Serological profile of TORCH Infection Among Antenatal Women at a Tertiary Care Center in North India (RESEARCH ARTICLE).
TORCH is an acronym which stands for Toxoplasmosis, Other (Varicella-Zoster virus infection, Syphilis, Parvovirus B19, Hepatitis B), Rubella virus, Cytomegalovirus infection and Herpes Simplex virus infection. (1) The term Bad Obstetric History (BOH) is applied to mothers in whom a previous poor pregnancy outcome is likely to have a bearing on the prognosis of her present pregnancy. BOH implies poor pregnancy outcomes in terms of intrauterine fetal death, intrauterine growth retardation, still births, two or more consecutive spontaneous abortions, early neonatal death and/or congenital anomalies. (2) The TORCH group of pathogens are responsible for serious congenital infections during pregnancy, leading to fetal damage or other anomalies. (1) Epidemiology of these infections is variable. Transmission of these pathogens may occur prenatally, perinatally, and postnatally. Transplacental passage of organisms, contact with vaginal and blood secretions, or exposure to breast milk are the common modes of transmission for CMV and HSV. (3) Poor hygienic conditions, water, soil and airborne respiratory droplets also favor their spread. (3)
Majority of the TORCH infections cause mild maternal illness, but fetal consequences are serious. Treatment of maternal infection frequently has no impact on fetal outcome. Early recognition of maternal disease and fetal monitoring once disease is recognized is vital. Knowledge of these diseases will help the clinician appropriately counsel mothers on preventive measures to avoid these infections, and will aid in counseling parents on the potential for adverse fetal outcomes when these infections are present. Evidence of infection may be evident in new born, infancy, or in later life. The clinical manifestations seen in infected newborn infant are abnormal growth or developmental abnormalities. The infection can also present as multiple clinical and laboratory abnormalities. Primary infection leads to more damage than the secondary or reactivated infection. (4) Each causative agent has distinct manifestation but features could also be overlapping. (4)
Most of the maternal infections are initially asymptomatic. Diagnosis based on clinical presentation is difficult. Thus, the diagnosis of these infections largely depends on serological evidence. Utilizing the TORCH panel for screening may help to prevent many of these potential birth defects, as some of the TORCH infections can be effectively treated if the mother is diagnosed early in her pregnancy. The detection of the IgM antibody against Toxoplasma, Rubella, HSV and CMV is the best diagnostic modality for these infections. (5) A national screening program for TORCH infections is lacking in India. A representative serological data for TORCH infection during pregnancy is lacking. So this study was undertaken to evaluate the seroprevalence of TORCH infections in pregnant women with bad obstetric history (BOH) attending a tertiary care hospital in North India. Ig M antibodies against T. gondii, Rubella, HSV and CMV were determined.
MATERIAL & METHODS
This prospective study was carried on over a period of one year from January 2017 to December 2017 in Department of Microbiology at a tertiary care center in North India. 419 serum samples from pregnant women in first trimester with a bad obstetric history were included in the study. The serum samples were accompanied with a requisition form for TORCH profile and a brief clinical history of the patient. The patients were in the age group of 18-40 years Anti- Toxoplasma, anti Rubella, anti HSV and anti- CMV IgM antibodies were assayed by an enzyme linked immunosorbent assay (ELISA) method using Calbiotech kits as per the manufacturer's instructions.
Gaussian (z) test, confidence interval was used for statistical analysis. The study was approved by institutional ethics committee.
The patients were distributed age wise i.e <20 years, 21-25 years, 26-30 years, 31-35 years and >36 years. The average age of the participants in this study was 28.05 [+ or -] 5.36 years. Overall 419 serum samples were tested against anti- Toxoplasma, anti- Rubella, anti HSV and anti-CMV IgM antibodies by EL ISA. Overall, 260(62.1%) samples were negative for TORCH pathogens while 159(37.9%) were positive.
Out of the total positive cases, 69 cases (16.4%) were found to be seropositive for Ig M anti Toxoplasma antibodies, 37(8.8%) were positive for Ig M anti Rubella, 10(2.3%) were positive for Ig M anti HSV and 43 (10.2%) were positive for Ig M anti CMV. (Tables 1 & 2).
In <20 yrs of age group, the total positive cases (12.5%), cases were distributed equally between IgM anti Toxoplasma (50%) and Ig M anti Rubella (50%), while none of the other markers were positive. In 21-25 yrs of age group, out of the total positive cases (47.5%), the majority of cases were positive for Ig M anti Toxoplasma and Ig M anti CMV (34.6%) followed by Ig M anti R(24.4%) and Ig M anti HSV(6.1%). In the 26-30 yrs of age group, out of total positive cases (45%), IgM anti Toxoplasma accounted for maximum number of cases (42%), followed by and Ig M anti CMV (27.5%), IgM anti Rubella (21.7%) and IgM anti HSV (8.6%). In 31-35 yrs of age group, out of total positive cases (28.5%), IgM anti Toxoplasma accounted for majority of the cases (53.8%), followed by Ig M anti CMV (26.9%), IgM anti Rubella (15.3%) and IgM anti HAV(3.8%). In >36 yrs of age group, out of the total positive cases (27.5%), Ig M anti Toxoplasma was positive in 63.6% of cases while Ig M anti Rubella was positive in 36.3%% of the cases. None of the other markers were positive (Table 3).
On analyzing age wise seropositivity of TORCH pathogens, maximum seropositivity was observed in 21-30 years age group. Age wise seropositivity of Ig M anti Toxoplasma and Ig M anti HSV was highest in 26-30 years being 18.9% and 3.9% respectively. In addition, age wise seropositivity of Ig M anti Rubella and Ig M anti CMV was highest in 21-25 years of age being 11.6% and 16.5%respectively. (Table 2, Figure 1)
Statistically, incidence of TORCH was not seen significantly above the average in any of the age groups.
Out of 159 positive cases (37.9%), 6 (3.7%) were found to be coinfected. The maximum number of coinfection cases was seen to be associated with Toxoplasma with 5 (83.3%) cases followed by Rubella with 1 case (16.6%).
Out of 69 cases positive for Toxoplasma, 5 cases (7.2%) were found to be coinfected. Out of these 5 cases, 2 cases (2.8%) were coinfected with rubella and 2 with CMV (2.8%) and 1 (1.4%) with HSV. In our study, 1 cases of coinfection were seen to occur between Rubella and CMV. (Table 4)
Maternal infections caused by TORCH agents leads to neonatal and fetal mortality. TORCH infections are important contributor to early and later childhood morbidity. (2) Primary infection could initially be in apparent or asymptomatic and thus difficult to diagnose on clinical basis. Serological diagnosis of TORCH infections should be done before or as soon as pregnancy is confirmed. (6) The overall seropositivity of TORCH infections in our study was 37.9%.Our findings were comparable with a study by Pradhan SV et al where the overall seroprevalence of TORCH pathogens was 33.7%. (7)
T. gondii is the causative agent of Toxoplasmosis and is an obligate intracellular protozoan parasite. (8) Toxoplasmosis is one of the most prevalent chronic infections occuring worldwide. (8) Toxoplasmosis is associated with fetal abnormalities like hydrocephaly, anomalies of the central nervous system, symmetric fetal growth retardation, and nonimmune hydrops. (9) Such scenarios demand maternal screening of anti-toxoplasma antibodies by ELISA. Toxoplasma-specific IgM antibodies are helpful in suggesting the time of infection. However, IgM antibodies have been known to persist till eighteen months post infection. (10) Negative Toxoplasma-specific IgM results are reassuring. However, positive results should be interpreted with caution, and followed by serial titers after three weeks. (10) About 20-90% of the world adult population is exposed to T. gondii. (11)
In our study, the prevalence of anti-toxoplasma specific IgM antibody was 16.5% in antenatal females with bad obstetric history. In India, toxoplasmosis seroprevalence is variably reported and ranges from from 5- 80%. (12-16) Our findings were comparable with studies of Rajendra et al., (2006), Yasodhara et al (2001), Sadik MS, et al.and Turbadkar D et al. where the prevalence of anti-toxoplasma specific IgM antibody was 14.66%, 13.1%,18% and 10.5% respectively. (13,14,15,16) A recent study from Chandigarh revealed increasing seropositivity to toxoplasma in women with BOH. (17)
The higher rate of seropositivity can be attributed to warm and humid environments, in our geographical region. Farming is the main occupation in this rural area which increases the exposure to the soil contaminated with faeces of cats. Contaminated water, poor sanitation and lack of hygiene are other factors leading to increased prevalence. Vaccination is not available against Toxoplasma thus primary prevention of Toxoplasmosis in pregnant mother can be achieved through education by health care authorities regarding risk factors and adopting preventive measures, which include washing hands frequently, washing all the vegetables and fruits and, proper handling of raw meat while preparation of food.Pregnant females should be adviced to stay away from pets, mainly cats.
Rubella is a mild viral illness characterized by exanthem and posterior cervical lymphadenopathy. WHO estimates that more than 100,000 children are born with CRS (congenital Rubella syndrome) every year. (18) Pregnant women infected in early weeks of pregnancy leads to serious manifestations in the fetus affecting the auditory function, heart and vision as congenital rubella syndrome (CRS). (19) Maternal Rubella infection in first eight weeks of pregnancy infects 90 - 100% .Almost all of the infected fetuses develop major clinical defects. (20) India epidemiological data reveals that 10-20% of women in childbearing age are susceptible to rubella infection. (21) Half of the rubella infections are subclinical. (21) Rubella infection during pregnancy causes congenital malformation in 10-54% of newborns. (7) In the present study seropositive rate was 8.8% which is comparable with studies of Yasodhara et al., (2001) and Denoj Sebatian et al., (2008) which revealed rates as 6.5% and 11.3% respectively. (14,22) MMR vaccine is part of universal immunization programme in India. Rubella prevention is dependent on early immunization. Sero-negative women should be immunized against rubella immediately after delivery.
Cytomegalovirus (CMV) is the most important cause of congenital infection causing long term neurodevelopment sequlae among children. (23) CMV infection can occur in any trimester of pregnancy. The estimated incidence of congenital CMV infection between 0.2 and 2.2% of all live births worldwide. (24) CMV infection is found universally. CMV is more prevalent in low socioeconomic conditions. Low and middle income group strata have higher rate of acquisition of CMV with seroprevalence rates ranging from 80-100%. (24) Most of the women in child bearing age are seropositive by that age.25Poor socio-economic conditions like overcrowding and a lack of hand hygiene, and day care centers, promote CMV transmission. (25) Routine antenatal screening along with behavioral and educational intervention is necessary to control CMV transmission.
The present study showed seropositivity of 10.2% for IgM antibodies to CMV. The findings were comparable in study by Turbadkar et al and Padmavathy M et al where seropositivity rates were 8.42% and 9.2% respectively. (2,16) However studies by Yasodhara et al., Rajendra Surpam et al., and Gumber et al., showed lower seropositivities of 5.8%, 5.33%, 4.67% respectively. (14,13,26) Such low seropostivity may be due to better standards of living.
Herpes simplex virus (HSV) is a ubiquitous, enveloped, and double stranded DNA virus. HSV belongs to the family of Herpesviridae.HSV is transmitted across mucosal membranes and nonintact skin and migrate to nerve tissues, where it persists in a latent state. (27,28) Neonatal herpes infection is a potentially devastating consequence of common genital HSV infection. (27,28) There is an increased incidence of genital herpes in pregnancy. Intrauterine HSV infection during early pregnancy is rare. Most neonatal herpes simplex virus infections are perinatally acquired. (28,29) Genital herpes during pregnancy leads to spontaneous abortion, intrauterine growth retardation, preterm labour, and congenital and neonatal herpes infections. (29) Prevention of neonatal disease consists of timely diagnosis and appropriate management in the mother including acyclovir therapy and caesarean delivery in the presence of active genital lesions. Subclinical infection in the mother is common, as only 9% of them have genital herpes at the time of delivery. (30) Serodiagnosis plays an important role in preventing neonatal herpes. The seroprevalence of Ig M antibodies to HSV was 2.3% in our study.
The seroreactivity of TORCH infections is seen maximally between the age group of 18-25 years in our study. This is due to the fact that this a common age group for getting married in India.
TORCH infections are a major cause of fetal morbidity and fetal loss. The fetal loss can be avoided by early identification and effective therapy. Pregnant women should be educated during antenatal visits regarding TORCH infections and their prevention. Universal vaccination remains a strong tool in eliminating congenital rubella syndrome. The epidemiology of TORCH needs better understanding which will guide the development of new strategies for the prevention of congenital infections. New approaches for prevention and treatment of congenital TORCH infection are necessary, including antiviral interventions and the development of a vaccine strategy. Good hygiene contributes immensely towards overall improved perinatal health and infection prevention.
(1.) Stegmann BJ, Carey JC .TORCH Infections. Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes infections. Curr Womens Health Rep. 2002; 2(4):253-8.
(2.) Padmavathy M, Mangala Gowri, Malini J, Umapathy BL, Navaneeth BV, Mohit Bhatia, Shruthi Harle.Seroprevalence of TORCH Infections and Adverse Reproductive Outcome in Current Pregnancy with Bad Obstetric History. J. Clin. Biomed. Sci. 2013; 3(2):62-71.
(3.) Natalie Neu, Jennifer Duchon, Philip Zachariah. TORCH Infections Clin Perinatol, 2015; 42: 77-103.
(4.) Robert F. Pass and Brenna Anderson. Mother-to-Child Transmission of Cytomegalovirus and Prevention of Congenital Infection. J. Pediatric Infect Dis. Soc. 2014; 3(1): S2-S6.
(5.) Shweta Sharma, Nandini Duggal, Saumya Agarwal, R. K. Mahajan, Anuradha, Charoo Hans. Seroprevalence of Toxoplasma, Rubella and CMV infections in Antenatal Women in a Tertiary care hospital in North India. J. Commun. Dis. 2015; 47(2): 23-26.
(6.) Rajnish Kumar Yadav, Siddhartha Maity, Sudipta Saha .A review on TORCH: groups of congenital infection during pregnancy. Journal of Scientific and Innovative Research. 2014; 3(2): 258-264.
(7.) SV Pradhan.Epidemiological and serological profiles of TORCH infection in pregnancy. Journal of Pathology of Nepal. 2015; 5(9):705-708.
(8.) Astrid M. Tenter, Anja R. Heckeroth, and Louis M. Weiss. Toxoplasma gondii: from animals to humans. Int J Parasitol. 2000; 30(12-13): 1217-1258.
(9.) Thomas J Bader, George A Macones and David A Asch. Prenatal Screening for Toxoplasmosis. Obstetrics & Gynecology. 1997; 90(3):457-464.
(10.) CDC-DPDx-Toxoplasmosis-Laboratory Diagnosishttps://www.cdc.gov/dpdx/ toxoplasmosis/dx.htm
(11.) Jaroslav Flegr, Joseph Prandota, Michaela Soviekova and Zafar H. Israili.Toxoplasmosis-A Global Threat. Correlation of Latent Toxoplasmosis with Specific Disease Burden in a Set of 88 Countries. PLoS One. 2014; 9(3): 902-03.
(12.) Sucilathangam et al: Serological survey of Toxoplasmosis in a district in Tamil Nadu. Indian J. Med. Res. 2013, 560-563.
(13.) Rajendra, B., Surpam, et al. Department of Microbiology, Indira Gandhi Govt. Medical College, Nagpur. Serological study for TORCH infections in women with BOH. J. Obstet. Gynecol. 2006; 6(1):947-1091.
(14.) Yasodhara, P., et al. 2001.Prevalence of specific IgM due to Toxoplasma, Rubella, Cytomegalo virus and Chlamydia trachomatis infections during pregnancy. IJMM, 19(2): 52-56.
(15.) Sadik MS, Fatima H, Jamil K, Patil C. Study of TORCH profile in patients with bad obstetric history. Biology and Medicine. 2012; 4(2): 95-101.
(16.) Turbadkar D, Mathur M, Rele M. Seroprevalence of torch infection in bad obstetric history. Indian J. Med. Microbiol. 2003; 21: 108-10.
(17.) Tekkesin N. Diagnosis of toxoplasmosis in pregnancy: a review. HOAJ Biology. 2012; 1:1-9.
(18.) WHO | Rubella :www.who.int/mediacentre/ factsheets/fs367/en.
(19.) Joan L. Robinson, Bonita E. Lee, Jutta K. Preiksaitis, Sabrina Plitt, and Graham A. Tipples Prevention of Congenital Rubella Syndrome-What Makes Sense in 2006?. Epidemiologic Reviews. 2006; 28:81-87.
(20.) The Problem-Measles&Rubella Initiative: https://measlesrubellainitiative.org/learn/theproblem/
(21.) Vijayalakshmi P, Anuradha R, Prakash K, Narendran K, Ravindran M, Prajna L, et al. Rubella serosurveys at three Aravind eye hospitals in Tamil Nadu, India. Bull World Health Organ. 2004; 82:259-64.
(22.) Denoj Sebastian, K. F. Zuhara and K. Sekaran Influence of torch infections in first trimester miscarriage in the Malabar region of Kerala. African Journal Of Microbiology Research. 2008; 2(3): 56-59.
(23.) Idris Abdullahi Nasir, Adamu Babayo, and Muhammad Sagir Shehu. Clinical Significance of IgG Avidity Testing and other considerations in the diagnosis of congenital Cytomegalovirus infection: A Review Update. Med Sci(Basel). 2016; 4(1): 5.
(24.) Sheetal Manicklal, Vincent C. Emery, Tiziana Lazzarotto,Suresh B. Boppana, and Ravindra K. Gupta. The "Silent" Global Burden of Congenital Cytomegalovirus. Clin Microbiol Rev. 2013; 26(1): 86-102.
(25.) Kusuma Nellimarla and R. Lakshmi Kumari. Seroprevalence of TORCH Infections in Pregnant Women with Bad Obstetric History in and around Kakinada Town, India Int.J.Curr.Microbiol.App. Sci. 2017; 6(4): 1899-1906.
(26.) Gumber, S., et al. Occurance of Cytomegalovirus and Herpes simplex virus infections in Pregnancy. IJMM, 2008: 204-205.
(27.) Gupta R, Warren T, and Wald A. "Genital herpes," The Lancet. 2007; 370:2127-37.
(28.) Gianluca Straface, Alessia Selmin, Vincenzo Zanardo, Marco De Santis, and Giovanni Scambia' Herpes Simplex Virus Infection in Pregnancy. Infect Dis Obstet Gynecol. 2012
(29.) Scott H. James, Jeanne S. Sheffield, and David W. Kimberlin. Mother-to-Child Transmission of Herpes Simplex Virus. J. Pediatric Infect Dis Soc. 2014; 3(1):19-23.
(30.) Christine Johnston, Lawrence Corey-Current Concepts for Genital Herpes Simplex Virus Infection: Diagnostics and Pathogenesis of Genital Tract Shedding. Clin. Microbiol. Rev. 2016; 29 (1): 149-16.
Department of Microbiology, Career Institute of Medical Sciences and Hospital, Lucknow, UP, India.
(Received: 18 October 2018; accepted: 08 December 2018)
Table 1. Month wise seropositivity of torch infections Month Total Positive TOXO IgM sample % p-value % p-value JAN 34 70.6 <0.001 32.4 0.048 FEB 30 26.7 0.164 16.7 0.980 MAR 21 61.9 0.023 4.8 0.012 APR 19 36.8 0.924 26.3 0.331 MAY 40 32.5 0.466 17.5 0.868 JUN 33 78.8 <0.001 63.6 <0.001 JUL 38 31.6 0.402 0.0 NA AUG 47 14.9 <0.001 0.0 NA SEP 40 35.0 0.701 0.0 NA OCT 38 31.6 0.402 0.0 NA NOV 42 47.6 0.207 38.1 0.004 DEC 37 8.1 <0.001 8.1 0.061 TOTAL 419 37.9 16.5 Month Rubella IgM CMV IgM HSV % p-value % p-value % p-value JAN 11.8 0.592 26.5 0.033 0.0 NA FEB 0.0 NA 10.0 0.956 0.0 NA MAR 9.5 0.910 42.9 0.003 4.8 0.611 APR 5.3 0.490 5.3 0.325 0.0 NA MAY 5.0 0.270 7.5 0.501 2.5 0.968 JUN 6.1 0.510 6.1 0.307 3.0 0.833 JUL 18.4 0.126 13.2 0.602 0.0 NA AUG 14.9 0.241 0.0 NA 0.0 NA SEP 10.0 0.800 12.5 0.674 12.5 0.053 OCT 13.2 0.427 15.8 0.353 2.6 0.929 NOV 7.1 0.677 0.0 NA 2.4 0.994 DEC 0.0 NA 0.0 NA 0.0 NA TOTAL 8.8 10.3 2.4 * p-values are calculated to compare the incidence rate month wise with the average using Gaussian (z) test. Table 2. Overall sero-positivity of Toxoplasma, Rubella, HSV and CMV Serological test Total Percentage of 95% CI for positive total positive Incidence Lower Upper IgM anti-Toxoplasma 69 16.4 12.85 19.95 IgM anti-Rubella 37 8.8 6.09 11.51 IgM anti-CMV 43 10.2 7.30 13.10 IgM anti-HSV 10 2.3 0.86 3.74 Table 3. Contribution of TORCH pathogens to age wise seropositivity in different groups of pregnant women Age Total Total positive Toxo group Sample No. (%) p-value No. (%) p-value <20 32 4(12.5) <0.001 2(6.25) 0.018 21-25 103 49(47.5) 0.051 17(16.5) 0.978 26-30 153 69(45.0) 0.078 29(18.9) 0.430 31-35 91 26(28.5) 0.047 14(15.3) 0.771 >36 40 11(27.5) 0.141 7(17.5) 0.855 419 159(37.9) -- 69(16.4) -- Age Rubella CMV HSV group No. (%) p-value No. (%) p-value No. (%) p-value <20 2(6.25) 0.551 0(0) NA 0(0) NA 21-25 12(11.6) 0.375 17(16.5) 0.085 3(2.9) 0.717 26-30 15(9.8) 0.677 19(12.4) 0.409 6(3.9) 0.307 31-35 4(4.3) 0.034 7(7.6) 0.349 1(1.0) 0.213 >36 4(10.0) 0.800 0(0) NA 0(0) NA 37(8.8) -- 43(10.2) -- 10(2.3) -- * p-values are calculated to compare age wise incidence rate with the average using Gaussian (z) test. Table 4. Coinfection among TORCH pathogens Coinfection Toxoplasma Rubella CMV HSV Total(6) Toxoplasma -- 2 2 1 5 Rubella -- -- 1 -- 1 Fig. 1. Overall seropositivity of TORCH pathogens in different age groups Toxo rubella CMV HSV <20 years 6.25 6.25 0 0 21-25 years 16.5 11.6 16.5 2.9 26-30 years 18.9 9.8 12.4 3.9 31-35 years 15.3 4.3 7.6 1 > 36 years 17.5 10 0 0 Note: Table made from bar graph.
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|Publication:||Journal of Pure and Applied Microbiology|
|Date:||Dec 1, 2018|
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