Neglected tropical diseases (NTDs) infect over two billion of the world’s poorest people and disproportionately burden low- and middle-income countries (LMIC), which have a higher likelihood of poor water, sanitation, and hygiene (WASH). Treatment and control of NTDs is included in Goal 3 of the United Nation’s Sustainable Development Goals [1
Leprosy, commonly known as Hansen’s disease, is a chronic infectious disease caused by Mycobacterium leprae
, and is classified as an NTD. An active leprosy infection causes deforming skin lesions and permanent peripheral neuropathy and physical deformity if it is not treated early. Despite multidrug therapy (MDT) and recent public health interventions, close to 200,000 new leprosy cases are reported yearly with 14 LMICs reporting over 94% of all new disease [2
]. While new leprosy cases in Ethiopia have declined each year, it remains a public health problem. In 2016, Ethiopia reported 3692 new leprosy cases and an incidence of 3.52 per 100,000 people [3
is associated with a complex immune response that differs based on type of leprosy: multibacillary (MB) and paucibacillary (PB). MB versus PB leprosy case types are classified by the number of lesions and results of skin smear tests [4
]. MB leprosy is associated with a weakened Th1 immune response and an upregulation of Th2 mediated cytokines and inflammatory markers. PB leprosy is accompanied by a strong Th1 immune response. The majority of transmission is from MB leprosy [2
The same causative agent, M. leprae
, causes PB and MB leprosy types, but the type of leprosy a person develops appears to be dependent on the individual’s immune system’s response to the bacteria. Innate immune genetic variability in toll-like receptor polymorphisms is thought to be a factor related to the leprosy type a person exhibits. Indeed, recent studies estimate that close to 95% of the world’s population is not susceptible to leprosy [5
]. Leprosy is thought to be transmitted primarily through nasal secretions or skin lesions of infected individuals; however, recent evidence suggests that zoonotic reservoirs, trauma-related skin-to-skin transmission, and environmental reservoirs may exist.
Schistosomiasis is another NTD caused primarily by three Schistosoma species, Schistosoma mansoni
, S. haematobium
, and S. japonicum
. Schistosoma are transmitted through cercariae, which enter through the skin when a human comes into contact with water contaminated by human waste [6
]. Recent studies have suggested that soil-transmitted helminth infection may facilitate or increase the risk of leprosy infection [7
]. Helminth infections typically up-regulate the Th2 immune response and down-regulate the Th1 immune response, meaning the diminished Th1 response may lead to a lesser likelihood of controlling M. leprae
infection, and therefore a higher likelihood of leprosy, in particular, MB leprosy [8
]. A geographic association of overlapping schistosomiasis and leprosy was found in a co-endemic area of Brazil [7
]. In Ethiopia, schistosomiasis infections affect close to five million persons and close to 4000 new leprosy cases are diagnosed each year [9
]. Due to overlapping endemicity, this makes Ethiopia a good candidate to further study associations between the two infections.
Environmental factors and exposure through poor WASH conditions are associated with several NTDs including schistosomiasis, trachoma, and soil-transmitted helminths [10
]. Despite several studies that have detected potentially viable M. leprae
in water and soil samples and established survivability of M. leprae
in soil, leprosy is largely ignored as a water or soil associated infection [11
]. Even the recent WHO 2016-2020 Global Leprosy Strategy fails to mention water quality, quantity, and access as a tool for managing or preventing disease [14
This study investigated the strength of association of WASH factors with leprosy infection through an unmatched case control study and further explored schistosomiasis-leprosy co-infections in the Amhara Region of Ethiopia. We hypothesized that poor WASH factors would be associated with a higher odds of leprosy infection and that there would be higher odds of having leprosy among subjects with schistosomiasis.
Forty cases and 41 controls were recruited. Leprosy cases were predominantly male with majority MB disease (n
= 83, %) and poor-moderate WASH access (Table 1
). JMP service level scores for drinking water, sanitation, and hygiene are found in Table 2
. Only one participant scored at the highest and safest tier of the sanitation ladder (tier 5). Thirty-three (41%) scored at the second lowest tier and 20 (25%) at the lowest tier. In other words, 53 (65%) participants used an unimproved sanitation source. Hygiene is a three-level ladder with 36 (44%) participants scoring at the top of the ladder with access to soap and water. This does not differentiate between types of handwashing facilities. Sixty-four (79%) participants had access to improved drinking water facilities, and 20 of these are premises’ access points.
In univariate analysis (Table 3
), unimproved water source (OR = 4.22, 95% CI 1.07, 16.22), lack of premises’ water access (OR = 2.83, 95% CI 1.05, 7.65), lack of soap (OR = 2.61, 95% CI 1.06, 6.42), lack of handwashing (OR = 4.56, 95% CI 1.69, 12.28), and open defecation (OR = 4.32, 95% CI 1.67, 11.18) were associated with leprosy. Lack of water treatment, time to fetch water, schistosomiasis, and distance to the lake were not conclusively associated with leprosy infection. In adjusted analysis, open defecation (OR = 19.86, 95% CI 2.24, 176.25) and lack of access to soap (OR = 7.31, 95% CI 1.07, 49.94) were associated with leprosy. Water source and lack of handwashing had point estimates suggestive of an association with leprosy infection. Lack of water treatment and time to fetch water were not associated with leprosy infection.
Odds ratio estimates based on relation to Lake Tana are included in Table 4
. Those with leprosy had greater odds of schistosomiasis in districts bordering Lake Tana (OR = 3.56, 95% CI 0.80, 15.85), while those with leprosy had lower odds (OR = 0.33, 95% CI 0.09, 1.19) of schistosomiasis in districts not bordering the lake; however, these were not statistically significant.
Overall WASH index scores were low for participants, particularly on the sanitation and hygiene ladders and, as predicted, our study found an association between several WASH factors, including soap access and open defecation, with leprosy infection. We also hypothesized that there would be an association between schistosomiasis and leprosy based upon previous studies linking helminth infection to leprosy infections and the immune response to helminth infections [7
]. Helminth infections up-regulate the Th2 immune response and down-regulate the Th1 response, which reduces the immune system’s ability to control M. leprae
infection. However, overall, schistosomiasis infection was not found to be significantly related to leprosy infection, although a larger study may have detected a difference given the results of the stratified analysis which suggested that schistosomiasis may have been associated with leprosy in regions nearer to the lake, where schistosomiasis is more highly endemic.
WASH index scores in general were low for the entire study population but were especially low for subjects with leprosy. While most individuals with leprosy had access to an improved water source, only 20% had water access in their home or yard. In sanitation, more than one-third of cases did not have access to any facility and none had access to an improved facility not shared with other households. Finally, half of leprosy cases did not have access to soap and water for handwashing. Water source, lack of premises’ access to water, lack of soap, lack of handwashing, and open defecation were statistically correlated with leprosy cases upon unadjusted analyses. Adjusted analyses showed open defecation and lack of soap were correlated with leprosy cases. Overall, these results support a relationship between WASH factors and leprosy cases.
These results are thus important due to the burden of both poor WASH and leprosy in LMICs. In fact, fourteen LMICs report over 94% of the nearly 200,000 new leprosy cases every year [2
]. While the transmission of new cases is thought to occur primarily through nasal secretions of infected individuals, recent evidence suggests that other transmission routes and factors, such as environmental reservoirs, should be considered [23
]. This project thus explored the previously understudied associations of WASH factors and leprosy infection and identifies the need for further study, including the relationship between schistosomiasis and leprosy.
Recent studies have suggested environmental reservoirs of leprosy may exist [24
]. Water that is shared or reused from a source patient may become environmental reservoirs for infection, possibly by aerosolization of M. leprae
. Contaminated water may be capable of transmitting viable M. leprae
, as recent studies have found potentially viable bacteria in water and in amoebas commonly found in untreated water [24
]. The transmissibility of leprosy bacteria found in the environment is difficult to prove, however, as M. leprae
does not grow in laboratory conditions [26
]. However, experimentally based studies with mouse foot pad cultures do prove the survivability of M. leprae
in soil and free-living amoeba [24
]. Studies on environmental reservoirs of leprosy have relied primarily on reverse-transcriptase polymerase chain reaction (rt-PCR) of leprosy to assess reliability, and one study quantifying mRNA from M. leprae
lends stronger support to the ability of these studies to assess viable bacteria in environmental samples [12
While studies have linked water to possible routes of infection, sanitation has not been implicated as a potential transmission route of leprosy [23
]. Potentially viable M. leprae
has been found in soil samples, but the route of transfer from person to environment is not understood [12
]. This is likely to be from shedding from the skin rather than stool, as viable M. leprae
is not known to be excreted in stool [12
]. Open defecation was associated with leprosy in this study, and we believe that open defecation is significant because it accounts for other factors including socio-economic status and potential exposure to soil-transmitted helminth infections which may then increase the risk of active leprosy [28
Our analysis of region-specific schistosomiasis infection points towards an association between schistosomiasis and leprosy within the Lake Tana area. This association may be due to increased exposure to water with schistosomiasis present. While proximity to a body of water should be considered as a WASH factor and as an important contributor to schistosomiasis infection, we do not know if there is a true difference in schistosomiasis-leprosy co-infections between communities near a body of water and far from a body of water since our study was not powered to detect a statistically significant difference in schistosomiasis status by proximity to the lake.
Due to the similarity in WASH access to other populations in developing countries, the associations found in this project are likely to be generalizable to populations with a large number of residents living in poverty and communities with endemic leprosy and schistosomiasis. The findings point towards a general association between WASH and leprosy and, while not necessarily significant in all findings, express the need for further research on water as a transmission route and associations with WASH factors and leprosy.
Our study faced several key limitations including a small sample size, which limited the model reliability and the overall statistical analysis of the project. MB leprosy cases were more likely to be detected in our study, potentially due to increased visibility of MB leprosy compared to PB. This could also have been observed due to an increase in Th2 responses, which can occur as a result of co-infection, poor nutrition, or other immune perturbations. Our results showed wide confidence intervals for several exposure variables due to the small sample size and similarity in survey responses among large proportions of study population. A further weakness of our study was the presence of unquantified confounders such as economic status of participants. Education was used to account for this factor in our study, but a more direct measure of SES could lead to better estimates. Other missing key confounders include potential presence of soil-transmitted helminth infections in addition to schistosomiasis. Our study is potentially limited by selection bias, which is common in case-control study designs due to sampling. Cases were selected from leprosy registries, and subjects on these registries may be more able to seek medical care, have adequate transportation, and more health education. Controls were selected from health offices and may be more likely than the target population to have underlying health conditions.
While this study does not prove a causal relationship between WASH factors and leprosy, it does elucidate the need for further study and analysis of these relationships between WASH and leprosy. Future studies should further consider WASH factors presented in this study and soil-transmitted helminth infections, water quantity, water quality, bathing frequency, water-reuse behaviors, and poverty-related factors as risks for leprosy. Future studies should also consider a larger sample size to study WASH factors and schistosomiasis infection as exposures for leprosy infection. Cohort studies may be considered to study schistosomiasis and WASH factors as exposure variables over time. Future studies can also be improved by active case-finding and visiting subjects at their residence rather than subjects’ health care centers.