Previously on the blog I’ve covered studies addressing the under-researched role of genital tract immune activation in increasing the risk of HIV acquisition, and the potential link between this phenomenon and global variation in HIV prevalence. A related issue is the impact of genital infections on the probability of acquiring HIV. Several recent papers (abstracts and links below) draw attention to the specific contributions of Mycoplasma genitalium and Schistosoma haematobium in this regard, highlighting the importance of considering these factors in the context of HIV prevention, and also emphasizing the need to better understand their contribution to the increased risk of heterosexual HIV transmission in sub-Saharan Africa.
AIDS. 2011 Dec 29. [Epub ahead of print]
Mavedzenge SN, Van der Pol B, Weiss HA, Kwok C, Mambo F, Chipato T, Van der Straten A, Salata R, Morrison C.
aWomen's Global Health Imperative, RTI International, San Francisco, California, USA bLondon School of Hygiene & Tropical Medicine, Department of Infectious Disease Epidemiology, London, UK cIndiana University School of Public Health, Division of Epidemiology & Biostatistics, Bloomington, IN, United States dBiostatistics Department, FHI, Durham, NC, United States eAMPATH Reference Laboratory, Eldoret, Kenya fUniversity of Zimbabwe, Harare, Zimbabwe gCenter for AIDS Prevention Studies, Department of Medicine, University of California San Francisco, CA, United States hCase Western Reserve University, Cleveland, Ohio, United States iClinical Sciences, FHI, Durham, NC, United States.
OBJECTIVE: Mycoplasma genitalium is an emerging sexually transmitted infection (STI) and has been associated with reproductive tract infections, and with HIV in cross-sectional studies. In this longitudinal study, we assess whether M. genitalium is associated with risk of acquiring HIV-1 infection.
DESIGN: Nested case-control study within a large prospective study in Zimbabwe and Uganda
METHODS: A total of 190 women who seroconverted to HIV-1 during follow-up ("cases") were matched with up to two HIV-negative controls. M. genitalium testing was performed by PCR-ELISA, using archived cervical samples from the HIV-1 detection visit and the last HIV-negative visit for cases, and equivalent visits in follow-up time for controls. Risk factors for HIV-1 acquisition were analyzed using conditional logistic regression, with M. genitalium as the primary exposure.
RESULTS: M. genitalium was a common infection in these populations (14.8% and 6.5% prevalence among cases and controls, respectively, at the visit prior to HIV-1 detection), and more prevalent than other non-viral STIs. We found a greater than two-fold independent increased risk of HIV-1 acquisition among women infected with M. genitalium at the visit prior to HIV-1 acquisition (AOR=2.42; 95%CI:1.01-5.80), and at time of HIV-1 acquisition (AOR = 2.18; 95%CI:0.98-4.85). An estimated 8.7% (95%CI:0.1-12.2%) of incident HIV-1 infections were attributable to M. genitalium.
CONCLUSIONS: This is the first longitudinal study to assess the relationship between M. genitalium and HIV-1 acquisition. If findings from this research are confirmed, M. genitalium screening and treatment among women at high-risk for HIV-1 infection may be warranted as part of an HIV-1 prevention strategy.
J Infect Dis. 2012 Jan;205(2):289-96. Epub 2011 Nov 18.
Vandepitte J, Muller E, Bukenya J, Nakubulwa S, Kyakuwa N, Buvé A, Weiss H, Hayes R, Grosskurth H.
MRC/UVRI Uganda Research Unit on AIDS, Entebbe.
Background. The importance of Mycoplasma genitalium in human immunodeficiency virus (HIV)-burdened sub-Saharan Africa is relatively unknown. We assessed the prevalence and explored determinants of this emerging sexually transmitted infection (STI) in high-risk women in Uganda.
Methods. Endocervical swabs from 1025 female sex workers in Kampala were tested for Mycoplasma genitalium using a commercial Real-TM polymerase chain reaction assay. Factors associated with prevalent Mycoplasma genitalium, including sociodemographics, reproductive history, risk behavior, and HIV and other STIs, were examined using multivariable logistic regression.
Results. The prevalence of Mycoplasma genitalium was 14% and higher in HIV-positive women than in HIV-negative women (adjusted odds ratio [OR], 1.64; 95% confidence interval [CI], 1.12-2.41). Mycoplasma genitalium infection was less prevalent in older women (adjusted OR, 0.61; 95% CI, .41-.90 for women ages 25-34 years vs <25 years; adjusted OR, 0.32; 95% CI, .15-.71 for women ≥35 years vs those <25 years) and in those who had been pregnant but never had a live birth (adjusted OR, 2.25; 95% CI, 1.04-4.88). Mycoplasma genitalium was associated with Neisseria gonorrhoeae (adjusted OR, 1.84; 95% CI, 1.13-2.98) and with Candida infection (adjusted OR, 0.41; 95% CI, .18-.91), and there was some evidence of association with Trichomonas vaginalis (adjusted OR, 1.56; 95% CI, 1.00-2.44).
Conclusions. The relatively high prevalence of Mycoplasma genitalium and its association with prevalent HIV urgently calls for further research to explore the potential role this emerging STI plays in the acquisition and transmission of HIV infection.
Am J Trop Med Hyg. 2011 Dec;85(6):1060-4.
Jourdan PM, Holmen SD, Gundersen SG, Roald B, Kjetland EF.
Centre for Imported and Tropical Diseases, Department of Infectious Diseases, Oslo University Hospital Ulleval, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; Research Unit, Sorlandet Hospital HF, Kristiansand, Norway; Centre for Development Studies, University of Agder, Kristiansand, Norway; Centre for Paediatric and Pregnancy Related Pathology, Department of Pathology, Oslo University Hospital Ulleval, Oslo, Norway.
The parasite Schistosoma haematobium frequently causes genital lesions in women and could increase the risk of human immunodeficiency virus (HIV) transmission. This study quantifies the HIV target cells in schistosome-infected female genital mucosa. Cervicovaginal biopsies with and without schistosomiasis were immunostained for quantification of CD4(+) T lymphocytes (CD3, CD8), macrophages (CD68), and dendritic Langerhans cells (S100 protein). We found significantly higher densities of genital mucosal CD4(+) T lymphocytes and macrophages surrounding schistosome ova compared with cervicovaginal mucosa without ova (P = 0.034 and P = 0.018, respectively). We found no increased density of Langerhans cells (P = 0.25). This study indicates that S. haematobium may significantly increase the density of HIV target cells (CD4(+) T lymphocytes and macrophages) in the female genitals, creating a beneficial setting for HIV transmission. Further studies are needed to confirm these findings and to evaluate the effect of anti-schistosomal treatment on female genital schistosomiasis.
PLoS Negl Trop Dis 5(12): e1396. doi:10.1371/journal.pntd.0001396
Pamela Sabina Mbabazi1, Olivia Andan1, Daniel W. Fitzgerald2, Lester Chitsulo1, Dirk Engels1, Jennifer A. Downs2
1 Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland, 2 Center for Global Health, Division of Infectious Diseases, Weill Cornell Medical College, New York, New York, United States of America
Urogenital schistosomiasis, caused by infection with Schistosoma haematobium, is widespread and causes substantial morbidity on the African continent. The infection has been suggested as an unrecognized risk factor for incident HIV infection. Current guidelines recommend preventive chemotherapy, using praziquantel as a public health tool, to avert morbidity due to schistosomiasis. In individuals of reproductive age, urogenital schistosomiasis remains highly prevalent and, likely, underdiagnosed. This comprehensive literature review was undertaken to examine the evidence for a cause-effect relationship between urogenital schistosomiasis and HIV/AIDS. The review aims to support discussions of urogenital schistosomiasis as a neglected yet urgent public health challenge.
We conducted a systematic search of the literature including online databases, clinical guidelines, and current medical textbooks. We describe plausible local and systemic mechanisms by which Schistosoma haematobium infection could increase the risk of HIV acquisition in both women and men. We also detail the effects of S. haematobium infection on the progression and transmissibility of HIV in co-infected individuals. We briefly summarize available evidence on the immunomodulatory effects of chronic schistosomiasis and the implications this might have for populations at high risk of both schistosomiasis and HIV.
Studies support the hypothesis that urogenital schistosomiasis in women and men constitutes a significant risk factor for HIV acquisition due both to local genital tract and global immunological effects. In those who become HIV-infected, schistosomal co-infection may accelerate HIV disease progression and facilitate viral transmission to sexual partners. Establishing effective prevention strategies using praziquantel, including better definition of treatment age, duration, and frequency of treatment for urogenital schistosomiasis, is an important public health priority. Our findings call attention to this pressing yet neglected public health issue and the potential added benefit of scaling up coverage of schistosomal treatment for populations in whom HIV infection is prevalent.
Urogenital schistosomiasis is a parasitic infection caused by a worm, Schistosoma haematobium, which lives in the bloodstream of infected individuals. It affects at least 112 million people, mostly in sub-Saharan Africa, and has been suggested to be a risk factor for becoming infected with HIV. We reviewed publications in order to examine whether it seems likely that this parasitic infection could be a risk factor for HIV. Evidence from many types of studies supports the hypothesis that urogenital schistosomiasis does increase a person's risk of becoming infected with HIV. Studies also suggest that individuals who have both urogenital schistosomiasis and HIV have a more aggressive HIV infection and can more easily transmit HIV to their sexual partners. Praziquantel is an oral, nontoxic, inexpensive medication that is safe in pregnancy and is recommended for treatment of schistosomiasis. In areas where both infections co-exist, regular administration of praziquantel both to young girls and to sexually-active women may be an important approach to reducing HIV transmission. Our findings support the importance of making praziquantel more available to people who live in areas of the world where both urogenital schistosomiasis and HIV infection are widespread.
The Lancet, Volume 378, Issue 9809, Pages 2069 - 2070, 17 December 2011
Jennifer Manne a b, Karolina Maciag c d
a Department of Global Health and Population, Harvard School of Public Health, Boston, MA 02115, USA
b Boston University School of Medicine, Boston, MA, USA
c Harvard—Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, Boston, MA, USA
d Broad Institute, Cambridge, MA, USA
We applaud Nancy Padian and colleagues (July 16, p 269) for their thorough Review of the HIV prevention research agenda. Although Padian and colleagues address many crucial ways to break the transmission cycle, we point out one important omission: the intersection between HIV transmission and neglected tropical diseases (NTDs). With increasing evidence that infections such as female urogenital schistosomiasis (FUS) and helminthiases substantially increase the risk of HIV infection and speed disease progression, it is essential that we no longer ignore the importance of the NTDs in the context of the HIV epidemic.
Specifically, preliminary research has shown a three-fold increase in sexual transmission and incidence of HIV/AIDS in women with genital ulcers caused by FUS, as well as a substantial geographical overlap between areas of high HIV prevalence and regions where FUS is endemic. Evidence also suggests that deworming reduces HIV viral load and that maternal helminth infection increases risk of mother-to-child HIV transmission.
Mounting evidence supports the addition of this intersection between HIV/AIDS and NTDs to the HIV prevention research agenda. Since treatments for several NTDs are cheaply available, integration of NTD and HIV/AIDS delivery platforms offers a rare and substantial opportunity for efficiency and savings, particularly in the face of escalating financial constraints to the maintenance and escalation of HIV/AIDS treatment. Finally, increased research to establish the population-level effects of NTDs on HIV/AIDS will offer an avenue for better understanding, prevention, and treatment of both HIV and several long-neglected infections of the “bottom billion”.
We declare that we have no conflicts of interest.
1 Padian N, McCoy SI, Abdool Karim SS, et al. HIV prevention transformed: the new prevention research agenda. Lancet 2011; 378: 269-278.
2 Sawers L, Stillwaggon E, Hertz T. Cofactor infections and HIV epidemics in developing countries: implications for treatment. AIDS Care 2008; 20: 488-494.
3 Downs JA, Mguta C, Kaatano GM, et al. Urogenital schistosomiasis in women of reproductive age in Tanzania's Lake Victoria region. Am J Trop Med Hyg 2011; 84: 364-369.
4 Hotez PJ, Mistry N, Rubinstein J, Sachs JD. Integrating neglected tropical diseases into AIDS, tuberculosis, and malaria control. N Engl J Med 2011; 364: 2086-2089.
5 Walson JL, Herrin BR, John-Stewart G. Deworming helminth co-infected individuals for delaying HIV disease progression. Cochrane Database Syst Rev 2009; 3. CD006419.