It is nothing short of heartbreaking. I have been writing medical fiction for quite some time now- my first foray into creative writing could be traced all the way back to the time when I was in Year 1, where I was mesmerised by the prospect of writing stories for my friends and family. This desire never left - on the contrary, it expanded to the unbending desire of being a successful writer. There are times when I consider being a novel writer an alternative career should I snap under the constant pressure of the hospital. Chief of all, I wrote three medical-themed novels, all of which feature some sort of medical issue. The first one encompasses issues such as immigration and xenophobia in the medical industry, as well as the darkness of the pharmaceutical industry. The second concerns a dystopian reality that dawned upon Australia (the endearing slang 'Straya' became the shorthand for dystopia, inequality and oppression), where the political radicals dispersed a biological weapon into the community, as an attempt to white-wash the country. Seeking inspiration from the hospital, I described a new form of HHV-8 (Human Herpesvirus) which could cause a very specialised type of lymph node enlargement. It would mainly arise in the chest, leading to chief respiratory symptoms such as shortness of breath and coughing.
The star among the three is about a powerful medical family tucked away in the outskirts of Richmond-upon-Thames - The Crestwood Family, in control of the Crestwood Foundation, a paramount trust for advocating studies and projects in the medical sciences. Parallels can be struck between this and Wellcome Trust, which is the largest UK-based health research charity. Within lies my two most favourite fictional characters: Archibald Crestwood (to be honest, I based it on me) and Georgina Walker. They never got married - because Georgina died of Whitmore's Disease before Archibald had the chance to propose. It was an extremely devastating moment for me, but it was necessary. For the purposes of this unconventional post, I'm going to paste a snippet of the scene here and explain what in the name of Jesus, Whitmore's Disease is.
'Hovering around the corridor, he missed his door and drifted to Georgina’s. It was locked, which was unremarkable. She was supposed to be in Thailand then, so perhaps she locked it in case of burglars. But then, he contemplated, she never trusted locks and was never paranoid enough to be persuaded to alter her habits. He thrust his hand on the door, his legs giving way as he summoned the last ounces of his energy reserves to prop himself up. ‘Gina? Are you in?’ He said sleepily. ‘Yes, Arch. I’m here.’ Her voice was slightly off and he might have heard her coughing through the door. Coughing. Is she alright? Anyway, he was too tired to make a sound judgement. Sleepless on the aircraft and burdened with the responsibility of dragging the luggage for two floors were sufficient in blunting his senses. The cough might be a deception, but so shall Georgina’s response. It sounded real enough anyway. His ears must be deceiving him. Climbing up his bed, he undressed and threw a blanket unceremoniously on top. Instead of dwelling into the unpleasantries of life, his dreams took him to uncharted terrains as the slender figure of Gina appeared under her halo, standing by his side. They ran, ran and ran. The untamed swathes of wilderness that awaited them. The flocks of googly-eyed flamingos and colourful songbirds soaring in the sky with them. Peter Pan and Wendy. Arch and Gina. These dreams would sometimes pop intrusively into his mind long after he got married. Dreams that drowned him in his tears.
‘Gina, are you alright?’ He woke up that night at eight p.m. Jet-lag. How am I supposed to sleep tonight? He groaned. Dressed in revealing bathrobes, he wanted to give Georgina a surprise, only to be given one. The door was eerily ajar. Peering into the room anxiously, he could see her splayed on the bed. A dead robin pricked by the thorns of a rose. Gasping for breath, she called for his name. Awash with nervousness, Archie slammed the door open and rushed to her side, trying to empower himself with doctorly calm. There were scrunched, blood-stained tissues strewn on the floor. The heart-wrenching fits of cough ensued, manifesting in uncontrolled abdominal spasms. They echoed across the hallway, to the house and the wider city. ‘Gina…’ He trailed off, for apart from calling out her name, he did not know what to do. His mind was blank. What happened to her? She is going to be fine. Marigold’s voice informed him. She had always been the voice of his conscience.
After a few minutes, she turned unconscious. Archie figured out what happened. It was a matter of whether he wanted to figure it out. Trained in internal medicine, he was unsure of whether he could remain impartial and unaffected should emotions meddle his clinical judgement. This was no ordinary patient. This was Gina. His Gina. He checked her pulse, resisting the fidgeting of his fingers. It was perilously high, in the high 90’s to over a hundred. It was hard to tell, since his maths ability was dented by his bouts of catastrophising. Breathing was erratic. Hyperventilation. Gasping for breath as if she were drowning. He called for an ambulance as he stroked her pale cheek tenderly. No, Gina. No, don’t. She will be fine, Archie. Georgina will be fine. No, Marigold. I’m scared, Marigold. Please, Gina. He pleaded to whatever God there was. Please don’t take her away from me. God almighty, I know you have always hated me. Trampled me like a doormat. But please, for this is my only request. Let me suffer for her.
Streaks of dark hair fell from her scalp, landing swiftly on his lap as he knelt beside her, fighting back tears, beady droplets of putrid liquid that formed pools on the floor. The desolate quietness of the room offered no consolation. Magpies landed on the window pane outside, singing their jolly tunes which translated as their version of mocking laughter. Symphonies of taunting derision arose from other birds that fluttered past. Right at the corner of his eye, resting on a low bough, was a fiery beastie. The robin he knew of ever since he was in the womb. It stood resolutely on the edge, refusing to take flight.
The ambulance arrived. A stretcher emerged, alongside a few paramedics. The nearest hospital would be UCLH, which was a few blocks away. Archie bit his lower lip as they lifted his fiancée onto the stretcher and wheeled her out of the house. At that point, despite his being a person famed for his medical expertise, he suffered from a dearth of options. Dearth of confidence; dearth of sufficient expertise to tease out what was going on. It could be a hidden disease that she didn’t tell him about, notwithstanding their engagement and that they swore to be together regardless of how trying the circumstances were. He even called Crestwood Manor’s bluff when Rose threatened to strike him out of their will. Might it be an acute infection? Meningo-encephalitis and septic shock – a sinister combination that is Satan’s perfect sidekicks. The medically plausible explanation for people taken away from their sleep. Good. This was the punishment meted out by God. Not only to Georgina, but him. He clasped her hand in his as he saw her wearing an oxygen mask on the ambulance. ‘Remember the jellied eel, Gina? Do you remember how much I hated it? Do you remember how we met? The time when I almost wore cologne? Gina, please tell me you remember it.’ She did not respond.
For the next few days, Georgina lapsed in and out of consciousness. A pallid countenance accompanied by clammy, lifeless limbs showing early signs of necrosis: deprived of blood, tissue started to die, appearing as dark as lumps of charcoal. There were times when she would grasp Archie’s hand tightly, putting the other hand on top. She was intubated and placed in intensive care. Archie had access privileges as a doctor, thus being saved the indignity most visitors had to face, including being denied access into the ICU. Archie whispered tearfully next to her ear, ‘Don’t worry. Trust me, I’ll make you better. You will be better. I will marry you as soon as you get better.’
Her apologetic eyes glimmered in tears, highlighted by a glint of golden-silver from the overhead lights. He convinced himself to interpret matters in a different light, for he knew. The other beds were occupied by individuals transgressing demographic boundaries, yet united by one stroke of similarity – their songs would end here. Their salvation would be their demise. It would take more than God’s mercy for Georgina to be wheeled out alive. This was the point where the beacon of hope dissolved bleakly in the canvas of dark and grey. Archie, don’t force yourself. Marigold pleaded in his head. Please, don’t say that, Marigold. Please don’t. He refused to succumb to fate even when he knew what awaited him.
At least Georgina was still there- her physical self and internal consciousness laid bare on the bed. The wisp of an existence. Her brown curls reminded him of the first time they met. The awkward moment when she kissed someone else. Unable to speak because of the tube, Archie was in bliss since she still recognised who he was. She smiled till her muscles ached whenever she saw his face, taut from crying, in the ward. It would be more dreadful and unbearable should it come to the inevitable stage of retrograde amnesia, where her encephalitis would rage a war against the feeble cortex, eroding the happy memories that gave them life.
‘Doctor Crestwood, the culture results are back.’ The trainee’s voice quivered in uncertainty, as if he doubted the veracity of the situation. ‘Come on, I’m listening agog!’ Archie raised his voice impatiently. He was normally tolerant of juniors but when it concerned more than a mere name on a file, his responses became terse and unrelenting. ‘Spit it out!’ The junior shrivelled up in fear and handed him the report. ‘They’ve tried everything. Pneumococci, Pseudomonas, I mean…the whole range. But nothing. Then, Dr Jane tried the rarer ones since the patient travelled to Southeast Asia. They confirmed it’s melioidosis. Burkholderia pseudomallei positive.’ Archie’s voice was stiff and coarse, vehement in protest. ‘This is impossible. Get your facts right, Peter. Melioidosis usually leads to pneumonia, not meningitis. Very rarely encephalitis. Very rarely septic shock. This patient has the whole sodding range.’ He stressed on the term ‘very rarely’, hoping to convince himself otherwise. The outcome was too hard to bear. ‘Sorry, Dr Crestwood. Her vitals are deteriorating. She’s got serious pulmonary oedema. The LFT’s are deteriorating as well. Once the liver is down, everything follows.’ He handed him further sheets of evidence, all being results from tests performed on the same day. The X-Ray was shown electronically – a blighting flash of black and white. Usually, apart from the bone and heart, one disgusted the whitish bits. Here, the electronic white glared at him ferociously throughout the lungs. Streaks of white emanated from the heart, following the major vessels and their branches. Even the heart was slightly enlarged – a sinister sign of heart failure. But then, as he was more and more convinced that she could not make it, he persuaded himself with the complacent knowledge that Peter was a mere registrar. Peter was his student. Just a student without adequate clinical experience. Just a student whose opinion wouldn’t matter in such situations. Taking his word for granted would mean dire consequences for Georgina. No, he refused. No, he had an alternative verdict. She would pull through. Give oxygen. Give fluids. Give the heck that would defy God’s will!
As he paced up and down the ICU ward anxiously, grappling with his emotional turmoil, he heard it. Arch. She was calling him. Her voice was no more than a whimper. Archie regarded her crestfallenly. Sickly and frail, her frame shrank immensely from the last time he saw her. He could see her hands glowing in sinister blue. Struggling to breathe, she beckoned him forward. Don’t cry in front of her. You will only make her scared. He muttered to himself as he knelt by her side. A loyal knight. Clasping her outstretched hand in his, squeezing it warmly, he bent forward and kissed it. ‘Gina, I love you.’ He said steadily. Behind the veneer of serenity in his voice, was a brain-whacking hurricane. She smiled. ‘Arch, thank you.’ She said feebly. Her sweet smile gradually faded. The dimples dissolved into the slab of flesh. The corners of her lips returned to their original positions; the hint of vividness dissipated as the semi-circle morphed into an oppressive flat line. Archie’s eyes never left her. He watched her close her eyes, for the very last time.'
The crux of the issue is - what did Archibald mean when he said Melioidosis isn't likely to manifest systemically? What is Burkholderia pseudomallei? To commence, let's just say it's an infection caused by a type of bacteria called Burkholderia pseudomallei. For those of you who reside in the tropics, including South East Asia and northern Australia (e.g. Northern Territory and Queensland), the disease is more prevalent. For instance, Thailand alone has 2,000-3,000 new cases each year. [1, 2] It does not usually pass the lips of doctors in the UK, as far as I know. The time when I first learnt of this microbe was when I was on attachment to the TB Clinic in Hong Kong, when one of the respiratory medicine specialists mentioned, in passing, the possibility of the patient having Melioidosis instead of tuberculosis or other forms of atypical pneumonia. However, understanding more about microbiology, as well as key topics in tropical medicine, becomes more and more important. After all, we are all subjected to the forces of globalisation. Aviation is at its height of power (well, COVID-19 temporarily shut airports and airline businesses down, but I firmly believe the future lies within the skies). People travel from one destination to another within much shorter periods of time. There is also a general trend of having 'holiday homes', where individuals purchase property overseas and spend a significant portion of their time per year in that country. Thus, as medical professionals, we are more likely to come across individuals presenting with all kinds of illness. Travel history has become indispensable in history-taking. Moreover, the UK is a multiracial country. Diversity is celebrated and we have people coming in from different countries. All the Brexit fiasco aside, inbound immigration is still strong. This also augments the need to understand more about tropical illnesses, even diseases which are endemic to a certain region. As a lesson from COVID-19, the disease could originate China and spread to the rest of the globe within a very short period of time. As clinicians, there is no place for complacency.
There are multiple routes of transmission. It can be spread through the inhalation or ingestion of contaminated particles or aerosols, or via direct contact. Individuals with skin wounds who travel or live in tropical areas are the most susceptible. This especially applies to farmers who work in rice paddies, which are quite common in countries such as China and Indonesia. Contaminated water containing the microbe interacts with established skin wounds, leading to subcutaneous infection. Speaking of water, near-drowning and drinking unfiltered tap water are also risk factors. It has to be noted that in many tropical countries, drinking tap water is not recommended. A Taiwan study has even suggested that climatic factors, including the arrival of the typhoon season, are capable of influencing the transmission of the microbe in endemic regions. This can be traced to the gradual permeation of contaminated aerosols. [3-5]
[8] - Chest X-Ray of patient with Acute Melioidosis Pneumonia. On the Chest X-Ray, we can see multiple regions of bilateral infiltrates, with predominance on the left (both lobes are affected) (remember, in radiology, almost everything is flipped). On the right, the consolidation covers mainly the upper lobe, assuming dominance over paratracheal and lateral aspects. I also suspect mediastinal lymph node enlargement (in the middle of the chest) - however, owing to resolution issues and the fact that I can't accurately measure the width of the mediastinum (the central, lighted-up strip), this remains unproven. As a minor note, at the bottom-left hand corner, there is blunting of the costophrenic angle which can be suggestive of a small pleural effusion.
In terms of clinical manifestations, we can divide them into two categories - localised and systemic. In medicine, 'localised' means 'specific to a particular location'. For instance, pneumonia caused by pneumococci can be known as an infection which is localised to the lungs. Systemic infections, however, involve multiple organs. If an infection gets serious, like when the microbe travels across the bloodstream, patients can develop a condition called sepsis. Sepsis is defined as the onset of 'life-threatening organ dysfunction caused by dysregulated host response'. [6] The focus is on the immune system's response to the infection, not necessarily the infection itself. Localised Melioidosis can manifest as skin abscesses, local inflammation and, more concerning, pneumonia. This is particularly true in patients with a condition called cystic fibrosis. It is a condition involving a mutated version of the gene CFTR. Patients have thick mucus and experience recurrent infections due to the increased retention of microbes. Within the realm of lung diseases, melioidosis can be acute or chronic, dependent on host response and general immune status. Moreover, the severity of the disease can be dependent on its spread. Systemic infection would involve the development of abscesses in different organs, including the liver and spleen. Organs which are less commonly involved include the central nervous system, joints and bones, as well as the cardiovascular system. A case report shows a 55-year old female farmer in India presenting with multiple abscesses in the spleen and high-grade fever. [7, 8]
Treatment is different from other types of pneumonia. There are two phases: (a) initial, intense phase, and (b) maintenance/eradication phase. If you think about DOTS (direct-observed therapy sessions) for tuberculosis, you can unearth a great deal of similarities between the two. The overarching aim of the initial phase is literally keeping the patient alive in the fury of sepsis. The eradication phase, on the other hand, as the name suggests, features our attempt in removing any residual microbe in the patient's body. For (a), we use intravenous injections meaning that we inject the drug straight into the bloodstream. This is the best way to achieve a more rapid and complete response. We use strong antibiotics such as Ceftazidime (3rd generation cephalosporin) and meropenem (ESBL; only reserved for severe cases). In the world of microbiology, meropenem and its friends (imipenem and carbapenem) are the strongest weapons in any clinician's set. If a microbial strain is resistant even to them, we can do nothing to defeat the microbe. Regimen (a) takes around 10-14 days. For regimen (b), we change the way of administration slightly. Seeing that patients have to go back to school or work, it's better to administer oral tablets. A formulation called co-trimoxazole (alternative: co-amoxiclav) taken for not less than 12 weeks is recommended. However, it has to be noted that co-trimoxazole should be proceeded with caution since it can cause severe skin reactions and systemic symptoms. [9, 10]
Medicine is an art. I've always loved applying what I've learnt from medicine to my novels. This also tells us that as medics, it is crucial to learn more about so-called 'tropical' diseases. In the far past, it might not concern clinicians in the UK much. However, as travel, globalisation and immigration become new buzzwords, it's time for us to get to grips with such deadly diseases. There is, unfortunately, no space nor time for complacency.
[1] Araúz AB, Castillo K, Santiago E, et al. (2020). Geographic Distribution and Incidence of Melioidosis, Panama. Emerging Infectious Diseases, 26(1), 118-121. https://dx.doi.org/10.3201/eid2601.180870.
[2] Punyagupta S. Melioidosis. Review of 686 cases and presentation of a new clinical classification In: Punyagupta S, Sirisanthana T, Stapatayavong B, editors. Melioidosis. Bangkok, Bangkok Medical Publisher, 1989; 217–229.
[3] Food and Water Safety | Travelers' Health. CDC. (2020). Retrieved 19 November 2020, from https://wwwnc.cdc.gov/travel/page/food-water-safety.
[4] Barnes JL, Ketheesan N. (2005). Route of Infection in Melioidosis. Emerging Infectious Diseases 11(4): 638–639. doi: 10.3201/eid1104.041051.
[5] Chen PS, Chen YS, Lin H, et al. (2015). Airborne Transmission of Melioidosis to Humans from Environmental Aerosols Contaminated with B. pseudomallei. PLoS neglected tropical diseases, 9(6), e0003834. https://doi.org/10.1371/journal.pntd.0003834.
[6] Singer M, Deutschman CS, Seymour CW, et al. (2016). The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 315(8):801-810. doi:10.1001/jama.2016.0287.
[7] Chinnakkulam Kandhasamy S, Elamurugan TP, Naik D, Rohith G & Nelamangala Ramakrishnaiah VP. (2020). Systemic Melioidosis With Ruptured Splenic Abscess. Cureus, 12(5), e7956. https://doi.org/10.7759/cureus.7956.
[8] Currie B. (2003). Melioidosis: an important cause of pneumonia in residents of and travellers returned from endemic regions. European Respiratory Journal, 22(3), 542-550. https://doi.org/10.1183/09031936.03.00006203.
[9] Dance D. (2014). Treatment and prophylaxis of melioidosis. International Journal Of Antimicrobial Agents, 43(4), 310-318. https://doi.org/10.1016/j.ijantimicag.2014.01.005.
[10] Bernstein LJ, Cooper J. (1978) Co-trimoxazole and Stevens Johnson Syndrome. The Lancet, 311(8071), 988. https://doi.org/10.1016/S0140-6736(78)90275-1.
[11] Cacoub P, Musette P, Descamps V, et al. (2011). The DRESS Syndrome: A Literature Review. The American Journal Of Medicine, 124(7), 588-597. https://doi.org/10.1016/j.amjmed.2011.01.017.
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