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The medical response to trench nephritis in World War One RL Atenstaedt1

1National Public Health Service for Wales and Institute of Medical and Social Care Research (IMSCaR), University of Wales, Bangor, UK

Around the 90-year anniversary of the Battle of the Somme, it Around the 90-year anniversary of the Battle of the Somme, it is important to remember the international effort that went is important to remember the international effort that went into responding to the new diseases, which appeared during into responding to the new diseases, which appeared during the First World War, such as trench nephritis. This condition the First World War, such as trench nephritis. Historical arose among soldiers in spring 1915, characterized by sources show that an epidemic of ‘trench nephritis’ during breathlessness, swelling of the face or legs, headache, sore may have been hantavirus induced, which was throat, and the presence of albumin and renal casts in urine. first isolated in 1976 from the lungs of the striped field mouse It was speedily investigated by the military-medical Apodemus agrarius.1–3 authorities. There was debate over whether it was new condition or streptococcal nephritis, and the experts agreed SYMPTOMS AND SIGNS that it was a new condition. The major etiologies proposed In the spring of 1915, Medical Officers began to receive were infection, exposure, and diet (including poisons). reports of a new actor emerging on the battlefields of France. Research pointed to the origin of the disease as being On 4 April 1915, Lieutenant-Colonel FA Symonds, Com- infective rather than toxic, but no definite cause was manding Officer of No. 1 Casualty Clearing Station, 1st discovered. A number of labels were given to the disease, Army, reported in his diary: ‘Dispatched by road 6 cases of including war nephritis. However, trench nephritis was the albuminuria to No. 10 Stationary hospital, St OMER. There one used most widely. Trench nephritis was a serious is at present a slight outbreak of acute nephritis which we are problem for the Allies, leading to 35 000 casualties in the attempting to trace cause to.’4 A couple of days later, he British and 2000 in the American forces. There were also added: ‘The small epidemic of albuminuria which has come hundreds of deaths. The condition was treated in line with under my notice is causing considerable interest. Here is pre-war regimens designed for acute nephritis. No significant marked oedema, severe albuminuria and a rise of tempera- preventative methods were implemented for trench tureyWhat is this disease and what is its cause?’4 A special nephritis, as there was no consensus regarding causation. correspondent went on to describe the most common The medical response to trench nephritis was largely symptoms of this affliction: ineffective, with medical commentators recognizing that there had been a lack of medical progress. Its outstanding phenomena are those commonly resulting Kidney International (2006) 70, 635–640. doi:10.1038/sj.ki.5001618; from sub-acute nephritis, including general dropsy and published online 5 July 2006 the presence of albumin and renal casts in the urine. In KEYWORDS: World War I; nephritis; hantavirus; military personnel most cases the onset of these phenomena seems to be rather sudden, but a history of a few days precedent sore throat or bronchial catarrh can commonly be obtained.5 The main symptoms were breathlessness, swelling of the face or legs, headache, and sore throat.6 Not surprisingly, the discovery of a previously unknown condition proved to be controversial. There was debate over whether it was a new disease or one already in existence, namely streptococcal nephritis. The idea was attacked by clinicians on the home front. For example, Dr R Saundby7 wrote from Birmingham: Correspondence: RL Atenstaedt, Institute of Medical and Social Care Research, University of Wales, Ardudwy, Normal Site, Bangor, Gwynedd LL57 Sir – I do not know who is responsible for labelling a 2PX, UK. E-mail: [email protected] streptococcal nephritis a ‘new disease’ but it seems to me Received 17 February 2006; revised 9 April 2006; accepted 18 April strange to do so. It has been well known to me – and I 2006; published online 5 July 2006 wager to many other clinicists – for many years that

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nephritis may follow non-specific sore throatsyMore- operate upon a larger area of the body so as to include the over, it is a familiar fact that streptococcal infection may kidneys as well? The vessels of these organs are extremely give rise to nephritis...so there is not only nothing new in sensitive to changes in temperature.14 this particular disease, but it is merely an illustration of a quite well known pathological process. He went on to recount specific examples where nephritis had definitely been attributed to exposure. For example, the However, this letter failed to generate further debate in the Germans had reported that the disease occurred in a medical press. 8 particular division of their army among those soldiers that A few months later, Lieutenant-Colonel N Raw reported had slept on bare pavement, but not among those who had on five cases of the ‘novel’ condition, which he termed ‘trench lain on wooden boards.14 nephritis.’ In his opinion, ‘trench nephritis’ was an apt name Diet was also assigned a role in the causation of trench because there, for the first time, seemed to be a clear nephritis. Captain JW McLeod and the Frenchman Major P association between the disease and conditions. Ameuille15 conducted extensive research on the connection It is significant that trench nephritis soon provoked active between diet and trench nephritis, concluding that the investigation by the medical authorities. Sir William Leish- vitality of the men’s kidneys could be lowered by their low man, Pathological Advisor to the British Expeditionary Force, vitamin C intake during wartime. This, in turn, led to kidney took a keen interest in trench nephritis. As early as May 1915, failure, as a consequence of the excessive metabolic effort he had discussed the recent series of cases of nephritis with Sir 9 required to process a high-protein diet. However, Captain William Beveridge, head of army sanitation services. About WL Brown16 disagreed with their argument, believing it was 100 of these had been reported during the previous month in improbable that 180 g of protein could cause nephritis in a scattered units. Leishman noted: ‘from the medical point of group of otherwise healthy men. view, they appear to present a number of unusual features, Another idea circulated during the war was that trench notably the rapid way in which they clear up when admitted 9 nephritis might be owing to the consumption of dietary to hospital.’ A couple of weeks later, the consulting physician, poisons. As a result of research undertaken, Bull17 concluded Colonel John Rose Bradford, called to see him.9 Bradford was 10 that trench nephritis was caused by excessive chlorine in the a trained physician and physiologist, and an eminent renal drinking water, combined with the harmful conditions of specialist, having performed important early experimental 11 trench warfare, such as exposure. Another poison, proposed work on this organ. For these reasons, Bradford’s opinion, 14 9 by Oliver, was dietary lead. Oliver had analyzed the urine of that trench nephritis was a new condition, was authoritative. 29 of his patients, finding lead in about half. He had tried to This burst of activity among those high up in the military- locate the source of this metal. An examination of their bully medical hierarchy was soon mirrored on the home front. In beef ration had yielded traces of lead, but not enough to November 1915, an editorial in the Medical Press & Circular cause illness. Metallic scrapings from the inside of the men’s described trench nephritis as an ‘epidemic’ and noted its cooking pans had also tested negative for lead. Lastly, he had distinctive clinical features, including the frequency with tried the effects of sterilized and non-sterilized, chlorinated which occurred, its great variability in and non-chlorinated water on the tins, but none had caused duration, a tendency to remission and relapse, and an 12 any leaching. He then hit upon a brilliant idea – maybe lead ultimately favorable prognosis. A discussion on the ‘new was escaping from bodily retained bullets and shrapnel? In epidemic,’ involving a number of influential experts, was held 13 support of this theory was the fact that he had found lead in at the Royal Society of Medicine in February 1916. The the urine of a soldier with shrapnel in the knee and shoulder, opinion of Sir , Regius professor of medicine at as well as other wounded men that he had examined.14 Oxford, that trench nephritis was a novel condition, was Other commentators were more explicit in linking trench widely endorsed. This forum’s acceptance of the condition nephritis and trench warfare. AG Fleming et al.,18 suggested gave it legitimacy. that most of their sufferers had drunk trench or shell-hole water. Sundell and Nankivell19 postulated a relationship SEARCH FOR A CAUSE between the nephritis and inhalation of irritant gases, and The major etiologies debated for trench nephritis, both in opened up the corpses of soldiers to learn more about the France and the UK, included infection, exposure, and diet disease process. On examining these post-mortem specimens, (including poisons). Sundell and Nankivell discovered that they showed a diffuse Writing in the BMJ, Sir Thomas Oliver14 firmly attributed intra- glomerulonephritis; similar changes had blame to exposure, as, in his experience, many combatants already been observed in chlorine gassing. Maher20 proposed associated the disease with the effects of trench warfare. He that pathological features of trench nephritis included used the analogy of rheumatism to explain why exposure glomerular ischemia, capilary thrombi, endocapillary pro- could potentially be the cause: liferation, and frequently epithelial crescents, suggesting an underlying . Is there any reason why the conditions which give rise to There were those who believed the disease could only be the joint and muscular pains should not in some instances caused by a specific organism, which, with luck, could be

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isolated and cultured. In a memorandum circulated in July Concurrent with speculation and debate on the etiology of 1915, Colonel S Westcott, DDMS 1st Corps, noted: ‘The trench nephritis, investigations were being carried out into specialists who are investigating epidemic dropsy are inclined the condition. A number of these were pursued on a small to attribute its cause to specific infections such as scarlet scale, by individual researchers in the field or in laboratories. fever, measles, German measles, tonsillitis etc.’21 Dr JC In 1915, a special inquiry into trench nephritis was opened, McWalter, writing in the same year, reported locating the called the Committee on War (Trench) Nephritis. After organism Balantidium coli in the urine of nephritis sufferers. 2 years, another body, the BEF Nephritis Sub-committee, was As most of the cases had received an anti-typhoid inoculation established in France. The Committee on War (Trench) before going to the front, he postulated that the disease might Nephritis, sponsored and funded by the Medical Research be a modified form of enteric fever.22 In October 1915, Committee (MRC), mounted surveillance into the condition Captain RG Abercrombie suggested that the cause of trench and also investigated epidemiological factors. It collected nephritis might be influenza, only to backtrack when he was together a number of cases in France for observation by unable to find this organism in the urine. He therefore played Bradford, and organized biological and chemical examina- safe, stating: ‘the writer is inclined to the belief that the tions by Major Wolf at the Base Hygiene Laboratory.26 In the disease is an infection by a definite organism, the nature of UK, it arranged for cases to be investigated by a team headed which is at present undiscovered.’23 by Brown27 at St Bartholomew’s Hospital. Brown’s team The majority of doctors considered a mixture of published a preliminary report in July 1915, arguing in favor environmental, dietary, and infectious causes for trench of an ultramicroscopic virus as the infective cause of trench nephritis. One of this group, Major BW Hogarth, a 49-year- nephritis. It was also influential, as the DMS, 1st Army, old general practitioner and a former territorial force specifically mentioned that he had received a copy from combatant,24 described his investigation of 75 cases of Beveridge.21 albuminuria in his division in France, all men who had However, not everyone agreed that a filter-passing virus spent time in the trenches.25 A mature doctor, with extensive caused trench nephritis. For example, Lieutenant RL clinical experience, it is not surprising that he first examined Thornley of No. 12 Mobile Laboratory examined blood the influence of exposure. Most of the soldiers had been samples taken from trench nephritics admitted to his severely affected by this, although he related (perhaps light- Casualty Clearing Station by incubating them on agar heartedly) that one case (No. 12) had ‘not been exposed medium for 5 days.28 Slides were then stained with carbol- nearly so much here as at home.’25 In 17 cases, he was able to fuchsin and examined under a microscope. He discovered link exposure to the onset of nephritis, although it was that every one of the 27 cases showed the presence of an excluded in a further 15: identical coccus. He inoculated a rat and a guinea-pig with an emulsion of this organism. The rat became sick and then In the remainder of the cases there was generally a history recovered within 24 h, although the guinea-pig seemed of excessive sweating on the march up to the trenches, or unaffected. On dissection of the rat, its spleen was enlarged some other form of exertion, followed by standing still or and he was able to recover his microbe from it. However, he lying in their damp clothes or lying on cold ground was unable to clearly link the presence of the coccus with the without blankets. The sudden and great alteration in disease. In fact, in the same month that his article appeared, surface temperature under these circumstances appears to the Commanding Officer of No. 2 Mobile Laboratory me to be the great predisposing cause of the illness.25 reported that Leishman had told him that the ‘so-called Micrococcus nephritis found...byyThornley has proved to be In his opinion, therefore, surface temperature was significant the Streptococcus faecalis or Enterococcus.’ 29 It was therefore a in etiology. However, Hogarth25 also considered dietary contaminant and not the true organism of the disease. factors in the etiology of the disease. Ultimately, he believed The second body to research trench nephritis, the BEF that nutrition was an unlikely cause, because of the variability Nephritis Sub-committee, was founded in February 1917. of the soldiers’ diet. He also ruled out alcohol consumption, Basing its research at No. 46 General Hospital, Etaples, it as total abstainers had also succumbed. He examined the recruited with the MRC Captain JA Wilson to fully investigate drinking water, supplied to the troops on carts, as some of his the bacteriology of trench nephritis.30 In the official report of men had reported that this tasted ‘funny.’ However, virtually his investigations, published in 1918, Wilson stated that he all the men took their water as tea, rendering the water safe was able to isolate many different microbes from the urine of for drinking. In addition to exposure and diet, it is significant these patients.30 In his estimation, however, these organisms that Hogarth25 also examined an infectious causation for were saprophytes and not related to the disease process. The trench nephritis, although he failed to discover any link blood had also proven sterile and smears taken from the between the condition and other infections, including scarlet tonsils produced no interesting organisms. Lastly, throat and enteric fevers. He finally concluded that as a series of swabs from patients and 30 healthy volunteers were cultured. cases, nephritis could be most aptly compared with The flora in the trench nephritis cases was similar to the pneumonia, which, although a specific disease, was predis- healthy controls, except for a higher incidence of streptococci, posed to by chills. although complement fixation directed against these organi-

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sms proved negative. In their final report, the MRC simply investigation for the Nephritis Sub-committee. His final stated that trench nephritis was an infective disease caused by report concluded: ‘Taken together, all the results of this work an unknown organism.31 Interestingly, they added that it was pointed clearly to the origin of the disease as being infective ‘probably propagated by lice or other vermin under trench rather than toxic, but no further light has been obtained conditions,’ without qualifying this statement.31 upon the question of the nature of the infection.’32 This Another series of experiments conducted in France was became the consensus view in the medical ranks. In June concerned with investigating the relationship between trench 1918, at a meeting of the Medical Investigation Committee, it nephritis and albuminuria, the cardinal sign of a weakened was decided to stop further research on this disease.9 kidney. In a paper published in September, McLeod, along with his collaborator Ameuille, noted the large number of LABELLING cases of acute nephritis in the British army and stated: When the disease first appeared, various names were attached to it such as ‘acute nephritis,’ ‘epidemic nephritis,’ and ‘trench All this points to one of two things – either an infectious kidney.’33 Gradually, the term ‘trench nephritis was adopted.’8 agent which is afforded particular opportunities owing to However, some authors wrote to the medical press, disagree- the intermingling of large bodies of men and so is able to ing with this label. For example, writing in August 1916, attack a large number of susceptible individuals who in Abercrombie34 suggested that the term was misleading, as their everyday life had no contact with such infection, or many of the affected soldiers had never been in the trenches some conditions associated with trench warfare which put at all. Furthermore, Abercrombie stated that use of this label an excessive strain upon the kidney.15 ought to be discontinued and the more general ‘war nephritis’ used in its place. This had some success; the The kidney could experience strain in one of two ways. It MRC used the term ‘war nephritis’ in their official report on could be secondary to cold and chills and an alien diet, or the the disease.30 However, the condition continued to be called organ could sustain damage by coming in contact with ‘trench nephritis’ by most doctors in the field and on the circulating bacterial toxins. If the former mechanism was home front. operating, it should have been possible to find symptomless albuminuria where nephritis was most rife – among British THE THREAT troops in the trenches. To investigate this, McLeod and According to the Official History of the War –Medical Services, Ameuille surveyed the incidence of albuminuria in five classes there were approximately 35 000 admissions for trench of troops: Class 1, 1861 French troops, territorial infantry just nephritis in the BEF during the conflict.35 More importantly, returned from the trenches: 1.66%; Class 2, 2220 British 95% of these cases occurred in front line men.36 For this troops examined at a divisional barracks: 4.8%; Class 3, 311 reason, the disease had a small but significant impact on the British troops who had spent a long time in the trenches Army’s manpower. Additionally, the US forces reported 2002 during the coldest part of the winter: 3.53%; Class 4, 2096 cases of nephritis from April 1917 to the end of the war.37 men living in billets in conditions similar to those found at Trench nephritis was initially viewed by many as a home: 2.91%; Class 5, 553 men recently recruited from relatively mild disease, with a mortality numbering only a England and in heavy training: 10.12%. The most surprising few percent, unlike the more serious nephritis that had been finding was the high incidence of albuminuria amongst seen in civilian practice before the War. A number of troops in heavy training in Britain. As trench nephritis was clinicians believed that the condition would resolve quickly rare at home, this seemed to disprove a connection between and was unlikely to compromise a soldier’s military value for asymptomatic albuminuria and nephritis, and suggested that an extended period. In total, there were 400 deaths in the BEF the frequent and prolonged exposures associated with trench owing to this condition,35 and the US forces reported only warfare did not produce degeneration of the kidney 115 deaths among their 2002 cases.37 independently of other causes. Furthermore, McLeod and In spite of low mortality from trench nephritis, of severe Ameuille termed the high level of albuminuria in training detriment to the war effort was the fact that patients often men ‘fatigue albuminuria’ and this explained the higher took a long time to recover. Writing in August 1916, incidence in the divisional men compared with those in the Abercrombie34 stated that he was unsure of the condition’s trenches, as the former were exercising more strenuously than long-term prognosis. To answer this question, he had traced the latter. The second significant result was the lower figure the clinical histories of 171 cases admitted to a ward in a base for the French troops compared to the British. McLeod and hospital in France.38 After undergoing treatment, 3% of the Ameuille concluded that this was owing to dietary factors, men died, 18% were invalided during the first period of with the average British soldier consuming protein in excess home treatment, 12% were invalided after returning to duty, of his bodily requirements, throwing greater strain on the but the majority (63%) showed no further nephritis. kidneys. Nevertheless, the average stay in hospital during the first To finally resolve the controversy over the link between period of home treatment was 89 days, a considerable period. albuminuria and trench nephritis, the physiological chemist Trench nephritis was the major nephrologic problem of MacLean and de Wesselow32 conducted an extensive World War I, accounting for 5% of medical admissions and

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more than 10% of military hospital bed occupancy at that designed to mitigate the effect of exposure in causing the time.20 kidney complaint. This economic consequence, superimposed on the loss of military manpower, no doubt provided a spur for tackling CONCLUSION the disease. It can be seen that the medical response to trench nephritis was largely ineffective. Medical commentators recognized TREATMENT that there had been a lack of progress. For example, an The Official History of the War – Medical Services admitted editorial in The Lancet, which appeared in September 1918, that no remedy had been found that could cure trench stated: nephritis.36 Therapy for the condition did not alter significantly from the disease’s first appearance in 1915 to yit often happens that knowledge of a new disease the end of the War. As its name suggests, trench nephritis was advances rapidly, sometimes with tiresome slowness, while recognized as organ-specific. In consequence of the general apparently the same amount of work is being put into it belief that nephritis involved an irritated kidney, secondary to by competent investigators. A strict example of this is toxic substances that poisoned this organ and not by direct given by war nephritis. The recent report of the Medical bacterial invasion,39 calming the inflamed organ seemed the Research Committee is of a negative character, throwing most logical option. Trench nephritis was therefore treated in little or no further light on the nature of the disease.43 line with pre-war regimens designed for acute nephritis. These involved removing the source of any poisoning, Beveridge also singled out this disease, writing: ‘There are still ‘resting’ the kidneys, and securing the action of the bowels problems of the late war left undetermined. Although the and skin in eliminating waste products.11 Medical authors incidence of nephritis declined in the last year of the war we generally recommended bed rest, a milk diet, and the cannot say that we have satisfactorily arrived at the aetiology administration of a weak diuretic. In trench nephritis, of the disease or have laid down adequate measures of 44 however, as there was no specific causative agent that could prevention.’ The medical profession failed to identify with be targeted, drug treatment was purely symptomatic.27 The certainty a causative agent, the Official History of the War – fact that no revolutionary therapy was developed is shown by Medical Services admitting: ‘The ultimate cause of war 45 the fact that the MRC report on the disease did not even nephritis has not been discovered.’ No preventative mention treatment.30 Dietetics (control of the diet) dom- measures could be put into effect for this reason, and no inates the related literature and there is no mention of ‘magic effective therapy was established. This was in spite of the bullets,’ only symptomatic pharmacology and physical setting up of a committee to research the condition in 1915 methods. and a further investigative commission beginning work in France in 1917. Although these bodies and the MRC seemed PREVENTION to have made some progress when they sponsored specific No significant preventative methods were implemented for research, there were many other investigations into the trench nephritis, as there was no consensus regarding disease that were haphazard and covered the same ground. causation. Some doctors postulated that the disease might No new knowledge was gleaned after WL Brown’s study at be owing to a filter-passing virus, although this was never St Bartholomew’s Hospital in 1915. proven and no vector was found for the organism. This meant that there was no agent that could be targeted by the ACKNOWLEDGMENTS 40 I thank my colleagues at the Institute of Medical and Social Care military-medical authorities. Brown believed that trench Research, University of Wales Bangor, and the National Public Health nephritis resulted from exposure after exertion. He therefore Service for Wales for providing support, particularly Professor Ian recommended that men should be warned against cooling Russell and Dr Sandra Payne. I also thank the Wellcome Trust for down too quickly after removing their packs and belts at the providing me with a grant to visit archives. This research formed part end of a march. His investigations had shown that the best of a DPhil at Oxford University, supported by Professor Paul Weindling. procedure was to fix a thick woolen scarf around the men’s waists, allowing cooling to take place slowly in the kidney 41 REFERENCES region. Lieutenant-Colonel PH Henderson also noted that 1. Bugert JJ, Welzel TM, Zeier M et al. Hantavirus infection-haemorrhagic cold and exposure, both of which, in his opinion, could lead fever in the Balkans-potential nephrological hazards in the Kosovo war. to trench nephritis, could be prevented by the use of hot Nephrol Dial Transplant 1999; 14: 1843–1844. 2. Lee HW, Lee PW. 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