Malaria

Cite this article as:
Phoebe Williams. Malaria, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.24980

A child is brought into Emergency with fever and lethargy, having returned from visiting relatives in India over the school holidays. You work your way through the considerations of fever in a returned traveler, and within hours the lab calls to report the presence of malaria parasites evident in the blood film. What next?

 

Despite significant gains in combatting malaria over the past 100 years, the malaria parasite continues to cause significant morbidity and mortality globally, responsible for 230 million clinical infections and almost half a million deaths each year. That’s 1,100 deaths a day, of which 745 occur in children < 5 years. To put that into perspective, I write this at a time when COVID-2019 has caused 14,000 deaths: and while this is a number that will grow exponentially and is an important pandemic rightly gaining significant attention, it is worth considering that in the past fortnight alone, malaria has killed the same number of people. While we focus our efforts on a new infectious disease, it’s paramount that other major killers aren’t ignored. Historically, resource diversion from investment in new pandemics has had significant consequences – such as the measles epidemic that killed 6,000 children in the Democratic Republic of Congo in 2019, when the bulk of healthcare funding was focused on combating Ebola.

Malaria is a regressive disease – that is, one that affects the poorest people in the world the most. In this era of global connectedness, it is important that we realize that we all have a role to play in ensuring this completely preventable and treatable disease is tackled in our generation, as malaria traps entire nations in poverty through its impact on growth, development, morbidity, and mortality.

 

Transmission and Epidemiology

Malaria transmission occurs across large areas of Africa, Latin America, South Asia, Southeast Asia, the Middle East, Eastern Europe, the South Pacific and parts of the Caribbean.

Malaria in humans is caused by a protozoan parasite of the genus Plasmodium, and includes the species Plasmodium falciparum, P. vivax, P. ovale, or P. malariae. Plasmodium knowlesi (thought to be previously only capable of infecting monkeys) has also recently been documented causing death in humans in South East Asia. The parasite is transmitted either via the Anopheles mosquito or from a mother to an infant via the placenta.

Every febrile or anaemic child returning from a malaria-endemic region within the past 12 months should always be investigated for malaria, regardless of whether they have previously lived in a there (and presume themselves to be ‘immune’) or took chemoprophylaxis.

 

Clinical presentation

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).

Falciparum spp.

Diagnosis

The biggest challenges in diagnosing malaria are:-

(i) thinking to test for it – as 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) falsely diagnosing malaria infection as the sole cause of a child’s illness in an endemic region. The latter is a common reason that bacteraemia and other causes of meningitis are missed in regions of the world where malaria is prevalent. Many children in these settings may have a low-level parasitaemia persistently present that may not be the cause of their clinical illness, and important empiric antimicrobials or further investigations are missed.

Unfortunately, there is no one diagnostic test that can distinguish between parasitaemia causing clinical malaria, and a febrile illness due to another cause in a patient who also has 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, to improve diagnostic accuracy and prevent the promotion of artemisinin resistance by ensuring the rational use of anti-malarial medications, parasitological diagnosis is now essential.

The gold standard diagnosis remains microscopy, if staff and facilities are available to perform this. A thick blood film allows the presence and density (percentage of parasitized erythrocytes) to be confirmed, while the thin film determines the Plasmodium species. The sensitivity and specificity of these tests are laboratory-dependant, and relies on astute scientists being familiar with the laboratory diagnosis of malaria.

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 at detecting low numbers of parasitaemia (an important prognostic factor) and are also insensitive at 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 just be malaria secondary to a positive RDT.

 

Why do some guidelines tell me I need to do three separate tests?

A single negative blood film, or negative antigen test, does not completely exclude the diagnosis of malaria 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). A number of organizations, therefore, recommend repeating blood films with fever spikes (to correlate with schizont rupture) until a positive test is returned, or until 3 negative films are confirmed, in patients with a high pre-test probability. This is not necessary for patients in whom the diagnosis of malaria 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 so tend to exhibit 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 resolution of infection. If resources allow, this is usually performed daily until negative (or until day 7 if well enough for discharge prior to 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.

 

Management

Uncomplicated malaria can be treated orally, provided the child can tolerate oral therapy. An artemesin-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: any patients with parasitaemia beyond 3 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 parasite from humans to mosquitoes. However, ensure you rule out the presence of G6PD deficiency in the patient first (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 reactive and result in malaria relapses, so require concurrent treatment with primaquine (again, only after G6PD deficiency has been excluded). If the patient has G6PD deficiency, once again, call your friendly ID team for subspecialist advice.

For the treatment of severe malaria, start parenteral therapy as soon as possible. Alongside managing the ABCDEFGs (particularly focusing on careful correction of fluid and glucose levels), commence parenteral Artesunate as soon as possible. For travelers 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, a FBC should be performed weekly for 4 weeks after completion of therapy to monitor for delayed haemolysis or the recrudescence of malaria parasites.

 

The Bottom Line

  • Malaria continues to kill 750 children per day, every day.
  • Always consider malaria in a febrile or anaemic child returning from a malaria-endemic country in the past 12 months.
  • The diagnosis of malaria requires parasitological confirmation (microscopy with thick and thin films, or a rapid diagnostic test); however these tests have imperfect sensitivity and specificity so may need to be repeated (with fever spikes, ideally) if you have a negative initial result in a child with a high pre-test probability.
  • Simultaneously, its important to consider dual diagnoses in children who are sick. Parasitaemia is not necessarily indicative of clinical malaria in children who are living in malaria-endemic regions and in children who present particularly unwell, malaria and bacteraemia can often coexist.
  • The most important initial aspect to management is differentiating uncomplicated from severe malaria. Oral therapy is appropriate for uncomplicated therapy, while urgent parenteral therapy is required for severe malaria.
  • Artemesinin-based therapy is the cornerstone of management for malaria.
  • With prompt diagnosis and treatment, the morbidity and mortality of malaria can be significantly diminished and outcomes are usually excellent.

 

Selected reference

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.

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

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

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>

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).

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

DFTB COVID Global Meetings

Cite this article as:
Tessa Davis. DFTB COVID Global Meetings, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.24108

The DFTB team has organised a series of online meetings in March. These meetings have the aim of connecting the paediatric emergency medicine communities – in the UK, in Aus/NZ, and globally.

The meetings are being recorded and will be accessible to those who registered. They are password protected.

If you would like to request access to any of the meetings, please register. The form to register is at the bottom of this page.

 

UK PEM Meeting – Thursday 25th June 2020

If you registered you can watch the videos here:

 

 

 

UK PEM Meeting – Thursday 14th May 2020

If you registered you can watch the videos here:

 

UK PEM Meeting – 17th March & 8th April 2020

If you registered you can watch the videos here:

8th April 2020

17th March 2020

See Grace Leo’s fabulous summary:

 

 

Clinician Care – 30th March 2020

Watch our recording right here.

 

Global PEM Meeting – 24th March 2020

See Grace Leo’s fabulous summary:

If you registered you can watch the video here:

ANZ PEM Meeting – 19th March 2020

See Grace Leo’s fabulous summary:

And if you registered you can watch the video here:

 

 

Register here to access the recordings:

To be able to register you will need a healthcare associated email address

COVID-19 and children: what do you need to know?

Cite this article as:
Boast A, Munro A. COVID-19 and children: what do you need to know?, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.23868

In late 2019, a new infectious disease emerged and spread to almost every continent, called COVID-19. As of March 11th 2020 it was declared a global pandemic by the World Health Organisation, meaning that is was being spread among multiple different countries around the world at the same time. It has changed the way we live our lives.

What we understand about SARS-CoV2 and COVID-19 has increased dramatically, with research being done at an extraordinary rate. For those of us whose business is looking after children, what do we need to know?

 

Editor’s note: This post is based on what we know today, Wednesday 15th of April 2020, and will be updated as new information becomes available.

 

What is COVID-19?

  • COVID-19 is the name of the disease caused by a new coronavirus, which has been named SARS-CoV-2. COVID-19 is the disease, and SARS-CoV-2 is the virus.
  • A coronavirus is a type of virus named after its unique appearance – with a ‘crown’ of proteins – when viewed with high power microscopy.
  • Coronaviruses very commonly infects humans (and some animals).
  • In humans, coronaviruses are a frequent cause of the ‘common’ cold – resulting in an upper respiratory tract infection with cough and coryza. There are, however, three types which can cause severe, even life-threatening disease in humans (SARS, MERS, and COVID-19).

 

What is the difference between COVID-19, SARS, and MERS?

Whilst they are all severe illnesses caused by coronaviruses, there are some important differences. Some useful things to consider include the R0 (how many people, on average, one case of the disease will spread to in others) and the Case Fatality Rate (CFR), an estimate of how many people who contract the disease will die from it. Neither of these statistics is hard and fast (and are both highly context-specific), but they provide a rough yardstick with which to compare infectious diseases.

  • SARS: This is an acronym for Severe Acute Respiratory Syndrome, a disease caused by the virus SARS-CoV. In 2002-3 the spread of SARS-CoV resulted in around 8,000 cases, with a CFR of approximately 10%. Similar to COVID-19, SARS-CoV originated in China, before spreading around the world, predominantly Europe, North America, and South America. The R0 from SARS is thought to be 3.
  • MERS: This is an acronym for Middle East Respiratory Syndrome, caused by the virus MERS-CoV . As the name suggested, it originated in the middle east in 2012, transmitted initially from camels to humans. MERS causes the most lethal infection of the coronaviruses, with a CFR of around 35%. The R0 from MERS is thought to be <1.
  • COVID-19:This is an acronym for COronaVIrus Disease 2019, the disease caused by the virus SARS-CoV-2. It is a zoonotic disease (meaning it was transmitted to humans from animals) and although the intermediate host has not yet been identified, it’s thought to most likely have originated in bats. It was initially identified in December 2019 in China, before spreading around the world. The CFR is unclear, as it is still uncertain how many people actually have the virus, and how many who currently are unwell will die from the disease. The overall CFR is thought to be about 1.3%. This is highly dependent on the country (and available health resources) but another significant factor is age, with only a handful of deaths reported in children <12 years who have confirmed COVID-19. The R0 for COVID-19 is still unclear but is thought to be 2-3.

 

What are the symptoms?

  • The symptoms of COVID-19 are similar to other respiratory viral infections. Importantly, in children the symptoms of COVID19 are more likely to be mild, and a significant proportion may be asymptomatic.
  • Infected children who are symptomatic most commonly present with cough and fever.
  • A small proportion of children also present with gastrointestinal symptoms (vomiting or diarrhoea) (~10%)
  • Sore throat and runny nose do not appear to be uncommon features in children (as opposed to adults)

 

How does COVID-19 affect children?

Evidence from across the globe (namely China, Spain, Italy and America), has shown that children are significantly less affected by COVID19 than adults. There are both fewer cases in children, and less children who are severely unwell. Younger infants appear to be most likely to be hospitalised. Overall, there have been only a small number of deaths in children with confirmed COVID-19 reported. A number of epidemiological and clinical papers on COVID-19 in children have been published, summarised on DFTB.

The exact reason why there are so few children with confirmed COVID-19 is unknown. Initially it was thought that due to the high rate of asymptomatic infection children were simply less likely to be swabbed and have confirmed infection. However, recent evidence from Iceland, Japan and Korea shows that children may also be less likely to become infected with SARS-CoV-2 following exposure.

It is yet unknown whether asymptomatic children can pass the infection on to others. In epidemiological studies children have not been found to have a significant role in household transmission. It appears children may continue to excrete the virus through their faeces (poo) for several weeks after the symptoms of infection have passed, but the role of this excretion in viral transmission is not clear (there is some evidence to show it is only viral particles rather than active virus). Regardless, hand hygiene remains of paramount importance in reducing spread.

 

If my child is unwell, can I give them ibuprofen?

There has been considerable social media interest in the use of ibuprofen in suspected or confirmed COVID-19. In the UK, the MHRA has deemed there is no evidence of increased risk of using ibuprofen even in cases of COVID-19.

 

What about neonates?

Neonates without comorbidities do not appear to be at an increased risk. A large number of case series having been published of babies born to mothers with COVID-19. Although some neonates have swabbed positive for SARS-CoV-2, there have been no reports of this being associated significant illness. Evidence about the possibility of transmission from mother to baby in the womb is currently unclear.

In the UK, the RCPCH has published guidelines (with the Royal College of Obstetrics and Gynaecology) recommending pregnant women with COVID-19 who are in labour should deliver their baby in an obstetric unit, however there is no need to separate mother and baby after birth, and the benefits of breast feeding outweigh any theoretical risks. Of note, the American Academy of Pediatrics has released conflicting guidelines, suggesting separation of the mother and baby.

 

What about children with chronic conditions?

There is limited data to guide us currently on how COVID-19 might affect children with underlying health conditions. There are small case studies of children with suppressed immune systems who have not developed severe illness, including children treated for cancer and inflammatory bowel disease. There is some evidence that children with respiratory or cardiovascular comorbidities may be at higher risk of hospitalisation, but it is still unclear. For children currently being treated for cancer, the UK Children’s Cancer and Leukaemia Group have posted guidance for families including which groups are extremely vulnerable and should be “shielding”.

 

Is there any treatment?

There is no proven treatment for COVID-19, however, there are many clinical trials underway for many different therapies. The WHO has clearly stated that experimental therapies should only be used in the context of a clinical trial. Hydroxychloroquine and remdesivir have been studied most extensively, but there remains no clear evidence of benefit. Importantly, hydroxychloroquine has been associated with significant adverse effects, highlighting the importance of its prescription only in the context of a clinical trial.

Notably, there are only a handful of clinical trials for children registered, so it is unlikely that any therapeutics will be widely used in children with COVID-19. As the disease is generally mild in children, it is not likely to often be necessary to provide anything further than supportive care.

Vaccines will hopefully provide protection against future outbreaks of COVID-19, though these are still early in the drug development pipeline and unlikely to be available this year.

 

What can I do to minimize my risk?

Two words – hand hygiene. As with other viruses spread by droplet (e.g. influenza) hand hygiene, particularly when out in public, plays a critical role in preventing transmission. Washing hands with soap and water, for an adequate amount of time, covering all areas of the hands is most effective. Hand sanitizer is effective, but no more so than usual hand washing

It is important to avoid contact with others who are acutely unwell. Wearing surgical masks will not protect you from respiratory viruses. Wearing one if you are unwell may protect others from your respiratory secretions.

Physical distancing is becoming increasingly important, with many countries now mandating various ‘lock-downs’. You should follow advice from your public health authorities, and it would be wise to reduce non essential physical or close personal contact with other people to a minimum 

 

What should I do if someone in my family becomes unwell?

 

Resources for health professionals

Many journals have made their COVID-19 resources open access including NEJMThe LancetBMJ, and JAMA

National professional resources can be found at:

 

Literature

For a comprehensive review of all paediatric English language literature to date which has informed this article please see our separate page for COVID-19 Evidence

PERN – Global Research: Stuart Dalziel at DFTB19

Cite this article as:
Team DFTB. PERN – Global Research: Stuart Dalziel at DFTB19, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.21852

Stuart Dalziel is a professor of paediatric emergency medicine in Tāmaki-makau-rau (Auckland), the director of research at Starship Hospital. He is a past chair of PREDICT and current chair of PERN. It is in this role that he spoke at DFTB19.

Change against the grain: Shweta Gidwani at DFTB19

Cite this article as:
Team DFTB. Change against the grain: Shweta Gidwani at DFTB19, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20875

Shweta Gidwani graduated from Seth G.S. Medical College, Mumbai, India in 2002. S. She has been involved in the development of emergency care service delivery and training programs in India for several years and was invited to join the International Emergency Medicine section at George Washington University as Adjunct Asst Professor in 2013 where she works on the India programs.

This talk, the opening talk proper after Mary set the scene, is a stark reminder of just how the world really works.

 

©Ian Summers

 

 

This talk was recorded live at DFTB19 in London, England. With the theme of  “The Journey” we wanted to consider the journeys our patients and their families go on, both metaphorical and literal. DFTB20 will be held in Brisbane, Australia.

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