The quality of evidence supporting the recommendations (I-III) and the rating scheme for the recommendations (A-E) are defined at the end of the "Major Recommendations" field.
Refer to the original guideline document for information on epidemiology, clinical manifestations, and diagnosis of serious and recurrent bacterial infections in human immunodeficiency virus (HIV)-exposed and HIV-infected children.
Bacterial Infections: Serious and Recurrent
Prevention Recommendations
Preventing Exposure
Because Streptococcus pneumoniae and Haemophilus influenzae are common in the community, no effective way exists to eliminate exposure to these bacteria. However, routine use of conjugated 7-valent pneumococcal conjugate and Haemophilus influenzae type b (Hib) vaccines in U.S. infants has dramatically reduced vaccine type invasive disease and nasopharyngeal colonization, conferring herd protection of HIV-infected contacts due to decreased exposure to Hib and pneumococcal serotypes included in the vaccine.
Food. In order to reduce the risk of exposure to potential gastrointestinal (GI) bacterial pathogens, health care providers should advise that HIV-infected children avoid eating the following raw or undercooked foods (including other foods that contain them): eggs, poultry, meat, seafood (especially raw shellfish), and raw seed sprouts. Unpasteurized dairy products and unpasteurized fruit juices should also be avoided (BIII). Of particular concern to HIV-infected infants and children is the potential for caretakers to handle these raw foods (e.g., during meal preparation) and then unknowingly transfer bacteria from their hands to the child's food, milk, formula, or directly to the child. Hands, cutting boards, counters, knives, and other utensils should be washed thoroughly after contact with uncooked foods (BIII). Produce should be washed thoroughly before being eaten (BIII).
Pets. When obtaining a new pet, caregivers should avoid dogs or cats aged <6 months or stray animals (BIII). HIV-infected children and adults should avoid contact with any animals that have diarrhea and should wash their hands after handling pets, including before eating, and avoid contact with pets' feces (BIII). HIV-infected children should avoid contact with reptiles (e.g., snakes, lizards, iguanas, and turtles) as well as chicks and ducklings because of the risk for salmonellosis (BIII).
Travel. The risk for foodborne and waterborne infections among immunosuppressed, HIV-infected persons is magnified during travel to economically developing countries. HIV-infected children who travel to such countries should avoid foods and beverages that might be contaminated, including raw fruits and vegetables, raw or undercooked seafood or meat, tap water, ice made with tap water, unpasteurized milk and dairy products, and items sold by street vendors (AII). Foods and beverages that are usually safe include steaming hot foods, fruits that are peeled by the traveler, bottled (including carbonated) beverages, and water brought to a rolling boil for 1 minute (AII). Treatment of water with iodine or chlorine might not be as effective as boiling and will not eradicate Cryptosporidia, but can be used when boiling is not practical (BIII).
Preventing First Episode of Disease
HIV-infected children aged ≤5 years should receive the Hib conjugate vaccine (AII). Clinicians and other health care providers should consider use of Hib vaccine among HIV-infected children >5 years old who have not previously received Hib vaccine (AIII). For these older children, two doses of any conjugate Hib vaccine, administered at least 1 to 2 months apart, can be used (AIII).
HIV-infected children aged 2 to 59 months should receive the heptavalent pneumococcal conjugate vaccine (PCV) (AII). A four-dose series of PCV is recommended for routine administration to infants at ages 2, 4, 6, and 12 to 15 months; previously unvaccinated infants and children aged 7 to 23 months are recommended to receive two to three doses depending on age at the time of first vaccination. Incompletely vaccinated children aged 24 to 59 months should receive two doses of PCV ≥8 weeks apart.
Children who previously received three PCV doses need only one additional dose. Additionally, children aged >2 years also should receive the 23-valent pneumococcal polysaccharide vaccine (PPV) (≥2 months after their last PCV dose), with a single revaccination with PPV 3 to 5 years later if the child is aged ≤10 years or after 5 years if the child is aged >10 years (CIII) (See Figures 1 and 2 in the original guideline document). Data are limited regarding efficacy of PCV among children aged ≥5 years and adults who are at high risk for pneumococcal infection. Administering PCV to older children with high-risk conditions (including HIV-infected children) is not contraindicated. One study reported that 5-valent pneumococcal conjugate vaccine is immunogenic among HIV-infected children aged 2 to 9 years. A multicenter study of pneumococcal immunization in a group of HIV-infected children not vaccinated with PCV in infancy demonstrated the safety and immunogenicity of two doses of PCV followed by one dose of PPV for highly active antiretroviral treatment (HAART)-treated, HIV-infected children aged 2 to 19 years (including some who had previously received PPV). In a placebo-controlled trial of a 9-valent pneumococcal conjugate vaccine among South African children, although vaccine efficacy was somewhat lower among children with HIV infection than those without (65% vs. 85%, respectively), the incidence of invasive pneumococcal disease was substantially decreased among HIV-infected vaccine recipients.
HIV-infected children are likely at increased risk for meningococcal disease, although not to the extent that they are at risk for invasive S. pneumoniae infection. Although the efficacy of conjugated meningococcal vaccine (MCV4) and meningococcal polysaccharide vaccine (MPSV4) among HIV-infected patients is unknown, HIV infection is not a contraindication to receiving these vaccines (CIII). Since 2005, conjugated meningococcal vaccine has been recommended for all children at 11 to 12 years of age. In June 2007, the Advisory Committee on Immunization Practices (ACIP) recommended that all unvaccinated adolescents aged 13 to 18 years should also be vaccinated. A multicenter safety and immunogenicity trial of conjugated meningococcal vaccine in HIV-infected 11 to 24 year olds is currently under way. In addition, it is recommended that children who are at high risk of meningococcal disease on the basis of other conditions (e.g., terminal complement deficiencies, anatomic or functional asplenia) receive MCV4 if aged 2 to 6 years (BIII). Although the efficacy of MCV4 and MPSV4 among HIV-infected children is unknown, because patients with HIV are likely at increased risk for meningococcal disease, HIV-infected children that do not fit into the above groups may elect to be vaccinated. Revaccination with MCV4 is indicated for children who had been vaccinated 3 years or more previously with the MPSV4 vaccine.
Since influenza increases the risk of secondary bacterial respiratory infections, following guidelines for influenza prevention can be expected to reduce the risk of serious bacterial infections in HIV-infected children (See Figures 1 and 2 in the original guideline document) (BIII).
To prevent serious bacterial infections among HIV-infected children who have hypogammaglobulinemia (IgG <400 mg/dL), clinicians should use IVIG (AI). In the pre-HAART era, IVIG was effective in preventing serious bacterial infections in symptomatic HIV-infected children, but this effect was most clearly demonstrated only in those not receiving daily trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis jirovecii pneumonia (PCP) prophylaxis. Thus, IVIG is no longer recommended for primary prevention of serious bacterial infections in HIV-infected children unless hypogammaglobulinemia is present or functional antibody deficiency demonstrated by either poor specific antibody titers or recurrent bacterial infections (CII).
TMP-SMX administered daily for PCP prophylaxis is effective in reducing the rate of serious bacterial infections (predominantly respiratory) in HIV-infected children without access to HAART (AII). Atovaquone combined with azithromycin, which provides prophylaxis for Mycobacterium avium complex (MAC) as well as PCP, has been shown in HIV-infected children to be as effective as TMP-SMX for the prevention of serious bacterial infections and is similarly tolerated. However, indiscriminate use of antibiotics (when not indicated for PCP or MAC prophylaxis or other specific reasons) might promote development of drug-resistant organisms. Thus, antibiotic prophylaxis is not recommended to be prescribed solely for primary prevention of serious bacterial infections (DIII).
In developing countries, where endemic deficiency of vitamin A and zinc is common, supplementation with vitamin A and zinc conferred additional protection against bacterial diarrhea and/or pneumonia in HIV-infected children. However, in the United States, while attention to good nutrition including standard daily multivitamins is an important component of care for HIV-infected children, additional vitamin supplementation above the recommended daily amounts is not recommended (DIII).
Discontinuing Primary Prophylaxis
A clinical trial, PACTG 1008, demonstrated that discontinuation of MAC and/or PCP antibiotic prophylaxis in HIV-infected children who achieved immune reconstitution (CD4 >15%) while receiving antiretroviral therapy did not result in excessive rates of serious bacterial infections.
Treatment Recommendations
Treatment of Disease
The principles of treatment of serious bacterial infections are the same in HIV-infected and -uninfected children. Collection of specimens for microbiologic studies should be obtained prior to initiation of antibiotic treatment. However, in patients with suspected serious bacterial infections, therapy should be administered empirically and promptly without waiting for results of such studies; therapy can be adjusted once culture results become available. The local prevalence of resistance to common infectious agents (i.e., penicillin-resistant S. pneumoniae and methicillin-resistant Staphylococcus aureas [MRSA]) and the recent use of prophylactic or therapeutic antibiotics should be considered when initiating empiric therapy. When the organism is identified, antibiotic susceptibility testing should be performed, and subsequent therapy based on the results of susceptibility testing (AII).
HIV-infected children whose immune systems are not seriously compromised (Centers for Disease Control and Prevention [CDC] Immune Class I) and who are not neutropenic can be expected to respond similarly to HIV-uninfected children and should be treated with the usual antimicrobial agents recommended for the most likely bacterial organisms (AIII). For example, for HIV-infected children outside of the neonatal period with suspected community-acquired bacteremia, bacterial pneumonia, or meningitis, empiric therapy with an extended-spectrum cephalosporin such as ceftriaxone or cefotaxime is reasonable until culture results are available (AIII). The addition of azithromycin can be considered for hospitalized patients with pneumonia to treat other common community-acquired pneumonia pathogens (Mycoplasma pneumoniae, C. pneumoniae). If MRSA is suspected or there is a high prevalence (e.g., >10%) of MRSA in the community, clindamycin or vancomycin can be added (choice based on local susceptibility patterns). Neutropenic children should also be treated with an anti-pseudomonal drug such as ceftazidime or imipenem, with consideration of adding an aminoglycoside if infection with Pseudomonas spp. is thought likely. Severely immunocompromised HIV-infected children with invasive or recurrent bacterial infections might require expanded empiric antimicrobial treatment covering a broad range of resistant organisms similar to that chosen for suspected catheter sepsis pending results of diagnostic evaluations and cultures (AIII).
Initial empiric therapy of HIV-infected children with suspected catheter sepsis should include coverage for both gram-positive and enteric gram-negative organisms, such as ceftazidime, which has anti-Pseudomonas activity, and vancomycin to cover MRSA (AIII). Factors such as response to therapy, clinical status, identification of pathogen, and need for ongoing vascular access will determine the need and timing of catheter removal.
Monitoring and Adverse Events, Including Immune Reconstitution Inflammatory Syndrome
The response to appropriate antibiotic therapy should be similar in HIV-infected and -uninfected individuals, with a clinical response generally observed within 2 to 3 days after initiation of appropriate antibiotics; radiologic improvement in patients with pneumonia may lag behind clinical response. Fatal hemolytic reactions to ceftriaxone in HIV-infected children with prior ceftriaxone treatment have been reported. While HIV-infected adults experience high rates of adverse and even treatment-limiting reactions to trimethoprim/sulfamethoxazole (TMP-SMX), serious adverse reactions to TMP-SMX in HIV-infected children appear to be much less of a problem.
An immune reconstitution inflammatory syndrome (IRIS) has not been described in association with treatment of bacterial infections in children.
Management of Treatment Failure
The type of bacteria isolated and the antibiotic drug susceptibility pattern should guide changes in antibiotic regimen. Failure of treatment of a serious bacterial infection in an HIV-infected child should prompt consideration that the bacterial pathogen is resistant to the antibiotic therapy; consideration that there is a nonbacterial cause of the pneumonia (e.g., tuberculosis [TB], PCP), meningitis (e.g., cryptococcus or TB), catheter-related infection (e.g., Candida spp.), or other serious infection; or consideration that there might be a sequestered focus of infection (e.g., an undrained occult abscess) (AIII).
Prevention of Recurrence
Status of immunization against Hib, pneumococcus, meningococcus, and influenza should be reviewed and updated, according to the recommendations outlined in the section Preventing First Episode of Disease above (see Figures 1 and 2 in the original guideline document) (AI).
TMP-SMX, administered daily for PCP prophylaxis, and azithromycin or atovaquone-azithromycin, administered for MAC prophylaxis, may also reduce the incidence of drug-sensitive serious bacterial infections in children with recurrent serious bacterial infections. While administration of antibiotic chemoprophylaxis to HIV-infected children who have frequent recurrences of serious bacterial infections may be considered, caution is required when using antibiotics solely for preventing the recurrence of serious bacterial infections because of the potential for development of drug-resistant microorganisms and drug toxicity. In rare situations in which antibiotic prophylaxis is not effective in preventing frequent recurrent serious bacterial infections, IVIG prophylaxis can be considered for secondary prophylaxis (AI).
Discontinuing Secondary Prophylaxis
As noted earlier, PACTG 1008 demonstrated that discontinuation of MAC and/or PCP antibiotic prophylaxis in HIV-infected children who achieved immune reconstitution (CD4 >15%) while receiving antiretroviral therapy did not result in excessive rates of serious bacterial infections.
Bacterial Infections: Bartonellosis
Prevention Recommendations
Preventing Exposure
Prevention of bartonellosis should focus on reducing exposure to vectors of the disease (i.e., the body louse [for Bartonella Quintana] and cats and cat fleas [for B. henselae]). Control of cat flea infestation and avoidance of cat scratches are therefore critical strategies for prevention of B. henselae infections in HIV-infected persons. To avoid exposure to B. quintana, HIV-infected patients should avoid and treat infestation with body lice.
Individuals with HIV infection, specifically those with severe immunosuppression, should consider the potential risks of cat ownership; risks of cat ownership for HIV-infected children should be discussed with caretakers. If a decision is made to acquire a cat, cats <1 year of age should be avoided (BII). HIV-infected persons should avoid playing roughly with cats and kittens to minimize scratches and bites and should promptly wash sites of contact if they are scratched or bitten (BIII). Also, cats should not be allowed to lick open wounds or cuts (BIII). No evidence indicates any benefit from routine culturing or serologic testing of cats for Bartonella infection or from antibiotic treatment of healthy, serologically positive cats (DII).
Preventing First Episode of Disease
No evidence supports the use of chemoprophylaxis for bartonellosis, such as following a cat scratch (CIII).
Discontinuing Primary Prophylaxis
Not applicable.
Treatment Recommendations
Treatment of Disease
Management of typical cat-scratch disease in immunocompetent patients is mainly supportive because the disease is usually self-limited and resolves spontaneously in 2 to 4 months. Enlarged, painful lymph nodes may need to be aspirated. Cat-scratch disease typically does not usually respond to antibiotic therapy; it is thought that the localized clinical manifestations of the disease may be due to an immunologic reaction in the lymph nodes with few viable Bartonella present by the time a biopsy is performed. In one double-blind, placebo-controlled study in a small number (N=29) of immunocompetent older children and adults with uncomplicated cat-scratch disease, azithromycin resulted in a more rapid decrease in initial lymph node volume by sonography, although there was no difference in clinical outcome. Thus, antibiotic treatment is generally not recommended for uncomplicated, localized disease.
The in vitro and in vivo antibiotic susceptibilities of Bartonella do not correlate well for a number of antibiotics; for example, penicillin demonstrates in vitro activity but has no in vivo efficacy. Although no systematic clinical trials have been done, antibiotic treatment of bacillary angiomatosis and peliosis hepatitis is recommended on the basis of reported experience in clinical case series as severe, progressive, and disseminated disease can occur, and without appropriate therapy, systemic spread can occur and involve virtually any organ. Guidelines for treatment of Bartonella infections have been published.
The drug of choice for treatment of systemic bartonellosis is erythromycin or doxycycline (AII). Clarithromycin or azithromycin treatment has been associated with clinical response, and either of these can be an alternative for Bartonella treatment (BIII).
For patients with severe disease, intravenous administration may be needed initially (AIII). Therapy should be given for 3 months for cutaneous bacillary angiomatosis and 4 months for bacillary peliosis, central nervous system (CNS) disease, osteomyelitis, or severe infections, as treatment must be of sufficient duration to prevent relapse (AII). Combination therapy with the addition of rifampin to either erythromycin or doxycycline is recommended for immunocompromised patients with acute, life-threatening infections (BIII). Because doxycycline has better CNS penetration than erythromycin, the combination of doxycycline and rifampin is preferred for treatment of patients with CNS Bartonella infection, including retinitis (AIII).
Endocarditis is most commonly caused by B. quintana, followed by B. henselae, but has also been linked to infection with B. elizabethae, B. vinsonii subsp. Berkhoffii, B. vinsonii subsp. Arupensis, B. kohlerae, and B. alsatica. For suspected (but culture-negative) Bartonella endocarditis, 14 days of aminoglycoside treatment (AII) accompanied by ceftriaxone (to adequately treat other potential causes of culture-negative endocarditis) with or without doxycycline for 6 weeks is recommended (BII). For documented culture-positive Bartonella endocarditis, doxycycline for 6 weeks plus gentamicin intravenously for the first 14 days is recommended (BII).
Penicillins and first-generation cephalosporins have no in vivo activity and should not be used for treatment of bartonellosis (DII). Quinolones and TMP-SMX have variable in vitro activity and an inconsistent clinical response in case reports; as a result, they are not recommended for treatment (DIII).
Monitoring and Adverse Events, Including Immune Reconstitution Inflammatory Syndrome
Response to treatment can be dramatic in immunocompromised patients. Cutaneous bacillary angiomatosis skin lesions usually improve and resolve after a month of treatment. Bacillary peliosis responds more slowly than cutaneous angiomatosis, but hepatic lesions should improve after several months of therapy.
Some immunocompromised patients develop a potentially life-threatening Jarisch-Herxheimer-like reaction within hours after institution of antibiotic therapy, and immunocompromised patients with severe respiratory or cardiovascular compromise should be monitored carefully following institution of therapy.
No cases of Bartonella-associated IRIS have been reported.
Management of Treatment Failure
In immunocompromised patients who relapse, retreatment should be continued for 4 to 6 months; repeated relapses should be treated indefinitely (AIII). Among patients who fail to respond to initial treatment, one or more of the second-line regimens should be considered (AIII).
Prevention of Recurrence
Relapses in bone and skin have been reported and are more common when antibiotics are given for a shorter duration (<3 months), especially in severely immunocompromised patients. In the setting of an immunocompromised HIV-infected adult experiencing relapse, long-term suppression of infection with doxycycline or a macrolide is recommended as long as the CD4 cell count is <200 cells/mm3 (AIII). Although there are no data for HIV-infected children, it seems reasonable that similar recommendations should be followed.
Discontinuing Secondary Prophylaxis
No specific data regarding the discontinuation of secondary prophylaxis are available at this time.
Bacterial Infections: Syphilis
Prevention Recommendations
Preventing Exposure
Congenital Syphilis
Effective prevention and detection of congenital syphilis depends on the identification of syphilis in pregnant women and, therefore, on the routine serologic screening of pregnant women during the first prenatal visit. In communities and populations in which the risk for congenital syphilis is high, serologic testing and a sexual history also should be obtained at 28 weeks gestation and at delivery. Moreover, as part of the management of pregnant women who have syphilis, information concerning treatment of sex partners should be obtained to assess the risk for reinfection. Routine screening of newborn sera or umbilical cord blood is not recommended. Serologic testing of the mother's serum is preferred rather than testing of the infant's serum because the serologic tests performed on infant serum can be nonreactive if the mother's serologic test result is of low titer or the mother was infected late in pregnancy. No HIV-exposed infant should leave the hospital unless the maternal serologic status has been documented at least once during pregnancy, and at delivery in communities and populations in which the risk for congenital syphilis is high.
Acquired Syphilis
Primary prevention of syphilis includes routine discussion of sexual behaviors that may place persons at risk for infection. Providers should discuss risk reduction messages that are client centered and provide specific actions that can reduce the risk for sexually transmitted disease (STD) acquisition and HIV transmission.
Routine serologic screening for syphilis is recommended at least annually for all sexually active HIV-infected persons, with more frequent screening (3 to 6 months) dependent on individual risk behaviors (e.g., multiple partners, sex in conjunction with illicit drug use, methamphetamine use, or partners that participate in such activities). The occurrence of syphilis in an HIV-infected person is an indication of high-risk behavior and should prompt intensified counseling messages and consideration of referral for behavioral intervention. Persons undergoing screening or treatment for syphilis should also be evaluated for all common STDs.
Discontinuing Primary Prophylaxis
Not applicable.
Treatment Recommendations
Treatment of Disease
Penicillin remains the treatment of choice for syphilis, congenital or acquired, regardless of HIV status.
Congenital Syphilis
Data are insufficient about whether infants who have congenital syphilis and whose mothers are coinfected with HIV require different evaluation, therapy, or follow-up for syphilis than is recommended for all infants. Some studies in adults have shown a lag in serological improvement in appropriately treated patients with HIV infection.
Infants should be treated for congenital syphilis if the mother has (1) untreated or inadequately treated syphilis (including treatment with erythromycin or any other nonpenicillin regimen), (2) no documentation of having received treatment, (3) received treatment ≤4 weeks before delivery, (4) been treated with penicillin but nontreponemal antibody titer did not decrease by 4-fold, or (5) ≥4-fold increase in nontreponemal antibody titer suggesting relapse or reinfection (AII). Infants should be treated regardless of maternal treatment history if there is an abnormal examination consistent with congenital syphilis, positive dark-field or fluorescent antibody test of body fluid(s), or serum quantitative nontreponemal serologic titer that is ≥4-fold greater than maternal titer (AII).
Treatment for proven or highly probable congenital syphilis (i.e., infants with findings, symptoms, or whose titers are ≥4-fold greater than maternal titer) is aqueous crystalline penicillin G at a dose of 100,000 – 150,000 units/kg/day, administered as 50,000 units/kg/dose intravenously every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days (AII). If congenital syphilis is diagnosed after 1 month of life, the dose of aqueous penicillin G should be increased to 50,000 units/kg/dose intravenously every 4 to 6 hours for 10 days (AII). An alternative to aqueous penicillin G is procaine penicillin G at a dose of 50,000 units/kg/dose intramuscularly (IM) daily in a single dose for 10 days (BII). However, aqueous penicillin G is preferred because of its higher penetration into the cerebrospinal fluid (CSF). There are no published reports of treatment failures with ampicillin or studies of the effectiveness of ampicillin for the treatment of congenital syphilis.
Asymptomatic infants born to mothers who have had adequate treatment and response to therapy, and with a normal physical examination and CSF findings, but who have a serum quantitative nontreponemal serologic titer that is <4-fold higher than maternal titer might be treated with a single dose of benzathine penicillin G 50,000 units/kg/dose IM with careful clinical and serologic follow-up (BII). However, certain health care providers would treat such infants with the standard 10 days of aqueous penicillin G because physical examination and laboratory test results cannot definitively exclude congenital syphilis in all cases (BII).
Acquired Syphilis
Acquired syphilis in children is treated with a single dose of benzathine penicillin G 50,000 units/kg IM (up to the adult dose of 2.4 million units) for early stage disease (e.g., primary, secondary, and early latent disease) (AII). For late latent disease, three doses of benzathine penicillin G 50,000 units/kg should be administered IM once weekly for three doses (AIII). Alternative therapies (e.g., doxycycline, ceftriaxone, or azithromycin) have not been evaluated among HIV-infected patients and should not be used as first- line therapy (EIII). Neurosyphilis should be treated with aqueous penicillin G 200,000 – 300,000 units/kg intravenously per day in divided doses given every 4 to 6 hours (maximum dose: 18 – 24 million units/day) for 10 to 14 days (AII). See the National Guideline Clearinghouse (NGC) summary of Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults for dosing recommendations for older HIV-infected adolescents with acquired syphilis.
Monitoring and Adverse Events, Including Immune Reconstitution Inflammatory Syndrome
All seroreactive infants (or infants whose mothers were seroreactive at delivery) should receive careful follow-up examinations and serologic testing (i.e., a nontreponemal test) every 2 to 3 months until the test becomes nonreactive or the titer has decreased 4-fold (AIII). Nontreponemal antibody titers should decline by age 3 months and should be nonreactive by age 6 months if the infant was not infected (i.e., if the reactive test result was caused by passive transfer of maternal IgG antibody) or was infected but adequately treated. The serologic response after therapy might be slower for infants treated after the neonatal period. It is not known if children with congenital syphilis who also are HIV infected take longer to become nonreactive and require retreatment.
Treponemal tests should not be used to evaluate treatment response because the results for an infected child can remain positive despite effective therapy. Passively transferred maternal treponemal antibodies can be present in an infant until age 15 months. A reactive treponemal test after age 18 months is diagnostic of congenital syphilis. If the nontreponemal test is nonreactive at this time, no further evaluation or treatment is necessary. If the nontreponemal test is reactive at age 18 months, the infant should be fully (re)evaluated and treated for congenital syphilis (BIII).
Infants whose initial CSF evaluations are abnormal should undergo a repeat lumbar puncture approximately every 6 months until the results are normal. A reactive CSF Venereal Disease Research Laboratory (VDRL) test or abnormal CSF indices that cannot be attributed to other ongoing illness requires retreatment for possible neurosyphilis.
HIV-infected children and adolescents with acquired early syphilis (i.e., primary, secondary, early latent) should have clinical and serologic response monitored at age 3, 6, 9, 12, and 24 months after therapy (BIII). Nontreponemal test titers should decline by at least 4-fold by 6 to 12 months after successful therapy, with examination of CSF and retreatment strongly considered in the absence of such a decline. For syphilis of longer duration, follow-up is indicated at 6, 12, and 24 months; a 4-fold decline should be expected by 12 to 24 months. If initial CSF examination demonstrated a pleocytosis, repeat lumbar puncture should be conducted at 6 months after therapy and then every 6 months until the cell count is normal. Follow-up CSF examinations can also be used to evaluate changes in the VDRL-CSF or CSF protein levels after therapy, but changes in these parameters occur more slowly than changes in CSF cell counts. Data from HIV-infected adults with neurosyphilis suggest that CSF abnormalities might persist for extended periods and close clinical follow-up is warranted.
There are no reported cases of syphilis (congenital or acquired) in an HIV-infected child manifesting as IRIS and only very rare reports of syphilis-associated IRIS in adults (primarily syphilitic ocular inflammatory disease).
Management of Treatment Failure
After treatment of congenital syphilis, children with increasing or stable nontreponemal titers at age 6 to 12 months or those who are seropostive with any titer at 18 months should be evaluated (e.g., including a CSF examination) and considered for retreatment with a 10-day course of parenteral penicillin (AIII).
The management of failures of treatment of acquired syphilis in older children and adolescents is identical to that in adults (See the National Guideline Clearinghouse [NGC] summary of Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults). Retreatment of patients with early-stage syphilis should be considered for those who (1) do not experience at least a 4-fold decrease in serum nontreponemal test titers 6 to 12 months after therapy, (2) have a sustained 4-fold increase in serum nontreponemal test titers after an initial reduction post-treatment, or (3) have persistent or recurring clinical signs or symptoms of disease (BIII). If CSF examination does not confirm the diagnosis of neurosyphilis, such patients should receive 2.4 million units IM benzathine penicillin G administered at 1-week intervals for 3 weeks (BIII). Certain specialists have also recommended a course of aqueous penicillin G IV or procaine penicillin IM plus probenecid (as described above for treatment of neurosyphilis) for all patients with treatment failure, although data to support this recommendation are lacking (CIII). If titers fail to respond appropriately after retreatment, the value of repeat CSF evaluation or retreatment has not been established.
Patients with late latent syphilis should be retreated if they (1) have clinical signs or symptoms of syphilis, (2) have a 4-fold increase in serum nontreponemal test titer, or (3) experience an inadequate serologic response (i.e., a <4-fold decline in nontreponemal test titer) within 12 to 24 months of therapy if initial titer was high (e.g., >1:32) (BIII). Such patients should have a repeat CSF examination performed. If the repeat CSF examination is consistent with CNS involvement, retreatment should follow the neurosyphilis recommendations (AIII); those without a CSF profile indicating CNS disease should receive a repeat course of benzathine penicillin, 2.4 million units IM weekly for 3 weeks (BIII), although certain specialists recommend following the neurosyphilis recommendations in this setting as well (CIII).
Retreatment of neurosyphilis should be considered if the CSF WBC count has not decreased 6 months after treatment completion or if the CSF-VDRL remains reactive 2 years after treatment (BIII).
Prevention of Recurrence
No recommendations have been developed for secondary prophylaxis or chronic maintenance therapy for syphilis in HIV-infected children.
Discontinuing Secondary Prophylaxis
Not applicable.
Definitions:
| Rating Scheme for Prevention and Treatment Recommendations |
| A |
Both strong evidence for efficacy and substantial clinical benefit support recommendation for use. Should always be offered. |
| B |
Moderate evidence for efficacy - or strong evidence for efficacy but only limited clinical benefit - supports recommendation for use. Should generally be offered. |
| C |
Evidence for efficacy is insufficient to support a recommendation for or against use. Or evidence for efficacy might not outweigh adverse consequence (e.g., drug toxicity, drug interactions) or cost of the treatment under consideration. Optional. |
| D |
Moderate evidence for lack of efficacy or for adverse outcome supports a recommendation against use. Should generally not be offered. |
| E |
Good evidence for lack of efficacy or for adverse outcome supports a recommendation against use. Should never be offered. |
| Quality of Evidence Supporting the Recommendation |
| I |
Evidence from at least one randomized, controlled trial. |
| II |
Evidence from at least one well-designed clinical trial without randomization, from cohort or case-controlled analytic studies (preferably from more than one center), or from multiple time-series studies. Or dramatic results from uncontrolled experiments. |
| III |
Evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees. |
