Gonorrhea, also spelled gonorrhoea, is a sexually transmitted infection (STI) caused by the bacterium Neisseria gonorrhoeae. Many people have no symptoms. Men may have burning with urination, discharge from the penis, or testicular pain. Women may have burning with urination, vaginal discharge, vaginal bleeding between periods, or pelvic pain. Complications in women include pelvic inflammatory disease and in men include inflammation of the epididymis. If untreated, gonorrhea can spread to joints or heart valves.
|Synonyms||Gonococcal infection, gonococcal urethritis, gonorrhoea, the clap|
|Gonococcal lesion on the skin|
|Symptoms||None, burning with urination, vaginal discharge, discharge from the penis, pelvic pain, testicular pain|
|Complications||Pelvic inflammatory disease, inflammation of the epididymis, septic arthritis, endocarditis|
|Causes||Neisseria gonorrhoeae typically sexually transmitted|
|Diagnostic method||Testing the urine, urethra in males, or cervix in females|
|Prevention||Condoms, having sex with only one person who is uninfected, not having sex|
|Treatment||Ceftriaxone by injection and azithromycin by mouth|
|Frequency||0.8% (women), 0.6% (men)|
Gonorrhea is spread through sexual contact with an infected person. This includes oral, anal, and vaginal sex. It can also spread from a mother to a child during birth. Diagnosis is by testing the urine, urethra in males, or cervix in females. Testing all women who are sexually active and less than 25 years of age each year as well as those with new sexual partners is recommended; the same recommendation applies in men who have sex with men (MSM).
Gonorrhea can be prevented with the use of condoms, having sex with only one person who is uninfected, and by not having sex. Treatment is usually with ceftriaxone by injection and azithromycin by mouth. Resistance has developed to many previously used antibiotics and higher doses of ceftriaxone are occasionally required. Retesting is recommended three months after treatment. Sexual partners from the last 2 months should also be treated.
Gonorrhea affects about 0.8% of women and 0.6% of men. An estimated 33 to 106 million new cases occur each year, out of the 498 million new cases of curable STI – which also includes syphilis, chlamydia, and trichomoniasis. Infections in women most commonly occur when they are young adults. In 2015, it caused about 700 deaths. Descriptions of the disease date as far back as the Old Testament.
Signs and symptoms
Half of women with gonorrhea do not have symptoms, whereas others have vaginal discharge, lower abdominal pain, or pain with sexual intercourse associated with inflammation of the uterine cervix. Most infected men with symptoms have inflammation of the penile urethra associated with a burning sensation during urination and discharge from the penis. In men, discharge with or without burning occurs in half of all cases and is the most common symptom of the infection. Men and women can acquire gonorrhea of the throat from performing oral sex on an infected partner, usually a male partner. Such infection does not produce symptoms in 90% of cases, and produces a sore throat in the remaining 10%. In advanced cases, gonorrhea may cause a general feeling of tiredness similar to other infections. It is also possible for an individual to have an allergic reaction to the bacteria, in which case any appearing symptoms will be greatly intensified.
The incubation period is 2 to 14 days, with most symptoms appearing between 4 and 6 days after infection. Rarely, gonorrhea may cause skin lesions and joint infection (pain and swelling in the joints) after traveling through the blood stream (see below). Very rarely it may settle in the heart causing endocarditis or in the spinal column causing meningitis (both are more likely among individuals with suppressed immune systems, however).
Gonorrhea is caused by the bacterium Neisseria gonorrhoeae. Also, previous infection does not confer immunity, and a person who has been infected can become infected again by exposure to someone who is infected, whether or not that person has any infectious signs or symptoms of their own.
The infection is usually spread from one person to another through vaginal, oral, or anal sex. Men have a 20% risk of getting the infection from a single act of vaginal intercourse with an infected woman. The risk for men that have sex with men (MSM) is higher. Active MSM may get a penile infection, while passive MSM may get anorectal gonorrhea. Women have a 60–80% risk of getting the infection from a single act of vaginal intercourse with an infected man. A pregnant women can pass on the infection to her unborn infant.
Among children it has been noted to spread through methods other than sex such as through contaminated objects. These objects have included baths, clothing, and towels. This however is very uncommon. The bacteria typically does not survive outside the body and usually will rapidly die within minutes to hours.
Traditionally, gonorrhea was diagnosed with gram stain and culture; however, newer polymerase chain reaction (PCR)-based testing methods are becoming more common. In those failing initial treatment, culture should be done to determine sensitivity to antibiotics. All people testing positive for gonorrhea should be tested for other sexually transmitted diseases such as chlamydia, syphilis, and human immunodeficiency virus.
The United States Preventive Services Task Force (USPSTF) recommends screening for gonorrhea in women at increased risk of infection, which includes all sexually active women younger than 25 years. Extragenital gonorrhea and chlamydia are highest in men who have sex with men (MSM). Additionally, the USPSTF also recommends routine screening in people who have previously tested positive for gonorrhea or have multiple sexual partners and individuals who use condoms inconsistently, provide sexual favors for money, or have sex while under the influence of alcohol or drugs.
Screening for gonorrhea in women who are (or intend to become) pregnant, and who are found to be at high risk for sexually transmitted diseases, is recommended as part of prenatal care in the United States.
As with most sexually transmitted diseases, the risk of infection can be reduced significantly by the correct use of condoms and can be removed almost entirely by limiting sexual activities to a mutually monogamous relationship with an uninfected person.
Those previously infected are encouraged to return for follow up care to make sure that the infection has been eliminated. In addition to the use of phone contact, the use of email and text messaging have been found to improve the re-testing for infection.
As of 2010, injectable ceftriaxone is one of the few effective antibiotics. This is typically given in combination with either azithromycin or doxycycline. As of 2015 and 2016 the CDC and WHO only recommends both ceftriaxone and azithromycin. Because of increasing rates of antibiotic resistance local susceptibility patterns must be taken into account when deciding on treatment.
It is recommended that sexual partners be tested and potentially treated. One option for treating sexual partners of people infected is patient-delivered partner therapy (PDPT), which involves providing prescriptions or medications to the person to take to his/her partner without the health care provider's first examining him/her.
The United States' Centers for Disease Control and Prevention (CDC) currently recommend that individuals who have been diagnosed and treated for gonorrhea avoid sexual contact with others until at least one week past the final day of treatment in order to prevent the spread of the bacterium.
Many antibiotics that were once effective including penicillin, tetracycline, and fluoroquinolones are no longer recommended because of high rates of resistance. Resistance to cefixime has reached a level such that it is no longer recommended as a first-line agent in the United States, and if it is used a person should be tested again after a week to determine whether the infection still persists. Cases of resistance to ceftriaxone have been reported but are still rare, though public health officials are concerned that an emerging pattern of resistance may predict a global epidemic. The UK's Health Protection Agency reported that 2011 saw a slight drop in gonorrhea antibiotic resistance, the first in 5 years.
Gonorrhea if left untreated may last for weeks or months with higher risks of complications. One of the complications of gonorrhea is systemic dissemination resulting in skin pustules or petechia, septic arthritis, meningitis, or endocarditis. This occurs in between 0.6 and 3% of infected women and 0.4 and 0.7% of infected men.
In men, inflammation of the epididymis, prostate gland, and urethra can result from untreated gonorrhea. In women, the most common result of untreated gonorrhea is pelvic inflammatory disease. Other complications include inflammation of the tissue surrounding the liver, a rare complication associated with Fitz-Hugh–Curtis syndrome; septic arthritis in the fingers, wrists, toes, and ankles; septic abortion; chorioamnionitis during pregnancy; neonatal or adult blindness from conjunctivitis; and infertility. Men who have had a gonorrhea infection have an increased risk of getting prostate cancer.
Newborn babies coming through the birth canal are given erythromycin ointment in the eyes to prevent blindness from infection. The underlying gonorrhea should be treated; if this is done then usually a good prognosis will follow. Adults may also have eyes infected with gonorrhoea and require proper personal hygiene and medications.
Among persons in the United States between 14 and 39 years of age, 46% of people with gonorrheal infection also have chlamydial infection.
The World Health Organization estimates that 88 million cases of gonorrhea occur each year, out of the 448 million new cases of all curable STI each year – that also includes syphilis, chlamydia and trichomoniasis. In 2013, it caused about 3,200 deaths, up from 2,300 in 1990.
In the United Kingdom, 196 per 100,000 males 20 to 24 years old and 133 per 100,000 females 16 to 19 years old were diagnosed in 2005. In 2013, the CDC estimated that more than 820,000 people in the United States get a new gonorrheal infection each year. Fewer than half of these infections are reported to CDC. In 2011, 321,849 cases of gonorrhea were reported to the CDC. After the implementation of a national gonorrhea control program in the mid-1970s, the national gonorrhea rate declined from 1975 to 1997. After a small increase in 1998, the gonorrhea rate has decreased slightly since 1999. In 2004, the rate of reported gonorrheal infections was 113. 5 per 100,000 persons.
In the US, it is the second-most-common bacterial sexually transmitted infections; chlamydia remains first. According to the CDC African Americans are most affected by gonorrhea. Blacks accounted for 69% of all gonorrhea cases in 2010.
The World Health Organization warned in 2017 of the spread of untreatable strains of gonhorrhea, following analysis of at least three cases in Japan, France and Spain, which survived all antibiotic treatment.
Some scholars translate the biblical terms zav (for a male) and zavah (for a female) as gonorrhea.
It has been suggested that mercury was used as a treatment for gonorrhea. Surgeons' tools on board the recovered English warship the Mary Rose included a syringe that, according to some, was used to inject the mercury via the urinary meatus into any unfortunate crewman suffering from gonorrhea. The name "the clap", in reference to the disease, is recorded as early as the sixteenth century.
In 1854, Dr. Wilhelm Gollmann addressed gonorrhea in his book, Homeopathic Guide to all Diseases Urinary and Sexual Organs. He noted that the disease was common in prostitutes and homosexuals in large cities. Gollmann recommended the following as cures: aconite to cure "shooting pains with soreness and inflammation;" mercury "for stitching pain with purulent discharge;" nux vomica and sulphur "when the symptoms are complicated with hemorrhoids and stricture of the rectum. Other remedies include argentum, aurum (gold), belladonna, calcarea, ignatia, phosphorus, and sepia.
Silver nitrate was one of the widely used drugs in the 19th century. However, It became replaced by Protargol. Arthur Eichengrün invented this type of colloidal silver, which was marketed by Bayer from 1897 on. The silver-based treatment was used until the first antibiotics came into use in the 1940s.
The exact time of onset of gonorrhea as prevalent disease or epidemic cannot be accurately determined from the historical record. One of the first reliable notations occurs in the Acts of the (English) Parliament. In 1161, this body passed a law to reduce the spread of "...the perilous infirmity of burning". The symptoms described are consistent with, but not diagnostic of, gonorrhea. A similar decree was passed by Louis IX in France in 1256, replacing regulation with banishment. Similar symptoms were noted at the siege of Acre by Crusaders.
Coincidental to, or dependent on, the appearance of a gonorrhea epidemic, several changes occurred in European medieval society. Cities hired public health doctors to treat afflicted patients without right of refusal. Pope Boniface rescinded the requirement that physicians complete studies for the lower orders of the Catholic priesthood.
Medieval public health physicians in the employ of their cities were required to treat prostitutes infected with the "burning", as well as lepers and other epidemic victims. After Pope Boniface completely secularized the practice of medicine, physicians were more willing to treat a sexually transmitted disease.
A vaccine for gonorrhea has been developed that is effective in mice. It will not be available for human use until further studies have demonstrated that it is both safe and effective in the human population.
As N. gonorrhoeae is closely related to N. meningitidis and they have 80–90% homology in their genetic sequences some cross-protection by meningococcal vaccines is plausible. A study published in 2017 showed that MeNZB group B meningococcal vaccine provided a partial protection against gonorrhea. The vaccine efficiency was calculated to be 31%.
- "Gonorrhea - CDC Fact Sheet (Detailed Version)". CDC. 17 November 2015. Archived from the original on 2 September 2016. Retrieved 27 August 2016.
- Morgan, MK; Decker, CF (August 2016). "Gonorrhea.". Disease-a-month : DM. 62 (8): 260–8. PMID 27107780. doi:10.1016/j.disamonth.2016.03.009.
- Workowski, KA; Bolan, GA (5 June 2015). "Sexually transmitted diseases treatment guidelines, 2015.". MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 64 (RR-03): 1–137. PMID 26042815.
- "Antibiotic-Resistant Gonorrhea Basic Information". CDC. 13 June 2016. Archived from the original on 8 September 2016. Retrieved 27 August 2016.
- Unemo, M (21 August 2015). "Current and future antimicrobial treatment of gonorrhoea - the rapidly evolving Neisseria gonorrhoeae continues to challenge.". BMC infectious diseases. 15: 364. PMC . PMID 26293005. doi:10.1186/s12879-015-1029-2.
- Newman, Lori; Rowley, Jane; Vander Hoorn, Stephen; Wijesooriya, Nalinka Saman; Unemo, Magnus; Low, Nicola; Stevens, Gretchen; Gottlieb, Sami; Kiarie, James; Temmerman, Marleen; Meng, Zhefeng (8 December 2015). "Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting". PLOS ONE. 10 (12): e0143304. Bibcode:2015PLoSO..1043304N. PMC . PMID 26646541. doi:10.1371/journal.pone.0143304.
- Global Burden of Disease Study 2013, Collaborators (22 August 2015). "Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.". Lancet. 386 (9995): 743–800. PMC . PMID 26063472. doi:10.1016/s0140-6736(15)60692-4.
- Emergence of multi-drug resistant Neisseria gonorrhoeae (PDF) (Report). World Health Organisation. 2012. p. 2. Archived from the original (pdf) on 12 September 2014.
- GBD 2015 Mortality and Causes of Death, Collaborators. (8 October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015.". Lancet. 388 (10053): 1459–1544. PMC . PMID 27733281. doi:10.1016/s0140-6736(16)31012-1.
- Smith, L; Angarone, MP (November 2015). "Sexually Transmitted Infections". The Urologic Clinics of North America. 42 (4): 507–18. PMID 26475947. doi:10.1016/j.ucl.2015.06.004.
- Moran JS (2007). "Gonorrhoea". Clin Evid (Online). 2007. PMC . PMID 19454057.
- Ljubin-Sternak, Suncanica; Mestrovic, Tomislav (2014). "Review: Clamydia trachonmatis and Genital Mycoplasmias: Pathogens with an Impact on Human Reproductive Health". Journal of Pathogens. 2014 (183167): 7. PMC . PMID 25614838. doi:10.1155/2014/183167.
- Brian R. Shmaefsky (1 January 2009). Gonorrhea. Infobase. p. 52. ISBN 978-1-4381-0142-2. Archived from the original on 2 November 2015.
- Zakher, Bernadette; Cantor MD, Amy G.; Daeges, Monica; Nelson MD, Heidi (16 December 2014). "Review: Screening for Gonorrhea and Chlamydia: A Systematic Review for the U.S. Prevententive Services Task Force". Annals of Internal Medicine. 161 (12): 884–894. doi:10.7326/M14-1022.
- Marr, Lisa (2007) . Sexually Transmitted Diseases: A Physician Tells You What You Need to Know (Second ed.). Baltimore, Maryland: Johns Hopkins University. ISBN 978-0-8018-8658-4. Archived from the original on 2 October 2015.
- Caini, Saverio; Gandini, Sara; Dudas, Maria; Bremer, Viviane; Severi, Ettore; Gherasim, Alin (2014). "Sexually transmitted infections and prostate cancer risk: A systematic review and meta-analysis". Cancer Epidemiology. 38 (4): 329–338. PMID 24986642. doi:10.1016/j.canep.2014.06.002.
- Trebach, Joshua D.; Chaulk, C. Patrick; Page, Kathleen R.; Tuddenham, Susan; Ghanem, Khalil G. (2015). "Neisseria gonorrhoeae and Chlamydia trachomatis Among Women Reporting Extragenital Exposures". Sexually Transmitted Diseases. 42 (5): 233–239. ISSN 0148-5717. doi:10.1097/OLQ.0000000000000248.
- Howard Brown Health Center: STI Annual Report, 2009
- Gollmann, Wilhelm (1854). Homeopathic Guide to all Diseases Urinary and Sexual Organ. Charles Julius Hempel. Rademacher & Sheek. Archived from the original on 8 September 2017.
- National Institute of Allergy and Infectious Diseases; National Institutes of Health, Department of Health and Human Services (2001-07-20). "Workshop Summary: Scientific Evidence on Condom Effectiveness for Sexually Transmitted Disease (STD) Prevention". Hyatt Dulles Airport, Herndon, Virginia. pp14
- Goodyear-Smith, F (November 2007). "What is the evidence for non-sexual transmission of gonorrhoea in children after the neonatal period? A systematic review.". Journal of forensic and legal medicine. 14 (8): 489–502. PMID 17961874. doi:10.1016/j.jflm.2007.04.001.
- "webmd – What Can You Catch in Restrooms? -". Archived from the original on 14 August 2009.
- Brian R. Shmaefsky (1 January 2009). Gonorrhea. Infobase. p. 48. ISBN 978-1-4381-0142-2. Archived from the original on 1 August 2017.
- Barry PM, Klausner JD (March 2009). "The use of cephalosporins for gonorrhea: The impending problem of resistance". Expert Opin Pharmacother. 10 (4): 555–77. PMC . PMID 19284360. doi:10.1517/14656560902731993.
- Deguchi T, Nakane K, Yasuda M, Maeda S (September 2010). "Emergence and spread of drug resistant Neisseria gonorrhoeae". J. Urol. 184 (3): 851–8; quiz 1235. PMID 20643433. doi:10.1016/j.juro.2010.04.078.
- Meyers D; Wolff T; Gregory K; et al. (March 2008). "USPSTF recommendations for STI screening". Am Fam Physician. 77 (6): 819–24. PMID 18386598.
- Health Care Guideline: Routine Prenatal Care. Fourteenth Edition. Archived 5 July 2008 at the Wayback Machine. By the Institute for Clinical Systems Improvement July 2010.
- section: Prevention Archived 20 July 2013 at the Wayback Machine.
- section: How can gonorrhea be prevented? Archived 16 December 2016 at the Wayback Machine.
- Desai, Monica; Woodhall, Sarah C; Nardone, Anthony; Burns, Fiona; Mercey, Danielle; Gilson, Richard (2015). "Active recall to increase HIV and STI testing: a systematic review". Sexually Transmitted Infections. 91 (5): sextrans–2014–051930. ISSN 1368-4973. doi:10.1136/sextrans-2014-051930.
- Centers for Disease Control and Prevention, (CDC) (Aug 10, 2012). "Update to CDC's Sexually Transmitted Diseases Treatment Guidelines, 2010: Oral Cephalosporins No Longer a Recommended Treatment for Gonococcal Infections.". MMWR. Morbidity and mortality weekly report. 61 (31): 590–4. PMID 22874837.
- "Antibiotic-resistant gonorrhoea on the rise, new drugs needed". World Health Organization. 7 July 2017. Archived from the original on 9 July 2017. Retrieved 10 July 2017.
- Baarda, Benjamin I.; Sikora, Aleksandra E. (2015). "Proteomics of Neisseria gonorrhoeae: the treasure hunt for countermeasures against an old disease". Frontiers in Microbiology. 6. ISSN 1664-302X. doi:10.3389/fmicb.2015.01190.
- "Expedited partner therapy in the management of sexually transmitted diseases" Archived 2 November 2009 at the Wayback Machine.. February 2006. Centers for Disease Control and Prevention (CDC).
- CDC (14 July 2014). "Gonorrhea - CDC Fact Sheet". Archived from the original on 16 December 2016. Retrieved 17 October 2014.
- Groopman, Jerome (1 October 2012). "Sex and the Superbug". The New Yorker. LXXXVIII (30): 26–31. Archived from the original on 9 October 2012. Retrieved 13 October 2012.
...public-health experts [see]...the emergence of a strain of gonorrhea that is resistant to the last drug available against it, and the harbinger of a sexually transmitted global epidemic.
- "Gonorrhoea treatment resistance risk falls but new diagnoses rise". Health Protection Agency. 12 September 2012. Archived from the original on 14 July 2014.
- "Prophylaxis for Gonococcal and Chlamydial Ophthalmia Neonatorum in the Canadian Guide to Clinical Preventative Health Care" (PDF). Public Health Agency of Canada. Archived (PDF) from the original on 10 March 2010.
- Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; & Mitchell, Richard N. (2007). Robbins Basic Pathology (8th ed.). Saunders Elsevier. pp. 705–706 ISBN 978-1-4160-2973-1
- Sadowska-Przytocka, A; Czarnecka-Operacz, M; Jenerowicz, D; Grzybowski, A (2016). "Ocular manifestations of infectious skin diseases.". Clinics in dermatology. 34 (2): 124–8. PMID 26903179. doi:10.1016/j.clindermatol.2015.11.010.
- Datta, SD; Sternberg, M; Johnson, RE; Berman, S; Papp, JR; McQuillan, G; Weinstock, H (Jul 17, 2007). "Gonorrhea and chlamydia in the United States among persons 14 to 39 years of age, 1999 to 2002.". Annals of Internal Medicine. 147 (2): 89–96. PMID 17638719. doi:10.7326/0003-4819-147-2-200707170-00007.
- GBD 2013 Mortality and Causes of Death, Collaborators (10 January 2015). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.". Lancet. 385 (9963): 117–71. PMC . PMID 25530442. doi:10.1016/s0140-6736(14)61682-2.
- "Gonorrhea – CDC Fact Sheet". CDC. 29 May 2012. Archived from the original on 16 December 2016. Retrieved 20 December 2013.
- "CDC – STD Surveillance – Gonorrhea". Archived from the original on 2008-03-06. Retrieved 2008-08-21.
- "CDC Fact Sheet – Chlamydia". Archived from the original on 16 December 2016. Retrieved 21 August 2008.
- "STD Trends in the United States: 2010 National Data for Gonorrhea, Chlamydia, and Syphilis". Centers for Disease Control and Prevention (CDC). 22 November 2010. Archived from the original on 24 January 2012.
- "Untreatable gonorrhoea 'superbug' spreading around world, WHO warns". The Daily Telegraph. 7 July 2017. Archived from the original on 7 July 2017.
- "Archived copy". Archived from the original on 3 October 2012. Retrieved 2 November 2012.
- Higgins, John (1587). The Mirror for Magistrates. as cited in the Oxford English Dictionary entry for "clap"
- Max Bender (1898). "Ueber neuere Antigonorrhoica (insbes. Argonin und Protargol)". Archives of Dermatological Research. 43 (1): 31–36. doi:10.1007/BF01986890.
- MedlinePlus Encyclopedia Neonatal Conjunctivitis
- W Sanger. History of Prostitution. NY, Harper, 1910.
- P. LaCroix. The History of Prostitution—Vol. 2. NY, MacMillan, 1931.
- Moen, Juliann (2017). Basic Healthcare Studies: Sexually Transmitted Disease. Lester Bivens. Alpha Editions. ISBN 9789386367570. Archived from the original on 8 September 2017.
- WE Leiky. History of European Morals. NY, MacMillan, 1926.
- Moen, Juliann (2017). Basic Healthcare Studies: Sexually Transmitted Disease. Lester Bivens. Alpha Editions. ISBN 9789386367570. Archived from the original on 8 September 2017.
- Jerse, AE; Bash, MC; Russell, MW (20 March 2014). "Vaccines against gonorrhea: current status and future challenges.". Vaccine. 32 (14): 1579–87. PMC . PMID 24016806. doi:10.1016/j.vaccine.2013.08.067.
- Gottlieb, Sami L.; Johnston, Christine (2017). "Future prospects for new vaccines against sexually transmitted infections". Curr Opin Infect Dis. 30 (1): 77–86. PMC . PMID 27922851. doi:10.1097/QCO.0000000000000343.
- Petousis-Harris, Helen (2017). "Effectiveness of a group B outer membrane vesicle meningococcal vaccine against gonorrhoea in New Zealand: a retrospective case-control study". Lancet. doi:10.1016/S0140-6736(17)31449-6.