Approach Considerations
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.
Pharmacologic Therapy
Anthelmintic drugs effective against hookworms include benzimidazoles (eg, albendazole, mebendazole) and pyrantel pamoate [41] . Treatments that may be employed include the following [43] :
Table 2: WHO and CDC treatment recommendations (Open Table in a new window)
Drug |
Adults |
Children (>24 months) |
Albendazole (preferred)* |
|
|
Mebendazole |
|
|
Pyrantel pamoate |
|
|
Thiabendazole |
|
|
*Albendazole is markedly superior to mebendazole
Albendazole, although not approved by the US Food and Drug Administration (FDA) for hookworm therapy in the United States, continues to have the highest apparent cure rate, especially for single-dose therapy.
The Centers for Disease Control and Prevention (CDC) continues to recommend a 400-mg single dose of albendazole on its Website (June 28, 2021), but notes that albendazole is still 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. [44] Rapid hookworm reinfection is common in endemic areas and is made particularly problematic by the high prevalence and worm burden in untreated adults who continue to contaminate soil.
Repeated community treatment may result in an emerging drug resistance. [45] In a Zanzibari population of children treated repeatedly over 5 years, cure and egg elimination rates both decreased significantly with time. [46] This suggests the need for a renewed emphasis on community-wide sanitation, education, and, possibly, vaccine development (see Prevention). [47]
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. [48] Other experimental drugs in development include small-molecule inhibitors of nematode carnitine palmitoyltransferase [49] and Bacillus thuringiensis Cry5B protein. [50]
Iron replacement 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. [51]
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 populations
Young children
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. [52] 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 (200 mg) in children over 24 months 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. [45] 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.
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 FDA has approved the use of 100mg mebendazole twice daily for 3 days for the treatment of hookworm in children older than 2 years. The potential benefits and risks of these agents in pediatric patients must be considered before treatment is pursued.
Pregnant and lactating women
Currently, pregnant or lactating women are recognized as being at high risk in endemic regions. The WHO recommends deworming treatment using single-dose albendazole or mebendazole during the second or third trimester for pregnant women with heavy hookworm infections. [43]
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. [53] 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. [51]
Prevention
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 annual (in communities where prevalence is above 20%) or biannual (in communities where prevalence is above 50%) mass therapy with single-dose albendazole or mebendazole to lower the overall worm burden until conditions permit a multicomponent physical and educational program. Community leaders should be trained about WHO recommendations. [43]
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 for highly endemic areas. [16]
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. [12] Most recently, multiple drug resistance has been observed in canine hookworm (Ancylostoma caninum) populations, indicating that widespread drug resistance is a growing concern in the treatment and control of hookworm. [54] Anthelmintic treatment delivered as part of a Ugandan national helminth control program decreased infection and morbidity among schoolchildren and improved hemoglobin concentration.
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. [55] At a population level, improvement in health outcomes has been disappointing, as referenced in numerous recent reviews. [56]
As understanding of the immunoepidemiology and the molecular pathogenesis of hookworm infection improves, [57] identification of a safe and effective vaccine remains a high priority, [47] although achieving progress remains scientifically and economically challenging. [58] 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. [29]
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. [59] 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. [16]
More recently, a bivalent vaccine targeting Na-Glutathione S-transferase-1 (Na-GST-1) and Na-Aspartic Protease-1 (Na-APR-1) has been developed. As of September 2020, this vaccine has been indicated to be safe and potentially effective in phase I clinical trials. [15] Phase II clinical trials are currently underway. [60]
The recent characterization of the N. americanus genome has potential for advancing knowledge of therapeutic and preventive strategies of control. [61] 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 and has had promising results in ongoing trials. [48]
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. [23] Such dual therapy has been shown effective in various geographic contexts. [62] Major partnerships of organizations are coordinating integrated management through the Global Network for Neglected Tropical Disease Control. [63] Such efforts provide hope for improving the health and economic development of millions worldwide.
Long-Term Monitoring
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. [64]
-
Adult hookworm attached to duodenal mucosa.
-
Hookworm filariform larva. Courtesy of Division of Parasitic Diseases, Centers for Disease Control and Prevention (CDC).
-
Adult Ancylostoma duodenale worm. Anterior end with mouth parts visible. Courtesy of Patrick W Hickey, MD.
-
Adult Necator americanus worm. Anterior end with mouth parts visible. Courtesy of Patrick W Hickey, MD.
-
Hookworm eggs examined on wet mount. Eggs of Ancylostoma duodenale and Necator americanus cannot be distinguished morphologically. Courtesy of Division of Parasitic Diseases, Centers for Disease Control and Prevention (CDC).
-
Hookworm rhabditiform larva (wet preparation). Courtesy of Division of Parasitic Diseases, Centers for Disease Control and Prevention (CDC).
-
Life cycle of hookworm. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/parasites/hookworm/biology.html].
-
Hookworm egg in an unstained wet mount at 400x magnification. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/hookworm/].
-
Hookworm rhabditiform larva. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/hookworm/].
-
Side-by-side image of the mouth parts of each species of human-infecting hookworm. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/parasites/hookworm/biology.html].
-
Cutaneous larva migrans. Courtesy of Wikipedia [WeisSagung, https://en.wikipedia.org/wiki/Cutaneous_larva_migrans].
Tables
Intensity |
Eggs per gram of feces |
Mild |
< 1,999 |
Moderate |
2,000-3,999 |
Heavy |
>4,000 |
Drug |
Adults |
Children (>24 months) |
Albendazole (preferred)* |
|
|
Mebendazole |
|
|
Pyrantel pamoate |
|
|
Thiabendazole |
|
|
