Brazilian Protocol for Sexually Transmitted Infections, 2020: sexually transmitted enteric infections

Abstract The sexually transmitted enteric infections topic is one of the chapters of the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. The document was developed based on scientific evidence and validated in discussions with specialists. This article presents epidemiological and clinical aspects of these infections and guidance for service managers on their programmatic and operational management. The aim is to assist health professionals with screening, diagnosis, and treatment of people with sexually transmitted enteric infections and their sexual partners, in addition to supporting strategies for their surveillance, prevention, and control.

Highlighted excerpt: The incidence of anorectal sexually transmitted infections has increased over the last years, mainly due to the increase in the practice of unprotected receptive anal sexual intercourse. FOREWORD This article addresses sexually transmitted enteric infections, a topic that comprises the Clinical Protocol and Therapeutic Guidelines (PDCT) for Comprehensive Care for People with Sexually Transmitted Infections (STI), published by the Health Surveillance Department of the Brazilian Ministry of Health. For elaborating the PDCT, a selection and analysis of the evidence available in the literature were performed, and a panel of specialists discussed it. The document was approved by the National Committee for the Incorporation of Technologies in the Brazilian National Health System (Conitec) and updated by the panel of specialists in STI in 2020 1 .

EPIDEMIOLOGICAL ASPECTS
Enteric pathogens and anorectal infections can be transmitted through different sexual practices without barrier protection in receptive anal or oroanal sex 2 . The transmission of diverse agents occurs naturally through the fecal-oral route, generally caused by consumption of contaminated food or water. Sexual transmission is well described, and it can happen through direct oroanal practice or indirectly through oral sex after anal penetration or through the use of fingers or fomites 3 .
Anorectal STI incidence has augmented over the last years, mainly due to the increased frequency of unprotected receptive anal sexual intercourse 4 . Anorectal intercourse is common, although its exact frequency stays unknown due to asymptomatic infections and the lack of accurate epidemiological data. People with symptoms or anorectal lesions are usually referred to coloproctologists for assessment and management 5 .
Risks to health arising from anal sex seem to be significantly underestimated by sexually active men and women in North America, Latin America, Asia, Africa, and other regions. Among heterosexual people, the reported prevalence of using condoms are almost universally lower in anal sex than in vaginal sex 6 . Hepatitis A is a generally self-limited acute infectious disease caused by the hepatitis A virus, transmitted through the fecaloral route by ingesting contaminated food and water or intimate contact with an infected person 15 . Outbreaks associated with sexual transmission in MSM are described since 2016 by the European Centre for Disease Prevention and Control 16,17 . Symptoms after a four-week average incubation period are more common in adults and include fever, discomfort, nausea, anorexia, abdominal pain, and jaundice. Recurring hepatitis and acute hepatic insufficiency can also occur 18 . Shigellosis caused by the Gram-negative bacterium Shigella spp. is characterized by severe bacillary dysentery 19,20 . Regular sexual transmission outbreaks of Shigella sonnei and Shigella flexneri among MSM are reported since the 1970s 21,22 . Sexually transmitted shigellosis is linked to different behaviors, including using douche, recreational drug use, and fisting, a practice consisting of forearm or hand introduction in the partner's vagina or anus 8-10,11 .
The foremost intestinal protozoan infections of interest within STI scope are giardiasis and amoebiasis. Annually millions of people develop these infections, but only 10% to 20% of the infected individuals become symptomatic. The risk of death is more remarkable for amoebiasis due to its invasive nature 34 . Such protozoan infections characteristically present higher prevalences in areas where sanitary conditions are inadequate, especially in Africa, in the Indian subcontinent, and parts of Central and South America. People who have traveled to developing countries are possible vectors 35 . Such infections are generally contracted through the fecaloral route by ingesting contaminated water or food 36 . The higher incidence of Entamoeba histolytica enteritis among homosexual men seems attributed to direct oral-anal sexual practice 37,38 or through sex toys or fellatio. It can denote high-risk behavior and multiple exposures 11 . Giardiasis underdiagnosis in this context is frequent due to the low suspicion of such transmission routes 39,40 .
In giardiasis, the most common symptoms include diarrhea, oily stool, flatulence, and abdominal swelling 41,42 . There can be proctitis 43 . The average incubation period for giardiasis is one to two weeks, and the symptoms average three to ten weeks 44 . For amoebiasis, the wide specter of intestinal infection varies from asymptomatic to transitory intestinal inflammation up to fulminant colitis, including megacolon, peritonitis, and hepatic abscess 35,45 . The incubation period of intestinal amoebiasis is one to four weeks 46 .
Campylobacter spp. is one of the most worldwide common causes of bacterial gastroenteritis 47,48 . Many outbreaks have been reported, including resistance to antimicrobial drugs such as ciprofloxacin and macrolides 49 , Extra-intestinal infection is rare. Still, it can lead to complications, including bacteremia, lung infection, meningitis, or reactive arthritis, mainly in immunocompromised people 47,48 . Ingestion of contaminated food and water and contact with pets are among the principal forms of transmission. There are reports of fecal-oral sexual transmission in places of sexual encounters with recreational drug use 50,1 .
HSV infections are characterized by chronicity and recurrence, with variable latency periods. There are two different strains: HSV-2, responsible for genital lesions, and HSV-1, for extragenital ones, specially orolabial 52 . However, it is possible to find inversions in such order, without clinical specter differences. HSV-1 is commonly acquired in childhood and adolescence, while HSV-2 is linked to sexual activity. The infection risk increases with the number of sexual partners throughout life 53 .
Gonorrhea is a common bacterial infection, transmitted almost exclusively through sexual or perinatal contact, affecting mainly the urethral and cervical mucous membranes and, less frequently, those in the rectum, oropharynx, and conjunctive 54 . Rectal N. gonorrhoeae infection is acquired through receptive anal intercourse and perineal contamination with cervicovaginal secretions. Around 35% of women with gonococcal cervicitis will present a concurrent rectal infection through infection contiguous dissemination 55 .

CLINICAL ASPECTS
The presence of rectal bleeding and wounds or lesions in the anal and perianal area, possibly with pruritus and pain, producing secretions, indicate STI 23 .
Enteric pathogens cause gastroenteritis, which can have low (rectum) symptoms, such as pain, mucopurulent anal discharge, tenesmus and hematochezia, and high symptomatology (colon), such as diarrhea with a sudden start. When evolved with rectal distensibility loss, diarrhea becomes intense, and when the duodenum is compromised, vomits, and abdominal pains associated with colic occur 56,57 .
In severe cases, significant morbidity and mortality can be associated with diarrhea, dehydration, bacteremia, hemolytic uremia, and Guillain-Barré syndrome  .
The most significant complications encompass inflammation of the rectal mucosa extending to the colon, with bleeding as a substantial sign, in addition to diarrhea, which leads to symptom intensification due to rectal distensibility loss. When the duodenum is compromised, vomits and abdominal pains associated with colic occur 56 .

DIAGNOSIS
Diagnosis based only on clinical aspects lacks specificity, requiring laboratory examination to identify the enteric infection etiological agent and define its sexual transmission.
Serological markers -IgM and anti-HAV IgG antibodies -are specific examinations for hepatitis A laboratory diagnosis. Leukopenia, aminotransferase, and high bilirubin findings are unspecific 60 .
For identifying Shigella spp., bacteria insulation is conducted in cultures, mainly in hemoculture and coproculture, in addition to sensitivity tests to antimicrobial drugs for following resistance and drug interaction possible cases.
Amoebiasis laboratory diagnosis is usually based on microscopic and serological methods, including enzyme-linked immunosorbent assay, ELISA, and indirect hemagglutination assay, latex agglutination, and tests based on nucleic acid amplification 62 .
Intestinal amoebiasis diagnosis in many countries usually depends on fecal sampling microscopic examination regarding the presence or lack of E. histolytica and Giardia lamblia. The proportion of asymptomatic people infected with this protozoan is not clear 62 .
The diagnosis must be confirmed by detecting E. histolytica-specific antigen in stool to distinguish it from other nonpathogenic amoebae. Serological tests can contribute to the diagnosis of invasive diseases, such as amoebiasis. However, their sensitivity can vary according to the disease's type and stage 63 . Eliminating cysts of G. lamblia can be intermittent and last for weeks. Therefore, many samples must be collected for diagnosis. Collecting three samples on different days ideally allows identifying cysts in more than 90% of the cases compared with 50% to 70% of those with a single sample. ELISA or antibody direct immunofluorescence can identify the parasite, with 88%-98% sensitivity and 87%-100% specificity 64 . Endoscopic methods with aspiration and duodenal biopsy may be needed in cases of diagnostic greater difficulty 64,65 .
Campylobacter spp. diagnosis is performed through isolation of the organism from stool samples or rectal swabs using selective media before starting antibiotic treatment. The culture identifies the subtype and susceptibility to antimicrobial drugs. Rapid tests for such pathogens, including antigen tests and nucleic acid-based tests, are available in Brazil 65 .
Diagnosis of herpes infection is based on the clinical aspect, especially if the condition is recurrent, and on laboratory examinations, such as viral culture, antigen detection, and polymerase chain reaction 53 . For diagnosis and laboratory investigation of gonorrhea in symptomatic cases, using a swab for anal culture, antibiogram, and molecular biology detection are recommended. On the other hand, for asymptomatic individuals with receptive anal practice without condom use, the recommendation is biannual follow-up through anal swab for detection through molecular biology, highlighting that culture is less sensitive than molecular biology techniques. Extragenital material samples, particularly anal and pharyngeal, and molecular biology tests must necessarily be validated for such collection sites 14 .
TREATMENT Treatment of this infection group requires, at first, the identification or suspicion of the etiological agent, and it must start as soon as possible, not only aiming at relieving the symptoms but likewise other STI, also reducing transmission risk to other persons. Treatment includes antibiotics and parasiticide, in addition to hydroelectrolytic and symptomatic support medications.
Unspecific treatment for hepatitis A is conducted with hydration and symptomatic methods. The vaccine is the most efficient way for preventing transmission, which can also be applied after exposure together with immunoglobulin in people presenting high-risk 66 . For prevention in sexual contact, using an oral condom is the indication 67 .
The primary treatment for non-complicated Shigella spp. is conducted with ciprofloxacin, including azithromycin and ceftriaxone as alternative therapies. Prevention is accomplished through washing hands and food for consumption, in addition to sexual practices with protective barriers [68][69][70][71] , People living with human immunodeficiency virus, HIV, may have more severe and long-lasting shigellosis, mainly with T-CD4+ lymphocyte counting less than 200 cells/mm³. Antimicrobial therapy may be extended for six weeks 72 . Meanwhile, changes in mucosae can be gateways for HIV 25 .
For amoebiasis and giardiasis treatment, using nitroimidazole compounds, such as metronidazole, tinidazole, and secnidazole, is the recommendation, with high cure proportions. Using such drugs is a contraindication for women in the first trimester of pregnancy, breastfeeding women, and people with neurological disorders 35 . Albendazole and nitazoxanide are antiparasitic medications with efficiency similar to metronidazole against giardiasis and can be used as an alternative, in daily doses, for five to three days, respectively 73 . For giardiasis, symptoms typically improve within five to seven days after starting treatment. In the case of chronic forms, improvement is slower. In case of diarrhea prolongation, it is possible to request a parasitological stool examination for excluding giardiasis persistence 74,75 . Complications include hypokalemia, undernutrition, growth delay, cognitive deficits, arthritis, myopathy, irritable bowel syndrome, and chronic fatigue 76,77 .
Campylobacter spp. infection is self-limited and mild. Treatment is conducted with oral or parenteral hydration, depending on the disease severity and dehydration degree. Avoiding agents inducing intestinal mortality, as they can prevent infection resolution, is needed 49 . Antibiotics must also be considered for high-risk cases, such as immunocompromised and older people, and in case of more severe cases, with fever, hematochezia, or intense abdominal pain 78 . Antibiotic resistance, particularly resistance to fluoroquinolone, increased sharply since the 1990s. Different outbreaks were reported, including with resistance to antimicrobial drugs such as ciprofloxacin and macrolides 48 .
Treatment of HSV infection is based on using aciclovir and its derivatives valaciclovir and famciclovir, which present 4/7 better absorption through oral route and bioavailability. Topical aciclovir or other antiviral is effective in reducing symptoms, and intravenous use of aciclovir is recommended for special situations, such as disseminated disease, meningoencephalitis pictures, and pneumonitis. In occurrence cases equal to or higher than six episodes per year, suppressive therapy is the recommendation. Suppressive treatment duration varies, but it is generally longer than six months 50 .
For confirming N. gonorrhoeae as the infectious agent, ceftriaxone associated with azithromycin is recommended 14 . Treatment can also be conducted with presumptive diagnosis based on anamnesis on the history of receptive anal sexual history without protection 79  The diseases addressed in this article are transmitted through unprotected sexual intercourse and contaminated water, and food ingestion. Therefore, in addition to condom regular use, the recommendation of not performing sexual actions that may facilitate direct contact with feces, basic prevention measures, and sanitation are crucial.
General basic preventive measures include frequently washing hands, especially when preparing food, before the meals and after going to the toilet; drinking filtrated and chlorinated water; washing fruit and vegetables, and not ingesting food suspected to be contaminated 83,84 .
Sanitation is comprehended as infrastructure and operational facilities for drinking water provision and sewage and urban cleaning with solid residue management and draining and urban rainwater management, generating better sanitary conditions for the population.
Vaccination against hepatitis A, which, according to the National Immunization Program, is recommended in a single dose for all children between 15 months and five years old, is also effective prevention. Coinfection with hepatitis A virus is frequent among HIV-infected MSM. Studies suggest that early vaccination against hepatitis A in people living with HIV may not provide reliable protection against infection development of such virus. Therefore, post-exposure prophylaxis, immunoglobulin application, and the monovalent vaccine may be considered in hepatitis A virus high-risk recent situations, regardless of prior vaccine situation 66 .
The cure control of sexually transmitted enteric infections occurs through clinical follow-up after specific treatment.