R: Community-directed delivery of doxycycline in Cameroon demonstrates effectiveness as a treatment for onchocerciasis (river blindness) in Africa that avoids adverse effects associated with ivermectin
Submitting InstitutionUniversity of Edinburgh
Unit of AssessmentClinical Medicine
Summary Impact TypeHealth
Research Subject Area(s)
Medical and Health Sciences: Clinical Sciences, Medical Microbiology, Public Health and Health Services
Summary of the impact
Impact: Health and welfare and public healthcare policy;
demonstrating that community-directed treatment of onchocerciasis with
doxycycline is effective where ivermectin is contra-indicated.
Significance: 12,936 onchocerciasis patients were treated safely
and protected for at least 4 years. The treatment regime has been adopted
by the US Centers for Disease Control and Prevention, the World Health
Organization and governments.
Beneficiaries: Patients with onchocerciasis; governments and
Attribution: Studies performed by a long-standing African-European
partnership formed and led by Taylor (UoE).
Reach: International; up to 8 million people in the Congo basin;
onchocerciasis patients in Africa where ivermectin is not appropriate plus
those in South America participating in focal eradication campaigns.
Professor David Taylor (Professor of Tropical Animal Health, UoE,
1994-present), demonstrated for the first time that doxycycline was an
effective treatment for onchocerciasis. This work led to the adoption of
the doxycycline treatment regime by the US Centers for Disease Control and
Prevention (CDC) and other international agencies, replacing ivermectin as
the first-line mass treatment.
Onchocerciasis (river blindness), caused by the filarial nematode Onchocerca
volvulus, is the second most common infectious blinding disease of
the developing world, afflicting 31 million people, 95% of whom live in
West or Central Africa. Seventy percent of patients experience severe and
debilitating skin disease that has major economic and social consequences
including poor school performance, low productivity, low income, higher
health-related costs, and extreme social stigmatization, especially among
Ivermectin has long been used in mass treatment campaigns to control
onchocerciasis. However, when these treatment programmes were extended to
Cameroon, where a proportion of the target population is co-infected with
the eye worm Loa loa, there was an unacceptable number of severe,
sometimes fatal, adverse reactions including encephalopathy. Ivermectin is
no longer considered safe for mass treatment programmes where O
volvulus and L loa are co-endemic.
Taylor has led an African-European partnership, funded by six successive
European Framework contracts, to improve treatment and control of
onchocerciasis. Human epidemiological and immunological studies in
Cameroon, Ghana and Togo were combined with immunological studies in
animal models, and with parasite proteomics and genomics. Infections with
O volvulus cannot be established in mice, but Bain (Paris) and
Taylor demonstrated that the filariae Litomosoides sigmodonitis
could produce potent infections in mice and that the parasitological
presentations replicated those of the human parasites [3.1], leading the
way for detailed immunological investigations [e.g., 3.2, 3.3]. In
parallel, the partnership developed a bovine model using O ochengi
[3.4]. Both models were pivotal to the work underpinning and leading to
the trial of doxycycline.
In 2000, it was identified that O volvulus harbours the
endosymbiotic Gram-negative bacteria Wolbachia. This opened the
possibility of therapy with antibiotics, led directly to consortium
partners demonstrating the efficacy of tetracyclines in the O ochengi
bovine model [3.4] and, crucially, human studies in the field that
demonstrated similar efficacy [3.5].
These results took on far greater significance when it was discovered
that L loa does not possess Wolbachia. This raised the
prospect of using doxycycline to selectively target O volvulus in
patients co-infected with L loa previously at risk of
ivermectin-induced side effects.
Doxycycline treatment requires administration of the drug three times a
day for 6 weeks, which is difficult to achieve conventionally in remote
regions of developing countries. To overcome this, Taylor and colleagues
conducted a community-directed treatment trial of doxycycline in five
hyper-endemic areas of Cameroon [3.6]. The study communities identified
trusted individuals whom the group subsequently trained to diagnose
infection, dispense drugs and record treatment and any side effects
(carried out under the supervision of the Ministry of Health, Cameroon).
21,000 people were recruited and 12,936 individuals were treated with
doxycycline, giving a therapeutic coverage of the eligible population of
73.8% and a compliance rate of 97.5% at the end of six weeks. No serious
side effects were registered.
References to the research
3.1 Maréchal P, Le Goff L, Hoffman W,...Taylor D, et al. Immune response
to the filaria Litomosoides sigmodontis in susceptible and resistant mice.
Parasite Immunol. 1997;19:273-9. DOI: 10.1046/j.1365-3024.1997.d01-209.x.
3.2 Le Goff L, Loke P, Ali H,... Taylor D, Allen J. Interleukin-5 is
essential for vaccine-mediated immunity but not innate resistance to a
filarial parasite. Infect Immun. 2000;68:2513-7. DOI:
3.3 van der Werf N, Redpath S, Azuma M, Yagita H, Taylor M. Th2
cell-intrinsic hypo- responsiveness determines susceptibility to helminth
infection. PLoS Pathog. 2013;9:e1003215. DOI:
3.4 Langworthy S, Renz A, Mackenstedt U, et al. Macrofilaricidal activity
of tetracycline against the filarial nematode, Onchocerca ochengi:
elimination of Wolbachia proceeds worm death and suggests a dependent
relationship. Proc Biol Sci. 2000;267:1063-9. DOI: 10.1098/rspb.2000.1110.
3.5 Hoerauf A, Spechts S, Marfo-Debrekyi Y, et al. Efficacy of 5 week
doxycycline treatment on adult Onchocerca volvulus. Parasitol Res.
2009;104:437-47. DOI: 10.1007/s00436-008-1217-8.
3.6 Wanji S, Tendongfor N, Nji T,...Taylor D. Community-directed delivery
of doxycycline for the treatment of onchocerciasis in areas of
co-endemicity with loiasis in Cameroon. Parasit Vectors. 2009;2:39. DOI:
Details of the impact
The WHO and its subsidiary African Programme for Onchocerciasis Control
(APOC) have reduced morbidity in many parts of west Africa and eliminated
onchocerciasis from some isolated foci in South America [5.1].
Onchocerciasis is now identified as a target for elimination from Africa
Because ivermectin is not suitable for use in children under 5 years or
in those co-infected with L Loa, and drug resistance is emerging,
it is unsuitable for mass treatment programmes in over 8 million Africans.
The work described above in Cameroon [5.2] demonstrated that doxycycline
could overcome the problem of L loa co-infection, provided
attention is paid to ensure community involvement in drug administration.
Impact on practitioners and services
Doxycycline is now defined as one of only two treatments effective for
onchocerciasis by the CDC [5.3]. CDC also notes that the alternative
(ivermectin) may cause dangerous side effects in the presence of L Loa
The Cameroon Academy of Sciences has recommended the use of doxycycline
for the treatment of river blindness to the Cameroon Government (2013)
[5.4]; the Government is now revising the national onchocerciasis control
strategy in accordance with these recommendations. Furthermore, in South
America, doxycycline is being used to treat residual cases and foci where
eradication rather than control is being targeted [5.5].
Impact on public policy
The Cameroon study's very high compliance rate of over 97.5% was
attributed to detailed training of health workers recruited directly from
the study community and the involvement of social scientists to ensure
local traditions were not compromised. Since the study, WHO/APOC has
advocated greater use of community-directed treatment programmes [5.1].
This approach is more expensive than traditional mass treatment programmes
but, as demonstrated, effective use of doxycycline would protect the
community for at least 4 years [5.2] and therefore be cost-effective.
Impact on the economy
A 2004 WHO study concluded that the disease burden of onchocerciasis was
about 884,000 disability-adjusted life years. This can be interpreted as a
loss of 15% gross national product in areas of high endemicity. Such
losses are being reduced through the adoption of doxycycline in mass
Impact on health and welfare
The Cameroon study showed that, when empowered, community health workers
can successfully deliver doxycycline for six weeks for the treatment of
onchocerciasis. It paves the way for the initiation of control programmes
for 8 million people across Cameroon, DR Congo and the Central African
At the end of the 6-week course of treatment with doxycycline, the
community as a whole reported both immediate and long-term benefits [3.6].
Relief from itching and the regression of nodules were indicative of
clearance of O volvulus. More rapid wound healing and reduction of
secondary bacterial infections were reported together with increased
appetite and sexual desire. The positive feedback from community members
who took part in the first phase of treatment motivated reluctant
individuals to adhere to treatment.
Resolution and prevention of skin disease is particularly important for
women as this avoids the major social stigma and societal exclusion
(including no marriage) that is associated with onchocerciasis.
Sources to corroborate the impact
5.1 World Health Organization, African Programme for Onchocerciasis
Control (APOC), 2012. Achievements of community-directed treatment with
5.2 Tamarozzi F, Tendongfor N, Enyong P, et al. Long term impact of large
scale community-directed delivery of doxycycline for the treatment of
onchocerciasis. Parasit Vectors. 2012;5:53. DOI: 10.1186/1756-3305-5-53.
5.3 CDC Resources for Health Professionals, Parasites — Onchocerciasis
(also known as River Blindness), 2013. http://www.cdc.gov/parasites/onchocerciasis/health_professionals/.
5.4 Cameroon Academy of Sciences, 2013. Recent advances in onchocerciasis
research and implications for control. [Available on request.]
5.5 Gustavsen K, Hopkins A, Sauerbrey M. Onchocerciasis in the Americas:
from arrival to (near) elimination. Parasit Vectors. 2011;4:205. DOI: