RIMDAMAL: Repeat Ivermectin Mass Drug Administrations for Control of Malaria: a Pilot Safety and Efficacy Study

• Sponsor: Colorado State University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02509481
• Collaborator: Institut de Recherche en Sciences de la Sante, Burkina Faso (Other), Centre Muraz (Other), Ministère de la Santé du Burkina Faso (Other)
• Enrollment: 2,712
• Locations: 2
• Arms: 2
• Duration (Months): 6
• Patients Per Site: 1356
• Patients Per Site Per Month: 225.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether repeated ivermectin mass drug administrations to Burkinabé villagers, performed in three week intervals over the rainy-season, is well-tolerated and safe, and also effective in reducing local malaria transmission and thus clinical malaria episodes in treated village children.

Condition or Disease	Intervention/Treatment	Phase
Malaria; Lymphatic Filariasis	Drug: Ivermectin; Drug: Albendazole	Phase 2/Phase 3

Detailed Description

Primary Objective: To determine the efficacy of repeated ivermectin mass drug administrations (IVM MDA) (150 µg/kg), given to the population of eligible patients in enrolled villages, for reducing the cumulative incidence of uncomplicated malaria episodes in enrolled village children (≤ 5 years of age) over the course of the treatment.

Hypothesis: Repeated IVM MDA starting at the beginning of the rainy season will be well tolerated and safe, and will reduce clinical malaria episodes in children by significantly reducing malaria transmission among treated villages.

Overview Study Design: Single-blind (outcomes assessor); parallel assignment with 2 arms; cluster-randomized control trial to determine the effect of repeated IVM MDA on malaria transmission and clinical malaria episodes. The unit of randomization will be the village (cluster). 8 villages total will be enrolled in two arms. The active comparator arm (4 villages) will receive a single standard MDA (IVM; 150-200 µg/kg + albendazole; 400 mg) soon after the start of the rainy season, while the experimental arm (4 villages) will receive the standard MDA on the same date, plus 5 more IVM MDA at 3 week intervals thereafter. The primary endpoint will be the cumulative incidence of clinical malaria episodes in children ≤5 year of age within each village.

Sites: This study will be conducted in villages along the main east-west and north-south road corridors in the Sud-Ouest administrative region of Burkina Faso.

Study Population: Indigenous Burkinabé from various ethnic groups (Dagara, Bobo, Lobi, Mossi, etc.). The entire eligible population of each enrolled village will receive the MDAs, following the standard inclusion/exclusion criteria of MDA for control of microfilaremia caused by Wuchereria bancrofti (lymphatic filariasis; LF). Clinical incidence of malaria will be assessed only in children living in enrolled villages who are ≤ 5 years of age, most of whom will not have received any treatment due to the standard MDA exclusion criteria of children < 90 cm.

Study Interventions: 2 arms: 1) Active comparator arm - single standard MDA with IVM (150 µg/kg) + albendazole (ALB;400 mg) soon after the beginning of the rainy season; 2) Experimental arm, single standard MDA with IVM (150 µg/kg) + ALB (400 mg) plus 5 more MDA with IVM alone (150 µg/kg) at 3 week intervals thereafter. Community health workers and trained by local health authority of the Sud-Ouest region will perform the first MDA in both arms with logistical assistance from the study investigators. Repeated MDAs will only occur in the experimental-arm villages, and be performed by the study investigators.

Follow-up Procedures: Trained nurses will visit each study village each week over the course of the study to investigate and record any adverse events or severe adverse events communicated by the study population. They will also perform active case surveillance each week on enrolled village children for clinical malaria episodes, defined as ≥38.0°C fever or history of fever in the last 24 hours + positive rapid diagnostic test for Plasmodium falciparum. Secondary measures will be collected by the nurses.

Sample Size: Assuming an 80% cumulative incidence of malaria episodes in the control arm and an intracluster correlation coefficient of 0.02, 4 clusters are needed per arm and 69 children enrolled per cluster to detect a conservative 40% reduction in incidence in the treatment arm with 80% power and a statistical confidence of 95%.

Safety Outcomes:

• Adverse events (seriousness, causality, expectedness)

Secondary Outcomes:

• Incidence of new P. falciparum infections acquired (molecular force-of-infection)

• Prevalence and intensity (eggs/larvae per gram of feces) of soil transmitted helminth infections in a subset of treated patients between 6-10 years of age.

• Indoor-resting Anopheles mosquito capture rate

• Outdoor-host seeking Anopheles mosquito capture rate

• Adult mosquito age structure (parity rate) in captured mosquitoes

• Plasmodium sporozoite rate/entomological inoculation rate in captured mosquitoes

• Rate of Wuchereria bancrofti in captured mosquitoes

Study Design

• Study Type: Interventional
• Actual Enrollment: 2712 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Repeat Ivermectin Mass Drug Administrations for Control of Malaria: a Pilot Safety and Efficacy Study
• Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Single MDA Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis.	Drug: Ivermectin; Other Names: Mectizan ; Drug: Albendazole
Experimental: Repeated MDA Same at Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter.	Drug: Ivermectin; Other Names: Mectizan ; Drug: Albendazole

Outcome Measures

Primary Outcome Measures

1. Incidence of Clinical Malaria Episodes [Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm]

   Cumulative incidence of malaria episodes in a cohort of village children ≤ 5 years of age (as assessed by active case surveillance in study villages - malaria episode defined as ≥38.0°C fever or history of fever in the last 24 hours + positive rapid diagnostic test for Plasmodium falciparum). Incidence is reported as malaria episodes per child over the course of the trial, a higher incidence is a worse outcome.

Secondary Outcome Measures

1. Adverse Events [Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm]

   The number of adverse events. Adverse events data were collected via passive case detection from total population.

2. Entomological Indicator of Parasite Transmission [Approximately 20 weeks, from before the start of the first MDA to 4 weeks following the last MDA in the Experimental arm]

   Change in human IgG reactivity (optical density; ∆OD) to an Anopheles salivary gland antigen (peptide gSG6-P1) over the trial period. A score of 0 indicates no change in seroreactivity from from immediately before to immediately after the trial, suggesting consistent mosquito biting throughout the trial. A positive score indicates increasing seroreactivity and thus increasing mosquito biting on participants from immediately before to immediately after the trial. A negative score indicates decreasing seroreactivity and thus decreasing mosquito biting on participants from immediately before to immediately after the trial.

3. Molecular Force of P. Falciparum Infection [Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm]

   Examination of new P. falciparum clones acquired from the beginning to the end of the intervention (molecular force of infection; mFOI) per child. Molecular genotyping used capillary blood taken at the time of diagnosis of each positive malaria episode and consisted of nPCR of the msp2 gene. We calculated the multiplicity of infection (MOI) per malaria episode, and then calculated the molecular force of infection (mFOI) associated with malaria episodes per child (over course of the trial)

4. Number of 6-10 Year Old Participants With Soil Transmitted Helminths (STH) [Approximately 20 weeks, from before the start of the first MDA to 4 weeks following the last MDA in the Experimental arm]

   Prevalence of soil transmitted helminth infections in children between 6-10 years old from the beginning to the end of the intervention

5. Entomological Inoculation Rate [6 sampling periods over 18 weeks, starting in week 2 following the first MDA, and sampling every 3 weeks thereafter until week 17 of the treatment phase.]

   The entomological inoculation rate (EIR per week per person) is the measure of the human biting rate per person per week, multiplied by the sporozoite rate (in biting mosquitoes) per week, an estimated from sampling mosquitoes from 8 households located in the center of each study village. The EIR was calculated for each of the 6 sampling weeks of the treatment phase.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Residence in the study site

• Able to understand the information and willing to give consent and assent (parent or guardian consent if study participant age is < 18 years)

Exclusion Criteria:

• Residence outside of in the study site

• Height ≤ 90 cm

• Permanent disability, serious medical illness that prevents or impedes study participation and/or comprehension

• Pregnancy

• Breast feeding if infant is within 1 week of birth

• Known allergy to the study drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Colorado State University	Fort Collins	Colorado	United States	80523
2	Institut de Recherche en Sciences de la Santé	Bobo Dioulasso	Houet	Burkina Faso	10400-000

Sponsors and Collaborators

• Colorado State University
• Institut de Recherche en Sciences de la Sante, Burkina Faso
• Centre Muraz
• Ministère de la Santé du Burkina Faso

Investigators

• Principal Investigator: Brian D. Foy, PhD, Colorado State University
• Principal Investigator: Roch K Dabire, PhD, Institute de Recherche en Sciences de la Santé

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Jul 30, 2015

More Information

Publications

None provided.

• Responsible Party: Colorado State University
• ClinicalTrials.gov Identifier: NCT02509481
• Other Study ID Numbers: 5375011; OPP1116536
• First Posted: Jul 28, 2015
• Last Update Posted: Jan 4, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by Colorado State University: malaria; lymphatic filariasis; mosquito; ivermectin; mass drug administration
• Additional relevant MeSH terms: Malaria; Filariasis; Elephantiasis, Filarial; Elephantiasis; Ivermectin; Albendazole

Study Results

Participant Flow

Recruitment Details	2712 participants from 8 villages were recruited to participate and enrolled. Importantly, the intervention (repeated ivermectin MDA) was given to most villagers and the safety outcome was assessed in this whole group. However, the primary outcome was assessed in a cohort of 590 enrolled village children ≤5 years old.

Arm/Group Title	Single MDA	Repeated MDA
Arm/Group Description	Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis. Ivermectin Albendazole	Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter. Ivermectin Albendazole
Period Title: Overall Study
STARTED	1265	1447
COMPLETED	1265	1447
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Single MDA	Repeated MDA	Total
Arm/Group Description	Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis. Ivermectin Albendazole	Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter. Ivermectin Albendazole	Total of all reporting groups
Overall Participants	1265	1447	2712
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	14	16	15
Sex: Female, Male (Count of Participants)
Female	620 49%	713 49.3%	1333 49.2%
Male	645 51%	734 50.7%	1379 50.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1265 100%	1447 100%	2712 100%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Burkina Faso	1265 100%	1447 100%	2712 100%
Height <90 cm (Count of Participants)
Count of Participants [Participants]	210 16.6%	267 18.5%	477 17.6%

Outcome Measures

1. Primary Outcome

Title	Incidence of Clinical Malaria Episodes
Description	Cumulative incidence of malaria episodes in a cohort of village children ≤ 5 years of age (as assessed by active case surveillance in study villages - malaria episode defined as ≥38.0°C fever or history of fever in the last 24 hours + positive rapid diagnostic test for Plasmodium falciparum). Incidence is reported as malaria episodes per child over the course of the trial, a higher incidence is a worse outcome.
Time Frame	Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm

Outcome Measure Data

Analysis Population Description

Note that the primary outcome measure comes only from malaria incidence measurements within this child cohort (590 children). It is not a measure of malaria incidence from all enrolled participants from the study villages (2712 participants).

Arm/Group Title	Single MDA	Repeated MDA
Arm/Group Description	Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis. Ivermectin Albendazole	Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter. Ivermectin Albendazole
Measure Participants	263	327
Mean (95% Confidence Interval) [episodes]	2.49	2.00

2. Secondary Outcome

Title	Adverse Events
Description	The number of adverse events. Adverse events data were collected via passive case detection from total population.
Time Frame	Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm

Outcome Measure Data

Analysis Population Description

Per protocol, the secondary outcome was a measure of all adverse events, excluding uncomplicated malaria episodes that were reported in the primary outcome, that occurred among the total enrolled population from the study villages (2712 participants).

Arm/Group Title	Single MDA	Repeated MDA
Arm/Group Description	Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis. Ivermectin Albendazole	Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter. Ivermectin Albendazole
Measure Participants	1265	1447
Number [adverse events]	24	45

3. Secondary Outcome

Title	Entomological Indicator of Parasite Transmission
Description	Change in human IgG reactivity (optical density; ∆OD) to an Anopheles salivary gland antigen (peptide gSG6-P1) over the trial period. A score of 0 indicates no change in seroreactivity from from immediately before to immediately after the trial, suggesting consistent mosquito biting throughout the trial. A positive score indicates increasing seroreactivity and thus increasing mosquito biting on participants from immediately before to immediately after the trial. A negative score indicates decreasing seroreactivity and thus decreasing mosquito biting on participants from immediately before to immediately after the trial.
Time Frame	Approximately 20 weeks, from before the start of the first MDA to 4 weeks following the last MDA in the Experimental arm

Outcome Measure Data

Analysis Population Description

We sampled finger capillary blood pre-intervention from a subset of enrolled participants located in 8 households at the center of each study village, and then re-sampled their blood immediately after the intervention period. Data were reported only from participants that gave both sets of samples (221 of 2712 participants).

Arm/Group Title	Single MDA	Repeated MDA
Arm/Group Description	Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis. Ivermectin Albendazole	Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter. Ivermectin Albendazole
Measure Participants	95	126
Mean (95% Confidence Interval) [change in IgG ELISA optical density]	-0.057	-0.124

4. Secondary Outcome

Title	Molecular Force of P. Falciparum Infection
Description	Examination of new P. falciparum clones acquired from the beginning to the end of the intervention (molecular force of infection; mFOI) per child. Molecular genotyping used capillary blood taken at the time of diagnosis of each positive malaria episode and consisted of nPCR of the msp2 gene. We calculated the multiplicity of infection (MOI) per malaria episode, and then calculated the molecular force of infection (mFOI) associated with malaria episodes per child (over course of the trial)
Time Frame	Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm

Outcome Measure Data

Analysis Population Description

Molecular genotyping was performed on blood samples from 132 enrolled cohort children who were selected using a random sequence generator. Genotyping was successful on blood spots corresponding to 153 malaria episodes, which allowed us to calculate the mFOI over the trial from 76 enrolled children from the cohort.

Arm/Group Title	Single MDA	Repeated MDA
Arm/Group Description	Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis. Ivermectin Albendazole	Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter. Ivermectin Albendazole
Measure Participants	38	38
Median (Inter-Quartile Range) [new P. faliciparum infections per child]	4	3

5. Secondary Outcome

Title	Number of 6-10 Year Old Participants With Soil Transmitted Helminths (STH)
Description	Prevalence of soil transmitted helminth infections in children between 6-10 years old from the beginning to the end of the intervention
Time Frame	Approximately 20 weeks, from before the start of the first MDA to 4 weeks following the last MDA in the Experimental arm

Outcome Measure Data

Analysis Population Description

This outcome was only measured in older enrolled children between 6-10 years of age, who were not in our primary outcome cohort, and who were eligible to be treated with ivermectin due to their height >90 cm (232 of 2712 participants).

Arm/Group Title	Single MDA	Repeated MDA
Arm/Group Description	Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis. Ivermectin Albendazole	Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter. Ivermectin Albendazole
Measure Participants	122	110
Number [participants]	3 0.2%	0 0%

6. Secondary Outcome

Title	Entomological Inoculation Rate
Description	The entomological inoculation rate (EIR per week per person) is the measure of the human biting rate per person per week, multiplied by the sporozoite rate (in biting mosquitoes) per week, an estimated from sampling mosquitoes from 8 households located in the center of each study village. The EIR was calculated for each of the 6 sampling weeks of the treatment phase.
Time Frame	6 sampling periods over 18 weeks, starting in week 2 following the first MDA, and sampling every 3 weeks thereafter until week 17 of the treatment phase.

Outcome Measure Data

Analysis Population Description

The mean EIR was calculated across the 6 sampling periods in the 8 study villages (4 villages in each arm). EIR was calculated from the number of mosquitoes captured in select houses and the number of enrolled participants who lived in each sampled house (324/1265 in single MDA arm, and 271/1447 in repeated MDA arm).

Arm/Group Title	Single MDA	Repeated MDA
Arm/Group Description	Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis. Ivermectin Albendazole	Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter. Ivermectin Albendazole
Measure Participants	324	271
Mean (Standard Deviation) [infectious bites per person per week]	0.2069 (0.2376)	0.1972 (0.2084)

Adverse Events

Adverse Event Reporting Description	Adverse events were measured from the total population of enrolled participants in the eight study villages (n=2712), and most of these participants received the study intervention (ivermectin MDA)
Arm/Group Title	Single MDA		Repeated MDA
Arm/Group Description	Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis. Ivermectin Albendazole		Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter. Ivermectin Albendazole
All Cause Mortality
	Single MDA		Repeated MDA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/1265 (0.4%)		15/1447 (1%)
Serious Adverse Events
	Single MDA		Repeated MDA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/1265 (0.8%)		19/1447 (1.3%)
Cardiac disorders
untreated decompensated hypertensive heart failure	1/1265 (0.1%)	1	0/1447 (0%)	0
Gastrointestinal disorders
acute intestinal obstruction	0/1265 (0%)	0	1/1447 (0.1%)	1
abdominal pain, loose stool, vomiting	0/1265 (0%)	0	1/1447 (0.1%)	1
vomiting, hematemesis, bloody stool, cardiovascular shock	0/1265 (0%)	0	1/1447 (0.1%)	1
Abdominal bloating, fecal matter obstruction, anuria, refusal to breastfeed	0/1265 (0%)	0	1/1447 (0.1%)	1
Hepatobiliary disorders
liver disease: ascites + bulky edema of the lower limbs.	0/1265 (0%)	0	1/1447 (0.1%)	1
liver cancer, cirrhosis of the liver	0/1265 (0%)	0	1/1447 (0.1%)	1
Infections and infestations
moderate to severe malaria	7/1265 (0.6%)	7	7/1447 (0.5%)	7
neonatal infection	1/1265 (0.1%)	1	0/1447 (0%)	0
fever, vomiting, anorexia	1/1265 (0.1%)	1	0/1447 (0%)	0
fever, anemia, cachexia	0/1265 (0%)	0	1/1447 (0.1%)	1
severe sepsis	0/1265 (0%)	0	1/1447 (0.1%)	1
fever and chills; suspected typhoid fever	0/1265 (0%)	0	1/1447 (0.1%)	1
Injury, poisoning and procedural complications
snakebite envenomation	0/1265 (0%)	0	1/1447 (0.1%)	1
Investigations
unspecified sudden death in the early morning	0/1265 (0%)	0	1/1447 (0.1%)	1
Respiratory, thoracic and mediastinal disorders
dyspnea	0/1265 (0%)	0	1/1447 (0.1%)	1
Infectious pneumopathy	1/1265 (0.1%)	1	0/1447 (0%)	0
Other (Not Including Serious) Adverse Events
	Single MDA		Repeated MDA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/1265 (1.1%)		26/1447 (1.8%)
Ear and labyrinth disorders
Perforated bilaterally suppurated otitis	1/1265 (0.1%)	1	0/1447 (0%)	0
acute otitis media	0/1265 (0%)	0	1/1447 (0.1%)	1
suppurative otitis	0/1265 (0%)	0	1/1447 (0.1%)	1
Eye disorders
Bilateral palpebral edema	1/1265 (0.1%)	1	0/1447 (0%)	0
Gastrointestinal disorders
febrile diarrhea	0/1265 (0%)	0	1/1447 (0.1%)	1
Abdominal pain, loose stool, vomiting	0/1265 (0%)	0	1/1447 (0.1%)	1
vomiting	0/1265 (0%)	0	3/1447 (0.2%)	3
General disorders
Tremor, palpitations, arthralgia	1/1265 (0.1%)	1	0/1447 (0%)	0
	0/1265 (0%)	0	1/1447 (0.1%)	1
Immune system disorders
pruritis	1/1265 (0.1%)	1	2/1447 (0.1%)	2
Infections and infestations
malaria	2/1265 (0.2%)	2	2/1447 (0.1%)	2
acute malnutrition	2/1265 (0.2%)	2	5/1447 (0.3%)	5
fever	1/1265 (0.1%)	1	0/1447 (0%)	0
diarrhea	1/1265 (0.1%)	1	0/1447 (0%)	0
stage 3 tooth decay with local tumefaction	1/1265 (0.1%)	1	0/1447 (0%)	0
headache and chills; suspected infectious origin	0/1265 (0%)	0	1/1447 (0.1%)	1
fever and chills; suspected typhoid	0/1265 (0%)	0	1/1447 (0.1%)	1
Injury, poisoning and procedural complications
unspecified injury	1/1265 (0.1%)	1	0/1447 (0%)	0
snakebite envenomation	1/1265 (0.1%)	1	0/1447 (0%)	0
first degree burn over 80% of lower right limb	0/1265 (0%)	0	1/1447 (0.1%)	1
unspecified injury	0/1265 (0%)	0	1/1447 (0.1%)	1
road accident	0/1265 (0%)	0	1/1447 (0.1%)	1
Musculoskeletal and connective tissue disorders
Swelling of the feet, hyperthermia and chills	0/1265 (0%)	0	1/1447 (0.1%)	1
Pregnancy, puerperium and perinatal conditions
Involuntary abortion at two months of pregnancy	0/1265 (0%)	0	1/1447 (0.1%)	1
Postpartum pelvic pain	0/1265 (0%)	0	1/1447 (0.1%)	1
Skin and subcutaneous tissue disorders
intercostal zoster from immune system depression	1/1265 (0.1%)	1	0/1447 (0%)	0
Chronic wound in the left ankle	0/1265 (0%)	0	1/1447 (0.1%)	1

Limitations/Caveats

We could not provide placebo MDA for the control villages, and the trial was not blinded to the study population or the study team. Adverse event analysis bias may have from the knowledge of the village populace as to what arm they were part of.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.