@article{fdi:010086376,
  title = {{O}nchocerca volvulus-specific antibody and cellular responses in onchocerciasis patients treated annually with ivermectin for 30 years and exposed to parasite transmission in central {T}ogo},
  author = {{J}ohanns, {S}. {I}. and {G}antin, {R}. {G}. and {W}angala, {B}. and {K}omlan, {K}. and {H}alatoko, {W}. {A}. and {B}anla, {M}. and {K}arabou, {P}. and {L}uty, {A}drian and {S}chulz-{K}ey, {H}. and {K}oehler, {C}. and {S}oboslay, {P}. {T}.},
  editor = {},
  language = {{ENG}},
  abstract = {{O}nchocerciasis is a neglected tropical disease, and a major cause of debilitating skin disease and ocular damage that can lead to irreversible blindness. {A}nnual mass drug administrations ({MDA}) of ivermectin strongly reduces the load of {O}nchocerca volvulus microfilaria (mf) in the skin and in the patients' eyes. {E}volution of onchocerciasis as a disease is prevented by {MDA}, but recent studies have shown that {O}. volvulus transmission has not been completely interrupted.{R}epeated {MDA} with ivermectin affects immune responses, such that activated immune defenses may enhance clearance of mf of {O}. volvulus. {L}ongitudinal surveys are required to determine the impact of ivermectin on the status of immunity, notably in risk zones where parasite transmission and active {O}. volvulus infections persist. {W}e examined the changes of {O}. volvulus parasite-specific antibody and cellular immune responsiveness in patients treated annually with ivermectin for 30 years. {T}reatment prevented patent {O}. volvulus infections, whilst parasite antigen-specific cytokine and chemokine responses increased but {O}.volvulus-specific antibody responses declined. {S}uch decreased antibody levels could weaken antibody-dependent cellular cytotoxic responses to infective and tissue-dwelling {O}. volvulus larvae. {S}trengthened monocyte attracting and activation regulated chemokine responses could enhance effector cell migration and activation against larval stages of {O}.volvulus, possibly also eliciting resistance to further parasite infections. {B}ackground{A}nnual mass drug administrations ({MDA}) of ivermectin will strongly reduce {O}nchocerca volvulus microfilariae (mf) in the skin and in the onchocerciasis patients' eyes. {I}vermectin treatment will also affect the expression of immunity in patients, such that activated immune defenses may help control and contribute to clearance of mf of {O}. volvulus. {L}ongitudinal surveys are a prerequisite to determining the impact of ivermectin on the status of anti-parasite immunity, notably in risk zones where parasite transmission and active {O}. volvulus infections persist. {M}ethodology/{P}rincipal findings{O}nchocerciasis patients were treated annually with ivermectin and their {O}nchocerca volvulus antigen ({O}v{A}g) specific {I}g{G} and cellular responses were investigated before and at 30 years post initial ivermectin treatment (30y{PT}).{R}epeated annual ivermectin treatments eliminated persisting {O}. volvulus microfilariae (mf) from the skin of patients and abrogated patent infections. {T}he {O}v{A}g-specific {I}g{G}1 and {I}g{G}4 responses were diminished at 30y{PT} to the levels observed in endemic controls. {P}rior to starting ivermectin treatment, {O}v{A}g-induced cellular productions of {IL}-10, {IFN}-gamma, {CCL}13, {CCL}17 and {CCL}18 were low in patients, and at 30y{PT}, cellular cytokine and chemokine responses increased to the levels observed in endemic controls. {I}n contrast, mitogen({PHA})- induced {IL}-10, {IFN}-gamma, {CCL}17 and {CCL}18 cellular production was diminished. {T}his divergent response profile thus revealed increased parasite antigen-specific but reduced polyclonal cellular responsiveness in patients. {T}he transmission of {O}. volvulus continued at the patients' location in the {M}o river basin in central {T}ogo 2018 and 2019 when 0.58% and 0.45%, respectively, of {S}imulium damnosum s.l. vector blackflies carried {O}. volvulus infections. {C}onclusions/{S}ignificance{R}epeated annual ivermectin treatment of onchocerciasis patients durably inhibited their patent {O}. volvulus infections despite ongoing low-level parasite transmission in the study area. {R}epeated {MDA} with ivermectin affects the expression of immunity in patients. {O}. volvulus parasite-specific antibody levels diminished to levels seen in infection-free endemic controls. {W}ith low antibody levels, antibody-dependent cellular cytotoxic responses against tissue-dwelling {O}. volvulus larvae will weaken. {O}. volvulus antigen inducible cytokine and chemokine production increased in treated mf-negative patients, while their innate responsiveness to mitogen declined. {S}uch lower innate responsiveness in elderly patients could contribute to reduced adaptive immune responses to parasite infections and vaccines. {O}n the other hand, increased specific cellular chemokine responses in mf-negative onchocerciasis patients could reflect effector cell activation against tissue invasive larval stages of {O}. volvulus. {T}he annual {S}imulium damnosum s.l. biting rate observed in the {M}o river basin was similar to levels prior to initiation of {MDA} with ivermectin, and the positive rt{PCR} results reported here confirm ongoing {O}. volvulus transmission.},
  keywords = {{TOGO}},
  booktitle = {},
  journal = {{PL}o{S} {N}eglected {T}ropical {D}iseases},
  volume = {16},
  numero = {5},
  pages = {e0010340 [25 p.]},
  ISSN = {1935-2735},
  year = {2022},
  DOI = {10.1371/journal.pntd.0010340},
  URL = {https://www.documentation.ird.fr/hor/fdi:010086376},
}