Transcript Soil-Transmitted Helminths (STH)

Soil-Transmitted Helminths
Elaine C. Jong MD
Clinical Professor of Medicine
University of Washington
Infectious Diseases
Travel & Tropical Medicine
[email protected]
April, 2013
Helminth Infections: Magnitude Of The Problem
Ascaris, Enterobius
Trichuris, hookworm
Schistosomiasis
Filariasis (W. bancrofti)
Strongyloides
Paragonimus
Onchocerciasis
Loa loa
Opisthorchis
Clonorchis
Fasciola hepatica
1 billion infections each
500-900 million each
200 million
115 million
50-100 million
21 million
17.8 million
3-13 million
10 million
7 million
2 million
Worm Kingdom
• Nematodes= Roundworms
• Ascaris lumbricoides (common
roundworm)
• Ancylostoma duodenale and Necator
americanus (hookworm)
• Trichuris trichiura (whipworm)
• Strongyloides stercoralis
• Enterobius enterobium (pin worm)
• Cestodes= Tapeworms
• Trematodes= Flukes
Questions
• What are the main risk factors for soiltransmitted helminths (STH)?
• What are some of the impacts of STH on
human health?
• What are effective interventions to interrupt the
transmission of disease?
• What is the accepted approach to diagnosis
and treatment of STH in less-developed areas
where such infections are highly endemic?
• How does this differ from the usual standard of
care in the United States?
Overview: Helminth Infections
• May be asymptomatic
• May be an incidental finding in lab exam of
clinical specimens
• Symptoms and disease usually associated
with heavy worm burdens
• With a few exceptions, most worms are
unable to multiply in their host
• Heavy worm burdens therefore tend to be the
result of repeated infections over time
• Worms can live for years in a human host—
>20 years in the case of certain flukes
Overview: Helminth Infections-2
• May be associated with gastrointestinal
symptoms:
• diarrhea, abdominal discomfort, abnormal stools,
rectal irritation/ itching
• May cause malnutrition and pediatric growth
retardation in endemic areas
• May affect productivity in adulthood
• May be associated with striking peripheral
blood eosinophilia
• during larval migratory stages, or
• location of either adult worms or eggs in tissues
outside the intestinal lumen
STH Transmission
Helminth infections, growth, and anemia
Transmission
of helminth
infection
Accumulation of
worm burden
• Malabsorption
• Gastrointestinal blood loss
• Chemical messages to host
Irondeficiency
anemia
Poor
growth
Poor
cognitive
development
Adapted from Chwaya HM, Stoltzfus RJ. In: Drompton DWT et al (eds), Controlling
disease due to helminth infections. Geneva, WHO, 2003. p.34
1.3 billion Ascaris infections worldwide
Source: de Silva NR et al.,
2003. TRENDS in
Parasitology.19:547-551
Ascaris Infections
Ascaris lumbricoides—common helminth infection
with ~1.3 billion persons infected
• 71% in Asia: China, India, SE Asia
• 13% in Latin America & Caribbean
• 8% sub-Saharan Africa
• Eggs relatively resistant to drying or extremes of
temperature
• Larvae migrating through the lungs cause
eosinophilic inflammation
• Heavy worm burdens in children may cause intestinal
obstruction
• Migrating and ectopic worms: intestinal perforation,
bile duct obstruction, peritonitis, appendicitis, etc.
Source: Jong EC, Stevens, DA. (eds) Netter’s Infectious Diseases 1e, Elsevier, 2012.
From: Teaching Slide Collection, Medical Parasitology, Markell & Voege
Ascaris adults
DPDx-CDC: www.dpd.cdc.gov./dpdx
Courtesy of Prof. E.C.Jong
DPDx-CDC: www.dpd.cdc.gov./dpdx
500-900 million hookworm infections
worldwide
Source: de Silva NR et al.,
2003. TRENDS in
Parasitology.19:547-551
HOOKWORM INFECTIONS
• Iron-deficiency anemia is the hallmark of chronic
hookworm disease
• Adult hookworms inhabit the upper half of the
small intestine
• Attach and suck blood with the aid of an organic
anticoagulant
• Ancylostoma duodenale = 0.15- 0.26 mL/ day/ worm
• Necator americanus = 0.03 mL/ day/ worm
• Additional blood loss from bleeding at sites of
attachment
• Blood loss and compensatory volume expansion
• Microcytic hypochromic anemia
• Hypoalbuminemia
• Cardiovascular changes in severe cases
Source: Jong EC, Stevens, DA. (eds) Netter’s Infectious Diseases 1e, Elsevier, 2012.
Hookworm Symptoms
• Pruritic erythema (“Ground Itch”)
• Pulmonary symptoms during larval
migration to the gut
• Transient gastroenteritis-like syndrome
as adult hookworms attach to the
intestinal mucosa
• Eosinophila noted in 30-60% of infected
patients
Who’s who?
500-900 million whipworm infections
worldwide
Source: de Silva NR et al.,
2003. TRENDS in
Parasitology.19:547-551
Whipworm Infections
• 500-900 million Trichuris trichiura infections
worldwide
• Approximately same distribution as Ascaris
• Ingestion of eggs in contaminated vegetables
or soil
• Inhabit the caecum & colon causing
inflammation, hemorrhagic patches
• Each female worm produces ~10,000 eggs per
day passed in the feces
• Heavy infection can cause growth retardation,
malnutrition, rectal prolapse
Source: Jong EC, Stevens, DA. (eds) Netter’s Infectious Diseases 1e, Elsevier, 2012.
Trichuris trichiura adult female
Source: CDC Parasitology Diagnositic Web Site http://www.dpd.dcd.gov/dpdx
Strongyloides infections
• Strongyloides stercoralis causes chronic
infections that are often silent
• Elevation of peripheral blood eosinophils
• Soil transmitted life cycle
• Autoinfection life cycle
• Can complete life cycle without leaving the human host
• Filariform larvae in fecal stream may penetrate perirectal skin causing rash “cutaneous larva currens”
• Infection may be self-perpetuating for decades after
leaving endemic area
• Hyperinfection occurs in immune-compromised hosts
• Dissemination with local inflammation, enteritis, pneumonitis,
microabscesses
Source: Jong EC, Stevens, DA. (eds) Netter’s Infectious Diseases 1e, Elsevier, 2012.
Patient with cutaneous larva currens rash
Courtesy of Prof. E.C.Jong
From: Teaching Slide Collection, Medical Parasitology, Markell & Voege
Strongyloides stercoralis filariform larva
Source: CDC Parasitology Diagnositic Web Site http://www.dpd.dcd.gov/dpdx
Enterobius vermicularis
• Ubiquitous infection of children (estimated 1.3 billion
infections worldwide)
• Adults live in the caecum, gravid females migrate to the
rectal area at night
• Common cause of perianal itching
• Appendicitis
• Peritonitis
• Vulvovaginitis
• Eggs mature after 4-6 hours outside intestine and
become infective
• Fecal-oral spread on fingers and fingernails
Source: Jong EC, Stevens, DA. (eds) Netter’s Infectious Diseases 1e, Elsevier, 2012.
Clinical Summary:
Soil-Transmitted Helminths
• Light infections may be asymptomatic
• Heavy worm burdens may be associated with
• Gastrointestinal symptoms: diarrhea, abdominal
discomfort, abnormal stools, rectal irritation/ itching
• Malnutrition, pediatric growth retardation, and anemia:
resulting from malabsorption and gastrointestinal blood
loss
• Cognitive impairment
Clinical Summary: STH, p.2
• Infections may be associated with striking
peripheral blood eosinophilia
• Larval migratory stages
• Location of either adult worms or eggs in tissues
outside the intestinal lumen
• Infections do not lead to protective immunity
• Heavy worm burdens usually acquired from
repeated exposure in contaminated environments
• Children acquire heavy worm burdens from contact
with the ground and poor hygiene
• Strongyloidiasis is unique—once infected, worm
burdens may persist/ increase through autoinfection
cycle
Parasite Diagnosis
• Identification of gross
specimens
• Stool for ova & parasite
microscopic exam
• Wet mount
• Trichrome stain
• Serology tests
• Not for routine STH
diagnosis
• May be useful for extraintestinal helminthic
infections
• Strongyloidiasis
(Strongyloides stercoralis)
• Trichinosis (Trichinella
spiralis)
• Toxocara canis/ catis
Drugs for STH Treatment
DRUG
Ascaris
Pyrantel
pamoate
(Antiminth)¹
√
Mebendazole
(Vermox)²
√
√
√
Thiabendazole
(Mintezol)³
(√)
√
√
√
Albendazole
(Albenza)ª
√
√
√
√
Ivermectin
(Stromectol)§
Trichuris
Hookworm Strongyloides
√
√ (intestinal
stages only)
¹Paralysis of worm nervous system; ²Inhibition of microtubules, glucose depletion;
³Inhibition of helminth-specific fumarate reductase; ªInhibition of cytoplasmic microtubules;
§ bind glutamate-gated chloride ion channels increasing membrane permeability to chloride
ions resulting in paralysis
WHO (1997) MODEL LIST OF
ESSENTIAL DRUGS
FOUR ANTIPARASITIC DRUGS LISTED:
• Albendazole
• Levamisole
• Mebendazole
• Pyrantel pamoate
www.who.int
Individual Diagnosis & Treatment
• Stool ova and parasite exam (O&P)
• Treat with drug of choice
• Best drug available
• FDA-approved, off label use
• Investigational new drug protocol/
orphan drug
• Repeat O&P for test of cure or fecal
egg count reduction (FECR) 4 or
more weeks after therapy
WHO community treatment
(May 2001, resolution 54.19)
• “Deworming campaigns” involve presumptive
treatment of high-risk groups
• Routine screening of stool specimens is labor-intensive
and not practical in many settings
• Use of WHO drugs at de-worming doses associated
with negligible and self-limiting side effects
• Target high risk groups (school-age children & women
of child-bearing age) (selective treatment)
• Treat all persons (mass treatment) with
“preventive chemotherapy” in particular regions
• Survey for severe adverse reactions related to the
widespread distribution of antihelminthic drugs
Summary of STH Prevention
• Hand washing
• Wearing shoes
• Behavior/ education
• Personal hygiene
• Geophagia
• Latrines
• Individual treatment
• Targeted mass
treatment
Articles
• Andrade C, Alava T, De Palacio IA, et al. Prevalence and intensity
of soil-transmitted helminthiasis in the city of Portoviejo (Ecuador).
Mem Inst Oswaldo Cruz, 96:1075-9, 2001.
• Glickman LT, Camara AO, Glickman NW, et al. Nematode
intestinal parasites of children in rural Guinea, Africa: prevalence
and relationship to geophagia. Int J Epidemiol, 28:169-74, 1999.
• Guyatt HL, Brooker S, Kihamia CM, et al. Evaluation of efficacy of
school-based anthelmintic treatments against anaemia in children
in the United Republic of Tanzania. Bull World Health Organ,
79:695-703. Epub 2001 Oct 24.
• Kawai K, Saathoff E, Antelman G, et al. Geophagy (Soil-eating) in
relation to anemia and helminth infection among HIV-infected
pregnant women in Tanzania.
• Kirwan P, Asaolu SO, Molloy SF, et al. Patterns of soil-transmitted
helminth infection and impact of four-monthly albendazole
treatments in preschool children from semi-urban communities in
Nigeria: a double-blind placebo-controlled randomised trial. BMC
Infect Dis. 2009;9:20.
• Ndyomugyenyi R, Kabatereine N, Olsen A, et al. Efficacy of
ivermectin and albendazole alone and in combination for treatment
of soil-transmitted helminths in pregnancy and adverse events: a
randomized open label controlled intervention trial in Masinid
district, western Uganda. Am J Trop Med Hyg. 2008; 79:856-63.
• Steinman P, Utzinger J, Du Z-W, et al. Efficacy of single-dose and
triple-dose albendazole and mebendazole against soil-transmitted
helminths and taenia spp.: a randomized controlled trial. PLoS
ONE. 2011; 6(9): e25003. doi:10.1371/jounal.pone.0025003.
• Vercruysse J, Behnke JM, Albonico M, et al. Assessment of the
antihelminthic efficacy of albedazole in school children in seven
countries where soil-transmitted helminths are endemic. PLoS
Negl Trop Dis. 2011; 5(3): e949. doi: 10.1371/journal.pntd.0000948.
• Watson JL, Herrin BR, John-Stewart G. Deworming helminth coinfected individuals for delaying HIV disease progression.
Cochrane Database Syst Rev. 2009; (3):CD006419.
• Ziegelbauer K, Speich B, Mäusezahl, et al. Effect of sanitation on
soil-transmitted helminth infection: systematic review and metaanalysis. PLoS Med. 2012; 9(1):e1001162.
doi:10.1371/journal.pmed.1001162.