M Silitongo¹, ML Mazaba², D Mulenga³, M Chirambo-Kalolekesha¹, EM Njunju¹, V Daka³, W Tinago⁴, E Rudatsikira ⁵, PM Syapiila ³, C Banda ³, T Marufu⁶, S Siziya⁷

1. Department of Basic Sciences, Michael Chilufya Sata School of Medicine, Copperbelt University, Ndola, Zambia

2. The Health Press, Zambia National Public Health Institute, Ministry of Health, Lusaka, Zambia

3. Department of Clinical Sciences, Public Health Unit, Michael Chilufya Sata School of Medicine, Copperbelt University, Ndola, Zambia

4. School of Medicine and Medical Science, University College Dublin, Dublin, Ireland

5. Department of Public Health, Nutrition and wellness, School of Health Professionals, Andrews University, Berrien Springs, Michigan, USA

6. Department of Community Medicine, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe

7. Dean’s Office, Michael Chilufya Sata School of Medicine, Copperbelt University, Ndola, Zambia

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Citation Style For This Article: Silitongo M, Mazaba Ml, Mulenga D, et.al. Cluster Survey Evaluation of Reasons of Vaccination Failure in Measles-Rubella Vaccination Campaign in Zambia, 2016. Health Press Zambia Bull. 2019;3(1); Pp 21-26.

Abstract

A pool of susceptible children to measles and rubella (MR) may increase partly due to non-vaccination of children and as a result lead to MR epidemics. The objective of this study was to establish reasons for non-vaccination in 2016 Measles-Rubella campaign in Zambia. A country-wide cross sectional study was conducted among children aged 9 months to 14 years of age. A total of 6,490 children participated in the survey with a response rate of 87.3%. The following were the common reasons for non-vaccination of children: Central province (56.8% stated that vaccine was not available); Copperbelt (26.3% reported family problems including illness of mother/care taker); Eastern (26.6% indicated that time for session was inconvenient); Luapula (23.8% were unaware of the need for vaccination); Lusaka (24.9% indicated fear of side effects); Muchinga (22.4% stated that mother/caretaker was too busy); Northern (17.0% reported that mother/caretaker was too busy); North-western (38.1% indicated that the vaccine was not available); Southern (53.0% reported that the vaccine was not available) and Western (26.4% were unaware of the need for vaccination) and National (23.5% indicated that the vaccine was not available). There is need to increase coverage in the distribution of MR vaccine to ensure that all children receive the vaccine. Health education and promotion activities must be conducted in communities to ensure that the concept of immunization is well received so that deliberate efforts will be applied to ensure that children are vaccinated..

Keywords: Measles, Rubella, reasons for non-vaccination, Zambia.

Introduction

Measles and Rubella are highly contagious viral infections [1,2]. Measles is caused by an enveloped ribonucleic acid (RNA) virus of the Morbillivirus genus in the family Paramyxoviridae [2,3] and is characterised by fever cough, running nose conjunctivitis and characteristic erythematous and maculopapular rash [3-5]. Meanwhile, rubella is caused by a single-stranded ribonucleic acid virus of the Togaviridae family and is the only member of the genus Rubivirus. The disease causes mild symptoms in children and adults whilst causing abortions, miscarriages and congenital rubella syndrome [6]. Despite both diseases causing morbidity and mortality in developing countries, they are both vaccine preventable diseases [5]. Developed countries have managed to control and eradicate these diseases by implementing measures such as giving a first dose of MMR at age 12-15 months, giving a second dose of MMR to school-age going children and vaccinating high-risk groups such as infants aged 6 to 11 months [7]. In an effort to control measles and rubella, developing countries have conducted vaccination campaigns [2,8-11]. Strategies implemented in Cuba included vaccinating men and women of childbearing age and developing integrated measles and rubella surveillance systems [12].

The Expanded Programme on Immunization in Zambia is one of the health priorities in addressing and reducing vaccine preventable diseases such as pneumonia, diarrhoea and measles, which have been the leading causes of death in children under the age of five years. The National Immunisation Programme introduced a number of new and underused vaccines between 2004 till 2013 starting with the tetravalent: DTP+Hib and switching to pentavalent DPT-HepB+Hib in 2005. Measles containing vaccine second dose (MCV2) and Pneumonia Conjugate Vaccine (PCV10) were introduced in the national immunisation programme in July 2013 while Rotavirus and Human Papilloma Vaccine (HPV) vaccines were introduced in Lusaka province as a demo project in 2012 and 2013 respectively and there was a Rota vaccine national roll-out was in November 2013. Following documentation of Congenital Rubella Syndrome and the measles case based surveillance, the results of which have shown that up to 30% of suspected measles cases tested positive for Rubella, justification for the introduction of rubella vaccine.

Zambia conducted two under 15 years integrated measles supplemental immunisation campaigns between 2003 and 2012. The measles-only supplemental immunisation activities (SIAs) offered a second opportunity for vaccination against measles through a mass vaccination campaign. Additionally, the country conducted countrywide follow-up mass measles vaccinations in 2007 and 2010, and a measles-rubella SIA was conducted in September 2016. The introduction of the measles-rubella combined vaccine and a two dose vaccination schedule is important in maintaining adequate vaccination coverage and keeping antibody levels against measles and rubella sufficiently high [1,11]. Failure to be vaccinated contributes to increasing a pool of susceptible children that may lead to epidemics. The objective of this study was to establish reasons for non-vaccination in 2016 Measles-Rubella campaign in Zambia.

Methods

Study area

A study was conducted in all 10 provinces of Zambia (Central, Copperbelt, Eastern, Luapula, Lusaka, Muchinga, Northern, North Western, Southern and Western). Zambia shares borders with the following countries: Malawi and Mozambique in the east, Democratic Republic of Congo and Tanzania in the north, Angola in the west, and Zimbabwe and Namibia in the south (Figure 1). The 10 province are further subdivide into districts, constituencies and wards. In 2010, there were 74 districts, 150 constituencies and 1,430 wards [13]. The number of districts in Zambia has since been increasing.

Zambia has a population of 13,092,666 with a population density of 17.4 persons per square kilometer [13]. About half (50.7%) of the population is male. Zambia has a young population with 45.4% of its population aged below 15 years. Officially, children start schooling at the age of seven years. They would be of age 7-13 years in Grades 1-7 (primary education) and 14 or 15 years in Grades 8 or 9 (lower secondary education). The overall net primary school attendance rate is 71.6% (72.2% of females and 70.9% of males; 79.6% in urban and 66.9% in rural areas). The under-five mortality rate stood at 75 deaths per 1000 live births in 2013/14 [14].

Study design, target population, sample size and sampling.

A cross sectional study was conducted among children aged 9 to 179 months. The required sample size for the number of clusters was determined using a method proposed by the World Health Organization [15] and considering a desired precision of +5%, expected immunization coverage of 95%, effective sample size of 162 in each province, a design effect for each province varied from 1.04 to 2.29 and a 10 percent non response rate. The required sample size of 228 clusters was obtained, giving 2736 households (12 households in each cluster).

A two-stage cluster sampling method was used to draw the sample. At the first sampling stage, the sampled Standard Enumeration Area(s) (SEAs) were selected within the provinces systematically with probability proportional to size (PPS) from the ordered list of SEAs on the census 2010 sampling frame. The measure of size for each (Enumeration Area) EA was based on the household size identified in the 2010 Census [13]. In order to ensure representation from the whole target area, the frame was sorted by district, constituency, ward, rural/urban, (Census Supervisory Area (CSA) and SEA. A systematic random sampling method was used to select households in the second stage of sampling.

Training and data quality

Training of research assistants was facilitated by national supervisors, statistician and local consultant. External Consultants from WHO IST AFRO and UNICEF ESARO provided technical support during training in addition to quality control during field work. The questionnaire was interviewer administered to the respondents. Data quality team consisting of WHO, UNICEF, MoH and the local consultant visited the survey teams in the field to check on the work conducted and the quality of data. During the visit, the team reviewed the completed questionnaires with the supervisors and interviewing teams for any errors or missing information and corrective measures were immediately taken. The quality control team ensured that they observed the process of one household being interviewed from the beginning to the end of the interview as means of verifying adherence to survey protocol.

Data Management and analysis

Household data were computerized using the Coverage Survey Analysis System (WIN-COSAS) software.  Double entry was done on all data sets to control for and correct any entry errors. Data analysis was conducted using SPSS. All analyses were weighted to adjust for varying response rates according to proportions of clusters and households that were selected in the stratum.

Table 1. Household response rates at provincial and national levels

Results

Totals of 2,389 households and 6,490 children were enrolled into the survey.  Table 1 shows response rate at provincial and national levels.  Response rates of above 85% were achieved in all the provinces except Copperbelt (75.5%) and Southern (76.0%) province. The national response rate was recorded at 87.3%. Overall, 5.0% (5.5% of males and 4.6% of females) of children were not vaccinated.

Reasons for non-vaccination of children are shown in Table 2.  Overall, in all the provinces except Lusaka and Western provinces, obstacles were the main reasons for non-vaccination of children.  In Lusaka province, the main reason for non-vaccination of children was fear of side reaction (24.9%). Meanwhile, in Western province the main reasons for non-vaccination was luck of availability of the vaccine (23.6%) and  unawareness of the  need for immunization (26.4%).  Specifically, the following were the common reasons for non-vaccination of children: Central province (56.8% stated that vaccine was not available); Copperbelt (26.3% stated family problems including illness of mother/care taker); Eastern (26.6% indicated that time for session was inconvenient and 20.4% were unaware of the need for vaccination); Luapula (23.8% were unaware of the need for vaccination); Lusaka (24.9% indicated fear of side effects); Muchinga (22.4% stated that mother/caretaker was too busy); Northern (17.0% reported that mother/caretaker was too busy and 16.5% decided to postpone until another time); North-western (38.1% indicated that the vaccine was not available and 19.4% said that the health worker was absent); Southern (53.0% said that the vaccine was not available) and Western (26.4% were unaware of the need for vaccination while 23.6% said the vaccine was not available).  Nationally, 23.5% said that the vaccine was not available while 13.0% were unaware of the need for immunization.

Source: https://zambiareports.com/wp-content/uploads/2015/11/Zambian-Map.jpg

Figure 1: Map of Zambia showing its provinces and neighbouring countries

Table 1: Reasons for child not being vaccinated by province in percentages

Discussion

This study investigated the causes of non-vaccination in the 2016 Measles/Rubella vaccination campaign. The main reason for non-vaccination in five of Zambia’s ten provinces was unavailability of vaccine. On the Copperbelt province, the main reason for non-vaccination was family problem including illness of mother/care taker whilst in Lusaka province it was the fear of side reactions. Inconvenient time of vaccination session and mother or caretaker being too busy were the main reasons in the Eastern and Northern provinces respectively. Lack of enough coverage during vaccination has also been cited as a cause of non-vaccination and Measles/Rubella outbreaks [2,16]. The 2010 – 2011 Measles outbreaks in Zambia were attributed to low routine immunisation coverage [17]. In Mozambique, some measles outbreaks have been associated with insufficient vaccine coverage to interrupt measles transmission [18]. In Nigeria where there is perennial, low routine vaccination coverage and where the quality of the mass immunization campaign is not high enough, large and persistent measles outbreaks continue to occur with high morbidity and mortality [19,20].

In Haiti, Tohme et al [16] reported 31% of non-vaccination being due to caregivers not being aware of the vaccination exercise. This was one of the main reasons for measles-rubella non-vaccination in Luapula, Eastern and Western provinces of Zambia. At national level in Zambia, the main reason for non-vaccination was unavailability of vaccine unlike in Haiti where vaccine unavailability was not among the main reasons. World Health Organisation (WHO) Global Burden of Disease (GBD) project indicate that approximately 1.7 million vaccine-preventable childhood deaths occurred in 2000, of which 46% were attributed to measles. The measles deaths occurred overwhelmingly among children living in poor countries with inadequate vaccination services [21]. Failure to control measles has usually been due to a failure to implement planned strategies adequately [22]. For complete elimination of Measles there is the need to raise the visibility of measles elimination and make adequate investments in strengthening health systems [2,23]. Sartorious et al [2] suggested that identifying and targeting emerging high-risk areas in resource-limited settings where vaccine coverage is low or waning appears a more viable strategy for preventing outbreaks in sub-Saharan.

Conclusion

The control and eventual eradication of measles and rubella partly hinge on the ability to vaccinate all children to avoid pool of susceptible children to increase that could lead to epidemics. There is need to increase coverage in the distribution of MR vaccine to ensure that all children receive the vaccine. Health education and promotion activities must be conducted in communities to ensure that the concept of immunization is well received so that deliberate efforts will be applied to ensure that children are vaccinated.

List of References 

1.  Takayama N. Measles and rubella. Rinsho Byori 2005;53:845-52.

2.   Sartorius B, Cohen C, Chirwa T, Ntshoe G, Puren A, Hofmana K. Identifying high-risk areas for sporadic measles outbreaks: lessons from South Africa. Bull World Health Organ 2013;91:174-183.

3.  WHO. Immunization, vaccines and biological: The immunological basis for immunization series: Module 7: Measles. Update 2009. Geneva, Switzerland: World Health Organization, 2009.

4.    Permar SR, Moss WJ, Ryon JJ, Monze M, Cutts F, Quinn TC, et al. Prolonged measles virus shedding in human immunodeficiency virus–infected children, detected by reverse transcriptase – polymerase chain reaction. J Infect Dis 2001;183:532–8.

5.   Moss WJ, Griffin DE. Global measles elimination. Nat Rev Microbiol 2006;4:900-8.

6. Zuckerman AJ,  Banatvala JE,  Pattison JR,  Griffiths PD, Schoub BD. Principles and practice of clinical virology, 5th Edition. John Wiley & Sons, Ltd,  2004.

7. Otten M, Kezaala R, Fall A, Masresha B, Martin R, Cairns L, et al. Public-health impact of accelerated measles control in the WHO African Region 2000-03. Lancet 2005;366:832–9.

8. WHO, UNICEF. Measles: mortality reduction and regional elimination strategic plan 2001–2005. Geneva: World Health Organization & United Nations Children’s Fund, New York; 2001.

9. Centers for Disease Control and Prevention (CDC). Progress toward measles elimination–Southern Africa, 1996–1998. MMWR Morb Mortal Wkly Rep 1999;48(27):585-9.

10.    Manakongtreecheep K, Davis R. A review of measles control in Kenya, with focus on recent innovations. Pan Afr Med J. 2017;27(Suppl3):15.

11. Pan American Health Organization Division of Vaccines and Immunization. Final report. Conclusions and recommendations. 14th meeting of the Technical Advisory Group on Vaccine Preventable Diseases. Brazil: PAHO; 2001.

12. Central Statistical Office [Zambia]. 2010 Census of population and housing: national analytical report. CSO, Lusaka, 2012.

13. Central Statistical Office (CSO) [Zambia], Ministry of Health (MOH) [Zambia], and ICF International. Zambia Demographic and Health Survey 2013-14. Rockville, Maryland, USA: Central Statistical Office, Ministry of Health, and ICF International, 2014.

14. WHO. Vaccination coverage cluster survey: Reference manual Annexes, July 2015. Accessed 2018 July 15. URL: http://www.who.int/immunization/monitoring_surveillance/Vaccination_coverage_cluster_survey_with_annexes.pdf.

15. Tohme RA, François J, Wannemuehler K, Magloire R, Danovaro-Holliday MC, Flannery B, et al. Measles and rubella vaccination coverage in Haiti, 2012: progress towards verifying and challenges to maintaining measles and rubella elimination. Trop Med Int Health. 2014;19:1105-15.

16.  Mpabalwani ME, Matapo B, Katepa-Bwalya N, Mukonka V, Mutambo H, Babaniyi OA. The 2010-2011 measles outbreak in Zambia: Challenges and lessons learnt for future action. East Afr J Public Health 2013;10:265–73.

17. Muloliwa AM, Camacho LAB, Verani JFS, Simões TC, Dgedge MC. Impact of vaccination on the incidence of measles in Mozambique in the period 2000 to 2011. Cad Saúde Pública (Rio de Janeiro) 2013;29:257-69.

18. Okonko O, Nkang AO, Udeze AO, Adedeji AO, Ejembi J, Onoja BA, et al. Global eradication of measles: a highly contagious and vaccine preventable disease-What went wrong in Africa? J Cell Animal Biol 2009;3(8):119-40.

19. Salako AA, Sholeye OO. Control of measles in Nigeria: A critical review of the literature. Br J Med Med Res 2015;5:160-8.

20. Centers for Disease Control and Prevention (CDC). Update: global measles control and mortality reduction–worldwide, 1991-2001. MMWR Morb Mortal Wkly Rep. 2003;52:471-5.

21. Cutts FT, Markowitz LE. Successes and failures in measles control. J Infect Dis. 1994;170(Suppl 1):S32-41.

22. Perry RT, Gacic-Dobo M, Dabbagh A, Mulders MN, Strebel PM, Okwo-Bele JM, et al. Global control and regional elimination of measles, 2000–2012. MMWR Morb Mortal Wkly Rep. 2014;63:103-7.

Contributors: Brave maxwell katemba, Brittany Gianetti, Chanda Groeneveld, Dien Mwansa Kaluba Musakanya, Brivine sikapande Josephine Simwinga,Raymond Hamoonga, Mazyanga Lucy Mazaba

1. information systems unit Zambia National public health institute

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Citation style for this article: Katemba BM, Gianetti B, Groeneveld C, et al. A retrospective analysis of measles trends and vaccination coverage in Zambia from 2016 to 2018. Health Press Zambia Bull. 2019;3(1); pp 1-2.

Introduction

Measles is a highly contagious infection caused by the measles virus (MeV). The MeV is transmitted from person-to-person via respiratory droplets or aerosolized small particles suspended in the air as a result of sneezing or coughing. On average, a single measles case infects 9-18 people (Ro= 9-18); in comparison, a person infected with influenza only infects 2-3 people (Ro= 2-3)1.

Prior to the introduction of the measles vaccine in the 1960s, measles was a leading cause of childhood mortality, accounting for 2 million deaths globally each year.  The number of measles deaths decreased drastically due to the initiation of the Expanded Program on Immunization in 1974 and subsequent increase in global measles vaccination coverage2. Approximately 110,000 measles deaths were reported in 2017.

The World Health Organization (WHO) recommends that a child receive the first dose of measles containing vaccine (MCV1) at 9 months. However, MCV1 can be administered at 6 months if the infant lives in an area experiencing a measles outbreak, is classified as an internally displaced person or a refugee, or is born with HIV.  The measles containing vaccine (MCV) is 85% effective in children vaccinated at 9 months. In countries that schedule MCV1 at 9 months, a second dose of MCV (MCV2) is recommended at 15-18 months. The estimated 2015 global coverage for MCV1 and MCV2 was 85% and 61%, respectively1.

In the 1990s measles immunisation coverage in Zambia was less than 70%, and measles outbreaks occurred on a yearly basis3. In 1991 Zambia reported 1,698 cases of measles, and in 1999 the number rose to 23,518 measles cases. During the 1999 measles outbreak the mortality rate in hospitalized children was 13.7%3. In response, Zambia launched supplemental immunisation activities (SIAs) targeting children between 9 months and 4 years of age to increase immunity in the under five population4. Zambia continued its routine MCV immunisation program and performed additional MCV SIAs in 2000, 2003, 2007, and 20103,4. Despite the incorporation of MCV SIAs, Zambia experienced a measles outbreak in 2010/2011 that resulted in 35,572 cases and 242 deaths (Case Fatality Rate: 0.64%)3,5.

In September 2018, Zambia launched a national immunsation campaign using a combined measles and rubella vaccine targeting all children between the ages of 9 months and 15 years. The routine childhood immunisation schedule in Zambia recommends administration of MCV1 at 9 months and MCV2 at 18 months. In 2015, the Zambian MCV1 and MCV2 coverage estimates were 90% and 47%, respectively6. Currently, Zambia seeks to achieve 95% child MCV coverage each year through its routine immunization program.

The number of measles cases and deaths due to measles in Zambia has been steadily declining over the past decade.  In order to determine the trends in measles cases in Zambia during the past few years, we analyzed national surveillance and immunisation data from 2016-2018.

Methods

To identify weekly trends in measles cases in Zambia, we conducted a retrospective analysis of measles data collected using the Integrated Disease Surveillance and Response (IDSR) system between 2016 and 2018. Data was extracted from the weekly 2016, 2017 and 2018 IDSR reports and analyzed using Microsoft Excel and STATA 13. To determine national MCV1 and MCV2 immunisation coverage from 2016-2018, we accessed childhood immunisation data reported in the Zambian Health Management Information Systems (HMIS). Vaccination coverage was calculated by dividing the reported annual number of MCV1 and MCV2 doses administered by the estimated number of children <1 year (MCV1) and <2 year (MCV2), as determined by projected census data adjusted for annual population growth. All surveillance data used in this paper were generated within the IDSR framework of Zambia and represents the national picture of reported measles cases.

Results

The IDSR definition of a suspected measles case is: any person with fever and maculopapular generalized rash and cough, coryza or conjunctivitis, or any person in whom a clinician suspects measles. Using the IDSR definition, Zambia reported a total of  688 in 2016, 606 in 2017 and 558 suspected measles cases in 2018 (Table 1).

In 2018, a spike in the number of suspected measles cases occurred on epidemiological week 17, during which 35 suspected cases were reported in North-western province (Figure 1 & Figure 2). Twenty suspected measles cases were reported in Luapula province in epidemiological week 30 (Figure 2). During this period, from July 5th to July 30th 2018, 24 suspected measles cases were reported in six districts in Luapula province (Mansa, Mwense, Mwansabombwe, Nchelenge, Lunga and Samfya). Sixteen patients

Figure 1: Reported suspected measles cases in Zambia 2016-2018

Figure 2: Trends in suspected measles cases by province (2018)

were treated for measles and discharged from health facilities, and one fatality was reported in the community. In response, a field investigation was undertaken in the affected districts. Blood samples from all 24 suspected measles cases were sent to the virology laboratory at University Teaching Hospital (UTH) for laboratory confirmation, and four measle cases from the Paul-Mambilima Regional Health Center in Mansa district were laboratory confirmed. As a result, a mass MCV campaign was carried out in the Paul-Mambilima Regional Health Center catchment area for children between the ages of 4 months and 15 years. The highest number of suspected measles cases (43 cases) was reported during week 47 (Figure 1). Twenty of the 43 cases were reported from Central province.

Without factoring the total population at risk per province, Luapula province reported the highest number of suspected measles cases (114 suspected cases) in 2018, and North-western province reported the second highest number of suspected measles cases (83 suspected cases). The lowest numbers of suspected measles cases were observed in Eastern (18 suspected cases) and Muchinga (6 suspected cases) provinces (Figure 3).

Suspected cases of measles are confirmed by laboratory testing.  Blood samples are collected from suspected cholera cases and sent to UTH for serologic testing for measles virus specific antibodies (IgM).  In 2016, 61% of all suspected cases had blood samples sent to UTH for laboratory confirmation. In 2017 and 2018 75% and 62% of suspected cases were tested at UTH, respectfully (Table 1).   Of the 420 blood samples sent for laboratory confirmation in 2016, only 6 (1.4%) tested positive for measles. In 2017, 456 samples were sent for laboratory confirmation and only 12 (2.6%) were positive (Table 1). In 2018, only 19 (5.5%) out of the 344 suspected blood samples tested positive. The highest number of confirmed measles cases (13 cases) in 2018 occurred during the third quarter (Table 1).

During this same period, MCV1 coverage in Zambia decreased from 97% in 2016 to 93% in 2018 (Figure 4). Despite the decrease in MCV1 coverage, MCV2 coverage increased from 58% in 2016 to 66% in 2018 (Figure 4).

Figure 3: Reported suspected measles cases by province  2018

Figure 4: Measles immunisation coverage in Zambia (2016 – 2018)

Discussion

In 2018 Zambia reported 558 suspected measles cases.  Peaks in the numbers of reported suspected measles cases occurred on epidemiological weeks 17, 30, and 47. A field investigation into an increase in suspected measles cases in Luapula province on week 30 led to a mass MCV campaign in Mansa district.  Slightly more than one third of all measles cases reported in 2018 were from Lupuala and North-western provinces.  These provinces border the Democratic Republic of the Congo, where ongoing conflicts and disease outbreaks have disrupted routine childhood immunisations and led to an increase in cases of vaccine-preventable diseases. As a result, the DRC reported 6,949 suspected cases of measles in 2018.

Similarly, the 2010-2011 measles outbreak in Zambia was largely influenced by cross-border transmission of measles from neighboring countries with low MCV coverage.   Spatial clustering of the 2010-2011 outbreak showed that frequent border crossing of the Chewa people between Zambia and Malawi led to measles importation in border towns8.

The measles virus can only remain in circulation in human populations if transmission is undisrupted.

In order to achieve herd immunity and prevent the transmission of measles, 90-95% of a population must be immune to the disease1. The goal of the Zambian government is to achieve 95% MCV coverage in children under 5 years old. In 2016, 97% of children under the age of 1 year received MCV1, and 58% of children under the age of 2 years received MCV2. MCV1 coverage decreased to 93% in 2018, below the 95% goal, yet MCV2 coverage increased to 66%. High levels of MCV1 and MCV2 must be maintained in order to eliminate measles in Zambia and reduce the risk of cross-border transmission of measles from neighboring countries.

Several factors can influence vaccine uptake, including availability of vaccines, proximity of populations to health facilities, cultural or religious beliefs, and poor knowledge of or misinformation about vaccines. In resource poor areas, researchers have found that some nurses are reluctant to open a multi-dose vaccine, for fear that they will waste the remaining doses. Furthermore, as measles cases become more rare, the perceived threat of measles in the population decreases, causing vaccination compliance to also decrease9.

Review of the 2016-2018 laboratory data showed that only 0.8% (2016) to 3.4% (2018) of suspected measles cases were identified as positive by laboratory confirmation.  This is partly due to the suspected measles case definition used by the IDSR. The suspected case definition is very broad, because the definition must be highly sensitive in order to detect all measles cases and prevent rapid spread of measles. It is less important for the case definition to be specific, so many other viral diseases are detected using the suspected measles case definition. However, another factor is that the proportion of blood samples collected from suspected measles cases for laboratory confirmation was only 62% in 2018. According to WHO, ≥ 80% of all suspected measles cases must provide blood samples in order to detect an outbreak10.  Therefore, Zambia must increase sample collection from suspected measles cases in order to attain the required minimum 80% to efficiently to detect an outbreak.

Conclusion & Recommendations

Due to improvements in routine childhood immunisation programs and national surveillance systems over the past 20 years, the number of suspected measles cases in Zambia has decreased drastically from 35,572 in 2010 to 558 in 2018.

While it is evident that Zambia is making progress towards achieving the 95% WHO recommended vaccination coverage, much work must be done to improve MCV2 coverage. In order to interrupt measles transmission in the country, areas with low vaccine coverage should be targeted, with an emphasis on strengthening immunisation coordination programs in border regions.

Zambia in partnership with the WHO and UNICEF have greatly improved measles surveillance over the last two decades by implementing IDSR. IDSR has helped with early detection of measles cases and the prevention of large scale outbreaks. However, it is important to continue to train healthcare workers in IDSR definitions in order to promote timely and accurate reporting of data. Sensitization of healthcare workers about measles case definitions and reporting procedures could also help increase the proportion of suspected measles cases for whom samples are collected and sent to UTH for laboratory confirmation.

Table 1: Measles laboratory confirmation in Zambia (2016-2018)

List of References

1. Moss WJ. Measles. Lancet. 2017;390(10111):2490–502.

2. Moss WJ, Griffin DE. Global measles elimination. Nat Rev Microbiol. 2006;4(12):900–8.

3. Mpabalwani M, Matapo B , Katepa-Bwalya M , Mukonka V, Mutambo H, Babaniyi OA. The 2010–2011 measles outbreak in Zambia: challenges and lessons learnt for future action. East Afr J of Public Health. 2013; 10(1): 265–273.

4. Centers for Disease Control and Prevention. Progress in Measles Control – Zambia, 1999—2004. MMWR Morb Mortal Wkly Rep. 2005;54(23):581-584.

5. Pinchoff J, Chipeta J, Banda GC, Miti S, Shields T, Curriero F, et al. Spatial clustering of measles cases during endemic (1998-2002) and epidemic (2010) periods in Lusaka, Zambia. BMC Infect Dis. 2015;15:121.

6. World Health Organization and United Nations Children’s Fund. Zambia: WHO and UNICEF Estimates of Immunization Coverage: 2015 Revision. 2017. URL: http://www.who.int/immunization/monitoring_surveillance/data/zmb.pdf

7. World Health Organization. Measles and Rubella Surveillance Data. URL: http://www.who.int/immunization/monitoring_surveillance/burden/vpd/surveillance_type/active/measles_monthlydata/en/

8. Brownwright TK, Dodson ZM, Van Panhuis WG. Spatial clustering of measles vaccination coverage among children in sub-Saharan Africa. BMC Public Health. 2017;17(1):957.

9. Rainey JJ, Watkins M, Ryman TK, Sandhu P, Bo A, Banerjee K. Reasons related to non-vaccination and under-vaccination of children in low and middle income countries: findings from a systematic review of the published literature, 1999-2009. Vaccine. 2011;29(46):8215–21.

10. Spika JS, Wassilak S, Pebody R, Lipskaya G, Deshevoi S, Guris D, et al. Measles and rubella in the World Health Organization European region: diversity creates challenges. J Infect Dis. 2003;187 Suppl 1:S191-197.

K Ndashe¹, S Munjita², N Tembo³, S Musanka², B Mumba¹

1. Department of Environmental Health, Faculty of Health Science, Lusaka Apex Medical University, Lusaka, Zambia

2. Department of Biomedical Sciences, School of Medicine, the University of Zambia, Lusaka, Zambia.

3. Department of Public Health, School of Health Sciences, University of Lusaka, Lusaka, Zambia.

Correspondence: Kunda Ndashe (ndashe.kunda@gmail.com)

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Citation style for this article: Ndashe K, Munjita S, Tembo N, Musanka S, Mumba B. Measles Viruses in Zambia: A Review on Circulating Wild-type Genotypes and Complications with Human Immunodeficiency Virus and control (2006-2016). Health Press Zambia Bull. 2019;3 (1); pp 7-14.

This work has been adapted from the original article “[ IMeasles Viruses in Zambia: A Review on Circulating Wild-type Genotypes and Complications with Human Immunodeficiency Virus]” by [Kunda Ndashe, Samuel Munjita, Novan Tembo, Sody Musanka, Bernadette Mumba and with input from the Journal of Preventive and Rehabilitative Medicine ]. Vol. 1, No. 1, 2018, pp. 5-11. doi: 10.21617/jprm.2018.0101.1

Measles is a highly contagious disease that most commonly affects children. The disease continues to record morbidity and mortality among infants in Zambia. We searched online databases such as PubMed, Scopus, Google Scholar, and National Center for Biotechnology Information (NCBI) database and ISI Web of Science and critically reviewed appropriate publications to extract consistent findings, the wild-type MeV present in Zambia, the complications of Measles and the Human immunodeficiency Virus and the control of Measles in Zambia. We included 18 research articles and 2 epidemiological bulletins in the synthesis. From the search of the NCBI database a total of 80 nucleotide sequences of 48 MeV isolates were obtained, 34 sequences (25 MeV isolates) from Zambia and 46 sequences (23 MeV isolates) WHO reference strains. Out of the 34 sequences from Zambia, 9 and 25 were H-gene and N-gene nucleotide sequences, respectively. This study identified 3 MeV genotypes in Zambia (B2, B3 and D2) spatially distributed in Lusaka, Ndola, Kitwe, Mwense and Samfya. Infants born from women who are HIV-1 seropositive had lower maternal antibodies and post initial vaccination antibodies to measles in HIV-1-infected infants waned off rapidly. The review re-emphasized the need for supplemental immunisation activities which include second opportunity to immunisation and case-based surveillance.

Key words: Measles virus, genotypes, control, Zambia

1. Introduction

Measles is a highly contagious disease that most commonly affects children. It is caused by an enveloped nonsegmented, negative stranded RNA Measles virus (MeV) of the genus Morbillivirus, family Paramyxoviridae [1]. The MeV genome encodes a total of eight proteins. The six structural proteins are the nucleocapsid protein (N), phosphoprotein (P), matrix protein (M), fusion protein (F), attachment protein (H), and the large error-prone RNAdependent RNA polymerase protein (L) [2]. Two additional nonstructural proteins (C and V) are encoded in the P transcription unit. While the C protein is translated from an overlapping reading frame within the P gene, the V protein is initiated from the same start codon as P, but a frame-shift is created by mRNA editing [3]. The outcome is that P and V share an N-terminal domain of 231 amino acids, but differ in their C-terminal domains (276 and 69 amino acids, respectively). The N and H gene sequences are most commonly used for genetic characterization of wild-type MeV [4]. The World Health Organisation (WHO) currently recognizes 8 clades, designated A, B, C, D, E, F, G, and H. Within these clades, there are 23 recognized genotypes, designated A, B1, B2, B3, C1, C2, D1, D2, D3, D4, D5, D6, D7, D8,D9, D10, E, F, G1, G2, G3, H1, and H2, and 1 provisional genotype, d11 [5].

In the developed world, measles immunisation programmes have reduced the number of cases reported annually to negligible levels [6]. Nonetheless, measles remains a major health problem in densely populated urban communities in sub-Saharan Africa [7]. In Zambia, measles is endemic with transmission peaks occurring between August and December, despite the relentless efforts of immunisation [8]. Since 1992, MeV has been isolated from children admitted to hospital in Lusaka, Zambia. Between 1992 and 1995, the University Teaching Hospital in Lusaka clinically diagnosed 1066 children with measles of which 203 (19.0%) were less than the 9 months of age which is the recommended time for measles vaccination in Zambia [8]. In another study conducted in Zambia, out of 277 children with clinical measles that were admitted to the University Teaching Hospital, of 149 samples tested, 132 (88.6%) were positive for IgM antibody while 14 (20.9%) of 67 samples, measles viruses were isolated [9]. The latter study highlights the importance of confirmatory tests in the diagnosis of measles to avoid misdiagnosis, since other clinical conditions may cause similar symptoms to measles. Genetic analysis of MeV in a region helps document the effectiveness of control measures. In areas that have endemic transmission of measles, virologic surveillance of cases detects a limited number of genotypes while in areas where endemic transmission of virus has been interrupted, a variety of genotypes are detected, reflecting the multiple sources of imported viruses [10]. The virologic surveillance information has shown that vaccination programs can reduce the number of co-circulating chains of transmission and eventually interrupt measles transmission [11]. However, viruses are continually being introduced from external sources, and if the number of susceptible individuals increases, sustained transmission of the newly introduced viral genotype is possible. This results in what appears as a rapid change in the endemic genotype [12, 13]. The genetic stability of MeV is exceptionally high, and it has been observed that it undergoes remarkably little sequence variation over long periods of time, both in laboratory settings and in the field [14]. Therefore, genetic analysis of MeV in endemic areas such as Zambia helps to document the genotype of circulating virus strains, effectiveness of immunisation and possible introduction of new genotypes from other countries or regions. The article reviews the wild-type MeV present in Zambia, the complications of Measles and the Human immunodeficiency Virus and the control of Measles in Zambia.

2. Methodology

We searched PubMed, Scopus, Google Scholar, and ISI Web of Science (up to November 17, 2017) using the following search terms: “Epidemiology of Measles in Zambia”, “Genotype of Measles Virus in Zambia”, “Measles and Human Immunodeficiency Virus in Zambia”. We supplemented database searches by screening bibliographies of the articles. Two independent reviewers (KN, NT) screened article titles and abstracts to select articles for full-text screening. The reviewers of the current paper assessed full texts independently; in case of disagreement, they consulted a third author (SM), and agreed upon a decision by consensus. We further searched the National Center for Biotechnology Information (NCBI) database for all available nucleotide sequences of MeV isolated from Zambia and WHO reference strains that are used for genetic analysis. The obtained MeV nucleotide sequences were then analysed using Bioedit and MEGA 6 software. Phylogenetic trees were constructed in MEGA6 using the neighbor-joining method with the Kimura two-parameter evolutionary model [15, 16].

3. Results

The primary search identified 58 papers. We removed 24 duplicates. We screened 34 articles to assess eligibility, and excluded 16 that did not meet the inclusion criteria. We included 18 articles in the synthesis. We also included 2 epidemiological bulletins and alert from WHO and CDC. From the search of the NCBI database a total of 80 nucleotide sequences of 48 MeV isolates were obtained, 34 sequences (25 MeV isolates) from Zambia and 46 sequences (23 MeV isolates) WHO reference strains (Table 1). Out of the 34 sequences from Zambia, 9 and 25 were Hgene and N-gene nucleotide sequences, respectively. Topologically, the phylogenetic tree of the N-gene, MeV was separated in 8 groups and the Zambian isolates identified in 3 groups (Figure 1). While phylogenetic tree of the H-gene showed that the Zambian isolates to belong to one group (Figure 2). The Zambian MeV isolates were clustered in the genotypes B2, B3 and D2. Geographical distribution of the MeV in Zambia revealed that genotype B3 was found in Lusaka, Ndola, Kitwe, Samfya and Mwense, genotype B2 in Kitwe and genotype D2 in Lusaka (Figure 3).

Table 1: Measles Virus isolates from Zambia and WHO reference strains

Figure 1: Phylogenetic relationships of the N-gene of MeV detected in clinical patients in Zambia and the WHO reference strains. Phylogenetic analysis was based on 456 bp of the N-gene. Isolate names for nucleotide sequences included in the analyses are given in parentheses

Figure 2: Phylogenetic relationships of the H-gene of MeV detected in clinical patients in Zambia and the WHO reference strains. Phylogenetic analysis was based on 1504 bp of the H-gene. Isolate names for nucleotide sequences included in the analyses are given in parenthese

Figure 2: Phylogenetic relationships of the H-gene of MeV detected in clinical patients in Zambia and the WHO reference strains. Phylogenetic analysis was based on 1504 bp of the H-gene. Isolate names for nucleotide sequences included in the analyses are given in parenthese

4. Discussion

The wild type measles virus genotypes circulating in Zambia Molecular analysis of MeV serves as an important tool to understand the circulating strains of the virus in a region and efforts made in controlling outbreaks through immunisation. This study identified 3 MeV genotypes in Zambia. The genotypes B2, B3 and D2 were isolated from patients clinically diagnosed with measles in Lusaka, Ndola, Kitwe, Mwense and Samfya. The genotype B3 was common in all the 5 districts while B2 and D2 genotypes were unique to Kitwe and Lusaka, respectively. The finding of this review agrees with other workers that have reported MeV in Zambia. Rota and Bellini (2003) and Riddell et al (2005) reported that the genotype D2 was circulating in Zambia and South Africa while Rota et al (2011) further revealed that between 2007 and 2009, 21 genotype B2 sequences were reported from the Democratic Republic of the Congo, Zambia, and Angola [11, 17, 18]. Results of the study further revealed that the genotypes were identified between 2006 and 2014 after Zambia had adopted strategies to accelerate measles control, which included conducting case based surveillance [19]. The complications of Measles and the Human immunodeficiency Virus The co-infection of measles and Human immunodeficiency Virus (HIV) has resulted in complications in the immunisation of the former. It has been reported that infants born to women infected with HIV have lower titres of maternal antibodies to MeV and are at higher risk of contracting measles before the mandatory age of vaccination which is at 9 months in most sub-Saharan countries [20, 21]. Moss et al (2007) in a study in Lusaka reported that HIV-1–infected Zambian children developed antibody levels considered to be protective after measles vaccination at approximately 9 months of age, with comparable frequency to that achieved by HIV-1– uninfected children [22]. The research further revealed that antibody levels to measles vaccine in HIV-1-infected children waned off rapidly surviving up to 2 to 3 years. Scott et al (2007) also reported that levels of maternal antibodies to MeV were lower during the first 9 months of life in Zambian infants born to HIV-1–infected women than in infants born to uninfected women furthermore these levels were lower in HIV-1–infected infants than in HIVseropositive but uninfected infants [23]. Therefore, the HIV-1- infected infants are at increased risk of measles before the mandatory age of routine vaccination at 9 months but are also less likely to have levels of maternal antibodies that would neutralize measles vaccine virus. The World Health Organisation (WHO) recommends a second measles vaccination for all children, either through repeated campaigns or a routine second dose [24].

Measles Control in Zambia

Before 2003, Zambia controlled measles through single dose administration of the measles containing vaccine (MCV) to infants at age of 9 months [19]. Between 1992 and 1999, an average of 11,787 suspected measles case were reported annually, ranging 5, 983 in 1998 to 23, 518 in 1999 [19, 26]. During the same period the national measles immunisation coverage ranged from 61% in 1993 to 93% in 1996. In the quest of controlling measles outbreaks, in 2003, Zambia adopted a strategy of supplemental immunisation activities (SIA) which included strengthening routine vaccination, providing a second opportunity for measles immunisation for all children between 9 months and 4 years, and conducting case-based surveillance [25]. Since it was reported by Moss et al (2007) that MeV antibody titres wane off rapidly in HIV-1- infected children, the second opportunity for measles immunisation offers booster vaccination for prolonged protection against the disease. Lowther et al (2009) reported that 3 years after a successful SIA that markedly decreased incidence and mortality of measles in Zambia, 84% of children within the study townships had a history of measles immunisation and only 67% had detectable antibodies to MeV in oral fluid samples [27]. This result suggested a build-up of susceptible children and a population at risk for measles outbreaks. It was observed that HIV-1-infected children did not contribute substantially to the pool of susceptible children. In 2016 the Ministry of Health (MoH) in its continued efforts to improve child health introduced the Measles Rubella vaccine (MR) in the national routine immunisation system. The vaccine was given to children at the same age as measles vaccine for the first and second doses at 9 months and 18 months respectively during routine immunisation [28]. The introduction of MR vaccine was a necessary step to accelerate progress towards achieving the global goal of measles and rubella elimination by the year 2020 set by the Measles and Rubella Initiative (M&R) Initiative [28]. Zambia reported improvements in under 5 mortality declining from 168 deaths per 1000 live births in 2002 to 75 deaths per 1000 live births in 2014 and are directly attributed to sustained immunisation coverage and other child health interventions [29].

5. Conclusion

Continued monitoring of the MeV genotypes in clinically diagnosed cases is necessary to document the circulating wild-types in order to monitor the efforts of immunisation campaigns. Zambia is well vested with human resource and laboratory capacity to conduct the routine MeV surveillance. Infants born from women infected with HIV1 should be given the first MeV vaccine at 6 months of age because they have lower levels of MDA to Measles. As recommended by WHO a second opportunity for measles vaccination for all children is necessary, because of the reported waning immunity among HIV-1–infected children. Therefore, sufficient resources ought to be allocated towards surveillance and vaccination campaigns by the Ministry of Health (MoH) in Zambia.

Recommendations

Knowledge gaps in the epidemiology of measles over an extended period need to be addressed in the elimination of the disease in Zambia. This information is incredibly valuable as predictable epidemiological patterns emerge as measles elimination is approached and achieved. These critical features, including the source, size and duration of outbreaks, the seasonality and age-distribution of cases, genotyping pointers and effective reproduction rate shall be necessary in the control of the disease.

Author contributions

K.N conceived of the research idea. K.N and SM1 developed the theory and performed the computations. N.T and SM2 verified the analytical methods. BM. encouraged K.N. to investigate [control of measles] and supervised the findings of this work. All authors discussed the results and contributed to the final manuscript.

Acknowledgements

We would like to thank Drs. Oswell Khondowe and Margaret Mweshi for the constructive criticism and guidance during the preparation of the manuscript.

List of References

1. Griffin DE. Measles virus. In Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE. Fields virology, vol. 1. Philadelphia (EUA): Lippincott Williams & Wilkins. 2001, pp 1042–1065.

2. Bankamp B, Lopareva EN, Kremer JR, Tian Y, Clemens MS, Patel R, Fowlkes AL, Kessler JR, Muller CP, Bellini WJ, Rota PA. Genetic variability and mRNA editing frequencies of the phosphoprotein genes of wild-type measles viruses. Virus research. 2008 Aug 1; 135 (2):298- 306.

3. Xu WB, Tamin A, Rota JS, Zhang L, Bellini WJ, Rota PA. New genetic group of measles virus isolated in the People’s Journal of Preventive and Rehabilitative Medicine 11 Republic of China1. Virus research. 1998 Apr 1; 54 (2):147-56.

4. Rima BK, Earle JA, Baczko K, Ter Meulen V, Liebert UG, Carstens C, Caraba J, Caballero M, Celma ML, FernandezMu R. Sequence divergence of measles virus haemagglutinin during natural evolution and adaptation to cell culture. Journal of General Virology. 1997 Jan 1; 78 (1):97-106. 5. World Health Organization. Update of the nomenclature for describing the genetic characteristics of wild-type measles viruses: new genotypes and reference strains. Weekly Epidemiological Records. 2003.78(27):229–232

6. Tulchinsky TH, Ginsberg GM, Abed Y, Angeles MT, Akukwe C, Bonn J. Measles control in developing and developed countries: the case for a two-dose policy. Bulletin of the World Health Organization. 1993; 71 (1):93.

7. Kambarami RA, Nathoo KJ, Nkrumah FK, Pirie DJ. Measles epidemic in Harare, Zimbabwe, despite high measles immunization coverage rates. Bulletin of the World Health Organization. 1991; 69 (2):213.

8. Oshitani H, Mpabalwani M, Kasolo F, Mizuta K, Luo NP, Bhat GJ, Suzuki H, Numazaki Y. Measles infection in hospitalized children in Lusaka, Zambia. Annals of tropical paediatrics. 1995 Jun 1; 15 (2):167-72.

9. Oshitani H, Suzuki H, Mpabalwani M, Mizuta K, Kasolo FC, Luo NP, Numazaki Y. Laboratory diagnosis of acute measles infections in hospitalized children in Zambia. Tropical Medicine & International Health. 1997 Jul 1; 2 (7):612-6.

10. Rota PA, Liffick SL, Rota JS, Katz RS, Redd S, Papania M, Bellini WJ. Molecular epidemiology of measles viruses in the United States, 1997–2001. Emerging infectious diseases. 2002 Sep; 8(9):902.

11. Rota PA, Brown K, Mankertz A, Santibanez S, Shulga S, Muller CP, Hübschen JM, Siqueira M, Beirnes J, Ahmed H, Triki H. Global distribution of measles genotypes and measles molecular epidemiology. The Journal of infectious diseases. 2011 Jul 1; 204(suppl_1):S514-23.

12. Rima BK, Earle JA, Yeo RP, Herlihy L, Baczko K, Ter Meulen V, Carabana J, Caballero M, Celma ML, Fernandez-Munoz R. Temporal and geographical distribution of measles virus genotypes. Journal of General Virology. 1995 May 1; 76(5):1173-80.

13. Santibanez S, Tischer A, Heider A, Siedler A, Hengel H. Rapid replacement of endemic measles virus genotypes. Journal of General Virology. 2002 Nov 1; 83 (11):2699-708.

14. Beauty SM, Lee B. Constraints on the genetic and antigenic variability of measles virus. Viruses. 2016 Apr 21; 8 (4):109.

15. Kimura M. A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. Journal of molecular evolution. 1980 Jun 1; 16 (2):111-20.

16. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Molecular biology and evolution. 2013 Oct 16; 30 (12):2725-9.

17. Riddell MA, Moss WJ, Hauer D, Monze M, Griffin DE. Slow clearance of measles virus RNA after acute infection. Journal of clinical virology. 2007 Aug 1; 39 (4):312-7.

18. Rota PA, Bellini WJ. Update on the global distribution of genotypes of wild type measles viruses. Journal of Infectious Diseases. 2003 May 15; 187 (Supplement_1):S270-6.

19. Centres for Disease Control and Prevention (CDC. Measles incidence before and after supplementary vaccination activities–Lusaka, Zambia, 1996-2000. MMWR. Morbidity and mortality weekly report. 2001 Jun 22; 50 (24):513.

20. Moss WJ, Cutts F, Griffin DE. Implications of the human immunodeficiency virus epidemic for control and eradication of measles. Clinical Infectious Diseases. 1999 Jul 1; 29 (1):106-12.

21. Taylor WR, Ma-Disu MA, Weinman JM. Measles control efforts in urban Africa complicated by high incidence of measles in the first year of life. American journal of epidemiology. 1988 Apr 1; 127 (4):788-94.

22. Moss WJ, Scott S, Mugala N, Ndhlovu Z, Beeler JA, Audet SA, Ngala M, Mwangala S, Nkonga-Mwangilwa C, Ryon JJ, Monze M. Immunogenicity of standard-titer measles vaccine in HIV-1-infected and uninfected Zambian children: an observational study. The Journal of infectious diseases. 2007 Aug 1; 196 (3):347-55.

23. Scott S, Moss WJ, Cousens S, Beeler JA, Audet UA, Mugala N, Quinn TC, Griffin DE, Cutts FT. The influence of HIV-1 exposure and infection on levels of passively acquired antibodies to measles virus in Zambian infants. Clinical infectious diseases. 2007 Dec 1; 45 (11):1417-24.

24. World Health Organization. Strategies for reducing global measles mortality. Weekly Epidemiology Records 2000; 75:411–6.

25. Centres for Disease Control and Prevention (CDC. Measles incidence before and after supplementary vaccination activities–Lusaka, Zambia, 1996-2000. MMWR. Morbidity and mortality weekly report. 2001 Jun 22; 50(24):513.

26. Mpabalwani ME, Matapo B, Katepa-Bwalya M, Mukonka V, Mutambo H, Babaniyi OA. The 2010-2011 measles outbreak in Zambia: Challenges and lessons learnt for future action. East African Journal of Public Health. 2013; 10 (1):265-73.

27. Lowther SA, Curriero FC, Kalish BT, Shields TM, Monze M, Moss WJ. Population immunity to measles virus and the effect of HIV-1infection after a mass measles vaccination campaign in Lusaka, Zambia: a cross sectional survey. Lancet 2009; 373:1025–32

28. More than 6 million Zambian children to be vaccinated against measles and rubella in a nationwide vaccination campaign. World Health Organisation. [Cited Feb 20 2018]. Available from: www.afro.who.int/news/more-6-millionzambian-children-be-vaccinated-against-measles-andrubella-nationwide

29. Mpabalwani EM, Simwaka CJ, Mwenda JM, Mubanga CP, Monze M, Matapo B, Parashar UD, Tate JE. Impact of rotavirus vaccination on diarrheal hospitalizations in children aged< 5 years in Lusaka, Zambia. Clinical Infectious Diseases. 2016 Apr 7; 62(suppl-2):S183-7.