Newer malaria interventions are coming on board, and whether these will be used of a large scale or targeted to certain epidemiological contexts remains to be seen. In each case, one will need to examine if in each context one can measure whether the intervention is universally accessible to and used by the intended population or subgroup.
After 30 years of research and testing, a malaria vaccine is ready to go through implementation testing in Malawi, Ghana and Kenya. This pilot of the vaccine, known as RTS,S, will be made available to children up to 2 years of age with the Malawi launching first during the week of World Malaria Day.
WHO explains that, “The malaria vaccine pilot aims to reach about 360,000 children per year across the three countries. Ministries of health will determine where the vaccine will be given; they will focus on areas with moderate-to-high malaria transmission, where the vaccine can have the greatest impact.” There will be a strong monitoring component to identify coverage levels as well as any implementation challenges and adverse effects that may only become visible in a larger scale intervention that the typical efficacy trials. Implementation is occurring in areas with a relatively strong existing malaria control effort, with an intent to learn how a vaccine can complement a total control package.
Mass Drug Administration (MDA, also known as preventive chemotherapy) has been a successful strategy for controlling and eliminating neglected tropical diseases with special reference to onchocerciasis, lymphatic filariasis, trachoma, soil transmitted helminths and schistosomiasis. MDA use in malaria has been limited due to a number of financial and logistical challenges, not the least of which is the need to achieve high coverage over several periods of distribution. This is why WHO recommends, “Use of MDA for the elimination of P. falciparum malaria can be considered in areas approaching interruption of transmission where there is good access to treatment, effective implementation of vector control and surveillance, and a minimal risk of re-introduction of infection.”
Another link with MDA for a different disease, onchocerciasis, has pointed to a potential new malaria intervention. Around ten years ago it was observed that after ivermectin treatment for onchocerciasis in Senegal survivorship of malaria vectors was reduced. Subsequently the potential effect of ivermectin has been intentionally researched with the outcome that, “Frequently repeated mass administrations of ivermectin during the malaria transmission season can reduce malaria episodes among children without significantly increasing harms in the populace.” Mathematical models for onchocerciasis control have predicted the need to achieve annual coverage targets below what could be called universal levels. Using ivermectin for mosquito control would require more frequent dosing and higher coverage.
Although not defined as ‘new’ it is important to include mention of additional vector interventions like larviciding and indoor residual spraying, as these present technical and coverage challenges. For example, larviciding interventions either chemical or biological, do not cover individuals. These focus on breeding sites in communities. This may require better use of the concept of geographical coverage as has been used in onchocerciasis control wherein the proportion of endemic villages reached is monitored.
For example, in Mali the NTD program aimed to achieve 80% program coverage of individuals eligible for preventive chemotherapy and 100% geographical coverage yearly. This means all villages should be reached. In reality, the program achieved 85% geographical coverage for lymphatic filariasis and over 90% for onchocerciasis.
In conclusion, we have seen that defining as well as achieving universal coverage of malaria interventions is a challenging prospect. For example, do we base our monitoring on households, villages, or populations? Do we have the funds and technical capacity to implement and sustain the level of coverage required to have an impact on malaria transmission and move toward elimination? Are we able to introduce new, complimentary and appropriate interventions as a country moves closer to elimination?
Njabuliso Lukhele of the Ministry of Health Swaziland shared Swaziland’s experiences in Vaccine Procurement at the recent Regional Immunization Technical Advisory Group (RITAG) Meeting, Johannesburg, South Africa, 05-08 December 2017. A summary of his presentation appears below.
As a Lower Middle Income Country (MIC), Swaziland is not and has never been eligible to receive financial support for its immunization programs through the GAVI Alliance. Therefore, 83% of the health care budget is financed through domestic sources, and only 17% comes from from WHO and UNICEF.
Swaziland has a comprehensive Multi-Year plan (cMYP) that drives investment in immunization covering the period 2017–2021. The Government of Swaziland has been fully funding 100% of vaccine costs and average 96% of routine immunization costs over the last years. The Government of Swaziland procures vaccines and distribute to all service providers (government, regional referral and mission hospitals, public as well as private sector clinics and health facilities).
The vaccine Procurement Process begins as Requisitions are sent by Expanded Program of Immunizations (EPI) unit to the procurement unit through the chief pharmacist through documented minutes. This Minute is approved by the Financial Controller (FC) acknowledging availability of funds to furnish the procurement of the vaccines. Then a Tender document is drafted by both the EPI and procurement unit. Advertisement of tender document then takes place. Tender runs for 30 days as per procurement policy. Procurement of vaccines is done through open tender.
The 5 top vaccines (PCV, IPV, OPV, Rota, Penta) in Swaziland represented 98% of the total costs in 2015-16. While this is a major internal financial obligation, Vaccine procurement for the relatively small population of Swaziland represents approximately 0.2 percent of the overall African market by volume and about 0.4 percent by value. This puts smaller countries at a disadvantage in terms of getting good pricing and negotiating with suppliers.
Swaziland was one of the first countries for the Middle Income Country (MIC) strategy mission The MIC strategy mission recommended the need on generating efficiencies in the management of the programme, in particular in the area of procurement, with a need to explore pooled procurement as well as other options with the aim of maximizing savings on the high costs of vaccines. Government desires to achieve economic efficiency in procurement and consideration of pool procurement mechanism.
The current supplier charged 81,256,196.50 Swaziland Lilangeni (SZL) or roughly $5.8 million for the total package of vaccines needed in 2016. If UNICEF were to provide the same package it would cost SZL 62,215,336.34. or $4.5 million. While commercial suppliers can be paid on delivery, UNICEF requires approval from Ministry of Finance for the advance payment with the need to make sure the funds are sufficient for full payment.
This comparative information had valuable advocacy effect. Earlier this year (2017) a MOU signed between MOH and UNICEF. A commitment letter was sent to UNICEF supply division. Now Swaziland has a more reliable supplier and a more affordable cost, enhancing the Ministry’s capacity to save lives of its citizens. Swaziland can also serve as an example for the many other MICs and countries who are ‘graduating’ from GAVI support.
Dr Denis Marke, CH/EPI Program Manager at the Sierra Leone Ministry of Health shared his experiences from a recent natural disaster at the WHO African Regional Immunization Technical Advisory Group meeting in Johannesburg, 5-8 December 2017. Below find his observations.
Heavy rains occurred in the early hours of 14th August 2017 that resulted in flash floods and mudslides that affected three communities (Sugar Loaf, Motomeh, and Kaningo) in the Western Area districts. The mudslides and flash floods blocked water ways and contaminated water sources in several low lying communities of Freetown, the capital city. Both mudslides and flooding destroyed houses, killing many people and displacing thousands of people. In addition, water and sewerage infrastructure were damaged.
Data collected from the emergency operations centre set up to manage the incident showed that 496 people died (168 females, 171 males of which 157 children). An additional 5,905 people were registered as displaced. The WHO assessment classified the incident as a Grade 1 emergency.
In analysis of health risks likely to affect the displaced people, cholera was ranked high on the account that there had been no confirmed Cholera outbreak since 2012. All historical outbreaks of cholera were analyzed and documented to a) Sierra Leone had had a history of 9 cholera outbreaks between 1970-2012; b) large outbreaks with case counts above 20,000 had occurred in 1994/5 and 2012; c) improved case-fatality ratios due to improvements in Health Worker skills and competencies in case management; d) almost all cholera epidemics occurred or peaked in the rainy season and e) shortening inter-epidemic periods, and thus another Cholera outbreak had been predicted since 2016.
A preventive Oral cholera vaccination concept for prevention of Cholera in Sierra Leone as part of the interventions in the emergency was mooted by WHO as the lead agency supporting the emergency response. A technical proposal for Oral Cholera vaccination was developed, presented and discussed at the Emergency Operations Centre and approved by the Ministry of Health and Sanitation. Support to implement the Oral Cholera vaccination was received from the Global Outbreaks and Alert Network, ICG, GAVI, UKaid, PIH and MSF.
Preparations for Oral Cholera vaccination broke records in terms of speedy planning and implementation. The OCV concept note was developed and approved by the MOH in 9 days. A proposal and request for OCV was approved by ICG in 72 hours. And the approved OCV doses were delivered in-country in 10 days. The national Regulatory Authority gave a waiver of vaccine registration, on the account of WHO pre-qualification and procurement through UNICEF supply division, and the OCV campaign conducted within 7 days of vaccine receipt. Notably, this was the FIRST cholera vaccination campaign EVER conducted in Sierra Leone and FIRST for that matter in an emergency.
The Objective of the OCV campaign was to provide two OCV vaccination doses to at least 95% of populations above 1 year of age living in communities affected by floods and mudslides and vulnerable populations in slums. The campaign took place in two rounds conducted on 14th – 19th September 2017 (first dose) and 5th – 10th October 2017 (second dose).
The Target Population for the Oral Cholera vaccination was all people aged >1 year resident in flood affected and slum communities of Western Area (Urban/Rural). Based on population projections for the affected communities, the estimated target was planned as 539,692 individuals.
The Oral Cholera vaccine delivery strategy was based on experiences from Oral Polio SIAs and it included four approaches: 1) House to House; 2) Schools-based temporary vaccination sites; 3) Fixed site at 22 affected Peripheral Health Units and 4) Outreach/mobile vaccination posts in camps of displaced people.
Overall the OCV Campaign reached 96.1% of the target population in the first round and 100% in the second round. Post campaign independent monitoring documented that the overall coverage was slightly lower than was reported using the administrative reporting system. Independent monitors also documented that the main reasons for accepting vaccination were a) health information given out by health workers about the dangers of cholera, b) assurance from health workers and community leaders that the vaccine was safe. Unlike all previous Polio vaccination campaigns, radio, community social mobilizers, health workers and TV were the main source of information about the campaign.
Where non-vaccinated people were found, the major reasons were a) Poor H2H team movements and penetration; b) absence of beneficiary; c) Acute sickness and d) unaware of vaccination dates/time. The poor team performance was attributed to the challenging terrains and clogged roads.
To verify community coverage, a post OCV Verification Survey was conducted from 21- 29 October 2017 in 140 clusters (enumeration areas). In total 2,908 Households studied and 6,987 individuals interviewed. Among people vaccinated 31.1% received only one dose and 68.6% received two doses.
In addition to oral cholera vaccination, Sierra Leone a) provided standard case definitions for cholera and trained camp commanders in the displaced populations to improve early detection of suspected cases; b) Updated and disseminated case management guidelines before conducting refresher training of case-management teams; c) Procured and prepositioned transport media for stool samples to be taken from suspected cases; d) Stock-piled and prepositioned at least 1 cholera case management kit; e) developed and disseminated IEC materials before conducting community engagement meetings with 48 Ward Councilors, 100 Market women, 120 teachers, 60 religious leaders and 40 CBO staff and f) Assured inclusion of cholera preparedness and response as a standing agenda of all EOC coordination mechanisms
This preventive effort not only kept cholera out of the area but also strengthened capacity to respond to future outbreaks and preventive campaigns. Coordination mechanisms have been established, vaccinators have been trained. Behavior change communication messages have been developed and a monitoring mechanism was tested to verify post-intervention results. Coming out of the Ebola epidemic of a few years ago, Sierra Leone is encouraged by its new abilities to respond to emergencies and prevent outbreaks.
We acknowledge the assistance of Dr William Baguma MBABAZI, Medical Epidemiologist, EPI/WHO Sierra Leone, in the preparation of this posting.
Dr. Anthony Laku who is currently the Immunization Program Officer in the South Sudan Ministry of Health presented the status of efforts to eliminate maternal and neonatal tetanus (MNT) in South Sudan at the fourth meeting of the WHO Regional Immunization Technical Advisory Group held 5-7 December 2017 in Johannesburg, South Africa. A summary of key challenges is shared below.
General Challenges to health delivery in South Sudan include a Maternal Mortality Ratio of 2054 per 100,000 live births. Also ~56% of population are not reached by Health Facilities; 60% of roads not accessible for half of the year; 45% of people live without access to safe water; and 86% of women have no formal education.
Delivery of immunization is hampered by persistent insecurity and inaccessibility. As of 31st August 2017, 7.5 million people are affected, and 3.9 million people are displaced, of which 2 million are in neighboring countries. The health services have varying degrees of difficulty in reaching the displaced people with immunization services.
Key strategies to eliminate MNT are as follows:
- Three doses to all Women of Reproductive Age (WRA) using supplementary immunization activities (SIAs)
- Provision of at least two doses of tetanus containing vaccines (TT) to all pregnant women and in high-risk areas
- Promotion of clean delivery services for all pregnant women, and
- Effective surveillance for MNT
So far the results have been below the targets for elimination. For example, 61% of 80 counties had less than 80% coverage in the third Round of Tetanus Containing Vaccines SIAs with 27/80 counties not reached at all. There was low estimated routine immunization (Penta3) coverage of only 26% in 2016. A limited number of skilled staff were available to ensure clean cord delivery (5% skilled delivery) with challenging implication on MNT elimination validation.
The protracted civil crisis in the country creates an uphill task for reaching key global targets including MNT elimination. Weak economic status in the country has had a ripple effect on staff motivation and commitment (e.g. delayed salaries).
Additional strategies were adopted for coverage improvement in 2017. A “Hit and Run” strategy was developed for insecure areas. Periodic Intensification of Routine Immunization was used in areas of intermittent crisis and or with high buildup of unimmunized populations. Overall the MNT elimination strategic plan was updated for 2018–2022.
Funding gaps exist for this new strategic plan with only 21% of needed finance is pledged. One approach to funding is aligning MNT elimination with funding in related areas such as the RMNCAH and Nutrition strategy and the Human Resource for Health Strategy. Despite these challenges South Sudan is persisting in efforts to eliminate MNT.
World Pneumonia Day (WPD) helps us focus on the major killers of children globally. While Pneumonia is responsible for more child mortality across the world, in tropical malaria endemic areas both create nearly equal damage (see WPD graphic showing Nigeria and DRC which are both have the highest burden for pneumonia, but also malaria). Of particular concern is case management at the clinic and community level where there is great need to differentiate between these two forms of febrile illness so that the right care is given and lives are saved.
Diagnostics are a particular challenge. While we now have malaria rapid diagnostic test kits that can be used at the community level, we must rely on breath counting for malaria. The Pneumonia Diagnostics Project (see video) “is working to identify the most accurate and acceptable devices for use by frontline health workers in remote settings in Cambodia, Ethiopia, South Sudan and Uganda.”
Ease of use at low cost must be achieved. One approach to solve the pneumonia diagnostics challenge at community and front line clinic level is to find “mobile phone applications or alternative energy for pulse oximetry,” to test low oxygen levels.
Vaccine development for both diseases is underway. The challenge for malaria results from the different stages of the parasites life-cycle. Lack of affordable vaccines for pneumonia limits at present widespread preventive action, though public-private partnerships offer hope.
Dispersable and correct dose for age prepackaged malaria drugs are already available. Now more child-friendly medicines for pneumonia are being developed. In low resource settings, “amoxicillin dispersible tablets are a better option, particularly for children who can’t swallow pills. They have a longer shelf-life, are cost-effective, don’t need refrigeration, and are easy to administer.”
Similarities in the problems and solutions to control these two diseases require that interventions must continue to be developed and implemented jointly in order to benefit children the most. As can be seen again from the WPD graphics (right), many children do not get needed treatment. Integrated case management at all levels is the answer.
â€œThis is a scientific advance rather than a practical one,â€ said Dr. William Schaffner, of Vanderbilt Universityâ€™s Medical School to the New York Times. So goes the fate of the latest in research reports on efforts to develop a malaria vaccine.Â Prof. Schaffner goes on to explain that, “Giving multiple IV doses of any vaccine is also impractical because it requires sterile conditions, trained medical personnel and follow-up. IV drips are particularly hard to administer to children.”
It seems that every possible media outlet in the planet picked up on the fact that this intravenous dose of irradiated/killed malaria parasites was 100% effective. Most though did not see this as just one more step in understanding the long string of immunological research processes needed to come up with a vaccine that can actually work under real life field conditions.
Just last year, hopes crashed on a long-tested malaria vaccine known as RTS,S that had been through clinical trials in several African countries.Â Not only did the vaccine need to be administered three times, but even then achieved limited effectiveness, though severe malaria appeared to have been reduced by around 50%. Just last year unfortunate results from monitoring showed that over time the vaccine lost the effectiveness it initially achieved.
It had been hoped that if this or another successful vaccine candidate could be ready for scale up, that it could be integrated into the existing child immunization programs of malaria endemic countries. Findings from recent Demographic and Health Surveys shown here remind us that even vaccines that have been routinely delivered to children for decades still have problems achieving adequate coverage.Â Two of those depicted, DPT and Polio, like the RTS,S required three doses. This is a logistical and management challenge to be sure, but also a social, cultural and behavioral one.
The vaccine search goes on with several research reports appearing monthly on new findings about human immune responses to malaria in it various forms.Â We trust that one day a vaccine that is effective as the existing child immunizations will come to market. Even then, as we can see from ‘normal’ vaccine coverage rates, we will not be able to rely totally on a malaria vaccine for preventing the disease. Of course none of the existing preventive measures reaches all people, and hence our malaria elimination strategies must continue to include a combination of approaches.
Tuberculosis is one of the big three receiving Global Fund support, and like HIV and malaria control efforts, the emphasis is on multiple interventions to ensure ultimate success. Compared to the other diseases, TB’s interventions have been mainly limited to immunization and directly observed treatment. Both of these interventions have recently met some major challenges that have also plagued the other big diseases.
Roger Bate and colleagues, who have focused on the problems of fake and substandard malaria drugs have turned their attention to TB. (see http://masetto.ingentaselect.co.uk/fstemp/a5829970064042ab6ec12023d514ef4f.pdf ). Their investigation at pharmacies in 19 Asian and African countries found around 9% of TB drugs were substandard/poor quality. The rate of fake medicines was 16% in Africa and 10% in Asia.
Governments in these countries were encouraged to give these issues greater attention including better regulation and collaboration with international policing efforts.
The need for new vaccines is a necessary development to maintain a strong disease control arsenal. For TB, “A new vaccine, modified Vaccinia Ankara virus expressing antigen 85A (MVA85A), was designed to enhance the protective efficacy of BCG.” (as reported in The Lancet http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2960177-4/abstract )
As the BBC report on this study pointed out, “BCG is only partially effective against the bacterium that causes TB, which is why several international teams are working on new vaccines.” (see BBC at http://www.bbc.co.uk/news/health-21302518 )
While the new vaccine “… was well tolerated and induced modest cell-mediated immune responses. Reasons for the absence of MVA85A efficacy against tuberculosis or M tuberculosis infection in infants need exploration.” Fortunately research on other vaccine candidates is underway.
Continued control and eventual elimination of malaria and TB will require research that is both basic (vaccines) and applied (drug quality) in order to develop, maintain and implement effective strategies. Disease research budgets should not be compromised in the ever changing world of pathogen/parasite evolution.
The March 2013 issue of Discover Magazine provides a chilling overview of why a standard vaccine against pertussis (whooping cough) is no longer as effective as we hoped. About 20 years ago the US switched from killed whole bacteria vaccine to one that contained five key proteins. The change was necessitated by some severe reactions to the original vaccine. http://discovermagazine.com/2013/march#.URdn-2fn_1k
[PVirot, WHO Ethiopia 2002.]
It has come to light that the effects of the current pertussis vaccine, given in combination with tetanus and diphtheria immunization (DPT) last only a short time, as little as one year for adults receiving the booster. It seems that the five chosen bacteria proteins may have evolved and that those in the vaccine confer less immunity.
There are efforts to find new adjuvants to enhance efficacy, but what we are witnessing is a constant battle for balance between finding both safe and effective health interventions. http://www.ncbi.nlm.nih.gov/pubmed/23291942
Why should malaria program people be concerned about pertussis? Recent trials of the new RTS,S/AS02D malaria vaccine is that research trials of this new malaria tool were designed to integrate it into existing childhood immunization programs, including DPT. Not only are we concerned about whether the malaria vaccine works, but whether there might be any negative interactions with other concurrent vaccines. http://www.ncbi.nlm.nih.gov/pubmed/23297680
Community members may not easily distinguish all the different diseases in a vaccination program, but the success or failure of any one component may affect their attitudes to the whole package.
In the case of malaria, an effective vaccine that guarantees more protection than those currently under trial, will be important tools in efforts to control the disease. Vaccines may not yet provide the key to elimination. Also as we can see, vaccines that were once effective may loose their edge, much as parasites and vectors may develop resistance to medicines and insecticides. That is why program managers must always ensure adequate resources for a multi-intervention approach.