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Don’t Forget about Malaria…

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Sunday (April 25th) is a day to refocus our lens on the past 14 months of living and working through the global COVID-19 pandemic and remember the ongoing global battle countless countries continue fighting against Malaria. Today is World Malaria Day, a day to celebrate the victories, reflect on the challenges, unite with our global colleagues, and remember those many children and individuals still losing their lives to a preventable disease. 

Malaria is a life-threatening disease caused by parasites transmitted to people through the bites of infected female Anopheles mosquitoes. It is preventable and curable.

My first experience of how dangerous malaria could be was in Kenya in 2003. I was a febrile third-year medical student, sitting in the back of a pick-up truck following a seemingly endless dirt track to the nearest Health Centre with my unconscious friend who had just had a seizure.  Whilst we both had a rocky few days, we both made full recoveries and are counted amongst the privileged few to survive without ongoing sequelae. Malaria had managed to get through the defensive mosquito nets and antimalarials. Still, we had access to a vehicle for rapid transport, access to money for treatment, and some knowledge as medical students to ensure we got to the right place, at the right time, and got the right treatment. Many are not so fortunate.

Fast forward five years to Uganda in 2008. I would never get used to the cries of mothers who had carried their children unimaginable distances to our rural hospital only for it to be too late and then to watch the sight of them carrying their lifeless bodies home to be buried. It all seemed futile – if only they had a bed net or could have gone to a clinic sooner. Sadly, as in many preventable diseases, the most deprived communities are affected disproportionately, and children under five carry the biggest death toll.

This year, we have been bombarded with daily infection rates and death tolls as increasingly large figures appear on our screens. Clinicians and the public alike were shocked and horrified by these growing numbers. Have we become “statistic-fatigued”? Do the numbers no longer hold their impact? For those not living in a malaria-endemic area, personal experiences are few and far between. These malaria statistics hold the stories of many but the identity of none. Let’s look afresh at these huge numbers and allow ourselves to be shocked and horrified, figures that have remained unacceptable for years, decades, and millennia.

The current yearly figures from WHO report 229 million cases of Malaria worldwide with a death toll of 409,000, the majority (67%) of these being children under five years old. That means a child is dying from Malaria every 2 minutes. This is not OK!

A picture of Africa showing that the majority iof malaria deaths occur there and 67% are in young children
Data taken from Targetmalaria.org

 

Over the past few years, a concerted global effort has saved hundreds of thousands of lives with preventative malaria programmes. The World Health Organisation (WHO) estimates over 1 billion malaria cases and 7 million deaths have been prevented since 2000. The number of countries being declared malaria-free is also increasing. This helps reduce huge systems and economic burdens on a country. The WHO’s E-2025 report announces that 26 countries and territories are within reach of zero malaria cases by 2025. This is encouraging, but many countries still have a long way to go, particularly in Africa.  

Every Win Counts

Rural Bo District – Sierra Leone, 2011, Sitting in the shell of a clinic built and subsequently abandoned by an NGO after the civil war, we see over one hundred children, sixty of whom are testing positive for malaria. A simple treatment with no health providers for two hours, one exceedingly difficult to access. 

Fast forward nine years, and I’m sitting in a similar rural setting in Bonthe District. Still, there is finally a referral process to ensure these children and their mothers can get to the referral hospitals in the major population centres for appropriate management and treatment. 

One of the most effective weapons in continuing this fight is the younger generation, who grew up in a time when Malaria is no longer an unconquerable giant but something that could be overcome.  The ‘Zero Malaria’ and ‘Drawing the Line’ campaigns empowered young people to keep taking ground. ‘’Malaria, we will not let you steal from us anymore… We are the generation that can end Malaria!’’

Young people across Africa have seen the impact of malaria on their lives and futures and are motivated to take action. Even if malaria doesn’t kill, it prevents young people from going to school, realising their full potential, and building their futures. Recent surveys have shown that young people are keen to volunteer to distribute mosquito nets, share information about malaria, and engage with their community and national policymakers to prioritise malaria. 

Malaria experiences from our colleagues at Mbarara University EMIG

As a medical student trained in Uganda – a country where malaria is a major public health problem associated with slow socio-economic development and poverty, and the most frequently reported disease at both public and private health facilities, one always hears, ‘Common things occur commonly, and rare things occur rarely”. 

Malaria goes beyond being common in our communities; “You can’t just convince a senior house officer or attending that you have learnt something from their ward if you don’t know how malaria manifests in their speciality– for example malaria in pregnancy or severe malaria in Paeds. We are expected to be “singing” (having them at our fingertips) the signs and symptoms, investigations, laboratory findings, treatment plans, and complications of malaria, like nothing else.

“It goes beyond experiencing malaria as clinicians—some of our colleagues had to become caretakers during their younger years for their parents suffering from malaria, which can leave some of them with traumatizing experiences. CoArtem and Panadol are like some food in the home. They should always be there” – Fourth-year medical student MUST-EMIG.

“Complications of malaria are one of the popular things that we are commonly tested on about on ward rounds” – Fourth-year medical student and founder of MUST-EMIG

So, back to 2021, COVID-19, and the challenges ahead…

There are real fears that the challenge of COVID-19 has been a huge threat to the progress made in eliminating Malaria. Many places have faced an increased burden on already fragile health systems. There have been disruptions to the distribution of materials, including mosquito nets and antimalarials, and reports of increasing reluctance to seek medical care for patients with a fever due to the fear of the stigma of COVID-19. The WHO estimates that malaria interventions have been reduced by between 15 and 25 per cent during the pandemic. Furthermore, in 2020, the COVID-19 pandemic likely caused 40-50,000 excess deaths from malaria that otherwise could have been prevented. 

Behind the scenes, underreporting also exists, and the reality of the global refugee crisis and countless internally displaced persons (IDP) means many are facing ‘syndemics’ of COVID-19 and malaria, combined with any other crisis du jour in a variety of environments. 

What has been happening with malaria elsewhere? 

Unsurprisingly, the number of malaria cases identified in 2020 in those with recent travel history to an endemic area has fallen. Malaria tests performed (on adults and children) at the Manchester Foundation Trust have fallen by 68% compared to 2019, with 92% fewer positive cases. As travel corridors reopen, those working in malaria-free countries will need to start thinking, ‘could this be malaria?’ once again. While this fall in testing numbers is unsurprising, it doesn’t mean you shouldn’t include malaria on your list of differentials when warranted. 

How does malaria present?

Malaria presents with an influenza-like syndrome, with malaise, headache, myalgia, nausea, and rigors (which may occur intermittently and correspond to the rupture of schizonts in the erythrocytic stage of the parasite’s lifecycle).

It is important to distinguish uncomplicated malaria from severe malaria, as their treatment (and risk of morbidity and mortality) differs significantly. Severe malaria was previously considered only to occur secondary to P. falciparum, although there are increasing case reports of patients with P. vivax or P. knowlesi malaria presenting severely ill.

The definition of severe malaria is the presence of one or more of the following clinical or laboratory features:

  • impaired consciousness +/- seizures (cerebral malaria)
  • severe dehydration or hypovolaemic shock
  • clinical or metabolic acidosis
  • hypoglycaemia
  • severe anaemia (Hb < 50g/L)
  • oliguria or acute kidney injury
  • jaundice
  • a blood parasite count of >100,000/uL (indicating more than 2% of red blood cells are parasitized).

Think Malaria

  • Fever or anaemia in a child who has recently returned from a malaria-endemic area
  • Ordering appropriate investigations (ideally timed with fever spikes)
  • Familiarise yourself with local protocols
  • Microscopy (thick and thin smears) remains the gold standard. Rapid Diagnostic tests are valuable, particularly in resource-limited settings, but are less sensitive.
  • Involve infectious disease services early if required!

OR

  • The inability to take any oral antimalarials even after administration of an antiemetic.
  • A child with malaria can have a bacterial co-infection; be sure to address that if suspected!
  •  It is vital to differentiate between uncomplicated and complicated (severe) malaria early.
  • Oral outpatient management for uncomplicated malaria is reasonable, but urgent inpatient management for severe malaria is required. 

How do you diagnose malaria?

The biggest challenges in diagnosing malaria are:-

(i) Remembering to test for it. If you’re seeing a patient in a health setting like Australia or the UK where malaria is not endemic, you may well not think of it unless you’ve specifically asked for the exposure history

(ii) Incorrectly diagnosing malaria as the sole cause of a child’s illness in an endemic region.

This is a common reason that bacteraemia and other causes of meningitis are missed in regions where malaria is endemic. Many children in these places have persistent low-level parasitaemia that may not be the cause of their clinical illness, and important empiric antimicrobials or further investigations may be missed.

Unfortunately, no diagnostic test can distinguish between parasitaemia causing clinical malaria and a febrile illness due to another cause in a patient with asymptomatic parasitaemia.

Until recently, clinical diagnosis was the prime method of diagnosing malaria. That is, a child presenting with a constellation of symptoms predictive of malaria in a malaria-endemic region was presumptively considered to have malaria. However, parasitological diagnosis is now essential to improve diagnostic accuracy and prevent the promotion of artemisinin resistance by ensuring the rational use of anti-malarial medications.

If staff and facilities can perform microscopy, the gold standard diagnosis remains microscopy. A thick blood film confirms the presence and density (percentage of parasitized erythrocytes), while the thin film determines the Plasmodium species. The sensitivity and specificity of these tests are laboratory-dependent and rely on astute scientists familiar with malaria’s laboratory diagnosis.

Rapid diagnostic tests (RDTs) (lateral flow immunochromatographic tests, often reported as an ‘ICT’ result) are an alternative way of quickly establishing the presence of malaria. They work by detecting specific malaria antigens within 15 minutes on a card that resembles a pregnancy test. However, RDTs are less sensitive to detecting low numbers of parasitaemia (an important prognostic factor) and insensitive to detecting most species aside from P. falciparum.

RDTs can also mislead a clinician in their diagnosis, as parasitaemia in a child living in a malaria-endemic region may not necessarily reflect infection, and other diagnoses (such as sepsis) are often missed if the diagnosis is assumed to be malaria secondary to a positive RDT.

Why do I need to do three separate tests?

A single negative blood film, or negative antigen test, does not completely exclude malaria diagnosis due to the imperfect nature of these tests. Simultaneously, parasitaemia may be low, or antibiotics being taken for other reasons may have enough antimalarial activity to modify or suppress malaria symptoms and parasite load (this is particularly common with trimethoprim-sulfamethoxazole, tetracyclines and quinolones). Several organizations, therefore, recommend repeating blood films with fever spikes (to correlate with schizont rupture) until a positive test is returned or until three negative films are confirmed in patients with a high pre-test probability. This is not necessary for patients in whom malaria diagnosis is unlikely.

Importantly, peripheral films will not identify parasites which have sequestered (such as into the placenta in malaria in pregnancy or deep into the capillary system of the brain in severe malaria), so bear in mind that the peripheral blood smear may reflect a low parasite density relative to the true parasite burden. P falciparum, P. malariae and P. knowlesi infect mature erythrocytes, exhibiting higher parasite densities, while P. vivax and P. ovale infect only young erythrocytes, so the parasite density for these species tends to be lower.

Once a diagnosis of uncomplicated or severe malaria has been made and treatment commenced, serial blood smears need to be examined to monitor the parasitological response and ensure the resolution of infection. If resources allow, this is usually performed daily until negative (or until day seven if well enough for discharge before complete parasitaemia clearance). In severe malaria, parasite density tends to be monitored more frequently (every 12 hours during the first 2-3 days). The mean time for parasite density clearance is 48-72 hours, although prolonged clearance times may occur in malaria acquired in SE Asia.

How do you treat malaria?

Uncomplicated malaria can be treated orally if the child tolerates oral therapy. An artemisinin-based combination therapy (artemether+lumefantrine, known by the tradename ‘Coartem’) is the treatment of choice for uncomplicated malaria, with additional considerations:

  1. For P. falciparum malaria acquired in Thailand, Vietnam, Cambodia, Laos, or Myanmar, patients with parasitaemia beyond three days may have P. falciparum with resistance to artemisinin-based therapy; call your friendly ID team for advice regarding other treatment options.
  2. For P. falciparum in patients being treated where ongoing malaria transmission is possible (including Northern Australia), add a single dose of primaquine to eliminate the transmissible stages of P. falciparum to prevent ongoing transmission of the parasite from humans to mosquitoes. However, first, rule out the presence of G6PD deficiency in the patient (in whom primaquine can cause severe haemolysis).
  3. For P. vivax and P. ovale malaria: These species can exist as dormant parasites (hypnozoites) in the liver that can result in malaria relapses, so they require concurrent treatment with primaquine (again, only after G6PD deficiency has been excluded). If the patient has G6PD deficiency, call your friendly ID team again for subspecialist advice.

When treating severe malaria, start parenteral therapy as soon as possible.

Alongside managing the ABCDEFGs (particularly focusing on carefully correcting fluid and glucose levels), commence parenteral Artesunate as soon as possible. For travellers from regions of Asia where resistance may be present (Thailand, Vietnam, Cambodia, Laos or Myanmar), combination therapy with IV artesunate + IV quinine is recommended (commencing each drug as quickly as they are available).

Adjunctive therapy with ceftriaxone and paracetamol is recommended, as bacteraemia is a common co-occurrence in severe malaria, and paracetamol can reduce the risk of haemolytic acute kidney injury.  Patients can switch from IV to oral treatment (with Coartem) once they have clinically improved and can tolerate oral therapy. Ideally, an FBC should be performed weekly for four weeks after completion of therapy to monitor for delayed haemolysis or the recrudescence of malaria parasites.

A call to action

Moving forward, there is a call to urgent action to ensure that all the progress that has been made is sustained and built upon. Global and national leaders need to continue to prioritise funding and facilitate research and development into new interventions as well as the delivery of effective prevention and treatments to the most vulnerable areas. There needs to be ongoing recognition and support for those healthcare workers delivering care in such challenging circumstances to ensure access to Malaria prevention, testing and treatment for all. 

Ultimately, there is hope. The end is in sight, and malaria eradication is possible. We had a great start with the Global Malaria Eradication Programme began in the 1950s, but the reality of the times prevented further success. Let’s not forget every child and family behind the statistics. Be outraged by the numbers but also encouraged by the wins. Keep talking about malaria. Encourage and support our global colleagues. Listen to their experiences, learn from them, and unite to eradicate Malaria.

What can you do today?

Share the post. Encourage our global colleagues today – we stand with you #endmalaria #zeromalaria #drawtheline #zeromalariastartswithme #worldmalariaday. Remember Malaria! Listen to your patients, take a travel history, and make referrals appropriately. Engage the ID team early if you are unsure! 

Selected references

Centers for Disease Control and Prevention (CDC). Malaria treatment (US) guidelines for clinicians. Atlanta, GA. Last updated: July 2018. www.cdc.gov/malaria/diagnosis_treatment/treatment.html

Dhiman, S. Are malaria elimination efforts on the right track? An analysis of gains achieved and challenges ahead. Infectious Diseases of Poverty; 2019; 8(14).

Dyer O. African malaria deaths set to dwarf covid-19 fatalities as pandemic hits control efforts, WHO warns. BMJ 2020; doi:10.1136/bmj.m4711

Mendenhall, E., 2020. The COVID-19 syndemic is not global: context matters. The Lancet, 396(10264), p.1731.

Plewes, K. et al. Aceteminophen as a renoprotective adjunctive treatment in patients with severe and moderately severe Falciparum malaria: A randomized, controlled, open-label trial. Clinical Infectious Diseases; 2018; 67(7); 991-999.

RBM Partnership to End Malaria. (2021). World Malaria Day 2021 Key Messages.

Singer, M., Bulled, N., Ostrach, B., & Mendenhall, E. (2017). Syndemics and the biosocial conception of health. The Lancet, 389(10072), 941–950. doi:10.1016/s0140-6736(17)30003-x 

White, NJ. The treatment of malaria. NEJM, 1996; 335:800

World Health Organization. (2020). World malaria report. Geneva, Switzerland: World Health Organization.

https://targetmalaria.org/ Accessed 13/4/2021

https://endmalaria.org/ Accessed 13/4/21

https://www.theglobalfund.org/en/ Accessed 13/4/21

Haematology Laboratory Manchester University Foundation Trust (personal communication)

World Health Organization (WHO): Malaria. Update in: International travel and health. Geneva; www.who.int/ith/en/

Malaria. In: Therapeutic guidelines, Australia. eTG complete [digital]. Melbourne: Therapeutic Guidelines Limited; 2019 Jun. <https://www.tg.org.au>

The World Health Organization (WHO): The World Malaria Report 2019. [Online], Available: https://www.who.int/malaria/publications/world-malaria-report-2019/en/ 

Dr Emma Hulme

MBChB, MPH, MRCGP, DTM&H, DCH, DRCOG, DFRSH

Emma works as a GP in a city practice and in the Emergency Department at the Royal Manchester Children’s Hospital. Before training in General Practice she worked in a number of countries overseas in maternal and child health roles and currently leads the Global DFTB Bubble. The rest of her time is spent chasing after her 3 little people and trying to find a quiet corner for 5 minutes peace!

Christopher McKenna, MPH

Chris is a former critical care paramedic turned final year medical student at the University of Queensland – Ochsner Clinical School in New Orleans, Louisiana. Originally from NJ, he has spent time working on pre-hospital system development in Somaliland and Sierra Leone, as well as time with various NGO/IGO in the Philippines. He is eager to return to Australia for his internship in 2022 with the ultimate goal of pursuing a career in PEM/EM. When not at the hospital, he can be found dreaming about travelling post-COVID, avoiding falling into the Gulf of Mexico/Mississippi River in the search of the perfect burger, or at pub trivia with his partner at a local brewery.

Authors

  • Dr Emma Hulme MBChB, MPH, MRCGP, DTM&H, DCH, DRCOG, DFRSH Emma works as a GP in a city practice and in the Emergency Department at the Royal Manchester Children’s Hospital. Before training in General Practice she worked in a number of countries overseas in maternal and child health roles and currently leads the Global DFTB Bubble. The rest of her time is spent chasing after her 3 little people and trying to find a quiet corner for 5 minutes peace! Christopher McKenna, MPH Chris is a former critical care paramedic turned final year medical student at the University of Queensland - Ochsner Clinical School in New Orleans, Louisiana. Originally from NJ, he has spent time working on pre-hospital system development in Somaliland and Sierra Leone, as well as time with various NGO/IGO in the Philippines. He is eager to return to Australia for his internship in 2022 with the ultimate goal of pursuing a career in PEM/EM. When not at the hospital, he can be found dreaming about travelling post-COVID, avoiding falling into the Gulf of Mexico/Mississippi River in the search of the perfect burger, or at pub trivia with his partner at a local brewery.

  • Phoebe is an advanced trainee in General Paediatrics and Paediatric Infectious Diseases. While 'home' is Sydney Children's Hospital, she is currently based half-way between Oxford and rural Kenya where she is working with the KEMRI-Wellcome Trust Research team on a PhD in antibiotic resistance. When not chasing her 6 year old triplets around, she can be found on the wards in Kilifi with her fourth child attached in a kikoi wrap.

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