PMID- 38491528
OWN - NLM
STAT- MEDLINE
DCOM- 20240318
LR  - 20240420
IS  - 1756-3305 (Electronic)
IS  - 1756-3305 (Linking)
VI  - 17
IP  - 1
DP  - 2024 Mar 15
TI  - Onchocerca volvulus microfilariae in the anterior chambers of the eye and ocular 
      adverse events after a single dose of 8 mg moxidectin or 150 microg/kg ivermectin: 
      results of a randomized double-blind Phase 3 trial in the Democratic Republic of 
      the Congo, Ghana and Liberia.
PG  - 137
LID - 10.1186/s13071-023-06087-3 [doi]
LID - 137
AB  - BACKGROUND: After ivermectin became available, diethylcarbamazine (DEC) use was 
      discontinued because of severe adverse reactions, including ocular reactions, in 
      individuals with high Onchocerca volvulus microfilaridermia (microfilariae/mg 
      skin, SmfD). Assuming long-term ivermectin use led to < 5 SmfD with little or no 
      eye involvement, DEC + ivermectin + albendazole treatment a few months after 
      ivermectin was proposed. In 2018, the US FDA approved moxidectin for treatment of 
      O. volvulus infection. The Phase 3 study evaluated SmfD, microfilariae in the 
      anterior chamber (mfAC) and adverse events (AEs) in ivermectin-naive individuals 
      with >/= 10 SmfD after 8 mg moxidectin (n = 978) or 150 microg/kg ivermectin (n = 494) 
      treatment. METHODS: We analyzed the data from 1463 participants with both eyes 
      evaluated using six (0, 1-5, 6-10, 11-20, 21-40, > 40) mfAC and three 
      pre-treatment (< 20, 20 to < 50, >/= 50) and post-treatment (0, > 0-5, > 5) SmfD 
      categories. A linear mixed model evaluated factors and covariates impacting mfAC 
      levels. Ocular AEs were summarized by type and start post-treatment. Logistic 
      models evaluated factors and covariates impacting the risk for ocular AEs. 
      RESULTS: Moxidectin and ivermectin had the same effect on mfAC levels. These 
      increased from pre-treatment to Day 4 and Month 1 in 20% and 16% of participants, 
      respectively. Six and 12 months post-treatment, mfAC were detected in  approximately 5% and  approximately 3% 
      of participants, respectively. Ocular Mazzotti reactions occurred in 12.4% of 
      moxidectin- and 10.2% of ivermectin-treated participants without difference in 
      type or severity. The risk for >/= 1 ocular Mazzotti reaction increased for women 
      (OR 1.537, 95% CI 1.096-2.157) and with mfAC levels pre- and 4 days 
      post-treatment (OR 0: > 10 mfAC 2.704, 95% CI 1.27-5.749 and 1.619, 95% CI 
      0.80-3.280, respectively). CONCLUSIONS: The impact of SmfD and mfAC levels before 
      and early after treatment on ocular AEs needs to be better understood before 
      making decisions on the risk-benefit of strategies including DEC. Such decisions 
      should take into account interindividual variability in SmfD, mfAC levels and 
      treatment response and risks to even a small percentage of individuals.
CI  - (c) 2024. World Health Organization.
FAU - Kanza, Eric M
AU  - Kanza EM
AD  - Centre de Recherche Clinique de Butembo, Universite Catholique du Graben, Site 
      Horizon, Butembo, Nord Kivu, Democratic Republic of the Congo.
AD  - Programme National de Lutte Contre Les Maladies Tropicales Negligees A 
      Chimio-Therapie Preventive (PNLMTN-CTP), Kinshasa, Democratic Republic of the 
      Congo.
FAU - Nyathirombo, Amos
AU  - Nyathirombo A
AD  - Centre de Recherche en Maladies Tropicale de L'Ituri, Hopital Generale de 
      Reference de Rethy, Ituri, Democratic Republic of the Congo.
AD  - Department of Ophthalmology, Faculty of Medicine, Gulu University, Gulu, Uganda.
FAU - Larbelee, Jemmah P
AU  - Larbelee JP
AD  - Clinical Research Center, Liberia Institute for Biomedical Research, Bolahun, 
      Liberia.
AD  - Ministry of Health, Monrovia, Liberia.
FAU - Opoku, Nicholas O
AU  - Opoku NO
AD  - Onchocerciasis Chemotherapy Research Center, Hohoe, Ghana.
AD  - Department of Epidemiology and Biostatistics School of Public Health, University 
      of Health and Allied Sciences, Hohoe, Ghana.
FAU - Bakajika, Didier K
AU  - Bakajika DK
AD  - Centre de Recherche en Maladies Tropicale de L'Ituri, Hopital Generale de 
      Reference de Rethy, Ituri, Democratic Republic of the Congo.
AD  - ESPEN, African Regional Office of the World Health Organization (WHO/AFRO/ESPEN), 
      Brazzaville, Republic of Congo.
FAU - Howard, Hayford M
AU  - Howard HM
AD  - Clinical Research Center, Liberia Institute for Biomedical Research, Bolahun, 
      Liberia.
AD  - Ganta United Methodist Hospital, Ganta City, Nimba County, Liberia.
FAU - Mambandu, Germain L
AU  - Mambandu GL
AD  - Centre de Recherche en Maladies Tropicale de L'Ituri, Hopital Generale de 
      Reference de Rethy, Ituri, Democratic Republic of the Congo.
AD  - Inspection Provinciale de La Sante de La Tshopo, Division Provinciale de La Sante 
      de La Tshopo, Kisangani, Province de La Tshopo, Democratic Republic of the Congo.
FAU - Nigo, Maurice M
AU  - Nigo MM
AD  - Centre de Recherche en Maladies Tropicale de L'Ituri, Hopital Generale de 
      Reference de Rethy, Ituri, Democratic Republic of the Congo.
AD  - Institut Superieur Des Techniques Medicales de Nyankunde, Bunia, Ituri, 
      Democratic Republic of the Congo.
FAU - Wonyarossi, Deogratias Ucima
AU  - Wonyarossi DU
AD  - Centre de Recherche en Maladies Tropicale de L'Ituri, Hopital Generale de 
      Reference de Rethy, Ituri, Democratic Republic of the Congo.
FAU - Ngave, Francoise
AU  - Ngave F
AD  - Centre de Recherche en Maladies Tropicale de L'Ituri, Hopital Generale de 
      Reference de Rethy, Ituri, Democratic Republic of the Congo.
FAU - Kennedy, Kambale Kasonia
AU  - Kennedy KK
AD  - Centre de Recherche Clinique de Butembo, Universite Catholique du Graben, Site 
      Horizon, Butembo, Nord Kivu, Democratic Republic of the Congo.
AD  - Department of Clinical Research, London School of Hygiene and Tropical Medicine, 
      London, UK.
FAU - Kataliko, Kambale
AU  - Kataliko K
AD  - Centre de Recherche en Maladies Tropicale de L'Ituri, Hopital Generale de 
      Reference de Rethy, Ituri, Democratic Republic of the Congo.
AD  - Centre de Sante CECA 20 de Mabakanga, Beni, Nord Kivu, Democratic Republic of the 
      Congo.
FAU - Bolay, Kpehe M
AU  - Bolay KM
AD  - Clinical Research Center, Liberia Institute for Biomedical Research, Bolahun, 
      Liberia.
AD  - National Public Health Institute of Liberia, Public Health & Medical Research, 
      Monrovia, Liberia.
FAU - Attah, Simon K
AU  - Attah SK
AD  - Onchocerciasis Chemotherapy Research Center, Hohoe, Ghana.
AD  - Department of Microbiology, University of Ghana Medical School, Accra, Ghana.
AD  - Baldwin University College, Accra, Ghana.
FAU - Olipoh, George
AU  - Olipoh G
AD  - Onchocerciasis Chemotherapy Research Center, Hohoe, Ghana.
AD  - National Assay Centre, Precious Minerals Marketing Company Ltd., Diamond House, 
      Accra, Ghana.
FAU - Asare, Sampson
AU  - Asare S
AD  - Onchocerciasis Chemotherapy Research Center, Hohoe, Ghana.
AD  - Bell Laboratories Inc, Window, WI, USA.
FAU - Mumbere, Mupenzi
AU  - Mumbere M
AD  - Centre de Recherche Clinique de Butembo, Universite Catholique du Graben, Site 
      Horizon, Butembo, Nord Kivu, Democratic Republic of the Congo.
AD  - Medicines Development for Global Health (MDGH), Melbourne, Australia.
FAU - Vaillant, Michel
AU  - Vaillant M
AD  - Competence Center for Methodology and Statistics, Luxembourg Institute of Health, 
      Strassen, Grand Duchy of Luxembourg.
FAU - Halleux, Christine M
AU  - Halleux CM
AD  - UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in 
      Tropical Diseases (WHO/TDR), World Health Organization, Geneva, Switzerland.
FAU - Kuesel, Annette C
AU  - Kuesel AC
AUID- ORCID: 0000-0002-1696-1784
AD  - UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in 
      Tropical Diseases (WHO/TDR), World Health Organization, Geneva, Switzerland. 
      kuesela@who.int.
LA  - eng
GR  - 001/WHO_/World Health Organization/International
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20240315
PL  - England
TA  - Parasit Vectors
JT  - Parasites & vectors
JID - 101462774
RN  - 70288-86-7 (Ivermectin)
RN  - 0 (Macrolides)
RN  - NGU5H31YO9 (moxidectin)
SB  - IM
MH  - Animals
MH  - Female
MH  - Humans
MH  - Anterior Chamber
MH  - Democratic Republic of the Congo
MH  - Double-Blind Method
MH  - Ghana
MH  - *Intestinal Volvulus
MH  - Ivermectin/adverse effects
MH  - Liberia
MH  - *Macrolides
MH  - Microfilariae
MH  - Onchocerca
MH  - *Onchocerca volvulus
MH  - *Onchocerciasis/drug therapy
MH  - Male
PMC - PMC10943894
OTO - NOTNLM
OT  - Diethylcarbamazine
OT  - Increase in ocular microfilariae
OT  - Ivermectin
OT  - Microfilariae in the anterior chamber
OT  - Microfilariae mobilization
OT  - Moxidectin
OT  - Ocular Mazzotti reactions
OT  - Ocular adverse events
OT  - Ocular microfilariae
OT  - Onchocerciasis
COIS- ACK and CMH are staff of WHO which funded the work of all co-authors on the study 
      whose data are analysed here through its department UNICEF/UNDP/World Bank/WHO 
      Special Programme for Research and Training in Tropical Diseases (TDR). ACK 
      retired from WHO in March 2023.
EDAT- 2024/03/16 21:43
MHDA- 2024/03/18 06:43
PMCR- 2024/03/15
CRDT- 2024/03/16 00:47
PHST- 2023/04/30 00:00 [received]
PHST- 2023/12/07 00:00 [accepted]
PHST- 2024/03/18 06:43 [medline]
PHST- 2024/03/16 21:43 [pubmed]
PHST- 2024/03/16 00:47 [entrez]
PHST- 2024/03/15 00:00 [pmc-release]
AID - 10.1186/s13071-023-06087-3 [pii]
AID - 6087 [pii]
AID - 10.1186/s13071-023-06087-3 [doi]
PST - epublish
SO  - Parasit Vectors. 2024 Mar 15;17(1):137. doi: 10.1186/s13071-023-06087-3.