Non-malarial infectious diseases of antenatal care in pregnant women in Franceville, Gabon

In recent years, health care has globally improved thanks to the introduction of a number of vaccines, the use of antibiotics and the development of antiretroviral medication for the treatment of HIV/AIDS. Unfortunately, infectious diseases remain a major cause of mortality in developing countries. More specifically, infections due to viruses, bacteria, fungi and parasites continue to create havoc and lead to a great morbidity which hinders development in resource-limited countries. These infectious agents do not induce systematically diseases, pathogenesisis also associated with host genetics, host immunity, infectious agent genetics and environmental factors.

Pregnancy is a specific physiological state in which the woman must tolerate the fetus, a foreign organism for the mother, since half of its genetic material is inherited from the father. Intuitively, the fetus should be rejected by the mother. However, the mother’s body naturally accepts the fetus by undergoing immune and morpho-physiological changes [1, 2]. Compared to non-pregnant women, the pregnant mother’s immune system is more susceptible to infectious diseases [3, 4]. Several consequences of infections during pregnancy have been associated with severe complications affecting the mother and/or the fetus and some health problems even lead to the death of one, the other or both [5]. Among these infections, HIV, Treponema pallidum, T. gondii, the rubella virus and human T-cell lymphotropic virus type 1 need a rigorous monitoring.

The World Health Organization(WHO) estimates that 1.4million pregnant women live with HIV in developing countries and that 90% of these women live in Africa [6]. In pregnant women, HIV infection is responsible for several poor health outcomes such as premature birth, low birth weight, miscarriage or newborn mortality [7‐10].Although in utero transmission of HIV rarely occurs, during delivery, 65% of mothers transmit the virus to their child [11].

Syphilis is caused by Treponema pallidum spirochete bacteria and the transmission risk from mother to fetus during pregnancy is quite high. This phenomenon was first described in 1497 [12, 13]. The main risk factors of T. pallidum transmission from mother to child are the evolution of maternal infection and in utero exposure time [10, 14]. Recent systematic reviews and meta-analysis show that syphilis is responsible for an increased frequency of fetus loss and stillbirth (21%), neonatal deaths (9.3%) and low birth weight (5.8%), when it is untreated in pregnant women [15]. Clinical evidence of congenital syphilis was seen in 15% of newborns from untreated women and the frequency of the disease was 10% higher than in babies from treated mothers [15]. T. pallidum transmission to the child can occur by blood diffusion or during the delivery by direct contact with the mother’s genital lesions.

Human T-cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus causing adult T-cell leukemia/lymphoma (ATL) and tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) [16, 17].HTLV-1 has also been associated with several inflammatory diseases, including pediatric infectious dermatitis [18, 19], uveitis [20, 21], and myositis [19, 22]. About 15 to 20 million infected people live with HTLV1 in endemic areas which include Japan, parts of sub-Saharan Africa, the Caribbean, South-America and the Middle-East regions [23]. Globally, HTLV-1 is prevalent in more than 2% of the adult population, and 2 to 8% of these infected individuals will develop severe HTLV-1-associated diseases such as adult T-cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-1-associated myelopathy during their lifetime [24].

Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. In pregnant women, although 29% of congenital T. gondii infections are usually asymptomatic, the infection can be delayed or become potentially severe once it manifests [25].Transmission of T. gondii from mother to the fetus depends on parasitaemia, the mother’s cellular immunity as well as the stage of placental development [26]. Congenital toxoplasmosis can lead to several symptoms including mild chorioretinitis, an inflammation of the choroid (a thin pigmented vascular coat) and the eye retina, which can persist in the child many years after birth and can cause miscarriage, intellectual disability, micro cephaly, hydrocephalus and seizures [25].

Rubella, also known as German measles, is an infection caused by the rubella virus. In pregnancy, this infection poses a high risk for abnormal fetal formation when it occurs in the first 11 weeks of gestation. This risk seems to be nonexistent after the18th week of pregnancy [27]. Rubella in pregnant women has been associated with spontaneous abortion and congenital abnormalities such as cataracts, heart defects and sensorineural deafness. Permanent abnormalities such as heart defects, pulmonary artery stenosis, hypoplasia, eye defects, intellectual and psychomotor disabilities, and speech defects have also been linked to rubella infection. Other outcomes of rubella during pregnancy include transient abnormalities in newborns and infants, developmental and late-onset abnormalities [28, 29]. Retardation of intrauterine growth seems to be the only consequence of infection in the third trimester of pregnancy [27].

In Gabon, infectious diseases are more prevalent than in other geographical zones of the world [30, 31]. Although data on malaria in Gabonese pregnant women are available, current reports on other infectious diseases that threaten the health of the mother, fetus and the newborn children are rare and scattered. Data on syphilis in pregnancy are quite old [32] and, although some research has been performed on toxoplasmosis, few of these studies have focused on pregnant women [33, 34]. As for rubella, it is rare to find data on this disease in Gabonese pregnant women. There is a dire need for new studies and new data on the infectious diseases of pregnant women in Gabon in order to assess the health risks for mothers and their children.

Franceville is the capital of the Haut-Ogooué province in the south-east of Gabon. It is located 512 km south-east of the country’s capital, Libreville (Fig. 1). Prevalences of HIV and HTLV in this city were reported in previous works [18, 35]. As is the case in the rest of the country, antenatal visits in pregnancy are concerned with HIV, rubella, syphilis, toxoplasmosis, malaria and hepatitis Band C. Therefore, the aim of this study was to evaluate the prevalence of these non-malaria infectious diseases diagnosed during the prenatal assessment of pregnant women in Franceville from May 2007 to July 2010.

Infectious diseases remain important risk factors for the health of mothers and their unborn children during pregnancy. This study is not only one of the few investigations of these conditions in Africa, it is also the first study in Gabon focusing on several non-malarial infections during pregnancy. The HIV prevalence in pregnant women found here is lower than the one previously reported in Gabon in studies on women in similar age groups (26 to 45 years old) [35], showing the regional specificity of HIV prevalence in the same country. This could be explained by socio-cultural factors. The reported HIV prevalence in this study has also increased compared to reports in similar studies conducted in Franceville since 1997 [34, 37, 38]. This could be one of the consequences of the decrease of means to fight against HIV these past few years in Gabon. Studies conducted in other African countries have shown similar HIV prevalence. A similar study conducted from 2009 to 2010 on Malian pregnant women found a comparable HIV prevalence (4.1%). In 2004, a study on rural Cameroonian pregnant women also reported similar HIV incidence (4.0%) [39, 40]. However, HIV prevalence reported in the Central African Republic in 2006 was higher (15%) [41], suggesting a difficulty to fight HIV in areas with political instability.

Age seemed to affect HIV prevalence in this study since a relatively higher HIV prevalence was observed in younger women. It suggests a high exposure and vulnerability of HIV infection among women in the younger age groups and potential risks of vertical transmission during their pregnancies in the future. Furthermore, HIV prevalence was also higher in our study compared to similar investigations from India and Europe [42, 43], although in those parts of the world, HIV pregnant women seem to be older (26 years and older) [42]. This could be related to socio-cultural habits.

In 2005, a study of 161 pregnant women in Franceville reported a 5% prevalence for HTLV-1 in this population [18] which is not significantly different from the 2.88% prevalence found in our study. It should be noted that the smaller sample size of the 2005 study may explain the observed difference in our findings. Our results, similar to those of a previous national HTLV-1 study conducted in 2005, confirm a decrease in HTLV-1 prevalence based on a 1986 Gabonese study [18, 34]. In studies conducted in Europe and in the United States of America (USA), the prevalence of this infection increased with age [44, 45] which is probably due to the accumulation of new infections through incremental sexual activity over a lifetime [46, 47]. We did not investigate genetic diversity for this virus, but it was previously found that HTLV-1b was the major subtype in Gabon and a few viral strain subtypes have also been found in pregnant Gabonese women [18].

The prevalence of T. pallidum reported in our study (2.5%) appears to be similar to prevalence reports from India [48, 49]. Surprisingly, in our study, age did not seem to significantly affect T. pallidum prevalence; the low prevalence of this infection could explain this finding. Our study shows a decline in the prevalence of T. pallidum when compared to the 10% prevalence found in Gabonese pregnant women in 1988 [50].This prevalence in our study population was lower than the one reported in the Democratic Republic of the Congo in 2011 (4.2%) and similar to the one reported in Benin (2.5%) [51, 52]. Syphilis is one of the infectious diseases that is of great interest to the global health community. The WHO recommends screening for T. pallidum in routine antenatal care visits in the first trimester of pregnancy in order to prevent adverse health pregnancy outcomes such as stillbirth, neonatal death, low birth weight and congenital deformities [52]. Data obtained from our studies provides empirical evidence to support the pursuit of the elimination of this disease. Syphilis is one of the diseases for which one of the health goals is eradication by using available antibiotherapies. Its residual prevalence indicates a resistance from some people to follow safe sexual behaviors. T. pallidum is a good indicator of sexual behaviors, which is confirmed by the fact that no significant difference was observed in the frequencies of sexually transmitted infections studied here. Moreover, we found that 3/24 (12.5%) pregnant women with syphilis were infected by one other sexually transmitted infection confirming that an integrated approach is necessary to deal with this disease. Services for the prevention of mother-to-child transmission of the human immunodeficiency virus (HIV) and other sexual and reproductive health initiatives ought to integrate syphilis elimination initiatives. The co-infections of HIV + HTLV-1 + T. pallidum were rarest in our study. Due to these low co-infections numbers, it was not possible to establish correlation between the diseases (Table 6). We found that social status had no impact on the occurrence of the common infections studied during pregnancy in Franceville.

There was a significant association between T. gondii seropositivity and increased age which can be attributed to the increased exposure to infection through the years (Table 3). The results of the current study highlight the need for awareness for toxoplasmosis as well as methods of prevention targeting not only pregnant women, but also women old enough to bear children.

The seronegative T. gondii prevalence (42,75%) found here was consistent with previous data (56%) from Franceville in 2007 [53]. Our results also seems to show a decline of seropositivity against T. gondii when compared to similar studies from 1995 and 1997 [54]. This decline may be explained by the recent improvements of hygiene in Franceville. Indeed, in industrialized countries, where hygiene is better, the prevalence of T. gondii is residual [55]. The high level of seronegative women against T. gondii and the high level of circulation of the parasite recently reported in Gabon [56] are disconcerting as these pregnant women run a higher risk of birthing babies with congenital toxoplasmosis. The T. gondii prevalence found here was consistent with the one reported in a study conducted in Lagos, Nigeria (60%) [57]. This similarity may be due to comparable climatic conditions, personal hygienic practices and socio-economic status in both countries.

We did not assess the immunoglobulin isotypes circulating in women to see if they expressed active T. gondii infection during their participation in the study. Previous data showed that IgM prevalence was stable between 1995 and 2007 (2.6%) [53].

Nearly 90% of the included pregnant women showed immunity against rubella suggesting a high transmission level of the rubella virus in Franceville. The prevalence of anti-rubella immunity decreased with age and seemed to be influenced by social status, since the students (and also the younger women) tended to show less immunity against this infection. This data is consistent with the increase in the number of contacts with the rubella virus according to age. Therefore, it could be considered an accumulative infection. A number of studies have attested to the presence of rubella immunity in different African countries such as Tanzania (2013), Benin (2013), Burkina Faso (2012), and Mozambique (2002) with a prevalence of 92.6%, 94% and 93.3% and 95.3%, respectively [51, 58‐60]. Our results also show that a few pregnant women did not have either T. gondii or rubella antibodies which render them and their unborn children more vulnerable to these two infections.

In a study conducted in the Central African Republic from 2011 to 2012, 6% of pregnant women were found to be triple infected with HIV, T. pallidum and T. gondii [41]. In our study, this type of triple co-infection was not detected nor was it possible to link co-infections to any particular demographic factor.

Toxoplasmosis, rubella, HIV, syphilis and HTLV-1 are frequent in varying degrees in pregnant women in Franceville. This evidence should obligate health officials to adopt systematic approaches for the detection and management of these infections that torment vulnerable populations such as pregnant women and their unborn children. Particular attention needs to be paid to younger women who are still students as this group seems to be most affected by these infections. Further studies are needed to improve access to diagnosis and treatment of these infections, particularly for pregnant women, which will contribute to better antenatal care in the country.