Necator Americanus Infection
Conditions
Keywords
Hookworm, Necator americanus, Mebendazole
Brief summary
Mebendazole tablets which are produced by most pharmaceutical manufacturers, including the State Pharmaceutical Manufacturing Corporation (SPMC) of Sri Lanka, contain a mixture of polymorphs A and C. However, there is some evidence to show that mebendazole polymorph C is the only form effective against the soil-transmitted helminths. This protocol describes a stratified, randomized, placebo-controlled trial that examined the efficacy of different mebendazole polymorphs produced by the SPMC in the treatment of hookworm infections.
Detailed description
Mebendazole has three polymorphic forms, identified as A, B and C. All of them are in accord with the US Pharmacopeia specifications (USP XXI) but they have distinct physiochemical characteristics (Himmelreich et al, 1977) and different therapeutic activities in experimentally infected mice with Trichinella spiralis infections (Rodriguez-Caabeiro et al, 1987). The original mebendazole tablets which were used to treat human infections had more than 90% of polymorph C (Van den Bossche et al, 1982), but most pharmacopeias currently do not specify the proportion of polymorph C that a tablet of mebendazole should contain, and the assay specified for measurement of the active ingredient measures all polymorphs together. There is some evidence to show that unlike polymorph C, polymorph A is ineffective in the treatment of hookworm and whipworm infections (Charoenlarp et al, 1993). The State Pharmaceutical Manufacturing Corporation of Sri Lanka produces both 500 mg and 100 mg tablets of mebendazole according to specifications laid down in the US Pharmacopeia. These tablets contain a mixture of polymorphs A and C. It is possible that increasing the content of mebendazole polymorph C in single dose tablets may improve cure rates and egg reduction rates, especially against hookworm and whipworm infections, where much variation in efficacy has been observed.
Interventions
DRUGMebendazole polymorph A and C 500 mg
Mebendazole tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg of mebendazole as a 50:50 mixture of Polymorphs A and C
DRUGMebendazole polymorph C
Mebendazole tablets manufactured by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg dose of mebendazole as Polymorph C alone
DRUGPlacebo
Placebo tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka
Sponsors
University of Kelaniya
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Necator americanus infection, as determined by examination of a single faecal smear, alone or with Ascaris lumbricoides or Trichuris trichiura
Exclusion criteria
* Children below the age of 2 years * Pregnant women * Individuals with diarrhea on day of treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cure Rate | Two weeks | Cure rate={(Number positive pretreatment - Number positive posttreatment)÷(Number positive pretreatment)}×100 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Faecal Egg Count Reduction 1 (FECR1) | Two weeks | FECR1= {\[(Arithmetic mean of pretreatment egg counts)-(arithmetic mean of posttreatment egg counts)\]÷(arithmetic mean of pretreatment egg counts)}×100 |
| Faecal Egg Count Reduction 2 (FECR2) | Two weeks | FECR2=〈Arithmetic mean {\[(pretreatment egg count)-(posttreatment egg count)\]÷(pretreatment egg count)}〉×100 |
Countries
Sri Lanka
Participant flow
Recruitment details
In order to identify those with hookworm infections, all individuals living in 219 households, in 8 estate divisions in Ratnapura District known to have a high prevalence of hookworm, were recruited to the study after obtaining their written, informed consent. Each person was requested to provide one faecal sample.
Pre-assignment details
Infants below the age of 2 years, pregnant women, and those with diarrhoea on the day of recruitment were excluded from the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Hookworm positive participants randomized to placebo | 70 |
| Mebendazole Polymorph A and C 500 mg Hookworm positive participants randomized to a single dose of Mebendazole polymorph A and C 500 mg | 70 |
| Mebendazole Polymorph C 500 mg Hookworm positive participants randomized to a single dose of Mebendazole polymorph C 500 mg | 74 |
| Total | 214 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 21 | 17 | 26 |
Baseline characteristics
| Characteristic | Mebendazole Polymorph A and C 500 mg | Mebendazole Polymorph C 500 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 18 Participants | 23 Participants | 17 Participants | 58 Participants |
| Age, Categorical >=65 years | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants | 47 Participants | 49 Participants | 144 Participants |
| Age Continuous | 36 years STANDARD_DEVIATION 19 | 32 years STANDARD_DEVIATION 18 | 34 years STANDARD_DEVIATION 18 | 34 years STANDARD_DEVIATION 18 |
| Region of Enrollment Sri Lanka | 70 participants | 74 participants | 70 participants | 214 participants |
| Sex: Female, Male Female | 37 Participants | 40 Participants | 37 Participants | 114 Participants |
| Sex: Female, Male Male | 33 Participants | 34 Participants | 33 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 70 | 0 / 70 | 0 / 74 |
| serious Total, serious adverse events | 0 / 70 | 0 / 70 | 0 / 74 |
Outcome results
Primary
Cure Rate
Cure rate={(Number positive pretreatment - Number positive posttreatment)÷(Number positive pretreatment)}×100
Time frame: Two weeks
Population: All participants who were hookworm positive at baseline, and who provided a faecal sample for examination at follow up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Cure Rate | 16.3 percentage of participants |
| Mebendazole Polymorph A and C 500 mg | Cure Rate | 28.3 percentage of participants |
| Mebendazole Polymorph C 500 mg | Cure Rate | 18.8 percentage of participants |
Secondary
Faecal Egg Count Reduction 1 (FECR1)
FECR1= {\[(Arithmetic mean of pretreatment egg counts)-(arithmetic mean of posttreatment egg counts)\]÷(arithmetic mean of pretreatment egg counts)}×100
Time frame: Two weeks
Population: All participants who were hookworm positive at baseline, and who provided a faecal sample for examination at follow-up, were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Faecal Egg Count Reduction 1 (FECR1) | -6.6 percentage of eggs excreted |
| Mebendazole Polymorph A and C 500 mg | Faecal Egg Count Reduction 1 (FECR1) | 86.1 percentage of eggs excreted |
| Mebendazole Polymorph C 500 mg | Faecal Egg Count Reduction 1 (FECR1) | 84.5 percentage of eggs excreted |
Secondary
Faecal Egg Count Reduction 2 (FECR2)
FECR2=〈Arithmetic mean {\[(pretreatment egg count)-(posttreatment egg count)\]÷(pretreatment egg count)}〉×100
Time frame: Two weeks
Population: All participants who were hookworm positive at baseline, and who provided a faecal sample for examination at follow up were included in the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Faecal Egg Count Reduction 2 (FECR2) | -108.1 percentage of eggs excreted | Standard Deviation 557.5 |
| Mebendazole Polymorph A and C 500 mg | Faecal Egg Count Reduction 2 (FECR2) | 66.2 percentage of eggs excreted | Standard Deviation 42.5 |
| Mebendazole Polymorph C 500 mg | Faecal Egg Count Reduction 2 (FECR2) | 49.8 percentage of eggs excreted | Standard Deviation 82.6 |