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Abstract
We present a 27-year old British nurse admitted to the Kerry Town Ebola Treatment Unit, Sierra Leone, with symptoms fitting suspect-Ebola virus disease (EVD) case criteria. A diagnosis of Plasmodium falciparum malaria and heat illness was ultimately made, both of which could have been prevented through employing simple measures not utilised in this case. The dual pathology of her presentation was atypical for either disease meaning EVD could not be immediately excluded. She remained isolated in the red zone until 72 h from symptom onset. This case highlights why force protection measures are important to reduce the incidence of both malaria and heat illness in deployed military and civilian populations. These prevention measures are particularly pertinent during the current EVD epidemic where presenting with these pathologies requires clinical assessment in the ‘red zone’ of an Ebola treatment unit.
- INFECTIOUS DISEASES
- INTERNAL MEDICINE
- PUBLIC HEALTH
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Key messages
The focus in managing the current Ebola outbreak must be to manage Ebola itself, but other diseases remain endemic and must be considered.
These endemic diseases, including malaria, pose a risk to both native and non-native healthcare workers.
Working in Personal Protective Equipment in the tropical climate poses healthcare workers with an additional heat illness risk.
Understanding these risks allows healthcare workers to mitigate them so that they can continue to concentrate on patient care.
Case summary
A 27-year old female British nurse working for a Non-Governmental Organisation (NGO) was admitted to the UK military Kerry Town Ebola Treatment Unit (KTTU) in Sierra Leone with rigours, fever (39.9°C), fatigue, headache and myalgia, which met the case definition for suspected Ebola virus disease (EVD).1 She was a Caucasian red zone worker whose responsibilities included overseeing hygiene and the management of dead bodies in the red zone; she was therefore at high risk of contracting EVD and excluding this disease was critical. The ‘red zone’ is the area of the Ebola treatment unit where patients either suspected or confirmed to have EVD and therefore the virus itself are isolated. Healthcare workers in the red zone typically wear a complete system of personal protective equipment (PPE) that includes a waterproof suit, rubber boots, two or more pairs of gloves, a surgical hat and a visor or goggles.
The patient had been working in Sierra Leone for 6 months prior to her presentation. While visiting the UK 6 weeks earlier she had been admitted to hospital when suffering from an undifferentiated febrile illness and associated leucopenia. As EVD and other tropical infections had to be excluded she was extensively investigated, but no definitive diagnosis was reached and she spontaneously recovered after several days.
She returned to Sierra Leone 4 weeks prior to her KTTU admission and had been well from discharge in the UK to the onset of symptoms leading to this admission. She was taking daily doxycycline malaria chemoprophylaxis, but had forgotten to take her tablets for eight consecutive days prior to admission. She had no recollection of being bitten but aside from sleeping under a mosquito net she took no formal measures to prevent mosquito bites. On her return from the UK she undertook no formal reacclimatisation to the tropical climate and slept in an air-conditioned room. On the day prior to her first symptoms she had worked a 12 h shift that included several hours in the red zone where she wore full PPE. In spite of feeling dehydrated and exhausted she went for a three mile run and undertook an aerobically challenging circuit session. Although previously she had been athletically fit, this was her first intensive fitness training in several months and she said she found the level of exertion difficult. She estimated that in Sierra Leone she had drunk several beers a night, around four times a week. Aside from a 3-week-old itchy rash on her back that she had put down to the heat and sweating, she was otherwise well. She took no medications and had no known drug allergies.
On examination, she was afebrile, mobile and gave a relatively clear history. She appeared mildly dehydrated and was tachycardic (HR of 132 beats per minute), but her BP, capillary refill and RR were normal. Her judgement appeared impaired on admission as, despite being a healthcare worker, she had to be told not to walk barefoot in the red zone; the following day she was increasingly lucid. There was no evidence of ear, throat or skin infection, no lymphadenopathy, neck stiffness, jaundice or anaemia and her abdomen was soft and non-tender with no organomegaly.
Laboratory investigations on admission (Table 1) showed she was neither anaemic nor thrombocytopaenic, but was markedly leucopenic. The initial creatine kinase (CK) was elevated. Circulating liver enzymes and C reactive protein levels were mildly deranged and her renal function was normal. A malaria rapid diagnostic test (RDT) was positive for Plasmodium falciparum; quantification of the parasite load was impossible as EVD had not been excluded, which meant microscopy was potentially hazardous for the laboratory staff. A pregnancy test, RDT for dengue fever and an initial EVD PCR test were negative. A diagnosis of uncomplicated P falciparum malaria was made and an oral treatment course of Riamet (artemether and lumefantrine) was initiated.
Abnormal laboratory findings over the course of the patient's admission
On day 2 she had improved clinically although her ongoing tachycardia took a further day to return to normal. Despite her clinical improvement, her CK increased significantly with increasing derangement in her liver function and a hypophosphataemia, while the haemoglobin and platelet levels remained normal and leucopenia persisted. She described her urine as ‘the colour of cider’, in spite of increased oral fluid intake. A malaria RDT was again positive. Blood cultures taken on days 1 and 2 each triggered as positive after 24 h of incubation using a BacT/ALERT 3D 60 device (Biomerieux, St Laurent, Canada), but the FilmArray (BioFire, Salt Lake City, USA) blood culture identification panel for a standard set of common pathogens was negative with both samples. The FilmArray is a multiplex PCR system used by UK Armed Forces field laboratories as a rapid diagnostic system to identify pathogens from blood or other samples, for example, stool.
Although malaria remained the most likely underlying disease process, these findings were atypical for malaria alone and a second pathological process was considered. These laboratory findings would be consistent with a concurrent mild to moderate heat illness as well as early EVD, and a decision was made to keep her in the ‘suspect EVD’ ward of the treatment unit until the disease could be excluded with an EVD PCR at 72 h from symptom onset. She continued to be treated with Riamet and aggressive oral hydration. On day 3 her EVD PCR was again negative and her blood picture had generally improved. She was discharged to her parent organisation and a recommendation was made for aeromedical evacuation back to the UK for further follow-up and to facilitate her complete recovery.
Discussion
This case raises several important points about investigating and managing non-Ebola disease during the current Ebola epidemic in West Africa. First, it raises difficult issues about the medical force protection of healthcare workers engaged in fighting the EVD epidemic, specifically relating to how avoidable diseases such as malaria and heat illness are successfully prevented in an EVD endemic environment where the symptoms can fit EVD-suspect case criteria. Second, it raises questions relating to the risk to patients without EVD remaining in the red zone for three days until EVD can be excluded.
Malaria prevention and typical presentation
Malaria is contracted following a bite from a female Anopheles species mosquito already infected by the malaria parasite.2 The infection can therefore be prevented by pharmacological3 and non-pharmacological4 measures that are clearly described in the Public Health England guidelines.5 These are easily remembered by the mnemonic:
Awareness of risk
Bite prevention
Chemoprophylaxis
Diagnose and treat promptly
In travellers, an increased awareness of the risk from malaria and information about the disease improve compliance with bite prevention measures6 and chemoprophylaxis. Bite prevention includes reducing mosquito numbers, through inhibiting breeding or killing mosquitoes or by preventing the remaining mosquitoes from biting humans. The UK Armed Forces reduce mosquito numbers using insecticides distributed in the inhabited area by ‘swing-fogging’ and using insecticides inside buildings.7 ,8 Bite prevention is achieved by wearing clothes impregnated with insecticide, with sleeves and trousers covering the peripheries, particularly at dawn, dusk and during the night when the mosquitoes prefer to feed and using effective insect repellents.9 Sleeping in an insecticide-impregnated net prevents bites during sleep.10 ,11 Prevention of malaria transmission includes using effective chemoprophylaxis medication and by treating malaria within the population (the only mammalian reservoir of the main human malaria species is other humans). In Sierra Leone, the recommended malarial chemoprophylaxis regimens are Malarone (atovaquone and proguanil), mefloquine or doxycycline; for this operation, Malarone was the preferred choice of the UK Armed Forces. Directly observed therapy is recommended by the US military12 ,13 to ensure malarial chemoprophylaxis doses are not forgotten. They have also trialled text messaging to successfully confirm the daily ingestion of malaria chemoprophylaxis in a deployed setting.14 Many of these measures have been effectively implemented by the UK Armed Forces in the past15 and when these standards have slipped malarial outbreaks have occurred.16 ,17 In the case of this patient, as a civilian healthcare worker for an NGO, none of these measures were used, aside from the use of mosquito nets. These omissions in the medical force protection by the individual and her NGO put the patient at an unnecessarily increased risk of contracting malaria.
Malaria is a great mimic, as many of its symptoms are typically non-specific.18 Typically, symptoms commence with rigours that develop into fever, restlessness and vomiting. Additional acute symptoms include diarrhoea, headache, cough, fatigue and myalgia. Severe malaria, seen most often with P falciparum, includes impaired consciousness, convulsions, tachypnoea, pulmonary oedema, jaundice, haemoglobinuria and bleeding. Laboratory tests typically show normocytic anaemia, thrombocytopaenia, hypoglycaemia, renal dysfunction and hyperlactatemia. When microscopy is available higher parasite loads correlate with more severe disease; to evaluate treatment efficacy, the US Centers for Disease Control and Prevention recommend twice daily blood smears to quantify the parasitaemia for 2–3 days, and then daily until negative, or day 7 of treatment.19 In this patient no anaemia or thrombocytopaenia was seen on admission though these, as well as an elevated lactate and mild renal dysfunction were seen on days 2 and 3. Secondary infection can occur20 ,21 and the positive blood cultures in this case may have been due to this, but may also have been secondary to the malaria triggering a false-positive result itself.22 As the patient was clinically improving and no organisms were detected on MultiArray testing, no antibiotic therapy was administered.
Heat illness prevention and typical presentation
In the case of this patient it was postulated that she had suffered from a heat illness in addition to her malaria. There were a number of risk factors present that may have combined to increase her risk of a heat illness;23–26 these included inadequate acclimatisation, fatigue from working long hours, dehydration, physical exertion from working in the red zone in PPE and her personal exercise training and alcohol consumption. These combined with her malarial fever to cause a prolonged hyperthermia and resulting heat illness, as indicated by the resulting rise in her circulating levels of liver enzymes and CK, mild impairment of renal function and low phosphate. An understanding of the acclimatisation process and the physical degradation that working in PPE in the red zone can cause and would allow a more accurate risk assessment of heat illness risk. The patient was aware of no institutional policies that might minimise the incidence of heat illness; furthermore, she also described occasional collapses of staff working in the red zone at her normal location. In addition to the heat illness risk, a collapse in the red zone may increase the risk of a PPE breach and consequently the risk of exposure to the Ebola virus. Guidance on heat illness prevention and management is widely promulgated within the UK Armed Forces27 and acclimatisation and maximum red-zone working periods were in use within Sierra Leone for military healthcare workers at the KTTU.
The symptoms of heat illness overlap with those of EVD and malaria and are non-specific. They include weakness and fatigue, headache, diarrhoea and vomiting, tachypnoea, impaired judgement and coordination, dizziness, syncope and prolonged impaired consciousness. The biochemical profile includes an elevated CK, impaired renal and liver function, hyperlactatemia and myoglobinaemia. If more severe heat illness occurs, all physiological systems may be injured with consequent derangement in their markers of specific system damage.
Typical presentation of EVD
Early EVD is characterised by non-specific symptoms.28–30 The majority of patients present with fever, fatigue, headache, anorexia, arthralgia, myalgia and abdominal pain. A significant minority also present with vomiting and diarrhoea, chest pain, cough, sore throat, difficulty swallowing, hiccups and confusion, though other symptoms are also seen. The most frequent laboratory findings31 include a leucopenia, deranged liver function tests and prolongation of the prothrombin and thromboplastin times. Although described as a viral haemorrhagic fever, EVD frequently has no, or only mild, haemorrhagic symptoms and these are seen relatively late in the disease. Secondary infection has been seen but does not appear typical.32 The definitive test for EVD is a PCR that will inevitably be positive by 72 h, but is usually positive before this.
The risk caused by atypical malaria presentation
The combination of heat illness and malaria in this case created an atypical presentation that resulted in a longer stay in the red zone. Had the malaria occurred in isolation, with typical findings on laboratory testing and atypical findings for EVD, her symptoms would have been considered to be purely due to the malaria and a negative EVD PCR would have facilitated her discharge on day 1 from the red zone.33 ,34 The excellent hygiene drills at the KTTU and isolating nature of the suspect area minimise the risk of cross-infection, but cannot completely exclude it. Admission to the red zone, even if only the ‘suspect EVD’ area as in this case, for a patient without EVD infection, potentially exposes them to contact with EVD-infected patients or their bodily fluids. In this case it exposed the patient to this risk for at least 2 days longer than had she presented with typical malaria features and been discharged following her initial negative EVD PCR.
Conclusions
This case illustrates how inadequate force protection measures, at both an individual and corporate level, acting synergistically in this case to produce a clinical scenario that resulted in a patient becoming avoidably unwell with a life-threatening disease. Understanding the epidemiology of the health risks in an operational theatre allows the foresight to mitigate these risks and in general terms the UK Armed Forces are effective in achieving this. The operation to fight the EVD epidemic in Sierra Leone is different to the traditional operations executed by the Armed Forces as it is led by the Department for International Development, rather than the Ministry of Defence and it incorporates numerous NGO and Sierra Leonean governmental partners. Understanding that these partner organisations have different and potentially lower levels of corporate force protection measures in place and that individuals will vary in their discipline in adhering to guidelines may inform force preparation and operational planning, should further cooperative operations of this type be contemplated in the future.
References
Footnotes
Contributors All the authors contributed to the clinical care, background research and authorship. AC is responsible for the overall content.
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.