PLOS NEGLECTED TROPICAL DISEASES
RESEARCH ARTICLE
Ivermectin and doxycycline treatments
against Onchocerciasis: Adaptations and
impact among semi-nomadic population in
Massangam Health District, Cameroon
Rogers Nditanchou 1 2 1ID *, Ruth Dixon , Kareen Atekem , Benjamin Biholong3,
Aude Wilhelm2, Richard Selby2, Joseph Oye1, Joseph Kamgno4,5, Daniel Boakye6,
Elena Schmidt2, Laura Senyonjo2
a1111111111
1 Sightsavers, Cameroon Country Office, Yaoundé, Cameroon, 2 Sightsavers, Haywards Heath Office,
a1111111111
Haywards Heath, United Kingdom, 3 National Programme for the Fight against Onchocerciasis and
a1111111111
Lymphatic Filariasis, Ministry of Public Health, Yaoundé, Cameroon, 4 Filariasis and other Neglected Tropical
a1111111111 Diseases Research Center, Yaoundé, Cameroon, 5 Faculty of Medicine and Biomedical Sciences, University
a1111111111 of Yaoundé I, Yaoundé, Cameroon, 6 Parasitology Department, Noguchi Memorial Institute for Medical
Research, University of Ghana, Accra, Ghana
* rnditanchou@sightsavers.org
OPEN ACCESS
Citation: Nditanchou R, Dixon R, Atekem K, Abstract
Biholong B, Wilhelm A, Selby R, et al. (2023)
Ivermectin and doxycycline treatments against We trialed strategies to reach semi-nomadic population with interventions targeting oncho-
Onchocerciasis: Adaptations and impact among cerciasis including a combination of community knowledge and Geographical Information
semi-nomadic population in Massangam Health System (GIS) technology; nomad-specific sensitization; and mobile outreach. The interven-
District, Cameroon. PLoS Negl Trop Dis 17(7):
tions included ivermectin (ivm) mass drug administration (MDA) and treating infected indi-
e0011463. https://doi.org/10.1371/journal.
pntd.0011463 viduals (found upon skin snip microscopy test) with doxycycline for 35 days. Microscopy-
negative snips were further tested by Polymerase Chain Reaction (PCR). After 8 months,
Editor: Maria Angeles Gómez-Morales, Istituto
Superiore di Sanità, ITALY individuals immigrating or emigrating constituted 47% of the initial population; 59% of indi-
viduals not born in the area have immigrated during the last five years; 28% (age>9) report-
Received: January 20, 2023
edly never taken ivm; 72% (compared to 51% previously) of eligible population (age� 5
Accepted: June 14, 2023
years) took ivm; and 47% (age > 8, not pregnant, not breastfeeding, not severely ill,) partici-
Published: July 12, 2023 pated in the test. A high prevalence of onchocerciasis,15.1%, was found upon microscopy &
Peer Review History: PLOS recognizes the PCR test; 9/10 tested by skin snip microscopy and PCR at follow-up were all negative.
benefits of transparency in the peer review Microfilaria prevalence and intensity upon skin snip microscopy reduced significantly from
process; therefore, we enable the publication of
baseline following the intervention (8.9% to 4.1%, p = 0.032; 0.18 to 0.16, p = 0.013, respec-
all of the content of peer review and author
responses alongside final, published articles. The tively). The strategies considerably increased reach to nomadic camps. Treating with doxy-
editorial history of this article is available here: cycline in combination with ivm is feasible and has led to a significant reduction in infection
https://doi.org/10.1371/journal.pntd.0011463 level within one year among the semi-nomads. Being potentially curative in one intervention
Copyright: © 2023 Nditanchou et al. This is an round, this combination should be considered for population group faced with challenges of
open access article distributed under the terms of achieving adequate coverage and adhesion to ivm MDA over prolonged period (>10 years).
the Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Data Availability Statement: All relevant data are
within the manuscript and its Supporting Materials.
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PLOS NEGLECTED TROPICAL DISEASES Impact of treating onchocerciasis with ivermectin and doxycycline among semi-nomads
Funding: This work received financial support from
the Coalition for Operational Research on Author summary
Neglected Tropical Diseases (COR-NTD), which is
funded at The Task Force for Global Health Community knowledge, satellite imagery, semi-nomadic sensitization and outreach strat-
primarily by the Bill & Melinda Gates Foundation, egies were employed to deliver ivermectin and doxycycline treatments against onchocerci-
by UK aid from the British government, and by the asis in semi-nomadic population. Doxycycline was offered only when skin snip
United States Agency for International examination revealed infection. We found that about 50% of the population has either left
Development through its neglected tropical
or joined the community within 8 months; 59% of people not born in the area arrived
diseases programme (NTD-SC # 186D to RN).
Some supplementary activities were funded by the during the last 5 years; 28% of those older than 9 years reported never taking ivermectin;
Royal Society of Tropical Medicine and Hygiene 72% (compared to 51% previously) of eligible population (�5 years) took ivermectin; and
(RSTMH SG to RN). The funders had no role in 47% participated in skin snip test. A high proportion of participants– 15% were infected.
study design, data collection and analysis, decision All the infected individuals (20) were treated, and no infection was found in almost all
to publish, or preparation of the manuscript.
those retested (9/10). This study highlights high rate of onchocerciasis and the challenges
Competing interests: The authors have no of offering continuous treatment for a prolonged period (>10 years) to a mobile popula-
competing interest. tion. It further demonstrates that combining ivermectin and doxycycline is preferrable in
mobile population as it is curative and can be given only one time.
Introduction
Onchocerciasis is a chronic parasitic disease caused by a nematode, Onchocerca volvulus (OV).
OV is transmitted to humans through the bites of infected black flies of the genus Simulium,
breeding in fast flowing waterways [1]. Prolonged infection can cause skin lesions, severe itch-
ing, and ocular disorders, including visual impairment which can lead to irreversible blind-
ness. Although considerable progress has been made in the control of onchocerciasis, there is
still an enormous task ahead to achieve the global target of elimination by 2030 [2]. The main
strategy for the control and elimination of onchocerciasis is the interruption of transmission
through annual Mass Drug Administration (MDA) using the Community-Directed Treatment
with ivermectin (CDTi) strategy [3]. However, in areas with unsatisfactory progress, comple-
mentary or alternative treatment strategies (ATS) [4] are required to meet elimination targets.
Studies in Massangam in the West Region of Cameroon during 2016 demonstrated unsatis-
factory progress. High prevalence of skin micro-filaria (mf) were found in three focal commu-
nities—Makouopsap (37.1%), Mankakoun (36.8%) and Njigouet/Njinja (27.5%) after more
than 20 years of consecutive annual CDTi [5]. To accelerate elimination, ATS including test
and treat with doxycycline (TTd) were implemented [6,7]. A qualitative assessment of the TTd
revealed barriers to reaching semi-nomadic population. These included their small, remote
and disperse settlements, high mobility, non-inclusion as Community-Directed Distributors
(CDD), inadequate consideration in programme planning, low education level, low awareness
of onchocerciasis or MDA, dis-trust, and discrimination by settled community, language, and
cultural differences [7].
Nomads are members of traditional groups of hunter-gatherers and pastoralists who do not
have a fixed habitation and regularly move locations. When there is a base to which the
nomads return seasonally, their lifestyle is termed semi-nomadic [8]. Nomadic and semi-
nomadic groups often face inequitable access to health interventions [9–11]. Not sufficiently
reaching this group for both TTd and ivermectin (ivm MDA) treatments represents an obvi-
ous equity concern and threatens elimination efforts. This paper describes adaptations made
to improve the reach among semi-nomadic populations and evaluates success (participation),
impact (prevalence and intensity) and lessons learnt as recommendations for programmes,
guiding integration of similar subgroups in different settings.
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PLOS NEGLECTED TROPICAL DISEASES Impact of treating onchocerciasis with ivermectin and doxycycline among semi-nomads
Methods
Ethics statement
Ethical approvals were obtained from the Ethics Review and Consultancy Committee (ERCC),
Cameroon Bioethics Initiative (CAMBIN) (Approval N˚ CBI/445/ERCC/CAMBIN) and the
National Ethics Committee for Human Research in Cameroon (Approval N˚ 2020/0/1203/
CE/CNERSH/SP). Consent forms were read and explained to participants in the language they
best understood, and they were encouraged to ask questions which were answered prior to
them signing or putting their fingerprint. In addition, parental consent for any individual aged
17 or under was obtained. COVID-19 prevention measures (masks, washing buckets, soap,
and hand sanitizers) were mandatory to ensure adherence with government COVID-19 poli-
cies [12].
Setting
The Massangam HD (Health District) in the West Region of Cameroon is situated in a savan-
nah-forest transition zone. It is characterized by mountainous terrain with altitude between
500 and 1000 m. The Mbam River is predominant in the area. The two main tributaries of the
Mbam are the rivers Noun and Nja both of which cross Massangam. These rivers provide
year-round breeding sites for Simulium blackflies, permitting year-round transmission of
Onchocerca volvulus [5]. This study was carried out in Massangam health area (subdistrict)
(Fig 1) and targeted the semi-nomadic population living in camps around the settled popula-
tion of the three communities previously determined to have high infection—Makouopsap,
Mankakoun and Njijia/Njigouet [5]. Structures within which semi-nomads live are referred to
as encampment. Generally, these are groups of huts in which extended semi-nomadic families
live. Families are commonly hierarchically organized under a family head. Encampments and
the people living in them constitute the semi-nomadic camps.
Study design
This study consisted of pre (baseline) and post (endline) intervention surveys. Baseline survey
and intervention were conducted from October to December 2019 and endline from August
to October 2020. At baseline and endline, sampling was comprehensive including all semi-
nomads in every camp and incorporating identification and census of semi-nomads, commu-
nity engagement, testing of individuals for onchocerciasis using skin snip biopsy (this also
served as the baseline survey). Infected individuals were treated with a 35-day course of doxy-
cycline in addition to ivermectin (intervention) (Fig 2).
Procedure
Prior to skin snip testing, culturally adapted communication materials were developed
informed by previous qualitative study [7]. Materials included banners, flyers, and posters.
video and audio tapes in four local languages–Pidgin English, French, Bamoun, and Fulfulde
were used to reinforce mobilization and sensitization. Reinforcement was done at three levels:
district level involving national, regional, and district programme staff, local administrative
authorities, and community leaders; community level involving community members; and
camp-to-camp sensitization and census in one visit by trained data collectors and community-
directed drug distributors (CDDs). We employed a systematic approach to camp identification
combining first community knowledge, and secondly GIS (Geographical Information System)
technology methods to verify coverage of community identification and close the gap.
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PLOS NEGLECTED TROPICAL DISEASES Impact of treating onchocerciasis with ivermectin and doxycycline among semi-nomads
Fig 1. Map of Massangam Health District showing the focal communities within the Massangam Health Area (Sub-District). The blue
line indicate rivers. (Sources: Hydrology-HydroSHEDS https://www.hydrosheds.org/; the administrative boundaries–Natural Earth https://
www.naturalearthdata.com/downloads/; Community locations were collected during the field activity by using GPS devices. Map was created
using ArcGIS software by Esri).
https://doi.org/10.1371/journal.pntd.0011463.g001
Community knowledge-based identification of camps
Community knowledge methods involved identification of camps by community members
(including chiefs and CDDs), listing and locating them on sketch maps. Data collectors were
guided by the CDDs (base on their knowledge) to the camp locations. Once in the camps, fur-
ther efforts were made to identify neighbouring camps that might not have been identified via
community listing by asking inhabitants of the camp–a technique termed snowballing. GPS
coordinate of community-identified camps visited were collected.
Geographic Information System-based identification of camps
GIS technology identification involve satellite image identification of potential camps, overlay-
ing with camp location collected during community identification, and then verification of sat-
ellite identified potential camp missed (by community methods). Potential camps were
identified on satellite image of the area. This identification was based on identifiable character-
istic features of encampments previously found [6,7]. Sources of satellite images used included:
Hydrology—HydroSHEDS https://www.hydrosheds.org/; (https://www.hydrosheds.org/); and
the administrative boundaries—Natural Earth https://www.naturalearthdata.com/downloads/.
Locations of community and satellite identified encampments were plotted on the map. Satel-
lite-identified camps not matching community identified location were noted (as community
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PLOS NEGLECTED TROPICAL DISEASES Impact of treating onchocerciasis with ivermectin and doxycycline among semi-nomads
Fig 2. Study design. All ivermectin eligible population (aged 5 years, not pregnant nor breast-feeding children
younger than 8 days) including those not tested (skin snip) were offered ivermectin (same day as test).
https://doi.org/10.1371/journal.pntd.0011463.g002
knowledge coverage gap). Missed potential camps were verified with guidance of a bespoke
ESRI ArcGIS Explorer live tracking App (https://explorer.arcgis.app/) developed and installed
on android smartphone.
To develop the App, first, an office-based exercise was undertaken using ArcGIS software
by Esri and satellite imagery to create map of potential encampments missed by the commu-
nity identification methods. Methodical step-by-step access routes to these remaining encamp-
ments were established including transport means (part using the car, the motorbike and by
foot). Potential natural barriers like streams or bushes to cross and distance information to
complete the roadmap navigation were included. The map was downloaded and installed on
smartphone via the ArcGIS online platform for offline use. The App also tracked actual loca-
tion of the phone on the map using the satellite-based navigation system, GPS (Global Posi-
tioning System). With this functionality, field team were able to navigate along the identified
route viewing their position until it matched with a (community) missed potential satellite
identified encampment. At this point, the team inspect their physical location and surrounding
200m radius searching for camps and if people are living in. As it was the first, the team also
had printed back up maps, same as those on the App but with inclusion of latitudes and longi-
tude, and a GPS and compass device in case of technology failure. Snowballing was also done
for any camp identified this way. Camps with people living were included in the list of camps
for test and treat and ivermectin interventions.
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PLOS NEGLECTED TROPICAL DISEASES Impact of treating onchocerciasis with ivermectin and doxycycline among semi-nomads
Skin snip microscopy examination
A screening (skin snip testing) team visited all identified camps after one to three days follow-
ing camp-to-camp sensitization and census. The team was comprised of a lab technician, an
assistant lab technician and a pair of CDDs (one from the settled community and one from the
semi-nomadic community). The team overnighted where necessary to allow those absent to
participate. Every eligible individual (aged >8 years, not severely ill, not pregnant or breast-
feeding) was verbally invited to participate in a screening test. Testing comprised of registra-
tion, physical examination, and skin snip (biopsies) collection at the two posterior iliac crests
using a 2 mm Holth-type corneoscleral punch. The Biopsies were put into wells of a 96 well-
micro-titre plate in which two drops of saline solution had been previously placed and sealed
with parafilm to avoid spillage and evaporation. It was then allowed to incubate for 24 hours at
room temperature. The incubation medium was examined under a compound microscope
(x10) for the presence (infected) or absence of O. volvulus mf [13]. This analysis was per-
formed by the team on field in the camps. The presence (positive) or absence (negative) of
onchocercal microfilaria (mf) were noted. If positive all emerged microfilaria (mf) were
counted and recorded. All negative snips were transferred into 1.5ml cryotubes onto which an
equal volume of isopropanol was added. The tubes were then labelled, packed in Ziplock bags
before putting in cool boxes, and transported within 10 days to Filariasis and other Neglected
Tropical Diseases Research Center laboratory in Yaoundé where they were stored at -20˚C
until tested by Polymerase Chain Reaction (PCR) (OV150) [14]. PCR test was delayed due to
Covid19 pandemic’s impact on supply chains [15].
All participants provided informed consent before they were screened (tested). During
screening, the team continued sensitization explaining to the semi-nomads the purpose of par-
ticipation. During the baseline survey, basic demographics, residency, travel and ivermectin
MDA participation histories were collected.
Ivermectin and doxycycline treatments
After skin snip, all eligible individuals (aged�5 years, not pregnant nor breast-feeding chil-
dren younger than 8 days) were offered ivermectin (ivm) obtained from the national pro-
gramme. Ivm was offered to all eligible–including those that refused skin snip procedure,
those participating in the test as well as those ineligible for doxycycline treatment. Individuals
found mf positive by microscopy were also immediately offered (within less than a week fol-
lowing test) doxycycline 100mg treatment per day for a period of 35 days. Doxycycline treat-
ment was initially provided to participants by CDDs accompanied by the research team,
including trained medical professionals. The treatment was observed by the research team for
the first two days before handing over to the CDD for weekly monitoring. Light meals were
provided before treatment and pictorial treatment diaries were provided to everyone for
recording timepoints of self-administration of medication, and how they felt afterwards.
Where possible, CDDs made check in phone calls twice a week to monitor adherence and dis-
cuss any issues. CDDs made pre-arranged weekly visit to camps, during which they reviewed
treatment diaries with each participant. During camp visits, CDDs collected empty and unused
doxycycline packets to verify treatment adherence and plan restocking of treatment supplies
for the following week. Additional information was collected on reasons for not taking medi-
cines (when required). The CDDs transferred the information from pictorial treatment diaries
to a standardised paper treatment register. Researchers collected all treatment registers and
diaries upon completion of treatment and later entered the data into an Excel electronic data
base.
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Endline survey
Eight months after the end of treatment, all camps were revisited, and all individuals registered
at baseline checked and noted if absence, presence, emigrated, or died. Furthermore, new
arrivals (immigrants) were recorded in registers. All individuals were invited for follow-up
skin snip screening. Consenting and eligible participants had samples collected and examined
by microscopy and PCR (of microscopy negative snips). For ethical reasons, ivermectin was
offered to everyone consenting and eligible during the test. Those later found positive were
additionally treated with doxycycline 100mg for 35 days. These treatment records were
excluded from analysis presented in this paper.
Data analysis
Data was transferred from Microsoft Excel into STATA Statistical Software (StataCorp LLC
4905 Lakeway Drive, College Station, Texas 77845 USA http://www.stata.com), for cleaning
and analysis. The data are found in S1 Data.
Population movement (immigration and emigration) were calculated as the proportion of
the baseline population who were immigrants or emigrants. Turnover was calculated as the
proportion of immigration, emigration and deaths combined, compared to the recorded base-
line population. The population age profile was determined by the mean, median, maximum,
and minimum ages. The cumulative population was determined as the sum of individuals who
were registered at any point (baseline or endline). Ivermectin MDA participation rate was cal-
culated as the percentage of the eligible population (age >5 years) who took medication—
number of eligible people who participated divided by total eligible population multiplied by
100.
Participation rate in skin snip test was calculated as the percentage of eligible individuals
who took part. Sensitivity of microscopic examination was determined as the ratio that tested
positive by microscopy against the total positive by microscopy and PCR combined. Preva-
lence of OV mf infection at baseline and endline was calculated as the proportion of those test-
ing positive by microscopy divided by those tested multiplied by 100. Prevalence estimate was
also calculated for participants that tested positive by either microscopy or PCR.
A multiple logistic regression adjusting for the following variables added a priori: age-
group, sex and community, survey points—baseline/endline, and individual participation—
single/repeat test categories—was performed to estimate the odds ratio of infection during
baseline and endline. Fitness of the model was estimated using LR (Likelihood Ratio) Chi-
square test and corresponding p-values (p<0.05 is considered statistically significant). Average
mf intensity from microscopy was calculated using the arithmetic mean to obtain mf intensity
measures of all skin snipped, inclusive of zero intensity counts. Baseline vs endline average
intensities were compared using Mann Whitney U test due to non-normal distribution of
intensity data indicated by histograms plot with highly skewed mf intensity distributions at
baseline and endline. Fisher Exact Test was used to compare outcome for doxycycline and ivm
treatments.
Results
Population characteristics
Sixty-two semi-nomadic camps were identified, of which 58 were identified through commu-
nity knowledge and 4 more identified through satellite image. Within camps, baseline and
endline census populations varied between 784 and 622 respectively (Fig 3). A population
reduction (emigration minus immigration and death) of 17% (n = 126) was noted. The
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PLOS NEGLECTED TROPICAL DISEASES Impact of treating onchocerciasis with ivermectin and doxycycline among semi-nomads
Fig 3. Semi-nomadic population turnover from baseline to endline Percentages are expressed as proportion of the endline population.
https://doi.org/10.1371/journal.pntd.0011463.g003
cumulative number of individuals recorded in the area during baseline, endline or both, was
862. Semi-nomadic population was estimated by capture-recapture approach to be 1180 indi-
viduals [16]. Population turnover (sum of emigrants, immigrants, and deaths) was 47%
(n = 354) of baseline population. Age among the population of 862 ranged from zero to 95
years, mean = 19.5 (+/-17.3) and median = 15 years. Among those not born in the area, 59.0%
(CI (Confidence Intervals): 55.3–62.5) (n = 428) have been in the community for 5 years or
less.
When asked about participation in ivm MDA for those aged more than 9 years, 28%
(CI:24–32) (n = 129) reported they have never participated. Furthermore, only 51% (n = 289)
of eligible semi-nomadic population aged�5 years reported at baseline that they took iver-
mectin in the preceding MDA. During the intervention (baseline), 72% (n = 359) of those�5
years took ivermectin.
Participation in the test and treat with doxycycline intervention
Participation is presented as a flowchart in (Fig 4), clarifying participation from registration,
treatment at baseline to endline testing. Test participation among registered, eligible popula-
tion was 47.1% (n = 225) at baseline, and 59.4% (246) at endline (Fig 4 and Table 1).
Of the 34 found positive by microscopy (Table 2) and PCR, 26 (76.5%) received ivermectin.
Out of the 8 infected who did not received ivermectin, 3 were detected by microscopy. None
of those detected by PCR received doxycycline treated due to delay in obtaining the result.
Infection was detected by microscopy in 8.9% (n = 20) of participants at baseline. Average
infection intensity was 0.18 mf per skin snip. All 20 infected individuals completed a 35-day
course of doxycycline treatment (Table 2). There were no reports of adverse effects. Out of the
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Fig 4. Flowchart showing the total and eligible population, number of participants in skin snip test, number infected and treated at baseline
and endline (endline vs baseline) (endline bold)
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161 microscopy-negative snips that were cross examined by PCR, 9% (n = 14) were found pos-
itive. This gives a microscopy sensitivity rate of 59% (n = 20/34). And an overall detected OV
mf prevalence of 15.1% (CI: 1.0–20.4) when considering both tests (Table 3).
Ten treated (out 20) individuals at baseline tested at endline and none of them were found
positive by microscopy. However, one of these 10 endline microscopy-negative snip was posi-
tive upon PCR examination. Out of the nine individuals who were positive upon PCR and
took ivm at baseline, five showed up for endline skin snip of which three were negative and
one positive upon microscopy and PCR test. Comparing the treatment outcome between
doxycycline and ivm groups using Fisher Exact Test (due to small sample size), there was no
significant association.
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Table 1. Skin snip test participation at baseline and endline across sex and age categories.
BASELINE
Categories # Eligible # Tested Percentage tested (CI) Odd Ratio (CI)*
Overall Overall 478 2251 47.1% (42.6–51.6) -
Sex Female 228 104 45.6% (39.2–52.1) Ref2
Male 250 121 48.4% (42.2–54.6) 1.14 (0.79–1.64; p = 0.49)
Age group3 9-15yrs 130 52 40.0% (31.9–48.7) Ref
16-25yrs 133 66 49.6% (41.2–58.1) 1.51 (0.92–2.47; p = 0.10)
26-40yrs 126 66 52.4% (43.7–61.0) 1.64 (0.99–2.72; p = 0.05)
>40yrs 89 41 46.1% (36.0–56.5) 1.29 (0.75–2.23; p = 0.36)
ENDLINE4
Categories # Eligible # Tested Percentage tested (CI) Odd Ratio (CI)
Overall Overall 414 246 59.4% (54.6–64.1) -
Sex Female 197 116 58.9% (51.9–65.6) Ref
Male 217 130 59.9% (53.2–66.2) 1.04 (0.70–1.55; p = 0.83)
Age group 9-15yrs 124 89 71.8% (63.2–79.0) Ref
16-25yrs 117 60 51.3% (42.3–60.2) 0.38 (0.21–0.71; p = 0.002)
26-40yrs 104 67 64.4% (54.8–73.0) 0.71 (0.38–1.34; p = 0.293)
>40yrs 69 30 43.5% (32.3–55.4) 0.35 (0.18–0.69; p = 0.002)
1 Out of the 225 tested, 185 (82.2%) received ivermectin.
2 Ref stands for Reference group. It is the group to which the others are compared.
3 Age group odd ratios controlled for length of stay in the community
4. Endline survey 8 months after the end of treatment.
*A multiple logistic regression adjusting for the following variables added a priori: age-group, sex and community, survey points—baseline/endline, and individual
participation—single/repeat test categories—was performed to estimate the odds ratio of infection during baseline and endline. Fitness of the model was estimated using
LR (Likelihood Ratio) Chi-square test and corresponding p-values (p<0.05 is considered statistically significant).
https://doi.org/10.1371/journal.pntd.0011463.t001
From 246 participants screened at endline survey, 4.1% (n = 10) were detected as positive
by microscopy. This is a significant reduction (p = 0.032) from baseline (Table 3). One individ-
ual that was negative upon microscopy at baseline was positive by microscopy at endline.
Average infection intensity reduced significantly from 0.18 at baseline to 0.16 (p = 0.013) at
endline. Out of 235 individuals tested negative by microscopy at endline and further examined
by PCR, 20 were positive- placing sensitivity of microscopy at 33.3% (10/30) and an overall
endline prevalence of 12.2% (Table 3). Eighteen (18) (10.7% n = 18/168) were from residents
present at baseline but not tested. Eleven individuals infected (14.1%n = 11/78) were detected
from new arrivals. When microscopy and PCR results were considered together, the reduction
in mf prevalence from baseline to endline was not statistically significant (p = 0.356).
Table 2. Treatment participation among those infected at baseline.
n Ivermectin only Doxycycline only Doxycycline & Ivermectin No treated
All 34 9(26.5%) 3 (8.8%) 17 (50.0%) 5 (14.7%)
Microscopy 20 0 3(15.0%) 17 (85.0%) 0
PCR 14 9 (42.9%) 0 0 5 (57.1%)
“All” refers to sum of infected individuals found upon microscopy and Polymerase Chain Reaction (PCR) exam. “Microscopy” refers those found infected by
microscopy; and “PCR” to those found infected upon PCR examination of microscopy negative snips. Ivermectin treatments targeted all eligible people (>5 years)
irrespective of test or treatment with doxycycline. Meanwhile, doxycycline treatments were offered, in addition, to infected individuals.
https://doi.org/10.1371/journal.pntd.0011463.t002
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PLOS NEGLECTED TROPICAL DISEASES Impact of treating onchocerciasis with ivermectin and doxycycline among semi-nomads
Table 3. Comparison of baseline and endline mf prevalence.
Baseline mf Prevalence Endline mf prevalence Prevalence reduction (pearson chi2) Prevalence reduction (adjusted OR**)
Microscopy 8.9% 4.1% χ2 = 4.58 OR = 0.42
(95% CI: 5.8–13.4) (95% CI: 2.2–7.4) (p = 0.032) (p = 0.032)
Microscopy or PCR* 15.1% 12.2% χ2 = 0.85 OR = 0.80
(95% CI: 11.0–20.4) (95%CI: 8.7–16.9) (p = 0.356) (p = 0.407)
Average intensity 0.18 (0.01, 0.35) 0.16 (0.00, 0.32) Z = 2.487 (p = 0.013)
*PCR only on microscopy negative snips
**controlling for age and sex
https://doi.org/10.1371/journal.pntd.0011463.t003
Discussion
This study revealed a significant population of young mobile semi-nomads, ranging from 862
censused to 1180 when capture-recapture method is applied to estimate the population [16].
The figure of 1180 is conservative as methods for capture (baseline) and recapture (endline)
are the same. This leads to high number of overlaps of the population between the two time-
points (baseline and endline), thus inflating the denominator with resultant shrinking of the
total population estimate. Population turnover was remarkably high within nine months,
almost 50% of the baseline population either emigrated, immigrated, or died by endline. This
insinuates about half the population are consistently mobile. Accounting for deaths, this
mobile population represents either nomadic, or transhumant population [17–19]. The
remaining 50% can be regarded as semi-nomadic (have a permanent base that they return to
after transhumance) or permanent (historic nomads now settled and do not move seasonally
anymore) [20]. As 59% of baseline population reported as having stayed in the community for
5 years or less, migratory, and seasonal movement has been ongoing and is continuing. Even
when the nomad settled—no longer moving seasonally, settled local indigenous community
still regard them (mostly of Fulani origin) as nomad. Thus, the population can be classified
into historic nomads, semi-nomads, nomads, and transhumant nomads. Transhumant refers
to mobile semi-nomads or nomads on the move. This distinction of nomadic subcategories,
coupled with the significant population size, impacts on onchocerciasis epidemiology and
MDA programming and performance.
Nomads are a moving hotspot of infection and transmission and can prolong time to reach
elimination or reverse elimination where achieved. An mf prevalence of 15% was found among
the semi-nomads at baseline in this study. Of these infected individuals, over 50% were likely to
move within a year. This effect is demonstrated among endline participants as 14% of new arriv-
als were carrying active onchocerciasis infection. Further compounding this problem, the
mobile community has a much lower MDA coverage rate. Only 51% of age-eligible nomads in
the most recent MDA took part in ivermectin MDA, falling below WHO (World Health Orga-
nisation) recommended minimum coverage of 85% among age-eligible population [2,3]. This
study also revealed high rate of never treated status as 28% of semi-nomadic population (>9
year) reported never have taken treatment. This is four times higher than that found in settled
indigenous population in the same area during 2016 [5,21]. This moving population missed
MDA because they are not present during MDA at both ends–where they go to and where they
depart from. Also, they can be present during MDA but not included due to their daily move-
ment with livestock and their far, small, remote and disperse settlements. Settled community
CDD who often led ivm MDA may not see the need to reach and treat nomads resulting from
their perception of them being outsider, troublemakers and destroying their crops. This fuels
discrimination, mistrust, and in turn refusal among the nomadic population.
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PLOS NEGLECTED TROPICAL DISEASES Impact of treating onchocerciasis with ivermectin and doxycycline among semi-nomads
The use of community and satellite camp identification, pairing of CDDs from nomad and
settled communities in a buddy-system, adapted sensitization in terms of language and chan-
nel, and mobile outreach increase programme reach among the semi-nomads. In addition,
delivering ivermectin and test in one outing appeared to improve acceptability and effective-
ness of TTd among the nomadic population. More than double the eligible population for test-
ing during previous intervention was reached (n = 212 vs 478). This increased participation is
comparable to settled population coverage in previous TTd (47% vs 54%)[6,7]. Additionally,
participation in ivermectin MDA delivered alongside TTd led to a coverage increase from 51%
of eligible population in previous MDA to 72% in this study. This joint ivermectin and TTd
delivery is impactful on both disease morbidity and transmission. This is potentially due to the
immediate clearing of mf by ivermectin, and production of new mf gradually reduced from
doxycycline impact on the adult worms [22–27]. All but one person retested after treatment
was negative suggesting that they may have been cured. However, the evaluation time is short.
A longer follow-up is required to ascertain that a sustained and a long-term absence of micro-
filariae has indeed been achieved. The macrofilaricidal impact of doxycycline makes it superior
to moxidectin and ivermectin both of which require repeated rounds over a long period to
allow macrofilaria to die. Other macrofilaricidal drugs are being developed [28,29] and once a
better one is found, it can be used in place of doxycycline. Doxycycline is part of WHO [4]
arsenal of alternative treatments and so we prefer piloting it in programme setting. The one
positive individual was only detected by PCR showing that the intensity of infection has
reduced. However, it can be argued that mf distribution in the skin is not uniform and false
negative upon skin snip sample examination, even with PCR, is likely. The low participation
(10/20) of those treated in test at endline survey obscured the impact but we have no reason to
believe that impact was lesser among non-participants. An individual having the highest count
per snip was among those retested and was not found positive by both PCR and microscopy.
The reduction in average infection intensity and prevalence indicates a reduction in trans-
mission [30]. Microscopic assessment that guided treatment decision at baseline missed at
least a third of infected individuals given 33.3% prevalence consider both microscopy and PCR
recorded in this study. If these missed individuals were detected and treated, reduction in
prevalence and intensity would have been more pronounced. This missed opportunity add to
the call for development of a more sensitive field test for detecting active onchocerciasis infec-
tion. Delivery of such a test, when combined with a curative intervention such as TTd, is rele-
vant to nomadic and other hard-to-reach populations. In the interim, OV16 test can be used
for TTd in treatment naïve individuals.
Conclusion
This study investigates a large nomadic population, finding a high infection of onchocerciasis.
This is a threat to achieving elimination or even reversing its achievement. The strategic adap-
tions employed in this study have increased effectiveness and acceptability of ivermectin and
test and treat with doxycycline. This has driven down infection intensity, and thereby, trans-
mission of onchocerciasis. Reinforced sensitisation, combined GIS and community knowledge
identification of nomad camps, and mobile outreach should be considered for inclusion into
routine programmatic operations to reach nomadic and similar hard-to-reach populations.
Future study should explore further the nomad populations, identifying different nomadic
groups such as nomads, semi-nomad, transhumant, historic (settled) nomads to better orien-
tate interventions. Test and treat with doxycycline, in combination with ivermectin treatment
should be considered among populations presenting challenges of effective and regular iver-
mectin treatment participation. Development of a more sensitive and less invasive test for
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PLOS NEGLECTED TROPICAL DISEASES Impact of treating onchocerciasis with ivermectin and doxycycline among semi-nomads
detecting active onchocerciasis infection will result in greater impact of test and treat with
doxycycline.
Supporting information
S1 Table. Individual skin snip data.
(XLS)
Acknowledgments
We remain indebted to NTD programme in Cameroon at National, Regional and District lev-
els and the community, including the semi-nomads who supported the activities. We are
thankful to the Centre for Research on Filariasis and other Tropical Diseases (CRFilMT) for
collecting and analysing samples. We are equally thankful to Alexandre Chailloux for develop-
ing GIS tools and drawing the maps.
Author Contributions
Conceptualization: Rogers Nditanchou, Ruth Dixon, Kareen Atekem, Joseph Oye, Daniel
Boakye, Laura Senyonjo.
Data curation: Rogers Nditanchou, Ruth Dixon, Aude Wilhelm.
Formal analysis: Rogers Nditanchou, Aude Wilhelm.
Funding acquisition: Rogers Nditanchou, Ruth Dixon, Elena Schmidt.
Investigation: Rogers Nditanchou, Kareen Atekem, Joseph Kamgno, Laura Senyonjo.
Methodology: Rogers Nditanchou, Ruth Dixon, Joseph Kamgno, Laura Senyonjo.
Project administration: Rogers Nditanchou, Ruth Dixon, Kareen Atekem, Benjamin
Biholong, Joseph Oye, Elena Schmidt.
Resources: Ruth Dixon.
Supervision: Rogers Nditanchou, Benjamin Biholong, Joseph Kamgno, Daniel Boakye, Laura
Senyonjo.
Validation: Rogers Nditanchou, Aude Wilhelm, Richard Selby, Daniel Boakye, Laura
Senyonjo.
Visualization: Rogers Nditanchou, Richard Selby.
Writing – original draft: Rogers Nditanchou.
Writing – review & editing: Ruth Dixon, Kareen Atekem, Aude Wilhelm, Richard Selby,
Joseph Oye, Daniel Boakye, Elena Schmidt, Laura Senyonjo.
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