doxycycline

Doxycycline is a widely used antibiotic of tetracycline. It is prescribed adults for the treatment of severe microbal diseases on the west market. It has a strong action, and therefore it is not taken by children. Due to the strong action the effect starts within several days.

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Gonorrhea is a sexually transmitted infection caused by the bacteria Neisseria gonorrheae of genus neisseria. It's a primary human pathogen. It causes infection of the genitourinary tract of both men and women who are sexually active and may also lead to other disseminated gonococci infection such as septic arthritis, gonnocococemia and opthalmioc neonatorum.

Neisseria gonorrheae is an intracellular obligate parasite.

Morphology

When a smear of urethral discharge is viewed under a microscope, the bacteria appear to be in pairs and are kidney shaped and thus termed as diplococci.

They are capsulated with a mucous capsule that is antiphagocytic i.e. prevent phagocytosis of the bacteria.

Classification

Like other bacteria neisseria gonorhhea belongs to the domain bacteria.

  • Donmain: bacteria
  • Phylum: proteobacteria
  • Class: betabacteriaa
  • Order: neisseiriaceae
  • Genus: neisseria
  • Species: gonorhohhea.

Other human pathogenic neisseria is the neisseria menengitidis that cause meningitis in man.

Laboratory features and cultural characteristics.

Just like other neisseria N. gonorrheae is difficult to culture using normal laboratory media such as blood agar.

They are facultative aerobe and anaerobes. Growth is enhanced in 5-10% carbon dioxide.

The growth ph range of N. gonorrheae is about 7.0-7.4 and optimum temperature growth of 36 degrees centigrade.

Culturing in Thayer - martin media

Thayer-martin media is heated Blood Agar that contains vancomysin, nystatin, and colistin antibiotics. It's a selective media for the isolation of neisseria gonorhhea bacteria. The antibiotics inhibit growth of other bacteria that may be in the sample especially the non pathogenic neisseria

Colonies in Thayer martin media appear small rounded, translucent and gibbous with the center slightly darker than the margin. The surface is finely granular and the margins are lobular or lobate when incubated for 24 hours. These colonies are also emulsifying easily.

On further incubation to about 48 hours the colonies become bigger measuring about 1.5-2.5mm in diameter with crenate margins and opaque raised centers.

Biochemical reactions

  1. They are oxidase positive; they produce cytochrome c oxidase enzyme which act on tertramethyl-p-phenylenediamine to indole phenols which turn purple
  2. They ferment glucose but they don't ferment maltose. This differentiates it from neisseria mengititidis which ferments maltose. It does not ferment sucrose and lactose.

Epidemiology

The world health organization (WHO) estimates that a incidence of 88 million new infections occur worldwide each year.

In the U.S.A alone, gonorrhea is the second highest cause of sexually transmitted infection just after Chlamydia.

The Center for Disease Control and Prevention estimates that in the U.S.A there were 820,000 people get new infection yearly. However, the infection rate decreased in the following years due to control programs put in place to counter the high incidence. In the US the most affected population in the blacks than the white as per the statistics in 2010.

UK is also a hard-hit country recording 196 infections in every 100,000 people.

Scientist has warned of emergence of incurable gonorrhea in 2017 as such cases were reported in Japan, France and Spain.

Pathology of Neisseria gonorhheae

One acquires infection by sexual contact or direct contact as seen in neonates during birth. The incubation period is about 4 to 5 days but may be slower up to 30 days in case of immunnosupression. Once the infection has occurred, the bacteria then attach itself on the surface of the cell by use of pilli or fimbrae. They only infect non ciliated cells. After attachment of the bacteria they enter the cell though the process of endoctytosis where they are carried into the cell where they multiply and cause infection after a few days the bacteria then causes lysis of the cell by production of the lipopolysacharide and the peptidoglycan. Due to its antigenic properties the peptidoglycan will activate the complement system of the cells while the lipopooligosacharide will activate production of the tumor necrosis factor (TNF). This leads to an inflammatory reaction characterized by migration of the leukocyte to the site of infection and cell lyses. Ironically the bacteria is not destroyed instead its released from the cell and they develop the fimbrae which make them antigenic and infectious again.

Diseases in human

The main infections in human are; gonorrhea, ophthalmic neonatorum, bacteremia and disseminated aseptic arthritis.

Clinical manifestations include;

  1. Acute urethritis in men
  2. Frequent urination and purulent penile discharge
  3. Stricture formation occur due to dysuria
  4. Anal rectal infection may occur

    Manifestation in women

    1. In some patients asymptomatic carriage may occur. Such patients are infectious but they do not suffer the ill effects of the infection.
    2. Salphingitis followed by pelvic inflammation may occur due to extending of the infection to the bertholin gland, fallopian tubes and the endometrium. If unchecked may lead to sterility.
    3. Pharyngitis may occur following oral sex and infection. This is termed as gonnococcal pharyngitis.
    4. If figure autoinoculation occurs it may lead to conjunctivitis in the adult.

Neonatal infections

In neonate's gonorrhea manifests itself as conjunctivitis. The infection starts as a discharge of watery fluid in the eye which become more purulent and finally blood discharge in the eye may occur. There is also itching of the eye which may make the baby uncomftable.

Disseminated gonorrhea

In human the best example of disseminated infection is the septic arthritis. This occurs following the dissemination of the bacteria from the local site of infection.

It's characterized by pain in the tendons of the joints. It mostly affects the knee joint.

Other gonoccocal infection includes gononoccocaemia i.e. the presence of bacteria in blood and gonoccal skin lesions may occur at other sites in skin though it's not a major disease.

Diagnosis

The main samples used for screening of Neisseria gonorrheae is the swabs from the site of infection mainly the vaginal swabs and penile discharge swabs. These swabs can also be obtained from the under eyelid incase of conjunctiva infection and the throat swabs in oral infection. The recommendation is that the swabs should not be obtained using splinters and cottons for they produce inhibitory effects on the bacteria. Instead swabs with wire, calcium or rayon should be used to obtain the swabs. The samples may be used for;

  1. Culturing.
  2. These bacteria are cultured in Thayer martin media for they cannot grow on other Medias. They can also be cultured in heated blood agar when swabs are obtained from non predilectic sites.

    If the center for diagnosis or laboratory is far they should be inoculates in transport media. The media is enriched with carbon dioxide for they will enhance growth of the bacteria. However one should ensure diagnosis is done within 48 hours.

  3. Gram staining.
  4. It's the most sensitive and specific way of screening for the Neisseria gonorrheae. They appear as diplococcus inside polymorphs and are kidney shaped and gram negative. However this occurs mainly in symptomatic men and women only.

  5. Oxidase test.
  6. They turn purple in oxidase reagent confirming that it is gonorrhea. The biochemical test should be used to confirm the gram staining results.

  7. Antibiotic resistance test.
  8. The bacteria produce extra chromosomal genes that code for production of beta lactamase enzyme which act on beta lactam antibiotics such as penicillin. Bacterial isolates from viable sources should be the only one used to test for resistance as to avoid contamination. Pieces of filter paper soaked in penicillin do not produce any inhibition on the media containing resistant bacteria.

  9. Nucleic Acid Amplification Test (NAAT).
  10. This is a more specific test method for the test of Chlamydia and neisseria. It detects presence of the bacterial nucleic acid in the sample. It's highly sensitive that can detect infection in asymptomatic men and women. In this test the DNA in the sample is amplified and compared with commercially prepared nucleic acid.

Considerations for screening

Done mainly among predisposed individuals who include;

Men who have sex with men. They have a high tendency of contracting infection as compared to straight men

Pregnant women. They should screen to prevent neonatal infections.

Sexually active women of 25 years and above have an increased chance of contracting an infection thus should screen at least once a year.

Individuals with multiple sex partners and those who engage in unprotected random sex should also screen regularly for gonorrhea.

Treatment

alertSince the emergence of drug resistant gonorrhea CDC recommended that a combination of drugs should be used to treat it and this is known as dual therapy. It involves the use of cephalosporin and azithromycin in order to reduce resistance to cephalosporin. Also, azithromycin should be preferred to doxycycline due to the fact that its administered as a single dose.

In an uncomplicated gonorrhea the regimen are; Ceftriaxone 250mg IM in a single dose plus Azythromycin 1g in a single dose. This is done simultaneously in a single dose as a dual therapy. This regimen is highly sensitive in treatment of non-complicated gonorhhea at local sites.

In case cefttriaxone is not available then an alternative of cefixime 400mg orally in a single dose with azithromycin can be used to treat uncomplicated infection.

In order to ensure that the regimen is dully followed the dose should be given on site by the physician.

Patients who have HIV should be treated the same way as other patients

Pregnant infected women should be treated as well with a regimen of Ceftriaxone 250mg single IM dose concurrently with a single dose of 1g Azythromycin.

Management

The main management of the infection is abstinence fro unprotected illicit sex and use of protection. Behavioral changes should be encouraged among the adolescent and married in order to avoid new infections.

Those who are diagnosed of gonorrhea should also ensure that they abstain from sex until confirmed free of the infection.

Sexual partner of an infected individual should also be screened for the disease in order to prevent re infection. If found to be infected, the partner should be put under regimen promptly as well.

Follow up

Follow up is done in order to monitor cephalosporin failure. Cephalosporin failure may occur due to drug resistance and is manifested by the presence of the symptoms seven days after the treatment regime is started and that the patient has not engaged in any sexual contact activity. Such patients should be monitored and treated again with alternative drugs.

Also, in follow ups all children with gonorhhea infection should be tested for Chlamydia as the both portray ophthalmic neonatorum.

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