Clinical trial NCT05085665
Conditions: Loiasis
Sponsor: Washington University School of Medicine
Start date: 2021-07-30; Completion date: 2021-09-30
Enrollment: 41 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study seeks to determine which Loa loa antigens are released into circulation when infected individuals are treated with ivermectin.

Detailed description:
A cohort of up to 50 participants with Loa loa microfilarial levels between 5,000 and 18,000 per ml/blood will be treated with ivermectin in an inpatient setting. Participants will be monitored for treatment-related adverse events for seven days post-treatment, and will have blood drawn on days 0, 1, 2, 3, and 7 post-treatment to assess for microfilarial load, cytokine, and antigen levels.

Arms: arm 1: All eligible participants received a single dose (150 ug/kg) ivermectin by mouth
Interventions: intervention 1: Ivermectin
Intervention descriptions: intervention 1: single dose, 150 ug/kg

Protocol documents:
Prot_SAP_ICF_000.pdf: 
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Principal Investigators 
Signatures 
Prof Joseph Kamgno (MD, PhD), Epidemiologist, Director of the Centre 
for Research on Filariasis and other Tropical Diseases (CRFilMT) and Vice- 
Dean in charge of Research and Cooperation at the Faculty of Medicine and 
Biomedical Sciences (FMBS), Yaoundé, Cameroon 
 
Dr. Philip Budge (MD, PhD), Assistant Professor of Medicine and 
Infectious Diseases, Washington University in St. Louis, USA 
 
 
 
 
Co-investigateurs 
Signatures 
Dr. Hugues C Nana Djeunga (PhD), Research Scientist and Lab 
Coordinator, CRFilMT, Yaoundé, Cameroon 
 
Dr. Marla Hertz (PhD), Senior Scientist, Department of Medicine, 
Infectious Disease Division, Washington University in St. Louis, USA 
 
Prof Gary Weil (MD), Professor of Medicine and Infectious Diseases, 
Washington University in St. Louis, USA  
 
Ms. Linda Djune Yemeli (Msc, PhD Student), Biochemist, Research 
Assistant, CRFilMT, Yaoundé, Cameroon 
 
 
 
 
Funder/Sponsor 
 
 
Funder: Doris Duke Foundation, 650 5th Ave, New York, NY 10019, USA 
Sponsor: Washington University in St. Louis, USA 
 
Cross-reactive antigenemia and treatment-related 
adverse events in loiasis 


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1. Ethical clearance request 
 
 
 
 
 
 
June 28, 2019 
 
To the President of the Cameroon National Ethics Committee for Research in 
Human Health (CNERSH)    
 
Subject: Request for Ethical Clearance 
 
Dear Mr. President, 
I am writing on behalf of the investigators (including myself) of the collaborative research 
project entitled ‘’ Cross-reactive antigenemia and treatment-related adverse events 
in loiasis’’ to request for ethical clearance. 
 
Lymphatic Filariasis (LF) is a debilitating parasitic infection endemic in tropical countries 
(including Cameroon) and targeted for elimination by 2020. The strategy to eliminate LF 
relies on yearly Mass Drug Administration (MDA) of albendazole and ivermectin (IVM) or 
diethylcarbamazine (DEC). Despite the success of this strategy (the transmission 
interruption have been achieved in many countries), none of the 11 loiasis-endemic 
African nations have interrupted LF transmission, because of (i) cross reactivity of LF-
RDT with Loa loa, and (ii) severe adverse events (SAEs) potentially fatal that have been 
reported among persons with very high L. loa microfilaria counts treated with IVM or DEC 
against LF or onchocerciasis. The objective of this study is to determine what are the 
cross-reactive L. loa antigens, and investigate how and when are they released, as well as 
whether their release contribute to treatment-related SAEs observed in persons with 
heavy loiasis infections. This study will provide insights in the progress towards 
elimination of LF. 
 
I remain at your disposal to bring any additional information if needed.  
Yours sincerely, 
 
Prof Joseph Kamgno. 
Prof Joseph Kamgno (MD, PhD), 
Director of the Centre for Research on Filariasis 
and other Tropical Diseases (CRFilMT) 
Vice-Dean in charge of Research and Cooperation, 
Faculty of Medicine and Biomedical Sciences, 
University of Yaounde 1 


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2. Contents 
1. 
Ethical clearance request ................................................................................................................ 2 
2. 
Contents .......................................................................................................................................... 3 
3. 
List of abbreviations ........................................................................................................................ 5 
4. 
Summary of the proposal ................................................................................................................ 6 
5. 
Résumé du protocole ...................................................................................................................... 6 
6. 
Introduction .................................................................................................................................... 7 
7. 
Research questions ......................................................................................................................... 9 
8. 
Research hypothesis ....................................................................................................................... 9 
9. 
Objectives ........................................................................................................................................ 9 
9.1. 
General objective .................................................................................................................... 9 
9.2. 
Specific objectives ................................................................................................................... 9 
10. 
Litterature review ..................................................................................................................... 10 
11. 
Methods .................................................................................................................................... 14 
11.1. 
Study design ...................................................................................................................... 14 
11.2. 
Study sites ......................................................................................................................... 14 
11.3. 
Period of the study ............................................................................................................ 15 
11.4. 
Study population ............................................................................................................... 15 
11.5. 
Selection criteria ............................................................................................................... 15 
11.5.1. 
Inclusion criteria ............................................................................................................ 15 
11.5.2. 
Exclusion criteria ........................................................................................................... 16 
11.6. 
Sample size ........................................................................................................................ 16 
11.7. 
Data and samples collection ............................................................................................. 17 
11.7.1. 
Cohort 1 (recruitment and monitoring) ........................................................................ 17 
11.7.2. 
Cohort 2 (recruitment and monitoring) ........................................................................ 18 
11.7.3. 
Laboratory evaluation ................................................................................................... 19 
11.8. 
Statistical analysis ............................................................................................................. 20 
12. 
Ethical considerations ............................................................................................................... 21 
12.1. 
Risks/Discomfort of the study ........................................................................................... 22 
12.2. 
Benefits of the Study ......................................................................................................... 23 
12.3. 
Confidentiality ................................................................................................................... 23 
13. 
Information notes ..................................................................................................................... 23 
13.1. 
Information note, Cohort 1 ............................................................................................... 23 
13.2. 
Information note,  Cohort 2 .............................................................................................. 26 
13.3. 
Notice d’information (Cohorte 1) ...................................................................................... 30 


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13.4. 
Notice d’information (Cohorte 2) ...................................................................................... 32 
14. 
Inform consents ........................................................................................................................ 36 
14.1. 
Assent form (Cohort 1: Participants aged from 18 to 20 years old) .................................. 36 
14.2. 
Assent form (Cohort 2: Participants aged from 18 to 20 years old) .................................. 37 
14.3. 
Inform consent form (Cohort 1: Participants aged ≥21 years old) .................................... 38 
14.4. 
Inform consent form (Cohort 2: Participants aged ≥21 years old) .................................... 39 
15. 
Formulaires de consentement éclairé ....................................................................................... 40 
15.1. 
Formulaire d’assentiment (Cohorte 1 : Participants âgés entre 15 et 20 ans) .................. 40 
15.2. 
Formulaire d’assentiment (Cohorte 2 : Participants âgés entre 18 et 20 ans) .................. 41 
15.3. 
Formulaire de consentement élaire (Cohorte 1 : Participants âgés de ≥21 ans) .............. 42 
15.4. 
Formulaire de consentement élaire (Cohorte 2 : Participants âgés de ≥21 ans) .............. 43 
16. 
Fiche de collecte de données/Survey form ............................................................................... 44 
16.1. 
Fiche de collecte de données cohorte 1 ............................................................................ 44 
16.2. 
Fiche de collecte de données cohorte 2 ............................................................................ 46 
17. 
Chronogram .............................................................................................................................. 49 
18. 
Detailed budget and Source of funding .................................................................................... 50 
18.1. 
Detailed budget ................................................................................................................. 50 
18.2. 
Source of funding .............................................................................................................. 50 
19. 
References ................................................................................................................................. 51 
20. 
Others documents ..................................................................................................................... 53 
20.1. 
Curriculum vitae of investigators ...................................................................................... 53 
20.2. 
Site Authorizations ............................................................................................................ 67 
20.3. 
Material/data sharing agreement ..................................................................................... 68 
20.4. 
Receipt for Evaluation fees ............................................................................................... 73 
 
 
 


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3. List of abbreviations 
AEs:  
Adverse Events  
CFA:  
Circulating Filarial Antigen 
DALYs: 
Disability-Adjusted Life Years  
DEC:  
Diethylcarbamazine 
FTS:  
Filariasis Test Strip  
GPELF: 
Global Program to Eliminate Lymphatic Filariasis  
ICT: 
 
Immuno-Chromatographic Test 
IVM:  
Ivermectin 
LF: 
 
Lymphatic filariasis  
MDA:  
Mass Drug Administration  
Mf: 
 
Microfilaria  
MMDP: 
Morbidity Management and Disability Prevention 
NTD:  
Neglected Tropical Disease  
RDT:  
Rapid Diagnostic Test 
SAEs:  
Severe Adverse Events  
TaNT:  
Test and Not Treat 
WHO:  
World Health Organization 
 
 


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4. Summary of the proposal 
Lymphatic filariasis (LF) is a disfiguring and disabling, mosquito-borne, parasitic 
neglected tropical disease. The majority of LF worldwide, and all LF in Africa, is caused by 
the filarial worm, Wuchereria bancrofti. The Global Program to Eliminate Lymphatic 
Filariasis (GPELF) is the world’s largest disease elimination program relying on 
population-based mass drug administration (MDA). Since its inception in 2000, more than 
7.1 billion doses of LF elimination medications have been administered to more than 890 
million people. However, none of the 11 loiasis-endemic African nations have interrupted 
LF transmission, partly due to two major obstacles in loiasis-endemic populations. (1) 
Severe adverse events (AEs), including coma and death, which sometimes occur when LF 
MDA medications are given to persons with heavy loiasis infections (>20,000 
microfilariae per mL of blood); (2) Up to 6% of persons in loiasis-endemic populations 
test positive by LF rapid diagnostic tests (RDTs) in the absence of W. bancrofti infection. 
Because a filarial antigenemia prevalence of 1% is the GPELF threshold for implementing 
MDA for LF, cross-reactivity with loiasis makes it impossible for national programs to 
determine with certainty where LF MDA is required and when it can be stopped. 
Therefore, improved RDTs that can reliably distinguish W. bancrofti infection from cross-
reactive loiasis are urgently needed to prevent unnecessary and potentially harmful mass 
drug administration in areas where LF is not endemic.  
 
This study aims to determine what the cross-reactive L. loa antigens are, how and when 
they are released, and whether their release contributes to treatment-related SAEs 
observed in persons with heavy loiasis infections. 
 
5. Résumé du protocole 
La filariose lymphatique (FL) est une maladie tropicale négligée parasitaire à 
transmission vectorielle (moustique) débilitante et invalidante. La plupart des cas 
d’infection associés à FL dans le monde, et tous ceux retrouvés en Afrique, est due à la 
filaire Wuchereria bancrofti. Le Programme Global pour l’Elimination de la Filariose 
Lymphatique (GPELF) s’appuie sur la distribution de masse des médicaments aux 
populations à risque. Depuis sa création en 2000, plus de 7,1 milliards de doses de 
médicaments (albendazole + ivermectine/diethylcarbamazine) contre la FL ont été 


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distribués à près de 890 millions de personnes à travers le monde. Cependant, aucun des 
11 pays Africains où la loase est endémique n’a réussi à interrompre la transmission de la 
filariose lymphatique pour deux principales raisons : (1) les effets secondaires graves 
(ESG) tels que le coma et la mort, qui surviennent souvent lorsque l’ivermectine ou la 
diethylcarbamazine sont administrés, dans la cadre de la lutte contre la FL, aux personnes 
ayant une forte charge de loase (˃ 20 000 microfilaires par ml de sang); (2) près de 6% 
de personnes dans les zones d’endémie à la loase réagissent (testées positives) aux tests 
de diagnostic rapide (TDR) de la FL, même en l’absence du parasite responsable de la FL 
(W. bancrofti). Compte tenu du fait qu’un taux d’antigènes filariens de 1% est 
recommandé par le GPELF pour l’implémentation de la distribution de masse des 
médicaments contre cette maladie, la réactivité croisée des antigènes de la loase rend 
impossible l’identification avec certitude des zones où la distribution de masse est 
nécessaire et là où elle doit être stoppée. Ainsi, une amélioration de l’efficacité des TDRs 
à distinguer l’infection à W. bancrofti de la loase est urgemment nécessaire pour éviter 
une administration de masse de médicaments inutile et potentiellement dangereuse dans 
les zones où la FL n’est pas endémique.  
 
Cette étude a pour objectifs de déterminer les antigènes de la loase ayant une réaction 
croisée avec les TDR dédiés à la FL, quand et comment ces antigènes sont produits et si 
leur libération contribue aux effets secondaires graves associés au traitement des 
personnes ayant une forte charge de loase. 
 
6. Introduction 
Lymphatic filariasis (LF) is a vector-borne neglected tropical disease (NTD) targeted for 
elimination as a public health problem. The infection transmitted by different species of 
mosquitoes (Culex, Anopheles and Aedes) is caused by thread-like filarial worms 
(nematodes) (CDC, 2019). In majority of the cases (90%), the infection is caused by 
Wuchereria Bancrofti and remainder by Brugia Species (Brugia malayi & Brugia timori). 
It is estimated that 120 million people in tropical and subtropical areas of the world are 
infected with lymphatic filariasis; among which, almost 25 million have genital disease 
(most commonly hydrocele in men) and almost 15 million (both men and women) have 
lymphoedema of the leg. The majority (57%) of population requiring preventative 
chemotherapy lives in the South-East Asia Region (9 countries) and remaining (37%) live 


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in the WHO Africa Region (35 countries). WHO estimates indicate that around 36 million 
people are living with these chronic disease manifestations globally. LF accounts for at 
least 2.8 million Disability-Adjusted Life Years (DALYs); this does not include significant 
co-morbidity of mental illness commonly experienced by patients and their caregivers 
(WHO, 2018). Fortunately, LF elimination is possible by interrupting the transmission 
cycle. Providing treatment on a large-scale to entire communities where the infection is 
present can stop the spread of infection. A key intervention strategy is MDA in all endemic 
areas with a microfilaria (Mf) or antigen prevalence of at least 1% (GPELF, 2017).  
 
The Global Programme to Eliminate LF (GPELF), the world’s largest disease elimination 
program relying on population-based mass drug administration, has worked towards 
elimination for nearly two decades. Since its inception in 2000, more than 7.1 billion doses 
of LF elimination medications have been administered to more than 890 million people 
(WHO, 2018). However, the disease is still persisting in 11 countries in Central and West 
Africa where Loiasis is also endemic. Loiasis, better known as the African eye worm, is a 
parasitic disease caused by the filarial nematode Loa loa and transmitted to humans by 
tabanids belonging to the genus Chrysops. It afflicts approximately 10 million people and 
clinical symptoms include localized skin swelling and irritation due to migration of the 
adult worms in subcutaneous tissue, as well as occasional passage of a worm across the 
eye under the bulbar conjunctiva (Boussinesq, 2006). Although loiasis has traditionally 
been considered benign and not classified on the WHO’ official list of NTD (Metzger WG 
2014), it poses two major obstacles for LF elimination. First, Severe adverse events (AEs) 
including coma and death sometimes occur when LF MDA medications are given to 
persons with heavy loiasis infections (>20,000 microfilariae per mL of blood) (Gardon et 
al., 1997). Secondly, up to 6% of persons in loiasis-endemic populations test positive by 
LF-RDTs in the absence of W. bancrofti infection (Pion et al., 2016 ; Wanji et al., 2015). 
Therefore, there is a need for a rapid test that can reliably distinguish W. bancrofti 
infection from cross-reactive loiasis. 
 
Recently many L. loa antigens that cause RDT cross-reactivity in two samples from 
persons with loiasis were identified. These included both secreted and somatic antigens, 
suggesting indiscriminate release of L. loa antigen from dying adult worms and/or 
microfilariae (Hertz et al., 2018). A similar pattern of antigen release has been observed 


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following treatment of microfilaremic LF patients with medications known to kill 
microfilariae (Anderson and Hertz, unpublished data), this suggests that filarial antigens 
might be released from dying worms. In addition, it was found that cross-reactivity with 
LF-RDTs is not constant in many loiasis patients despite persistence of high microfilarial 
loads. All these data above suggest intermittent release and/or clearance of cross-reactive 
antigen in persons with loiasis. Understanding how, why, and when cross-reactive Loiasis 
antigen are released and cleared will be essential to defining strategies to distinguish true 
LF-RDT positives from cross-reactive loiasis.   
 
7. Research questions 
This study addresses the following questions:  
§ What are the cross-reactive L. loa antigens, and how and when are they released? 
§ Does their release and their quantity correlate with the occurrence and the 
severity of treatment-related AEs and cytokine profiles? 
 
8. Research hypothesis 
§ Death of L. loa microfilariae releases antigens responsible for RDT cross-reactivity, 
and an imbalance in release and clearance of these antigens accounts for their 
intermittent presence in serum. 
§ The antigen profile of those with spontaneous antigenemia will not differ 
significantly from ivermectin-induced antigenemia. 
§ The nature and duration of treatment-related adverse events will correlate with 
the presence and levels of cross-reactive antigen and cytokine profiles. 
 
9. Objectives 
9.1. General objective 
§ 
To define the cross-reactive antigen profile of persons with spontaneous loiasis 
antigenemia and in those treated with Ivermectin, and to determine whether 
specific L. loa antigens are related to treatment-related adverse events. 
 
9.2. Specific objectives 
§ To characterize and quantify spontaneous cross-reactive L. loa antigens; 


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§ To characterize and quantify treatment-induced cross-reactive L. loa antigens; 
§ To compare spontaneous and treatment-induced cross-reactive L. loa antigens 
profiles and define the kinetics of antigen clearance; 
§ To determine whether specific L. loa antigens are associated with the occurrence 
and severity of treatment related AEs and cytokine profiles. 
 
10. Litterature review 
LF is a vector-borne neglected tropical disease targeted for elimination as a public health 
problem. The infection transmitted by different species of mosquitoes (Culex, Anopheles 
and Aedes) is caused by a thread like filarial nematodes roundworms (CDC, 2019). Three 
species of lymphatic dwelling ﬁlarial worms (Wuchereria bancrofti, Brugia malayi and B. 
timori) cause lymphatic ﬁlariasis in humans. The majority of the cases worldwide (90%), 
and all cases of LF in Africa are caused by Wuchereria Bancrofti (Michael et al.,  1996). 
Adult worms reside in the lymphatic vessels interrupting the normal function of the 
lymphatic system. The worms have life span of about 6–8 years and produce millions of 
Mf (immature larvae) that circulate in the blood. Mosquitoes are infected with Mf by 
consuming blood when biting an infected person. Mf then mature into the infective L3 
larval stage within the mosquito. When mosquitoes harbouring L3 larvae bite people, 
the larvae are deposited on the skin from where they can enter the body. The L3 larvae 
then migrate to the lymphatic vessels where they develop into adult worms, thus 
continuing a cycle of transmission (CDC, 2019). LF infection can cause a variety of clinical 
manifestations, including genital disease (hydrocele and/or chylocele) and lymphoedema 
of the limbs, which can be complicated by recurrent bacterial superinfections called acute 
attacks, which are extremely painful and are accompanied by fever. The majority of 
infected people are asymptomatic, but virtually all of them have subclinical lymphatic 
damage. It takes years to manifest chronic and disfiguring conditions. These conditions 
lead to mental, social and financial losses contributing to social stigma and poverty (WHO, 
2018).  
 
It is estimated that 120 million people in tropical and subtropical areas of the world are 
infected with lymphatic filariasis; among them, almost 25 million men have genital 
disease (most commonly hydrocele) and almost 15 million men and women, have 
lymphoedema of the leg. The majority (57%) of population requiring preventative 


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chemotherapy live in the South-East Asia Region (9 countries) and remaining (37%) live 
in the African Region (35 countries). An estimation of WHO indicated that around 36 
million people are living with these chronic disease manifestations globally. LF accounts 
for at least 2.8 million DALYs; this does not include significant co-morbidity of mental 
illness commonly experienced by patients and their caregivers (WHO, 2018). 
 
Elimination of LF as a public health problem means reducing infection prevalence in an 
area to below target thresholds and providing the recommended basic package of care in 
all areas with lymphoedema or hydrocele patients (WHO, 2018). GPELF has worked 
towards elimination for nearly two decades; first by interrupting transmission by MDA 
using different regimen combinations of albendazole, IVM and diethylcarbamazine (DEC), 
and second by alleviating suffering through morbidity management and disability 
prevention (MMDP) (WHO, 2017). Since its inception in 2000, more than 7.1 billion doses 
of LF elimination medications have been administered to more than 890 million people 
(WHO, 2018). Overall significant progress has been made towards elimination, but 
greater efforts are required in the WHO Africa Region, where many countries remain 
behind the elimination targets (WHO, 2017). In 2016, the WHO Africa region was 
estimated to have 371.2 million people requiring MDA across 32 endemic countries, with 
a reported coverage of 56.9% (WHO, 2017). While this marks an increase in coverage 
from previous years there are still 17 African countries yet to start or scale-up MDA to full 
nationwide geographical coverage (Molyneux et al., 2014). The reasons for limited 
coverage are complex and related to several factors including but not limited to political 
will, conflict, financial commitment, technical support, difficult to access populations, 
stakeholder interest, poverty, poor infrastructure, limited human capacity, competing 
priority diseases, and co-endemicity with L. loa (Hope et al., 2018). 
 
Loiasis, also known as African eye-worm disease, is a vector-borne parasitic infection 
caused by L. loa, a filarial worm endemic to Central and West Africa (Pion et al., 2017). It 
is restricted to the equatorial rain forest regions of Central and West Africa.  
Epidemiological data collected from 11 African countries indicates that at least 10 million 
people are infected (Zoure et al.,  2011). L. loa is transmitted by daytime biting flies of the 
genus Chrysops during a blood meal. The fly injects into the human host infective larvae 
(L3 development stage) that develop over time into adult worms that reside and migrate 


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in the subcutaneous tissues. These then mate to produce Mf that circulate in peripheral 
blood (Pion et al., 2017). The major clinical manifestations of loiasis are Calabar swellings 
(evanescent episodic angioedema) and occasional subconjunctival migration of the adult 
worm (eye-worm). Less specific manifestations include urticaria, pruritus, myalgias, and 
arthralgia (Herrick et al., 2015). Moreover, L. loa infection can cause renal, cardiac, 
pulmonary and neurological diseases, and a recent study found L. loa infection to be 
associated with a decreased life expectancy (Chesnais et al., 2017). The primary health 
risk from loiasis is the risk for severe or fatal AEs that can occur when individuals with L. 
loa Mf loads >30,000/mL are treated in MDA programs for LF and onchocerciasis (river 
blindness) (Gardon et al., 1997).  
 
Loiasis has recently emerged as a disease of public health importance, not because of its 
own clinical manifestations but because of its negative impact on the control of 
onchocerciasis and LF in areas of co-endemicity (Zouré et al., 2011). In fact, loiasis poses 
two problems for LF elimination: 
§ First, severe AEs including coma and death sometimes occur when LF MDA 
medications are given to persons with heavy loiasis infections (>20,000 
microfilariae per mL of blood) (Gardon et al., 1997). In fact, systemic AEs are 
common following treatment of filarial infections, including LF, onchocerciasis 
and loiasis, and are thought to be due to inflammation caused by dying filarial 
worms (Budge et al., 2018). These can be severe or fatal in persons with loiasis 
and high microfilarial loads. It has been shown that circulating Mf can reach 
500,000 Mf/mL in loiasis and the risk of AEs is positively associated with this Mf 
density, with Mf counts >50,000 Mf/mL conferring high risk for serious/fatal AEs 
(Gardon et al., 1997). The “Test and Not Treat” (TaNT) studies have recently 
demonstrate that there was no risk for serious AEs following ivermectin 
treatment of persons with loiasis Mf counts <20,000 Mf/mL (Kamgno et al., 2018; 
Kamgno et al.,  2017).  Among persons with microfilaremic LF or low-level loiasis, 
treatment-related AEs remain common but are mild and self-limited, usually 
resolving within 2-3 days following treatment. Typical reactions include fever, 
headache, myalgias, and malaise, which are similar to those seen following 
treatment of LF (Budge et al., 2018). Treatment-related AEs in LF are thought to 
be related to the immune response to filarial or Wolbachia antigens released by 


Loiasis Antigenemia Version 1.2 25 June 2019 
13 
 
dying Mf (Kumaraswami et al., 1988; Taylor et al., 2001). However, since L. loa 
does not harbour endosymbiont Wolbachia (McGarry et al., 2003), the 
pathogenesis of AEs following loiasis treatment may differ. In LF and loiasis, 
eosinophil counts and serum concentrations of type 2 cytokines increase 
following treatment with antifilarial drugs (Herrick et al., 2017; Andersen et al., 
2018). The relationship between specific cytokine activation and AEs in people 
with loiasis has not been elucidated. In LF, there is a post treatment increase in 
circulating filarial antigen and filarial DNA in patients who went on to develop 
moderate AEs compared to those who had mild or no AEs (Andersen et al., 2018).  
 
§ Second, L. loa infection complicates the mapping of LF distribution since standard 
RDTs for LF [e.g. BinaxNOW Filariasis immunochromatographic test (ICT) and/or 
the new Alere Filariasis Test Strip (FTS Alere, Scarborough, ME, USA)] (Weil et al., 
2013), cross-react with L. loa, resulting in false positives for W. bancrofti, with 
strong associations between ICT positivity and L. loa Mf counts (around 30% and 
50% of ICTs reacting to L. loa when densities were > 15,00 Mf/ml and > 30,000 
Mf/ml respectively) (Pion et al., 2016). Other studies also shown that up to 6% of 
persons in loiasis-endemic populations test positive by LF-RDTs in the absence of 
W. bancrofti infection (Wanji et al.,  2015; Pion et al., 2016). This makes it 
impossible for national programs to determine with certainty where LF MDA is 
required and when it can be stopped, given that a filarial antigenemia prevalence 
of 1% is the GPELF threshold for implementing MDA for LF. 
 
Recently, many L. loa antigens that cause LF-RDT cross-reactivity in two samples from 
persons with loiasis were identified. Surprisingly, these included both secreted and 
somatic antigens, suggesting indiscriminate release of L. loa antigen from dying adult 
worms and/or Mf (Hertz et al., 2018). A similar pattern of antigen release has been 
observed following treatment of patients with microfilaremic LF with medications known 
to kill Mf (Anderson et al, unpublished data). In addition, it was found that cross-reactivity 
with LF RDTs is not constant in many loiasis patients despite persistence of high Mf loads. 
These data suggest intermittent release and/or clearance of cross-reactive antigen in 
persons with loiasis.  
 


Loiasis Antigenemia Version 1.2 25 June 2019 
14 
 
 
11. Methods 
11.1. Study design 
This study is a prospective cohort study that will include two cohorts of persons with 
loiasis.   
• Cohort 1 (spontaneous antigenemia). This cohort will prospectively enroll 50 
adults with cross-reactive antigenemia and L. loa Mf counts >20,000 Mf/mL. 
Participants will be followed for one year and tested every three months for 
persistence of antigenemia. This cohort will not receive any filariasis treatment. 
Cohort 1 will allow us to define the cross-reactive antigen profile of persons with 
spontaneous loiasis antigenemia, and determine whether this varies with time. 
• Cohort 2 (induced antigenemia). This cohort will include 50 adults with low to 
moderate L. loa microfilaremia (greater than 5,000, but less than 18,000 Mf/mL) 
who do not have cross-reactive antigenemia at the time of enrollment. All will 
receive ivermectin (150 μg/kg, once) and will be monitored daily for one week 
post-treatment to document AEs and collect venous blood for measurement of 
cytokines and cross-reactive L. loa antigens. Cohort 2 will allow us to identify 
cross-reactive L. loa antigens released by ivermectin treatment and define the 
kinetics of antigen clearance, and to determine whether the release of specific L. 
loa antigens or the amount of released antigen correlate with the occurrence and 
severity of treatment-related AEs and cytokine profiles. 
 
11.2. Study sites 
Study site for cohort 1 (spontaneous antigenemia) 
The study site for cohort 1 will be the Okola health district (HD). The Okola HD is a 
degraded forest area located at 20 km from Yaoundé that is highly endemic for loiasis and 
hypomesoendemic for onchocerciasis (Zoure et al., 2011). Participants in this cohort will 
be recruited from among those excluded from the ongoing TaNT study due to Mf counts 
>20,000/mL. 
 
Study site for cohort 2 (induced antigenemia)  


Loiasis Antigenemia Version 1.2 25 June 2019 
15 
 
This cohort will be recruit and monitored in the Awae HD (Mefou and Afamba Division, 
Centre Region), which is located about 50 km south of Yaoundé, the political capital city 
of Cameroon. Because loiasis is highly endemic and onchocerciasis is hypoendemic in the 
area, no mass ivermectin distribution has ever been implemented in this area. 
 
11.3. Period of the study 
This study will be carried out over three years as shown in the chronogram. Data and 
sample collection in the field will begin in 2019 after ethical clearance have been granted. 
 
11.4. Study population 
Individuals eligible for this study will be of both sexes, aged from 18 years old and over, 
as follow: 
§ Participants of both sexes aged from 18 years and over in the ongoing TaNT study 
in Okola that were excluded from treatment due to Mf counts >20,000 Mf/mL will 
be included in the cohort 1 (spontaneous antigenemia). 
§ Participants of both sexes aged from 18 years and over in the Awae HD where no 
MDA of ivermectin is ongoing will be included in cohort 2 (induced antigenemia) 
 
11.5. Selection criteria 
11.5.1. Inclusion criteria 
Inclusion criteria will be defined according to the cohort: 
§ 
Participants who will be included in cohort 1 will meet the following criteria: 
- 
Age ≥ 18 years  
- 
Ability to give informed consent 
- 
Loiasis Mf count > 20,000 Mf/mL 
- 
Resident of study area  
- 
No evidence of severe or systemic comorbidities  
- 
Consent to storage of blood samples for future study 
 
§ Participants who will be included in cohort 2 will meet the following criteria: 
- 
Age ≥ 18 years 
- 
Ability to give informed consent 


Loiasis Antigenemia Version 1.2 25 June 2019 
16 
 
- 
Loiasis Mf count between 5,000 Mf/mL and <18,000 mf/mL (to account for 
potential imprecision in the Mf counts, we will used a cut-off of 18,000 to 
ensure that no one with >20,000 Mf/mL is included)  
- 
Resident of study area  
- 
No evidence of severe or systemic comorbidities  
- 
Absence of non-L. loa Mf (i.e. W. bancrofti or M. perstans) on thick blood 
smear 
- 
Consent to storage of blood samples for future study 
 
11.5.2. Exclusion criteria 
Exclusion criteria will differ from one cohort to the other one. Participants who plans to 
move from study area during subsequent 12 months will be excluded from cohort 1, while 
participants will be excluded from cohort 2 if they meet the following criteria: 
- 
Pregnancy or breastfeeding 
- 
Alcohol or drug abuse 
- 
History of severe adverse reaction to ivermectin 
- 
Onchocerciasis (history of positive Ov16 test or positive skin snip) 
- 
M. perstans infection (positive day blood smear) 
 
11.6. Sample size 
The sample size has been calculated according to the objectives and the corresponding 
cohort: 
§ The objective Cohort 1 is to identify one or more antigens that are sufficiently 
prevalent among persons with cross-reactive loiasis, that they can be used as 
biomarker(s) to distinguish cross-reactive loiasis from LF. We define a potential 
biomarker as an antigen that is detectable in at least 90% of the population of 
interest. Assuming that one or more antigens is present in at least 90% of the 
population of interest (those with cross-reactive loiasis), a sample size of 50 
patients will give us 95% confidence in excluding antigens that are present in less 
than 80% of samples (1-sided Wilson score lower than the 95% confidence 
interval). 
§ The objectives of cohort 2 are to define the cross-reactive antigen profile released 
by ivermectin treatment and the kinetics of antigen clearance, and to determine 


Loiasis Antigenemia Version 1.2 25 June 2019 
17 
 
whether the release of specific L. loa antigens or the amount of released antigen 
correlate with the occurrence and severity of treatment-related AEs and cytokine 
profiles. The sample size of 50 was chosen for cohort 2 to provide direct 
comparison to the objective of cohort 1 and will provide a similar level of 
confidence about the prevalence of antigens for this population. 
 
11.7. Data and sample collection 
Data and sample collection will be organized according to the objectives of the different 
cohorts. 
 
11.7.1. Cohort 1 (recruitment and monitoring) 
This cohort will include participants of the ongoing TaNT in Okola, who were excluded 
from IVM treatment due to Mf count ≥20,000 Mf/mL. Those participants will be visited in 
their home or other designated location. After providing consent for screening, they will 
be test for cross-reactivity using FTS. In addition, a LoaScope Mf count will be done for 
those who have not done this test during the last three months. Those with positive FTS 
test results who consent to participate to the study will be enrolled in cohort 1. If, after 
screening all available participants excluded from TaNT due to high Mf counts, fewer than 
50 FTS positive subjects are found, we will enroll some of the FTS negative subjects with 
highest MF loads. 
 
The day of enrolment, each participant will provide 10 mL venous blood for subsequent 
mass spectrometry (detection of cross-reactive L. loa antigens) and quantitative ELISA 
(determination of the level of cross-reactive L. loa antigens). Additionally, daytime 
calibrated thick blood smear will be performed for L. loa and Mansonella species detection 
and quantification. Furthermore, nocturnal calibrated thick blood smears and dried blood 
spot (DBS) will be done for detection and quantification of W. bancrofti by microscopy 
and PCR. 
 
For this cohort, the follow up will be done 3, 6, 9 and 12 months after enrolment. During 
each visit, a FTS test will be done for each participant and those who will be positive will 
provide 10 mL venous blood for subsequent mass spectrometry (detection of cross-


Loiasis Antigenemia Version 1.2 25 June 2019 
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reactive L. loa antigens) and quantitative ELISA (determination of the level of cross-
reactive L. loa antigens). 
 
11.7.2. Cohort 2 (recruitment and monitoring) 
Screening for Cohort 2 will involve community-based testing of potential participants. 
Initial screening tests will examine a small amount (~200 µL) of capillary blood (obtained 
by fingerprick) for the presence of L. loa Mf (measured using the LoaScope), and absence 
of filarial antigen (using the FTS test). Individuals meeting inclusion criteria and providing 
informed consent will undergo further testing to rule out co-infection with other filarial 
species (O. volvulus, M. perstans) that may contribute to treatment-related AEs. Cohort 2 
participants will then be admitted to the local health center for observation. All 
participants will receive a single dose of ivermectin (150 µg/kg) the day after admission. 
This dose is the same as that given for onchocerciasis MDA annually. Physical examination 
will be performed daily starting on day –1 (pre-treatment, the day of admission). Vital 
signs will be recorded on admission and at least daily through day 7. Venous blood will be 
drawn before treatment on day 0, and on days 1, 2, 3, and 7 post-treatment. Procedure for 
data and samples collection for this cohort are resumed in the table below. 
 
Visit 
Cohort 2 activities and assessments 
Screening 1 
(0-4 
weeks 
pre-
treatment) 
• 
Consent for screening 
• 
LoaScope Mf count  
• 
FTS  
• 
Daytime thick blood smear (Loa, Mansonella Mf count)  
• 
Skin snips (rule out Onchocerciasis) 
• 
Urine pregnancy test (if female) 
Enrollment  
(Day 0)  
• 
FTS (exclude if positive) 
• 
LoaScope Mf count 
• 
Thick blood smear 
• 
Admit to health center 
• 
Pre-treatment physical examination 
• 
Pre-treatment AE questionnaire (defer if febrile or other systemic illness) 
• 
Venous blood (pre-treatment) for cytokines, antigen ELISA 
• 
Ivermectin treatment 
• 
Vital signs and AE monitoring q8hrs 


Loiasis Antigenemia Version 1.2 25 June 2019 
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Day 1 
• 
FTS 
• 
LoaScope Mf count 
• 
Venous blood (antigen ELISA, cytokines, +/- mass spec) 
• 
Physical exam 
• 
Vital signs and AE monitoring q8hrs  
Day 2 
• 
FTS (if not positive day 1) 
• 
LoaScope Mf count 
• 
Venous blood (antigen ELISA, cytokines, +/- mass spec) 
• 
Physical exam 
• 
Vital signs and AE monitoring q8hrs 
Day 3 
• 
LoaScope Mf count 
• 
Thick blood smear 
• 
Venous blood (antigen ELISA, cytokines, +/- mass spec) 
• 
Physical exam 
• 
Vital signs and AE monitoring q8hrs 
Day 4 – 6 
• 
LoaScope Mf count (if not zero on day 3) 
• 
Venous blood (antigen ELISA, cytokines) 
• 
Physical exam 
• 
Vital signs and AE monitoring daily 
Day 7 
• 
FTS 
• 
LoaScope Mf count 
• 
Thick blood smear 
• 
Venous blood (antigen ELISA, cytokines) 
• 
Physical exam 
• 
Vital signs and AE monitoring daily 
Follow-up 
• 
Weekly FTS until negative (if not negative on day 7) 
 
11.7.3. Laboratory evaluation 
§ FTS test  
The Alere/Abbott Diagnostics FTS test cassettes will be used, according to manufacturer 
specifications. Briefly, 75 μL of finger prick blood will be added to a sample application 
pad that contains dried anti-filarial polyclonal antibody that has been labeled with 
colloidal gold. The labeled antibody binds to circulating filarial antigen (CFA) if it is 
present. Blood cells are retained in the sample pad, and the labeled antigen–antibody 
complexes flow down a nitrocellulose strip with the plasma. The immune complexes are 
immobilized when they bind to a monoclonal antibody to CFA that has been striped across 


Loiasis Antigenemia Version 1.2 25 June 2019 
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the nitrocellulose membrane, and this results in a positive test with a visible “T-line.” The 
procedural control “C-line” develops when excess labeled polyclonal antibody crosses a 
line that contains a secondary antibody to the immunoglobulin that was in the sample 
pad. Thus, samples that contain CFA produce visible T- and C-lines in the FTS, while 
negative samples only produce the C-line (Chesnais et al., 2016). 
 
§ Calibrated thick blood smears  
Nocturnal as well as daytime calibrated thick blood smear will be performed according to 
established protocol on 70 µL of fingerprick blood. These will be stained and read by 
experienced microscopists at CRFilMT.   
 
§ LoaScope Mf counts  
LoaScope Mf count will be done on fingerstick blood as described in (Kamgno et al., 2017). 
 
§ Mass spectrometry and ELISA 
Venous blood samples will be separated by centrifugation. Plasma will be frozen and 
shipped to Washington University in St. Louis for antigen testing (Weil lab ELISA 
protocol), and for specific antigens by mass spectrometry as previously described (Hertz 
et al., 2018). 
 
§ Skin Snips 
For cohort 2 participants will have skin snips (one punch over each iliac crest) to rule out 
onchocerciasis. The skin will be disinfected before a snip is taken with a sterile scleral 
punch. Each snip will be weighed on an analytical balance and incubated for at least 8 
hours in isotonic saline in a well of a flat-bottomed micro-titre plate at ambient 
temperature. Microfilariae will be counted by microscopy. Mf number and skin snip 
weight will be recorded; skin microfilarial density will be calculated and recorded as 
mf/mg.  
 
11.8. Statistical analysis 
Data analysis will be specific to the cohorts: 
§ Cohort 1 


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The prevalence of antigens on Day 0 and at follow-up will be described using frequency 
(percentages) and their 95% confidence intervals will be reported. Potential biomarkers 
and the antigen profile of Cohort 1 will be defined as described according to demographic 
data (age, sex, village), L. loa Mf counts, and presence of M. perstans. The presence of 
detectable cross-reactive antigen at each follow-up study will be analysed as a binary 
outcome and differences in the proportion of samples positive for cross-reactive antigen 
compared using Fischer’s exact test. 
 
§ Cohort 2 
Potential biomarkers and the antigen profile for Cohort 2 will be defined as described for 
Cohort 1. For the purpose of comparing spontaneous antigenemia (Cohort 1) to 
ivermectin induced antigenemia (Cohort 2), the cross-reactive antigen profile of Cohort 1 
will be defined as the collection of antigens found in >90% of baseline samples. 
Comparison between the antigen profiles of Cohorts 1 and 2 will be assessed as the 
proportion of samples in Cohort 2 containing detectable amounts of the potential 
biomarkers identified in Cohort 1. The association of quantitative antigen levels and AE 
occurrence and severity will be assessed comparing total circulating filarial antigen levels 
(measured by Weil Lab ELISA) among participants with no AEs to those with mild AEs or 
moderate AEs and examining differences using t-tests or Mann-Whitney U tests. Data 
management for Cohort 2 will be the same as for Cohort 1. 
 
12. Ethical considerations 
Before the beginning of this study, an ethical clearance will be requested to National 
Ethics Committee for Research in Human Health of Cameroon and to the Institutional 
Review Board of the Washington University in St. Louis. 
 
Participation in this study will be voluntary and the refusal to participate will have no 
consequences for the persons who refuse to take part in the study. The objectives and 
schedule of the study will be explained to the potential participants and those who agree 
to participate will sign an informed consent form and keep a copy. The sampling will be 
performed with non-invasive or sterile and disposable equipment. All participants in 
Cohort 2 will benefit from general medical consultations with free study-related 
medication. The laboratory filarial test results will be communicated individually to each 


Loiasis Antigenemia Version 1.2 25 June 2019 
22 
 
participant in strict compliance with the confidentiality rules. The results of this study will 
be made available to the Ministry of Public Health and the health services of the targeted 
districts. 
 
12.1. Risks/Discomfort of the study  
 
Risk of blood draws 
Drawing blood may be painful; as such, we shall assure the participants that the prick and 
venous puncture will last only a few seconds. Blood collection will be performed by 
trained professionals. Blood drawing will be carried out with sterile and single use 
materials. The risk is then very limited for the participants.  
 
Risk of treatment (cohort 2 only) 
This medication is safe and is provided as MDA to more than 100 million persons in Africa each 
year by programs to eliminate LF and onchocerciasis. The most common side effects are diarrhea, 
dizziness and nausea. Persons with filarial infections including onchocerciasis, LF, or loiasis 
sometimes experience rash, hives, itching, difficulty breathing, tightness in the chest, swelling of 
the mouth, face, lips, or tongue; eye pain, swelling, or redness. Seizures, fainting, mild decrease in 
leukocyte counts, elevated liver function tests, and cardiovascular effects that included 
tachycardia and orthostatic hypotension have been reported, but these adverse events are rare 
and not necessarily related to IVM treatment.  Risks of treatment in this study will be minimized 
by ruling out onchocerciasis by skin snip prior to treatment, and by including only subjects with 
L. loa Mf counts <20,000 per mL in cohort 2, which has been demonstrated to be safe in this 
population (Kamgno et al., 2018; Kamgno et al.,  2017). 
  
Risk of skin snips (cohort 2 only) 
This procedure is associated with a small risk of bleeding and infection. The skin will be 
disinfected before a snip is taken with a sterile scleral punch. The snip (about 2 mg) will 
cause a superficial wound of the skin at the iliac crests, which will be covered with a 
plaster for one day. These procedures are routine and designed to minimize risks of 
infection or bleeding. The scar will be 2 mm or less in size. 
 


Loiasis Antigenemia Version 1.2 25 June 2019 
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12.2. Benefits of the Study  
The main benefit for participants will be to know their status about the diseases tested. 
Another benefit will be the satisfaction of contributing to the advancement of science. 
 
12.3. Confidentiality  
Participant identities, test results, and medical information will be maintained in a 
confidential manner by the study team and will not be released to anyone outside the staff 
conducting the project. Confidentiality of individual data will be protected insofar as 
legally as possible. The report of this study will be transmitted to the Regional Ethic 
Committee for Research in Human Health for the Centre region as well as to the Ministry 
of Public Health. Participants will be informed about their personal test results will be 
disclosed only to the participant in a private setting. 
 
13. Information notes 
This study will have two separate information notes, according to the objectives and the 
cohort. 
 
13.1. Information note, Cohort 1 
I am Professor Joseph KAMGNO, Medical Doctor, and Director of the Centre for Research on 
Filariasis and other Tropical Diseases (CRFilMT). Our team works with the Ministry of Public 
Health and other international organizations to research strategies to control filariasis.  
 
We invite you to participate in this research project entitled ‘’ Cross-reactive antigenemia and 
treatment-related adverse events in loiasis’’ whose objective is to determine why some people 
with loiasis test positive for lymphatic filariasis even though they do not have lymphatic filariasis, 
and whether this varies with time. Participation in the study is entirely voluntary and you 
may choose not to participate or to withdraw at any moment. 
 
Now we will describe the research study and explain to you how it will take place.   
 
 
 
 
 
1- Study title: Cross-reactive antigenemia and treatment-related adverse events in loiasis.  
 
2- Principal investigator: Joseph KAMGNO  


Loiasis Antigenemia Version 1.2 25 June 2019 
24 
 
 
3- Authorization number of the Rational Ethic Committee for Research in Human Health: 
 
4- Background Information 
Lymphatic Filariasis (LF) (elephantiasis) and loiasis (African eye worms) are important public 
health problem in our country. LF manifests itself mainly by lymphedema (swollen limbs), genital 
diseases (swollen scrotum) and recurrent acute attacks which are extremely painful and 
accompanied by fever. On the other hand, symptoms of loiasis include specific manifestations as 
swellings of the hands called Calabar swelling, or migration of the worm that causes loiasis across 
the white surface of the eye. To eliminate LF, Mass Drugs Administration (MDA) of Ivermectin, 
and Albendazole are organized each year by the Ministry of Public Health. However, MDA for LF 
is very difficult in areas where loiasis is common because some people with loiasis test positive 
for LF even though they do not have the disease.  This makes it very difficult to tell whether MDA 
for LF is actually needed.  
 
5- Purpose of the study 
The objective of this study is to determine why some people with loiasis test positive for lymphatic 
filariasis even when they do not have the disease, and to test whether this varies with time.  
 
6- Research procedures 
6.1- Study Population 
This study will include people who are at least 18 years old who have loiasis and a positive LF test.  
People with very high levels of loiasis are more likely to have a positive LF test, so we will be 
testing people living in the Okala Health District who previously tested (during the TaNT study) 
and were found to have loiasis levels of at least 20,000 Mf/mL of blood. 
 
6.2- Study Design  
If you participate in this study, the study team will visit you in your home or village every three 
months for one year.  At each visit, a study nurse or technician will prick your finger to obtain a 
few drops of blood that he/she will used to test how heavy your loiasis infection is using a 
handheld microscope called a LoaScope. This is the same procedure as you have had done 
previously in the Test and Not Treat Study. At the first study visit, we will also use a few drops of 
fingerprick blood to test for loiasis and related infections. Additionally, the study team will draw 
10 mL of venous blood to test for loiasis antigens to help identify why many people with loiasis 
test falsely positive for LF.  On the first study day the study team will also visit you at night for a 
second fingerprick to test for W. bancrofti, the parasite that causes LF.   


Loiasis Antigenemia Version 1.2 25 June 2019 
25 
 
 
At each subsequent study visit (3 months, 6 months, 9 months, and 12 months after the first visit), 
the study team will visit you in your home of village and will again collect daytime blood by 
fingerprick and by vein.  All these visits will be during the day; the only time you will be asked to 
give blood at night is at the first study visit. 
 
7- Risks/Discomfort of the study procedures. Drawing blood may be painful; as such, we shall 
assure the participants that the prick and venous puncture will last only a few seconds. Blood 
drawing will be carried out by trained professionals using sterile and single use materials.  
 
8- Benefits of the Study 
The main benefit for you will be to know your status about these diseases. Another benefit will be 
the satisfaction of contributing to the advancement of science. At any study visit if you have a 
health concern, a consultation will be done by a medical Doctor or a nurse, and you will receive 
generic drug (or prescription if the drug is not available). 
 
9- Compensation/Indemnification/Motivation 
Participants in this cohort 1 will receive 5000 CFA francs (~$8.65) at each study visit to 
compensate for their travel and lost work time.   
 
10- Confidentiality and Reporting of Findings 
Your name, test results, and medical information will be maintained in a confidential manner by 
the study team and will not be released to anyone outside the staff conducting the project. 
Confidentiality of individual data will be protected insofar as legally as possible. The report of this 
study will be transmitted to the Regional Ethic Committee for Research in Human Health for 
centre region as well as to the Ministry of Public Health. However, your personal results will be 
given to you and you only. 
 
11- Voluntary feature of the participation  
Participation in the study is entirely voluntary. You may withdraw from the study at any time. This 
will not affect at all your health care within the community. 
 
12- New information  
Storage of collected samples: your samples will be stored and transferred to the Washington 
University for further analysis. We will NOT test them for HIV nor perform any human genetic 
Commented [BP1]: We work at Washington University (in 
St. Louis, Missouri).  « University of Washington » refers to a 
different university (in Seattle, Washington State). 


Loiasis Antigenemia Version 1.2 25 June 2019 
26 
 
exam on your samples. Even in our research team, we will not share your name with any person 
using those samples. Samples collection supplies will be disposed according to security norms. 
 
13- People to contact for further information 
If you have any questions or concerns, or you feel you might have been hurt by the study, please 
contact Professor Joseph KAMGNO (Tel.: 222 202 442, PO Box 5797, Yaoundé). He is the Principal 
Investigator of this study. 
 
14. Future Contact 
We will keep your contact information.  In the future, you may be asked to participate in follow up 
studies that would help to eliminate LF or Loiasis.  At any time, you may choose not to participate 
in future studies. 
 
13.2. Information note, Cohort 2 
I am Professor Joseph KAMGNO, Medical Doctor, and Director of the Centre for Research on 
Filariasis and other Tropical Diseases (CRFilMT). Our team works with the Ministry of Public 
Health and other international organizations to research strategies to control filariasis.  
 
We invite you to participate in a research project entitled ‘’ Cross-reactive antigenemia and 
treatment-related adverse events in loiasis’’. The objective of this study is to learn more about 
what happens in the body when people infected with the parasite, Loa loa, are treated with the 
medication ivermectin. Participation in the study is entirely voluntary and you may choose 
not to participate or to withdraw at any moment. 
 
Now we will describe the research study and explain to you how it will take place. 
  
 
 
1- Study title: Cross-reactive antigenemia and treatment-related adverse events in loiasis.  
 
2- Principal investigator: Joseph KAMGNO  
 
3- Authorization number of the Rational Ethic Committee for Research in Human Health: 
 
4- Background Information 
Lymphatic Filariasis (LF) (elephantiasis) and loiasis (African eye worms) are important public 
health problem in our country. LF causes leg or genital swelling, and recurrent acute attacks which 
are extremely painful skin infections accompanied by fever. On the other hand, symptoms of 


Loiasis Antigenemia Version 1.2 25 June 2019 
27 
 
loiasis include swelling, of the hands called Calabar swelling, or migration of the parasitic worm 
across the white surface of the eye. To eliminate LF, Mass Drugs Administration (MDA) of 
ivermectin and albendazole are organized each year by the Ministry of Public Health. However, 
MDA for LF is very difficult in areas where loiasis is common because some people with loiasis 
test positive for LF even though they do not have the disease.  This makes it very difficult to tell 
whether MDA for LF is actually needed.  In addition, one of the medications used for LF MDA 
(ivermectin), can be dangerous for people with loiasis who have very heavy infections.  
 
When ivermectin is used to treat LF or loiasis, it kills the microscopic parasites that live in the 
blood.  When these parasites die, it causes inflammation in the body that may cause headaches, 
muscle aches, fever, fatigue, weakness, itching, and other symptoms that make people feel ill.  
When parasite levels are low, these symptoms typically last about one day and resolve on their 
own. However, when parasite levels are high (more than 20,000 parasites per millilitre of blood), 
the symptoms caused by dying parasites can be more severe.  For people with extremely high 
parasite levels (more than 50,000 parasites per millilitre of blood), the inflammation caused by 
dying parasites can be life-threatening. For this reason, ivermectin should not be given to anyone 
with parasite levels greater than 20,000 Mf/mL of blood.   
 
5- Purpose of the study 
The objective of this study is to determine what parasite proteins are released into the blood when 
people with loiasis are treated with ivermectin, and whether specific parasite proteins are 
responsible for the inflammatory responses caused by dying parasites.  
 
6- Research procedures 
6.1- Study Population 
This study will include adults at least 18 years old, who have loiasis at levels that are safe to treat 
with ivermectin (between 5,000 – 18,000 parasites per millilitre of blood), and who have not been 
previously treated with ivermectin. 
 
6.2- Study Design  
People who wish to enroll in the study will first be tested to determine if they are eligible.  This 
will be done by testing a few drops of blood obtained by fingerprick and examining it under a 
microscope to count the number of loiasis (Loa loa) parasites. A few drops of fingerprick blood 
will also be tested for the presence of parasite antigens. In addition, two small skin snips (one over 
each hip) will be take to test for parasites in the skin.  
 


Loiasis Antigenemia Version 1.2 25 June 2019 
28 
 
Eligible participants who wish to participate in the study will asked to come to the local health 
center for treatment, where they will stay for seven days. Each participant will be treated with a 
single dose of ivermectin (150 µg/kg) and will be monitored closely so the study team can observe 
and treat any symptoms that might develop. A physical examination and monitoring of vital signs 
at least once a day. A small amount of venous blood (10 mL) will be collected from each participant 
on the day prior to treatment, the day of treatment, and on days 1, 2, 3, and 7 post-treatment. This 
blood will be tested for parasite antigens and for evidence of inflammation caused by dying 
parasites. 
 
7- Risks/Discomfort of the study procedures 
 
Risk of treatment 
Some people with loiasis feel ill for one or two days after receiving ivermectin. Symptoms may 
include fever, headache, muscle pain, joint pain, cough, chest pain, rash, itching, fatigue, high or 
low blood pressure, nausea, abdominal pain, or diarrhea. These symptoms are caused the body’s 
response to the dying parasites. In people with less than 20,000 parasites per millilitre of blood, 
the symptoms are usually mild and resolve on their own. If you participate in the study and 
experience such symptoms a study physician or nurse will examine you and provide appropriate 
treatment. 
 
Risk of blood collection 
Participants in the study will have a small amount of blood drawn from a vein or fingerprick 
several times throughout the study. Drawing blood may be painful; but the prick or venous 
puncture will last only a few seconds. Blood collection will be performed by trained professionals 
using sterile, single use materials to minimize the risk of bleeding or infection. 
 
Risk of skin snips 
There is a small risk of  
 
 
8- Benefits of the Study 
The main benefit for you will be to know your status about these diseases. Another benefit will be 
the satisfaction of contributing to the advancement of science. Participants with some intestinal 
worms, lice, or scabies will benefit from receiving ivermectin, which is often used to treat these 
conditions. 
 


Loiasis Antigenemia Version 1.2 25 June 2019 
29 
 
9- Compensation/Indemnification/Motivation 
Participants who will undergo both phases of screening will benefit from medical consultation 
and delivery of generic drugs. Those who enroll will receive XAF 15,000 (~$25) on completion of 
the study. 
 
10- Confidentiality and Reporting of Findings 
Your name, test results, and medical information will be maintained in a confidential manner by 
the study team and will not be released to anyone outside the staff conducting the project. 
Confidentiality of individual data will be protected insofar as legally as possible. The report of this 
study will be transmitted to the Regional Ethic Committee for Research in Human Health for 
centre region as well as to the Ministry of Public Health. However, your personal results will be 
given to you and you only. 
 
11- Voluntary feature of the participation  
Participation in the study is entirely voluntary. You may withdraw from the study at any time. This 
will not affect at all your health care within the community. 
 
12- New information  
Storage of collected samples:  your samples will be stored and transferred to Washington 
University (USA) for further analysis. We will not test them for HIV nor perform any human 
genetic tests on your samples. Even in our research team, we will not share your name with any 
person using those samples. Samples collection supplies will be disposed according to security 
norms. 
 
13- People to contact for further information 
If you have any questions or concerns, or if you feel you might have been hurt by the study, please 
contact Professor Joseph KAMGNO (Tel.: 222 202 442, PO Box 5797, Yaoundé). He is the Principal 
Investigator of this study. 
 
14. Future Contact 
We will keep your contact information.  In the future, you may be asked to participate in follow up 
studies that would help to eliminate LF or Loiasis.  At any time, you may choose not to participate 
in future studies. 
 


Loiasis Antigenemia Version 1.2 25 June 2019 
30 
 
Notices d’information 
Cette aura deux notices d’information, ton des objectifs et des cohortes 
 
13.3. Notice d’information (Cohorte 1) 
Je suis le Professeur Joseph KAMGNO, Médecin, Directeur du Centre de Recherche sur les 
Filarioses et autres Maladies Tropicales (CRFilMT). Notre équipe travaille avec le Ministère de la 
Santé Publique et d’autres Instituts de recherche internationaux sur les meilleurs moyens de lutte 
contre les filaires.   
 
Nous vous invitons à participer à ce projet de recherche intitulé : ‘’Réaction croisée des 
antigènes et effets secondaires liés au traitement de la loase’’ dont l’objectif est de définir le 
profil des antigènes à réactivité croisée chez les personnes avec une antigénémie spontanée et de 
déterminer si ce profil vari avec le temps.  La participation à cette étude est volontaire et vous 
pouvez choisir de ne pas y participer ou de vous retirer à n’importe quel moment.  
 
Maintenant nous allons décrire l’étude et vous présenter comment elle va se dérouler. 
        
 1-Titre de l’étude : Réactivité croisée des antigènes et effets secondaires liés au traitement de la 
loase. 
 
2- Investigateur principal : Joseph KAMGNO.  
  
3-Numéros d’autorisation du Comité National d’Éthique pour la Recherche en Santé 
Humaine (CNERSH) :   
 
4- Introduction  
La filariose lymphatique (FL) et la loase sont d’importants problèmes de santé publique dans 
notre pays. La FL se manifeste principalement par les lymphœdèmes, les hydrocèles et 
l’éléphantiasis. La loase quant à elle a pour manifestations spécifiques les œdèmes de Calabar, et 
la migration sous-conjonctivale des vers adultes. La FL cause la perte d’environ 2,8 million 
d'espérance de vie corrigée de l'incapacité (EVCI) chaque année due uniquement à l’incapacité 
des personnes affectées de vaquer à leur occupation. Pour éliminer cette maladie, des campagnes 
de distribution de masse de médicaments (Ivermectine, Albendazole, Diethylcarbamazine) sont 
organisées chaque année. Mais cette activité se heurte à un véritable obstacle qu’est la loase. En 
effet, pour débuter la distribution de masse, la prévalence de la FL (évaluée par les tests de 


Loiasis Antigenemia Version 1.2 25 June 2019 
31 
 
diagnostic rapide (TDR)) doit être ≥1%. Cependant, dans les zones ou la loase est aussi 
endémique, près de 6%de la population sont testés positif par les TDR de la FL en l’absence de W. 
bancrofti, le parasite responsable de la FL. En plus, l’Ivermectin cause des effets secondaires 
graves chez des personnes avec une charge de loase ˃20 000 Mf/ml de sang. Il est donc nécessaire 
d’identifier les antigènes de L. loa responsables des FL-TDR faux positifs et de voir si la production 
de ces antigènes est responsable des effets secondaires observés lors du traitement de la loase. 
 
5- But de la recherche  
L’objectif principal de cette partie de définir le profil des antigènes qui induisent la réction croisée 
chez les personnes avec une antigénémie spontanée et de déterminer si ce profil vari avec le 
temps.   
 
6- Procédures de la recherche  
6.1- Populations concernées par l’étude  
Cette partie de l’étude concerne les personnes âgées de 18 ans et plus, ayant été exclues de l’étude 
TaNT d’Okola suite à leur charge de loase ≥20 000 Mf/ml de sang. 
 
 6.2- Protocole de l’étude  
Les examens consisteront à la déterminer la charge de loase et la présence des antigènes 
spontanés par Loascope et FTS respectivement. Ces deux examens seront faits à partir d’un 
prélèvement de sang capillaire au bout du doigt. A partir du même prélèvement, les gouttes 
épaisses calibrées diurne, nocturnes, ainsi que des spots de sang sur papier filtre seront faits. 
Additionnellement, 10 ml de sang veineux seront prélevés pour l’identification et la quantification 
des antigènes par spectrométrie de masse et ELISA.    
 
7- Risques/ Inconforts éventuels associés à l’étude  
Le prélèvement de sang (capillaire et veineux) est un peu douloureux ; nous rassurerons donc les 
participants que la piqure ne durera que quelques secondes. Nous aimerions préciser que ce 
prélèvement sera réalisé par des professionnels expérimentés. Les prélèvements seront réalisés 
avec du matériel stérile et à usage unique, ce qui réduit le risque pour les participants.   
 
8- Bénéfices potentiels de l’étude  
Le principal bénéfice sera de connaître votre statut vis-à-vis de ces maladies. Outre le fait de 
connaître leur statut vis-à-vis de ces maladies parasitaires, une retombée très importante de cette 
étude sera la possibilité de participer à l’évolution de la science. 
 


Loiasis Antigenemia Version 1.2 25 June 2019 
32 
 
 9- Compensation/Indemnisation/Motivation  
Une compensation financière de 5000 Francs CFA (~$8.65) est prévue pour chaque visite. 
Pendant les visites, vous bénéficierez également de consultations médicales. 
 
10- Confidentialité  
 Le rapport de cette étude sera transmis au Comité Régional d’Ethique pour la Recherche en Santé 
Humaine (CNERSH) du centre, ainsi qu’au Ministère de la santé publique. Cependant, vos résultats 
personnels ne seront communiqués qu’à vous et à vous seul.   
 
11- Caractère volontaire de la participation 
 Votre participation à cette étude est volontaire. Vous pourrez vous retirer de l’étude à tout 
moment sans que ceci n’affecte vos soins de santé dans votre communauté.  
  
12- Nouveaux renseignements  
Conservation des échantillons de prélèvement : vos échantillons seront conservés et transférés à 
nos collaborateurs de l’Université Washington a St. Louis pour certaines analyses. Par ailleurs, 
nous n'allons tester aucun de ces échantillons pour le VIH. Nous n'allons pas non plus effectuer un 
test de génétique humaine sur vos échantillons. Même au sein de notre équipe, nous ne 
communiquerons pas votre nom à quiconque susceptible d’utiliser ces échantillons. Les 
échantillons seront conservés aussi longtemps que nécessaire pour aider les programmes 
d'élimination de la FL. Le matériel de prélèvement sera quant à lui détruit suivant les normes de 
sécurité.   
 
13. Personnes à contacter en cas de besoin  
 Si vous avez d’autres questions ou estimez que vos droits n’ont pas été respectés dans le cadre de 
cette étude, vous pouvez contacter le Professeur Joseph KAMGNO (Tél. : 222 202 442, BP 5797, 
Yaoundé). Il est le principal investigateur de cette étude.  
 
14. Futur contact Nous conserverons vos informations de contact  
Dans l'avenir, vous pourrez être invité à participer à des études de suivi qui faciliteraient les 
efforts pour éliminer du paludisme et de la schistosomiase. À tout moment vous pouvez choisir de 
ne pas participer à ces études futures. 
 
13.4. Notice d’information (Cohorte 2) 
Je suis le Professeur Joseph KAMGNO, Médecin, Directeur du Centre de Recherche sur les 
Filarioses et autres Maladies Tropicales (CRFilMT). Notre équipe travaille avec le Ministère de la 


Loiasis Antigenemia Version 1.2 25 June 2019 
33 
 
Santé Publique et d’autres Instituts de recherche internationaux sur les meilleurs moyens de lutte 
contre les filaires.   
 
Nous vous invitons à participer à  la deuxième partie du projet de recherche intitulé : ‘’Réactivité 
croisée des antigènes et effets secondaires liés au traitement de la loase’’ dont les objectifs 
sont (i) de déterminer les antigènes à réactivité croisée de L. loa induits suite au traitement par 
l’Ivermectine et de (ii) déterminer si la production de ces antigènes spécifiques et/ou leur 
quantité est en corrélation avec l’apparition et la sévérité des effets secondaires observés suite au 
traitement par l’Ivermectine. La participation à cette étude est volontaire et vous pouvez 
choisir de ne pas y participer ou de vous retirer à n’importe quel moment.  
 
Maintenant nous allons décrire l’étude et vous présenter comment elle va se dérouler. 
        
 1-Titre de l’étude : Réactivité croisée des antigènes et effets secondaires liés au traitement de la 
loase. 
 
2- Investigateur principal : Joseph KAMGNO.   
 
3-Numéros d’autorisation du Comité National d’Éthique pour la Recherche en Santé 
Humaine (CNERSH) :   
 
4- Introduction  
La filariose lymphatique (FL) et la loase sont d’importants problèmes de santé publique dans 
notre pays. La FL se manifeste principalement par les lymphœdèmes, les hydrocèles et 
l’éléphantiasis. La loase quant à elle a pour manifestations spécifiques les œdèmes de Calabar, et 
la migration sous-conjonctivale des vers adultes. La FL cause la perte d’environ 2,8 million 
d'espérance de vie corrigée de l'incapacité (EVCI) chaque année due uniquement à l’incapacité 
des personnes affectées de vaquer à leur occupation. Pour éliminer cette maladie, des campagnes 
de distribution de masse de médicaments (Ivermectine, Albendazole, Diethylcarbamazine) sont 
organisées chaque année. Mais cette activité se heurte à un véritable obstacle qu’est la loase. En 
effet, pour débuter la distribution de masse, la prévalence de la FL (évaluée par les tests de 
diagnostic rapide (TDR)) doit être ≥1%. Cependant, dans les zones ou la loase est aussi 
endémique, près de 6%de la population sont testés positif par les TDR de la FL en l’absence de W. 
bancrofti, le parasite responsable de la FL. En plus, l’Ivermectin cause des effets secondaires 
graves (incluant le coma et la mort) chez des personnes avec une charge de loase ˃20 000 Mf/ml 
de sang. Il est donc nécessaire d’identifier les antigènes de L. loa responsables des FL-TDR faux 


Loiasis Antigenemia Version 1.2 25 June 2019 
34 
 
positifs et de voir si la production de ces antigènes est responsable des effets secondaires observés 
lors du traitement de la loase. 
 
5- But de la recherche  
Les objectifs de cette partie de l’étude sont (i) de déterminer les antigènes à réactivité croisée de 
L. loa induits suite au traitement par l’Ivermectine et de (ii) déterminer si la production de ces 
antigènes spécifiques et/ou leur quantité est en corrélation avec l’apparition et la sévérité des 
effets secondaires observés suite au traitement par l’Ivermectine.   
 
6- Procédures de la recherche  
6.1- Populations concernées par l’étude  
Cette partie de l’étude va inclure les personnes âgées de 18 ans et plus vivant dans le district de 
santé d’Awae n’ayant pas suivi un traitement par l’Ivermectine. 
 
 6.2- Protocole de l’étude  
Les examens consisteront à analyser quelques goutes de sang capillaire (~200 µl) obtenu au bout 
du doigt. Les microfilaires de L. loa seront mesurées par Loascope et les antigènes qui induisent 
la réaction croisée par FTS. 10 ml de sang veineux seront prélevés pour l’identification et la 
quantification des antigènes par spectrométrie de masse et ELISA et les participants seront 
internés dans un centre de santé. Par la suite ils seront traités par une dose (150mg) d’Ivermectine 
et seront suivis pendant 07 jours, durant lesquels ils seront surveillés pour les effets secondaires 
et fourniront 10 ml de sang veineux (pour l’identification et la quantification des antigènes par 
spectrométrie de masse et ELISA) chaque jour. Pendant l’hospitalisation pour les maux éventuels, 
vous recevrez des médicaments génériques.  
 
7- Risques/ Inconforts éventuels associés à l’étude  
Le prélèvement de sang (capillaire et veineux) est un peu douloureux ; nous rassurerons donc les 
participants que la piqure ne durera que quelques secondes. Nous aimerions préciser que ce 
prélèvement sera réalisé par des professionnels expérimentés. Les prélèvements seront réalisés 
avec du matériel stérile et à usage unique, ce qui réduit le risque pour les participants.   
 
8- Bénéfices potentiels de l’étude  
Le principal bénéfice sera de connaître votre statut vis-à-vis de ces maladies. Outre le fait de 
connaître leur statut vis-à-vis de ces maladies parasitaires, une retombée très importante de cette 
étude sera la possibilité de participer à l’évolution de la science. Vous bénéficierez également de 
consultation et recevrez des médicaments génériques. 


Loiasis Antigenemia Version 1.2 25 June 2019 
35 
 
 
 9- Compensation/Indemnisation/Motivation  
Les participants bénéficieront de consultations médicales lors du screening et une somme 15,000 
Francs CFA (~$25) sera remis aux participant qui seront hospitalisé à la fin de l’étude pour 
compenser tout le temps perdu à l’hôpital. 
 
10- Confidentialité  
 Le rapport de cette étude sera transmis au Comité Régional d’Ethique pour la Recherche en Santé 
Humaine (CNERSH) du centre, ainsi qu’au Ministère de la santé publique. Cependant, vos résultats 
personnels ne seront communiqués qu’à vous et à vous seul.   
 
11- Caractère volontaire de la participation 
 Votre participation à cette étude est volontaire. Vous pourrez vous retirer de l’étude à tout 
moment sans que ceci n’affecte vos soins de santé dans votre communauté.   
 
12- Nouveaux renseignements  
Conservation des échantillons de prélèvement : vos échantillons seront conservés et transférés à 
nos collaborateurs de l’Université Washington a St. Louis pour certaines analyses. Par ailleurs, 
nous n'allons tester aucun de ces échantillons pour le VIH. Nous n'allons pas non plus effectuer un 
test de génétique humaine sur vos échantillons. Même au sein de notre équipe, nous ne 
communiquerons pas votre nom à quiconque susceptible d’utiliser ces échantillons. Les 
échantillons seront conservés aussi longtemps que nécessaire pour aider les programmes 
d'élimination de la FL. Le matériel de prélèvement sera quant à lui détruit suivant les normes de 
sécurité.  
 
13. Personnes à contacter en cas de besoin  
 Si vous avez d’autres questions ou estimez que vos droits n’ont pas été respectés dans le cadre de 
cette étude, vous pouvez contacter le Professeur Joseph KAMGNO (Tél. : 222 202 442, BP 5797, 
Yaoundé). Il est le principal investigateur de cette étude.  
 
14. Futur contact Nous conserverons vos informations de contact  
Dans l'avenir, vous pourrez être invité à participer à des études de suivi qui faciliteraient les 
efforts pour éliminer du paludisme et de la schistosomiase. À tout moment vous pouvez choisir de 
ne pas participer à ces études futures. 
 


Loiasis Antigenemia Version 1.2 25 June 2019 
36 
 
14. Informed consents 
14.1. Assent form (Cohort 1: Participants aged from 18 to 20 years old) 
 
I, the undersigned, M / Ms / Miss ......................................................................................., attest to having been 
invited to participate in the research work entitled ‘’Cross-reactive antigenemia and treatment 
related adverse events in loiasis’’ whose principal investigator is Professor Joseph KAMGNO 
(Director of the Center for Research on Filariasis and other Tropical Diseases). 
 
§ 
I understood the information note that was provided to me; moreover, this information 
leaflet has been read and explained by the investigators; 
§ 
I understood the purpose and objectives of this study; 
§ 
I received all the answers to the questions I asked; 
§ 
The risks and benefits of this study were presented to me and explained; 
§ 
I understand that I am free to accept or refuse to participate in this study; 
§ 
My consent does not discharge the investigators of the research of their responsibilities; I 
therefore retain all my rights guaranteed by law. 
 
I freely agree to participate in this study under the conditions specified in the information leaflet 
by (1) answering questions from the investigators, (2) communicating my medical information, 
(3) submitting myself to the fingerprick as well as venous blood samples for the examinations of 
filariasis, and (4) to be present at each follow up visit. 
 
I agree that my samples taken for this study may be used in subsequent studies. 
 
 
yes 
 
 
no 
 
(please check one box only) 
 
Done at ………………………………… on ………. /………. / 2019   
 
__________________________________________  
          
 
        _____________________________________ 
Signature of the Principal Investigator 
 
                      Fingerprint of the participant 
 
                                                                                      
                                                                                                                             __________________________ 
 
                                                                                                             Name and Signature witness 
 


Loiasis Antigenemia Version 1.2 25 June 2019 
37 
 
14.2. Assent form (Cohort 2: Participants aged from 18 to 20 years old) 
 
I, the undersigned, M / Ms / Miss ......................................................................................., attest to having been 
invited to participate in the research work entitled ‘’Cross-reactive antigenemia and treatment 
related adverse events in loiasis’’ whose principal investigator is Professor Joseph KAMGNO 
(Director of the Center for Research on Filariasis and other Tropical Diseases). 
 
§ 
I understood the information note that was provided to me; moreover, this information 
leaflet has been read and explained by the investigators; 
§ 
I understood the purpose and objectives of this study; 
§ 
I received all the answers to the questions I asked; 
§ 
The risks and benefits of this study were presented to me and explained; 
§ 
I understand that I am free to accept or refuse to participate in this study; 
§ 
My consent does not discharge the investigators of the research of their responsibilities; I 
therefore retain all my rights guaranteed by law. 
 
I freely agree to participate in this study under the conditions specified in the information leaflet 
by (1) answering questions from the investigators, (2) communicating my medical information, 
(3) submitting myself to the fingerprick as well as venous blood and skin snip samples for the 
examinations of filariasis, and (4) to be admitted to a health center for treatment with single dose 
ivermectin and actively monitored for adverse events during seven days. 
 
I agree that my samples taken for this study may be used in subsequent studies. 
 
 
yes 
 
 
no 
 
(please check one box only) 
 
Done at ………………………………… on ………. /………. / 2019   
 
__________________________________________  
          
 
        _____________________________________ 
Signature of the Principal Investigator 
 
                      Fingerprint of the participant 
 
                                                                                      
                                                                                                                             __________________________ 
 
                                                                                                              Name and Signature witness 
 


Loiasis Antigenemia Version 1.2 25 June 2019 
38 
 
 
14.3. Informed consent form (Cohort 1: Participants aged ≥21 years 
old) 
 
I, the undersigned, M / Ms / Miss ......................................................................................., attest to having been 
invited to participate in the research work entitled "Cross-reactive antigenemia and treatment 
related adverse events in loiasis" whose principal investigator is Professor Joseph KAMGNO 
(Director of the Center for Research on Filariasis and other Tropical Diseases). 
 
§ 
I understood the information note that was provided to me; moreover, this information 
leaflet has been read and explained by the investigators; 
§ 
I understood the purpose and objectives of this study; 
§ 
I received all the answers to the questions I asked; 
§ 
The risks and benefits of this study were presented to me and explained; 
§ 
I understand that I am free to accept or refuse to participate in this study; 
§ 
My consent does not discharge the investigators of the research of their responsibilities; I 
therefore retain all my rights guaranteed by law. 
 
I freely agree to participate in this study under the conditions specified in the information leaflet 
by (1) answering questions from the investigators, (2) communicating my medical information, 
(3) submitting myself to the fingerprick as well as venous blood samples for the examinations of 
filariasis, and (4) to be present at each follow up visit 
 
I agree that my samples taken for this study may be used in subsequent studies. 
 
 
yes 
 
 
no 
 
(please check one box only) 
 
Done at ………………………………… on ………. /………. / 2019   
 
_________________________                  
 
 
                     ___________________________ 
Signature of the Principal Investigator 
                                  Signature of the participant


39 
 
14.4. Inform consent form (Cohort 2: Participants aged ≥21 years old) 
 
I, the undersigned, M / Ms / Miss ......................................................................................., attest to having been 
invited to participate in the research work entitled "Cross-reactive antigenemia and treatment 
related adverse events in loiasis" whose principal investigator is Professor Joseph KAMGNO 
(Director of the Center for Research on Filariasis and other Tropical Diseases). 
 
§ 
I understood the information note that was provided to me; moreover, this information 
leaflet has been read and explained by the investigators; 
§ 
I understood the purpose and objectives of this study; 
§ 
I received all the answers to the questions I asked; 
§ 
The risks and benefits of this study were presented to me and explained; 
§ 
I understand that I am free to accept or refuse to participate in this study; 
§ 
My consent does not discharge the investigators of the research of their responsibilities; I 
therefore retain all my rights guaranteed by law. 
 
I freely agree to participate in this study under the conditions specified in the information leaflet 
by (1) answering questions from the investigators, (2) communicating my medical information, 
(3) submitting myself to the fingerprick as well as venous blood and skin snip samples for the 
examinations of filariasis, and (4) to be admitted to a health center for treatment with single dose 
ivermectin and actively monitored for adverse events during seven days. 
 
I agree that my samples taken for this study may be used in subsequent studies. 
 
 
yes 
 
 
no 
 
(please check one box only) 
 
 
Done at ………………………………… on ………. /………. / 2019   
 
 
_________________________                  
 
 
                     ___________________________ 
Signature of the Principal Investigator 
                                  Signature of the participant


40 
 
15. Formulaires de consentement éclairé 
15.1. Formulaire d’assentiment (Cohorte 1 : Participants âgés entre 15 
et 20 ans) 
 
Je soussigné M/Mme/Mlle …………………………………………………………………………… atteste avoir été 
invité à participer au travail de recherche intitulé «Réactivité croisée des antigènes et effets 
secondaires associés au traitement de la loase» dont l’investigateur principal est le Professeur 
Joseph KAMGNO (Directeur du Centre de Recherche sur les Filarioses et autres Maladies 
Tropicales. 
§ 
J’ai bien compris la notice d’information qui m’a été remise concernant l’étude ; par 
ailleurs, cette notice d’information a été lu et expliqué par les investigateurs ; 
§ 
J’ai bien compris le but et les objectifs de cette étude ; 
§ 
J’ai reçu toutes les réponses aux questions que j’ai posées ; 
§ 
Les risques et bénéfices de cette étude m’ont été présentés et expliqués ; 
§ 
J’ai bien compris que je suis libre d’accepter ou de refuser de participer à cette étude ; 
§ 
Mon consentement ne décharge pas les investigateurs de la recherche de leurs 
responsabilités ; je conserve de ce fait tous mes droits garantis par la loi. 
 
J’accepte librement de participer à cette étude dans les conditions précisées dans la notice 
d’information en (1) répondant aux questions des investigateurs, (2) communiquant mes 
informations médicales, (3) me soumettant aux prélèvements de sang veineux et capillaire pour 
la réalisation des examens de filarioses, identification des antigènes par spectrométrie de masse 
aussi bien que leur quantification par ELISA et enfin (4) d’être présent pour chaque visite de suivi. 
Je donne mon accord pour que mes échantillons prélevés pour cette étude soient utilisés dans les 
études ultérieures. 
 
Fait à ………………………………… le ………. /………. / 2019 
 
_________________________                                                                  ___________________________ 
Signature Investigateur Principal 
                                   Empreinte digitale du participant  
 
                                                                                           
                                                                                                            __________________________ 
 
                                                                                             Nom et Signature du témoin 


Loiasis Antigenemia Version 1.2 25 June 2019 
41 
 
15.2. Formulaire d’assentiment (Cohorte 2 : Participants âgés entre 18 
et 20 ans) 
 
Je soussigné M/Mme/Mlle …………………………………………………………………………… atteste avoir été 
invité à participer au travail de recherche intitulé «Réactivité croisée des antigènes et effets 
secondaires associés au traitement de la loase» dont l’investigateur principal est le Professeur 
Joseph KAMGNO (Directeur du Centre de Recherche sur les Filarioses et autres Maladies 
Tropicales. 
§ 
J’ai bien compris la notice d’information qui m’a été remise concernant l’étude ; par 
ailleurs, cette notice d’information a été lu et expliqué par les investigateurs ; 
§ 
J’ai bien compris le but et les objectifs de cette étude ; 
§ 
J’ai reçu toutes les réponses aux questions que j’ai posées ; 
§ 
Les risques et bénéfices de cette étude m’ont été présentés et expliqués ; 
§ 
J’ai bien compris que je suis libre d’accepter ou de refuser de participer à cette étude ; 
§ 
Mon consentement ne décharge pas les investigateurs de la recherche de leurs 
responsabilités ; je conserve de ce fait tous mes droits garantis par la loi. 
 
J’accepte librement de participer à cette étude dans les conditions précisées dans la notice 
d’information en (1) répondant aux questions des investigateurs, (2) communiquant mes 
informations médicales, (3) me soumettant aux prélèvements de sang veineux et capillaire pour 
la réalisation des examens de filarioses, identification des antigènes par spectrométrie de masse 
aussi bien que leur quantification par ELISA et enfin (4) être admis dans un centre de santé pour 
y recevoir un traitement par ivermectine à dose unique et surveiller activement pour les effets 
indésirables sur une période de sept jours. 
Je donne mon accord pour que mes échantillons prélevés pour cette étude soient utilisés dans les 
études ultérieures. 
 
Fait à ………………………………… le ………. /………. / 2019   
 
_________________________                                                                  ___________________________ 
Signature Investigateur Principal 
                                   Empreinte digitale du participant  
 
                                                                                                           __________________________ 
 
                                                                                             Nom et Signature du témoin 


Loiasis Antigenemia Version 1.2 25 June 2019 
42 
 
15.3. Formulaire de consentement élaire (Cohorte 1 : Participants âgés 
de ≥21 ans) 
 
Je soussigné M/Mme/Mlle …………………………………………………………………………… atteste avoir été 
invité à participer au travail de recherche intitulé «Réactivité croisée des antigènes et effets 
secondaires associés au traitement de la loase» dont l’investigateur principal est le Professeur 
Joseph KAMGNO (Directeur du Centre de Recherche sur les Filarioses et autres Maladies 
Tropicales. 
 
§ 
J’ai bien compris la notice d’information qui m’a été remise concernant l’étude ; par 
ailleurs, cette notice d’information a été lu et expliqué par les investigateurs ; 
§ 
J’ai bien compris le but et les objectifs de cette étude ; 
§ 
J’ai reçu toutes les réponses aux questions que j’ai posées ; 
§ 
Les risques et bénéfices de cette étude m’ont été présentés et expliqués ; 
§ 
J’ai bien compris que je suis libre d’accepter ou de refuser de participer à cette étude ; 
§ 
Mon consentement ne décharge pas les investigateurs de la recherche de leurs 
responsabilités ; je conserve de ce fait tous mes droits garantis par la loi. 
 
J’accepte librement de participer à cette étude dans les conditions précisées dans la notice 
d’information en (1) répondant aux questions des investigateurs, (2) communiquant mes 
informations médicales, (3) me soumettant aux prélèvements de sang veineux et capillaire pour 
la réalisation des examens de filarioses, identification des antigènes par spectrométrie de masse 
aussi bien que leur quantification par ELISA et enfin (4) d’être présent pour chaque visite de suivi. 
Je donne mon accord pour que mes échantillons prélevés pour cette étude soient utilisés dans les 
études ultérieures. 
 
Fait à ………………………………… le ………. /………. / 2019   
 
 
_________________________                          
 
 
          ___________________________ 
Signature Investigateur Principal 
                        
          Signature du participant


43 
 
15.4. Formulaire de consentement élaire (Cohorte 2 : Participants âgés 
de ≥21 ans) 
 
Je soussigné M/Mme/Mlle …………………………………………………………………………… atteste avoir été 
invité à participer au travail de recherche intitulé «Réactivité croisée des antigènes et effets 
secondaires associés au traitement de la loase» dont l’investigateur principal est le Professeur 
Joseph KAMGNO (Directeur du Centre de Recherche sur les Filarioses et autres Maladies 
Tropicales. 
 
§ 
J’ai bien compris la notice d’information qui m’a été remise concernant l’étude ; par 
ailleurs, cette notice d’information a été lu et expliqué par les investigateurs ; 
§ 
J’ai bien compris le but et les objectifs de cette étude ; 
§ 
J’ai reçu toutes les réponses aux questions que j’ai posées ; 
§ 
Les risques et bénéfices de cette étude m’ont été présentés et expliqués ; 
§ 
J’ai bien compris que je suis libre d’accepter ou de refuser de participer à cette étude ; 
§ 
Mon consentement ne décharge pas les investigateurs de la recherche de leurs 
responsabilités ; je conserve de ce fait tous mes droits garantis par la loi. 
 
J’accepte librement de participer à cette étude dans les conditions précisées dans la notice 
d’information en (1) répondant aux questions des investigateurs, (2) communiquant mes 
informations médicales, (3) me soumettant aux prélèvements de sang veineux et capillaire pour 
la réalisation des examens de filarioses, identification des antigènes par spectrométrie de masse 
aussi bien que leur quantification par ELISA et enfin (4) être admis dans un centre de santé pour 
y recevoir un traitement par ivermectine à dose unique et surveiller activement pour les effets 
indésirables sur une période de sept jours. 
Je donne mon accord pour que mes échantillons prélevés pour cette étude soient utilisés dans les 
études ultérieures. 
 
Fait à ………………………………… le ………. /………. / 2019   
 
 
_________________________                          
 
 
              ___________________________ 
Signature Investigateur Principal 
                        
          Signature du participant


44 
 
16. Fiche de collecte de données/Survey form 
 
16.1. Fiche de collecte de données cohorte 1 
                                                   
                                           
INFORMATIONS GENERALES SUR LE PATIENT 
Région : ___________      District de sante : ____________                       Aire de santé : ______________               
Date : _____________                         N° TaNT 2019: |______________________|    Code équipe : |_____|    
N° d’ordre dans village : |____|____|____|                                         N° ID final : |____|____|____|____|  
Code du patient : |____||____||____| Identifiant final : |_____||_____||_____||_____|   
Nom : ______________________       Prénom : ______________________                       Sexe (M/F) : |____|   
Age : |____|     tel : |_________________________________________________________________| 
……………………………………………………………………………………………………………………………………………. 
 
MORBIDITE 
Œdème de Calabar Oui |____|        Non  |____| 
Urticaire*  Oui |____|        Non  |____| 
Migration vers adulte dans l’œil * Oui |____|  Non  |____|    Prurit* Oui |____|  Non  |____| 
* le personnel de santé doit vérifier ces lésions   
 
……………………………………………………………………………………………………………………………………………. 
PRELEVEMENTS 
Screening 
FTS   Positif |_____|      Négatif  |_____| (Préciser le grade** si positif : 1 |__|    2  |__|   3  |__|) 
Loascope : Oui |____| Non |____| (|___________|/ml)  
** Par rapport au trait contrôle, le trait test est (1) moins intense ; (2) de même intensité ; (3) plus intense 
 
Jour 0 
Prélèvement veineux (10 ml) : Oui |____| Non |____| (|___________|/ml)   
GEC diurne: Oui |____| Non |____| L. loa :(|___________|/ml) Mansonella:(|___________|/ml)  
GEC nocturne Oui |____| Non |____| (|___________|/ml) BDS nocturne Oui |____| Non |____| 
 
03 Mois 
FTS   Positif |_____|      Négatif  |_____| (Préciser le grade** si positif : 1 |__|    2  |__|   3  |__|) 
Prélèvement veineux (10 ml) : Oui |____| Non |____| (|___________|/ml)  *** 


Loiasis Antigenemia Version 1.2 25 June 2019 
45 
 
** Par rapport au trait contrôle, le trait test est (1) moins intense ; (2) de même intensité ; (3) plus intense 
*** Fait si FTS positif 
 
06 Mois 
FTS   Positif |_____|      Négatif  |_____| (Préciser le grade** si positif : 1 |__|    2  |__|   3  |__|) 
Prélèvement veineux (10 ml) : Oui |____| Non |____| (|___________|/ml)  *** 
** Par rapport au trait contrôle, le trait test est (1) moins intense ; (2) de même intensité ; (3) plus intense 
*** Fait si FTS positif 
 
09 Mois 
FTS   Positif |_____|      Négatif  |_____| (Préciser le grade** si positif : 1 |__|    2  |__|   3  |__|) 
Prélèvement veineux (10 ml) : Oui |____| Non |____| (|___________|/ml)  *** 
** Par rapport au trait contrôle, le trait test est (1) moins intense ; (2) de même intensité ; (3) plus intense 
*** Fait si FTS positif 
 
12 Mois 
FTS   Positif |_____|      Négatif  |_____| (Préciser le grade** si positif : 1 |__|    2  |__|   3  |__|) 
Prélèvement veineux (10 ml) : Oui |____| Non |____| (|___________|/ml)  *** 
** Par rapport au trait contrôle, le trait test est (1) moins intense ; (2) de même intensité ; (3) plus intense 
*** Fait si FTS positif 
 
…………………………………………………………………………………………………………………………… 
REMARQUES 
_______________________________________________________________________________________________________________ 
_______________________________________________________________________________________________________________ 
Noms et signature du chef d’équipe (après vérification des informations) 
 
 
 
 
 
 
 


Loiasis Antigenemia Version 1.2 25 June 2019 
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16.2. Fiche de collecte de données cohorte 2 
                                                                                                
INFORMATIONS GENERALES SUR LE PATIENT 
Région : ___________      District de sante : ____________                       Aire de santé : ________________________               
Date : _____________                                Village : ________________________                           Code village : |________| 
N° d’ordre dans village : |______|______|______|                                         N° ID final : |______|______|______|______|  
Nom : ______________________       Prénom : ______________________                     Sexe (M/F) : |____|   Age : |____|     
Tel : |_________________________________________________________________| 
……………………………………………………………………………………………………………………………………………. 
MORBIDITE 
Œdème de Calabar Oui |______|        Non  |______| 
Urticaire*  Oui |______|        Non  |______| 
Migration vers adulte dans l’œil * Oui |______|  Non  |______|    Prurit* Oui |______|  Non  |______| 
* le personnel de santé doit vérifier ces lésions   
 
……………………………………………………………………………………………………………………………………………. 
PRELEVEMENTS 
Screening 
FTS   Positif 
|_____|      Négatif  |_____| (Préciser le grade** si positif : 1 |__|    2  |__|   3  |__|) 
Loascope : Oui |____| Non |____| (|___________|/ml)  
GEC diurne: Oui |____| Non |____| L. loa :(|___________|/ml) Mansonella:(|___________|/ml)  
Skin Snip : Oui|____| Non|____|       (Snip Gauche: |____|mg, |____|mf    /    Snip Droit: |____|mg , |____|mf) 
Test rapide de grossesse : Oui |____| Non |____|  
(Positif |____| Négatif |____|)             
** Par rapport au trait contrôle, le trait test est (1) moins intense ; (2) de même intensité ; (3) plus intense 
 
Jour 0 
FTS***   Positif|_____|    Négatif  |_____| (Préciser le grade** si positif : 1 |__|    2  |__|   3  |__|) 
Loascope : Oui |____| Non |____| (|_________|/ml) GEC  Oui |____| Non |____| (|_________|/ml)  
Admission au centre de santé : Oui |____| Non |____| 
Examens cliniques prétraitement : Date __________  Time _________ 
Questionnaire Effets secondaires prétraitement**** : Oui |____| Non |____| 
Prélèvement veineux (10 ml) prétraitement : Oui |____| Non |____|  
Traitement par une dose (150 mg) d’Ivermectine : Oui |____| Non |____| Date __________ ; Time 
_______ 
Surveillance des signes vitaux après chaque 8 heures : Oui |____| Non |____|  
** Par rapport au trait contrôle, le trait test est (1) moins intense ; (2) de même intensité ; (3) plus intense 
*** Exclus si positif 


Loiasis Antigenemia Version 1.2 25 June 2019 
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**** Voir questionnaire effets secondaires 
  
Jour 1 
FTS   Positif|_____|    Négatif  |_____| (Préciser le grade** si positif : 1 |__|    2  |__|   3  |__|) 
Prélèvement veineux (10 ml) post-traitement: Oui |____| Non |____|  
Examens cliniques post-traitement: Oui |____| Non |____|  
Questionnaire Effets secondaires post-traitement ****: Oui |____| Non |____| 
Surveillance des signes vitaux après chaque 8 heures: Oui |____| Non |____|  
** Par rapport au trait contrôle, le trait test est (1) moins intense ; (2) de même intensité ; (3) plus intense 
**** Voir questionnaire effets secondaires 
 
Jour 2 
FTS*****  Positif|_____|   Négatif  |_____| (Préciser le grade** si positif : 1 |__|    2  |__|   3  |__|) 
 
GEC  Prélèvement veineux (10 ml) post-traitement: Oui |____| Non |____|  
Examens cliniques post-traitement: Oui |____| Non |____|  
Questionnaire Effets secondaires post-traitement ****: Oui |____| Non |____| 
Surveillance des signes vitaux après chaque 8 heures: Oui |____| Non |____|  
** Par rapport au trait contrôle, le trait test est (1) moins intense ; (2) de même intensité ; (3) plus intense 
*****  Si pas positif au jour 1 
 
Jour 3 
Loascope : Oui |____| Non |____| (|_________|/ml)  
Prélèvement veineux (10 ml) post-traitement: Oui |____| Non |____|  
Examens cliniques post-traitement: Oui |____| Non |____|  
Questionnaire Effets secondaires post-traitement ****: Oui |____| Non |____| 
Surveillance des signes vitaux après chaque 8 heures: Oui |____| Non |____|  
 
Jour 3-6 
Prélèvement veineux (10 ml) post-traitement: Oui |____| Non |____|  
Examens cliniques post-traitements Oui |____| Non |____|  
Questionnaire Effets secondaires post-traitement ****: Oui |____| Non |____| 
Surveillance des signes vitaux après chaque 8 heures: Oui |____| Non |____|  
****** Si pas zéro au jour 3 
 
Jour 7 
FTS   Positif|_____|    Négatif  |_____| (Préciser le grade** si positif : 1 |__|    2  |__|   3  |__|) 


Loiasis Antigenemia Version 1.2 25 June 2019 
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Loascope : Oui |____| Non |____| (|_________|/ml) GEC  Oui |____| Non |____| (|_________|/ml)  
Examens cliniques post-traitements Oui |____| Non |____| 
Prélèvement veineux (10 ml) prétraitement: Oui |____| Non |____|  
** Par rapport au trait contrôle, le trait test est (1) moins intense ; (2) de même intensité ; (3) plus intense 
…………………………………………………………………………………………………………………………… 
 
REMARQUES 
_______________________________________________________________________________________________________________ 
_______________________________________________________________________________________________________________ 
Noms et signature du chef d’équipe (après vérification des informations) 
 
 
 


 
17. Chronogram  
 
 
 
 
 
 
 
 
 
 
 
 
                    Years
Activities
July Aug Sep Oct Nov Dec Jan Feb Mar Apr May June July Aug Sept Oct Nov Dec Jan Feb Mar Apr May June July
Aug
Sep
Ethical clearance / administrative authorization
Cohort 1
     Screening and enrolment
     Follow-up visits
     Laboratory analysis (LCMS, CFA ELISA)
Cohort 2
     Screening and enrolment
     Ivermectin treatment and monitoring
     Laboratory analysis (LCMS, CFA & cytokines  ELISA)
Valorization
     Preparation and submit publication
     Meeting attendance
Prepare and submit R01
Final Report (Thesis defense)
2019
2020
2021


50 
 
18. Detailed budget and Source of funding 
18.1. Detailed budget 
 
 
18.2.  Source of funding 
This study will be funded by the Doris Duke Charitable Foundation (650 5th Ave, New 
York, NY 10019, USA). 
 
 


51 
 
19. References 
Andersen BJ, Kumar J, Curtis K, et al. «Changes in Cytokine, Filarial Antigen, and DNA 
Levels Associated With Adverse Events Following Treatment of Lymphatic Filariasis .» 
J Infect Dis, 2018: 217(2):280-287. 
Boussinesq M. «Loiasis.» Ann Trop Med Parasitol, 2006: 100(8):715-731. 
Budge PJ, Herbert C, Andersen BJ, Weil GJ. «Adverse events following single dose 
treatment of lymphatic filariasis: Observations from a review of the literature.» PLoS 
neglected tropical diseases, 2018: 12(5):e0006454. 
Cédric B. Chesnais, Johnny Vlaminck, Billy Kunyu-Shako, Sébastien D. Pion, Naomi-
Pitchouna Awaca-Uvon, Gary J. Weil, Dieudonné Mumba, and Michel Boussinesq. 
«Measurement of Circulating Filarial Antigen Levels in Human Blood with a Point-of-
Care Test Strip and a Portable Spectrodensitometer.» Am. J. Trop. Med. Hyg, 2016: 
94(6),1324–1329. 
Center 
of 
Diseases 
Control 
and 
Prevention. 
2 
March 
2019. 
https://www.cdc.gov/parasites/lymphaticfilariasis/biology.html (accès le June 12, 
2019). 
Chesnais CB, Takougang I, Paguele M, Pion SD, Boussinesq M. «Excess mortality associated 
with loiasis: a retrospective population-based cohort study.» Lancet Infect Dis, 2017: 
17(1):108-116. 
Gardon J, Gardon-Wendel N, Demanga N, Kamgno J, Chippaux JP, Boussinesq M. «Serious 
reactions after mass treatment of onchocerciasis with ivermectin in an area endemic 
for Loa loa infection.» Lancet, 1997: 350(9070):18-22. 
Global programme to eliminate lymphatic filariasis. «progress report.» Wkly Epidemiol 
Rec, 2017: 93(44):589–604. 
Herrick JA, Legrand F, Gounoue R, et al. «Posttreatment Reactions After Single-Dose 
Diethylcarbamazine or Ivermectin in Subjects With Loa loa Infection.» Clinical 
infectious diseases : an official publication of the Infectious Diseases Society of America, 
2017: 64(8):1017-1025. 
Herrick JA, Metenou S, Makiya MA, Taylar-Williams CA, Law MA, et al. «Eosinophil-
associated processes underlie differences in clinical presentation of loiasis between 
temporary residents and those indigenous to Loa-endemic areas.» Clin Infect Dis, 2015: 
60: 55–63. 
Hertz MI, Nana-Djeunga H, Kamgno J, et al. «Identification and characterization of Loa loa 
antigens responsible for cross-reactivity with rapid diagnostic tests for lymphatic 
filariasis.» PLoS neglected tropical diseases, 2018: 12(11):e0006963. 
Kamgno J, Nana-Djeunga HC, Pion SD, et al. «Operationalization of the test and not treat 
strategy to accelerate the elimination of onchocerciasis and lymphatic filariasis in 
Central Africa.» Int Health, 2018: 10(suppl_1):i49-i53. 


Loiasis Antigenemia Version 1.2 25 June 2019 
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Kamgno J, Pion SD, Chesnais CB, et al. «A Test-and-Not-Treat Strategy for Onchocerciasis 
in Loa loa-Endemic Areas.» N Engl J Med, 2017: 377(21):2044-2052. 
Louise A. Kelly-Hope, Janet Hemingway, Mark J. Taylor and David H. Molyneux. 
«Increasing evidence of low lymphatic filariasis prevalence in high risk Loa loa areas 
in Central and West Africa: a literature review .» Parasites & Vectors , 2018: 11:349 . 
Metzger WG, Mordmuller B. «Loa loa—does it deserve to be neglected? .» The Lancet 
Infectious Diseases, 2014: 14: 353–357. 
Michael E, Bundy DA, Grenfell BT. «Re-assessing the global prevalence and distribution of 
lymphatic filariasis.» Parasitology, 1996: 112: 409–428. 
Molyneux DH, Hopkins A, Bradley MH, Kelly-Hope LA. «Multidimensional complexities of 
filariasis control in an era of large-scale mass drug administration programmes: a can 
of worms.» Parasit Vectors, 2014: 7:363. 
Paul E. Simonsen, Peter U. Fischer, Achim Hoerauf, Gary J. Weil. «The Filariases.» Manson's 
Tropical Diseases, 23rd Edition, 2014: 54:765.e1. 
Pion S, Chesnais C. «Loiasis.» Switzerland Springer International Publishing, 2017: 427–
444. 
Pion SD, Montavon C, Chesnais CB, Kamgno J, Wanji S, Klion AD, et al. «Positivity of antigen 
tests used for diagnosis of lymphatic filariasis in individuals without Wuchereria 
bancrofti infection but with high Loa loa microfilaremia.» Am J Trop Med Hyg, 2016: 
95:1417–23. 
Wanji S, Amvongo-Adjia N, Koudou B, et al. «Cross-Reactivity of Filariais ICT Cards in 
Areas of Contrasting Endemicity of Loa loa and Mansonella perstans in Cameroon: 
Implications for Shrinking of the Lymphatic Filariasis Map in the Central African 
Region.» PLoS neglected tropical diseases, 2015: 9(11):e0004184. 
Weil GJ, Curtis KC, Fakoli L, Fischer K, Gankpala L, Lammie PJ, et al. «Laboratory and field 
evaluation of a new rapid test for detecting Wuchereria bancrofti antigen in human 
blood.» Am J Trop Med Hyg, 2013: 89:11–5. 
WHO. «Summary of global update on preventive chemotherapy implementation in 2016: 
crossing the billion.» Wkly Epidemiol Rec, 2017: 92: 589–93. 
World Health Organization. 19 April 2018. https://www.who.int/news-room/fact-
sheets/detail/lymphatic-filariasis (accès le June 12, 2019). 
World Health Organization. Integrating neglected tropical diseases in global health and 
development: Fourth WHO report on neglected tropical diseases. Geneva: WHO, 2017. 
Zouré HGM, Wanji S, Noma M, Amazigo UV, Diggle PJ, Tekle AH, et al. «The Geographic 
Distribution of Loa loa in Africa: Results of Large-Scale Implementation of the Rapid 
Assessment Procedure for Loiasis (RAPLOA).» PLoS Negl Trop Dis , 2011: 5(6): e1210. 


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20. Others documents 
20.1. Curriculum vitae of investigators 
 
Joseph KAMGNO (MD, MPH, PhD)  
Date of birth: January 19, 1965 
Nationality: Cameroonian 
Gender: Male 
 
Position and address 
Posts held: Executive Director (CRFilMT), Deputy Dean in charge of Research and 
Cooperation (Faculty of Medicine and Biomedical Sciences of the University of Yaoundé 
I), Technical advisor (NOTF, MoH)  
Phone: (Office): 00237 22 20 24 42 (Mobile): 00237 77 78 97 36 
Fax:  00237 22 20 24 43; Email: kamgno@crfilmt.org  
 
Education and trainings 
§ Degrees: MD, MPH, PhD 
§ Main proficiencies: General Medicine; Clinical trials; Biostatistics and 
Epidemiology; Geographic Information System; Ethics in research; Database 
construction.  
 
Main Research activities 
§ More than 10 clinical trials for the treatment of filariasis (onchocerciasis, loiasis, 
lymphatic Filariasis);  
§ Mapping of filariasis (onchocerciasis, loiasis, lymphatic Filariasis) and other 
tropical diseases; 
§ Clinical impact of loiasis; 
§ Impact of mass drug administration on the prevalence, intensity and transmission 
of filariasis in Central Africa;  
§ Elaboration of the surveillance system and training for the management of post-
ivermectin adverse events in Cameroon, Democratic Republic of Congo, Angola, 
South Sudan.  
 


Loiasis Antigenemia Version 1.2 25 June 2019 
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Publications (about 100 of which the 05 most significant) 
Kamgno J, Pion S, Chesnais C, Bakalar M, D'Ambrosio M, Mackenzie CD, Nana-Djeunga 
HC, Gounoue-Kamkumo R, Njitchouang GR, Nwane P, Tchatchueng-Mbougua JB, Wanji 
S, Stolk WA, Fletcher DA, Klion AD, Nutman TB, Boussinesq M (2017). “Test and not 
treat” for onchocerciasis control in a Loa loa endemic area. New England Journal of 
Medicine. DOI: 10.1056/NEJMoa1705026. 
Nana-Djeunga H, Tchouakui M, Njitchouang GR, Tchatchueng-Mbougua J, Nwane P, 
Domche A, Bopda J, Mbickmen-Tchana S, Akame J, Tarini A, Epee E, Biholong B, Zhang 
Y, Tougoue JJ, Kabore A, Njiokou F & Kamgno J (2017). First Evidence of Lymphatic 
Filariasis Transmission Interruption in Cameroon: 3 Progress towards Elimination. 
PLoS Neglected Tropical Diseases 11(6): e0005633. 
Gardon J., Gardon-Wendel N., Demanga-Ngangue, Kamgno J., Chippaux J.P. & 
Boussinesq M. (1997). Serious reactions after mass treatment of onchocerciasis with 
ivermectin in an area endemic for Loa loa infection. Lancet, 350, 18-22. 
Gardon J., Boussinesq M., Kamgno J., Gardon-Wendel N., Demanga-Ngangue & Duke 
B.O.L. (2002). Effects of standard and high doses of ivermectin on adult worms of 
Onchocerca volvulus: a randomised controlled trial. Lancet, 360, 203-210. 
Pion S.D.S., Kamgno J., Demanga-Ngangue & Boussinesq M. (2002). Excess mortality 
associated with blindness in the onchocerciasis focus of the Mbam Valley, Cameroon. 
Annals of Tropical Medicine and Parasitology, 96, 181-189. 
 
Society’s Membership and expertise 
§ Member of the American Society of Tropical Medicine and Hygiene (ASTMH)  
§ Member of the Cameroon Society of Epidemiology (CaSE) 
§ Member of the Mectizan/Albendazole Expert committee 
§ Member of the Expert Committee for the Evaluating Moxidectin development 
 
 
Philip BUDGE (MD, PhD)  
 
CITIZENSHIP:  USA 
 
ADDRESS AND TELEPHONE NUMBERS: 
Washington University School of Medicine 
660 South Euclid Avenue 
Campus Box 8051,  
St. Louis, MO 60110-1093 


Loiasis Antigenemia Version 1.2 25 June 2019 
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(314) 747-5532 
pbudge@wustl.edu 
 
PRESENT POSITION: 
Assistant Professor of Medicine, Infectious Diseases Division, Washington University School 
of Medicine, St. Louis, MO 
 
EDUCATION: 
1991 – 1998  
BS (Molecular Biology), Brigham Young University, Provo, UT  
1998 – 2007  
MD, PhD (Microbiology and Immunology), Vanderbilt University School 
of Medicine, Nashville, TN 
2004 (Jan – Aug) 
Postdoctoral Fellowship, Department of Molecular Physiology and 
Biophysics, Vanderbilt University School of Medicine, Nashville, TN  
2007 – 2009  
Internal Medicine Internship and Residency, Vanderbilt University 
Medical Center, Nashville, TN 
2009 – 2011  
Epidemic Intelligence Service, Centers for Disease Control and 
Prevention (Division of Parasitic Diseases and Malaria), Atlanta, GA 
2011 – 2014  
Infectious Diseases Fellowship, Vanderbilt University Medical Center, 
Nashville, TN  
 
ACADEMIC POSITIONS / EMPLOYMENT: 
2014 – present 
Assistant Professor of Medicine, Division of Infectious Diseases, 
Washington University School of Medicine, St. Louis, MO 
 
UNIVERSITY AND HOSPITAL APPOINTMENTS AND COMMITTEES: 
2011 – 2014  
Hospitalist (part time), Scoville Internal Medicine Service, Department 
of Medicine, Vanderbilt University Medical Center, Nashville, TN 
2013 
Internal Review Committee, Vascular Surgery Program, Office of 
Graduate Medial Education, Vanderbilt University School of Medicine, 
Nashville, TN 
2013 – 2014  
Hospitalist (part time), Williamson Medical Center, Franklin, TN 
2014 – present 
Physician, Barnes-Jewish Hospital, St. Louis, MO 
2014 – 2016 
Governing Board, Infectious Disease Clinic, Washington University in 
St. Louis School of Medicine 
2015 
Rapid Improvement Event Team, Infectious Disease Clinic, Washington 
University in St. Louis School of Medicine 
 


Loiasis Antigenemia Version 1.2 25 June 2019 
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MEDICAL LICENSURE AND BOARD CERTIFICATION: 
2009 – 2014  
Tennessee medical license 44675  
 
 
 
 
2012 – 2022  
American Board of Internal Medicine, certificate in Internal Medicine
 
  
2013 – 2023  
American Board of Internal Medicine, certificate in Infectious Diseases
 
  
2014 – present 
Missouri medical license 2014018769 
HONORS AND AWARDS: 
2000 – 2007  
Medical Scientist Training Program, Vanderbilt University School of 
Medicine 
2001 – 2003  
Intramural Research Training Award, National Institutes of Health 
2007 
Max Kade Fellowship, American Austrian Foundation  
2007 
Outstanding Senior Medical Student in Infectious Diseases, Vanderbilt 
University School of Medicine 
2007 
Overall Fellowship, Vanderbilt University School of Medicine  
2012 
Golden Pen Award, Florida Environmental Health Association  
2012 – 2013 
Kirschstein National Research Service Award Department of Preventive 
Medicine, Vanderbilt University Medical Center 
2013 – 2014  
Kirschstein National Research Service Award Division of Infectious 
Diseases, Department of Medicine, Vanderbilt University Medical 
Center 
2014 
Outstanding Fellow in Infectious Diseases, Vanderbilt University 
Medical Center 


Loiasis Antigenemia Version 1.2 25 June 2019 
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EDITORIAL RESPONSIBILITIES: 
Reviewer: 
American Journal of Tropical Medicine and Hygiene (2014-2015, 2017-
2018) 
BioMed Research International (2013) 
Biomedical Engineering/Biomedizinische Technik (2018) 
The BMJ (2018) 
Journal of Clinical Microbiology (2016) 
Lancet Infectious Diseases (2016) 
Lymphatic Research and Biology (2018) 
Parasitology Research (2019) 
PLoS Neglected Tropical Diseases (2013 – 2019) 
PLoS One (2013 – 2014) 
Transactions of the Royal Society of Tropical Medicine & Hygiene 
(2015, 2018) 
Tropical Medicine and Infectious Diseases (2017, 2019) 
 
NATIONAL SCIENTIFIC PANELS: 
2018 
NIAID Small Business Innovation Research (SBIR) Study Section: Topic 
59, Diagnostics to Enable Malaria and Neglected Tropical Diseases 
(NTDs) Elimination 
 
PROFESSIONAL SOCIETIES AND ORGANIZATIONS: 
2007 – present 
American Society of Tropical Medicine and Hygiene 
2011 – present  
Infectious Disease Society of America 
 
INVITED PROFESSORSHIPS AND LECTURESHIPS: 
Jan 2014 
“Global elimination of lymphatic filariasis: progress and challenges”, 
Division of Infectious Diseases, Saint Louis University, St. Louis, MO 
Feb 2014 
“Global elimination of lymphatic filariasis: progress and challenges”, 
Division of Infectious Diseases, Washington University, St. Louis, MO 
Oct 2015 – 2018  
“Parasitic Diseases in 35 Minutes”, V.T. Andriole Board Review 
Course, IDSA Annual Meeting (ID Week) 
Apr 2017 
“Progress towards elimination of LF”. ID Grand Rounds, Vanderbilt 
University, Nashville, TN 
Apr 2017 
Harrison Society Career Development Panel. Vanderbilt University, 
Nashville, TN 
Jun 2019 
 
“Doxycycline for Filarial Lymphedema”. Lymphatic Forum 2019. Austin, 
TX 


Loiasis Antigenemia Version 1.2 25 June 2019 
58 
 
 
RESEARCH SUPPORT: 
Active 
Governmental  
NIH/NIAID K08 AI121422-01A1 
 
(07/01/2016 – 06/30/2021) 
Improved antigen detection tests for filarial infections 
Role: principle investigator 
Total direct cost: $855,606 
 
USAID LEDoxy Study 
 
 
(03/14/2016 – 06/11/2019) 
A multi-center, double-blind randomized, 24-month study, to compare 
the efficacy of doxycycline 200 mg [once daily] versus placebo in 
improving filarial lymphedema (independent of active filarial infection) 
Role: co-investigator 
Total direct cost: $137,846 
 
Non-Governmental  Bill and Melinda Gates Foundation OPP GH 5342  (11/1/2009 – 
10/31/2019) 
Optimization of chemotherapy for control and elimination of 
onchocerciasis and lymphatic filariasis 
Role: co-investigator 
Total direct cost: $29,853,900 
 
 
Bill and Melinda Gates Foundation   
(2019 – 2024, pending) 
DOLF Next-Gen: Next-generation studies to optimize chemotherapy 
for elimination of lymphatic filariasis and onchocerciasis. 
Role: co-investigator 
Total direct cost: $24,731,775 
 
Doris Duke Charitable Foundation  
Clinical Scientist Development Award (CSDA) 
(07/1/2019 – 
06/30/2022)  
Cross-reactive antigenemia and treatment-related adverse events in 
loiasis 
Role: principle investigator 
Total direct cost: $450,000 


Loiasis Antigenemia Version 1.2 25 June 2019 
59 
 
 
Past 
 
 
Vanderbilt Physician Scientist Development Award (2014) 
Low-Resource Detection of High-Level Loiasis 
Role: principle investigator 
Total cost:  $75,000 (declined) 
 
NIH Loan Repayment Program, NIAID 
(7/1/2014 – 6/30/2018) 
Improved antigen detection tests for filarial diseases 
Role: Awardee 
Total cost: $57,587 
 
CLINICAL TITLE AND RESPONSIBILITIES: 
2014 – present 
Attending Physician, Internal Medicine 
2014 – present 
Consulting Physician, Infectious Diseases 
 
TEACHING TITLES AND RESPONSIBILITIES: 
Centers for Disease Control and Prevention 
Sep 2010  
Lecturer, Haitian Ministry of Health Epidemiology Training Division of 
Parasitic Diseases and Malaria 
Vanderbilt University School of Medicine 
2012 – 2013  
Small Group Instructor, Epidemiology 1: Research Design 
Washington University School of Medicine 
Aug 2014 
Panelist, Global Health Career Panel, Global Health Scholars Pathway 
in Internal Medicine 
Sep 2014 
Panelist, Engineering World Health panel on innovating low cost 
technology to solve global health problems 
Fall 2014 – 2018  
Lecturer, Global Health Clinical Cases, Global Health Scholars Pathway 
in Internal Medicine 
Nov 2014 
Faculty Host, Forum for International Health and Tropical Medicine 
(FIHTM) medical student dinner discussion 
Dec 2015  
Lecturer, Internal Medicine House Staff Noon Conference, parasitic 
diseases 
Fall 2016, 2019  
Lecturer, Infectious Disease Core Curriculum (for ID Fellows). 
Helminths I & II 
Spring 2017 – 2019 
Lecturer, Anthropology 161: “Gender, Youth, and Global Health” 


Loiasis Antigenemia Version 1.2 25 June 2019 
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Spring 2017 – 2019  Small Group Instructor, Medical Microbiology (2nd year medical school 
curriculum) 
Apr 2017 
Lecturer, FIHTM Global Health Symposium 
Fall 2017 
Preceptor, Reading Elective (Tarik Salih): Preventive Medicine in the 
Primary Care Setting 
Dec 2017 
Panelist, 
“Faculty 
Professional 
Development”, 
2017 
Midwest 
Universities for Global Health Meeting 
Dec 2017 
Lecture: “Global Outbreak Response and Disease Eradication”, Forum 
for International Health and Tropical Medicine (FIHTM) student group 
Spring 2019  
Lecturer (“Helminths”), Medical Microbiology (2nd year medical school 
curriculum) 
 
TRAINING / MENTEE RECORD: 
Current Trainees / Mentees 
2016 – present 
Marla Hertz 
 
Postdoctoral Fellow 
2018 – present 
Irene Hamlin  
Undergraduate Student 
2019 – present  
Aja Drain 
 
Undergraduate Student 
 
Past Trainees / Mentees 
2010 – 2011 
Amanda Akosa 
Volunteer, Centers for Disease Control and 
Prevention  
2016 – 2017 
Carly Herbert  
Undergraduate Student 
2018  
Celia Zhou 
WUSM Summer Research Program in Global 
Health 
2018 – 2019 
Georgia Redd 
Undergraduate Student 
2018 – 2019 
Grant Owen  
Undergraduate Student 
2018 – 2019 
Phil Glaessner 
Undergraduate Student 
 
 
BIBLIOGRAPHY: 
Peer Reviewed Manuscripts 
1. Budge PJ, Lebowitz J, Graham BS. Antiviral activity of RhoA-derived peptides against 
respiratory syncytial virus is dependent on formation of peptide dimers. Antimicrob Agents 
Chemother. 2003: 47: 3470-3477. PMID: 14576104. 
2. Budge PJ, Li Y, Beeler JA, Graham BS, RhoA-derived peptide dimers share mechanistic 
properties with other polyanionic inhibitors of respiratory syncytial virus (RSV), including 
disruption of viral attachment and dependence on RSV G. J Virol 2004: 78: 5015-5022. 
PMID: 15113882. 


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3. Budge PJ, Graham BS, Inhibition of respiratory syncytial virus by RhoA-derived peptides: 
implications for the development of improved antiviral agents targeting heparin-binding 
viruses. J Antimicrob Chemother 2004: 54: 299-302. PMID: 15254023. 
4. Herzog B, Cardenas J, Hall RK, Villena JA, Budge PJ, Giguere V, Granner DK, Kralli A, 
Estrogen-related receptor alpha is a repressor of phosphoenolpyruvate carboxykinase 
gene transcription. J Biol Chem 2006: 281: 99-106. PMID: 16267049. 
5. Kallen AJ, Brunkard J, Moore Z, Budge P, Arnold KE, Fosheim G, Fineli L, Beekmann SE, 
Polgreen PM, Gorwitz R, Hageman J, Staphylococcus aureus community-acquired 
pneumonia during the 2006 to 2007 influenza season. Ann Emerg Med 2009: 53: 358-365. 
PMID: 18534715. 
6. Centers for Disease Control and Prevention, Balamuthia mandrillaris transmitted through 
organ transplantation—Mississippi, 2009. MMWR Morb Mortal Wkly Rep 2010: 59: 1165-
1170. PMID 20847719. (Primary contributor—MMWR articles did not attribute personal 
authorship at that time). Reprinted in (1) JAMA 2010: 304: 2008-2012, and (2) Am J 
Transplant 2011: 11:173-176. 
7. Mathieu E, Dorkenoo A, Otogbe FKJ, Budge PJ, Sodahlon YK, A laboratory-based 
surveillance system for Wuchereria bancrofti in Togo: a practical model for resource-poor 
settings. Am J Trop Med Hyg 2011: 84: 988-993. PMID: 21633038. 
8. Pelletreau S, Nyaku M , Dembele M , Sarr B , Budge P, Ross R, Mathieu E. The field-
testing of a novel integrated mapping protocol for neglected tropical diseases. PLoS Negl 
Trop Dis 2011: 5: e1380. PMID: 22102921. 
9. Lopez C, Budge P, Chen J, Bilyeu S, Mirza A, Custodio H, Irazuzta J, Visvesvara G, 
Sullivan KJ, Primary amebic meningoencephalitis: a case report and literature review. 
Pediatr Emerg Care 2012: 28: 272-276. PMID: 22391923. 
10. Ailes E, Budge P, Shankar M, Collier S, Brinton W, Cronquist A, Chen M, Thornton A, 
Beach MJ, Brunkard JM, Economic and health impacts associated with a Salmonella 
typhimurium drinking water outbreak—Alamosa, CO, 2008. PLoS One 2013: 8: e57439. 
PMID: 23526942. 
11. Budge PJ, Lazensky R, Van Zile KW, Elliott KE, Dooyema CA, Visvesvara GS, Beach MJ, 
Yoder JS, Primary amebic meningoencephalitis in Florida: a case report and 
epidemiological review of Florida cases. J Environ Health 2013: 75: 26-31. PMID: 
23621053. 
12. Budge PJ, Little KM, Mues KE, Kennedy ED, Prakash A, Rout J, Fox LM, Impact of 
community-based lymphedema management on perceived disability among patients with 
lymphatic filariasis in Orissa State, India. PLoS Negl Trop Dis 2013: 7: e2100. PMID: 
23516648. 
13. Budge PJ, Dorkenoo AM, Sodahlon YK, Fasuyi OB, Mathieu E, Ongoing surveillance for 
lymphatic filariasis in Togo: assessment of alternatives and nationwide reassessment of 
transmission status. Am J Trop Med Hyg 2014: 90: 89-95. PMID: 24189363. 
14. Budge PJ, Griffin MR, Edwards KM, Williams JV, Verastegui H, Hartinger SM, Maeusezahl 
D, Johnson M, Klemenc JM, Zhu Y, Gil AI, Lanata CF, Grijalva CG; RESPIRA PERU 
Group, A household-based study of acute viral respiratory illness in Andean children. 
Pediatr Infect Dis J 2014: 33: 443-447. PMID: 24378948. 
15. Budge PJ, Griffin MR, Edwards KM, Williams JV, Verastegui H, Hartinger SM, Maeusezahl 
D, Johnson M, Klemenc JM, Zhu Y, Gil AI, Lanata CF, Grijalva CG; RESPIRA PERU 
Group, Impact of home environment interventions on the risk of influenza-associated ARI 
in Andean children: observations from a prospective household-based cohort study. PLoS 
One 2014: 9: e91247. PMID: 24622044. 


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16. Mues KE, Deming M, Kleinbaum DG, Budge PJ, Klein M, Leon JS, Prakash A, Rout J, 
Fox LM, Impact of a community-based lymphedema management program on episodes of 
adenolymphangitis (ADLA) and lymphedema progression—Odisha State, India. PLoS 
Negl Trop Dis 2014: 8:e3140. PMID: 25211334. 
17. Wu A, Budge PJ, Williams JV, Griffin MR, Edwards KM, Johnson M, Zhu Y, Hartinger SM, 
Verastegui H, Gil AI, Lanata CF, Grijalva CG, Incidence and risk factors for respiratory 
syncytial virus and human metapneumovirus infections among children in the remote 
highlands of Peru. PLoS ONE 2015: 10: e0130233. PMID: 26107630. 
18. Budge PJ, Sognikin E, Akosa A, Mathieu EM, Deming M, Accuracy of coverage survey 
recall following an integrated mass drug administration for lymphatic filariasis, 
schistosomiasis, and soil transmitted helminthiasis. PLoS Negl Trop Dis. 2016: 10:e4358. 
PMID: 26766287. 
19. Farnon ED, Kokko K, Budge PJ, Mbaeyi C, Lutterloh E, Qvanrstrom Y, da Silva AJ, Shieh 
W, Roy S, Paddock CD, Sriram R, Zaki SR, Visvesvara G, Kuehnert MJ, Transmission of 
Balamuthia mandrillaris by organ transplantation. Clin Infect Dis. 2016. 63: 878-88. PMID 
27358357. 
20. Yahathugoda C, Weiler MJ, Rao R, De Silva L, Dixon JB, Weerasooriya MV, Weil GJ, 
Budge PJ. Use of a novel portable 3D scanner to measure limb volume and circumference 
in patients with filarial lymphedema. Am J Trop Med Hyg. 2017: 97(6):1836-1842. PMID: 
29141750. 
21. Budge PJ, Herbert C, Andersen BJ, Weil GJ. Adverse events following single dose 
treatment of lymphatic filariasis: observations from a review of the literature. PLoS Negl 
Trop Dis. 2018: 12:e0006454. PMID 29768412. 
22. Hertz MI, Nana-Djeuna H, Kamgno J, Njouendou AJ, Chunda VC, Wanji S, Rush A, Fischer 
PU, Weil GJ, Budge PJ. Identification and characterization of Loa loa antigens responsible 
for cross-reactivity with rapid diagnostic tests for lymphatic filariasis.  PLoS Negl Trop Dis. 
2018: 12:e0006963. PMID 30444866 
23. Weil GJ, Bogus J, Christian M, Dubray C, Djuardi Y, Fischer PU, et al. The safety of double- 
and triple-drug community mass drug administration for lymphatic filariasis: A multicenter, 
open-label, 
cluster-randomized 
study. 
PLoS 
Med. 
2019;16(6):e1002839. 
doi:10.1371/journal.pmed.1002839. PubMed PMID: 31233507 
Invited Publications 
1.   Mejia-Chew C, Budge PJ. Helminthic Infections. Washington Manual of Infectious Disease 
Subspecialty Consult. 
2. Budge PJ, Odom John AR. The longest mile: moving malaria from clinical care to 
elimination of transmission. Clin Chem. 2019. doi:10.1373/clinchem.2019.303719. 
PubMed PMID: 31171527 
 
Hugues NANA DJEUNGA (PhD)  
Date of birth: July 24, 1982 
Nationality: Cameroonian 
Gender: Male 
 
Position and address 


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2012-present: Researcher 
Centre for Research on Filariasis and other Tropical Diseases (CRFilMT) 
Street 1302, Quartier Fouda | PO Box 5797 Yaoundé, Cameroon  
Tel. Office: 00237 222 20 24 42| Mobile 1: 00237 699 07 64 99| Mobile 2: 00237 
651 88 56 39 | Fax: 00237 222 20 24 43 | Web site: www.crfilmt.org | E-mail: 
nanaclotaire@yahoo.fr | nanadjeunga@crfilmt.org 
 
Education and trainings 
Degrees: PhD in Molecular Parasitology and Population Genomics, Department of 
Animal Biology and Physiology, University of Yaoundé I (UYI), Yaoundé, Cameroon 
 
Main proficiencies:  Parasitology, Molecular Biology and Bioinformatics; Population 
Genomics and Genetic Epidemiology; Biostatistics and Epidemiology; Geographic 
Information System; Ethics in research; Hazardous Waste Management and Biosafety.  
 
Main Research activities 
§ Filariasis: epidemiology and mapping of onchocerciasis, loiasis, lymphatic Filariasis 
in Cameroon; impact of loiasis; impact of treatments on endemicity and 
transmission of onchocerciasis and lymphatic filariasis; drug resistance studies; 
severe adverse events management 
§ Sleeping sickness: analysis of domestic and wild animal reservoir of trypanosomes, 
assessment of risk factors in Cameroonian foci, design and evaluation of 
transmission risk indices, interactions between trypanosomes, tsetse flies and 
endosymbiotic bacteria 
§ Malaria: epidemiology of malaria and genetic diversity of Plasmodium falciparum 
msp-1 block 2, a possible candidate vaccine against malaria 
§ Schistosomiasis and Soil Transmitted Helminthiasis: epidemiology and risk 
factors of schistosomiasis and soil transmitted helminths in Cameroon 
 
Publications (40 of which the 05 most significant) 
Nana-Djeunga HC, Fossuo-Thotchum F, Pion SD, Chesnais CB, Kubofcik J, Mackenzie 
CD, Klion AD, Boussinesq M, Nutman TB, Kamgno J (2019). Loa loa microfilariae in skin 
snips: consequences for onchocerciasis monitoring and evaluation in L. loa endemic 
areas. Clinical Infectious Diseases. In press. 


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Chesnais CB, Nana-Djeunga HC, Njamnshi AK, Lenou-Nanga CG, Boullé C, Zoung-Kanyi 
Bissek AC, Kamgno J, Colebunders R, Boussinesq M, (2018). The temporal relationship 
between onchocerciasis and epilepsy: a population-based cohort study. Lancet 
Infectious Diseases. http://dx.doi.org/10.1016/S1473-3099(18)30425-0. 
 
Kamgno J, Pion S, Chesnais C, Bakalar M, D'Ambrosio M, Mackenzie CD, Nana-Djeunga 
HC, Gounoue-Kamkumo R, Njitchouang GR, Nwane P, Tchatchueng-Mbougua JB, Wanji 
S, Stolk WA, Fletcher DA, Klion AD, Nutman TB, Boussinesq M (2017). “Test and not 
treat” for onchocerciasis control in a Loa loa endemic area. New England Journal of 
Medicine. DOI: 10.1056/NEJMoa1705026. 
 
Nana-Djeunga H, Tchouakui M, Njitchouang GR, Tchatchueng-Mbougua J, Nwane P, 
Domche A, Bopda J, Mbickmen-Tchana S, Akame J, Tarini A, Epee E, Biholong B, Zhang 
Y, Tougoue JJ, Kabore A, Njiokou F & Kamgno J (2017). First Evidence of Lymphatic 
Filariasis Transmission Interruption in Cameroon: 3 Progress towards Elimination. 
PLoS Neglected Tropical Diseases 11(6): e0005633. 
 
Nana-Djeunga H, Bourguinat C, Pion SDS, Kamgno J, Gardon J, Njiokou F, Boussinesq 
M & Prichard RK (2012). Single Nucleotide Polymorphism in β-tubulin selected in 
Onchocerca volvulus following repeated ivermectin treatment: possible indication of 
resistance selection. Molecular and Biochemical Parasitology 185: 10-18 
 
 
Society’s Membership and expertise 
§ Member of the Cameroon Academy of Young Scientists (CAYS) 
§ Member of the American Society of Tropical Medicine and Hygiene (ASTMH)  
§ Member of the African Research Network for Neglected Tropical Diseases (ARNTDs)  
§ Member of the Cameroon Society of Epidemiology (CaSE) 
§ Member of the Editorial Board of American Journal of Clinical Immunology and 
Infectious Diseases, Global Journal of infectious diseases and Clinical Research 
§ Reviewer for Infectious Diseases and Poverty, BMJ Open, Journal of Public Health 
and Epidemiology, SciMedCentral, Tropical Medicine and Health, Journal of Medical 
Chemistry, HINDAWI, Journal of Veterinary Medicine and Animal Health, Jacobs 
Journal of Clinical Case Reports 
§ Temporary Consultant for Drugs for Neglected Diseases Initiative (DNDi), World 
Health Organization (WHO) and the former African Programme for Onchocerciasis 
Control (APOC)  
 


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Marla HERTZ (PhD)  
Edit 
 
 
Linda DJUNE YEMELI (MSc, PhD Candidate)  
Date of birth: December 10, 1990 
Nationality: Cameroonian 
Gender: Female 
 
Position and address 
2018-present: Research Assistant 
Centre for Research on Filariasis and other Tropical Diseases (CRFilMT) 
Street 1302, Quartier Fouda | PO Box 5797 Yaounde, Cameroon  
Tel. Office: 00237 222 20 24 42| Mobile 1: 00237 655 11 96 48 | Mobile 2: 00237 
670 14 35 88 | Fax: 00237 222 20 24 43 | Web site: www.crfilmt.org | E-mail: 
djunelinda@gmail.com 
 
Education and trainings 
Degrees: PhD Candidate, Department of Biochemistry, University of Yaoundé I, 
Yaounde, Cameroon 
 
Main proficiencies: Immunology and immunological technics, molecular biology and 
biomolecular technics, and other biochemistry technics. Basic technic in parasitology, 
good understanding of ethics in biomedical research, good understanding of informed 
consent process.  
 
Other Relevant trainings 
§ Training on OV-16 ELISA technic by CDC (CRFilMT)  
§ Certification of First Yaoundé Advance Course in Immunology (University of 
Yaoundé 1)  
§ Training on HRP2 ELISA technic, for malaria diagnosis (Laboratory of research on 
malaria, Centre Pasteur de Yaoundé)  


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§ Training on diagnosis of measles by ELISA  
§ Training on ELISA and PBMCs isolation (Laboratory of research on malaria, Centre 
Pasteur de Yaoundé)  
§ Training on microscopic detection of malaria parasites (Laboratory of Public Health 
Biotechnology, Biotechnology center)  
§ Training on stool analysis by Kato-Katz technic (IMPM of Nkomo)  
§ Training on biomolecular technics (Laboratory of Public Health Biotechnology, 
Biotechnology center)  
 
Main Research activities 
§ Malaria and Schistosomiasis: molecular and rapid diagnostic of malaria; influence 
of Schistosoma mansoni on Plasmodium falciparum hrp2 gene deletion, and therefore 
on malaria HRP2 rapid diagnostic test; Immune interaction between malaria and 
schistosomiasis parasites (influence of schistosomiasis on malaria pathogenesis)  
§ Other Tropical Diseases: Onchocerciasis, Lymphatic Filariasis and Soil 
Transmitted Helminthiasis. 
 
Society’s Membership and expertise 
§ Member of the EDCTP-CANTAM project, since December 2018  
§ Close to 3 years research experience as member of Molecular Diagnosis Group  
§ Member of the Laboratory of Public Health Biotechnology, Biotechnology center, 
University of Yaoundé 1  
 
 
Gary J Weil (MD, PhD)  
Edit 
 
 
 
 
 
 


67 
 
20.2. Site Authorizations 
 
MINISTERE DE LA SANTE PUBLIQUE                                 REPUBLIQUE DU CAMEROUN 
           ******************************                                                         ******************** 
DELEGATION REGIONALE DU CENTRE                                           Paix-Travail-Patrie 
           ******************************                                                              ********** 
      DISTRICT DE SANTE D’OKOLA 
           ***************************** 
 
Yaoundé, le 27 juin 2019 
 
A Monsieur le Président du Comité National 
d’Ethique pour le Recherche en Santé Humaine 
(CNERSH)  
 
Objet : Accord de principe 
 
Monsieur le Président, 
 
J’ai l’honneur de venir auprès de votre haute bienveillance, soutenir la demande de 
clairance éthique pour l’étude intitulée « Cross-reactive antigenemia and treatment-
related adverse events in loiasis ». L’investigateur principal de cette étude est le Prof 
Joseph Kamgno et le laboratoire porteur du projet est le Centre Recherche sur les 
Filarioses et autres Maladies Tropicales (CRFilMT) dont il est le Directeur. 
 
J’ai pris connaissance du protocole de cette étude qui permettra de (i) définir le profil des 
antigènes de la loase, responsables des résultats faux-positifs lors du diagnostic de la 
filariose lymphatique par les tests de diagnostic rapides, et de (ii) déterminer si la 
production de ces antigènes spécifiques et/ou leur quantité est en corrélation avec 
l’apparition et la sévérité des effets secondaires observés suite au traitement des 
personnes avec une forte charge de loase par l’Ivermectine. En effet le district de santé 
d’Okola est fortement endémique pour la loase, ce qui a rend difficile la cartographie de 
la filariose lymphatique par TDRs, ainsi que le traitement de masse par l’Ivermectine. 
L’identification des antigènes de la loase ayant réactivité croisée et leur relation avec les 
effets secondaires liés au traitement par l’Ivermectine contribuera à la mise au point de 
TDRs plus fiable et aidera à mieux comprendre la cause des effets secondaires liés au 
traitement par l’Ivermectine.  
 
Dans l’attente d’une suite favorable, veuillez agréer Monsieur le Président l’expression de 
ma haute considération. 
 
 
Chef de Service de Santé du District d’Okola 


68 
 
20.3. Material/data sharing agreement 
 
Preamble 
This document defines the arrangements for material transferring and data sharing 
between the Centre for Research on Filariasis and other Tropical Diseases 
(CRFilMT) and Washington University in Saint Louis (WUSTL) under the project 
"Cross-reactive antigenemia and treatment-related adverse events in loiasis" that 
binds them.  
 
I. 
PARTIES TO THE AGREEMENT 
Institution providing the material and/or data: Centre for Research on 
Filariasis and other Tropical Diseases (CRFilMT), Yaounde, Cameroon
 
(“Provider”) 
Contact person: Joseph KAMGNO (MD, MPH, PhD) 
Title: Director of the CRFilMT and Vice-Dean in charge of Research and 
Cooperation at the Faculty of Medicine and Biomedical Sciences of the University 
of Yaoundé I.  
 
Address: Street 1308, Quartier Fouda | PO Box 5797 Yaoundé, Cameroon  
Phone number: 00237 677 789 736 | 00237 222 202 442 
 
Email: kamgno@crfilmt.org  
 
 
 
 
 
 
Fax number: 00237 222 202 443 
 
Institution receiving the material and/or data:   
Washington University in 
St. Louis (“Recipient”) 
Contact person: Philip Budge, MD, PhD  
 
 
 
Title: Assistant Professor of Medicine and Infectious Diseases 
Address: 4444 Forest Park Ave room 4186c, St. Louis, MO, 63108.  USA 
Phone number:  +1-314-747-5532 or +1-314-747-5198 
Email: pbudge@dom.wustl.edu   
 
 
 
 
Fax number: +1-314-454-5293 
II. 
PURPOSE AND TERM OF AGREEMENT 
A. 
Purpose of material and/or data sharing 


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To investigate what are the cross-reactive L. loa antigens, how and when are 
they released, and if their releases contribute to treatment-related adverse 
events observed in individuals with heavy loiasis infection. This study is of 
great importance for mapping, transmission assessment survey, surveillance 
and validation of the elimination of lymphatic filariasis in areas where loiasis 
is co-endemic. Indeed, it was demonstrated that people harboring high L. loa 
microfilarial densities can exhibit false-positive rapid diagnostic tests result 
while targeting LF.  
 
B. 
Legality and credibility of parties 
1. The Centre for Research on filariasis and other Tropical Diseases (CRFilMT) 
is a non-profit organization working in the medical field whose mission is 
to contribute to the improvement of the living conditions of the populations 
through an appropriate and applied scientific and medical research. The 
CRFilMT had signed a collaboration agreement with the Ministry of health 
of Cameroon as well as with many other national and international 
institutions and was positioned in 2009 as reference in Central Africa for 
surveillance of different filariasis. In addition, the CRFilMT also received in 
2009 an official testimony of satisfaction from the Ministry of health of 
Cameroon. 
2. Washington University in St. Louis, a corporation established by special act 
of the Missouri General Assembly approved February 22, 1853 and acts 
amendatory thereto, having its principal office at One Brookings Drive, St. 
Louis, MO 63130, USA 
 (WUSTL) is among the top-ranked medical 
research institutions in the United States. 
 
C. 
Period of performance 
This Agreement shall be effective when signed by both parties and shall 
continue until terminated pursuant to the termination clause contained 
herein. 
 
III. 
MATERIAL AND DATA MANAGEMENT PLAN 


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Sample collection will be done after approval by WUSTL Institutional Review Board 
(IRB) and Cameroon Regional Ethic Committee for Research in Human Health for 
Centre region, only on those individuals who will agree to participate in the study by 
signing a consent form. Thick blood smears will be prepared and stored at the CRFilMT 
in a locked cabinet designated for sample storage. Venous blood samples will be used 
for the preparation of dried blood spots and isolation of plasma samples. These plasma 
samples will be transferred in anonymously recoded 4.8 ml cryovial tubes containing 
and stored at -20°C at the CRFilMT. These anonymous samples (“Samples”) will then 
be shipped to WUSTL where they will be processed, blinded from the personal 
information of the subjects (“Results”). Hard copies with personal information of 
subjects will be stored at CRFilMT in a locked cabinet designated for data storage. 
Samples collection materials or used Samples will be destroyed according to the 
validated security norms. 
 
IV. 
ACCESS TO MATERIAL AND/OR DATA 
A. 
Method of access and transfer 
Thick blood smears slides and hard copies of data collection forms, stored in 
locked cabinet, will only be accessible at the CRFilMT after specific 
authorizations. DBS and plasma Samples shipped at WUSTL will be processed 
to determine and quantify cross-reactive loiasis antigens and cytokines. 
Secured electronic databases generated by CRFilMT and WUSTL will be shared 
between both parties.    
 
B. 
Persons having access to data 
Only principal investigators (and/or authorized designee) will have access to 
data and/or stored material. Prior to the transfer of any data, team members 
and researchers who will have access to the data should request specific 
authorization to the principal investigators (both at CRFilMT and WUSTL). 
 
C. 
Frequency of data exchange 
Data will be exchanged as needed to meet reporting requirements as well as on 
an ongoing basis between CRFilMT and WUSTL teams for the entire length of 
the project.   


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V. 
SECURITY OF DATA AND CONFIDENTIALITY OF SUBJECT RECORDS 
Neither CRFilMT team, nor WUSTL team will attempt to identify individuals’ records 
by any method. Datasets containing protected personal information shall be encrypted. 
All reasonable precautions shall be taken to secure the data from individuals who do 
not specifically have authorized access. Data shall be kept on a password-protected file 
server located in a secure environment, both at CRFilMT and at WUSTL. Project data 
will be kept in a separate directory on the server which is also password-protected and 
will be accessible only by principal investigators or designee with specifically 
authorized access. 
 
The report of this study will be transmitted to the Cameroon Regional Ethic Committee 
for Research in Human Health for Centre region as well as to the Ministry of Public 
Health. However, subject personal results will be given to them in strict compliance 
with privacy rules. 
 
VI. 
WARRANTY AND LIMITATION OF LIABILITY 
A. 
Warranty 
Any Samples or Results delivered pursuant to this Agreement is understood to 
be experimental in nature and may have hazardous properties. THE PARTIES 
MAKE NO REPRESENTATIONS AND EXTEND NO WARRANTIES OF ANY KIND, 
EITHER EXPRESSED OR IMPLIED. THERE ARE NO EXPRESS OR IMPLIED 
WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR 
PURPOSE, OR THAT THE USE OF THE SAMPLES OR THE RESULTS WILL NOT 
INFRINGE ANY PATENT, COPYRIGHT, TRADEMARK, OR OTHER PROPRIETARY 
RIGHTS 
 
B. 
Limitation of Liability 
Except to the extent prohibited by law, the Recipient assumes all liability for 
damages which may arise from its use, storage or disposal of the Samples. The 
Provider will not be liable to the Recipient for any loss, claim or demand made 
by the Recipient, or made against the Recipient by any other party, due to or 


Loiasis Antigenemia Version 1.2 25 June 2019 
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arising from the use of the Samples by the Recipient, except to the extent 
permitted by law when caused by the gross negligence or willful misconduct of 
the Provider. 
 
Except to the extent prohibited by law, the Provider assumes all liability for 
damages which may arise from its use of the Results. The Recipient will not be 
liable to the Provider for any loss, claim or demand made by the Provider or 
made against the Provider by any other party, due to or arising from the use of 
the Material by the Provider, except to the extent permitted by law when caused 
by the gross negligence or willful misconduct of the Recipient. 
 
This agreement must be formally approved and signed by both parties before any 
material transfer or data sharing takes place. Both parties will ensure that the material 
transfer and the data sharing agreements are known and understood by all staff involved 
in the process. 
 
Centre for Research on Filariasis and other Tropical Diseases (CRFilMT) 
 
 
 
 
 
 
 
 
________________________ 
Name    
 
 
 
 
 
Position 
 
 
 
 
 
 
 
 
________________________ 
Signature         
 
 
 
 
Date 
 
 
Washington University in Saint Louis (WUSTL) 
 
 
 
 
 
 
 
 
________________________ 
Name    
 
 
 
 
 
Position 
 
 
 
 
 
 
 
 
________________________ 
Signature         
 
 
 
 
Date 
 


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20.4. Receipt for Evaluation fees