Ibrahim, Saira

Lalani, El-Nasir

Moss, Paul

Siddiqui, Amna Rehana

Siddiqui, Anwar Ali

English

eCommons@AKU

eCommons@AKUCommunity Health Sciences Department of Community Health SciencesJune 2017Human Cytomegalovirus: a neglected publichealth area of significant relevance to women, thefoetus and new born. Time for action!Amna Rehana SiddiquiAga Khan University, rehana.siddiqui@aku.eduSaira IbrahimAga Khan UniversityAnwar Ali SiddiquiAga Khan University, anwar.siddiqui@aku.eduPaul MossUniversity of Birmingham, United KingdomEl-Nasir LalaniAga Khan University, el-Nasir.lalani2@aku.eduFollow this and additional works at: http://ecommons.aku.edu/pakistan_fhs_mc_chs_chsPart of the Family Medicine Commons, and the Primary Care CommonsRecommended CitationSiddiqui, A. R., Ibrahim, S., Siddiqui, A., Moss, P., Lalani, E. (2017). Human Cytomegalovirus: a neglected public health area ofsignificant relevance to women, the foetus and new born. Time for action!. JPMA. The Journal of the Pakistan Medical Association,67(6), 827-829.Available at: http://ecommons.aku.edu/pakistan_fhs_mc_chs_chs/277Persistent infection with human cytomegalovirus (HCMV)infection is extremely common in many parts of theworld. Indeed, in the Pakistani population this is reportedto be more than 90%, when measured using HCMVspecific IgG antibody.1-4 HCMV-IgMsero-prevalence was4.3%, but the rate for both IgM and IgG was also 4.1%,indicating that reactivation of latent HCMV infection orreinfection with a new strain is the major cause of IgMseropositivity rather than primary infection.1 Mujtaba Get al (2016) report 97.5% and 58.5% IgG seropositivity inpregnant women and neonates respectively.2 Twoadditional studies by Rizvi CB et al (2015), and MahmoodR et al (2014) report a prevalence of 96.5% and 97.8%inblood donors.3,4 Similar findings are reported from studiesdone in Asian, African, and South American countries, incontrast to the much lower HCMV prevalence in NorthAmerican and European countries.5-9 HCMV prevalence ishigh in low-middle income countries, tending to be 20-30% higher in non-white than in white populations.6,7Primary HCMV infection in healthy individuals is usuallyasymptomatic, and may present with a mild febrile illness,mimicking infectious mononucleosis.10 HCMV Infectionpersists for life in a latent form with periodic reactivationor reinfection by a different strain. Common modes oftransmission include saliva, tears, milk, urine, stools, bloodand bodily fluids, and organ transplant.5,10 CongenitalHCMV infection (placental transmission) can result fromprimary or secondary (reactivation or re-infection)maternal infection occurring anytime during pregnancy.Congenital HCMV infection can cause intra-uterinegrowth retardation; brain maldevelopment syndromes;congenital and progressive hearing loss;thrombocytopenia; vision loss; motor disabilities such ascerebral palsy; liver and spleen disorders includinghepato-splenomegaly; and other illnesses.5,6 Notably,infants acquiring primary maternal HCMV infectiondisplay much severe form of HCMV-associated sequelae.The epidemiology of vertical transmission of HCMVinfection and related congenital anomalies in Pakistanipopulation is not well studied. hHCMV prevalence inSouth Asian women was higher HCMV prevalence whowere born in South Asia compared to those born in UK.6In the west HCMV infects 2 to 4% of pregnant women forthe first time as a primary infection during pregnancy, andit is transmitted to the foetus, resulting in a congenitalinfection in 40% of these pregnant women.5,8 However, inPakistan the number of pregnant women infected duringpregnancy is not known, but is most probably muchhigher.2 Congenital CMV in low- and middle-incomecountries and is mostly due to secondary maternalinfections; whereas, in western settings with moderatelevels of seroprevalence (70% in USA) 25% of congenitalCMV are due to primary and 75% due to secondarymaternal infections, in countries where seroprevalence isrelatively low (50% European countries), primary andsecondary infections contribute equally for occurrence ofcongenital CMV infection.9Individuals with HCMV can be co-infected with otherwidely distributed herpes viruses like Epstein-Barr, andvaricella-zoster.10 These viral infections have a tendencyto persist for a lifetime as latent infections. In order tokeep the virus in check the immune system mounts aconstant response, impacting its effectiveness againstother infections, cancer, auto-immune diseases, andresponse to vaccinations.  Such a phenomenon could beone of the reason as to why in Pakistan some of theseconditions (cancer, autoimmune, other) present earlierthan in the western populations. Moreover, such immunesuppression in elderly population has been reported toreduce life expectancy.11HCMV infected blood transfusion can cause severe illnessor death among elderly or persons with low immunity.3 Infact, allogenic stem cell transplant center in Islamabadreported 88% of its patients over a period of five yearswere HCMV positive and similar number of donors werealso CMV positive.12 Mortality in post-transplant patientswas mainly due to CMV enterocolitis/pneumonia, and lackof anti-viral medicines was also one of the majorJ Pak Med Assoc827EDITORIALHuman Cytomegalovirus: a neglected public health area of significant relevanceto women, the foetus and new born. Time for action!Amna Rehana Siddiqui,1 Saira Ibrahim,2 Anwar Ali Siddiqui,3 Paul Moss,4 El-Nasir Lalani51Departments of Community Health Sciences, 2,3Biological & BiomedicalSciences, 5Pathology & Laboratory Medicine, Aga Khan University, Pakistan,4Institute of Immunology & Immunotherapy, University of Birmingham,United Kingdom.Correspondence: Anwar Ali Siddiqui. Email: anwar.siddiqui@aku.eduproblem.12 Antiviral drug therapy for HCMV preventionand treatment for transplants and selective cases ofhearing loss by congenital HCMV carries a high cost oftreatment that could vary from US$25,000 toUS$30,000.8,13,14HCMV is a seminal neglected public health area ofsignificant relevance to women and children. It infectslarge swaths of population in the developing world,however, most people across the globe have never heardof it.5-9 Health care providers do not counsel mothersabout CMV transmission.15 There is significant lack ofknowledge and awareness among health care providersand the general population in Pakistan regarding HCMV,modes of transmission and potential consequences ofbecoming infected. One group who should be madeaware of HCMV are females in the reproductive age groupand breast feeding mothers. This group is prone as well asa reservoir for HCMV infection, and a source oftransmission to the foetuses and neonates.5,6,9,15,16 Sero-negative women may acquire infection during pregnancywith significant sequelae for the foetus. There is an urgentneed for health care professionals in particular all thoseengaged in prenatal, antenatal and postpartum care ofwomen in rural, peri-urban and urban areas to beeducated about HCMV and its mode of transmission.9,15,16This requires a vigorous education campaign by local,provincial and national public health organizations. It is the authors contention that much can be done now toreduce HCMV infection in women of child bearing ageand pregnant women thereby reducing HCMVtransmission to the foetus and newborn.  How can this bedone?  In the west an approach aptly called the, "CMVVaccine" has been proposed by experts.  There have beensuccessful attempts to develop a vaccine for HCMV thatstill needs validation studies.16,17 The administration ofthe "CMV Vaccine" contextualized for the Pakistanipopulation will reduce HCMV transmission and infectionof the foetus and new born.8,9,15,16 Further to vaccinedevelopment, a randomized trial of immunoglobulin andplacebo among pregnant women did not reduce verticaltransmission of HCMV infection.18There are implications for areas of prevention to beadopted by parents, health care givers, population ingeneral for diagnosis and management of HCMVinfection. Estimates of disabilities due to HCMV infectionare lacking from Pakistani and similar type of populations.However, western setting population share advancementin clinical virology in all areas of diagnostics andmanagement of HCMV especially since Acquired ImmuneDeficiency Syndrome (AIDS) patients and transplantrecipients remain at high risk of HCMV infection.19 Lowlevels of viral replication in latently infected individuals,maintain viral genomes in mononuclear cells and bonemarrow, allow subsequent replication in response toinflammation, and low immune states like pregnancy,chemotherapy, corticosteroid therapy.  Hence guidelinesare needed for infections in such vulnerable hosts in adeveloping country setting.  In Pakistani population, major task with health careproviders is to recommend hygienic precautions such asappropriate hand washing and wearing gloves duringdiaper change of children especially when performed byseronegative individuals. Raising awareness byinstructing mothers and family members to avoidintimate contact with infants and young children may alsoaid in reducing horizontal transmission of HCMVinfection. Other than contact with children, sexual contactmay also transmit HCMV to seronegative women. Bloodtransfusion is common due to endemic thalassemia traitand alternative strategies need to be investigated toreduce the disabilities, morbidity and mortality indebilitated patients who need blood transfusion.  As such,6.6% of the adult population remain at risk of HCMVinfection in Pakistan1 and it is likely that limited use ofsharing edibles, and utensils and other hygienicbehaviour were responsible for lack of transmission ofHCMV infection. However, this needs to be tested infuture research to identify the hygienic behavioursdetermining reduced risk of HCMV transmission in acountry like Pakistan with a very high HCMV prevalence.Low socioeconomic status as a determinant of HCMVinfection can only be modified, by stringentimplementation of public health strategies includingHCMV prevention and vaccination programmes on anational level to remove the increasing transmission inexisting cohorts of uninfected population.  References1. Ibrahim S, Siddiqui AA, Siddiqui AR, Ahmed W, Moss P, Lalani EN.Socio-demographic factors associated with IgG and IgMseroprevalence for human cytomegalovirus infection in adultpopulations of Pakistan: a seroprevalence survey. BMC PublicHealth 2016; 16: 11122. Mujtaba G, Shaukat S, Angez M, Alam MM, Hasan F, Zahoor ZaidiSS, et al. Seroprevalence of Human Cytomegalovirus (HCMV)infection in pregnant women and outcomes of pregnancies withactive infection.  J Pak Med Assoc 2016; 66: 1009-143. Rizvi CB,  Raza A, Siddiqui MF, Alam R.  Sero-prevalence of HumanCytomegalovirus among blood donors in Lahore, Pakistan. AdvLife Sci 2015; 2: 171-54. Mahmood R, Malik F, Hussain S, Ashfaq KM, Akhtar T, Alam MR, etal. Seroprevalence of cytomegalovirus among blood donors inlocal population. Int J Pharm Chem 2014; 4:146-50.5. Zuylen WJvan, Hamilton ST, Naing Z, Hall B, Shand A, RawlinsonWD. Congenital cytomegalovirus infection: Clinical presentation,Vol. 67, No. 6, June 2017Human Cytomegalovirus: a neglected public health area of significant relevance to women... 828epidemiology, diagnosis, and prevention.  Obstet Med 2014; 7:140-6 6. Manicklal S, Emery V, Lassarotto T, Boppana SB, Gupta RK. Thesilent global burden of congenital cytomegalovirus infection.  ClinMicrob Rev 2013; 26: 86-1027. Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirusseroprevalence and demographic characteristics associated with,infection. Rev Med Virol 2010; 20: 202-13.8. Cytomegalovirus. In: Kimberlin D, Brady M, Jackson M, Long S, eds.Red Book. Report of the Committee of Infectious Diseases. 30thed. Elk Grove Village, IL: American Academy of Pediatrics; 2015:317-22.9. Kirby T. Congenital cytomegalovirus-a neglected health problem.Lancet Infect Dis 2016; 16: 900-1.10. Pembrey L, Raynor P, Griffiths P, Chaytor S, Wright J, Hall AJ.Seroprevalence of Cytomegalovirus, Epstein Barr Virus andVaricella Zoster Virus among Pregnant Women in Bradford: ACohort Study. PLoS ONE 2013; 8: e81881. 11. Savva, GM, Pachnio A, Kaul B, Morgan K, Huppert FA, Brayne C, etal. Cytomegalovirus infection is associated with increasedmortality in the older population. Aging Cell 2013; 12: 381-7.12. Ullah K, Raza S, Ahmed P, Chaudhry QU, Satti TM, Ahmed S, et al.Post transplant infection: Single center experience from thedeveloping world. Int  J Infect Dis 2008; 12: 203-1413. Ahmed A. Antiviral treatment of cytomegalovirus infection. InfectDisord Drug Targets 2011; 11: 475-503 14. Schnitzler MA. Costs and consequences of cytomegalovirusinfection.  Am J Health Syst Pharm. 2003; 60: S5-8 15. Cannon MJ. Congenital cytomegalovirus (CMV) epidemiologyand awareness. J Clin Virol 2009; 46Suppl 4: S6-10. 16. Yow MD, Demmler GJ. Congenital cytomegalovirus disease-20years is long enough. N Engl J Med 1992; 326: 702-3.17. Harrison GJ. Current controversies in diagnosis, management, andprevention of congenital cytomegalovirus: updates for thepediatric practitioner. Pediatr Ann 2015: 44: e115-25.18. Revello MG, Lazzarotto T, Guerra B, Spinillo, Ferrazzi E, KustermannA, et al. A Randamized trial of Hyperimmune globulin to preventcongenital cytomegalovirus infection.  N Engl J Med  2014; 370:1316-26.19. Razonable RR, Hayden RT.  Clinical utility of viral load inmanagement of cytomegalovirus infection after solid organtransplantation.  Clin Mic Rev 2013; 26: 703-27.J Pak Med Assoc829 A. R. Siddiqui, S. Ibrahim, A. A. Siddiqui, et al

Human Cytomegalovirus: a neglected public health area of significant relevance to women, the foetus and new born. Time for action!

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Human Cytomegalovirus::a neglected public health area of significant relevance to women, the foetus and new born. Time for action!

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Human Cytomegalovirus: a neglected public health area of significant relevance to women, the foetus and new born. Time for action!

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