in many countries, including developed countries in Europe and Asia^{ref1,
ref2,
ref3,
ref4,
ref5,
ref6}.
Brazil : autochthonous transmission in Brazil was halted by vaccination in 2000. From 2001-2004 only 4 cases were recorded, all imported from Europe & Japan. A small outbreak in 2005 was initiated by a surfer returning infected from the Maldives. In 2006 47 people were affected in Bahia State^ref
transmission of the D6 measles virus genotype -- which began in 1995 and caused large outbreaks in Argentina, Bolivia, Brazil, the Dominican Republic, and Haiti -- was interrupted in September 2001. The subsequent transmission of the D9 measles virus genotype in Venezuela was interrupted in November 2002, 14 months after it had started. In 2006 12 cases were reported in Venezuela : the first measles case was reported in a 33 year old airline pilot from Miranda who traveled to Madrid in February 2006 and became ill on his return. The case was confirmed as measles in a private clinic and resulted in an outbreak among direct contacts of the patient, including 5 children under 14 years of age and 4 adults over 30 years old^ref

The World Health Organisation Regional Committee for Europe met in Bucharest, Romania on 12 to 15 Sep 2005 and issued the following statement. While immunization coverage levels vary widely from country to country, poor vaccination coverage is by no means limited to the less developed member states. In 2004, Austria, Belgium, Ireland, Italy, Switzerland, Turkey, and the United Kingdom reported measles coverage under 85% for the 1st dose of measles-containing vaccine (MCV1) (WHO target coverage rate is 95%). The statistics can also mask differences within countries, where vulnerable communities, minority groups and remote rural communities often lack access to immunization. From 17 to 23 Oct 2005, the WHO Regional Office for Europe is launching an awareness and advocacy campaign to put immunization back in the spotlight. 6 member states across the WHO European Region, namely Belarus, Ireland, Italy (South Tyrol region), Serbia and Montenegro, Tajikistan, and the former Yugoslav Republic of Macedonia, will launch the 1st European Immunization Week. The objective is to increase vaccination coverage by drawing attention to and increasing awareness of the importance of every child's need and right to be protected from vaccine-preventable diseases. The focus will be on activities to reach vulnerable groups. The number of member states of the EU reporting a measles incidence of less than one per million population (one criterion for measles elimination) has increased from 13 in 2001 to 27 (52%) in 2004. The number of measles cases reported has also declined by 92% over the last decade, but > 27 000 cases were still reported in 2004. Measles outbreaks have occurred during the last 4 years in at least 13 member states in western, central, and eastern parts of the Region. Almost 50% of imported measles cases within the European Union (EU) are from other EU countries. The region is also an important exporter of measles to the region of the Americas, with 37% of all measles cases imported into the USA between 1993 and 2001
Europe :

Greece : between 1 Sep 2005 and 12 Feb 2006, 171 cases of measles were reported, of which 53 (31%) have been laboratory confirmed (by detection of measles IgM), 99 (58%) are probable cases (clinical criteria according to case definition), and 19 (11%) are still awaiting laboratory confirmation. This is the first outbreak of measles in Greece since 1996. In 2006 some 150 measles cases have been recorded in the cities of Thessaloniki, Alexandroupoli and Xanthi, with 100 of them being admitted to Thessalonikiis hospital. In 2004 there was 1 case reported, no cases were reported in 2003, 5 cases in 2002, 12 cases in 2001, 56 cases in 2000, 69 cases in 1999, 66 cases in 1998, 136 cases in 1997 and 6082 cases in 1996 (information on numbers of cases of measles per year are available for 1980 through 2004). 94 patients (55%) belong to Roma (gypsy) families and 25 (15%) to immigrant families; 52 cases (30%) belong to the non-minority general population, most of whom (71%) are 15 years old or more. Of 110 patients with known vaccination status, 98 (89%) were unvaccinated for measles and 12 (11%) had received one dose of measles-containing vaccine. 8 cases made up 2 hospital clusters (4 cases in each). 103 patients (60%) were admitted to hospital, and 27 (16%) had complications (mainly pneumonia and bronchiolitis), all of whom have recovered. Measles vaccination was introduced in Greece in the early 1970s, when vaccines became commercially available, and vaccination at the age of 15 months was introduced in the national immunisation schedule in 1981; measles-mumps-rubella vaccine (MMR) was introduced in 1989. Vaccination with a second dose of MMR at the age of 11-12 years was introduced in the national immunisation schedule in 1991, and in 1999 this dose was shifted to 4-6 years^ref.

Ukraine : introduced measles vaccine in 1968 (using monovalent Leningrad strain) and a 2-dose schedule for measles was introduced in 1986. 1st-dose measles vaccine coverage has been reported > 90% since 1992, but until 2000, coverage was based on the proportion of children vaccinated among those due to be vaccinated during a given year. Implementation rates by territory ranging from < 20% to > 150% were due to frequent vaccine shortages followed by catch-up activities when vaccine became available. Mumps, measles and rubella (MMR) vaccine was introduced in 2000 as a 2-dose programme at 12-15 months and 6 years; however, monovalent measles vaccine continued to be used and coverage with MMR vaccine was low until 2003. During 2001-2002 about 25 000 cases and 14 deaths were reported. This outbreak affected western, southern and central regions, but 1/3 of regions reported relatively few cases. Over half the cases in this outbreak affected people aged 15 and over. Since Feb 2005 to the end of February 2006, 19 673 cases of measles had been reported : 17 281 (88%) occurred during January and February 2006. While 7415 (38%) of the total cases have been reported from Kyiv city (also known as Kiev) and Kyiv Oblast, where the outbreak appears to have started, all 27 administrative territories of the country are now reporting cases. All but 5 of these territories have reported at least 100 cases each^ref. Other sporadic cases of D6 genotype measles virus infection were observed at the same time in both adjacent and more remote countries and were considered to be imported cases: 2 cases in Belarus, 9 cases in the Russian Federation, 2 cases in the USA, 1 case in Spain, and 12 in Venezuela

UK : 77 cases in 2005, 72 cases in 2006 until March 23, 2006^ref. The number of cases in the Dumfries and Galloway measles outbreak has reached 21 as of 25 Apr 2006^ref. In the end-of-year report on measles activity in the UK for 2005, there was mention of a B3 genotype associated with measles activity in a "travelling community"^ref. The most recent HPA report on measles activity in the UK (23 Mar 2006) mentions involvement of the "travelling community", suggesting perhaps that the B3 genotype is involved in the 2006 activity as well^ref. A boy's death from the disease in April 2006 was the 1st UK fatality in 14 years. Surrey and Sussex could have up to 156 cases, and South Yorkshire may have 180. In 2005, there were just 77 cases across England and Wales^ref. The Health Protection Agency has received reports of 449 confirmed cases of measles in England and Wales to the end of May 2006. This compares to 438 cases for the whole of 2003 and will therefore represent the highest number of cases in one year since our current method of monitoring began in 1995. In the year that MMR vaccine was introduced there were just over 86 000 notifications of measles. Coverage among 2-year-olds in June 2005 was 83%, up from 78.9% in January 2003^ref. Trends in reported cases of measles in the UK can be found here^ref. In 2006, there were 736 confirmed cases of measles reported by the United Kingdom Health Protection Agency (HPA)^ref

Germany : 1 death in 2005. since 1 Jan to 3 May 2006, 1018 cases of measles have been reported in the federal state of Nordrhein-Westfalen caused by genotype D6 However, until now, no direct contact with any Ukrainian patients by the patients in Nordrhein-Westfalen has been established. Very recently, a 2nd genotype (D4) has been isolated from 2 patients. In contrast to previous outbreaks, when mostly small children were affected, half (49%) of the patients in this outbreak (n=323) are aged between 10 and 19 years, and 18% are patients aged over 20 years (n=116). Particularly efficient transmission has been noted in the Nordrhein region, where 56 cases of measles per 100 000 inhabitants have been reported in the city of Duisburg, 33 per 100 000 inhabitants in the district of Wesel and 53 per 100 000 inhabitants in the district of Monchengladbach^{ref1,
ref2,
ref3,ref4,
ref5}. 3 cities in that region, Cologne, Dortmund, and Gelsenkirchen, are hosting soccer games in the 2006 World Cup, and 6 of the 8 teams from the Americas are scheduled to play in those cities^ref. Measles outbreaks have also been reported in Denmark, Greece, Spain, Sweden and Ukraine^ref.
Poland : 11 cases (9 laboratory-confirmed) in 2004, 13 (1 laboratory-confirmed) in 2005, 60 (43 laboratory-confirmed) in 2006^ref. The 1st dose of monovalent measles vaccine for children aged 13-15 months was introduced in Poland in 1975. In 2003, the monovalent vaccine was replaced by measles, mumps and rubella (MMR) vaccine. A 2nd dose of measles vaccine at the age of 7 years was introduced in 1991. In 2005 MMR vaccine replaced the 2nd dose of monovalent vaccine, and was given at 10 years of age. No booster vaccination is routinely used. Immunisation coverage has been improving since 1991. The proportion of 3 year old children vaccinated with the 1st dose at country level increased from 93.5% in 1991 to 97.4% in 2004. The proportion of 8 year old children vaccinated with the 2nd dose at country level increased from 46.9% in 1991 to 95.6% in 2003. Immunisation coverage at regional level improved between 1991 and 2003, and has been maintained at a consistently high level since 1998^ref. Results from a serologic survey in 1998 indicated that young people aged 15 to 19 years were the most susceptible to measles infection. The incidence during an outbreak in 1998 (N=2255) confirmed these findings, and people aged 16-20 years were the group most affected by the disease^ref. It has been established^ref that measles cases from the outbreak in Ukraine have been imported into Belarus (2 cases), the Russian Federation (9 cases), Spain (1 case) and the United States (2 cases). Therefore it is likely that these cases in Poland originated also from importations from Ukraine. Measles virus of D6 genotype has been identified from cases in Ukraine and from imported cases. These D6 viruses have 99.7% sequence homology in the 450 nucleotides of the N gene based on data received from 2 of the 3 WHO European regional measles and rubella reference laboratories and one of the 3 WHO global specialised laboratories. Unfortunately direct confirmation of the origin of the Polish outbreak by genome sequence analysis will not be possible since it appears that no viable virus was isolated from the Polish cases
Belarus : between January and June 2006, 87 measles cases were notified in Belarus. Particularly efficient transmission has been noted in 3 regions: Minsk city (38 cases), Minsk region (29 cases), and Grodno region (17 cases)^ref. Routine immunization against measles began in Belarus in 1967. In 1987, a 2 dose vaccination schedule (at the ages of 12 months and 6 years) with measles monovalent vaccine was adopted. In 1996, one dose of measles, mumps and rubella (MMR) vaccine replaced the monovalent measles immunizations, and in 2000, a 2-dose MMR schedule was introduced. The vaccination coverage of both the 1st and 2nd doses of the vaccine has been > 95% for the last 10 years. Due to vaccination, the measles incidence rate in Belarus decreased from 600-800 per 100 000 population at the beginning of the 1960s to 1-5 per 100 000 population at the end of the 1990s. Since 2000, the measles incidence rate in Belarus has been < 1 per 100,000 population, and in 2004 and 2005, it was < 1 per 1,000,000 (only 2 cases in 2004 and only one case in 2005 were reported)
Italy : in Toscana (often known in English as Tuscany - a region of central Italy with about 3.5 million inhabitants), coverage with the first measles-containing-vaccine (MCV) dose by 24 months of age was 44% in 1993, 65% in 1998, and 89% in 2003 [2], according to 3 cluster sampling surveys. In children 6-10 years old attending primary school, MCV coverage was estimated to be 88 per cent for the 1st dose, and 66 per cent for the 2nd dose by December 2004. Although the elimination plan has so far been very successful in achieving its goals, a continually insufficient coverage rate for measles vaccine during the past 15 years has created a large pool of susceptible adolescents and young adults. Between 20 Jan and 5 May 2006, 40 cases of measles were reported to the local health unit in the province of Grosseto in Toscana. The index case was a 23 year old woman who showed symptoms suggestive of measles after returning from a visit to India. She initially presented with fever and was treated with antibiotics. She then developed a generalised rash, which was diagnosed as a drug reaction, and she was admitted to hospital in Grosseto on 20 Jan 2006. During her admission to hospital, she came into contact with a nursing student, who developed measles 14 days later, on 3 Feb 2006, and was the 1st secondary case to be reported. As patients were not always properly isolated (for example, during transportation between different wards), 12 patients (30 per cent) in this outbreak were thought to have acquired infection through nosocomial transmission. 8 of the cases (20%) were in health care workers. 26 cases (65%) were laboratory confirmed, while the remaining 14 were epidemiologically linked. Measles virus genotype D4 was confirmed in samples from 7 patients. No biological samples for measles confirmation were collected from the 1st patient, the 23 year old woman who had returned from India, as samples should be taken within 7 days of rash onset, and the diagnosis was too late. However, measles virus was isolated from the 1st secondary case and had the same genomic sequence as all the other cases. Complications recorded in the hospitalised patients included cholestatic hepatitis with cytonecrosis (7 cases; 50%), thrombocytopenia (2; 14%), and 1 case (7%) with each of respiratory distress, brain oedema, otitis media, haemorrhagic lesions, bacteraemia with isolation of Streptococcus capitis, and oral candidiasis. None of the patients died. Only one patient reported having received measles vaccination, in 1982. Measles virus genotype D4 has been found to circulate in India^ref, and outbreaks related to importation of this genotype were recently reported in Europe^{ref1,
ref2,
ref3}. In this outbreak, measles transmission following importation occurred in a hospital. A similar experience recently occurred in northern Italy, in the autonomous province of Bozen^ref, where a cluster of 5 measles cases, 3 of which were related to nosocomial transmission, were reported. This underlines the importance of verifying immunity and offering MMR vaccination to susceptible health care workers^ref
Romania : 12 deaths in 2005
Austria : > 150 cases since May to 3 Jul 2006^ref1,
ref2

Oceania :

Australia : in April 2006 7 cases were confirmed (1 adult, 36 years old, and 6 children under 11 years old), all of whom were un-immunized. The measles virus appears to have been introduced by overseas visitors who were part of an entourage accompanying a religious leader (AMMA) which arrived in Perth on 31 Mar 2006. The entourage visited other Australian States and Territories over the following 2-week period. Whilst in Perth, AMMA held several meetings of up to 1000 people. The WA cases all attended meetings or had contact with members of the entourage, and the 1st cases became ill on 13 Apr 2006. AMMA has it's origins in Kerala India, but today has centers in 33 countries worldwide. Of note is that a prior outbreak of measles in South Australia was associated with a tourist returning from India. Background information on the measles elimination strategy in Australia^ref. Endemic measles transmission in Victoria was interrupted in the early 1990s^ref. The last national measles outbreak occurred in 1993 during which Victoria reported few cases, suggesting reasonable measles control in the state at that time. In 1998 Australia conducted a national measles catch-up campaign targeting all children aged between 12 months and 11 years. In 1999, several months after the completion of the campaign, an outbreak of measles in Victoria was initiated by the return of a 21-year-old infected Australian tourist from Bali, Indonesia. This outbreak involved 75 people, mostly young adults, and highlighted the underlying susceptibility of young Australian adults, born between 1966 and 1981, to measles infection due to inadequate vaccination or non-infection during childhood because of a reduction in virus circulation after the vaccine was introduced^ref1,
ref2
In September 2005, the 37 countries and areas of the World Health Organization (WHO) Western Pacific Region (WPR) established a goal to eliminate measles in the region by 2012. After multiple outbreaks in 1996 and 1997, measles supplementary immunization activities (SIAs) in 1997 and 1998 resulted in apparent interruption of measles transmission in WPR. Since then, importations have resulted in limited outbreaks in French Polynesia and Guam, a large outbreak in the Marshall Islands in 2003, and an outbreak in Fiji during Feb to May 2006. In 2006 an outbreak produced 132 measles cases in Fiji (2006 estimated population: 832 432), the most populous country in the South Pacific. To achieve and sustain measles elimination and prevent importation-associated outbreaks, the WPR office of WHO recommends that countries achieve and maintain vaccination coverage of > 95% with 2 doses of measles vaccine in every district. The WPR office further recommends that countries ensure measles surveillance that 1) detects one or more suspected measles cases per 100 000 population per year in > 80% of districts, 2) tests serum samples from > 80% of persons with suspected measles, and 3) obtains a viral isolate from every chain of measles transmission. Fiji's Expanded Program on Immunization introduced measles vaccine in 1982 as a single dose for children aged 9 months. From 1982 to 1998, reported routine measles vaccination coverage increased from 20 to 80%. Measles SIAs were conducted in 1998, targeting children aged 9 months to 14 years and achieving an administrative vaccination coverage rate of 85%, and in 2001, targeting children aged 9 months to 5 years and achieving an administrative coverage of 86%. In 003, Fiji introduced a 2-dose schedule for measles-rubella vaccine, with doses administered at ages 1 year and 6 years, the latter at school entry. An SIA with measles-rubella vaccine targeting children aged 6 to 11 years was conducted during 2003 to 2004; administrative vaccination coverage was not reported. During 2001 to 2004, routine vaccination coverage with one dose of measles-rubella vaccine averaged 83% annually. Findings from a 2005 survey of children aged 12 to 23 months indicated nationwide vaccination coverage of 80% with 1 dose of measles-rubella vaccine, although pockets of lower coverage were identified. Before 2006, the last laboratory-confirmed measles outbreak in Fiji occurred during Sep 1997 to Apr 1998, when 955 measles cases were reported, of which 86% were in children aged less than15 years. Since late 1998, Fiji had been considered measles-free. Isolated clinical measles cases had been reported, and rubella, but not measles, had been confirmed by laboratory testing. On 17 Feb 2006, the Ministry of Health (MOH) in Fiji received a report of 3 infants, with rash onsets on Feb 8 and 11, who had been admitted to a divisional hospital because of suspected measles and pneumonia. The 3 infants lived near the international airport at Nadi in the Western Division. On 23 Feb 2006, measles was confirmed by serologic testing for the presence of anti-measles virus IgM at the national laboratory in Fiji and verified on Feb 28 by the WHO Measles Regional Reference Laboratory at the Victorian Infectious Diseases Reference Laboratory in Australia, where an isolate was identified as measles genotype H1. During the period 17 Feb to 9 Jun 2006, a total of 132 suspected measles cases were reported to MOH, including 22 that were laboratory-confirmed (anti-measles virus IgM-positive). Among the 132 measles patients, 119 (90%) resided in the Western Division and 13 (10%) in the Central and Eastern divisions. Within the Western Division, one subdivision had 58 (44%) of the measles cases. Routine vaccination coverage with 1 dose of measles-rubella vaccine in this subdivision had been reported as 49% in 2004 and 68 percent in 2005. A total of 76 (58%) patients were aged less than 5 years; the highest incidence (378 cases per 100 000 population) was among children aged 6 to 11 months. 31 (23%) patients required hospitalization; no deaths were reported. For 41 children aged 12 to 59 months for whom MOH could obtain detailed case investigation data, 12 (29%) had received 1 dose of measles-rubella vaccine, 10 (24%) had not been vaccinated, and 19 (46%) had unknown vaccination status. As of August 8, no additional laboratory-confirmed measles cases had been reported with rash onset after 21 May 2006. Reporting of acute fever and rash cases was intensified in Fiji's 21-hospital sentinel surveillance network, initially created for acute flaccid paralysis surveillance as part of the global poliomyelitis eradication initiative. Daily telephone calls were made to all sentinel hospitals for reports on new patients. Illnesses with rash and fever were confirmed as measles if they met the WHO measles clinical case definition.? To encourage case reporting, the national coordinator of the Expanded Program on Immunization provided daily surveillance summaries by e-mail and fax to all hospitals, selected health centers, and partner agencies. Triage and measles treatment recommendations, based on WHO Integrated Management of Childhood Illnesses guidelines^ref, were distributed to all health facilities and health workers to ensure that suspected measles cases were managed appropriately and to prevent measles virus transmission in health-care facilities. Vitamin A, a key part of WHO case-management guidelines to reduce measles morbidity and mortality, was distributed in capsules to all hospitals and health centers in late March. A multiphase social mobilization and communication plan was developed using WHO's Communication-for-Behavioral-Impact approach^ref, to prompt individual and family action. The initial phase, "Beware," informed the public about the measles outbreak and promoted reporting of suspected cases. The 2nd phase, "Vaccinate," promoted an immunization campaign, prompting parents and guardians to bring children in the targeted age group to vaccination sites made visible by large banners. Activities included distribution of 60 000 fact sheets to schools and community and religious organizations, announcements on television and radio, and advertisements in cinemas and newspapers. To protect children in the age groups accounting for > 60% of cases and most at risk for severe outcomes, 91 595 children aged 6 months to less than 6 years were targeted with measles-rubella vaccine during the period 20 Mar to 3 May 2006. A goal of > 95% vaccination coverage was set for all administrative levels. Plans at the subdivisional level were developed for budget estimates and distribution of bundled vaccine and injection-safety items. Campaign training workshops, including classes on vaccination safety, were conducted for health-care workers throughout the country. Vaccination-coverage rates with measles-rubella vaccine were reported twice weekly from all vaccination sites to promptly identify areas needing external assistance. Rapid vaccination-coverage monitoring, using a 20-household convenience sample format, was conducted in urban and other areas at risk for measles. If >= 2 homes contained unvaccinated children, the area was targeted for repeat vaccinations. Of 32 areas surveyed, 12 (38%) required follow-up. MOH subsequently reported that 89 747 (98%) of targeted children had received measles-rubella vaccine as of 24 May 2006. Among 20 Fijian subdivisions, 2 had reported coverage < 95 %: Suva (91%) in the Central Division and Macuata (90%) in the Northern Division. No serious adverse events from vaccination were reported. The measles outbreak in Fiji described in this report, like the 2003 outbreak in the Marshall Islands, underscores that absence of measles virus transmission should not create a false sense of security and that high population immunity is essential to preventing future outbreaks^ref. As an island, Fiji's isolation from countries where measles is endemic, combined with its small population, likely contributed to the lack of reported measles cases from late 1998 through 2005^ref1,
ref2. Low routine vaccination coverage, combined with persistent pockets of susceptible adolescents and adults despite previous SIAs and outbreaks, might have left the country vulnerable to an outbreak via importation. Achieving > 95 % population immunity (i.e., through high vaccination coverage with 2 doses of measles vaccine) will halt measles transmission within a population^ref. In Fiji, the high incidence of measles in a single subdivision with historically low routine measles vaccination coverage and the occurrence of measles in all age groups highlight the importance of monitoring measles vaccination coverage at subnational levels and in older age groups (i.e., aged > 15 years) to ensure that pockets of measles susceptibility do not develop. The first identified cases of measles in this outbreak were in children already hospitalized with pneumonia. Because recognition of measles might decrease after measles virus transmission has been interrupted for long periods, national programs should remind clinicians to be vigilant and to report suspected cases, particularly in areas of low vaccination coverage. To increase sensitivity and timeliness of surveillance, primary-care facilities and outpatient departments might be included as reporting sites, and community-based informants used to report suspected measles cases. The findings in this report are subject to at least 3 limitations. First, surveillance was conducted through sentinel site reporting and, as a result, all suspected measles cases might not have been reported. Second, not all suspected measles cases were laboratory-confirmed; therefore, some suspected cases might have had etiologies other than measles. Finally, the estimated vaccination coverage achieved in the ORI was based on administrative data. Because uncertainties often exist regarding the denominator used to calculate administrative coverage, these data generally are less reliable than survey-based coverage estimates. Targeting children aged 6 months to < 6 years during the ORI was important because this group accounted for > 60% of cases and was more vulnerable to severe measles outcomes. The Fijian MOH rapidly achieved high vaccination coverage with measles vaccine. At the same time, a sharp decrease in reported cases among all age groups occurred. The effectiveness of the ORI is greater when the itervention occurs early in the course of an outbreak^ref. In Fiji, the campaign began 6 weeks after the 1st case was reported; 8 weeks later, the last case was reported. The commitment by MOH and its partners to reach > 95% of targeted children was essential to interrupting measles virus transmission and preventing spread of the measles virus to other vulnerable Pacific Islands^ref.

diseases like measles have wiped out many tribal peoples worldwide :

in the 19th century, the disease wiped out at least half of the Great Andamanese on one island and all those on another island. That tribe, once 5000 strong, now numbers only 41 people.
in 1978, following the construction of a highway through their forest, 4 Yanomami communities in Brazil lost 50% of their population to measles.
when 108 Jarawa contracted measles in 1999, the local authorities also denied that the Jarawa had contracted the disease, but were forced to concede several weeks later following the testimony of doctors on the islands. Survival International has repeatedly warned that the authorities' failure to keep outsiders out of the Jarawa reserve, and to close the road that runs illegally through the reserve, put the Jarawa at risk of potentially fatal diseases. Another outbreak occurred in May 2006^ref

Genomics : for purposes of molecular epidemiology 8 clades of measles virus strains have been defined (A to G), and within these clades 22 distinct genotypes have been recognised (some of which appear now to be extinct) on the basis of the nucleotide sequence of the most variable gene, the SH gene. The different lineages are useful properties for establishing links between outbreaks and routes of transmission of the virus, but there is no clear association of the different lineages with different clinical symptoms
Proteomics :

viral envelope hemagglutinin (HA) glycoprotein

from the vaccine or Vero cell-adapted Edmonston strain of measles virus binds to complement control protein (CCP) repeats 1 and 2 of CD46 / MCP (a ubiquitous cellular receptor found on all nucleated cells; somatic - but not germinal - tissues of some New World monkey express an alternatively spliced form of MCP lacking CCP1, which, although retaining complement-regulatory activity, render these species less susceptible to strains of the measles virus whose HA requires both CCP1 and CCP2 for attachment)
lymphotropic measles virus preferentially use CD150 / signalling lymphocyte activation molecule (SLAM) (expressed on on activated B cells, T cells, and monocytes^{ref1,
ref2,
ref3,
ref4,
ref5})
HA from wild-type measles virus but not vaccine strains is an agonist for TLR2 .

envelope fusion (F) glycoprotein^ref : a functional F/H complex is an absolute requirement not only for attachment to the cellular MV receptors CD46 and SLAM and entry into target cells^{ref1,
ref2,
ref3}, but also for contact-mediated suppression of T cells in vitro andin vivo^ref1,
ref2. Another requirement for MV contact inhibition is proteolytic cleavage of the fusion protein, whereas membrane fusion is not necessary^ref
nucleocapsid (N) protein is recognized by IRF-3 and triggers the induction of interferon production. Measles virus is a serologically nontypical virus. Neutralising antibody elicited by the Edmonston vaccine strain is capable of neutralising all strains of measles virus. Nonetheless some regions of the measles virus genome (e.g. a 450 stretch of nucleotides in the N gene) exhibit considerable genetic variability which is useful in identifying and tracking the spread of measles virus strains. Regions of the N gene may exhibit as much as 12% nucleotide variability
C non-structural protein
V non-structural protein blocks IFN-a/b signaling by inhibiting Jak1 (and hence STAT1 and STAT2 phosphorylation) through a macromolecular complex including RACK1 and IFNAR1

Transmission : inhalatory or conjunctival route
Pathogenesis: MV establishes a systemic infection, which starts in the respiratory tract, spreads to the local lymphatic tissues and disseminates by cell-associated viraemia to a wide range of organs and tissues. The infection normally induces an efficient MV-specific immune response which eliminates the infection and confers life-long protection against measles. At the same time, however, MV infection leads to immunosuppression, which favours secondary infections. These opportunistic infections are the major cause of death among measles patients. Leukocytes thus act both as vectors for dissemination of the virus throughout the body and as targets for the immunosuppresive effects of MV^{ref1,
ref2,Schneider-Schaulies,
S. & ter Meulen, V (1999). Pathogenic aspects of measles virus infections.
Archives of Virology Supplement 15, 139–158}. MV can cause apoptosis^{ref1,
ref2,
ref3,
ref4}, inhibit the lymphoproliferative response^ref, and induce interferons and other cytokines^ref1,
ref2. Infected PBMC upregulate NF-kB p52 subunit (which homodimers that are considered to be mainly transcriptionally repressive^ref), the anti-apoptotic Bcl-3 (which binds p50 and p52 homodimers^ref converting the latter from a repressive to a transactivating transcription factor^ref. Furthermore, binding of Bcl-3 to p52 or p50 homodimers may free NF-B sites on the DNA from the repressive homodimers and thus provide access for transactivating NF-B dimers, for instance the p50p65 heterodimer^ref. Bcl-3 also counteracts apoptosis^ref and recently Bcl-3 was found to protect activated T cells against apoptosis by inhibiting activation-induced cell death^ref. Apoptosis of infected cells may inhibit viral multiplication and many viruses appear to have developed anti-apoptotic countermeasures^ref. It remains to be determined whether the MV-induced Bcl-3 upregulation protects the virus against apoptosis of its host cell. The Bcl-3 and NF-B p52 genes were also found to be upregulated by vaccinia virus and HPV-16, respectively^ref1,
ref2), IRF7, chaperones, transcription factors and other proteins of the endoplasmic reticulum stress response, the pro-apoptotic and growth arrest-inducing CHOP/GADD153 protein^ref. The ER stress response can play a key role in induction of apoptosis, and increasing evidence also points to a role in the IFN response^ref. MV infection induces the ER stress response due to the flux of viral glycoproteins through the ER. The migration of MV glycoproteins towards the cell surface is slow and incomplete^{ref1,
ref2,
ref3}. In pulse–chase experiments, MV glycoproteins were associated with ER chaperones for prolonged intervals^ref, indicating that folding of the MV glycoproteins into their correct conformation is an extensive task for the ER folding machinery. ERp57 is a protein disulphide isomerase, which forms complexes with the ER chaperones calreticulin and calnexin. These complexes are believed to mediate folding of nascent glycoproteins in the ER^ref1,
ref2. Induction of these three genes as well as that of GRP78, which is also an ER chaperone, improves the capacity of the ER to handle incoming viral glycoproteins, thus protecting the cell against protein aggregation. Herp is a recently discovered stress-induced integral protein of the ER membrane. Herp has a ubiquitin-like domain, but the function of Herp and its role in the ER stress response remains to be determined^ref. Activating transcription factor 4 (ATF-4), also called cAMP response element binding protein 2 (CREB-2), and transcription factor II-I (TFII-I) are both involved in the activation of promotors of genes upregulated by ER stress^ref1,
ref2. ATF-4 was also found to be upregulated by other viruses in microarray studies^ref1,
ref2. The CHOP/GADD153 protein has been reported to block transition from the G₁ to the S phase of the cell cycle^ref. Arrest of lymphocytes in the G₀ or G₁ phase of the cell cycle is believed to be an important mechanism behind the reduced lymphoproliferative response and the immunosuppression in patients with measles^{ref1,
ref2,
ref3}. Thus, although purely speculative, it is possible that the ER stress response, through the induction of CHOP/GADD153, is involved in the MV-induced reduction of lymphocyte proliferation. MV-induced upregulation of 2',5'-oligoadenylate synthetase (2-5A) and ICAM-1 has previously been described^ref1,
ref2. Membrane protein E16 (CD98 light chain) is an amino acid transporter, which is disulphide-linked to the 4F2 (CD98 heavy chain) glycoprotein^ref. Interestingly, the CD98 heavy chain appears to modulate cell fusion by Newcastle disease virus and human parainfluenza virus type 2^ref. E16 was also upregulated by cytomegalovirus^ref. A strong and broad IFN response comprising several IFN subtypes requires the positive feedback regulation of IRF3 and 7 in virus-infected cells. IRF-3 is constitutively expressed and activated post-translationally, whereas IRF-7 is regulated at the transcriptional level^ref. Servant et al.^ref recently demonstrated MV-induced IRF-3 activation, and in the present study we demonstrate MV-induced upregulation of the IRF-7 gene. Several studies have shown that MV strains differ in their IFN-inducing properties, and it has been suggested that virulent MVs can inhibit the induction of type 1 IFN^{ref1,
ref2,
ref3}. Naniche et al.^ref recently reported that wild-type isolates, which had been isolated and passaged on lymphoid cells, were much weaker inducers of type 1 IFN than the Edmonston strain and the Edmonston-derived Moraten vaccine strain. The present study is in agreement with this finding, since the wild-type MV isolate was a weaker inducer of the IFN-a and -b genes than the Edmonston strain. However, this difference in induction of host cell genes was not confined to the type 1 IFN genes. The Edmonston strain and the DK96A1 wild-type appeared to upregulate the same cellular genes, but the wild-type isolate was a weaker inducer of almost all the studied MV-induced genes than the Edmonston strain. In the present study, this difference could be explained by a better in vitro growth of the Edmonston than the wild-type isolate. This is the first large-scale study of the role of MV infection in host cell gene expression. As a starting point, we chose to examine non-selected primary PBMCs and to minimize the influence of non-viral factors by using viruses (and mock material) passed on PBMC cultures. Since MV does not grow to high titres in PBMC cultures, only a low m.o.i. could be obtained. The PBMCs were analysed when most cells were infected, but at a time where cells at all stages of infection were present in the culture. Future studies may preferably be carried out with high-titre virus stocks in order to establish more synchronized infections, which can be assayed at different time points. More pronounced modulation of the expression levels than seen in the present study are also likely to be obtained with homogeneous cell populations such as cell lines or selected PBMC subpopulations. Microarray-based analyses of virus-induced modulation of host cell gene expression have been reported for several other viruses^{ref1,
ref2,
ref3,
ref4}. The number of genes found to be differentially expressed in virus-infected cells was highly variable, but most of these studies identified a higher number of genes than the present study, and both up- and downregulated genes were found. Several factors including characteristics of the individual viruses and the experimental strategies are likely to influence the number of differentially regulated genes that can be identified. The use of mitogen-stimulated PBMCs may be an important factor, since PHA-L treatment is likely to induce a wide range of cellular genes. Virus-induced downregulating signals may be overridden and virus-induced upregulations may to a large extent drown in PHA-L-stimulated PBMCs.
=> measles / morbilli / rubeola (a.k.a. morbillo in Italy) : the incubation period from exposure to rash onset for measles is approximately 10 days (range 7-18 days); on rare occasions the incubation period can be as long as 19-21 days => prodromic rash

typical variant : fever => in 80%: Köplik's spots, sign or enanthema (small, irregular, bright red spots (hyperhemic mucosa) on the buccal and lingual mucosa, with a minute bluish white speck in the center of each; seen in the prodromal stage (infectious period)), pseudomembranous tonsillitis => morbilliform maculopapular exanthema due to endothelial replication and DTH (trunk => thorax => head, no on hand palms and foot soles) => acute rhinitis, tracheobronchitis , 3C (cough, conjunctivitis , acute rhinitis / common cold), photophobia .
atypical variant : no Köplik enanthema, morbilliform maculopapular exanthema accompanied by petechiae (legs and arms => trunk => face). "atypical measles" brought back memories of a

^ref

hemorrhagic measles : inner and outer hemorrhages, encephalitis , giant cell pneumonia / Hecht's pneumonia , very high fever.
hypertoxic measles in individuals with CMI deficiency .
attenuated measles in babies before mo. 6 (natural IgGs) or with seroprophylaxis

The infectious period for measles is from 4 days before to 4 days after onset of rash.
Complications :

mesenteric lymphadenitis
persistent keratoconjunctivitis
bacterial overinfections (acute otitis media , otogenous meningitis , mastoiditis , sinusitis , alveolar pneumonia )
croup
postinfectious encephalomyelitis (PIE) 1-2 weeks after beginning of exanthema (0.1-0.2% => lethality : 10-15%, 33% of survivors experience recovery with neuropsychic disorders)
measles inclusion bodies encephalitis (MIBE) some months after acute infection : only in immunocompromised hosts (1 out of 10), lethal.
multiple sclerosis (MS) after some years (?)
Hodgkin's lymphoma (HL)
for NHL a personal history of measles lowered the risk in a Canadian study^ref1,
ref2. The presence of measles virus antibodies was of 81.66% in children and of 90.78% in adults with different malignant haemopathies in Cuba^ref. In Japan measles virus genome was detected in 9.5% by RT-PCR and 15.6% through hybridization in bone marrow aspirates from adults with malignant diseases : the genomes were all in the same cluster, D5, the strain circulating during the study period, and no evidence of persistent infection was obtained^ref. Ironically live attenuated oncolytic measles virus is currently a promising strategy to induce regression of human lymphoma^ref. The levels of MCP expression on T and myeloid cell lines are usually 2-8-fold higher than those on their normal counterparts, whereas Burkitt's lymphoma B cell lines express less MCP than B cell lineages carrying no EB virus. The STABC isoform of the ST domain of CD46 is up-regulated in T and myeloid leukaemia cell lines^ref. Regression of Burkitt's lymphoma in association with measles infection^ref.

Globally 1 every 800 die and 1 every 500 has serious brain damage. Permanent immunity.
Vaccination was thought to provide life-long immunity similar to natural infection. Immunity against measles was supposedly maintained in adult populations by subclinical re-infection. Serological confirmation of subclinical re-infection was obtained by pre-exposure in household-exposed parents who developed asymptomatic secondary immune responses with a concomitant increase in specific IgG neutralizing test antibodies and haemagglutination inhibition titres^ref1,
ref2. IgM antibodies against measles virus were detected in 10 (23%) of 44 bus-tour participants who had been exposed to measles during a 3-day trip and none developed typical measles symptoms. All cases were defined by serological evidence^ref. Measles virus was isolated from PBMC in mild cases of measles where the patient had previously been immunized^ref. Recently, measles virus was isolated in a case of infection by household contact without any symptoms^ref. The index case was identified as a secondary measles infection with positive isolation of measles virus and serological evidence. Measles virus was isolated from urine of the patient’s mother without IgM antibodies or a booster of neutralizing antibodies and the genomic sequence of the isolated virus was identified as similar to that obtained from the index case. In our previous examination in paediatric populations, the measles virus genome was detected in 36 of 78 individuals (40 of 159 samples) who were immunized more than 2 months before, and was identified as a circulating wild strain in all cases. Among 13 healthy individuals more than 2 months after natural infection, the measles virus genome was detected in six (seven out of 26 samples). There was no close relationship between the PCR positivity and the period since immunization or natural infection. PCR-positive samples were obtained from April 1993 to January 1995, in accordance with regional measles outbreaks. Thus, asymptomatic measles infections are probably very common manifestations of measles during outbreaks in highly immune populations^ref. Following this line of research, we examined PBMC obtained from healthy adults for the measles virus genome but failed to detect the genome. Remaining portions of bone-marrow aspirate samples were examined after cytological examination, bacterial culture and so on. Measles virus genome was detected in 17 of 179 individuals (9.5%) by RT–PCR and ethidium bromide staining. Through dot-slot hybridization, it was detected in 28 of 179 individuals (15.6%). There was no relationship between the detection rate of measles virus genome and haematological malignant disease. In patients with malignant lymphoma and acute leukaemia, the detection rate of measles virus genome was slightly higher than in those with non-malignant haematological diseases, reflecting immunosuppression due to basic illness or chemotherapy. Subclinical infection was confirmed in adulthood and the detection of measles virus genome was not related to the illness. Recently, it was hypothesized that some non-infectious diseases, inflammatory bowel diseases and autistic developmental disorders, might be related to the MMR vaccine. Measles virus genome has been detected in PBMC of patients with autoimmune hepatitis

, inflammatory bowel diseases

, intractable convulsion, and autism

^{ref1,
ref2,
ref3,
ref4}. However, there was no evidence of the presence of measles virus using N gene RT–PCR^ref and, epidemiologically, no supportive evidence was reported^ref. The pathological relationship of the persistence of measles virus to the onset of diseases is still controversial. Measles virus genome RNA was detected in autopsy brain material with high positivity and some were identified as current strains by sequence analysis^ref. Asymptomatic measles infections occur even in the adult population with unexpectedly high frequency, and this supports the preservation of measles immunity. The presence of the measles virus genome is not directly connected to the pathogenesis of illness but might be a symptomatic infection, with no relationship between the detection of the measles virus genome and specific diseases^ref.
Laboratory examinations :

syncytia seen in secretions during prodromal phases

Debré's phenomenon : absence of measles rash at the site of injection of convalescent measles serum which has not prevented the appearance of the eruption
anti-measles virus IgM in :

saliva^ref

RT-PCR on^ref :

blood
nasopharyngeal aspirate
throat swabs
urine
oral fluid samples from isolated cases that are to be used for molecular studies should ideally be collected within 7 days of onset of illness and stored at – 70 °C until required for testing. During large outbreaks or epidemics where large numbers of samples may be collected this is not so critical, and samples obtained and used for other purposes (e.g. antibody detection) may also be used for molecular studies. However, the likelihood of detection of virus genome is much reduced^ref

Prevention : attenuated vaccine

. There are conflicting results regarding the prevention of secondary cases (measles transmission and clinical infection) by post-exposure immunisation of despite rapid diagnosis :

1 negative report^ref
2 positive reports :

prevent infection in a single household when a very early vaccine that contained a high dose of Edmonston measles virus strain (subsequently, all monovalent measles and MMR vaccines used in the UK have contained lower doses of Schwartz or Moraten strains) was given to family contacts one day after appearance of the rash and 96 h after onset of coryzal symptoms in the index case^ref
protection from vaccination in children vaccinated after exposure in a school setting^ref

Differences might be due to differences in timing of administration, vaccine formulation or interpretation of observations made on small numbers of cases. Vaccination rates in some states and cities have dropped to levels that would allow an outbreak of measles to be sustained if a case gets into the community. This could have severe consequences as evidenced by measles outbreaks in the US between 1989 and 1991, mainly among unvaccinated, preschool-aged children that infected > 55 000 people and resulted in 123 deaths. MMR vaccination rates in the UK have dropped to the lowest level in at least 8 years, primarily due to unfounded concerns by parents that the vaccine is linked to autism

. The lowered immunization rates already appear to be leading to increases of mumps, rubella, and measles. In Scottish children under age 15, suspected cases of measles have jumped by 18% in the last 18 months -- and rubella by 22% and mumps by 27%. Most of these cases will turn out to be due to other causes but the trend does suggest the diseases are on the increase. The current rate of MMR vaccine coverage in the United Kingdom stands at about 86%, and in some areas the coverage rate has dropped as low as 61%. Health officials think a vaccine coverage rate of about 95% is necessary to prevent outbreaks and anything below 90% could allow outbreaks to flourish. In the US, MMR vaccine coverage is about 91.6%, but several areas have rates of only 87% or lower, including Arizona (except for Maricopa County), Montana, Oklahoma, Oregon, Shelby County Tennessee, Houston Texas, and parts of Colorado (close to 20% of kids are not immunized). Some states have vaccination rates below the 90% mark, including Alaska, most of California, Idaho, Kentucky, Louisiana, Nevada, Washington, and Wyoming. The numbers are averages for these whole states, so there could be pockets where the coverage rates are much lower. Even if some local populations have only 50% immunization coverage, they could be overlooked within an average of 91% for the whole state. Keeping the immunization coverage uniformly high is essential because an increasing number of unvaccinated people makes it easier for a case of measles to take hold and, in turn, boost the likelihood of spreading the disease to vaccinated individuals -- because no vaccine confers 100% protection. The real threat is the same thing that has driven down immunization rates in the United Kingdom and Japan, and that is parental resistance to having their children immunized. In the Marshall Islands measles outbreak that began in Summer 2003 and has resulted in 752 cases and 3 deaths, the vaccination coverage was about 75%. This is of concern because people infected in that outbreak are known to have traveled into the United States. Mexico also recently had measles cases imported from Asia, and this could easily spread across the border into the USA
Between 2000 and June, 2003, 82.1 million children were targeted for vaccination during initial supplemental immunisation activities (SIA) in 12 countries and follow-up SIA in 7 countries. The average decline in the number of reported measles cases was 91%. In 17 of the 19 countries, measles case-based surveillance confirmed that transmission of measles virus, and therefore measles deaths, had been reduced to low or very low rates. The total estimated number of deaths averted in the year 2003 was 90,043. Between 2000 and 2003 in the African Region as a whole, the percentage decline in annual measles deaths was around 20% (90043 of 454000)^ref.
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