Global, Regional, and Country-Level Cost of Leptospirosis Due To Loss of Productivity in Humans
Global, Regional, and Country-Level Cost of Leptospirosis Due To Loss of Productivity in Humans
Global, Regional, and Country-Level Cost of Leptospirosis Due To Loss of Productivity in Humans
Global, regional, and country-level cost of leptospirosis due to loss of productivity in humans
*Corresponding author:
Suneth.Agampodi@ivi.int
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
1
medRxiv preprint doi: https://doi.org/10.1101/2023.04.10.23288387; this version posted April 11, 2023. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY 4.0 International license .
Abstract
Background
Leptospirosis, a prevalent zoonotic disease with One Health priority and a disease of poverty, lacks
global economic burden estimates. This study aims to determine the global, regional, and country-
level cost of leptospirosis due to loss of productivity.
Methodology/Principal Findings
The cost of leptospirosis due to loss of productivity (referred to as productivity cost hereafter) was
estimated by converting the disability-adjusted life years (DALYs) lost due to leptospirosis to a
monetary value using the per capita gross domestic product (GDP). The country-specific DALYs
lost were obtained from the global burden of leptospirosis study published previously. For the cost
conversion of DALYs, non-health GDP per capita (GDP- per capita health expenditure) was used.
Country-specific GDP and health expenditure data were obtained from the World Bank data
repositories. Estimates were done using both nominal and international dollars.
The estimated global productivity cost of leptospirosis in 2019 was Int$ 29.3 billion, with low and
high estimates ranging from Int$ 11.6 billion to 52.3 billion. China (Int$ 4.8 billion), India (Int$
4.6 billion), Indonesia (Int$ 2.8 billion), Sri Lanka (Int$ 2.1 billion), and the United States (Int$
1.3 billion) had the highest productivity cost due to leptospirosis. Eight out of 10 countries with
the highest burden were in the Asia-Pacific region. In addition, lower middle-income countries
had an annual productivity cost of Int$ 13.8 billion, indicating that the disease is poverty-related.
Conclusion
Although significant, the cost estimate due to loss of productivity is merely a fraction of the overall
economic burden of this disease, which also includes other direct, indirect, and intangible costs.
The existing partial estimates of the different components of economic cost suggest a profound
economic burden that demands the inclusion of leptospirosis in the global health agenda for
comprehensive disease control and prevention efforts, including vaccine development.
Author Summary
Leptospirosis is a widespread disease that affects humans and animals and is mostly affecting
individuals living in resource-poor settings, in particular in tropical and subtropical regions. To
understand the economic impact of this disease, we estimated the cost of this disease, assuming
that all deaths and disabilities due to the disease will lead to a loss of human productivity. The
country-level estimates were done using the published data from the World Bank on per capita
gross domestic product (GDP) after removing the per capita health expenditure from the GDP. The
estimated average annual cost of leptospirosis due to loss of productivity was $29.3 billion in 2019,
which could be as high as $52.3 billion. The countries with the highest costs were China ($4.8
billion), India ($4.6 billion), Indonesia ($2.8 billion), Sri Lanka ($2.1 billion), and the United
States ($1.3 billion). Most countries with the highest costs were in the Asia-Pacific region, and
lower-middle-income countries had an annual cost of 13.8 billion US dollars. The estimate of lost
productivity represents, however, a fraction of the overall economic burden caused by
leptospirosis, highlighting the need for immediate action to control and eliminate the disease and
its inclusion in the global health agenda.
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medRxiv preprint doi: https://doi.org/10.1101/2023.04.10.23288387; this version posted April 11, 2023. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY 4.0 International license .
Introduction
Leptospirosis is one of the most widespread zoonotic diseases globally [1, 2]. Human leptospirosis
is caused by more than 35 species of pathogenic and intermediate Leptospira [3] transmitted
primarily through environmental sources. Rodents (in particular rats) and farm animals, including
cattle, pigs, sheep, and other domestic (dogs) and peri-domestic mammals, are the maintenance
hosts for the human leptospirosis [4]. Humans are accidental hosts, and the infection mostly causes
mild flu-like symptoms [5]. Even though early oral antibiotic treatment is often effective, late
presentation during the immune phase of the disease usually leads to complications. Around 10-
15% of the cases may develop severe complications with multiorgan failures requiring specialized
care. The well-known Weil’s disease [6], reported more than a century ago with severe hepatic
and renal dysfunctions, represents only a fraction of severe complications. Fatal complications
without jaundice, such as severe pulmonary hemorrhages and myocarditis, are increasingly
reported in recent literature [7, 8].
Since the Global Burden of Disease (GBD) study [8] does not include leptospirosis as a separate
entity, the comparative burden of leptospirosis compared to other NTDs were not available in the
literature until recently. In 2015, Costa et al. [9] estimated the leptospirosis incidence worldwide
using country-level data available from national surveillance programs and estimated 1.03 million
cases (95% CI 434,000-1,750,000) and 58,900 deaths (95% CI 23,800-95,900) due to leptospirosis
annually [9]. However, these figures are believed to be vastly underestimated due to limited
awareness of the disease, non-specific clinical presentations, limited availability of diagnostic
facilities, and poor reliable surveillance systems [10]. In addition, the available diagnostic tests are
suboptimal, with the best available tests missing almost 40% of the cases [11]. Based on the 2015
GBD, Torgerson et al. have estimated that approximately 2.90 million (Uncertainty Interval ER
1.25-4.54 million) disability-adjusted life years (DALYs) are lost per annum globally due to
leptospirosis [12]. They emphasized that the burden of leptospirosis is about 70% of the global
burden of cholera estimated by the 2010 GBD and much more than several other diseases listed as
neglected tropical diseases.
Leptospirosis is a disease of poverty, even in high-income settings [13, 14]. An increase per capita
household income of 1$ per day was associated with > 11% risk reduction in leptospira antibody
positivity rate in Brazil, a country with a high burden of leptospirosis [2]. Several other analytical
studies also show a direct and significant association of leptospirosis with the economic status [2,
15]. While the risk and impact are mostly borne by urban and rural poor communities, the
economic impact of leptospirosis at the country level is also estimated to be extremely high. In
Brazil, the estimated financial impact of leptospirosis amounted to $ 4.33 million in non-earned
wages, while hospitalization costs were estimated to be around $ 157,000 in 2010 [16]. The
outbreak of leptospirosis associated with 2011 floods and mudslides in Rio de Janeiro was
estimated to cost up to $ 100,800 [17]. In Manila, The Philippines, the total economic value of
preventing leptospirosis was estimated to be $ 124.97 million per annum [18], which was 1.13%
of metro Manila’s GDP. Saizan et al. estimated that preventing leptospirosis in Kelantan, Malaysia,
would save around $ 106.7 to 315 million per annum [19]. In 2021, the economic impact of
leptospirosis in New Zealand was estimated to be around $ 4.42 (95% CI: 2.04–8.62) million per
annum [20].
Despite being identified as the most widespread zoonotic disease, a disease with One Health
priority, and a disease of poverty, estimates of the global burden of leptospirosis in economic terms
represented an important gap. Our study aims at estimating the global, regional, and country-level
cost of leptospirosis attributed to the loss of productivity in humans.
3
medRxiv preprint doi: https://doi.org/10.1101/2023.04.10.23288387; this version posted April 11, 2023. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY 4.0 International license .
Methods
DALYs were used for the first time to estimate the burden of diseases in the 1993 World Health
Report [21]. It was defined as “A unit used for measuring both the global burden of diseases and
the effectiveness of health interventions, as indicated by reductions in the disease burden.” The
underlying rationale, assumptions, and technical basis were published later in 1994 [22]. The GBD
estimates were done for the year 1990 for the first time using DALYs [23]. Despite early rationale
criticisms [24], DALYs have become the most widely used indicator for disease burden
assessment.
In 2001, the World Health Organization (WHO) Commission on Macroeconomics and Health [25]
converted the DALYs lost to a monetary value using the Gross Domestic Product (GDP) per capita
with the human capital approach proposed by Weisbrod in 1961 [26]. This method was easy to
understand because it assumed that each DALY lost had a cost equivalent to the GDP per capita
of the country. Therefore, the total cost of lost productivity due to disease could be calculated by
multiplying the total number of annual DALYs lost by the GDP per capita of the country. This
proposed approach was subsequently used to evaluate the economic value of DALYs lost due to
violence [27] and cancer [28]. The concept is that a loss of health (in DALYs) of a person in each
country will lead to a loss of economic contribution to this country as compared to the contribution
of a healthy person, defining the average GDP per capita of the country. The economic value was
calculated by multiplying country-specific GDP by disease-specific DALYs for each country. The
WHO guideline on Identifying the Economic Consequences of Disease and Injury report proposed
that health expenditure should not be included in these calculations [29]. Hence, in subsequent
studies [30-36], non-health GDP or net GDP was used to evaluate the economic value of DALYs
lost. Non-health GDP is “the component of a country's GDP that excludes total health
expenditure.” It determines value costs unrelated to direct health spending resulting from illness
or death. More recently, the WHO’s productivity loss due to illnesses in Africa [37] used the same
methodology to evaluate the productivity loss due to DALYs lost. In our study, we used a similar
approach in calculating the productivity cost of DALYs lost due to leptospirosis (Box 1).
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medRxiv preprint doi: https://doi.org/10.1101/2023.04.10.23288387; this version posted April 11, 2023. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY 4.0 International license .
The most recent data for GDP per capita and per capita health expenditure by country was obtained
from the World Bank [38]. We used the World Bank 2019 data for these estimates as the COVID-
19 pandemic period may have drastically shifted these numbers. GDP per capita based on
purchasing power parity international dollars (Int$), as well as nominal GDP, were used for these
estimates to provide a better understanding of productivity loss. Whenever 2019 data are missing,
we use the most recent data available. For missing details on per capita health expenditure, the
Institute of Health Metrics and Evaluation country-specific estimates were used [39].
Leptospirosis-related estimated DALYs lost by country and region were obtained from the
Torgerson study [12]. Since calculating uncertainty intervals using the conventional 95%
confidence limits is impossible, we calculated the lower and upper estimates for the productivity
cost using the 95% confidence limits for DALYs estimated previously using the same equation as
above. The results are presented as the ‘estimate range’ (ER). The productivity cost of DALYs lost
due to leptospirosis was calculated at the country, WHO region, and global levels. Upper and lower
estimates for regional and global levels were calculated as a sum of each country's upper and lower
estimates.
Results
All data needed for the productivity cost estimates was available for 196 countries and territories.
The global annual productivity lost due to leptospirosis based on 2019 GDP was Int$ 29.3 billion
with low and high estimates of Int$ 11.6 and Int$ 52.3 billion, respectively. This was based on a
nominal $ 13.9 (ER 5.5 – 24.8 billion) loss of productivity using actual GDP. China (Int$ 4.8
billion ER 1.9 – 8.3 billion) and India (Int$ 4.6 ER 2.0 – 8.2 billion) had the highest economic
burden due to DALYs lost. Indonesia followed these countries with an annual productivity cost of
Int$ 2.8 billion (ER Int$ 1.1-5.1 billion). The only other country with more than Int$ 2 billion
annual loss was Sri Lanka (Int$ 2.1 billion, ER .8 – 4.0 billion). The top 20 countries with
productivity cost by Int$ and US$ are displayed in Figure 1, and all the countries with estimates
are listed in Supplementary Table 1.
Fig 1. Top 20 countries with the highest cost of leptospirosis due to loss of productivity.
All figures are given in international dollars (Int$). Y axis numbers are in millions.
The global distribution of productivity cost due to leptospirosis (Fig 2) shows that the highest
economic burden is clustered in the Asia-Pacific region.
Fig 2. The global distribution of the cost of leptospirosis due to loss of productivity.
High-burden countries other than China, India, and Sri Lanka in the region include Thailand,
Vietnam, Indonesia, and Malaysia, each country having a productivity cost of more than Int$ 500
billion due to leptospirosis. The only country outside the region with a productivity cost of over a
billion dollars was the USA, with an estimated Int$ 1.4 loss per year (ER Int$ .5 -2.5 billion).
For the WHO regions, the highest economic burdens were in the South-East Asia region and the
Western Pacific region (Table 1), accounting for 38.9% and 28.3% of the global burden,
respectively.
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(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY 4.0 International license .
Table 1. Global distribution of estimated annual productivity cost of leptospirosis due to DALYs
lost by WHO region.
Productivity Upper and lower estimates Productivity Upper and lower estimates
WHO Regions
cost (Int$)1 (Int$) cost (US$) (US$)
African 1,937,996,407 739,094,557 -3,337,325,680 775,863,188 295,728,661 -1,335,295,766
Eastern 1,284,118,102 516,267,661 -2,135,490,689 399,211,603 159,188,707 -669,281,417
Mediterranean
European 1,937,421,097 802,695,456 -3,426,223,900 1,286,012,864 537,356,028 -2,270,458,608
Region of the 4,430,758,412 1,733,096,813-7,969,553,002 3,023,193,450 1,195,628,678-5,404,925,390
Americas
South East Asia 11,385,519,772 4,573,376,496-20,400,597,987 3,640,451,762 1,460,752,247-6,517,502,271
Western Pacific 8,289,452,560 3,233,631,946-15,061,334,503 4,788,401,223 1,868,051,914-8,632,437,265
The productivity loss by income level (Table 2) shows that 53 lower middle-income countries
and territories listed had the highest burden, with a total of more than Int$ 13 billion, accounting
for almost half (47.1%) of the global burden.
Table 2. Global distribution of estimated annual productivity cost of leptospirosis due to DALYs
lost, by income level.
Income Level (# of Productivity Upper and lower estimates Productivity Upper and lower estimates
countries) cost (Int$) (Int$) cost (US$) (US$)
High (63) 4,991,838,706 2,003,990,113-9,039,553,914 4,029,419,816 1,621,044,478-7,250,787,445
Upper Middle (53) 9,710,429,956 3,806,465,983-17,203,489,291 5,176,081,465 2,031,428,599-9,142,054,649
Lower Middle (53) 13,794,730,030 5,493,031,496-24,744,093,891 4,428,531,402 1,757,442,046-7,946,895,527
Low (26) 768,267,660 294,675,337 -1,343,388,665 279,101,408 106,791,113 -490,163,096
Discussion
The productivity cost or the human capital approach was not widely used in evaluating the
economic impact on health until recently. Previously, researchers have looked at the different
components of the economic burden of leptospirosis. The social gradient and socio-economic
status measured in monetary terms have been investigated so far as a risk [2, 40], out-of-pocket
expenditure [41], cost of hospitalization [16], opportunity cost [18], social cost [17], and cost of
prevention [19] related to human leptospirosis in different geographical locations. In addition to
the human leptospirosis-related costs, leptospirosis in domestic animals also contributed to a
massive economic cost [42-44]. The reproductive loss in farm animals related to leptospirosis and
the cost of prevention and control of animal leptospirosis could be much higher than the cost of
human leptospirosis. For example, in New Zealand, the production loss cost in beef cattle, sheep,
and deer was estimated to be around US$ 7.92 million, while the median vaccination cost in cattle,
sheep, and deer was US$ 6.15 million. In contrast, the human leptospirosis-associated estimated
cost was US$ 4.42 million [20]. Yet, comprehensive cost of illness studies and global economic
burden estimates for human leptospirosis or leptospirosis as a One Health burden is not available.
In the backdrop of the lack of any global economic burden estimates on leptospirosis, our
conservative estimates show that 2.9 million DALYs accrued due to leptospirosis annually could
6
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(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY 4.0 International license .
have accounted for a loss of productivity of Int$ 29.3 billion in countries included in this analysis.
The upper estimate using the upper value of 95% confidence limits of DALYs shows over Int$
52.3 billion annual loss. The highest economic impact was on the Asia-Pacific, with China, India,
Indonesia, Sri Lanka, and Thailand having the maximum burden. This result is not unexpected
because the high disease burden in Sri Lanka, Thailand, and Indonesia is well documented [45-
47]. The high productive cost of leptospirosis in Sri Lanka, compared to larger countries such as
China and India, may seem unrealistic based solely on incidence rates. However, it is important to
recognize that Sri Lanka's proactive approach towards physician awareness, clinical detection, and
notification of leptospirosis was triggered by a large outbreak in 2008 [48]. This outbreak led to
increased disease awareness, surveillance, and reporting in the country [49]. As a result of these
efforts, Sri Lanka may provide a more accurate representation of the true incidence and economic
cost of leptospirosis compared to other countries that may not have had a similar outbreak or
response. Therefore, it is reasonable to assume that the burden of leptospirosis in many other
resource-poor settings and countries, in particular in Africa, may be grossly underestimated due to
limited awareness of the disease, poor sensitivity of the diagnostic test, lack of disease surveillance
and reporting, as well as limited resources for prevention and control efforts. This underestimation
has already been reported in India [50].
As a disease with a heavy productivity cost burden, leptospirosis requires more global attention on
control and preventive strategies. The published systematic reviews on leptospirosis
chemoprophylaxis show no beneficial effect [51]. Because the severe complications and deaths
are typically in the immune phase, the role of antibiotics at that stage is also debatable [52]. The
complex transmission pattern of leptospirosis involving more than 30 species of Leptospira, a wide
range of reservoir animals, and the ecological conditions in tropical countries with abundant
environmental exposure to water and wet soil makes it extremely difficult to control leptospirosis
through source reduction. The only place of source reduction possible is in farming communities
through extensive animal vaccination. However, animal vaccination strategies still need
improvements in many settings [53, 54]. Primary prevention through human vaccination seems
more logical than source reduction, which also deserves consideration in highly exposed workers.
Even though human vaccine studies were initiated early in the 20th century [55], effective pan-
serovar vaccines are not available for human leptospirosis. The most recent work on virulent
modification proteins of Leptospira species shows a possible candidate for a pan-serovar vaccine,
yet the studies are still in the early stages [56, 57].
Our estimates have several limitations. First, the productivity loss estimate was done using GDP,
which tends to be an overestimation when the groups which are not economically active are also
included in the sample. On the other hand, this study only provides productivity loss estimates, not
the economic burden of leptospirosis. Direct costs, other indirect costs, and intangible costs are
not included, and the cost of animal leptospirosis is not considered. The basic parameter used,
DALYs, has many limitations [24, 58] as an indicator of burden estimates. The DALYs estimated
for leptospirosis also have severe limitations due to the use of national data in the estimation
process [12]. Taken together, the actual global economic burden of leptospirosis could be much
higher than estimated in our study. These numbers are estimated to worsen with the ecosystem
dysfunctions due to climate change, especially with outbreaks of leptospirosis post floodings and
cyclones of increasing frequency and intensity.
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(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY 4.0 International license .
Conclusions
Our study highlights the significant productivity cost imposed by human leptospirosis, which is
only a fraction of the overall economic impact. The projection of a rise in leptospirosis cases due
to unplanned urbanization and climate change highlights the urgency to address this issue through
a comprehensive One Health approach that integrates animal and human health. Therefore,
policymakers and health organizations are invited to prioritize leptospirosis as a Neglected
Tropical Disease and allocate resources toward developing and implementing effective prevention
and control measures, in particular vaccine development.
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