|Year : 2016 | Volume
| Issue : 3 | Page : 142-147
Seroepidemiology of cytomegalovirus antibodies in Hiv-positive and Hiv-negative adults in Nigeria
Mukhtar Abdulmajid Adeiza1, MM Dalhat2, B. O. P. Musa1, HM Muktar3, SB Garko1, AG Habib4
1 Department of Medicine, Infectious Disease and Immunology Unit, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
2 Nigerian Field Epidemiology and Laboratory Training Program, Abuja, Nigeria
3 Department of Haematology and Blood Transfusion, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
4 Infectious and Tropical Disease Unit, College of Health Sciences, Bayero University Kano, Kano, Nigeria
|Date of Submission||16-Jan-2016|
|Date of Acceptance||07-Jun-2016|
|Date of Web Publication||19-Sep-2016|
Mukhtar Abdulmajid Adeiza
Department of Medicine, Ahmadu Bello University Teaching Hospital, PMB 06, Shika, Zaria
Introduction: Cytomegalovirus (CMV) is the most common viral opportunistic infection in HIV/AIDS reported in the Western literature. There is a paucity of reports on the seroprevalence of CMV antibodies in Nigeria despite the high HIV burden. Few studies were carried out in pregnant women and healthy blood donors. This analytical cross-sectional study was conducted to describe the seroepidemiology of CMV antibodies in HIV-positive and healthy adults in Nigeria. Materials and Methods: Between August 2012 and March 2013, a structured questionnaire was administered to 250 HIV-positive patients attending the HIV clinic and 250 HIV-negative controls matched for age and gender. Participants were screened for quantitative CMV immunoglobulin G (IgG) and qualitative CMV immunoglobulin M (IgM) antibodies by enzyme-linked immunosorbent assay. Information was collected on sociodemographic characteristics, risk for HIV infection, and anthropometric measurements. Data were analyzed with SPSS Version 17. Results: A total of 500 participants were recruited. Females comprised 54%. Median age for males was 39 years (range 17-65 years), whereas for females, it was 35 years (range 16-62 years) (P = 0.002). In HIV-positive patients, CMV IgG and IgM antibodies were detected in 215 (86%) and 33 (13.2%), respectively, but in HIV-negative controls, it was 182 (72.8%) and 7 (2.8%), respectively (P = 0.001). In HIV-positive patients, CMV IgG age-specific seroprevalence was highest in the 16-25 years age group (93.5%), whereas CMV IgM, it was highest in the 26-35 years age group (16.1%). Mean quantitative CMV IgG antibody titer was higher in HIV-positive patients (P = 0.001). There was no gender difference between groups. Conclusion: Seroprevalence of CMV antibodies is high in Nigeria. HIV preventive strategies and routine screening of HIV patients and blood donors for CMV antibodies before blood transfusion are recommended to minimize the potential risk of transfusion transmitted CMV infection.
Keywords: Antibodies, cytomegalovirus, HIV, Nigeria
|How to cite this article:|
Adeiza MA, Dalhat M M, Musa B, Muktar H M, Garko S B, Habib A G. Seroepidemiology of cytomegalovirus antibodies in Hiv-positive and Hiv-negative adults in Nigeria. Sub-Saharan Afr J Med 2016;3:142-7
|How to cite this URL:|
Adeiza MA, Dalhat M M, Musa B, Muktar H M, Garko S B, Habib A G. Seroepidemiology of cytomegalovirus antibodies in Hiv-positive and Hiv-negative adults in Nigeria. Sub-Saharan Afr J Med [serial online] 2016 [cited 2017 Jun 26];3:142-7. Available from: http://www.ssajm.org/text.asp?2016/3/3/142/190852
| Introduction|| |
Cytomegalovirus (CMV), a β-herpes virus, also known as human herpes virus 5, is the largest virus to infect human beings. It is a major cause of non-Epstein-Barr virus infectious mononucleosis in the general population and an important pathogen in immunocompromised hosts. CMV infection is the most common viral opportunistic infection in patients with HIV/AIDS. 
Most studies worldwide have shown the seroprevalence of CMV to be between 40% and 90%; increasing with age and poor socioeconomic status. , In Asia and Africa, several studies have documented the prevalence of CMV infection. ,, Autopsy studies from Australia have shown that up to 76% of HIV-infected patients had clinical or pathological evidence of CMV disease at the time if death.  In vitro studies suggest that CMV and HIV co-infection act synergistically in the development of immune suppression; with CMV being an important co-factor in HIV pathogenesis. 
Among the HIV-infected population in the USA, a 50% seroprevalence of CMV was observed among HIV infected children.  In Ghana, West Africa, 59.2% of HIV/AIDS adults were co-infected with CMV.  In Nigeria, however, there is still paucity of information, and most studies on the seroprevalence of CMV infection have been carried out mainly on pregnant women and healthy blood donors. ,
CMV infection poses an important public health problem and may cause serious end-organ disease. In patients with HIV/AIDS, CMV causes a devastating end-organ disease. The potential for rapid loss of sight, chronic crippling diarrhea, and sudden loss of neurologic function makes CMV the most feared of the opportunistic infections in advanced HIV infection. ,
The predominant mechanism of infection is reactivation of CMV from a latent state. As immune deficiency advances, reactivation and opportunistic invasive disease due to CMV becomes common. Retinitis and enterocolitis are the most frequent manifestations, but involvement of virtually every organ or tissue has been described. ,
In developing regions of the world including Nigeria where the HIV/AIDS pandemic is rapidly unfolding, CMV remains a neglected, largely undiagnosed, and untreated disease.  Workable diagnostic and therapeutic strategies have not been defined, and CMV is absent from the current World Health Organization guidelines for the management of HIV in resource-limited settings. 
Despite the synergism of CMV infection and the HIV/AIDS pandemic documented in Europe and North America with the attendant contribution to morbidity and mortality, there is a paucity of information on this interaction in sub-Saharan Africa including Nigeria. Because the seroepidemiology of CMV infections remains undefined, it is poorly recognized as a possible contributor to HIV-related morbidity and mortality in developing countries and as such no resources are allocated to screening, diagnosis, and management of its complications.
The objective of this study was to describe the seroepidemiology of CMV infection in HIV-positive and HIV-negative. The information generated will be useful planning CMV preventive interventions.
| Materials and methods|| |
Study Population and Study Design
In an analytic cross-sectional study, five hundred participants comprising 250 HIV-positive patients and 250 HIV-negative controls were recruited from the HIV clinic and HIV counseling center of the Ahmadu Bello University Teaching Hospital Zaria from August 2012 to March 2013. Participants were included in the study group if they were HIV-positive and antiretroviral therapy naïve, and aged >15 years, whereas the control group comprised apparently healthy HIV-negative subjects who accepted to participate in the study. A systematic sampling method was employed. HIV positive patients were selected after a diagnosis of HIV in the clinic or wards, whereas controls were selected from the HIV counseling and testing center if they screened negative. An interviewer-administered questionnaire was used to obtain information on sociodemographic characteristics, and risk factors for HIV infection. All participants had anthropometric measurements (weight, height) taken and body mass index (BMI) was calculated.
Serum samples were obtained from each study participant by centrifugation of 5 ml whole blood. Sera were kept frozen at ≤20°C when analysis could not be carried out immediately. Sera were examined for anti-CMV immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies in the immunology laboratory of our institution by a commercial DRG IgG and IgM ELISA (DRG International Inc., USA), with sensitivity of 100% and 90.2%, and specificity of 97.6% and 93.5%, for IgG and IgM, respectively.  The tests were carried out according to the manufacturer's specification and the optical density was read off using a photometer at wavelength 450 nm. The test was qualitative IgM ELISA, in which positive results signified an acute infection and quantitative IgG ELISA, where positive results signified past infection. The presence of both antibodies signified re-infection.
This study was approved by the hospital research and ethics committee of the Ahmadu Bello University Teaching Hospital Zaria. The purpose and procedures of the study were explained to all the participants, and a written informed consent was obtained from all of them and from the next of kin of minor participants. Participants were free to opt out at any stage of the study.
The statistical analysis was performed using the software SPSS version 17.0. For calculation of the sample size, we used a reference seroprevalence of 84.2%  as expected frequency of the factor under study. Quantitative variables were expressed as means and compared using student t-test. Qualitative variables were compared using the Pearson's Chi-square. P ≤ 0.05 was considered statistically significant.
| Results|| |
A total of 500 participants were recruited for the study. This comprised 250 HIV-positive patients and 250 HIV-negative controls. The sociodemographic characteristics of the patients and controls are shown in [Table 1]. Male to female ratio was 0.85:1. Mean age for males was 39.70 ± 11.10 years (median: 39, range 17-65 years), whereas mean age for females was 35.50 ± 8.70 years (median: 35, range 16-62 years), (P = 0.002). This was statistically significant. The mean age of patients and controls was 36.80 ± 10.10 years and 37.41 ± 10.48 (P = 0.566).
The BMI and quantitative CMV IgG antibody titer is shown in [Table 2]. The BMI in HIV-positive patients and HIV-negative controls was compared. The difference was statistically significant (P < 0.001) with a mean BMI of 21.80 ± 4.21 kg/m in the HIV-positive patients compared to 24.01 ± 4.09 kg/m in the HIV-negative controls. The quantitative CMV IgG antibody titers among HIV-positive patients and HIV-negative controls were 8.68 ± 8.11 IU/ml and 5.36 ± 4.86 IU/ml, respectively. This difference was statistically significant (P < 0.001).
|Table 2: Body mass index and cytomegalovirus immunoglobulin G titer in HIV-positive patients and HIV-negative controls|
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Among the HIV-positive subjects, 225 (90%) reported heterosexual contact; 98 (39.2%) engaged in unprotected sex with multiple sexual partners [Figure 1]. Two subjects (1%) were engaged in men having sex with men contact. A history of previous blood transfusion was present in 23 (9.2%) of the subjects, but there was no history of injection drug use.
CMV IgG antibodies was detected in 215 (86%) of HIV-patients and 182 (72.8%) of HIV-negative controls [Table 3]. The seroprevalence was compared using McNemar's Chi-square (P < 0.001), and the difference in overall seroprevalence of CMV IgG antibodies between both groups was statistically significant. CMV IgM antibodies was detected in 33 (13.2%) of HIV-positive patients and 7 (2.8%) of HIV-negative controls [Table 3]. The seroprevalence was compared using McNemar's Chi-square (P < 0.001), and the difference in overall seroprevalence of CMV IgM antibodies between both groups was statistically significant.
|Table 3: Seroprevalence of cytomegalovirus immunoglobulin G and immunoglobulin M antibodies among HIV-positive patients and HIV-negative controls|
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In HIV-positive patients, CMV IgG age-specific seroprevalence was highest in the 16-25 years age group 75/86 (93.5%), whereas CMV IgM age-specific seroprevalence was highest in the 26-35 years age group 5/31 (16.1%) [Table 4]. However, in the HIV-negative controls, CMV IgG age-specific seroprevalence was highest in the 46-55 years age group 31/38 (81.6%), whereas CMV IgM age-specific seroprevalence was highest in the 56-65 years age group 1/14 (7.1%).
|Table 4: Age-specific cytomegalovirus immunoglobulin G and immunoglobulin M seroprevalence among HIV-positive patients and HIV-negative controls|
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In HIV-positive patients, CMV IgG and IgM gender-specific seroprevalence was higher in males 101/114 (88.6%) and 16/114 (14%), respectively, compared to females. However, in HIV-negative controls, CMV IgG and IgM seroprevalence was higher in females 104/136 (76.5%) and 4/136 (2.9%), respectively, compared to males. Overall, the relationship between gender and CMV IgG/IgM seroprevalence were not statistically significant.
| Discussion|| |
The seroprevalence of CMV IgG antibodies among HIV-positive patients in this study was 86% compared with HIV-negative subjects (72.8%). Overall, CMV IgG seroprevalence in Zaria was similar to the 84.2% reported by Okwori in pregnant women in Bida but lower than the 92% and 96% reported in healthy blood donors from Lagos and Jos, Nigeria, respectively. , It was also similar to the 87% reported by Kothari from India.  Most other studies from Africa and Asia have quoted higher seroprevalence rates ,, except Adjei et al. in Accra Ghana  in which CMV IgG seroprevalence was 77.6% in healthy blood donors and 59.2% in HIV/AIDS patients. This lower CMV IgG seroprevalence in the HIV-positive patients in the Ghanaian study is in contrast to the current study and can be explained by the small HIV-positive population used in that study when compared to the number of healthy controls. Similarly, higher seroprevalence rates in HIV-positive children has also been reported  and this is thought to be due to immunosuppression which predisposes patients to a higher burden of CMV infection.
The high prevalence rates observed in the above countries suggest that quiet a number of people in the study areas have previously been exposed to CMV, and this is contrary to the pattern seen in Western countries such as Australia, Germany, and the US where the CMV IgG seroprevalence is around 50-60%. ,, The possible explanation for this difference may have to do with the prevailing socioeconomic, environmental, and climatic factors and also the lower HIV prevalence in these countries.
Seroprevalence to CMV IgM antibodies was found to be 13.2% in HIV-positive patients and 2.8% in HIV-negative controls. Previous studies in West Africa have reported rates of 0% by Adjei et al.  in Accra, Ghana, 3.1% by Ojide et al. in Benin,  and 19.5% by Akinbami et al. in Lagos both in Nigeria among healthy blood donors.  Active infection usually results from reactivation of latent CMV infection or a new exposure to CMV and this disparity may be attributable to the varying methodologies employed. In three Indian studies, Kothari et al. and Kumar et al. reported a CMV IgM prevalence of 0% and 0.07%, respectively, in healthy blood donors, , whereas Mujtaba et al. reported a prevalence of 10.3% in AIDS patients.  In our study, all HIV-infected CMV IgM antibody positive patients were also CMV IgG antibody positive confirming that all patients developed reactivation of latent infection triggered by immunosuppression and not from primary infection; however, re-infection may also be a possibility. This finding is similar to that of Matos et al. in Brazil.  The higher CMV IgG and IgM prevalence observed in the HIV-infected patients in the current study compared to the healthy controls could be explained by immunosuppression and the role of the HIV genome in reactivating CMV infection.  Heterosexual transmission might also play an important role since this was the predominant route of acquiring HIV infection in this study.
In this study, 54% of the participants were females while 46% were males. This is in contrast to studies in male predominant healthy blood donors ,,,, and pregnant women , in which there was insufficient power for statistical comparison between the genders. The CMV IgG and IgM gender-specific seroprevalence in HIV-positive patients was higher in males, whereas in HIV-negative controls, it was higher in females. This notwithstanding, there was no statistically significant gender difference between the groups as has previously been reported in Africa and Asia. ,
The CMV IgG and IgM age-specific seroprevalence was highest in the 16-25-year and the 26-35-year age groups in the HIV-positive patients, respectively; whereas it was highest in the 46-55- and 56-65-year age groups, respectively, in the HIV-negative controls. This is similar to the pattern in HIV-positive patients in Ghana, a population similar to ours.  Seroprevalence rate did not vary in any particular direction or trend with the different age groups as was reported by Ojide et al.  in Benin city, Nigeria, and corroborated by Adjei et al.  in Ghana. The clustering of higher CMV IgG and IgM seroprevalence in the younger age groups of HIV-positive patients in this study is in contrast to the pattern seen in HIV-negative controls and other studies carried out in developed countries like the US where seroprevalence rates increased with age, with a peak around 80 years.  This may be related to the higher burden of HIV infection and force of sexual transmission in the younger age group. This study, however, and similar studies in Africa did not include participants older than 65 years of age.
| Conclusion|| |
Seroprevalence rates of CMV IgG and IgM are high in HIV-positive patients and HIV-negative controls in Zaria, Nigeria. However, the burden of infection is highest in the younger age groups among the HIV-positive patients. HIV prevention strategies and targeted screening of donors for blood transfusion to HIV infected patients or leukoreduction should be employed to minimize the potential risk of transfusion transmitted CMV infection. A limitation of this study is the lower specificity of CMV serology compared to CMV pp65 antigen capture assay and CMV DNA-polymerase chain reaction but further studies to characterize the risks and modes of transmission of CMV infection in Nigeria using these tools is recommended.
We thank the principal investigator and staff of the Nasara treatment and care center, ABUTH/PEPFAR Shika-Zaria.
Financial Support and Sponsorship
Conflicts of Interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]