Generally, a longer duration of treatment is advised as the duration of infection increases. To be effective, the treponemicidal concentration should be maintained for at least 7 days to cover the number of division times (30-33/h) in early syphilis. Treponemes divide more slowly in late disease. For neurosyphilis, use one of the non-benzathine PCN regimens, preferably 12-24 million U/d intravenously for 10-14 days. Monitor the CSF as an index of adequate treatment. A CSF examination 6 months following treatment should demonstrate a normal blood cell count and decreasing protein content. Std Screening nearby North Dakota. CSF examinations should be repeated every 6 months for 2 years (thereafter, no relapses have been reported) or until the CSF is normal. An increase in the blood cell count is an indication for re-treatment. Std Screening Near Me Ohio.
No vaccine is available. Epidemiologic investigation (ie, accurate identification and timely reporting to public health facilities) and preventive treatment of sexual contacts are important. Clinical awareness is the key to prevention. All clinicians and laboratories based in the United States are expected to report, within 48 hours, cases of syphilis to their local or state health department according to established policy. All test results are held in confidence. Partners exposed within the 90 days preceding the patient's diagnosis of primary, secondary, or early latent syphilis should be treated presumptively. Partner notification may have to extend to 2 years for patients with secondary syphilis who have a clinical relapse or those with early latent syphilis. Patients with concomitant HIV infection or those on non-PCN treatment should be monitored for life.
Because of resistance with oral cephalosporins, only 1 regimen, dual treatment with ceftriaxone IM and azithromycin PO, is recommended for treatment of gonorrhea in the United States. Dual therapy with ceftriaxone and azithromycin should be administered together on the same day, preferably simultaneously and under direct observation. In addition, persons infected with N gonorrhoeae frequently are coinfected with C trachomatis; this finding has led to the longstanding recommendation that persons treated for gonococcal infection also be treated with a regimen that is effective against uncomplicated genital C trachomatis infection, further supporting the use of dual therapy that includes azithromycin. 3
Although cephalosporins remain an effective treatment for gonococcal infections, the CDC has reported that resistance to cefixime increased from 0.2% in 2000 to 1.4% in 2010 and back down to 0.4% in 2013, and resistance to ceftriaxone increased from less than 0.1% to 0.4% in 2011 and back down to 0.05% in 2013. 4 However, the reported rates of resistance to ceftriaxone have been much higher in countries such as Japan, Spain, and France. 4 Oral cephalosporins are no longer recommended as first-line treatment for gonorrhea because of increasing resistance. Additionally, a high prevalence of tetracycline resistance among GISP isolates was observed, particularly among patients with elevated MICs to cefixime. 5
HSV is a DNA virus. HSV has 2 subtypes: herpes simplex virus 1 (HSV-1) and HSV-2. The two types are differentiated by glycoproteins on the lipid bilayer envelope. Glycoprotein G1 is associated with HSV-1 and glycoprotein G2 is associated with HSV-2. Although each is a distinct virus, they share some antigenic components, such that antibodies that react to one type may "neutralize" the other. Most individuals who are infected with HSV are unaware that they have contracted the virus with only approximately 10-15% of infected individuals reporting recognition of their infection. 1 Another factor in the underestimation of the prevalence of genital herpes is because HSV-1 can also cause the genital disease.
HSV-1 infections were traditionally associated with the oral area causing herpes labialis (fever blisters), gingivostomatitis and keratoconjunctivitis, whereas HSV-2 infections occurred in the genital region. However, because of increasing oral-genital contact, either HSV type may be found in either location. Currently, approximately 15% of genital HSV infections are caused by HSV-1, however, HSV-1 is increasingly recognized as the etiologic agent of genital herpes infection with a large proportion of new genital infections being caused by HSV-1 in young women.
Herpes simplex virus is transmitted from person to person through direct contact. Virus contacting mucosa or disrupted skin initiates the infection. Incubation is approximately 2-12 days where the HSV virus replicates in the dermis and epidermis. This results in cellular destruction and inflammation. The virus then becomes latent in the sensory ganglia and reactivate periodically with either asymptomatic shedding or recurrent ulcerative lesions. Recurrences and subclinical shedding are much more frequent for genital HSV-2 infection than for genital HSV-1 infection.
A nonprimary first-episode infection is a first genital HSV outbreak in a woman who has heterologous HSV antibodies. For example, if a woman develops a nonprimary first-episode HSV-2 infection on the labia, she would have antibodies against HSV-1 prior to and at the time of her genital outbreak. Because of the partial protection of the preexisting antibodies, systemic symptoms during these outbreaks tend to be fewer and shorter in duration. The duration of lesions is also shorter (averaging 15 days), and shedding lasts for only approximately 7 days.
A recurrent infection is defined as a genital HSV outbreak in a woman with homologous IgG antibodies to the HSV type. Recurrent infections occur most frequently during the first 3 months after a primary infection, especially with HSV-2. These lesions are classically unilateral on the labia. Approximately 14% of all pregnant women with a history of genital HSV infection experience recurrent lesions or prodromal symptoms at delivery. However, among women with recurrent lesion at the time of delivery, only 3% of neonates will be infected. Recurrent HSV outbreaks may be symptomatic or asymptomatic. When present, most symptoms are localized (eg, pain, itching, vaginal discharge).
Type-specific HSV serologic assays have been approved by the US Food and Drug Administration (FDA) for commercial use. These assays distinguish HSV-1 from HSV-2 antibodies on the basis of differences in the surface glycoprotein G between the two HSV subtypes. The Centers for Disease Control and Prevention (CDC) now recommends the use of glycoprotein G-based assays for all HSV type-specific serologic testing. Immunoglobulin M (IgM)-specific serology is generally not useful because this test may be positive during recurrent genital or oral episodes. Use of type-specific serology in conjunction with HSV culture makes it possible to determine the type of genital infection.
Hensleigh and colleagues evaluated 23 pregnant women with severe first-episode infections that were presumed to be primary by the clinician. All had HSV cultures and type-specific serology at the time of presentation. Of the 23 women, 1 (4%) had primary HSV-1, 3 (13%) had nonprimary first-episode infections (all HSV-2), and 19 (83%) had recurrent infection (14 with HSV-2). 6 This study demonstrated both the utility of HSV serology in determining the type of infection and the overdiagnosis of primary infections during pregnancy.
Unfortunately, in a proficiency test administered by the American College of Pathology to 172 participating laboratories, more than 50% reported the presence of HSV-2 antibodies from a sample that contained only HSV-1 antibodies. All of the labs using a glycoprotein G-based assay correctly identified only HSV-1 antibodies. Std screening nearest North Dakota. 7 These test results underscore the importance for clinicians to know the type of assays used by their laboratory when ordering type-specific serology to distinguish the type of genital HSV infection. If the assay is not a glycoprotein G-based test, the accuracy of the typing should be challenged.
To determine the frequency and sequelae of HSV shedding at the time of delivery, Brown and colleagues obtained HSV cultures (from both cervix and external genitalia) within 48 hours of delivery in 40,023 women. 9 HSV was isolated in 202 women (0.5%), of whom approximately one half had no prior history of genital HSV. Serology was also available in 177 of the 202 cases (see image below). Based on the serology of these 177 women, 26 (15%) had first-episode disease, and 151 (85%) had recurrent infection.
The significance of neonatal HSV infection varies and depends on the extent of the infection (see Table 1). Localized infections are the most common and benign type. However, serious infections can occur and can lead to death or long-term CNS morbidity. Neonatal HSV infections can be classified as disseminated disease (25%); central nervous system disease (30%); and disease limited to the skin, eyes or mouth (45%). Mortality has decreased to 30% for disseminated disease and 4% for central nervous system disease over the past two decades. Approximately 20% of affected neonates will have long term neurologic sequelae.
HSV culture has long been the criterion standard for diagnosis of HSV infection, with a sensitivity of 70% and a specificity of nearly 100%. A final culture report may take up to 7 days. The sensitivity of HSV culture is related to the HSV type and the location from which the culture is taken. The culture yield is highest during the prodrome and lowest during the second half of the outbreak, especially with recurrent lesions. Sensitivity of HSV viral culture is lower for HSV-2 than for HSV-1. In asymptomatic women, the yield is greatest when cultures are taken from the cervix and the site of recurrence, even if no lesion is visualized. When obtaining HSV cultures, request that the lab type the specimens for both HSV-1 and HSV-2 strains so that the results can be compared with type-specific serology to determine the type of clinical infection.
Polymerase chain reaction (PCR) is a molecular test that is being increasingly used and that may ultimately replace HSV culture as the criterion standard. 11 , 12 , 13 Like the viral culture, PCR can distinguish HSV-1 from HSV-2. The test takes approximately 1 day for results to be returned and has the potential for a higher detection rate than HSV culture. In one study, 9% of women in labor who had culture-negative results for HSV had PCR-positive results. Std Screening closest to North Dakota. 12 Additionally, increased levels of HSV DNA may be associated with an increased risk of neonatal transmission. Std screening closest to North Dakota. Unfortunately, PCR does not differentiate actively replicating HSV from latent HSV DNA.
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Acyclovir , a nucleoside analogue, was the first antiviral therapy approved for the treatment and prevention of HSV infection. Acyclovir selectively inhibits viral DNA replication of HSV, while having little effect on normal cells. Acyclovir is selective for HSV-infected cells because it requires phosphorylation by a viral enzyme (thymidine kinase) to acyclovir monophosphate. Phosphorylation does not occur in uninfected cells, where it remains virtually undetectable. After its conversion to acyclovir monophosphate in infected cells, other cellular enzymes convert it to acyclovir triphosphate, which acts to inhibit HSV-specific DNA polymerase, resulting in termination of the DNA transcript.
During pregnancy, acyclovir crosses the placenta and concentrates in the amniotic fluid. Postpartum, acyclovir concentrates in breast milk. Fetal serum concentrations are equivalent to maternal serum concentrations. A potential drawback of acyclovir therapy is delayed and decreased antibody response to a primary HSV infection. Whether this is due to a decreased viral load or to immune suppression is unknown. Std screening nearby North Dakota. Acyclovir has been labeled a category B drug (no teratogenic effects were found in animal studies, but no or limited human studies are available).
Recognizing that recurrent infections occur more frequently within the first year after a primary infection, Scott et al randomized 46 gravidas with first genital outbreak during pregnancy to either acyclovir (400 mg tid) or placebo beginning at 36 weeks' gestation. 17 Patients receiving acyclovir experienced a significant reduction in the percentage of HSV recurrences at delivery (36% vs 0%) and cesarean deliveries for HSV (36% vs 0%). Std Screening Near Me North Carolina. However, the reduction in the total number of cesarean deliveries in enrolled women was not statistically significant (40% vs 19%).
In 1998, Brocklehurst and colleagues performed a double-blind placebo-controlled trial that involved 63 women with a history of recurrent HSV infection. 18 These women were randomized to either acyclovir (200 mg qid) or placebo, both beginning at 36 weeks' gestation. Nonsignificant reductions were found in recurrent HSV outbreaks at delivery, cesarean deliveries for HSV, and total cesareans in the acyclovir group. No infant in either group developed neonatal HSV, and no gravida experienced toxicity from acyclovir. Std Screening near North Dakota. The authors concluded that the sample size was too small to demonstrate a significant benefit from acyclovir and recommended that acyclovir be used only in clinical trials.