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You have your medals,Now, give one to Them.Spouse MedalChild MedalParent MedalLet them know you care.
Save Our Benefit DoD Podcasts In The FightASM Job Advantage
Military OneSource provides free, online resources to service members and their families via the Morale, Welfare and Recreation Digital Library. You'll find eBooks and audiobooks on virtually every topic, as well as databases and reference books that can help you learn a new skill, keep kids engaged and serve as a homework source, or prepare you to land your next job.
The Morale, Welfare and Recreation Digital Library is an incredible free resource for service members and their families. Just log into your Military OneSource account or create a username and password to get started and enjoy browsing.
Service members and their families can use Space-Available flights – formally known as Military Airlift Command or MAC flights – to travel around the country and world at little to no cost. Though sometimes unpredictable, military flights are perfect for families with flexible plans and limited travel budgets. With the right planning and documentation, Space-A travel can be the best way to take a trip with your family.
Space-A travel basics
These flights are not commercial, but rather military flights with a mission. That means there are certain restrictions to travel, including:
By MaryTherese Griffin, Warrior Care and Transition
ARLINGTON, Va. -- It's likely at some point in life one will hear a phrase like, "two heads are better than one" or "teamwork makes the dream work". However, phrases like these all boil down to a simple four letter word, help.
By Master Sgt. Michel Saure
DENTON, Md. -- The "Old Soldier" has a basement full of history.
At the age of 88, he has to walk gingerly down the steps. Coming around a bend in the stairway, he points to a "Moran St." sign encased behind glass in a wooden box.
"They named a street at Fort Meade after me, too, right there," he says, almost in passing.
Posted by ED Staff
When asked to share their thoughts on the benefits of school choice and their homeschool experience, this military family did what they do every day: they turned the occasion into a learning opportunity. Dan, his wife Jenna, and their six kids gathered at the dinner table to shape a response – as individual, independent thinkers and as a family.
In this interview, slightly edited for length and clarity, the family describes the transformative of impact school choice.
By Terri Moon CronkDoD News, Defense Media Activity
WASHINGTON, Nov. 1, 2017 Service members eligible to opt into the Blended Retirement System in 2018 can now take a free course to learn to use the online comparison calculator to aid in determining whether the new BRS or the legacy retirement system is a better choice for their circumstances, Defense Department officials said.
The calculator provides individual military retirement benefit estimates for service members who are eligible to opt into the new system in 2018, allowing them to compare options under both systems.
The Defense Department joins the nation in honoring the commitment, sacrifices and contributions families of service members make every day in support of the military and the nation.
As the nation marks Warrior Care month in November, the Defense Department honors the courage of wounded, ill or injured service members, and highlights the programs that support their return to duty or transition to the civilian community.
DoD News, Defense Media Activity
WASHINGTON, Nov. 30, 2016 - Walgreens pharmacies join the TRICARE retail pharmacy network on Dec. 1, 2016, while CVS pharmacies, including those in Target stores, will leave the network on the same day, according to the Defense Health Agency.
"The network will still have more than 57,000 locations across the country," Dr. George Jones, DHA's Chief of Pharmacy Operation, said in a release. "About 98 percent of beneficiaries still have a network pharmacy within 5 miles of their home."
WASHINGTON, Nov. 29, 2016 - First Lady Michelle Obama hosted nearly 200 service members, spouses, children, veterans and wounded warriors at this year's annual White House holiday décor preview as part of a Joining Forces initiative celebration.
"For the past eight years, celebrating the holidays and having you all be the first that see the decorations … has been one of our favorite White House traditions," the first lady said.
The dates shown are from the United States Post Office. You should verify with your local Post Office for services available, date changes, and to acquire the appropriate United States Customs forms, FREE Express and Priority shipping supplies.
From USPS.com
If you're mailing or shipping holiday cards and gifts, for Hanukah, Kwanza, Christmas, or other holiday traditions, find the deadline for getting cards and packages sent on time by reviewing the 2016 Holiday Shipping Dates below.
By Mike CaseyNovember 25, 2016
FORT LEAVENWORTH, Kan. -- The Army is picking up the pace to make more training mobile applications available for Soldiers' smartphones and computer tablets.
Recently, a team of Soldiers and civilians at Fort Eustis, Virginia, started using software to ensure Army mobile apps meet government security requirements and other standards.
by Maj. John CallahanNovember 18, 2016
TOGIAK, Alaska - In a rare daytime appearance, Santa and about 50 of his elves - including Alaska Gov. Bill Walker and First Lady Donna Walker - came early this year to visit Christmas cheer upon the schoolchildren of this remote village in Southwest Alaska.
The early visit was made possible by the Alaska National Guard's Operation Santa Claus, now in its 60th year. Each year since 1956, volunteers have come together to process and package donated Christmas toys, school supplies, books and staple foods. Most of these "elves" are affiliated with the Alaska Army or Air National Guard; others step forward from local businesses and community groups. Alaska Air National Guard crews then fly the elves and their collected goodies to a selected handful of villages a year.
By Petty Officer First Class Gary A. Prill, U.S. Fleet Forces Command Public Affairs
NORFOLK (NNS) -- United States Fleet Forces Command began a six-month pilot program Oct. 29 with the pre-launch of the Navy's newest tool to counter destructive decisions, the LiveSafe smartphone application.
The pilot program will allow Sailors and their families assigned to Hampton Roads, Virginia and Rota, Spain a chance to download and interact with the application prior to its release.
NAVADMIN 219/16 now makes it a requirement to submit and have your TA Command Approved 14 days prior to your course start date for all classes starting on or after January 1st, 2017!
So, if you are considering taking classes starting Monday January 2nd, 2017 you will need to have submitted and have your request Command approved by the 19th of December!
Some things in healthcare just defy logical explanation. For example, why in an era where we can alter human genes using CRISPR, why are we still using loose leafs of paper to document something as important as one's immunizations? In other words, why doesn't our health system place more emphasis on getting these "simple" things right? At Zobreus, we're committed to doing exactly that. We've built technology that allows any clinic to easily upload your shot data to a centralized portal. And instantly, those vaccination records are available to you on your mobile device. All of this in our gorgeous, award-winning user interface.
By Jim GaramoneDoD News, Defense Media Activity
WASHINGTON, Nov. 23, 2016 Tomorrow isnt Thanksgiving for Americas enemies.
While the vast majority of Americans will be sitting down with family for a fall feast, hundreds of thousands of U.S. service members will be on guard around the world, ensuring their fellow citizens enjoy a day of peace.
For them, it is another duty day.
WASHINGTON, Nov. 22, 2016 — On Oct. 21, the Defense Department launched a new call and outreach center that offers confidential peer support to active duty service members, National Guardsmen, reservists and family members through 24/7 chat, phone and text.
The DoD "BeThere" peer support call and outreach center is staffed by peers who are veteran service members and family members of veterans, and aims to provide support for everyday problem-solving of career and general life challenges.
Release No: 115 Nov. 22, 2016
By Staff Sgt. Alexx PonsAir Force Personnel Center Public Affairs
"JOINT BASE SAN ANTONIO-RANDOLPH, Texas" – The Air Force Personnel Center is currently accepting nominations for the Air Force Association Joan Orr Air Force Spouse of the Year Award.
This award honors significant contributions made by non-military spouses of Air Force military members. The nominee's spouse must be an active duty Air Force, Air National Guard or Air Force Reserve member.
Release No: 114 Nov. 21, 2016
"JOINT BASE SAN ANTONIO-RANDOLPH, Texas" - Air Force Personnel Center officials have nominated four Airmen for the 2016 Government Employees Insurance Company Military Service Award.
The categories and nominees are as follows:
(From the MILITARY ONESOURCE November 2016 Newsletter)
Military service is characterized by hard work and sacrifice, and families give service members the love and support they need to function well and stay mission ready.
November is Military Family Month, and we salute the strength and vibrancy of our military families. There are also many services through the DoD and Military OneSource to help keep families healthy and strong. Here are some highlights:
The April tax deadline may seem a long way off, but there are things you can do now to get ready. Military OneSource offers free tax preparation and filing services to help you approach tax season with confidence. These services are available to service members and eligible family.
This assistance is especially valuable this year since the IRS made two major changes for filing in 2017 –
Adoption can be rewarding for everyone involved. It can also raise a lot of questions. How do I get started? Does it cost a lot of money? What is the adoption process like? Whether you are just starting out or pursuing a kinship or stepparent adoption, Military OneSource can help. Call Military OneSource any time at 800-342-9647 to ask for an adoption consultation.
By Army 1st Lt. Daniel Johnson2nd Brigade Combat Team, 101st Airborne Division
QAYYARAH WEST AIRFIELD, Iraq, Nov. 21, 2016 - Smoke rose in the distance from an oil field set on fire during the battle between Iraqi forces and the Islamic State of Iraq and the Levant as Army Sgt. Addison Owen stood outside his tent. Owen, an infantryman with Bravo Company, 1st Battalion, 26th Infantry Regiment, is no stranger to Iraq; this is his second time deployed to the country.
On his first deployment he fought beyond the oil field, but now he is part of a multinational effort to assist the Iraqi forces.
On Veterans Day, November 11th, we're inviting our veterans and active duty military to enjoy a free entrée* from our favorites below. Don't forget that family members dining with them enjoy 10% off of their meals.
Olive Garden Free Veteran's Day Meals 2015
DALLAS - Holiday shoppers can budget easy this year when they shop at Army & Air Force Exchange Service, which, for a limited time, is offering fee-free layaway on computers, laptops, tablets and notebooks - items that are not normally eligible for layaway.
From now until Dec. 14, the Exchange will waive its standard $3 service fee for all layaway purchases that are paid in full within 30 days and picked up on time. Layaway will not be offered for computers, laptops, tablets and notebooks purchased Nov. 27-28.
In proclaiming November as Military Family Month, President Barack Obama urged Americans to show enduring gratitude to military families and their loved ones for contributing to the nation's legacy. Obama said "their courage serves as a model of character and distinction, and their devotion to our country must be met with the recognition it deserves."
Learn more in the Defense.gov special report, Military Family Support: http://www.defense.gov/News/Special-Reports/1115_familysupport
By David VergunArmy News Service
WASHINGTON, Nov. 7, 2014 - President Barack Obama awarded the Medal of Honor to Union Army 1st Lt. Alonzo H. Cushing yesterday for helping to stop Confederate Army Maj. Gen. George E. Pickett's Charge at Gettysburg on July 3, 1863.
Helen Loring Ensign accepted the medal during the ceremony, held in the White House's Roosevelt Room, on behalf of Cushing, her first cousin, twice removed. Some 24 other descendants were present as well.
WASHINGTON, Nov. 6, 2014 - First Lady Michelle Obama and an all-star cast hosted military children at the White House today for a workshop in advance of the taping of a concert for the PBS "In Performance at the White House" series.
Country legend Willy Nelson, rapper Common, Navy vet and songwriter Ted Peterson and Army Sgt. Christiana Ball, a singer who won the Army's Rising Star competition, joined the first lady in the East Room. Robert Santelli, the executive director of the Grammy Museum, moderated the discussion.
By Claudette RouloAmerican Forces Press Service
WASHINGTON, Nov. 26, 2013 - Real warriors ask for help when they need it. Like retired Army Maj. Ed Pulido, who sought out the help he and his family needed after he was wounded in Baqubah, Iraq.
Pulido's vehicle hit a roadside bomb in August 2004. He suffered shrapnel wounds to the left side of his body and broke his knee in three places. Surgeons were unable to repair the damage to his leg, and it was amputated almost two months after he was wounded.
Jenny RodriguezKatie Audience Coordinator | 1iota Productions, LLC
American Forces Press Service
WASHINGTON, Nov. 20, 2013 - Today, the White House Office of Science and Technology Policy joined with a coalition of private-sector partners from the telecommunications industry to launch "Warriors 4 Wireless," a new nonprofit program aimed at connecting veterans and returning service members to jobs in the rapidly growing wireless telecommunications industry.
A White House release said the program includes stakeholders from Joining Forces -- a national initiative that provides opportunities and support to military members and their families -- as well as from the private sector, the federal government, the U.S. military, and industry trade associations committed to scaling successful training models for veterans with wireless-relevant skills.
Departments of Veterans Affairs/Housing and Urban Development
WASHINGTON, Nov. 21, 2013 - The Departments of Veterans Affairs and Housing and Urban Development today announced that a new national report shows a 24-percent drop in homelessness among veterans since 2010.
The report also showed an 8 percent reduction between January 2012 and January 2013. The decline keeps U.S. government plans on track to meet the goal of ending veterans' homelessness in 2015.
By Terri Moon CronkAmerican Forces Press Service
WASHINGTON, Nov. 21, 2013 - Reading, writing and arithmetic might be easier for some people than others, but for service members and veterans with traumatic brain injuries, returning to school can be challenging.
Whether it's attending college, technical school or honing skills to re-enter the workplace, service members and veterans now have access to a comprehensive guide that covers topics from A to Z to help them go back to school, said Navy Lt. Cdr. Cathleen Shields, acting director of education at the Veterans Brain Injury Center.
WASHINGTON, Nov. 21, 2013 - While programs are in place to combat predatory lending practices that target service members and their families, better rules and enforcement are needed, witnesses told a Senate Commerce, Science and Transportation Committee yesterday.
Predatory lending practices impact not only a service member's financial readiness, but also mission readiness, witnesses told lawmakers in a hearing about the lending practices targeted towards the military.
They have a mobile Christmas app which they believe would benefit spouses of military personal either deployed or away from their family during the Christmas holiday. The app will create a Christmas video of Santa and his reindeer coming to the family's home.
The video will begin with a jolly Santa Claus flying across the sky with his reindeer, then landing on the roof of the user's home. Once inside, Santa will be shown placing gifts under the tree and writing the letter to the children before walking over to the plate of cookies and taking a bite. After a final farewell, Santa disappears back into his sleigh and heads into the night.
WASHINGTON, Nov. 14, 2013 - Service members' families also serve the nation and are the force behind the total force, a senior Defense Department official said yesterday.
"Our military members are as effective as they can be because of the support their families provide them," Barbara Thompson, director of DOD's office of family policy and children and youth told American Forces Press Service and the Pentagon Channel. "[DOD] wants to make sure the people who are important in the lives of our service members -- spouses, children, parents, partners, aunts, uncles, siblings and cousins -- are part of the military family."
WASHINGTON, Nov. 13, 2013 - Defense Department and Transportation Security Administration officials today announced a partnership to expand "TSA Precheck" expedited screening benefits to all U.S. armed forces service members, including those serving in the Coast Guard, Reserves and National Guard, during their official or leisure travel.
As a result of the agreement, these individuals will be able to enjoy the benefits of the program at the 100 participating airports across the country beginning Dec. 20, officials said.
From a Defense Commissary Agency News Release
FORT LEE, Va., Nov. 12, 2013 - Cashiers at military commissaries soon will begin scanning customers' Defense Department ID cards as part of the checkout process, Defense Commissary Agency officials said.
The commissary here, where DeCA has its headquarters, became the first store to scan ID cards Oct. 22 as the first part of a rollout throughout the agency that began Nov. 10 and will be completed by mid-January, officials said.
Departments of Defense, Veterans Affairs
WASHINGTON, Nov. 8, 2013 - The departments of Defense and Veterans Affairs reaffirmed their commitment to serve and care for the nation's military veterans in a joint message issued by Acting Undersecretary of Defense Jessica L. Wright and Undersecretary of Veterans Affairs for Benefits Allison A. Hickey.
The message reads as follows:
Defense Intelligence Agency
WASHINGTON, Nov. 7, 2013 - Two extraordinary groups of people will be honored today during a ceremony at the Defense Intelligence Agency's headquarters at Joint Base Anacostia-Bolling here.
Four heroes will be inducted into the DIA Patriots Memorial and three former employees will receive the agency's Torch Bearers Award. DIA will add four names to its Patriots Memorial, which commemorates DIA employees and others who have died in service to the United States and commemorates their exceptional sacrifice in support of DIA's mission.
WASHINGTON, Nov. 7, 2013 - Every day is Veterans Day in the federal sector's quest to help former servicemen and women find employment, Labor Secretary Thomas E. Perez said yesterday during an event to honor to the nation's military veterans.
At the department's annual veterans' recognition, Perez said federal agencies working together have made significant strides in helping veterans find jobs, but work remains to be done.
COLUMBUS, Ga., Nov. 6, 2013 - Healthy military families are essential to guaranteeing the health of the overall force, the country's senior noncommissioned officer said here today.
Marine Corps Sgt. Maj. Bryan B. Battaglia, senior enlisted advisor to the chairman of the Joint Chiefs of Staff, and his wife, Lisa, addressed Military Family Summit attendees at the National Infantry Museum and Soldier Center here.
By Amaani LyleAmerican Forces Press Service
WASHINGTON, Nov. 5, 2013 - In a show of commitment and support to those who serve alongside uniformed service members, 60 new corporations joined the Military Spouse Employment Partnership in an induction ceremony here today.
With a prolific career in both government and the private sector, Frank Vollrath, assistant secretary of defense for readiness and force management, praised MSEP's global success rate.
By Nick SimeoneAmerican Forces Press Service
WASHINGTON, Nov. 28, 2012 - The Defense Department and South Carolina officials are notifying military members and families who paid state income taxes there that they may have been victims of information/identity theft as a result of several recent cyber intrusions.
South Carolina's Department of Revenue reported nearly four million Social Security numbers and several hundred thousand credit and debit card numbers belonging to current and former taxpayers may have been stolen during cyber intrusions in August and September.
U.S. Army Public Health Command Public Affairs Office
ABERDEEN PROVING GROUND, Md., Nov. 28, 2012 - U.S. Army Public Health Command headquartered here played a significant public health role in the aftermath of the March 11, 2011, Japanese earthquake and tsunami.
The command's responders monitored radiation levels from the damaged Fukushima Daiichi nuclear power plant, checked the safety of water and food and assessed search-and-rescue dogs coming into the country to assist in finding the missing.
By Marine Corps Lance Cpl. Scott WhitingMarine Corps Base Camp Lejeune
CAMP LEJEUNE, N.C., Nov. 28, 2012 - Christmas is right around the corner, and with the holidays comes an influx of mail sent to service members stationed overseas.
The United States Postal Service recently released their deadlines for ensuring mail sent overseas arrives in time for the busy holiday season.
WASHINGTON (Army News Service, Nov. 16, 2012) --- Special agents from the Army Criminal Investigation Command are once again warning Internet users worldwide to be extra vigilant and not to fall prey to Internet scams or impersonation fraud -- especially scams promising true love, but only end up breaking hearts and bank accounts.
Criminal Investigation Command, known as CID, continues to receive hundreds of reports from people worldwide of various scams involving persons pretending to be U.S. Soldiers serving in Afghanistan or elsewhere, according to CID special agents.
Military wives needed for tv show for a chance to reunite with your military spouse.
A National TV talk show wants you - and we are casting now!!
The show will tape Decemeber 6th in NYC - and all of your expenses are paid
By Army Sgt. 1st Class Tyrone C. Marshall Jr.American Forces Press Service
WASHINGTON, Nov. 19, 2012 - Defense Department officials are sending a new spouse survey to select active-duty families to assist in determining programs that best suit their needs.
During an interview with the Pentagon Channel, Cathy Flynn, a program analyst with the Pentagon's military community and family policy office, discussed how these surveys affect future programs serving military families.
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Revision as of 16:16, 14 March 2011
Karate schools are not regulated or licensed by any agency, nor do they fall under the Bureau for Private Postsecondary Education because they are purely recreational. If they advertise that a person who completes their training can be placed in a job, they must be regulated by the Bureau.
Complaints concerning a contractual agreement may be considered a civil matter to be resolved in Small Claims Court or by retaining a private attorney.
See Also: Athletic Commission for regulations regarding children's headgear, etc.
Consumer Resource & Referral Guide
Directory of State Agencies
Directory of Federal Agencies
Return to DCA Home Page

subset: commoncrawl


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Dear Dr Bob,
I was recently diagnosed with HIV on 22nd Feb 08.
After a few blood tests, my HIV specialist informed me that I have also contracted syphilis.
I was told that I need to redo a CD4 count again to confirm further treatment for syphilis.
If my CD4 count is normal, I will have to undergo a lumbar puncture procedure to confirm if the syphilis virus has spread to my brain. If the virus has spread to my brain, then I will need to be admitted to hospital for 2 weeks to be put on the drip to administer proper medicine to kill the virus. If the virus has not spread to the brain, then basically I just need to be given 3 jabs; 1 jab per week which is sufficient to kill the virus.
If my CD4 count is below normal, then I will have to go for a brain scan and my HIV specialist will only be able to determine the next course of action to treat my syphilis infection on the outcome of the scan report.
I am really lost at this point of time as I am not sure if this is the right course of action to be administered to patients suffering from syphilis coupled with HIV infection. Is there a simpler way to treat syphilis without going for lumbar puncture procedure? I am also worried if I am to be admitted to hospital for 2 weeks; my company will come to know of my HIV infection and I may very well lose my job. Also I am extremely worried about all the costs involved as medical treatment in Singapore is expensive.
I hope you can help me out and give me proper guidance what other alternatives do I have?
Thanks a lot.
Hello JC,
The interaction of HIV disease and syphilis is complex, to say the least. Without a much more detailed history, review of your laboratory studies and the benefit of a physical examination, it will be difficult for me to provide very specific recommendations regarding additional evaluation and optimal treatment for your coinfection. I will make some general comments and also provide a detailed reference below.
Regarding the need for a lumbar puncture, evaluation of cerebral spinal fluid for evidence of neurosyphilis is recommended for anyone with neurologic, ophthalmic or otologic signs or symptoms; all patients with late latent syphilis lasting more than one year or syphilis of unknown duration. If you fall into any one of those categories, a lumbar puncture is warranted no matter what your CD4 count is. Brain scans are not routinely recommended for evaluation of syphilis. Late latent syphilis is diagnosed by a positive blood test without physical signs or symptoms of either the primary or secondary stages of syphilis. (As I mentioned this can be quite a confusing and complex topic!)
Regarding treatment, intravenous penicillin G for 10-14 days is recommended for neurosyphilis. Primary, secondary, early latent and late latent syphilis in HIV-infected patients is treated with intramuscular injections of benzathine penicillin G.
A more detailed discussion of syphilis/HIV coinfection is reprinted below. This may be more information than you wanted. If you are uncertain of your current physician's recommendations, I would suggest you get a second opinion. You should stress the need for confidentiality with your physicians in Singapore to protect your privacy and employment. That an illness would be cause for job termination is reprehensible.
Good luck.
Dr. Bob
Syphilis and HIV
HIV InSite Knowledge Base Chapter June 2006
Introduction and Overview
This chapter discusses the epidemiology, clinical manifestations, and treatment of syphilis in individuals with HIV. The interaction of syphilis and HIV infection is complex and remains the subject of ongoing research.(1-6) Epidemiologic studies demonstrate that sexually transmitted diseases (STDs) including syphilis, and particularly genital ulcers associated with primary syphilis, are associated with an increased risk of HIV acquisition.(7-12) Although case reports have suggested that coexisting HIV infection may alter the natural history of syphilis, only a few such effects have been demonstrated in large observational studies,(13-19) notably presentation with multiple or deeper chancres and overlap of primary- and secondary-stage features of syphilis in coinfected patients.(20,21) Initial serologic responses to early syphilis were shown to be generally equivalent in HIV-negative and -positive individuals.(20) Like many acute infections in the HIV-infected patient, early syphilis may decrease CD4+ T-cell counts (CD4 cell counts) and increase HIV RNA in plasma and semen, although evidence for these effects has been mixed.(22-24) Reports of false-positive and false-negative results on serologic tests for syphilis in HIV-infected persons raise questions regarding the specificity and sensitivity of serologic diagnoses in such patients.(25-32) Obtaining biopsy specimens from suspicious lesions and using special stains for spirochetes should be considered in patients who are seronegative for syphilis. Cerebrospinal fluid (CSF) abnormalities in early syphilis and persistence of nontreponemal antibodies after treatment have both been observed in HIV infection, raising concerns about a possible increased risk of clinically important neurologic disease.(25-27,29-31,33-44)
Routine, periodic screening for STDs in HIV-infected patients is strongly recommended, including serologic testing for syphilis.(45,46) Although data from prospective, controlled treatment studies are limited, this chapter presents recommendations for managing HIV-infected patients with syphilis based on the best available data.(47) Data suggest that current recommendations for treating early syphilis of less than 1 year in duration are adequate for most patients, whether or not they have HIV infection. Long-acting penicillin G is the antibiotic of choice. The only oral alternatives recommended by the U.S. Centers for Disease Control and Prevention (CDC)--doxycycline and tetracycline--should be reserved for those few who are truly allergic to penicillin, and such agents are never indicated for the treatment of neurosyphilis. One agent, azithromycin, has shown promise for incubating and early syphilis;(48,49) however, given the recent identification of resistance, it cannot be recommended for general use in the United States.(50,51) Follow-up serologic testing at recommended intervals is essential for assessing treatment adequacy;(52) these assessments are often complicated by the potential for reexposure in sexually active persons. Evaluation of the CSF for evidence of neurosyphilis is recommended for any patient with neurologic, ophthalmic, or otologic signs or symptoms; all patients with treatment failure; and HIV-infected patients with late latent syphilis lasting more than 1 year or with syphilis of unknown duration. Options to consider in some HIV-infected patients, although of unproven benefit, include increasing the duration of penicillin treatment in patients with early syphilis, evaluating the CSF for evidence of neurosyphilis earlier in the course of syphilis infection or after treatment, and evaluating the CSF in patients with lower CD4 cell counts or a nontreponemal serologic test titer greater than 1:32.
Epidemiologic studies demonstrate that history of an STD, including syphilis, is associated with an increased risk of HIV disease among both gay men (7,9) and heterosexuals (8) because sexual behaviors that increase the risk of acquiring STDs also increase the risk of acquiring HIV. Furthermore, genital ulcerations and inflammation caused by STDs are implicated as cofactors for acquiring or transmitting HIV infection.(9-11) Recent data suggest that when they already have other STDs, individuals are 3 to 5 times more likely to acquire HIV if exposed to the virus through sexual contact.(10)
In U.S. areas reporting high rates of syphilis infection in the early 1980s, the percentage of early syphilis cases occurring among gay and bisexual men decreased from 50% to 70% in the late 1970s to 5% to 15% in 1990.(53) These data were thought to reflect changes in sexual practices that reduced the risk of HIV infection among gay and other men who have sex with men (MSM) and suggested that education efforts encouraging safer-sex practices were effective. During the 1990s, the geographic distribution of heterosexual HIV transmission closely paralleled that of syphilis. Most of the health districts with the highest rates of syphilis in 1995 were concentrated in the southern United States, where the HIV prevalence among childbearing women also was highest. Therefore, increases in the incidence of STDs in any population may presage future increases in HIV, illustrating the importance of STD diagnosis and treatment as an HIV preventive strategy.
Despite significant decreases in cases of syphilis in the United States in the 1990s, as well as the CDC's initiative to eliminate the disease domestically by 2005, syphilis incidence has risen dramatically since 2000, particularly among MSM.(3,54-60) (See the CDC's Syphilis Surveillance Project Annual Report for a detailed epidemiologic update.) In 2004, 7,980 cases of primary and secondary syphilis were reported nationally, representing an 11.2% increase over 2003 and a 33% increase over the previous decade's nadir of 5,979 cases, reported in 2000.(61) A number of states have experienced particularly large recent increases in syphilis, concentrated among MSM. In 2005 in California, for instance, 1,489 cases of primary and secondary syphilis were reported, representing an increase of more than 700% from 1999. Of the 2005 cases, 79% were MSM and of those, 61% were HIV positive by self-report, and a majority (60%) reported multiple anonymous sex partners.(62) Recently, the Syphilis Elimination Effort has been launched as a national initiative to bring together health care providers, policy makers, community leaders, and state and local public health agencies to reduce syphilis rates in the United States.
Suggested causes of this resurgence in syphilis among MSM include increases in the number of anonymous sex partners, decreases in condom use, use of the Internet for meeting sex partners, and more widespread use of methamphetamine and proerectile agents, among other drugs.(4,63-67) Oral sex has been implicated in 14% of syphilis infections in a large U.S. city.(68) Moreover, the indirect contribution of antiretroviral treatment (ART) to higher syphilis transmission rates among those infected with HIV has been well described.(69) These epidemiologic trends underscore the importance of clinicians' awareness of key behavioral risk factors, their consideration of syphilis in the differential diagnosis of similarly presenting disorders, and their familiarity with current recommendations regarding risk assessment, screening, and clinical management of syphilis.
Limited epidemiologic data suggest that neurosyphilis remains an uncommon infection in HIV-infected patients. A retrospective surveillance investigation of neurosyphilis trends in San Francisco from 1985 through 1992 found no evidence of increasing rates of neurosyphilis during the study interval.(70) Reports of symptomatic neurologic involvement totaled 2 to 5 cases per year. No cases of early neurosyphilis were identified in HIV-uninfected patients. More recent surveillance has confirmed a consistently low incidence of neurosyphilis in San Francisco, found in 2.7% (33/1,232) of all syphilis cases (all stages) in 2002 to 2003.(71)
The immune system plays an important role in protecting against syphilis.(72,73) Impairment of both cell-mediated and humoral immunity by HIV (74) may limit the host's defenses against Treponema pallidum, thereby altering the clinical manifestations or natural course of syphilis infection. In animal models, selective impairment of cell-mediated immunity shortens the incubation time of syphilis, increases the number and spreading of lesions, and slows healing time.(75) Molecular pathogenetic mechanisms to explain the role of the spirochete in facilitating HIV transmission may include up-regulation of gene expression, such as that of the CCR5 co-receptor used in HIV entry.(76,77) HIV-induced meningeal inflammation may facilitate penetration of spirochetes into the central nervous system (CNS) and thus contribute to the development of symptomatic neurosyphilis.
Clinical Manifestations and Course
Case reports suggest that the unusual clinical manifestations of syphilis may be more common and the course more rapid in patients with HIV infection. Although prospective studies largely have not corroborated these observations, such anecdotal reports have driven the hypotheses that among patients coinfected with HIV and T pallidum, cutaneous lesions may be more severe, symptomatic neurosyphilis may be more likely to develop, the latency period before the development of meningovascular syphilis may be shorter, and the efficacy of standard therapy for early syphilis may be reduced.
Primary and Secondary Syphilis
The conventional staging of syphilis is unaltered by HIV coinfection. Symptoms may appear within several days of exposure (mean, 21 days; range, 14-90 days).(4,78) In primary syphilis, 1 or more ulcers (chancres) develop, presumably at the site of exposure, usually on the genitals or anus. Patients may be unaware of these typically painless lesions, especially if located inside the vagina or anus. Regional, shotty, nontender lymphadenopathy may develop. If the ulcer or ulcers become infected secondarily, then painful lesions, adenopathy, or both may be observed. The chancre(s) then resolves, with or without treatment. Most primary lesions resolve by the time secondary syphilis presents; however, the primary and secondary stages may overlap.
In the secondary stage, symptoms typically include generalized or localized skin eruptions and mucosal lesions. Lesions may be mild or florid and usually include a wide morphologic variety of rashes--ranging from macular, papular, pustular, papulosquamous, to annular--that may cover the palms and soles. Constitutional symptoms (eg, sore throat, low-grade fever, malaise, myalgias, arthralgias, generalized lymphadenopathy) also may be present. Less common symptoms and signs include mucous patches in the oropharynx, condylomata lata (moist, wartlike papules occurring mostly in genital or perianal areas), and patchy alopecia. The rash of secondary syphilis can mimic many dermatologic conditions, such as tinea versicolor, pityriasis rosea, scabies, fixed drug eruptions, and erythema multiforme; in HIV-infected individuals taking ART, it has been misdiagnosed as an antiretroviral drug reaction.
In general, "infectious syphilis" refers to the primary and secondary stages because syphilitic chancres, mucous patches, and condylomata lata are highly infectious lesions. Dry rashes, by exception, are typically noninfectious. Like primary lesions, secondary symptoms and signs will resolve without therapy; such resolution marks the beginning of the latent period of disease.
Most HIV-infected patients with T pallidum infection present with typical dermatologic clinical features of primary and secondary disease, such as chancres and diffuse maculopapular rashes.(20,34,40,79,80) In a study among patients seen in an STD clinic, however, patients with HIV infection were more likely than HIV-negative individuals to present with signs and symptoms of secondary syphilis and were more likely to have chancres still present at the time of secondary syphilis diagnosis.(80) In a multicenter study of STD clinic patients with early syphilis, HIV-infected patients were more likely to present with multiple chancres, but the size of the chancres, characteristics of the skin rash, and duration of the chancres or rash before presentation did not differ according to HIV status.(20) Atypical chancres have been reported,(81) including lesions appearing as fissures or abrasions. Two reports also described gummatous penile ulceration.(82,83) Unusual rashes include papular or nodular eruptions,(27,84) nodular or ulcerative lesions with necrotic centers (ie, lues maligna),(18,19,27,28,85-90) and keratoderma.(91) These skin lesions have been characterized as more aggressive forms of secondary syphilis in HIV-infected persons, yet the same dermatologic presentations are found in HIV-uninfected persons.(92) These isolated findings do not reveal the frequencies of these uncommon cutaneous manifestations, and therefore, whether the clinical course and clinical spectrum of syphilis differ in HIV-infected and HIV-uninfected populations remains unclear. In general, syphilis should be included in the differential diagnosis of mucocutaneous abnormalities in the HIV-infected patient, and diagnostic evaluation and empiric treatment should be applied as discussed below.
Latent and Tertiary Syphilis
In latent syphilis, serologic evidence of infection is found despite absence of symptoms and signs of the primary and secondary stages. Relapses of secondary syphilis symptoms and signs may occur early in the latent stage. Early latent syphilis is defined by CDC as infection less than 12 months in duration, evidenced in the previous year by a negative serologic test, symptoms or signs of primary or secondary syphilis, or contact with a sex partner with early-stage syphilis.(47) If none of these criteria suggest that infection was acquired in the preceding 12 months, then the duration of infection is unclear and the case is referred to as syphilis of unknown duration. In this case, even if the patient had a negative or 4-fold lower nontreponemal serologic test result more than 12 months ago, it is usually impossible to determine the time of acquisition since the previous test, assuming that risk behaviors occurred throughout this time period. When the precise time of acquisition is in doubt because the CDC's early latent criteria are not met, these patients should be treated conservatively as if the infection were present for more than 1 year. These cases require CSF evaluation and treatment with benzathine penicillin G, 7.2 million units divided in 3 weekly doses (ie, 2.4 million units per dose), assuming no evidence of neurosyphilis was found.
Tertiary syphilis refers to disease presenting with late manifestations, encompassing c ardiovascular features such as aortitis with aneurysm formation, late neurologic sequelae (general paresis, tabes dorsalis), and formation of gummas (indolent but potentially destructive granulomatous lesions that may occur in any organ but chiefly involve skin, bone, and liver). Of note, neurosyphilis is not a stage, but rather a site of infection, where symptoms may manifest either earlier or later in the course of infection.
Neurosyphilis refers to a site of infection involving the neurologic system. As such, neurosyphilis may occur at any stage of syphilis. Neurosyphilis in patients with HIV infection is well described.(15,70,93-97) Reports of neurosyphilis in HIV-infected persons are similar to cases reported before the HIV epidemic.(98-100) The precise extent and significance of neurologic involvement in HIV-infected patients with syphilis, reflected by either laboratory or clinical criteria, remain incompletely characterized. Furthermore, the alteration of host immunosuppression by ART in recent years has further complicated such characterization.
The clinical spectrum of neurosyphilis and the typical interval between primary infection and neurologic symptoms were described early in the HIV epidemic.(100) Approximately 35% to 40% of persons with secondary syphilis have asymptomatic CNS involvement, as demonstrated by any of the following on CSF examination: an abnormal cell count, protein level, or glucose level; or demonstrated reactivity to Venereal Disease Research Laboratory (VDRL) antibody test. Acute syphilitic meningitis usually occurs within the first 2 years of infection; 10% of cases are diagnosed at the time of the secondary rash. Patients present with headache, meningeal irritation, and cranial nerve abnormalities, typically involving cranial nerves at the base of the brain (especially II, VI, VII, and VIII).
Meningovascular syphilis occurs a few months to 10 years (average, 7 years) after the primary infection. Unlike the sudden onset of thrombotic or embolic stroke syndromes, meningovascular syphilis is associated with prodromal symptoms lasting weeks to months before focal deficits of a vascular syndrome are identifiable. Prodromal symptoms include unilateral numbness, paresthesias, extremity weakness, headache, vertigo, insomnia, and psychiatric abnormalities such as personality changes. The focal deficits initially are intermittent or progress slowly over a few days. By contrast, general paresis and tabes dorsalis are parenchymatous forms of neurosyphilis that occur, in general, 10 to 30 years after primary infection. General paresis causes symptoms similar to those of any dementia and of many psychiatric illnesses such as depression and paranoia. Tabes dorsalis is associated with a triad of symptoms (lightning pains, dysuria, and ataxia) and a triad of signs (the Argyll Robertson pupil [accommodation in the absence of light reaction], areflexia, and loss of proprioceptive sense).
Most cases of symptomatic neurosyphilis reported among HIV-infected persons are early forms of neurosyphilis; namely, acute syphilitic meningitis and meningovascular neurosyphilis.(70) A case report of medical medullary syndrome with meningovascular syphilis has been described in an HIV-infected man.(96) Tabes dorsalis has been reported in 1 HIV-infected man who had been exposed 7 years earlier (94) and in another man treated for primary syphilis 7 years earlier.(101) Other reports have described cases of syphilitic meningomyelitis with spastic paraparesis (102,103) and syphilitic polyradiculopathy with progressive leg pain and weakness.(104) Status epilepticus,(105) presenting with or without cerebral parenchymal lesions attributed to syphilis,(106-108) has been described.
Data suggest that asymptomatic CNS involvement at the time of early syphilis infection is common, but not more common in HIV-infected persons than in uninfected persons.(18,20,33,35) One study (35) found viable T pallidum in the CSF of 12 of 40 (30%) patients with primary or secondary syphilis and no neurologic symptoms, including 3 of 10 (30%) HIV-infected patients, and another report (20) identified T pallidum in the CSF in 32 of 131 (24%) patients with early syphilis, including 11 of 43 (26%) HIV-infected patients. Whether neurologic complications of syphilis occur more frequently and earlier in HIV-infected patients has not been evaluated definitively. Most cases of early neurosyphilis in HIV-infected individuals, however, are currently identified at the initial syphilis diagnosis,(70) and, in at least 1 series, among those with CD4 counts less than 200 cells/L.(109) Therefore, most experts believe that HIV-infected patients with early syphilis have an increased risk of neurologic complications, but the magnitude of any such risk is uncertain. Careful neurologic evaluation in any patient with syphilis or HIV is of paramount importance. If such evaluation reveals abnormalities, neurosyphilis should be included in the differential diagnosis.
Ocular and Otologic Neurosyphilis
Ocular and otologic manifestations of neurosyphilis in HIV-infected persons have been reported widely.(110-112) The most common ocular findings in patients with concurrent HIV infection are uveitis,(113-116) chorioretinitis,(117) and retrobulbar neuritis.(118) Reports have also described retinitis or neuroretinitis,(119,120) scleritis,(121,122) and papillitis, vitreitis, and optic perineuritis.(110,112) The most common presenting symptoms are decreased vision and eye pain. In addition to the abnormalities of the optic cranial nerve II and the ocular motor nerves III and VI that can occur with acute syphilitic meningitis, these other ocular manifestations of syphilis have commonly been associated with the secondary stage of syphilis infection and CNS involvement. One case report described a gumma involving the optic nerve.(123)
Otologic syphilis is one of the few forms of sensorineural hearing loss that can be treated effectively if detected early in the course, based on clinical suspicion followed by CSF evaluation and treatment for neurosyphilis. Although the incidence of otologic symptoms in patients with HIV infection is apparently low, 1 report described 5 cases of otosyphilis in persons with coexisting HIV infection.(111) Otologic findings in these patients included progressive hearing loss, tinnitus, imbalance, and a sensation of ear fullness. Three patients had been treated for primary syphilis 2 to 5 years before the onset of symptoms. Only 1 of these 5 patients had acute syphilitic meningitis and an abnormal CSF profile coincident with the diagnosis of otosyphilis. One case report described otosyphilis involving an internal auditory-canal gumma.(124)
These clinical manifestations of ocular and otologic syphilis have also been observed among persons without HIV infection. It is unknown whether ocular and otologic findings occur more frequently in HIV-infected persons. Careful ophthalmologic and otologic examinations of symptomatic HIV-infected persons and inclusion of syphilis in the differential diagnosis remain essential.
Other Clinical Manifestations of Syphilis
Syphilis is a systemic infection. Hematogenous dissemination of the organism occurs early in the course of infection, and disease ultimately may involve any organ system. Symptomatic involvement of organs other than the skin, mucous membranes, and CNS is rare, presumably because the treponeme replicates at relatively low temperatures. Nonetheless, case reports of HIV-infected patients with pneumonitis,(125) hepatitis,(126-128) osteitis,(129,130) and gastritis (131,132) due to syphilis have been published. Gummatous syphilis, a tertiary form of syphilis, also has been described in HIV-infected persons.(133-135)
Diagnosis of Syphilis in HIV-Infected Patients
General Considerations
The diagnosis of syphilis may be more complicated in HIV-infected patients because of false-negative and false-positive serologic results for T pallidum and atypical clinical presentations in the presence of HIV infection. However, serologic tests appear to be accurate and reliable for the diagnosis of syphilis and the evaluation of treatment response in most HIV-infected patients. The clinician should seek confirmatory evidence for the diagnosis from any available source, including the patient's history, clinical findings, direct examination of lesion material for spirochetes, and serologic tests for syphilis. The importance of a careful clinical examination of HIV-infected patients at risk for syphilis cannot be overstated. Painless primary syphilis lesions, especially involving the rectum and vagina, often go unnoticed, and secondary syphilis rashes, other mucocutaneous lesions, and constitutional symptoms may be subtle or misleading and resolve without treatment. CNS disease can occur during any stage of syphilis. Clinical evidence of neurologic involvement warrants CSF examination.
If at all feasible, the clinician should perform dark-field examination or direct fluorescent antibody (DFA) staining of exudate from suspicious lesions of primary syphilis. For patients with suspicious lesions but negative serologic results, positive findings on dark-field examination or DFA stain can be diagnostic. Clinicians should also use dark-field examination or DFA staining of selected secondary lesions, such as condylomata, to establish the diagnosis of secondary syphilis. However, it is important to confirm by DFA that the treponema seen in dark-field-positive oral lesions are T pallidum, because nontreponemal spirochetes occur in the upper gastrointestinal tract, especially the mouth. Although a multiplex polymerase chain reaction (PCR) test for genital ulcerative lesions has been developed, with excellent sensitivity (approximately 95%) for syphilis as well as herpes simplex virus and chancroid, there are no current plans to market this test in the United States.(136)
Serologic tests for syphilis are the cornerstone of diagnosing untreated syphilis infection, independent of HIV status. Nontreponemal assays, such as the rapid plasma reagin (RPR) card or VDRL test, use cardiolipin-, lecithin-, and cholesterol-containing antigen to measure antilipoidal antibodies and are often used initially to diagnose syphilis. Treponemal assays (Treponema pallidum particle agglutination [TP-PA] and fluorescent treponemal antibody absorbent [FTA-Abs]) are used to confirm the results of positive nontreponemal tests in a 2-step, reflex process. The sensitivity of nontreponemal and treponemal tests for syphilis increases with duration of infection, and ranges from approximately 75% in the primary stage to virtually 100% in the secondary stage.(137) In general, the sensitivity of treponemal tests continues to approximate 100% in late syphilis, in contrast to nontreponemal tests, which are more practical and cost-effective for initial screening but have diminished sensitivity in late syphilis. Despite the higher sensitivity of treponemal tests, they have not been recommended for initial screening in the United States, primarily because of cost.
Because the sensitivity of nontreponemal tests is lower that that of treponemal tests in the primary stage, a negative nontreponemal test in an HIV-infected individual with a genital lesion cannot exclude primary syphilis. It may be useful to consider both a nontreponemal and a (nonreflexed) treponemal test as a diagnostic strategy in newly infected persons with suspicious lesions. For instance, in a recent evaluation of 39 dark-field-confirmed syphilis cases, VDRL was reactive in 30 (77%), whereas TP-PA was positive in 37 (95%). Using a strategy of initially obtaining both VDRL and TP-PA would have identified 100% of primary syphilis cases, compared with only 72% of cases using a conventional reflex strategy.(138)
Unusual serologic responses have been reported in HIV-infected persons with syphilis. Most reports involved higher than expected serologic titers, but false-negative serologic results and delayed appearance of seroreactivity have also been reported, albeit rarely. Nevertheless, both treponemal and nontreponemal serologic tests for syphilis are accurate in most patients with syphilis and HIV coinfection.(47) Clinicians should obtain serum samples from any patient in whom the diagnosis of syphilis is suspected. Clinicians should also screen all sexually active patients with HIV infection for asymptomatic syphilis infection on a routine, periodic basis, generally every 6 months, if risk warrants.(45) Reports of nontreponemal antibody test results should be quantitative and describe the lowest dilution (ie, the titer) at which the test result is reactive. In general, nontreponemal test titers may be higher among HIV-positive patients than among HIV-negative persons.(29) In 1 study, the median RPR titer among HIV-infected patients with early syphilis was 1:128, in comparison with a median titer of 1:64 among HIV-negative patients.(20)
The specificity of the nontreponemal serologic tests for syphilis may be compromised in HIV-infected persons.(25,29,30,139) Very high VDRL or RPR titers of greater than 1:64 have been reported in HIV-infected patients without syphilis.(140) These nontreponemal tests detect antibodies directed against a cardiolipin-lecithin antigen. In patients with immunoglobulin abnormalities, the RPR or VDRL test result may be falsely positive. Many persons with HIV infection have both anticardiolipin-lecithin antibodies and polyclonal gammopathy. A positive RPR or VDRL test result may be biologically false positive if the confirmatory test is negative, and thus may not represent active syphilis infection. However, in patients epidemiologically at risk for syphilis infection, newly reactive nontreponemal and treponemal serologic syphilis test results usually indicate active disease. The serofast state is not uncommon among HIV-infected persons and refers to the persistence of a reactive nontreponemal syphilis test, usually 1:16 or less, with variation no greater than 1 to 2 dilutions over time, despite adequate therapy and no evidence of reexposure. However, reinfection may be difficult to rule out in some patients, and reactivation or relapse of a previously treated infection is also possible in a person with HIV infection.
A negative RPR or VDRL test result may not rule out syphilis in patients with HIV infection. Although the sensitivity of these serologic tests in diagnosing secondary syphilis is generally very high, rare case reports have described seronegative secondary syphilis in patients with HIV infection,(27,28,31,139,141) suggesting that some patients may fail to develop normal antibody responses to T pallidum. In addition, a negative treponemal test may not rule out syphilis. In a study of patients with RPR tests reactive at a dilution of greater than 1:8, antibodies to T pallidum membrane antigens were detected in a few patients with persistently negative FTA-Abs test results.(26) This finding raises the possibility that some reactions that appear to be biologically false positive may in fact represent syphilis with negative treponemal serologic tests. This study raises questions about the sensitivity of the treponemal test in diagnosing syphilis in HIV-infected patients. However, until further data are available, clinicians should consider the sensitivity of treponemal tests to be high in HIV-infected persons with untreated syphilis beyond the primary stage of infection. If asymptomatic patients have a positive nontreponemal test and negative confirmatory treponemal test results, it is very unlikely that they have active syphilis.
An increasing number of commercial and public laboratories have begun to use an enzyme immunoassay (EIA) that is specific for T pallidum, previously widely used by blood banks, as an initial serologic screening and diagnostic test for syphilis.(142-144) Initial positive tests must be reflexed to nontreponemal testing to obtain titers for the purpose of following treatment outcome. If the EIA is positive and the reflexed nontreponemal test is negative, further testing should be done using a different treponemal serologic test, given specificity concerns with the EIA test. Laboratories and localities performing these tests should also offer technical assistance and training for interpretation of results because most providers are unaccustomed to initial testing with treponemal tests. EIA-positive/nontreponemal test-negative results can occur in a number of clinical scenarios, including very early syphilis, remote syphilis that is untreated or partially treated, and with a false-positive treponemal test. To avoid missing an incipient case of syphilis when risk is present, repeating the nontreponemal test in approximately 2 to 4 weeks is recommended.
When clinical syndromes compatible with primary or secondary syphilis occur and when the findings on dark-field examinations and serologic tests are negative, clinicians should rule out the "prozone" phenomenon. This phenomenon refers to cases in which a nontreponemal serologic test is read as falsely negative because the specimen was not tested after sufficient dilution, so that the high antigen concentration did not allow detectable formation of antigen-antibody complexes.(145) When the diagnosis is in doubt, clinicians should biopsy suspicious lesions and evaluate the specimens for spirochetes using stains such as the Steiner silver stain (146) or specific DFA stains for T pallidum. Because T pallidum does not grow on artificial media, inoculation of laboratory animals (usually rabbit testicles) is the only method currently available to isolate the organism from fluids or tissues of an infected patient. This method is available only in a few research laboratories.
Clinicians should consult with an infectious diseases or laboratory medicine specialist about tests available in their areas. If biopsy specimens do not reveal spirochetes, or if techniques are not available to identify spirochetes, but clinical suspicion of syphilis remains high, clinicians may wish to presumptively treat HIV-infected patients for early syphilis and follow them closely with serial serologic testing at 1 or 2 weeks after treatment to detect any delayed antibody response.
Indications for Cerebrospinal Fluid Examination
Based on the first prospective study since the beginning of the antibiotic era (20) of patients with syphilis of less than 1 year in duration, which included follow-up for 12 months after treatment, the CDC's current STD treatment guidelines recommend CSF examination in individuals diagnosed with late latent syphilis, syphilis of unknown duration, neurologic signs or symptoms, or suspected treatment failure (Figure 1).(47) Nonetheless, this area of syphilis management remains controversial. CSF abnormalities often occur among both HIV-negative and HIV-positive patients who have primary or secondary syphilis.(20,35) Such abnormalities in HIV-infected patients are of unknown prognostic significance, and the majority respond appropriately to the currently recommended penicillin therapy.(20) Therefore, in the absence of neurologic signs or symptoms, CSF examination is currently not generally recommended before treatment in HIV-infected patients with primary, secondary, or early latent syphilis.
Based on case reports of neurosyphilis and isolation of T pallidum from the CSF of HIV-infected patients who had completed standard therapy for early syphilis, some clinicians believe that routine CSF examination should occur earlier in the course of syphilis in HIV coinfected patients, such as before treatment in all such patients (37) or 6 months after single-dose penicillin therapy for syphilis of less than 1 year in duration.
A recent multicenter study identified an increased risk of laboratory-defined, asymptomatic neurosyphilis in certain HIV-infected patients: a nearly 6-fold increase with primary, secondary, or latent syphilis and a serum titer of 1:32 or higher; and a more than 3-fold increase with syphilis and a CD4 count of 350 cells/L or lower. In patients with both of these findings, laboratory-defined neurosyphilis was more than 18 times more likely.(43) However, this study provided no longitudinal data for comparing the effectiveness of intravenous penicillin with that of intramuscular benzathine penicillin G (which is currently recommended by CDC) in patients with primary, secondary, and early latent syphilis and a titer of 1:32 or greater. A subsequent study similarly demonstrated an increased risk of laboratory-defined asymptomatic neurosyphilis in HIV-infected patients with a serum RPR titer of 1:32 or higher.(147)
Such data have prompted other experts to propose a tiered algorithm that combines CD4 count and nontreponemal test titer to identify settings in which lumbar puncture (LP) should be considered or recommended. Some experts suggest considering LP for HIV-infected patients with a nontreponemal titer greater than 1:32 independent of syphilis stage, and in those with early-stage infection and CD4 count less than 350 cells/L, regardless of titer.(148) Other experts recognize that although asymptomatic neurosyphilis is well known to be common in patients with primary, secondary, and early latent syphilis, for decades such patients--including those with serologic syphilis titers greater than 1:32 and CD4 counts less than 350 cells/L--have been treated with benzathine penicillin G, without neurologic complications in the vast majority. Thus, the benefit of treating a laboratory finding of unknown prognostic significance, at the cost of significant public health resources, is unclear.
Given these complexities, clinical judgment is required in deciding to perform LP and in diagnosing neurosyphilis. Furthermore, the clinical benefit of treating patients with laboratory-defined asymptomatic neurosyphilis has not been fully established, and the prospective study mentioned above found no benefit of such treatment at 1 year of follow-up.(20) However, the demonstration of syphilis titer and CD4 count predictors underscores the need to consider neurosyphilis in patients with high serum syphilis titers and advanced HIV infection, and to document an adequate serologic response through close follow-up of advanced HIV patients with high-titer early syphilis treated with intramuscular benzathine penicillin G in the absence of a CSF examination. Whenever the decision is made to perform an LP in a patient with syphilis, it is critical that this diagnostic procedure not interfere with timely treatment of a potentially infectious case.
Clinicians should examine the CSF for evidence of neurosyphilis in all HIV-infected patients (or patients at risk for HIV infection) who can safely undergo LP and have any unexplained behavioral abnormalities, psychological dysfunction, or ocular, auditory, or other neurologic symptoms or signs, especially those consistent with neurosyphilis. Clinicians should also examine the CSF of patients with primary, secondary, or early latent syphilis if treatment fails (eg, if the serum nontreponemal antibody titer does not decrease by 4-fold [2 dilutions] by 6-12 months for primary or secondary syphilis); if a sustained (greater than 2 weeks) 4-fold (2 dilution) or greater increase occurs; or if signs or symptoms attributable to syphilis persist, recur, or develop in the absence of reinfection.
Diagnosis of Neurosyphilis
Neurosyphilis should be considered in the differential diagnosis of neurologic disease in HIV-infected persons. The diagnosis of neurosyphilis is based on CSF findings of a reactive VDRL, presence of white blood cells, or elevated protein concentration. The VDRL is the only serologic test for syphilis approved for use on CSF specimens. If the CSF VDRL test result is negative, the diagnosis of neurosyphilis is complicated by the lack of another reliable diagnostic test and the difficulty of distinguishing between neurologic disease caused by T pallidum and that caused by HIV itself or by other CNS pathogens occurring in patients with advanced HIV disease.
Most persons with symptomatic neurosyphilis and coexisting HIV infection have a positive CSF VDRL test result and significantly elevated CSF leukocytes.(70,149) Some case reports, however, have described symptomatic neurosyphilis in HIV-infected patients whose initial CSF VDRL test results were negative, suggesting that neurosyphilis may go untreated if clinicians consider only the CSF VDRL test when making therapeutic decisions.(150) In these reported patients, the CSF VDRL test result became positive after penicillin therapy. These reports underscore the need for clinical judgment when diagnosing active neurosyphilis in HIV-infected persons and the need for better diagnostic tests.
Detection of minimally increased CSF leukocytes (5-10 cells/L) is common in HIV-infected patients in the absence of other CNS infections. In the HIV/syphilis coinfected patient, elevated CSF leukocytes of greater than 10 to 20 white blood cells/L should prompt serious consideration of a diagnosis of neurosyphilis if no other etiology is identified. The CSF FTA-Abs test may help rule out neurosyphilis if it is negative, but a positive result is nonspecific.(151)
Until improved diagnostic tests are available, clinicians may wish to initiate treatment for neurosyphilis when serologic tests for syphilis are positive, CSF leukocyte count and protein concentration are elevated but the CSF VDRL test result is negative, and all other possible etiologies have been excluded. Researchers have suggested measurement of other CSF markers, such as immunoglobulins or treponemal antigens and direct detection of treponemes,(152) but these methods have not yet been studied adequately.(153) Although detection of treponemal DNA using PCR testing is under development,(136,154,155) to date PCR has been insufficiently sensitive to aid the diagnosis of neurosyphilis.(20,137) All patients treated for neurosyphilis should be followed closely with serologic titers at 6, 12, 18, and 24 months and with repeat LPs at 6, 12, and 24 months to determine whether initial CSF abnormalities return to normal after therapy. After treatment, pleocytosis should decrease by 6 months and the CSF should be entirely normal by 2 years.
Based on available data and published consensus recommendations,(47) HIV-infected patients with primary, secondary, and early latent syphilis should be treated according to the recommendations for HIV-negative patients with primary, secondary, and early latent syphilis (Table 1). HIV-infected patients with late latent syphilis or syphilis of unknown duration should have a CSF examination before treatment and be managed accordingly.
Penicillin G regimens are recommended, whenever possible, for all stages of syphilis in HIV-infected patients (Table 1). Doxycycline and cephalosporins are not recommended by CDC's STD treatment guidelines because no studies have established an effective dose and duration for HIV-infected patients. Erythromycin and, more recently, azithromycin are not recommended. Although azithromycin once demonstrated promise for the oral treatment of incubating and early syphilis,(48,49) the recent identification of resistance (eg, as high as 56% in San Francisco in 2004) means that this drug cannot be recommended for general use in the United States.(50,51) Although amoxicillin has the theoretical benefit of penetration into the CSF and achievement of treponemicidal levels,(156,157) no difference in outcome was identified in a double-blind, randomized, controlled trial comparing benzathine penicillin G with or without amoxicillin in patients with syphilis of less than 1 year in duration.(20) In addition, no proven alternatives to penicillin are available for treating patients with neurosyphilis, congenital syphilis, or syphilis in pregnancy. Therefore, for patients with confirmed penicillin allergy, skin testing, if available, and desensitization are recommended.
Isolated case reports of treatment failure have raised questions about the efficacy of current treatment recommendations for syphilis in HIV-infected patients. Published case reports and expert opinion suggest that, in comparison with HIV-negative patients, HIV-infected patients with early syphilis may have a higher risk of neurologic complications and a higher rate of treatment failure with currently recommended regimens. The magnitude of these risks, however, although not precisely defined, is probably small. No therapies have proven more effective in preventing neurosyphilis in HIV-infected patients than the therapies recommended for HIV-uninfected patients. Careful follow-up at recommended intervals after therapy is probably the most important part of clinical management and often does not receive the consideration it deserves; greater attention is typically focused on treatment regimens and debates over when to perform LP.
To assess accurately the serologic response to treatment, providers should collect a serologic test titer on the day of treatment, especially in patients with early syphilis. Titers may rise rapidly in early infection, and failure to collect a serologic sample on the day of treatment will complicate measurement of a 4-fold decrease, especially if the previously collected titer was low.
Before administering any treatment, clinicians should warn all patients about the possibility of a Jarisch-Herxheimer reaction, which occurs most often in secondary syphilis and with penicillin therapy, and may be more common in HIV-infected patients.(20) This reaction is characterized by fever, fatigue, and transient worsening of any mucocutaneous symptoms, and usually subsides within 24 hours. These symptoms can be alleviated with acetaminophen and should not be mistaken for drug allergy. In addition, clinicians should inform HIV-infected patients that currently recommended regimens may be less effective for them than for patients without HIV infection and that close serologic follow-up is therefore essential.
Primary, Secondary, and Early Latent Syphilis in HIV-Infected Patients
Before treating, clinicians must carefully examine HIV-infected patients with primary, secondary, or early latent syphilis for clinical evidence of neurologic involvement (eg, optic and auditory symptoms, cranial nerve palsies) (Figure 2). For HIV-infected patients with incubating, primary, secondary, or early latent syphilis and with no clinical evidence of neurologic involvement, the same treatment regimen as for patients without HIV infection is recommended: 2.4 million units of benzathine penicillin G administered intramuscularly at a single session (Table 1). In addition to this regimen, some experts have recommended extra treatment (such as multiple doses of benzathine penicillin G, as recommended for latent syphilis, or other supplemental antibiotics).(37,158) However, these approaches have theoretical benefit only, with no evidence of significant clinical benefit vis-à-vis the added cost. In penicillin-sensitive patients, the clinician should confirm allergy. If compliance and close follow-up are ensured and the patient is not pregnant and refuses desensitization, the clinician may consider doxycycline (100 mg orally twice daily for 14 days). No data are available, however, on the efficacy of tetracyclines for treating syphilis in HIV-infected patients. Azithromycin is not an acceptable alternative, as discussed above. Ceftriaxone may be considered as an alternative therapy, although the optimal dose is not yet defined and close clinical and serologic follow-up is essential. If ceftriaxone is used for the treatment of early syphilis, some experts recommend 1 g daily, given intramuscularly or intravenously, for 8 to 10 days.(47,159,160) Regarding all alternatives to penicillin, if compliance and close follow-up cannot be ensured, then desensitization to penicillin and management in consultation with an infectious diseases specialist are recommended.
Late Latent Syphilis or Syphilis of Unknown Duration in HIV-Infected Patients
A careful clinical examination and CSF analysis should precede and guide the treatment of HIV-infected patients with late latent syphilis or syphilis of unknown duration (Figure 2). If the CSF examination yields no evidence of neurosyphilis, then a total of 7.2 million units of benzathine penicillin G is recommended (administered as 3 doses of 2.4 million units by intramuscular injection weekly for 3 successive weeks) (Table 1). If a CSF examination is not possible, the clinician should offer treatment for neurosyphilis; however, an LP is preferred to yield CSF markers for follow-up evaluations. In penicillin-sensitive patients, skin testing may be used to confirm allergy, after which desensitization to penicillin is recommended. If compliance and close follow-up are ensured and the patient is not pregnant and refuses desensitization, the clinician may consider doxycycline (100 mg orally twice daily for 28 days). No data are available, however, on the efficacy of tetracyclines for treating syphilis in HIV-infected patients. Azithromycin is not an acceptable alternative, as discussed above. Ceftriaxone has not been evaluated thoroughly for late latent syphilis and an optimal dose has not been defined, so close clinical and serologic follow-up is essential if this agent is used.
Tertiary Syphilis in HIV-Infected Patients
A careful clinical examination and CSF analysis should precede and guide the treatment of HIV-infected patients with tertiary syphilis. If the CSF examination yields no evidence of neurosyphilis, then a total of 7.2 million units of benzathine penicillin G is recommended (administered as 3 doses of 2.4 million units by intramuscular injection weekly for 3 successive weeks). If a CSF examination is not possible, the clinician should offer treatment for neurosyphilis; however, an LP is preferred to yield CSF markers for follow-up evaluations. In penicillin-sensitive patients, skin testing may be used to confirm allergy, after which desensitization to penicillin is recommended. Some clinicians treat all patients who have cardiovascular syphilis with a neurosyphilis regimen, regardless of the results of CSF evaluation. An infectious diseases consultation should be obtained when managing patients with tertiary syphilis.
Neurosyphilis in HIV-Infected Patients
For HIV-infected patients diagnosed with neurosyphilis (including ocular or auditory syphilis with or without positive LP results), aqueous crystalline penicillin G is the treatment of choice (administered as 18-24 million units intravenously per day; ie, 3-4 million units every 4 hours or continuous infusion for 10-14 days) (Table 1; Figure 2). The clinician should desensitize penicillin-sensitive patients; preliminary skin testing to evaluate penicillin allergy may obviate the need for desensitization. If intravenous administration is impossible, then aqueous procaine penicillin G is an alternative (administered as 2.4 million units intramuscularly daily plus probenecid 500 mg by mouth 4 times daily for 14 days). Procaine injections are painful, however, and patient compliance may be difficult to ensure.
To approximate the 21-day course of therapy for late latent disease and to address concerns about slowly dividing treponemes, most experts now recommend 3 weekly doses of benzathine penicillin G (total 7.2 million units intramuscularly) after the completion of a 14-day course of aqueous crystalline or aqueous procaine penicillin G for neurosyphilis.
No oral antibiotic alternatives are recommended for the treatment of neurosyphilis. Neither the tetracyclines nor azithromycin has been studied adequately in HIV-infected patients to support the recommendation of either for the treatment of neurosyphilis. In addition, the resistance to azithromycin recently documented precludes this option. The only alternative that has been studied is ceftriaxone 2 g intramuscularly for 14 days. Although this drug has excellent CNS penetration and a longer half-life than penicillin, the small sample size of this study precludes recommendation of this agent as standard therapy.(42) This regimen may be considered in special circumstances when neither intravenous penicillin nor procaine penicillin is feasible.
Follow-Up of HIV-Infected Patients Treated for Syphilis
Treatment failure can occur with any regimen in patients with or without HIV infection. Because the possibility of clinical relapse after syphilis therapy may be slightly higher in HIV-infected patients, the importance of closely following HIV-infected patients with syphilis cannot be overstated. Clinicians should monitor all patients carefully for persistent or recurrent symptoms, for any signs of neurologic involvement, and for increasing serologic titers.
After treatment for syphilis, patients should be reexamined clinically at 1 to 2 weeks and retested with a quantitative nontreponemal test at 3, 6, 9, 12, and 24 months after treatment for primary, secondary, and early latent syphilis and at 6, 12, 18, and 24 months after treatment for late latent syphilis or syphilis of unknown duration (Table 1; Figure 2). The objectives of such follow-up in HIV-infected patients include the following:
Documenting whether a Jarisch-Herxheimer reaction has occurred, which, when stage of infection is uncertain, may suggest earlier infection requiring epidemiologic follow-up
Documenting serologic improvement or treatment failure
Monitoring resolution, persistence, or recurrence of clinical signs and symptoms and development of any new signs or symptoms, especially those involving the CNS
Ensuring compliance with treatment and, if applicable, effective partner notification and safer-sex practices
Clinicians should monitor patients more frequently and longer if any questions exist about the adequacy of their clinical or serologic response. Clinicians must evaluate patients using the same nontreponemal test on each occasion because titers from the VDRL and RPR tests are not interchangeable.
Determining a therapeutic cure of syphilis is problematic because no simple test is available. A persistently reactive RPR or VDRL test result, typically less than 1:16 but in some cases significantly higher, may represent not an active syphilis infection but rather the serofast state, a nonpathologic, stable reactive serology. Moreover, clinical symptoms and signs of early syphilis may resolve even without treatment. Finally, serologic criteria for treatment failure have been based on curves of serologic response to treatment in patients with normal immune function.(161-163)
In a prospective study, 81% to 87% of patients with primary, secondary, or early latent syphilis had an adequate serologic response by 12 months after treatment (Table 2).(20) In the minority of patients with primary and secondary syphilis who failed to show a 4-fold decrease in nontreponemal titer after treatment, serologically defined treatment failure was more common among HIV-infected patients. This study found that although the serologic response sometimes differed between HIV-infected patients and HIV-uninfected patients after therapy for early syphilis, the difference usually was not clinically important.
The criteria for treatment failure currently include the following findings:
Persistence, recurrence, or development of clinical signs or symptoms of syphilis in the absence of reinfection
Sustained (greater than 2 weeks) 4-fold (2 dilution) increase in the nontreponemal test titer (assuming the same test type was used [eg, VDRL, RPR])
Failure of the initial nontreponemal test titer to decrease 4-fold (2 dilutions) by 6 to 12 months for primary, secondary, or early latent syphilis and by 12 to 24 months for late latent syphilis or syphilis of unknown duration (Figure 2)
Failure of nontreponemal test titers to decline 4-fold or serorevert by 12 months after therapy for primary, secondary, or early latent syphilis raises the theoretical concern that the patient has not been adequately treated for syphilis. Limited data are available to guide evaluation of the response to therapy in a patient with late latent syphilis or syphilis of unknown duration, especially if the initial nontreponemal serologic titer was low. If the nontreponemal titer fails to decline 4-fold between 12 and 24 months, especially if the initial titer was higher than 1:2, then the patient with late latent syphilis or syphilis of unknown duration may be experiencing treatment failure.
In all patients experiencing treatment failure as defined by rising titers or development of signs or symptoms of syphilis in the absence of reinfection, and in cases of possible treatment failure as defined by inadequate serologic response, especially if treated for primary, secondary, or early latent syphilis without an initial CSF examination, experts recommend CSF examination and repeat treatment with 3 weekly injections of benzathine penicillin G (2.4 million units intramuscularly every week) for a total of 7.2 million units, unless CSF examination indicates that neurosyphilis is present. Such patients should be monitored with repeat serologic testing every 6 to 12 months. Unless the patient has recurrent or new clinical signs or symptoms or a sustained, 4-fold increase in serologic titer in the absence of reinfection, most experts believe that no further therapy is needed. Those patients with persistent nontreponemal antibodies of unknown clinical significance should be monitored annually for evidence of clinical or serologic relapse. In cases of late latent syphilis or syphilis of unknown duration in which the initial titer was very low, treatment with 7.2 million units of benzathine penicillin G was documented, CSF examination was negative, and the risk of reinfection is thought to be very low, some experts would elect to monitor the titer without further evaluation and treatment and to reevaluate and treat only on the basis of recurrent signs or symptoms or a sustained, 4-fold increase in titer.
For patients with neurosyphilis, repeat serologic testing as described previously and CSF examinations at 6-month intervals are recommended until the findings have stabilized. Abnormal white blood cell count and protein level in the CSF should decrease by 6 months if no coexisting CNS infections are present, but CSF VDRL test results may remain reactive for at least 2 years. If the CSF white blood cell count is not normal or the CSF VDRL remains reactive at 2 years, and if no other cause is identified, then the patient should be reevaluated and re-treated for neurosyphilis.
Clinical Relapse Following Treatment
Mucocutaneous Syphilis
Clinicians have reported slow resolution of syphilitic skin lesions after penicillin therapy in patients with HIV infection.38 The first prospective study in the postantibiotic era examining the interval from treatment to resolution of the signs and symptoms of primary or secondary syphilis found that the resolution of chancre took somewhat longer for HIV-infected patients (median, 16.5 days) than for HIV-negative persons (median, 13 days).(20) The time to resolution of skin rash, however, did not differ by HIV status (median, 53 vs 49 days, respectively). In this study, mucocutaneous signs and symptoms of secondary syphilis recurred in 1 HIV-infected patient 6 months after treatment. It is plausible that in addition to neurologic relapse, other manifestations of syphilis could recur in a small number of HIV-infected persons after treatment.
Although neurologic relapse after penicillin therapy and optic, auditory, and neurologic signs and symptoms in early syphilis are not unique to HIV-infected patients, they are uncommon in HIV-uninfected patients.(99,100,164) Recent case reports of neurologic relapse after benzathine penicillin G and ceftriaxone therapy for syphilis in patients with HIV infection (13-16,104,165,166) have raised concerns about the adequacy of treatment regimens in HIV-infected patients with syphilis. One patient presented with eye pain, double vision, dizziness, and headache;(13) 2 weeks later, he was found in a stuporous state with a hemiparesis, homonymous hemianopsia, and expressive aphasia. CSF evaluation revealed mononuclear pleocytosis (32 cells/L), elevated protein level (92 mg/dL), and a CSF VDRL titer of 1:4. This case is consistent with meningovascular syphilis. This patient had been treated with benzathine penicillin G for secondary syphilis 5 months before this neurologic event, and the serum VDRL titer had decreased from 1:256 to 1:16. Although the serum VDRL titer around the time of the stroke was 1:256, careful contact tracing and close follow-up after the initial treatment suggested that reinfection had not occurred.
Meningovascular neurosyphilis also was diagnosed in a patient within 6 months after treatment with ceftriaxone, 2 g intravenously daily for 14 days, for latent syphilis.(165) Another patient developed syphilitic ophthalmitis with irreversible blindness 96 hours after starting high-dose intravenous penicillin treatment for syphilitic meningitis.(14) Before her treatment for syphilitic meningitis, she had received 7.2 million units of benzathine penicillin G for early syphilis. Twenty-four weeks after completing the 10-day course of 24 million units of crystalline penicillin G daily, she developed meningovascular neurosyphilis. In a prospective study of more than 500 patients with early syphilis, however, no cases of symptomatic neurosyphilis were identified during the 12-month follow-up.(20)
A follow-up study of patients treated for neurosyphilis showed that HIV-infected patients had slower resolution of serum RPR and CSF VDRL tests after treatment.(44) Most experts believe that in comparison with HIV-negative patients, HIV-infected patients with syphilis may have an increased risk of neurologic complications and higher rates of treatment failure with currently recommended regimens; the magnitude of these risks is uncertain but probably low.(47) Although advanced HIV disease is typical in these cases, specific factors associated with neurologic complications or treatment failure in these few individuals are currently unknown, and perhaps represent individual variations in yet-to-be characterized immunologic factors.
Managing Sexual Contacts
Complementing their role in the medical management of syphilis, medical providers are crucial for effective public health responses and control of this infection.(167) It is important to identify and treat the sexual contacts of infected patients, especially those with early syphilis. For patients with primary syphilis, all contacts within 3 months before the appearance of the chancre should be evaluated clinically and serologically. For patients with secondary syphilis and no history of a chancre, contacts for 6 months before the onset of secondary syphilis signs should be evaluated clinically and serologically. For patients with early latent syphilis and no history of symptoms or signs suggestive of primary or secondary syphilis, contacts for the previous 12 months should be evaluated clinically and serologically. Efforts should be made to diagnose syphilis by history, clinical findings, and serologic testing before such contacts are treated.
All persons exposed to a patient with primary, secondary, or early latent syphilis within the previous 3 months may be infected yet seronegative, and therefore should be treated presumptively for early syphilis independent of a syphilis test result. Follow-up serologic tests should be done at 1 week after treatment to help establish a definitive diagnosis of syphilis in seronegative contacts.
All cases of infectious syphilis (primary, secondary, and early latent) must be reported promptly to local health departments. Most states require reporting within 24 hours of evaluating any suspected cases of infectious or early syphilis.
Indications for Screening for HIV Infection and Other Sexually Transmitted Diseases
Many of the diagnostic options discussed here (eg, criteria for performing LP), and the therapeutic options presented subsequently, are recommended for patients with coexisting HIV infection. Therefore, it is important to know the HIV status of patients with syphilis when considering diagnostic and therapeutic op