Four healthy hookworm-naive volunteers will be exposed to 50 L3 Necator americanus larvae once and will retain infection for up to 2 years.

Four volunteers will be exposed to 50 Necator americanus L3 larvae. Volunteers will be followed on a weekly basis until week 12 after infection. If volunteers develop a patent infection, defined by detectable egg production in stool by microscopy at any timepoint within week 9 to 12, they will be scheduled to donate faeces on request.

Two years after infection or if volunteers do not excrete eggs detectable by microscopy on week 9 to 12, volunteers will be treated with a 3-day regimen of albendazole to abrogate the infection. Retreatment with albendazole will be given to volunteers who remain positive for hookworm after treatment.

Six months after the treatment, volunteers will undergo their last visit.

Inclusion Criteria:

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

1. Subject is aged ≥ 18 and ≤ 45 years.
2. Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
3. Subject is able to communicate well with the investigator, is available to attend all study visits.
4. Subjects are able to respond to phone or email within 24 hours during the first 12 weeks of the study.
5. Subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period.
6. For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study.
7. Subject has signed informed consent

A potential subject who meets any of the following criteria will be excluded from participation in this study:

1. Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immune-deficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following:

   • history of severe asthma or other health conditions that may require future steroid use;
   • body weight <50 kg or Body Mass Index (BMI) <18.0 or >30.0 kg/m2 at screening;
   • positive HIV, HBV or HCV screening tests;
   • the use of immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period;
   • having one of the following laboratory abnormalities: ferritine <10 ug/L, transferrine <2.04 g/L or Hb <7.5 mmol/L for females or <8.5 mmol/L for males.
   • history of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years;
   • any history of treatment for severe psychiatric disease by a psychiatrist in the past year;
   • history of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset.

2. Known hypersensitivity to or contra-indications for use of albendazole. Including co-medication known to interact with albendazole metabolism (e.g. carbamazepine, phenobarbital, phenytoin, cimetidine, theophylline, dexamethasone).

3. Known type 1 hypersensitivity to amphotericin B or gentamicin.

4. For female subjects: positive urine pregnancy test at screening.

5. Positive faecal PCR or Kato-Katz for hookworm at screening, any known history of hookworm infection or treatment for hookworm infection or possible exposure to hookworm in the past.

6. Being an employee or student of the department of Parasitology of the LUMC.

7. Current or past scars, tattoos, or other disruptions of skin integrity at the intended site of larval application.

8. Subjects with planned travel to hookworm-endemic areas with a stay in non-hygienic environment during this trial.