The elimination of human African trypanosomiasis: Achievements in relation to WHO road map targets for 2020

BackgroundIn the 20th century, epidemics of human African trypanosomiasis (HAT) ravaged communities in a number of African countries. The latest surge in disease transmission was recorded in the late 1990s, with more than 35,000 cases reported annually in 1997 and 1998. In 2013, after more than a decade of sustained control efforts and steady progress, the World Health Assembly resolved to target the elimination of HAT as a public health problem by 2020. We report here on recent progress towards this goal.Methodology/principal findingsWith 992 and 663 cases reported in 2019 and 2020 respectively, the first global target was amply achieved (i.e. fewer than 2,000 HAT cases/year). Areas at moderate or higher risk of HAT, where more than 1 case/10,000 people/year are reported, shrunk to 120,000 km² for the five-year period 2016–2020. This reduction of 83% from the 2000–2004 baseline (i.e. 709,000 km²) is slightly below the target (i.e. 90% reduction). As a result, the second global target for HAT elimination as a public health problem cannot be considered fully achieved yet. The number of health facilities able to diagnose and treat HAT expanded (+9.6% compared to a 2019 survey), thus reinforcing the capacity for passive detection and improving epidemiological knowledge of the disease. Active surveillance for gambiense HAT was sustained. In particular, 2.8 million people were actively screened in 2019 and 1.6 million in 2020, the decrease in 2020 being mainly caused by COVID-19-related restrictions. Togo and Côte d’Ivoire were the first countries to be validated for achieving elimination of HAT as a public health problem at the national level; applications from three additional countries are under review by the World Health Organization (WHO).Conclusions/significanceThe steady progress towards the elimination of HAT is a testament to the power of multi-stakeholder commitment and coordination. At the end of 2020, the World Health Assembly endorsed a new road map for 2021–2030 that set new bold targets for neglected tropical diseases. While rhodesiense HAT remains among the diseases targeted for elimination as a public health problem, gambiense HAT is targeted for elimination of transmission. The goal for gambiense HAT is expected to be particularly arduous, as it might be hindered by cryptic reservoirs and a number of other challenges (e.g. further integration of HAT surveillance and control into national health systems, availability of skilled health care workers, development of more effective and adapted tools, and funding for and coordination of elimination efforts).     

Estimating and Mapping the Population at Risk of Sleeping Sickness

Background

Human African trypanosomiasis (HAT), also known as sleeping sickness, persists as a public health problem in several sub-Saharan countries. Evidence-based, spatially explicit estimates of population at risk are needed to inform planning and implementation of field interventions, monitor disease trends, raise awareness and support advocacy. Comprehensive, geo-referenced epidemiological records from HAT-affected countries were combined with human population layers to map five categories of risk, ranging from “very high” to “very low,” and to estimate the corresponding at-risk population.

Results

Approximately 70 million people distributed over a surface of 1.55 million km² are estimated to be at different levels of risk of contracting HAT. Trypanosoma brucei gambiense accounts for 82.2% of the population at risk, the remaining 17.8% being at risk of infection from T. b. rhodesiense. Twenty-one million people live in areas classified as moderate to very high risk, where more than 1 HAT case per 10,000 inhabitants per annum is reported.

Discussion

Updated estimates of the population at risk of sleeping sickness were made, based on quantitative information on the reported cases and the geographic distribution of human population. Due to substantial methodological differences, it is not possible to make direct comparisons with previous figures for at-risk population. By contrast, it will be possible to explore trends in the future. The presented maps of different HAT risk levels will help to develop site-specific strategies for control and surveillance, and to monitor progress achieved by ongoing efforts aimed at the elimination of sleeping sickness.     

Accelerating elimination of sleeping sickness from the Guinean littoral through enhanced screening in the post-Ebola context: A retrospective analysis

BackgroundActivities to control human African trypanosomiasis (HAT) in Guinea were severely hampered by the Ebola epidemic that hit this country between 2014 and 2016. Active screening was completely interrupted and passive screening could only be maintained in a few health facilities. At the end of the epidemic, medical interventions were progressively intensified to mitigate the risk of HAT resurgence and progress towards disease elimination.Methodology/Principal findingsA retrospective analysis was performed to evaluate the medical activities that were implemented in the three most endemic prefectures of Guinea (Boffa, Dubreka and Forecariah) between January 2016 and December 2018. Passive screening using rapid diagnostic tests (RDTs) was progressively resumed in one hundred and one health facilities, and active screening was intensified by visiting individual households and performing RDTs, and by conducting mass screening in villages by mobile teams using the Card Agglutination Test for Trypanosomiasis. A total of 1885, 4897 and 8023 clinical suspects were tested in passive, while 5743, 14442 and 21093 people were actively screened in 2016, 2017 and 2018, respectively. The number of HAT cases that were diagnosed first went up from 107 in 2016 to 140 in 2017, then subsequently decreased to only 73 in 2018. A progressive decrease in disease prevalence was observed in the populations that were tested in active and in passive between 2016 and 2018.Conclusions/SignificanceIntensified medical interventions in the post-Ebola context first resulted in an increase in the number of HAT cases, confirming the fear that the disease could resurge as a result of impaired control activities during the Ebola epidemic. On the other hand, the decrease in disease prevalence that was observed between 2016 and 2018 is encouraging, as it suggests that the current strategy combining enhanced diagnosis, treatment and vector control is appropriate to progress towards elimination of HAT in Guinea.     

Assessing Progress in Reducing the At-Risk Population after 13 Years of the Global Programme to Eliminate Lymphatic Filariasis

Background

In 1997, the World Health Assembly adopted Resolution 50.29, committing to the elimination of lymphatic filariasis (LF) as a public health problem, subsequently targeted for 2020. The initial estimates were that 1.2 billion people were at-risk for LF infection globally. Now, 13 years after the Global Programme to Eliminate Lymphatic Filariasis (GPELF) began implementing mass drug administration (MDA) against LF in 2000—during which over 4.4 billion treatments have been distributed in 56 endemic countries—it is most appropriate to estimate the impact that the MDA has had on reducing the population at risk of LF.

Methodology/Principal Findings

To assess GPELF progress in reducing the population at-risk for LF, we developed a model based on defining reductions in risk of infection among cohorts of treated populations following each round of MDA. The model estimates that the number of people currently at risk of infection decreased by 46% to 789 million through 2012.

Conclusions/Significance

Important progress has been made in the global efforts to eliminate LF, but significant scale-up is required over the next 8 years to reach the 2020 elimination goal.     

Revisiting the immune trypanolysis test to optimise epidemiological surveillance and control of sleeping sickness in West Africa

Background

Because of its high sensitivity and its ease of use in the field, the card agglutination test for trypanosomiasis (CATT) is widely used for mass screening of sleeping sickness. However, the CATT exhibits false-positive results (i) raising the question of whether CATT-positive subjects who are negative in parasitology are truly exposed to infection and (ii) making it difficult to evaluate whether Trypanosoma brucei (T.b.) gambiense is still circulating in areas of low endemicity. The objective of this study was to assess the value of the immune trypanolysis test (TL) in characterising the HAT status of CATT-positive subjects and to monitor HAT elimination in West Africa.

Methodology/Principal Findings

TL was performed on plasma collected from CATT-positive persons identified within medical surveys in several West African HAT foci in Guinea, Côte d''Ivoire and Burkina Faso with diverse epidemiological statuses (active, latent, or historical). All HAT cases were TL+. All subjects living in a nonendemic area were TL−. CATT prevalence was not correlated with HAT prevalence in the study areas, whereas a significant correlation was found using TL.

Conclusion and Significance

TL appears to be a marker for contact with T.b. gambiense. TL can be a tool (i) at an individual level to identify nonparasitologically confirmed CATT-positive subjects as well as those who had contact with T.b. gambiense and should be followed up, (ii) at a population level to identify priority areas for intervention, and (iii) in the context of HAT elimination to identify areas free of HAT.     

Case Based Measles Surveillance in Pune: Evidence to Guide Current and Future Measles Control and Elimination Efforts in India

Background

According to WHO estimates, 35% of global measles deaths in 2011 occurred in India. In 2013, India committed to a goal of measles elimination by 2020. Laboratory supported case based measles surveillance is an essential component of measles elimination strategies. Results from a case-based measles surveillance system in Pune district (November 2009 through December 2011) are reported here with wider implications for measles elimination efforts in India.

Methods

Standard protocols were followed for case identification, investigation and classification. Suspected measles cases were confirmed through serology (IgM) or epidemiological linkage or clinical presentation. Data regarding age, sex, vaccination status were collected and annualized incidence rates for measles and rubella cases calculated.

Results

Of the 1011 suspected measles cases reported to the surveillance system, 76% were confirmed measles, 6% were confirmed rubella, and 17% were non-measles, non-rubella cases. Of the confirmed measles cases, 95% were less than 15 years of age. Annual measles incidence rate was more than 250 per million persons and nearly half were associated with outbreaks. Thirty-nine per cent of the confirmed measles cases were vaccinated with one dose of measles vaccine (MCV1).

Conclusion

Surveillance demonstrated high measles incidence and frequent outbreaks in Pune where MCV1 coverage in infants was above 90%. Results indicate that even high coverage with a single dose of measles vaccine was insufficient to provide population protection and prevent measles outbreaks. An effective measles and rubella surveillance system provides essential information to plan, implement and evaluate measles immunization strategies and monitor progress towards measles elimination.     

Mapping of schistosomiasis and soil-transmitted helminthiases across 15 provinces of Angola

IntroductionSchistosomiasis (SCH) and soil transmitted helminthiases (STH) have been historically recognized as a major public health problem in Angola. However, lack of reliable, country wide prevalence data on these diseases has been a major hurdle to plan and implement programme actions to target these diseases. This study aimed to characterize SCH and STH prevalence and distribution in Angola.MethodsA country wide mapping was conducted in October 2018 (1 province) and from July to December 2019 (14 provinces) in school aged (SAC) children in 15 (of 18) provinces in Angola, using WHO protocols and procedures. A total of 640 schools and an average of 50 students per school (N = 31,938 children) were sampled. Stool and urine samples were collected and processed using the Kato-Katz method and Urine Filtration. Prevalence estimates for SCH and STH infections were calculated for each province and district with 95% confidence intervals. Factors associated with SCH and STH infection, respectively, were explored using multivariable logistic regression accounting for clustering by school.ResultsOf the 131 districts surveyed, 112 (85.5%) are endemic for STH, 30 (22.9%) have a prevalence above 50%, 24 (18.3%) are at moderate risk (prevalence 20%-50%), and 58 (44.3%) are at low risk (<20% prevalence); similarly, 118 (90,1%) of surveyed districts are endemic for any SCH, 2 (1.5%) are at high risk (>50% prevalence), 59 (45.0%) are at moderate risk (10%-50% prevalence), and 57 (43.5%) are at low risk (<10% prevalence). There were higher STH infection rates in the northern provinces of Malanje and Lunda Norte, and higher SCH infection rates in the southern provinces of Benguela and Huila.ConclusionsThis mapping exercise provides essential information to Ministry of Health in Angola to accurately plan and implement SCH and STH control activities in the upcoming years. Data also provides a useful baseline contribution for Angola to track its progress towards the 2030 NTD roadmap targets set by WHO.     

Burden of congenital rubella syndrome (CRS) in India based on data from cross-sectional serosurveys, 2017 and 2019–20

BackgroundIndia has set a goal to eliminate measles and rubella/Congenital Rubella Syndrome (CRS) by 2023. Towards this goal, India conducted nationwide supplementary immunization activity (SIA) with measles-rubella containing vaccine (MRCV) targeting children aged between 9 months to <15 years and established a hospital-based sentinel surveillance for CRS. Reliable data about incidence of CRS is necessary to monitor progress towards the elimination goal.MethodsWe conducted serosurveys in 2019–20 among pregnant women attending antenatal clinics of 6 hospitals, which were also sentinel sites for CRS surveillance, to estimate the prevalence of IgG antibodies against rubella. We systematically sampled 1800 women attending antenatal clinics and tested their sera for IgG antibodies against rubella. We used rubella seroprevalence data from the current survey and the survey conducted in 2017 among antenatal women from another 6 CRS surveillance sites to construct a catalytic models to estimate the incidence and burden of CRS.ResultThe seroprevalence of rubella antibodies was 82.3% (95% CI: 80.4–84.0). Rubella seropositivity did not differ by age group and educational status. Based on the constant and age-dependent force of infection models, we estimated that the annual incidence of CRS in India was 225.58 per 100,000 live births (95% CI: 217.49–232.41) and 65.47 per 100,000 live births (95% CI: 41.60–104.16) respectively. This translated to an estimated 14,520 (95% CI: 9,225–23,100) and 50,028 (95% CI: 48,234–51,543) infants with CRS every year based on age-dependent and constant force of infection models respectively.ConclusionsOur findings indicated that about one fifth of women in the reproductive age group in India were susceptible for rubella. The estimates of CRS incidence will serve as a baseline to monitor the impact of MRCV SIAs, as well progress towards the elimination goal of rubella/CRS.     

Eradication of Yaws: Historical Efforts and Achieving WHO's 2020 Target

Background

Yaws, one of the 17 neglected tropical diseases (NTDs), is targeted for eradication by 2020 in resolution WHA66.12 of the World Health Assembly (2013) and the WHO roadmap on NTDs (2012). The disease frequently affects children who live in poor socioeconomic conditions. Between 1952 and 1964, WHO and the United Nations Children''s Fund (UNICEF) led a global eradication campaign using injectable benzathine penicillin. Recent developments using a single dose of oral azithromycin have renewed optimism that eradication can be achieved through a comprehensive large-scale treatment strategy. We review historical efforts to eradicate yaws and argue that this goal is now technically feasible using new tools and with the favorable environment for control of NTDs. We also summarize the work of WHO''s Department of Control of Neglected Tropical Diseases in leading the renewed eradication initiative and call on the international community to support efforts to achieve the 2020 eradication goal. The critical factor remains access to azithromycin. Excluding medicines, the financial cost of yaws eradication could be as little as US$ 100 million.

Conclusions

The development of new tools has renewed interest in eradication of yaws; with modest support, the WHO eradication target of 2020 can be achieved.     

Applicability and cost-effectiveness of the Systolic Blood Pressure Intervention Trial (SPRINT) in the Chinese population: A cost-effectiveness modeling study

BackgroundThe Systolic Blood Pressure Intervention Trial (SPRINT) showed significant reductions in death and cardiovascular disease (CVD) risk with a systolic blood pressure (SBP) goal of <120 mm Hg compared with a SBP goal of <140 mm Hg. Our study aimed to assess the applicability of SPRINT to Chinese adults. Additionally, we sought to predict the medical and economic implications of this intensive SBP treatment among those meeting SPRINT eligibility.Methods and findingsWe used nationally representative baseline data from the China Health and Retirement Longitudinal Study (CHARLS) (2011–2012) to estimate the prevalence and number of Chinese adults aged 45 years and older who meet SPRINT criteria. A validated microsimulation model was employed to project costs, clinical outcomes, and quality-adjusted life-years (QALYs) among SPRINT-eligible adults, under 2 alternative treatment strategies (SBP goal of <120 mm Hg [intensive treatment] and SBP goal of <140 mm Hg [standard treatment]). Overall, 22.2% met the SPRINT criteria, representing 116.2 (95% CI 107.5 to 124.8) million people in China. Of these, 66.4%, representing 77.2 (95% CI 69.3 to 85.0) million, were not being treated for hypertension, and 22.9%, representing 26.6 (95% CI 22.4 to 30.7) million, had a SBP between 130 and 139 mm Hg, yet were not taking antihypertensive medication. We estimated that over 5 years, compared to standard treatment, intensive treatment would reduce heart failure incidence by 0.84 (95% CI 0.42 to 1.25) million cases, reduce CVD deaths by 2.03 (95% CI 1.44 to 2.63) million cases, and save 3.84 (95% CI 1.53 to 6.34) million life-years. Estimated reductions of 0.069 (95% CI −0.28, 0.42) million myocardial infarction cases and 0.36 (95% CI −0.10, 0.82) million stroke cases were not statistically significant. Furthermore, over a lifetime, moving from standard to intensive treatment increased the mean QALYs from 9.51 to 9.87 (an increment of 0.38 [95% CI 0.13 to 0.71]), at a cost of Int$10,997 per QALY gained. Of all 1-way sensitivity analyses, high antihypertensive drug cost and lower treatment efficacy for CVD death resulted in the 2 most unfavorable results (Int$25,291 and Int$18,995 per QALY were gained, respectively). Simulation results indicated that intensive treatment could be cost-effective (82.8% probability of being below the willingness-to-pay threshold of Int$16,782 [1× GDP per capita in China in 2017]), with a lower probability in people with SBP 130–139 mm Hg (72.9%) but a higher probability among females (91.2%). Main limitations include lack of specific SPRINT eligibility information in the CHARLS survey, uncertainty about the implications of different blood pressure measurement techniques, the use of several sources of data with large reliance on findings from SPPRINT, limited information about the serious adverse event rate, and lack of information and evidence for medication effectiveness on renal disease.ConclusionsAlthough adoption of the SPRINT treatment strategy would increase the number of Chinese adults requiring SBP treatment intensification, this approach has the potential to prevent CVD events, to produce gains in life-years, and to be cost-effective under common thresholds.

Tao Chen and colleagues estimate the cost-effectiveness of intensive blood pressure intervention in Chinese populations at high risk for cardiovascular disease.     

Establishing and Applying a Schistosomiasis Early Warning Index (SEWI) in the Lower Yangtze River Region of Jiangsu Province,China

Background

China has made remarkable progress in schistosomiasis control over the past decades. Transmission control has replaced morbidity control as the country moves towards the goal of elimination and the current challenge is to find a sensitive measure capable of gauging transmission risk in low-prevalence areas. The study aims to develop a Schistosomiasis Early Warning Index (SEWI) and demonstrate its use in Jiangsu Province along the lower Yangtze River.

Methodology/Principal Findings

The Delphi approach, a structured communication technique, was used to develop the SEWI. Two rounds of interviews with 30 public health experts specialized in schistosomiasis control were conducted using 40 indicators that reflected different aspects of schistosomiasis transmission and control. The necessity, feasibility, and sensitivity of each indicator were assessed and the weight value of each indicator determined based on these experts'' judgment. The system included 3 first-order indicators, 7 second-order indicators, and 30 third-order indicators. The 3 first-order indicators were endemic status, control measures, social and environmental factors, with the weight values 0.366, 0.343 and 0.291, respectively. For the 7 second-order indicators, the highest weight value was for control measures for snails (0.175) and the lowest for transmission route (0.110). We estimated and mapped the SEWI for endemic areas at the county scale in Jiangsu Province finding that the majority of the endemic areas were characterized as medium transmission risk (SEWI risk values between 0.3 and 0.6), while areas where transmission interruption had been officially declared showed SEWI values <0.30. A few isolated areas (e.g. endemic islands in the Yangtze River) produced SEWI values >0.60. These estimates are largely in agreement with the endemicity levels based on recent epidemiological surveys.

Conclusions/Significance

The SEWI should be useful for estimation of schistosomiasis transmission surveillance, particularly with reference to the elimination of the disease in China.     

Diagnostic testing holds the key to NTD elimination

“Fit-for-purpose” diagnostic tests have emerged as a prerequisite to achieving global targets for the prevention, control, elimination, and eradication of neglected tropical diseases (NTDs), as highlighted by the World Health Organization’s (WHO) new roadmap. There is an urgent need for the development of new tools for those diseases for which no diagnostics currently exist and for improvement of existing diagnostics for the remaining diseases. Yet, efforts to achieve this, and other crosscutting ambitions, are fragmented, and the burden of these 20 debilitating diseases immense. Compounded by the Coronavirus Disease 2019 (COVID-19) pandemic, programmatic interruptions, systemic weaknesses, limited investment, and poor commercial viability undermine global efforts—with a lack of coordination between partners, leading to the duplication and potential waste of scant resources. Recognizing the pivotal role of diagnostic testing and the ambition of WHO, to move forward, we must create an ecosystem that prioritizes country-level action, collaboration, creativity, and commitment to new levels of visibility. Only then can we start to accelerate progress and make new gains that move the world closer to the end of NTDs.

Ahead of the second-ever World Neglected Tropical Disease (NTD) Day in January 2021, and amid the global Coronavirus Disease 2019 (COVID-19) crisis, the World Health Organization (WHO) launched a new roadmap for the prevention, control, elimination, and eradication of NTDs—a group of 20 diseases affecting more than one billion people worldwide [1]. Diagnostic testing is central to safeguarding decades of progress in NTDs and must be strategically leveraged to reach the goals laid out in the new NTD roadmap.Stepping back, we recognize the massive progress that has been made to combat NTDs. Today, 500 million fewer people need treatment for these debilitating diseases than in 2010, and 40 countries or areas have eliminated at least one of the 20 [1]. Yet, despite these gains, NTDs continue to impose a devastating human, social, and economic toll on the world’s poorest and most vulnerable communities [2–6]. COVID-19 is compounding the situation by wreaking havoc on health systems, which impacts progress on NTDs: this includes interruptions to mass treatment campaigns for diseases controlled through preventive chemotherapy (PCT) or individual case management interventions, as well as rerouting the already sparse available funding and resources [7].Diagnostic testing has been central to the COVID-19 response even with the introduction of vaccines. The rapid ramp up of research and development (R&D), the scaling up of low-cost and decentralized testing, and country-led approaches to tailored testing strategies for COVID-19, as well as lessons learned, can also provide new thinking around testing for NTDs. The new NTD roadmap offers a series of multisectoral actions and intensified, cross-cutting approaches to get us back on track—with diagnostics central to unlocking and accelerating this progress [1].However, the NTD roadmap shows that, of all 20 diseases or disease groups, just 2 (yaws and snakebite envenoming) are supported by adequate and accessible diagnostic tools. Six have no diagnostic tests available at all, with tools for each of the remaining conditions in urgent need of adaptation, modification, and/or improved accessibility (likely a more cost-effective option than the development of new diagnostics for these NTDs) [1]. This has to change. NTDs cannot continue to be neglected in favor of other competing priorities, or we risk losing the progress made to date.Until the COVID-19 pandemic thrust testing into the spotlight, diagnostics have been a “silent partner” in healthcare, receiving little by way of international attention and funding, specific country strategies, and dedicated budget lines. NTDs are no exception. Just 5% of the (limited) funding made available to NTDs has been invested in new diagnostics, compared with 44% and 39% on basic research and medicines and vaccines, respectively [1]. For most NTDs, diagnostics are a market failure situation, and as such, are not commercially viable enough to attract private investment. Consequently, very few diagnostic developers engage in this area—contrary, for example, to COVID-19, where developers are in the hundreds. Furthermore, as some diseases approach the last mile of elimination, falling infection rates precipitate the need for increasingly sensitive tests [1]. But progress in R&D is slow and fragmented, with a lack of engagement and coordination between governments, industry, donors, and development actors, leading to the duplication—and potential waste—of scant resources. While serial testing using multiple diagnostic tools or techniques can compensate for low sensitivity [8], such approaches are associated with increased costs of testing, sample collection, and transportation.Closing the diagnostic gap then, is a prerequisite to achieving the global ambition for NTDs, with the new NTD roadmap giving a blueprint for action. It is for this reason that we call on governments, industry, donors, and development actors to

• Prioritize country-level diagnostic action: As we enter a new era in NTD management and control, we need to shift from traditional, donor-led models to country-driven initiatives. Government ministries must engage with, and advocate on behalf of, their poorest and most vulnerable populations so that no one is left behind. Political frameworks should prioritize diagnostics for NTDs in line with local disease burdens, and as part of fully funded, national health action plans that include a commitment to seeing the process through. Capacity building for diagnostics is also essential at country, sub-regional, and regional levels, including the establishment of laboratory networks, so that testing can be implemented in field settings.
• Collaborate and create: There is never going to be a one-size-fits-all for NTD diagnostics. If targets are to be achieved, we need global frameworks that enable industry, manufacturers, and pharmaceutical companies to engage in the whole process, from R&D to supply chain logistics. Companies need to share knowledge, learnings, and innovation across multiple diseases. This will mean breaking silos and finding new ways to harness the power of existing products, technologies, and infrastructures. Further, it will mean creating economies of scale through regional manufacturing hubs and finding new, cross-cutting approaches to drive systemic change. To obtain the maximum access to technology and relevant intellectual property rights for NTD diagnostics, it is important to ensure that such rights are broadly available (non-exclusively) in NTD-endemic countries and are affordable (e.g., zero royalty rights).
• Commit to new levels of visibility: The resources needed to realize that this ambition is limited, with a lack of visibility around the diagnostic landscape undermining progress in NTD management and control. Creating an ecosystem with visibility, transparency, and integration at its core will help streamline programmatic action, reduce the risk of duplication, and leverage the full potential from this limited pool. To do this, industry, donors, and other development actors must provide the information needed to map both funding and product landscapes. Using this information to create a virtual product pipeline will bring an unprecedented level of transparency to diagnostic developments—harmonizing multisectoral efforts and creating a robust information platform from which new collaborations, synergies, and innovation can grow. Developing an online open-access diagnostic pipeline for WHO NTD roadmap priority pathogens would serve multiple purposes: (i) drive advocacy to address critical product and funding gaps; and (ii) reduce the likelihood of duplication of efforts. Together, this would strengthen partnerships across all stakeholders, from donors to industry partners, to accelerate development, evaluation, and adoption of diagnostic solutions for NTDs. The newly established NTD Diagnostic Technical Advisory Group (DTAG) to WHO NTD department has already identified the priority diagnostic needs for NTD programs not only in terms of developing new tools, but also the accessibility of existing tools [9]. Several sub-groups that focus more narrowly on single diseases or specific topics (i.e., skin NTDs or cross-cutting) have been established and have been tasked to develop tool and biomarker agnostic target product profiles (TPPs), which are now available (for the most part) on WHO website for use by any diagnostic manufacturer to support development of their specific technology. Alignment with these diagnostic priorities by all stakeholders is strongly recommended to facilitate attainment of WHO 2030 NTD roadmap goals.

• Establish NTD biobanks: Biobanks are required for the clinical evaluation and validation of new diagnostic tests. Establishing local biobanks would support a country-driven approach as well as allowing for head-to-head comparisons between tests and assessments of cross-reactivity across different NTDs.
• Invest in existing diagnostics: The development of new diagnostics is a complex process, and the time from development to implementation can be lengthy. Training laboratory staff in the use of existing diagnostics and the establishment of robust quality control systems are effective approaches to achieving shorter-term improvements.

There is a long road ahead, but the past 10 years have shown us what can be achieved when governments, industry, donors, and development actors are bound by a shared, global goal. As we look forward to the next decade, we must prioritize country-level action, collaboration, creativity, and commitment to new levels of visibility, if we are to finally end the neglect of NTDs.     

The burden of skin disease and eye disease due to onchocerciasis in countries formerly under the African Programme for Onchocerciasis Control mandate for 1990, 2020, and 2030

BackgroundOnchocerciasis (“river blindness”) can cause severe morbidity, including vision loss and various skin manifestations, and is targeted for elimination using ivermectin mass drug administration (MDA). We calculated the number of people with Onchocerca volvulus infection and onchocercal skin and eye disease as well as disability-adjusted life years (DALYs) lost from 1990 through to 2030 in areas formerly covered by the African Programme for Onchocerciasis Control.MethodsPer MDA implementation unit, we collated data on the pre-control distribution of microfilariae (mf) prevalence and the history of control. Next, we predicted trends in infection and morbidity over time using the ONCHOSIM simulation model. DALY estimates were calculated using disability weights from the Global Burden of Disease Study.ResultsIn 1990, prior to MDA implementation, the total population at risk was 79.8 million with 26.0 million (32.5%) mf-positive individuals, of whom 17.5 million (21.9%) had some form of onchocercal skin or eye disease (2.5 million DALYs lost). By 2030, the total population was predicted to increase to 236.1 million, while the number of mf-positive cases (about 6.8 million, 2.9%), people with skin or eye morbidity (4.2 million, 1.8%), and DALYs lost (0.7 million) were predicted to decline.ConclusionsMDA has had a remarkable impact on the onchocerciasis burden in countries previously under the APOC mandate. In the few countries where we predict continued transmission between now and 2030, intensified MDA could be combined with local vector control efforts, or the introduction of new drugs for mopping up residual cases of infection and morbidity.     

Congo polio immunisation campaign gets go ahead

Since the World Health Organization (WHO) set a goal in 1988 of eradicating polio worldwide by 2000, the incidence of the disease has declined by 90% around the world, with national immunization days conducted in more than 120 countries. More than 450 million children were immunized in 1998 alone. Now, with only about 5000 annual cases of polio occurring, complete eradication can be achieved. To that end, and in a first-ever initiative, the heads of the World Health Organization (WHO) and UNICEF, jointly appealed to UN Secretary General Kofi Annan for help in bringing immunization against polio to children in war-torn Democratic Republic of Congo. Mr. Annan subsequently announced an initiative to negotiate several special ceasefire agreements in Congo so that approximately 10 million children under age 5 years can be immunized against poliomyelitis during July-September 1999. Both the president of Congo, Laurent Kabila, and rebel leaders have given their preliminary assurances that weapons will be laid down while Congolese children are sought out and vaccinated. A joint WHO-UNICEF planning mission will travel to Kinshasa in April to advise the Congolese Ministry of Health, which has main responsibility for the areas under governmental control. The $15 million project is expected to cover 3 rounds of immunization to bring population immunity to the highest possible level.     

A Literature Review of Economic Evaluations for a Neglected Tropical Disease: Human African Trypanosomiasis (“Sleeping Sickness”)

Human African trypanosomiasis (HAT) is a disease caused by infection with the parasite Trypanosoma brucei gambiense or T. b. rhodesiense. It is transmitted to humans via the tsetse fly. Approximately 70 million people worldwide were at risk of infection in 1995, and approximately 20,000 people across Africa are infected with HAT. The objective of this review was to identify existing economic evaluations in order to summarise cost-effective interventions to reduce, control, or eliminate the burden of HAT. The studies included in the review were compared and critically appraised in order to determine if there were existing standardised methods that could be used for economic evaluation of HAT interventions or if innovative methodological approaches are warranted. A search strategy was developed using keywords and was implemented in January 2014 in several databases. The search returned a total of 2,283 articles. After two levels of screening, a total of seven economic evaluations were included and underwent critical appraisal using the Scottish Intercollegiate Guidelines Network (SIGN) Methodology Checklist 6: Economic Evaluations. Results from the existing studies focused on the cost-effectiveness of interventions for the control and reduction of disease transmission. Modelling was a common method to forecast long-term results, and publications focused on interventions by category, such as case detection, diagnostics, drug treatments, and vector control. Most interventions were considered cost-effective based on the thresholds described; however, the current treatment, nifurtomix-eflornithine combination therapy (NECT), has not been evaluated for cost-effectiveness, and considerations for cost-effective strategies for elimination have yet to be completed. Overall, the current evidence highlights the main components that play a role in control; however, economic evaluations of HAT elimination strategies are needed to assist national decision makers, stakeholders, and key funders. These analyses would be of use, as HAT is currently being prioritized as a neglected tropical disease (NTD) to reach elimination by 2020.     

Estimating Geographical Variation in the Risk of Zoonotic Plasmodium knowlesi Infection in Countries Eliminating Malaria

BackgroundInfection by the simian malaria parasite, Plasmodium knowlesi, can lead to severe and fatal disease in humans, and is the most common cause of malaria in parts of Malaysia. Despite being a serious public health concern, the geographical distribution of P. knowlesi malaria risk is poorly understood because the parasite is often misidentified as one of the human malarias. Human cases have been confirmed in at least nine Southeast Asian countries, many of which are making progress towards eliminating the human malarias. Understanding the geographical distribution of P. knowlesi is important for identifying areas where malaria transmission will continue after the human malarias have been eliminated.Conclusions/SignificanceWe have produced the first map of P. knowlesi malaria risk, at a fine-scale resolution, to identify priority areas for surveillance based on regions with sparse data and high estimated risk. Our map provides an initial evidence base to better understand the spatial distribution of this disease and its potential wider contribution to malaria incidence. Considering malaria elimination goals, areas for prioritised surveillance are identified.     

Development of Self-Management Indicators for Chronic Hepatitis B Patients on Antiviral Therapy: Results of a Chinese Delphi Panel Survey

ObjectiveThis study aimed to develop a set of indicators that could be used to measure and monitor the self-management performance for chronic hepatitis B (CHB) patients on antiviral therapy in China.MethodsA two-round Delphi study via e-mail correspondence was conducted, with a group of 30 Chinese experts. The Delphi questionnaire consisted of 53 indicators identified from a literature review. Experts rated and scored the importance of indicators on a five-point Likert scale. Consensus was considered to be reached if a median score in the top tertile (4-5) and ≥80% of panel ratings in the top tertile (4-5) after Round 2. The included indicators were validated with a group of 106 CHB patients.ResultsThe response rates for the first and second rounds were 90.9% (n=30) and 86.7% (n=26), respectively. Three new indicators were suggested in the first round. 55 indicators were included in the second round after modified. 45 (81.8%) indicators achieved on the level of consensus, all of which had an inter-quartile range of 1 or below. The final set included 4 domains and 45 indicators which were well accepted and understandable by CHB patients.ConclusionThis Delphi study produced a set of 45 self-management indicators for CHB patients on antiviral therapy in China. These indicators could be used to measure and monitor the patients’ self-management performance, with the goal of improving the quality of life in this population.     

The Availability and Consistency of Dengue Surveillance Data Provided Online by the World Health Organization

Background

The use of high quality disease surveillance data has become increasingly important for public health action against new threats. In response, countries have developed a wide range of disease surveillance systems enabled by technological advancements. The heterogeneity and complexity of country data systems have caused a growing need for international organizations such as the World Health Organization (WHO) to coordinate the standardization, integration, and dissemination of country disease data at the global level for research and policy. The availability and consistency of currently available disease surveillance data at the global level are unclear. We investigated this for dengue surveillance data provided online by the WHO.

Methods and Findings

We extracted all dengue surveillance data provided online by WHO Headquarters and Regional Offices (RO’s). We assessed the availability and consistency of these data by comparing indicators within and between sources. We also assessed the consistency of dengue data provided online by two example countries (Brazil and Indonesia). Data were available from WHO for 100 countries since 1955 representing a total of 23 million dengue cases and 82 thousand deaths ever reported to WHO. The availability of data on DengueNet and some RO’s declined dramatically after 2005. Consistency was lacking between sources (84% across all indicators representing a discrepancy of almost half a million cases). Within sources, data at high spatial resolution were often incomplete.

Conclusions

The decline of publicly available, integrated dengue surveillance data at the global level will limit opportunities for research, policy, and advocacy. A new financial and operational framework will be necessary for innovation and for the continued availability of integrated country disease data at the global level.     

Diversity of response to Trypanosoma brucei gambiense infections in the Forecariah mangrove focus (Guinea): perspectives for a better control of sleeping sickness

At a time when human African trypanosomiasis (HAT) elimination again seems a reachable goal in many parts of sub-Saharan Africa, it is becoming increasingly important to characterise the factors involved in disease resurgence or maintenance to develop sustainable control strategies. In this study conducted in the Forecariah mangrove focus in Guinea, HAT patients and serological suspects (SERO) were identified through mass screening of the population with the Card Agglutination Test for Trypanosomiasis (CATT) and were followed up for up to 2 years. Analysis of the samples collected during the follow-up of HAT patients and SERO was performed with PCR (TBR1/TBR2) and the trypanolysis serological test (TL) in order to clarify the role played by these individuals in the epidemiology of HAT. PCR positivity was higher in TL⁺ than in SERO TL⁻ (50% vs. 18%, respectively). Whereas CATT plasma titres decreased both in treated HAT patients and SERO TL⁻, SERO TL⁺ maintained high CATT titres. Four out of 17 SERO TL⁺ developed HAT during the study. These results strongly suggest that SERO TL⁺ individuals are asymptomatic carriers. In the context where disease prevalence is sufficiently low, treating SERO TL⁺ individual may thus be of crucial importance in order to cut transmission.     

Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting

Background

Quantifying sexually transmitted infection (STI) prevalence and incidence is important for planning interventions and advocating for resources. The World Health Organization (WHO) periodically estimates global and regional prevalence and incidence of four curable STIs: chlamydia, gonorrhoea, trichomoniasis and syphilis.

Methods and Findings

WHO’s 2012 estimates were based upon literature reviews of prevalence data from 2005 through 2012 among general populations for genitourinary infection with chlamydia, gonorrhoea, and trichomoniasis, and nationally reported data on syphilis seroprevalence among antenatal care attendees. Data were standardized for laboratory test type, geography, age, and high risk subpopulations, and combined using a Bayesian meta-analytic approach. Regional incidence estimates were generated from prevalence estimates by adjusting for average duration of infection. In 2012, among women aged 15–49 years, the estimated global prevalence of chlamydia was 4.2% (95% uncertainty interval (UI): 3.7–4.7%), gonorrhoea 0.8% (0.6–1.0%), trichomoniasis 5.0% (4.0–6.4%), and syphilis 0.5% (0.4–0.6%); among men, estimated chlamydia prevalence was 2.7% (2.0–3.6%), gonorrhoea 0.6% (0.4–0.9%), trichomoniasis 0.6% (0.4–0.8%), and syphilis 0.48% (0.3–0.7%). These figures correspond to an estimated 131 million new cases of chlamydia (100–166 million), 78 million of gonorrhoea (53–110 million), 143 million of trichomoniasis (98–202 million), and 6 million of syphilis (4–8 million). Prevalence and incidence estimates varied by region and sex.

Conclusions

Estimates of the global prevalence and incidence of chlamydia, gonorrhoea, trichomoniasis, and syphilis in adult women and men remain high, with nearly one million new infections with curable STI each day. The estimates highlight the urgent need for the public health community to ensure that well-recognized effective interventions for STI prevention, screening, diagnosis, and treatment are made more widely available. Improved estimation methods are needed to allow use of more varied data and generation of estimates at the national level.