Hookworm Disease Treatment & Management
- Author: David R Haburchak, MD, FACP; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD more...
Most cases of classic hookworm disease can be managed on an outpatient basis with anthelmintic and iron therapy, complemented by appropriate diet. Patients with anemia and malnutrition may require both iron supplements and nutritional support (including folate supplementation). Some patients with severe anemia and congestive heart failure may require hospitalization.
Blood transfusion is indicated in rare cases of acute severe gastrointestinal (GI) hemorrhage. In patients with chronic anemia, blood transfusions (ie, packed red blood cells [RBCs]) should be administered slowly and are usually followed by a diuretic to prevent rapid fluid overload.
For patients with cutaneous larva migrans who have minimal symptoms, specific anthelmintic treatment may be unnecessary.
Eosinophilic enteritis may mimic acute appendicitis or intestinal perforation, and, in some cases, diagnosis has been made during laparotomy. However, treatment for eosinophilic enteritis is medical (ie, mebendazole administration) rather than surgical.
Specialty consultations are usually unnecessary unless the anemia is severe or blood indices are equivocal. The primary physician typically monitors anemia treatment.
Anthelmintic drugs effective against hookworms include benzimidazoles (eg, albendazole, mebendazole) and pyrantel pamoate.[35, 36] Treatments that may be employed include the following:
Albendazole in a single 400-mg dose or daily for 3 days 
Mebendazole 100 mg twice daily for 3 days (more effective than a single 500-mg dose)
Thiabendazole applied topically to attack migrating larvae in cutaneous larva migrans
Pyrantel pamoate in several 11 mg/kg doses, usually over 3 days
Albendazole, although not approved by the US Food and Drug Administration (FDA) for hookworm therapy in the United States, continues to have highest apparent cure rate, especially for single-dose therapy. Rates of cure have been decreasing worldwide, possibly due to resistance. A single-dose trial performed in Ghana and reported in 2013 reported a cure rate of only 43%, compared with a 72% cure rate in a 2008 reported systemic review. A 2011 reported trial from China indicated the following cure rates at 3-4 weeks: albendazole single dose 69%, 3 daily doses 92%; and 3 days of 500 mg mebendazole 54%. A 2012 report from Laos demonstrated a single-dose albendazole cure rate of 36% and single 500-mg mebendazole cure rate of 18%.
The Centers for Disease Control and Prevention (CDC) continues to recommend a 400-mg single dose of albendazole on its Website (1 May 2014), but notes that albendazole is not FDA approved for the treatment of hookworm infection. The Sanford Guide to Antimicrobial Therapy recommends albendazole 400 mg daily for 3 days or mebendazole 100 mg twice daily for 3 days.
Although benzimidazoles are an effective chemotherapeutic option, reinfection remains a notable problem because exposure to the hookworm does not confer long-term immunity. Rapid hookworm reinfection is common in endemic areas and is made particularly problematic by the high prevalence and worm burden in adults who are untreated and who continue to contaminate soil.
Repeated community treatment may result in an emerging drug resistance.[43, 44] In a Zanzibari population of children treated repeatedly over 5 years, cure and egg elimination rates both decreased significantly with time. This suggests the need for a renewed emphasis on community-wide sanitation, education, and, possibly, vaccine development (see Prevention).
Because of developing resistance in areas with frequent periodic deworming (eg, Java), newer drugs to treat hookworm disease are being sought. Unfortunately, the market for new antiparasitic drugs is small. A promising alternative to albendazole is tribendimidine, a synthetic drug developed in China; in initial trials, tribendimidine appears to be equal or even superior to single-dose albendazole.
Iron replacement[48, 28, 49] and nutritional supplementation (protein and vitamins, including folate) should be part of the management strategy and may have greater efficacy than anthelmintic therapy in reducing morbidity in selected populations (eg, pregnant women and patients who are not infected with HIV). Such combined therapy has been successful in Peru and Brazil but less so in Kenya.[50, 51] Severe anemia affects children and pregnant women disproportionately because of their low preexisting iron stores.
Wheezing and cough are managed with inhaled beta agonists. Steroids may cause pulmonary symptoms to become exacerbated, particularly in patients with Strongyloides infection.
Treatment in special population s
Although very rare in nonambulatory children (< 2 years), hookworm infection in this age group can carry significant mortality. A fulminant form of acute hookworm infection causing acute GI tract hemorrhage has been described in infants. The means of transmission is unknown, but likely environmental. These infants (often >2 months) present with melena or frank rectal bleeding, abdominal distention, hypotension, and profound anemia.
Experience with anthelmintic drugs is limited for children in this age group. The World Health Organization (WHO) recommends administering half the adult dosage of albendazole or mebendazole in patients with heavy hookworm infections. The dosage of pyrantel is determined on the basis of the child’s weight.
Published reports addressing the use of albendazole or mebendazole in children younger than 6 years are limited. In 2007, a pair of randomized clinical trials were conducted in Vietnam to evaluate the efficacy of mebendazole. The initial study compared the efficacy of single-dose mebendazole with that of placebo among schoolchildren aged 6-11 years. In this study, single-dose mebendazole did not significantly reduce the disease burden as determined by fecal sample egg counts.
In the follow-up randomized clinical trial, which included subjects aged 16 years and older, triple-dose mebendazole, triple-dose albendazole, and single-dose albendazole were compared with placebo. The findings indicated that triple-dose albendazole was the most effective regimen in these individuals; the cure rate for this regimen was 79%, compared with cure rates of 45% for single-dose albendazole, 35% for placebo, and 26% for triple-dose mebendazole.
Limited studies such as these underscore the observation that drug pharmacokinetics and pharmacodynamics may be altered in pediatric populations and that additional studies are warranted. Moreover, confounding factors such as sample size, geographic variation, and diagnostic protocols often make direct study comparison difficult.
In 2007, a joint World Bank/WHO conference was held to address the topic of drug efficacy and monitoring in treatment of soil-transmitted helminth infections, with the aim of standardizing large-scale treatment programs. In response, a 2010 study found that in 7 countries, a standardized single-dose albendazole protocol cured 98.2% of Ascaris lumbricoides infections and 87.8% of hookworm infections, but only 46.6% of Trichuris trichiura infections. Additional studies, however, still suggest geographic variations in hookworm sensitivity.
The FDA has approved mebendazole for the treatment of hookworm in children older than 2 years. Albendazole is used off-label for hookworm treatment and is not advised for use in children younger than 6 years. Albendazole appears to be superior to mebendazole for curing hookworm infection in children, achieving cure rates of approximately 90% for Ancylostoma and 75% for Necator. The potential benefits and risks of these agents in pediatric patients must be considered before treatment is pursued.
Pregnant and lactating women
In the past, treatment of pregnant or lactating women was discouraged because of concerns about potential teratogenicity. Currently, these populations are recognized as being at high risk in endemic regions, and treatment may be warranted after careful clinical consideration of the risks and benefits. The WHO recommends deworming treatment (eg, albendazole, mebendazole, or pyrantel pamoate) during the second or third trimester for pregnant women with heavy hookworm infections.
A significant correlation has been observed between maternal anemia (nutritional or parasitic) and an increased risk of bearing premature and low-birth-weight (LBW) infants. In comparison with neonates of average weight, LBW infants subsequently have higher overall morbidity and mortality.
One strategy for reducing the incidence of low birth weight is prenatal treatment of mothers for presumptive parasitic infections. In a clinical trial conducted among pregnant mothers in Peru, where the prevalence of hookworm infection is high, prenatal treatment with mebendazole in addition to iron supplementation brought about a small but significant reduction in the incidence of very-LBW neonates. . Subsequent to this study, however, a 2008 systematic review and another 2012 systematic review both concluded that there was no clear beneficial impact of antihelminthics on anemia in pregnancy or maternal, newborn, or child health outcomes.
Community control of hookworm infection is difficult unless substantial improvements in socioeconomic conditions, sanitation, education, and footwear availability can be achieved. Successful programs have included economic, sanitary, and mass-treatment components. Current WHO recommendations for hookworm infection include periodic mass therapy to lower the overall worm burden until conditions permit a multicomponent physical and educational program. Community leaders should be trained about WHO recommendations.
Cost studies comparing various management strategies favor community-wide, single-dose albendazole chemotherapy at intervals of 12-18 months. Some programs have been more intensive, with dosing frequency up to quarterly in school children, and recommended thrice yearly by the WHO for highly endemic areas.
With regard to sanitation, sanitary excreta disposal is the most effective deterrent, but it is not feasible in many developing countries. Wearing footwear cannot entirely prevent infection because larvae can penetrate any skin surface that comes in contact with contaminated soil. In addition, A duodenale larvae can be ingested.
Mass chemotherapy remains a mainstay of hookworm control strategies. It should be kept in mind that mass or targeted chemotherapy programs may not control hookworm infection, because reinfection is common in endemic areas, and dormant extraintestinal larvae of A duodenale may be resistant to currently available anthelmintic agents.
A concern with mass chemotherapy is that continued use of drugs may lead to reduced efficacy; treatment failures have been observed. A 2007 study assessed the health impact of a national control program that targeted schistosomiasis and intestinal nematodes in Uganda, which has provided population-based anthelmintic chemotherapy since 2003. Anthelmintic treatment delivered as part of a national helminth control program decreased infection and morbidity among schoolchildren and improved hemoglobin concentration.
One unintended consequence of community deworming, however, has been reported increases in allergic diseases.
Although school-based deworming programs probably will not adequately control the prevalence of hookworm infection, they can have a substantial effect on children’s nutritional status, cognitive development, and productivity. Children with hookworm anemia have considerably lower scores on cognitive function tests and exhibit delayed acquisition of language and motor skills. When the infection and the associated anemia are treated, their educational performance and productivity improve.[28, 49, 60]
As understanding of the immunoepidemiology and the molecular pathogenesis of hookworm infection improves, identification of a safe and effective vaccine remains a high priority, though achieving progress remains challenging. The development of an efficacious vaccine requires molecular targeting of both larval and adult stages in order to break the reproductive cycle. In this regard, the Ancylostoma -secreted proteins (ASPs) are one group of potentially promising targets.[63, 64, 65]
In a hamster model using N americanus ASP-2 (Na -ASP-2) hookworm vaccine, encouraging results were achieved with respect to lowering worm burdens and inhibiting growth delay. In 2006, a phase I clinical trial of Na -ASP-2 vaccine demonstrated that the vaccine was both safe and well tolerated. In addition, the vaccine evoked sustained cellular immune responses and elevated immunoglobulin titers. Unfortunately, this vaccine has been withdrawn from development because of urticarial reactions in previously infected recipients.
The recent characterization of the N americanus genome has potential for advancing knowledge of therapeutic and preventive strategies of control. Other larval and adult stage targets have been identified, and additional preclinical studies are being conducted. With additional investigation and further trials, these vaccines will offer an appealing novel strategy to prevent hookworm infections globally.
It is to be hoped that the combined use of periodic deworming, improved sanitation, and an (at least partially) effective hookworm vaccine will decrease the medical, social, and economic burden of anemia due to hookworm in developing countries. The emergence of benzimidazole resistance is a growing concern, and new drugs are being sought. A promising agent is tribendimidine, which was first synthesized in China in the 1980s.
Integrated control of hookworm infection together with other helminth infections can be provided with a package of medicines costing approximately $0.50 per patient per year. Such dual therapy has been shown effective in various geographic contexts. Major partnerships of organizations are coordinating integrated management through the Global Network for Neglected Tropical Disease Control. Such efforts provide hope for improving the health and economic development of millions worldwide.
The recommended procedure is to repeat the stool examination using a concentration technique after 2-3 weeks; positive results indicate the need for retreatment. The entire course of iron therapy must be completed to replenish iron stores, even after hemoglobin values return to normal.
It is important to be alert for possible reinfection, which is common in endemic areas. Dormant extraintestinal larvae of A duodenale may be resistant to currently available anthelmintic agents (which may have poor systemic absorption) and may be responsible for relapse.
As worm burden decreases in both individuals and population, more sensitive testing methods such as PCR will likely be required to ensure eradication.
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