Don’t Forget about Malaria…

Cite this article as:
Emma Hulme and Chris McKenna. Don’t Forget about Malaria…, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.32891

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

Malaria is a life-threatening disease caused by parasites that are 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, but 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 just seemed so 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 years old 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 of us not living in a malaria-endemic area, the 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 5 years old. That means a child is dying from Malaria every 2 minutes. This is not OK!

Data taken from Targetmalaria.org

 

A concerted global effort over the past few years has saved hundreds of thousands of lives with preventative malaria programmes. The World Health Organisation (WHO) estimates in excess of 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 is announcing that 26 countries and territories are within reach of zero malaria cases by 2025. This is really encouraging yet there is still a long way to go for many countries, particularly in Africa.  

Every Win Counts

Rural Bo District – Sierra Leone, 2011, Sitting in the shell of a clinic that had been built and subsequently abandoned by an NGO after the civil war, we see over one hundred children, sixty of these testing positive for malaria. A simple treatment, but 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, but 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, those that grew up in a time where Malaria is no longer an unconquerable giant, but something that can 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 in distributing mosquito nets, sharing information about malaria, as well as engaging with their community and national policymakers to prioritise malaria. 

Malaria experiences from our colleagues at Mbarara University EMIG

As a medical student who has been trained in Uganda – a country where malaria is a major public health problem that is 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, the treatment plans, and the 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 to care 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, as well as 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’s 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. 

So 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 have 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 start to re-open, those working in malaria-free countries will need to start thinking ‘could this be malaria?’ once again. While this fall in testing numbers is not surprising, it doesn’t mean that you shouldn’t include malaria on your list of differentials when warranted.  There is a great refresher on the website and here’s a memory jog for those of us who haven’t thought about malaria for a while.

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!
  • Severe malaria includes the clinical suspicion with confirmed parasitological and at least one of the following: 
  • High parasite density (≥5%)
  • Impaired consciousness
  • Seizures
  • Circulatory collapse/shock
  • Pulmonary oedema or acute respiratory distress syndrome (ARDS)
  • Acidosis
  • Acute kidney injury
  • Abnormal bleeding or disseminated intravascular coagulation (DIC)
  • Jaundice (must be accompanied by at least one other sign)
  • Severe anemia (Hb <7 g/dL)

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 uncomplicated vs complicated (severe) malaria early.
  • Oral outpatient management for uncomplicated malaria is reasonable, but urgent inpatient management for severe malaria is required. 

A call to action

Moving forwards 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 health care 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 started 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 keep standing united together 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, ensure you make referrals appropriately. Engage the ID team early if you are unsure! 

Selected references

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.

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 

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)

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.

COVID and Hydroxychloroquine

Cite this article as:
Alison Boast. COVID and Hydroxychloroquine, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.24968

There has been lots of media attention around hydroxychloroquine use for COVID-19 in recent days, largely stemming from this press release where Donald Trump discussed its effectiveness.

 

However, as many have since pointed out, the evidence is very limited, and care needs to be taken when trying new drugs in a clinical context, even in a pandemic. There are many risks associated with using a drug for a new indication, particularly in patients who are otherwise unwell.

 

What is hydroxychloroquine?

Hydroxychloroquine is a prescription medication currently used in both adults and children for autoimmune diseases including lupus and for the treatment of malaria.

 

What is the evidence so far?

The evidence for hydroxychloroquine can be divided into two types – in vitro (in the test tube) and in vivo (in people).

In vitro evidence

The in vitro evidence for hydroxychloroquine is promising. It works in two ways:

  1. Direct inhibition of SARS-CoV-2
  2. Immune modulation

Severe disease occurs in COVID-19 due to the pro-inflammatory cascade and cytokine sstorm causing acute respiratory distress syndrome (ARDS). The inflammatory cytokine interleukin-6 (IL-6) has been particularly implicated in this pathway, and there is evidence to show that hydroxychloroquine has anti-inflammatory effects decreasing the production of a number of cytokines including IL-6.

In vivo evidence

The evidence for hydroxychloroquine in COVID-19 is currently limited to a few small prospective studies in adults. These studies have many methodological limitations increasing the risk of bias, and more randomised controlled trials are required before commenting on its efficacy. There are also concerning reports of cardiac toxicity with hydroxychloroquine use, which highlights the importance of only using new drugs in the context of clinical trials.

 

What evidence is there in children?

In short – none!

So far there have been no clinical trials of hydroxychloroquine in children. As it is already used in children with other conditions, we do know that is safe in the ‘well’ child and have some information about appropriate dosing. However, if it is prescribed to children with moderate to severe disease COVID-19, we cannot assume that the distribution around the body and clearance (pharmacokinetics) and its interaction with the body (pharmacodynamics) is the same.

 

Where to from here?

As per the World Health Organisation experimental therapies should not be used outside of registered clinical trials. The future use of hydroxychloroquine in children with COVID-19 is therefore dependent on whether clinical trials are conducted.

 

Why is this important?

For any new therapeutic agent to be used in children it requires the same rigorous assessment in clinical trials in adults. Often due to ethical issues and the inherent challenges of performing clinical trials with children, these studies do not occur. This is a huge issue in paediatrics in general, as almost all new drugs are only tested thoroughly in adults.

Paediatricians are often forced to prescribe drugs ‘off label’ (use of drugs for a different age group, indication, dosage, frequency or route) or ‘unlicensed’ (where a drug is used despite it not being approved by the licencing body such as Therapeutic Goods Australia). Many commonly used drugs are actually prescribed ‘off label’ including ondansetron, salbutamol and even paracetamol. There are well-documented risks of adverse effects with off-label and unlicensed prescribing. Without clinical trials there is no other option.

 

In conclusion…

It would be great if hydroxychloroquine was the wonder-drug we were all waiting for, with the in vitro data certainly promising. However, further clinical trials to assess its efficacy and safety are required, particularly before its use in children.

 

References

Liu J, Cao R, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020;6:16.

Mackenzie AH. Dose refinements in long-term therapy of rheumatoid arthritis with antimalarials. Am J Med. 1983;75(1a):40-5.

Yao X, Ye F, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of SARS-CoV-2. Clin Infect Dis. 2020.

Chen Z, Hu J, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. medRxiv. 2020. **PREPRINT

Chen J, Liu L, et al. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19. J Zhejiang Univ (Med Sci). 2020;49(1):0-.

Gautret P, Lagier JC, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020:105949.

Coomes EA, Haghbayan H. Interleukin-6 in COVID-19: A Systematic Review and Meta-Analysis. medRxiv. 2020:2020.03.30.20048058. **PREPRINT

Savarino A, Boelaert JR, et al. Effects of chloroquine on viral infections: an old drug against today’s diseases? Lancet Infect Dis. 2003;3(11):722-7.

Imaging in COVID

Cite this article as:
Nuala Quinn, Cian McDermott and Gabrielle Colleran. Imaging in COVID, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.24680

The current pandemic is providing a challenge in healthcare settings whose resources are rapidly becoming strained. From the early experiences in China, it appears that children who are infected with COVID-19 have a milder course typically than that seen in adults. The radiological findings in adults include multifocal bilateral ground-glass opacities and consolidation. This is often peripheral or basal in distribution. They tend to evolve from either these bilateral ground-glass opacities on the periphery to consolidation then crazy paving. The limited initial data in children suggest that multi-lobar involvement is much less common. This is consistent with the hypothesis that children appear to have milder disease. Findings peak at 7 to 14 days and then gradually resolve. We do not yet know the radiologic sequelae.  Experience taken from the adult population in Ireland has also noted air leak complications including pneumomediastinum and pneumothorax. Pleural effusions, lymphadenopathy, and tiny lung nodules seem to be less common manifestations.

 

X-ray

The chest x-ray is, in general, the first-line imaging in children with respiratory pathology. And it is being used in COVID-19. This (pre-publication) CXR is from a case in a tertiary paediatric hospital. It shows bilateral mid-zone and left lower zone patchy consolidation and pneumomediastinum.

Ming-Yen et al describe five patients who had both chest x-rays and a CT of the thorax. Two patients showed normal CXR findings, despite having a CT examination on the same day showing ground-glass opacities. The positive CXR findings seem to appear later in the disease progression. Within the Guangdong province of the authors, a CT of the thorax is now being requested on every patient suspected of having COVID-19 regardless of risk. However, the radiation associated with CT in children does not, and cannot, support this in the paediatric setting. In sticking to the ALARA (As Low As Reasonably Achieivable) we should consider the use of another evidence-based resource – point-of-care ultrasound (POCUS).

Point of care ultrasound (POCUS) is fast becoming an established part of paediatric emergency medicine. Lung ultrasound is a mainstay of POCUS for a variety of diagnoses including pneumonia and pleural effusion. Now, there is rapidly evolving evidence on COVID-19 and POCUS lung findings.

So, how do we use ultrasound to look for ground-glass opacification and consolidation in children with suspected viral respiratory tract infection?

 

Sonographic characteristics

 

Lung US is more sensitive than CXR for interstitial patterns, small effusions, and subpleural thickening. The POCUS characteristics are similar to other causes of viral pneumonia, but in COVID-19, two studies (Huang et al and Peng et al) also described localized pleural effusions. They are more often seen with bacterial pneumonia in children, rather than viral. Large volume pleural effusions are uncommon – if you are seeing this then you need to consider other pathology.

B-lines are short-path reverberation artefacts that are found in many pathological and nonpathological states. *ISP is interstitial syndrome pattern, i.e. extensive B lines which may coalesce. This pattern is not unique to COVID-19. It is also commonly seen in pulmonary oedema. In COVID-19 these may appear in characteristic focal, multifocal and confluent patterns.

Small subpleural consolidations may be also seen. These are small hypoechoic areas inferior to the pleural line. If there is bibasal consolidation on the ultrasound, there may also be dynamic bright air bronchograms present. In COVID-19, a pleuropathy develops. This results in a thickened, irregular appearance of the pleura. There may also be skip lesions – normal pleura alongside thickened pleura with associated B-lines.

It is important to note that children may be clinically well with any of the positive lung POCUS findings.

Technique tips

The technique for POCUS lung is well described. However, for children and COVID, the following may be helpful:

  • Use the linear probe to assess pleura and look for pleural line thickening, small superficial effusions, skip lesions and B-lines.
  • Use the curvilinear or phased for lung windows. It may also be better for posterior pathology such as consolidation and air bronchograms.
  • Turn off the harmonics and spatial functioning.

And if you don’t know what any of that means then head over to Practical Pocus for a free online course and follow @Zedunow for their daily updates.

 

Decontamination and machine preparation

Infection control measures are key – the machine should go in clean and come out clean! ACEP have published an excellent COVID US cleaning protocol which is really worth a look at.

Remember to strip the machine of all non-essential items such as trays, holders and inserts and where possible avoid keyboards and use the touchscreen. Rather than multi-use bottles of gel, you should be using single-use sachets.

Handheld devices provide an alternative, with less cleaning required.

 

Photo courtesy of Cian McDermott

A word on CT

The CT findings associated with COVID-19 have been widely described: ground-glass opacities and consolidation with or without vascular enlargement, interlobular septal thickening ,and air bronchograms. Most of the studies are in affected adults and the high reported sensitivity will be affected by patient selection bias. Like the chest x-ray, it may be falsely negative in the first few days of illness. A normal CT early in disease could be falsely reassuring. Indeed, the general guidance from numerous faculties of radiology does not currently recommend CXR or CT to diagnosed COVID-19. Viral testing remains the gold standard.

 

Finally, a word on ALARA

ALARA, or making every effort to limit exposure to radiation As Low As Reasonably Achievable, is particularly relevent in COVID-19. Imaging should only be conducted for those patients where imaging will impact management of the condition. These recommendations may change as our knowledge of COVID evolves. CXR, CT and POCUS each have their own limitations, but there is emerging evidence that POCUS, in the hands of a competent practitioner, is superior in ease of access, diagnostic ability and ease of decontamination, particularly at a time when infection control is so crucial.

 

Selected references

Kanne JP, Little BP, Chung JH, Elicker BM, Ketai LH. Essentials for Radiologists on COVID-19: An Update-Radiology Scientific Expert Panel. Radiology. 2020 Feb 27:200527. https://pubs.rsna.org/doi/pdf/10.1148/radiol.2020200527.

Liu M, Song Z, Xiao K.High-Resolution Computed Tomography Manifestations of 5 Pediatric Patients With 2019 Novel Coronavirus.J Comput Assist Tomogr. 2020 Mar 25.

Ming-Yen N et al. Imaging Profile of the COVID-19 Infection: Radiologic Findings and Literature Review. Radiology 2020 Feb 13 https://doi.org/10.1148/ryct.2020200034

Huang Y et al. A Preliminary Study on the Ultrasonic Manifestations of Peripulmonary Lesions of Non-Critical Novel Coronavirus Pneumonia (COVID-19) SSRN 2020 Feb 28 https://dx.doi.org/10.2139/ssrn.3544750

Peng, Q., Wang, X. & Zhang, L. Findings of lung ultrasonography of novel corona virus pneumonia during the 2019–2020 epidemic. Intensive Care Med (2020). https://doi.org/10.1007/s00134-020-05996-6

Li Y, Xia L. Coronavirus Disease 2019 (COVID-19): Role of Chest CT in Diagnosis and Management. AJR Am J Roentgenol. 2020 Mar 4:1-7. doi:10.2214/AJR.20.22954

 

International Society Guidelines

Royal Australian and New Zealand College of Radiologists

Canadian Association of Radiologists 

American College of Radiology statement on CXR and CT findings in COVID19

Royal College of Radiology statement on CT in COVID

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

More questions than answers

Cite this article as:
Andrew Tagg. More questions than answers, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.24133

Given the rapidly changing climate for all things COVID19 the DFTB wanted more information. We know our strength is in our community so we hosted a series of webinars linking healthcare workers with a special interest in paediatrics. No one person is an expert but we are all in the same situation facing similar challenges. These are some of the questions that came out of the discussions. With the proviso that information is changing on a daily basis and resources in terms of staff, space and stuff is different, let’s dive in.

This data is correct as of 19th March 2020. Please let us know in the comments if you spot anything new.

Science

NSAIDs

There has been a suggestion that non-steroidal agents are unsafe for use in SARS-CoV2-19 patients. As we have already seen the evidence for anything in the paediatric realm is very slim.  However, as of the 17th of March 2020 the WHO has recommended against using ibuprofen in patients with symptoms suggestive of COVID19. What does this mean in real terms? We don’t know which children are asymptomatic carriers.

If you look at the source of the message it is even more striking – the French health minister suggested that anti-inflammatory drugs could exacerbate symptoms. He suggested that we should not prescribe NSAID’s or cortisone/steroids to patients with suspected COVID19. Given that one of the few drugs that work in one of our more prevalent respiratory diseases, croup, is a steroid then I think we need to look to more evidence of harm over benefit. If you want a great, easy read on the matter then check out fullfact.org.

ACE-I

Very little is known on the potential impact of ACE inhibitors on COVID19 in adults, let alone children. The Venn diagram of children with the disease and on perindopril (say) is represented by two separate and distinct circles at the moment. If you are curious as to how there may be an interaction then read this great Tweetorial from Jonny Wilkinson.

It is also worth taking a looking at this letter in the Lancet to better understand the theory.

Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?. The Lancet Respiratory Medicine. 2020 Mar 11.

Vaccines and various treatments

To claim that there is a cure just around the corner or that a certain combination of vitamins and herbs will keep the virus away is pure quackery. Rather than tell you what research is going on then dashing your hopes when there is a negative outcome we’ll reserve our judgement at this stage.

 

Sorting and Streaming

A common challenge mentioned by all sites is just how do we triage? How do we sort patients so that we are not mixing potentially infected with non-infected patients? There cannot be a one size fits all approach as the needs of a single provider clinic are every different from those of a district general hospital and these are very different from a tertiary paediatric centre. Rural and remote populations have different resources to the big, shiny hospitals complete with fish tanks and meerkat enclosures.

Triage

A number of hospitals are using a concierge based approach. As a patient approaches the department they are met by a greeter (who is usually a member of the nursing staff), dressed in full PPE. They help determine the first decision point – possible COVID19 or unlikely COVID19. The latter group is pretty easy to spot. Determining what patient sub-types fall into the former is more of a challenge. In the initial phase of the disease, most hospitals have looked for the presence of respiratory symptoms PLUS a fever. If you look at the published and pre-print paediatric data around 2/3 of children with the disease have a fever and a large proportion appear to be asymptomatic. A number of patients also present with predominantly GI symptoms. Should they be treated as potential carriers? (And who should change their nappies given they can shed SARS-CoV2-19 for up to 40 days?)

An alternative triage approach utilizes a more 21sst century solution with carers/patients logging important information on a tablet-style device before their secondary medical triage. This would require the user to clean the interface after use – something that is already tough.

Children with special medical needs

There is insufficient data to make hard and fast rules about the management of children with complex healthcare needs. Adults with multiple comorbidities have increased mortality so it is biologically plausible that the same will hold true in the paediatric population. Pre-notification of attendance can help as these kids are brought in via a different entrance.

Many places are trying to replace standard outpatient visits with telehealth options on an ad hoc basis with little guidelines available on how to do this without just picking up your own mobile phone. This is not an ideal solution but is being offered to many children with diabetes, chronic respiratory conditions or children with rheumatological conditions requiring immunosuppressive agents.

The RCPCH recommends that children who have an exacerbation of their chronic respiratory illness and require admission should be considered to have COVID19 until proven otherwise.

Internal streaming

Once the children have been streamed into a respiratory disease cohort should we assume they all have COVID19 until proven otherwise? Should we treat the patient with clinical bronchiolitis or croup as a potential carrier? And what about those that are wheezy but don’t have a fever? Just what do we do then?

The number of critically ill children presenting to the ED is likely to be small but it has been suggested that these are rapidly assessed and transported to a negative pressure room in PICU for the full workup, whether they need intubation or not.

Testing

Children do not come into the hospital on their own. They often bring carers, parents, grandparents, aunts and uncles. Adjusting the policy on attendant carers is a tough sell to those that are looking after the potentially infected child. Most mixed EDs seem to be keeping the family unit together for testing. It would be interesting to know if any tertiary paediatric centres are testing the grown-ups that come with the children.

Just how accurate is the PCR test? And just how long does it take a result to come back? We are looking into the former question and can sense the frustration around the latter. Cohorting patients in negative pressure rooms just waiting five days for a swab result is not helping us clear the decks. We should be mindful, though, that there are things we can control and things we cannot. This is one of those things we have no control over at the moment.

Mixed departments

Most of us do not have the luxury of working in a tertiary paediatric centre where the only adults are dressed as clowns or doctors (or doctor-clowns). Some departments are making provisions by moving their paediatric space to allow for adult overflow. The RCPCH has also stated that paediatricians should be prepared to see patients up to the age of 25. That makes sense in a mixed environment but one wonders what happens in centres that do not routinely see any adults. With outpatients and elective surgery being cancelled across hospitals, there is a potential surfeit of doctors with markedly reduced day to day work.

There is also the question of what happens in adult hospitals when a COVID19 positive sole parent gets admitted. What happens to their swab-negative child? In some cases, the decision has been to treat them as a boarder but this can make many staff members feel uncomfortable.

Sicker children

At the time of writing this the mortality in children is exceedingly low. This is very reassuring but business will continue as usual. Treatment options may be limited dependent on restrictions with regard to aerosol-generating procedures. There have been mixed messages as to whether nebulization of medication. leads to increased healthcare worker risk. Some places are now controlling the use of nebulized treatment, as well as mandating consultant approval of high flow nasal cannula oxygenation. In centre without access to a PICU on-site how are these children being managed? What have measures have paediatric retrieval services put in place to deal with the potential increase in referrals?

Intubation teams are already being considered at a number of sites – teams of doctors, similar to a MET team, that are ready to provide critical care at the sound of a bleep, in the hope that this will reduce exposure to one of the highest risk aerosol-generating procedures – intubation. In mixed adult/paediatric hospitals it is also important to consider the implications of intubation in a resource replete setting. Some hospitals are starting to consider this and set up ethics committees to set rules early and consider just who should have access to that last ventilator. The decision is not as easy as you think.

 

Stuff

Personal protective equipment

There have been some mixed messages about what type of PPE should be worn in what scenario.  Public Health England has this handy table to guide you and, as always, be mindful of your local guidelines if they differ.

Some hospitals are requiring all healthcare providers to undergo mandatory, face-to-face training in donning and doffing PPE prior to deployment. It has been suggested that we should wear the highest standard of PPE for every encounter in order to present nosocomial transmission. Unfortunately, supplies are limited and so we should use the most appropriate PPE for the task in hand.

Aerosol generating procedures

There seems to be a lot of confusion about what an aerosol-generating procedure is. As always, it is important to follow your local clinical guidelines. But if you disagree with them, then let the evidence guide you, and seek to change the guidelines. Concerns have been raised about everything from just examining the throat, using nebulizers (a daily question), and whether we should be using HME filters on the Neopuff. Rest assured we are looking at this and a blog post will follow.

 

Staffing

Rosters

We are already overstretched – both on the floor and in the back office. Corona conditions are making this even more apparent as we are wondering whether we should stretch our elastic workforce just that little bit more before the wave hits so that we have a rested and well cohort, ready to go. Those of us that work in mixed EDs know that paediatric workforce planning is furthest from our minds as we read of the Italian situation.

Should (when?) the pandemic stretch on for months considerations need to be given to staff longevity. Will there be a burnt-out generation of ED physicians who have seen and been exposed to too much? What about those who have had much-needed leave cancelled? Perhaps some of the daily load can be taken up with doctors from those specialities who have a lower case burden? Orthopaedic registrars could oversea minor-injuries clinics in a remote location. Dermatology trainees could answer the question of “What on earth is that rash?” in a medical/non-COVID assessment area?

Healthcare workers that work across sites are already being asked to reduce cross-campus travel.

Though we go to work for our patients we also need to be mindful that we too may become patients. None of us is immune to catching the disease. In its mild form, it will be an inconvenience to us, our loved ones, and our colleagues. But healthcare workers will die. Healthcare workers have already died. How do we mitigate the risks for the more vulnerable? What should we do with the older, more at-risk, paediatrician, the immunosuppressed healthcare worker, the pregnant trainee? These are questions that have not yet been answered.

Everyday life

As we are being asked to work longer hours how many hospitals have made provision for routine, everyday tasks? How many have designated areas for staff to catch some sleep before driving home? How many are providing scrubs for staff to change into or are helping with the laundry? The last thing most of us feel like when we get home is loading up the washing machine (and then putting it out to dry. But how clean are your everyday clothes? Your stethoscope? Your phone?

How are workplaces supporting that other basic physiological need – food? With supermarkets reducing their opening hours how are healthcare workers being supported? McDonald’s in the UK is offering free drinks to those with NHS cards but you can only last so long on caffeinated brown water.

Information dissemination

The situation with SARS-CoV19-2 is a rapidly evolving one with advice changing on a daily basis. Most hospitals have set up incident management teams that meet at an executive level to discuss the changes that may impact our day to day – cancelling elective surgery, moving departments. Making sure that information trickles down from an operational level to a clinical level can be hard, especially with a workforce that might be relying on bank or agency staff. A lot of departments are trialling WhatsApp groups as a means of sharing the very latest information but it is still possible for a key piece of information to be lost in the stream.

Education

Most hospitals have now cancelled face-to-face education sessions. There are plenty of of resources available to help educators plan sessions remotely. This series from ALiEM is the standout.  The DFTB team hope to be adding more resources for you shortly (especially if we get put in isolation).

Students

A number of universities have pulled their students from clinical placements or placed restrictions on their interactions with patients e.g. not to see a respiratory patient. Many feel that they should be doing something and a number of great initiatives have been suggested. One group has launched a childcare service for healthcare providers. With schools in the UK due to close early for the Easter break this will come as a welcome relief to many who may usually rely on (at-risk) relatives. It has also been suggested that they would make excellent scribes to speed up the standard clerking process. Let us know what else is going on.

Morale

At the moment we are all nervous anticipation, stepping over wavelets or paddling our boards out ready to catch the big wave. This sense of nervous excitement is palpable in the emergency room. The feeling getting is getting stronger as regular hospital services wind down. How do we maintain our own morale in the face of hard shifts? How do we look after each other when a colleague gets ill? How do we make sure that strangers fro other services are welcome in the safe space we call work?

 

At this time of great uncertainty, it is important that we remain kind, that we show #PandemicKindness to those we meet. Everyone is working their hardest and to the best of their abilities. Take time to recognise that, whether it is the security officer that has to ask you for your ID to allow you into the building or the cleaners that we rely on. Take your time to thank them for their hard work, offer them a coffee (or a tea if they are in the Northern hemisphere. Remember that the ED is often overstretched so that serum rhubarb may not have been ordered. Be mindful that those of us who are dealing with adults as patients too and recognise that they need our kindness now, more than ever.

Please feel free to answer any of these questions in the comments section. Share your resources, your experiences, so that we may learn from each other. E-mail us at hello@dontforgetthebubbles.com with your ideas and suggestions. And be safe.

COVID19 and ACE inhibitors

Cite this article as:
Cathy Quinlan. COVID19 and ACE inhibitors, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.24225

Why do my patients keep asking me about ACE inhibitors and COVID-19?

Hypertension is a common problem affecting 3.5% of children and adolescents and correlating with increased cardiovascular risk in young adults. Common first-line therapies include angiotensin converting enzyme inhibitors (ACEi), such as ramipril, lisinopril and enalapril.

Over the last few weeks, a storm has erupted over the use of ACEi with the suggestion that they could be associated with severe COVID-19. A statement by the European Society of Cardiology, was quickly followed by most national hypertension societies, including the American Society of Pediatric Nephrology and the High Blood Pressure Research Council of Australia, recommending the continuation of ACEi in patients with COVID-19. 

 

How are ACEi linked with COVID-19?

The COVID-19 literature to date has suggested increased mortality for adults with hypertension and for those with diabetes, a patient cohort frequently treated with ACEi. Although medication use has not been reported in patients with COVID-19, a letter to the Lancet postulated that the use of ACEi could be implicated in the increased mortality rate described in patients with hypertension. 

Human coronoviruses, such as SARS-CoV-2, gain entry to the cell through ACE2 which is expressed by epithelial cells of the lung and kidney. Thus a treatment that increases the expression of ACE2 at the cell surface could increase the severity of COVID-19 infection. There is animal evidence that circulating ACE2 levels are increased by treatment with ACEi. But also conflicting evidence in humans showing no association between circulating ACE2 levels and the use of ACEi. 

Interestingly, there is clinical data to suggest that ACE inhibition may actually be a potential therapy for viral pneumonia. Though it should be noted that this is confined to retrospective, observational data, clinical trials are underway to examine the use of recombinant ACE2 and losartan in adults with COVID-19, highlighting that the use of ACEi in patients with COVID-19 is not clearcut. 

 

How does this impact our patients?

A growing body of evidence, summarised by the DFTB team here, shows that children are at much less risk of severe disease than adults. Indeed, only 1 of 731 patients with confirmed COVID-19 infection in the largest study to date, had clinically critical disease. The data on ACEi in COVID-19 is inconclusive and pending further data there is no evidence to change anti-hypertensive management in children at this point in time. 

 

The Bottom Line

There is currently no evidence, in children or adults, to support changing blood pressure medication due to the COVID-19 pandemic.

 

I want to know more!

If you want to read more about HTN then please review the 2017 Hypertension guidelines from the American Academy of Paediatrics.

If you’d like to know more about ACE2, hypertension, and COVID-19 then check out the dedicated ACE2 NephJC page.

For up to date reviews of the COVID-19 literature as it pertains to the kidney along with management guidelines check out the COVID-19 NephJC page

If you are aware of resources that you think would be useful to the nephrology community then please tag it with #CoronaKidney and they will be added to the page after they are reviewed.