| Abstract|| |
Background: Measles remains a major cause of childhood morbidity and mortality. Control of measles is complicated by pattern of measles transmission in which children are infected after they lose their protection from maternal measles antibodies (MMAs). As such, infants become measles prone before the age of measles immunization. This study, therefore, aimed at predicting changing epidemiology of measles in children in Maiduguri, Borno State, Nigeria. Materials and Methods: One hundred and thirty six infants at the age of seven months were enrolled in this study using the stratified random sampling method, and were tested for MMAs using enzyme-linked immunosorbent assay. Results: Sixty nine (50.7%) of the infants were males and 67 (49.3%) females, giving an approximate male to female ratio of 1.03:1. Comparing mean MMA levels of infants, for those who were protective and those who were unprotective was significant (P<0.0001). Most of the infants (125, 91.9%) had unprotective MMAs at seven months of age. Conclusion: Majority of infants in this study had unprotective MMAs at seven months of age and are more susceptible to measles. There is the need to monitor similar trend of events in other parts of Nigeria and abroad in order to report changing ecology of measles.
Keywords: Changing measles epidemiology, infants, maternal measles antibodies
|How to cite this article:|
Ahmadu BU, Mava Y, Ambe JP, Abdallah JA, Ovansa EO. Predicting changing measles epidemiology in an urban West African population. Ann Trop Med Public Health 2013;6:179-82
|How to cite this URL:|
Ahmadu BU, Mava Y, Ambe JP, Abdallah JA, Ovansa EO. Predicting changing measles epidemiology in an urban West African population. Ann Trop Med Public Health [serial online] 2013 [cited 2021 Jan 25];6:179-82. Available from: https://www.atmph.org/text.asp?2013/6/2/179/116502
| Introduction|| |
Forty years after measles vaccines were licensed, measles continues to cause death and severe disease in children.  Countries in Africa are mostly hit by recurring measles epidemics that has significant impact on health and economic development of the Region.  Conditions associated with measles epidemics in most African countries are limited public awareness of prevailing health risks and weak health systems. [2-4] Others are limited capacity for timely identification and response to measles outbreaks in communities.  Measles epidemics are associated with high morbidity and mortality and often occur in large geographical areas. For instance, between 2004 and 2008, 44 countries reported a total of 749, and 713 measles cases, with some having case fatality rates of 10%. ,
Despite the availability of an inexpensive highly effective measles vaccine, a notable proportion of cases and deaths occur in infants younger than nine months of age, before attaining the age at which measles immunization is recommended in developing countries.  Current measles vaccine may not elicit high antibody levels when administered to infants less than nine months of age because of the persistence of maternal measles antibodies (MMAs).  As a result, many infants experience several months during which MMA fell below levels that can protect them against measles virus (MV), but may interfere with antibody production in response to measles vaccine. During this period, infants may develop severe measles if exposed to MV.  High-dose measles vaccination in early infancy was explored in the past as a strategy to overcome MMA, and enable successful immunization of infants during this period.  However, excess mortality of female infants that was attributed to changing measles immunization time led to abandonment of this approach.  In view of the above, this study was undertaken to predict changing epidemiology of measles in Maiduguri, Borno state, Nigeria.
| Materials and Methods|| |
The study was carried out at the Departments of Paediatrics and immunology of the University of Maiduguri Teaching Hospital (UMTH) Maiduguri, Nigeria. The UMTH is a tertiary center located in North-Eastern Nigeria and a center of excellence for infectious diseases and immunology. It also serves as a referral site for the six North-Eastern States and neighboring countries of Chad, Cameroon, and Niger Republics. Maiduguri, the capital of Borno State, is located in semi-arid zone lying on latitude 11.5°N and longitude 13.5°E, with temperature range of 36.6 to 41.9°C, and annual rainfall of 1.14 to 771.90 mm.
Study review and informed consent
The Ethics Committee of the UMTH reviewed and approved the study protocol. A written version of the informed consent form was available in English, the official language of Nigeria. Because the literacy rate in Maiduguri, Borno state, is low,  linguistics interpreter of the informed consent form in local language mainly (Kanuri) was sought for. Care-givers had unlimited liberty to deny consent or opt out of the study without any consequences as confidentiality was maintained.
Subject selection and serum collection
We conducted a randomized descriptive study of infants who were attending Paediatric clinics at the UMTH. The minimum sample size for this study was determined using statistical formula, which computes approximately six percent prevalence for measles in Maiduguri at 95 confidence interval, at alpha levels of 0.05. , This equalled about 90; however, 50% of this was added to maximize power. Therefore, the study population comprised of 136 infants. An infant was eligible for participation in this study if he/she met the following study inclusion criteria: (i) was term at the time of delivery and (ii) had attended the age of seven months. Those who had contacts with measles cases or had history suggestive of measles, that is fever, maculopapular rash, and coryza, or those who received blood transfusion in the previous month were excluded to avoid falsely high levels of measles antibodies. The subjects that formed our study population were enrolled using stratified random sampling method. Where an infant in the strata did not fulfil the inclusion criteria above, the immediate next infant who qualified was selected. After ensuring subject eligibility, three milliliters of venous blood were collected from each participant. Blood samples were centrifuged and sera obtained were stored in a refrigerator at -20°C until the time of measles IgG using Enzyme-linked immunosorbent assay (ELISA) kits.
Laboratory assays for measles antibodies
MMAs were measured by ELISA (Demeditec diagnostic Gmbh Kiel Germany) kit.  The ELISA well plates were coated with Edmonston MV strain and results were standardized and presented in units per milliliter (U/ml). , MMAs <8 U/ml were classified as negative, equivocal with levels of 8 to 12 U/ml and positive when levels are >12 U/ml.  Protective titers for MMA were defined as levels of MMA >12 U/ml, and unprotective titers as levels of MMA ≤12 U/ml. 
Appropriate statistical method was used to analyze data obtained from this study using SPSS statistical software version 16, Illinois, Chicago USA. A P value <0.05 was considered significant. Tables were used appropriately for illustrations.
| Results|| |
A total of 136 newborn infants participated in this study. Sixty nine (50.7%) of them were males, as shown in [Table 1]. The male to female ratio is approximately 1.03:1.
Overall mean MMA of infants was 6.37 ± 10.97 at 95% CI of 4.51-8.23 U/ml. [Table 2] shows levels of mean MMA of infants that participated in this study. Comparing levels of mean MMA in infants, for those who were protective and those who were unprotective was significant (P<0.0001).
[Table 3] below shows MMA profile of subjects. Majority of these infants (125, 91.9%) had unprotective MMA.
|Table 2: Levels of mean maternal measles antibody distribution in infants that formed the study population|
Click here to view
| Discussion|| |
Almost all the subjects enrolled in the present study were unprotected against measles. Similar observation was reported by other workers elsewhere. , However, in New Guinea, none of the infants had protective levels of MMA by seven months of age.  It is possible that during pregnancy, mothers of these infants may be transferring lower MMA across the placenta relative to that observed in developed countries. Some workers have demonstrated that placental transfers of MMA in mothers found in developing countries are lower when compared with developed ones. , This may not be unconnected to human immunodeficiency virus (HIV) infection that was found to lower placental passage of MMA;  however, this may not be a cause in our study, because HIV prevalence in Nigeria is low about five percent.  Some authors have observed placental malaria infection to also reduce placental transfer of MMA.  Given that malaria is holoendemic in Nigeria, this may contribute to children starting out with low MMA that may not last long in infancy. 
Levels of MMA at birth have been identified by other investigators to have an inverse relationship with the rate of MMA decay in infants.  Such infants who had higher levels of MMA at birth lost it more rapidly relative to those infants with lower MMA at birth. This could be a reason for the high proportion of infants found with unprotective MMA in this study. Nonetheless, however, lower levels of MMA at birth could also be lost rapidly. This again is another reason to explain our finding. Maternal history of natural or measles vaccine exposure was considered to be the principal determinant of MMA of infants at birth, and also during infancy. This finding was further supported by several studies that documented the boosting effect of measles exposure. ,, However, many other researchers argued that apart from the most obvious factor, infant age, very few factors were identified that had significant impact on the levels of MMA across different ages in infancy.  It is likely that other possible determinants of MMA might contribute to MMA at birth rather than at different ages in infancy.
Of all these, the likely explanation for most of these infants being unprotected against measles at seven months of age could be the changing epidemiology of measles such that MMA of mothers are decreased relative to those found in the measles pre-vaccine era in developing countries.  With recent improvements in measles campaign practices, our finding would be anticipated. This may be possibly due to more proportion of mothers having measles vaccine-induced MMA that are lower than MV-induced MMA.  Children delivered to measles-vaccinated mothers would therefore receive less MMA by placental transfer. , Furthermore, measles campaign strategies have lessened the exposure of mothers to MV, a scenario that prevents boosting effect of MV. ,, As a result, infants are not going to receive increased MMA and may be vulnerable to measles early in infancy than previously thought of. Hence, in the future, we would anticipate bigger epidemics of measles early in infancy due to this poor passive protection of MMA.
Our inability to obtain maternal measles immunization profile or previous history of measles was a limitation to this study. This could have given us an insight to the possible source of MMA in our subjects. Obtaining MMA in mother-infant pairs at birth in our study population could have revealed the starting levels of MMA in our infants. Whether our subjects had higher or lower MMA at birth, being that MMA at birth may influence subsequent levels in infancy. However, our study design was not permissive for this. Future research incorporating these aspects, with infants recruited at birth and followed up across different ages during infancy is advocated.
| Conclusion|| |
Majority of infants in this study had unprotective MMA at seven months of age and are more prone to measles. Monitoring of similar pattern of events in other parts of Nigeria and beyond is required in order to report changing ecology of measles.
| Acknowledgement|| |
The authors thank Dr. M Sandabe, Dr. J Usman, and Dr. N Haruna for their untiring efforts and assistance during this work. The authors are also grateful to Mr. Bukbuk D and Dawurung JS of the Department of immunology, UMTH, for their technical help.
| References|| |
|1.||Perry RT, Halsey NA.The Clinical Significance of Measles: A Review. J Infect Dis 2004;189:1374-81. |
|2.||Regional committee for Africa. Recurring epidemics in the WHO African Region Malabo, Equatorial Guinea: Situation analysis, preparedness and response. WHO; 2010.p. 1-6. |
|3.||Lagunju IA, Orimadegun AE, Odeyemi DG. Measles in Ibadan: a continous scourge. Afri J Med Sci 2005; 34: 383-7. |
|4.||Ahmed PA, Babaniyi IB, Otuneye AT. Review of childhood measles admissions at the National Hospital, Abuja. Niger J Clin Pract 2010;13:413-6 |
|5.||Assaad F. Measles: Summary of worldwide impact. Rev Infect Dis 1983; 5:452-9 |
|6.||Milagritos DT, Samba OS, Medina-Moreno S, Yu L, Marcela FP, KotloffK, et al. A serosurvey to identify the window of vulnerability to wild-type measles among infants in rural mali.Am J Trop Med Hyg 2005;73:26-31. |
|7.||Raote GJ, Bhave SY.Clinical profile of measles-a prospective study of 150 hospital based children. Indian Pediatr 1992;29:45-8. |
|8.||Job JS, Halsey NA, Boulos R, Holt E, Farrel lD, Albrecht P, et al. Successful immunization of infants at 6 months of age with high dose Edmonston-Zagreb measles vaccine. Pediatr Infect Dis J1991;10:303-11. |
|9.||Aaby P, Knudsen K, Whittle HC, Lisse IM, ThaarupJ, PoulsenA.Long-term survival after Edmonston-Zagreb measles vaccination in Guinea-Bissau: Increased female mortality rate. J Pediatr 2003;122:904-8. |
|10.||Naing L, Winn T, Rusli BN. Practical issues in calculating the sample size for prevalence studies. Arch Orofac Sci 2006;1:9-14. |
|11.||Product information instruction manual. Enzyme immunoassay for the detection and the quantitative determination of human IgG antibodies against measles virus in serum and plasma. Demeditec diagnostics Germany; 2009. p. 1-8. |
|12.||Abdurraham MB, Greenwood BM, Olafimihan O, Whitle HC. Measles antibody levels from birth to 9 months of age in Nigerian infants. Afr J Med Med Sci 1982;11:113-5. |
|13.||Rogers S, Sanders RC, Alpers MP. Immunogenicity of standard dose Edmonston-Zagreb measles vaccine in highland Papua New Guinean children from four months of age. J Trop Med Hyg 1991;94:88-91. |
|14.||Victor MC, Peter MS, Roland WS.Factors determining prevalence of maternal antibody to measles virus throughout infancy: A review. Clin Infect Dis 2000;31:110-9. |
|15.||World Health Organisation. Country health system fact sheet Lagos, Nigeria. 2006. |
|16.||Ogala WN. Malaria. In: Azubuike JC, Nkanginieme KE, editors. Paediatrics and Child Health in a Tropical Region.2 nd ed.Owerri: African Educational Services; 2007. p. 596-604. |
|17.||Gothefors L.The impact of vaccines in low and high income countries. Ann Nestle Eng 2008;66:55-69. |
Baba Usman Ahmadu
Department of Paediatrics, Federal Medical Centre Yola, Adamawa State
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3]