Lymphatic filariasis and its sequelae

Lymphatic filariasis (LF) is endemic in 72 countries of Africa, Asia, Oceania, and the Americas.[1] Various species of mosquitoes, depending on world region, transmit the parasites, Wuchereria bancrofti, Brugia malayi, and Brugia timori, to humans. As of 2017, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) had been successful in promoting mass drug administration (MDA) in 67 countries with the goal of stopping new infections–the first “pillar” of the GPELF program–and 21 countries had already completed MDA.[1] The second pillar of the GPELF addresses the needs of people already infected. As many as 40 million people live with the disabling effects of LF, including about 15 million persons with chronic lymphedema, primarily of the legs, but also of the arms, breasts, and scrotum, and about 25 million men with hydrocele.[2] In addition, tens of millions of persons infected with LF are still at risk of developing lymphedema or hydrocele due to damage to the lymphatic system caused by the parasite.[3]

By 2017, only 38 LF-endemic countries had reported services to manage morbidity and prevent disability among affected persons.[1] The vast majority of those programs address only lymphedema.[4] Simple habits of leg hygiene and infection control can slow or stop the progression of lymphedema by reducing the frequency of episodes of infection, called acute dermatolymphangioadenitis (ADLA). Both lymphedema and ADLA diminish productivity.[4–12] Community programs to promote leg hygiene have been successful at trivial cost.[13–15] An economic study of such a community program in Odisha, India estimated that the lifetime benefits of disability prevented, restored work capacity, and reduced medical expense would be 130 times the cost of the intervention.[16]

In regions endemic with W. bancrofti, the most common manifestation of LF is hydrocele.[17] Hydrocele is the accumulation of fluid around the testis in the tunica vaginalis, expanding the fluid volume within the scrotal sac due to blockage or dysfunction of the lymphatic vessels.[4, 18] Hydrocele can be corrected with surgery with few complications. For most men hydrocelectomy reduces or corrects filarial hydrocele and permits resumption of regular activities of daily living and gainful employment.[19–25]

A few countries have organized intensive campaigns in which scores of men are recruited for surgery during a few days or weeks. The present study reports on one such campaign in 2015 in Malawi and evaluates the lifetime economic costs of filarial hydrocele and the lifetime benefits of the surgery from a societal perspective compared to the cost of the surgery. The calculations include only earnings losses and gains for the patients and costs of surgery, omitting costs or gains to family caregivers and community members, which were not measured.

The effects of filarial hydrocele and of hydrocelectomy

Hydrocele is frequently a painful condition that leads to reduced mobility, social exclusion, and depression, all of which reduce the ability to engage in productive activities.[4, 19–25] The productivity loss takes different forms. Some men with hydrocele are unable to work; others may work fewer days per week or hours per day and may be less productive while working. The principal obstacles to undergoing hydrocelectomy reported by men in resource-poor countries include its substantial cost and lack of nearby surgical facilities.[26] Filarial hydrocele disproportionately affects poor men, for whom the cost of hydrocelectomy can be prohibitive. Men in rural areas have less access to surgical facilities and less correct information about the effectiveness of surgery.

The economic impact of filarial hydrocele has been investigated in several countries. A study in east central India (Odisha State) in 2002 found that men with filarial hydrocele worked 14% fewer hours per day than controls.[25] Another study in 1999 in south India found filarial hydrocele patients worked 18% fewer hours per day than controls.[27] A third study in 1996 examined the productivity of 39 male weavers in south India, of whom 29 had hydrocele and 12 had lymphedema. The research compared them with matched controls without chronic lymphatic filariasis. The men worked similar numbers of hours, but those with hydrocele or lymphedema produced 27% less cloth.[28] There are also qualitative studies of productivity losses from filarial hydrocele. A 1996 study in Ghana, for example, reported that people with chronic manifestations of lymphatic filariasis (lymphedema and hydrocele) worked only in short bursts or turned to sedentary but less remunerative jobs, such as basket weaving.[22] See also [19–21, 23, 29].

Efficacy, complications, and serious adverse events are also important considerations in evaluating the benefits and costs of these surgical campaigns, as with any medical or public health intervention. Stanton et al.[30] interviewed 40 men in southern Malawi who had undergone hydrocelectomy 6 months to 2 years earlier. They found that very few men reported any problem with pain, mobility, anxiety, engagement in usual activities, or social participation after surgery. Responding to questions about each of those 5 issues, only a single respondent reported more than a mild problem. Ahorlu et al. reported on their 1999 study of 40 men in a hydrocelectomy campaign in Ghana and found that the men reported “no complications during and after the surgery [and] everybody recovered well.”[31] In contrast, Thomas et al. reported on 5 “mass surgery weeks” between 2002 and 2005 in Nigeria that performed 301 hydrocelectomies; follow-up of 115 of those patients in 2005 found that 7% had a recurrence of the previous condition and 4% developed a new hydrocele.[32] In 2011, Mante and Gueye reported on 3,000 hydrocelectomies in 10 West African countries among which the recurrence rate varied between 3% and 5%.[33]

A study of hydrocelectomy in Edmonton, Canada with a substantial (9.3%) treatment failure rate[34] has been cited in research on the costs of filarial hydrocelectomy.[24] None of the hydroceles in Edmonton, however, was of filarial origin; they were caused by trauma, infection, or tumor. The procedure was performed in an outpatient setting, with an annual average of 3.5 hydrocelectomies per surgeon. The high failure rate in the Edmonton study thus sheds little light on campaigns carried out on an inpatient basis in a Level II hospital with surgeons specifically trained to treat filarial hydrocele, as was recommended in a 2002 meeting of the GPELF.[35]

LF prevention and treatment in Malawi

Malawi, one of the world’s poorest countries, launched a preventive chemotherapy campaign in 2008 and has now completed at least five rounds of MDA. The country conducted the Transmission Assessment Survey (TAS) and carries out surveillance in every endemic district.[1] In 2015 a surgery campaign and surveys were coordinated by the Malawi Ministry of Health, with technical and financial support from the Centre for Neglected Tropical Diseases (CNTD) at the Liverpool School of Tropical Medicine (LSTM). (For a detailed description of the campaign’s methods, see [36].)

Ethics statement

Ethical approval for the research was granted by the Institutional Review Board of the Liverpool School of Tropical Medicine, Liverpool, UK (15.047) and the National Health Sciences Research Committee, Ministry of Health, Malawi (15/3/1406). The data used for this economic analysis were stripped of personal identifiers and thus the economic analysis of the data did not require additional ethical clearance.

The survey

During the hydrocelectomy campaign in Malawi, a pre-operative survey was administered to 201 men in December 2015. The interviews were conducted in 6 hospitals in Chikwawa and Nsanje Districts, which have the highest poverty rates in the country.[37] While nearly 85% of Malawi’s population lives in rural areas, more than 97% of Chikwawa’s population and 92% of Nsanje’s population live in rural areas.[38] These districts are the most severely affected by lymphatic filariasis in Malawi.[39, 40] Follow-up interviews were conducted 3 months and 6 months after the surgery; 152 men (76%) were selected randomly, stratified across the six hospitals. Of those 152 respondents, 137 (68%) could be located for the 6-month follow-up.[36]

The questionnaire was developed by the LSTM research team at the CNTD and translated into the local language by the Malawi LF Programme team. Informed consent was obtained with a written form that was signed and dated by the patient. Tablets for recording responses were given to nurses trained for this task who interviewed patients during pre-surgical assessment. Hydrocelectomy patients were examined by a nurse who evaluated the size of the hydrocele, following the classification of Capuano and Capuano.[41] The men were assigned to one of 6 stages according to the size of the scrotum. The data were collated electronically via Open Data Kit (ODK, https://opendatakit.org/) software and downloaded into Excel spread sheets (Microsoft Corporation, Redmond, WA, USA).

Measuring productivity loss from filarial hydrocele in Malawi

Our measure of productivity loss from untreated filarial hydrocele was based on the following question in the pre-operative survey: “How many days (add partial days together to make full days) [have you] been unable to work in the last month due to your hydrocele?” In Malawi, the number of work days in a month is conventionally considered to be 26.[42, 43] For the 11% of respondents who reported more than 26 work days lost to hydrocele disability in the previous month, we record their days lost as 26.

We used other questions in the survey to test the validity of the days-of-work-lost question as our measure of productivity loss. We calculated summary disability scores for mobility, pain, and participation in usual activities, both taken separately and summed into a single measure. (Each of the 3 disability scores was based on 4, 5, or 6 questions for a total of 45 questions. Responses were coded as follows: no problem = 0, mild problem = 1, moderate problem = 2, and severe problem = 3. For example, a respondent reporting “moderate problem” on all 45 questions would have a summary score of 90. (See [36] for more information about disability scores reported by respondents.)

In a simple linear regression with days of work lost as the dependent variable and the sum of the 3 disability measures as the independent variable, the t-statistic was 6.1 (with an adjusted R-squared of 0.16, significant at the .0000 level). That correlation suggests that the days-of-work-lost variable is a useful measure of the work-capacity or productivity dimension of the economic burden of filarial hydrocele. In contrast, hydrocele stage did not have a statistically significant relationship with either the sum of the 3 disability measures (adjusted R-squared of 0.01, significant at the 0.08 level) or with days of work lost (adjusted R-squared of 0.00 significant at the 0.33 level). All regressions in this work were estimated using STATA/SE 15.1 (StataCorp., College Station TX).

Calculating daily earnings loss from filarial hydrocele

Because there are no studies that specifically measure rural male earnings in Malawi, we combine 2 methods to estimate the average value of a day’s earnings in rural Malawi, which allows us to assign a monetary value to each respondent’s daily productivity loss due to filarial hydrocele. In rural parts of a country such as Malawi, income typically comes to the family in a variety of ways that do not lend themselves to quantitative measurement. Measuring the loss in earning capacity imposed by filarial hydrocele is especially challenging in agricultural areas where an important share of household income consists of food grown and consumed by the family. Another form of income is surplus agricultural production sold for cash or bartered. In many families, only a small share of income takes the form of cash wages generated by either occasional or regular employment. What follows presents 2 ways of estimating average daily earnings of hydrocele patients.

The hydrocelectomy campaign in Malawi took place at the end of 2015. The last follow-up interviews were conducted in June 2016. We begin our calculations of the stream of lifetime earnings losses in July 2016.

Calculating lifetime earnings loss from filarial hydrocele

We determine the value of the annual earnings loss due to filarial hydrocele for men in the survey by multiplying each respondent’s reported work days lost in the previous month by US$1.64 and multiplying that monthly figure by 12. To calculate lifetime earnings loss due to filarial hydrocele, we estimate the number of years that respondents can be expected to remain in the workforce after hydrocelectomy.

Age progression.

If hydrocele stage progressed with age, it could be desirable to adjust the men’s current disability for expected future disability. In the survey, however, the correlation between age and stage of hydrocele (1 through 6) as assessed by medical staff was not statistically significant. In a simple linear bivariate regression of age and stage for men under 65 (the age for which we calculate earnings lost or gained), the R-squared was .001. Furthermore, Table 1 suggests no age progression of hydrocele severity except for the 10 men in the survey younger than 30. Accordingly, we assumed no age progression of hydrocele in our calculations of future loss of productivity from hydrocele and gains in productivity from surgery.

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Table 1. Mean stage of hydrocele and patient age.

https://doi.org/10.1371/journal.pntd.0008003.t001

Costs of hydrocelectomy

The economic costs of hydrocelectomy include the costs of the surgery itself and the loss of earnings during recuperation. Both of those are one-time costs incurred in late 2015 and the first half of 2016 and are not discounted. The direct cost of the surgery, or budgetary cost, is the cost from the perspective of government or donor agencies funding the surgery. Economists, however, would add a second cost, the loss of earnings that the men bear during recuperation from the surgery.

Earnings loss

The average number of work days lost among the men younger than 65 was 6.4 per month or 76.8 per year. The value of each day of earnings lost was estimated to be $1.64, and thus the average annual earnings loss was US$126. That includes 67 men who reported no lost work days due to hydrocele. Assuming no future adverse events associated with the hydrocelectomy and no recurrence of hydrocele, the average discounted real present value of lifetime earnings loss for men younger than 65 years was US$1,684.

Benefits of surgery

In the six-month follow-up survey, the 137 respondents were asked how many days (adding partial days together to make full days) they had been unable to work in the last month due to their groin. None of the respondents reported any days of work lost. The surgery eliminated the loss of earnings for all respondents due to the inability to work once the recovery period had elapsed.

Costs of hydrocelectomy

Cost of foregone earnings during recovery was calculated from the pre- and post-operative surveys. In the 3-month post-operative survey (n = 152), average reported work time lost due to surgery was 35 days, with only 1 man reporting no work time lost. In the pre-operative survey, of the 140 men younger than 65 years, 49% had reported missing 36 or more days of work due to hydrocele in the year prior to surgery. For them, there was no net worktime loss due to inability to work during recuperation. The surgery created an opportunity cost only for the 51% of men who had reported missing fewer than 35 days of work due to hydrocele. The average earnings loss during recovery for the whole group of 140 men younger than 65 was US$28.

The total average cost, in economic terms, of the hydrocelectomy was the sum of US$68 (the medical or budgetary cost of the surgery) and US$28 (the average net loss of earnings during recovery), for a total cost of US$96.

Benefit-cost ratio

A benefit-cost analysis compares the economic benefits of an intervention to the economic cost of the intervention. The average annual earnings loss due to hydrocele was US$126, nearly double the US$68 cost of the surgery. In other words, the surgery more than paid for itself in the first year after the procedure. But the benefits of the surgery continued for the rest of the men’s working lives. For the baseline assumption that the average age of departure from the workforce is 65 years, the ratio of the economic benefit of surgery to the direct or budgetary costs is US$1684/US$68 or 24.8 (Table 2). The ratio of the economic benefit of the surgery to the total economic cost is US$1684/US$96 or 17.5 (Table 2).

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Table 2. Benefit-cost ratios at different ages of departure from the workforce and different costs of hydrocelectomy, budgetary costs and economic costs.

https://doi.org/10.1371/journal.pntd.0008003.t002

Sensitivity analysis

If, on average, men leave the workforce at age 60, the benefit-cost ratio ranges from 23.2 to 16.4 for budgetary and economic costs respectively, as shown in Table 2. If, on average, men leave the workforce at 70, the benefit-cost ratio ranges from 28.5 to 20.2 for budgetary and economic costs respectively.

Using WHO’s 2015 estimate of hydrocelectomy cost, we found the range of possible benefit-cost ratios for hydrocelectomy was 21.1 to 4.7 by varying cost from US$80 to US$360.[51] Simultaneously varying WHO’s cost of surgery and the average age of departure from the workforce from 60 years to 70 years, the benefit-cost ratio varied from 4.4 to 24.2, as shown in Table 2.

Factors that could lead to overestimation of the benefit-cost ratio for hydrocelectomy

Factors that could lead to underestimation of the benefit-cost ratio for hydrocelectomy

Factors with ambiguous effects on the benefit-cost ratio for hydrocelectomy

Conclusion

Our goal was to produce a lower-bound estimate of the benefit-cost ratio for filarial hydrocelectomy. The Discussion addresses 2 factors that might have produced overestimation of the benefit-cost ratio. We argue that those factors were unlikely to be important. We also considered numerous factors grouped into 8 categories that could have produced underestimation of the benefit-cost ratio. We conclude that the effect of the latter could have led to a substantial underestimation of the benefit of surgery.

This analysis of a hydrocelectomy campaign in Malawi shows that the economic benefits of surgery for filarial hydrocele are 24.8 times the cost of the intervention. The benefit-cost ratio is robust to differences in assumptions about the length of working lives and cost of surgery. The cost of hydrocelectomy makes it difficult for poor men in low-income countries to pay for the operation, but the lifetime benefits–to the man, his family, and his community–far exceed the costs of repairing the hydrocele. There is a presumption that hydrocelectomy is too expensive and thus infeasible in low-income regions, but this study demonstrates that the benefits of the procedure far outweigh its costs. Scaling up subsidies to hydrocelectomy campaigns should be a priority for governments and international aid organizations to fulfill the second pillar of the Global Programme to Eliminate Lymphatic Filariasis, preventing and alleviating disability among the many millions of persons already affected.