SEROEPIDEMIOLOGY OF TOXOPLASMA , RUBELLA , CYTOMEGALOVIRUS AND HERPES SIMPLEX VIRUS-2 IN WOMEN WITH BAD OBSTETRIC HISTORY . PART II . CYTOMEGALOVIRUS AND HERPES SIMPLEX VIRUS INFECTIONS

Bad obstetric history (BOH) is reported worldwide and is associated with social and psychological impacts. Cytomegalovirus and herpes simplex virus play an important role in the induction of adverse outcomes of pregnancy. Highest CMV IgG prevalence rate was reported for India (91.05%), while the lowest rate was reported for Iran (14.28%). Unfortunately, six studies in Iraq reported a high prevalence of CMV IgM in non-married, pregnant and women with BOH. The range of recent CMV infection in pregnant women with BOH was from 1.4% in Jordan to 60.2% in Iraq. In women with BOH, the highest HSV 2 prevalence (16.8%) was noted in India, while the lowest rate (1.69%) was reported in India also. In Arab countries, among women with BOH, HSV 2 IgG and IgM seroprevalence higher rates were reported for Iraq. This literature review highlights the high bacterial and viral maternal infection rate in the developing world. Urgent, concerted action is required to reduce the burden of these infections. In addition to raising awareness about the severity of the problem of maternal infections in the developing world, data from this review will be beneficial in guiding public health policy, research interests and donor funding towards achieving improvement in health care delivery.


Herpes simplex virus
Herpes simplex virus (HSV) is an ubiquitous, enveloped, and double stranded DNA virus, belonging to the family of Herpesviridae transmitted across mucosal membranes and nonintact skin, that migrate to nerve tissues, where they persist in a latent state [270].HSV-1 predominates in oro-facial lesions, and it is typically found in the trigeminal ganglia, whereas HSV-2 is most commonly found in the lumbo-sacral ganglia [271].Nevertheless these viruses can infect both oro-facial areas and the genital tract.In some developed countries type 1 has recently emerged as the prominent causative agent in genital lesions [272].Changes in sexual behaviours of young adults may partly explain its higher incidence [273,274].Herpes simplex virus (HSV) infections are caused by two strains, HSV-1 and HSV-2.Oro-labial infection is mainly caused by HSV-1, however, this strain is responsible for up to 53% of primary genital herpetic infection [270].HSV-2 genital infection is much more likely to recur than genital HSV-1 infection, thus the presence of antibody to HSV-2 and a compatible clinical history would be strong presumptive evidence that the disease is recurrent genital herpes [275][276][277].In addition to agent factor, genetic may play a role in susceptibility to HSV infection [278].Primary genital HSV-1 or HSV-2 infection in pregnant women can result in abortion, premature labor and congenital and neonatal herpes [279][280][281].HSV-2 infections in the newborn are particularly severe and frequently involve the CNS [282].Recent changes in HSV-1 and HSV-2 infection epidemiology have been reported, with type incidence changes and sequential genital infections with HSV-1 and HSV-2 [272,283].
Little is known about the risk factors associated with HSV seropositivity in pregnant Iraqi women.Identification of the risk factors may help to improve the control measures of HSV infection.Although there is improve in the diagnosis and treatment of TORCH infections, it still represents a problem in developing countries.Clinical diagnosis of TORCH is difficult, since most of the maternal infections with adverse outcomes are initially asymptomatic.Routine TORCH complex screening during pregnancy is not recommended in Iraq and the extent to which it is performed is unknown.A first primary infection develops when a susceptible person (lacking of preexisting HSV-1 and HSV-2 antibodies) is exposed to HSV.Indeed, a first non-primary episode occurs when a person with preexisting HSV antibodies (against type 1 or 2) experiences a first episode with the opposite HSV type.Recurrent infection occurs in a person with preexisting antibodies against the same HSV type [271].Infections during pregnancy may be transmitted to newborns: HSV-1 and HSV-2 may cause eye or skin lesions, meningo-encephalitis, disseminated infections, or foetal malformations.In recent years, genital herpes has become an increasing common sexually transmitted infection.From the late 1970s, HSV-2 seroprevalence has increased by 30%, resulting that one out of five adults is infected [284,285].HSV seroprevalence in patients with STD varies from 17% to 40% (6% in the general population and 14% in pregnant women) [286,287].Age and sex are important risk factors associated with the acquisition of genital HSV-2 infection.In fact, the prevalence of HSV infection rises with age, reaching the maximum around 40 years [284].This infection appears related to the number of sexual partners, and regarding sex it is more frequent in women than in men [288,289].In addition, ethnicity, poverty, cocaine abuse, earlier onset of sexual activity, sexual behavior, and bacterial vaginosis can facilitate a woman's risk of infection before pregnancy [290,291].Regarding pregnant population, there is a high prevalence of genital herpes, however, it is varies from country to others, depending on social and sexual behaviors and activity [289,[292][293][294].The risk of neonatal infection varies from 30% to 50% for HSV infections that onset in late pregnancy (last trimester), whereas early pregnancy infection carries a risk of about 1% [295][296][297].Thirty-one studies [1,3,90,91,96,204,256,298-320] outlining the prevalence of maternal Herpes simplex virus 2 (HSV-2) were identified (Tabl.VII).These studies detected the presence of antibodies to HSV as a marker of maternal infection.Median prevalence of IgG HSV-2 was 18.2% which was reported for Belgium [315,357].In pregnant women, higher seroprevalences were noted in Germany (82%), Turkey (63.1%),Zimbabwe (51.1%), and Iran (43.75%) [298,299,309,313].However, the lowest seroprevalences were reported in two studies in Turkey [204,314], which reported a rates of 4.4% and 5%.In women with BOH, the highest prevalence (33.58%) was reported in India [3], while the lowest one (18.6%)was reported in India also [91].

Gaps in existing knowledge
In the process of reviewing the subject, we identified several facility-based retrospective studies reporting causes of maternal mortality.Many of these studies attributed a proportion of deaths to infection or sepsis, but were unable to provide microbiological or serological evidence of the specific underlying mortality causes.Our review confirms the suspected high prevalence of parasitic and viral maternal infections in the developing world, as demonstrated by the median prevalence rates calculated for each pathogen studied.Of particular concern are the aetiology of infection.The literature review highlights a gap in existing knowledge on the epidemiology and impact of maternal infection, especially on the aetiology of infectious agents that lead to puerperal sepsis and subsequent mortality.Increased surveillance and diagnostic capabilities in healthcare facilities and in the community is needed to identify the aetiological agents responsible for puerperal sepsis and maternal mortality.The prevalence of maternal infection reported by the studies identified in this literature review may be an underestimate of actual rates of infection as not all pregnant women in developing countries may have access to or choose to access formalized antenatal care.This could be due to financial constraints, difficulties in accessing these facilities and personal or cultural beliefs.In addition, antenatal care services may not have the capacity to routinely screen for maternal infections, especially those that are asymptomatic and those that require serological tests such as PCR and ELISA to diagnose, due to limited resources or expertise.These infrastructural problems are essential contributors to the persistence of high maternal morbidity and mortality in developing countries and need to be overcome in order to accurately characterize the burden of maternal infections in these countries.

Conclusion
This literature review highlights the high bacterial and viral maternal infection rates in the developing world.Urgent, concerted action is required to reduce the burden of these infections.In addition to raising awareness about the severity of the problem of maternal infections in the developing world, data from this review will be beneficial in guiding public health policy, research interests and donor funding towards achieving improvement in health care delivery.

Table V . Characteristics and results of studies reporting prevalence of maternal CMV infection (continued). Article Location, setting of study Type, duration of study Population Results
[266]immery MN[266]Iraq, Diwanya, Hospital Case control, 5 months 125 Aborted women 49.6% IgG, 22.4% IgM

Table VIII . Characteristics and results of studies in Arab countries reporting prevalence of maternal HSV-2 infection
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