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Table of Contents:
Taxonomy Information
  1. Species:
    1. Measles virus. (Website 1):
      1. Common Name: Measles, Rubeola.
      2. GenBank Taxonomy No.: 11234
      3. Description: Measles virus (MV) is the most contagious virus known to humankind and a leading cause of mortality in children worldwide. It primarily causes acute disease in humans, with attack rates of more than 90% in non-immune populations. In 2002, there were 3040 million cases of measles, resulting in 777 000 deaths(Dhimanet al., 2004). Despite the highly contagious nature of the disease, MV can be controlled effectively by immunization with live attenuated vaccines. The effectiveness of MV vaccines is well illustrated by the epidemiology of the disease in the United States. Prior to 1963, before use of the earliest vaccines, there were over 500,000 reported cases per year. Twenty years later, MV incidence was less than 2,000 cases per year(Parks et al., 2001).
      4. Variant(s):
        • Measles virus Edmonston :
          • GenBank Taxonomy No.: 11235
          • Parents: Measles virus.
          • Description: Edmonston wild-type (wt) measles virus(Parks et al., 2001). In 1954, the measles virus was isolated from an 11-year old boy from the US, David Edmonston, and adapted and propagated on chick embryo tissue culture (CE). The CE adapted strain, known as Edmonston A, was too virulent for vaccine purposes. The strain was attenuated by means of further passages on CE fibroblasts, resulting in a 2nd generation attenuated virus designated as Edmonston B. Again, the strain was too virulent to be applied on a large scale. Laboratories continued to pass Edmonston B on CE until a 3rd generation of more attenuated strains was developed. These strains, which are known by different names and differ from each other in the number of times the parent strain was passed on CE, provide the seeds for the vaccines now commercially available. The measles vaccines supplied through the World Health Organization's programme on Immunization in the Americas are prepared from seeds derived from Edmonston B(EPI Newsl., 1980).
        • Measles virus leningrad-16 :
        • Measles virus HU2 :
        • Measles virus IP-3-Ca :
          • GenBank Taxonomy No.: 11237
          • Parents: Measles virus.
          • Description: A measles virus genome originally derived from brain cells of a subacute sclerosing panencephalitis patient expressed in IP-3-Ca cells an unstable MV matrix protein and was unable to produce virus particles. Transfection of this virus genome into other cell lines did not relieve these defects, showing that they are ultimately encoded by viral mutations. However, these defects were partially relieved in a weakly infectious virus which emerged from IP-3-Ca cells and which produced a matrix protein of intermediate stability(Cattaneo et al., 1988).
        • Measles virus philadelphia-26 :
          • GenBank Taxonomy No.: 70148
          • Parents: Measles virus.
          • Description: Comparison of P gene nucleotide sequence of Ph26 with that the Edmonston strain of MV revealed a single synonymous nucleotide difference(Vanchiere et al., 1995).
        • Measles virus Yamagata-1 :
          • GenBank Taxonomy No.: 11239
          • Parents: Measles virus.
          • Description: Two virus clones were isolated from a defective SSPE (subacute sclerosing panencephalitis) virus, the Yamagata-1 strain, and designated as the YA and YF clones. The YA clone-infected cells produced neither cell-free virus nor cell-associated virus, whereas the YF clone-infected cells produced both cell-associated and cell-free virus. No difference of epitopes on structural proteins was observed between these two clones. Both clones had hemadsorption activity(Haga et al., 1992).
        • Measles virus ETH10/99 :
          • GenBank Taxonomy No.: 151529
          • Parents: Measles virus.
          • Description: In December 1998, a measles outbreak was reported in the regional state of Oromia in western Ethiopia, affecting three districts. The three strains were named as MVs/Bedelle.ETH/5.99 (ETH10/99) from a 5-year-old child from the Bedelle outbreak and MVs/Addis Ababa.ETH/50.98 (ETH54/98) and MVs/Addis Ababa.ETH/2.99 (ETH55/99) from sporadic cases in Addis Ababa, respectively, in a 10- and in a 2-year-old child(Nigatu et al., 2001).
        • Measles virus ETH54/98 :
          • GenBank Taxonomy No.: 151530
          • Parents: Measles virus.
          • Description: In December 1998, a measles outbreak was reported in the regional state of Oromia in western Ethiopia, affecting three districts. The three strains were named as MVs/Bedelle.ETH/5.99 (ETH10/99) from a 5-year-old child from the Bedelle outbreak and MVs/Addis Ababa.ETH/50.98 (ETH54/98) and MVs/Addis Ababa.ETH/2.99 (ETH55/99) from sporadic cases in Addis Ababa, respectively, in a 10- and in a 2-year-old child(Nigatu et al., 2001).
        • Measles virus ETH55/99 :
          • GenBank Taxonomy No.: 151531
          • Parents: Measles virus.
          • Description: In December 1998, a measles outbreak was reported in the regional state of Oromia in western Ethiopia, affecting three districts. The three strains were named as MVs/Bedelle.ETH/5.99 (ETH10/99) from a 5-year-old child from the Bedelle outbreak and MVs/Addis Ababa.ETH/50.98 (ETH54/98) and MVs/Addis Ababa.ETH/2.99 (ETH55/99) from sporadic cases in Addis Ababa, respectively, in a 10- and in a 2-year-old child(Nigatu et al., 2001).
        • Measles virus genotype A :
          • GenBank Taxonomy No.: 262307
          • Parents: Measles virus.
          • Description: Reference strains: Edmonston-wt.USA/54 (Status: Active)(WHO Report, 2003). Vaccine virus strains originating from the same progenitor of genotype A have been used successfully throughout the world over a 30 year period(Santibanez et al., 2005).
        • Measles virus genotype B1 :
        • Measles virus genotype B2 :
        • Measles virus genotype B3 :
          • Parents: Measles virus.
          • Description: Reference strains: New York.USA/94, Ibadan.NIE/97/1 (Status: Active)(WHO Report, 2003). Isolated in Congo, Democratic Republic of the Congo, Gambia, Ghana, Kenya, Nigeria, Sudan(WHO Report, 2001).
        • Measles virus genotype C1 :
        • Measles virus genotype C2 :
        • Measles virus genotype D1 :
        • Measles virus genotype D2 :
        • Measles virus genotype D3 :
        • Measles virus genotype D4 :
          • GenBank Taxonomy No.: 170525
          • Parents: Measles virus.
          • Description: Reference strains: Montreal.CAN/89 (Status: Active)(WHO Report, 2003). Isolated in Ethiopia, India, Iran, Kenya, Namibia, Pakistan, Russian Federation, South Africa, Zimbabwe(WHO Report, 2001).
        • Measles virus genotype D5 :
        • Measles virus genotype D6 :
          • GenBank Taxonomy No.: 170527
          • Parents: Measles virus.
          • Description: Reference strains: New Jersey.USA/94/1 (Status: Active)(WHO Report, 2003). Isolated in Argentina, Brazil, Bolivia, Dominican Republic, Germany, Italy, Luxembourg, Poland, Russian Federation, Spain, Turkey(WHO Report, 2001).
        • Measles virus genotype D7 :
        • Measles virus genotype D8 :
        • Measles virus genotype D9 :
        • Measles virus genotype E :
        • Measles virus genotype F :
        • Measles virus genotype G1 :
        • Measles virus genotype G2 :
        • Measles virus genotype G3 :
        • Measles virus genotype H1 :
        • Measles virus genotype H2 :
        • Measles virus AIK-C :
          • GenBank Taxonomy No.: 36408
          • Parents: Measles virus.
          • Description: The AIK-C strain of measles vaccine was developed in 1976 in Japan from the Edmonston strain by plaque cloning through passage in sheep kidney cells and chicken embryonic cells at 33 C(Kumada et al., 2004).
        • Measles virus Edmonston-Zagreb :
          • GenBank Taxonomy No.: 70149
          • Parents: Measles virus.
          • Description: Further attenuation of the EdmonstonMusser virus was initiated by D. Iki (Institute of Immunology, Zagreb) in 1963 by passaging the virus in human diploids (Wi-38) through 19 passages with a triple purification of the virus by plaquing during the 9th, 11th and 13th passages when pre-seed was produced. In each plaquing, only large plaques were selected. Purification of the virus by plaquing developed a homogenous, genetically stable population of the viral particles originated from a single plaque, called the EdmonstonZagreb strain(Baricevic et al., 2005). Edmonston-Zagreb replicates best and induces substantial thymocyte death(Valsamakis et al., 2001).
        • Measles virus Halle :
          • GenBank Taxonomy No.: 11236
          • Parents: Measles virus.
          • Description: Although the Halle strain was originally reported to have been isolated from a patient with subacute salerosing panencephalitis, this lytic virus is now suspected to be a laboratory contaminant derived from the Edmonston strain and is classified with the vaccine MV strains(Lecouturier et al., 1996).
        • Measles virus Moraten :
          • GenBank Taxonomy No.: 132484
          • Parents: Measles virus.
          • Description: The vaccine strain Moraten (Mor) rapidly induced high levels of ICAM-1 mRNA and protein expression, whereas the vaccine strain CAM-70 and the Edmonston wild type (Edwt) strain were far less effective, even when they were used at very high multiplicities of infection (MOIs). Furthermore, induction of ICAM-1 by Mor was not dependent on de novo expression of MV or cellular proteins(Harcourt et al., 1999).
        • Measles virus MVi/Calgary.CAN/40.01 :
        • Measles virus MVi/Prague.CZH/60/2 :
        • Measles virus Rubeovax :
        • Measles virus Schwarz :
          • GenBank Taxonomy No.: 132487
          • Parents: Measles virus.
          • Description: Further passages of Edmonston A and B on chicken embryo fibroblasts (CEF) produced the more attenuated Schwarz and Moraten viruses, whose sequences have recently been shown to be identical(Combredet et al., 2003). The Moraten and Schwarz strains are highly genetically related, reflecting their common ancestry and similar passage history, and they are safe and effective for most children. Their use has dramatically reduced the incidence of measles, from over 100 million cases in the prevaccine era to approximately 31 million cases in 1997. However, fatal infections have been documented in immunodeficient children vaccinated with these strains(Valsamakis et al., 1999).
        • Measles virus UK140/94 :
          • GenBank Taxonomy No.: 151532
          • Parents: Measles virus.
          • Description: The entire N gene of two strains, UK140/94 and UK160/94, identifed in the UK in 1994 was sequenced for comparison, and these two strains were renamed as MVi/Manchester.-UNK/30.94 and MVi/Manchester.UNK/32.94 according to the WHO nomenclature(Nigatu et al., 2001).
        • Measles virus UK160/94 :
          • GenBank Taxonomy No.: 151533
          • Parents: Measles virus.
          • Description: The entire N gene of two strains, UK140/94 and UK160/94, identifed in the UK in 1994 was sequenced for comparison, and these two strains were renamed as MVi/Manchester.-UNK/30.94 and MVi/Manchester.UNK/32.94 according to the WHO nomenclature(Nigatu et al., 2001).
        • Measles virus type N :
Lifecycle Information
  1. Measles Virus Lifecycle
    1. Stage Information:
      1. Human cells infection:
        • Size: Purified virions examined by negative staining in the electron microscope exhibited a pleomorphic range of particle sizes varying in diameter between 300 nm and 1000 nm. Purified nucleocapsids had dimensions of 21 nm (diameter) X 1254(+/- 7) nm (length) and a central core of diameter about 5 nm. Full-length nucleocapsids were composed of 204 (+/- 3) protein discs. The pitch of the nucleocapsid helix was calculated to be 6.1 nm and the helix angle, alpha, to be 8 degrees 16'. Approximate volume calculations indicate that each enveloped virus particle contains multiple nucleocapsids.
        • Shape: The measles virus particles are pleomorphic, spherical structures.. Both in vivo and in vitro the measles nucleo-protein profiles were surrounded by 'fuzzy' material which could be resolved in a pentagon shape and this stained specifically with ruthenium red. The tubules found in MS appeared not to have a 'fuzzy' coat and also did not stain with ruthenium red. The main difference observed between infected tissue culture cells and mouse brain was that in the latter no alignment of measles nucleoprotein was observed under the cell membrane and no budding particles were seen.
        • Description: Measles virus is an enveloped, negative, nonsegmented strand RNA virus. Two virus-encoded glycoproteins are inserted into the viral envelope: the hemagglutinin (H) protein, which mediates virus attachment to susceptible cells and hemagglutination of certain simian erythrocytes, and the fusion (F) protein, which, together with H, is responsible for fusion with the cell membrane and virus entry. During the incubation period, the virus replicates in the respiratory tract and then spreads to local lymphoid tissue. Amplification of the virus in lymph nodes produces a primary viremia that results in the spread of virus to multiple lymphoid tissues and other organs, including the skin, kidney, gastrointestinal tract, and liver, where it replicates in epithelial cells, endothelial cells, and monocytes-macrophages. Most of the infected cells in peripheral blood are monocytes, although T and B lymphocytes support viral replication after stimulation in vitro(Horvat et al., 1996).
Genome Summary
  1. Genome of Measles virus.
    1. Measles Virus Genome
      1. GenBank Accession Number: NC_001498
      2. Size: Nucleotide sequence analysis of the IC-B strain revealed thatthe length of the entire genome (15,894 nucleotides) and the overall genome organizations of the IC-B strain were identical to those of the Edmonston (Ed) strain(Takeuchi et al., 2000).
      3. Gene Count: Protein-encoding nucleotide sequences of the N, P, M, F, H, and L genes were determined for a low-passage isolate of the Edmonston wild-type (wt) measles virus and five Edmonston-derived vaccine virus strains, including AIK-C, Moraten, Schwarz, Rubeovax, and Zagreb. Comparative analysis demonstrated a high degree of nucleotide sequence homology; vaccine viruses differed at most by 0.3% from the Edmonston wt strain(Parks et al., 2001).
      4. Description: The 16-kb MV genome encodes eight known proteins from six nonoverlapping cistrons arranged 3'-N-P-M-F-H-L-5'. The major structural polypeptide is encoded by the N (nucleocapsid) gene. The P cistron specifies three polypeptides: P, C, and V. The P (phosphoprotein) polypeptide is a subunit of the viral RNA polymerase. The C and V polypeptides are nonstructural proteins that are translated from P mRNAs through the use of alternative reading frames; C protein is synthesized from a downstream translation start signal, whereas V protein is translated from an edited mRNA that contains an extra G residue(Parks et al., 2001).
Biosafety Information
  1. General biosafety information
    1. Level: Biosafety level 2 practices, containment equipment and facilities for activities involving known or potentially infectious clinical materials or cultures.
    2. Applicable: Measles Virus Precautions(Website 2).
    3. Precautions: PROTECTIVE CLOTHING: Laboratory coat; gloves when direct contact with infectious materials is unavoidable; gloves and gown (tight wrists and ties in back) when working in a biosafety cabinet. OTHER PRECAUTIONS: Procedures that are likely to generate aerosols should be conducted in a biosafety cabinet(Website 2).
Culturing Information
  1. Measles Virus Culturing :
    1. Description: Measles virus is excreted from infected cases only for the first 57 days after rash onset, often in low titer, necessitating a laboratory with cell culture or polymerase chain reaction (PCR) expertise to detect the virus. For these reasons, attempts to detect virus from suspected measles cases is not considered to be a useful diagnostic tool. However, the detection of measles virus, subsequent genomic analysis, and the availability of an extensive sequence database for wild type measles viruses have enabled molecular epidemiologic studies of measles(Featherstone et al., 2003).
    2. Medium: B95-8, an Epstein-Barr (EB) virus-transformed marmoset B-lymphoblastoid cell line, and its derivative B95a, capable of attachment to a substrate surface, were 10,000-fold more sensitive to measles virus present in clinical specimens than were Vero cells. B95-8 and B95a cells were thus thought to be useful host cells for the isolation of measles virus. Quantitation of measles virus present in clinical specimens showed that a large quantity of virus, exceeding 10(6) 50% tissue culture infective doses per ml of a nasal-swab eluate, is shed into secretions by patients with acute measles, consistent with the contagiousness of the disease. Measles viruses isolated in B95a cells differed in some biological properties from those adapted to Vero cells. First, the viruses isolated in B95a cells did replicate in Vero cells, but release into the fluid phase was less efficient than that of Vero cell-adapted viruses. Second, minor antigenic differences were found between virus strains isolated in B95a cells and those isolated in Vero cells from the same clinical specimens. Third, the viruses isolated and propagated in B95a cells caused clinical signs in experimentally infected monkeys resembling those of human measles. It was suspected that measles virus is subject to host cell-mediated selection and that the viruses grown in B95a cells are more representative of measles virus circulating among humans than are the viruses selected in Vero cells(Kobune et al., 1990). CELLS. B95a is an Epstein-Barr virus-transformed marmoset B cell line. Vero and Cos cells are fibroblast cell lines established from African green monkey kidney. Cos cells are transformed by SV40.The following human cell lines were also used; Jurkat (T cell), BJAB (EB virus-transformed B cell), K562 (erythroleukemia), and HeLa. All of the cell lines used express CD46 on the cell surface. Human peripheral blood mononuclear cells (PBMC) were isolated as described previously. Vero, HeLa, and Cos cells were grown in Dulbeccos modified Eagles medium supplemented with 7% heat-inactivated fetal bovine serum, 2 mM L glutamine, 0.15% sodium bicarbonate, and 50 mg/ml kanamycin. B95a, Jurkat, BJAB, K562 and PBMC were grown in RPMI 1640 medium supplemented with 7% heat-inactivated fetal bovine serum, 2 mM L-glutamine, and 50 mg/ml Kanamycin. Culture medium for PBMC also contained 2 mg/ml phytohemagglutinin (PHA).VIRUS PRODUCTION. HeLa, Vero or Cos cells are plated in 6-well plate (100000 cells per well), and infectedwith one of the MV strains at a multiplicity of infection (m.o.i.) of 0.1. After 2 h of infection, cells were washed with phosphate-buffered saline (PBS) twice, replenished with 2 ml of fresh medium, and incubated at 37C in a 5% CO2 incubator. Jurkat, K562, BJAB or B95a cells (1000000 cells) were infected at a m.o.i. of 0.1. After 2 h of infection, they were washed twice, replenished with 5 ml of medium(Tanaka et al., 1998).
    3. Optimal Temperature: 37 C(Tanaka et al., 1998).
Epidemiology Information:
  1. Outbreak Locations:
    1. During 1989 and 1990 reported measles cases in the United States increased 6- to 9-fold over the annual mean of 3000 between 1985 and 1988. To evaluate recent epidemiology we summarized measles outbreaks. Confirmed measles cases reported to the National Notifiable Disease Surveillance System during 1987 through 1990 were analyzed. An outbreak was defined as more or equal 5 epidemiologically linked cases. There were 815 outbreaks, accounting for 94% of the 52,846 cases reported. Similar to 1985 and 1986, 3 patterns of measles transmission during outbreaks were identified: (1) predominantly among unvaccinated pre-school age children less than 5 years of age (38% of outbreaks); (2) predominantly among vaccinated school age children 5 to 17 years of age (40%); and (3) predominantly among unvaccinated and vaccinated post-school age persons older or equal 18 years of age (22%). Most outbreaks were small (median,12 cases), but very large outbreaks occurred (maximum size, 10,670). Although school age outbreaks (58%) predominated during 1987 and 1988, preschool age (40%) and post-school age (23%) outbreaks were more important during 1989 and 1990. Recent epidemiology suggests that to achieve elimination of measles, ACIP recommendations must be fully implemented, including (1) routine administration of the first dose of measles vaccine from 12 to 15 months of age and (2) use of a routine two-dose schedule to prevent school age and post-school age outbreaks(Hutchins et al., 1996).
    2. Of the 540 measles cases (annual incidence, less than 1/million population) reported during 1997-2001 in the United States, 362 (67%) were associated with international importation: 196 imported cases, 138 cases epidemiologically linked to imported cases, and 28 cases associated with an imported measles virus genotype. The remaining 178 (33%) "unknown-source" cases were analyzed as potential evidence of endemic measles transmission. A total of 83 counties (2.6% of the 3140 US counties) in 27 states reported unknown-source cases; 49 counties reported only 1 unknown-source case, and the maximum reported by any county was 10. Nationally, unknown-source cases were reported in 103 of the 260 weeks. The largest unknown-source outbreak included 13 cases and lasted 5 weeks. The rarity of unknown-source cases, wide gaps in geographic and temporal distribution, and the short duration of the longest unknown-source outbreak indicate that endemic transmission of measles was not sustained in the United States during this period(Papania et al., 2004).
    3. During 2001-2003, of the total 216 measles cases reported, 96 (44%) were imported, and 120 were indigenous. Of the indigenous cases, 59 (49%) were import-linked, 18 (15%) were imported virus, and 43 (36%) were unknown source cases. Import-associated cases (i.e., imported, import-linked, and imported virus cases) accounted for 80% of all reported cases. During 2001--2003, the highest percentage (47%) of imported measles cases was reported in 2001. Imported cases occurred in 55 international visitors traveling to the United States and 41 U.S. residents exposed to measles while traveling abroad. The largest numbers of imported cases were from China and Japan. The 96 imported cases during 2001-2003 resulted in 42 chains of indigenous transmission. The greatest numbers of cases linked epidemiologically to an imported case were 10 in 2001, 12 in 2002, and nine in 2003. The longest durations of measles transmission following imported cases were 34 days in 2001, 27 days in 2002, and 62 days in 2003. Of the unknown source cases, 29 (67%) were isolated cases, eight (19%) were in chains of transmission involving two cases, and six (19%) were in two outbreaks (i.e., three or more linked cases). During 2001--2003, nine genotypes were identified among measles viruses detected in the United States. Measles virus was isolated from 27 chains of transmission, including 14 (16%) of 87 isolated cases, four (31%) of 13 two-case chains of transmission, and nine (56%) of 16 outbreaks. The most commonly identified genotypes were D7 and H1, which occurred in six and five chains of transmission, respectively. During 2001-2003, a total of 21 states reported no confirmed measles cases, and 23 reported one to nine cases. States reporting more than 10 cases (Alabama [12], California [50], Hawaii [27], New York [24], Pennsylvania [18], and Washington [16]) accounted for 69% of all cases. Fifteen states reported unknown source cases, and two states (California [14] and Hawaii [6]) reported more than five such cases. Of the 3,140 counties in the United States, 78 reported one or more confirmed cases; 14 counties reported four or more cases (range: four to 27 cases). Twenty-six counties reported unknown source cases, but no county reported more than six. Of 155 (72%) cases in U.S. residents, 116 (75%) occurred in vaccine-eligible persons (i.e., aged more than 12 months and born after 1957); 27 (23%) had received 1 dose of measles-containing vaccine (MCV), nine (8%) had received 2 doses of MCV, and 80 (69%) were either not vaccinated or had unknown vaccination status. Of 61 (28%) cases in non-U.S. residents, 42 (69%) occurred in vaccine-eligible persons; five (12%) had received 1 dose of MCV, one (2%) had received 2 doses of MCV, and 36 (86%) were either not vaccinated or had unknown vaccination status(CDC Report, 2004).
    4. During 1987-1992, there were 165 measles-associated deaths in the multiple-cause mortality database at the National Center for Health Statistics (NCHS) and 184 reported to the measles surveillance system at the National Immunization Program (NIP). It was estimated that 259 measles deaths actually occurred; the reporting efficiencies were 64% for the NCHS and 71% for the NIP. Overall the death-to-case ratio was 2.54 and 2.83 deaths/1000 reported cases, using the NCHS and NIP data, respectively. Pneumonia was a complication among 67% of measles-related deaths in the NCHS data and 86% of deaths in the NIP data. Encephalitis was reported in 11% of deaths in both databases. Preexisting conditions related to immune deficiency were reported for 16% of deaths in the NCHS system and 14% in the NIP; the most common was human immunodeficiency virus infection. Overall, 90% of deaths reported to the NIP occurred in persons who had not been vaccinated against measles. During 1993-1999, only 1 acute measles-related death was reported to the NCHS and no deaths were reported to the NIP. This is consistent with the extremely low reported incidence of measles in the United States during these years(Gindler et al., 2004).
  2. Transmission Information:
    1. From: Human(Hahm et al., 2003). , To: Human(Hahm et al., 2003).
      Mechanism: The causative agent, measles virus (MV), is generally transmitted by aerosolized secretions deposited on upper-respiratory-tract mucosal surfaces. Exposure leads to local respiratory tract replication; infection of regional lymphoid tissues then occurs followed by viremia and systemic dissemination as revealed by the characteristic skin rash. Most children recover uneventfully from the illness, but serious complications can occur, including pneumonia and involvement of the central nervous system(Parks et al., 2001). Airflow studies demonstrated that droplet nuclei generated in the examining room used by the source patient were dispersed throughout the entire office suite. Airborne spread of measles from a vigorously coughing child was the most likely mode of transmission(Bloch et al., 1985). People with measles are usually infectious for one to two days before the rash appears but the total period during which an individual is infectious is not known(Bedford, 2004). Measles virus is a highly contagious agent which causes a major health problem in developing countries(Santos et al., 2003). During the resurgence of measles in the United States between 1989 and 1992, only viruses of genotype D3 were isolated. In contrast, virological surveillance conducted after the resurgence period showed that at least 12 different genotypes were associated with the greatly reduced number of measles cases. Eight different genotypes were identified for 27 chains of transmission in which the source of infection was unknown. The diversity of measles virus genotypes observed in the United States between 1994 and 2001 reflected multiple imported sources of virus and indicated that no genotype of measles is endemic in the United States. Therefore, the data obtained from virological surveillance are consistent with the conclusions made by disease surveillance and epidemiological investigations that measles is no longer an endemic disease in the United States(Rota et al., 2004).
  3. Environmental Reservoir:
    1. Measles Virus Environmental Reservoir:
      1. Description: Humans are the only natural reservoir of measles virus(Hahm et al., 2003).
      2. Survival: The outbreak supports the fact that measles virus when it becomes airborne can survive at least one hour(Bloch et al., 1985). Antiseptics such as PVP-I (povidone-iodine) solution, PVP-I gargle, PVP-I cream, chlorhexidine gluconate, alkyldiaminoethyl-glycine hydrochloride, benzalkonium chloride (BAC) and benzethonium chloride (BEC) were used. PVP-I was effective against all the virus species tested. PVP-I drug products, which were examined in these experiments, inactivated all the viruses within a short period of time. Rubella, measles, mumps viruses and HIV were sensitive to all of the antiseptics, and rotavirus was inactivated by BAC and BEC, while adeno-, polio- and rhinoviruses did not respond to the other antiseptics. PVP-I had a wider virucidal spectrum, covering both enveloped and nonenveloped viruses, than the other commercially available antiseptics(Kawana et al., 1997).
  4. Intentional Releases:
    1. Intentional Release Information:
      1. Description: In 2001 the World Health Organization and the United Nations Children's Fund published a strategic plan for the control of measles in which it was suggested that a meeting of experts should be convened in 2005 to evaluate the possibility of global eradication of measles. Eradication (i.e., the global elimination of the disease) can bring enormous benefits as cases will no longer occur and vaccination and surveillance efforts can be scaled down (and even completely ended). A recent study suggested that if measles were eliminated by 2010, the United States (USA) could save $500 million to $4.5 billion. These savings are less than previously estimated for the United States, partly because of the assumption that measles vaccines will continue to be delivered in response to possible bioterrorism threats(Carabin and Edmunds, 2003).
      2. Emergency Contact: Travelers are at increased risk for several infections, including familiar infections such as measles that are widely distributed but more common in developing countries. Vaccines can markedly decrease the risk for many of these infections and are an important part of pretravel preparation. Travel provides an opportunity to review and update routine vaccines in adults and assess risk from unusual infections(Wilson, 2001).
Diagnostic Tests Information
  1. Organism Detection Test:
    1. FACS-measured immunofluorescence assay :
      1. Description: A Fluorescence activated cell scanner (FACS)-measured immunofluorescence assay was developed for the detection of antibodies directed against the hemagglutinin (H) and fusion (F) glycoproteins of measles virus (MV). Human melanoma cell lines transfected with either the MV H or F genes, which showed a high surface expression of the respective proteins in their native conformation, were used as target cells. The cells were incubated with diluted plasma samples, and stained subsequently with fluorescein isothiocyanate (FITC)-conjugated secondary antibodies. The FACS-measured fluorescence signals correlated directly with the amount of specific immunoglobulins over a wide concentration range. The use of different conjugates enabled the separate detection of MV-specific IgG, IgM, IgA and IgG subclasses, with relatively low backgrounds. Hemagglutinin-specific IgG, IgM and IgA fluorescence signals were shown to correlate well with MV-specific IgG ELISA titers and MV-specific IgM or IgA capture ELISA OD450-values, respectively. The polyclonal conjugates with specificity for human immunoglobulins offered sufficient cross-reactivity to detect MV-specific IgG, IgM and IgA in plasma samples of cynomolgus macaques, making this technique a useful tool for studying serological responses in vaccination and challenge experiments in non-human primate models(de Swart et al., 1998).
  2. Immunoassay Test:
    1. Serum-based IgM Enzyme Immunoassay :
      1. Description: ELISA/EIA (Enzyme Immunoassay) test. Serum-based IgM EIAs are the current recommended laboratory assays for the confirmation of clinically diagnosed measles. Both indirect and capture EIA formats appear to work reasonably well, with most tests having high reported sensitivity (83% - 89%; higher after the first week of rash onset) and specificity (95% - 100%) with serum specimens collected 3 - 28 days after rash onset. The EIAs can be done with a single serum specimen, are relatively rapid and simple to perform by trained laboratory technicians, require only a small volume sample (20 mkL of serum), and can be used to diagnose acute measles infection from the time of rash onset until 4 weeks after rash onset(Bellini, Helfand, 2003).
    2. ELISA-IgG avidity assay :
      1. Description: A measles-specific enzyme-linked immunosorbent assay (ELISA)-IgG avidity test for serologic evaluation of the efficacy of measles vaccines with only one blood sample was evaluated after vaccination with three measles vaccine strains. Avidity indices were determined by the urea elution technique in samples presenting antibody titers more or 100 mIU/ml. All 127 sera collected 2-8 weeks after primary vaccination with Biken-CAM70 measles vaccine had low avidity indices (LAI, when less or 29%) with a time-dependent increase in avidity. In samples collected 6-10 weeks after vaccination with Edmonston-Zagreb, LAI were also observed in all 31 sera tested (mean 15%) and in 233/242 (96.3%) filter paper samples from primary vaccination with Schwarz vaccine (mean 14%). There was no difference in the mean avidity among the three groups of primary vaccinees, although the Schwarz group had higher antibody titers. In contrast, only 1/36 (2.8%) serum samples from children who were seropositive at the time of measles vaccination had LAI (mean 56%), despite the fact that they were collected early (2-5 weeks after vaccination). Of 90 serum samples from children vaccinated in the past with two doses and of 42 cord blood serum samples, none had LAI. It is concluded that this test is a good tool for evaluating serologically the efficacy of a single dose schedule of measles vaccine. With only one postvaccination sample, the test can discriminate nonresponders (antibody titers below 100 mIU/ml), primary responders (antibody titers more or 100 mIu/ml with LAI), and those previously immunized (antibody titers more or 100 mIU/ml with high avidity indices). The seroconversion rate can be calculated after excluding the latter(de Souza et al., 1997).
  3. Nucleic Acid Detection Test: