Background
To investigate and report the prevalence of viral sexually transmitted infections (STIs) other than HIV is important for the introduction or improvement of a wide range of health policies and programs in all regions. It is known that more than 30 microorganisms are sexually transmitted including herpes simplex virus type 2 (HSV-2), hepatitis B virus (HBV), human papillomavirus (HPV) and human immunodeficiency virus (HIV). Estimations according to the World Health Organization (WHO) indicate that more than 1 million STIs are acquired every day.
Almost 300 million people are infected with HPV, which if becoming persistent may cause cervical cancer [
1]. More than 400 million individuals are estimated to be infected with HSV-2 which causes genital herpes [
2]. Approximately 250 million people have chronic HBV infection which can cause liver cirrhosis and hepatocellular carcinoma [
3]. According to the Joint United Nations program on HIV/AIDS (UNAIDS), approximately 37 million people are living with HIV which may cause acquired immune deficiency syndrome (AIDS). These general numbers are based on reports and studies performed around the world. However, the prevalence of viral STIs is unknown in rural areas in Bolivia where the majority of indigenous people are settled.
Bolivia has a population of around ten million people and 40 to 70% are self-identified as indigenous peoples [
4]. Although new policies have been introduced to improve the general health programs, Bolivia still has the highest rates of cervical cancer in South America with a yearly incidence of 38.5/100,000 and a mortality rate of 18.2/100,000 according to the Information Centre of HPV and Cancer Catalan Institute of Oncology (ICO). Globally, the major risk factor for developing cervical cancer are HPV types 16 and 18 [
5]. An ongoing cytology-based screening program for all women was introduced in Bolivia in 2006, but it reaches mostly urban areas and has a poor coverage that did not exceed 17% for Pap smear test and 20% for visual inspection under acetic acid [
6]. Unfortunately 50 to 80% of the screened women do not attend the follow-up appointments [
7], and there is no system of quality control and assurance of diagnoses. Therefore, neoplasia caused by persistent HPV-infection is rarely detected during early stages of disease but most often occur at diagnosis of cervical cancer and thereby barely curable. A vaccine targeting HPV 16, 18, 6 and 11 was however introduced in Bolivia in April 2017 and this program will reduce the mortality rates of cervical cancer. The vaccine is given to school-girls aged 10–12 years and the coverage of the vaccination was 88% in 2017 and 61% in 2018 [
8].
HSV-2 infection is a risk factor for the acquisition of HIV in people who practice unsafe sex, and it is known that the virus is more prevalent in women compared to men. In 2012 the general seroprevalence of HSV-2 of people aged 15–49 years in the Americas is estimated to be 14.4%, while the highest world-wide prevalence is in African populations with an overall estimated prevalence of 31.5% [
2].
The Amazonas is an area of high endemicity of HBV, with reported prevalences ranging from 8 to 25% [
9]. Countries in South America, including Bolivia, have introduced general childhood vaccination against HBV, leading to a decreased incidence. However, in Bolivia the vaccination coverage rate is still one of the lowest in South America [
10], and its impact on HBV prevalence in rural areas is uncertain.
In 2017, UNAIDS reported that about 21,000 people are living with HIV in Bolivia with a general prevalence of 0.3%, and that only 36% of those infected are on treatment. A later report indicates an increase of HIV incidence [
11]. The general knowledge regarding disease transmission and treatment is low in urban areas [
12], and probably even lower in rural communities.
In rural areas the poor population have limited information about STIs, little/no access to the national health care system, and no resources for treatment. This study therefore seeks to obtain data about the prevalence and possible risk factors of viral STIs in women living in rural areas on the way to the Amazonas of the Department of La Paz in Bolivia, which will help to improve the screening programs and health policies.
Discussion
In Bolivia, the prevalence of viral STIs has increased during the last 10 years, but this has mainly been investigated in larger towns and cities. In the present study, we assessed the presence of viral STIs in 394 women living around villages and towns in the north of the Department of La Paz and found that the burden of HSV-2, HBV and HPV is higher than in larger cities.
The HSV-2 seroprevalence varies between South America and Caribbean countries and relate to behavioral and social conditions. It increases with age [
2], and was in the present study of a rural female population (53%) compared to the overall prevalence in women in the Americas which is estimated to be 14.4%. Our study confirmed the previous observations that the prevalence of HSV-2 increased with age and number of children. It was higher than what has been found in rural places of for example Haiti and Costa Rica where reported prevalences are 42 and 38%, respectively [
22,
23], and similar to prevalences in Durban, Tanzania, and a region in Brazil [
19,
24,
25]. Our observation that HSV-2 was more prevalent in small villages compared to the small and large towns differs from what has been observed in Haiti, Tanzania and Brazil where the prevalence of HSV-2 was higher in urban compare to rural areas. However, studies in Australia showed that the HSV-2 prevalence is higher in indigenous people [
26].
In female African populations, acquisition of HSV-2 infection is associated with risk factors such as prostitution, limited access to health care, and unnegotiable unsafe sex with their partners due to economic dependence [
27]. We have no information regarding possible prostitution in our study population, but these women have a very limited access to health care or health information. In addition, Bolivian men from certain indigenous populations show a high rate of infidelity [
28] and the vast majority of the women in this study reported unprotected sex with their partner. Because of cultural reasons, we were not able to ask about the number of sexual partners to all participants; however, women with only one sexual partner have high risk of acquiring STIs, due to the scarcity of condom use, which is 4% in this study [
29]. Prolonged use of hormonal contraception can be considered a risk factor to acquire a genital infection [
30]. We did not assess the longevity of hormonal contraceptive use so we could not confirm this in our study population.
Twenty-seven percent of the women in this study had an ongoing infection with one or several HR-HPV. This is higher than the 8 to 18% previously reported in rural and urban regions of Bolivia, which indicates that the prevalence of HPV in rural north of La Paz might be higher than in other regions of Bolivia [
31‐
33]. HPV infection was most common in younger women, which is in accordance with previous studies [
34]. This study did not find a significant difference or association between the number of children and the infection of HPV, but 19% of women positive for HPV that have more than four children are at high risk to develop squamous-cell cancer [
35], if they are not screened and treated.
The 12 high risk HPV types we analyzed are the most important ones due to their association with the development of cervical cancer. These genotypes represent the class I carcinogens for cervical cancer according to the (WHO/IARC), and the most common high-risk HPV types we identified were HPV 56, 39 and 31. Previous studies from Bolivian small towns have identified HPV 31 and 58 as the most common HPV high-risk types [
31] while in cities HPV 16, 31, 51 and 58 [
32], were most common. This indicates that the pattern of HPV high-risk types for cervical cancer may vary between different regions [
36], and also Western Europe [
37], where HPV 16 and 18 predominate. This is an important finding because the studies conducted in Bolivian cities have supported the introduction of the HPV 16/18/6/11 vaccine in Bolivia. Fortunately, the vaccine confer some cross protection to the HPV types 31, 33 and 45, which are genetically related to 16 and 18 [
38], but it is not known if the vaccine protects against HPV 39 and 56.
Almost 10% of the women in this study had antibodies to HBV, which is similar to the 8% reported in other South American countries such as Colombia and Brazil, and thus confirms the high seroprevalence of HBV in the Amazonas region [
9,
39]. Native Bolivians living in neighboring Department in close proximity to the Amazonas have an even higher HBV burden with a seroprevalence of 27.5% [
40]. In our study, 16% of those with HBV-specific antibodies were also positive for HBsAg indicating a chronic infection. Thus, we estimate that 2% of women living in these rural areas are chronic HBV carriers. The HBV vaccination that was introduced in Bolivia in year 2000 has fortunately reduced the HBV prevalence in younger age groups [
10].
No positive cases for HIV was found, which is in agreement with the low estimates by UNAIDS with only a 0.3% of prevalence in adults aged 15 to 49 years, and zero cases from a study of 885 healthy women mostly urban populations in Bolivia [
12]. The program for HIV/AIDS in Bolivia show a higher prevalence in major cities such as Santa Cruz, Cochambamba and La Paz with a total prevalence of 1.3, 1, and 0.3%, respectively in pregnant women [
41], with an increase of new cases [
11]. Overall, the prevalence of HIV is low in Bolivia compared to e.g. Brazil, which is interesting given the high prevalence of HSV-2 as well as of unprotected sex, both of which are major risk factors for HIV transmission.
Almost 70% of the rural women included in this study were positive for at least one of the four viral STIs. Approximately 15% of the women had more than one viral STI, and the majority of these co-infections involved HSV-2 and HPV. We did not find a positive association between HSV-2 and HPV infections indicating that these infections do not predispose for each other. However, several studies show that HSV-2 infection is an important risk factor for the development of invasive cervical cancer in HPV-infected women [
42‐
44]. Thus, the high incidence of HSV-2, particularly in women living in rural villages, might represent one underlying mechanism for the high incidence of cervical cancer in Bolivian women.
There are certain limitations to this study. First, STIs are stigmatizing in which might have generated a bias in the recruitment process. Second, many women from villages were afraid to participate because they reported that the Pap smear test was painful, and many of them have never encounter a cytological inspection by medical staff. Third, due to the high rate of illiteracy we could only collect data through oral interviews which might have produced some bias in our data.
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