Introduction

Leprosy, also called Hansen’s disease, is an infectious neglected tropical disease (NTD) known since ancient times, which mainly affects the skin, peripheral nerves and eyes. One of the challenges of the elimination of leprosy lies in its long incubation period during which no signs or symptoms are present but transmission to others is assumed to already take place. The average incubation period is five years, but the presentation of the first obvious signs or symptoms of the disease can take up to 20 years [1].

Since 1982, it has been possible to treat leprosy effectively with multidrug therapy (MDT) [2, 3]. Additionally, since 1995 the World Health Organization (WHO) has provided MDT free of charge for all newly diagnosed patients [3]. Unfortunately, on top of the long incubation period, the diagnosis of leprosy is often delayed because of physical and social barriers, and lack of awareness. These issues contribute to ongoing transmission of the infection to other individuals and also pose risks for the development of irreversible physical impairments [2, 4–8]. For this reason, Smith and colleagues (2014) argue that passive case finding and treatment of patients does not reduce the delay in diagnosis of leprosy effectively, and therefore, will not prevent disability in newly diagnosed patients [9]. Hence, early detection of leprosy cases is crucial to start treatment before permanent disabilities have developed [10, 11].

Since 2018, WHO recommends the administration of single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for leprosy for contacts of leprosy patients [12]. To determine the most effective method to implement active case finding activities (integrated skin screening) combined with SDR-PEP administration in Ethiopia, Mozambique and Tanzania, a large-scale intervention study called ‘PEP4LEP’ was designed [13]. Main outcomes of this project are the rate of leprosy patients detected and the delay in diagnosis. To enable comparison of intervention outcomes in the three East African project countries, it was necessary to develop a standardized methodological tool to determine the case detection delay (CDD) in number of months. The concept of CDD as used in the current study is defined as the period between the onset of the first signs or symptoms of the disease and the diagnosis of leprosy [2, 12, 14]. This period both includes the ‘patient delay’, which is defined as the duration between notice of the first sign or symptom by the patient to the first health care provider consultation and ‘health-system delay’, which is the duration between the first health care provider consultation and the moment of leprosy diagnosis [15]. A ‘sign’ can be described as an objective and observable phenomenon (e.g. by a medical professional), such as a skin patch or a palpable enlarged nerve, whereas a ‘symptom’ is a subjective experience that can only be identified by the patient themselves, such as pain or a tingling sensation [16, 17]. For reasons of readability of the current article, when mentioned ‘signs’ in the further text this should be read as ‘signs and symptoms’.

Main outcomes of the PEP4LEP project are the rate of leprosy patients detected and the delay in diagnosis [13]. To enable comparison of intervention outcomes in the three East African project countries, it was necessary to develop a standardized methodological tool to determine the CDD in number of months. The concept of CDD as used in the current study is defined as the period between the onset of the first signs of the disease and the diagnosis of leprosy [2, 14].

Ethiopia has the second highest number of annually detected leprosy patients in Sub-Saharan Africa (SSA): 3,201 new cases in 2019 [18]. The number of newly detected patients in Mozambique and Tanzania were 2,220 and 1,603 respectively in 2019. Although the prevalence of leprosy has significantly decreased in these countries since the implementation of MDT, the number of new cases per year has only slightly dropped in the past decade [10]. Ongoing transmission is further suggested by the number of children (<15 years of age) that were diagnosed in 2019: 507 in Ethiopia, 211 in Mozambique, and 53 in Tanzania, of whom 94 presented with grade 2 disabilities in all three countries combined [18]. Consequently, the WHO has identified all three countries as part of the 23 ‘global priority countries’ for leprosy [18].

To assess the CDD of leprosy in these three Sub-Saharan African countries (Fig 1), it is necessary to design a methodological tool that is validated and adapted to the cultural context of these countries [19]. Several studies have investigated the CDD of leprosy in countries like Bangladesh [20], Brazil [21–23], India [15], Nepal [24] and Paraguay [25]. However, literature on the delay in diagnosis in the cultural context of Ethiopia, Mozambique and Tanzania is lacking or outdated [26–29]. Although several questionnaires have been designed to determine the CDD of leprosy [23, 24, 30], a specific standardized questionnaire for multi-country use does not exist. Therefore, the objective of this study was to design a methodological tool to determine the delay in diagnosis of leprosy in number of months, that is validated for usage in Ethiopia, Mozambique and Tanzania, and adaptable to other cultural settings.

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Fig 1. PEP4LEP study locations–created with ArcGIS Pro. Base layer of the map available via: https://www.arcgis.com/home/item.html?id=64aff05d66ff443caf9711fd988e21dd

https://doi.org/10.1371/journal.pntd.0010038.g001

Methods

Study design

This sub-study was a cross-sectional instrument development and validation study. The study took place in Ethiopia, Bisidimo Hospital in Harar, East Hararghe Zone; in Mozambique in Murrupula Hospital, Nampula Province; and in Tanzania in Morogoro district and in Mwanza district. The study was divided into two phases, the study design is visualised in Fig 2.

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Fig 2. Visualisation of study design.

https://doi.org/10.1371/journal.pntd.0010038.g002

Phase 1: Instrument development.

An instrument was developed in phase 1 of the study, which took place in Ethiopia only. A draft questionnaire was developed based on a literature review, complemented with semi-structured interviews with health professionals, a pilot and a focus group discussion (FGD) with persons affected by leprosy and an expert panel with leprosy experts.

Phase 2: Validation process.

Phase two included three pilot studies in Ethiopia, Mozambique and Tanzania. In Ethiopia, this included test-retest administration of the developed instrument. For this sample, a criterion sampling strategy was used. In Mozambique and Tanzania, a local health worker administered the questionnaire to persons affected by leprosy. Afterwards, these affected persons were interviewed to establish the general validity as well as the cultural validity of the questionnaire. Also, local key informants and health workers were included in additional semi-structured interviews in Mozambique and Tanzania.

A consensus workshop was organized that included the main researchers of phase 1 and of the three pilot studies. The workshop focused on reaching consensus on a final version of the questionnaire, applicable in the several study settings.

Study population

The study population comprised of leprosy patients, persons affected by leprosy, local key informants and health workers. In this study, a leprosy patient is defined as someone who is under treatment for leprosy. A person affected by leprosy is cured from the disease, but is living with its consequences such as disability and/or stigma. Details about the inclusion- and exclusion criteria, as well as the sampling strategies are described in Table 1. Subjects were eligible to participate if they: 1) were willing to participate, and 2) gave informed consent. There were two exclusion criteria: 1) difficulties in communication, and 2) participants under 18 years old who could not be accompanied by a parent or legal guardian.

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Table 1. In-, exclusion criteria and sampling strategy per sample.

https://doi.org/10.1371/journal.pntd.0010038.t001

Results

The review of the available literature resulted in six relevant questionnaires that were previously used to determine the CDD of leprosy Brazil [23], India [15], Nepal [24], and Sierra Leone [30], and to determine the CDD of tuberculosis in East Hararghe Zone [33] and Ethiopia [34]. Aids applied in questionnaires in the cultural context of Ethiopia were identified in three studies, including the use of a local calendar [35], and seasonal and religious festivals or events [36, 37]. Furthermore in some studies pictures or cards were used as visual support for the tool/questionnaire [38, 39]. In the initial interviews (Sample 1), relevant parts of the questionnaires, as well as potential annexes, were discussed. Based on this, the following items were included 1) introduction and instructions, 2) questions regarding CDD, 3) annexes to support administration of the questionnaire, and 4) a sheet to calculate the CDD.

An overview of general characteristics of the study population per study sample can be found in Table 2. Sample 1 included six participants in professions such as (senior) general practitioner, nurse and dermato(venero)logist. Years of working experience varied from 6 to 15 years. Sample 7 consisted of 5 healthcare workers with 5 to 10 years of work experience. Sample 9 consisted of three key informants including a leprosy specialized physician, the head of the national leprosy and TB programme, a general practitioner (GP) experienced in dermato(venero)logy, and six healthcare workers who had experience with leprosy patients. Furthermore, the expert panel (Sample 4) consisted of researchers in the field of leprosy. In total, 89 persons affected by leprosy were included in the study. Of these, 15 participated in study phase 1 and 74 participated in phase 2. Among these samples, 68 to 100% of the participants were residents from rural areas. Older leprosy patients in these areas often lacked any formal education and were illiterate, which must be taken into account in the operational suitability of the methodological tool.

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Table 2. Overview of general characteristics of the study population per study sample.

https://doi.org/10.1371/journal.pntd.0010038.t002

Measurement consistency

During the pilot study in Ethiopia of the questionnaire (Phase 2), the majority of respondents reported that the onset of the disease was between one and two years before the diagnosis. The relation of the CDD of leprosy patients to the disability grade at the moment of diagnosis is shown in the boxplots in Fig 3. The answers given to the questions ‘When did you see the first signs of your disease?’ and ‘Can you explain how long you have had these signs?’ were inconsistent, as respondents reported two different moments of onset of the disease. Overall, the answers to the two questions were consistent for 28 patients. In the remaining 18 cases, when inquiring about signs individually, additional or different signs were listed during the moment of onset of the first sign or before. In 11 cases this led to a discrepancy in the number of months ago that the first sign was experienced, with an on average difference of 9.5 months.

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Fig 3. Case detection delay in relation to the disability grade at the moment of diagnosis, leprosy patients in Ethiopia, Sample 5 (n = 49).

https://doi.org/10.1371/journal.pntd.0010038.g003

To five patients in Sample 5, the CDD questionnaire was administered twice by the same interviewer with three days apart. For one patient the case detection delay outcome differed between the two moments of interviewing by two months. Table 3 shows the count of the matching and non-matching answers between the two subsequent administrations to the same five participants. The non-matching responses were either because patients reported different times of onset of the disease and/or of specific signs in the two administrations, or because certain signs that were reported as experienced in the first administration were not in the second one. Notably, the answers provided in regard to the time of onset of enlarged nerves did not match for any of the repeated administrations of the questionnaire.

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Table 3. Count of matching / non-matching responses in test-retest validation.

https://doi.org/10.1371/journal.pntd.0010038.t003

Discussion

The objective of this study was to design a questionnaire to determine the CDD of leprosy in number of months. While designing the methodological tool, cultural validity was ensured by investigating conceptual understanding, item relevance, semantic understanding, operational suitability and measurement consistency of the tool in the cultural context of three East-African countries: Ethiopia, Mozambique and Tanzania. Insight in the previously mentioned themes has led to the design of questionnaires that can be used to determine the CDD of leprosy in the three study countries. The questionnaire includes guidelines on how to administer the questionnaire and two annexes (a local calendar, picture set) to support administration of the questionnaire. The questionnaire’s administration duration is approximately 15 minutes.

Unfortunately, previous research does not elaborate on either the item relevance or the semantic understanding of questionnaires on CDD. Little knowledge is available regarding the operational applicability of such questionnaires in similar contexts, which hampers comparability of outcomes of this study. In accordance with outcomes of the present study however, in previous studies similar questionnaires were used in East Hararghe Zone, administered by trained local data collectors [45–48]. Although all health professionals in Sample 1 agreed on the preferred moment of questionnaire administration (i.e., right after diagnosis, to prevent loss to follow-up), this is not in line with previous findings. For instance, Henry et al. (2016) proposed administering the questionnaire at least one month after the diagnosis, to prevent emotional distress. But it should be considered that this study was conducted in tertiary referral centres in Brazil (23). The best moment for administration may depend on the logistics of the leprosy control services in the country.

In literature, there seems to be no consensus on a reliable period for people to recall health related events, and periods range from days or weeks to years [49, 50]. However, recalling the existence of signs seems to be easier than recalling for example pain intensity and quality of life [49]. Major signs or ‘high impact conditions’ as well as more unusual signs are recalled better than minor signs/‘low impact conditions’ or more commonly occurring signs [49, 51]. In leprosy research, it could therefore be the case that late signs (e.g., paralysis or ulcer) are easier recalled than early signs (e.g., painless rash / single skin lesion) because of impact and severity. Amjadi et al. (2004) stated that the accuracy of recall of the onset of rheumatoid arthritis symptoms tends to decline over a five-year period [52]. When administering our questionnaire, we advise to include patients who were diagnosed up to six months back, and who are usually still using MDT to treat their leprosy, to minimize potential problems of recall [53]. A calendar was added as a supplement to support the accuracy of recalling the first signs [8, 36]. For each cultural setting, an appropriate calendar should be identified/designed and included, before implementing the questionnaire.

Conclusion

This study has led to the development of a questionnaire to determine the CDD of leprosy in the context of Ethiopia, Mozambique and Tanzania. A standardized version was made in English by removing all culturally specific information to enable adaptation to other cultural contexts. The questionnaire, including annexes and Question-by-Question Guide, can be requested by contacting the corresponding author. English, Oromiffa (Afaan Oromo), Portuguese and Swahili language versions of the questionnaire will also be digitally published on https://www.infolep.org [54].

Further research into the measurement consistency of the questionnaire is recommended before implementation in future projects.

Acknowledgments

The Ethiopian team from AHRI/ALERT and Haramaya University for facilitating and supporting data collection in the field. The study participants, Dr. Alene and Mr. Abrahim. The leprosy experts for their contribution in the expert panel: Paul Saunderson, Ulla-Britt Engelbrektsson and Wim van Brakel. Valerie van der Meij, Adele Barlassina and Marije Tawil for conducting the pilot studies in Tanzania, Ethiopia and Mozambique. The PEP4LEP project team.