INTRODUCTION
Toxoplasma gondii and rubella virus can cause intrauterine infections and congenital anomalies in the fetus, resulting in congenital toxoplasmosis (CT) and congenital rubella syndrome (CRS).[1] Infection with T. gondii is acquired primarily by eating infected meat, unwashed fruits or vegetables, and sometimes drinking water contaminated by oocysts.[2,3] Before pregnancy, infection with T. gondii confers little or no risk to the fetus.[4,5] In the neonate, manifestations of CT might include hydrocephalus, microcephaly, intracranial calcifications, retinochoroiditis, strabismus, blindness, psychomotor, and mental retardation.[6,7] While infection in early pregnancy poses a small risk of fetal transmission (<6%), rates of transmission range between 60% and 81% in the third trimester.[8] Conversely, although the transmission of T. gondii during embryogenesis is rare, it results in far more serious effects on the fetus.[9]
Rubella is the most devastating viral congenital infection which can lead to low birth weight, deafness, myopia, cataracts, glaucoma, congenital heart disease, and intellectual disability in the fetus.[10] CRS is a condition that occurs in a developing baby in the womb whose mother is infected with the rubella virus in the first trimester of pregnancy. Despite the decrease in number of CRS cases worldwide, rubella remains a public health problem in Africa.[11,12] To prevent CRS, the World Health Organization (WHO) recommends initiating rubella surveillance to estimate disease burden and to monitor the impact of rubella-control activities.[13] In 2008, the number of infants born with CRS exceeded 110,000, making rubella a leading cause of congenital anomalies,[13] with the highest burden in the Southeast Asian region and African region.[13,14] While, the global annual incidence of CT was estimated to be 190,100 cases in the same areas.[15] Therefore, early diagnosis is vital to ensure the proper management of infected persons. This study aimed to determine for the first time the simultaneous seroprevalence of toxoplasmosis and rubella among pregnant women in Dakar few years after the rubella vaccine integration.
MATERIALS AND METHODS
This retrospective study was performed at the Military Hospital of Ouakam from January 2016 to December 2021 in pregnant women during the first trimester of their pregnancy. Only the first result of each patient was considered; other repetitive results of the same patient were not included in the study. All positive or borderline IgM test results were checked twice. After obtaining fully informed verbal consent from each pregnant woman who came for a routine antenatal checkup, 5 ml of venous blood was taken and clinical data were collected. Serum samples were separated by centrifuging at 4000 rpm for 10 min and screened for rubella and T. gondii immunoglobulin G (IgG) and IgM antibodies by a chemiluminescent microparticle immunoassay for the quantitative determination of IgG and IgM antibodies to T. gondii and rubella in human serum using Abbott kits (Architect i1000SR, USA) according to the manufacturer’s instructions. Specific IgM and IgG test results were interpreted as nonreactive, gray zone, or reactive as per the manufacturer’s guidelines [Table 1].
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Table 1: Interpretation of toxoplasmosis and rubella immunoglobulin M and immunoglobulin G antibodies
Statistical methods
Serology data from 2016 to 2021 were extracted from the laboratory electronic medical record system (Filemaker Pro™ software). Available information included date of the test, age, toxoplasmosis, and rubella IgG and IgM results. Only the first result of each patient was considered; other repetitive results of the same patient were not included in the study. Data analysis was processed with Epi Info. For descriptive statistics, percentages are presented with their corresponding 95% confidence intervals. For inferential statistics, P < 0.05 was considered statistically significant.
Ethical considerations
This study was a hospital-based research conducting in routine conditions in accordance with the Declaration of Helsinki. To respect the confidentiality, an identification code was automatically assigned by the laboratory software to each patient. Signed informed consent was obtained from each pregnant woman before her enrollment. Furthermore, data on women’s sociodemographic characteristics and residency were collected from the participants’ medical records based on prior permission from the administration officials of Military Hospital of Ouakam, a public referral hospital, located in the capital city of Dakar.
RESULTS
Characteristics of the study participants
Over the course of the study period from 2016 to 2021, the results of a total of 2589 patients were analyzed in terms of anti-Toxoplasma and anti-rubella. The median age of the study cohort was 29.7 years (interquartile range: 23.14–34.86). The most represented age range was 25 - 30, with 40.02 (n=1036). By study period, 2021 recorded 22.21% (n=575) of study participants. Other characteristics of the study population are detailed in Table 2.
Table 2: Distribution of the participants by age group and study period
Toxoplasmosis and rubella seroprevalence
Among the 2589 women included in the study, the positivity rates of IgG antibodies were 35.84% (n = 928) and 87.14% (n = 2256), respectively, for toxoplasmosis and rubella. Regarding IgM antibodies, 43 samples (1.66%) were positive for toxoplasmosis and 9 (0.35%) for rubella. By age group, the seroprevalence of toxoplasmosis increases significantly from 30.2% (15–24 years old) to 41.6% (≥35 years old). For rubella infection, the highest seroprevalence rate was observed in the 15–24-year-old group. According to the study period, T. gondii seroprevalence was significantly higher in 2017 with 40.5% and low in 2021 while rubella seroprevalence varied slightly from 2016 to 2021 [Table 3].
Table 3: Seroprevalence of toxoplasmosis and rubella by age group and study period
Anti-Toxoplasma IgG and anti-rubella IgG were found in 814 (36.08%) pregnant women. Positive IgG and IgM profiles for toxoplasmosis and rubella were, respectively, observed in 37 (3.99%) and 8 (0.35%) pregnant women.
IgG antibody titers to Toxoplasma gondii and rubella in the study population
The mean value of anti-toxoplasmosis IgG titer was 41.72 UI/mL. According to the age group, the highest titer was recorded in pregnant women aged over 35 years with 47.72 UI/mL (26.57–68.86) and the lowest in the 31–35-year age group with 33.95 UI/mL (23.11–44.79) (P = 0.62). The mean IgG titer for rubella was 96.34 IU/mL. The highest titer was found in the 15–24-year age group with 122.71 IU/mL (112.02–133.40) and the lowest in women over 35 years of age with 75.23 IU/mL (67.59–82.87) (P < 0.0001) [Figure 1].
Figure 1: IgG antibody titers regarding age group. IgG: Immunoglobulin G
Regarding the study period, a significant difference was noted in the distribution of the mean titer of anti-rubella IgG (P = 0.0048) but not for toxoplasmosis (P = 0.80) [Figure 2].
Figure 2: IgG antibody titers according the study period. IgG: Immunoglobulin G
DISCUSSION
Toxoplasmosis is present in every country and seropositivity rates range from <10% to over 90% depending on a variety of factors, including dietary habits, lifestyle, socioeconomic status, and geographical conditions,[16,17] whereas rubella remains an important pathogen globally with approximately 100,000 cases of CRS estimated to occur each year.[18]T. gondii and rubella virus are common causes of infection in all age groups, and the infections are generally asymptomatic. The important consequence of primary infection in pregnant women in the first trimester is vertical transmission to the fetus, resulting in CT or CRS. The only way to prevent the risks of such infections during pregnancy is by serological screening of women of childbearing age or vaccination for rubella. This study presents the first data on the simultaneous seroprevalence of toxoplasmosis and rubella in Senegal.
Regarding toxoplasmosis which increases significantly with age group, an overall seroprevalence of 35.84% found in this study is higher than those previously reported in the same laboratory in 2010[19] with 31.15%, respectively. This finding would suggest an increase in the seroprevalence rate of toxoplasmosis over the past decade. However, these variations could be explained by the sensitivity differences of the two determination methods used. In Senegal, previous studies on toxoplasmosis have reported comparable findings. Indeed, Ndiaye et al. reported a seroprevalence of 35.8% in 109 patients during their study on the serological assessment of toxoplasmosis in pregnant women in 2002.[20] Several years later, they reported a seroprevalence of 34.5% in their study carried out from 2002 to 2006 in the same laboratory in 941 pregnant women.[21] In addition, recently, Tine et al. reported an overall seroprevalence of 35.4% with pregnant women aged >30 years more likely to carry T. gondii IgG.[22] These findings suggest that trends in toxoplasmosis in Dakar have not considerably changed over the past two decades, resulting in the persistence of risk factors. In our study, the IgG- and IgM-positive profile corresponding to a recent infection was found and confirmed in 37 patients in a second sample which might correspond to a seroconversion rate of 3%. However, the avidity test to establish the date of infection was not performed. In Africa, higher seroprevalence rates than in our study have been reported in several countries. In Nigeria, Onadeko et al. found that 75.4% of pregnant women were positive for T. gondii antibodies.[23] A seroprevalence rate of 56% was reported in pregnant women attending two hospitals in Franceville (Gabon) by Mpiga et al.[24] In Congo and Côte d’Ivoire, the same seroprevalence of 60% was reported by Makuwa et Adoubryun, respectively, in women of childbearing age.[25,26] However, lower rates than those reported in our study have been documented in Niger and Burkina Faso, with 18.2% and 20.3%, respectively.[27,28]
Concerning rubella which is a vaccine-preventable disease, available data on the burden, i.e. the incidence or morbidity burden of rubella and CRS in Senegal, are very sparse (patchy). However, there are reports of rubella virus circulation and CRS with 811 cases of rubella reported from 2004 to 2012. Over a period of 6 years (2006 to 2011), data from the Albert Royer Children’s Hospital laboratory revealed a seroprevalence of 66% (n = 278) in CRS-suspected children.[29] Furthermore, the only published data in women of childbearing age of Senegal were reported in 2003 by Dromigny et al. with 90.1% of seroprevalence.[30] In our study, a comparable rate of 87.14% was found, suggesting a wide circulation of the virus in the population. Since the 1980s, the WHO recommended the national use of routine childhood rubella vaccination. The main goal of vaccination is to reduce the incidence of rubella virus infection and CRS. Three WHO regions (American, European, and Western Pacific Region) have rubella and CRS elimination goals.[31] In Senegal, rubella vaccination is recently introduced into the National Immunization Program (NIP) in 2013.[29] Before, vaccines against rubella were commercialized and rarely delivered.[30] In many African countries, rubella seroprevalence rates higher than those in our study have been reported. In Benin, a study revealed a seroprevalence of 94%[32] in pregnant women living in rural areas, while 94,7% and 92.3% were noted respectively in urban and rural areas in Burkina Faso,[33] 95.5% in Nigeria,[34] and 92.7% in Tanzania,[35] while a seroprevalence of 93% was documented in Sudan.[36] Lower seroprevalence rates were found in Burkina Faso with 77%,[28] in Nigeria 68.5%,[37] and Sudan 65.4%.[36] These findings indicate high circulation of the virus in the continent due to low immunization coverage.
By study period and age, the highest seroprevalence rates were observed in 2020 and in the youngest age group (15–24 years). No significant differences were noted in the immunity profile of pregnant women (P = 0.143), even though seroprevalence usually increases with age.[38,39] Indeed, Senegal introduced the combined measles and rubella vaccine in 2013 as a catch-up vaccination campaign for children aged 9 months to 15 years before integrating into the routine NIP to replace the measles vaccine.[29] The national vaccination campaign took place nationwide in November 2013 with approximately 6 million children vaccinated. Thus, certain pregnant women aged 15–25 years in our study could be vaccinated during this campaign which would explain the highest rates of seroprevalence and antibody production among them and noted at the end of the study period.
CONCLUSIONS
Data from this first-time study regarding simultaneous seroprevalence of toxoplasmosis and rubella among pregnant women in Senegal indicate a continuing high risk of CT in Dakar, thus the need for a preventive program. Whereas with rubella vaccination which recently introduced, the high seroprevalence rate observed suggests that the virus is widely circulating in the population. However, the highest rates observed among the youngest age group and in the study period 2020–2021 would indicate a protective effect of vaccination. Further studies are needed to fully assess the efficacy of rubella vaccination in women of childbearing age.
Ethical statement
This study was hospital-based research conducted in routine conditions per the Declaration of Helsinki. The laboratory software automatically assigned an identification code to each patient to respect confidentiality. Data on women’s sociodemographic characteristics and residency were collected from the participant’s medical records based on prior permission from the administration officials of the Military Hospital of Ouakam (NDS Number 134, 04/22), a public referral hospital located in the capital city of Dakar.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
Thanks are due to all the individuals who participated in this study and the staff of the microbiology unit of Military Hospital of Ouakam.
REFERENCES
1. Avcioglu F, Behcet M, Kurtoglu MG. Evaluation of toxoplasma, rubella, and cytomegalovirus serological results in women of childbearing age. Rev Assoc Med Bras (1992) 2020;66:789–93.
2. Robert-Gangneux F, Dardé ML. Epidemiology of and diagnostic strategies for toxoplasmosis. Clin Microbiol Rev 2012;25:264–96.
3. Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet 2004;363:1965–76.
4. Vogel N, Kirisits M, Michael E, Bach H, Hostetter M, Boyer K, et al. Congenital toxoplasmosis transmitted from an immunologically competent mother infected before conception. Clin Infect Dis 1996;23:1055–60.
5. Gavinet MF, Robert F, Firtion G, Delouvrier E, Hennequin C, Maurin JR, et al. Congenital toxoplasmosis due to maternal reinfection during pregnancy. J Clin Microbiol 1997;35:1276–7.
6. McAuley J, Boyer KM, Patel D, Mets M, Swisher C, Roizen N, et al. Early and longitudinal evaluations of treated infants and children and untreated historical patients with congenital toxoplasmosis:The Chicago collaborative treatment trial. Clin Infect Dis 1994;18:38–72.
7. Swisher CN, Boyer K, McLeod R. Congenital toxoplasmosis. The toxoplasmosis study group. Semin Pediatr Neurol 1994;1:4–25.
8. Dunn D, Wallon M, Peyron F, Petersen E, Peckham C, Gilbert R. Mother-to-child transmission of toxoplasmosis:Risk estimates for clinical counselling. Lancet 1999;353:1829–33.
9. Berrébi A, Assouline C, Bessières MH, Lathière M, Cassaing S, Minville V, et al. Long-term outcome of children with congenital toxoplasmosis. Am J Obstet Gynecol 2010;203:6 e1-6.
10. Parlak M, Çim N, Nalça Erdin B, Güven A, Bayram Y, Yıldızhan R. Seroprevalence of toxoplasma, rubella, and cytomegalovirus among pregnant women in Van. Turk J Obstet Gynecol 2015;12:79–82.
11. Binnicker MJ, Jespersen DJ, Harring JA. Multiplex detection of IgM and IgG class antibodies to
Toxoplasma gondii, rubella virus, and cytomegalovirus using a novel multiplex flow immunoassay. Clin Vaccine Immunol 2010;17:1734–8.
12. Katow S. Rubella virus genome diagnosis during pregnancy and mechanism of congenital rubella. Intervirology 1998;41:163–9.
13. Rubella vaccines:WHO position paper. Wkly Epidemiol Rec 2011;86:301–16 Available from:
https://www.who.int/publications/i/item/WER8629 [Last accessed on 2022 May 14].
14. Centers for Disease Control and Prevention (CDC). Rubella and congenital rubella syndrome control and elimination –Global progress, 2000-2012. MMWR Morb Mortal Wkly Rep 2013;62:983–6.
15. Torgerson PR, Mastroiacovo P. The global burden of congenital toxoplasmosis:A systematic review. Bull World Health Organ 2013;91:501–8.
16. Pappas G, Roussos N, Falagas ME. Toxoplasmosis snapshots:Global status of
Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis. Int J Parasitol 2009;39:1385–94.
17. Ocak S, Zeteroglu S, Ozer C, Dolapcioglu K, Gungoren A. Seroprevalence of
Toxoplasma gondii, rubella and cytomegalovirus among pregnant women in southern Turkey. Scand J Infect Dis 2007;39:231–4.
18. Lambert N, Strebel P, Orenstein W, Icenogle J, Poland GA. Rubella. Lancet 2015;385:2297–307.
19. Lo G, Diouf NN, Faye B, Seck MC, Diawara PS, BA I, et al. Prevalence of Toxoplasmosis among pregnant women in Military hospital of Ouakam, Dakar. Med Afr Noire 2012;59:364–8.
20. Ndiaye D, Ndiaye A, Sène PD, Ndiaye JL, Faye B, Ndir O. Evaluation of serological tests of toxoplasmosis in pregnant women realized at the laboratory of parasitology and mycology of le Dantec teaching hospital in 2002. Dakar Med 2007;52:58–61.
21. Ndiaye D, Sène PD, Ndiaye M, Faye B, Ndiaye JL, Ndir O. Update on toxoplasmosis prevalence based on serological tests in pregnant women in Dakar, Senegal from 2002 to 2006. Med Trop (Mars) 2011;71:101–2.
22. Tine RC, Dieng T, Sylla K, Sow D, Lelo S, Dia M, et al. Trends in toxoplasmosis seroprevalence among pregnant women attending the Fann teaching hospital in Dakar Senegal. J Parasitol Vector Biol 2017;9:14652.
23. Onadeko MO, Joynson DH, Payne RA, Francis J. The prevalence of toxoplasma antibodies in pregnant Nigerian women and the occurrence of stillbirth and congenital malformation. Afr J Med Med Sci 1996;25:331–4.
24. Mpiga Mickoto R, Akue JP, Bisvigou U, Mayi Tsonga S, Nkoghe D. Serological study on toxoplasmosis among pregnant women from Franceville, Gabon. Bull Soc Pathol Exot 2010;103:41–3.
25. Makuwa M, Lecko M, Nsimba B, Bakouetela J, Lounana-Kouta J. Toxoplasmose et la femme enceinte au Congo. Médecine Afr Noire 1992;3:493–5.
26. Adou-Bryn KD, Ouhon J, Nemer J, Yapo CG, Assoumou A. Serological survey of acquired toxoplasmosis in women of child-bearing age in Yopougon (Abidjan, Côte d'Ivoire). Bull Soc Pathol Exot 2004;97:345–8.
27. Develoux M, Candolfi E, Hanga-Doumbo S, Kien T. Toxoplasmosis in Niger. A serological analysis of 400 subjects. Bull Soc Pathol Exot Filiales 1988;81:253–9.
28. Linguissi LS, Nagalo BM, Bisseye C, Kagoné TS, Sanou M, Tao I, et al. Seroprevalence of toxoplasmosis and rubella in pregnant women attending antenatal private clinic at Ouagadougou, Burkina Faso. Asian Pac J Trop Med 2012;5:810–3.
29. PEV S. Programme élargi de vaccination du Sénégal Available from:
http://www.gavi.org 2013 [Last accessed on 2022 May 13].
30. Dromigny JA, Nabeth P, Perrier Gros Claude JD. Evaluation of the seroprevalence of rubella in the region of Dakar (Senegal). Trop Med Int Health 2003;8:740–3.
31. Patel MK, Gibson R, Cohen A, Dumolard L, Gacic-Dobo M. Global landscape of measles and rubella surveillance. Vaccine 2018;36:7385–92.
32. De Paschale M, Ceriani C, Cerulli T, Cagnin D, Cavallari S, Cianflone A, et al. Antenatal screening for
Toxoplasma gondii,
Cytomegalovirus, rubella and
Treponema pallidum infections in Northern Benin. Trop Med Int Health 2014;19:743–6.
33. Tahita MC, Hübschen JM, Tarnagda Z, Ernest D, Charpentier E, Kremer JR, et al. Rubella seroprevalence among pregnant women in Burkina Faso. BMC Infect Dis 2013;13:164.
34. Obijimi O, Ajetomobi A, Sule W, Oluwayelu D. Prevalence of rubella virus-specific immunoglobulin-g and-m in pregnant women attending two tertiary hospitals in Southwestern Nigeria. Afr J Clin Exp Microbiol 2013;14:1349.
35. Mwambe B, Mirambo MM, Mshana SE, Massinde AN, Kidenya BR, Michael D, et al. Sero-positivity rate of rubella and associated factors among pregnant women attending antenatal care in Mwanza, Tanzania. BMC Pregnancy Childbirth 2014;14:95.
36. Hamdan HZ, Abdelbagi IE, Nasser NM, Adam I. Seroprevalence of cytomegalovirus and rubella among pregnant women in Western Sudan. Virol J 2011;8:217.
37. Bamgboye AE, Afolabi KA, Esumeh FI, Enweani IB. Prevalence of rubella antibody in pregnant women in Ibadan, Nigeria. West Afr J Med 2004;23:245–8.
38. Gomwalk NE, Ezeronye OU. Sero-epidemiology of rubella in Imo State of Nigeria. Trans R Soc Trop Med Hyg 1985;79:777–80.
39. Lawn JE, Reef S, Baffoe-Bonnie B, Adadevoh S, Caul EO, Griffin GE. Unseen blindness, unheard deafness, and unrecorded death and disability:Congenital rubella in Kumasi, Ghana. Am J Public Health 2000;90:1555–61.
