February 2023 Science & Research Report

By Dr. Derick Pasternak, Malaria Science & Research Coordinator, MPI

In a “documentary video from the New England Journal of Medicine, physicians and scientists from across the world discuss the epidemiology of malaria and outline key strategies for prevention and treatment of the disease. The narrative takes a deep dive into prevention of the disease, including strategies to control mosquito vectors, new vaccines, and monoclonal antibodies. The video anticipates the challenges of eliminating malaria, given the emergence of drug-resistant strains, and looks to promising new therapies on the horizon… This video includes footage and photos provided by the Global Fund to Fight AIDS, Tuberculosis, and Malaria; MMV Medicines for Malaria Venture; Caz Tanner; Suphak Nosten for Shoklo Malaria Research Unit; and Saw HTEE K Paung for Shoklo Malaria Research Unit.”

 For further reading, the following articles, referenced in the video, are available at the Journal’s website: A Malaria Vaccine for Africa — An Important Step in a Century-Long Quest. in the March 17, 2022, issue; Safety and Efficacy of a Monoclonal Antibody against Malaria in Mali. in the November 17, 2022, issue; and Low-Dose Subcutaneous or Intravenous Monoclonal Antibody to Prevent Malaria. in the November 17, 2022, issue.  All of these had been included in the relevant monthly literature report (and there is another study on a monoclonal antibody in this report).

 “Trafficked medical products kill almost half a million Sub-Saharan Africans every year, and action is needed to stem the flow, the United Nations Office on Drugs and Crime (UNODC) states in its new threat assessment report… Trafficking these products is also taking a direct economic toll on affected countries. The World Health Organization (WHO) estimates that caring for people who have used falsified or substandard medical products for malaria treatment in sub-Saharan Africa costs between $12 million to $44.7 million every year.”  The report is available at https://www.unodc.org/documents/data-and-analysis/tocta_sahel/TOCTA_Sahel_medical_2023.pdf

PEER REVIEWED PUBLICATIONS:

Prevention

Vaccines

The economics of the vaccine program in the three pilot countries of Ghana, Kenya, and Malawi was studied by Baral R & al.  They report in Cost of Introducing and Delivering RTS,S/AS01 Malaria Vaccine Within the Malaria Vaccine Implementation Program, Vaccine. 2023 Jan 27: S0264-410X(23)00064-6, doi: 10.1016/j.vaccine.2023.01.043 that “[a]t a vaccine price of $5 per dose, the incremental cost per dose administered across countries ranges from $2.30 to $3.01 (financial), and $8.28 to $10.29 (economic). The non-vaccine cost of delivery ranges between $1.04 and $2.46 (financial) and $1.52 and $4.62 (economic), by country. Considering only recurrent costs, the non-vaccine cost of delivery per dose ranges between $0.29 and $0.89 (financial) and $0.59 and $2.29 (economic), by country. Introduction costs constitute between 33% and 71% of total financial costs.”

 

Vaccine effectiveness in preventing malaria in a society is dependent on its acceptance by the public. Kabir Sulaiman S & al. studied what vaccine hesitancy. They report in Prevalence, Determinants, and Reasons for Malaria Vaccine Hesitancy Among Caregivers of Under-Five Children in Nigeria: Results from a Nationwide Cross-Sectional Survey, Vaccine. 2023 Jan 30: S0264-410X(23)00089-0, doi: 10.1016/j.vaccine.2023.01.060 that the following factors are associated with stronger hesitance: High income, large families, religion other than Islam. Causes of hesitance are also explored.

 

Nielsen CM & al. studied a vaccine not yet approved for use and concluded that the originally recommended injection schedule should be lengthened for optimal immune response.  The paper is Delayed Boosting Improves Human Antigen-Specific Ig and B Cell Responses to the RH5.1/AS01B Malaria Vaccine, JCI Insight. 2023 Jan 24;8(2):e163859, doi: 10.1172/jci.insight.163859.

 

Three articles focus on vivax malaria which is increasing in frequency in certain regions of Africa and elsewhere:  Roobsoong W & al., The Challenges of Plasmodium vivax Human Malaria Infection Models for Vaccine Development, Front Immunol. 2023 Jan 5; 13:1006954, doi: 10.3389/fimmu.2022.1006954. “Human Malaria Infection models (CHMI) have been critical to advancing new vaccines for malaria…Developing a safe and effective vaccine against vivax malaria is essential for controlling and eliminating” this very complex disease.  da Veiga GTS & al. review the efforts to develop protection against it in Plasmodium vivax Vaccine: What Is the Best Way to Go, Front Immunol. 2023 Jan 16; 13:910236, doi: 10.3389/fimmu.2022.910236. Mazhari R & al., Identification of Novel Plasmodium vivax Proteins Associated with Protection Against Clinical Malaria, Front Cell Infect Microbiol, 2023 Jan 25; 13:1076150, doi: 10.3389/fcimb.2023.1076150 is actually from SE Asia, purporting to have found specific proteins in P. vivax that can be used to prevent vivax malaria.

 

Deveci G & al., A Single Dose of Genetically Attenuated Malaria Blood-Stage Parasites Protects Against Two Plasmodium Species Infections, Vaccine. 2023 Jan 16: S0264-410X(23)00003-8, doi: 10.1016/j.vaccine.2023.01.004 claims success in applying their preparations in vitro to two different Plasmodium species.  However, the relevance of this finding to the species that infect humans is questionable.

 

Vector control and protection from vectors

As reported in Insecticide Susceptibility Status of Anopheles gambiae (s.l.) in and Surrounding Areas of Lake Tana, Northwest Ethiopia, Trop Med Health. 2023 Jan 13; 51(1):3, doi: 10.1186/s41182-023-00497-w, Kendie FA & al. found the mosquitoes collected in the area studied to be overwhelmingly sensitive to four insecticides.  Only 9.3% of those collected were resistant to all four insecticides studied.

 

A novel method of studying and perhaps controlling the vectors is described in Mechan F & al., Unmanned Aerial Vehicles for Surveillance and Control of Vectors of Malaria and Other Vector-Borne Diseases, Malaria J, 2023 Jan 20, 22:23, doi: 10.1186/s12936-022-04414-0#Sec2.  The paper describes actual use as well potential uses in the future.

 

As documented in many studies already, Diallo OO & al. also found and reported in Factors Associated with the Ownership and Use of Insecticide-Treated Nets {ITNs} in Guinea: An Analysis of the 2018 Demographic And Health Survey, Malaria J, 2022 Jan 26, 22:29, doi: 10.1186/s12936-023-04463-z that ownership of ITNs is highly variable (25% to 54%), but even among those owning nets, use varied between 35% and 90%.

 

Tangena JA & al., Unravelling the Impact of Insecticide-Treated Bed Nets on Childhood Malaria in Malawi, Malaria J, 2022 Jan 13, 22:16, doi: 10.1186/s12936-023-04448-y reports some interesting and unexpected conclusions, such as” child malaria prevalence had a negative association with ITN population access and a positive association with ITN use.” (This finding is somewhat similar to that of Kubana & al. in Rwanda (see below in Epidemiology).

 

“[LLINs] provide both direct and indirect protection against malaria. As pyrethroid resistance evolves in mosquito vectors, it will be useful to understand how the specific benefits LLINs afford individuals and communities may be affected. Here we use modelling to show that there is no minimum LLIN usage needed for users and non-users to benefit from community protection. Modelling results also indicate that pyrethroid resistance in local mosquitoes will likely diminish the direct and indirect benefits from insecticides, leaving the barrier effects intact, but LLINs are still expected to provide enhanced benefit over untreated nets even at high levels of pyrethroid resistance. The paper is Unwin HJT & al., Quantifying the Direct and Indirect Protection Provided by Insecticide Treated Bed Nets Against Malaria, Nat Commun. 2023 Feb 8; 14(1):676, doi: 10.1038/s41467-023-36356-9.

 

“Since its first report in Anopheles mosquitoes in 1950s, insecticide resistance has spread very fast to most sub-Saharan African malaria-endemic countries, where it is predicted to seriously jeopardize the success of vector control efforts, leading to rebound of disease cases.” According to Suh PF & al., Impact of Insecticide Resistance on Malaria Vector Competence: A Literature Review, Malaria J, 2023 Jan 17, 22:19, doi: 10.1186/s12936-023-04444-2, “… actual … knowledge [of] key factors to vectorial competence, such as the immunity and microbiota communities of the insecticide resistant vector is still very insufficient to definitively infer on the epidemiological importance of these vectors against the susceptible counterparts.”

 

Another field trial of LLINs reported this month is Accrombessi M & al., Efficacy of Pyriproxyfen-Pyrethroid Long-Lasting Insecticidal Nets (LLINs) and Chlorfenapyr-Pyrethroid LLINs Compared with Pyrethroid-Only LLINs for Malaria Control in Benin: A Cluster-Randomised, Superiority Trial, Lancet. 2023 Jan 24: S0140-6736(22)02319-4, doi: 10.1016/s0140-6736(22)02319-4. The authors conclude that “[o]ver 2 years, chlorfenapyr-pyrethroid LLINs provided greater protection from malaria than pyrethroid-only LLINs in an area with pyrethroid-resistant mosquitoes. … This study confirms the importance of chlorfenapyr as an LLIN treatment to control malaria in areas with pyrethroid-resistant vectors…” Killeen GF & Sougoufara S, Getting Ahead of Insecticide-Resistant Malaria Vector Mosquitoes, Lancet. 2023 Jan 24: S0140-6736(23)00102-2, doi: 10.1016/s0140-6736(23)00102-2 is the accompanying editorial, supporting the findings and referring to a similar study performed in Tanzania.

 

A study similar to the above is Maiteki-Sebuguzi C & al., Effect of Long-Lasting Insecticidal Nets with and Without Piperonyl Butoxide {PBO} on Malaria Indicators in Uganda (LLINEUP): Final Results of a Cluster-Randomised Trial Embedded in a National Distribution Campaign, Lancet Infect Dis. 2023 Feb; 23(2):247-25, doi: 10.1016/s1473-3099(22)00469-8.  In Uganda, PBO LLINs outperformed pyrethroid-only LLINs for 25 months.  While the conclusion is consistent with that reported from Benin, the compound added to the pyrethroid was different in this study. Zinszer K & Talisuna AO, Fighting Insecticide Resistance in Malaria Control, Lancet Infect Dis. 2023 Feb; 23(2):138-139, doi: 10.1016/s1473-3099(22)00518-7 is the editorial in the same issue.

 

Mbuba E & al., Multi-Country Evaluation of the Durability of Pyrethroid Plus Piperonyl-Butoxide Insecticide-Treated Nets: Study Protocol, Malaria J, 2023 Jan 27, 22:30, doi: 10.1186/s12936-023-04465-x is the announcement of another study of PBO-pyrethroid impregnated nets in Tanzania, Côte d’Ivoire, and India, with a description of the protocol.

 

Another approach to pyrethroid resistance is reported in Giesbrecht D & al., Durable Wall Lining for Malaria Control in Liberia: Results of a Cluster Randomized Trial, Malaria J, 2023 Jan 12, 22:15, doi: 10.1186/s12936-022-04429-7 and claimed to be superior to pyrethroid-impregnated bed nets in locations of low elevation, but not in villages of higher elevation.  However, the components of “durable wall lining are not described.

 

“The continued spread of insecticide resistance in mosquito vectors of malaria and arboviral diseases may lead to operational failure of insecticide-based interventions if resistance is not monitored and managed efficiently.” Corbel V & al., A New WHO Bottle Bioassay Method to Assess the Susceptibility of Mosquito Vectors to Public Health Insecticides: Results From a WHO-Coordinated Multi-Centre Study, Parasit Vectors. 2023 Jan 20; 16(1):21, doi: 10.1186/s13071-022-05554-7 “aimed to develop and validate a new WHO glass bottle bioassay method as an alternative to the WHO standard insecticide tube test to monitor mosquito susceptibility to new public health insecticides…” The authors state that they were able to validate the bioassay.

 

Bouraima A & al., Measuring Entomological Parameters Before Implementing a Study on Asymptomatic Carriers of Plasmodium falciparum in the Zè District in Southern Benin, Malaria J, 22:24, doi: 10.1186/s12936-023-04450-4 verified that the Anopheles vectors in the area were at least partially resistant to the insecticides studied. “…transfluthrin-treated sandals (TS) [and] transfluthrin-treated eave ribbons (TER)” both reduced insect biting.

 

Killing larvae is one aspect of vector control.  Just as with patient treatment, the local flora is enlisted in this effort, which is addressed by two papers this month: Bohounton RB & al., Euclasta condylotricha Flowers Essential Oils: A New Source of Juvenile Hormones and Its Larvicidal Activity Against Anopheles gambiae s.s. (Diptera: Culicidae), PLoS One, 2023 Jan 23;18(1):e0278834, doi: 10.1371/journal.pone.0278834 studied a grass widely distributed in Africa and found that its essential oils “showed a strong larvicidal activity…” Tawidian P &al. The Potential of a New Beauveria bassiana Isolate for Mosquito Larval Control, J Med Entomol. 2023 Jan 12; 60(1):131-147, doi: 1093/jme/tjac179 describes the possible use of a known parasitic fungus for the same purpose.

 

“If An. stephensi introduction is facilitated through seatrade, similar to other invasive mosquitoes, … identification of at-risk countries [is] needed to increase surveillance and response efforts.” Ahn J & al., Modeling Marine Cargo Traffic to Identify Countries in Africa With Greatest Risk of Invasion by Anopheles stephensi, Sci Rep. 2023 Jan 17; 13(1):876, doi: 10.1038/s41598-023-27439-0 used “maritime trade data “to (1) identify coastal African countries which were highly connected to select An. stephensi endemic countries, (2) develop a prioritization list of countries based on the likelihood of An. stephensi introduction through maritime trade index (LASIMTI), and (3) use network analysis of intracontinental maritime trade to determine likely introduction pathways. Sudan and Djibouti were ranked as the top two countries with LASIMTI in 2011, which were the first two coastal African countries where An. stephensi was detected. With Djibouti and Sudan included as source populations, 2020 data identify Egypt, Kenya, Mauritius, Tanzania, and Morocco as the top countries with LASIMTI. Network analysis highlight South Africa, Mauritius, Ghana, and Togo.”

 

Mosquito control by means other than LLINs and indoor residual spraying is described in  Mmbando AS & al., Small-Scale Field Evaluation of Transfluthrin-Treated Eave Ribbons and Sandals for the Control of Malaria Vectors in Rural Tanzania, Malar J. 2023 Feb 4; 22:43, doi: 10.1186/s12936-023-04476-8.

Janson KD & al. describe an alternative to using human volunteers to study the feeding behavior of mosquito vectors in Development of an Automated Biomaterial Platform to Study Mosquito Feeding Behavior, Front Bioeng Biotech, 2023 Feb 9, 11:1103748, doi: 10.3389/fbioe.2023.1103748.

 

Chemoprophylaxis

None this month

 

Other

None this month

 

Diagnosis

General diagnostics

Yu H & al. undertook to evaluate Malaria Screener, a smartphone-based application for malaria diagnosis in the field.  Using microscopy and PCR as controls, they report diagnostic accuracies between 71.8 and 74.1 percent. Then under laboratory conditions, using a different algorithm (PlasmodiumVF-Net) accuracy increased by about 10%.  Their paper is Patient-Level Performance Evaluation of a Smartphone-Based Malaria Diagnostic Application, Malaria J, 2023 Jan 27, 22:33, doi: 10.1186/s12936-023-04446-0.

 

Field diagnostics

“Malaria rapid diagnostic tests (mRDTs) have played an important role in the early detection of clinical malaria in an endemic area. While several mRDTs are currently on the market, the availability of mRDTs with high sensitivity and specificity will merit the fight against malaria. [Mwangonela ZE & al.] evaluated the field performance of a novel One Step Malaria (P.f/P.v) Tri-line and One Step Malaria (P.f) rapid test kits in Pwani, Tanzania.” They report in Field Evaluation of the Novel One Step Malaria Pf and Pf/Pv Rapid Diagnostic Tests and the Proportion of HRP-2 Gene Deletion Identified on Samples Collected in the Pwani Region, Tanzania, Bull Natl Res Cent, 2023; 47(1):17, doi: 10.1186/s42269-023-00992-4 that “One Step Malaria P.f/P.v Tri-line and One Step Malaria P.f rapid test kits have similar sensitivity and specificity as the standard mRDT that is currently in the market, demonstrating the potential to contribute in the fight against malaria in endemic settings. However, the identified malaria parasites population with HRP-2 gene deletion pose a threat to the current mRDT usability in the field and warrants further investigations.”

 

New diagnostic methods

Aris TA & al., Robust Image Processing Framework for Intelligent Multi-Stage Malaria Parasite Recognition of Thick and Thin Smear Images, Diagnostics (Basel), 2023 Jan 31; 13(3):511, doi: 10.3390/diagnostics13030511 is one of a number of articles in the cited issue of Diagnostics regarding  the use of computerized decision-making in malaria diagnosis.  At this time all relate to laboratory diagnosis, not field work.

 

Treatment

Treatment results

“In 2020, Dihydroartemisinin-Piperaquine (DHAP) was adopted as a second-line antimalarial for treatment of uncomplicated malaria in Ghana following a review of the country’s antimalarial medicines policy.” Abuaku B & al., Therapeutic Efficacy of Dihydroartemisinin-Piperaquine Combination for the Treatment of Uncomplicated Malaria in Ghana, Front Cell Infect Microbiol. 2023 Jan 6; 12:1058660, doi: 10.3389/fcimb.2022.1058660 reports that this combination remains highly effective.

 

Egwu CO & al. “assessed the level of antimalarial drug treatment failure in Ebonyi State, Nigeria. Both survey and in vitro analyses were adopted.” According to their paper, Assessment of the Antimalarial Treatment Failure in Ebonyi State, Southeast Nigeria, J Xenobiot. 2023 Jan 3;13(1):16-26doi: 10.3390/jox13010003 “artemisinin combination therapies (ACTs) remain the mainstay in the treatment of malaria, even though other non-artemisinin drugs are still used. [Their survey] also revealed that many patients still self-medicate, although, this may not be connected to the treatment failure seen among some malaria subjects…”

 

The problem of treating HIV-infected patients for malaria is addressed in Nyangulu W & al., Artemether-Lumefantrine Efficacy Among Adults on Antiretroviral Therapy in Malawi, Malaria J, 2023 Jan 27, 22:32, doi: 10.1186/s12936-023-04466-w. They found 94% “adequate clinical and parasitological response” in 411 episodes of malaria in 186 patients over five years. “Participants who experienced treatment failure had lower day 7 median lumefantrine levels” than those who were cured.

 

Belay H & al., Therapeutic Efficacy of Chloroquine for the Treatment of Uncomplicated Plasmodium vivax Infection in Shewa Robit, Northeast Ethiopia, PLoS One. 2023 Jan 12; 18(1):e0277362, doi: 10.1371/journal.pone.0277362 “aimed to assess the therapeutic efficacy of chloroquine among uncomplicated P. vivax infections at Shewa Robit Health Center, Northeast Ethiopia” and concluded on the basis of 90 participants enrolled that “chloroquine remains an efficacious and safe drug … for treating uncomplicated P. vivax …”

Side effects and complications

None this month

Drug resistance

Tolerance in the title of Yu X & al., Ring-Stage Growth Arrest: Metabolic Basis of Artemisinin Tolerance in Plasmodium falciparum, iScience. 2022 Dec 5; 26(1):105725, doi: 10.1016/j.isci.2022.105725 refers to resistance.  This paper describes the cellular effect of the PfKelch13 mutation that causes resistance.

 

New drug research

Monoclonal antibodies are an avenue of research pursued by several teams. Lyke KE & al., Low-Dose Intravenous and Subcutaneous CIS43LS Monoclonal Antibody for Protection Against Malaria (VRC Part C): A Phase 1, Adaptive Trial, Lancet Infect Dis, 2023 Jan 25, doi: 10.1016/S1473-3099(22)00793-9 is a report on “the third part of a three-part, first-in-human, phase 1, adaptive trial, conducted at the University of Maryland, Baltimore Center for Vaccine Development and Global Health, Baltimore, MD, USA. We enrolled adults aged 18–50 years with no previous malaria vaccinations or infections, in a sequential, dose-escalating manner. Eligible participants received the monoclonal antibody CIS43LS in a single, open-label dose of 1 mg/kg, 5 mg/kg, or 10 mg/kg intravenously, or 5 mg/kg or 10 mg/kg subcutaneously. Participants underwent controlled human malaria infection by the bites of five mosquitoes infected with Plasmodium falciparum 3D7 strain approximately 8 weeks after their monoclonal antibody inoculation.” Except for the lowest dose, CIS43LS was found to be effective in preventing infection, while the control subjects were all infected. The substance was deemed safe.

Chinnappanna NKR & al., Recent Approaches in the Drug Research and Development of Novel Antimalarial Drugs with New Targets, Acta Pharm. 2023 Jan 24; 73(1):1-27, doi: 10.2478/acph-2023-0001 is a review that “concentrates on the most current scientific and technical progress in the innovation of new antimalarial medications. The protein kinases, choline transport inhibitors, dihydroorotate dehydrogenase inhibitors, isoprenoid biosynthesis inhibitors, and enzymes involved in the metabolism of lipids and replication of deoxyribonucleic acid, are among the most fascinating antimalarial target proteins presently being investigated. The new cellular targets and drugs which can inhibit malaria and their development techniques are summarised in this study.”

Cocculus hirsutus is a tropical, invasive creeper with the common name broom creeper. Nardella F & al. modified one of 94 substances derived from it and found it to be inhibiting P. falciparum in vitro and P. berghei in the mouse model. Their paper, Hemisynthetic Alkaloids Derived from Trilobine are Antimalarials with Sustained Activity in Multidrug-Resistant Plasmodium falciparum, iScience, 2023 Jan 11; 26(2):105940, doi: 10.1016/j.isci.2023.105940 claims that identified a target of drug action different from that of current antimalarials.

 

Negm WA & al. argue that in addition to plant-derived drugs such as quinine and the artemisinins, one should look at marine origins. They state in Marine Organisms as Potential Sources of Natural Products for the Prevention and Treatment of Malaria, Royal Soc Chem Adv, 2023 Feb 2; 13(7):4436-4475, doi: 10.1039/d2ra07977a that [m]arine organisms have been investigated, including sponges, soft corals, algae, and cyanobacteria [and] have been shown to produce many bioactive compounds that potentially affect the causative organism …, including the chloroquine (CQ)-resistant strains of P. falciparum. … The … article presents a comprehensive review of marine-derived natural products with antimalarial activity.” 

Yahiya S & al., A Novel Class of Sulphonamides Potently Block Malaria Transmission by Targeting Plasmodium Vacuole Membrane Protein, Disease Models and Mechanisms, 2022 Jan 30, 16(2): dmm049950, doi: 10.1242/dmm049950 is primarily a report of molecular mechanisms of the antimalarial effect of a previously unused sulfonamide.  It is included in this report because of its potential benefits and the implication that other sulfonamides may have similar effects.

 

Plant extracts and traditional treatments

Chaniad P & al. argue that a plant based folk remedy (Arjuna tree) in use in Asia may form the basis of future drug development. As reported in, Antimalarial Efficacy and Toxicological Assessment of Medicinal Plant Ingredients of Prabchompoothaweep Remedy as a Candidate for Antimalarial Drug Development, BMC Complement Med Ther. 2023 Jan 18; 23(1):12, doi: 10.1186/s12906-023-03835-x, tests on the extract were inhibitory to the Plasmodium falciparum in the laboratory and toxicity studies (apparently in humans) demonstrated safety.

“Glycyrrhiza glabra L., Fabaceae, or licorice has shown potential therapeutic effects on fever, … and malaria. [Rashidzadeh H & al.] aimed to assess the antimalarial activity of different fractions of root extract from twelve ecotypes from Iran.” They report in Anti-Plasmodial Effects of Different Ecotypes of Glycyrrhiza glabra Traditionally Used for Malaria in Iran, Rev Bras Farmacogn. 2023 Jan 16:1-6, doi: 10.1007/s43450-022-00353-8 that “[i]n comparison to control, every analyzed ecotype has a remarkable parasite inhibitory effect..”

Other

Arena L & al. argue in Malaria Patient Spectrum Representation in Therapeutic Clinical Trials of Uncomplicated Malaria: A Scoping Review of the Literature, Malar J, 2023 Feb 10, 23:50, doi: 10.1186/s12936-023-04441-5 that almost without exception, studies of malaria treatment used patient samples unrepresentative of those suffering from the disease.  Reviewing the exclusion criteria criticized by the authors, it is one has to come to the conclusion that those are all related to confounding factors or patient rights issues. 

 

Peto TJ & al. refer to a recent WHO “moratorium on rectal artesunate (RAS) for pre-referral treatment of severe childhood malaria” in WHO Should Accelerate, Not Stall, Rectal Artesunate Deployment for Pre-Referral Treatment of Severe Malaria, Trans R Soc Trop Med Hyg. 2023 Feb 1: trad002, doi: 10.1093/trstmh/trad002, with which they strongly disagree.  However, the original WHO text states:

“Rectal artesunate (RAS) for severe malaria: MPAG highlighted that this is an important and urgent review given that the malaria-endemic countries that have yet to introduce the intervention are awaiting further guidance from WHO before deploying RAS. MPAG members highlighted that the main

issue is not RAS per se, but rather more broadly how to ensure that there is a continuum of care. Of particular importance are questions on the presence and functionality of the referral system where RAS is deployed. MPAG emphasized the importance of coordinating with other WHO departments focused on primary health care and mother and child health to ensure the successful implementation of this intervention. It was agreed that the Global Malaria Programme should inform MPAG of the outcome of the technical meeting as soon as it is available.” (https://www.who.int/publications/i/item/9789240063303, dated Oct 2022, downloaded 15 Feb 2023), which is not a moratorium, simply a delay in recommendation.

 

Campaigns and Policies

 

 

“[T]hree MDA rounds were implemented by [DRC] Ministry of Public Health and Médecins sans Frontières from September 2020 to January 2021 in four health areas selected for epidemiological (high malaria incidence) and logistic reasons. Reported mortality and morbidity were compared in locations where MDA has been performed and locations where it has not. Grout L & al., Effect of Large-Scale Mass Drug Administration for Malaria on Mortality and Morbidity in Angumu Health Zone, Ituri, Democratic Republic of Congo, Malar J. 2023 Feb 6; 22(1):44, doi: 10.1186/s12936-023-04469-7 reports significant reduction in malaria mortality and morbidity in the communities in which MDA was given, though less dramatic than that reported by Echodu & al. in the paper above.

 

“The Malaria Frontline Project (MFP) supported the National Malaria Elimination Program for effective program implementation in the high malaria-burden states of Kano and Zamfara adapting the National Stop Transmission of Polio (NSTOP) program elimination strategies.” Adewole A & al., Malaria Frontline Project: Strategic Approaches to Improve Malaria Control Program Leveraging Experiences from Kano and Zamfara States, Nigeria, 2016-2019, BMC Health Serv Res, 2023 Feb 11; 23(1):147, doi: 10.1186/s12913-023-09143-x is a report of a survey, the subjects being health care workers in the areas in question. Judged by self-reporting before and after training, the workers’ knowledge and adherence to diagnostic and treatment guidelines increased dramatically as a result of implementing the program.

 

“The COVID-19 pandemic has disrupted malaria control activities globally. Notably, high levels of excess malaria morbidity and mortality in low- and middle-income countries (LMICs) were reported… Park J & al., Barriers Against and Strategies for Malaria Control During the COVID-19 Pandemic in Low- and Middle-Income Countries: A Systematic Review, Malar J. 2023 Feb 3; 22:41, doi: 10.1186/s12936-023-04452-2 aims to better identify barriers against and strategies for malaria control” through a search of relevant literature. “The lockdown measures, which mainly threatened geographic accessibility and availability of malaria control services, were identified to be the main barrier hindering effective mobilization of community health workers and resources. Among the identified strategies, clear risk communication strategies would alleviate psychosocial barriers, which challenged acceptability. Some strategies that cross-cut points across all four dimensions would, require systems-level integration to enhance availability and affordability of malaria control.”

“Progress in reducing both malaria cases and deaths has stalled with regression seen in many geographies. While significant attention is given to the contributing challenges of drug and insecticide resistance, … residual transmission may be driven by (a combination of) (1) sub-optimal intervention coverage, quality, acceptance, and/or usage, (2) drug resistance, (3) insecticide resistance, (4) refractory, resistant and adaptive vector and human behaviours that lower intervention effectiveness, (5) lack of, limited access to, and/or willingness to use healthcare systems, (6) diagnostic sensitivity along with the parallel issue of hrp2/3 mutations, (7) (inter)national policy, (8) the research and development pipeline, and (9) external factors such as natural disasters and conflict zones.” The paper is Paaijmans KP & Lobo NF, Gaps in Protection: The Actual Challenge in Malaria Elimination, Malar J. 2023 Feb 7; 22:46, doi: 10.1186/s12936-023-04473-x.

 

“Seasonal malaria chemoprevention (SMC) is a safe and effective intervention for preventing malaria in children under 5 years of age. Lead mothers are community health volunteers that help caregivers comply with monthly administration of anti-malarial drugs during SMC campaigns.” Okereke E & al., Optimizing the Role of ‘Lead Mothers’ in Seasonal Malaria Chemoprevention (SMC) Campaigns: Formative Research in Kano State, Northern Nigeria, Malaria J. 2023 Jan 12; 22:13, doi: 10.1186/s12936-023-04447-z reports that “through their strong connection to communities and unique relationship with caregivers, lead mothers can and do influence caregivers to adopt healthy behaviours during SMC campaigns. However, there is room for improvement in how they are recruited, trained and supervised. There is need to improve lead mothers’ knowledge and skills through adequate training and supporting materials.”

 

The process of designing vector control based on field studies is described in Kouassi BL & al., Entomological Monitoring Data Driving Decision-Making for Appropriate and Sustainable Malaria Vector Control in Côte d’Ivoire, Malaria J. 2023 Jan 12; 22(1):14, doi: 10.1186/s12936-023-04439-z. The results “supported the selection of clothianidin-based products and an optimal spraying time for the first indoor residual spraying (IRS) campaign …”

 

“Evidence suggests a vicious cycle between rice cultivation and malaria control in Rwanda. Rice fields offer an attractive breeding ground for malaria vectors, which increases the disease burden in rice farming communities, and, consequently, reduces productivity in the rice sector. Community-based larval source management in rice fields is propagated as a sustainable solution to break this cycle.” Rulisa A & al., Local Resource Mobilization for Malaria Vector Control Among Rwandan Rice Farmers: A Pilot Study into the Role of Community Ownership, J Health Popul Nutr. 2023 Jan 23; 42(1):6, doi: 10.1186/s41043-023-00345-x report on a “larviciding pilot involving three groups; one group where rice farmers sprayed their fields under expert supervision, one group where rice farmers organised the larviciding campaign themselves, and a (non-sprayed) control group.” The results in terms of farmers’ willingness to invest in the campaign showed that the self-organized group developed the highest motivation.

 

The care of patients for malaria creates economic burdens on society, including governments, health care providers, and patients. Ismail NE & al. investigated the effects on patients’ and families’ economic well-being in Economic Burdens of Uncomplicated Malaria in Primary Health Care (PHC) Facilities of Plateau State, Nigeria: Patients’ Perspectives, Int J Environ Res Public Health. 2023 Jan 8; 20(2):1093, doi: 10.3390/ijerph20021093.  Whereas the amounts derived for direct and indirect costs were slight in US Dollars, their impact on a society in a low-income society is significant.

 

Epidemiology                                                        

Climate change, biodiversity and environment

“In the coming century, most scientific evidence projects that climate change will be responsible for a massive redistribution of global biodiversity. Today, the world is already +1.2°C warmer than in the pre-industrial period, and this transition is already underway: tropical species are spreading towards the poles, and species everywhere are tracking their thermal niche along elevational gradients.” Carlson CJ & al., Rapid Range Shifts in African Anopheles Mosquitoes over the Last Century, Biology Letters, 2023 Feb 15, doi: 10.1098/rsbl.2022.0365 reports on the “use one of the most comprehensive datasets ever compiled by medical entomologists to track the observed range limits of African malaria mosquito vectors (Anopheles spp.) from 1898 to 2016. Using a simple regression approach, [the authors] estimate that these species’ ranges gained an average of 6.5 m of elevation per year, and the southern limits of their ranges moved polewards 4.7 km per year.” An article by A. Mandavilli in The New York Times on the same date comments on the article, also referring to other pathogens and vectors that were the subjects of other studies.

 

Wang C & al., Changes in the Associations Between Malaria Incidence and Climatic Factors Across Malaria Endemic Countries in Africa and Asia-Pacific Region, J Environ Manage. 2023 Jan 10; 331:117264, doi: 10.1016/j.jenvman.2023.117264 acknowledges that there remain a=many confounding factors in analyzing the effects of climate change, but nonetheless concludes that “increasing temperature within the range of 12-30 °C can generate positive effects on malaria incidence, but the nature and extent of precipitation effects vary across countries and at a large regional scale.”

 

“A new database of the Entomological Inoculation Rate (EIR) was used to directly link the risk of infectious mosquito bites to climate in Sub-Saharan Africa” by Yamba EI & al. “Applying a statistical mixed model framework to high-quality monthly EIR measurements collected from field campaigns in Sub-Saharan Africa, [they] analyzed the impact of rainfall and temperature seasonality on EIR seasonality and determined important climate drivers of malaria seasonality across varied climate settings in the region. However, their report, Climate Drivers of Malaria Transmission Seasonality and Their Relative Importance in Sub-Saharan Africa, Geohealth. 2023 Jan 29; 7(2): e2022GH000698, doi: 10.1029/2022gh000698 is unable to draw any overall conclusions, stating that “rainfall and temperature seasonality were found to be significantly associated with malaria seasonality in all parts of Sub-Saharan Africa except in west Central Africa. Topography was found to have significant influence on which climate variable is an important determinant of malaria seasonality in East Africa. Seasonal malaria transmission onset lags behind rainfall only at markedly seasonal rainfall areas such as Sahel and East Africa; elsewhere, malaria transmission is year-round.”

 

General epidemiology

“[T]here is a wealth of practical experience among national malaria control programs and partners working to improve and use malaria surveillance data to guide programming” according to Fountain A & al., Surveillance as a Core Intervention to Strengthen Malaria Control Programs in Moderate to High Transmission Settings, Am J Trop Med Hyg. 2022 Jun 6; 108(2_Suppl):8-13, doi: 10.4269/ajtmh.22-0181. “Granular and timely data are critical to understanding geographic heterogeneity, appropriately defining and targeting interventions packages, and enabling timely decision-making at the operational level. Resources to be targeted based on surveillance data include vector control, case management commodities, outbreak responses, quality improvement interventions, and human resources, including community health workers…”

 

“A growing body of evidence suggests that malaria parasitemia in pregnant women is correlated with parasitemia in children aged < 5 years in moderate to high transmission areas, allowing for monitoring parasitemia in real time.” Gutman JR & al., Routine Healthcare Facility- and Antenatal Care-Based Malaria Surveillance: Challenges and Opportunities, Am J Trop Med Hyg. 2022 Jun 6; 108(2_Suppl):4-7, doi: 10.4269/ajtmh.22-0182 states that while “use of routinely collected ANC data faces many of the same challenges experienced by other routinely collected health facility data, the opportunity to improve parasite prevalence monitoring and the associated health benefits to mothers and infants of early detection of parasitemia make these efforts valuable.”

 

Simon-Oke AI & al., Prevalence of Malaria and COVID-19 Infection in Akure North Local Government Area of Ondo State, Nigeria, J Parasitol Res. 2023 Jan 5; 2023:9529563, doi: 10.1155/2023/9529563 cites “prevalence” data for the two diseases, but the population studied were those who presented at health centers with suspicion of one another of the two diseases.  That makes interpretation of the situation of the entire population very difficult.

 

Habibzadeh points out a potential result of apparently heightened general immunity induced by malaria in Malaria and the Incidence of COVID-19 in Africa: An Ecological Study, BMC Infect Dis. 2023 Feb 3; 23(1):66, doi: 10.1186/s12879-023-08032-2. According to this study, “each 10% increase in the prevalence [of malaria] was associated with 28% decrease in the cumulative incidence of COVID-19.”

 

In the Sahel and other areas, malaria infections are seasonally variable. Stadler E & al. investigated how the parasite survives the dry season. Their paper, Evidence for Exposure Dependent Carriage of Malaria Parasites Across the Dry Season: Modelling Analysis of Longitudinal Data, Malar J. 2023 Feb 3; 22:42, doi: 10.1186/s12936-023-04461-1 reports on children up to age 12 and concludes that “[c]arriage of malaria parasites over the months-long dry season in Mali is most likely in the older, more exposed and more immune children. These children may act as super-spreaders facilitating the fast spread of parasites at the beginning of the next transmission season.”

 

Dahoui MMC & al. identified four different species of Anopheles and uneven human biting, which they report in Entomological Drivers of Uneven Malaria Transmission in Urban Lowland Areas in Bouaké, Côte d’Ivoire, Malar J. 2023 Jan 31; 22:34, doi: 10.1186/s12936-023-04457-x.

 

Over 2015 to 2020, malaria prevalence plummeted in the capital of Mauritania from 29.2% to 2.1%. El Moustapha I & al., Changing Epidemiology of Plasmodium vivax Malaria in Nouakchott, Mauritania: A Six-Year (2015-2020) Prospective Study, Malar J. 2023 Jan 17;22:18, doi: 10.1186/s12936-023-04451-3 report that close to 75% of malaria cases are due to P. vivax in this city. “Malaria transmission was essentially seasonal, with a peak occurring soon after the rainy season (October-November)…”

 

Nguiffo-Nguete D & al. aim to “elucidate the contribution of P. malariae to malaria transmission in Cameroon” in Plasmodium malariae Contributes to High Levels of Malaria Transmission in a Forest-Savannah Transition Area in Cameroon, Parasit Vectors. 2023 Jan 25; 16(1):31, doi: 10.1186/s13071-022-05635-7. Among 156 subjects studied, malaria was present in between 50 and 65%, depending on the diagnostic test used. P. falciparum was the most frequent cause of malaria, P. malariae either alone or together with P. falciparum was responsible for as many as a third of the cases.

 

Hubbard A & al., Implementing Landscape Genetics in Molecular Epidemiology to Determine Drivers of Vector-Borne Disease: A Malaria Case Study, Mol Ecol. 2023 Jan 16, doi: 10.1111/mec.16846 claims to show that “Lake Victoria acts as a barrier to transmission between areas north and south of the Winam Gulf.”

 

Population dynamics

Abbas F & al. “investigated the levels of knowledge about the causes, symptoms, and prevention of malaria in areas with high … and low …incidence of local malaria cases” through interviewing 431 heads of households. In Socio-Demographic Trends in Malaria Knowledge and Implications for Behaviour Change Interventions in Zanzibar, Malar J. 2023 Feb 2; 22:39, doi: 10.1186/s12936-023-04472-y they found old age “to be significantly associated with low knowledge of malaria … The majority of study participants who had secondary and higher education levels had good knowledge of malaria… Participants characterized as middle-income had good knowledge compared to those characterized as low-income …”

 

Kubana E & al., A Comparative Analysis of Risk Factors of Malaria: Case Study Gisagara and Bugesera District of Rwanda. RDHS 2014/2015. A Retrospective Study, BMC Public Health. 2023 Jan 25; 23(1):168, doi: 10.1186/s12889-023-15104-0 concludes that high elevation is associated with lower risk of malaria than low elevation.  Interestingly it also concluded in one of the districts studied that not having a bed net reduced the risk!

 

Aliyo A & al. collected data through face-to-face interviews of 421 households “with a structured pretested questionnaire and visual observation for household malaria prevention practices” and report in Pastoral Community Malaria Prevention Practice and Associated Factors Among Households in Three Districts of the Borena Zone, Southern Ethiopia, Health Serv Res Manag Epidemiol. 2023 Jan 12; 10:23333928221144555, doi: 10.1177/23333928221144555. The factors significantly associated with malaria prevention practice were malaria prevention knowledge … and the absence of Plasmodium parasites among children …. [H]ouseholds staying outdoors at night … were negatively associated with household malaria prevention.” Fewer than half of households had LLINs and about 5% had had IRS.

 

It stands to reason that in geographic areas where malaria is prevalent, “refugees are vulnerable to malaria due to crowded conditions and limited healthcare access.” Kuhrt K & al., A Prospective Case Control Study to Evaluate Shock Index for Identifying Patients at Risk of Clinically Important Malaria in Refugee Settings, Trop Doct. 2023 Jan 18: 494755221134975, doi: 10.1177/00494755221134975 asserts that refugees presenting in clinical shock should be suspected of having severe malaria.

 

Spatiotemporal studies

Balcha F & al., Prevalence of Asymptomatic Malaria and Associated Factors Among Pregnant Women at Boset District in East Shoa Zone, Oromia Region, Ethiopia: A Cross-Sectional Study, Malaria J, 2023 Jan 25, 22:28, doi: 10.1186/s12936-023-04460-2.

 

Medjigbodo AA & al., Asymptomatic Plasmodium Infection Among Primary Schoolchildren and Anopheles-Mediated Malaria Transmission: A Cross-Sectional Study in Ouidah; South-Western Benin, Parasite Epidemiol Control. 2023 Jan 19; 21: e00285, doi: 10.1016/j.parepi.2023.e00285.

 

Ngum NH & al., Prevalence of Malaria and Associated Clinical Manifestations and Myeloperoxidase Amongst Populations Living in Different Altitudes of Mezam Division, North West Region, Cameroon, Malaria J, 2023 Jan 19, 22:20, doi: 10.1186/s12936-022-04438-6.

 

Oyibo W & al., Malaria Parasite Density and Detailed Qualitative Microscopy Enhances Large-Scale Profiling of Infection Endemicity in Nigeria, Sci Rep. 2023 Jan 28; 13(1):1599.

doi: 10.1038/s41598-023-27535-1.

 

Tetteh AK & al., Prevalence of Asymptomatic Malaria Parasitemia Among Blood Donors in Cape Coast, Ghana: A Cross-Sectional Study, J Trop Med. 2023 Jan 4; 2023:8685482 doi: 10.1155/2023/8685482.