Our conclusion is that this has been very successful, with each of the three staff members contributing significantly to essential activities in WHO-NTD’s continued progress against the diseases, itself reflected in the strong performance against logframe indicators (one indicator, relating to integration, was not met but a revision to this is proposed):

• Economic evidence has been developed and disseminated, including via peer-reviewed publications. The health economist has led this work, as well as a successful campaign to have NTDs included in the Sustainable Development Goals (Chapter 3).
• Largescale drug donations have been better managed than prior to 2012, expanding WHO-NTD’s reach to ever more people who suffer from the diseases. The software platform used for this is developed and administered by the logistician and programme epidemiologist, and has become a means to drive improved programming by countries (Chapter 4).
• Interaction with other stakeholders, including Development Partners, countries and WHO Regional and Country Offices and countries, has become increasingly effective, even as some capacity challenges remain.
• Data is increasingly gathered and used by WHO-NTD. This has been strongly influenced by both the economic evidence and drug donation software platform referred to above.
• Partly as a result of these improvements, significant additional resources have been mobilised, from international development partners, pharmaceutical companies and, gradually, from endemic countries. WHO-NTD is facilitating a series of in-country dialogues to stimulate further the last of these sources.
• The inclusion of NTDs already in the SDGs and (from early 2018) in the African Leaders Malaria Alliance (ALMA) scorecards, will help keep NTDs high on policy agendas, and should make further resources likely also.

While hard to quantify and attribute precisely, it is likely that DFID’s investment in these three staff positions has yielded excellent returns and the elimination of some NTDs has been brought sooner than it otherwise would.

Suggested citation:

Whitaker, D., Franzen, S. and Ollier, L. (2018). World Health Organization Department of Neglected Tropical Diseases: Support for Capacity Strengthening and Visceral Leishmaniasis Programme Coordination (2012–2017). London, UK: High-Quality Technical Assistance for Results (HEART).

The event aimed to:

• Educate missions about the critical need for scaling up TB research
• Sensitise missions to the need for commitments to increase TB research funding
• Sensitise missions and key stakeholders on the importance of investing in the full spectrum of TB research, from basic science to R&D to applied health research
• Promote principles to guide research to ensure efficiency in development and equitable access
• Reach a shared vision on priority tools and applied health research needs

Introduction and Keynote Speech

Opening remarks: Mark Harrington, Executive Director, Treatment Action Group

Keynote speaker: Dr. Soumya Swaminathan, Deputy Director General for Programmes, World Health Organization

Panel 1: A Step-Change TB Research: why TB research is critical and how to respond

Opening remarks and moderator: Professor Charlotte Watts, Chief Scientific Advisor, DFID
Panel: 

• Ms. Eloisa Zepeda-Teng, TB survivor, Philippines
• Tereza Kasaeva, Director, WHO Global TB Programme
• Irene Ayakaka, Makere University and Uganda Tuberculosis Implementation Research Consortium

Respondent: Minister Counselor Philip Gough, Permanent Mission of Brazil to the United Nations

Panel 2: Devoting the Resources

Moderator: Dr. Lucica Ditiu, Executive Director of the Stop TB Partnership
Panel:

• Joanne Liu, International President, Doctors Without Borders
• Mike Frick, Senior Project Officer, Treatment Action Group
• Cheri Vincent, Chief, Infectious Diseases Division, US Agency for International Development (USAID)

Respondent: Mrs. Paulomi Tripathi, First Secretary, Permanent Mission of India to the United Nations

Panel 3: Designating Research Outcomes as Global Public Goods

Moderator: Mark Harrington, Executive Director, Treatment Action Group
Panel:

• Paula Fujiwara, Scientific Director, The Union
• Tenu Avafia, Team Leader, Human rights, law, and treatment access, UNDP HIV, Health and Development Group

Closing remarks: Rt. Hon. Nick Herbert, Member of Parliament, U.K.

Event organisation and sponsorship:

The briefing was organised by Médecins Sans Frontières, Stop TB Partnership, Treatment Action Group, and The Union.

Sponsors include Permanent Mission of Brazil to the United Nations, Permanent Mission of India to the United Nations, United Nations Development Programme and World Health Organization.

Related resources:

• Reading pack: Emerging issues in tuberculosis

This collection of videos has been produced in partnership with the K4D programme.

This presentation was delivered as part of a professional development training session for DFID health advisers in March 2018. Subject experts from the Liverpool School of Tropical Medicine (LSTM) presented the latest evidence on the communicable diseases (HIV, malaria, tuberculosis and neglected tropical diseases) that affect the poorest people in DFID partner countries.

Through the K4D programme and in partnership with HEART, a number of reading packs on the topic of communicable diseases have been produced. Related reading packs include:

• Emerging issues in HIV
• Malaria: Key challenges and potential solutions
• Emerging issues in tuberculosis
• The global challenge of NTDs  

The current malaria burden

Great progress has been made in reducing the global burden of malaria since the turn of the century, with approximately 700 million cases averted and malaria mortality in Africa decreasing by 37% since 2000. This decrease in malaria transmission has been largely achieved by the scale up of insecticide-based measures targeting the Anopheles mosquitoes that transmit the disease. Harder to measure, but likely a major contributory factor to the decline in cases, are factors related to improvements in health systems, housing, and household income that have occurred across large areas afflicted by malaria.

Persistence of malaria

Malaria remains a disease of poverty, and hence, progress has been slowest in countries with the weakest health infrastructure and regions that are plagued by civil unrest. In addition, growing resistance to drugs and insecticides threatens some of the recent gains.

Indeed, continent wide trends extrapolated from modelling studies of the past and current burden of malaria do not always represent the picture on the ground. In some countries, such as Burkina Faso, Uganda, and Mali, malaria has remained stubbornly persistent despite high coverage of the WHO recommended strategy of universal coverage with vector control and prompt access to diagnosis and treatment.

Furthermore, the dramatic reductions in malaria transmission since 2000 have precipitated a renewed call to eliminate malaria as a public health problem. This has significantly altered the dialogue, and as a consequence, the investment in resources and research towards measures aimed at ‘shrinking the malaria map’ have increased. Today, just 15 countries account for 80% of the malaria burden; all but one of these are in sub-Saharan Africa, but they are not the focus of the elimination efforts. Indeed modelling studies have predicted that, even with 90% coverage with all currently recommended interventions, plus the addition of multiple rounds of mass drug administration to clear the parasite reservoir, elimination is unlikely to be achieved across much of Africa.

Resistance to malaria drugs

The spread of resistance also threatens progress against malaria and, unless the pace at which new tools are evaluated and implemented is accelerated, risks derailing control efforts and curtailing any ambitions of elimination.

Below, four of the key challenges currently facing malaria are briefly outlined, together with some measures that could help address these challenges.

Key Challenge 1: Increasing access to proven interventions

There are five key pillars to WHO’s strategy to prevent malaria:

• Universal coverage with measures that target the adult mosquito vector: long lasting insecticidal nets (LLINs) or indoor residual spraying (IRS);
• Rapid diagnosis and treatment with artemisinin combination therapy;
• Intermittent preventative treatment of malaria in pregnancy;
• Seasonal malaria chemoprevention (in some settings only);
• Surveillance to target malaria interventions more effectively.

These interventions have been massively scaled up in the past five years with impressive results. But important coverage gaps and inequities in access to these proven tools remain. An estimated £2.6bn was spent on malaria prevention in 2017 but WHO estimates that this is only about half the amount required. With competing demands on over-stretched budgets, demonstration of value for money is critical. Vector control is already recognised to be one of the most cost effective public health interventions in existence but the impact of interventions across multiple vector borne diseases is rarely accounted for. For example LLINs are estimated to cost $1.27 per malaria case averted. But these are frequently deployed in areas where vector borne diseases are co-endemic; if the impact on lymphatic filariasis , leishmaniasis , etc. were also accounted for the case for investing in vector control would be even stronger. This is a missed opportunity to leverage more funding.

In addition to funding, the capacity gap needs to be addressed. There is a chronic lack of capacity in many malaria endemic countries which impinges on all aspects of malaria prevention from implementation to evaluation. Furthermore, although universal coverage with a handful of proven interventions is the current gold standard for malaria prevention, this will undoubtedly change as bespoke packages of locally appropriate interventions are required to drive malaria cases down; this will require personnel at country (and global) level with the necessary expertise to select and evaluate the most appropriate package of interventions.

Key challenge 2: Residual transmission

The gains in malaria control have been largely driven by scale up of current interventions. However it is clear that, even if implementation of these tools achieves very high levels, malaria transmission will persist. This was demonstrated in a modelling study led by Imperial College (Walker Griffin, Ferguson & Ghani, 2016) and is illustrated below in maps that show the package of available tools needed to reach pre-elimination settings (<1 case/1000 people/year) assuming 90% coverage with each tool. The panel on the left (Fig. 1) shows that this target is impossible across much of Africa with existing tools of LLINs, IRS and Seasonal Malaria Chemoprophylaxis (SMC). If SMC is substituted for three rounds of mass drug administration (MDA), the picture (Fig. 2) improves but thresholds would not be reached in all regions.

Outdoor biting mosquitoes

Part of the problem is that current vector control interventions largely target mosquitoes that rest and blood feed indoors. Although this is the predominant behaviour pattern exhibited by the major malaria vectors in Africa, substantial amounts of transmission occurs outside the home, either by mosquitoes feeding before people retire to bed, or by mosquitoes feeding on individuals working or resting outdoors during the peak periods of malaria biting activity.

Hence to reduce malaria transmission further, additional measures that target outdoor biting mosquitoes need to be layered on top of the current indoor based interventions. Although there has been some encouraging data in recent years on pilot studies targeting outdoor transmission, much more remains to be done and it will be many years before these tools are ready to be implemented at scale.

Mass drug administration

Mass drug administration approaches are also being piloted in several settings with SMC now a recommended intervention for children living in areas in the Sahel with highly seasonal transmission (Bâ et al., 2018). The idea of these population scale drug administration programmes is to reduce the level of malaria parasites by targeting both symptomatic and asymptomatic infections. These interventions are often very effective in the short term but are expensive and challenging to sustain and risk exacerbating the levels of drug resistance.

Key Challenge 3: Resistance to insecticides and drugs

All WHO-approved LLINs contain pyrethroid insecticides; all drugs recommended for malaria treatment contain artemisinins. Hence the emergence of impactful levels of resistance to these chemistries in the mosquitoes and parasites could unravel the current gains unless off the shelf alternatives are ready to replace these.

The Medicines for Malaria Venture (MMV), launched in 1999, and the Innovative Vector Control Consortium, founded in 2005, are both product development partnerships aimed at ensuring a steady pipeline of new drugs and insecticides, accessible to the communities where they are needed. Both of these ventures have had success. For example, as a direct result of these PDPs, longer lasting formulations of insecticides are increasing the impact of IRS and new drugs to treat severe malaria in children are widely used. But the pathway from discovery to delivery is long, and, in particular for new insecticides, there is a high risk that our current tool box will be depleted by resistance before new alternatives are readily available.

Resistance management approaches

In addition to new chemistries, resistance management approaches urgently need to be implemented to reduce the selection and spread of resistance. The first reports of artemisinin resistance resulted in a rapid mobilisation of resources to contain or eliminate artemisinin resistance where it already exists and prevent its spread to new regions. This has largely been successful with artemisinin parasites to date confined to South East Asia.

The response to insecticide resistance has been slower. No non-pyrethroid LLINs are currently available. New LLINs containing pyrethroids plus a synergist, PBO, which increases the potency of the insecticide against pyrethroid resistant mosquito populations are in production, but it has taken 10 years from the first of these receiving WHO approval as a standard LLIN to any large-scale deployment of these nets. Reducing the selection pressure in mosquitoes is complicated by the widespread use of existing insecticides in agriculture and in other public health products such as aerosols.

There are exciting opportunities to exploit the behaviour of mosquitoes to simultaneously reduce the amount of insecticide used whilst increasing the impact on disease vectors which warrant much further study. Promising results from trials of eaves baffles, partial IRS, and barrier nets with vertical panels on the roof of the net treated with an alternative insecticide class, to name just a few, give rise to encouragement that, with sufficient investment and robust trial design, we may be able to maintain the efficacy of vector control using existing chemistries whilst we await the promise of new insecticides from the PDP initiative.

Key Challenge 4: Accelerating access to new tools

In many malaria endemic countries, national malaria control strategy deviates very little from global recommendations issued by WHO. For countries with high burdens of malaria the key priority has been reducing malaria transmission by increasing coverage with proven tools, and hence the WHO policy of universal coverage with these interventions is entirely appropriate.

However, as transmission declines, or existing tools fail, more locally appropriate strategies are needed. Two of the major challenges in adapting and adopting national or regionally appropriate strategies are capacity gaps and the slow speed at which some new tools received WHO recommendation.

Addressing the capacity gaps in disease endemic countries in order to accelerate the generation and uptake of evidence at the local level must be an urgent priority.

Major challenges include:
• Poor surveillance to identify hotspots of transmission;
• Inadequate knowledge on the distribution, behaviour and resistance profiles of local vectors;
• Weak links between research institutes and control programmes in country;
• Existence of multiple donors (many with their own agendas);
• Reporting requirements that put further pressure on over stretched control programmes.

The list of challenges is seemingly endless and it is only by improving capacity in country that these can begin to be addressed. The lack of capacity clearly constrains the ability of countries to set their own agendas for reducing disease burden. In addition, critical data gaps can lead to inefficiencies and missed opportunities. Investment in institutes and individuals in malaria endemic countries must be a higher priority for national governments and donors.

Improvements to the speed at which new tools are evaluated and policy recommendations issued are also needed at the global level, particularly in the field of vector control. Whilst clearly rigorous and transparent processes for evaluating the safety and efficacy of any new drugs or tools are essential, there are cases where a pragmatic approach to ensuring that new tools ‘do no harm’ and evaluating their efficacy during a phased roll out and evaluation may be needed. Current WHO guidelines put a very strong emphasis on randomised control trials. These are widely accepted as the gold standard for drugs, vaccines, and other medical interventions but are not so readily adapted to evaluating all vector control tools that act at the community—rather than individual—level, and alternative approaches may be needed in parallel. There is an urgency to addressing this issue. While the debate on the evidence base needed for new tools rolls on, millions currently remain dependent on tools whose efficacy is being eroded by resistance.

Footnotes
[1] Commonly known as elephantiasis, lymphatic filariasis is caused by filarial parasites which are transmitted to humans through mosquitoes and black flies. The disease causes painful and debilitating swelling due to impairment of the lymphatic system (WHO, 2017c).

Readings

Bâ, E.-H., Pitt, C., Dial, Y., Faye, S. L., Cairns, M., Faye, E. Milligan, P. (2018). Implementation, coverage and equity of large-scale door-to-door delivery of Seasonal Malaria Chemoprevention (SMC) to children under 10 in Senegal. Scientific Reports, 8(1). doi:10.1038/s41598-018-23878-2

Churcher, T. S., Lissenden, N., Griffin, J. T., Worrall, E., & Ranson, H. (2016). The impact of pyrethroid resistance on the efficacy and effectiveness of bednets for malaria control in Africa. ELife, 5(e16090). https://doi.org/10.7554/eLife.16090

Killeen, G. F. (2014). Characterizing, controlling and eliminating residual malaria transmission. Malaria Journal, 13, 330. https://doi.org/10.1186/1475-2875-13-330

Tesfazghi, K., Traore, A., Ranson, H., N’Fale, S., Hill, J., & Worrall, E. (2016). Challenges and opportunities associated with the introduction of next-generation long-lasting insecticidal nets for malaria control: a case study from Burkina Faso. Implementation Science, 11(103), 1-12. https://doi.org/10.1186/s13012-016-0469-4

Walker P.G.T., Griffin, J.T., Ferguson, N.M. & Ghani, A.C. (2016). Estimating the most efficient allocation of interventions to achieve reductions in Plasmodium falciparum malaria burden and transmission in Africa: A modelling study. Lancet Global Health, (4,) e474–484.

WHO. (2017a). Global vector control response 2017–2030. Geneva: Switzerland: World Health Organization. Retrieved from: http://apps.who.int/iris/bitstream/handle/10665/259205/9789241512978-eng.pdf?sequence=1

WHO. (2017b). World malaria report 2017. Geneva: Switzerland: World Health Organization. Retrieved from: http://apps.who.int/iris/bitstream/handle/10665/259492/9789241565523-eng.pdf?sequence=1

WHO (2017c). Lymphatic filariasis: Fact sheet. Retrieved from: http://www.who.int/mediacentre/factsheets/fs102/en/

WHO (2018). Leishmaniasis: Fact sheet. Retrieved from: http://www.who.int/mediacentre/factsheets/fs375/en/

Questions to guide reading

1. Has the focus on malaria elimination put some countries at higher risk of malaria?
2. How do countries make decisions on the most appropriate national strategy for malaria control when they are frequently bound by global policies?
3. What role can donors and implementers play in helping generate the evidence needed to evaluate new vector control tools?
4. What are the key factors that need to be addressed to support the retention of staff in malaria control programmes and local research institutes?
5. Malaria is a vector borne disease. What are the opportunities for delivering and demonstrating better value for money by greater integration with other vector borne disease programmes?

Suggested Citation

Ranson, H. (2018). Malaria: Key challenges and potential solutions. K4D Reading Pack. Brighton, UK: Institute of Development Studies.

Related Resources

See the HEART talks post Communicable diseases: Key challenges and potential solutions for a brief overview of communicable diseases.

Other reading packs in this series include:

• Emerging issues in HIV
• Emerging issues in tuberculosis
• The global challenge of NTDs  

Key concepts

Tuberculosis (TB) is a bacterial infection that can cause disease in any part of the body, sometimes many years after initial infection. TB is transmitted between people when someone with active disease in their lungs or throat coughs and generates droplets containing Mycobacterium tuberculosis. There is a spectrum of infectiousness: people who produce larger amounts of TB bacteria in their sputum are more infectious, while people with TB in parts of their bodies other than the lungs are generally considered to be non-infectious.

People who have prolonged close contact with infectious TB cases (such as household members) or those who have weakened immune systems (such as very young children and people living with HIV) are at the greatest risk of becoming infected with Mycobacterium tuberculosis. In countries with a high burden of TB, the age at which people most commonly become infected with TB is as a young child or in adolescence.

Typical symptoms of active TB include: cough, fever, night sweats, weight loss, coughing up blood, and loss of appetite. If TB disease occurs in a part of the body other than the lungs, there may be local symptoms (such as symptoms of meningitis or swollen lymph nodes in the neck).

TB infection (latent TB) refers to people who have been exposed to someone with infectious TB and have immunological evidence of infection (such as a positive tuberculin skin test) but don’t have any symptoms or signs of active TB disease. People with latent TB infection are not infectious to others. Approximately 5-10% of people who are latently infected with TB will progress to develop active TB over the course of their lifetime. However, a number of factors increase the risk of progression from latent TB infection to disease. In general, 50% of people who go on to develop active TB will do so within the first two years of infection. People at the extremes of age (very young or very old) are at greater risk of developing active TB disease due to weakened immune systems. Additionally, people living with HIV infection have a substantially increased risk of TB disease compared to HIV-negative people; instead of having a 5-10% lifetime risk of TB, in some settings, an HIV-positive person’s risk of developing active TB disease approaches 10% per year. Other conditions and medications that weaken the immune system, such as diabetes, malnutrition, alcoholism, treatment with immunosuppressant drugs, smoking, occupational exposure to silica dust (for example in miners), and air pollution also increase the risk of progression to TB disease.

Prevention, Diagnosis and Treatment

The TB life course

Vaccination against TB

The Bacillus Calmette-Guérin (BCG) vaccine has been used for nearly 100 years and provides moderate protection against infection and progression to TB disease among particular population groups. BCG provides protection against severe disseminated TB and TB meningitis when given to young children, and it can reduce the risk of development of pulmonary TB by about 60% when given to children living in northern latitudes. However, protection seems to be lower for children living in the tropics. The TB vaccine pipeline is limited, and we currently need a renewed focus on research, development, and translation.

Preventing TB

TB is the quintessential disease of poverty. Poor nutrition, unhealthy household and working conditions, and limited access to high quality health care are all strongly associated with increased risk of TB infection and disease.

Addressing the social determinants of TB is critical to improving TB care and prevention.

Priority interventions include:

• access to universal healthcare coverage;
• improved housing quality;
• improved and sustained infection control and quality of care within prisons, healthcare settings, and other congregate settings;
• adequate social protection systems to mitigate the catastrophic costs associated with TB disease.

Finding TB cases

With up to half of TB cases undiagnosed in some settings, efforts to find and treat people with TB need to be considerably enhanced. Until the introduction of the End-TB Strategy in 2015 (see below), the greatest emphasis was placed on finding individuals with sputum smear-positive pulmonary TB (microbiological evidence of TB in the lungs), with the rationale that these individuals were most infectious to others. In practice, this meant that TB case finding initiatives predominately focused on passive case detection—that is offering screening to people attending health facilities with symptoms of TB. However, it is increasingly recognised that passive case detection, while necessary, is not sufficient to close the TB case detection gap. This is because many people with TB symptoms find it difficult and expensive to access health centres and often delay seeking care until the disease is advanced. Additionally, focusing mostly on people with symptoms of pulmonary TB means that patients with other forms of TB may be less emphasised in national policies.

The End-TB Strategy promotes universal access to TB care and prevention. Due to the limitations of the passive case detection approach, recognition of the potential importance of active case finding for TB is rising. Active case finding involves first, systematically identifying populations at risk of TB and with poor access to care and second, offering universal screening and linkage to diagnosis and treatment services to these populations. Particular groups targeted for active case finding will depend on local epidemiology, priorities, and resources but may include: people living with HIV attending HIV care clinics; prisoners; healthcare workers; community members; migrants; and people attending health facilities for any reason.

Evidence for the effectiveness of active case finding approaches is still being established, but there is historical precedence: TB has been successfully controlled in many European and North American settings using active case finding approaches, in conjunction with improvements to living conditions.

Diagnosis of active TB

Diagnosis of active TB can be made by inspecting stained sputum under a light or fluorescence microscope for bacteria of the Mycobacteria species (sputum smear microscopy). However, this approach is resource intensive, requires a high and sustained degree of microscopy quality—often at primary care level—,poses an infection risk to health workers, and has suboptimal sensitivity (about 40% of cases of active TB will be missed by this approach).

Another diagnostic technique involves incubating a TB culture sputum within a culture bottle for 6-12 weeks. Newer automated culture systems (the MGIT system) give an automated signal once the growth of Mycobacterium tuberculosis is detected. Although the most accurate diagnostic tool, TB culture is slow, expensive, requires advanced laboratory capacity, and poses infection risk to health workers, and therefore is not widely available in low resource settings.

A chest x-ray can also be used to look for the presence of typical signs of pulmonary TB disease. Chest x-rays may be used to screen large numbers of people rapidly (e.g. during active case finding interventions). However, this requires expensive x-ray equipment and trained radiographers and radiologists. Often, diseases other than TB (such as pneumonia) are mistaken for TB, meaning that an additional confirmatory test is usually required. Increasingly, computer-aided X-ray diagnosis—where image recognition software evaluates an x-ray and gives a probability of TB—is becoming available, although it has not yet been evaluated at scale.

The GeneXpert MTB/Rif platform is a relatively new TB diagnostic test that uses a molecular reaction within a completely encased cartridge to amplify TB proteins within a body fluid sample (sputum, stool, urine, etc.) to provide an automated TB diagnosis within 2 hours. Evidence shows that where GeneXpert is available, the time between presentation with TB symptoms and initiation of treatment is substantially reduced, although this has not translated into a reduction in case fatality. GeneXpert also allows for rapid identification of disease resistance to one of the key drugs to treat TB (rifampicin). Many countries have begun expanding availability of GeneXpert MTB/Rif through their primary and secondary health care systems. However, some current limitations include: the high unit cost per test (it is approximately 100 times more expensive than sputum smear microscopy); lower sensitivity for detecting TB among people living with HIV (although this may be improved in the anticipated second generation cartridge); and maintenance and sustainability issues.

The lateral flow urinary lipoarabinomannan assay (LF-LAM) is a point of care detection test for active TB that has been developed in recent years. People with active TB secrete in their urine a protein from the TB cell wall, which can be detected by the presence of a visual intensity reaction after the urine is incubated at room temperature for about 25 minutes on a test strip. The LF-LAM test can be done rapidly at the bedside, without laboratory infrastructure, and does not pose an infectious risk to health workers. Two randomised control trials have demonstrated that, among hospitalised patients with advanced HIV infection, the LF-LAM test has high diagnostic accuracy and is associated with reduced risk of death where implemented. Nevertheless, there remain some challenges with this test. Accuracy is currently poor for HIV-negative people and for people living with HIV who are not seriously ill. Additionally, some simplification of the test read strip is required to minimise misinterpretation errors.  Hopefully, future generations of this test will address these issues.

Whole genome sequencing (WGS)—where the entire genetic code of TB organisms isolated from patients is described and compared to a reference set of genomes—has now been introduced routinely in England to guide clinical decision-making, earlier detection of resistance, and to support outbreak and epidemiological investigation. However, WGS requires sophisticated laboratory and bioinformatics infrastructure and currently requires that TB be cultured and DNA extracted before sequencing can be done. Additionally, the clinical and public health utility beyond research projects in low resource settings is uncertain. Nevertheless, the speed of advances in the sequencing field may mean that WGS rapidly appears on the horizon as a TB diagnostic tool.

Overall, the currently available diagnostics for active TB are suboptimal—particularly when compared to diagnostics for HIV where a simple finger-prick blood test is cheap, widely available, rapid, and highly accurate.

Evidence from a number of settings shows that the diagnostic and care-seeking pathways and prolonged treatment courses for TB are major contributors to patients experiencing catastrophic costs from TB.

Latent TB diagnosis and treatment

Currently the diagnosis of latent TB infection and prediction of which individuals will go on to develop active disease and require treatment is suboptimal. The tests available for the detection of latent TB rely on the body’s immune response to exposure to Mycobacterium tuberculosis. One such test is the tuberculin skin test (TST), where TB proteins are injected within skin layers. The size of the immune reaction is read after 48-72 hours to determine the likelihood of infection being present and of that individual progressing to develop the disease. Other tests available include the TSPOT test, with requires that a venous blood sample be incubated with TB proteins in a laboratory. In the future, a blood test that uses a particular gene signal associated with risk of TB progression may become available. The test shows early promise, although larger studies are required.

Treatment of latent TB infection can reduce the risk of development of active TB disease, particularly for high risk individuals, such as children and people living with HIV. Currently, treatment regimens available include a 6-month course of isoniazid (known as isoniazid preventive therapy (IPT)), a 3-month course of rifapentine and isoniazid, and a 1-month course of isoniazid and rifapentine, which may be superior for people living with HIV.

Achieving high coverage of latent TB diagnosis, treatment, and adherence has been extremely challenging in most settings. Novel diagnostics, shortened and more effective treatment regimens, and operational research to improve outcomes are urgently required.

Antituberculosis treatment

Antituberculosis treatment is a combination of antibiotics that must be taken for at least 6 months to treat active TB disease. At a minimum, four different drugs are required to achieve high treatment success rates, and TB is usually curable if good levels of adherence to treatment are sustained throughout the 6-month treatment period. National TB programmes recommend a standardised 6-month treatment regimen of at least four antibiotics: rifampicin, isoniazid, pyrazinamide and ethambutol tablets. This is known as standard short course therapy as evidence from many years of trials, laboratory studies, and observational studies shows that this approach is likely to result in a successful treatment outcome for most people with TB. Standard short course TB treatment can usually be given to patients on an outpatient basis, provided they are able to take their medication with a high degree of reliability or have someone able to support them to do so.

Side effects are relatively common with antituberculosis treatment and may range from mild to life-threatening. Additionally, many of the antituberculosis drugs may interact with other medications (particularly oral contraceptives, antibiotics, and antiretroviral medications for treating HIV), meaning that treatment and dosing regimens may have to be modified.

Occasionally, the standard short course TB treatment may need to be adapted or prolonged. This is usually because there is evidence that the TB bacteria has developed resistance to the standard short course drugs, or because there is TB in a part of the body other than the lungs, such as TB meningitis or TB of the bone. In these cases, injectable drugs may be required for a long period, often necessitating prolonged inpatient hospital stays.

All TB treatment cases should be recorded in a standard TB treatment register that records the patient characteristics, site of TB disease in the body, the results of any investigations for TB and treatment outcomes (cured, completed treatment, failed treatment, died, transferred out, or lost to follow-up). TB treatment registers form the basis national and international TB surveillance systems.

Multi-and extensively-drug resistant TB (MDR-TB and XDR-TB)

MDR TB occurs when the TB organism is resistant to two of the drugs that comprise the standard short course treatment regimen (rifampicin and isoniazid). XDR TB occurs when the TB organism is resistant to rifampicin and isoniazid, as well as some of the second line drugs used to treat MDR-TB. MDR-TB and XDR-TB usually occur when a patient has had suboptimal treatment for active TB (either an inappropriate drug regimen or poor adherence), meaning that the TB bacteria evolves to develop resistance. However, in some places, such as in health care-associated outbreaks or in weak health systems in Eastern Europe, widespread MDR-TB prevalence of resistant disease among TB cases signifies that resistant organisms may be directly transmitted between people. MDR-TB and XDR-TB require prolonged courses of complicated and potentially toxic antibiotic treatments, often lasting up to 18-20 months, with a considerable amount of time spent in confinement as an inpatient receiving daily injections. Outcomes for people with MDR-TB and XDR-TB are poor, and mortality rates are high. Management of MDR-TB and XDR-TB is complex and expensive, and most countries in low resource settings have low capacity to respond to outbreaks of resistant infection, to rapidly diagnose resistant cases, or to support the management of people requiring treatment.

In recent years, the development of two new antituberculosis drugs—bedaquilline and delamanid, the first new TB drugs in nearly 50 years—and potential high-levels of treatment success obtained using combinations of these drugs with other TB drugs in a shortened 9-month regimen—has given hope that a more tolerable, outpatient treatment approach could be successful. This so-called “Bangladesh regimen” is currently been trialled in a multi-country study, and preliminary results show that this regimen can support patients to return to work earlier and reduce catastrophic household costs. Full results are awaited.

Epidemiology of TB

TB is now the leading infectious killer worldwide, and causes more deaths per year than HIV and malaria combined. An estimated one-quarter of the world’s population have latent TB, although rates are substantially higher in some settings, such as in sub-Saharan Africa.

In 2016, 10.4 million new cases of TB occurred, and 1.8 million people died of TB. It is estimated that globally 39% of people with active TB disease went undetected by national treatment programmes. In Africa, this figure is higher, with nearly half of cases remaining undetected.

The estimated incidence of active TB disease per head of population is highest in the countries of sub-Saharan Africa, reflecting the effect of the HIV epidemic. TB incidence approaches as high as 2% per year in urban settings such as Cape Town. In terms of absolute numbers however, six countries (India, Indonesia, China, Nigeria, Pakistan and South Africa) amount for at least 60% of all new TB cases.

Of the 6.3 million new cases of TB registered by national TB programmes, 0.5 million had MDR-TB, and 0.5 million had HIV co-infection, with 82% of TB deaths among HIV-positive people occurring in sub-Saharan Africa.

The global incidence of TB has been slowly declining at an estimated rate of 1.5% per year, though there are considerable regional disparities. However, this overall decline is insufficient to meet global TB elimination goals, and intensified funding, research, development, and implementation of novel TB prevention and care approaches are required.

Estimated TB incidence under current and potential trends

The End TB Strategy and Sustainable Development Goals (SDGs)

The End TB strategy was adopted by the World Health Organisation (WHO) in 2015 and has an overall goal of ending the global TB epidemic.

Three specific targets have been developed:

• 95% reduction in TB deaths in 2035 compared to 2015 levels;
• 90% reduction in TB incidence in 2035 compared to 2015 levels;
• no households affected by catastrophic costs.

A number of End-TB milestone targets have been set for 2020 and for 2030.

It is clear that the End TB Strategy closely aligns with the SDGs.

In particular, the following SDG targets are well-aligned with the End-TB strategy:

• SDG 3: Ensure healthy lives and promote well-being for all at all ages
• SDG 1: End poverty in all its forms everywhere
• SDG 2: End hunger, achieve food security and improved nutrition and promote sustainable agriculture
• SDG 5: Achieve gender equality and empower all women and girls
• SDG 7: Ensure access to affordable, reliable, sustainable and modern energy for all
• SDG 8: Promote inclusive and sustainable economic growth, employment and decent work for all
• SDG 10: Reduce inequality within and among countries
• SGD 11: Make cities and human settlements inclusive, safe, resilient and sustainable

Ending the TB epidemic will require substantial efforts beyond biomedical interventions. Expanding access to universal health care, strengthening social protection systems and committing to achieving the SDGs will need coordinated action at all levels of society.

With the experience gained from identifying and responding to the MDR-TB and XDR-TB epidemics, TB can be seen as a pathfinder case study for responding to the growing threat of antimicrobial resistance (AMR).

The Global Action Plan on AMR promotes:

• the need for an effective “one health” approach involving coordination among numerous international sectors and actors;
• improving awareness and understanding of antimicrobial resistance through effective communication, education and training;
• strengthening knowledge and evidence base through surveillance and research;
• reducing the incidence of infection through effective sanitation, hygiene and infection prevention measures;
• optimising the use of antimicrobial medicines in human and animal health;
• developing the economic case for sustainable investment that takes account of the needs of all countries and increasing investment in new medicines, diagnostic tools, vaccines and other interventions.

Catalysing partnership to action for TB

Funding for TB research, development and implementation has lagged considerably behind other major infectious diseases for decades. However, with the growing realisation that insufficient progress is currently being made on addressing the TB epidemics and the underlying determinants of TB, the global community has begun to mobilise.

In September 2018, a UN High Level Meeting of heads of states at the UN General Assembly will take place, focusing specifically on TB. This provides a unique opportunity for the global TB community, countries, regions, civil society and ministers to coalesce around a shared momentum to concentrate efforts to meeting the End TB targets and SDGs.

Readings

Chatham House. (2012). Social Protection Interventions for Tuberculosis Control: The Impact, the Challenges, and the Way Forward. Retrieved from: https://www.chathamhouse.org/sites/files/chathamhouse/public/Research/Global%20Health/170212summary.pdf

Corbett, E.L., & MacPherson, P. (2013). Tuberculosis screening in high human immunodeficiency virus prevalence settings: turning promise into reality. The International Journal of Tuberculosis and Lung Disease, 17(9):1125-1138. doi:10.5588/ijtld.13.0117

Fitchett, J.R., MacPherson, P. & Corbett, E.L. (2016). Implementing the End TB Strategy and the intersection with the Sustainable Development Goals, 2016–2030. Transactions of the Royal Society of Tropical Medicine & Hygiene, 110(3), 145–147. doi:10.1093/trstmh/trw010

Lönnroth, K., Castro, K.G., Muhwa Chakaya, J., Singh Chauhan, L., Floyd, K., Glaziou, P. & Raviglione, M.C. (2010). Tuberculosis control and elimination 2010-50: cure, care and social development. The Lancet, 375(9728), 1814-29. doi:10.1016/S0140-6736(10)60483-7

World Health Organization (WHO). (2017). Global Tuberculosis Report 2017. Retrieved from: http://apps.who.int/iris/bitstream/10665/259366/1/9789241565516-eng.pdf?ua=1

Questions to guide reading

1. Where you work, what populations and groups are under-served by TB diagnosis, care, and prevention services? How can these groups be more effectively reached?
2. Does your country’s national TB plan emphasise TB prevention, social protection, universal health care access and elimination of catastrophic costs? If not, how can you influence key policymakers to raise awareness of these issues?
3. In your setting, what are the key knowledge gaps in TB that could be addressed by operational research studies? Do you know who to work with in the Ministry of Health and National TB Programme to foster a culture of research, innovation and development?
4. With the upcoming UN High Level Meeting on TB, what influence does your Ministry of Health have on setting an agenda towards accelerated action for ending the TB epidemic?
5. Can your Ministry of Health articulate the importance of health systems strengthening for the prevention of MDR-TB in line with the Global Action Plan on AMR?

Suggested citation

MacPherson, P. (2018). Emerging Issues in tuberculosis. K4D Reading Pack. Brighton, UK: Institute of Development Studies.

Related Resources

See the HEART talks post Communicable diseases: Key challenges and potential solutions for a brief overview of communicable diseases.

Other reading packs in this series include:

• Emerging issues in HIV
• Malaria: Key challenges and potential solutions
• The global challenge of NTDs  

Introduction

The concept of neglected tropical diseases (NTDs) emerged more than a decade ago and has been recognised as a valid way to categorise diseases that affect the poorest individuals in poor populations. Substantial progress in control and elimination has been achieved and policy momentum has been generated through continued bilateral, philanthropic, and nongovernmental development organisation (NGDO) support, together with huge donations of drugs from pharmaceutical companies. Some 70 countries are implementing programmes—with varying levels of dependency on donor support. WHO has defined a Roadmap to reach 2020 targets, which was endorsed by member states in a World Health Assembly Resolution in 2013.

NTDs are addressed through five strategies as defined in a World Health Assembly Resolution of 2013:

• preventive chemotherapy,
• intensified disease management,
• vector control,
• veterinary public health measures for zoonotic neglected diseases, and
• improved water and sanitation.

The research agenda has also defined the need for affordable products (diagnostics, drugs and insecticides). However, challenges, such as insecurity and weak health systems, continue to prevail in the poorest countries, inhibiting progress in scaling up and also in achieving Roadmap goals.

More information on the most common NTDs can be found in Annex 1 in the downloadable PDF.

Challenges and “endgame” targets

The continued drive for the control or elimination of NTDs has had many successes, but to address challenges in reaching ‘end game’ targets of elimination and eradication, there is a need for adaptive approaches as well as multi-disciplinary collaboration and intersectoral action.

This requires greater engagement of endemic countries through the recognition of the burden of NTDs and their role as drivers of poverty, as impediments to socio economic development, and the cost-effectiveness and cost-benefit of interventions. The advent of the NTD movement has resulted in massive up-scaling of the delivery of essential and quality medicines to around a billion people annually. Recipients are often the poorest of the poor, thus forging the global aspiration that universal health coverage is possible, equitable, and affordable, as reflected within the 2030 Sustainable Development Goals (SDGs). However, significant challenges remain, including profound socio-political upheavals (conflict, migration), dynamic epidemiological settings (climate change, environmental degradation, urbanization), and a need for innovative approaches to programme delivery as well as scientific and technological advances.

To reach ‘end game’ targets, the NTD community will need to continue to adapt to these global events and changing policy environments to support the development of responsive and resilient programmes that can sustain progress toward NTD targets in the ever-changing world.  Innovative thinking will need to be embedded within regional and national health systems. Policy makers, health managers, and front health workers are the mediators between challenge and change at the global and local level. The health system is the critical mediator of the interactions between these key challenges and opportunities.

We have suggested that NTDs represent “a global pandemic” and question why only 0.6% of Official Development Assistance for health is devoted to a group of infections that kill circa 350,000 people annually and inflict poverty on over a billion people, especially when compared to the response to Ebola which killed “only” 12,000 in a year.  The NTD community can focus on successes (one BILLION annual treatments; elimination successes), but the challenges to achieving WHO Road Map targets are less prominent in debates and need to be addressed by a reappraisal of what is possible with the limited resources. We ask, is the glass half full or half empty?

The challenges of elimination and eradication and the achievement of WHO Road Map Targets-resources (human and financial), effectiveness of available tools, innovation, the role of vector control, accessing remote populations, security and conflict, and the high costs of the “last mile” in elimination and eradication programmes, suggest that realistically such programmes have a 20 year plus time frame which require longer term perspectives often beyond donor horizon.

The impact of the socio-political, geographic, ecological, and climate impacts on NTD epidemiology and the difficulty of treatment and control in rapidly expanding and complex urban settings exemplify major challenges.

Can the health community respond to rapidity of change on epidemiology? Can new products be introduced and resourced in sufficient time to make an impact? WHO imposes rigorous requirements before it recommends introducing new policies to treat or control infectious organisms and vectors. Yet, many organisms have the capacity to respond to selective pressures faster than any policy response. This makes policy guidance and implementation of that policy behind the curve of what is critically needed should problems such as resistance occur.

Country ownership and engagement

It is important that endemic countries are aware of the problems NTDs pose to their populations and the economic and social benefits that accrue from implementing recommended WHO strategies. The value and leverage provided by drug donations of NTD drugs and the low delivery costs at often less than USD$0.50 per person/annum represent huge opportunities to provide essential drugs valued at USD$ 2–3 billion/year. The delivery costs represent a small percentage of per capita national health expenditure even for the poorer countries which have the highest burden of NTDs.

Hence, the pharmaceutical donations play a crucial role as do NGDOs as contributors and implementers of NTD programmes “for as long as needed”. There is also a crucial role of CEO Round table as an advocacy link to Bill Gates, whilst President Jimmy Carter has been an essential advocate for the Guinea Worm Eradication Programme and locally in Nigeria ex-President Yakubu Gowon. There is however a need for a greater country commitment and also more bilateral donors to engage beyond USAID and DFID. The challenge is how this can this be achieved. One of the challenges within countries is working with other compatible programmes, such as malaria vector control in Africa for filariasis[1]; HIV/AIDS and schistosomiasis[2]. There are significant opportunities for programme synergies: polio programmes have assisted surveillance for guinea worm and laboratory diagnosis for worms has recently been examining stool samples collected by the global polio programme networks who sample children to detect STH prevalence; bed nets for the prevention of malaria and lymphatic filariasis (LF); and improved WASH for prevention of several NTDs, such as schistosomiasis, STH, trachoma and guinea worm. However, there remains a need for greater appreciation of the benefits of linking country programmes.

The challenge is for the health sector to engage with the WASH and education sectors for soil-transmitted helminths (STH)[3]. Similarly, for rabies control via dog vaccination who pays—the health or veterinary sector? Can the “One Health” concept be operationalised?

 NTDS and health systems

The role of NTDs programmes have in strengthening health systems are exemplified by: improved drug and supply chain management; improved surveillance and reporting systems; evaluation and monitoring; enhanced engagement of community with distribution systems (mass drug administration (MDA) programmes reach ‘beyond the end of the road’); empowered communities that are involved in other health issues; improved laboratory capacity; promotion of improved surgery practice; and enhanced cross programme links (see above).

Country ownership of NTD programmes should be recognised as being an integral part of the health system and not separate from it. Populations are entitled to the multiple benefits provided by drug donations—products all on the Essential Medicine List[4] which poor people have a right to access. 

NTDs—the disability and mental health dimensions

The burden of NTDs of mortality and morbidity as reflected in global burden of disease[5] studies has been underestimated and inappropriately attributed; misclassification of NTDs which cause cancers (trematodes), injuries (rabies/snakebite), and neurological conditions (epilepsy) mean that published figures do not truly reflect the problems posed by NTDs.

In addition, there is an unrecognised mental health burden of NTDs and co-morbidity and disability including caregivers (see Reading 2) in particular in LF, onchocerciasis, leishmaniasis, Buruli ulcer, leprosy, and trachoma. The morbidity of mental health caused by NTDs has not until recently been recognised either by the NTD community nor by the mental health community whilst the stigma and physical disability caused by clinical conditions directly categorise NTDs as major causes of a range of disabilities.

Some future challenges

Social science studies have a key role to play in understanding the community perspectives of MDA and the culture-specific approaches needed to improve drug delivery to different populations.

There is a need for more extensive use of technology in surveillance and communication (mapping, SMS, MMS and photo identification of cases) to ensure targeted delivery of implementation.

A major challenge will be to reaching remote populations in equatorial regions—for example, the Yanomami in Brazil and Venezuela; eastern Congo; Papua New Guinea. These settings are characterised by dense tropical rain forests and limited transport access to isolated communities with limited or no access to formal government health care provision. It is questionable whether elimination can be achieved and verified in these settings.

Greater recognition of the role of insects as vectors and snails as intermediate hosts is often overlooked. Elimination programmes should focus on transmission interruption as the key means of impacting on prevalence. For example, compare the impact of bed nets on malaria mortality from 2000–2015: most of the health gain has been through insecticide treated bed nets. Furthermore, success of river blindness programme from 1974–2000 was due almost entirely to blackfly control. Capacity strengthening for medical entomology[6] is seriously deficient and many NTDs are vector transmitted. The threat of epidemic dengue in Africa, new Chikungunya outbreaks; and the Zika experience are warnings of emergent vector borne viruses given expansion of certain Aedes mosquito populations: Aedes albopictus into Europe and Aedes aegypti in southern USA. Yellow Fever (transmitted by A. aegypti) has the best vaccine against any infectious disease and is produced in Brazil, and yet we have emerging epidemics in Brazil as well as in Africa. Allied to this is the monitoring for insecticide resistance, which will be a pre-requisite but for which few skills are available.

Innovation has been the key to progress and examples of innovation are well documented for NTDs. For example, the Community Directed Treatment for the river blindness programme resulted in increased health delivery of other interventions beyond the reach of the formal health system, such as filters for guinea worm; innovative health education tools (board games, exercise books, and printed cloth); the dose pole for measuring drugs needed as a surrogate for weight; and the use of SMS and MMS for reporting. These types of innovations have had a massive impact. Emerging new tools derived from basic research are limited and unlikely to be deployable in the time frame of 5 years. Innovation is not just the search for a magic bullet (which will be expensive to deploy).

However, is eradication sensu strictu possible given the definition—permanent reduction to zero of the world wide incidence of infection caused by a specific agent as a result of deliberate efforts; intervention measures are no longer needed—?

Polio and guinea worm have recorded, respectively, 12 and 30 cases in 2017, but challenges in certification need to be overcome. Polio in Pakistan and Afghanistan and inability to access insecure areas in Mali, Sudan, and South Sudan in the Guinea Worm Programme demonstrate common challenges. Yaws is another NTD which is believed to be possible to eradication.

Research needs are well-defined and have been for many years; however, few products are in the pipeline and dependence is still on drugs from other sectors (animal health) and the pyrethroids, which were developed for agricultural pest control. Whilst each specific organism requires a specific drug, a single effective new insecticide would have multi-disease impact for vector-borne NTDs as well as malaria, yet far less is being spent proportionately on vector control research than on disease specific drugs. New insecticides or other vector control measures are in the pipeline but time to implementation of new products (from agrichemical sector) will be on a 5–10 year horizon whilst insecticide resistance continues to spread rapidly.

The NTDs and SDGs–a summary of links

Maintaining the NTD brand as a key contributor to achieving the SDGs (Reading 6) and challenges of key sector beyond health such as WASH and Education. Most of the SGDs have an NTD dimension beyond health targets: poverty, partnerships, education, water and sanitation. NTDs will be a ‘litmus test’ of SDG progress given numbers of SDGs relevant to NTDs.

• SDG 1 End poverty: NTDs create and drive the medical poverty trap.
• SDG 2 End hunger – achieve food security – improve nutrition: Parasitic worms greatly impact nutrition and growth; guinea worm is often called the ‘disease of the empty granary’ because peak transmission coincides with the agricultural season, leaving individuals unable to tend fields.
• SDG 3 Ensure health lives: Universal Health Coverage. Goal for NTDs programmes to reach over one billion people with treatments. NTDs have been specified in the health targets along with malaria, HIV, and TB.
• SGD 4 Education: NTDs impact the health of school children, their attendance, and educational performance. Children are also affected indirectly because they act as carers and because parents cannot afford fees due to NTDs.
• SDG 5 Achieve Gender equality: There is a disproportionate impact of NTDs on girls and women due to anaemia caused by schistosomiasis and hookworm and urogenital schistosomiasis and HIV transmission. Therefore, there needs to be improved access to praziquantel for women and girls.
• SDG 6 Ensure access to water and sanitation: Reduce the transmission of worms, schistosomiasis, guinea worm, and trachoma through WASH improvements.
• SDG 11 Sustainable cities: Urban transmission of dengue and Zika can be reduced by improving planning to reduce vector breeding.
• SDG 12 Combat climate change: Arrest the spread of potential vectors from tropical areas which carry diseases such as dengue, chikungunya, and schistosomiasis (Corsica).
• SGD 15 Sustainable forests, combat desertification, halt biodiversity loss: All factors which enhance emergence of vector borne NTDs.
• SDG 17 Global Partnerships: NTDs success based on strong multi partner alliances of endemic countries, private sector, bilateral agencies, WHO/World Bank/NGDOs, civil society, academia, and philanthropy.

Footnotes

[1] Mosquitoes of the genus Anopheles (in rural areas of Africa and elsewhere) carry the parasite W. bancrofti which causes filariasis. These mosquitos also carry the parasites that causes malaria and thus vector-control programmes aimed at malaria prevention can have beneficial spill over effects on filariasis prevention.

[2] Urogenital schistosomiasis is also considered to be a risk factor for HIV infection, especially in women (WHO, 2018).

[3] Such as roundworm (ascariasis), hookworm (Necator americanus and Ancylostoma duodenale), and whipworm (trichuriasis), which can cause anaemia (particularly in pregnant women and children), vitamin A deficiency, malnutrition and impaired growth, delayed development, and intestinal blockages. (WHO, 2018)).

[4] Essential medicines are those that satisfy the priority health care needs of the population. They are selected with due regard to public health relevance, evidence on efficacy and safety, and comparative cost-effectiveness. Essential medicines are intended to be available within the context of functioning health systems at all times in adequate amounts, in the appropriate dosage forms, with assured quality and adequate information, and at a price the individual and the community can afford. The implementation of the concept of essential medicines is intended to be flexible and adaptable to many different situations; exactly which medicines are regarded as essential remains a national responsibility (WHO, 2017).

[5] The WHO global burden of disease (GBD) measures burden of disease using the disability-adjusted-life-year (DALY). This time-based measure combines years of life lost due to premature mortality and years of life lost due to time lived in states of less than full health. The DALY metric was developed in the original GBD 1990 study to assess the burden of disease consistently across diseases, risk factors and regions (WHO, 2018).

[6] The study of insects that cause disease or that serve as vectors of organisms that cause disease in humans.

Readings

Reading 1:

Molyneux, D. (2014). Neglected tropical diseases: now more than just ‘other diseases’: The post-2015 agenda. International Health, 6(3), 172–180. doi:10.1093/inthealth/ihu037

Reading 2:

Litt, E., Baker, M.C. & Molyneux, D. (2012). Neglected tropical diseases and mental health: A perspective on comorbidity. Trends in Parasitology, 28(5), 195–201. doi:10.1016/j.pt.2012.03.001

Reading 3:

Molyneux, D. (2017). The London declaration on neglected tropical diseases: 5 years on. Transactions of The Royal Society of Tropical Medicine and Hygiene, 110(11), 623–625. doi:10.1093/trstmh/trw082

Reading 4:

Molyneux, D. (2015). Eradication and elimination: Facing the challenges, tempering expectations. International Health, 5(1), 299–301. doi:10.1093/inthealth/ihv050

Reading 5:

Molyneux, D. (2010). Neglected tropical diseases—beyond the tipping point? The Lancet Series on Neglected Tropical Diseases, 375(9708), 3–4. doi:10.1016/S0140-6736(09)61914-0

Reading 6:

Bangert, M., Molyneux, D., Lindsay, S.W., Fitzpatrick, C. & Engels, D. (2017). The cross-cutting contribution of the end of the neglected tropical diseases to the sustainable development goals. Infectious Diseases of Poverty, 6(73). doi:10.1186/s40249-017-0288-0

Key websites

• WHO: Neglected tropical diseases: http://www.who.int/neglected_diseases/en/
• CDC: Neglected tropical diseases: https://www.cdc.gov/globalhealth/ntd/index.html
• PLOS Neglected tropical diseases: http://journals.plos.org/plosntds/s/journal-information

Questions to guide reading

1. NTDs—a global pandemic: Why is only 0.6% of Official Development Assistance for health devoted to a group of infections that kill circa 350,000 people annually and inflict poverty on over a billion? Compare response to Ebola which killed “only” 12,000 in a year.
2. How can we engage the WASH and Education sectors for STH and schistosomiasis to play a key role in provision of services and drug distribution via schools? Similarly, for rabies control via dog vaccination, who pays?
3. Health or veterinary sector. Can the “One Health” concept be operationalised?
4. NTD community focuses on successes (one BILLION annual treatments; elimination successes), but the challenges to achieving WHO Road Map targets are less prominent in debate and need to be addressed by re-appraisal of what is possible with the limited resources: Is the glass half full or half empty?

Suggested citation

Molyneux, D. (2018). The global challenge of NTDs: The classic interface of poverty, health and development. K4D Reading Pack. Brighton, UK: Institute of Development Studies.

Related Resources

See the HEART talks post Communicable diseases: Key challenges and potential solutions for a brief overview of communicable diseases.

Other reading packs in this series include:

• Emerging issues in HIV
• Malaria: Key challenges and potential solutions
• Emerging issues in tuberculosis

Key concepts

HIV (human immunodeficiency virus) is a viral infection of humans that can be transmitted by sexual contact, from mother-to-infant during pregnancy, delivery or breastfeeding, or by injecting drug use.

AIDS (acquired immunodeficiency syndrome) refers to the clinical syndrome caused by HIV infection, and is characterised by a weakened immune system that results in increased susceptibility to severe infections, cancers and death. HIV-infection was first recognised among men who have sex with men in Los Angeles, USA, in 1981, but since then has been identified in all continents of the globe. On average, it takes approximately 10-12 years from a person being infected with HIV to them developing AIDS, although other symptoms appear earlier.

ART (antiretroviral therapy) refers to the combination of medications (usually three different drugs) that are taken daily and suppress HIV virus replication. Although ART doesn’t cure HIV, taking the correct medication with good adherence allows the immune system to recover, avoid opportunistic infections, and people to regain strength and return to their livelihoods. Increasingly, ART can be given as a single fixed-dose combination single pill once daily with very few side effects. Evidence suggests that people with HIV taking ART can expect a life-expectancy similar to that of HIV-negative individuals.

HIV viral load (VL) is a measurement of the number of copies of HIV virus per cubic centimetre of blood. Rates of HIV viral load can reach very high levels (up to 10⁷ copies/cm³) in the 4-6 week period immediately after infection, and as the immune system becomes very weak years after infection. HIV viral load is strongly related to infectivity, with very high levels associated with increased risk of the virus being passed during sexual contact or other exposure. A key aim of ART is to reduce the HIV viral load to an undetectable level in the blood, indicating that viral replication is suppressed. Raised viral load whilst taking ART may indicate treatment failure, resistance to the drugs, or poor adherence.

Epidemiology of HIV

Globally in 2016, an estimated 37 million people were living with HIV infection, with the countries Eastern and Southern Africa (53% of all infections) disproportionately affected.

Rates of new HIV infections have declined substantially from a peak of 1.9 million in 2005 to 1.0 million in 2016. However, some groups have shown greater declines in new infections than others. In particular, women have higher treatment coverage and better adherence to ART than men, and rates of death from AIDS-associated illnesses were 27% lower among women than men in 2016.

In Southern and Eastern Africa, reductions in HIV deaths have been rapid, and strongly linked to the roll-out of ART programmes since the early 2000s. Between 2004 and 2016, there was a 62% decline in the number of deaths attributable to HIV infection in this region. Reductions in HIV deaths have also been observed in the Caribbean, North America, West and Central Europe, and Western and Central Africa. However, declines have been more gradual in Latin America, and there have been worrying recent increases in the Middle East and North Africa and in Eastern Europe and Central Asia.

Recent increases in new HIV infections have been seen among key population groups at increased risk of infection, including men-who-have-sex-with-men (MSM), transgender people, sex workers and people who inject drugs.

90-90-90 targets

UNAIDS has defined targets for ending the AIDS epidemic, known as the 90-90-90 targets.

These are that by 2020:

• 90% of people living with HIV should have been tested and made aware of their status;
• 90% of people diagnosed with HIV should be taking ART;
• 90% of people taking ART should have a suppressed HIV viral load.

Modelling suggests that if these targets are achieved, the global number of new infections would be reduced to less than 500,000 per year.

By the end of 2016, substantial progress had been made towards achieving the 90-90-90 targets. Globally, an estimated 70% of people with HIV knew their status, 77% were taking ART and 82% were virally suppressed. A number of countries in sub-Saharan Africa, including Botswana, Rwanda and Malawi have reported that they are close to achieving the 90-90-90 targets.

However, substantial work remains to be done. Although globally we are on track to have 30 million people taking ART by 2030, rates of new infection are not falling quickly enough, suggesting a more differentiated approach to identifying and treating hard-to-reach groups is needed.

The HIV care cascade is a key advance in understanding care, treatment and prevention gaps, and analysis of a country’s or a region’s cascade can provide insights into how to best improve HIV care systems.

The global HIV care cascade, 2016

Recent advances in HIV treatment and prevention

HIV testing services

HIV testing is the entry point to comprehensive care and prevention. WHO recommends that all individuals at risk of HIV receive an HIV test annually (or more frequently if ongoing exposure) and when they come into contact with a health provider. However, a substantial HIV testing gap remains, with only half of adults in sub-Saharan Africa reporting having had a test within the previous 12 months. Men have particularly low rates of HIV testing.

In addition to improving HIV testing services within health centres—which many people struggle to access, or only do so once their illness is advanced—a broad mixture of HIV testing services are required to meet the needs of local populations. This should include high-quality community-based HIV testing initiatives such as mobile campaigns, door-to-door testing programmes, school-based HIV testing, workplace-based HIV testing, and event-based HIV testing (such as associated with sporting events, or on national testing days). Evidence shows that extensive pre-test counselling is detrimental, and WHO now recommends that only very brief counselling should be provided, except in exceptional cases

In recent years, HIV self-testing—defined as someone performing and interpreting their own HIV test, perhaps supported by a family member, friend or health worker—has become widely available, driven by convenient oral fluid and blood-based kits. Data from a number of large studies in Africa, Asia, Europe and the Americas shows that HIV self-testing programmes can achieve high rates of coverage and are extremely popular with testers because of their low cost, convenience and confidentiality.

It is critical that following an HIV test, comprehensive programmes are in place to link people to either HIV treatment or prevention services. Too often individuals are not successfully linked to the care that they require, increasing risk of death, and of passing infection to others. Interventions such as home-based ART initiation can improve rates of linkage.

HIV treatment as prevention

Over the last decade, a number of mathematical models and observational studies have provided evidence to suggest that achieving high population levels of ART coverage could result in substantial reductions in new HIV infections and deaths. By rapidly identifying people with HIV and reducing their viral load to an undetectable level, their viral load will become “undetectable” and they will be substantially less likely to transmit infection to others. This “test and treat” strategy is known as treatment as prevention.

The HPTN052 study—a study where people living with HIV were randomly allocated to start ART immediately, or were delayed until their immune system had weakened¬ showed that the risk of HIV infection among their partners decreased by 93% when people living with HIV started ART immediately. This was a landmark study, showing that ART can provide highly effective and durable HIV prevention, and WHO recommended in 2013 that all individuals with HIV, regardless of immune system levels, should be initiated onto ART.

Additionally, further studies have shown that people who are immediately initiated onto ART have substantially lower rates of opportunistic infections, cancers, and death.

At least four large randomised studies are evaluating the population effects of universal HIV testing and immediate ART initiation strategies on rates of new infections and are expected to report results shortly.

HIV treatment as prevention (TASP) therefore appears to be by far the most effective intervention that we have, both for preventing new infections, and for improving the health of people living with HIV. However, key challenges will include: sustaining high levels of HIV testing and linkage to treatment; reaching key populations and marginalised groups; and sustained health system support.

Pre-exposure prophylaxis

Pre-exposure prophylaxis (PrEP) refers to an intervention where HIV-negative individuals who are at increased risk of HIV infection take a daily or intermittent (e.g. before sexual contact) dose of ART. Several large randomised control trials have shown that, among a variety of populations, including men-who-have-sex-with-men, transgender individuals, sex workers and people who inject drugs, substantial reductions in new HIV infections can be achieved with PReP.

Key challenges with PrEP include ensuring that those most likely to benefit from PReP (especially marginalised groups and key populations) are able to access services, and ensuring high quality risk reduction counselling, adherence and support.

Voluntary male medical circumcision

Uncircumcised men are at increased risk of HIV infection due to the high numbers of cells receptive to infection in the foreskin of the penis. Three large randomised trials done in sub-Saharan Africa have conclusively demonstrated that voluntary medical male circumcision (VMMC) can reduce men’s relative risk of HIV infection by around 40%. Although efforts have been made to implement VMMC in high HIV prevalence countries, sustaining services has been challenging.

Readings

Avert. (2017). Pre-exposure prophylaxis (PrEP) for HIV prevention: Retrieved from: https://www.avert.org/professionals/hiv-programming/prevention/pre-exposure-prophylaxis

Ford, N., et al. (2018). The WHO public health approach to HIV treatment and care: looking back and looking ahead. The Lancet Infectious Diseases, 18(3), e76–e86. doi:10.1016/S1473-3099(17)30482-6

Geng, E.H. & Havlir, D.V. (2017). The science of rapid start—From the when to the how of antiretroviral initiation. PLOS Medicine, 14(7), e1002358. doi:10.1371/journal.pmed.1002358

UNAIDS (United Nations Programme on HIV/AIDS). (2017). UNAIDS Data 2017. Retrieved from: http://www.unaids.org/sites/default/files/media_asset/20170720_Data_book_2017_en.pdf

UNAIDS. (2018). HIV prevention. Retrieved from: http://www.unaids.org/en/topic/prevention

WHO (World Health Organisation). (2016). WHO: HIV self-testing – Questions and answers [Video], Durban, South Africa: Retrieved from: https://www.youtube.com/watch?v=BA5E9wsEbPw

Questions to guide reading

1. What mixture of HIV prevention interventions should be prioritised for the setting in which you work?
2. How can marginalised and key populations be supported in accessing HIV testing, treatment and prevention services?
3. How can health services sustain high quality delivery of HIV care and prevention services in the face of expanding demand, new interventions, and financial pressure?
4. What role do education and behaviour change interventions have in the TASP era?

Suggested citation

MacPherson, P. (2018). Emerging Issues in HIV. K4D Reading Pack. Institute of Development Studies: Brighton, UK: Institute of Development Studies.

Related Resources

See the HEART talks post Communicable diseases: Key challenges and potential solutions for a brief overview of communicable diseases.

Other reading packs in this series include:

• Malaria: Key challenges and potential solutions
• Emerging issues in tuberculosis
• The global challenge of NTDs  

A recent systematic review looking at short term water, sanitation and hygiene (WASH) interventions in emergency response found that ‘[d]espite regular use, emergency WASH strategies have a limited evidence-base’ and as delivering assistance has generally been
prioritised over research, much of the available literature is about ‘best practice’ rather than ‘evidence based’ programming (Yates et al, 2017, p. i). As a result ‘evidence remains low and lacking’ (Yates et al, 2017, p. iii). An analysis of emergency WASH looking for gaps and spaces for innovation found that ‘sanitation issues were identified as the major area with gaps and potential for innovation’ (Bastable & Russell, 2013, p. ii). Both solid waste and faecal sludge management fall under sanitation within WASH. Key gaps are around ‘excreta disposal issues such as latrines in areas where pits cannot be dug, desludging latrines, no-toilet options and the final treatment or disposal of the sewage’ (Bastable & Russell, 2013, p. iii).

Most of the available literature uncovered by this rapid review is grey literature, offering guidance on solid waste and faecal sludge management, rather than peer reviewed papers. It is not always clear what evidence the guidance papers used in this rapid review are based on. However, they have been written and produced by people and organisations who have worked extensively on WASH in emergencies.

A lot of available evidence focuses on water treatment plants, pre-assembled Mobile Water Treatment Equipment (MWTE), or modular water treatment kits (to be assembled in the field) which are used to clean water for drinking in emergency systems, which is not within the scope of this review. The WWTP findings listed are based on peer reviewed journals, global funding agency reports, as well as grey literature. Model information is taken from global manufacturers specialising in WWTP production, however, there is a paucity of information describing models used in specific settlements/refugee camps in low-income/slum areas.

Senior experts consulted for this review confirm that there are very little published evaluations on affordable wastewater treatment plants used in emergency settings. Although there are reports of camp areas specifically for women and children, most wastewater treatment plants are in settlements and sites to be used by both genders, therefore the data included in this review is gender-blind. No specific data searches were made for disabled WWTP users.

Wastewater treatment plants (WWTPs) remove contaminants from wastewater. The treatment to remove these contaminants includes physical, chemical, and biological processes to produce environmentally safe treated wastewater (Grange / HIF – Humanitarian Innovation Fund, 2016:10). Adequate sanitation provision is vital to promote health and prevent the spread of disease from wastewater in long-term temporary settlements such as refugee camps. As sites tend to be overcrowded, facilities can be far from adequate.

Join Future Health Systems on Thursday, January 28, 2016 from 3:00 PM to 5:00 PM (EST) as Melissa Leach, the Director of the Institute for Development Studies, UK, walks through the kinds of architectures and capacities that could strengthen the social dimensions of epidemic preparedness and response, across activities from foresight, anticipation and contextual research to developing rapid response networks and strengthening trust in health systems. She will draw on the experiences of IDS under the R2HC-funded Ebola Response Anthropology Platform (ERAP), the Ebola: Lessons for Development initiative, and related work on the multiple drivers of zoonotic disease.

DISCUSSANTS:

Lauren Sauer, Dept. of Emergency Medicine and Center for Refugee and Disaster Response, Johns Hopkins Univerisity

Susan Shepler, School of International Service, American University

MODERATOR:

Shan Soe-Lin, Program Director at Results for Development Institute

WHEN:

Thursday, January 28, 2016 from 3:00 PM to 5:00 PM (EST)

WHERE:

Results for Development – 1111 19th Street, NW, Suite 700 Washington, DC 20036

Please visit the Future Health Systems website for more details.