Common Intestinal Helmithic infestations

Introduction

Intestinal helminthiasis including infestation with soil-transmitted helminthes (STH) is a common disease among school children causing considerable morbidity in children, affecting their cognitive development and physical growth. STH consists of Ascaris lumbricoides, Trichuris trichiura, Strongyloides stercoralis, Necator americanus and Ancylostoma duodenale. Other helminthic infestation also common among children and family members including adults is Enterobius vermicularis. Intestinal helminthiasis is among the major public health issues in tropical and sub-tropical countries.¹

In Myanmar, ascariasis is the most common infection followed by trichuriasis. Currently, trichuriasis surpasses ascariasis. Hookworm infestation and strongyloidiasis is generally low but high in some populations and in adults. Enterobiasis is still high among school children.

Transmission, pathogenic effects and laboratory diagnosis

The main reservoir for ascariasis and trichuriasis is children; however, adults are source of infestation for hookworm.² Adult female helminths reside in the human small intestines and pass eggs or larvae in stools contaminating the soil and water. The eggs or larvae require two to three weeks maturation outside the body (in the soil) before infecting humans; hence they are called soil transmitted helminthes. A. lumbricoides and T. trichiura spread via the fecal-oral route with ingestion of embryonated eggs, while hookworms and Strongyloides spread by penetration through skin or mucous membranes by filariform larvae when coming in contact with contaminated soil or water. Enterobius has different modes of transmission: ingestion, inhalation, retrograde infection, and autoinfection.³ Strongyloidiasis also has autoinfection cycle by penetrating the gut wall or peri-anal skin of the same person.⁴

Infestation with STH is associated with anaemia, malnutrition, and impaired physical and cognitive development (stunting). Morbidity and mortality increase with worm burden; those with light infestations are almost always asymptomatic. Patients with heavy infestation with Trichuris may have prolapsed rectum, particularly in children.³

The repeated exposure of hookworms larvae can result in an erythematous papulo-vesicular rash and intense itching (“ground itch”); appearing most commonly on the hands and feet.⁵ Infestations with S. stercoralis are frequently nonspecific; in chronic infection, larva currens (a migratory, serpiginous, urticarial rash), diarrhea, abdominal discomfort, nausea, and anorexia, or cough and shortness of breath are presenting features. In immunosuppressed individuals, the infestation causes hyper infection and death with case-fatality rates near 90%.^6,4 Pruritus ani is the main presenting feature for enterobiaisis caused by migrating gravid females for laying eggs on the peri-anal skin at night (up to 15,000 eggs ) and in some cases weight loss occurs.⁷

The direct microscopic examination of faeces is the most common technique used in the majority of clinical laboratories until now. Due to intermittent shedding of eggs, at least three stool specimens collected within 10 days is required, and for Strongyloides larvae up to 7 serial stool specimens collected on different days is required to increase sensitivity from 30 % to 100%. ^8,1,3 For STH, fecal floatation or fecal sedimentation methods increase sensitivity; FLOTAC techniques, Stoll’s dilution egg-counting method, quantitative fecal examination through Kato-Katz or McMaster method determined the type and load of the particular parasite.

Baermann method, Harada Mori culture technique, and the Koga agar plate (KAP) culture can also be applied for strongyloidiasis. Antigen detection methods can also be used. Serological assays for hookworms and Strongyloides are more sensitive and specific than the conventional microscopic method as they detect specific antibodies such as IgG and IgG4. The sensitivity of qPCR to identify A. lumbricoides, hookworms and S. stercoralis was found to be 85.7 – 95%, 93-96.9% to 92%, and 83.3%, respectively.^1,3

The “peri-anal tape” method which is most effective for enterobiasis when taking after arising in the morning before the individual defecates or bathes. Examination of a single swab detects approximately 50% of infections, however, three consecutive perianal swabs showed high sensitivity rate (90%).⁹

Global burdens

Findings from WHO revealed that more than three billion of the world’s population are infected either by one or more intestinal parasites especially STH.¹⁰Approximately one-half of the people of Southeast Asia living in poverty have one or more STH infestation.⁵

The hookworms infest 440 to over 480 million people worldwide; T. trichiura 460 to 508 million, and A. lumbricoides, 700 to 820 million respectively.¹ The global prevalence of strongyloidiasis is from a range of 30 million to more than 300 million.³ According to a 1999 report from the Partnership for Child Development, the global prevalence and number of cases of intestinal helminthes infection in school-age children were 35% (320million) for A. lumbricoides; 25% (233million) for T. trichiura; 26% (239 million) for hookworms, and 14% (128million) for others.³ Globally, more than 44 million pregnant women are infected with hookworm and the prevalence rate was 32.0% in 306 pregnant women in Ethiopia. There was a positive association with domestic animals, unavailability of latrines, and habit of walking barefeet.¹¹

Epidemiological patterns of STH infection in 11 Southeast Asian countries are similar to those reported in other parts of the world according to a survey report on 280 studies.¹² In some areas, A. lumbricoides is the predominant helminth, while in other areas T. trichiura or hookworms are the commonest parasites. Prevalence of hookworm was high in well-drained sandy soil types whereas low in clay soils.⁵ The predominant hookworm is ^N. americanus which has worldwide distribution; A. duodenale is focally endemic in some defined locations.⁵ The prevalence and intensity of STH infestations in some regions were significantly higher in adults.^13-14 Children as young as 6 months old can be infected.

Enterobiasis has a worldwide distribution and about 209 million people are estimated to be infected. The prevalence rates reached up to 30 – 50% and over 30 % for children aged 5 – 10 years.^7,4

Burden of common intestinal helminthes in Myanmar

In Myanmar, decreasing trends of helminthiasis and STH prevalence were reflected by surveys on data obtained from 38 eligible papers out of 110 research papers (from 1969 to 2018) retrieved from the Department of Medical Research, web page and Library of Medical Universities. Total helminthiasis prevalence decreased from 80.95% (1969-1984) to 23.48% (2016-2018); Ascaris was the commonest (65% to 20.96%), followed by Trichuris (34.59% to 8.9%). Other STH eggs detection rate in stool between (1969 and 2018) were as follow: hookworm (generally < 5.6%) and Strongyloides species larvae (generally < 3 %) with high prevalence in some study populations. Egg detection rate (EDR) for Enterobius was between 0.68% and 4.4% (from 1969 to 2018); higher rate (31.1%-47.2%) was observed among school going age and pre-school children using tape method.

However, STH surveys done among general population in 2015 and among schoolchildren in August 2016 reported that prevalence of STH is still high; T. trichiura was the most prevalent STH. These two research data pointed out the ineffectiveness of currently used mass drug administration (MDA) strategy against trichuriasis (Albendazole 400mg single dose). It is also reported that adults might be the source of infection for hookworms as higher infection rate and worm burden were seen in adults.^14,15

Regarding hookworm infestation in Myanmar, prevalence is high among adults such as mine workers (16% -31%), persons from slum area (44.8%), and persons who dig gold in Shwe-Gyin (5.8%). Prevalence of hookworm infestation was low in children (ranged between 0.38% and 2% except in KyiMyintaing (4.17%). Similarly, high prevalence of strogyloidiasis was seen in some populations mainly in adults; 5.7% in the Lower Myanmar (Htantabin, Thabaung, Thanlyin) (2015), 3.7% in HIV infected patients and 5% in persons from slum area by culture method, 13% – 15.8% in mine workers by wet mount.16 Infection rate is low in school children (0.5%, 1.2% and 1.5%).

In Myanmar, MDA included only pre-school age children (pre-SAC) and younger SAC (KG to the fourth grade) and was extended to the entire SAC population (including the fifth grade and above) during the 2017–2018 academic year.¹⁵ Above data showed the changing trends of STH infection to adults; adult become reservoir and source of infestation. Therefore, all the people including adults in endemic areas should be included in MDA programme.

Enterobius detection rate was generally low (negative, from 0.65% to 4.4%) reported in 13 papers published between 1968 and 2018. However, higher rates were detected in 6 studies; 3 studies done on both children and adults were 13.2%, 40%, 30% detected in 1970 in Mandalay, in Ot Pho and in Dayepho, respectively by wet mount and concentration method. Three studies on schoolchildren that used perianal swab method yielded high positivity; 31.1% in pre-primary school children in North Okkalapa in 2004, 47.2% in primary schoolchildren in 3 different townships around Yangon City, in 2015 and 46.42% in 433 kindergarten students in Maupin Township in 2017, respectively indicating enterobiasis is still common among school children of Myanmar and new MDA schedules should be applied. ^17,18 There is no data detected by peri-anal tape method among adult population. Mixed helminthic infestation among Myanmar children is about 29%.¹⁹

Treatment

To reduce intestinal parasitic infestations (IPIs) MDA for helminthic infestations are recommended. WHO advises targeted treatment two to three times a year for school-age children with a prevalence exceeding 70% and once per year for prevalence between 50 and 70%. The 2012 London Declaration on Neglected Tropical Diseases aims to achieve preventive chemotherapy (PCT) coverage of 75 % of all pre-SAC and SAC at risk of STH by 2020. Deworming of general population is applied when there is greater than 50% of cumulative STH infection prevalence. To control and eliminate STH infections, PCT using annual or biannual single-dose albendazole (400 mg) or mebendazole (500 mg) has been provided as a public-health intervention for all SAC.³

Among the broad-spectrum antihelminthics, albendazole as a single dose is recommended and the most effective anthelmintic drug against A. lumbricoides and hookworms. Mebendazole 100 mg orally twice daily for three days or 500 mg orally once can also be selected. Dosage is the same for children and adults. Three days twice daily dosing is cumbersome and makes mebendazole less applicable for mass treatment campaigns compared to albendazole.²⁰ Single‐dose albendazole showed high cure rates against A. lumbricoides infection but generally treated for 1-3 days. Mebendazole is an equivalent alternative to albendazole. Pyrantel pamoate achieved high egg reduction rates against A. lumbricoides, but moderate low efficacies against hookworms and T.³ (Table-1).

For trichuriasis, albendazole and mebendazole are the drugs of choice for treatment. However, efficacy of single-dose albendazole against T. trichiura rarely exceeds 50 % and cure rates (CR) ranged between 2.6% (0.0–5.6 %) and 64.5 % (44.4–84.7 %). US CDC recommended albendazole 400 mg orally once a day for 3 days for treatment of trichuriasis. Alternatively, Ivermectin 200 ug/kg daily can be used but it is less effective.²⁰

A slight reduction of egg detection rate (EDR) for T. trichiura after 3 years (2017, 2018, and 2019) of 2-4 times a year repeated MDAs (albendazole – 400 mg in a single dose) done on schoolchildren in Yangon Region. EDR of A. lumbricoides significantly decreased from 23.3% in 2017 to 3.6% in 2019; EDR of T. trichiura was 26.9% in 2017 and 20.2% in 2019.21 The main reason may be the unsatisfactory efficacy of currently recommended drugs against T. trichiura infection. Drug resistance (substitution of a single amino acid from phenylalanine (Phe, TTC) to tyrosine (Tyr, TAC) in the β-tubulin at position 200 due to mutation) may also explain the poor cure rates in infection with T. trichiura using a benzimidazole therapy.²⁰

The first-line drug for S. stercoralis is ivamectin (IVM). IVM (200 µg/kg), a single dose was shown to be effective in uncomplicated chronic strongyloidiasis. The cure rate is 94.6% in Ethiopia, 95.2% in Switzerland, 96.8% in Thailand, 98.7% in Thailand, 98.3% in Cambodia, and 96% in Japan, 85.7% in Italy, and 84.07% in Nigeria.²² It can also be given once daily for 2 days. However, albendazole 400 mg twice a day for 7 days remains the most widely used drug for the treatment of uncomplicated strongyloidiasis due to the unavailability of ivamectin. Thiabendazole (25 mg/kg/d) for 3 days is an elective treatment. Immunocompromised patients and patients with hyperinfection syndrome need to be treated until a sputum or stool culture is negative for 2 weeks. In some cases, antibiotics are required to treat bacterial infections as well. Ivermectin is not recommended in children < 5 years.⁴

The medications used for enterobiasis are either mebendazole (100 mg), pyrantel pamoate (11 mg/kg of base), or albendazole (400 mg) given as a single dose and then repeated after 14 days. The second dose is to prevent re-infection by adult worms that hatch from any eggs that not killed by the first treatment. All household members should be treated at the same time.9 Improving access to adequate water, sanitation and hygiene (WASH) at the household level and in school is essential to prevent infections of STH especially T. trichiura.

New Regimens tested for Trichuris

New regimens found to be effective are albendazole 100 mg orally once a day for 3 days, albendazole two doses given on two consecutive days [CR of 67 % (52–82 %)] and two doses given on three consecutive days [CR up to 83 % (73–93 %)]. Double dose albendazole given at a single dose also led to higher CR 43.4 % (32.2–54.6 %) compared to the standard dose CR 15.4 % (8.4–20.6 %).²⁰

Oxantel pamoate and nitazoxanide have shown poor CR for the treatment against T. trichiura. Alternative drugs such as tribendimidine and drug combinations (ivermectin, oxantel pamoate, and moxidectin) are for possible use in T. trichiura infection.²³ Albendazole plus ivermectin achieved a CR of 27.5 % (19.0–36.0 %). Regime using two albendazole doses of 400 mg plus two mebendazole doses of 500 mg administered 8 h apart achieved a CR of 56 % (46.4–66.7 %). Ivamection 200ug/kg orally once a day for 3 days can also be used. ²⁰

Anthelminthic Vaccines and New Drugs

Currently, there are no licensed anthelminthic vaccines for humans. Candidate vaccines are only for hookworm in clinical trials. Three candidate hookworm vaccines have been tested in phase 1 clinical trials in the USA and in Brazil. The first candidate, the Na-ASP-2 vaccine contains an antigen produced by the larval stage of N. americanus. Two vaccine products based on the Na-APR-1 (N. americanus aspartic protease-1) and Na-GST-1 (N. americanus glutathione-S-transferase-1) antigens are currently being tested in a series of phase 1 trials in both hookworm-naïve and hookworm- exposed volunteers.² New drug under development is the pore-forming crystal (Cyr) proteins expressed by Bacillus thuringiensis. Cry5B has been shown to have in vivo activity against zoonotic Ascaris suum and the zoonotic hookworm species Ancylostoma ceylanicum.²

Conclusion

For laboratory diagnosis, repeated stool examination give better result than single test; at least 3 stool specimens for STH, 7 serial stool examinations for strongyloidiasis, 3 consecutive perianal swabs for diagnosis of enterobiasis.

The prevalence of STH is still high and T. trichiura was the most prevalent STH; this may be due to the unsatisfactory efficacy of current MDA against trichuriasis. For enterobiasis, anthelminthic should be repeated after 14 days (2 doses regime). Adults serve as source of infection for hookworms both in the world and in Myanmar, currently. To reduce trichuriasis new MDA regimens should be applied. Moreover, to eradicate adult source MDA should extend to adults.

References

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Author Information

Win Win Maw¹, Aung Phyo Wai², Hnin Zi³

1. 1. MBBS, PhD (Medical Microbiology)(Shimane, Japan), DipMedEd. Professor / Head (retired), Department of Microbiology, University of Medicine -2, Yangon
2. MBBS, MMedSc (Parasitology) (Khon Kaen University, Thailand); PhD candidate, Department of Microbiology, Shimane University Faculty of Medicine, Izumo, 693-8501, Japan.
3. MBBS, MMedSc (Microbiology), PhD (Medical Microbiology), DipMedEd. Associate Professor, Department of Microbiology, University of Medicine -2, Yangon