Caracterización de las variables del clima de aula, propuestas por Moos y Trickett.

Several intestinal parasites have being implicated as the major contributors of morbidity in HIV infected persons in Nigeria. Intestinal parasites frequently encountered include Cryptosporidium parvum, Isospora belli, Entamoeba histolytica, Giardia intestinalis, Truchuris trichiuria, Ascaris lumbricoides, Stronglyoides stercoralis and hook worm species.^47-49

I. Cryptosporidium parvum:

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Cryptosporidium parvum is regarded as the common cause of persistent diarrhoea in children and severe prolonged diarrhoea in HIV/AIDS patients.^82-85 Cryptosporidiosis occur in most people by human to human faeco-oral transmission but infection may also occur from animal to person and water borne transmission.⁸² Before the advent of antiretroviral therapy, Cryptosporidium parvum was identified as the common cause of severe chronic watery diarrhoea among AIDS patients.⁸³ Cryptosporidiosis is more prevalent in areas with poor waste disposal system, poor water supply systems and in those working in animal husbandry.⁸⁴ Cryptosporodiosis has been reported in 3.4%

of HIV infected children in the United States of America and Europe.⁸⁵ Serological studies indicate that prior to the availability of highly active antiretroviral therapy, 10-15% of patients with AIDS developed cryptosporidiosis during their lifetime in the USA and Europe.⁸⁵ In developing countries, the prevalence of cryptosporidiosis in AIDS patients was reported to be as high as 64%.^83,86 A study in Benin City, Nigeria, reported a 27.6% prevalence of cryptosporidiosis among HIV/AIDS patients prior to commencement of antiretroviral therapy (ART).³⁴ This was consistent with an unpublished work done by Onyekwena in Jos, Nigeria.⁴² Cryptosporidium species was not isolated from stool samples of HIV/AIDS patients who were on HAART in Brazil.³³ Improved immune status, direct effect of some antiretroviral drugs, good hygienic practice and the use of cotrimoxazole prophylaxis have been fingered as factors responsible for the low prevalence of this parasite among patients on HAART.³³

Cryptosporidium parvum can survive, multiply and reproduce in the gastrointestinal tract, respiratory tract and the billiary tract.⁸² When the infective form of the parasite is ingested, it immediately invades the intestinal epithelium where it sporulates to produce sporozoites. The sporozoites invade the enterocytes and mature into an adult worm.^82,85 Electro-microscopic studies have shown that cryptosporidium species may cause several enterocytic changes which include

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mitochondrial swelling, microvillous loss and dilatation of endoplasmic reticulum.⁸² These changes, however, have not been linked to persistent diarrhoea seen in infected patients.^82,83 Mechanism by which cryptosporodium causes diarrhea include a combination of increased intestinal permeability and chloride secretion which are all thought to be caused by host response to infection.⁸²

Clinical features of cryptosporidiosis among immunocompetent patients include acute watery diarrhea lasting for 7-10 days, abdominal cramp and low grade fever.^82,83 In severely immunocompromised patients, especially those infected with HIV, the clinical features consist of gradual onset of diarrhea which subsequently gets profuse and cholera like-which and can be complicated by fluid depletion and malabsorption.⁸² There may be substantial weight loss and wasting. Billiary involvement may include acalculus cholecystitis, sclerosing cholangitis, papillary stenosis or pancreatitis.⁸² These are comonly seen in AIDS patients with low CD4 cell count.^82-85 Physical findings are non-specific.^82,83 The introduction of HAART marked a turning point in the management of cryptosporidiosis among HIV patient. Improved immune status reduced the frequency and the severity of this disease which ultimately impacted positively on the health status of these patients.³³

In our hospital setting, diagnosis is made by faecal smear using modified acid fast stain and stool antigen test. Cryptosporidium parvum oocyst in an acid fast stain smear appears as small oval pink red stained bodies measuring 4-6um in diameter.⁸² Other diagnostic tests include the polymerase chain reaction (PCR) technique, immunologic florescence assay or enzyme linked immunosorbent assay, electron microscopy of the stool and imaging studies.^82,83

Treatment is non-specific.⁸² Several drugs have been tried without 100% effectiveness.⁸² The introduction of anti-retroviral drugs has markedly reduced the prevalence of cryptosporidiosis

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among HIV/AIDS patient.³³ It has been demonstrated that a 3 day course of Nitaxozanide can significantly reduce the duration and the severity of diarrhea among children in the USA.⁸⁴ This correlates with a study done among Egyptian children which reported an 88% clinical response.⁸² However, a study in Zambia reported no significant difference between Nitazoxanide and placebo in clinical response.⁸⁵

Supportive treatment are mainly those measures not directed at cryptosporidium parvum. It is aimed at ameliorating life threatening symptoms and signs. Rehydration, correction of electrolyte inbalance and nutritional supplementation are life saving measures in severe cryptosporidiosis in HIV infected and uninfected person. The use of antimotility drug such as Atropine-Diphenoxylate (lomotil) is helpful in reducing the frequency of diarrhea.⁸²

II. Isospora belli

Isospora belli is a coccidian Protozoa responsible for severe prolonged diarrhoeal disease among HIV/AIDS patients.^81,86 It is the second commonest opportunistic protozoa when CD4 falls below 200 cell/L after Cryptosporidium parvum. ^34,81 Isosporiasis has been reported in most developing countries where poor sanitary practices and poor sewage disposal system are widespread.^81,86 The infection is very rare among immunocompetent patients which may manifest as a self-limiting acute watery diarrhoea. In severely immunocompromised patients (e.g HIV/AIDS), diarrhoea is prolonged and severe and leads to severe dehydration and severe wasting.⁸⁶ The introduction of ARV’s has reduced the prevalence and severity of this infection among HIV/AIDS patients.³³ Transmission of infective stage of Isospora belli is by human to human faeco-oral route. But infection may also occur by water borne transmission. Isosporiasis is most prevalent in areas with poor waste disposal system and a concomitant high rate of HIV transmission.⁸⁷

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Arun Kumar et al identified isospora belli as the second most common opportunistic intestinal protozoa isolated from stool sample of HIV patients in India.⁸⁸ Cardoso et al reported a rate of 4.04% in northwestern region of Sao Jose, Braziland Mohammed et al observed a prevalence rate of 7.4% in Jimma, Ethiopia.^89,90

Akinbo et al reported a 3.1% prevalence of this parasite among HIV/AIDS patients in Edo state, Nigeria.⁸⁶ Akinbo et also observed that there was no significant association between isosporiasis and gender or age group among the patients in Edo state, Nigeria. However, worthy of note is the marked increase in the prevalence of this infection among HIV/AIDS patients when the CD4 count falls below 200cell/l.⁸⁶

On ingestion of the infective form of this parasite, it migrates to the small intestine and matures into a sporozoite.⁸⁷ The sporozoite invades the epithelial lining of the upper small intestine, destroying the brush border.⁸⁷ This may be the cause of diarrhoea seen in infected patients.

Isosporiasis presents as a self limiting acute watery diarrhea among immunocompetent patients.⁸⁷ Common clinical features of isosporiasis among immunocompromised patients include severe chronic diarrhea, malabsorption, malnutrition and severe wasting which may result in significant mortality.⁸⁷

Diagnosis is made by finding the typical oocyst in faecal sample specimen.^87,88 The modified Ziehl-Neelsen stain is commonly in use to identify the oocyst of I.belli microscopically.⁸⁷

Treatment of isosporiasis is non-specific, however, cotrimoxazole (septrin) has been found to be helpful.^33,87 Furthermore, protease inhibitors have some anti-protozoal effect on isospora species.³³

III. Entamoeba histolytica

Entamoeba histolytica has been identified as a common gastrointestinal protozoa isolated from the stool sample of both immunocompetent and immunocompromised patients.^33,34,91 Amoebiasis is a

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common cause of abdominal cramp and bloody mucoid stool (colitis) among children in sub-Saharan region where bad hygienic practices, low socioeconomic status, poverty and ignorance are common national indices.^22,91 Entamoeba histolytica has been described as one of the commonest intestinal pathogenic protozoas isolated from the stool samples of HIV/AIDS patients.

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The infective form of this parasite can be transmitted in an encapsulated form known as the cyst, which enhances its survival outside the human body.^81,87 The cyst can be transmitted by contaminated water or food or spread directly by person to person contact. This explains why the parasite is widespread in sub-Sahara Africa where poverty and overcrowding is prevalent. With the high prevalence of HIV infection in this region, a coinfection is more likely with devastating consequences on the host.^87,91

Samuel et al observed that an estimated 50 million people suffer from this infection on yearly basis, worldwide.⁹² Ahaver et al report a 3.3% prevalence of this infection among adults in Abuja, Nigeria.⁹³ Unlike the C.parvum and I.belli, E. histolytica is not an opportunistic parasite but several authors have reported an increase in the prevalence of amoebiasis among HIV/AIDS patients.^26,30,32 A 3.3% prevalence was reported in Benin city Nigeria.³⁴ This was close to the prevalence (5.8%) observed among HIV patients in Abuja, Nigeria. Some authors, however, reported higher prevalence.^48,87

Intestinal infections occur through the ingestion of the mature quadranucleate infectious cyst, in contaminated food or drink, and also by hand to mouth contact.^87,91 These are passed unaltered through the stomach as the cyst wall is resistant to gastric juice. In the terminal ileum, encystment takes place. This releases a motile trophozoite which invades the sub mucous layer of the colon

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causing necrosis of the intestinal mucosa. Invasion into the blood stream may lead to extra intestinal lesion.^87,91

It is believed that many individuals carry the pathogen without any obvious clinical disease(asymptomatic cyst passers).^87,91 In immunocompetent patients, about 90% of infection is asymptomatic and the remaining 10% produces a spectrum of clinical syndrome.⁸⁷ Incubation period is variable which may be as short as few days or as long as many months.^87,95 The usual course is chronic with intermittent diarrhea and abdominal cramp.^87,94,95 This may progress to bloody diarrhea with mucus and is sometimes accompanied by systemic symptom such as nausea, vomiting, headache and anorexia.^87,95 Complications are unusual but more common among Immunocompromised patients (e.g HIV/AIDS).^,87,95 They may present with severe symptoms such as amoebic colitis, weight loss, amoebic liver abscess, pleuropulmonary amoebiasis.⁹⁵

Diagnosis is made by detection of motile trophozoite containing red cells in the stool sample during stool examination.^91,93 Other investigations include barium enema examination which may show colonic ulceration but are rarely diagnostic.⁹⁴ The amoebic florescent antibody test is positive in at least 90% of patients with liver abscess and 60-70% with active colitis. Seropositivity is low in asymptomatic passers.^87,94,95,

Metronidazole is the drug of choice in the treatment of amoebiasis. Metronidazole 800mg three times daily for 5 days is given in amoebic colitis.^94,95 A lower dose of 400mg three times daily for 5 days is usually adequate in liver abscess. Some patient may require surgical drainage of abscess.^94,95 alternative drugs include tinidazole, dihydroemetine, diloxanide furoate and chloroquine.⁹⁴

36 IV. Ascaris lumbricoides

Ascaris lumbricoides is the largest intestinal nematode of humans, reaching up to 40cm in length.⁸⁷ Peter and his team, in a review of the prevalence of neglected tropical diseases (NTD) in sub-Sahara Africa region, ranked Ascariasis as the third most common intestinal parasitic infestation in sub-Sahara African (SSA) region after E.hystoltica and hookworm.²² Ascaris lumbricoides, has been described as the most common intestinal helminths encountered during stool examination of HIV/AIDS patients.^30,31,33

The actual worldwide prevalence of this parasitic infection is not known. The WHO observed that about one sixth of the world population may be harboring this parasite with the SSA region having 21% of it.²⁷ Peter et al, in a peer review of the prevalence of NTDs observed about 173 million (25%) of SSA population is infected with A. lumbricoides.²² This was twenty five times higher than the observation (0.8%) made by Wilday et al among poor communities in Poland.⁷³

A 33.5% prevalence of ascariasis has been reported among HIV/AIDS patients in Benin City, Nigeria by Akinbo et al.³⁴ This is in keeping with reports by Odesiji et al in southwestern Nigeria.⁴⁹ However Babatunde et al and Abaver et al in Ilorin southwestern Nigeria and Abuja, north central Nigeria reported a lower prevalence of 6.7% and 2.5% respectively.^32,93 Overall, ascariasis is more prevalent in the subtropics where the warm moist soil serves as a suitable intermediate habitat for the infective stage of this parasite.^87,91,93 Bad sewage disposal habits and other unhygienic practices enhance the transfer of this parasite to other human host.²⁷ Overcrowding, low socioeconomic status, malnutrition and HIV infection enhance the spread and severity of this parasite among the populace.^27,34

An ingested egg hatches in the duodenum into a larva and penetrates the intestinal mucosa.^87,91 It is transfered via the blood stream into the lungs. It invades the alveolar space ascends the trachea

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and descends into the oesophagus to reach the small intestine. The mature adult worm lays immature eggs which are passed out through faeces.^87,91 These eggs undergo maturation and can find their way into the human host via contaminated hand, vegetables, currency e.tc.^87,91

In immunocompetent patients, clinical features include abdominal pain, malnutrition and Ileum.⁹⁵ Among immunocompromised patients there has not been observed differences in clinical manifestation. Kar et al reported a case of severe eosinophilic pneumonitis in an HIV positive patient which may mimic Pneumocystic jirovice pneumonia and pulmonary tuberculosis (PTB).⁹⁶ Ascariasis may also be a cause of unexplained severe wasting, frequent non-etiologic cough and frequent unexplained diarrhea seen among HIV positive patients.⁹⁵

Diagnosis is made microscopically by finding ova in the faeces.⁹⁵ Adult worm can be expelled rectally or orally.⁹⁵

Mebendazole 100mg 12 hourly for 3 days, albendazole 400mg or piperazine 4g as a single dose are effective against ascariasis.⁹⁵

V. Hookworms

Hookworm is another common intestinal helminth isolated from stool samples of HIV infected people in Nigeria.³⁴ It consists of two species i.e. Ankylostoma duodenale and Necator americanus.

Necator americanus is most endemic in west, east and central Africa.⁹¹ It is the main cause of iron deficiency anaemia.^95,97 Most infected individuals are asymptomatic.⁹² Hookworm disease develops from contribution of three factors -a heavy worm burden, prolonged duration of infection and inadequate iron intake - resulting in iron deficiency anaemia and hypoprotienemia.^87,97

Necator americanus is the most prevalent hookworm specie in the subtropics with the older children being the most vulnerable. Peter et al in a study of NTDs in Sub-sahara African region reported a 25% prevalence of hookworm infestation.²² The study ranked hookworm as the most

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common soil transmitted helminth in SSA region.²² Babatunde et al in a cross sectional study among seronegative and seropositive patients in Ilorin, Nigeria observed no difference (7.8% and 7.8% ) of Hookworm infestation among them.³² Conversely, Abaver et al observed a small rise 7.8% among seronegative patients compared to 3.8% among seropositive patients.⁹³ This was attributed to the large disproportionate sample size between the two groups. Previous study reported a 3.3% prevalence of hookworm infestation among HIV/AIDS patients in Osun State, South-west Nigeria.⁴⁹

The adult hookworm lives in the jejunum and duodenum.⁹¹ Its eggs are passed in the faeces.^95,97 In warm moist soil, it develops into filariform infective stage. It then penetrates human skin and is then carried to the lungs and finally to the intestine through the oesophagus.⁹⁵

Acute clinical features include pruritic maculopapular dermatitis, cough with blood stained sputum and epigastric pain.^95,97 A well nourished person with light infection may be asymptomatic.^95,97 The major consequences of chronic infection are iron deficiency anaemia and hypoproteinemia. Symptoms are minimal if iron intake is adequate. But marginally nourished individuals will develop symptoms of progressive iron deficiency anaemia and hypoproteinemia.⁸⁷ This may be the cause of several cases of severe wasting syndrome and frequent severe anaemia seen in HIV/AIDS patients. Consequently, hookworm infestation may further worsen the condition of the HIV positive patient which enhances rapid progression to AIDS.

Diagnosis is made by identification of characteristic ova in stool sample.^87,97 Oral Mebendazole 100mg 12hourly for 3 days is preferred, but a single dose of albendazole 400mg is the best choice.⁹¹ Anaemia can be treated with supplemental iron tablets.

VI. Enterobius vermicularis

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Enterobius vermicularis is common throughout the world. It is described as a common intestinal helminths among homosexuals infected with HIV.³³ After the ova is swallowed, development takes place in the small intestine, but the adult worms are found in the colon.⁹⁷

The gravid female worm lays ova around the anus causing intense itching, especially at night. The ova are often carried to the mouth on fingers and so re-infection takes place.^87,97

Ova are detected by applying adhesive surface of cellophane tape to the peri anal skin in the morning which is then examined on a glass slide under microscope.⁹⁵

A single dose of Albendazole 400mg or piperazine 4g is effective and may be repeated after 2 weeks to control infection.⁹⁵

VII. Strongyloides stercoralis

Strongyloides stercoralis is distinguished by its’ ability to replicate in the human host. This capacity permits ongoing cycles of human autoinfection, as infective larva are internally produced.^95,97 Strongyloidiasis can exist for decades without further exposure of the host to exogenous infective stage. Strongyloides stercoralis is also a known cause of helminthiasis among HIV infected patients.³³ Miscarello et al observed that decrease in CD4 was significantly associated with strongyliodiasis in AIDS patients in Italy.⁹⁸ This has led many to believe strongyloides stercoralis may be an opportunistic parasite. ⁹⁸

Dada-adegbila et al in a study to determine the prevalence of strongyloidiasis among immunocompetent patients in Ibadan, Nigeria reported 11% prevalence of this parasite.⁹⁹ Abaver et al did not find any ova of Strongyloides stercoralis in the stool samples of immunocompetent patients in Abuja, Nigeria but reported 2.5% prevalence of the parasites among HIV positive patients.⁹³ Miscarello et al observed 11% prevalence of this parasite among HIV positive patient

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in Italy.⁹⁸ Other factors that increase the risk of strongyliodiasis include steroid therapy, malnutrition, homosexuality, alcoholism, instutionalisation and contact with animals.⁹⁸

Humans acquire Strongyloides species when they come in contact with filariform larva in highly contaminated soil.⁹⁸ It penetrates the skin or mucous membrane. The larva travels through the blood stream to reach the lungs and then ascends the trachea into the oesophagus. It usually lodges in the mucosa of the upper part of the small intestine, often in large numbers, causing persistent eosinophilia.⁹⁸ There, the adult female worm releases eggs which hatch into rhabtidiform larva that migrate to the intestinal lumen and pass out with faeces into the surrounding soil.

Alternatively, rhabtidiform larva in the lumen can develop directly into filariform larva that penetrates the colonic wall or perianal skin and enter the circulation to repeat the migration that establishes ongoing reinfection.⁹⁸

In immunocompetent states most patients are asymptomatic.⁹⁸ Clinical features include abdominal pain, diarrhea, recurrent urticaria often involving the wrist and buttocks, wheezing, cough and coma.⁹⁷ It can also present as epigastric pain which mimics peptic ulcer disease pain, except that peptic ulcer disease (duodenal) is aggravated by food ingestion.⁹⁷ Other symptoms include colitis, gastrointestinal bleeding, weight loss and small bowel obstruction.⁹¹ Systemic strongloidiasis is very common among immunosuppressed patients.⁸⁹ Dada et al observed a very strong positive correlation between systemic strongyloidiasis (hyperinfection syndrome) and immunosupression among HIV positive patients in Ibadan, Nigeria.⁹⁹ This was in agreement with a work done in Italy by Miscarello et al.⁹⁸ Strongyloidiasis can mimic some common but deadly opportunistic infection in the HIV positive patient.^95,98 This infection could also worsen the condition of AIDS patients.⁹⁵ Diagnosis is made by serial examination of stool samples.⁹⁵ The presence of motile rhabtidiform larva in the faeces is diagnostic. However, single sample examination detects only one third of

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uncomplicated infection, which calls for a repeated stool sample examination.^95,97 An enzyme linked immunosorbent assay has been advocated in patients with repeated negative stool sample.⁹⁵ In disseminated strongyloidiasis, sputum, bronchoalveolar lavage fluid or surgical drainage fluid can give a high yield of migratory filariform larva.⁹⁷

Strongyloidiasis can be eradicted with ivermectin (200ug/kg/day for 1-2days) or albendazole 400mg daily for 3days. Ivermectin should be extended to 5-7days in disseminated strongyloidiasis.

Ivermectin 200ug/kg as a single dose, or two doses of 200ug/kg on successive days, is effective.⁹⁵ Albendazole is given orally in the dose of 15mg/kg body weight 12 hourly for 3 days. A second course may be required.⁸⁷

2.9 PREVENTION OF HELMINTHS INFECTION AMONG PATIENTS ON HAART