Comparative Study of Different Methods to Detect ...

Egyptian Journal of Medical Microbiology, October 2010

Vol. 19, No. 4

Comparative Study of Different Methods to Detect Primary and non Primary Cytomegaloviral Infection in Pregnant Women Gehan A. Elshennawy, Ahmed M. Asaad Departments of Microbiology & Immunology, Faculty of Medicine, Zagazig University ABSTRACT Accurate diagnosis of cytomegalovirus (CMV) primary infection in pregnant women is important, since CMV is the most common cause of congenital infection in humans. No single diagnostic test for CMV infection is currently available for pregnant women at all stages of gestation. Improved accuracy in estimating the timing of primary infection can be used to identify women at higher risk of giving birth to congenitally infected infants. This study aimed to diagnose primary and non-primary CMV infections in pregnant women by measuring IgM and IgG in sera and by detection of CMV DNA in blood. Also to compare CMV IgG avidity test with PCR for diagnosis of primary infection. A number of 750 pregnant women enrolled from two groups: group I, ≤20 week gestation (n = 491) and group II, > 20 weeks gestation (n = 259) were tested for CMV IgM, CMV IgG and CMV IgG avidity in their sera. These serological tests were repeated on the subsequent trimesters to detect if seroconversion had been occurred. Also PCR was performed on all IgG seropositive women (n = 435), using the following primers: HCMV1 (5`CCTAGTGTGGAT-GACCTACGGGCCA3') and HCMV2 (5`CAGACACAGTGTCCTCCCGCT-CCTC3'). A control group included 750 deidentified blood donners. The study detected that in subjects less than 20 years, 35.3% (n = 265) of blood donners about this age were IgG seropositive. CMV seropositivity rate steadily increased with age, reaching a plateau (n = 485, 64.7%) at the age of 47 years. The results also indicated that the majority of women were CMV IgG seropositive (n = 435, 58%) with 60 women (8%) being also CMV IgM positive. In the IgM-positive women, 16 women (2.1%) had low IgG avidity, indicating a primary CMV infection and a high risk of intra-uterine transmission and 44 women (5.9%) had high IgG avidity indicating recurrent or reinfection. CMV DNA was detected in blood samples by PCR from 14 women out of 16 diagnosed as primary infection by the IgG, IgM and low IgG avidity. IgG avidity test had 82.4% sensitivity, 95.3% specificity, 87.5% positive predictive value (PPV), 93.2% negative predictive value (NPV) and 91.7% accuracy in detection of primary infection (compared to PCR as a gold standard). Women at high risk of intra-uterine transmission was identified at all stages of pregnancy. Fourteen infants with asymptomatic CMV infection were diagnosed by serology and PCR. IgG avidity test had 77.8% sensitivity, 100% specificity, 100% PPV, 77.8% NPV, and 87.5 accuracy in detection of intra-uterine infection compared to PCR. In conclusion CMV screening in pregnancy by employing a sensitive, specific and accurate screening for CMV DNA by PCR seems the most efficient strategy to identify primary CMV infections and can predict CMV intrauterine transmission. This help to meet the need for rapid diagnosis, allowing effective therapeutic intervention. pregnancy, the highest risk of disease is linked to a primary infection acquired during pregnancy(4). Perinatal infections can result through virus transmission from many parts of the birth canal(5); however, the majority of these infections are asymptomatic(6). Primary CMV infection is the most common infection during pregnancy that may have long-term neurodevelopmental sequalae in children born to these mothers, occurring in approximately 1% of all live births(7,8). The usefulness of prenatal testing for CMV has been questioned due to the absence of clearly effective intervention(9,10) and to evidence for severe congenital malformation

INTRODUCTION Human cytomegalovirus (CMV) is a herpes virus which is distributed in the human population(1). Primary CMV infection occurs in 0.15 to 2.0% of all pregnancies and may be transmitted to the fetus in up to 40% of cases even in CMV seropositive mothers(2). Up to 15% of intrauterine CMV infections result in symptomatic congenital disease at birth, and 10 to 15% of those born with asymptomatic congenital CMV will develop significant clinical sequelae in infancy(3). Even if CMV is transmitted following a reactivation or a reinfection of women already infected before

93

Egyptian Journal of Medical Microbiology, October 2010

resulting from viral reactivation(11,12). Continuing advancements in technology, however, mean reliable and inexpensive serologic tests are available, prenatal diagnostic procedures with acceptable negative predictive values (NPV) can be performed, and trials of neonatal antiviral treatments are ongoing(13). Proposed diagnostic algorithms have focused on first-trimester screening, since the time of infection can be accurately obtained in the absence of seroconversion data, and the clinical sequelae of congenital CMV is usually more severe if transmission occurs early in gestation(14,15). A high positive predictive value (PPV) and NPV for clinical disease have been determined for quantitative PCR testing of amniotic fluid(16); however, there is an increased risk of a false-negative result if fewer than 7 weeks have elapsed between the onset of maternal infection and the time of amniocentesis(17,18). In addition, amniotic fluid testing prior to 21 weeks gestation only has a 30 to 45% sensitivity rate, while testing after 21 weeks gestation increases the sensitivity to 74%(19,20). Such time constraints are important if termination is considered as a management option(21), since neonatal signs include intrauterine growth restriction (IUGR), microencephalopathy, hepatosplenomegaly, petichae, jaundice, chorioretinitis, thrombocytopenia and anemia, and long-term sequalae consist of sensorineural hearing loss, mental retardation, delay in psychomotor development and visual impairment(22). Amniocentesis also increases the risk of spontaneous abortion, which in some cases may be greater than the risk of intrauterine CMV transmission. Many parents desire antenatal diagnosis of intrauterine infection so that they are informed of the possible outcomes for their child, as opposed to antenatal testing for selective termination(6). There is therefore a need for a low-risk, noninvasive diagnostic test. Laboratory methods are required to diagnose acute CMV infections since most present nonspecific symptoms. Women are not routinely screened for CMV prior to conception so CMV seroconversion is infrequently documented, making diagnosis of primary CMV infections difficult(23). Clinicians must be aware that the initial serology for CMV can be confusing because IgM antibody may remain positive for 9 to 12 months after an acute infection(24). IgG avidity test has been used to clarify primary and/or non-primary infections by measuring the binding affinity of IgG

Vol. 19, No. 4

antibodies. IgG of low avidity are produced at the onset of infections, and subsequent maturation of the antibody increases its avidity over time(25,26). Furthermore, since the risk of CMV intrauterine transmission increases with advancing gestation, there is a need for diagnostic tests that can be used at all stages of gestation. The diagnosis of asymptomatic neonates is emphasized, since half of the children who suffer from CMV sequelae are asymptomatic at birth(3,27). Also, knowledge of the risk of conditions such as sensorineural hearing loss in asymptomatic neonates, can allow close monitoring, early diagnosis, and early intervention, whereas failure to detect and follow up asymptomatic neonates may have serious consequences for the development of the child(28). CMV glycoprotein B vaccine has the potential to decrease incident cases of maternal and congenital CMV infection(29). This work aimed to detect CMV (primary and non-primary infections) among pregnant women at all stages of gestation by measuring IgM and IgG in sera and by detection of CMV DNA in blood. Also, to compare CMV IgG avidity test with PCR for diagnosis of CMV primary infection in pregnant women.

MATERIALS & METHODS A case-control study was conducted on 750 pregnant women attending the outpatient Clinic of Obstetric and Gynecology Departments, Zagazig University Hospitals between January 2009 – March 2010. Two cohorts were studied. The first cohort consisted of 750 de-identified blood donners at blood Bank who were tested for CMV serostatus during the same period of study. The second cohort consisted of 750 pregnant women, secreened for CMV by serology. The women were presenting for routine antenatal care. All women given a written consent for approval. The women were divided into two groups according to the period of gestation. Group I consisted of 491 women at 20 week or less than 20 weeks of gestation (mean 15 weeks). Group II consisted of 259 patients who consented at the time of glucose tolerance testing (GTT) for gestational diabetes at more than 20 weeks gestation (mean 28 weeks). Specimens: Whole blood samples were collected from all IgG seropositive women presenting for routine antenatal care. At Clinical

94

Egyptian Journal of Medical Microbiology, October 2010

Vol. 19, No. 4

A third enzyme immunoassay, also was used for the avidity of CMV IgG by a commercial kit (Radium CMV IgG-avidity EIA, Pomezia, Italy), according to the manufacturer's instructions, except for the wash step after the first antibody incubation, when 8M urea was added in parallel with PBS-Tween 20, as previously described(26). The results were scored as avidity index (AI) percentage. The AI was expressed as follows: Percentage of AI = Absorbance result of CMV per well with urea wash/absorbance result of CMV per well without urea wash x 100. Low avidity was considered when AI was 35%(6). Statistical analysis: Normally distributed continuous variables were compared by using a two-sample student t-test. Cross-tabulation and chi-square (with Yates' continuity correction) or Fisher exacts tests were used to examine the relationship between variables using a 95% confidence interval as a measure of association.

Microbiology Laboratory, Zagazig Faculty of Medicine, blood samples were centrifuged at 2,000 Xg for 20 min, and the buffy coat was removed at stored at -20°C. PCR: DNA extraction was performed using silica-based nucleic acid isolation kit (Malamite, Czech Republic), according to the manufacturer's instructions. The CMV DNA was detected by PCR amplification using specific primers (Quiagen, USA) as previously reported(30). The sequences of the used primers were: HCMV1 5`CCTAGTGTGGATGACCTACGGGCCA-3' and HCMV2 5`CAGACACAGTGTCCTCCCGCTCCTC-3'. The PCR amplification mixture consisted of pure Taq ready-to-go PCR bead (Amersham Bioscience, Buckinghamshire, UK), 0.4 mM of each primer and 1 µg of the DNA extract in a total volume of 25 µl. Two drops of mineral oil (Sigma, USA) were added to overlay each sample. The amplification was performed in a thermal cycler (Cyclogene Techne, UK). The reaction mixtures were heated to 96°C for 4 minutes, followed by 36 amplification cycles, each consisting of 10 seconds at 94°C, 10 seconds at 58°C and 20 seconds at 72°C. A final extension cycle of 72°C for 2 minutes was included(31). The amplified products were electrophoresed in 3% agarose gel. A DNA molecular weight marker (100 to 1000 bp) was run in parallel. The gels were stained with ethidium bromide and visualized under ultraviolet trans-illuminator (Cole-Parmer, USA). The positive PCR result was determined by the size of the amplified products (249 bp DNA amplicon). Serology: CMV IgG and IgM were detected in patient sera by using a commercial microparticle enzyme immunoassay (Abbott Diagnostics, Wiesbaden-Delkenheim, Germany). Briefly, the AX SYM IgM assay was a qualitative, indirect immunoassay. The solid phase was coated with three recombinant antigens expressing immunodominant regions of the four CMV antigens PPI 50, P52, P65 and P38(32). Specific antibodies to these antigens were captured in the solid phase and recognized by conjugated anti-human IgM. According to the manufacturer's recommendations, a sample was negative for CMV IgM if the index signal was 0.500, whereas a signal between 0.400 and 0.499 is considered a gray zone (Gz) result(33).

RESULTS Screening 750 de-identified blood donners (first cohort) at Zagazig University Hospitals was done. This study screened 382 (51%) seropositive subjects by CMV IgG assay. In subjects younger than 20 years of age, more than one-third of the donners about this age (n = 265, 35.3%) were CMV IgG seropositive. CMV seropositivity rate steadily increased with age, reaching a plateau at the age of 47 years, with less than two-thirds (n = 485, 64.7%) were infected. Among the population of blood donners, there were 153 men (49.2%) and 223 women (50.8%) however, there were more CMV-seropositive women (n = 439, 58.5%) than men (n = 311, 41.5%), but the difference did not give statistical significance (P = 0.66). According to the prevalence of seropositivity for CMV among the second cohort, 58% women (number = 435) were CMV IgG positive while 42% (number = 315) were seronegative. The age range of the pregnant women was 20 to 44 years (the mean age was 26.2±7.6). There was no significant difference (P>0.05) between the mean age of seropositive and seronegative women. Women with IgGnegative and IgM positive result were screened 3 weeks later to confirm the serostatus of the patient. CMV IgG avidity was determined for all patient specimens that were positive for both IgG and IgM. There were no statistical differences (P= 0.96) in the mean age, parity or

95

Egyptian Journal of Medical Microbiology, October 2010

Vol. 19, No. 4

IgG negative, IgM negative and PCR negative or CMV IgG positive, IgM negative and PCR negative. Samples were obtained from all infants within 3 days after birth, with neonatal blood tested for serology and PCR. None of the infants in the control groups (tested by PCR and by serology) were positive for CMV. Fourteen cases of intra-uterine transmission of CMV from IgM positive mothers who had low avidity IgG and positive PCR while 3 cases of intrauterine transmission from 3 mothers with positive IgM, positive PCR and high IgG avidity were detected. These neonates were asymptomatic at birth, except for only one infant who had a hearing loss at birth. The asymptomatic infants had normal hearing tests prior to discharge from the hospital and have been enrolled for regular follow-up hearing tests (Table 2). IgG avidity test had a sensitivity of 82.4%, specificity of 95.3%, PPV of 87.5%, NPV of 93.2% and an accuracy of 91.7% in detecting primary CMV infection, compared to PCR as a gold standard (Table 3). IgG avidity test was 77.8% sensitive, 100% specific, had PPV and NPV of 100% and 77.8% respectively and 87.5% accuracy in diagnosis of CMV intrauterine infection (Table 4).

CMV serostatus between the two groups (group I and group II) of patients. From the 750 women tested, 315 (42%) had never been infected with CMV and 375 (50%) had positive IgG indicating a past infection with CMV. The remaining 8% (60 women) were CMV IgG and IgM positive. Sixteen women (2.1%) were IgG positive IgM positive and had low IgG avidity (7 from group I and 9 from group II) indicating a primary CMV infection and a high risk of intra-uterine transmission. Retrospective testing of the first-trimester screens for the nine women from group II showed that they were CMV seronegative in the first trimester, indicating seroconversions during the second and third trimester of pregnancy. Fourteen patients (out of 16 patients with positive IgG, positive IgM and low IgG avidity) had positive PCR and two patients had negative PCR result. Forty-four patients with positive IgG, positive IgM and high IgG avidity (30 from group I and 14 from group II) were detected, 41 patients out of them had negative PCR and three patients had positive PCR results (Table 1). All IgM positive mothers and an equal number of control patients were monitored until birth. Mothers in the control group were CMV

Table (1): Prevalence of CMV among studied groups of pregnant women (n = 750). CMV immunoglobulin PCR No of women at status >20 weeks IgG IgM IgG + ≤ 20 weeks avidity gestation group (I) gestation group (II) (n=259) (n=491) N % N % N % N % ND Not Not 207 27.6 108 14.4 done done + ND 0 0.0 375 100 247 33 128 17.9 + + Low 14 1.96 2 0.27 7 0.9 9 1.2 + + High 3 0.4 41 5.5 30 4 14 1.9 No significant difference between group I and group II (X2 = 0.001 and P-value = 0.96).

96

Total no of women examined (n=750) N 315

% 42

375 16 44

50 2.1 5.9

Egyptian Journal of Medical Microbiology, October 2010

Table (2): Descriptive statistics of 16 women at risk of intrauterine transmission N = 16 Gestation at testing (wks) ⎯X±SD 23.3±7.5 Range 10-32 No Group I 6 II 10 CMV (IgG) +ve 16 CMV (IgM) +ve 16 CMV IgG low avidity 16 PCR -ve 2 +ve 14 CMV status of fetus Uninfected 2 Infected 14

Vol. 19, No. 4

% 37.5 62.5 100.0 100.0 100.0 12.5 87.5 12.5 87.5

This table demonstrates that 2 women with positive IgG and IgM and had low IgG avidity and negative PCR did not have intrauterine transmission indicating that avidity test had a false positive result. Table (3): Diagnostic indices and predictive values of IgG avidity testing in comparison to PCR for detection of primary CMV infection. PCR Sensit- Specif- +ve PV -ve Accur Total ivity icity PV -acy +ve -ve No % No % No % IgG avidity test Low 14 23.3 2 3.3 16 26.7 82.4% 95.3% 87.5% 93.2% 91.7% High 3 5.0 41 68.3 44 73.3 Total 17 28.3 43 71.6 60 100 Table (4): Diagnostic indices and predictive values of IgG avidity test in comparison to PCR for diagnosis of intrauterine CMV infection. Sensitivity Specificity +ve PV -ve PV Accuracy IgG avidity 77.8% 100% 100% 77.8% 87.5% PCR 100% 100% 100% 100% 100% the burden of congenital CMV-related disease(38), any therapeutic intervention is effective only if administered early, and this further stresses on the need to identify primary CMV infection among pregnant women as soon as possible. The basis for prevention still relies on a sensitive and accurate serological diagnosis(4,6,14,39). The rate of CMV IgG seroprevalence in blood donors was shown to increase with age, from 35.3% at less than 20 years of age to 64.6% till the age of 47 years. Within the blood donor population there were significantly more women infected with CMV than men, a finding in agreement with risk factors for other sexually transmitted viruses, such as human

DISCUSSION Cytomegalovirus transmission from pregnant women with a primary infection to the newborn is still a major issue, because of the combination of the high pathogenicity of an infection acquired early during pregnancy and the sustained risk of acquiring infection throughout the childbearing age(34). Recently, a treatment with hyperimmune IgG has been demonstrated to be safe and effective in reducing CMV disease(35,36). Furthermore, an early report on the safety and effectiveness of ganciclovir therapy during pregnancy has also been published(37). While these strategies might be able to reduce

97

Egyptian Journal of Medical Microbiology, October 2010

papillomavirus(40) and herpes simplex viruses(41). This increased risk is consistent with a demonstrated higher efficiency of male-tofemale transmission(42). This was in agreement with the results reported by Munro et al., who found that CMV IgG seroprevalence in blood donners increased with age from 43.9% at less than 20 years of age to 72.4% after the age of 50 years(4). Unlike the blood donor population, the rate of CMV infection in the pregnant women cohort did not increase with age but instead was consistently high in women whose ages were between 24-28 years (about 70%). This finding also agreed with that of Munro et al.(4). Since the overall incidence of sympotomatic congenital CMV is low (~ 0.05%) and risk factors are not well-defined, it has been difficult to develop strategies for detection of CMV infection, especially for asymptomatic primary infection in pregnant women. Some obstetricians propose CMV testing of all pregnant women; others screen for CMV antibody only in women considered at risk (Pediatric nurses, teachers, day care workers)(39). CMV IgM has been shown to peak during the first 1 to 3 months after primary infection in pregnant women and then persist at a low level for 18 to 39 weeks, with detection depending upon both the individual patient and the sensitivity of the IgM assay used(43,44). After the initial onset of infection, the rise in IgM titer may occur prior to the rise in IgG titer, making CMV IgG avidity testing reliant on the sensitivity of the CMV IgM test. To ensure that all CMV IgM-positive samples were detected and screened for IgG avidity, the AxSYM CMV IgM test was used, since it is one of the most sensitive commercial CMV IgM tests available(6.23,45.46). In agreement with published findings, the rate of IgM detection by the AxSYM was great (8%) in the present study. Sensitive CMV IgM tests may have a high number of false-positive results(44,46); however, all IgM results were verified by CMV IgG avidity testing, and the use of PCR as a gold standard. The results ensured that all individuals at risk of a primary infection were identified by AxSYM IgM assay and a false positive result was obtained only in 2 cases.. In the study of Sharma et al., 57 pregnant women were screened for CMV, out of which, 17 (22.66%) had evidence of recurrent CMV infection as demonstrated by the presence of specific IgM antibodies. All cases were positive for specific IgG antibodies(8). In another study done by Correa et al., 1131 pregnant women

Vol. 19, No. 4

were screened for CMV, (32.6%) of women were seropositive; 27 women (2.4%) developed active infection during pregnancy(47). In the study of Jahromi et al., the number and percentage of CMV-IgG was 235 (94%) and 150 (75%) in case and control groups, respectively (P-value = 0.0001). In the case group 13 (5.2%) women were positive for CMV-IgM, while no positive sample was detected in control group (P-value = 0.001)(48). Genitle et al. detected that the AxSYM CMV IgM assay was highly sensitive, as it picked up 5 more cases with a low AgG avidity index that were negative according to other commercial immunoassays(33). In the study of Lazzarotto et al., AxSYM assay was more suitable screening assay for CMV IgM and can detect all 13 specimens from women with documented transmission of the virus to the fetus (n = 13). Behring assay detected CMV IgM in only 4 specimens in the same study(49). CMV IgG avidity has been shown to distinguish primary CMV infections from reactivated infections in pregnant women, and the maturation rate and duration of the antibody has been shown to correlate with patient viremia. Low-avidity IgG in pregnant women persists for approximately 17 weeks, with full maturation of the antibody occurring approximately 25 weeks after onset of symptoms(50). Screening in first trimester prior to 17 weeks gestation should therefore detect primary infections during this time. IgG avidity testing was non-invasive compared to amniotic fluid testing and can be conducted during late gestation with no risk to the patient(6). In this study, avidity test had a sensitivity of 82.4% and a specificity of 95.3%. In the study of Lagruo et al., the CMV IgG avidity assay reliably excluded patients with recent infections and showed an excellent specificity (98%)(51). In immunocompetent persons, CMV detection in blood is thought to be indicative of a primary CMV infection(52). In the present study, CMV DNA was detected in blood samples from 14 women with diagnosed primary CMV infection and were detected at all periods of gestation. In the study of Munro et al., CMV DNA was detected in blood samples from 3 women (out of 7 with diagnosed primary infection). One women was at gestation less than 20 weeks and 2 women were at more than 20 weeks of gestation(4). No correlation has been shown to exist between CMV viremia or CMV DNA detection in blood and intrauterine transmission(52);

98

Egyptian Journal of Medical Microbiology, October 2010

however, in the present study intrauterine transmission occurred in 14 mothers who were viremic at the time of testing. PCR was 100% sensitive, specific and accurate technique in prediction of CMV intrauterine infection. Munro et al., found 2 case of intrauterine transmission and were also viremic and were detected in the third trimester(4). In conclusion, the employment of sensitive, specific and accurate screening of CMV by PCR seems the most efficient strategy to detect primary CMV infection and can predicts CMV intrauterine transmission. This may help to meet the need for rapid diagnosis, allowing effective therapeutic intervention. Acknowledgments Great thanks for Prof. Dr. Anwar Ezzat Ismail for his assistance in collecting data and obtaining samples from Women at Obstetric and Gynaecology Department, Faculty of Medicine, Zagazig University Hospitals; and all participating Women and Pediatricians.

7.

8.

9.

10.

REFERENCES 1.

2.

3.

4.

5.

6.

Alford CA, Stagno S, Pass RF, Britt WJ (1990): Congenital and perinatal cytomgelovirus infections. Rev Infect Dis; 12: S743-S745. Nagamori T, Koyano S, Inoue N, Yamada H, Oshima M, Minematsu T, Fujieda K (2010): Single cytomegalovirus strain associated with fetal loss and then congenital infection of a subsequent child born to the same mother. J CLin Virol; 49 (2): 134-6. Dahle AJ, Fowler KB, Wright JD, Boppana SB, Britt WJ, Pass RF (2000): Longitudinal investigation of hearing disorders in children with congenital cytomegalovirus. J Am Acad Audiol; 11: 283-290. Revello MG, Gerna G (2002): Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant. Clin Microbiol Rev; 15: 680-715. Mathijs JM, Rawlinson WD, Jacobs S, Bilous AM, Milliken JS, Dowton DN, Cunningham AL (1991): Cellular localization of human cytomegalovirus reactivation in the cervix. J Infect Dis; 163: 921-922. Munro SC, Hall B, Whybin R, Leader L, Robertson P, Maine GT, et al. (2005): Diagnosis of an screening for

11.

12.

13. 14.

15.

16.

99

Vol. 19, No. 4

cytomegalovirus infection in pregnant women. J Clin Microbiol; 43 (9): 47134718. Donner C, Liesnard C, Brancart E, Rodesch F (1994): Accuracy of amniotic fluid testing before 21 weeks' gestation in perinatal diagnosis of congenital cytomegalovirus infections. Prenatal Diagn; 14: 1055-1059. Sharma A, Rasul ES, Hazarika NK (2007): A serological study of cytomegalovirus infection in pregnant and non-pregnant women at Gauhati Medical College and Hospital. Journal of the Indian Medical Association; 105 (6): 320, 322-3. Ahlfors K, Ivarsson SA, Harris S (1999): Report on a long-term study of maternal and congenital cytomegalovirus infection in Sweden: review of prospective studies available in the literature. Scand J Infect Dis; 31:443-457. Hagay ZJ, Biran G, Ornoy A, Reece EA (1996): Congenital cytomegalovirus infection: a long-standing problem still seeking a solution. Am J Obstet Gynecol;. 174: 241-245. Boppana SB, Rivera LB, Fowler KB, Mach M, Britt WJ (2001): Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity. N Engl J Med; 344:1366-1371. Gaytant MA, Rours GI, Steegers EA, Galama JM, Semmekrot BA (2003): Congenital cytomegalovirus infection after recurrent infection: case reports and review of the literature. Eur J Pediatr; 162: 248253. Griffiths PD (2002): Strategies to prevent CMV infection in the neonate. Semin Neonatol; 7:293-299. Kumar ML, Prokay SL (1983): Experimental primary cytomegalovirus infection in pregnancy: timing and fetal outcome. Am J Obstet Gynecol; 145:56-60. Stagno S, Pass RF, Cloud G, Britt WJ, Henderson RE, Walton PD, Veren DA, Page F, Alford CA (1986): Primary cytomegalovirus infection in pregnancy: incidence, transmission to fetus, and clinical outcome. JAMA; 256:1904-1908. Guerra, B, Lazzarotto T, Quarta S, Lanari M, Bovicelli L, Nicolosi A, Landini MP (2000): Prenatal diagnosis of symptomatic congenital cytomegalovirus infection. Am J Obstet Gynecol; 183: 476482.

Egyptian Journal of Medical Microbiology, October 2010

Vol. 19, No. 4

27. Fowler KBD, McCollister FPE, Dahle AJP, Boppana SMD, Britt WJMD, Pass RFMD (1997): Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital cytomegalovirus infection. J Pediatr; 130:624-630. 28. Yoshinaga-Itano C (2003): Early intervention after universal neonatal hearing screening: impact on outcomes. Mental Retardation and Developmental Disabilities Res Rev; 9:252-266. 29. Pass RF, Zhang C, Evans A, Simpson T, Andrews W, et al. (2009): Vaccine prevention of maternal cytomegalovirus infection. N Engl J Med; 360: 1191-9. 30. Pershing DH, Smoth TF, Tenover FC, White TJ (1993): Diagnostic molecular biology. American Society for Microbiology, Washington, D.C. 31. Michalek J, Horvath R (1993): High incidence of Epstein-Barr virus, cytomgegalovirys and human herpesvirus 7 infections in children with cancer. BMC Pediatrics; 2: 1-11. 32. Maine GT, Stricker R, Schuyler M, Spesard J, Brojanae S, Iriarte B, et al. (2000): Development and clinical evaluation of a recombinant-antigen-based Cytomegalovirus Immunoglobulin M automated immunoassay using the Abbott AxSYM analyzer. J Clin Microbniol; 38: 1476-1481. 33. Genitle M, Galli C, Panotti P, Di Marco PS, et al. (2009): Measurement of the sensitivity of different commercial assays in the diagnosis of CMV infection in preganncy. Eur J Clin Microbiol Infect Dis; 28: 977-981. 34. Lazzarotto T, Guerra B, Lanari M, Gabriella L, Landini MP (2008): New advances in the diagnosis of congenital cytomegalovirus infection. J Clin Virol; 41:192-197. 35. Adler PA, Nigro G, Pereira L (2007): Recent advances in the prevention and treatment of congenital cytomegalovirus infections. Semin Perinatol; 31: 10-18. 36. Nigro G, Alder SP, La Torre R, Best Am, for the congenital Cytomegalovirus Collaborating Group (2005): Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med; 353: 1350-1362. 37. Puliyanda DP, Silverman NS, Lehman D, Vo A, Bunnapradist S, Radha RK, et al. (2005): Successful use of oral ganciclovir

17. Bodeus M, Hubinont C, Bernard P, Bouckaert A, Thomas K, Goubau P (1999): Prenatal diagnosis of human cytomegalovirus by culture and polymerase chain reaction: 98 pregnancies leading to congenital infection. Prenatal Diagn; 19:314-317. 18. Lipitz, S, Yagel S, Shalev E, Achiron R, Mashiach S, Schiff E (1997): Prenatal diagnosis of fetal primary cytomegalovirus infection. Obstet Gynecol; 89:763-767. 19. Donner C, Liesnard C, Brancart F, Rodesch F (1994): Accuracy of amniotic fluid testing before 21 weeks gestation in prenatal diagnosis of congenital cytomegalovirus infection. Prenatal Diagn. 14:1055-1059. 20. Liesnard C, Donner C, Brancart F, Gosselin F, Delforge ML, Rodesch F (2000): Prenatal diagnosis of congenital cytomegalovirus infection: prospective study of 237 pregnancies at risk. Obstet Gynecol; 95:881-888. 21. Breborowicz GH (2001): Limits of fetal viability and its enhancement. Early Pregnancy; 5:49-50. 22. Fowler KB, Boppana SB (2006): Congenital cytomegalovirus (CMV) infection and hearing deficit. J CLin Virol; 35: 226-231. 23. Nielsen SL, Sorensen I, Andersen HK (1988): Kinetics of specific immunoglobulins M, E, A, and G in congenital, primary, and secondary cytomegalovirus infection studied by antibody-capture enzyme-linked immunosorbent assay. J Clin Microbiol; 26:654-661. 24. Duff P (2010): Diagnosis and management of CMV infection in pregnancy. Perinatology; 1: 1-6. 25. Lappalainen M, Koskela P, Koskiniemi M, Ammala P, Hiilesmaa V, Teramo K, Raivio KO, Remington JS, Hedman K (1993): Toxoplasmosis acquired during pregnancy: improved serodiagnosis based on avidity of IgG. J. Infect. Dis. 167:691697. 26. Grangeot-Keros L, Mayaux MJ, Lebon P, Freymuth F, Eugene G, Strieker R, Dussaix E (1997): Value of cytomegalovirus (CMV) IgG avidity index for the diagnosis of primary CMV infection in pregnant women. J Infect Dis;; 175 (4): 944-946.

100

Egyptian Journal of Medical Microbiology, October 2010

38.

39.

40.

41.

42.

43.

44.

45.

for the treatment of intrauterine cytomegalovirus infection in a renal allogralf recipient. Transpl Infect Dis; 7: 71--74. Barbi M, Binda S, Caroppo S, Calvario A, Cierminario C, Bozzi A et al. (2006): Multicity Italian study of congenital cytomegalovirus infection. Pediatr Infect Dis J; 25:156--159. Hyde TB, Schmid DS, Cannon MJ (2010): Cytomegalovirus seroconversion rates and risk factors: implications for congenital CMV. Reviews in Medical Virology, 20: 311-326. Kreimer AR, Alberg AJ, Viscidi R, Gillison ML (2004): Gender differences in sexual biomarkers and behaviors associated with human papillomavirus-16, -18, and 33 seroprevalence. Sex Transm Dis; 31:247-256. Gottlieb SL, Douglas JM, Jr, Schmid DS, Bolan G, Iatesta M, Malotte CK, Zenilman J, Foster M, Baron AE, Steiner JF, Peterman TA, Kamb ML, Project RSG (2002): Seroprevalence and correlates of herpes simplex virus type 2 infection in five sexually transmitted-disease clinics. J Infect Dis; 186:1381-1389. Mertz GJ, Benedetti J, Ashley R, Selke SA, and Corey L (1992): Risk factors for the sexual transmission of genital herpes. Ann Intern Med; 116:197-202. Kraat YJ, Stals FS, Landini MP, Bruggeman CA (1993): Cytomegalovirus IgM antibody detection: comparison of five assays. Microbiologica; 16: 297-307. Daiminger A, Bader U, Eggers M, Lazzarotto T, Enders G (1999): Evaluation of two novel enzyme immunoassays using recombinant antigens to detect cytomegalovirus-specific immunoglobulin M in sera from pregnant women. J Clin Virol; 13:161-171. Lazzarotto T, Galli C, Pulvirenti R, Rescaldani R, Vezzo R, La Gioia A, Martinelli C, La Rocca S, Agresti G, Grillner L, Nordin M, van Ranst M, Combs B, Maine GT, Landini MP (2001): Evaluation of the Abbott AxSYM cytomegalovirus (CMV) immunoglobulin M (IgM) assay in conjunction with other CMV IgM tests and a CMV IgG avidity assay. Clin Diagn Lab Immunol; 8:196198.

Vol. 19, No. 4

46. Maine GT, Stricker R, Schuler M, Spesard J, Brojanac S, Iriarte B, Herwig K, Gramins T, Combs B, Wise J, Simmons H, Gram T, Lonze J, Ruzicki D, Byrne B, Clifton JD, Chovan LE, Wachta D, Holas C, Wang D, Wilson T, Tomazic-Allen S, Clements MA, Wright GL, Lazzarotto T, et al. (2000): Development and clinical evaluation of a recombinant-antigen-based cytomegalovirus immunoglobulin M automated immunoassay using the Abbott AxSYM analyzer. J Clin Microbiol; 38:1476-1481. 47. Correa CB, Kouri V, Verdasquera D, Martinez PA, Alvarez A, Aleman Y, et al. (2010): HCMV seroprevalence and associated risk factors in pregnant women, Havana City, 2007 to 2008. Prenat Diagn; 30 (9): 888-92. 48. Jahromi AS, Makiani MJ, Farjam MR, Madani A, Amirian M, Eftekhri TE, Hamidipour S (2010): Cytomegalovirus immunity in pregnancy in south of Iran. Am J Infect Dis; 6 (1): 8-12. 49. Lazzarotto T, Galli C, Pulvirenti R, Bescaldani R, et al. (2001): Evaluation of the abbott AxSYM cytomegalovirus (CMV) immunoglobulin M (IgM) assay in conjunction with other CMV IgM test and a CMV IgG avidity assay. Clin Diag Lab Immunol; 1 (1): 196-198. 50. Lazzarotto T, Spezzacatena P, Pradelli P, Abate DA, Varani S, Landini MP (1997): Avidity of immunoglobulin G directed against human cytomegalovirus during primary and secondary infections in immunocompetent and immunocompromised subjects. Clin Diagn Lab Immunol 4:469-473. 51. Lagrou K, Bodeus M, Van Ranst M, Goubaau P (2009): Evaluation of the new architect cytomegalovirus immunoglobulin M (IgM), IgG, and IgG avidity assays (traingledown). J Clin Microbiol; 47 (6): 1695-1699. 52. Revello MG, Zavattoni M, Sarasini A, Percivalle E, Simoncini L, Gerna G (1998): Human cytomegalovirus in blood of immunocompetent persons during primary infection: prognostic implications for pregnancy. J Infect Dis; 177:1170-1175.

101

‫‪Egyptian Journal of Medical Microbiology, October 2010‬‬

‫‪Vol. 19, No. 4‬‬

‫دراﺳﺔ ﻣﻘﺎرﻧﺔ ﻟﻠﻄﺮق اﻟﻤﺨﺘﻠﻔﺔ ﻓﻰ اﻟﻜﺸﻒ ﻋﻦ ﻋﺪوى ﻓﻴﺮوس اﻟﺘﻀﺨﻢ اﻟﺨﻠﻮى اﻷوﻟﻰ‬ ‫وﻏﻴﺮ اﻷوﻟﻰ ﻓﻰ اﻟﺴﻴﺪات اﻟﺤﻮاﻣﻞ‬ ‫ﺟﻴﻬﺎن أﺣﻤﺪ اﻟﺸﻨﺎوى‪ ،‬أﺣﻤﺪ ﻣﺮاد أﺳﻌﺪ‬ ‫ﻗﺴﻢ اﻟﻤﻴﻜﺮوﺑﻴﻮﻟﻮﺟﻴﺎ – آﻠﻴﺔ اﻟﻄﺐ – ﺟﺎﻣﻌﺔ اﻟﺰﻗﺎزﻳﻖ‬ ‫ﻳﻌﺘﺒﺮ ﺗﺸﺨﻴﺺ اﻟﻌﺪوي اﻟﻤﺒﺪﺋﻴﺔ ﺑﻔﻴﺮوس اﻟﺘﻀﺨﻢ اﻟﺨﻠﻮي ﻓﻲ اﻟﺴﻴﺪات اﻟﺤﻮاﻣﻞ هﺎم ﺟﺪًا وﺧﺼﻮﺻًﺎ أن هﺬا اﻟﻔﻴﺮوس ﻣﻦ أﺷﻬﺮ أﺳﺒﺎب‬ ‫اﻟﻌﺪوي اﻟﻮراﺛﻴﺔ ﻓﻲ اﻹﻧﺴﺎن‪ .‬ﺗﻬ ﺪف ه ﺬﻩ اﻟﺪراﺳ ﺔ إﻟ ﻲ ﺗ ﺸﺨﻴﺺ اﻟﻌ ﺪوي اﻟﻤﺒﺪﺋﻴ ﺔ وﻏﻴ ﺮ اﻟﻤﺒﺪﺋﻴ ﺔ ﺑﻔﻴ ﺮوس اﻟﺘ ﻀﺨﻢ اﻟﺨﻠ ﻮي ﻟ ﺪي اﻟ ﺴﻴﺪات‬ ‫اﻟﺤﻮاﻣﻞ ﻋﻦ ﻃﺮﻳﻖ ﻗﻴﺎس اﻷﺟﺴﺎم اﻟﻤﻀﺎدة ﻣﻦ اﻟﻨﻮع ﺟﻰ‪ ،‬و إم ﻓﻰ أﻣﺼﺎل هﺆﻻء اﻟﺴﻴﺪات وأﻳﻀﺎ ﻋﻦ ﻃﺮﻳﻖ إﺳﺘﺨﺪام ﺗﻔﺎﻋ ﻞ ﺳﻠ ﺴﻠﺔ إﻧ ﺰﻳﻢ‬ ‫اﻟﺒﻠﻤ ﺮة ﻓ ﻲ دم ه ﺆﻻء اﻟ ﺴﻴﺪات‪ .‬آﻤ ﺎ ﻳ ﺘﻢ أﻳ ﻀًﺎ ﻣﻘﺎرﻧ ﺔ ﻃﺮﻳﻘ ﺔ ﻗﻴ ﺎس ﻧ ﺴﺒﺔ اﻹﺗﺤ ﺎد اﻟﺨﺎﺻ ﺔ ﺑﺎﻷﺟ ﺴﺎم اﻟﻤ ﻀﺎدة ﺟ ﻰ ﺑﻄﺮﻳﻘ ﺔ ﺗﻔﺎﻋ ﻞ اﻟﺒﻠﻤ ﺮة‬ ‫اﻟﻤﺘﺴﻠﺴﻞ ﻟﻠﻜﺸﻒ ﻋﻦ اﻟﻌﺪوي اﻟﻤﺒﺪﺋﻴﺔ‪.‬‬ ‫ﺷﻤﻠﺖ هﺬﻩ اﻟﺪراﺳﺔ ﻋﺪد ‪ ٧٥٠‬ﻣﻦ اﻟﺴﻴﺪات اﻟﺤﻮاﻣﻞ ً‪ .‬ﺗﻢ إﺧﺘﺒﺎر أﻣﺼﺎل هﺆﻻء اﻟﺴﻴﺪات ﻟﻠﻜﺸﻒ ﻋﻦ وﺟﻮد اﻷﺟﺴﺎم اﻟﻤﻀﺎدة ﻣﻦ اﻟﻨﻮع‬ ‫إم‪ ،‬ﺟﻰ وﻧﺴﺒﺔ إﺗﺤﺎد اﻷﺟﺴﺎم اﻟﻤﻀﺎدة ﺟﻰ‪ ،‬آﻤﺎ ﺗﻢ ﺗﻜﺮار هﺬﻩ اﻹﺧﺘﺒﺎرات ﻓﻲ ﻓﺘﺮة اﻟﺜﻼﺛﺔ أﺷﻬﺮ اﻟﺘﺎﻟﻴﺔ ﻣﻦ اﻟﺤﻤ ﻞ ﻟﻠﻜ ﺸﻒ ﻋﻤ ﺎ إذا ﻣ ﺎ ﺣ ﺪث‬ ‫ﺗﻐﻴﻴﺮ ﻓﻲ وﺟﻮد اﻷﺟﺴﺎم اﻟﻤﻀﺎدة ﻓﻰ أﻣﺼﺎل هﺆﻻء اﻟﺴﻴﺪات ﻳﺸﻴﺮ إﻟ ﻲ ﺣ ﺪوث ﻋ ﺪوي‪ .‬وﻗ ﺪ ﺗ ﻢ ﻋﻤ ﻞ إﺧﺘﺒ ﺎر ﺗﻔﺎﻋ ﻞ اﻟﺒﻠﻤ ﺮة اﻟﻤﺘﺴﻠ ﺴﻞ ﻟ ﺪي‬ ‫اﻟﺴﻴﺪات اﻟﻼﺗﻲ ﺗﻢ إآﺘﺸﺎف اﻷﺟﺴﺎم اﻟﻤﻀﺎدة ﺟﻰ ﻓﻲ أﻣﺼﺎﻟﻬﻦ ﻟﻠﻜﺸﻒ ﻋﻦ ﻓﻴﺮس اﻟﺘﻀﺨﻢ اﻟﺨﻠﻮي‪ .‬وﻗﺪ ﺷﻤﻠﺖ هﺬﻩ اﻟﺪراﺳﺔ أﻳﻀًﺎ ﻋﺪد ‪٧٥٠‬‬ ‫ﻣﻦ ﻣﺘﺒﺮﻋﻲ اﻟﺪم ﻏﻴﺮ ﻣﻌﺮوف ﺣﺎﻟﺔ اﻹﺻﺎﺑﺔ ﻟﺪﻳﻬﻢ ﺑﻬﺬا اﻟﻔﻴﺮوس آﻤﺠﻤﻮﻋﺔ ﺿﺎﺑﻄﺔ‪ .‬وﻗ ﺪ أﻇﻬ ﺮت ه ﺬﻩ اﻟﺪراﺳ ﺔ أﻧ ﻪ ﻓ ﻲ ه ﺆﻻء اﻷﺷ ﺨﺎص‬ ‫آﺎﻧﺖ اﻹﺻﺎﺑﺔ ﺗﻤﺜﻞ ﻧﺴﺒﺔ ‪ %٣٥٫٣‬ﻟﺪي اﻷﺷﺨﺎص أﻗﻞ ﻣﻦ ‪ ٢٠‬ﺳﻨﺔ وإرﺗﻔﻌﺖ ﻧﺴﺒﺔ اﻹﺻﺎﺑﺔ ﻣﻊ زﻳﺎدة أﻋﻤﺎرهﻢ ﺣﺘﻲ وﺻﻠﺖ ﻣﺮﺣﻠ ﺔ اﻟﺜﺒ ﺎت‬ ‫ﻋﻨﺪ ﻋﻤﺮ ‪ ٤٧‬ﺳﻨﺔ ﺑﻨﺴﺒﺔ ‪.%٦٤٫٧‬‬ ‫وﻗﺪ أﺑﺮزت هﺬﻩ اﻟﺪراﺳﺔ ﻋﻦ ﻋﺪة ﻧﺘﺎﺋﺞ ﻣﻨﻬﺎ أن ﻣﻌﺪل اﻹﺻﺎﺑﺔ ﺑﻬﺬا اﻟﻔﻴﺮوس ﻟ ﺪي اﻟ ﺴﻴﺪات اﻟﺤﻮاﻣ ﻞ آ ﺎن ‪) %٥٨‬اﻟﻌ ﺪد ‪ ٤٣٥‬ﺳ ﻴﺪة(‬ ‫ﻋﻦ ﻃﺮﻳﻖ اﻟﻜﺸﻒ ﻋﻦ اﻷﺟﺴﺎم اﻟﻤﻀﺎدة ﺟﻰ‪ ،‬ﻣﻨﻬﻢ ‪) %٨‬اﻟﻌﺪد ‪ ٦٠‬ﺳ ﻴﺪة( ﺗ ﻢ ﻇﻬ ﻮر اﻷﺟ ﺴﺎم اﻟﻤ ﻀﺎدة إم ﻓ ﻲ أﻣ ﺼﺎﻟﻬﻦ‪ .‬أﻣ ﺎ إﺧﺘﺒ ﺎر ﻧ ﺴﺒﺔ‬ ‫إﺗﺤﺎد اﻷﺟﺴﺎم اﻟﻤﻀﺎدة ﺟﻰ ﻓﺄﻇﻬﺮ أﻧﻪ هﻨﺎك ﻧﺴﺒﺔ ‪) %٢٫١‬اﻟﻌﺪد ‪ ١٦‬ﺳﻴﺪة( آﺎﻧﺖ ﻟﺪﻳﻬﻦ ﻧﺴﺒﺔ إﺗﺤﺎد ﻣﻨﺨﻔﻀﺔ‪ ،‬وهﺬا ﻳ ﺪل ﻋﻠ ﻲ ﺣ ﺪوث ﻋ ﺪي‬ ‫ﻣﺒﺪﺋﻴﺔ ﺑﺎﻟﻔﻴﺮوس وﺧﻄ ﻮرة إﻧﺘﻘ ﺎل ه ﺬا اﻟﻔﻴ ﺮوس ﻟﻠﺠﻨ ﻴﻦ وآ ﺎن هﻨ ﺎك ﻋ ﺪد ‪ ٤٤‬ﺳ ﻴﺪة )‪ (%٥٫٩‬ﻟ ﺪﻳﻬﻦ ﻧ ﺴﺒﺔ اﺗﺤ ﺎد ﻋﺎﻟﻴ ﺔ‪ .‬أﻣ ﺎ ﺗﻔﺎﻋ ﻞ اﻟﺒﻠﻤ ﺮة‬ ‫اﻟﻤﺘﺴﻠﺴﻞ ﻓﺄﻇﻬﺮ إﺻﺎﺑﺔ ‪ ١٤‬ﺳﻴﺪة ﻣﻦ اﻟﻌﺪد ‪ ١٦‬اﻟﻤﺼﺎﺑﺎت واﻟﻼﺗﻲ ﺗﻢ اﻟﻜﺸﻒ ﻋﻦ اﻟﻔﻴﺮوس ﻟﺪﻳﻬﻦ ﺑﺈﺧﺘﺒﺎر ﻧﺴﺒﺔ اﻹﺗﺤﺎد اﻟﻤﻨﺨﻔ ﻀﺔ ﻟﻸﺟ ﺴﺎم‬ ‫اﻟﻤﻀﺎدة ﺟﻰ‪ .‬ﻋﻠﻲ هﺬا ﻓﺈن اﻹﺧﺘﺒﺎر اﻟﻤ ﺬآﻮر أﺧﻴ ﺮًا أﻇﻬ ﺮ ﻧ ﺴﺒﺔ ﺣ ﺴﺎﺳﻴﺔ ‪ %٨٢٫٤‬ﺧ ﺼﻮﺻﻴﺔ ‪ ،%٩٥٫٣‬ﻗﻴﻤ ﺔ ﺗﻮﻗ ﻊ ﻣﻮﺟﺒ ﺔ ‪ ،٨٧٫٥‬ﻗﻴﻤ ﺔ‬ ‫ﺗﻮﻗﻊ ﺳﺎﻟﺒﺔ ‪ %٩٣٫٢‬ودﻗﺔ ﺑﻨﺴﺒﺔ ‪ %٩١٫٧‬ﻓﻲ اﻟﻜﺸﻒ ﻋﻦ اﻟﻌﺪوي اﻟﻤﺒﺪﺋﻴﺔ )وذﻟﻚ ﻣﻘﺎرﻧ ﺔ ﺑﺈﺧﺘﺒ ﺎر ﺗﻔﺎﻋ ﻞ اﻟﺒﻠﻤ ﺮة اﻟﻤﺘﺴﻠ ﺴﻞ آﻤﻌﻴ ﺎر ذهﺒ ﻲ(‬ ‫وﺑﺪراﺳﺔ اﻷﻃﻔﺎل اﻟﻤﻮﻟﻮدﻳﻦ ﻟﻬﺆﻻء اﻟﺴﻴﺪات )اﻟﻌ ﺪد ‪ (١٦‬وﺟ ﺪ أﻧ ﻪ ﻳﻮﺟ ﺪ ﺑﻴ ﻨﻬﻢ ‪ ١٤‬ﻃﻔ ﻞ ﻳﺤﻤ ﻞ اﻹﺻ ﺎﺑﺔ ﺑﻬ ﺬا اﻟﻔﻴ ﺮوس ﺗ ﻢ ﺗﺸﺨﻴ ﺼﻬﻢ ﺑﻜ ﻞ‬ ‫اﻟﻄ ﺮق اﻟﻤ ﺴﺘﺨﺪﻣﺔ ﻓ ﻲ ه ﺬﻩ اﻟﺪراﺳ ﺔ‪ .‬آﻤ ﺎ أﻇﻬ ﺮت اﻟﺪراﺳ ﺔ أن إﺧﺘﺒ ﺎر ﻧ ﺴﺒﺔ إﺗﺤ ﺎد اﻷﺟ ﺴﺎم اﻟﻤ ﻀﺎدة ﺟ ﻰ ﻟ ﻪ ﻧ ﺴﺒﺔ ﺣ ﺴﺎﺳﻴﺔ ‪،%٧٧٫٨‬‬ ‫ﺧﺼﻮﺻﻴﺔ ‪ ،%١٠٠‬ﻗﻴﻤﺔ ﺗﻮﻗﻊ ﻣﻮﺟﺒﺔ ‪ %١٠٠‬ﻗﻴﻤﺔ ﺗﻮﻗﻊ ﺳﺎﻟﺒﺔ ‪ ،%٧٧٫٨‬ودﻗﺔ ﺑﻨﺴﺒﺔ ‪ %٨٧٫٥‬ﻓﻲ اﻟﻜﺸﻒ ﻋﻦ ﺣﺪوث إﻧﺘﻘﺎل اﻟﻔﻴﺮوس ﻣ ﻦ‬ ‫اﻷم اﻟﻤﺼﺎﺑﺔ إﻟﻲ اﻟﺠﻨ ﻴﻦ )وذﻟ ﻚ أﻳ ﻀًﺎ ﻣﻘﺎرﻧ ﺔ ﻣ ﻊ ﺗﻔﺎﻋ ﻞ اﻟﺒﻠﻤ ﺮة اﻟﻤﺘﺴﻠ ﺴﻞ( وﺑﺈﻳﺠ ﺎز ﻳﻤﻜ ﻦ اﻟﻘ ﻮل أن إﺧﺘﺒ ﺎر ﺗﻔﺎﻋ ﻞ اﻟﺒﻠﻤ ﺮة اﻟﻤﺘﺴﻠ ﺴﻞ ﻓ ﻲ‬ ‫ﺗﺸﺨﻴﺺ ﻓﻴﺮوس اﻟﺘﻀﺨﻢ اﻟﺨﻠﻮي هﻮ إﺧﺘﺒﺎر ﺣﺴﺎس وﻟ ﻪ ﺧ ﺼﻮﺻﻴﺔ ودﻗ ﺔ ﻋﺎﻟﻴ ﺔ ﻓ ﻲ اﻟﻜ ﺸﻒ ﻋ ﻦ اﻟﻌ ﺪوي اﻟﻤﺒﺪﺋﻴ ﺔ ﺑﻬ ﺬا اﻟﻔﻴ ﺮوس آﻤ ﺎ أﻧ ﻪ‬ ‫ﻳﺴﺘﻄﻴﻊ أﻳﻀًﺎ ﺑﺪﻗﺔ ﺗﺤﺪﻳﺪ ﻋﻤﺎ إذا آﺎن هﻨﺎك إﺣﺘﻤﺎﻟﻴﺔ إﻧﺘﻘﺎل هﺬا اﻟﻔﻴ ﺮوس ﻣ ﻦ اﻷم إﻟ ﻲ اﻟﺠﻨ ﻴﻦ وﺑﺎﻟﺘ ﺎﻟﻲ ﻓ ﺈن ه ﺬا اﻹﺧﺘﺒ ﺎر ﺳ ﻮف ﻳ ﺴﺎﻋﺪ ﻓ ﻲ‬ ‫اﻟﺘﺸﺨﻴﺺ اﻟﺴﺮﻳﻊ واﻟﺘﺪﺧﻞ اﻟﻄﺒﻲ اﻟﻤﻨﺎﺳﺐ ﻟﻬﺬﻩ اﻟﺤﺎﻻت‪.‬‬

‫‪102‬‬