Zero Malaria Starts with Universal Coverage: Part 3 Innovations and New Interventions

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?

Zero Malaria Starts with Universal Coverage: Part 2 Preventive and Curative Treatments

April hosts several important global health days or observances. On World Health Day 2019 WHO stressed that, “Universal health coverage (UHC) is WHO’s number one goal. Key to achieving it is ensuring that everyone can obtain the care they need, when they need it, right in the heart of the community.” Nationwide monitoring through the Demographic and Health Surveys (DHS), the Malaria Indicator Surveys (MIS) and the Multi-Indicator Cluster Surveys (MICS) can document the status of appropriate malaria treatment and intermittent preventive treatment in pregnant women (IPTp).

Definitions of indicators have evolved for treatment-related malaria interventions. When Intermittent Preventive Treatment for pregnant women (IPTp) began in the early 2000s, the recommended dosing was twice during pregnancy after the first trimester one month apart in high and/or stable transmission areas. Due to lessening efficacy of sulfadoxine-pyrimethamine (SP), the dosage recommendation has changed to at least three times, still a month apart from the beginning of the second trimester.

This updated policy was broadcast widely between 2012 and 2013, but it took countries some time to build capacity and scale up for the expanded coverage goals. UNICEF Data5 again show that between 2014 and 2017 coverage was far below either 80% of pregnant women, let alone reaching them universally (Figure 2). Most countries achieved 30% or less coverage. Zambia at 50% was the highest. Low coverage leaves both pregnant women and the unborn child at risk for anemia and death in the former and low birth weight, still birth or miscarriage for the latter. The World Malaria Report of 2018 estimates that three doses of IPTp were received by only 22% of pregnant women in the target countries in 2017.

The concept of IPT was investigated for infants and children during by a consortium of researchers in several African Countries. It was found that IPTi with SP could have a positive effect on preventing malaria. To operationalize this concept, the World Health Organization developed what is known as Seasonal Malaria Chemoprevention (SMC) that would be delivered in the Sahel region of West Africa where malaria transmission itself is seasonal and where there are some countries with very low transmission with implications for malaria elimination.

The SMC delivery process was not linked to immunization but provided by community health workers and volunteers. SP and Amodiaquine (SP-AQ) were used in combination and provided monthly, three or four times during the rainy/high transmission season. Coverage was targeted at children below school age. It is only recently that SMC has been scaled up to reach all eligible countries or states and regions within designated countries.

WHO states that SMC focuses on, “children aged 3–59 months (and) reduces the incidence of clinical attacks and severe malaria by about 75%.” In some countries the coverage is extended to primary school aged children, making comparisons and calculations of coverage (universal por otherwise) challenging.

The World Malaria Report of 2018 notes that, “In 2017, 15.7 million children in 12 countries in Africa’s Sahel subregion were protected through seasonal malaria chemoprevention (SMC) programs. However, about 13.6 million children who could have benefited from this intervention were not covered, mainly due to a lack of funding.” This implies that 54% of eligible children were reached.  Coverage of SMC can refer to receiving any of the doses or as having received all the monthly doses offered by a nation’s malaria control program. Specifically, the World Malaria Report 2018 drew on surveys in 7 countries that provided 4 monthly doses to determine that 53% of children received all doses.

Determining coverage for malaria treatment for sick people is not as straightforward as finding out the numbers who slept under an ITN or swallowed IPTp doses, and even those are not simple. As defined, correct treatment first consists of parasitological diagnosis, which at the primary care level could be by microscopy or rapid diagnostic test (RDT). The next issue is treating only those with positive tests. Finally, the treatment must consist of age- or weight-specific doses of an approved artemisinin-based combination therapy (ACT) drug. Very few clinic records or surveys document whether the treatment given is ‘correct’ by these standards.

WHO addresses the need for achieving universal access to malaria diagnostic testing and notes this will not be easy. They provide a successful example of Senegal, where following the introduction of malaria RDTs in 2007, malaria diagnostic testing rates rose rapidly from 4% to 86% (by 2009). Logistics, funding, training and supportive supervision complicate implementation.

UNICEF Data report that performance of malaria diagnostics in febrile children in surveys between 2014-17 was approximately 30% on average for countries with national surveys within that time frame (Figure 3). Only 4 countries achieved 50% or better. Most surveys then go on to report the number of febrile children who received ACTs, but do not necessary indicate how many who were correctly diagnoses were given ACTs vs those who received ACT but did not receive a test or tested negative.

The Nigeria 2015 Malaria Indicator Survey Illustrates this dilemma. Among 2600 children who reported having a fever in the two weeks preceding the survey, 66.1% sought advice (or care). Overall, 12.6% of febrile children received a diagnostic test as defined in the question as to whether the child was stuck on the finger or heel to obtain blood. Among the febrile children 37.6% reportedly were given some type of antimalarial drug. Overall 15.5% of febrile children were given an ACT. Even if ACTs were given only to tested children, not all tests would have been positive.

The overall implication of measuring treatment without a link to testing is that if more children receive any, let alone the correct drugs, is that evidence for actual presence of disease. We have a long way to go to measure malaria treatment coverage correctly, not to mention achieving universal coverage with appropriate treatment. Different malaria treatment-related interventions with different steps and different target groups in different regions of Africa and the World make defining, no less achieving UHC, a huge challenge.

Zero Malaria Starts with Universal Coverage: Part 1 Nets

WHO says, “Malaria elimination and universal health coverage go hand in hand,” at a special event during the 72st World Health Assembly. To achieve zero malaria, the goal of involving everyone from the policy maker to the community member must have a focus on achieving universal health coverage (UHC) of all malaria interventions ranging from insecticide treated bednets (ITNs) to appropriate provision of malaria diagnostics and medicines. Many of the studies to date have focused on ITNs, which include long-lasting insecticide treated nets (LLINs), but nationwide monitoring through the Demographic and Health Surveys (DHS), the Malaria Indicator Surveys (MIS) and the Multi-Indicator Cluster Surveys (MICS).

UNICEF’s website provides a data repository that includes the most recent DHS, MIS and MICS survey data per country between 2014 and 2017. For the indicator of one ITN per to people in a household, shows Angola at only 13%, most countries for which recent data are available reached between 40-50%. Only two achieved above 60% on a point-in-time survey, Uganda at 62% and Sao Tome and Principe at 95%. The website shows information that where there were multiple surveys in a country during the period, there were variations, sometimes quite wide, over the years. Aside from the fact that the surveys may have had slightly different procedures, the problem remains of achieving and sustaining UHC for ITNs.

Another factor that affects maintaining UHC for ITNs, assuming the target can be met is the durability of nets. The physical integrity as well as the insecticide efficacy can decline over time. Intact nets may lose their insecticide through improper washing and drying, yet still prevent mosquito bites to the individual sleeping under them. Nets with holes may still maintain a minimal level of effective insecticide and may not fully prevent bites but ultimately kill the mosquito that flies through. Researchers in Senegal have been grappling with these challenges.

Program managers must themselves grapple with whether such compromised nets count toward universal coverage as well as how often to conduct net replacement campaigns. A report from community surveys in Uganda during 2017 found that, “Long-lasting insecticidal net ownership and coverage have reduced markedly in Uganda since the last net distribution campaign in 2013/14.” UHC for ITNs is always a moving target.

A frequently unaddressed issue in seeking to improve ITN coverage is whether it makes a difference in malaria disease. A study in Malawi reported that although ITNs per household increased from 1.1 in 2012 to 1.4 in 2014, the prevalence of malaria in children increased over the period from 28% to 32%. The authors surmised that factors such as insecticide resistance, irregular ITN use and inadequate coordinated use of other malaria control interventions may have influenced the results. This shows that UHC for ITNs cannot be viewed in isolation.

This brings up the issue of the role of the many different vector control measures available. Researchers in Côte d’ Ivoire examined the use of eave nets and window screening. At present eave nets are mainly deployed in research contexts but use of window and door screening and netting are a commercially available interventions that households employ on their own. One wonders then whether UHC should focus on how the household and the people therein are protected by any malaria vector intervention.

Here the discussion should focus on the question raised by colleagues in the USAID/PMI Vectorworks Project. WHO declared a goal of universal ITN coverage in 2009 using the target f one ITN/LLIN for every two household members. Vectorworks found that a decade on only one instance of a country briefly achieving 80% of this UHC net target, whereas no others reached above 60%. In fact, the bigger the household, the less chance there was of meeting the two people for one ITN target. Just because people live in a household that has the requisite number of nets, does not guarantee the actual target for sleeping under a net can be achieved because of practical or cultural realities in a household. Neither the minimal indicator of having at least one net in a household, or the ideal or ‘perfect’ indicator of UHC are satisfactory for judging population protection.

The Vectorworks team suggests that, “Population ITN access indicator is a far better indicator of ‘universal coverage’ because it is based on individual people,” and can be compared to, “The proportion of the population that used an ITN the previous night, which enables detailed analysis of specific behavioral gaps nationally as well as among population subgroups.” Population access to ITNs therefore, provides a batter basis for more realistic policies and strategies.

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 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?

A useful perspective would be determination if households and individuals even benefit from any part of the malaria package, even if everyone does not have access and utilize all components. This may be why zero malaria has to start with each person living in endemic areas.

Scaling up Malaria in Pregnancy Prevention at the Community Level

Community meeting to introduce community based IPTp

Elaine Roman and Kristin Vibbert of the Jhpiego malaria team describe below an important community-based intervention to prevent malaria in pregnancy. Follow their links to learn more.

The World Health Organization (WHO) 2018 World Malaria Report revealed that of 33 countries where intermittent preventive treatment (with sulfadoxine-

Quality Assured SP Packets

pyrimethamine/SP) is recommended for pregnant women, only 22% of eligible pregnant women received three doses of intermittent preventive treatment during pregnancy (IPTp3) with SP in 2017 (). Therefore, it is crucial that innovative interventions to scale up the provision of IPTp are needed to protect lives of mothers, fetuses and newborns.

The Transforming Intermittent Preventive Treatment for Optimal Pregnancy (TIPTOP), a five-year project, is one such innovative effort that aims to contribute to reduced maternal and neonatal mortality in four countries: DRC, Madagascar, Mozambique, and Nigeria by expanding access to quality-assured (QA) SP.

TIPTOP Infographic

The TIPTOP project is implementing a community-based approach to expand coverage of IPTp3 to a minimum of 50% in project areas, helping to reach the hardest-to-reach pregnant women and to ensure there are no missed opportunities for pregnant women to receive QA SP. Through rigorous research and routine monitoring, TIPTOP will generate evidence for WHO to inform a potential policy decision on global intermittent preventive treatment of malaria in pregnancy.

TIPTOP is also setting the stage for scale up, supporting Ministries of Health to pilot test SP distribution at the community level in settings that will not only yield quality data in real-life program settings but also lend to program learning, including documenting best practices and lessons learned. Further, in coordination with Medicines for Malaria Venture (MMV), TIPTOP is creating demand for and expanding access to QA SP.

Now that procurement, training, supervision, community education, monitoring and evaluation systems are nearly built, full implementation on the ground will be phased in over the next few months.

World Kidney Day and Severe Malaria

A new review by Conroy, Datta, and John highlights the connection between the kidneys and malaria on this World Kidney Day. They explain that “15 years ago, renal failure was considered a rare complication in children with Severe Malaria, yet it is now recognized as one of the strongest predictors of mortality in severe malaria.”

While severe malaria is related to reduced kidney perfusion, Conroy et al. note that, “additional studies are needed to evaluate the spectrum of AKI over hospitalization to define the etiology and pathophysiology of acute kidney injury in pediatric severe malaria.” In the diagram to the right, they show that kidney involvement is among the most deadly forms of severe malaria.

These problems are not limited to Africa. Dayanand and colleagues describe “single or multi-organ dysfunction involving liver, kidney, and brain” occurring in Mangaluru, India.

Brown et al. warn travelers including people returning to endemic areas after a long absence to be aware of severe malaria dangers once they return to non-endemic countries. “Severe malaria can cause significant multiorgan dysfunction including acute kidney injury (AKI). The pathogenesis is not clearly understood but proposed mechanisms include acute tubular necrosis (ATN) due to impediments in renal microcirculation, infection-triggered proinflammatory reactions within the kidney, and metabolic disturbances.”

The World Health Organization’s Third Edition on its guidelines on managing severe malaria addresses acute kidney injury with attention to reversing dehydration, addressing reduced urine output and even the need for dialysis. Clearly the best response is prompt diagnosis and treatment when malaria is in its very early stages, and better yet, using insecticide treated bednets to prevent the problem in the first place.

 

 

Malaria: Global Funding, Not Just the Global Fund

The Global Fund sixth Replenishment Conference will take place in October 2019 to raise new funds and mobilize partners toward ending AIDS, TB and malaria by 2030 in alignment with the Sustainable Development Goals. The target is to raise at least US$14 billion “to help save 16 million lives, avert 234 million infections and help the world get back on track to end these diseases.”

It is not exactly clear how much of this US$14 billion would be pegged for malaria, especially since there are cross-cutting health systems strengthening components to many grants. That said, the total seems to pale in light of the 2018 World Malaria Report estimated investment needs of US$6.6 billion alone for malaria from 2020 onward.

Of course the Global Fund is calling on the private sector to “mobilize at least US$1 billion to step up the fight.” It is not clear whether this should be included in the US14 billion or in addition.

The RBM Partnership notes that “Accounting for more than half of all external resources and 44% of total malaria funds available, the Global Fund represents the leading source of funding for malaria prevention and treatment.” Such non-Global Fund external resources have come from partners like the World Bank, the US President’s Malaria Initiative, DfID and a host of other bilateral, NGO and corporate sources. The implication is that at most 15-20% of current financial investment in malaria has been borne endemic countries.

RBM also highlights that at the recent African Union meeting, “African Heads of State and Government adopted the 2018 African Union Malaria Progress Report which was prepared by malaria experts from countries in Africa…” This means that the leaders acknowledged that malaria investments and significant achievements already made “are under threat and accelerated action is needed now to get countries back on track.” This led the current chair of the Africa Malaria Leaders Alliance, His Majesty King Mswati III of the Kingdom of Eswatini, to say, “It will take significant resources to achieve malaria elimination.  Now, more than ever, we must boost our domestic resources from both the public and private sectors.”

Analysis in the ALMA Scorecard shows in the fourth quarter of 2018 most countries have acquired the needed funds to finance malaria commodities. The analysis does not point out the source of these funds. The 2030 target is only 11 years away. Serious national planning, political will and advocacy are needed not only to prevent resurgence of malaria to pre-RBM days, but also to reduce and eliminate a disease responsible for so much economic loss and loss of life.

Equity in Malaria Programming, the example of bednets

The WHO defines Equity as “the absence of avoidable, unfair, or remediable differences among groups of people, whether those groups are defined socially, economically, demographically or geographically or by other means of stratification. ‘Health equity’ or ‘equity in health’ implies that ideally everyone should have a fair opportunity to attain their full health potential and that no one should be disadvantaged from achieving this potential.”

WHO goes on to say that, “Countries and programs need to disaggregate selected health indicators by key stratifiers including demographic characteristics (gender, age), place of residence (urban/rural, subnational), socioeconomic status (wealth, education), as well as other characteristics (migrant/minority status etc.).”

Writing for the Tropical Disease Research Program, H. Kristian Heggenhougen, Veronica Hackethal, and Pramila Vivek in the publication, The behavioural and social aspects of malaria and its control, say that …

“What must now be clear is our conviction that any review of factors for world-wide malaria control must give specific attention to issues of socio-economic inequity and disease epidemiology.” Malaria is not an equal opportunity killer, but disproportionately affects certain segments of the population. Heggenhougen et al. continue that, “while we argue for a focused attack on malaria, we cannot avoid noting that without attention to these larger matters – inequity and marginalization – any improvement in health, including malaria, may be short-lived.”

The Demographic and Health Survey (DHS) and its Malaria Indicator Survey (MIS) provide an important snapshot on equity issues in the rollout and coverage of major malaria.   In particular, we look at the issue of long lasting insecticide-treated nets in two countries, Ghana (2016 MIS) and Liberia (2016 MIS), to demonstrate how equity issues can be seen. Two three measures are considered, wealth quintile, location (urban/rural) and gender/sex.

In Ghana we see that having at least one net for the household is more common in lower income groups. These groups are more vulnerable. Although not specifically shown in the MIS, one might assume that people in the higher income groups have better quality housing that provides less opportunity for mosquito entry. Likewise households in rural areas, where anopheles are more likely to breed, have a higher proportion of nets. So while nets are not ‘equally distributed by these characteristics, they are more favorably available in those households that may be more vulnerable to malaria.

When we look at the indicator of universal coverage where it is expected that there should be one net for every two household members, the proportion meeting that goal is much lower than simply having a net in the household for all groups.  That said the pattern of higher proportions among rural and lower income groups remains. Within households, the Ghana MIS a nearly equal proportion of female (43%) and male (41%) had slept under a net the night prior to the survey.

Overall, Liberia has much lower LLIN coverage than Ghana. The pattern for location is similar to that of Ghana, but for wealth, the poorest group (Q1) have lower coverage that wealth quintile groups 2-4. Also as in Ghana the Female (40%) and male (38%) are very similar.

We encourage readers to review the recent MIS and/or DHS reports from the countries where they work and look for differences in net availability as well as uptake of other malaria control interventions to determine the level of equity in intervention access and use, but also as one sees in Liberia, take action to ensure that strategies are in place to reach the poorest and most vulnerable segment of society.

Guinea: The Challenge of Malaria Control in a Post-Ebola Context

The preliminary 2018 Demographic and Health Survey (DHS) data have been released for Guinea (Conakry). Since the last DHS in 2012, Guinea and its neighbors experienced the largest Ebola outbreak in history, an event that damaged already weak health systems.

The previous DHS showed very weak malaria indicators. Only 47% of households had at least one ITN, which averages to 0.8 ITNs per person (compared to the universal coverage of 2.0). Among vulnerable groups only 26% of children below the age of 5 years slept under an ITN, as did 28% of pregnant women. Very few, 18%, pregnant women got two doses of IPTp, and only 5% of febrile children received ACTs (testing was not reported then).

Not much has changed concerning ITN coverage as reported in 2018. Slight improvements are seen in IPTp (which now requires 3 or more doses) and malaria testing and treatment for children. Ironically none of the indicators has passed the original 2006 Roll Back Malaria target of 60%, let alone 80% for 2010 and not of course the drive for universal coverage.

DHS has released a preliminary report for 2018 and the malaria component is summarized in the charts posted here. The national coverage for ITNs is 44%, slightly lower than 2012, but the average per household member is slightly higher at 1.1. Again, these numbers do not mark significant progress. Looking at wealth and ITN ownership there is a slight benefit in terms of equity in net possession among those with lower income, but this must be seen in the overall context of very low basic coverage.

Having a net in the household and using it are different challenges as seen in the reports of sleeping under the net on the night prior to the survey among children under 5 years of age and pregnant women. The sad finding is that even in households that own a net, the coverage of these two groups remains very low. This is reflected in the low net per person ratio nationally (1.1).

One would almost wonder if malaria is a neglected disease in Guinea. The reality is that since 2003, Guinea has received around $172 million US dollars in malaria project funding from the Global Fund. Its most recent annual funding from the US President’s Malaria Initiative (PMI) is around $14 million.  Of that PMI funding 24% was designated for nets and related activities, while 52% was to be spent on medicines, diagnostics and pharmaceutical management. These investments include systems strengthening and capacity building in addition to commodities.

PMI provides the needed context: “Since the country was declared Ebola-free in in June of 2016, Guinea continues to make positive advances towards building a strong health system in line with the health recovery plan. The government continues to mobilize internal and external resources for rolling out the health system recovery plan, but much remains to be done if this plan is to yield the intended results.” Areas in particular need of strengthening within the National Malaria Control Program include coordination, health information systems, leadership, supervision and logistics.

Three years have passed since the last Ebola case in Guinea. Hopefully the country can stave off another outbreak and at the same time strengthen its health system. Guinea may not yet be targeted for malaria elimination, but until systems are strengthened, the resources going into malaria control will not be able to push malaria indicators toward saving more lives.

A child’s personal experiences with malaria lead to a life career fighting the disease

Gbenga Jokodola tells his story of growing up to fight malaria in Nigeria. Gbenga has a MPH in Field Epidemiology from the University of Ibadan, and a BPharm from Ahmadu Bello University. He is currently working with Malaria Consortium as a Zonal Project Manager on the Seasonal Malaria Chemoprevention (SMC) Project, delivering preventive care to over 400,000 children between the ages of 3 – 59 months in Jigawa and Katsina States of Nigeria. He has worked on several malaria projects over the years sponsored by Unicef, the Global Fund, Catholic Relief Services and the Bill & Melinda Gates Foundation. As he narrates below, his early experiences with malaria were formative of his present focus in life.

At 3 months of age Gbenga was probably still protected from malaria by maternal antibodies and did not realize what malaria held in store for his future

Growing up in Zaria, northern Nigeria in the 70s and 80s was one of the best experience any child could ask for. I lived with my parents in two rented rooms in a compound on one of the streets in Sabon Gari Zaria – a community that had virtually all the tribes in Nigeria and of course, with all the love and communal living you can ever get from a true Nigerian community.

In such loving setting we enjoyed as children, I imagined that mosquito communities also lived around our pit latrine and backyard. I imagined that parent-mosquitoes trained their off-springs very well on how to bite and fly away tactfully, how to dodge the usual clap-like manner we use in killing mosquitoes, which homes to avoid visiting, and so on.

I was reputed to be a strong boy then, one of the few kids who were “strong”; I was a “tough” boy who rarely fell ill to malaria. Then, it was common to hear, “Gbenga is a strong boy”. I ate and slept in any room in our compound – with or without covering from mosquito and was hailed for doing so by my friends who often fall ill to malaria.

Life lesson as a Primary School pupil: There is no immunity against malaria

One day, the “malaria forces” (mosquitoes) taught me a life lesson: Indeed, there is no immunity against malaria.

My local Government primary school rotated school attendance between morning and afternoon every week. As an 8-year-old, while preparing for my afternoon school I suddenly felt very cold and sleepy at the same time and decided to lie down briefly on my senior brother’s 6-spring bed in our sitting room. Shortly after, I was shivering and sweating profusely under 3 of my mother’s wrappers.

Help was not immediately near as most people were out. My head was pounding like I was a piece of yam being pounded with a pestle in my mother’s mortar. My stomach was churning. All the while, I kept saying “I am a strong boy, I will not be sick”! I was in that state for over an hour. I began to wonder if I was strong after all and will not end up dying. I could no longer talk but my teeth were chattering.

Gbenga second from left at about 7 years old in company of Sisters and friends in the compound

Sweating profusely, yet I was cold! I was helpless. It was in this state that one of our neighbor’s daughters walked into our sitting room, wondering if there was any food to eat. Immediately she saw the “strong man” shivering under 3 wrappers, she raised an alarm. Her shout saved me as neighbors immediately rushed into our sitting room. Among them was a relation of the landlord, a beautiful “Aunty” Esther, who was visiting from the Ahmadu Bello University school of Nursing. As soon as she came over, she said: “this is malaria!”.

Aunty Esther immediately organized and rescued me that day; she saved the life of the “strong man”! She quickly sought iced-cold water and toweled my body with my father’s “untouchable” towel hanging on the door of the inner room. Ah, what a good feel it was! She then gave me a sweet syrup which I later found out to be Paracetamol syrup. After about 30 minutes, she returned with a plate of hot rice and stew, encouraging me to eat before treatment with anti-malarial medication. I struggled to eat the rice, angry that I had lost my ever-available appetite! I only took few spoons, amidst the encouragement I received from all present.

I was then given an injection by Aunty Nurse Esther, tucked back into the bed and told to prepare to sleep. She then said, “Gbenga, no school for you today, okay? You even need to get well before you resume school”. Everyone knew I loved school. I had to lose a precious school day (and three more days) to malaria! So, I simply focused on staying alive, wondering which “wicked” mosquito bit me. That was the day I dramatically lost my title of “strong man” to malaria, painfully realizing that I was not immune to malaria at all!

My treatment against malaria was continued with further jabs of the needle (twice a day) over the course of the next 3 days at the Dispensary/Primary Health Unit “Aunty” Esther directed my parents to. I got well and resumed school after the third day. Later, I researched and found out I was treated with a sedative, Chloroquine and Paracetamol.

Gbenga with classmates at First Baptist Church, Benin Street, Sabon Gari Zaria

My parents later introduced “Sunday-Sunday Medicine” (one Sweetened pyrimethamine tablet weekly) against Malaria to our diet on Sundays. With this painful encounter with Malaria, I resolved to fight mosquitoes; I was determined to regain my “strong man” title. I made up my mind to be a community health worker, saving communities from diseases like malaria.

Fast-forward to Year 2007: My new twist in combating Malaria

By the year 2007, my personal malaria episodes had lessened with greater knowledge of the disease. In addition, the application of the preventive, diagnostic and treatment procedures reduced my malaria episodes to about 1 in 3 years. With each episode, I normally use laboratory test (microscopy) to confirm if severity is +, ++, or even +++. Thereafter, I get a prescription from a Physician on appropriate medication to use.

However, while practicing in Abuja, I encountered a tearful case of death from malaria, of an 8-year old beautiful daughter of a colleague. Three days prior to her death, a Community Pharmacist had dispensed anti-malarial medication to her, based on prescription tendered by the father from a Government hospital he had earlier taken her to. The news of her death brought back memories of how I would have died as

ACCESS-SMC Project: Scaling up access to seasonal malaria chemoprevention in the Sahel

an 8-year old from this same Malaria. Yes, this same Malaria! That death of the 8-year old triggered a fresh resolve in me to step up my fight with mosquitoes and combat malaria squarely at community, state, National and global levels.

Still at War with Malaria in 2018

Now armed with post-graduate training in Public Health/Epidemiology and field-based experience, my Malaria diagnosis strategy has now changed. I now use Rapid Diagnostic Test Kits (RDT). If confirmed positive, I receive prescription on the most applicable Artemisinin-based combination Therapy (ACT) to use.

My malaria story continues and will only end when mosquitoes are defeated – when children and adults no longer fall ill nor die from mosquito bites that cause malaria.

You can follow Gbenga on Twitter.

Asymptomatic Malaria – we need to eliminate what we can’t see

After the World’s first attempt at eradicating the complicated disease malaria mainly through a single tool, a period of control set in where the aim was to reduce mortality through prompt and presumptive treatment of fevers with anti-malarials, particularly in young children. During this period in the 1980s and 1990s it was recognized that parasite-based diagnostic capabilities in the form of microscopy were limited, so in malaria endemic areas, it was worth providing inexpensive medicines like chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) to febrile children in order to save lives. When the fevers did not resolve, other illnesses explored.

The difficulty arose in identifying cases that did not offer clinical clues that they might be malaria. Today countries approaching malaria elimination face challenges, such as seen in Zanzibar where, “outdoor transmission, a large asymptomatic parasite reservoir and imported infections, require novel tools and reoriented strategies to prevent a rebound effect and achieve elimination.”[i] Here we examine the challenge of asymptomatic malaria infections.

Background

By 1998 when the Roll Back Malaria partnership formed, there had been enough research done so that the malaria community had a better arsenal of interventions including insecticide-treated bed nets, artemisinin-based combination therapy (ACT) and intermittent preventive treatment with SP during pregnancy. The Abuja Declaration of 2000 set a target of 80% coverage of these interventions by the year 2010.

While ACTs overcame the challenges of parasite resistance that had developed for the single drugs, CQ and SP, it cost several times more than those medicines. The need for easy-to-use, inexpensive, point-of-care diagnostics was recognized so that not only would ACTs be targeted only to parasitologically confirmed malaria cases, but also in the process, overuse and misuse would not contribute to parasite resistance of these new drugs.[ii] Unfortunately, the development and dissemination of antigen-based rapid diagnostic tests (RDTs), lagged behind the availability of ACTs meaning that health workers unfortunately continued their business as usual with presumptive treatment using ACTs. 

The benefits of RDTs were generally two-fold. First, they could be used by front-line, auxiliary and community-based health workers. Secondly, they tended to identify more cases than microscopy. The big challenge was convincing health workers to use them and trust the results, because the era of presumptive treatment had given these staff a false sense of confidence in their own clinical diagnostic abilities.

Although reaching the 2010 coverage targets has remained illusive for most endemic countries, there has been enough progress for major reductions in incidence (despite a recent upsurge).[iii] As the proportion of actual malaria cases among febrile illness patients declines, concern has risen that transmission might continue among people with subclinical or asymptomatic malaria. Here we explore the extent of this problem and new directions in parasitological testing needed to ensure continued progress toward elimination in each endemic country.

Understanding the Risk of Asymptomatic Malaria

Risk can relate to geographical, epidemiological, and socio-demographic factors as well as history of malaria interventions. Kenya has stratified the country by higher and lower malaria transmission areas. Even the higher areas are comparatively low compared to its higher transmission neighbors. Studying the prevalence of asymptomatic malaria in some of these higher transmission areas in the west of the country was seen as a way to better identify people at risk and learn about intervention effectiveness. An examination of apparently healthy children (no symptoms) revealed a Plasmodium falciparum malaria prevalence 36.0% (27.5%, 44.5%) by RDT and 22.3% (16.0%, 28.6%) by thick film microscopy.[iv] Living in a household with electricity was protective but the adjusted odds ratio of prevalence comparing households with and without indoor residual spray showed only borderline benefit. Unfortunately, in Zanzibar, asymptomatic malaria infection was not associated “with use of any vector control.”1

A major challenge in detecting cases through routine health care systems is care seeking patterns of care seeking for fever. The 2018 World Malaria Report acknowledges that there are major equity challenges in care seeking wherein families with higher incomes, better education and living in urban areas are more likely to seek help for their febrile children that rural, poor and less educated families who would be more at risk. Care seeking without the signs of fever is more challenging. A dual strategy of enabling better service utilization as well as outreach to detect cases will be necessary to detect asymptomatic cases.3

In Burkina Faso, the prevalence of asymptomatic malaria infection in children under 5 years of age was estimated at 38.2% in 24 of its 70 health districts. Those at most risk for asymptomatic malaria infection included the following:[v]

  • older children (48–59 vs < 6 months: OR: 6.79 [5.62, 8.22])
  • children from very poor households (Richest vs poorest: OR: 0.85 [0.74–0.96])
  • households located more than 5 km from a health facility (< 5 km vs ? 5 km: OR: 1.14 [1.04–1.25])
  • localities with inadequate number of nurses (< 3 vs ? 3: 0.72 [0.62, 0.82]
  • rural areas (OR: 1.67 [1.39–2.01])

Nine districts reported significantly higher risks (Batié, Boromo, Dano, Diébougou, Gaoua, Ouahigouya, Ouargaye, Sapouy and Toma. The researchers concluded that, “Such national spatial analysis should help to prioritize areas for increased malaria control activities.”

A study in Ghana found that, “children and pregnant women had higher prevalence of submicroscopic gametocytes (39.5% and 29.7%, respectively) compared to adults
(17.4%).”[vi]

An additional concern is emerging in terms of sharing of malaria parasite species between humans and primates, especially as urbanization and deforestation push these two populations into closer contact. For example Mapua and colleagues working in Central Africa Republic, “found the human malaria parasite P. ovale wallikeri in both asymptomatic humans and western lowland gorillas in Dzanga Sangha Protected Areas. Molecular analysis revealed that the genotype of the P. ovale wallikeri DNA found in a gorilla was genetically identical to that of a human isolate within the mt cytb and mt cox 1 genes, indicating potential human–ape transmission.”[vii] They noted similar sharing of parasites in the region between humans and chimpanzees.

Detecting and Responding to Asymptomatic Cases

WHO’s Framework for Malaria Elimination[viii] recognizes the important role of case detection and subsequent treatment as well as broader community level preventive responses around detected cases. In the context of elimination WHO notes that case detection “requires use of a diagnostic test to identify asymptomatic malaria infections.” WHO stresses that a case is a case, regardless of whether it is symptomatic or asymptomatic, as long as the diagnostic process confirms presence of malaria infection.

It is important to monitor Plasmodium parasitemia in areas where malaria transmission has declined and efforts to achieve malaria elimination are underway, such as Zambia, where 3,863 household members were tested.[ix] Only 2.6% were positive by either microscopy, RDT, or PCR. Of these, 48 (47%) had subpatent parasitemia, and 85% of those with subpatent parasitemia were asymptomatic. “Compared with individuals without parasitemia, individuals with subpatent parasitemia were significantly more likely to be aged 5–25 years.” The authors suggested that their findings pointed to the need for active or reactive case detection to identify asymptomatic individuals and thus better target individuals with subpatent parasitemia with appropriate malaria interventions.

WHO explains that active case detection (ACD) takes place in areas of limited or under-utilization of health care services.4 It may start with initial screening for symptoms, followed by appropriate parasitological laboratory confirmation. In low-transmission settings or as part of a focus investigation, “ACD may consist of testing of a defined population group without prior symptom screening (population-wide or mass testing) in order to identify asymptomatic infections.” Elimination cannot be achieved until even asymptomatic infections have stopped. The challenge is the expense of community-wide screening.

Reactive Case Detection (RCD), according to WHO, takes place in settings low transmission intensity where the few “occurring malaria cases are highly aggregated.”4 When a case is identified, usually through identification of an actual infected patient at a local clinic, the community where the patient comes from is visited and a “net is cast around the index case” where household members and neighbors within a selected radius are tested. In this process asymptomatic cases are also identified.

Our existing diagnostic tools may be inadequate. McCreesh and colleagues reported on subpatent malaria in Namibia that, “fever history and standard RDTs are not useful to address this burden. Achievement of malaria elimination may require active case detection using more sensitive point-of-care diagnostics or presumptive treatment and targeted to high-risk groups.” This includes loop-mediated isothermal amplification (LAMP) using dried blood spots, which they tested.[x] Likewise from experience in a Zambian study, Kobayashi and co-researchers suggest, “more sensitive diagnostic tests or focal drug administration may be necessary to target individuals with subpatent parasitemia to achieve malaria elimination.”[xi]

Responses to detecting asymptomatic cases start at the individual level with prompt treatment of those found through RCD to be infected. Then focused preventive interventions such as distribution of insecticide treated bednets can be provided to those in the cluster or village. Follow-up would be needed for such ‘hot spots.’ 

On a broader basis we have Seasonal Malaria Chemoprevention (SMC) as practiced in Sahelian countries where during the peak transmission (rainy) season intermittent preventive treatment is given to children monthly by community health workers and volunteers. Of course, many of these children would be asymptomatic carriers and SMC could benefit the reduction of parasites in circulation. At present SMC focuses on pre-school aged children, but Thera and co-researchers stress the importance of reaching school aged children who are also often asymptomatic carriers.[xii]

Another intervention being tested for mass drug administration (MDA) use providing the community with ivermectin, a drug that has been highly effective in controlling filarial diseases and also found to kill mosquitoes who take a blood meal from a person who has recently taken it.[xiii] This strategy is still being tested, but again MDA means all community members, especially those with asymptomatic infection, would be reached.

A major question requires further research. To what extent do asymptomatic, submicroscopic and subpatent parasitemia contribute to continued malaria transmission? Another question is how can we address malaria infection in other primates? We know that scientists recommend targeting of malaria elimination interventions based on mapping of these infections.5 We therefore need to study the actual transmission potential of this phenomenon.


[i] Björkman A, Shakely D, Ali AS, Morris U, Mkali H, Abbas AK, Al-Mafazy A-W, Haji KA, Mcha J, Omar R, Cook J, Elfving K, Petzold M, Sachs MC, Aydin-Schmidt B, Drakeley V, Msellem M and Mårtensson A. From high to low malaria transmission in Zanzibar—challenges and opportunities to achieve elimination. BMC Medicine (2019) 17:14, https://doi.org/10.1186/s12916-018-1243-z

[ii] Global Malaria Programme. Universal access to malaria diagnostic testing – An operational manual. World Health Organization. November 2011 (rev. February 2013). https://www.who.int/malaria/publications/atoz/9789241502092/en/

[iii] Global Malaria Programme. World malaria report 2018. World Health Organization. 19 November 2018. https://www.who.int/malaria/publications/world-malaria-report-2018/en/

[iv] Peprah S, Tenge C, Genga IO, Mumia M, Were PA, Kuremu RT, Wekes WN,  Sumba PO, Kinyera T, Otim T, Legason ID, Biddle J, Reynolds SJ, Talisuna AO, Biggar1 RJ, Bhatia K, Goedert JJ, Pfeiffer RM, Mbulaiteye SM. A Cross-Sectional Population Study of Geographic, Age-Specific, and Household Risk Factors for Asymptomatic Plasmodium falciparum Malaria Infection in Western Kenya. The American Journal of Tropical Medicine and Hygiene, Volume 100, Issue 1, Jan 2019, p.54-65. DOI: https://doi.org/10.4269/ajtmh.18-0481.

[v] Ouédraogo M, Samadoulougou S, Rouamba T, Hien H, Sawadogo JEM Tinto H, Alegana VA, Speybroeck N and Kirakoya?Samadoulougou F. Spatial distribution and determinants of asymptomatic malaria risk among children under 5 years in 24 districts in Burkina Faso. Malaria Journal 2018; 17:460 https://doi.org/10.1186/s12936-018-2606-9

[vi] Lamptey H, Ofori MF, Kusi KA, Adu B, Owusu-Yeboa E, Kyei-Baafour E, Arku AT, Bosomprah S, Alifrangis M, Quakyi IA. The prevalence of submicroscopic Plasmodium falciparum gametocyte carriage and multiplicity of infection in children, pregnant women and adults in a low malaria transmission area in Southern Ghana. Malar J. 2018 Sep 17;17(1):331. doi: 10.1186/s12936-018-2479-y.

[vii] Mapua MI, Hans-Peter Fuehrer HP, Petrželková KJ, Todd A, Noedl H, Qablan MA, and Modrý D. Plasmodium ovale wallikeri in Western Lowland Gorillas and Humans Central African Republic. Emerging Infectious Disease journal. Volume 24, Number 8—August 2018. https://wwwnc.cdc.gov/eid/article/24/8/18-0010_article

[viii] Global Malaria Programme. A framework for malaria elimination. ISBN 978-92-4-151198-8. World Health Organization 2017, http://www.who.int/malaria/publications/atoz/9789241511988/en/

[ix] Kobayashi T, Kanyangarara M, Laban NM, Phiri M, Hamapumbu H, Searle KM, Stevenson JC, Thuma PE, Moss WJ and the Southern Africa International Centers of Excellence for Malaria Research. Characteristics of Subpatent Malaria in a Pre-Elimination Setting in Southern Zambia. The American Journal of Tropical Medicine and Hygiene, 10 December 2018, DOI: https://doi.org/10.4269/ajtmh.18-0399

[x] McCreesh P, Mumbengegwi D, Roberts K, Tambo M, Smith J, Whittemore B, Kelly G, Moe C, Murphy M, Chisenga M, Greenhouse B, Ntuku H, Kleinschmidt I, Sturrock H, Uusiku P, Gosling R, Bennett A, Hsiang MS. Subpatent malaria in a low transmission African setting: a cross-sectional study using rapid diagnostic testing (RDT) and loop-mediated isothermal amplification (LAMP) from Zambezi region, Namibia. Malar J. 2018 Dec 19;17(1):480. doi: 10.1186/s12936-018-2626-5.

[xi] Kobayashi T, Kanyangarara M, Laban NM, Phiri M, Hamapumbu H, Searle KM, Stevenson JC, Thuma PE, Moss WJ, For The Southern Africa International Centers Of Excellence For Malaria Research.Characteristics of Subpatent Malaria in a Pre-Elimination Setting in Southern Zambia. Am J Trop Med Hyg. 2018 Dec 10. doi: 10.4269/ajtmh.18-0399. [Epub ahead of print]

[xii] Thera MA, Konea AK, Tangaraa B, Diarraa E, Niarea A, Dembeleb A, Sissokoa MS, Doumboa OK. School-aged children based seasonal malaria chemoprevention using artesunate-amodiaquine in Mali. Parasite Epidemiology and Control 3 (2018) 96–105. https://doi.org/10.1016/j.parepi.2018.02.001

[xiii] Smit MR, Ochomo EO, Aljayyoussi G, Kwambai TK, Abong’o BO, Chen T, Bousema T, Slater HC, Waterhouse D, Bayoh NM, Gimnig JE, Samuels AM, Desai MR, Phillips-Howard PA, Kariuki SK, Wang D, Ward SA, ter Kuile FO. Safety and mosquitocidal efficacy of high-dose ivermectin when co-administered with dihydroartemisinin-piperaquine. www.thelancet.com/infection Published online March 27, 2018 http://dx.doi.org/10.1016/S1473-3099(18)30163-4