Category Archives: Artesunate

Malaria News Today 2020-09-15

Malaria Journal released three articles ranging from the relation between malaria and agricultural irrigation, artemisinin resistance on the Myanmar-China border, and efforts at costing malaria elimination interventions. PLoS Medicine examined the quality of malaria clinical management in children. Finally, Frontiers in Cellular and Infection Microbiology reported on a new drug against malaria and toxoplasmosis. Click on links to read more details.

Minimal tillage and intermittent flooding farming systems show a potential reduction in the proliferation of Anopheles mosquito larvae in a rice field in Malanville, Northern Benin

Irrigation systems have been identified as one of the factors promoting malaria disease around agricultural farms in sub-Saharan Africa. However, if improved water management strategy is adopted during rice cultivation, it may help to reduce malaria cases among human population living around rice fields.

A clear reduction of larva density was observed with both intermittent flooding systems applied to minimal tillage (MT?+?IF?+?NL) and intermittent flooding applied to deep tillage (DT?+?IF?+?AL), showing that intermittent flooding could reduce the abundance of malaria vector in rice fields. Recommending intermittent flooding technology for rice cultivation may not only be useful for water management but could also be an intentional strategy to control mosquitoes vector-borne diseases around rice farms.

No evidence of amplified Plasmodium falciparum plasmepsin II gene copy number in an area with artemisinin-resistant malaria along the China–Myanmar border

The emergence and spread of artemisinin resistance in Plasmodium falciparum poses a threat to malaria eradication, including China’s plan to eliminate malaria by 2020. Piperaquine (PPQ) resistance has emerged in Cambodia, compromising an important partner drug that is widely used in China in the form of dihydroartemisinin (DHA)-PPQ. Several mutations in a P. falciparum gene encoding a kelch protein on chromosome 13 (k13) are associated with artemisinin resistance and have arisen spread in the Great Mekong subregion, including the China–Myanmar border. Multiple copies of the plasmepsin II/III (pm2/3) genes, located on chromosome 14, have been shown to be associated with PPQ resistance.

DHA-PPQ for uncomplicated P. falciparum infection still showed efficacy in an area with artemisinin-resistant malaria along the China–Myanmar border. There was no evidence to show PPQ resistance by clinical study and molecular markers survey. Continued monitoring of the parasite population using molecular markers will be important to track emergence and spread of resistance in this region.

Costing malaria interventions from pilots to elimination programmes

Malaria programmes in countries with low transmission levels require evidence to optimize deployment of current and new tools to reach elimination with limited resources. Recent pilots of elimination strategies in Ethiopia, Senegal, and Zambia produced evidence of their epidemiological impacts and costs. There is a need to generalize these findings to different epidemiological and health systems contexts. Drawing on experience of implementing partners, operational documents and costing studies from these pilots, reference scenarios were defined for rapid reporting (RR), reactive case detection (RACD), mass drug administration (MDA), and in-door residual spraying (IRS). These generalized interventions from their trial implementation to one typical of programmatic delivery. In doing so, resource use due to interventions was isolated from research activities and was related to the pilot setting. Costing models developed around this reference implementation, standardized the scope of resources costed, the valuation of resource use, and the setting in which interventions were evaluated. Sensitivity analyses were used to inform generalizability of the estimates and model assumptions.

Populated with local prices and resource use from the pilots, the models yielded an average annual economic cost per capita of $0.18 for RR, $0.75 for RACD, $4.28 for MDA (two rounds), and $1.79 for IRS (one round, 50% households). Intervention design and resource use at service delivery were key drivers of variation in costs of RR, MDA, and RACD. Scale was the most important parameter for IRS. Overall price level was a minor contributor, except for MDA where drugs accounted for 70% of the cost. The analyses showed that at implementation scales comparable to health facility catchment area, systematic correlations between model inputs characterizing implementation and setting produce large gradients in costs. Prospective costing models are powerful tools to explore resource and cost implications of policy alternatives. By formalizing translation of operational data into an estimate of intervention cost, these models provide the methodological infrastructure to strengthen capacity gap for economic evaluation in endemic countries. The value of this approach for decision-making is enhanced when primary cost data collection is designed to enable analysis of the efficiency of operational inputs in relation to features of the trial or the setting, thus facilitating transferability.

Quality of clinical management of children diagnosed with malaria: A cross-sectional assessment in 9 sub-Saharan African countries between 2007–2018

Appropriate clinical management of malaria in children is critical for preventing progression to severe disease and for reducing the continued high burden of malaria mortality. This study aimed to assess the quality of care provided to children under 5 diagnosed with malaria across 9 sub-Saharan African countries. We used data from the Service Provision Assessment (SPA) survey. SPAs are nationally representative facility surveys capturing quality of sick-child care, facility readiness, and provider and patient characteristics across 9 countries, including Uganda (2007), Rwanda (2007), Namibia (2009), Kenya (2010), Malawi (2013), Senegal (2013–2017), Ethiopia (2014), Tanzania (2015), and Democratic Republic of the Congo (2018).

In this study, we found that a majority of children diagnosed with malaria across the 9 surveyed sub-Saharan African countries did not receive recommended care. Clinical management is positively correlated with the stocking of essential commodities and is somewhat improved in more recent years, but important quality gaps remain in the countries studied. Continued reductions in malaria mortality will require a bigger push toward quality improvements in clinical care. Despite increases in the distribution of malaria tests and effective antimalarial medications, significant gaps in the quality of care for pediatric malaria are present in these 9 countries. Further improvements in quality of malaria care may require a better understanding of remaining barriers and facilitators to appropriate management.

Novel drug could be a powerful weapon in the fight against malaria and toxoplasmosis

Princeton researchers are making key contributions toward developing a promising new treatment for the widespread and devastating diseases toxoplasmosis and malaria.
The Princeton scientists specialize in preparing the drug compound into a medicine that is both safe and effective for humans and able to reach its intended sites of action in the body in sufficient doses. An international team of scientists found the new drug—designated JAG21—to be highly effective against parasites in cell-based studies in the lab. After the discovery, team representatives contacted Princeton’s Robert Prud’homme for help in translating the JAG21 compound into a deliverable medication. Prud’homme is a co-author of a study, published in June 2020 in Frontiers in Cellular and Infection Microbiology, that describes the compound and its excellent preliminary results in mice.

Malaria News Today 2020-09-03

Various updates were found in newsletters and journal abstracts online today. These looked at mosquitoes – what attracts them to people, how ookinetes move in the midgut, and how perlite from volcanic rock may be a barrier repellent. Nigeria reports that there is no ACT resistance – so far.  And malaria partners join to coordinate actions in Uganda.  Click on links to read details.

Nigeria yet to detect resistance of malaria parasite to ACTs, says ministe

Contrary to reports that Africa has for the first time identified resistance strain of the malaria parasite to the drug of choice, Artemisinin Combination Therapy (ACT), the Minister of Health, Dr. Osagie Emmanuel Ehanire, on Monday said a study conducted in three states of the country showed there is no such phenomenon in Nigeria.  “However, we are still monitoring the situation. We insist that people should conduct a malaria test before using the drug of choice. This we hope will help prevent any kind of resistance of the malaria parasite to ACTs.”

Ministry of Health launches the Malaria Free Uganda Fund

Health Minister Dr Jane Ruth Aceng told journalists in Kampala today that the idea of having this new board was reached after realizing that different entities have been conducting the same malaria control related work. She said that the ministry resolved that mainstreaming responsibility will remove financial and operational bottlenecks that deter them from achieving set targets for elimination of the disease. The fund with a board of 11 members is chaired by Kenneth Wycliffe Mugisha of the Rotarian Malaria Partners-Uganda.

Volcanic Rock Yields a New Kind of Insecticide for Mosquitoes

Insecticide resistance to pesticides has become widespread in mosquito populations, making insecticides less effective over time. Therefore, there is an urgent need for insecticides with alternative modes of action. tested a material derived from volcanic rock, perlite, as a potential non-chemical insecticide against Anopheles gambiae, one of the primary mosquitoes that spreads malaria in Africa. In their new report published in August in the Journal of Medical Entomology, they show that perlite has encouraging potential as a mechanical insecticide. Perlite is believed to act by causing dehydration in the mosquitoes. read more…

Mosquitoes love pregnant, beer-drinking exercisers with Type O blood

Mosquitoes spread Zika, West Nile, Chikungunya, Dengue, and Malaria, resulting in 700 million illnesses a year and a million deaths. Even if you don’t get sick from a mosquito bite, the blood thinner they pump into your flesh before draining your blood causes swelling and itching. This article in Smithsonian Magazine lists the factors that make some people more tempting targets than others to mosquito bites. They include:

  • Blood type: “One study found that in a controlled setting, mosquitoes landed on people with Type O blood nearly twice as often as those with Type A.”
  • Carbon Dioxide: “people who simply exhale more of the gas over time—generally, larger people—have been shown to attract more mosquitoes than others.”
  • Exercise: “mosquitoes find victims at closer range by smelling the lactic acid, uric acid, ammonia and other substances expelled via their sweat”
  • Skin bacteria: “scientists found that having large amounts of a few types of bacteria made skin more appealing to mosquitoes”
  • Beer: “Just a single 12-ounce bottle of beer can make you more attractive to the insects”
  • Pregnancy: “pregnant people exhale about 21 percent more carbon dioxide and are on average about 1.26 degrees Fahrenheit warmer than others”
  • Clothing color: “wearing colors that stand out (black, dark blue or red) may make you easier to find”
  • Genetics: “underlying genetic factors are estimated to account for 85 percent of the variability between people in their attractiveness to mosquitoes”

Live In Vivo Imaging of Plasmodium Invasion of the Mosquito Midgut

Malaria is one of the most devastating parasitic diseases in humans and is transmitted by anopheline mosquitoes. The mosquito midgut is a critical barrier that Plasmodium parasites must overcome to complete their developmental cycle and be transmitted to a new host. Here, we developed a new strategy to visualize Plasmodium ookinetes as they traverse the mosquito midgut and to follow the response of damaged epithelial cells by imaging live mosquitoes. Understanding the spatial and temporal aspects of these interactions is critical when developing novel strategies to disrupt disease transmission.

Reduction in malaria-attributable deaths following a rectal artesunate pre-referral treatment pilot in Burkina Faso, 2018

Ousmane Badolo,* Stanislas Nébié, Youssouf Sawadogo, Thierry Ouedraogo, Bonkoungou Moumouni, Mathurin Dodo, Lolade Oseni, Gladys Teteh, and William Brieger, presented a poster entitled, “Reduction in malaria-attributable deaths following a rectal artesunate pre-referral treatment pilot in Burkina Faso, 2018,” at the 68th Annual Meeting of the American Society of Tropical Medicine and Hygiene.

Background: In 2017, 4.32 percent of malaria cases were documented as severe malaria in Burkina Faso. The National Case Management Guidelines (August 2017) recommends that the First line treatment for severe malaria be injectable artesunate except in pregnancy where injectable quinine is used for the 1st trimester and injectable artesunate used for the 2nd and 3rd trimesters.

The guidelines recommend pre-referral treatment of severe disease at peripheral health facilities using rectal artesunate for children under 5, parenteral artesunate, artemether, or quinine for older children and adults. The guidelines also recommend pre-referral treatment of severe disease by community health workers with rectal artesunate for children under 5 only. The National Malaria Control Program is currently piloting pre-referral rectal artesunate for children under five years of age by CHWs in three districts in North and Sahel regions, where malaria mortality is the highest.

Results: Comparison Severe Malaria cases and death among <5 before and after the pre-referral treatment in Sahel region is seen in the Table. Pre-referral treatment was able to reduce fatality by 45%.

Comparison of monthly fatality of severe malaria among <5 year (October 16 to April 17; October 17 to April 18 and October 18 to April 19) in the Sahel region is seen in the Graph. This shows a substantial decline in severe malaria following introduction ofthe  pre-referral rectal artesunate pilot.

Several Lessons were Learned based on the Encouraging preliminary results. The involvement of the community in health activities allows good visibility of the intervention resulting in good acceptability and adherence. The community can take charge of its own health if it is well supervised. Good functionality of the “canary fridge” device when used in hot areas.  Ability to use other meeting and supervisory opportunities to implement the strategy.  Challenges identified can be corrected by close monitoring.

Insecurity in Northern Burkina Faso is a major constraint, but pre-referral treatment of severe malaria is needed to decrease mortality from malaria. Despite implementation difficulties, this experience has contributed to a reduction in deaths due to severe malaria in the Sahel region, which is also facing increasing insecurity.

An evaluation of the implementation with data collection for a one-year implementation period will provide lessons for the national scale up of pre-referral artesunate implementation.

*Affiliations: PMI Improving Malaria Care Project, Jhpiego Baltimore, MD, United States, Johns Hopkins University, Baltimore, MD, United States

This poster was made possible by the generous support of the American people through the United States Agency for International Development (USAID) under Cooperative Agreement No. AID-624-A-13-00010 and the President’s Malaria Initiative (PMI). The contents are the responsibility of the authors and do not necessarily reflect the views of USAID, PMI or the United States Government.