Review - (2023) Volume 14, Issue 3
Received: 04-Mar-2023, Manuscript No. ipacm-23-13558; Editor assigned: 06-Mar-2023, Pre QC No. ipacm-23-13558 (PQ); Reviewed: 15-Mar-2023, QC No. ipacm-23-13558; Revised: 24-Mar-2023, Manuscript No. ipacm-23-13558 (R); Published: 29-Mar-2023, DOI: 10.36648/1989-8436X.23.14.03.234
Background: Cytomegalovirus, also known as “Human Cytomegalovirus” infects people of all ages. The virus derives its name from its ability to cause cell enlargement, Cyto means cell, while megalo means enlargement. It shares a common characteristic of lifelong latency with other members of Herpesviridae such as: Epstein Bar Virus, Varicella Zoster Virus, Herpes simplex 1 and 2, and Kaposi Sarcoma Herpes Virus. These are associated with several illnesses such as oral and genital blisters, congenital disorders, encephalitis, and Kaposi Sarcoma, among others. The virus poses a significant threat to public health worldwide, especially due to its latency and absence of effective medical treatment despite self-limitation.
Methodology: This review covers a systematic review, meta-analysis, and scoping review on cytomegalovirus with a view to assess the viral burden among the studied populations and identify reported states within Northern Nigeria endemic with the virus. The review also identified active infections and effect of the virus on the reported people.
Results: Active pollutions with Cytomegalovirus have been reported among pregnant women in Kebbi State (IgM 1.10%), IgM of 57.90% among blood donors, and 7.10% in HIV patients in Sokoto State, 14.40% IgM among HIV patients with retinitis in Kano, and 11.40%, among HIV patients, 10.50% in Pregnant women and 23.90% among women of reproductive age respectively, in Kaduna State all in Northwest Nigeria. Similarly, in the North, Central active infections were reported in Benue (3.50%) among pregnant women, 19.80% among HIV patients in Bida, and 2.60% among blood donors in Niger State, 24.90% among pregnant women in Kwara State, 21.70% among pregnant women in Kogi State, 10.60% in HIV Children and adolescent in the FCT Abuja, 9.50% among recurrent miscarriage women as well as 4.80% in normal women in Plateau State respectively. Cytomegalovirus decreases CD4 counts among HIV Patients, causes miscarriages among pregnant women, retinitis in HIV patients, and renders blood ineligible for Donation. Therefore, regular medical checkup and treatment of infected cases to prevent complications are recommended.
Prevalence; Nigeria; Molecular; Epidemiology
Cytomegalovirus, commonly known as CMV, is an enveloped virus with a double-stranded complex DNA molecule that encodes over 200 viral proteins and belongs to a family of viruses called Herpesviridae and Betaherpesvirinae subfamily [1, 2]. Moreover called “Human Cytomegalovirus (HCMV)”, it infects people of all ages and has a similar characteristic of lifelong latency to other members of the family such as: Epstein Bar Virus, Varicella Zoster Virus, Herpes simplex 1 and 2 and Kaposi Sarcoma Herpes Virus (KSHV), among others [3]. Members of the family cause a variety of diseases including oral and genital blisters, congenital disorders, encephalitis, and Kaposi Sarcoma [4]. Cytomegalovirus shares the subfamily “Betaherpesvirinae” with Muromegalavirus (infects Mice and rats), Proboscis virus (causes acute hemorrhagic disease in elephants), Quwivirus (guinea pigs and bats as hosts), and Roseolovirus (Mammals as host, infects T lymphocytes in humans) [5, 6]. The Human Cytomegalovirus is spherical in shape with a double-stranded linear DNA in an icosahedral capsid surrounded by a lipid bilayer enveloped which composed of various glycoproteins such as glycoprotein B (gB), gN, gH, gM, gO, gL, and gN useful in cell attachment and penetration [7, 8] (Figure 1).
Figure 1: The Structure of Human Cytomegalovirus.
Like other viruses, the life cycle of cytomegalovirus begins with the virion attachment to the host cells via interaction of viral envelope glycoproteins (gH, gN, gO, etc.) with host cell surface receptors delivering the capsid and tegument proteins into the cell. The capsid migrates to the nucleus where the viral genome is freed. The tegument proteins regulate host response as well as genome replication in the order of early and immediate (IE 1) gene expression, delayed early (IE 2) gene expression, and late gene expression, respectively. The late gene expression initiates capsid assembly in the nucleus, which associates with the tegument proteins and migrates to the viral assembly complex where they acquire further tegument and envelope (virions encapsulation of replicated DNA as capsids) .These migrate to the cytoplasm where secondary development occurs at the Endoplasmic Reticulum and Golgi Apparatus before being release together with dense non-infectious agents by exocytosis [9, 10] (Figure 2).
Figure 2: The Life Cycle of Cytomegalovirus.
Genetic diversity has been reported in Cytomegalovirus through genotyping of the viral glycoproteins gB1, gN4AN1, gB3, gH2, gB2, gB4,) from PCR positive clinical samples (urine, saliva, and plasma) producing gB2, gN3BN1, gB1, 2, 4, gH1, gB1, gB2 subtypes among others. The diversity in viral glycoproteins plays a great role in viral tropism and spread. Mutated genes such as UL9, UL1, RL6, RL5A, and US9 due to deletions and insertions in Cytomegalovirus genome have been reported with shared ancestral features. Virulence genes such as UL55 (codes for gB for attachment ) and US9 (codes gpUS9 cell-to--to-cell spread in epithelia cells) play a key role in virus tropism while UL83 ( codes for matrix protein, inhibits antigen processing of 72-kDa IE protein), US3 ( gp32/33, retains Major Histocompatibility Complex(MHC) class 1 molecules loaded with peptides in Endoplasmic Reticulum ER) and US2/ US11 (gp24/gp33, directs detained MHC class 1 molecules from ER to proteasome for degradation) are genes that enable the virus to evade the host immunity.
The Human Cytomegalovirus is described as the most successful human viral pathogen due to its transmission routes which are utero-perinatal and postnatal with the ability to remain latent in the host for a very long time without evoking clinical signs and symptoms. It can be activated by critical illness, drugs, inflammatory and stress mediators, immunosuppression, organ transfer, among other factors. The virus has been reported among women within child bearing age posing a significant risk for perinatal or neonatal transmission. The common mode of transmission of the virus is through direct contact of soft tissues or open sores with body fluids of infected persons such as blood, tears, urine, breast milk, semen, saliva, and infant contact with the mother’s genital secretions during birth. The virus spreads within an individual causing multi-systemic effect involving many tissues and organs such as lungs, liver, eye (retina), muscles, brain, and gut among others [10]. Although latency results in asymptomatic infections, viral activation leads to symptoms such as fever, encephalitis (brain inflammation) causing seizures and coma, pneumonia with hypoxemia, liver inflammation (hepatitis), large ulcers, shortness of breath, and vision problems. Cytomegalovirus can cause sore throat, fatigue, hepatitis, mononucleosis, and swollen glands [3]. Complications can result from gastrointestinal problems (diarrhea, colon inflammation, abdominal pain, and blood in the stool), pneumonitis, and inflammation of the brain (encephalitis), and liver problems. Immunocompromised persons such as HIV patients and organ transplant recipients are at serious risk for Cytomegalovirus contraction. Infected pregnant women pass the virus to either the unborn child in the womb via blood circulation or through contact of the baby with genital secretions during delivery. Cytomegalovirus can be diagnosed in the laboratory by the following ways:
1. Serologic investigations for IgM in active infection and IgG due to a previous exposure/recovery.
2. Detection of viral antigen or DNA using Polymerase Chain Reaction (PCR).
3. Culture of urine samples particularly in infants.
4. Biopsy in immunocompromised patients.
Cytomegalovirus infection is self-limiting with occasional recovery without medication, especially in adults, but medications (antivirals) can be administered to children and adults with weak immunity to slow viral replication. Although Ganciclovoir may have adverse effects, it reduces viral spread in those with congenital or recurring CMV infections, so organ damage may require hospitalization. Cytomegalovirus is a public health concern globally. Therefore, this paper involves a systematic review, metaanalysis, and scoping review with the aim of investigating the molecular epidemiology of cytomegalovirus in Northern Nigeria.
Epidemiology of Human Cytomegalovirus
Epidemiology is the study of the distribution (frequency and pattern) and determinants in relation to causes and risk factors for health-related issues and diseases in a specified population with application for prevention and control. Several factors are involved in the epidemiology of Human Cytomegalovirus. Although the virus is highly prevalent globally, its prevalence has a direct correlation with socio-economic status and advance age. Organ recipients, persons with weakened immunity, and those on immunosuppressive drugs are at a high risk of CMV contraction. A CMV prevalence of 94.50% was reported among persons with platelet disorders, 83.30% in those with anemia and leukemia, and 91.00% in a cross-sectional study among patients with hematological diseases in the Western Brazilian Amazon. A high prevalence of the virus has been reported in developing countries where the socio-economic status are low compared to Europe, some parts of Australia, and North America with low prevalence. Human Cytomegalovirus Immunoglobulin G (IgG) prevalence of 39.30% and 48.0% was reported among adult men in France and United States, respectively, but among women of reproductive age this was 45.60%-95.70% (Europe), 60.20% (Japan), 58.30%-94.50% (LATAM), and 24.60%-81.0% (North America. Maternal and congenital CMV Seroprevalence of 98.1% and 8.4%, respectively, was reported among mothers and infants in Columbia. Genetic variability in Human Cytomegalovirus has been described as complex and enables the virus access to multiple hosts with the ability to thrive well even in unfavorable conditions. This diversity in Human Cytomegaloviruses has been linked to changes in the envelope glycoproteins (gM, gO. gN, gH, etc) producing subtypes. Polymorphism (variants) of HCMV was reported in UL54 (P342S, S384F, K434R, S673F, T754M, R778H, C814S, M827I, G878E, S880L, E888K and S976N) and in UL97 (M615T) among DNAemia patients in Taiwan. In a Phylogenetic analysis of UL146, UL144, and UL55 genes, distinct strains of HCMV were reported among different families.
In Africa, Human Cytomegalovirus is a common etiologic agent of congenital infections in children as well as pneumonia and meningitis, particularly among immunosuppressed hospitalized patients. The endemicity has been described high in young infants 18 months of age with a prevalence rate of 83.00% in Zambia while in Nigeria high prevalence among prospective blood donors was significantly associated with overcrowding. The progression in the burden of HIV in Africa with its increasing morbidity and mortality has been associated with the effect of Human Cytomegalovirus either as a secondary pathogen or co-pathogen with HIV exerting a concerted effects against the immune system of their host with a consequent inflammatory effects.
Human Cytomegalovirus in Nigeria
Nigeria consists of 36 states and the Federal Capital Territory (FCT) distributed in six geopolitical zones such as North West, North East, North Central, South-South, South West and South East respectively. Northern Nigeria is made up of three geopolitical zones which include: North West, North East and North Central also known as Middle Belt (Figure 3).
Figure 3: Map of Nigeria Showing the States, FCT and Six Geopolitical Zones.
There have been several reports on the prevalence of Human Cytomegalovirus in Nigeria. Anti-HCMV IgG prevalence rate of 86.00% and 13.20% for IgM among HIV patients with 72.00% IgG with 2.80%IgG in HIV negative persons has been reported in Nigeria. A prevalence rate of 3.80% was reported among infants in Lagos through Polymerase Chain Reaction with two positive symptomatic subjects with liver and spleen enlargement and pneumonia related illness. Furthermore, a Seroprevalence of 97.2% of IgG against Cytomegalovirus was reported among normal pregnant women in Lagos, Nigeria. In a related study, a prevalence of 60.00% IgG to the virus was reported among pregnant women in Oshogbo Ogun State. In Abakaliki Ebonyi State, a HCMV infection prevalence of 11.30% was reported among HIV positive women and 16.70% of HIV positive pregnant women.
In North West Nigeria, 1.1% anti-CMV IgM was reported among pregnant women in ante-natal clinics in Birnin-Kebbi, Kebbi State while 93.30% with IgG antibodies in a related report. An anti-CMV IgG of 97.80% was reported among pregnant women attending Usman Danfodiyo University Teaching Hospital (UDUTH) in Sokoto State. Similarly, a prevalence of 4.82% IgG and 57.90 IgM CMV antibodies was reported among blood donors and 16.60% IgG with 7.10% IgM CMV antibodies among HIV positive patients in Sokoto. An anti-CMV IgG of 91.10% was reported among pregnant women attending Murtala Mohammed Specialist Hospital (MMSH), Kano, Nigeria. Similarly, 100.00% prevalence of anti-HCMV IgG and PCR Viraemia of 14.40% in HIV infected adults with retinitis attending Aminu Kano Teaching Hospital (AKTH) was reported in Kano, Nigeria. In Kaduna State, anti-HCMV IgG prevalence of 99.40% and IgM of 11.40% was reported among HIV patients (in Zaria, Kwoi, and Kaduna Metropolis) while a CMV IgG antibody prevalence of 94.80% was reported among pregnant women with 100% IgG antibody prevalence in non-pregnant women attending selected hospitals in Kaduna State. Similarly anti-HCMV IgM of 10.50% was reported among pregnant women attending ante-natal clinic at the General Hospital Kafanchan (GH Kaf), Kaduna State. Furthermore. In Zaria Kaduna State, anti- HCMV IgG of 94.70% and IgM of 23.90% was reported among women of reproductive age in selected hospitals (Table 1).
| S/N | State | Location | Test Type | IgG Prevalence Rate (%) | Active Infection/IgM Prevalence Rate (%) | Population |
|---|---|---|---|---|---|---|
| i. | Kebbi | Birnin Kebbi | ELISA | NRS | 1.1 | Pregnant Women- |
| Birnin Kebbi | ELISA | 93.3 | NRS | Pregnant Women | ||
| ii. | Sokoto | UDUTH, Sokoto | ELISA | 97.8 | NRS | Pregnant Women |
| Sokoto | ELISA | 4.82 | 57.9 | Blood Donors | ||
| Sokoto | ELISA | 16.6 | 7.1 | HIV Patients | ||
| iii. | Zamfara | NRS | NRS | NRS | NRS | NRS |
| Katsina ,Jigawa | ||||||
| iv. | Kano | MMSH Kano | ELISA | 91.1 | NRS | Pregnant Women |
| AKTH Kano | ELISA/PCR | 100 | 14.4 | HIV Patients with Retinitis | ||
| ELISA | 98 | NRS | Pregnant Women | |||
| v. | Kaduna | Zaria, Kwoi, Kaduna | ELISA | 99.4 | 11.4 | HIV Patients |
| Kaduna | ELISA | 94.8 | NRS | Pregnant Women | ||
| Kaduna | ELISA | 100 | NRS | Non -Pregnant Women | ||
| vi. | Kafanchan | ELIZA | NRS | 10.5 | Pregnant Women | |
| vii. | Zaria | ELISA | 94.7 | 23.9 | Women of Reproductive Age |
Table 1. Cytomegalovirus in Northwest Nigeria.
In the North Central/Middle Belt, a prevalence of 93.30% anti-CMV IgG seropositive and anti-CMV IgM of 3.50% with a significant association with gravidity. In pregnant women was reported in Makurdi, Benue State. Similarly, anti-CMV IgM prevalence of 19.80% among HIV patients in Bida and 96.20% IgG with 2.60% IgM among blood donors in Minna, Nigeria State. In Kwara State, a CMV IgG prevalence of 98.20% and IgM of 24.90% was reported among pregnant women in Ilorin. A prevalence of anti-HCMV IgM of 21.70% was reported among pregnant women in Lokoja, Kogi State. A prevalence of anti- HCMV IgG of 74.00% was reported among eligible blood donors in Keffi, Nasarawa State, while 10.60% anti-HCMV IgM among HIV infected Children and Adolescents in the Federal Capital Territory (FCT) Abuja, respectively. A Seroprevalence of CMV IgG of 85.70% and 9.50% IgM antibodies among women with recurrent miscarriages and 76.20% IgG and 4.80% IgM antibodies among normal women was reported in Jos Plateau State. In the North East, while no literature was located through various search engines for the spread of Cytomegalovirus in Taraba, Gombe, Bauchi, and Adamawa States as at the time of this report. A 100.00% anti-CMV IgG was reported among HIV positive and 98.60% in HIV negative patients attending University of Maiduguri Teaching Hospital (UMTH) in Borno State, An anti-CMV IgG prevalence of 90.00% was reported among pregnant women attending ante-natal in Nguru in Yobe State out of which 92.80% had still birth and 86.6% miscarriages (Table 2).
| S/N | State | Location | Test Type | IgG Prevalence Rate (%) | Active Infection/IgM Prevalence Rate (%) | Population |
|---|---|---|---|---|---|---|
| i. | Benue | Makurdi | ELISA | 93.3 | 3.5 | Pregnant Women |
| ii. | Niger | Bida | ELISA | NRS | 19.8 | HIV Patients |
| Minna | ELISA | 96.2 | 2.6 | Blood Donors | ||
| iii. | Kwara | Ilorin | NRS | 98.2 | 24.9 | Pregnant Women |
| iv. | Kogi | Lokoja | ELISA | NRS | 21.7 | Pregnant Women |
| v. | Nasarawa | Keffi | ELISA | 74 | NRS | Blood Donors |
| vi. | FCT | Abuja | ELISA | NRS | 10.6 | HIV Children and Adolescents |
| vii. | Plateau | Jos | ELISA | 85.7 | 9.5 | Recurrent Miscarriages Women |
| Jos | ELISA | 76.2 | 4.8 | Normal Women | ||
| viii. | Gombe, Bauchi, Taraba and Adamawa | NRS | NRS | NRS | NRS | NRS |
| ix. | Borno | UMTH | ELISA | 100 | NRS | HIV Positive |
| UMTH | ELISA | 98.6 | NRS | HIV Negative | ||
| x. | Yobe | Nguru | ELISA | 90 | NRS | Pregnant Women |
| Nguru | ELISA | 92.8 | NRS | Women with Still Birth | ||
| Nguru | ELISA | 86.6 | NRS | Miscarriage Women |
Table 2. Cytomegalovirus in North Central and North East, Nigeria.
There was little literature on the molecular study of Human Cytomegalovirus in Northern Nigeria at the time of compiling this report. Nevertheless, Cytomegalovirus glycoprotein B gene (gB) detected through PCR was reported among anti-CMV IgM positive prevalence of 11.40 in HIV patients in Kaduna. Similarly, Glycoprotein gB as well as variable genes gB1 (83.70%) and gB2 (16.30%), detected through PCR was reported among anti- CMV IgM prevalence of 19.80 in HIV patients in Bida and 2.60% among blood donors in Minna all in Niger State. Cytomegalovirus decreases CD4 counts and contributes to retinitis among HIV patients, miscarriage in pregnant women and renders blood donors ineligible (Table 3).
| State | Location | Population | IgM Prevalence | Glycoprotein Gene | Variable Gene | Effect of Cytomelavirus |
|---|---|---|---|---|---|---|
| Kaduna | Kaduna | HIV Patients | 11.4 | gB | NRS | NRS |
| Niger | Bida | HIV Patients | 19.8 | gB | gB1, gB2 | Deceases CD4 Counts |
| Minna | Blood donors | 2.6 | NRS | NRS | Renders blood ineligible for donation | |
| Kano | Kano | HIV Patients | 14.4 | NRS | NRS | Decreases CD4, Causes Retinitis |
| Plateau | Jos | Pregnant | 9.5 | NRS | NRS | Recurrent Miscarriages |
| Yobe | Nguru | Pregnant | NRS | NRS | NRS | Miscarriages in Women |
| Women | ||||||
| Nguru | Pregnant Women | NRS | NRS | NRS | Still Birth |
Table 3. Genetic Variability, Effects of Human Cytomegalovirus in Northern Nigeria.
This review confirms previous reports that cytomegalovirus poses a significant threat to public health globally. The virus infects Immuno-compromised persons with complications development. The presence of immunoglobulin g (IgG) signifies passed infection while IgM is an active infection. Active infections with Cytomegalovirus have been reported among pregnant women in Kebbi State (IgM 1.10%), IgM of 57.90% among blood donors, and 7.10% in HIV patients in Sokoto State, 14.40% IgM among HIV patients with retinitis in Kano, and 11.40%, among HIV patients, 10.50% in Pregnant women and 23.90% among women of reproductive age respectively, in Kaduna State all in Northwest Nigeria. Similarly, in the North Central, active infections were reported in Benue (3.50%) among pregnant women, 19.80 among HIV patients in Bida, and 2.60% among blood donors in Niger State, 24.90% among pregnant women in Kwara State, 21.70% among pregnant women in Kogi State, 10.60% in HIV Children and adolescent in the FCT Abuja, 9.50% among recurrent miscarriage women as well as 4.80% in normal women in Plateau State respectively .There is no report of active infections in the whole of the North Eastern States Such as Gombe, Bauchi, Adamawa and Taraba States respectively but passed infections with IgG reports in Borno State (100% and 98%) and Yobe State (90%, 92.80% and 86.60%) respectively. Therefore, cytomegalovirus has been reported in Northern Nigeria among HIV patients, pregnant women, and blood donors at different locations within the region. The virus has been associated with decreased CD4 count among HIV patients, recurrent miscarriages, and still births among pregnant women, renders blood ineligible for donation, and is implicated in retinitis among HIV patients. Therefore, regular medical checkups, avoidance of exposure of soft tissues and open sores to infected body fluids, and medical attention to infected cases to avoid complications and viral spread are recommended for proper control of the virus. More study is recommended in Gombe, Adamawa, Bauchi and Taraba States respectively. Adequate viral control is necessary for the improvement of public health.
All authors declare no conflict of interest, financial or nonfinancial.
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Citation: Waje T, Agbo EB, Umar AF, Iliyasu MY, (2023) A Review on Molecular Epidemiology of Cytomegalovirus in Northern Nigeria. Arch Clinic Microbio, Vol. 14 No. 3: 234.
