Current Understanding of Trichomonas vaginalisÕ Effects on HIV transmission and its Implications on African Americans

 

 

Long Nguyen

 


Hum Bio 153

Parasites and Pestilence

Professor S. Smith

 

Abstract

            Trichomoniasis is a highly prevalent STI in the U.S. and worldwide. Despite this, little effort has been put forth to control this disease because many health agencies do not see it as a threat to public health. However, this appears to not be the case, as recent findings have implicated trichomoniasis in increased HIV transmission. Unfortunately, there have been no experimentally proven mechanisms, although some studies have made progress. These findings are particularly important because it can change the way everyone views trichomoniasis. Perhaps once trichomoniasisÕ harmful potential has been acknowledged, policy change and implementation of governmental control programs will reduce the burden of this disease, and therefore HIV as well. These changes are particularly important for African Americans, who suffer from disproportionate rates of both infections. But in the meantime, the most effective avenue would be educating the general population about the threat trichomoniasis poses. 

Introduction

Trichomoniasis is one of the most common sexually transmitted infections (STIs) in the United States. It has been estimated that trichomoniasis infects approximately 7.4 million Americans a year, and at least 180 million people a year worldwide (Weinstock, 2004). It accounts for approximately 50% of all the curable infections in world (Schwebke, 2004). Despite exceeding both Chlamydia (3 million/year) and gonorrhea (650,000/year) in incidence in the U.S., trichomoniasis is less known and receives far less attention (Soper, 2003). In fact, it is not viewed as an important public health concern compared to other STIs, exemplified by the fact it is not a reportable disease and that no federally-funded control programs exist for it (Soper). But as recent studies have shown, trichomoniasis is reason for concern because of its association with increased HIV transmission. There are a few hypotheses for the mechanism behind this relationship. This paper aims to evaluate studies that have tested these hypotheses as well as examine the implications they have on public health, especially with regards to the highest risk group, African-Americans.

Background

Trichomoniasis is caused by the protozoan parasite, Trichomonas vaginalis, which is spread by vaginal intercourse. T. vaginalis is typically pyriform (pear) shaped, containing 4 anterior flagella, one posterior flagellum, an undulating membrane, one nucleus, an axostyle, and several energy-producing organelles (Schwebke, 2004). It exists solely in the trophozoite form, without a known cyst stage. The trophozoites reproduce asexually via binary fission. During infection, the parasite binds to the vaginal epithelial cells, eliciting an aggressive, local cellular immune response and causing inflammation (Shafir, 2009). In addition to laminating itself into the host cell, T. vaginalis has been seen to release a lytic factor that destroys nucleated cells and erythrocytes (Schwebke). Most men are asymptomatic; whereas only about half of women are asymptomatic (trichomoniasis.org).  Symptomatic men suffer from urethral discharge, pruritus, and dysuria. Symptomatic women suffer from vaginal discharge, pruritus, irritation, odor, and edema or erythema (Schwebke). Complications for men and women are prostatitis and vaginitis, respectively. Trichomoniasis is generally curable with metronidazole or sometimes tinidazole, which are both flagyl.

Possible Mechanisms of the Trichomoniasis and HIV association

            It has been more widely discussed that trichomoniasis increases the likelihood of HIV transmission (CDC, 2001). Studies in Africa have showed 1.5 to 3-fold increase in HIV transmission in people infected with trichomoniasis (Shafir, 2009). There are also many instances in Africa where female sex workers and hospital-admitted females showed a significant association the two infections. Despite these consistent findings, the mechanisms behind them still need to be elucidated.  There are three popular hypotheses.

            The first of these hypotheses is that T. vaginalis disrupts the vaginal epithelial monolayers, allowing easier access for HIV entry into the bloodstream (Shafir, 2009). It is well known that T. vaginalis isolates are cytotoxic to urogenital epithelial cells, but it is unclear whether or not it disrupts the integrity of the polarized monolayers of these cells (Guenthner, 2005). Very few studies have provided empirical evidence for this claim. But one study done by Guenthner et al. at the CDC, was able to test this hypothesis in vitro. Primary prostate epithelial cells (PrEC), ectocervical epithelial cells (CerEC), and endometrial epithelial cells line (HEC1A) were all exposed to low doses of two different T. vaginalis laboratory isolates, Balt42 and JH31. They found that both isolates caused at least 50%, and in some cases complete, reduction in the transepithelial resistance by 18 hours after exposure. Next, the researchers moved on to use T. vaginalis isolates from symptomatic and asymptomatic patients. Similar results were observed. Parasite dose exposure was positively associated with severity and rate of disruption of the urogenital epithelial monolayers.

            Now that the researchers have established that T. vaginalis causes the disruption of the urogenital epithelial monolayer integrity, they must determine whether these perforations are what the HIV virus utilizes to invade T. vaginalis infected people. Laboratory and patient isolates of T. vaginalis were each used in conjunction with HIV-1. An HIV-1 p24 assay was performed to quantitate the viral load of HIV. It was apparent that monolayers coinfected with T. vaginalis and HIV had a 4 to 4.6 fold increase of HIV in the basolateral compartments compares to epithelial monolayers without T. vaginalis. Monolayers with lower doses of T. vaginalis had lower levels of monolayer disruption and less HIV infiltration in the basolateral compartments. Despite these seemingly conclusive results, it is still not completely clear if the HIV virus uses the perforations to cross the monolayers. This hypothesis relies on two theories for it to be true (trichomoniasis disrupting the integrity of urogenital epithelial monolayers and HIV using these lesions during actual human infection), so doubts can be cast upon it. Nonetheless, these results note the importance of urogenital epithelial monolayer disruption in HIV infection.

            Another mechanism that is often discussed is that T. vaginalis causes the recruitment of HIV-target cells into the urogenital epithelium, allowing for HIV entry and replication (Shafir, 2009). HIV is known to infect CD4-containing cells, including macrophages and some T cells (Chan, 1997). It is in these cells that they replicate by using the host machinery. The inflammation caused by T. vaginalis is thought to allow for the HIV virus to rapidly increase its viral load. Guenther et al. from the previously mentioned study also investigated this hypothesis in vitro. Mammalian cultures were introduced to HIV-1 with and without T. vaginalis. Cultures with T. vaginalis showed increased HIV replication, suggesting that the HIV virus can more easily locate and enter the specific immune cells it needs to infect.  Additionally, they found that TNF-α, a cytokine involved in systemic inflammation and regulation of immune cells, was found in high levels for cells infected with T. vaginalis and HIV. This suggests that the TNF-α pathway may be involved in the mechanism.  Unlike the other hypothesis, this experiment yields more conclusive results because of its ability to show a more direct association, without relying on multiple theories to be true.

            A less popular, although perfectly possible, hypothesis is that T. vaginalis secretes a protease that degrades an inhibitor that protects us from HIV infection. Secretory leukocyte protease inhibitors (SLPIs) are produced in our body and are present in many mucosal surfaces where they inhibit trypsin, a serine protease (Draper, 1998). It was also suggested that they also have antimicrobial properties and other functional effects on inflammatory cells (Jin, 1997). SLPI has been shown to prevent HIV transmission in saliva and through the oral mucosa (Draper). It is therefore likely that they play a role in the cervix, where they are also found, but in lower levels. In 1998, Draper et al. from the University of Pittsburgh attempted to verify this hypothesis.  They saw that the trichomonal proteases degraded SLPI into 2 smaller peptides in vitro. In addition, they tested the functionality of the cleaved SLPI. SLPI was shown to be unable to inhibit trypsin, implying that it may also be unable to perform its other functions as well. This study was not particularly useful in verifying the plausibility of this hypothesis. They were able to establish the degradation of SLPI by trichomonal proteases, but they failed to show the direct effects it has on HIV transmission. Additionally, they used the loss in ability to inhibit trypsin as a proxy for all of SLPIÕs function. Overall, the mechanism in which SLPI protects us from HIV is still unclear, which is why there is a lack of general support for this hypothesis.

            It has been quite difficult to shed light on the actual mechanism behind T. vaginalis increasing HIV transmission. As of right now, these hypotheses are just speculation because of the lack of sufficient experimental evidence. Guenther et al.Õs study testing HIV-target cell recruitment strongly validates its hypothesis, but there is a need for the results to be repeated in order for it to be truly accepted. Therefore, the mechanism is still unclear. T. vaginalis can act on one or a combination of these proposed mechanisms. There may even be others that have not yet been considered. Further research needs to be done to undoubtedly prove a T. vaginalis-HIV mechanism, so that health agencies can finally accept trichomoniasis as a public health threat. This is important because as we will soon see, the neglect of trichomoniasis unfairly affects African Americans.

African Americans, Trichomoniasis, and HIV

            The issue of T. vaginalis increasing susceptibility of HIV transmission is an important one because it places African Americans at higher risk of HIV infection, which is still currently incurable. Several studies have shown an overwhelming disproportionate amount of African Americans, particularly women, infected with trichomoniasis. When looking at trichomoniasis prevalence in various big cities across the U.S., African Americans were the largest racial group to be infected (Shafir, 2009). Odds ratios were calculated for African-Americans in these cities. It varied across the map, ranging from a 1.5 to nearly 10 times greater risk of being infected with trichomoniasis in the African-American population. One study even showed a 58% prevalence among young, inner-city, black men (Shafir). This high prevalence of trichomoniasis in the African American community is important because it can help explain why they are the highest risk group for HIV. In 2007, the CDC reported African Americans comprising approximately 51% of all cases of HIV. This trend can be a result of T. vaginalis playing a critical role in spreading HIV in the African American population. There is a seemingly close relationship among African-Americans, trichomoniasis, and HIV.

            There are several possible explanations for these observed trends. African-American men are less likely to use condoms than other racial groups for many different reasons. Studies say that African American men do not use condoms as frequently because of the higher frequency of condom breakage and slipping and some report a decrease in sexual fulfillment (Shafir, 2009). A recent study also showed that young African American women reported having sex with an intoxicated partner on several occasions (Crosby, 2008). Partners that are intoxicated during sex are more likely to engage in risky behavior, e.g. unprotected sex. The women in that study were significantly more likely to have an STI. The high prevalence of drug users in the African American community also plays a role in high trichomoniais and HIV rates. They are more likely to share infected needles. Also, African American women using drugs are more likely to trade sex for drugs or money than non-drug users.

In addition to the lack of condom use, other social factors play into why African-Americans are so disproportionately affected by trichomoniasis and HIV. A study showed that African American women are not as likely to notify their male partners of their trichomoniasis infection as non-African American women (Lichtenstein, 2005). Because the male partners are not informed about their infection, they can continue to spread T. vaginalis. It is also important to note the high reinfection rates of trichomoniasis seen in African American women. Trichomoniasis is therefore more likely to remain in African-American population because of the perpetual spreading of the disease. Last but not least is the obvious disparity in education. African-Americans tend to live in urban, poor, inner-cities where they lack the resources to adequately inform them on the importance and ways in preventing STIs (Shafir, 2009).


Implications on Public Health

Now that we have explored the reasons why trichomoniasis is so prevalent in the African-American community, we can use that knowledge to try to decrease the prevalence of both trichomoniasis and HIV.

Currently, the major barrier in reducing trichomoniasis and HIV among African Americans is the general regard of trichomoniasis as not dangerous and unimportant. Until government health agencies change their views and their policies concerning trichomoniasis, the public will remain unaware of the detriment of trichomoniasis. The lack of knowledge and fear for trichomoniasis are hindering the chances of greatly reducing infection rates of trichomoniasis and, by association, HIV. Perhaps more attention will be given to trichomoniasis if there were more substantial data supporting the trichomoniasis-HIV mechanism hypotheses. Progress in establishing mechanisms has been made with the study pertaining to the recruitment of HIV-target cells. But repetition of results is necessary for proving the mechanism to be true. Once those experiments have been established and accepted, then maybe trichomoniasis will finally be rightfully viewed as a public health threat and interventions can be carried out.

But until that happens, education on getting tested for STI regularly should be an important aspect of controlling trichomoniasis-related HIV infection. As mentioned earlier, many cases of trichomoniasis are asymptomatic, so clearing the infection before an HIV exposure is crucial. And since trichomoniasis is far more prevalent than HIV (7.4 million vs. 40,000) (Weinstock, 2004), its early detection and treatment has the potential to significantly reduce the chance of HIV infection. It is important to note that his is applicable to everyone, not just African-Americans.

Education will also encourage African American women to notify their partners about their trichomoniasis infection. If women are made more aware of the association between trichomoniasis and HIV, they may be more inclined to tell their partners about their infection because HIV is much more formidable than trichomoniasis. By reducing the amount of trichomoniasis reinfection, and possibly the spread to new partners, the African American population can reduce its susceptibility to HIV infection.

Conclusion

            Trichomoniasis is a more dangerous infection than many people believe it is. There is a strong need for more research to verify the hypotheses behind the trichomoniasis-HIV mechanism. Trichomoniasis will not receive acknowledgement as a public health threat until then. It will continue to be a non-reportable disease with no government funded control programs, quietly perpetuating the spread of HIV. As we wait for more experimental evidence, education programs should be implemented to combat the edemicity of trichomoniasis and HIV in the U.S., especially in the highest afflicted population, African Americans.   

 

 

 

 

 

 

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