Tropical Health Matters

The search for adjunctive therapy to aid in recovery from cerebral malaria is explored in Malaria Journal. A faster acting crystalline form of an insecticide is studied. In Nigeria the National Malaria Elimination Program advocates for equal footing with COVID-19 action. Links to full stories and abstracts are found below.

Dimethyl fumarate reduces TNF and Plasmodium falciparum induced brain endothelium activation in vitro

Neida K. Mita-Mendoza, and colleagues studied Cerebral malaria (CM) which is associated with morbidity and mortality despite the use of potent anti-malarial agents. Brain endothelial cell activation and dysfunction from oxidative and inflammatory host responses and products released by Plasmodium falciparum-infected erythrocytes (IE), are likely the major contributors to the encephalopathy, seizures, and brain swelling that are associated with CM. The development of adjunctive therapy to reduce the pathological consequences of host response pathways could improve outcomes.

To accurately reflect clinically relevant parasite biology a unique panel of parasite isolates derived from patients with stringently defined CM was developed. The effect of TNF and these parasite lines on primary human brain microvascular endothelial cell (HBMVEC) activation in an in vitro co-culture model was tested. HBMVEC activation was measured by cellular release of IL6 and nuclear translocation of NF?B. The transcriptional and functional effects of dimethyl fumarate (DMF), an FDA approved drug which induces the NRF2 pathway, on host and parasite induced HBMVEC activation was characterized. In addition, the effect of DMF on parasite binding to TNF stimulated HBMVEC in a semi-static binding assay was examined.

The findings provide evidence that targeting the nuclear factor E2-related factor 2 ( NRF2) pathway in tumour necrosis factor (TNF) and parasite activated human brain microvascular endothelial cell (HBMVEC) mediates multiple protective pathways and may represent a novel adjunctive therapy to improve infection outcomes in CM.

Fast-acting insecticide polymorph could boost malaria-control efforts

Chemistry World reports on a faster-acting version of a common insecticide could boost malaria control efforts. The new crystalline form of deltamethrin is absorbed by mosquitoes 12 times faster than commercial forms and could help to limit malaria transmission despite growing rates of insecticide resistance.

Microcystals of contact insecticides like deltamethrin are crucial ingredients in indoor sprays and treated bed nets used to combat malaria-spreading mosquitoes. But many mosquito populations are developing resistance to these compounds, which is harming efforts to control the disease.

Treat Malaria as National Health Emergency, NEMP tells Federal Government

The Coordinator of National Malaria Elimination Programme (NEMP), has asked the federal government to tackle malaria as a national health emergency in the same manner COVID-19 pandemic is being handled. Against the background of increasing poverty in the country, Civil Society in Malaria Control, Immunisation and Nutrition (ACOMIN) has said there is a direct linkage between malaria scourge and the level of poverty in communities.

Speaking at a meeting with the civil society group involved in anti malaria advocacy, Coordinator of NEMP, said the current level of funding of the health sector by government is unacceptably low.

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.

Mosquito populations vary across nations and can be spurred by change in land use and deforestation as seen in Madagascar. Urine and saliva have potential in diagnostics but have lower sensitivity than blood tests. Not all insects have similar genes, and mosquitoes evolved a different gene to handle body segmentation. The DHS Program has released recent Malaria Indicator Surveys for Ghana and Uganda, but indicators are below targets. The emerging roles for neutrophils in malaria will be discussed at a webinar. Finally cost-effectiveness issues around RDTs is noted. More information can be obtained via the hyperlinks.

Variation in Anopheles distribution and predictors of malaria infection risk across regions of Madagascar

Deforestation and land use change is widespread in Madagascar, altering local ecosystems and creating opportunities for disease vectors, such as the Anopheles mosquito, to proliferate and more easily reach vulnerable, rural populations. Knowledge of risk factors associated with malaria infections is growing globally, but these associations remain understudied across Madagascar’s diverse ecosystems experiencing rapid environmental change. This study aims to uncover socioeconomic, demographic, and ecological risk factors for malaria infection across regions through analysis of a large, cross-sectional dataset.

The presence of aquatic agriculture (both within and surrounding communities) is the strongest predictive factor of habitats containing Anopheles larvae across all regions. Ecological and socioeconomic risk factors for malaria infection vary dramatically across study regions and range in their complexity. Risk factors for malaria transmission differ dramatically across regions of Madagascar. These results may help stratifying current malaria control efforts in Madagascar beyond the scope of existing interventions.

Evaluating the potential of using urine and saliva specimens for malaria diagnosis in suspected patients in Ghana

This study aimed at detecting PfHRP2 and pLDH malaria antigens in urine and salivary specimens of suspected malaria patients using RDT kits, and identifying factors influencing the detection of these antigens. Malaria rapid test kit (SD Bioline RDT kit) was used to detect malaria antigens, PfHRP2 and pLDH, in blood, urine and saliva samples received from patients suspected of malaria. Subsequently, malaria parasitaemia was determined.

A total of 706 suspected malaria patients provided all three specimens. Prevalence of malaria by microscopy and RDT was 44.2% and 53.9%, respectively. Compared to blood, the sensitivities of urine and saliva were 35.2% and 57.0% respectively. Haemoglobin concentration?<?9.9 g/dL, body temperature?>?38.7 °C and occult blood influenced the detection of malaria antigens in both urine and saliva. Furthermore, the antigens were not detected in urine and saliva when parasitaemia was?<?60,000 parasites/µL and?<?40,000 parasites/µL, respectively.

Saliva, with or without blood contamination, was found to be more efficient that urine samples. Therefore these non-blood specimens have the potential to be used as non-invasive samples for malaria diagnosis. However, this approach is useful in severe to moderate anaemia, hyperthermia, parasitaemia?>?60,000 parasites/µL and samples contaminated with blood.

Mosquitos lost an essential gene for body segmentation with no ill effects

University of Maryland entomologists discovered that a gene critical for survival in other insects is missing in mosquitoes—the gene responsible for properly arranging the insects’ segmented bodies. The researchers also found that a related gene evolved to take over the missing gene’s job. Although laboratory studies have shown that similar genes can be engineered to substitute for one another, this is the first time that scientists identified a gene that naturally evolved to perform the same critical function as a related gene long after the two genes diverged down different evolutionary paths.

The work emphasizes the importance of caution in genetic studies that use model animals to make conclusions across different species. It also points to a new potential avenue for research into highly targeted mosquito control strategies. The research study was published in the September 30, 2020, issue of the journal Communications Biology. “Every single arthropod has a segmented body plan. And you would think it develops the same way in all of them. But what we found is that it doesn’t,” said Alys Jarvela. “That means different genes probably regulate male fertility in mosquitoes, and they might be unique to the mosquito, which could potentially provide a powerful avenue for controlling mosquitoes without harming other insects such as butterflies and bees,” Jarvela said.

Two New Malaria Indicator Surveys Available

Ghana 2019 MIS/DHS Infographic. Malaria prevalence going down from 27% in 2014 to 14% in 2019. Still below target in terms of ITN coverage of and in households.

Uganda 2018-19 MIS/DHS Infographic.  Wide regional variation in malaria prevalence from 1-5% in the southwest to 34% in the northeast. ITN use by children and pregnant women below 2/3rds, while only 2/5 pregnant women got 3 doses of IPT.

Emerging Roles for Neutrophils in Malaria

Aubrey Cunnington and an interdisciplinary translational research group studying host-pathogen interactions in severe infections, focussing on malaria in particular. See for example,  “A More Granular View of Neutrophils in Malaria”

Neutrophils are abundant innate immune cells with crucial roles in immunity and vascular inflammation. Recent evidence indicates that neutrophils have a dual role in malaria, contributing to both pathogenesis and control of Plasmodium. We discuss emerging mechanisms behind these opposing functions and identify key outstanding questions.

Cost-effectiveness analysis of malaria rapid diagnostic test in the elimination setting

As more and more countries approaching the goal of malaria elimination, malaria rapid diagnostic tests (RDT) was recomended to be a diagnostic strategy to achieve and maintain the statute of malaria free, as it’s less requirements on equipment and expertise than microscopic examination. But there are very few economic evaluations to confirm whether RDT was cost-effective in the setting of malaria elimination. This research aimed to offer evidence for helping decision making on malaria diagnosis strategy.

The results showed that RDT strategy was the most effective (245 cases) but also the most costly (United States Dollar [USD] 4.47 million) compared to using microscopy alone (238 cases, USD 3.63 million), and RDT followed by microscopy (221 cases, USD 2.75 million). There was no strategy dominated. One-way sensitivity analysis reflected that the result was sensitive to the change in labor cost and two-way sensitivity analysis indicated that the result was not sensitive to the proportion of falciparum malaria. The result of Monte Carlo simulation showed that RDT strategy had higher effects and higher cost than other strategies with a high probability. Compared to microscopy and RDT followed by microscopy, RDT strategy had higher effects and higher cost in the setting of malaria elimination.

Today the issue of water is important for malaria mosquito propagation, both in irrigation and flooding. Artificial skin enables testing of mosquito biting. Fake medicines for malaria and other conditions threaten Africa’s health. Archived RDTs can aid surveillance. Finally there is concern for co-infection with both malaria and dengue leading to severe disease. Follow links below to read details.

Impact of sugarcane irrigation on malaria vector Anopheles mosquito fauna, abundance and seasonality in Arjo-Didessa, Ethiopia

Despite extensive irrigation development in Ethiopia, limited studies assessed the impact of irrigation on malaria vector mosquito composition, abundance and seasonality. This study aimed to evaluate the impact of sugarcane irrigation on species composition, abundance and seasonality of malaria vectors. Adult Anopheles mosquitoes were collected using CDC light traps from three irrigated and three non-irrigated clusters in and around Arjo-Didessa sugarcane irrigation scheme in southwestern Ethiopia.

Overall, 2108 female Anopheles mosquitoes comprising of six species were collected. The ongoing sugarcane irrigation activities in Arjo-Didessa created conditions suitable for malaria transmitting Anopheles species diversity and abundance. This could drive malaria transmission in Arjo-Didessa and its environs in both dry and wet seasons. Currently practiced malaria vector interventions need to be strengthened by including larval source management to reduce vector abundance in the irrigated areas.

Prevalence of and risk factors for severe malaria caused by Plasmodium and dengue virus co-infection

A systematic review and meta-analysis examined co-infection with both Plasmodium and dengue virus (DENV) infectious species could have serious and fatal outcomes if left undiagnosed and without timely treatment. The present study aimed to determine the pooled prevalence estimate of severe malaria among patients with co-infection, the risk of severe diseases due to co-infection, and to describe the complications of severe malaria and severe dengue among patients with co-infection. Relevant studies published between databases between 12 September 1970 and 22 May 2020 were identified and retrieved.

The present study found that there was a high prevalence of severe malaria among patients with Plasmodium and DENV co-infection. Physicians in endemic areas where these two diseases overlap should recognize that patients with this co-infection can develop either severe malaria or severe dengue with bleeding complications, but a greater risk of developing severe dengue than severe malaria was noted in patients with this co-infection.

South Sudan: Flooding deepens a humanitarian crisis in Pibor area

Today, however, the Pibor River has swelled to make parts of the town inaccessible and is threatening the clinic. Many neighborhoods cannot be reached by foot, and a local ferry is too expensive for many who live in the area. A mobile MSF team is providing medical care in hard-to-reach areas. “Our focus is now on malaria, measles and flooding,” said Josh Rosenstein, MSF deputy head of mission. “Today we are reaching out to the community through our daily mobile clinics, treating the most severe illnesses. We’re also implementing our flood contingency plan, which includes building additional flood defenses around the clinic to ensure we can continue to provide medical services, as the water level is rising at an alarming speed.”

Stratifying malaria receptivity in Bangladesh using archived rapid diagnostic tests

Surveillance of low-density infections and of exposure to vectors is crucial to understand where malaria elimination might be feasible, and where the risk of outbreaks is high. Archived rapid diagnostic tests (RDTs), used by national malaria control and elimination programs for clinical diagnosis, present a valuable, yet rarely used resource for in-depth studies on malaria epidemiology. 1022 RDTs from two sub-Districts in Bangladesh (Alikadam and Kamalganj) were screened by qPCR for low-density Plasmodium falciparum and Plasmodium vivax infections, and by ELISA for Anopheles salivary gland antibodies as a marker for exposure to vectors.

Concordance between RDT and qPCR was moderate. qPCR detected 31/1022 infections compared to 36/1022 diagnosed by RDT. Exposure to Anopheles was significantly higher in Kamalganj despite low transmission, which could be explained by low bed net use. Archived RDTs present a valuable source of antibodies for serological studies on exposure to vectors. In contrast, the benefit of screening archived RDTs to obtain a better estimate of clinical case numbers is moderate. Kamalganj could be prone to outbreaks.

New tool mimics human skin to allow detailed study of mosquito biting

eLife: Researchers develop a human skin mimic to study mosquito biting in high resolution without using humans as ‘bait.’ The tool, which uses an artificial blood meal and a surface that mimics human skin, will provide detailed understanding of blood feeding without using human subjects as bait. It can also fit conveniently into a backpack, allowing the study of mosquitoes in laboratory and natural environments.

Blood feeding is essential for mosquitoes to reproduce, but it is during blood feeds on human hosts that they pass on pathogens such as malaria. It consists of a bite ‘substrate’ – a transparent, temperature-controlled surface that mimics body temperature to attract mosquitoes. An artificial meal is applied on top of this and covered with a commonly used membrane that mosquitoes can pierce. The meal resembles blood, allowing mosquitoes to engorge and increase their weight by two to threefold. This bite substrate is then placed in a transparent cage, and an external camera records the mosquitoes’ behaviour. The team tested biteOscope with four medically important species of mosquito.

Counterfeiting of Fake Drugs in Africa: current situation, causes and countermeasures

The more desirable a product is the higher the tendency to replicate it and meet that parcel of consumers that want to join the trend but cannot pay the price. Profit is one of the many reasons that make counterfeit an attractive business for many.  Africa, unfortunately but not surprisingly, is one of the most affected continents, comprehensible since its markets have become a huge target for second generation goods, with a major focus on pharmaceutical drugs.

The World Health Organization (hereinafter, WHO) stated that 42% of all fake medicine reported to them between the years of 2013 and 2017 was linked to the African continent and we expect that these numbers fall short of reality. Africa is seriously affected by it and one clear example is the anti-malarial medication. Anti-malarials and antibiotics are amongst the most commonly reported as fake or substandard medical products.

In the past week more attention was drawn to the apparently never-ending year-long Ebola outbreak in the northeast of the Democratic Republic of the Congo. Regarding other diseases, there is new information on the RTS,S malaria vaccine, river prawns have been found to play a biological control role in schistosomiasis, and an update from the World Health Organization on essential medicines and diagnostics. New malaria vector control technologies are discussed.

Second Largest Ebola Outbreak One Year On

Ronald A. Klain and Daniel Lucey in the Washington Post observed raised concern that, “the disease has since crossed one border (into Uganda) and continues to spread. In the absence of a trajectory toward extinguishing the outbreak, the opposite path — severe escalation — remains possible. The risk of the disease moving into nearby Goma, Congo — a city of 1 million residents with an international airport.”

They added their voices to a growing number of experts who are watching this second biggest Ebola outbreak in history and note that, “As the case count approaches 2,500 with no end in sight, it is time for the WHO to declare the outbreak a public health emergency of international concern — a ‘PHEIC’ — to raise the level of global alarm and signal to nations, particularly the United States, that they must ramp up their response.” They call for three actions: 1) improved security for health workers in the region, 2) stepped up community engagement and 3) extended health care beyond Ebola treatment. The inability to adequately respond to malaria, diarrheal diseases and maternal health not only threated life directly, but also threated community trust, putting health workers’ lives at risk.

Olivia Acland, a freelance journalist based in DRC, reporting for the New Humanitarian describes the insecurity and the recent “wave of militia attacks in the Democratic Republic of Congo’s northeastern Ituri province has left hundreds dead and roughly 300,000 displaced in recent weeks, triggering a new humanitarian crisis in a region.” Specifically, “Ituri, a fertile region rich in gold deposits, has been an epicentre of conflict in Congo for decades. Between 1999 and 2003, around 60,000 people were killed here, as a power struggle between rebel groups escalated into ethnic violence,” related to traditional tensions between Hema cattle herders and Lendu farmers with roots in Belgian colonization.

Updates from the DRC Ministry of Health report on average 11 new Ebola cases per day in the past week. So far over 160,000 people have been vaccinated, and yet the spread continues. The Ministry also describes new protocol contains three vaccinations strategies that can be used depending on the environment in which confirmed cases are found including:

• Classic Ring: The classic strategy of vaccinating contacts of confirmed cases and contact contacts.
• Enlarged ring: It is also possible to vaccinate all inhabitants of houses within 5 meters around the outbreak of a confirmed case.
• Geographical Ring: In an area where team safety can not be guaranteed, they can vaccinate an entire village or neighborhood.

Malaria Vaccines, Essential Drugs and New Vector Control Technologies

Halidou Tinto and colleagues enrolled two age groups of children in a 3-year extension of the RTS,S/AS01 vaccine efficacy trial: 1739 older children (aged 5–7 years) and 1345 younger children (aged 3–5 years). During extension, they reported 66 severe malaria cases. Overall they found that, “severe malaria incidence was low in all groups, with no evidence of rebound in RTS,S/AS01 recipients, despite an increased incidence of clinical malaria in older children who received RTS,S/AS01 compared with the comparator group in Nanoro. No safety signal was identified,” as seen in The Lancet.

WHO has updated the global guidance on medicines and diagnostic tests to address health challenges, prioritize highly effective therapeutics, and improve affordable access. Section 6.5.3 presents antimalarial medicines including curative treatment (14 medicines) for both vivax and falciparum and including tablets and injectables. Prophylaxis includes 6 medicines including those for IPTp and SMC. The latest guidance can be downloaded at WHO.

Paul Krezanoski reports on a new technology to monitor bednet use and tried it out in Ugandan households. As a result. “Remote bednet use monitors can provide novel insights into how bednets are used in practice, helping identify both households at risk of malaria due to poor adherence and also potentially novel targets for improving malaria prevention.

In another novel technological approach to vector control, Humphrey Mazigo and co-researchers tested malaria mosquito control in rice paddy farms using biolarvicide mixed with fertilizer in Tanzanian semi-field experiments. The intervention sections (with biolarvicide) had lowest mean mosquito larvae abundance compared to control block and did not affect the rice production/harvest.

Prawns to the Rescue in Senegal Fighting Schistosomiasis and Poverty

Anne Gulland reported how Christopher M. Hoover et al. discovered how prawns could be the key to fighting poverty and schistosomiasis, a debilitating tropical disease. They found that farming the African river prawn could fight the disease and improve the lives of local people, because the African river prawn is a ‘voracious’ predator of the freshwater snail, which is a carrier of schistosomiasis.

The researchers in Senegal said that, “market analysis in Senegal had shown there was significant interest among restaurant owners and farmers in introducing prawns to the diet.” The prawn could also for the basis of aquaculture in rice paddies and remove the threat of schistosomiasis from the rice workers.

—- Thank you for reading this week’s summary. These weekly abstractings have replaced our occasional mailings on tropical health issues due to fees introduced by those maintaining the listserve website. Also continue to check the Tropical Health Twitter feed, which you can see running on this page.

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

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

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

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

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

Ousmane Badolo, Stanislas Nebie, Youssouf Sawadogo, Thierry Ouedraogo, Moumouni Bonkoungou, Mathurin Dodo, Danielle Burke, William Brieger, and Gladys Tetteh of Jhpiego and the Improving Malaria Care Project (USAID) in Burkina Faso presented a poster on helping hospitals develop a malaria response plan. Their findings are shared below.

In Burkina Faso Malaria cases peak from June-September (rainy season), exceeding hospital capacity and causing high number of deaths, especially in children under 5 years of age. The Improving Malaria Care Project, funded by USAID/President’s Malaria Initiative, provided support to National Malaria Control Program to develop and implement malaria preparedness and response plans in all 11 regional hospitals

The Objectives of this effort aimed to describe development and implementation of malaria preparedness and response plan. From this the project planned to share lessons learned and challenges Malaria Preparedness and Response Plan Development and Implementation Process is seen in the attached chart.

In preparation of hospital staff for planning, the training reached Nurses and midwives were largest groups of trained providers at 52% and 30%, respectively. Providers were selected by hospital management team from pediatric maternity and emergency units.

Severe Malaria Cases Trend Regional Hospital in Burkina Faso is seen in the attached graph. In a second graph, Malaria Case Fatality Rate Trend at Regional Hospitals in Burkina Faso is shown. Even though there were more cases of severe malaria in 2017, Malaria case fatality rate decreased after implementing malaria response plan.

Challenges faced by the hospitals included Lack of funding for response plan activities, which were not included in the routine hospital work plan. Also there was a Lack of beds in some hospital rooms, especially in pediatric unit. Timing of clients coming to hospital posed a challenge as many do not come early and sometimes come when only complications start.

Lessons learned from the intervention include the fact that On-the-job training is opportunity to improve providers’ skills. Response plans must consider that providers’ refreshment, and securing blood and other commodities may improve severe malaria case management. Monthly data collection and analysis may highlight progress in malaria planning through case management and orient decision-making. Follow-up visits strengthened provider engagement on severe malaria case Management

In Conclusion, Response plans may provide a way to reduce malaria mortality. Each hospital should consider incorporating response plan into its annual work plan

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.

February is Heart Month in some countries. This is a good time to explore how malaria affects the heart and cardiovascular health.

In 1946 Howard Sprague observed that although “malaria is a disease from which no organ or tissue is exempt, this paper is concerned with its influence upon the circulation, and more particularly upon the heart itself.” He then outlined four ways by which this influence happens:

1. its chronic and recurrent nature
2. the systemic toxemia of the paroxysm
3. the profound anemia produced by hemolysis and suppression of hemopoiesis
4. the occlusion of capillaries and arterioles of the myocardium

Since that time other researchers have elaborated on malaria and the cardiovascular system.

Mishra et al. raise a concern that, “The role of the heart in severe malaria has not received due attention.” They point out the following:

• hypotension, shock and circulatory collapse observed in severe malaria patients
• raised cardiac enzymes in complicated malaria
• compromised microcirculation and lactic acidosis as well as excessive production of pro-inflammatory cytokines
• Intravascular fluid depletion associated with severe malaria leading to impaired microcirculation … among others

They conclude that “Sudden cardiac deaths can also occur due to cardiac involvement,” but worry that, “It is not feasible to assess the cardiac indices in resource poor settings.”

A study by Ray and co-researchers indicated “involvement of cardiovascular system in severe malaria as evidenced from ECG and echocardiography. The study also revealed that cardiovascular instabilities are common in falciparum malaria, but can also be observed in vivax malaria.” A fatal case of imported malaria where the sole finding revealed at the postmortem evaluation was an acute lymphocytic myocarditis with myocardiolysis was described by Costenaro and colleagues.

In another example, Onwuamaegbu, Henein, and Coats reviewed the potential role of malaria in chronic and severe malaria and the connection to chronic heart failure. They concluded that, “Our review of the literature suggests that there are significant similarities in the cachexia seen in CHF and that of malaria, especially as related to the effects of muscle mass and immunology.” Clinical manifestations in P. falciparum malaria also include reduced cardiac output as was reported in an imported case of malaria by Johanna Herr and co-workers.

Marrelli and Brotto note that, “Sequestration of red blood cells, increased levels of serum creatine kinase and reduced muscle content of essential contractile proteins are some of the potential biomarkers of the damage levels of skeletal and cardiac muscles.” They explain that, “These biomarkers might be useful for prevention of complications and determining the effectiveness of interventions designed to protect cardiac and skeletal muscles from malaria-induced damage.”

Not just malaria as a disease is involved, but also the medicines used to treat it. Ngouesse and colleagues draw attention to antimalarial drugs with cardiovascular side effects. They draw particular attention to the dangers of halofantrine, quinine and quinidine, but also note mild and/or transient effects of other antimalarials.

Guidelines exist for proper and prompt malaria case management, especially protocols for caring for patients with severe malaria. These and the medicines required must be more readily available to front line health staff. And of course is we are more diligent in preventing malaria through long lasting insecticide-treated nets and other measures, our worries about severe malaria and CVD complications will reduce.

At the recently concluded American Society of Tropical Medicine and Hygiene 2014 Annual Meeting, USAID’s MAPS Project presented a poster on severe malaria in Nigeria. The authors, Yetunde Oke, Banji Ipadeola, Bolatito Aiyenigba, Grace Nwankwo, Justice Adaji, Olatunde Olotu, Aniefiok Akpasa, and Abba Umar, share their findings below.

Severe malaria is a life threatening medical condition that requires emergency interventions including prompt and effective treatment to prevent death (WHO 2000). The AQUAMAT* study showed a relative reduction in mortality of 22.5% with use of parenteral artesunate compared to quinine in the management of severe P. falciparum malaria and the Nigeria national policy on malaria diagnosis and treatment has been revised based on this evidence.

However, implementation of this guideline is still a challenge. The goal of this study was to determine baseline capacity and management practices for severe malaria in selected secondary health facilities in Nigeria with the aim of designing interventions to address specific gaps identified.

A cross?sectional study was conducted to assess twenty?four secondary public health facilities in three states (Benue, Kogi and Oyo States) in Nigeria in August 2013. Data on the capacity of health care providers; malaria services provided at different service delivery points (three months preceding the survey).

Medical supplies were collected using modified WHO severe malaria assessment tools. Data  entry was done  using the SPSS software programme and analysis done with STATA version 10.0.

Total number of confirmed malaria cases reported in the three states over the three months preceding the assessment was 18, 695 and diagnosis of severe malaria was made in 8.6% of the total malaria cases. Out of the severe malaria cases, 75.9% were discharged, 3.8% referred and 1.5% died.

Fifty per cent of the health care providers had attended training on malaria case management 12 months preceding the survey. The majority of providers managed severe malaria with injectable artemether (45.8%), quinine (37.5%) compared with artesunate (29.2%).

Most of the health facilities (95.8%) practiced parasite-based diagnosis of malaria but only (29.2%) monitored the parasite clearance of patients with severe malaria. 70% of the facilities did not have basic supplies for ancillary management of severe malaria. 66.7% and 30% of the health facilities experienced stock?out of parenteral artesunate and parenteral  quinine respectively  in the previous three months.

Health system strengthening with emphasis on capacity building of health care providers, medical commodity security and improvement in supportive/ancillary management of severe malaria is needed to reduce the mortality attributable to severe malaria.

On this final day of the American Society of Tropical Medicine and Hygiene’s 62nd Annual Conference, there is a featured symposium on Malaria: Biology and Pathogenesis – Human Responses to falciparum. Presentations are listed below with links to the abstracts online.

Demonstration of enhanced strain-specific Plasmodium falciparum multifunctional T cell cytokine expression among Malian children immunized with the FMP2.1/AS02A vaccine by Shawna F. Graves et al.

The Study suggests that AMA1 vaccination induced an AMA1-specific CD4+ response; however, recognition of the vaccine antigen is not dependent upon c1L alone. In summary, AMA1-specific T cell cytokine expression was notably increased in children vaccinated with an AMA1-based vaccine compared to rabies. The possible role of CD4+ TNF-?+IL-2+-expressing T cells in vaccine-induced strain-specific protection against clinical malaria requires further exploration.

Fatal Pediatric Cerebral Malaria is Associated with Intravascular Inflammation and Coagulation that is Exacerbated by HIV-1 Co-infection by Sarah Hochman and colleagues.

We hypothesize that the intravascular inflammation and coagulation seen in CM autopsies contribute to the pathogenesis of pediatric CM and that dysregulation of these processes in HIV infection contribute to CM mortality.

Immune responses of rhesus monkeys to a self-assembling protein nanoparticle (SAPN) vaccine displaying Plasmodium falciparum CSP B- and T-cell epitopes by David E. Lanar and co-researchers.

We have previously studied in mice the immune responses induced against Plasmodium falciparum circumsporozoite protein (PfCSP) epitopes using a self-assembling protein nanoparticle (SAPN) platform. In conclusion, a PfCSP-KMY-SAPN vaccine for malaria was safe and immunogenic in rhesus monkeys. Immune responses to the vaccine were greatly enhanced if the nanoparticle was formulated with the adjuvant GLA-SE.

Non-invasive Pulse Oximetry to Predict Mortality in African Children with Malaria by Andrea L. Conroy et al.

The mortality rate for children admitted with malaria was 3.1%. We evaluated whether non-invasive pulse oximetry would predict disease outcome in malaria and compared the findings to venous lactate, an established prognostic marker in malaria. These data suggest that pulse oximetry alongside assessment of venous lactate may be useful in the triage and treatment of children with severe malaria. Additional advantages in pulse oximetry are low operating costs and real-time patient monitoring.

Placental malaria induces excessive vasculogenesis by  Tara C. Bracken and colleagues.

Placental malaria (PM) results from sequestration of Plasmdium falciparum-infected erythrocytes and the resulting inflammatory responses in the maternal placental blood space. PM induces maternal anemia, preterm birth, low birth weight, or stillbirth, especially in primigravidae. The active/active chronic group had a significantly higher percentage of excessive vasculogenesis.

Retinal microvascular dysfunction in pediatric cerebral malaria is associated with death and neurological sequelae by Ian J. MacCormick and co-authors.

Our results suggest that central nervous system ischemia and leakage across blood-tissue barriers may be important contributors to the severity of pediatric Cerebral Malaria.