Fifty years of struggle to control cutaneous leishmaniasis in the highest endemic county in Iran: A longitudinal observation inferred with interrupted time series model

Negligible data are available following major social activities and environmental changes on leishmaniasis. Therefore, how interactions between these events influence cutaneous leishmaniasis (CL) risk is not well-known. This longitudinal study was undertaken to explore the impact of interventions conducted between 1971 and 2020 in Bam county, which has had the highest disease burden in Iran. Only confirmed CL cases during this period were taken into account. Data were analyzed by SPSS 22 using the X² test to assess the significance of the difference between proportions. Moreover, we used interrupted time series (ITS) to assess the impact of three environmental events during this period. Overall, 40,164 cases of CL occurred in the past five decades. Multiple complex factors were among the leading causes that synergistically induced the emergence/re-emergence of CL outbreaks in Bam. The main factors attributed negatively to CL control were cessation of malaria spraying activity, expansion of the city spaces, and a massive earthquake creating new breeding potentials for the vectors. The highest impact on CL incidence during these years was related to the earthquake [coefficient = 17.8 (95% CI: 11.3, 22.7); p-value < 0.001]. Many factors can contribute to CL outbreaks in endemic foci. They also can cause new foci in new areas. Since humans are the single reservoir for CL in this area, early detection and effective management significantly contribute to controlling CL to reduce the disease burden. However, essential evidence gaps remain, and new tools are crucial before the disease can ultimately be controlled. Nevertheless, sustained funding and more trained task forces are essential to strengthen surveillance and case management and monitor the interventions’ impact.     

Leishmaniasis and poverty

Leishmaniasis, a neglected tropical disease, has strong but complex links with poverty. The burden of leishmaniasis falls disproportionately on the poorest segments of the global population. Within endemic areas, increased infection risk is mediated through poor housing conditions and environmental sanitation, lack of personal protective measures and economically driven migration and employment that bring nonimmune hosts into contact with infected sand flies. Poverty is associated with poor nutrition and other infectious diseases, which increase the risk that a person (once infected) will progress to the clinically manifested disease. Lack of healthcare access causes delays in appropriate diagnosis and treatment and accentuates leishmaniasis morbidity and mortality, particularly in women. Leishmaniasis diagnosis and treatment are expensive and families must sell assets and take loans to pay for care, leading to further impoverishment and reinforcement of the vicious cycle of disease and poverty. Public investment in treatment and control would decrease the leishmaniasis disease burden and help to alleviate poverty.     

Generation of Luciferase-Expressing Leishmania infantum chagasi and Assessment of Miltefosine Efficacy in Infected Hamsters through Bioimaging

Background

The only oral drug available for the treatment of leishmaniasis is miltefosine, described and approved for visceral leishmaniasis in India. Miltefosine is under evaluation for the treatment of cutaneous leishmaniasis in the Americas although its efficacy for the treatment of human visceral leishmaniasis caused by Leishmania infantum chagasi has not been described. Drug efficacy for visceral leishmaniasis is ideally tested in hamsters, an experimental model that mimics human disease. Luciferase has been validated as a quantitative tool for the determination of parasite burden in experimental leishmaniasis. However, there are no reports of luciferase detection in the model of progressive visceral leishmaniasis in hamsters. Therefore, the aims of this study were to generate recombinant Leishmania infantum chagasi expressing the luciferase gene (Lc-LUC), characterize the biological properties of this transgenic line as compared with the wild-type parasites and evaluate miltefosine effectiveness in Lc-LUC infected hamsters.

Methodology/Principal Findings

A transgenic line containing a luciferase encoding gene integrated into the ribosomal DNA locus was obtained and shown to produce bioluminescence which correlated with the number of parasites. Lc-LUC growth curves and susceptibility to pentavalent antimony and miltefosine in vitro were indistinguishable from the wild-type parasites. The effectiveness of pentavalent antimony was evaluated in Lc-LUC infected hamsters through bioimaging and determination of Leishman Donovan Units. Both methods showed concordant results. Miltefosine was effective in the treatment of Lc-LUC-infected hamsters, as demonstrated by the reduction in parasite burden in a dose-dependent manner and by prolongation of animal survival.

Conclusions/Significance

Luciferase expressing parasites are a reliable alternative for parasite burden quantification in hamsters with advantages such as the possibility of estimating parasite load before drug treatment and therefore allowing distribution of animals in groups with equivalent mean parasite burden. Miltefosine was effective in vivo in an L. infantum chagasi experimental model of infection.     

Disease burden and epidemiology of soil-transmitted helminthiases and schistosomiasis in Asia: the Japanese perspective

The disease burden due to soil-transmitted helminthiases (STH) and schistosomiasis is not well documented in Asia. Both STH and schistosomiasis are chronic diseases but case detection is not easy because of the absence of clinical symptoms. STH and schistosomiasis are, however, endemic in Asia and their burden is significant. At the preparatory meeting for the Hashimoto Initiative in Japan in 1997, STH and schistosomiasis were categorized as Group 2 diseases. Parasitic infections in this category were well understood at the time but sophisticated control strategies were lacking. Japan has promoted comprehensive collaborative projects to reduce the burden of STH and schistosomiasis throughout Asia, creating an international network to collect epidemiological information and to implement and improve disease control, thus extending the school-based control method that had proved so successful in Japan.     

Present situation of visceral leishmaniasis in China

Visceral leishmaniasis or kala azar is a disease that is distributed world-wide from countries around the Mediterranean Sea to Africa, the Middle East, Asia and South America (Fig. 1). Visceral leishmaniasis was highly prevalent in China but since 1958, after a nationwide campaign, it has been brought under control. Only sporadic cases occur in the hilly and newly reclaimed desert areas in NW China.     

Beyond Attributable Burden: Estimating the Avoidable Burden of Disease Associated with Household Air Pollution

Background

The Global Burden of Disease (GBD) studies have transformed global understanding of health risks by producing comprehensive estimates of attributable disease burden, or the current disease that would be eliminated if a risk factor did not exist. Yet many have noted the greater policy significance of avoidable burden, or the future disease that could actually be eliminated if a risk factor were eliminated today. Avoidable risk may be considerably lower than attributable risk if baseline levels of exposure or disease are declining, or if a risk factor carries lagged effects on disease. As global efforts to deliver clean cookstoves accelerate, a temporal estimation of avoidable risk due to household air pollution (HAP) becomes increasingly important, particularly in light of the rapid uptake of modern stoves and ongoing epidemiologic transitions in regions like South and Southeast Asia.

Methods and Findings

We estimate the avoidable burden associated with HAP using International Futures (IFs), an integrated forecasting system that has been used to model future global disease burdens and risk factors. Building on GBD and other estimates, we integrated a detailed HAP exposure estimation and exposure-response model into IFs. We then conducted a counterfactual experiment in which HAP exposure is reduced to theoretical minimum levels in 2015. We evaluated avoidable mortality and DALY reductions for the years 2015 to 2024 relative to a Base Case scenario in which only endogenous changes occurred. We present results by cause and region, looking at impacts on acute lower respiratory infection (ALRI) and four noncommunicable diseases (NCDs). We found that just 2.6% of global DALYs would be averted between 2015 and 2024, compared to 4.5% of global DALYs attributed to HAP in the 2010 GBD study, due in large part to the endogenous tendency towards declining traditional stove usage in the IFs base case forecast. The extent of diminished impact was comparable for ALRI and affected NCDs, though for different reasons. ALRI impacts diminish due to the declining burden of ALRI in the base case forecast, particularly apparent in South Asia and Southeast Asia. Although NCD burdens are rising in regions affected by HAP, the avoidable risk of NCD nonetheless diminishes due to lagged effects. Because the stove transition and the decline of ALRI are proceeding more slowly in Sub-Saharan Africa, avoidable impacts would also be more persistent (3.9% of total DALY due to HAP) compared to South Asia (3.6%) or Southeast Asia (2.5%).

Conclusions

Our results illustrate how a temporal dynamic calculation of avoidable risk may yield different estimates, compared to a static attributable risk estimate, of the global and regional burden of disease. Our results suggest a window of rising and falling opportunity for HAP interventions that may have already closed in Southeast Asia and may be closing quickly in South Asia, but may remain open longer in Sub-Saharan Africa. A proper accounting of global health priorities should apply an avoidable risk framework that considers the role of ongoing social, economic and health transitions in constantly altering the disease and risk factor landscape.     

The neglected tropical diseases of Latin America and the Caribbean: a review of disease burden and distribution and a roadmap for control and elimination

The neglected tropical diseases (NTDs) represent some of the most common infections of the poorest people living in the Latin American and Caribbean region (LAC). Because they primarily afflict the disenfranchised poor as well as selected indigenous populations and people of African descent, the NTDs in LAC are largely forgotten diseases even though their collective disease burden may exceed better known conditions such as of HIV/AIDS, tuberculosis, or malaria. Based on their prevalence and healthy life years lost from disability, hookworm infection, other soil-transmitted helminth infections, and Chagas disease are the most important NTDs in LAC, followed by dengue, schistosomiasis, leishmaniasis, trachoma, leprosy, and lymphatic filariasis. On the other hand, for some important NTDs, such as leptospirosis and cysticercosis, complete disease burden estimates are not available. The NTDs in LAC geographically concentrate in 11 different sub-regions, each with a distinctive human and environmental ecology. In the coming years, schistosomiasis could be eliminated in the Caribbean and transmission of lymphatic filariasis and onchocerciasis could be eliminated in Latin America. However, the highest disease burden NTDs, such as Chagas disease, soil-transmitted helminth infections, and hookworm and schistosomiasis co-infections, may first require scale-up of existing resources or the development of new control tools in order to achieve control or elimination. Ultimately, the roadmap for the control and elimination of the more widespread NTDs will require an inter-sectoral approach that bridges public health, social services, and environmental interventions.     

Chemical control and insecticide resistance status of sand fly vectors worldwide

BackgroundPhlebotomine sand flies are prominent vectors of Leishmania parasites that cause leishmaniasis, which comes second to malaria in terms of parasitic causative fatalities globally. In the absence of human vaccines, sand fly chemical-based vector control is a key component of leishmaniasis control efforts.Methods and findingsWe performed a literature review on the current interventions, primarily, insecticide-based used for sand fly control, as well as the global insecticide resistance (IR) status of the main sand fly vector species. Indoor insecticidal interventions, such as residual spraying and treated bed nets are the most widely deployed, while several alternative control strategies are also used in certain settings and/or are under evaluation. IR has been sporadically detected in sand flies in India and other regions, using non-standardized diagnostic bioassays. Molecular studies are limited to monitoring of known pyrethroid resistance mutations (kdr), which are present at high frequencies in certain regions.ConclusionsAs the leishmaniasis burden remains a major problem at a global scale, evidence-based rational use of insecticidal interventions is required to meet public health demands. Standardized bioassays and molecular markers are a prerequisite for this task, albeit are lagging behind. Experiences from other disease vectors underscore the need for the implementation of appropriate IR management (IRM) programs, in the framework of integrated vector management (IVM). The implementation of alternative strategies seems context- and case-specific, with key eco-epidemiological parameters yet to be investigated. New biotechnology-based control approaches might also come into play in the near future to further reinforce sand fly/leishmaniasis control efforts.     

Neglected Tropical Diseases in Sub-Saharan Africa: Review of Their Prevalence,Distribution, and Disease Burden

The neglected tropical diseases (NTDs) are the most common conditions affecting the poorest 500 million people living in sub-Saharan Africa (SSA), and together produce a burden of disease that may be equivalent to up to one-half of SSA''s malaria disease burden and more than double that caused by tuberculosis. Approximately 85% of the NTD disease burden results from helminth infections. Hookworm infection occurs in almost half of SSA''s poorest people, including 40–50 million school-aged children and 7 million pregnant women in whom it is a leading cause of anemia. Schistosomiasis is the second most prevalent NTD after hookworm (192 million cases), accounting for 93% of the world''s number of cases and possibly associated with increased horizontal transmission of HIV/AIDS. Lymphatic filariasis (46–51 million cases) and onchocerciasis (37 million cases) are also widespread in SSA, each disease representing a significant cause of disability and reduction in the region''s agricultural productivity. There is a dearth of information on Africa''s non-helminth NTDs. The protozoan infections, human African trypanosomiasis and visceral leishmaniasis, affect almost 100,000 people, primarily in areas of conflict in SSA where they cause high mortality, and where trachoma is the most prevalent bacterial NTD (30 million cases). However, there are little or no data on some very important protozoan infections, e.g., amebiasis and toxoplasmosis; bacterial infections, e.g., typhoid fever and non-typhoidal salmonellosis, the tick-borne bacterial zoonoses, and non-tuberculosis mycobaterial infections; and arboviral infections. Thus, the overall burden of Africa''s NTDs may be severely underestimated. A full assessment is an important step for disease control priorities, particularly in Nigeria and the Democratic Republic of Congo, where the greatest number of NTDs may occur.     

Spatiotemporal distribution of cutaneous leishmaniasis in Sri Lanka and future case burden estimates

BackgroundLeishmaniasis is a neglected tropical vector-borne disease, which is on the rise in Sri Lanka. Spatiotemporal and risk factor analyses are useful for understanding transmission dynamics, spatial clustering and predicting future disease distribution and trends to facilitate effective infection control.MethodsThe nationwide clinically confirmed cutaneous leishmaniasis and climatic data were collected from 2001 to 2019. Hierarchical clustering and spatiotemporal cross-correlation analysis were used to measure the region-wide and local (between neighboring districts) synchrony of transmission. A mixed spatiotemporal regression-autoregression model was built to study the effects of climatic, neighboring-district dispersal, and infection carryover variables on leishmaniasis dynamics and spatial distribution. Same model without climatic variables was used to predict the future distribution and trends of leishmaniasis cases in Sri Lanka.ResultsA total of 19,361 clinically confirmed leishmaniasis cases have been reported in Sri Lanka from 2001–2019. There were three phases identified: low-transmission phase (2001–2010), parasite population buildup phase (2011–2017), and outbreak phase (2018–2019). Spatially, the districts were divided into three groups based on similarity in temporal dynamics. The global mean correlation among district incidence dynamics was 0.30 (95% CI 0.25–0.35), and the localized mean correlation between neighboring districts was 0.58 (95% CI 0.42–0.73). Risk analysis for the seven districts with the highest incidence rates indicated that precipitation, neighboring-district effect, and infection carryover effect exhibited significant correlation with district-level incidence dynamics. Model-predicted incidence dynamics and case distribution matched well with observed results, except for the outbreak in 2018. The model-predicted 2020 case number is about 5,400 cases, with intensified transmission and expansion of high-transmission area. The predicted case number will be 9115 in 2022 and 19212 in 2025.ConclusionsThe drastic upsurge in leishmaniasis cases in Sri Lanka in the last few year was unprecedented and it was strongly linked to precipitation, high burden of localized infections and inter-district dispersal. Targeted interventions are urgently needed to arrest an uncontrollable disease spread.     

Proposal of Health Information System (HIS) as tool for the epidemiological surveillance of leishmaniasis in urban areas

In recent years leishmaniasis has become a serious Public Health problem in Italy. The coexistence of infected dogs, vectors and humans, makes urban areas suitable environment for the spread of this zoonotic disease. With the purpose to improve the current system for the control of leishmaniasis in urban areas, the authors report their experiences carrying out a Health Information System (HIS) for the surveillance of the disease in the city of Messina. The HIS project is built on a dataset containing geographical data on urban environment, census tracts at parish level and data of human and canine leishmaniasis cases reported in the last years. The HIS allows the spatial representation of the disease occurrence and can be used as a novel epidemiological tool to perform area-based surveillance.     

Concerted Efforts to Control or Eliminate Neglected Tropical Diseases: How Much Health Will Be Gained?

Background

The London Declaration (2012) was formulated to support and focus the control and elimination of ten neglected tropical diseases (NTDs), with targets for 2020 as formulated by the WHO Roadmap. Five NTDs (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths and trachoma) are to be controlled by preventive chemotherapy (PCT), and four (Chagas’ disease, human African trypanosomiasis, leprosy and visceral leishmaniasis) by innovative and intensified disease management (IDM). Guinea worm, virtually eradicated, is not considered here. We aim to estimate the global health impact of meeting these targets in terms of averted morbidity, mortality, and disability adjusted life years (DALYs).

Methods

The Global Burden of Disease (GBD) 2010 study provides prevalence and burden estimates for all nine NTDs in 1990 and 2010, by country, age and sex, which were taken as the basis for our calculations. Estimates for other years were obtained by interpolating between 1990 (or the start-year of large-scale control efforts) and 2010, and further extrapolating until 2030, such that the 2020 targets were met. The NTD disease manifestations considered in the GBD study were analyzed as either reversible or irreversible. Health impacts were assessed by comparing the results of achieving the targets with the counterfactual, construed as the health burden had the 1990 (or 2010 if higher) situation continued unabated.

Principle Findings/Conclusions

Our calculations show that meeting the targets will lead to about 600 million averted DALYs in the period 2011–2030, nearly equally distributed between PCT and IDM-NTDs, with the health gain amongst PCT-NTDs mostly (96%) due to averted disability and amongst IDM-NTDs largely (95%) from averted mortality. These health gains include about 150 million averted irreversible disease manifestations (e.g. blindness) and 5 million averted deaths. Control of soil-transmitted helminths accounts for one third of all averted DALYs. We conclude that the projected health impact of the London Declaration justifies the required efforts.     

Efficacy and community-effectiveness of insecticide treated nets for the control of visceral leishmaniasis: A systematic review

Visceral leishmaniasis (VL) has been targeted for elimination from Southeast Asia (SEA). The disease has been endemic in SEA, and in other parts of the world involving both humans and animals. One of the key strategies for combating VL is controlling for the vector sandfly. There are a few vector control strategies that are currently in practice. We sought to assess the efficacy and community effectiveness of insecticide treated nets (ITNs) in controlling the burden of sandfly and the occurrence of VL among humans. We conducted a systematic review following a study protocol and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria. 6331 initial hits were retrieved from Google Scholar, Lilacs, PubMed, Science Direct, WHOlis, WHOiris and PAHOiris. 25 met the full inclusion criteria. Findings show that the insecticide impregnated bednets and the commercially treated long lasting insecticidal nets (LLINs) are effective in controlling sandflies, with mortalities as high as 75% lasting over a year; although their role in controlling VL in the community was not extensively studied, since effectiveness was usually measured with sandflies densities. Findings also show that insecticide impregnated bednets are low cost and well accepted in the community, however, early erosion of insecticides from nets could occur. Some studies also showed that killing of sandflies may not translate into reduction of VL, therefore sandfly knock down and killing data needs to be interpreted with caution. Conclusions of this review are (1) combining insecticide impregnated bednets, as targeted interventions, with another vector control measure, particularly indoor residual spraying, and in conjunction with case detection, could be the way forward to controlling VL in resource limited settings. (2) Given the current low incidence of VL in SEA, it can be difficult to further research the community effectiveness of those control measures in reducing VL.     

The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths

Background

Envenoming resulting from snakebites is an important public health problem in many tropical and subtropical countries. Few attempts have been made to quantify the burden, and recent estimates all suffer from the lack of an objective and reproducible methodology. In an attempt to provide an accurate, up-to-date estimate of the scale of the global problem, we developed a new method to estimate the disease burden due to snakebites.

Methods and Findings

The global estimates were based on regional estimates that were, in turn, derived from data available for countries within a defined region. Three main strategies were used to obtain primary data: electronic searching for publications on snakebite, extraction of relevant country-specific mortality data from databases maintained by United Nations organizations, and identification of grey literature by discussion with key informants. Countries were grouped into 21 distinct geographic regions that are as epidemiologically homogenous as possible, in line with the Global Burden of Disease 2005 study (Global Burden Project of the World Bank). Incidence rates for envenoming were extracted from publications and used to estimate the number of envenomings for individual countries; if no data were available for a particular country, the lowest incidence rate within a neighbouring country was used. Where death registration data were reliable, reported deaths from snakebite were used; in other countries, deaths were estimated on the basis of observed mortality rates and the at-risk population. We estimate that, globally, at least 421,000 envenomings and 20,000 deaths occur each year due to snakebite. These figures may be as high as 1,841,000 envenomings and 94,000 deaths. Based on the fact that envenoming occurs in about one in every four snakebites, between 1.2 million and 5.5 million snakebites could occur annually.

Conclusions

Snakebites cause considerable morbidity and mortality worldwide. The highest burden exists in South Asia, Southeast Asia, and sub-Saharan Africa.     

Biogenic nanoporous silicon carrier improves the efficacy of buparvaquone against resistant visceral leishmaniasis

Visceral leishmaniasis is a vector-borne protozoan infection that is fatal if untreated. There is no vaccination against the disease, and the current chemotherapeutic agents are ineffective due to increased resistance and severe side effects. Buparvaquone is a potential drug against the leishmaniases, but it is highly hydrophobic resulting in poor bioavailability and low therapeutic efficacy. Herein, we loaded the drug into silicon nanoparticles produced from barley husk, which is an agricultural residue and widely available. The buparvaquone-loaded nanoparticles were several times more selective to kill the intracellular parasites being non-toxic to macrophages compared to the pure buparvaquone and other conventionally used anti-leishmanial agents. Furthermore, the in vivo results revealed that the intraperitoneally injected buparvaquone-loaded nanoparticles suppressed the parasite burden close to 100%. By contrast, pure buparvaquone suppressed the burden only by 50% with corresponding doses. As the conclusion, the biogenic silicon nanoparticles are promising carriers to significantly improve the therapeutic efficacy and selectivity of buparvaquone against resistant visceral leishmaniasis opening a new avenue for low-cost treatment against this neglected tropical disease threatening especially the poor people in developing nations.     

Leishmaniasis worldwide and global estimates of its incidence

As part of a World Health Organization-led effort to update the empirical evidence base for the leishmaniases, national experts provided leishmaniasis case data for the last 5 years and information regarding treatment and control in their respective countries and a comprehensive literature review was conducted covering publications on leishmaniasis in 98 countries and three territories (see 'Leishmaniasis Country Profiles Text S1, S2, S3, S4, S5, S6, S7, S8, S9, S10, S11, S12, S13, S14, S15, S16, S17, S18, S19, S20, S21, S22, S23, S24, S25, S26, S27, S28, S29, S30, S31, S32, S33, S34, S35, S36, S37, S38, S39, S40, S41, S42, S43, S44, S45, S46, S47, S48, S49, S50, S51, S52, S53, S54, S55, S56, S57, S58, S59, S60, S61, S62, S63, S64, S65, S66, S67, S68, S69, S70, S71, S72, S73, S74, S75, S76, S77, S78, S79, S80, S81, S82, S83, S84, S85, S86, S87, S88, S89, S90, S91, S92, S93, S94, S95, S96, S97, S98, S99, S100, S101'). Additional information was collated during meetings conducted at WHO regional level between 2007 and 2011. Two questionnaires regarding epidemiology and drug access were completed by experts and national program managers. Visceral and cutaneous leishmaniasis incidence ranges were estimated by country and epidemiological region based on reported incidence, underreporting rates if available, and the judgment of national and international experts. Based on these estimates, approximately 0.2 to 0.4 cases and 0.7 to 1.2 million VL and CL cases, respectively, occur each year. More than 90% of global VL cases occur in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and western Asia from the Middle East to Central Asia. The ten countries with the highest estimated case counts, Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North Sudan, Costa Rica and Peru, together account for 70 to 75% of global estimated CL incidence. Mortality data were extremely sparse and generally represent hospital-based deaths only. Using an overall case-fatality rate of 10%, we reach a tentative estimate of 20,000 to 40,000 leishmaniasis deaths per year. Although the information is very poor in a number of countries, this is the first in-depth exercise to better estimate the real impact of leishmaniasis. These data should help to define control strategies and reinforce leishmaniasis advocacy.     

The Global Burden of Trachoma: A Review

Trachoma is the commonest infectious cause of blindness worldwide. Recurrent infection of the ocular surface by Chlamydia trachomatis, the causative agent, leads to inturning of the eyelashes (trichiasis) and blinding corneal opacification. Trachoma is endemic in more than 50 countries. It is currently estimated that there are about 1.3 million people blind from the disease and a further 8.2 million have trichiasis. Several estimates for the burden of disease from trachoma have been made, giving quite variable results. The variation is partly because different prevalence data have been used and partly because different sequelae have been included. The most recent estimate from the WHO placed it at around 1.3 million Disability-Adjusted Life Years (DALYs). A key issue in producing a reliable estimate of the global burden of trachoma is the limited amount of reliable survey data from endemic regions.     

Neglected tropical diseases in Central America and Panama: Review of their prevalence,populations at risk and impact on regional development

A review of the literature since 2009 reveals a staggering health and economic burden resulting from neglected tropical diseases in Panama and the six countries of Central America (referred to collectively here as ‘Central America’). Particularly at risk are the 10.2 million people in the region who live on less than $2 per day, mostly in Guatemala, Honduras, Nicaragua and El Salvador. Indigenous populations are especially vulnerable to neglected tropical diseases. Currently, more than 8 million Central American children require mass drug treatments annually (or more frequently) for their intestinal helminth infections, while vector-borne diseases are widespread. Among the vector-borne parasitic infections, almost 40% of the population is at risk for malaria (mostly Plasmodium vivax infection), more than 800,000 people live with Chagas disease, and up to 39,000 people have cutaneous leishmaniasis. In contrast, an important recent success story is the elimination of onchocerciasis from Central America. Dengue is the leading arbovirus infection with 4–5 million people affected annually and hantavirus is an important rodent-borne viral neglected tropical disease. The leading bacterial neglected tropical diseases include leptospirosis and trachoma, for which there are no disease burden estimates. Overall there is an extreme dearth of epidemiological data on neglected tropical diseases based on active surveillance as well as estimates of their economic impact. Limited information to date, however, suggests that neglected tropical diseases are a major hindrance to the region’s economic development, in both the most impoverished Central American countries listed above, as well as for Panama and Costa Rica where a substantial (but largely hidden) minority of people live in extreme poverty.     

Bayesian latent class models for identifying canine visceral leishmaniosis using diagnostic tests in the absence of a gold standard

BackgroundLike many infectious diseases, there is no practical gold standard for diagnosing clinical visceral leishmaniasis (VL). Latent class modeling has been proposed to estimate a latent gold standard for identifying disease. These proposed models for VL have leveraged information from diagnostic tests with dichotomous serological and PCR assays, but have not employed continuous diagnostic test information.Methods/Principal findingsIn this paper, we employ Bayesian latent class models to improve the identification of canine visceral leishmaniasis using the dichotomous PCR assay and the Dual Path Platform (DPP) serology test. The DPP test has historically been used as a dichotomous assay, but can also yield numerical information via the DPP reader. Using data collected from a cohort of hunting dogs across the United States, which were identified as having either negative or symptomatic disease, we evaluate the impact of including numerical DPP reader information as a proxy for immune response. We find that inclusion of DPP reader information allows us to illustrate changes in immune response as a function of age.Conclusions/SignificanceUtilization of continuous DPP reader information can improve the correct discrimination between individuals that are negative for disease and those with clinical VL. These models provide a promising avenue for diagnostic testing in contexts with multiple, imperfect diagnostic tests. Specifically, they can easily be applied to human visceral leishmaniasis when diagnostic test results are available. Also, appropriate diagnosis of canine visceral leishmaniasis has important consequences for curtailing spread of disease to humans.     

The current burden of Japanese encephalitis and the estimated impacts of vaccination: Combining estimates of the spatial distribution and transmission intensity of a zoonotic pathogen

Japanese encephalitis virus (JEV) is a major cause of neurological disability in Asia and causes thousands of severe encephalitis cases and deaths each year. Although Japanese encephalitis (JE) is a WHO reportable disease, cases and deaths are significantly underreported and the true burden of the disease is not well understood in most endemic countries. Here, we first conducted a spatial analysis of the risk factors associated with JE to identify the areas suitable for sustained JEV transmission and the size of the population living in at-risk areas. We then estimated the force of infection (FOI) for JE-endemic countries from age-specific incidence data. Estimates of the susceptible population size and the current FOI were then used to estimate the JE burden from 2010 to 2019, as well as the impact of vaccination. Overall, 1,543.1 million (range: 1,292.6-2,019.9 million) people were estimated to live in areas suitable for endemic JEV transmission, which represents only 37.7% (range: 31.6-53.5%) of the over four billion people living in countries with endemic JEV transmission. Based on the baseline number of people at risk of infection, there were an estimated 56,847 (95% CI: 18,003-184,525) JE cases and 20,642 (95% CI: 2,252-77,204) deaths in 2019. Estimated incidence declined from 81,258 (95% CI: 25,437-273,640) cases and 29,520 (95% CI: 3,334-112,498) deaths in 2010, largely due to increases in vaccination coverage which have prevented an estimated 314,793 (95% CI: 94,566-1,049,645) cases and 114,946 (95% CI: 11,421-431,224) deaths over the past decade. India had the largest estimated JE burden in 2019, followed by Bangladesh and China. From 2010-2019, we estimate that vaccination had the largest absolute impact in China, with 204,734 (95% CI: 74,419-664,871) cases and 74,893 (95% CI: 8,989-286,239) deaths prevented, while Taiwan (91.2%) and Malaysia (80.1%) had the largest percent reductions in JE burden due to vaccination. Our estimates of the size of at-risk populations and current JE incidence highlight countries where increasing vaccination coverage could have the largest impact on reducing their JE burden.