Screening for Sexually Transmitted Diseases during the Domestic Medical Examination for Newly Arrived Refugees
Sexually transmitted infections (STIs) are a major cause of acute illness and infertility worldwide. The World Health Organization (WHO) estimates that 448 million new cases of curable STIs occur annually worldwide in adults aged 15-49 years. The largest number of new infections occurs in the region of South and Southeast Asia, followed by sub-Saharan Africa, Latin America, and the Caribbean. In low-income countries, STIs rank in the top five disease categories for which adults seek health care.
The prevalence of STIs in refugee populations is not well characterized and likely varies among populations. Because certain refugee groups are at potentially high risk for STIs, it is important to screen for certain STIs to minimize or prevent acute and chronic sequelae, as well as prevent transmission to others.
Overseas Pre-Departure Screening and Testing
Refugees undergo health screening prior to resettlement in the United States to identify conditions that exclude resettlement until after treatment. For refugees 15 years of age or older, clinical evaluation (laboratory for syphilis) and treatment for identified infection are considered mandatory for the following infections:
- Syphilis (laboratory testing required)
- Granuloma inguinale
- Lymphogranuloma venereum
Note: HIV has been removed from the list of excludable infections and as of January 2010 is no longer routinely tested overseas (see domestic guidelines for HIV testing during refugee new arrival screening: www.cdc.gov/immigrantrefugeehealth/guidelines/domestic/screening-hiv-infection-domestic.html).
A complete overseas screening medical examination for syphilis consists of a medical history, physical examination, and serologic testing. Further testing is performed as necessary to confirm a suspected diagnosis. For the other STIs (i.e., gonorrhea, chancroid, lymphogranuloma venereum, and granuloma inguinale), the evaluation includes a medical history and physical examination. Therefore, with the exception of syphilis, negative overseas STI screening does not exclude STIs.
Recommendations for Post-Arrival Screening and Evaluation
The Office of Refugee Resettlement and the Centers for Disease Control and Prevention recommend that all refugees receive a new-arrival medical evaluation on arrival to the United States. HIV testing is strongly encouraged in newly arriving refugee populations according to current CDC guidelines (www.cdc.gov/immigrantrefugeehealth/guidelines/refugee-guidelines.html). However, testing for HIV is particularly important and encouraged for any refugee with a confirmed non-HIV STI. In addition, the following STIs should be considered during this examination:
- Granuloma inguinale/donovanosis
- Lymphogranuloma venereum
- Genital herpes
- Genital warts
A complete screening medical examination for all STIs includes a thorough medical history, physical examination and, for specific disorders, diagnostic testing. Although history taking is challenging due to language and cultural barriers, the optimal medical history should include inquiries regarding sexual contact with a person who has or had a known STI or symptoms of an STI, signs and symptoms of current infection (e.g., genital discharge, dysuria, genital lesion, ulcer, or rash), and/or prior diagnostic evaluation and treatment of STIs. Information on treatment of sex partners should be obtained to assess risk of re-infection.
Pertinent elements of the physical examination for STIs include palpation of lymph nodes and an external anal and genital examination, including inspection for discharge, ulcers, or rashes. In previously traumatized refugees (e.g., sexual assault victims), the anal and genital examination may be postponed until the refugee establishes a trusting relationship with a provider. Signs and symptoms and specific information on diagnostic testing available for select STIs are described below. With the exception of the routine testing for syphilis (for refugees > 15 years of age) and chlamydia testing (for women ≤ 25 years of age or older with risk factors as in U.S. CDC guidelines), no data support the utility of routine testing for other non-HIV STIs in refugees. Further study to elucidate prevalence rates and the utility of screening in refugee populations is encouraged. The following summarizes the currently recommended testing:
- Syphilis: Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR) or equivalent test.
- All persons ≥15 years of age, regardless of the overseas results.
- Children < 15 years of age who meet one or more of the following criteria:
- Sexually active or history of sexual assault.
- All children who are at risk (i.e., mother who tests positive for syphilis) should be evaluated according to current guidelines.
- All refugees from countries that are endemic for treponemal subspecies (e.g., yaws, bejel, pinta).
- Confirmatory testing [i.e., fluorescent treponemal antibody (FTA), treponema pallidum particle agglutination assay (TPPA), or enzyme-linked immunosorbent assay (EIA)] should be performed on all refugees who test positive by VDRL or RPR. Further evaluation, including evaluation for neurosyphilis, and treatment should be instituted according to current guidelines, found at www.cdc.gov/std/treatment/.
- Chlamydia: Nucleic acid amplification tests
- Females ≤ 25 years old who are sexually active or those with risk factors (e.g., new sexual partner or multiple sexual partners).
- Consider for children who have a history of sexual assault. However, management and evaluation of such children require consultation with an expert.
- Persons with symptoms or leukoesterase (LE) detected in urine sample.
- Gonorrhea: Nucleic acid amplification tests
- Consider for children who have a history of sexual assault. However, management and evaluation of such individuals require consultation with an expert.
- Persons who have symptoms or leukoesterase (LE) detected in urine sample.
NOTE: HIV testing is strongly encouraged in newly arriving refugee populations according to current CDC guidelines. However, testing for HIV is particularly important and encouraged for any refugee with a confirmed non-HIV STI.
Further information on STIs, including treatment guidelines, is available at CDC STD website and MMWR Sexually Transmitted Diseases Treatment Guidelines, 2010 1. In addition, updated laboratory guidance for syphilis, gonorrhea and chlamydia is available here.
Syphilis, which is caused by the bacterium Treponema pallidum, has often been called the "great imitator" because so many of its signs and symptoms are indistinguishable from those of other diseases.
Typical signs and symptoms of various stages of syphilis include—
- Primary stage
- Generally occurs 10-90 days after exposure
- Ulcer or chancre at the infection site, usually the genitals, rectum, tongue or lips
- Secondary stage
- Generally occurs 2-10 weeks after the chancre appears
- Skin rash marked by red or reddish-brown macules on the palms and soles or other parts of the body, mucocutaneous lesions, lymphadenopathy, anorexia, fever, headaches, weight loss, fatigue
- Latent stage (early latent and late latent)
- No signs and symptoms present
- Begins when primary and secondary symptoms disappear and may last for years
- Early latent syphilis can relapse to secondary syphilis and become infectious (again)
- Tertiary stage
- Generally occurs 10-20 years after infection
- Cardiac or ocular manifestations (e.g., aortitis, optic atrophy, uveitis, gradual blindness), auditory abnormalities (e.g., asymmetric deafness, tinnitus), neurologic manifestations (e.g., tabes dorsalis, meningitis, dementia), gumma
- Neurosyphilis may occur at any stage of disease.
- Congenital syphilis
- Prevention and detection of congenital syphilis depend on identification of syphilis in pregnant women by serology. For specific guidelines on screening and identification of congenital syphilis, see the 2010 congenital section of the syphilis treatment guidelines.
Serologic tests for syphilis include screening tests that use nonspecific cardiolipin antigens and confirmatory tests that use specific T. pallidum antigens (Table 1). A nontreponemal test such as Venereal Disease Research Laboratory (VDRL), rapid plasma reagin (RPR) or an equivalent test may be used for screening. Positive results on these nontreponemal tests should be confirmed by using a treponemal test, such as fluorescent treponemal antibody absorption (FTA-ABS) or other treponemal test.
Screening tests such as the VDRL and RPR are relatively simple to perform and provide rapid results. However, interpretation of results demands trained personal. In addition, laboratory equipment and quality control can present challenges in non-U.S. settings (Table 2). Both VDRL and RPR quantitative titer usually correlate with disease activity and are used to monitor the effect of treatment. If treatment is successful, the antibody titer gradually declines. A fourfold change in titer (e.g., from 1:16 to 1:4) is necessary to demonstrate a clinically significant difference between two nontreponemal tests. Sequential serologic tests in individuals should be performed by using the same testing method, because quantitative results from the two tests cannot be compared directly; RPR titers are frequently slightly higher than VDRL titers. The timing of follow-up testing is dictated by the clinical presentation and the stage of infection, as well as the HIV status of the refugee, and are detailed in the current treatment guidelines 1.
|Nontreponemal (reagin) Test||Treponemal (specific) Test|
Unlike nontreponemal tests, treponemal tests (e.g., FTA) do not usually revert to nonreactivity after successful treatment of syphilis. Screening with treponemal tests (i.e., use of rapid syphilis tests) is not recommended in high-prevalence settings, because these tests will be reactive in persons with previous successful treatment as well as those with untreated or incompletely treated infection. Therefore, treatment of persons with treponemal positive tests, without previous positive nontreponemal testing (i.e. VDRL, RPR), may result in overtreatment.
|Nontreponemal Test (e.g., RPR, VDRL)||Treponemal (specific) Test (e.g., FTA-ABS, TPPA)||Likely Interpretations and Comments|
|Nonreactive *||Not routinely done if screening is nonreactive|
* Note: Nontreponemal testing may have a false-negative result during primary syphilis in the very early stages, tertiary syphilis in the very late stages, or syphilis with concomitant HIV infection. Suggest retesting or alternative testing if clinical suspicion is high. See treatment guidelines for details. 1
Cerebrospinal Fluid Examination
Involvement of the central nervous system can occur during any stage of syphilis. Therefore, any person who has clinical evidence of neurologic involvement (e.g., motor or sensory deficits, cranial nerve palsies, or symptoms and signs of meningitis) and a positive treponemal test should have a lumbar puncture performed to obtain cerebrospinal fluid (CSF). A reactive VDRL performed on a CSF sample, in combination with elevated CSF white blood cells (≥10 wbc/mm3) or protein, is suggestive of neurosyphilis. Because VDRL-CSF might be nonreactive even when neurosyphilis is present, an FTA-ABS test on CSF may be helpful if the result of the VDRL-CSF test is negative.
Neurosyphilis may be a difficult diagnosis, particularly in HIV-positive individuals. The treatment guidelines provide in-depth information on diagnosis and treatment, and expert consultation may be needed when deciding how to evaluate an individual or interpret testing 1.
Other Diagnostic Tests
Syphilis infection must be correctly diagnosed to ensure that the refugee with syphilis receives correct treatment and to prevent further spread of the disease. When clinical findings are suggestive of primary syphilis but serologic tests are nonreactive or their interpretation is unclear, alternative tests should be considered (e.g., biopsy of a lesion, darkfield microscopy, or direct fluorescent antibody staining of lesion exudate or tissue).
The diagnosis of congenital syphilis is complicated by transplacental transfer of maternal nontreponemal and treponemal IgG antibodies to the fetus, making it difficult to interpret reactive serologic tests for syphilis in newborns born to mothers seropositive for syphilis. Pathologic examination of the placenta or umbilical cord by using specific fluorescent antitreponemal antibody staining is recommended. Darkfield microscopic examination or direct fluorescent antibody staining of suspicious lesions or body fluids should also be performed (e.g., nasal discharge). Other tests (e.g., complete blood count with platelets, bone radiographs) may be performed to support a diagnosis of congenital syphilis.
Other Treponema pallidum infection
Infection with other T. pallidum subspecies (e.g., T. pallidum subsp. pertenue, T. pallidum subsp. endemicum, and T. carateum) is acquired through contact with infected skin and results in rashes and may cause disfiguring skin lesions. Unlike syphilis, these infections are not considered sexually transmitted. Long-term infection can lead to deformations of bone and nasopharyngeal tissue. Infection with any of these subspecies can produce positive results for both treponemal and nontreponemal tests used for diagnosis of syphilis. Therefore, it is important to obtain a thorough history of both sexual and nonsexual exposures to assist in differentiating between syphilis and other T. pallidum subspecies infections. Lesions should be evaluated for treponemes by darkfield or fluorescence microscopy. Note: Darkfield microscopy of oral lesions will not allow distinction between syphilitic and nonsyphilitic treponemes.
Because the diseases caused by T. pallidum subsp. pertenue, T. pallidum subsp. endemicum, and T. carateum (i.e., yaws, bejel/endemic syphilis, and pinta, respectively) usually occur during childhood, CDC recommends that all refugee children from areas where treponemes are known to be endemic (Table 3) undergo nontreponemal serologic testing at the initial health screening 2. If the screening test is positive, a treponemal confirmatory test should be performed.
Chlamydia, the most frequently reported STI in the United States, has the highest prevalence in persons 15-25 years of age. Asymptomatic infection is common in the U.S. and, in accordance with current CDC guidelines, screening of sexually active refugee women ≤ 25 years old, or of women older than 25 with risk factors (e.g., new sexual partner or multiple sexual partners) is recommended. In women, untreated infection can cause pelvic inflammatory disease, ectopic pregnancy, and infertility. Rarely, genital chlamydia infection can cause arthritis that can be accompanied by skin lesions and inflammation of the eye and urethra (Reiter’s syndrome).
Women with symptoms may have an abnormal vaginal discharge or burning sensation when urinating. Other symptoms include abdominal pain, low back pain, nausea, fever, pain during intercourse (dyspareunia), or bleeding between menstrual periods. Men with signs or symptoms might have penile discharge, burning and itching or burning sensation when urinating. Pain and swelling of the testicles occur but are uncommon. Autoinoculation may occur in men or women and can be associated with conjunctivitis.
Chlamydia trachomatis infection in infants most frequently presents as conjunctivitis that develops 5-12 days after birth. It can also cause an afebrile pneumonia with onset 1-3 months after birth. Signs of C. trachomatis pneumonia include a repetitive staccato cough with tachypnea and hyperinflation and bilateral diffuse infiltrates on chest radiograph.
Diagnostic Testing for Chlamydia
Diagnosis of C. trachomatis urogenital infection in women can be made by testing urine or cervical specimens. Urethral C. trachomatis infection in men can be diagnosed by testing urethral swab or urine specimens.
Nucleic acid amplification tests (NAATs) are the most sensitive tests available for detection of C. trachomatis. These tests can be performed on cervical, urethral, urine, or self-collected vaginal swab specimens. Direct immunofluorescent antibody test is used to detect C. trachomatis from nasopharyngeal specimens, tracheal aspirates, and lung biopsy tissue in infants. Further information on diagnostic testing can be obtained at (www.cdc.gov/std/chlamydia/default.htm#treat).
Gonorrhea, which is caused by the bacterium Neisseria gonorrhoeae, is the second most commonly reported bacterial STI in the United States. The majority of gonococcal urethral infections in men produce symptoms. However, among women, 30%-40% or more of infections do not produce recognizable symptoms. Untreated infection can result in complications such as pelvic inflammatory disease (PID), infertility, and ectopic pregnancy.
Signs and symptoms of gonorrhea may appear 2-10 days or as long as 30 days after exposure to an infected person.
In men, signs and symptoms may include—
- Pain or burning sensation when urinating
- Penile discharge
- Painful or swollen testicles
- Rectal infection: typically asymptomatic, but discharge, anal itching, soreness, bleeding, or painful bowel movements may occur
In women, signs and symptoms may include—
- Pain or burning sensation when urinating
- Vaginal discharge
- Itching or burning of the vagina
- Intermenstrual bleeding
- Rectal infection: typically asymptomatic, but discharge, anal itching, soreness, bleeding, or painful bowel movements may occur
Other sites of infection include the eyes (gonococcal conjunctivitis) and pharynx. Disseminated gonococcal infection is associated with intermittent fever, arthralgia, and skin lesions ranging from maculopapular or pustular to hemorrhagic. Arthritis and tenosynovitis, particularly involving the wrists, knees, and ankles, may occur.
Gonococcal infection among infants usually results from exposure to infected cervical exudate at birth. It is usually an acute illness that develops 2-5 days after birth and may present as ophthalmia neonatorum that can result in perforation of the globe of the eye and blindness. Ophthalmic prophylaxis at birth is effective at preventing this complication. Other manifestations in infants are scalp abscesses, rhinitis, vaginitis, urethritis, arthritis, meningitis, and sepsis.
Diagnostic Testing for Gonorrhea
Specific diagnostic testing for gonorrhea may be performed on endocervical, vaginal, male urethral or urine specimens. For screening purposes, urine samples tested by nucleic acid amplification tests (NAAT) are highly sensitive and specific. No data support routine screening in refugees. A gram stain of discharge or on a urethral swab showing gram-negative diplococci supports the diagnosis and may be sufficient to confirm gonorrhea in symptomatic men.
Because nonculture-based tests do not permit antimicrobial susceptibility testing, in cases of persistent gonococcal infection following treatment, bacterial culture and antimicrobial susceptibility testing should be assessed.
Persons infected with N. gonorrhoeae are frequently coinfected with Chlamydia trachomatis. Therefore, persons who test positive for N. gonorrhoeae should also receive treatment for chlamydia.
Chancroid can be a cause of genital ulcer, especially in Asia, Africa and the Caribbean, and an important cofactor of HIV transmission in countries most severely affected by HIV. Infection with the bacterium Haemophilus ducreyi results in painful, superficial ulcers, often with regional lymphadenopathy.
Genital ulcers may be single or multiple, or in women lesions may be located within the vagina or on the cervix. Unlike a syphilitic chancre, which is painless, the chancroid ulcer is painful, tender, and nonindurated. Symptoms usually occur 4-10 days after exposure. The lesion at the site of infection is initially a pustule that breaks down to form a painful, soft, ulcer with a necrotic base with irregular borders. Multiple lesions and inguinal adenopathy often develop. With lymph node involvement, fever, chills and malaise may also develop. Other symptoms of chancroid include painful urination, vaginal discharge, rectal bleeding, pain with bowel movements, and dyspareunia.
Diagnostic Testing for Chancroid
The combination of a painful genital ulcer and tender suppurative inguinal adenopathy suggests the diagnosis of chancroid. A probable diagnosis of chancroid can be made if all the following criteria are met:
- One or more painful genital ulcers (regional lymphadenopathy is also typical)
- No evidence of T. pallidum infection by darkfield examination of ulcer exudate or by syphilis serologic testing performed at least 7 days after onset of ulcers
- Test for herpes simplex virus performed on the ulcer exudate is negative
A definitive diagnosis of chancroid requires the identification of H. ducreyi on special culture media that is not widely available from commercial sources. Nucleic acid amplification tests can be performed in clinical laboratories that have developed their own tests.
Granuloma inguinale is a chronic, relapsing granulomatous anogenital infection caused by the bacterium Calymmatobacterium (Donovania) granulomatis, which is endemic in tropical and developing areas, including India, Guyana, New Guinea, central Australia, and southern Africa. Symptoms usually occur 1-12 weeks after infection. The infection begins with the appearance of relative painless nodules that break down into shallow, sharply demarcated ulcers with a beefy-red friable base of granulation tissue. The lesions may occur on the skin, genitalia, or perineal areas and slowly spread to the lower abdomen and thighs. The lesions may develop secondary bacterial infection or may be coinfected with another sexually transmitted pathogen.
Diagnostic Testing for Granuloma inguinale/donovanosis
Diagnosis requires visualization of Donovan bodies (numerous bacilli in the cytoplasm of macrophage demonstrated with Giemsa or Wright’s stain) in smears of scrapings from the ulcer base or histologic sections. Culture of C. granulomatis is difficult to perform and not routinely available.
Lymphogranuloma venereum (LGV) is caused by three subtypes of C. trachomatis, serovars L1, L2, or L3. It is most often seen in tropical areas of Asia, Africa, South America, and the Caribbean. Symptoms appear 3-30 days after infection and usually present as a painless ulcer or papule at the site of inoculation. Inguinal and femoral lymphadenopathy may also occur. Rectal exposure can result in mucoid or hemorrhagic rectal discharge, painful bowel movement, and constipation. Late manifestations include rectal and perirectal inflammation that can lead to rectal strictures and rectovaginal and perianal fistulas. Constitutional symptoms such as fever may occur.
Diagnostic Testing for LGV
Diagnosis is based on clinical suspicion, epidemiologic information, and C. trachomatis testing. Genital and lymph node specimens (e.g., lesion swab, aspirate) may be tested for C. trachomatis by culture, direct immunofluorescence, or nucleic acid detection. To differentiate LGV from non-LGV C. trachomatis, special testing is generally necessary (e.g., genotyping) and may necessitate consultation with laboratory experts. Chlamydia serology (complement fixation titers >1:64) can support the diagnosis in the appropriate clinical context.
Genital herpes is a chronic, lifelong infection caused by herpes simplex virus (HSV), type 1 and type 2. Most cases of recurrent genital herpes are caused by HSV-2. Many persons with HSV-1 or HSV-2 have mild or unrecognized infections but intermittently shed the virus in the genital tract. When genital ulcers do occur, they appear typically as one or more blisters on or around the genitals or rectum. The blisters break, leaving tender ulcers that may take 2-4 weeks to heal the first time they occur. Other symptoms, such as fever, headache, muscle aches, malaise, and swollen lymph glands, may occur before appearance of the lesions. After the first episode of genital herpes, symptoms usually recur, but they tend to be milder and briefer. After the lesions erupt, they typically heal in 6-10 days.
Neonatal herpes is a rare but serious condition occurring among infants exposed to HSV during birth. Although the disease may be limited to skin, eyes, or mucus membranes, disseminated disease involving the lungs, liver, adrenal glands and central nervous system disease (e.g., encephalitis) may also occur and is associated with serious consequences.
Diagnostic Testing for Genital Herpes
Both virologic and type-specific serologic tests for HSV are available for diagnosis. Isolation of HSV in cell culture is the preferred virologic test for genital lesions. However, the sensitivity of the culture is low, especially for recurrent lesions. Polymerase chain reaction (PCR) tests for HSV DNA are more sensitive but are not FDA-approved for testing genital specimens. Viral culture isolates can be typed to determine if HSV-1 or HSV-2 is the cause of the infection.
Type-specific serologic tests (e.g., ELISA, immunoblot) may be useful—
- In clinical diagnosis of genital herpes without laboratory confirmation
- For recurrent genital symptoms or atypical symptoms with negative HSV culture
- When a sexual partner has known genital herpes
Genital warts are the most recognized sign of genital human papillomavirus (HPV) infection. HPV types 6 and 11 are usually associated with genital warts. Other HPV types that affect the anogenital region (e.g., types 16, 18, 31, 33, and 35) are associated with cervical neoplasia.
Genital warts are usually flat, papular, or pedunculated growths on the genital mucosa and often occur in clusters. They can appear on the penis, vulva, the vagina, cervix or rectum, rectum, groin or thigh within weeks or months after sexual contact with an infected person.
Diagnostic Testing for Genital Warts
Diagnosis of genital warts is made by visual inspection. Biopsy may confirm the diagnosis but is generally needed only when the lesions do not respond to appropriate therapy or worsen during therapy.
A definitive diagnosis of HPV infection is based on detection of viral nucleic acid (i.e., DNA or RNA) or capsid protein. Tests that detect several types of HPV DNA in cells scraped from the cervix are available but are only indicated for use in very limited circumstances (see www.cdc.gov/std).
Trichomoniasis, caused by the protozoan Trichomonas vaginalis, is the most common curable STI in sexually active women. The most common sites of infection are the vagina in women and urethra in men.
Some men with trichomoniasis do not have signs or symptoms. Others may have an irritation inside the penis, mild discharge, or slight burning after urination. Many infected women have frothy, malodorous yellow-green vaginal discharge with irritation and itching of the genital area. There can also be small red ulcerations on the vaginal wall or cervix. Symptoms usually appear within 5-28 days after exposure.
Diagnostic Testing for Trichomoniasis
Diagnosis of vaginal trichomoniasis is usually performed by microscopy of vaginal secretions and evaluation of wet preparation slide for trichomonads. Other tests for trichomoniasis in women include immunochromatographic capillary flow dipstick test and nucleic acid probe test. Although these tests tend to be more sensitive than vaginal wet preparations, false positives may occur, especially in low-prevalence populations. Culture is the most sensitive method of diagnosis. In women in whom trichomoniasis is suspected but not confirmed by microscopy, vaginal secretions may be cultured for T. vaginalis. In men, a wet preparation is insensitive, and culture testing of urethral swab, urine, and semen is required for optimal sensitivity. Frequently, this infection is treated presumptively based on clinical signs and symptoms when testing is not available.
The health-care provider must counsel all refugees with STIs and their contacts to reduce their risk of future STIs. Preventive measures should include using barrier protection methods such as condoms, reducing the number of sexual partners, and knowing the health status and HIV infection status of partners.
Further information on the prevention of STIs is available at CDC’s website at http://www.cdc.gov/STD/.
- Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2010. Morb Mort Wkly Rep (MMWR) 2010;59(12): 1-110.
- Centers for Disease Control and Prevention. Notice to readers: Recommendations regarding screening of refugee children for treponemal infection. MMWR Morb Mortal Wkly Rep 2005;54(37):933-934.