Perspectives on school-based malaria interventions: a conversation with Dr Miriam Laufer and Dr Lauren Cohee
Dr Miriam K Laufer and Dr Lauren M Cohee are paediatric infectious disease specialists based at the University of Maryland School of Medicine, with a primary research interest in malaria and global child health. In this interview, they shared their knowledge and experience around novel chemoprevention strategies for malaria, focusing on school-based malaria interventions.
Q: Could you tell us a little bit about you and your research interests?
Miriam Laufer (ML): I am a pediatric infectious diseases physician. In addition to my clinical work in the hospital, I have been working in malaria and global health research for around 20 years. I started out my career focusing on antimalarial drug resistance and clinical trials of drugs to treat and prevent malaria. Results of those studies led to my interests in malaria in pregnancy and its impact on infant health and also on HIV-malaria interactions. As a result of my collaborations with colleagues in Malawi, I was invited to join the Malawi International Center of Excellence in Malaria Research (funded by the US National Institutes of Health) in 2010 to lead the basic surveillance studies to understand the burden of malaria disease and infection in Malawi. The high prevalence of malaria infection in school-aged children was one of our most notable findings. Not only do they have more malaria than any other group, but they are also more likely than other age groups to carry gametocytes, the infectious form of the malaria parasites.
I have come to realize that school-age children are a medically neglected population. Most child health programs focus on disease prevention and treatment of children under five years of age. Then programs exist for women when they are pregnant. In between, children have extensive health-related needs that do not receive programmatic attention. They have acute illnesses that frequently go untreated, chronic infections with potential to transmit to the community through infecting their household members or vectors of infection (malaria, schistosomiasis, influenza, etc.) and emerging chronic illnesses. In addition, many opportunities for disease prevention in adolescence and early adulthood are missed because no platforms exist for vaccinating this group, including vaccines again human papillomavirus, influenza, pertussis and meningococcus.
Lauren Cohee (LC): I am a pediatric infectious disease physician. While I am clinically trained, my interest and focus has always been on research. Coincidentally, my first exposure to global health research was conducting a primary school-based survey of water, sanitation and health education and schistosomiasis prevalence in Tanzania. I began conducting malaria research at the U.S. Centers for Disease Control and Prevention before pursuing my medical training. After finishing medical school and pediatric residency, I moved to the University of Maryland to work with Dr Miriam Laufer and the malaria research program as well as to complete pediatric infectious disease fellowship training.
As a part of the Malawi International Center of Excellence in Malaria Research (funded by the US National Institutes of Health), I led the implementation of a series of household-based surveys of malaria epidemiology. In these surveys, we found that across multiple transmission settings in Malawi school-age children have the highest prevalence of P. falciparum infection. Moreover, we showed that school-age children have the highest prevalence of infections containing gametocytes, the stage of the malaria parasite required for human-to-mosquito transmission, suggesting that school-age children may be key group maintaining malaria transmission. Both biological and social factors likely contribute to the peak prevalence in this age group. School-age children have developed some immunity to malarial disease but are not yet able to suppress or clear infections as well as adults. We and others have also shown that school-age children are least likely to report sleeping under bed nets and to receive prompt, effective treatment. Stemming from these findings, my current research interests are to further characterize the contribution of school-age children to transmission, to identify optimal strategies to decrease the burden of malaria in school-age children, and ultimately to improve the health and educational attainment of school-age children.
Q: Why do you think school-aged children could be an important group to target with chemo-preventive strategies? Which are the main benefits of this strategy? Evidence suggests that the strategy could have a broader effect by decreasing transmission at the community level. Could you give more details about this?
ML: The huge burden of malaria in school-age children (SAC) impacts both the individual children and the communities in which they live. SAC do not receive the same level of medical attention as younger children and we found that when they were sick, they often did not access the formal health sector and did not get tested or treated for malaria. Infection with or without symptoms also likely impacts their ability to attend school and learn. But even beyond the deleterious impact of malaria on the health of SAC, they also likely serve as an important reservoir of malaria transmission. SAC have high rates of malaria infection with transmissible gametocytes and are unlikely to receive treatment. We also know they are the group least likely to sleep under bednets, so they provide a readily accessible source of infected blood meals for the Anopheles malaria vectors.
Because the infections are often asymptomatic, waiting for children to seek out health care for their illnesses may improve their health but likely will not capture all of the potentially transmissible infections. We have concluded that the most effective strategy is likely to give intermittent antimalarial treatment during the rainy season to children in schools. It is a simple platform for delivery of the intervention, provides an opportunity to integrate with other health programs, and may improve school attendance and performance.
LC: There are three key reasons to target school-age children for malaria chemo-preventive strategies. First, malaria has a substantial negative impact on the health and education of schoolchildren themselves. While school-age children rarely die of malaria, they still shoulder considerable burden of the disease. Prevalence of infection is often higher in school-age children than in younger children and adults. The vast majority of these infections are thought to be asymptomatic infections as children attend school and rarely seek treatment. However, these infections are better termed pauci-symptomatic; they are associated with anaemia and schoolchildren report generally feeling unwell and perform worse in school. When schoolchildren do experience fever and more overt symptoms of disease, they are often absent from school, but again, rarely seek treatment. When malaria infections in school-age children are cleared or prevented, children feel better, they are less likely to develop clinical malaria, their haemoglobin levels increase, and they perform better in school.
The second reason to target school-age children is that this age group is a key reservoir malaria transmission. In many settings, school-age children have the highest prevalence of infections containing gametocytes, the parasite stage required for human-to-mosquito transmission. School-age children are available to be bitten by vector mosquitos as they are the age group least likely to report using bed nets. If we can clear and prevent infections in schoolchildren, mosquitos biting these children will not acquire or pass on the infection to other people, potentially leading to a decrease in infection in the community.
The third reason to target school-age children is that school-based interventions are feasible. Schools are an excellent platform for interventions. School enrollment and attendance have increased dramatically across the malaria-endemic world enabling access to this population. There are a number of other interventions that utilize schools as a platform, for example, school feeding programs to improve nutrition and deworming campaigns to achieve very similar goals as malaria interventions – decrease infection, anaemia, and community transmission. Combining these interventions could lead to both increased effectiveness and efficiency to improve child health and educational attainment.
The main benefits of this strategy are to improve the health and education of school-children as well as to contribute to community-level malaria control by reducing transmission. This two-pronged benefit of chemoprevention is unlikely to be realized by other approaches to decreasing the burden of malaria in school-age children, such as screen-and-treat or test-and-treat strategies. Our school-based studies in Malawi suggest that currently available screening tools do not detect a substantial proportion of infections containing gametocytes, especially in lower prevalence settings, where a screen-and-treat approach would be most appealing.
There is considerable evidence that school-age children are key reservoirs of human-to-mosquito malaria transmission. School-based malaria chemoprevention substantially decreases the prevalence of infection in this age group, the result of which is that Anopheles vector mosquitos that feed on school-age children do not acquire the parasite and do not pass on the infection to the next person they bite. We have used data from simultaneous school- and community-based studies to estimate this impact. We estimate that a substantial proportion of the gametocyte burden in the community could be eliminated by school-based treatment interventions. To date, the only trial to measure this impact specifically is a cluster-randomized trial in Uganda, which demonstrated a reduction in the prevalence of infection in communities surrounding intervention schools. Similar results were seen when seasonal malaria chemoprevention was extended to school-age children in Senegal. While these results are promising, further evaluation is needed to determine the full potential of school-based chemoprevention to decrease malaria transmission.
Q: In your opinion, which are the main challenges when trying to deploy this novel strategy?
ML: There are a few challenges. Funding and resources: a school-based program will require human resources as well as the procurement of supplies. Thus, like any intervention, its relative cost-benefit needs to be considered among other highly attractive interventions that are available such as new LLINs, RTS,S vaccine and enhanced case management.
From a logistical perspective, to conduct a clinical study of a school-based intervention, individual-level consent is often required. In a cluster-randomized trial of multiple schools, the ability to obtain consent limits the number of children who successfully participate in the program. In the sub-Saharan Africa setting, written informed consent is obtained in person and requires a parent or guardian to be notified, agree to attend the school and spend time undergoing the consent process. We and others have struggled to obtain satisfactory coverage of interventions due to this challenge.
LC: The first challenge is determining how to prioritize this intervention among other malaria control interventions, such as bed nets, RTS,S vaccine, etc. Malaria interventions are typically prioritized if they decrease disease burden, measured as clinical malaria cases and malaria-related mortality, or if they decrease transmission. School-based chemoprevention partially achieves both of these aims. While school-based chemoprevention does decrease incidence of clinical malaria and the prevalence of infection and anaemia in schoolchildren, there is limited impact on overall numbers of malaria cases because school-age children make up a smaller proportion of reported cases than younger children – both because they are less likely than younger children to be overtly symptomatic and they are less likely receive diagnosis and treatment even when they are sick. Increased emphasis on the impact of malaria on educational attainment and economic outcomes may help further prioritize school-based chemoprevention as a burden reduction intervention. Similarly, decreasing the reservoir of malaria transmission by targeting school-age children will likely incrementally decrease transmission, but it is unlikely to lead to elimination. Nonetheless, high burden areas need additional interventions to help reduce transmission. In concert with other interventions, school-based chemoprevention may contribute to transmission reduction in the highest-burden areas.
The second challenge is defining optimal implementation strategies. School-based chemoprevention interventions have thus far been undertaken as clinical trials. To implement school-based chemoprevention as a program requires close coordination of the health and education sectors and delivery of the intervention by either trained teachers or health workers or a combination of both cadres. We need to learn from other school-based interventions as well as malaria interventions in other subgroups utilizing existing delivery platforms, e.g. prevention of malaria in pregnancy delivered through antenatal care visits. Moreover, it is possible to integrate malaria chemoprevention with other school-based health and nutrition interventions. Careful consideration and evaluation of implementation strategies is a key component when deploying school-based chemoprevention.
ML: The malaria research and policy leaders recognize the high burden of malaria in SAC. The challenges are: 1) Should the goal of a school-based intervention be child health or reduced transmission? 2) Where does a school-based intervention fall among the other available interventions? and 3) Can a school-based malaria program be part of a comprehensive program for child health?
LC: Compared to 2017, there is increased appreciation of and interest in malaria in school-age children. Several additional studies have been published, including both the community-level and the student-level results from the cluster-randomized trial in Uganda, which confirm the potential of school-based chemoprevention. We have conducted both study and individual participant data meta-analyses of thirteen trials of school-based preventive treatment. These results are currently under review for publication and are promising in terms of generating attention and momentum to move forward with chemoprevention.
Q: In your opinion, what next steps should the malaria community take?
ML: The time is right to carefully design and implement pilot studies of school-based malaria treatment and prevention that measure the impact on child health, school performance and community-level transmission. Operational research will help to determine the real-world effectiveness and costs associated with school-based interventions. We will be able to better understand who does and does not participate, the acceptability of the intervention, strategies to balance the distribution of responsibility between the health and education sectors and the impact on community-level malaria transmission.
LC: Further demonstration of the impact of school-based chemoprevention on malaria transmission is critical in order to prioritize this intervention among the available malaria control interventions. Given the established benefit to students themselves, a key component of fully evaluating the potential community-level benefit is to implement school-based chemoprevention under real-world, i.e. not clinical trial conditions. One of the primary challenges for school-based clinical trials is obtaining consent from parents who ordinarily do not come to school with their children. Implementing this intervention as a program will no doubt present other challenges, but will likely achieve greater uptake than has been achieved in clinical trials. Pilot programs will also provide the opportunity for implementation and operational research to guide development of future programs.
We in the malaria community also need to engage in plans to develop integrated school-health programs. Integration with other health interventions will increase the impact and cost-efficiency of malaria chemoprevention as many of the health challenges of school-age children are multifactorial. For example, anaemia, which contributes to decreased cognitive function, may be caused by micronutrient deficiency, helminth infection and malaria. In the highest-risk populations, all three etiologies are likely present and by simultaneously addressing all etiologies we are more likely to decrease anaemia and improve cognitive function. Thus by working together, we can do more to improve the health and long term outcomes of this vulnerable age group.
Dr Miriam Laufer is Professor of Pediatrics and Associate Director of the Center for Vaccine Development and Global Health, University of Maryland School of Medicine. Know more about her research in MESA Track.
Dr Lauren Cohee is an Instructor of Pediatrics and faculty member in the Malaria Research Program in the Center for Vaccine Development and Global Health. Know more about her research in MESA Track.