Julie Jacobson

Helminth infections: the great neglected tropical diseases

Helminths are parasitic worms. They are the most common infectious agents of humans in developing countries and produce a global burden of disease that exceeds better-known conditions, including malaria and tuberculosis. As we discuss here, new insights into fundamental helminth biology are accumulating through newly completed genome projects and the nascent application of transgenesis and RNA interference technologies. At the same time, our understanding of the dynamics of the transmission of helminths and the mechanisms of the Th2-type immune responses that are induced by infection with these parasitic worms has increased markedly. Ultimately, these advances in molecular and medical helminth biology should one day translate into a new and robust pipeline of drugs, diagnostics, and vaccines for targeting parasitic worms that infect humans.

Estimated global incidence of Japanese encephalitis: a systematic review.

OBJECTIVE To update the estimated global incidence of Japanese encephalitis (JE) using recent data for the purpose of guiding prevention and control efforts. METHODS Thirty-two areas endemic for JE in 24 Asian and Western Pacific countries were sorted into 10 incidence groups on the basis of published data and expert opinion. Population-based surveillance studies using laboratory-confirmed cases were sought for each incidence group by a computerized search of the scientific literature. When no eligible studies existed for a particular incidence group, incidence data were extrapolated from related groups. FINDINGS A total of 12 eligible studies representing 7 of 10 incidence groups in 24 JE-endemic countries were identified. Approximately 67,900 JE cases typically occur annually (overall incidence: 1.8 per 100,000), of which only about 10% are reported to the World Health Organization. Approximately 33,900 (50%) of these cases occur in China (excluding Taiwan) and approximately 51,000 (75%) occur in children aged 0-14 years (incidence: 5.4 per 100,000). Approximately 55,000 (81%) cases occur in areas with well established or developing JE vaccination programmes, while approximately 12,900 (19%) occur in areas with minimal or no JE vaccination programmes. CONCLUSION Recent data allowed us to refine the estimate of the global incidence of JE, which remains substantial despite improvements in vaccination coverage. More and better incidence studies in selected countries, particularly China and India, are needed to further refine these estimates.

Integration of Water, Sanitation, and Hygiene for the Prevention and Control of Neglected Tropical Diseases: A Rationale for Inter-Sectoral Collaboration

Improvements of water, sanitation, and hygiene (WASH) infrastructure and appropriate health-seeking behavior are necessary for achieving sustained control, elimination, or eradication of many neglected tropical diseases (NTDs). Indeed, the global strategies to fight NTDs include provision of WASH, but few programs have specific WASH targets and approaches. Collaboration between disease control programs and stakeholders in WASH is a critical next step. A group of stakeholders from the NTD control, child health, and WASH sectors convened in late 2012 to discuss opportunities for, and barriers to, collaboration. The group agreed on a common vision, namely “Disease-free communities that have adequate and equitable access to water and sanitation, and that practice good hygiene.” Four key areas of collaboration were identified, including (i) advocacy, policy, and communication; (ii) capacity building and training; (iii) mapping, data collection, and monitoring; and (iv) research. We discuss strategic opportunities and ways forward for enhanced collaboration between the WASH and the NTD sectors.

A Public Health Response against Strongyloides stercoralis: Time to Look at Soil-Transmitted Helminthiasis in Full

Strongyloides stercoralis infections have a worldwide distribution with a global burden in terms of prevalence and morbidity that is largely ignored. A public health response against soil-transmitted helminth (STH) infections should broaden the strategy to include S. stercoralis and overcome the epidemiological, diagnostic, and therapeutic challenges that this parasite poses in comparison to Ascaris lumbricoides, Trichuris trichiura, and hookworms. The relatively poor sensitivity of single stool evaluations, which is further lowered when quantitative techniques aimed at detecting eggs are used, also complicates morbidity evaluations and adequate drug efficacy measurements, since S. stercoralis is eliminated in stools in a larval stage. Specific stool techniques for the detection of larvae of S. stercoralis, like Baermanns and Kogas agar plate, despite superiority over direct techniques are still suboptimal. New serologies using recombinant antigens and molecular-based techniques offer new hopes in those areas. The use of ivermectin rather than benzimidazoles for its treatment and the need to have curative regimens rather than lowering the parasite burden are also unique for S. stercoralis in comparison to the other STH due to its life cycle, which allows reproduction and amplification of the worm burden within the human host. The potential impact on STH of the benzimidazoles/ivermectin combinations, already used for control/elimination of lymphatic filariasis, should be further evaluated in public health settings. While waiting for more effective single-dose drug regimens and new sensitive diagnostics, the evidence and the tools already available warrant the planning of a common platform for STH and S. stercoralis control.

Comparison of the immunogenicity and safety of measles vaccine administered alone or with live, attenuated Japanese encephalitis SA 14-14-2 vaccine in Philippine infants

Japanese encephalitis (JE) virus is a major cause of disease, disability, and death in Asia. An effective, live, attenuated JE vaccine (LJEV) is available; however, its use in routine immunization schedules is hampered by lack of data on concomitant administration with measles vaccine (MV). This study evaluated the immunogenicity and reactogenicity of LJEV and MV when administered at the same or separate study visits in infants younger than 1 year of age. Three groups of healthy infants were randomized to receive LJEV at age of 8 months and MV at 9 months (Group 1; n=100); MV and LJEV together at 9 months (Group 2; n=236); or MV and LJEV at 9 and 10 months, respectively (Group 3; n=235). Blood was obtained 4 weeks after each vaccine administration to determine antibody levels for measles and JE. Reactogenicity was assessed by parental diaries and clinic visits. Four weeks after immunization, measles seroprotection rates (defined as > or =340 mIU/ml) were high and comparable in all three groups and specifically, rates in the combined MV-LJEV (Group 2) were not statistically inferior to those in Group 3 receiving MV separately (96% versus 100%, respectively). Likewise, the LJEV seroprotection rates were high and similar between the three groups. The reactogenicity profiles of the three vaccine schedules were also analogous. LJEV and MV administered together are well tolerated and immunogenic in infants younger than 1 year. These results should facilitate incorporation of LJEV into routine immunization schedules with MV.

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.

Evidence and rationale for the World Health Organization recommended standards for Japanese encephalitis surveillance

BackgroundJapanese encephalitis (JE) is the most important form of viral encephalitis in Asia. Surveillance for the disease in many countries has been limited. To improve collection of accurate surveillance data in order to increase understanding of the full impact of JE and monitor control programs, World Health Organization (WHO) Recommended Standards for JE Surveillance have been developed. To aid acceptance of the Standards, we describe the process of development, provide the supporting evidence, and explain the rationale for the recommendations made in the document.MethodsA JE Core Working Group was formed in 2002 and worked on development of JE surveillance standards. A series of questions on specific topics was initially developed. A literature review was undertaken and the findings were discussed and documented. The group then prepared a draft document, with emphasis placed on the feasibility of implementation in Asian countries. A field test version of the Standards was published by WHO in January 2006. Feedback was then sought from countries that piloted the Standards and from public health professionals in forums and individual meetings to modify the Standards accordingly.ResultsAfter revisions, a final version of the JE surveillance standards was published in August 2008. The supporting information is presented here together with explanations of the rationale and levels of evidence for specific recommendations.ConclusionProvision of the supporting evidence and rationale should help to facilitate successful implementation of the JE surveillance standards in JE-endemic countries which will in turn enable better understanding of disease burden and the impact of control programs.

Between-Country Inequalities in the Neglected Tropical Disease Burden in 1990 and 2010, with Projections for 2020

Background The World Health Organization (WHO) has set ambitious time-bound targets for the control and elimination of neglected tropical diseases (NTDs). Investing in NTDs is not only seen as good value for money, but is also advocated as a pro-poor policy since it would improve population health in the poorest populations. We studied the extent to which the disease burden from nine NTDs (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths, trachoma, Chagas disease, human African trypanosomiasis, leprosy, visceral leishmaniasis) was concentrated in the poorest countries in 1990 and 2010, and how this would change by 2020 in case the WHO targets are met. Principal Findings Our analysis was based on 1990 and 2010 data from the Global Burden of Disease (GBD) 2010 study and on projections of the 2020 burden. Low and lower-middle income countries together accounted for 69% and 81% of the global burden in 1990 and 2010 respectively. Only the soil-transmitted helminths and Chagas disease caused a considerable burden in upper-middle income countries. The global burden from these NTDs declined by 27% between 1990 and 2010, but reduction largely came to the benefit of upper-middle income countries. Achieving the WHO targets would lead to a further 55% reduction in the global burden between 2010 and 2020 in each country income group, and 81% of the global reduction would occur in low and lower-middle income countries. Conclusions The GBD 2010 data show the burden of the nine selected NTDs in DALYs is strongly concentrated in low and lower-middle income countries, which implies that the beneficial impact of NTD control eventually also largely comes to the benefit of these same countries. While the nine NTDs became increasingly concentrated in developing countries in the 1990–2010 period, this trend would be rectified if the WHO targets were met, supporting the pro-poor designation.

Disability from Japanese encephalitis in Cambodia and Viet Nam.

A cohort of Japanese encephalitis (JE) survivors in Cambodia and Viet Nam were assessed at least 4 months after hospital discharge in order to understand the extent of disability after JE. We used a simple assessment tool which focuses on the impact on daily life. In total, 64 disability assessments were conducted: 38 in Cambodia and 26 in Viet Nam. In Cambodia, 4 (11%) children had severe sequelae, suggesting the children would likely be dependent, 15 (39%) had moderate sequelae and 17 (45%) had mild sequelae. In Viet Nam, two (8%) persons had severe sequelae, five (19%) had moderate sequelae and eight (31%) had mild sequelae. In many JE-endemic areas there are no multi-disciplinary teams with sophisticated equipment to assess patients after JE disease. This assessment tool can assist with patient management and generate data to support the need for programmes to prevent disease and improve outcomes for survivors.

Outcome and extent of disability following Japanese encephalitis in Indonesian children.

OBJECTIVES The study aimed to assess outcome, including level of disability, following Japanese encephalitis (JE) in children in Indonesia. METHODS A cohort of children diagnosed with laboratory-confirmed JE from January 2005 to August 2006 was followed-up, with disability measured at least 4 months after discharge from hospital. An assessment tool that can be used to rapidly determine practical level of disability and the likelihood that a child will be able to live independently after illness, the Liverpool Outcome Score, was used. RESULTS Of 72 children with JE, determination of outcome was possible for 65 (90%). Sixteen died in hospital or before follow-up assessment (25%). Sixteen children (25%) had severe sequelae, indicating their function was impaired enough to likely make them dependent. Five (7%) had moderate sequelae and 12 (18%) had minor sequelae. The remaining 16 children (25%) were considered to have recovered fully. CONCLUSIONS Half of the children with JE either died or were left with serious disabilities likely to impair their ability to lead independent lives, demonstrating the severe impact of JE. Immunization can effectively prevent JE, and an immunization program could avert some of the economic and social burden of JE disease in Indonesia.