Changes in the Etiology of Sexually Transmitted Diseases in Botswana between 1993 and 2002: Implications for the Clinical Management of Genital Ulcer Disease

Paz–Bailey, Gabriela; Rahman, Mafiz; Chen, Cheng; Ballard, Ronald C.; Moffat, Howard; Kenyon, Tom; Kilmarx, Peter H.; Totten, Patricia A.; Astete, Sabina G.; Boily, Marie‐Claude; Ryan, Caroline

doi:10.1086/496979

Cited by 86 publications

(50 citation statements)

References 43 publications

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“…HSV-2 seroprevalence ranges from 16% among 14-49 year olds in the United States (2) to greater than 80% in some areas of subSaharan Africa (3); seroprevalence in women is up to twice as high as men, and increases with age (2,4). Although HSV-2 is the leading cause of genital ulcer disease worldwide (5,6), most people are not aware of the infection (7), and may transmit the virus during periods of subclinical shedding (8,9). In contrast to other sexually transmitted infections (STIs) that may be concentrated among "core groups," such as gonorrhea (10), HSV-2 is widespread even among people with low or moderate levels of sexual activity.…”

Section: Introductionmentioning

confidence: 99%

HSV-2: in pursuit of a vaccine

Johnston

Koelle²,

Wald³

2011

J. Clin. Invest.

127

111

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Herpes simplex virus type 2 (HSV-2) is one of the most prevalent sexually transmitted infections worldwide. In addition to recurrent genital ulcers, HSV-2 causes neonatal herpes, and it is associated with a 3-fold increased risk for HIV acquisition. Although many HSV-2 vaccines have been studied in animal models, few have reached clinical trials, and those that have been tested in humans were not consistently effective. Here, we review HSV-2 pathogenesis, with a focus on novel understanding of mucosal immunobiology of HSV-2, and vaccine efforts to date, in an attempt to stimulate thinking about future directions for development of effective prophylactic and therapeutic HSV-2 vaccines.

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Section: Introductionmentioning

confidence: 99%

HSV-2: in pursuit of a vaccine

Johnston

Koelle²,

Wald³

2011

J. Clin. Invest.

127

111

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“…erpes simplex virus 2 (HSV-2) infects over 500 million people worldwide (1) and is the leading cause of genital ulcer disease (2) and increases the risk of HIV acquisition (3). Herpetic genital ulcers in the immunocompetent person are localized with respect to time and anatomic site (4), consistent with reactivation of virus from the ganglion innervating this region.…”

mentioning

confidence: 99%

Virologic and Immunologic Evidence of Multifocal Genital Herpes Simplex Virus 2 Infection

Johnston

Zhu

Jing

et al. 2014

J Virol

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Genital herpes simplex virus (HSV) reactivation is thought to be anatomically and temporally localized, coincident with limited ganglionic infection. Short, subclinical shedding episodes are the most common form of HSV-2 reactivation, with host clearance mechanisms leading to rapid containment. The anatomic distribution of shedding episodes has not been characterized. To precisely define patterns of anatomic reactivation, we divided the genital tract into a 22-region grid and obtained daily swabs for 20 days from each region in 28 immunocompetent, HSV-2-seropositive persons. HSV was detected via PCR, and sites of asymptomatic HSV shedding were subjected to a biopsy procedure within 24 h. CD4؉ and CD8 ؉ T cells were quantified by immunofluorescence, and HSV-specific CD4 ؉ T cells were identified by intracellular cytokine cytometry. HSV was detected in 868 (7%) of 11,603 genital swabs at a median of 12 sites per person (range, 0 to 22). Bilateral HSV detection occurred on 83 (67%) days with shedding, and the median quantity of virus detected/day was associated with the number of sites positive (P < 0.001). In biopsy specimens of asymptomatic shedding sites, we found increased numbers of CD8 ؉ T cells compared to control tissue (27 versus 13 cells/mm 2 , P ‫؍‬ 0.03) and identified HSV-specific CD4 ؉ T cells. HSV reactivations emanate from widely separated anatomic regions of the genital tract and are associated with a localized cellular infiltrate that was demonstrated to be HSV specific in 3 cases. These data provide evidence that asymptomatic HSV-2 shedding contributes to chronic inflammation throughout the genital tract. IMPORTANCEThis detailed report of the anatomic patterns of genital HSV-2 shedding demonstrates that HSV-2 reactivation can be detected at multiple bilateral sites in the genital tract, suggesting that HSV establishes latency throughout the sacral ganglia. In addition, genital biopsy specimens from sites of asymptomatic HSV shedding have increased numbers of CD8 ؉ T cells compared to control tissue, and HSV-specific CD4 ؉ T cells are found at sites of asymptomatic shedding. These findings suggest that widespread asymptomatic genital HSV-2 shedding is associated with a targeted host immune response and contributes to chronic inflammation throughout the genital tract. H erpes simplex virus 2 (HSV-2) infects over 500 million people worldwide (1) and is the leading cause of genital ulcer disease (2) and increases the risk of HIV acquisition (3). Herpetic genital ulcers in the immunocompetent person are localized with respect to time and anatomic site (4), consistent with reactivation of virus from the ganglion innervating this region. However, most HSV genital shedding is subclinical, with rapid onset and clearance (5, 6). Such subclinical reactivation may be more widespread in the genital area (7), consistent with frequent leakage of virus into the genital skin and mucosa with localized host containment (8, 9). Mathematical models suggest that observed shedding patterns are the result of ove...

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“…It is difficult to assess the current epidemiology of chancroid because of syndromic management of GUDs and a lack of reporting and diagnostic tools. Some publications regarding the epidemiology of GUDs have described declining numbers of chancroid cases worldwide (8,29,40), while others have shown that H. ducreyi infections are still found in pockets throughout the world (2,5,15,31). H. ducreyi has recently been shown to be the cause of lower limb cutaneous ulcers in patients from the South Pacific (24,30,46).…”

mentioning

confidence: 99%

Passive Immunization with a Polyclonal Antiserum to the Hemoglobin Receptor of Haemophilus ducreyi Confers Protection against a Homologous Challenge in the Experimental Swine Model of Chancroid

et al. 2011

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Haemophilus ducreyi, the etiologic agent of chancroid, has an obligate requirement for heme. Heme is acquired by H. ducreyi from its human host via TonB-dependent transporters expressed at its bacterial surface. Of 3 TonB-dependent transporters encoded in the genome of H. ducreyi, only the hemoglobin receptor, HgbA, is required to establish infection during the early stages of the experimental human model of chancroid. Active immunization with a native preparation of HgbA (nHgbA) confers complete protection in the experimental swine model of chancroid, using either Freund's or monophosphoryl lipid A as adjuvants. To determine if transfer of anti-nHgbA serum is sufficient to confer protection, a passive immunization experiment using pooled nHgbA antiserum was conducted in the experimental swine model of chancroid. Pigs receiving this pooled nHgbA antiserum were protected from a homologous, but not a heterologous, challenge. Passively transferred polyclonal antibodies elicited to nHgbA bound the surface of H. ducreyi and partially blocked hemoglobin binding by nHgbA, but were not bactericidal. Taken together, these data suggest that the humoral immune response to the HgbA vaccine is protective against an H. ducreyi infection, possibly by preventing acquisition of the essential nutrient heme.

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Changes in the Etiology of Sexually Transmitted Diseases in Botswana between 1993 and 2002: Implications for the Clinical Management of Genital Ulcer Disease

Cited by 86 publications

References 43 publications

HSV-2: in pursuit of a vaccine

HSV-2: in pursuit of a vaccine

Virologic and Immunologic Evidence of Multifocal Genital Herpes Simplex Virus 2 Infection

Passive Immunization with a Polyclonal Antiserum to the Hemoglobin Receptor of Haemophilus ducreyi Confers Protection against a Homologous Challenge in the Experimental Swine Model of Chancroid

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