Strengthening Immunization Systems through Serosurveillance (SISS)

The Challenge

Sero-epidemiology is a potentially powerful tool to measure population immunity to vaccine-preventable diseases, identify immunity gaps, and guide immunization activities. However, there is a need to evaluate how to design, implement and evaluate serological surveillance systems and make the best use of the data to guide vaccination programs and policy. The SISS project addresses epidemiological, technical, and operational issues critical to the generation and interpretation of valid and timely serological data to identify immunity gaps and guide routine, supplemental and targeted immunization activities.

Approach

Multiple measles and rubella serosurveys were conducted in India and Zambia to demonstrate the feasibility and utility of serological surveillance to guide immunization programs. In India, measles and rubella serosurveys were conducted before and after mass vaccination campaigns in four districts to document increases in population immunity and remaining immunity gaps. In Zambia, measles and rubella serosurveys leveraged a national biorepository and were nested within post-coverage evaluation surveys, measles and rubella SIAs, and the fever/rash surveillance system. Comparisons between seroprevalence estimates obtained from community-based surveys and residual specimens from health care facilities and laboratories were done in both countries. The SISS project developed the website Serosurvey Tools to assist others in the design, implementation, analysis, and interpretation of serological surveys.

Resources

• Strengthening Immunization Systems through Serosurveillance (SISS): Final Report - Lessons Learned and Recommendations

Publications

Zambia:

• Arambepola R, Yang Y, Hutchinson K, Mwansa FD, Doherty JA, Bwalya F, et al. Using geospatial models to map zero-dose children: factors associated with zero-dose vaccination status before and after a mass measles and rubella vaccination campaign in Southern province, Zambia. BMJ Glob Health. 2021;6.
• Carcelen AC, Hayford K, Moss WJ, Book C, Thuma PE, Mwansa FD, Patenaude B. How much does it cost to measure immunity? A costing analysis of a measles and rubella serosurvey in southern Zambia. PLoS One 2020;15:e0240734.
• Carcelen AC, Mutembo S, Matakala KH, Chilumba I, Mulundu G, Monze M, Mwansa FD, Moss WJ, Hayford K. Impact of a Measles and Rubella Vaccination Campaign on Seroprevalence in Southern Province, Zambia. Am J Trop Med Hyg 2021;104:2229-2232.
• Carcelen AC, Winter AK, Moss WJ, Chilumba I, Mutale I, Chongwe G, Monze M, Mulundu G, Nkamba H, Mwansa FD, Mulenga L, Rhoda DA, Hayford K, Mutembo S. Leveraging a national biorepository in Zambia to assess measles and rubella immunity gaps across age and space. Sci Rep 2022;12:10217.
• Carcelen AC, Prosperi C, Mutembo S, Chongwe G, Mwansa FD, Ndubani P, Simulundu E, Chilumba I, Musukwa G, Thuma P, Kapungu K, Hamahuwa M, Mutale I, Winter A, Moss WJ, Truelove SA. COVID-19 vaccine hesitancy in Zambia: a glimpse at the possible challenges ahead for COVID-19 vaccination rollout in sub-Saharan Africa. Hum Vaccin Immunother 2022;18:1-6.
• Carcelen AC, Limaye RJ, Mutembo S, Hamahuwa M, Thuma PE, Moss WJ, Hayford K. Acceptability of serosurveys in southern Zambia: data collector and caregiver perspectives. Discov Soc Sci Health. 2023;3(1):3. doi: 10.1007/s44155-023-00032-6. Epub 2023 Feb 20.
• Carcelen AC, Prosperi C, Hamahuwa M, Kapungu K, Chongwe G, Mwansa FD, Ndubani P, Simulundu E, Bwalya IC, Matakala KH, Musukwa G, Mutale I, Betha E, Chaavwa N, Kampamba L, Matoba J, Munachoonga P, Mufwambi W, Situtu K, Thuma PE, Sakala C, Kayeye P, Truelove SA, Winter AK, Ferrari MJ, Moss WJ, Mutembo S. Feasibility and acceptability of collecting dried blood spots (DBS) from children after vaccination during supplementary immunization activities to estimate measles and rubella seroprevalence. PLOS Glob Public Health. 2024;4(6):e0002985.
• Hayford K, Mutembo S, Carcelen A, Matakala HK, Munachoonga P, Winter A, et al. Measles and rubella serosurvey identifies rubella immunity gap in young adults of childbearing age in Zambia: The added value of nesting a serological survey within a post-campaign coverage evaluation survey. Vaccine. 2019;37:2387-93.
• Kostandova N, Mutembo S, Prosperi C, Mwansa FD, Nakazwe C, Namukoko H, Nachinga B, Chongwe G, Chilumba I, Matakala KH, Musukwa G, Hamahuwa M, Mufwambi W, Matoba J, Situtu K, Mutale I, Kong AC, Simulundu E, Ndubani P, Hasan AZ, Truelove SA, Winter AK, Carcelen AC, Lau B, Moss WJ, Wesolowski A. Who is missed in a community-based survey: Assessment and implications of biases due to incomplete sampling frame in a community-based serosurvey, Choma and Ndola Districts, Zambia, 2022. PLOS Glob Public Health. 2024;4(4):e0003072.
• Mak J, Patenaude BN, Mutembo S, Pilewskie ME, Winter AK, Moss WJ, Carcelen AC. Modeling the Cost of Vaccinating a Measles Zero-Dose Child in Zambia Using Three Vaccination Strategies. Am J Trop Med Hyg. 2024;111(1):121-8.
• Mutembo S, Carcelen A, Mwansa FD, Searle K, Wanyiri JW, Book C, et al. Integrating Blood Collection within Household Surveys: Lessons Learned from Nesting a Measles and Rubella Serological Survey within a Post-Campaign Coverage Evaluation Survey in Southern Province, Zambia. Am J Trop Med Hyg. 2018;99:1639-42.
• Mutembo S, Yang Y, Carcelen A, Winter AK, Mwansa FD, Chilumba I, Mutale I, Chongwe G, Monze M, Mulundu G, Nkamba H, Mulenga L, Hayford K, Moss WJ. Measles immunity gaps among children and adolescents with HIV in zambia despite high measles vaccination and antiretroviral therapy coverage. AIDS. 2023.
• Prosperi C, Truelove S, Carcelen AC, Chongwe G, Mwansa FD, Ndubani P, Simulundu E, Bwalya IC, Hamahuwa M, Kapungu K, Matakala KH, Musukwa G, Mutale I, Betha E, Chaavwa N, Kampamba L, Matoba J, Munachoonga P, Mufwambi W, Situtu K, Thuma PE, Sakala C, Kayeye P, Winter AK, Ferrari MJ, Moss WJ, Mutembo S. High measles and rubella vaccine coverage and seroprevalence among Zambian children participating in a measles and rubella supplementary immunization activity. PLOS Glob Public Health. 2025;5(8):e0003209.
• Winter AK, Takahashi S, Carcelen AC, Hayford K, Mutale W, Mwansa FD, Sinyange N, Ngula D, Moss WJ, Mutembo S. An evaluation of the early impact of the COVID-19 pandemic on Zambia's routine immunization program. PLOS Glob Public Health. 2023;3(5):e0000554.
• Yang Y, Kostandova N, Mwansa FD, Nakazwe C, Namukoko H, Sakala C, Bobo P, Masumbu PK, Nachinga B, Ngula D, Carcelen AC, Prosperi C, Winter AK, Moss WJ, Mutembo S. Challenges Addressing Inequalities in Measles Vaccine Coverage in Zambia through a Measles-Rubella Supplementary Immunization Activity during the COVID-19 Pandemic. Vaccines (Basel). 2023;11(3).

India

• Hasan AZ, Kumar MS, Prosperi C, Thangaraj JWV, Sabarinathan R, Saravanakumar V, et al. Implementing Serosurveys in India: Experiences, Lessons Learned, and Recommendations. Am J Trop Med Hyg. 2021;105:1608-17.
• Kaduskar O, Bhatt V, Prosperi C, Hayford K, Hasan AZ, Deshpande GR, et al. Optimization and Stability Testing of Four Commercially Available Dried Blood Spot Devices for Estimating Measles and Rubella IgG Antibodies. mSphere. 2021;6:e0049021.
• Murhekar MV, Gupta N, Hasan AZ, Kumar MS, Kumar VS, Prosperi C, et al. Evaluating the effect of measles and rubella mass vaccination campaigns on seroprevalence in India: a before-and-after cross-sectional household serosurvey in four districts, 2018-2020. Lancet Glob Health. 2022;10:e1655-e64.
• Prosperi C, Kaduskar O, Bhatt V, Hasan AZ, Vivian Thangaraj JW, Kumar MS, et al. Diagnostic Accuracy of Dried Blood Spots Collected on HemaSpot HF Devices Compared to Venous Blood Specimens To Estimate Measles and Rubella Seroprevalence. mSphere. 2021;6:e0133020.
• Prosperi C, Thangaraj JWV, Hasan AZ, Kumar MS, Truelove S, Kumar VS, et al. Added value of the measles-rubella supplementary immunization activity in reaching unvaccinated and under-vaccinated children, a cross-sectional study in five Indian districts, 2018-20. Vaccine. 2023;41:486-95.
• Prosperi C, Hasan AZ, Winter AK, Chaaithanya IK, Salvi NR, Chauhan SL, Kulkarni RN, Lachyan A, Gawali P, Kapoor M, Bhatt V, Kaduskar O, Deshpande GR, Esteban I, Ramasamy S, Kumar VS, Truelove SA, Kumar MS, Thangaraj JWV, Sangal L, Mehendale SM, Sapkal GN, Gupta N, Hayford K, Moss WJ, Murhekar MV. Measles and rubella seroprevalence in adults using residual blood samples from health facilities and household serosurveys in Palghar District, Maharashtra, India, 2018 - 2019. Epidemiol Infect. 2024;152:e161.
• Prosperi C, Hasan AZ, Winter AK, Chaaithanya IK, Salvi NR, Sharma S, Bansal AK, Chauhan SL, Kulkarni RN, Lachyan A, Gawali P, Kapoor M, Shrivastava AK, Chonker SK, Bhatt V, Kaduskar O, Deshpande GR, Esteban I, Sabarinathan R, Saravana Kumar V, Truelove SA, Kumar MS, Thangaraj JWV, Sangal L, Mehendale SM, Sapkal GN, Gupta N, Hayford K, Moss WJ, Murhekar MV. Increased measles and rubella seroprevalence in children using residual blood samples from health facilities and household serosurveys after supplementary immunization activities in two districts in India. Epidemiol Infect. 2024;152:e143.
• Salvi N, Itta KC, Lachyan A, Hasan AZ, Prosperi C, Kumar MS, et al. Experiences of sharing results of community based serosurvey with participants in a district of Maharashtra, India. PLoS One. 2022;17:e0271920.
• Thangaraj JWV, Prosperi C, Kumar MS, Hasan AZ, Kumar VS, Winter AK, Bansal AK, Chauhan SL, Grover GS, Jain AK, Kulkarni RN, Sharma SK, Soman B, Chaaithanya IK, Kharwal S, Mishra SK, Salvi NR, Sarmah NP, Sharma S, Varghese A, Sabarinathan R, Duraiswamy A, Rani DS, Kanagasabai K, Lachyan A, Gawali P, Kapoor M, Chonker SK, Sangal L, Mehendale SM, Sapkal GN, Gupta N, Hayford K, Moss WJ, Murherkar MV. Post-campaign coverage evaluation of a measles and rubella supplementary immunization activity in five districts in India, 2019-2020. PLoS One. 2024;19(3):e0297385.

General

• Alvarado-Facundo E, Audet S, Moss WJ, Beeler JA. Development of a high-throughput assay to measure measles neutralizing antibodies. PLoS One. 2019;14(8):e0220780
• Holroyd TA, Schiaffino F, Chang RH, Wanyiri JW, Saldanha IJ, Gross M, Moss WJ, Hayford K. Diagnostic accuracy of dried blood spots for serology of vaccine-preventable diseases: a systematic review. Expert Rev Vaccines. 2022;21:185-200.
• Lutz CS, Hasan AZ, Bolotin S, Crowcroft NS, Cutts FT, Joh E, Loisate S, Moss WJ, Osman S, Hayford K. Comparison of measles IgG enzyme immunoassays (EIA) versus plaque reduction neutralization test (PRNT) for measuring measles serostatus: a systematic review of head-to-head analyses of measles IgG EIA and PRNT. BMC Infect Dis. 2023;23(1):367.
• Pilewskie M, Prosperi C, Bernasconi A, Esteban I, Niehaus L, Ross C, Carcelen AC, Moss WJ, Winter AK. The Use of Residual Blood Specimens in Seroprevalence Studies for Vaccine-Preventable Diseases: A Scoping Review. Vaccines (Basel). 2025;13(3).
• Winter AK, Martinez ME, Cutts FT, Moss WJ, Ferrari MJ, McKee A, Lessler J, Hayford K, Wallinga J, Metcalf CJE. Benefits and Challenges in Using Seroprevalence Data to Inform Models for Measles and Rubella Elimination. J Infect Dis. 2018;218(3):355-64.