Molecular relationship between field and vaccine strain of measles virus and its persistence in Pakistan
© Shah et al; licensee BioMed Central Ltd. 2012
Received: 10 November 2011
Accepted: 30 January 2012
Published: 30 January 2012
Countrywide 5.9 million, 0-11 Month old children are immunized annually by EPI (Expended Program on Immunization) against 8 vaccine preventable diseases including measles and so on. Unfortunately the basic immunity centers are not uniform throughout the country. Each center provides services to about 27000 people which is inadequate. The purpose of this study was to explore the development of EPI Pakistan in terms of immunization of measles.
Nucleotide sequences were analyzed by neighbor joining method (bootstrap test) using Bio- edit and MEGA-5 software to find evolutionary relationship between wild type measles strain and vaccine strain (Edmonston strain) used in Pakistan. For statistical analysis of data SPSS 16 was used.
Currently 1.3 vaccinators are working at each U C (union council) which according to national EPI policy should be at least 2. About 56% and 44% children of age 0-11 months did not received second dose of measles in the last two years respectively. Out of these 4231 cases which were reported last year, 1370 have received their first dose of measles vaccine.
Seroconversion and seroprevalence study of the vaccine and field strain of measles virus is needed to confirm whether its failure is due to service unavailability or vaccine in-affectivity.
Immunization is a sole component of preventive medicine and is an important need of the day. Immunization reduces the cost of treating diseases and thus helps in poverty reduction and social and economic development of the country . Globally EPI was initiated by the WHO In 1974  and in Pakistan it was started in 1978 with the definitive objective of eliminating six common diseases (Tetanus, Diphtheria, Tuberculosis, Pertussis, Polio, and Measles) in the country which are vaccine preventable .
For many years childhood immunization program coverage remains low in Africa and Asia due to several reasons. These countries carry an inconsistent burden of global measles deaths. Approximately 610,000 infants and young children died in 2002 in these continents. In 1997 a new resolution was adopted by Eastern Mediterranean Region of the WHO to eliminate measles by 2010 . The plan of National Immunization Days has remarkable impact on immunization coverage . Annually 5.9 million 0-11 month old children are immunized by EPI Pakistan to protect them against 8 vaccine preventable diseases including measles. Unfortunately the basic immunization providing centers are not uniform in the country. About 6,000 fixed centers providing immunization services are present throughout the country. Each center provides services to about 27,000 populations, which is inadequate and its distribution is also not uniform. Presently 1.3 vaccinator are working at each UC (union council) which according to national EPI policy should be at least 2. In last 15 years the < 5 years mortality rates have shown some reduction but still it is 94 out of 1000 live births which is obviously terrifyingly . About 56% and 44% children of age 0-11 months did not received measles II in the last two years respectively. Pakistan has made significant improvement in EPI coverage in comparison to India and Afghanistan. But more forceful implementation strategy is required to compete with other countries of the region.
Material and methods
Several Government documents, survey reports and unpublished program documents were reviewed. Online searches were also made to find literature on coverage and surveillance of measles in Pakistan in websites of the World Health Organization (WHO), United Nations Children Fund (UNICEF) and other sources. EPI program official database was also analyzed for this study. 12 nucleotide sequences of polyprotein gene of measles virus strain reported in different areas of Pakistan and that of Edmonston strain used in measles vaccine in Pakistan were retrieved from NCBI gene Bank Data Base. To study evolutionary relation between wild type measles strain and Edmonston strain, nucleotide sequences were analyzed by neighbor joining method (bootstrap test) using Bio- edit and MEGA-5 software. For statistical analysis and graph construction SPSS 16 was used.
1. Need of Measles Vaccine
Dose vise Schedule of different vaccine followed in Pakistan.
No. of Doses
At birth,6,10 and 14 weeks
At 9 month and 2nd year of life
At 6,10 and 14 weeks after birth
2. Vaccine Production in Pakistan
Current measles vaccine being used in Pakistan have been attenuated and produced in chick embryo fibroblasts. The minimum quantity of vaccine virus per human dose is determined by the national regulatory authority but is generally considered to be 1000 viral infective units . The vaccine induces both humoral and cellular immune responses comparable to those following natural infection, although the serological titers are usually lower. IgM, IgG and IgA antibodies may be detected in both serum and nasal secretions, and IgG persists for many years. Declining antibody titer may be boosted by revaccination or by exposure to circulating measles virus.
3. Immunization Progress against Measles in Pakistan
4. Measles outbreaks in Pakistan
The main reason behind the question "that how the vaccinated children got the disease" is that most of them do not receive booster dose which is very important as recommended by WHO and Pakistan's regulatory authorities. In the last decade, years 2001, 2006 and 2010 years are considered to be epidemic. 3849 cases were reported in 2001 and 6480 in 2006 at EPI center Islamabad. Due to high efforts of bodies responsible for immunization, the number of reported cases reduced gradually in the next three years. However due to floods in 2010 and the terrorist activities in the past three years in KPK and FATA region a huge number of children failed to received their first dose of vaccine and almost all of them who have previously received their first dose, failed to boost up immunity against measles.
5. Reasons for poor coverage
The key reason for this poor performance is the inadequate service delivery. Firstly the EPI centers are far away from the citizens and they cannot afford the cost to reach the center, secondly unavailability of vaccinators was found to be the main reasons. The 2006 Coverage Evaluation Survey of EPI indicated that 12.6% of mother's reasons for failing to immunize their children were distant vaccine center and unavailability of vaccinators .
The second most common contributing factor for low coverage is the Lack of recipient awareness about the immunization service and its benefits for their children. Low coverage in Punjab is the lack of parental awareness about the need for vaccination, as indicated by The Coverage Evaluation Survey Punjab 2003 .
Another main hurdle in vaccination progress is that, the health facility doctors neither refer the children for vaccination to the EPI center nor welcome any EPI activity at their health centers.
The administrative reports claimed high coverage but only around half of the targeted children were fully immunized as shown in all surveys conducted during 1995 to 2007 [15–17, 19, 20]. Concerns are found among different stake holders about the inconsistency between the reported data and independent assessments. Discrepancy in provincial performance was also evident in these surveys. Poor performance and limited access to the immunization service of EPI Pakistan, as revealed through a series of studies, is the most common cause for the large number of reported cases in the last decade [16, 19, 21–25]. Inadequate numbers of vaccinators was one of the main reasons for limited access to service [22, 24]. All provinces have a much lower number of vaccinators than required according to the national policy except in Sindh (115%). Last year Proportions of vaccinators available against the standard were 52%, 70% and 72%, in Punjab, Khyber Pakhtunkhwa and Baluchistan provinces, respectively. A vaccinator working for 15-17 days every month making only 18-26 contacts each day is sufficient for an average-sized Union Council with a population of 25,000. However, this task becomes more challenging due to wide geographical dispersion of this target population. This inadequacy could be overcome by using EPI-trained lady health workers for delivering vaccination services. LHWs are embedded in and easily accepted by community. They have substantial potential for enhancing EPI coverage in their catchment area.
Most of the children who have received their first dose against measles are often deprived of their second dose, due to which a large number of cases are reported each year. The low rates of coverage and dropout rates suggest that there is significant scope for improving efficiency of the EPI. Further, to confirm efficacy of measles vaccine we need seroconversion and seroprevalence study of the vaccine and field strain of measles virus in the country.
- World Health Organization: State of the World's Vaccines and Immunization. 2002, GenevaGoogle Scholar
- World Health Organization, Expanded Programme on Immunization: Immunization policy: global programme for vaccines and immunization. Geneva 1996, WHOGPV/GEN/95.03 Rev.1.Google Scholar
- Ali SZ: Health for all in Pakistan: achievements, strategies and challenges. East Mediterranean Health J. 2000, 6: 832-7.Google Scholar
- World Health Organization: The work of WHO in the Eastern Mediterranean Region annual report of the regional director. Alexandria, Egypt: WHO. 1997, 109-11.Google Scholar
- Hong R, Banta JE: Effects of extra immunization efforts on routine immunization at district level in Pakistan. East Mediterranean Health J. 2005, 11: 745-52.Google Scholar
- National Institute of Population Studies (NIPS) [Pakistan], Macro International Inc: Pakistan Demographic and Health Survey 2006-07. 2008, Islamabad, Pakistan: National Institute of Population Studies and Macro International Inc, [http://www.measuredhs.com/pubs/pdf/PB1/Pakistan_2006-07_Briefing_Kit_all_6[PB1].pdf]Google Scholar
- griffin Diane, Moss William: Can we eradicate Measles?. American society for Microbiology. 2006, [http://forms.asm.org/microbe/index.asp?bid=44732]Google Scholar
- Shann FA: little bit of measles does you good, Even if measles is eradicated, immunization may still be desirable in developing countries. BMJ. 1999, 319 (7201): 4-5. 10.1136/bmj.319.7201.4.PubMed CentralView ArticlePubMedGoogle Scholar
- Ministry of Health - Government of Pakistan: [http://22.214.171.124/wps/portal/Moh/!ut/p/c1/04_SB8K8xLLM9MSSzPy8xBz9CP0os3h_Nx9_SzcPIwMDs2BTAyMfN08TXyd_4xAXY_1wkA6z-FA3rwBnd2cjAwtzkApXTz9jE0NfQwNDE4i8AQ7gaKDv55Gfm6pfkJ2d5uioqAgAsRf4PA!!/dl2/d1/L2dJQSEvUUt3QS9ZQnB3LzZfT0ZMTzlGSDIwT1Y4MDAyVEo3RUZUSzIwNzA!/?WCM_GLOBAL_CONTEXT=/wps/wcm/connect/MohCL/ministry/home/sahomegeneral/sageneralright/a_expanded+program+on+immunization]Google Scholar
- Saitou N, Nei M: The neighbor-joining method: A new method for reconstructing phylogenetic trees. Molecular Biology and Evolution. 1987, 4: 406-425.PubMedGoogle Scholar
- Tamura K, Nei M, Kumar S: Prospects for inferring very large phylogenies by using the neighbor-joining method. Proceedings of the National Academy of Sciences (USA). 2004, 101: 11030-11035. 10.1073/pnas.0404206101.View ArticleGoogle Scholar
- Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S: MEGA5: Molecular Evolutionary Genetics Analysis using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods 2011. Molecular Biology and Evolution.Google Scholar
- WHO technical report Series: Requirements for measles, mumps and rubella vaccines and combined vaccine (live)1994. annex 3: No. 840, Page 118 of 201Google Scholar
- WHO/UNICEF estimate of national immunization coverage 1980-2008, Pakistan. 2009, Geneva: World Health Organization, [http://www.who.int/immunization_monitoring/en/globalsummary/timeseries/tswucoveragebycountry.cfm?country=PAK,accessed 24 April 2010]
- Pakistan social & living standards measurement survey 2004-2005. 2005, Islamabad, Federal Bureau of StatisticsGoogle Scholar
- Coverage evaluation survey 2006. 2007, Islamabad, Ministry of Health, Expanded Programme on ImmunizationGoogle Scholar
- Pakistan demographic and health survey 2006-2007. 2008, Islamabad, National Institute of Population StudiesGoogle Scholar
- Abid Raza Azhar: Measles elimination in Pakistan. 2011, UNICEF, Washington, [http://webcache.googleusercontent.com/search?hl=en&gbv=2&gs_sm=e&gs_upl=1984l6406l0l6750l4l4l0l0l0l0l469l1188l3-1.2l3l0&q=cache:I4o2Hz4AImwJ:http://measlesinitiative.org/mi-files/Tools/Presentations/Annual%20Measles%20Partner%20Meeting%202011/Tackling%20Big%20Challenges/5%20Final%20Pakistan%20Measles%20update%20AARAZA%2012Sept11.pptx+Dr.+Azhar+Abid+Raza,+Measles+elimination+in+Pakistan,+UNICEF,+Washington+13-14+Sept+2011.&ct=clnk]]Google Scholar
- Coverage evaluation survey - Punjab 2003. 2003, Lahore, Director General Health Services of PunjabGoogle Scholar
- Pakistan integrated household survey, round 1: 1995-1969. 1997, Islamabad, Federal Bureau of StatisticsGoogle Scholar
- Faisal A: Understanding barriers to immunization in Pakistan. 2009, Islamabad, Ministry of Health, Expanded Programme on ImmunizationGoogle Scholar
- Ahmad N, Akhtar T, Roghnani MT, Ilyas HM, Ahmaad M: Immunization coverage in 3 districts of North West Frontier Province (NWFP). Journal of Pakistan Medical Association. 1999, 49 (12): 301-305.Google Scholar
- Mansuri FA, Baig LA: Assessment of immunization service in the perspective of both the recipients and the providers: a reflection from focus group. J Ayub Med Coll Abbottabad. 2003, 15 (1): 14-8.PubMedGoogle Scholar
- Usman HR, Kristensen S, Rahbar MH, Vermund SH, Habib F, Chamot E: Determinants of third dose of diphtheria-tetanus-pertussis (DTP) completion among children who received DTP1 at rural immunization centers in Pakistan: a cohort study. Tropical Medicine & International Health. 2009, 15 (1): 140-147.Google Scholar
- National EPI policy and strategic guidelines. 2005, Islamabad, Ministry of Health, Expanded Programme on ImmunizationGoogle Scholar
- Felsenstein J: Confidence limits on phylogenies: An approach using the bootstrap. Evolution. 1985, 39: 783-791. 10.2307/2408678.View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.