Tropical Health Matters

San Barro, Ousmane Badolo, Mathurin Bonzi, Moumouni Bonkoungou Youssouf Sawadogo, Andre Kone, Thierry Ouedraogo, Mathurin Dodo, Lolade Oseni, Gladys Tetteh, and William Brieger explain an innovation of Sponsorship of target children during the Seasonal Malaria Chemoprevention (SMC) campaign in order to improve malaria prevention follow-up and coverage in the Reo health district of Burkina Faso in 2021.

Malaria is a major public health problem in Burkina Faso. According to health statistics for 2020, malaria accounted for 39.8% of health center consultations, 54.1% of hospitalizations and 27.4% of deaths. Children under 5 years of age pay the highest toll with 72.4% of deaths.

In 2021, the Reo Health District and the other six districts of the Centre-Ouest region were supported by the PMI Impact Malaria Project to implement Seasonal Malaria Chemoprevention (SMC). This includes monthly preventive doses of Sulfadoxine-pyrimethamine/amodiaquine for 4 months during the main malaria transmission season. A recent multi-country article in The Lancet showed that while 75% of eligible children received a dose in any given month, only 53% received a dose on all four months.

Coverage reports indicate that better follow-up is needed once children start the SMC process. Thus, during the SMC Campaign, the district management team introduced an innovation  consisting of “sponsorship” of SMC target children as a new follow-up mechanism. These sponsors are Community Distributors (CDs) or Community Based Organizations (CBOs). They voluntarily agreed to follow up with five children each, between July and October 2021 in order …

1. To ensure that the children actually took the medication
2. To monitor whether these children did not get sick between two cycles
3. To inform the nurse in charge of the health center in case of illness of a sponsored child
4. To encourage parents to use bed nets to protect their children. In total, 1468 children were monitored and 224 (15.26%) had malaria.

This innovation on SMC distribution contributed to protect 84% of the children. Challenges include the lack of financial resources to support the sponsors and the inaccessibility of some areas due to the rains. When medicines are correctly administered to children and they are regularly monitored, protection is better.

Moumouni Bonkoungou, Ousmane Badolo, Mathurin Bonzi, Youssouf Sawadogo, Andre Kone, Thierry Ouedraogo, Gauthier Tougri, Mathurin Dodo, Edward Kenyi, Gladys Tetteh, and William Brieger working with the US PMI Impact Malaria project implemented Seasonal Malaria Chemoprevention (SMC) in collaboration with the National Malaria Control Program (NMCP) of Burkina Faso in 3 regions. Their findings are seen below and are presented at the Annual Meeting of the American Society of Tropical Medicine and Hygiene in Seattle.

According to health statistics for 2020, in Burkina Faso, malaria accounts for 40% of medical consultations and 27% of deaths. Children under 5 years of age account for 72% of malaria deaths. 

In 2021, the SMC consists of the administration of three days of monthly treatments of amodiaquine plus sulfadoxine-pyrimethamine to all eligible children (3-59 months of age) during the high malaria transmission season (June to October). The objective is to maintain therapeutic concentrations of these antimalarials during the period of high transmission. 

In 2021, 19 of 70 health districts (27%) were supported by the project to implement SMC with more than 838,000 children under 5 years treated, including 180,000 from the Sud-Ouest region (Dano, Batie, Kampti, Gaoua, and Diebougou health districts). In this region of high rainfall, the number of severe malaria cases in children under 5 years decreased from 17,760 in 2017 (before SMC) to 14,609 in 2021 with SMC after 4 years of SMC implementation, i.e., a reduction of 17%. 

The number of malaria deaths also decreased from 133 in 2017 (before SMC) to 118 in 2021, a reduction of 11%. Kampti health district recorded the highest reduction of deaths of 78% [33 to 7 deaths] between 2017 and 2021 and Dano district had a reduction in severe malaria cases by 28% between 2017 and 2021. 

The main challenges with SMC include a delay in referral of fever cases by community distributors to health facilities during the campaign, management of vomiting during the 2nd or 3rd dose, and failure to retain the treatment cards by the parents. Seasonal Malaria Chemoprevention is a proven intervention and appears to be an important

component of the malaria prevention strategy in Burkina Faso but consideration should be given to address ongoing implementation challenges.

The Demographic and Health Survey Program has released final and summary reports for both DHS and Malaria Indicator Surveys (MIS) for 2021 from several malaria endemic African countries. Below is a brief summary of some of the findings from Madagascar, Nigeria, Burkina Faso, Mali, Côte d’Ivoire, and Senegal. Click the link on each country to download a copy for yourself.

The proportion of the population who slept under an insecticide treated bednet the night before the survey varied. In Madagascar it was 49%, While in Nigeria it was 59%. Mali achieved the highest coverage at 73%, while Burkina Faso had the lowest previous night coverage at 41%.

Senegal showed a worrying decrease from 63% in 2016 to 46% in 2021. Côte d’Ivoire did not report total household use, but indicated that 72% of homes had at least one net, with 58% of children below 5 years of age and 64% of pregnant women sleeping under them.

At least three doses of sulfadoxine-pyremethamine is recommended for Intermittent preventive treatment of malaria in pregnant women. The national average was 38% for at least 3 doses in Senegal, although ironically 92% had been reached with the first dose. In Mali only 35% received at least a third dose. Burkina Faso started out with 92% for the first dose, but reached 57% with three or more. Côte d’Ivoire started with 80% receiving their first dose and concluded with only 35% receiving a third. Both Madagascar and Nigeria had the lowest 3-dose coverage at 31%.

Malaria testing and treatment using rapid diagnostic tests and artemisinin-based combination therapy (ACT) was reported. Nigeria demonstrates the challenges of following guidelines. Although 63% of children under 5 years of age were reported to have had a fever in the two weeks preceding the survey, only 24% of those received a diagnostic test. The summary results report that 74% of those with fever “who took any anti-malaria medicine” used the recommended ACT. The implication is that many received medicine without confirmatory testing such that some may have gotten ACT who needed another medicine and some who actually had malaria may have missed the correct treatment.

A similar low level of testing was seen in Senegal (22%), Mali (23%), and Madagascar (20%). Côte d’Ivoire reported 38% of febrile children having been tested. Burkina Faso performed better for testing with 65%.

These brief findings indicate that implementation of Malaria interventions are far from ideal. We know that some of the blame can be placed on health service disruptions due to demands of COVID-19 activities by health ministries and partners. Still, with 8 years remaining until 2030, Reinvigorated efforts are needed in all endemic countries if these six examples are indicative of the challenges we face.

Sarah McHugh  has contributed this posting to the Blog site for the JHU site for the course Social and Behavioral Foundations of Primary Health Care. Although malaria transmission and infection rates in Senegal have declined in the past two decades from over 300 incidences of malaria infection per 1000 people at risk in 2000 to about 50 in 2020, malaria remains a burden and Senegal is still working with partners and stakeholders to research potential control and elimination strategies. Malaria is endemic in Senegal, where all of its inhabitants are at risk of contracting the disease and the country has a tropical zone of the country, where there is year-round transmission of malaria and a Sahelian zone, where transmission is high during and after the rainy season. (Map: Malaria interventions across transmission zones in Senegal) The WHO currently recommends that children under five years of age who reside in areas that have high seasonal malaria transmission (where most of the annual malaria cases occur during four months of the year) receive SMC during the months of high transmission. Although not currently recommended by the WHO, Senegal is the only SMC country that includes children up to ten years of age in SMC distribution. (SMC District MAP: PMI supported SMC districts in Senegal)

In the past week, news has featured challenges to malaria elimination around the globe. Starting in Papua New Guinea which accounted for accounted for 86% of all cases in the Western Pacific Region in 2020. While there are 39% fewer cases in the region since 2000, there was an increase of 300,000 cases between 2019 and 2020. It is mainly in the six countries of the Greater Mekong subregion where progress has been steady.

Moving east to the Brazilian Amazon, one finds wildcat gold mining operations are not only destroying Native American ecosystems but are carving huge holes in the earth which are perfect breeding conditions for mosquitoes. This means that malaria cases among the Yanomami indigenous people living in the Brazilian Amazon have increased by more than 12 times since 2014.

Also within South America, one finds that although Paraguay was certified by the World Health Organization (WHO) as free of local transmission of malaria in 2018, experts are warning that travelers entering the country from areas with malaria transmission could easily reintroduce the disease. Hence vigilance is urged.

Crossing next to sub-Saharan Africa, one reads of studies showing an increasing link between malaria and agriculture across the region. As population expands in the region, more food, water and agricultural commodities are required. Irrigation and deforestation to clear land for agriculture increase the risk of childhood malaria in sub-Saharan Africa. The experts recommend that African ministries of agriculture, health, and environment need to collaborate on safer development policies and practices, not only to curb malaria, but the devastating effects of climate change.

Finally continuing back to Asia, one finds what might be termed an epidemiological conflict between Nepal, which is nearing malaria elimination for 2025, and its southern neighbor India, which is a source of imported malaria. Although the number of indigenous cases is nearing zero, health authorities fear that imported cases of of malaria from India are so high that local transmission could be reignited.

Malaria is clearly a global health problem. Collaboration and coordination across continents is needed to eliminate the scourge.

PRESS RELEASE                                                 

New Partnership launched to accelerate elimination of relapsing P. vivax malaria that poses a risk to an estimated 2.5 billion people worldwide

• The Partnership for Vivax Elimination (PAVE) will support endemic countries in achieving their Plasmodium vivax (P. vivax) malaria elimination goals.
• PAVE will advance the development of quality-assured, child-friendly treatments for relapse prevention, and generate and consolidate evidence to support malaria-endemic countries in developing and implementing new strategies to eliminate P. vivax malaria.

Geneva/Seattle, 14^th July 2021 –

The new Partnership for Vivax Elimination (PAVE) launching today, will support countries in the elimination of P. vivax – a complex and persistent type of malaria that poses a risk to more than one-third of the world’s population.

As part of PAVE, Medicines for Malaria Venture (MMV), PATH, Menzies School of Health Research, and Burnet Institute will work with in-country partners to conduct feasibility studies looking at the best way to use different P. vivax relapse treatments and diagnostics at different levels of the healthcare system in endemic countries including Brazil, Ethiopia, India, Indonesia, Papua New Guinea, Peru and Thailand.

PAVE will also continue to support countries, including Cambodia, Colombia, Lao PDR, and Vietnam, with market analytics and readiness planning for new tools and approaches as they seek to optimize P. vivax case management according to World Health Organization (WHO) guidance and accelerate progress towards their malaria elimination goals.

PAVE is led by MMV and PATH and combines a new investment of USD 25 million from Unitaid with work under existing grants from the Bill & Melinda Gates Foundation (BMGF), the UK Foreign, Commonwealth and Development Office (FCDO) and MMV core funding.  Consolidating these projects under PAVE will ensure coordination of efforts and clear communications with partners around the world. Recognizing that even more work is needed, PAVE will provide a vehicle for advocacy to bring further attention and resources to the challenge of eliminating P. vivax malaria.

Accounting for between 5.9 and 7.1 million estimated clinical cases every year, P. vivax is the most common type of malaria outside of sub-Saharan Africa. It presents a major challenge to achieving global malaria targets because of the difficulties in eliminating hypnozoites, a form of the parasite that remains in a person’s liver even after successful blood-stage treatment, leading to malaria relapses and contributing significantly to transmission.

Tackling P. vivax, by treating both the blood- and liver-stages of infection – known as radical cure – is essential to achieve the WHO 2030 targets of reducing global malaria case incidence by at least 90% and eliminating malaria transmission in 35 countries; as well as target 3.3 of the Sustainable Development Goals: end the epidemics of AIDS, TB and malaria by 2030.

PAVE will continue to work closely with WHO, National Malaria Control Programmes, and country-based partners to support the introduction and use of effective diagnostics and treatments for P. vivax malaria, including shorter-course primaquine and single-dose tafenoquine liver-stage treatments and better point-of-care glucose-6-phosphate dehydrogenase (G6PD) diagnostics needed to identify patients that are at risk of having adverse reactions to the class of drugs currently used for liver-stage treatments. Patients with the genetic disorder known as G6PD deficiency need to be screened because they are at risk of developing haemolytic anaemia when taking these drugs.

GSK and MMV have developed a paediatric version of tafenoquine, which iscurrently under review by regulators. PAVE aims to add to this and complete the full set of relapse prevention treatments suitable for children by supporting, with funding provided by Unitaid, the development of a quality-assured, child-friendly formulation of primaquine.

“Malaria elimination is one of the main objectives of the Ministry of Health of Peru. For this reason, MINSA appreciates the support of the PAVE initiative to find new tools for an optimized radical cure for the treatment of P. vivax malaria. This will contribute to the National Malaria Elimination Program’s “Plan Malaria Cero”. Said Veronica Soto Calle, Executive Director of the Directorate for the Prevention and Control of Metaxenic Diseases and Zoonoses, Ministry of Health of Peru (MINSA). “In this sense, we salute the launch of PAVE, an expansion of the VivAccess initiative, and its commitment to supporting endemic countries in their efforts to eliminate malaria.”

“With COVID-19-related interruptions threatening progress against malaria, investing in game-changing innovations remains one of our best chances to advance the frontier towards the elimination of malaria in all countries. By accelerating the adoption of a shorter radical cure and better diagnostics, we can reduce the burden of P. vivax malaria and draw the line against this disease,” said Philippe Duneton, Executive Director of Unitaid.

“We are thrilled to further expand this important work,” said Elodie Jambert, Director, Access and Product Management at MMV. “Families and communities affected by relapsing malaria have been suffering for too long. The new paediatric treatment options, and the real-world evidence that we will generate as part of PAVE, will represent a big step forward in eliminating this disease.”

“PATH is excited to continue our close engagement with MMV started under the VivAccess grant in working to generate evidence that will support scale-up of life-saving drugs and diagnostics for P. vivax malaria” said, PATH’s Ethiopia Country Director, Tirsit Grishaw. “By combining efforts with the National Malaria Elimination Program as well as the National Malaria Elimination Strategy, PAVE will help shift the paradigm for P. vivax case management.”

We occasionally share global health posts from the Blog, “Social, Cultural, and Behavioral Issues in PHC and Global Health“, a site that provides students from the Johns Hopkins Bloomberg School of Public Health a chance to learn about and create advocacy material. Below is a posting from May 10, 2021 by Sally Farrington Thompson.

Uganda suffers from one of the highest burdens of malaria in Sub-Saharan Africa and in the world. Many Ugandans are familiar with bed nets and many have visited health clinics for malaria treatment. But still, malaria affects a high percentage of the country’s population.

In 2019, I traveled to outside of Kampala, Uganda to visit a malaria education and prevention program run by the National Malaria Controlle Program within the Ugandan Ministry of Health and USAID’S President’s Malaria Initiative (PMI). The program is referred to a Malaria Smart School where education about malaria is incorporated into the curriculum of each grade.

Each classroom has what is called a “malaria corner” where students’ projects on the anatomy of mosquitos, malaria parasite life cycle, the spread of malaria, and artistic expressions about malaria are featured.

The Malaria Smart School also incorporates education on malaria into song, dance, and art. In this way, students are learning more about how malaria is spread than any generation before them, which is also an important factor considering their population is so large! Pictured below is a poem written by the malaria smart school students. The poem was recited along with dance and acting.

The Ugandan Ministry of Health and PMI have been pleased with the Malaria Smart School program. It was evident during my visit that the students have gained a comprehensive knowledge of malaria and a knowledge they share and are passing onto their families and people they live with. In fact, one of the primary goals of this program was to break behavior cycles in the community regarding malaria through the students’ learning. The result of this program is that children are able to teach older generations proper preventative strategies about malaria, treatment options, and even basic scientific epidemiology of malaria.

This is already disrupting behaviors, leading older generations to seek proper care and follow proper mitigation efforts to combat malaria. If these programs were to expand to other regions in Uganda, within even a generation, there would be a significant decline in malaria cases because of the knowledge learned and passed on by these children. The Malaria Smart School program is one many countries should model in their national malaria control programs, and with outside support from partnering organizations like PMI, this model could really impact the global burden of malaria.

Ironically, blood transfusion helps with severe malaria, but can be dangerous in mild cases. And with severe malaria delay in treatment is a major risk. Malaria parasites can be surprisingly diverse, even in one home. Health system performance, drug quality and patient adherence are key factors in the effectiveness of anti-malarials. Read more on each article or abstract in the links provided.

The impact of delayed treatment of uncomplicated P. falciparum malaria on progression to severe malaria

Mousa A et al. conducted a systematic review and a pooled multicentre individual-patient meta-analysis in PLoS Medicine. Despite the reported association of delay in receiving treatment for uncomplicated malaria (UM) with an increased risk of developing severe malaria (SM), access to treatment remains low in most high-burden areas. Researchers performed a pooled individual-participant meta-analysis with the aim to ascertain the correlation between treatment delay and presenting with SM using Ovid MEDLINE and Embas.

Findings revealed significantly higher risk of severe disease in children and adults who had longer delays from symptom onset to treatment-seeking; this relationship was noted to be the strongest for progression to severe malarial anaemia. Per estimates, nearly half of the severe anaemia cases in both children and adults could be averted if they presented within the first 24 hours of symptom onset.

Malaria parasites in Nigeria are genetically diverse: a danger but also a useful tool

Segun Isaac Oyedeji notes that his team’s research has already confirmed that in malaria-endemic countries such as Nigeria, infected individuals carry P. falciparum parasites that are genetically complex or diverse. What we didn’t know was how diverse the parasites are in the micro environment, such as within households and among children of the same family.

Oyedeji thought that knowing the population structure within households could help us understand more about the pattern and development of the disease. It could also inform development of appropriate guidelines and control measures. He found that even in the micro environment, P. falciparum parasites exhibit high genetic diversity. This finding was similar to results from larger communities in malaria endemic regions and has the same important implications. The implication is that a one-size fits all intervention or approach against the parasites may not be effective. There were children living under the same roof and infected by parasites that were genetically different.

New evidence to guide the practice of blood transfusions in children with severe malaria

The Barcelona Institute for Global Health (ISGlobal) described a new study that shows that transfusions could help increase survival, even at higher haemoglobin levels than those currently recommended. The results show that blood transfusion increased the survival of patients with severe disease.

In cases with complications, such as impaired consciousness or elevated lactate in blood, transfusion improved survival even in children whose levels of haemoglobin were higher the recommended threshold of 60g /l. For example, among patients with impaired consciousness, the authors observed improved survival upon transfusion with haemoglobin levels as high as 105 g / l. However, in the case of mild cases, transfusion was associated with an increase in mortality.

Global estimation of anti-malarial drug effectiveness for the treatment of uncomplicated Plasmodium falciparum malaria 1991–2019

Giulia Rathmes and colleagues note that anti-malarial drugs play a critical role in reducing malaria morbidity and mortality, but their role is mediated by their effectiveness. Effectiveness is defined as the probability that an anti-malarial drug will successfully treat an individual infected with malaria parasites under routine health care delivery system. Anti-malarial drug effectiveness (AmE) is influenced by drug resistance, drug quality, health system quality, and patient adherence to drug use; its influence on malaria burden varies through space and time. This study used data from 232 efficacy trials.

The global effectiveness of artemisinin-based drugs was 67.4% (IQR: 33.3–75.8), 70.1% (43.6–76.0) and 71.8% (46.9–76.4) for the 1991–2000, 2006–2010, and 2016–2019 periods, respectively. The use of artemisinin-based combination therapy (ACT) with a competent partner drug and having multiple ACT as first-line treatment choice sustained high levels of effectiveness. High levels of access to healthcare, human resource capacity, education, and proximity to cities were associated with increased effectiveness. Effectiveness of non-artemisinin-based drugs was much lower than that of artemisinin-based.

This study provides evidence that health system performance, drug quality and patient adherence influence the effectiveness of anti-malarials used in treating uncomplicated falciparum malaria. These results provide guidance to countries’ treatment practices and are critical inputs for malaria prevalence and incidence models used to estimate national level malaria burden.

Recent publications in Malaria Journal, The Lancet and eLife tackle several challenges to saving lives and malaria elimination. Problems include low access to bednets for children in Ethiopia, high prevalence of asymptomatic malaria in Ghanaian adults, risk of co-infection with other infectious diseases, and gaps in current interventions to prevent malaria in pregnancy and children. On the hopeful side, new targets for drug therapy are being identified. Read more on each by following the links below.

Long-lasting insecticide-treated bed net ownership, utilization and associated factors among school-age children in Southern Ethiopia

Zerihun Zerdo and colleagues examined net use among children in malaria-prone areas of

Dara Mallo and Uba Debretsehay districts because malaria is one of the major causes of morbidity and mortality among school-age children (SAC) in sub-Saharan Africa. This study was part of a baseline assessment in a cluster-randomized controlled trial.

The ownership of at least one LLIN by households of school-aged children (SAC) was about 19.3% (95% CI 17.7–21.0%) but only 10.3% % (95% CI 7.7–13.7%) of these households had adequate access of bed nets to the household members. Ownership of bed net was lower than universal coverage of at least one bed net for two individuals. It is important to monitor replacement needs and educate mothers with low education level with their SAC on the benefit of consistent utilization of bed nets.

Prevalence of and risk factors for Plasmodium spp. co-infection with hepatitis B virus: a systematic review and meta-analysis

Kotepui and Kotepui observed that Plasmodium spp. and hepatitis B virus (HBV) are among the most common infectious diseases in underdeveloped countries. Therefore they examined co-infection in people living in endemic areas of both diseases. The PubMed, Web of Science, and Scopus databases were searched. Observational cross-sectional studies and retrospective studies assessing the prevalence of Plasmodium species and HBV co-infection were examined. and found 22 studies to include in a systematic review and meta-analysis. Overall, the pooled prevalence estimate of Plasmodium spp. and HBV co-infection was 6% (95% CI 4–7%, Cochran’s Q statistic?<?0.001, I2: 95.8%).

No difference in age or gender and risk of Plasmodium spp. and HBV co-infection group was found. The present study revealed the prevalence of Plasmodium spp. and HBV co-infection, which will help in understanding co-infection and designing treatment strategies. Future studies assessing the interaction between Plasmodium spp. and HBV are recommended.

High prevalence of asymptomatic malaria infections in adults, Ashanti Region, Ghana, 2018

Melina Heinemann and co-researchers noted that Ghana is among the high-burden countries for malaria infections and recently reported a notable increase in malaria cases. While asymptomatic parasitaemia is increasingly recognized as a hurdle for malaria elimination, studies on asymptomatic malaria are scarce, and usually focus on children and on non-falciparum species. Therefore asymptomatic adult residents from five villages in the Ashanti Region, Ghana, were screened for Plasmodium species by rapid diagnostic test (RDT) and polymerase chain reaction (PCR) during the rainy season. Samples tested positive were subtyped using species-specific real-time PCR.

Molecular prevalence of asymptomatic Plasmodium infection was 284/391 (73%); only 126 (32%) infections were detected by RDT. While 266 (68%) participants were infected with Plasmodium falciparum, 33 (8%) were infected with Plasmodium malariae and 34 (9%) with P. ovale. The sub-species P. ovale curtisi and P. ovale wallikeri were identified to similar proportions. Non-falciparum infections usually presented as mixed infections with P. falciparum.

Most adult residents in the Ghanaian forest zone are asymptomatic Plasmodium carriers. The high Plasmodium prevalence not detected by RDT in adults highlights that malaria eradication efforts must target all members of the population. Beneath Plasmodium falciparum, screening and treatment must also include infections with P. malariae, P. o. curtisi and P. o. wallikeri.

Scientists shed new light on mechanisms of malaria parasite motility

eLife reports a new insight on the molecular mechanisms that allow malaria parasites to move and spread disease within their hosts has just been published. The first X-ray structures of the molecular complex that allows malaria parasites to spread disease highlight a novel target for antimalarial treatments.

The movement and infectivity of the parasite Plasmodium falciparum, and ultimately its ability to spread malaria among humans, rely on a large molecular complex called the glideosome. The new findings provide a blueprint for the design of future antimalarial treatments that target both the glideosome motor and the elements that regulate it.

New Lancet Series: Malaria in early life

Malaria infections are harmful to both the pregnant mother and the developing fetus. Malaria is associated with a 3–4 times increased risk of miscarriage and a substantially increased risk of stillbirth, and it disproportionately affects children younger than 5 years. Falciparum malaria is responsible for more than 200 000 child deaths per year in Africa and vivax malaria causes excess mortality in children in Asia and Oceania. In a duet of papers, we review 1) the deleterious effects of malaria in pregnancy on the developing fetus and 2) the current strategies for prevention and treatment of malaria in children.

Paper 1 is “Deleterious effects of malaria in pregnancy on the developing fetus: a review on prevention and treatment with antimalarial drugs” by Makoto Saito, Valérie Briand, Aung Myat Min, and Rose McGready. The authors are concerned that one in ten maternal deaths in malaria endemic countries may result from Plasmodium falciparum infection, that malaria is associated with a 3–4 times increased risk of miscarriage and a substantially increased risk of stillbirth. While current treatment and prevention strategies reduce, but do not eliminate, malaria’s damaging effects on pregnancy outcomes. They conclude that there is a need for alternative strategies to prevent malaria in pregnancy.

Paper 2 is “Treatment and prevention of malaria in children” by Elizabeth A Ashley and Jeanne Rini Poespoprodjo. They examine the following interventions: Triple antimalarial combination therapies, the RTS,S/AS01 vaccine, seasonal malaria chemoprevention and preventing relapse in Plasmodium vivax infection with primaquine.

The American Journal of Tropical Medicine and Hygiene has several new articles on malaria. Abstracts are shared. Two articles examine the role of travel in malaria transmission, both cross-border and rural-urban. Another considers the effect on pharmacokinetics of lumefantrine due to gut bacteria. In Uganda indoor spraying has reduced transmission, but asymptomatic cases remain among children. The challenges of asymptomatic malaria to elimination efforts is also examined in India. Links to the articles are found below.

Evidence of Microbiome–Drug Interaction between the Antimalarial Lumefantrine and Gut Microbiota in Mice

The antimalarial drug lumefantrine exhibits erratic pharmacokinetics. Intersubject variability might be attributed, in part, to differences in gut microbiome–mediated drug metabolism. We assessed lumefantrine disposition in healthy mice stratified by enterotype to explore associations between the gut microbiota and lumefantrine pharmacokinetics. Gut microbiota enterotypes were classified according to abundance and diversity indices from 16S rRNA sequencing. Pharmacokinetic parameters were computed using noncompartmental analysis. Two distinct enterotypes were identified.

Maximal concentration (C max) and total drug exposure measured as the area under the drug concentration–time curve (AUC0–24) differed significantly between the groups. The mean and standard deviation of C max were 660 ± 220 ng/mL versus 390 ± 59 ng/mL (P = 0.02), and AUC0–24 was 9,600 ± 2,800 versus 5,800 ± 810 ng × h/mL (P = 0.01). In healthy mice intragastrically dosed with the antimalarial drug lumefantrine in combination with artemether, lumefantrine exposure was associated with gut bacterial community structure. Studies of xenobiotic–microbiota interactions can inform drug posology and elucidate mechanisms of drug disposition.

Malaria Transmission, Infection, and Disease following Sustained Indoor Residual Spraying of Insecticide in Tororo, Uganda

Tororo, a district in Uganda with historically high malaria transmission intensity, has recently scaled up control interventions, including universal long-lasting insecticidal net distribution in 2013 and 2017, and sustained indoor residual spraying (IRS) of insecticide since December 2014. We describe the burden of malaria in Tororo 5 years following the initiation of IRS. We followed a cohort of 531 participants from 80 randomly selected households in Nagongera subcounty, Tororo district, from October 2017 to October 2019. Mosquitoes were collected every 2 weeks using CDC light traps in all rooms where participants slept, symptomatic malaria was identified by passive surveillance, and microscopic and submicroscopic parasitemia were measured every 4 weeks using active surveillance. Over the 2 years of follow-up, 15,780 female anopheline mosquitos were collected, the majority (98.0%) of which were Anopheles arabiensis.

The daily human biting rate was 2.07, and the annual entomological inoculation rate was 0.43 infective bites/person/year. Only 38 episodes of malaria were diagnosed (incidence 0.04 episodes/person/year), and there were no cases of severe malaria or malarial deaths. The prevalence of microscopic parasitemia was 1.9%, and the combined prevalence of microscopic and submicroscopic parasitemia was 10.4%, each highest in children aged 5–15 years (3.3% and 14.0%, respectively). After 5 years of intensive vector control measures in Tororo, the burden of malaria was reduced to very low transmission levels. However, a significant proportion of the population remained parasitemic, primarily school-aged children with submicroscopic parasitemia, providing a potential reservoir for malaria transmission.

Malaria Diagnosed in an Urban Setting Strongly Associated with Recent Overnight Travel: A Case–Control Study from Kampala, Uganda

Malaria is frequently diagnosed in urban Kampala, despite low transmission intensity. To evaluate the association between recent travel out of Kampala and malaria, we conducted a matched case–control study. Cases were febrile outpatients with a positive malaria test; controls were febrile outpatients with a negative test. For every two cases, five controls were selected, matching on age. Data were collected on recent overnight travel out of Kampala (past 60 days), destination and duration of travel, and behavioral factors, including sleeping under an insecticide-treated net (ITN) during travel. From July to August 2019, 162 cases and 405 controls were enrolled. The locations of residence of cases and controls were similar. More controls were female (62.7% versus 46.3%, P < 0.001). Overall, 158 (27.9%) participants reported recent overnight travel.

Travelers were far more likely to be diagnosed with malaria than those who did not travel (80.4% versus 8.6%, OR 58.9, 95% CI: 23.1–150.1, P < 0.001). Among travelers, traveling to a district not receiving indoor residual spraying of insecticide (OR 35.0, 95% CI: 4.80–254.9, P < 0.001), no ITN use (OR 30.1, 95% CI: 6.37–142.7, P < 0.001), engaging in outdoor activities (OR 22.0, 95% CI: 3.42–141.8, P = 0.001), and age < 16 years (OR 8.36, 95% CI: 2.22–56.2, P = 0.03) were associated with increased odds of malaria. Kampala residents who traveled overnight out of the city were at substantially higher risk of malaria than those who did not travel. For these travelers, personal protection measures, including sleeping under an ITN when traveling, should be advocated.

Prevalence of Asymptomatic Malaria Parasitemia in Odisha, India: A Challenge to Malaria Elimination

The prevalence of malaria in India is decreasing, but it remains a major concern for public health administration. The role of submicroscopic malaria and asymptomatic malaria parasitemia and their persistence is being explored. A cross-sectional survey was conducted in the Kandhamal district of Odisha (India) during May–June 2017. Blood samples were collected from 1897 individuals for screening of asymptomatic parasitemia. Samples were screened using rapid diagnostic tests (RDTs) and examined microscopically for Plasmodium species. Approximately 30% of randomly selected samples (n = 586) were analyzed using real-time PCR (qPCR), and the genetic diversity of Plasmodium falciparum was analyzed.

The prevalence of Plasmodium species among asymptomatic individuals detected using qPCR was 18%, which was significantly higher than that detected by microscopy examination (5.5%) or RDT (7.3%). Of these, 37% had submicroscopic malaria. The species-specific prevalence among asymptomatic malaria-positive cases for P. falciparum, Plasmodium vivax, and mixed infection (P. falciparum and P. vivax) by qPCR was 57%, 29%, and 14%, respectively. The multiplicity of infection was 1.6 and 1.2 for the merozoite surface protein-1 gene (msp1) and (msp2), respectively. Expected heterozygosity was 0.64 and 0.47 for msp1 and msp2, respectively. A significant proportion of the study population, 105/586 (18%), was found to be a reservoir for malaria infection, and identification of this group will help in the development of elimination strategies.

Travel Is a Key Risk Factor for Malaria Transmission in Pre-Elimination Settings in Sub-Saharan Africa: A Review of the Literature and Meta-Analysis

By sustaining transmission or causing malaria outbreaks, imported malaria undermines malaria elimination efforts. Few studies have examined the impact of travel on malaria epidemiology. We conducted a literature review and meta-analysis of studies investigating travel as a risk factor for malaria infection in sub-Saharan Africa using PubMed. We identified 22 studies and calculated a random-effects meta-analysis pooled odds ratio (OR) of 3.77 (95% CI: 2.49–5.70), indicating that travel is a significant risk factor for malaria infection.

Odds ratios were particularly high in urban locations when travel was to rural areas, to more endemic/high transmission areas, and in young children. Although there was substantial heterogeneity in the magnitude of association across the studies, the pooled estimate and directional consistency support travel as an important risk factor for malaria infection.