Adrian Hopkins

Elimination of onchocerciasis from Africa: possible?

Human onchocerciasis, a parasitic disease found in 28 African countries, six Latin American countries and Yemen, causes blindness and severe dermatological problems. In 1987, efforts to control this infection shifted from vector approaches to include the mass distribution of ivermectin - a drug donated by Merck & Co. for disease control in Africa and for disease elimination in the Americas. Currently, almost 25 years later, with the Americas being highly successful and now approaching elimination, new evidence points towards the possibility of successful elimination in Africa. We suggest several major changes in the programmatic approach that through focused goal-directed effort could achieve global elimination of onchocerciasis by 2025.

Southern Sudan: an opportunity for NTD control and elimination?

Southern Sudan has been ravaged by decades of conflict and is thought to have one of the highest burdens of neglected tropical diseases (NTDs) in the world. Health care delivery, including efforts to control or eliminate NTDs, is severely hampered by a lack of infrastructure and health systems. However, the post-conflict environment and Southern Sudans emerging health sector provide the unprecedented opportunity to build new, innovative programmes to target NTDs. This article describes the current status of NTDs and their control in Southern Sudan and outlines the opportunities for the development of evidence-based, innovative implementation of NTD control.

Control of neglected tropical diseases in Burundi: partnerships, achievements, challenges, and lessons learned after four years of programme implementation.

The NTD programme in Burundi was supported by the investment group Legatum and Geneva Global.

Neglected tropical diseases in Africa: a new paradigm

Programmes to control onchocerciasis have been ongoing for over 40 years. What was once a devastating blinding and disabling disease, particularly in West Africa, has largely been eliminated at least as a public health problem. Efforts continue to eliminate the transmission of the disease. However, as the elimination agenda has developed so have efforts to control/eliminate other neglected tropical diseases (NTDs). The African Programme for Onchocerciasis Control will close at the end of 2015. There has been considerable discussion as to what should replace it and the World Health Organization Africa Region has been consulting widely during the first part of 2015 and has established a new project framework that will be presented to a wider group of stakeholders to mobilise support with the aim of the coordination of NTD activities in the region. This will be called the Expanded Special Project for Elimination of Neglected Tropical Diseases (ESPEN). This will put the countries in the driving seat but offer technical advice, capacity building and financial support, where needed, to enable countries to implement their NTD Master Plans, and also to implement recommendations of the Regional Programme Review Group. An NTD forum will be held periodically to consult with stakeholders.

Integrating Data and Resources on Neglected Tropical Diseases for Better Planning: The NTD Mapping Tool (NTDmap.org)

Neglected tropical diseases (NTDs) affect more than 1,000,000,000 poor and marginalized people worldwide [1]. NTDs are caused by diverse pathogens with differing modes of transmission and a range of vectors and intermediate hosts, which have their own ecological peculiarities. While there is considerable overlap in the geographical distribution of different NTDs at a national level [1], epidemiological differences of individual NTDs give rise to marked geographical variation at local levels. Since cost-effectiveness of intervention is greatest when targeted to areas having a high burden of multiple diseases, maps of the distribution of the different NTDs are essential for planning and implementing NTD interventions, as well as for providing visualization of program progress, so important for advocacy. In recent years there have been concerted, and very successful, efforts to develop detailed information resources on the geographical distribution of different NTDs (Table 1). Table 1 Currently available resources on the geographical distribution of NTDs. An important element of targeted NTD intervention is the delivery of mass drug administration (MDA) for treating the five major “preventive chemotherapy” NTDs, including lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), and trachoma [2]. MDAs targeting these NTDs are implemented alongside improvements in water and sanitation and hygienic behavior, as well as vector control. To help galvanize such global health efforts, the World Health Organization (WHO) and the NTD community defined targets to be achieved by 2020 and strategies to reach these targets (Table 2). As countries make progress towards the 2020 goals with an ever-increasing amount of data being collected, it is important to develop readily accessible tools that policymakers and program staff and partners can use to access, visualize, and compare data. Table 2 The five main NTDs and the drugs and strategies used to target them programmatically. In this Innovation to Application article, we describe the creation of an innovative NTD mapping tool (www.ntdmap.org) developed by a consortium of research and program partners for use particularly by program implementers. Its functionality and accessibility have been designed specifically to meet the needs of national programs and international partners. This tool provides an online resource allowing users to visualize and manipulate geographical data on a range of variables for the planning and managing of integrated NTD programs.

Parasitological, Hematological and Biochemical Characteristics of a Model of Hyper-microfilariaemic Loiasis (Loa loa) in the Baboon (Papio anubis)

Background Loiasis, a filarial infection caused by Loa loa usually thought to cause relatively minor morbidity, can cause serious and often fatal reactions in patients carrying very high levels of circulating Loa loa microfilariae (mf) following administration of microfilaricidal drugs. An experimental model of this condition would greatly aid the definition of the optimal management of this important clinical presentation. Methodology/Principle Findings Fifteen baboons (Papio anubis) were infected with 600 infective larvae (L3) isolated from Chrysops vector flies. Animals were observed for any clinical changes; blood samples were collected every 1–2 months for 22 months, and analysed for parasitological, hematological and biochemical profiles using standard techniques. All animals became patent but remained clinically normal throughout the study. The parasitological pre-patent period was between 4–8 months, with a majority (60%) of animals becoming patent by 5 months post infection (MPI); all animals were patent by 8 MPI. Microfilarial loads increased steadily in all animals and reached a peak at 18 MPI. By 10 MPI >70% of animals had mf >8,000 mf/mL, and at 18 MPI >70% of animals had mf >30,000mf/mL with 50% of these animals with mf >50,000mf/mL. Absolute eosinophil, creatinine, Ca2+ and K+ levels were generally above normal values (NV). Positive associations were seen between microfilariaemia and eosinophilia, Hb, Ca2+, and gamma-GT values, whilst significant negative associations were seen between microfilariaemia and potassium, glucose and mononuclear leukocyte levels. Conclusions Infection of splenectomised baboons with L. loa can induce levels of circulating microfilariae, and corresponding haematological profiles, which parallel those seen in those humans in danger of the severe post-microfilariacide clinical responses. Utilization of this experimental model could contribute to the improved management of the loiasis related adverse responses in humans.

From River Blindness to Neglected Tropical Diseases—Lessons Learned in Africa for Programme Implementation and Expansion by the Non-governmental Partners

After more than 20 years of action against some of the most debilitating neglected tropical diseases (NTDs), lessons have been learned by the non-governmental development organisations (NGDOs) in the light of changes in programme strategies and partnerships. This article aims to summarise the development of the non-governmental networks supporting the NTD programmes, starting with the original 1992 model to combat onchocerciasis (river blindness), and will review the lessons learned that have equipped the NGDOs to step up their support to NTD control and elimination. At the beginning of the 1990s, a small group of seven NGDOs began to work together to support onchocerciasis control [1]. Today, more than 50 international and national NGDOs (of which 30 collaborate at the international level) work together to control or eliminate five priority NTDs affecting more than one billion of the poorest people [2]. This is a significant contribution to the objectives of World Health Assembly resolutions and the London Declaration on NTDs [3], as well as addressing Millennium Development Goal (MDG) 1, “Eradicate extreme poverty and hunger;” MDG 6 “Combat HIV/AIDS, malaria, and other diseases;” and MDG 8, “Develop a global partnership for development.” In 2013, the first annual report of the London Declaration on Neglected Tropical Diseases recorded increased treatments and funding and significant progress towards the World Health Organization (WHO)’s roadmap for implementation for control, elimination, or eradication by 2020. This achievement has been made possible by developing networks of NGDOs and partnerships with governments of the endemic countries, with international and bilateral agencies, with drug donation programmes for specific diseases, and with the communities affected by those diseases [4]. By 2011, NGDOs reported support in 125 countries to more than 330 million treatments for five priority diseases: onchocerciasis, trachoma, lymphatic filariasis (LF), schistosomiasis, and soil-transmitted helminthiasis (STH) [5]. These diseases have effective mass drug administration (MDA) strategies supported by donated or very-low-cost drugs available to control or eliminate them [6,7].

Growth, Challenges, and Solutions over 25 Years of Mectizan and the Impact on Onchocerciasis Control

The Mectizan Donation Program (MDP) was established in 1987 to oversee Merck’s donation of Mectizan (ivermectin, MSD) for the control of onchocerciasis (river blindness) worldwide [1]. This was accelerated and expanded when Merck made a groundbreaking announcement in 1987: it would donate ivermectin, completely free of charge, as much as needed and for as long as needed, for the elimination of river blindness as a public health problem in all endemic countries. P0rior to the donation of Mectizan, vector control was the only strategy used to control the disease. The World Health Organization’s Onchocerciasis Control Program (OCP) led the effort for 25 years, which resulted in very low endemicity in some West African countries. When Mectizan was donated, the implementation of mass drug administration (MDA) emerged as the primary strategy to control and eliminate onchocerciasis. The success of MDA led to the concept that drugs for other neglected tropical diseases (NTDS) could be distributed using the same strategy. When MDP began, there was no distribution mechanism to reach the entire population at risk for onchocerciasis, particularly those living in remote, rural areas with poor health infrastructures. Merck approached a number of United Nations and international development agencies to request help distributing the drug, but because of lack of an established model, none came forward to facilitate distribution of the drug [2]. Determined to get the drug to the people who needed it, Merck established an independent program (MDP) and expert committee to develop a distribution mechanism to ensure the drug was distributed in a medically responsible manner with thorough supervision and monitoring [3]. The Mectizan Expert Committee (MEC) is made up of individuals with a broad range of expertise in global health, tropical diseases, entomology, parasitology, and disease control. The MEC meets twice-yearly and includes participation by WHO Headquarters, WHO Africa Regional Office (AFRO), the African Program for Onchocerciasis Control (APOC), the Onchocerciasis Elimination Program for the Americas (OEPA), the World Bank, and the Centers for Disease Control and Prevention (CDC). The Onchocerciasis Control Programme (OCP) in West Africa began coordinating Mectizan distribution in some of the highly endemic areas for onchocercal blindness, while non-governmental development organizations (NGDOs) worked with Ministries of Health to cover the remaining areas of Africa. As mapping activities expanded, showing the real extent of the disease, it was clear that NGDOs and Ministries of Health did not have the resources to scale up as required. As a result, the Ministries and NGDOs, together with support fromWHO and

Ivermectin treatment of Loa loa hyper-microfilaraemic baboons (Papio anubis): Assessment of microfilarial load reduction, haematological and biochemical parameters and histopathological changes following treatment

Background Individuals with high intensity of Loa loa are at risk of developing serious adverse events (SAEs) post treatment with ivermectin. These SAEs have remained unclear and a programmatic impediment to the advancement of community directed treatment with ivermectin. The pathogenesis of these SAEs following ivermectin has never been investigated experimentally. The Loa/baboon (Papio anubis) model can be used to investigate the pathogenesis of Loa-associated encephalopathy following ivermectin treatment in humans. Methods 12 baboons with microfilarial loads > 8,000mf/mL of blood were randomised into four groups: Group 1 (control group receiving no drug), Group 2 receiving ivermectin (IVM) alone, Group 3 receiving ivermectin plus aspirin (IVM + ASA), and Group 4 receiving ivermectin plus prednisone (IVM + PSE). Blood samples collected before treatment and at Day 5, 7 or 10 post treatment, were analysed for parasitological, hematological and biochemical parameters using standard techniques. Clinical monitoring of animals for side effects took place every 6 hours post treatment until autopsy. At autopsy free fluids and a large number of standard organs were collected, examined and tissues fixed in 10% buffered formalin and processed for standard haematoxylin-eosin staining and specific immunocytochemical staining. Results Mf counts dropped significantly (p<0.05) in all animals following ivermectin treatment with reductions as high as (89.9%) recorded; while no significant drop was observed in the control animals. Apart from haemoglobin (Hb) levels which recorded a significant (p = 0.028) drop post treatment, all other haematological and biochemical parameters did not show any significant changes (p>0.05). All animals became withdrawn 48 hours after IVM administration. All treated animals recorded clinical manifestations including rashes, itching, diarrhoea, conjunctival haemorrhages, lymph node enlargement, pinkish ears, swollen face and restlessness; one animal died 5 hours after IVM administration. Macroscopic changes in post-mortem tissues observed comprised haemorrhages in the brain, lungs, heart, which seen in all groups given ivermectin but not in the untreated animals. Microscopically, the major cellular changes seen, which were present in all the ivermectin treated animals included microfilariae in varying degrees of degeneration in small vessels. These were frequently associated with fibrin deposition, endothelial changes including damage to the integrity of the blood vessel and the presence of extravascular erythrocytes (haemorrhages). There was an increased presence of eosinophils and other chronic inflammatory types in certain tissues and organs, often in large numbers and associated with microfilarial destruction. Highly vascularized organs like the brain, heart, lungs and kidneys were observed to have more microfilariae in tissue sections. The number of mf seen in the brain and kidneys of animals administered IVM alone tripled that of control animals. Co-administration of IVM + PSE caused a greater increase in mf in the brain and kidneys while the reverse was noticed with the co-administration of IVM + ASA. Conclusions The treatment of Loa hyper-microfilaraemic individuals with ivermectin produces a clinical spectrum that parallels that seen in Loa hyper-microfilaraemic humans treated with ivermectin. The utilization of this experimental model can contribute to the improved management of the adverse responses in humans.

Transitioning from river blindness control to elimination: steps toward stopping treatment

Abstract The transition from onchocerciasis control to elimination requires country programmes to rethink their approach to a variety of activities as they move from addressing morbidity to addressing transmission of the parasite. Although the 2016 WHO guidelines provide extensive recommendations, it was beyond the scope of the document to provide guidance on all aspects of the transition. This paper will discuss some of the important issues that programmes are grappling with as they transition to elimination and provide some potential approaches that programmes can use to address them. Although there are some data to support some aspects of the suggested approaches, operational research will be needed to generate data to support these approaches further and to determine how programmes could best tailor them to their own unique epidemiological challenges. Good communication between the national programmes and the broader global programme will facilitate the clear articulation of programmatic challenges and the development of the evidence to support programme decision-making.