Genital schistosomiasis
Encyclopedia
Genital schistosomiasis is a parasitic infection of the genitals which affects women, causing chronic illness. The infectious agent (one of five species of flatworms, Schistosoma haematobium) is transmitted via tainted water. It is the eggs shed by the worm and not the worm itself, however, which cause the damage. An estimated 9–13 million women are afflicted with genital schistosomiasis, primarily in 53 countries in sub-Saharan Africa and the eastern Mediterranean. The disease may be controlled with antiparasitics and improved education and hygiene.

Mucosal findings

Mucosal grainy, sandy patches seem to be pathognomonic for S. haematobium infection in the female
Female
Female is the sex of an organism, or a part of an organism, which produces non-mobile ova .- Defining characteristics :The ova are defined as the larger gametes in a heterogamous reproduction system, while the smaller, usually motile gamete, the spermatozoon, is produced by the male...

 genitals. S. haematobium infection probably also causes mucosal bleeding and inflammation. Grainy, sandy patches are significantly associated with S. haematobium ova only (OR 4.89, 95%CI 2.14-11.17, p<0.001). Genital S. haematobium ova are also significantly associated with homogenous yellow sandy patches in the genital mucosa (OR 2.94, 95%CI 1.35-6.44, p=0.007), mucosal bleeding (OR 8.13, 95%CI 2.01-32.9, p=0.003) and abnormal blood vessels (OR 5.16, 95%CI 2.04-13.07, p=0.001). The three latter phenomena are, however, also associated with other reproductive-tract diseases. Ova presence is not a predictor for ulcer
Genital ulcer
A Genital ulcer is an ulcer located on the genital area, usually caused by a sexually transmitted disease such as genital herpes, syphilis, chancroid, or thrush. Some other signs of having genital ulcers include enlarged lymph nodes in the groin area, or vesicular lesions, which are small, elevated...

s, papillomata, leukoplakia, polyps or cell atypia. The findings are the same in all adult age groups—indicating that genital lesions do not undergo a change with age, or that women by the age of 20 have already passed into a chronic state of infection. The full clinical significance of genital schistosomiasis has yet to be established. The concomitant blood-vessel friability and inflammation may give weight to circumstantial evidence for bidirectional transmission of HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

.

Epidemology

Up to 75% of women excreting S. haematobium ova in the urine may have schistosome ova in the uterine cervix, vagina
Vagina
The vagina is a fibromuscular tubular tract leading from the uterus to the exterior of the body in female placental mammals and marsupials, or to the cloaca in female birds, monotremes, and some reptiles. Female insects and other invertebrates also have a vagina, which is the terminal part of the...

 or vulva
Vulva
The vulva consists of the external genital organs of the female mammal. This article deals with the vulva of the human being, although the structures are similar for other mammals....

. Furthermore, some women reportedly have genital schistosomiasis even without urinary schistosomiasis. Studies in Tanzania
Tanzania
The United Republic of Tanzania is a country in East Africa bordered by Kenya and Uganda to the north, Rwanda, Burundi, and the Democratic Republic of the Congo to the west, and Zambia, Malawi, and Mozambique to the south. The country's eastern borders lie on the Indian Ocean.Tanzania is a state...

 and Zimbabwe
Zimbabwe
Zimbabwe is a landlocked country located in the southern part of the African continent, between the Zambezi and Limpopo rivers. It is bordered by South Africa to the south, Botswana to the southwest, Zambia and a tip of Namibia to the northwest and Mozambique to the east. Zimbabwe has three...

 have shown that up to 41% of women may have involvement of the lower reproductive tract without schistosome ova in the urine. However, genital schistosomiasis as a cause of morbidity is only rarely accounted for in overview publications, although there are exceptions.

Localization

S. haematobium oviposition may be distributed in pathophysiologically-vital areas in the pelvis
Pelvis
In human anatomy, the pelvis is the lower part of the trunk, between the abdomen and the lower limbs .The pelvis includes several structures:...

. Post mortem studies and histopathological material from surgery in the reproductive tract have shown that S. haematobium may be distributed in all the pelvic organs. Ova are most commonly found in the cervix, followed by the vagina, ovaries, Fallopian tubes, vulva and (rarely) the uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...

. There are only a few case reports of severe acute
Acute
Acute may refer to:* Acute accent* Acute angle* Acute * Acute * Acute toxicity...

 disease (such as ascites
Ascites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...

) with ovarian schistosomiasis, ectopic pregnancy
Ectopic pregnancy
An ectopic pregnancy, or eccysis , is a complication of pregnancy in which the embryo implants outside the uterine cavity. With rare exceptions, ectopic pregnancies are not viable. Furthermore, they are dangerous for the parent, since internal haemorrhage is a life threatening complication...

, and heavy infestation of the uterus during pregnancy.

Diagnosis

The crushed biopsy of genital tissue is considered the gold standard
Gold standard
The gold standard is a monetary system in which the standard economic unit of account is a fixed mass of gold. There are distinct kinds of gold standard...

 for the parasitological diagnosis of genital S. haematobium. However, the ova are located in highly-focal clusters and may be missed, especially with histological sectioning of a biopsy. Because this method leaves a wound in the genital area, and because women in parts of the schistosomiasis- and HIV-endemic areas might not have any choice regarding sexual intercourse
Sexual intercourse
Sexual intercourse, also known as copulation or coitus, commonly refers to the act in which a male's penis enters a female's vagina for the purposes of sexual pleasure or reproduction. The entities may be of opposite sexes, or they may be hermaphroditic, as is the case with snails...

 or be able to suggest the use of a barrier contraceptive method, taking a biopsy is an HIV transmission risk for the patient (and her partner) until the wound has healed.

Wet smears and Pap tests can contribute to the diagnosis, but have low sensitivity. In a cytology laboratory in Harare, Zimbabwe
Zimbabwe
Zimbabwe is a landlocked country located in the southern part of the African continent, between the Zambezi and Limpopo rivers. It is bordered by South Africa to the south, Botswana to the southwest, Zambia and a tip of Namibia to the northwest and Mozambique to the east. Zimbabwe has three...

, 44 of 1901 Pap smears were found positive; in Kampala, Uganda
Uganda
Uganda , officially the Republic of Uganda, is a landlocked country in East Africa. Uganda is also known as the "Pearl of Africa". It is bordered on the east by Kenya, on the north by South Sudan, on the west by the Democratic Republic of the Congo, on the southwest by Rwanda, and on the south by...

, only 1 in 30,000 smears were positive. Urinary filtration or dipsticks are insensitive indicators for genital S. haematobium. Moreover, the techniques themselves have been proven to be of poor value (or untested) in women of childbearing age. Increased levels of eosinophil cationic protein
Eosinophil cationic protein
Eosinophil Cationic Protein also known as ribonuclease 3 is a basic protein located in the eosinophil primary matrix. In humans, the eosinophil cationic protein is encoded by the RNASE3 gene.ECP is released during degranulation of eosinophils...

, Neopterin
Neopterin
Neopterin is a catabolic product of guanosine triphosphate , a purine nucleotide.Neopterin belongs to the chemical group known as pteridines. It is synthesised by macrophages upon stimulation with the cytokine interferon-gamma and is indicative of a pro-inflammatory immune status...

 or Immunoglobulin A
Immunoglobulin A
Immunoglobulin A is an antibody that plays a critical role in mucosal immunity. More IgA is produced in mucosal linings than all other types of antibody combined; between three and five grams are secreted into the intestinal lumen each day....

 in cervico-vaginal lavage have only limited value in the diagnosis of female genital schistosomiasis.

Treatment

For clearance of urinary ova excretion and reduction of morbidity, a single oral dose of praziquantel
Praziquantel
Praziquantel is an anthelmintic effective against flatworms. Praziquantel is not licensed for use in humans in the UK; it is, however, available as a veterinary anthelmintic, and is available for use in humans on a named-patient basis....

 40 mg/kg (or 60 mg/kg in 2 divided doses) is recommended with food and drink in order to minimise gastrointestinal side effects. Based on a number of reports, WHO
Who
Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...

 has decided to also recommend praziquantel to pregnant and lactating women. Treatment for urinary schistosomiasis has been found equally effective in HIV-positive and -negative patients. Praziquantel does not seem to influence plasma HIV viral load in S. mansoni-infected
Schistosoma mansoni
Schistosoma mansoni is a significant parasite of humans, a trematode that is one of the major agents of the disease schistosomiasis. The schistosomiasis caused by Schistosoma mansoni is intestinal schistosomiasis....

 individuals.

As of 2011, one study has directly explored the treatment of genital schistosomiasis. Although urinary ova excretion decreased following treatment (OR, 10.3 95% CI 3.8-27.8, p<0.001), praziquantel was not associated with a significant reduction in genital lesions or contact bleeding (p=0.31-0.94). Sandy patches remained strongly associated with contact bleeding and vessel abnormalities, even after treatment, and findings were independent of HIV status. Such lesions (common, and apparently refractory to treatment for at least 12 months) may be an important risk factor for both the acquisition and transmission of the human immunodeficiency virus in sexually-active women.

In the urinary tract, the effect of praziquantel has largely been determined by resolution of lesions detectable by ultrasound scan
Medical ultrasonography
Diagnostic sonography is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions...

 and decreased ova excretion in the urine. Sandy patches in the bladder have been found post-mortem, in surgical specimens or as seen by cystoscopy
Cystoscopy
Cystoscopy is endoscopy of the urinary bladder via the urethra. It is carried out with a cystoscope.Diagnostic cystoscopy is usually carried out with local anaesthesia...

; however, there have been no large-scale cystoscopic studies on the natural course of sandy patches or the effect of praziquantel on the clinical morphology of bladder lesions. The outcome of treatment in the urinary tract may be variable, depending on four factors:
  • Age of the patient
  • Pre-treatment intensity of infection
  • Degree of fibrosis
    Fibrosis
    Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...

     or calcification
    Calcification
    Calcification is the process in which calcium salts build up in soft tissue, causing it to harden. Calcifications may be classified on whether there is mineral balance or not, and the location of the calcification.-Causes:...

  • Site of the lesion


Urinary-tract lesions in younger patients are more responsive to treatment, and this may be so in the genital tract as well. However (as mentioned previously), given the same age group and exposure rates, lesions in the bladder decrease faster than lesions in the upper ureteres after treatment. Hence, the effects of treatment in the urinary tract cannot automatically be extrapolated to the genital tract.

Praziquantel (which kills the mature worm) is the standard treatment for all types of schistosomiasis, and there will be a decrease in S. haematobium
Schistosoma haematobium
Schistosoma haematobium is an important digenetic trematode, and is found in the Middle East, India, Portugal and Africa. It is a major agent of schistosomiasis; more specifically, it is associated with urinary schistosomiasis....

 ova excretion in the urine 4–26 weeks after treatment. Occasionally, repeated courses are be necessary to cure S. haematobium in the urinary tract—even in children, and sometimes in returned travellers long after the worm should have matured. Case reports indicate that praziquantel may have an immunomodulatory effect on lesions, so the lesions resolve. However, although praziquantel kills the egg-laying worms, lesions not yet visible may develop around ova already deposited in tissues. Once ova deposition has occurred in the cervix, ova excretion and lesion development are independent processes; praziquantel affects the former almost immediately, but possibly not the latter.

Egg excretion in the urine of lesions in genital mucosa are not directly comparable, and little is known about the effect of treatment in the genital tract. Prior to the Zimbabwean study there had been no longitudinal study, and only a few case reports on the effects of treating genital schistosomiasis. The case reports describe regression of sandy patches in lower-genital-tract schistosomiasis after treatment with praziquantel for a course of 1 week to 6 months. After less than two years, treatment has been described to resolve schistosomal infertility (with pregnancy) in up to 6 of 13 infertile women.

It has been hypothesised (and debated) that the release of worm fragments upon death enhances immunological protection against reinfection, and possibly also removes the immunosuppressive effect of the adult worm. Moreover, there is a second effect on transmission. By interfering with the cycle, there will be decreased infection of the snails and decreased excretion of cercaria and infection of humans, especially if mass chemotherapy is carried out in the low-transmission season. Other forms of treatment— such as arthemeter (recently tested), metrifonate
Metrifonate
Metrifonate or trichlorfon is an irreversible organophosphate acetylcholinesterase inhibitor.it is a prodrug which is activated non-enzymatically into 2,2-dichlorovinyl dimethyl phosphate ....

 (for S. haematobium, recently withdrawn from the market), niridazole
Niridazole
Niridazole is a schistosomicide. It is used to treat schistosomiasis, the helmintic disease caused by certain flatworms from the genus Schistosoma . It is also known by its trade name Ambilgar. It is usually is given as tablets. Niridazole has central nervous system toxicity and can cause...

, oxamniquine
Oxamniquine
Oxamniquine is an anthelmintic with schistosomicidal activity against Schistosoma mansoni, but not against other Schistosoma spp. Oxamniquine is a potent single-dose agent for treatment of S...

, hycanthone
Hycanthone
Hycanthone is a schistosomicide. It is a metabolite of lucanthone....

, amoscanate
Amoscanate
Amoscanate , also known as nithiocyamine, is an experimental anthelmintic agent of the arylisothiocyanate class which was found to be highly effective in animals against the four major species of schistosomes which infect humans, and is also highly active against hookworm infection. However,...

 and antimony (no longer in use for schistosomiasis)—will not be discussed here.

WHO has recommended mass treatment for women and children in schistosomiasis-endemic areas, to prevent long-term morbidity. This is often done through schools, most often with the active participation of the teaching staff. Mass treatment has been recommended at six-month to three-year intervals, depending whether there is a continuous high or seasonal low transmission (more often with the former). Studies have found that the prevalence of schistosomiasis is higher in non-enrolled children. Moreover, girls are often underrepresented in schools; in an Egyptian study, it was estimated that 59% of infected boys but only 18% of infected girls were reached through school programmes.

Effects of travel

"Travellers" are defined as coming from non-endemic areas and exposed for a limited time, whereupon they return to a non-endemic site. Schistosomiasis (in particular genital schistosomiasis) has been neglected in travellers, despite the risk of infection with certain types of increasingly-common travels such as rafting and other forms of ecotourism
Ecotourism
Ecotourism is a form of tourism visiting fragile, pristine, and usually protected areas, intended as a low impact and often small scale alternative to standard commercial tourism...

. 18% of asymptomatic travellers to Africa, exposed to freshwater and subsequently screened at the Hospital for Tropical Diseases in London, were found to have schistosomiasis. Katayama fever, fatigue and dysuria
Dysuria
In medicine, specifically urology, dysuria refers to painful urination.Difficult urination is also sometimes described as dysuria.It is one of a constellation of irritative bladder symptoms, which includes urinary frequency and haematuria....

 are the commonest presentations in symptomatic travellers. There are, however, a few case reports where genital schistosomiasis has been found years after a reasonably short exposure.

The manifestations of schistosomal disease in non-genital organs, immunological considerations, immunodiagnosis, S. haematobium parasite adaptation, snail control and schistosomiasis’ relationship to cancer are beyond the scope of this article. Although S. mansoni, S. intercalatum
Schistosoma intercalatum
Schistosoma intercalatum is an important parasite. It is one of the major agents of schistosomiasis.A freshwater snail Bulinus forskalii is an intermediate host for Schistosoma intercalatum....

, S. japonicum
Schistosoma japonicum
Schistosoma japonicum is an important parasite and one of the major infectious agents of schistosomiasis.This parasite has a very wide host range, infecting at least 31 species of wild mammals, including 9 carnivores, 16 rodents, one primate , two insectivores and three artiodactyls and therefore...

 and S. matthei may affect the genital organs and the magnitude of the problem is not known.

See also

  • Parasitology
    Parasitology
    Parasitology is the study of parasites, their hosts, and the relationship between them. As a biological discipline, the scope of parasitology is not determined by the organism or environment in question, but by their way of life...

  • Schistosomiasis
    Schistosomiasis
    Schistosomiasis is a parasitic disease caused by several species of trematodes , a parasitic worm of the genus Schistosoma. Snails often act as an intermediary agent for the infectious diseases until a new human host is found...

  • Schistosoma haematobium
    Schistosoma haematobium
    Schistosoma haematobium is an important digenetic trematode, and is found in the Middle East, India, Portugal and Africa. It is a major agent of schistosomiasis; more specifically, it is associated with urinary schistosomiasis....

  • Schistosoma japonicum
    Schistosoma japonicum
    Schistosoma japonicum is an important parasite and one of the major infectious agents of schistosomiasis.This parasite has a very wide host range, infecting at least 31 species of wild mammals, including 9 carnivores, 16 rodents, one primate , two insectivores and three artiodactyls and therefore...


External links

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