https://orcid.org/0000-0003-2657-9543
Figures
Abstract
Backgrounds
Chemoprophylaxis with single-dose rifampicin (SDR) is a preventive measure recommended by the World Health Organization to limit leprosy transmission. This study was carried out to assess the acceptability and feasibility of this measure in Benin.
Methods
This intervention-oriented study, including contacts of people affected by leprosy (PALs), was conducted in two linear phases from September 2019 to August 2020 in Benin. In the first phase, we assessed contacts’ knowledge of leprosy and their perceptions of SDR through interviews conducted after their informed consent. In the second phase, contacts were educated about leprosy and the importance of SDR in leprosy control. Eligible contacts were clinically examined, and new leprosy patients were treated with multidrug therapy while consented healthy contacts received the SDR.
Results
9,941 contacts were registered around 197 PALs. After interviewing 394 contacts, the majority (88.8%) had insufficient leprosy knowledge. Of these contacts, 58.6% agreed to receive chemoprophylaxis. They were willing to take the necessary time for treatment (74.5%), travel long distances (83.1%) and take the drug as often as possible (90.0%). Marital status (p = 0.008), education level (p = 0.000) and knowledge of leprosy (p = 0.000) were statistically linked to chemoprophylaxis acceptance. Contacts who lived alone, who weren’t educated and had little knowledge of leprosy were respectively 2.18, 2.75 and 43.13 times more likely to refuse chemoprophylaxis.
Of the 9,941 sensitized contacts, 6,798 were clinically examined, and 6,416 received SDR. The average age of contacts who received chemoprophylaxis was 27.3 years (±19.8), with a predominance of women (52.7%). Eight (8) new patients were identified and treated with multidrug therapy.
Author summary
Despite the decline in leprosy cases in recent years, the incidence rate has stagnated, indicating that the transmission has not yet been broken. New approaches to reducing the number of cases and curbing disease transmission, such as early case detection, clinical contact examination and chemoprophylaxis, are now being recommended. In leprosy control, rifampicin chemoprophylaxis for contacts of patients is a preventive intervention that can prevent the transmission of infection among household members. We report here the experience of an intervention-oriented study in four leprosy-endemic localities in Benin. We first assessed the leprosy contacts knowledge of the disease, the acceptability and feasibility of single-dose rifampicin (SDR) before administering it to those who gave informed consent. Of these contacts, 58.6% agreed to receive chemoprophylaxis and were willing to take the necessary time for treatment and travel long distances to take the drug as often as possible. However, contacts who lived alone who weren’t educated and had little knowledge of leprosy were more likely to refuse chemoprophylaxis with SDR. It is therefore important to improve education and knowledge of the disease to contribute to the acceptance of chemoprophylaxis.
Citation: Djossou P, Mignanwande ZFM, Anagonou SGE, Cerda I, Toussaint A, Houezo JG, et al. (2025) Acceptability and feasibility of chemoprophylaxis with single-dose rifampicin in four leprosy-endemic districts in Benin. PLoS Negl Trop Dis 19(4): e0013057. https://doi.org/10.1371/journal.pntd.0013057
Editor: Ana LTO Nascimento, Instituto Butantan, BRAZIL
Received: September 16, 2024; Accepted: April 14, 2025; Published: April 28, 2025
Copyright: © 2025 Djossou et al. This is an open access article distributed under the terms of 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: The main data contributing to this manuscript are freely available and accessible on the website of National Program of Buruli Ulcer and Leprosy of Benin: https://www.pnllub.org/documentheque/.
Funding: This study was funded by the Fondation Raoul Follereau (FRF 119900026; http://www.raoulfollereau.org) and the Fondation ANESVAD (grant REG-3723/23; http://www.anesvad.org/fr/) to PD; ZFMM; SGEA; JGH; GES; RCJ.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Leprosy, like other neglected tropical diseases, is one of the oldest diseases and is most prevalent among people living in poor communities [1].
Its transmission is favored by promiscuity and close, prolonged skin contact with untreated patients [2–4]. However, close and prolonged contact with an untreated leprosy patient is a major risk factor [5–7].
Despite the decrease in the number of leprosy cases detected, thanks to the introduction of effective treatment since the early 1980s, it is not possible to reduce incidence to zero and eliminate the source of infection [8]. Therefore, new approaches to reducing the number of cases and curbing disease transmission, such as early case detection, clinical contact examination and chemoprophylaxis, are now recommended [9].
In leprosy control, rifampicin chemoprophylaxis for contacts of patients is a preventive intervention that can prevent the transmission of infection among household members [10]. Numerous randomized controlled trials have shown that postexposure chemoprophylaxis (PEP) reduces leprosy transmission, although its efficacy is controversial [11–14]. The effectiveness of PEP has been shown in Brazil, India, Indonesia, Burma, Cambodia, Bangladesh, Sri Lanka, Myanmar, Tanzania and Morocco [8,15–20].
In Benin, leprosy remains a public health problem as its transmission persists in endemic communities despite the ongoing efforts of the country’s health authorities. Thus, 150 to 200 new leprosy cases are detected each year in Benin [21]. In 2022, national statistics also showed that the proportion of leprosy cases with grade 2 disability among new cases detected was 54%, with multibacillary (MB) cases accounting for 97%. These data highlight the public health problem that leprosy remains, despite the reduction in the number of cases [22]. To limit leprosy transmission, the prevention strategy of chemoprophylaxis with single-dose rifampicin (SDR) should be implemented in these endemic communities, following the examples of other leprosy-endemic countries [8,15–20]. The present study was therefore conducted to assess the acceptability and feasibility of chemoprophylaxis with SDR in the communities of Djidja, Ouinhi, Zagnanado and Kétou in Benin.
Methods
Ethics statement
The National Health Research Ethics Committee (CNERS) of the Benin of Ministry of Health reviewed the study proposal and approved the study on April 4, 2019 (No. 21/MS/DC/SGM/DRFMT/CNERS/SA/). Ethical considerations were respected during data collection. All participants who met the inclusion criteria were informed of the study’s objectives, procedures, advantages and disadvantages. The written and oral informed consent was obtained from all participants included in this study. From the parent/guardian of each participant under 18 years of age, written and oral informed consent was obtained.
Setting
The study was carried out in four municipalities in Benin: Djidja, Ouinhi, Zagnanado (Zou Department) and Kétou (Plateau Department). These communities and the 96 villages investigated, which have different sociosanitary characteristics, were selected based on their leprosy endemicity according to National Buruli Ulcer and Leprosy Control Program of Bénin (PNLLUB) data.
According to data from Benin’s National Institute of Statistics and Economic Analysis (INSAE), the populations of Djidja, Ouinhi, Zagnanado and Kétou were estimated to be 146,681, 70,507, 65,377 and 186,834 inhabitants, respectively [23].
Study design and population
This intervention-oriented study, conducted from September 2019 to August 2020, was implemented in two (02) phases and included contacts of people affected by leprosy. The first phase assessed contacts’ knowledge of leprosy and perceptions of SDR. The second phase involved raising contacts’ awareness of the importance of SDR, followed by its administration.
The overall study population consisted of intra and extra domestic contacts of all persons affected by leprosy (PALs) registered over the period 2006-2016 in the study area. These contacts were family members of PALs and residents of neighbouring houses.
For the assessing knowledge of leprosy and perceptions of SDR, participants included were contacts aged 18 years old and over, available on the day of the survey and having given their consent.
For the awareness sessions, all contacts and PALs had participated. However, for the contact clinical examination and SDR administration, the participants included were:
- - Family contacts living in the same households as the index patients (PALs);
- - Direct neighbours whose plots touched the plots of the index patients;
- - People living within a radius of no more than 150 m around the home of the PALs.
The participants not included were:
- - Contacts who were absent on the day of the survey;
- - Contacts who refused to participate in the study;
- - Pregnant women;
- - Children under 2 years old;
- - People with reported leprosy who had been treated or were receiving treatment;
- - People with tuberculosis and Buruli ulcer
Sampling
Exhaustive sampling was used to select PALs from the period 2006–2016. Thus, 197 PALs were identified in the communities of Djidja, Ouinhi, Zagnanado and Kétou after an active search based on information provided by PNLLUB database. According to their proximity to the PALs, 9,941 contacts were registered.
For the assessment phase of leprosy knowledge and perceptions of SDR, the sample size of contacts interviewed around PALs was determined using the software Epi Info version 7.2.2.2. As the proportion of patients accepting chemoprophylaxis was not known in the localities covered by the study and given that no study of chemoprophylaxis had been carried out, we estimated a value of 50%. Assuming an acceptable margin of error of 5%, the sample size of contact was 384. For compliance reasons (assuming there will be non-responses and participants who would not be found), 394 contacts were selected. Contacts were chosen based on their proximity to a patient, i.e., a member of the patient’s household or compound or a close neighbour.
For the awareness and SDR administration phase, a rational selection was made of the contacts clinically examined and who received the SDR, according to the inclusion criteria.
Variables
The dependent variable was acceptance of the use of rifampicin for chemoprophylaxis and the independent variables included sociodemographic data such as age, sex, education level, occupation and level of knowledge of the contacts about leprosy.
Data collection
Interviewing contacts about leprosy and acceptability of SDR
Informing participants and obtaining consent.
Eligible participants were verbally informed about the purpose of the study, its various stages and its benefits for the communities. The written and oral informed consent was obtained from all participants included in this study. From the parent/guardian of each participant under 18 years of age, written and oral informed consent was obtained. They were then invited to participate.
Awareness and administration of rifampicin chemoprophylaxis
Contacts’ awareness about leprosy and chemoprophylaxis.
Following the first phase, and after a reminder of the purpose, the various stages and the benefits of the study for the communities, awareness-raising was carried out in each intervention village, using the tools based on the results of the contact interviews (points of attention for community awareness-raising).
Contacts were informed of the next procedures of the study and possible outcomes (confirmed leprosy, no leprosy, eligible contact for SDR) of the different clinical examination methods. They were informed not only of the benefits of chemoprophylaxis with SDR such as reduction in the probability of contracting leprosy but also of its common side effects such as urine discolouration as well as less frequent or extremely rare adverse effects.
All eligible contacts were invited to participate in the next stages of the study (clinical contact examination, administration of SDR) after their consent. For the participant under 18 years old, the parent/guardian written and oral informed consent was obtained.
Clinical examination of contacts and administration of chemoprophylaxis with rifampicin.
Once consent has been obtained, contacts were clinically examined by leprosy specialists who looked for leprosy signs. Detected cases of leprosy were categorized according to the WHO classification [24–26]. Consenting healthy contacts received a supervised dose of rifampicin according to their age and weight. The dosage was applied according to WHO recommendations [27]. New leprosy patients were systematically treated with multidrug therapy.
Data processing and analysis
The data collected were entered and analysed using SPSS 25 software. Frequencies and proportions were calculated for the qualitative variables. For quantitative variables, the means and standard deviations were determined. To assess the level of knowledge of PAL contacts, questions were formulated on a questionnaire. For each correct answer given, a score was assigned, and the maximum total score possible for an interviewed contact was ten (10). The total score obtained was used to classify the contact interviewed in one of 2 categories:
- - Bad knowledge if the score obtained is < 5;
- - Good knowledge if the score obtained is ≥ 5.
These scores were proposed and validated by leprosy specialists based on the relevance and importance of the appropriate answers to each question.
Univariate analysis
The proportions of the dependent variable (acceptance of chemoprophylaxis) were compared with those of the various independent variables. Association between the different variables were investigated using the chi-square test and Fisher’s exact test. The significance threshold was 5%.
Multivariate analysis
Variables with a P-value less than or equal to 0.2 were selected for multivariable analysis. Logistic regression was used with a progressive top-down elimination process to identify variables significantly associated with acceptance of chemoprophylaxis. P-values of 0.05 were considered statistically significant. The adequacy of the final model was investigated using the Hosmer-Lemeshow test.
Results
PALs identified and contacts registered
In this study, 197 PALs (index cases) were identified: 90 in Djidja, 40 in Ouinhi, 30 in Zagnanado and 37 in Kétou. Among these patients, 132 (67.0%) were multibacillary (MB) and 65 (33%) paucibacillary (PB).
Around the 197 PALs, 9,941 contacts were registered for the subsequent stages of the study.
Knowledge of leprosy and perceptions of chemoprophylaxis
Sociodemographic characteristics of the respondents.
Of the 9,941 contacts registered around the 197 PALs, 394 were interviewed about leprosy and acceptability of chemoprophylaxis. The average age of contacts was 38.0 years (±13.4). Most contacts were married (81.2%), male (50.5%), and Fons ethnic group (78.2%), had not attended school (50.5%), practiced Christianity (68.3%), were cultivators (50.5%), housekeepers (15.0%), students (11.4%) and retailers (8.4%) (Table 1).
Basic knowledge of the contacts of PALs.
Among the 394 people interviewed in the four communities, the majority (74.9%) recognized leprosy most often because of the presence of visible deformities. Almost all of these people (99.2%) knew nothing about the signs of leprosy onset. Few contacts (39.8%) knew the real cause of leprosy (a microorganism). The contagiousness of leprosy was known by 89.8% of the contacts, and 17.8% knew the mode of transmission (human-to-human). Most contacts thought that leprosy was curable (97.2%) and to treat it, they had to go to hospital (86.5%) (Table 2).
Perceptions of chemoprophylaxis among the contacts of PALs.
Of the 394 contacts interviewed about chemoprophylaxis with rifampicin in the communities of Djidja, Ouinhi, Zagnanado and Kétou, 58.6% wanted to receive it (Fig 1). Of the contacts who agreed to receive chemoprophylaxis with rifampicin, the majority were willing to take the drug in any form (73.6%). These contacts were willing to take the necessary time for treatment (74.5%) and travel long distances (83.1%). They were also willing to take the drug as many times as required (90.0%), even if it had undesirable side effects (83.5%) (Table 3).
The results showed that the majority of those questioned (58.6%) were in favour of chemoprophylaxis against leprosy. This was also reflected in the opinions gathered, such as that of this septuagenarian from the village of Fonkpodji in Djidja, who said: “We have been waiting a very long time for a drug that can prevent leprosy, and now it is finally here. I will take it several times according to your recommendations if it can protect me and my family from this humiliating disease that affects so many people in our region.” Indeed, this father of a family has recognized the need to prevent the disease in himself and his family to avoid the humiliation that this pathology entails.
For others who accepted chemoprophylaxis, the cost of this preventive intervention remained a problem for the population. This highlights the economic limitations of these populations, who often have a modest income but want to preserve their health whatever the possibility. In Agonvè, in the municipality of Zagnanado, a woman in her fifties said: “This medicine that you are offering us free of charge will protect us and our families from this disease that causes so much damage to its victims. We accept it with open arms because it is for our own good”.
Although most individuals were willing to receive chemoprophylaxis, some people did not accept the idea, even if the intervention was free of charge. The reasons given were generally doubts about the drug administered and fears of possible side effects. In Kétou, in a locality made up of the Holli ethnic group, the community refused chemoprophylaxis. One individual stated: “You give us this kind of medication and then we see health problems such as loss of sight, which many of us are currently experiencing without any solution following the mass distribution of a medication in the past. We do not want to make our situation worse, so we do not want to receive your medication”. This refusal is then motivated by past events not related to the present study and which are said to have caused irreversible health damage in the community. Awareness-raising sessions such as behaviour change communication could change their view on chemoprophylaxis. In the community of Zagnanado, a divorced woman who refused chemoprophylaxis said: “Personally, I don’t trust your medicine because I have never heard of it before. So, I prefer not to take it.” Here again, it is possible to enable the populations to better understand and control the implications of chemoprophylaxis by organizing awareness-raising and study popularization sessions.
The multivariate analyses showed that variables such as marital status (p=0.008), education level (p=0.000) and knowledge of leprosy (p=0.000) were significantly related to the contacts’ acceptance of chemoprophylaxis with rifampicin. However, contacts who lived alone (single, widowed, or divorced), those with no education and those with poor knowledge of leprosy were 2.18, 2.75 and 43.13 times more likely to refuse chemoprophylaxis with rifampicin, respectively (Tables 4 and 5).
Implementation of chemoprophylaxis in the communities of Djidja, Ouinhi, Zagnanado and Kétou
Clinical examination of contacts and chemoprophylaxis administration.
Following the leprosy and chemoprophylaxis awareness sessions, 6,798 contacts (68.4%) were clinically examined out of the 9,941 contacts recorded. 6,416 (94.4%) received rifampicin chemoprophylaxis and 382 (5.6%) did not (Fig 1). 2,472 contacts received chemoprophylaxis around 90 PALs in Djidja; 1,579 contacts received chemoprophylaxis around 40 PALs in Ouinhi; 1,564 contacts received chemoprophylaxis around 30 PALs in Zagnanado and 801 contacts received chemoprophylaxis around 37 PALs in Kétou. The average age of contacts who received chemoprophylaxis was 27.3 years (±20.3), with a predominance of females (52.7%) (Table 6).
New cases of leprosy detected during chemoprophylaxis.
During clinical examination of contact, height (8) new cases of leprosy (4 MB and 4 PB) were detected. Four (04) (2 MB and 2 PB) were detected in Djidja, two (02) (1 MB and 1 PB) were detected in Ouinhi and two (02) (1 MB and 1 PB) were detected in Zagnanado.
Discussion
The present study on chemoprophylaxis is the first on this strategy in Benin. It enrolled 9,941 contacts around 197 PALs in four communities where leprosy is endemic: Djidja, Ouinhi, Zagnanado and Kétou.
In the first phase of this study, devoted to assessing contacts’ knowledge of leprosy and their perceptions of the SDR, 394 people were interviewed. The participants were married men and women, the majority of whom were uneducated (50.5%) and Christian (68.3%). For the most part, these contacts had erroneous knowledge of the cause of leprosy, its mode of transmission and the signs of disease onset. This could lead some people to be unreceptive to chemoprophylaxis. This situation also highlights the need for health education in these communities. The same point was made by Rajkumar et al., who stipulated in their study that it would be necessary to promote knowledge of leprosy within the community by means of an educational intervention that would enable knowledge and methods of leprosy control to be discussed [28].
Of the 394 contacts interviewed, 231 (58.6%) agreed to receive chemoprophylaxis, while 163 (41.4%) refused it. Of the contacts who agreed to receive chemoprophylaxis, the majority were willing to take the drug in any form (74.5%). These contacts were even willing to take the necessary time for treatment (74.5%) and travel long distances (83.1%). They were also willing to take the drug as often as necessary (90.0%), even if it had undesirable side effects (83.5%). These results show that chemoprophylaxis with SDR is socially accepted in the communities of Djidja, Ouinhi, Zagnanado and Kétou. Similar results were obtained by Ferreira et al. and Apte et al. who reported that clinical contact examination and the distribution of SDR were very well accepted by the main stakeholders: index patients, contacts, health workers and supervisors [10,29]. The same is true for Schoenmakers et al., who found that the implementation of contact tracing and the administration of SDR in different leprosy control programmes was shown to be feasible and well accepted [30]. In addition, Richardus et al. demonstrated the feasibility of SDR in seven endemic countries in Asia, Africa and South America [15].
Of the 394 contacts interviewed in this study, 163 (41.4%) expressed a refusal to receive chemoprophylaxis. The reasons given by some contacts for refusing chemoprophylaxis were generally doubts about the drug administered and fear of its possible side effects. Cases of refusal of chemoprophylaxis were also reported in a study carried out in Cambodia by Cavaliero et al. [18].
In our study, multivariate analysis revealed that marital status (p=0.008), education level (p=0.000) and knowledge of leprosy (p=0.000) were significantly related to the acceptance of chemoprophylaxis with rifampicin in the four communities. Indeed, contacts who were not living with a partner (single, widowed, or divorced), who had no education and who had poor knowledge of leprosy were 2.185, 2.759 and 43.134 times more likely to refuse chemoprophylaxis with rifampicin, respectively. These factors could be corrected by improving contacts’ level of knowledge about the disease. This could be achieved through local awareness campaigns (in hamlets or villages where cases of leprosy are detected). Once contacts’ knowledge of leprosy has improved, they will be able to understand and integrate the meaning and role of chemoprophylaxis with rifampicin. These results are in line with those obtained by Cortela et al., who found that the receipt of postexposure chemoprophylaxis (PEP) was influenced by understanding, acceptance and expectation of the intervention. According to the same study, understanding was related to the care of the health team. Acceptance or nonacceptance of the drug was linked to fear, confidence and protection, the operationality of the strategy, self-esteem and insecurity about the intervention.
Following the first phase of our study, which uncovered leprosy-related gaps in the communities, awareness sessions were organized, and 9,941 contacts were registered. Then, 6,416 contacts (94.4%) received the SDR and 382 (5.6%) were disqualified based on noninclusion criteria among the 6,798 contacts examined. The average age of the people who received chemoprophylaxis was 27.3 years (±20.3), with a predominance of women (52.7%). These results reflect the situation at the national level, which shows a predominance of females in the Beninese population according to the 4th global population and housing census conducted by the National Institute of Statistics and Economic Analysis [23].
Of the 9,941 contacts registered during our study, 3,143 (31.6%) were not clinically examined. Reasons included absence the day of examination (50.4%), lack of consent (30.9%) and refusal to wait (18.7%). Lack of consent reflects a lack of understanding and recognition of the importance of SDR, and therefore a lack of receptiveness to the intervention on the part of some people, despite the organization of awareness-raising sessions for them. It would be important to amplify these awareness-raising sessions to increase the chances of convincing these latecomers to adhere to the intervention. If there were a sufficient number of medical teams, waiting times could be reduced by receiving participants as early as possible. This would make it easier for the participants, who are mostly farmers, to benefit from the intervention and to be able to go about their farming activities.
This result is similar to that obtained by Cavaliero et al. in a study carried out in 2021 in Cambodia, where it was found that out of 10,410 identified contacts of 555 index patients, 72.0% were clinically examined, while most of the others were absent the day of examination [31].
Overall, chemoprophylaxis with rifampicin was mostly accepted by the communities of Djidja, Ouinhi, Zagnanado and Kétou in Benin. The same overall observation was made by Richardus et al. (2021), who found that PEP with SDR was generally well accepted by index patients, their contacts and healthcare workers in their multicountry study [15]. However, it is important to increase awareness of leprosy and measures to prevent it to ensure greater acceptance of chemoprophylaxis with rifampicin for future interventions in at-risk communities in Benin.
Despite these results, our study has some limitations. The perceptions of health staff and leprosy patients were not presented in this study. In addition, the effectiveness of SDR was not addressed, and by extension, the effect on reducing leprosy transmission was not studied. Contact follow-up was not carried out in this study, given the relatively short study period. Indeed, the average incubation period of leprosy is relatively long (5 to 10 years), short-term contact monitoring was not feasible. Further studies will consider this aspect.
Conclusion
This study showed that chemoprophylaxis with SDR is socially accepted and can be implemented in leprosy-endemic communities in Benin. Marital status, education level and knowledge of leprosy among contacts of PALs are factors influencing the acceptance of chemoprophylaxis.
The little knowledge of contacts about leprosy revealed by this study, especially about the cause, mode of transmission and clinical signs of the disease, calls not only for community awareness-raising interventions but also for knowledge, attitude and practice studies to be carried out to gain a better understanding of the situation. It would be desirable for this type of study to be carried out prior to any rifampicin chemoprophylaxis intervention in leprosy-endemic communities. This would guarantee a high level of acceptance of the strategy, thanks to educational sessions that would have already considered the realities of each community.
Supporting information
S1 Appendix. STROBE-checklist-v4-cross-sectional.
https://doi.org/10.1371/journal.pntd.0013057.s001
(PDF)
S2 Appendix. Questionnaire Assessment the level of knowledge of PAL contact.
https://doi.org/10.1371/journal.pntd.0013057.s002
(PDF)
S4 Appendix. Assessment of the level of knowledge of PAL contact (Score).
https://doi.org/10.1371/journal.pntd.0013057.s004
(DOCX)
Acknowledgments
We would like to thank the National Buruli Ulcer and Leprosy Control Program (PNLLUB) and the National Program for the Control of Neglected Tropical Diseases (PNLMTN) for their administrative and technical support in carrying out this study. We would also like to thank the Foundation Raoul Follereau (http://www.raoulfollereau.org) and the Foundation ANESVAD (http://www.anesvad.org/fr/) for funding the study.
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