- Email: [email protected]
PCV 10 introduction in National Immunization Program of Nepal
Pediatric Infectious Disease 8 (2016) 67–71
Contents lists available at ScienceDirect
Pediatric Infectious Disease journal homepage: www.elsevier.com/locate/pid
Original Article
PCV 10 introduction in National Immunization Program of Nepal K.P. Paudel Kanti Children’s Hospital, Maharajgunj, Kathmandu, Nepal
A R T I C L E I N F O
A B S T R A C T
Article history: Available online 3 June 2016
Nepal adopted immunization program as expanded program on Immunization in 1977 and it is considered a successful program in Nepal for its role in the reduction of infant and under-five mortality in the country. Pneumonia is a major killer of children and Streptococcus pneumoniae is the common cause of it. Based on the studies done in Nepal covering the existing serotypes, National Committee on immunization practice recommended PCV 10 for its immunization program and it was rolled out in phase-wise manner to all over the country after its introduction in January 2015. The schedule of PCV 10 in the routine National Immunization Program of Nepal is 2p + 1 at 6 weeks, 10 weeks, and 9 months of age. Immunogenicity and impact study are ongoing and it is too early to comment on the further efficacy of this vaccine. ß 2016 Indian Academy of Pediatrics, Infectious Disease Chapter. Published by Elsevier B.V. All rights reserved.
Keywords: Nepal Immunization Pneumonia PCV 10
1. Introduction Nepal is a landlocked country which shares its northern border with China and eastern, western, and southern borders with India. It covers a total land area of 147,181 km2 and has a total population of 28 million1 and less than one year cohort of the country is 660,000.2 Topographically, Nepal is divided into three distinct ecological zones: the mountain (Himal), hill (Pahad), and plain land (Terai) (Fig. 1). For administrative purposes, before adopting the federal system, Nepal was divided into five development regions and 75 districts.1 Districts are further divided into Village Development Committees (VDCs) and municipalities. As per the Nepal’s constitution 2015, health is considered as a right of the people.3 The Ministry of Health and Population (MOHP) in its Nepal National Health Sector Programme Implementation Plan (NHSP-II, 2010–2015) has a goal to improve the health and nutritional status of the Nepali population, especially for the poor and socially excluded. In the area of child health, it had a target to reduce under-five mortality to a level of 38 and infant deaths to 32 per 1000 live births by 2015 with several interventions including: sustaining community-based integrated management of childhood illness (CB-IMCI), maintaining immunization coverage above 90%, and scaling up community-based newborn care.4 The immunization program is one of the government’s highest priority programs.2,4 The immunization program has helped in
E-mail address: [email protected].
reducing the deaths of children and mothers from vaccine preventable diseases (VPDs) and has contributed in achieving Millennium Development Goals (MDG) 4 and 5. The government through its policy documents has emphasized reaching poor and marginalized population with equitable services including immunization. Since the past decades, new vaccines are available in the markets, and the government has put all available means to reduce morbidity and mortality. In this regard, it is essential to have a long-term immunization plan with priority activities identified and as well as a financial sustainability plan. The comprehensive multi-year plan 2011–2016 of Child health division provided a plan to achieve the immunization-related goals expressed by the government in various policy documents, resolutions as well as different national and international forums. The plan also took into consideration the Global Immunization Vision and Strategy (GIVS). The objectives, strategies, and activities set forth in the plan provide the framework required to meet the goal of ‘‘reducing infant and child mortality and morbidity associated with vaccine-preventable diseases (VPDs).’’ This plan also provided guidelines for the introduction of new vaccines, eradication, elimination and control of targeted VPDs, and strengthening of routine immunization. The National Committee on Immunization Practice was established in 2009 to provide vaccine-related recommendations to the government. NCIP provides recommendations on introduction of new vaccines and other immunization-related policies to the government. Nepal introduced Hepatitis B in 2002 and HiB as pentavalent vaccine in 2009 with GAVI co financing. JE vaccines were introduced in 2008 in routine immunization using government funds. The
http://dx.doi.org/10.1016/j.pid.2016.06.003 2212-8328/ß 2016 Indian Academy of Pediatrics, Infectious Disease Chapter. Published by Elsevier B.V. All rights reserved.
K.P. Paudel / Pediatric Infectious Disease 8 (2016) 67–71
68
Fig. 1. Map of Nepal with 5 administrative development regions.
Government of Nepal (GON) introduced rubella vaccine in routine immunization along with Measles after completing a Measles Rubella campaign in 2012. Considering that pneumonia is a major cause among deaths in under-five children and that streptococcus is a significant standing cause of pneumonia, otitis media, and meningitis in children under five years of age, Nepal seriously worked in generation of surveillance data on Pneumococcal diseases since 2005 and applied for GAVI support in the introduction of Pneumococcal vaccine in routine Immunization in Nepal.5 2. Objective of the study To review the national introduction and roll out of Pneumococcal vaccine PCV 10 in routine National Immunization Program of Nepal.
throughout country. The national schedule has seen various additions till recent introduction of Measles Rubella Second dose and HPV demonstration in 2 districts (Table 1).2,4 There is sustained coverage of more than 90% of the various antigens in the national program and the country is still struggling to reach beyond 90% in case of Measles Rubella and the unimmunized population is nearly 3% and nearly 10% of dropout or incomplete immunizations (Figs. 2 and 3).6 Sentinel surveillance for Invasive bacterial disease was conducted at two sites, Patan Hospital and Kanti Children’s Hospital since 2005; however, from 2011, it was continued only in Patan Hospital and it included Hib, pneumococcal, and meningococcal diseases. This study was supported previously by ‘Hib and pneumococcal initiative’ and later by WHO. In this study, the Pneumococcal serotype distribution at Patan Hospital Kathmandu 2005–2012 showed the Serotypes 1, 5, 14 predominant serotypes (Fig. 4).7–9
3. Materials and methods 4.1. Comparison of PCV 10 with PCV 13 in Nepalese context The information and statistics available at the Child Health Division of Department of Health Services form the basis of this article. Similarly, related publications from WHO and UNICEF and related studies in Nepal are the secondary sources of information. 4. Results The Immunization Program of Nepal started with initiatives to eradicate Small Pox and formal routine immunization program started in the year 1977 with piloting of 2 antigens BCG and DPT in 3 districts and it took nearly 10 years to roll out these antigens
As there are 2 Pneumococcal conjugate vaccines available in the market, it was extensively compared in Nepalese context and presented in NCIP meeting (Table 2).9 It is clear that the common serotypes 1, 5, and 14 are present in both PCV 10 and PCV 13 and over to PCV 10 PCV 13 has 3, 6A, 19A. PCV 10 was available in 2 dose vials and NCIP based on the experts’ presentations decided to recommend for PCV 10 for inclusion in NIP in Nepal. A randomized controlled open-label immunogenicity study of the 10-valent Pneumococcal conjugate vaccine. This study showed comparisons between two dose priming with booster to a
Table 1 Timeline of introduction of various vaccines in the Nepal’s national schedule.5 Name of vaccine
Introduction
Doses
Age of administration
BCG DPT-HepB-Hib OPV IPV PCV MR
1977 1977/2003/2009 1988 18 Sep 2014 18 Jan 2015 M 1988: 2012 MRSD: 15 Sep 2015
1 3 3 1 3 2
At birth 6, 10, 14 weeks 6, 10, 14 weeks 14 weeks 6, 10 weeks and 9 months At 9 and 15 months
2+ 1
Pregnant women 12 months (31 districts); after JE campaign 2016 – nation wide
Td JE
2009
K.P. Paudel / Pediatric Infectious Disease 8 (2016) 67–71
69
Fig. 2. The coverage of different antigens in Nepal National Immunization Program in 2014.2
Fig. 3. The coverage status of different vaccines in Nepal’s National Immunization Program: the trend of last 3 years.2
three dose priming schedule in Nepalese infants. The study was carried out at 18 weeks, 10 months, and 2–4 years. The results showed the follow-up at 2–4 years of age demonstrated significantly higher proportions in the 2p + 1 versus 3p + 0 group with IgG concentrations 0.2 mg/ml for serotypes 1, 5, 6B, and 18C (Figs. 5 and 6).8–10 Based on the study presented in the meeting NCIP meeting on August 2014 because of IPV roll out recommends the following PCV
immunization schedule at 6 weeks, 14 weeks and 9 months. This meeting decided the switch of PCV second dose from 14 weeks to 10 weeks because of the fear that multiple vaccines injection (IPV, PCV, DPT-HepB-Hib) at 14 weeks will be unacceptable to many families and for fear of dropout of injection and postponing to further visit (18 weeks) and even this will have huge cost implication to the government. PCV eligibility at the time of introduction was all children from 6 weeks onwards, and for
Table 2 Comparison of PCV 10 over PCV 13.
Serotypes Conjugate Presentation Volume per dose Cold chain volume Costing
PCV-10
PCV-13
1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Non-typeable Haemophilus influenzae, tetanus toxoid, or diphtheria toxoid. Single dose syringe or as 1 or 2 dose vial. 0.5 ml 4.8 cm3/dose Less ($3.5 for 2 dose presentation)
1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. Nontoxic diphtheria CRM 197 (CRM, cross-reactive material) carrier protein. Single dose, fully liquid vial. 0.5 ml 13.2 cm3/dose More expensive ($3.5 for 1 dose presentation)
70
K.P. Paudel / Pediatric Infectious Disease 8 (2016) 67–71
Fig. 4. Serotypes of Pneumococci at Patan Hospital.
Table 3 National rollout of PCV 10 at Nepal. Development region
PCV start
Western development region Eastern development region Central DR, Mid Western DR, FarWestern DR
18 January 2015 April 2015 July 2015
catch-up, dose eligible cohort were children under 1 year of age. The PCV 10 vaccine was added to Nepal’s National Immunization Program since 18 January 2015 and gradually over 6 months time, it was scaled up throughout the country (Table 3).9,10 5. Conclusion
Fig. 5. PCV 10 proportion greater than 0.35 mg/ml at 18 weeks.
Nepal’s National Immunization Program is a priority and it is a successful program in the field of child health of the country and this new addition to its National Immunization Program will be a major milestone given the deaths and morbidity with Pneumococcal diseases. Since the schedule adopted by the country is very new, further evidences on the impact as well as the immunogenicity study will be useful in the further revision of the program to give feedback to its immunization advisory body and the program division. Conflicts of interest The author has none to declare. References
Fig. 6. PCV 10 proportion greater than 0.35 mg at 2–4 years.
1. Central Bureau of statistics (CBS) Government of Nepal. http://www.cbs.gov.np/. 2. Annual Report 2014. DOHS Government of Nepal. Available from: http://dohs.gov. np/wp-content/uploads/2014/04/Annual_Report_2070_71.pdf. 3. Nepal Constitution Assembly. Constitution of Nepal 2072(2015). 4. National Immunization Program. Reaching Every Child. Comprehensive Multi-year Plan 2068–2072 (2011–2016). Child Health Division, Department of Health Services. MOHP; 2011, May. 5. Child Health Profile of Nepal 2013. Child Health Division, Ministry of Health and Population, Government of Nepal. 6. Government of Nepal, UNFPA. Nepal Demographic health Survey 2011. Available from: http://dhsprogram.com/pubs/pdf/FR257/FR257%5B13April2012%5D.pdf.
K.P. Paudel / Pediatric Infectious Disease 8 (2016) 67–71 7. Shah AS, Deloria KM, Sharma PR, et al. Invasive pneumococcal disease in Kanti Children Hospital, Nepal as observed by South Asian pneumococcal alliance network. Clin Infect Dis. 2009;48(suppl 2):S123–S128. 8. Chhetri UD, Shrestha S, Pradhan R, et al. Clinical profile of invasive pneumococcal diseases in Patan Hospital, Nepal. Kathmandu Univ Med J (KUMJ). 2011;9(January– March (33)):45–49.
71
9. Williams EJ, Thorson S, Maskey M, et al. Hospital-based surveillance of invasive pneumococcal disease among young children in urban Nepal. Clin Infect Dis. 2009;48(suppl 2):S114–S122. http://dx.doi.org/10.1086/596488. 10. Bryant KA, Block SL, Baker SA, et al. Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine. Pediatrics. 2010;125(May (5)):866–875. http:// dx.doi.org/10.1542/peds.2009-1405.
Contents lists available at ScienceDirect
Pediatric Infectious Disease journal homepage: www.elsevier.com/locate/pid
Original Article
PCV 10 introduction in National Immunization Program of Nepal K.P. Paudel Kanti Children’s Hospital, Maharajgunj, Kathmandu, Nepal
A R T I C L E I N F O
A B S T R A C T
Article history: Available online 3 June 2016
Nepal adopted immunization program as expanded program on Immunization in 1977 and it is considered a successful program in Nepal for its role in the reduction of infant and under-five mortality in the country. Pneumonia is a major killer of children and Streptococcus pneumoniae is the common cause of it. Based on the studies done in Nepal covering the existing serotypes, National Committee on immunization practice recommended PCV 10 for its immunization program and it was rolled out in phase-wise manner to all over the country after its introduction in January 2015. The schedule of PCV 10 in the routine National Immunization Program of Nepal is 2p + 1 at 6 weeks, 10 weeks, and 9 months of age. Immunogenicity and impact study are ongoing and it is too early to comment on the further efficacy of this vaccine. ß 2016 Indian Academy of Pediatrics, Infectious Disease Chapter. Published by Elsevier B.V. All rights reserved.
Keywords: Nepal Immunization Pneumonia PCV 10
1. Introduction Nepal is a landlocked country which shares its northern border with China and eastern, western, and southern borders with India. It covers a total land area of 147,181 km2 and has a total population of 28 million1 and less than one year cohort of the country is 660,000.2 Topographically, Nepal is divided into three distinct ecological zones: the mountain (Himal), hill (Pahad), and plain land (Terai) (Fig. 1). For administrative purposes, before adopting the federal system, Nepal was divided into five development regions and 75 districts.1 Districts are further divided into Village Development Committees (VDCs) and municipalities. As per the Nepal’s constitution 2015, health is considered as a right of the people.3 The Ministry of Health and Population (MOHP) in its Nepal National Health Sector Programme Implementation Plan (NHSP-II, 2010–2015) has a goal to improve the health and nutritional status of the Nepali population, especially for the poor and socially excluded. In the area of child health, it had a target to reduce under-five mortality to a level of 38 and infant deaths to 32 per 1000 live births by 2015 with several interventions including: sustaining community-based integrated management of childhood illness (CB-IMCI), maintaining immunization coverage above 90%, and scaling up community-based newborn care.4 The immunization program is one of the government’s highest priority programs.2,4 The immunization program has helped in
E-mail address: [email protected].
reducing the deaths of children and mothers from vaccine preventable diseases (VPDs) and has contributed in achieving Millennium Development Goals (MDG) 4 and 5. The government through its policy documents has emphasized reaching poor and marginalized population with equitable services including immunization. Since the past decades, new vaccines are available in the markets, and the government has put all available means to reduce morbidity and mortality. In this regard, it is essential to have a long-term immunization plan with priority activities identified and as well as a financial sustainability plan. The comprehensive multi-year plan 2011–2016 of Child health division provided a plan to achieve the immunization-related goals expressed by the government in various policy documents, resolutions as well as different national and international forums. The plan also took into consideration the Global Immunization Vision and Strategy (GIVS). The objectives, strategies, and activities set forth in the plan provide the framework required to meet the goal of ‘‘reducing infant and child mortality and morbidity associated with vaccine-preventable diseases (VPDs).’’ This plan also provided guidelines for the introduction of new vaccines, eradication, elimination and control of targeted VPDs, and strengthening of routine immunization. The National Committee on Immunization Practice was established in 2009 to provide vaccine-related recommendations to the government. NCIP provides recommendations on introduction of new vaccines and other immunization-related policies to the government. Nepal introduced Hepatitis B in 2002 and HiB as pentavalent vaccine in 2009 with GAVI co financing. JE vaccines were introduced in 2008 in routine immunization using government funds. The
http://dx.doi.org/10.1016/j.pid.2016.06.003 2212-8328/ß 2016 Indian Academy of Pediatrics, Infectious Disease Chapter. Published by Elsevier B.V. All rights reserved.
K.P. Paudel / Pediatric Infectious Disease 8 (2016) 67–71
68
Fig. 1. Map of Nepal with 5 administrative development regions.
Government of Nepal (GON) introduced rubella vaccine in routine immunization along with Measles after completing a Measles Rubella campaign in 2012. Considering that pneumonia is a major cause among deaths in under-five children and that streptococcus is a significant standing cause of pneumonia, otitis media, and meningitis in children under five years of age, Nepal seriously worked in generation of surveillance data on Pneumococcal diseases since 2005 and applied for GAVI support in the introduction of Pneumococcal vaccine in routine Immunization in Nepal.5 2. Objective of the study To review the national introduction and roll out of Pneumococcal vaccine PCV 10 in routine National Immunization Program of Nepal.
throughout country. The national schedule has seen various additions till recent introduction of Measles Rubella Second dose and HPV demonstration in 2 districts (Table 1).2,4 There is sustained coverage of more than 90% of the various antigens in the national program and the country is still struggling to reach beyond 90% in case of Measles Rubella and the unimmunized population is nearly 3% and nearly 10% of dropout or incomplete immunizations (Figs. 2 and 3).6 Sentinel surveillance for Invasive bacterial disease was conducted at two sites, Patan Hospital and Kanti Children’s Hospital since 2005; however, from 2011, it was continued only in Patan Hospital and it included Hib, pneumococcal, and meningococcal diseases. This study was supported previously by ‘Hib and pneumococcal initiative’ and later by WHO. In this study, the Pneumococcal serotype distribution at Patan Hospital Kathmandu 2005–2012 showed the Serotypes 1, 5, 14 predominant serotypes (Fig. 4).7–9
3. Materials and methods 4.1. Comparison of PCV 10 with PCV 13 in Nepalese context The information and statistics available at the Child Health Division of Department of Health Services form the basis of this article. Similarly, related publications from WHO and UNICEF and related studies in Nepal are the secondary sources of information. 4. Results The Immunization Program of Nepal started with initiatives to eradicate Small Pox and formal routine immunization program started in the year 1977 with piloting of 2 antigens BCG and DPT in 3 districts and it took nearly 10 years to roll out these antigens
As there are 2 Pneumococcal conjugate vaccines available in the market, it was extensively compared in Nepalese context and presented in NCIP meeting (Table 2).9 It is clear that the common serotypes 1, 5, and 14 are present in both PCV 10 and PCV 13 and over to PCV 10 PCV 13 has 3, 6A, 19A. PCV 10 was available in 2 dose vials and NCIP based on the experts’ presentations decided to recommend for PCV 10 for inclusion in NIP in Nepal. A randomized controlled open-label immunogenicity study of the 10-valent Pneumococcal conjugate vaccine. This study showed comparisons between two dose priming with booster to a
Table 1 Timeline of introduction of various vaccines in the Nepal’s national schedule.5 Name of vaccine
Introduction
Doses
Age of administration
BCG DPT-HepB-Hib OPV IPV PCV MR
1977 1977/2003/2009 1988 18 Sep 2014 18 Jan 2015 M 1988: 2012 MRSD: 15 Sep 2015
1 3 3 1 3 2
At birth 6, 10, 14 weeks 6, 10, 14 weeks 14 weeks 6, 10 weeks and 9 months At 9 and 15 months
2+ 1
Pregnant women 12 months (31 districts); after JE campaign 2016 – nation wide
Td JE
2009
K.P. Paudel / Pediatric Infectious Disease 8 (2016) 67–71
69
Fig. 2. The coverage of different antigens in Nepal National Immunization Program in 2014.2
Fig. 3. The coverage status of different vaccines in Nepal’s National Immunization Program: the trend of last 3 years.2
three dose priming schedule in Nepalese infants. The study was carried out at 18 weeks, 10 months, and 2–4 years. The results showed the follow-up at 2–4 years of age demonstrated significantly higher proportions in the 2p + 1 versus 3p + 0 group with IgG concentrations 0.2 mg/ml for serotypes 1, 5, 6B, and 18C (Figs. 5 and 6).8–10 Based on the study presented in the meeting NCIP meeting on August 2014 because of IPV roll out recommends the following PCV
immunization schedule at 6 weeks, 14 weeks and 9 months. This meeting decided the switch of PCV second dose from 14 weeks to 10 weeks because of the fear that multiple vaccines injection (IPV, PCV, DPT-HepB-Hib) at 14 weeks will be unacceptable to many families and for fear of dropout of injection and postponing to further visit (18 weeks) and even this will have huge cost implication to the government. PCV eligibility at the time of introduction was all children from 6 weeks onwards, and for
Table 2 Comparison of PCV 10 over PCV 13.
Serotypes Conjugate Presentation Volume per dose Cold chain volume Costing
PCV-10
PCV-13
1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Non-typeable Haemophilus influenzae, tetanus toxoid, or diphtheria toxoid. Single dose syringe or as 1 or 2 dose vial. 0.5 ml 4.8 cm3/dose Less ($3.5 for 2 dose presentation)
1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. Nontoxic diphtheria CRM 197 (CRM, cross-reactive material) carrier protein. Single dose, fully liquid vial. 0.5 ml 13.2 cm3/dose More expensive ($3.5 for 1 dose presentation)
70
K.P. Paudel / Pediatric Infectious Disease 8 (2016) 67–71
Fig. 4. Serotypes of Pneumococci at Patan Hospital.
Table 3 National rollout of PCV 10 at Nepal. Development region
PCV start
Western development region Eastern development region Central DR, Mid Western DR, FarWestern DR
18 January 2015 April 2015 July 2015
catch-up, dose eligible cohort were children under 1 year of age. The PCV 10 vaccine was added to Nepal’s National Immunization Program since 18 January 2015 and gradually over 6 months time, it was scaled up throughout the country (Table 3).9,10 5. Conclusion
Fig. 5. PCV 10 proportion greater than 0.35 mg/ml at 18 weeks.
Nepal’s National Immunization Program is a priority and it is a successful program in the field of child health of the country and this new addition to its National Immunization Program will be a major milestone given the deaths and morbidity with Pneumococcal diseases. Since the schedule adopted by the country is very new, further evidences on the impact as well as the immunogenicity study will be useful in the further revision of the program to give feedback to its immunization advisory body and the program division. Conflicts of interest The author has none to declare. References
Fig. 6. PCV 10 proportion greater than 0.35 mg at 2–4 years.
1. Central Bureau of statistics (CBS) Government of Nepal. http://www.cbs.gov.np/. 2. Annual Report 2014. DOHS Government of Nepal. Available from: http://dohs.gov. np/wp-content/uploads/2014/04/Annual_Report_2070_71.pdf. 3. Nepal Constitution Assembly. Constitution of Nepal 2072(2015). 4. National Immunization Program. Reaching Every Child. Comprehensive Multi-year Plan 2068–2072 (2011–2016). Child Health Division, Department of Health Services. MOHP; 2011, May. 5. Child Health Profile of Nepal 2013. Child Health Division, Ministry of Health and Population, Government of Nepal. 6. Government of Nepal, UNFPA. Nepal Demographic health Survey 2011. Available from: http://dhsprogram.com/pubs/pdf/FR257/FR257%5B13April2012%5D.pdf.
K.P. Paudel / Pediatric Infectious Disease 8 (2016) 67–71 7. Shah AS, Deloria KM, Sharma PR, et al. Invasive pneumococcal disease in Kanti Children Hospital, Nepal as observed by South Asian pneumococcal alliance network. Clin Infect Dis. 2009;48(suppl 2):S123–S128. 8. Chhetri UD, Shrestha S, Pradhan R, et al. Clinical profile of invasive pneumococcal diseases in Patan Hospital, Nepal. Kathmandu Univ Med J (KUMJ). 2011;9(January– March (33)):45–49.
71
9. Williams EJ, Thorson S, Maskey M, et al. Hospital-based surveillance of invasive pneumococcal disease among young children in urban Nepal. Clin Infect Dis. 2009;48(suppl 2):S114–S122. http://dx.doi.org/10.1086/596488. 10. Bryant KA, Block SL, Baker SA, et al. Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine. Pediatrics. 2010;125(May (5)):866–875. http:// dx.doi.org/10.1542/peds.2009-1405.