Diarrhoea during military deployment: Current concepts and future directions

Article (PDF Available)inCurrent Opinion in Infectious Diseases 25(5):546-54 · August 2012with201 Reads
DOI: 10.1097/QCO.0b013e3283582ebc · Source: PubMed
Abstract
Diarrhoea among military travellers deployed globally in conflict and peacekeeping activities remains one of the most important health threats. Here we review recent advances in our understanding of the epidemiology, laboratory identification, treatment and chronic health consequences of this multi-cause infection, and consider the implications for public health management and future research. The incidence of diarrhoea among deployed military personnel from industrialized countries to lesser developed countries is approximately 30% per month overall, with clinical incidence between 5 and 7% per 100 person-months. The risk appears to be higher early during deployment and is associated with poor hygienic conditions and contaminated food sources. Gaps remain in our understanding of the cause, given the lack of laboratory capability in austere conditions of deployment; however, recent advances in molecular methods of characterization hold promise in improving our detection capabilities. While there have been improvements in understanding of best treatments, more work needs to be done in transforming this knowledge into action and optimizing single-dose antibiotic treatment regimens. Finally, the under-recognized burden of chronic consequences of these infections is gaining awareness and reinforces the need to find effective preventive strategies. Our understanding of the epidemiology of diarrhoea is improving but further research is needed to fully account for acute operational-focused health impacts as well as the chronic enduring disease impacts. Improved field diagnostics would be of great value to support these efforts.
C
URRENT
O
PINION
Diarrhoea during military deployment: current
concepts and future directions
Patrick Connor
a
, Chad K. Porter
b
, Brett Swierczewski
c
, and Mark S. Riddle
b
Purpose of review
Diarrhoea among military travellers deployed globally in conflict and peacekeeping activities remains one
of the most important health threats. Here we review recent advances in our understanding of the
epidemiology, laboratory identification, treatment and chronic health consequences of this multi-cause
infection, and consider the implications for public health management and future research.
Recent findings
The incidence of diarrhoea among deployed military personnel from industrialized countries to lesser
developed countries is approximately 30% per month overall, with clinical incidence between 5 and 7%
per 100 person-months. The risk appears to be higher early during deployment and is associated with poor
hygienic conditions and contaminated food sources. Gaps remain in our understanding of the cause, given
the lack of laboratory capability in austere conditions of deployment; however, recent advances in
molecular methods of characterization hold promise in improving our detection capabilities. While there
have been improvements in understanding of best treatments, more work needs to be done in transforming
this knowledge into action and optimizing single-dose antibiotic treatment regimens. Finally, the under-
recognized burden of chronic consequences of these infections is gaining awareness and reinforces the
need to find effective preventive strategies.
Summary
Our understanding of the epidemiology of diarrhoea is improving but further research is needed to fully
account for acute operational-focused health impacts as well as the chronic enduring disease impacts.
Improved field diagnostics would be of great value to support these efforts.
Keywords
diagnostics, epidemiology, irritable bowel syndrome, military, travellers’ diarrhoea
INTRODUCTION
Historically, diarrhoea has been the scourge of
almost all identifiable military campaign s. Referen-
ces attest to its imp ortance in force generation and
preservation and can be found as far back as the
first crusades. In the 19th century, conflicts in the
Crimea, the China Wars and the Boer wa rs were
significant in raising both public and military aware-
ness of the role diarrhoea plays in expeditionary
warfare, as well as how armies managed what was
starting to be recognized as a preventable attrition
[1]. In more modern times, both world wars, the
Korean war, the war in Vietnam and the current
conflicts in Iraq and Afghan istan have exempli fied
the persistent nature of the problem despite signifi-
cant advances in both environmental protection
measures, understanding as to the microbiological
causes of the disease itself and advances in manage-
ment [24].
Military diarrhoea is, in its essence, travellers’
diarrhoea. They are both illnesses suffered by indi-
viduals travelling from a developed to an under-
developed area of the world, and attributed to
being exposed to enteric pathogens previously not
encountered or to which no protective immunity
has been acquired. What separates military diar-
rhoea from travellers’ diarrhoea is its population
a
Enteric Diseases Research Group, Royal Centre for Defence Medicine,
Birmingham, UK,
b
Enteric Diseases Department, Naval Medical
Research Center, Silver Spring, Maryland, USA and
c
US Army Research
Unit Kenya, Nairobi, Kenya
Correspondence to Col Patrick Connor, FR CP, AGAF L/RAMC, Military
Enteric Disease Group, Department of Military Medicine, Royal Centre
for Defence Medicine, Birmingham B15 2SQ, UK. Tel: +44 121 415
8860; e-mail: pconnor@doctors.org.uk
Curr Opin Infect Dis 2012, 25:546554
DOI:10.1097/QCO.0b013e3283582ebc
www.co-infectiousdiseases.com Volume 25 Number 5 October 2012
R EVIEW
dynamics, the context for treatment and the impact.
Military populations are typically large, move en
masse and may stay in an area for a long period
of time. The impact of this is typically recurrent
episodes and the potential for mini-epidemics, caus-
ing significant morbidity. Viral causes are of secon-
dary importance compared to bacterial causes,
though are important early on during deployment
and are a frequent cause of outbreaks [5,6]. The
importance of military diarrhoea as a health pro-
blem is exemplified by the growing number of
scientific publications on this subject matter
(Fig. 1), and would suggest that this problem will
remain given the geopolitical instabilities and the
perpetual need to use military forces for both com-
bat and peace-time operations. Thus, this review
provides an update of recent research efforts in
the areas of epidemiology, field diagnostics and
chronic health consequences.
UPDATE IN EPIDEMIOLOGY
The incidence and cause of diarrhoea among
military and similar populations (e.g. expatriates,
long-term travellers) were recently reviewed by a
study by Riddle et al. [7], in which a total of 52 studies
published from 1999 to 2005 were included. US
military populations (63%) made up a majority of
study populations, with foreign military, expatriate
(including non-governmental organizations and
embassy populations) and student populations
accounting for the rest. The geographic distribution
from which these studies were conducted included
37% from the Middle East, 31% from south-east
Asia, 24% from Latin Amer ica/Caribbean and 6%
from sub-Saharan Africa, revealing a current gap in
our understanding. Similar to short-term traveller
studies, enterotoxigenic Escherichia coli (ETEC),
Campylobacter and Shigella were identified as causing
3845% of diarrhoea, with regional and population
differences (Fig. 2) [8]. Furthermore, it was described
in this review that among military populations in
recent times, incidence based on self-report is higher
than incidence based on studies using passive
surveillance or clinical-based methods (29 versus
7 versus 6 episodes per 100 person-mon ths, respect-
ively) without regional differen ces [7].
Recent studies have provided much needed data
from the African region, as well as corroborated the
current estimates of incidence among militaries
KEY POINTS
Diarrhoea among military deployments remains an
important cause of morbidity in terms of acute and
chronic health effects.
Diagnostic methods are improving and hold promise to
provide improved epidemiological understanding, as
well as provide real-time information with public health
and clinical management implications.
Effective treatment regimens for travellers’ diarrhoea
exist, although improvements in utilization are needed.
Our understanding of the chronic health problems
associated with these acute infections in unique stressful
environments is evolving, and draws important attention
to the importance of primary prevention.
1950
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0
5
10
15
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Number of
publications
30
35
40
45
50
FIGURE 1. Yearly trends in papers indexed by PubMed on diarrhoea in military populations, 19502011. Medline trend:
automated yearly statistics of PubMed results for any query, 2004. Web resource at URL: HTTP://DAN.CORLAN.NET/
MEDLINE-TREND.HTML. Accessed 14 February 2012. (Archived by WebCite at HTTP://WWW.WEBCITATION.ORG/
65RKD48SV). Search terms: military AND diarr. Source: Alexandru Dan Corlan.
Update on military travellers diarrhoea Connor et al.
0951-7375 ß 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins www.co-infectiousdiseases.com 547
during deployment. A pa ir of studies describes
the epidemiology based on the experience of the
French military in N’Djamena, Chad. A prospective
study was conducted using clinic-based surveillance
for diarrhoea during a 5-month French military
deployment using standard travellers’ diarrhoea
case definitions, collection of stool samples and
survey [9
&
]. In this study a total of 240 cases of
diarrhoea were clinically identified, with an esti-
mated incidence rate of 4.9 cases per 100 person-
months. Among 196 samples collected from the
240 cases, pathogens were identified in 40% of
samples, with enteric viruses being the most com-
mon (28.1%). It is important to note that evaluation
for diarrhoeagenic E. coli was not performed. Risk
factors identified included a four-fold increased risk
if the individual had sick contacts, and a decreased
risk among thos e who stated they always took meals
from the military food establishment. Data on self-
reporting of travellers’ diarrhoea in this population
were further provided, indicating that the incidence
was three-fold higher, and only 42% of the troops
reported seeking medical care, mainly for the first
episode [10]. These data would appear to be in line
with previously reported incidence estimates from
the Riddle et al. [7] systematic review, and highlight
the fact that only a proportion of cases with diar-
rhoea who are ill seek care.
Additional studies from recent deployments
among US troops deployed to the Sinai region of
Egypt and British troops in Afghanistan are also
notable. A report from a prospective cohort study
of travellers’ diarrhoea conducted between May
2004 and January 2005 among US troops at the
Multinational Force and Observers (MFO) camp in
the southern Sinai followed 211 volunteers during
their 5-month deployment with baseline entry ques-
tionnaire, stool specimen at study entry and when
acutely ill, and routinely whether ill or not every
6 weeks [11]. Of the 211 volunteers, 145 (68.7%)
completed one or more follow-up visits and an over-
all incidence of 25.2 episodes per 100 person-
months [95% confidence interval (CI) 21.230.0]
was noted. Among 72 of 77 diarrhoea-associated
clinic visits stools were collected and bacterial
pathogens most commonly isolated including ETEC
in 42% samples and Campylobacter jejuni in 10%.
Finally, a medical record review of 1903 cases
(mean of 10.3 new cases per day) from the front lines
of Afghanistan at a British Army Regimental Aid Post
between April and October 2009 describes the impact
of diarrhea [12
&
]. In this study, there were 117 cases of
diarrhoea and/or vomiting and a further 16 cases of
dysentery, representing approximately 7% of acute
care visits during this period. These enteric illnesses
were second to dermatological conditions (23.5%,
mostly dry skin and heat rash) as a leading cause of
disease and nonbattle injury. Of important notice
was that a change from an open pit latrine (with
burning twice a day) to a buried system of stool
sanitation appeared to decrease the incidence.
Beyond ‘the numbers’ we are, however, learning
the important impacts that military diarrhoea has
on personnel and mission effectiveness. The follow-
ing description s are extracted from sources with
recent experience in Afgh anistan and demonstrate
the unique nature of this problem.
During OPERATION HERRICK 8 (AprilOct
2008, Afghanistan), 200 British paratroopers were
deployed to Forward Operating Base (FOB) Inker-
man in Helmand province. Living conditions were
basic and toilet facilities were deep-trench latrines
holes dug into the ground, which are then filled in
when full. Further latrines are then dug elsewhere
on the base. Within a few weeks of arrival, diarrhoea
caused significant degradation to individuals and
the unit’s ability to perform its role. Each soldier was
lost for at least 8 days with each episode, and at one
time, 50% of the fighting force was unfit for duty
due to diarrhoea [13].
Questionnaires completed during this period
suggested that over a 2-month period, 98% of
soldiers in the FOB had at least one episode of
diarrhoea, 33% complained of continuous diar-
rhoea for the prior 2 months and weight measure-
ments indicated an average weight loss of 6 kg in the
same time period. Repeated environmental assess-
ments of the FOB showed no remediable risks, but
analysis of the questionnaires for risk factors showed
that patrolling through open water or ditches
was the only independent factor associated with
US military
Civilian
travellers
None identified
ETEC
EAEC
30.4
19
5.5
6.2
10.4
45.7
45.6
13.3
9.9
6.6
5
3.9
7.3
6.6
8.4
22.2
Campylobacter
Norovirus
Shigella
Salmonella
Rotavirus
FIGURE 2. Attributable causes of acute diarrheal illness
based on systematic reviews of travellers’ diarrhoea and
military diarrhea. Sources: (1) Military population [7]; (2)
Traveller population [8]. EAEC, enteroaggregative E. coli;
ETEC, enerotoxigenic E. coli.
Gastrointestinal infections
548 www.co-infectiousdiseases.com
Volume 25 Number 5 October 2012
diarrhoea (P. Connor, personal communication).
Irrigation ditches in this part of Afghanistan are
an integral part of life, and during this period of
the conflict they provided a much needed safe
haven during a fire-fight as they allowed soldiers
to take cover below line of sight.
Such descriptions provide some of the clearest
insight into the challenges that acute diarrhoeal
illness poses during current (and future) operations.
Incapacitation occurs with each attack, and repeated
attacks cause significant, and cumulative, physical
degradation. Mitigation of risk through improved
food, water and sanitation is critical, but an under-
standing that not all risk can be avoided is important.
DEVELOPMENTS AND NEEDS IN THE
AREA OF FIELD DIAGNOSTICS AND
ADVANCED CHARACTERIZATION
Diarrhoea can be caused by a variety of microbial
pathogens which can create a significant diagnostic
problem due to the difficulty in providing sensitive
and accurate identification of pathogen cause [14]. It
is common in diarrhoeal disease surveillance studies
to find that a large percentage of diarrhoea cases have
an unknown cause, which can be attributed to poor
sample collection/storage, an incomplete repertoire
of skills or a lack of modern technology with a broad
range of identification capabilities. Approaches for
the identification of diarrhoeal pathogens comprise
traditional microbiology, microscopy and antigen
detection. Although microscopy for ova and parasite
identification is fairly inexpensive, it can be time- and
labour-intensive, and diagnosis usually depends
on the microscopist’s level of expertise [15,16].
Traditional culture methods for enteric bacteria
can often times yield low results if antibiotic use is
not controlled, and certain preservation medium is
used which can decrease the recovery of some bac-
teria such as Shigella [17,18]. Antigen detection kits
have emerged as a highly sensitive alternative
method for identification to traditional micro-
biology, but these assays can be expensive and are
limited to a small number of enteric viruses and
protozoan parasites [19]. Furthermore, in an austere
forward deployed environment, logistical barriers
may commonly prevent the availability of laboratory
equipment and reagents and transport of quality
specimens shipped out of theatre for analysis by
current traditional methods of diagnosis.
Recent advances in other technologies focused
on nucleic acid and protein detection have been
shown to provide more timely and accurate identi-
fication of diarrhoeal pathogens as opposed to
traditional methods and may be better suited for
laboratories in forward deployed areas. Multiple
studies have shown PCR assays to be significantly
superior to traditional methods for identification of
enteropathogens in terms of sensitivity and time
[20,21]. More recently, multiplex PCR assays have
been developed and validated to identify multiple
enteropathogens in a single reactio n [2224]. Liu
et al. [25] using a Luminex bead multiplex PCR assay
reported sensitivity and specificity ranging from
89 to 97% for the detection of Campylobacter,
Salmonella, Shigella and Vibrio, respectively. This
assay has also been adapted for the identification
of soil-transmitted helminths and parasit ic protozoa
to include E. hist olytica, Cryptosporidium and Giardia
lamblia [26]. A recent stud y by Velasco et al. [27
&&
]
used singleplex PCR to detect enteric bacteria from
frozen stool sam ples collected from US Navy and
Marine personnel participating in a joint exercise in
the Republic of the Philippines. In forward deployed
areas, storage for frozen stool samples may not be
available and an alternative method for the collec-
tion andstorage of stool samples that doesnot require
processing and freezing would be beneficial for sur-
veillance studies in these deployed personnel. A
previous study showed that ETEC and enteroaggre-
gative E. coli were detected significantly more often
by multiplex PCR using DNA extracted from stool
smeared on occult blood cards than from traditional
laboratory methods [28]. Molecular diagnostics
could be more advantageous in military populations
due to the high degree of detection of enteric patho-
gens compared to traditional methods. Furthermore,
additional studies aimed to identify better methods
of stool collection and storage that do not require
refrigeration would also benefit military micro-
biology laboratories in forward deployed areas.
MANAGEMENT OF TRAVELLERS’
DIARRHOEA
The most cost-effective response to this threat to
military readiness is to prevent the exposure leading
to diarrhoea. There are currently two strategies for
primary prevention: exposure avoidance, and pro-
phylactic measures [including chemoprophylaxis,
immunoprophylaxis (active and passive), immuno-
modulators/bowel flora competitors (such as probi-
otics)]. The first strategy is to prevent exposure to
potential pathogens focusing on environmental
measures, with the provision of clean food and water
and appropriate disposal of waste. Although this
strategy is reasonably effective when it is possible
to develop the proper infrastructure, it can break
down during rapid deployments and in small forward
deployed outposts. Even in large-scale deploy-
ments conducted under strict security measures that
prohibit routine exposure to indigenous food and
Update on military travellers diarrhoea Connor et al.
0951-7375 ß 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins www.co-infectiousdiseases.com 549
water, diarrhoea remains a serious problem. For
example, during the joint multinational military
exercise conducted in Egypt (Operation Bright Star
’01), which was conducted entirely under a strict
security environment which limited on- and off-base
access, 9% of personnel reported developing diar-
rhoea [29]. Controlling the base area infrastructure
may be possible, but patrolling patterns in high-risk
areas often involves uncontrollable exposure to local
pathogens. Pretravel education and counselling of
individuals on reducing risk behaviours (e.g. avoid
ice/tap water, undercooked meat, and unwashed/
unpeeled fruits/vegetables) is also common practice;
however, although this intuitively makes sense,
multiple studies have failed to show any consistent
evidence that a reduction in these types of risky
behaviour results in reduction of disease incidence
[30]. Antibiotic chemoprophylaxis represents a sec-
ond available strategy, and efforts are underway to
evaluate the effectiveness and practicality of newer
antimicrobials (rifaximin) as a chemoprophylaxis
option, although additional data are needed to evalu-
ate the effectiveness in regions other than Central
America and for pathogens other than diarrhoea-
genic E. coli. Although such a strategy could be con-
sidered in some military settings (e.g. short-term
critical missions, port visits, initial periods of deploy-
ment), it may be impracticable in many deployments
given the extensive durations of exposure and the
lack of safety and efficacy information on long-term
use for this indication [31].
A third strateg y to mitigate the impact of trav-
ellers’ diarrhoea using secondary prevention is
through timely and effective treatment. The UK
military have guidelines published in their ‘Clinical
Guidelines for Operations’ series, which consider
not just the man agement of the individual with
diarrhoea, but also the effect on the unit, and
the prevention of developing epidemics. The US
Military has guidance for treatment of travellers’
diarrhoea in the region of current deployment
including Iraq and Afghanista n, but not other
regions [32]. Furthermore, there are published
guidelines on the general approach to treatment
of travellers’ diarrhoea which provide evidence-
based recommendations for treatment in nonmili-
tary travellers [17 ,33]. However, such guidelines
may not consider military-specific factors including
issue of adherence, lack of indiv idual-level provision
of antibiotics and different treatment thresholds to
minimize operational impact events and risk for
dehydration and heat-related illness. Two recent
review articles have been published which provide
evidence with military considerations on the man-
agement of nondysentery travellers’ diarrhoea, as
well as chronic diarrhoea in the returning traveller,
and thus will not be reviewed here [34,35]. Figure 3
outlines the management approach reproduced
from Gutie
´
rrez et al. [35].
For dysentery or febrile diarrhoea, the use of
adjunct loperamide is controversial. Concern has
been raised that the use of loperamide and anti-
biotics in dysentery infections can precipitate shock
and enterocolitis [36,37], and may not be as effective
as multidose/multiday regimens since fevers or
dysentery often imply invasive disease and is often
caused by Shigella, Salmonella or Campylobacter, and
more rarely enterohaemorrh agic E. coli (EHEC) or
an invasive parasite such as Entamoeba histolytica.
Campylobacter and Shigella may typically require
more than a single dose of antibiotics, although this
has not been definitively shown. These concerns
have led to the current recommendations for avoid-
ing the use of loperamide or other antimotility
agents and using an antibiotic alone [3841]. How-
ever, the data substantiating the primary safety con-
cerns in a healthy adult traveller population are
lacking, and evidence running counter to both safety
and efficacy assumptions exists [4246], suggesting
that loperamide-adjuncted antibiotic regimens may
offer additional benefit to patients with inflamma-
tory diarrhoea. Further study is warranted.
Despite all the available evidence, reports
emerging from the past decade consistently find
that the medical care provided for acute diarrhoea
in these deployment settings is heterogeneous, is
not in accordance with available guidelines and is
substandard in some cases [47,48]. The most recent
study by Hayat et al. [49
&
] reports the results of a
survey conducted among a convenience sample of
117 US military clinical providers with a broad rang e
of training and operational experience. Although
most were aware of the standard definition of
travellers’ diarrhoea (77%), knowledge about the
epidemiology was lower, with less than 24% cor-
rectly answering questions on cause of diarrhoea,
and 31% believing that a viral pathogen (not bac-
terial) was the primary cause of watery diarrhoea
during deployment. For management of a clinical
scenario of moderate travellers’ diarrhoea it was
reported that approximately two-thirds would not
use antibiotics to treat, and one of the five providers
felt that severe inflammatory diarrhoea was best
treated with hydration only. Better management
practice patterns were reported for those with a
Doctor of Medicine or Doctor of Osteopathy degree,
greater knowledge of travellers’ diarrhoea epide-
miology and more favourable attitudes towards
antimotility or antibiotic therapy. However, even
among these sub-groups there was relatively poor
adherence to current bes t evidence [49
&
]. The reason
for these inadequacies may include the lack of
Gastrointestinal infections
550 www.co-infectiousdiseases.com
Volume 25 Number 5 October 2012
institutionalization of clear guidelines and training
that may be disseminated and used among deployed
personnel. Also, single-dose regimens, adjuncted
with loperamide, have shown promise in small trials
and pose an attractive option for the combat setting
as they are simple, inexpensive and may, therefore,
be associated with decreased costs in terms of health-
care utilization and duty-days lost [5054]. A large
multisite randomized controlled trial evaluating
single-dose loperamide-adjuncted regimens for treat-
ment of acute watery diarrhoea and dysentery is
underway and will provide the necessary evidence
to develop global treatment guidelines for the forces
(ClinicalTrials.gov Identifier: NCT01618591). The
dissemination and translation of such evidence into
practice will be an important challenge.
POST-INFECTIOUS SEQUELAE: THE
LINGERING EFFECT OF DIARRHOEA
DURING DEPLOYMENT
The pathogens associated with travellers’ diarrhoea
and military diarrhoea have been linked to several
chronic health sequelae affecting multiple organ
systems. Perhaps the most well described from a
mechanistic perspective is the link between Campy-
lobacter infection and GuillainBarre
´
syndrome [55].
Similarly, incident rheumatological manifestations
following gastrointestinal infection with several
invasive bacteria have been reported, although the
disease mechanisms are less well understood [56].
Although these sequelae are important, their relative
low incidence makes them a difficult outcome of
study in travel populations. In contrast, functional
gastrointestinal disorders (FGDs) following acute
enteric infection appear to occur at rates amenable
to studying the effect of travellers’ diarrhoea and
military diarrhoea on disease risk.
Systematic reviews of postinfectious irritable
bowel syndrome (IBS) risk have reported just over
a seven-fold increase in incident IBS following acute
enteric infection [57,58]. These studies have focused
on a variety of exposures from specific pathogens
to general infectious gastroenteritis; additionally,
reports of travel-related exposures and postinfec-
tious IBS risk are increasing (Table 1) [5964].
Patient
with
complaint
of
diarrhoea
Weight
loss, GI
bleeding,
anaemia,
nocturnal
sx?
<14 days
14–30
days
Yes
No
> 30 days
Initiate labs for
structural aetiologies
and refer to GI specialist
Adequate
work up
/Rx course
for
infectious
aetiology
Yes
Acute
Persistent
Blood/
fever
No
Yes
Stool culture
and/or empiric abx
treatment
Acute watery
diarrhoea
Chronic
Culture/
O&P,
triage EIA
capability
Empiric abx and /or
antiparasitic Rx
No
Yes
Bacterial/
parasitic
aetiology
identified
Yes
Treat based on
pathogen ID
No
Consider lactose
intolerance,
tropical sprue dx/tx
follow up in 4–6
weeks
No
Symptoms
of
malabsorp
-tion
Yes
No
Consider lactose
intolerance,
tropical sprue dx/tx
follow up in 4–6
weeks
Evaluate for
functional
gastrointestinal
disorders (Rome III)
FIGURE 3. Diagnostic and treatment algorithm for acute and chronic diarrhoea among military travellers. abx, antibiotic;
dx/tx, diagnosis and treatment; EIA, enzyme immunoassay; GI, gastrointestinal; ID, identification; O&P, ova and parasites;
Rx, treatment; sx, symptom.
Update on military travellers diarrhoea Connor et al.
0951-7375 ß 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins www.co-infectiousdiseases.com 551
Utilizing a prosp ective cohort study, Pitzurra et al.
[64] reported in the past year that among European
travellers to developing world countries, those
reporting at least a single episode of diarrhoea
experienced more than a five-fold increase in IBS
risk compared to travellers without travellers’ diar-
rhoea. This effect was even higher (six-fold) in those
experiencing multiple travellers’ diarrhoea episodes.
Whereas these data support an increased IBS
risk among travellers with travellers’ diarrhoea,
deployed military populations represent a specific
sub-population of travellers with unique demo-
graphics and exposures, and recent reports have
expanded our understanding in this area. A study
by Trivedi et al. [63] found associations between
FGD among 121 US military travellers returning
from routine deployment (>6 month follow-up)
to the Middle East where it wa s reported that there
was an over five-fold increase in incident IBS among
those who experienced an episode of travellers’
diarrhoea during travel compared to those who
did not (17.2 versus 3.7%; P ¼ 0.12). Importantly,
this study also showed significant impacts of these
incident disorders on health-related quality of life.
In addition, through use of US Department of
Defense medical encounter datab ases linked to post-
deployment health surveys, it was reported that
incident IBS risk among military personnel follow-
ing deployment to Iraq or Afghanistan showed a
similar increased risk [adjusted odds ratio (OR) 6.26;
95% confidence interval (CI) 2.5, 15.4] of IBS among
those self-reporting gastroenteritis during deploy-
ment compared to those with no self-reported gas-
troenteritis, with an apparent higher risk in persons
with more severe acute illness [65]. Importantly , an
increased risk of other FGDs, namely functional
constipation and functional dyspepsia, was also
observed furthering prior reports on the risk of these
FGDs following enteric infection [6670]. In total,
these data support a 2010 Institute of Medi-
cine report linking Gulf War deployment with
gastrointestinal symptom s consistent with FGDs
[71], and further evidence suggests that increased
psychological stressors such as war trauma may
increase visceral sensitivity and, concurrent with
an acute infection that may result in dysmotility,
mucosal inflammation and increased intestinal per-
meability may be contributory [72].
Whereas data on rheumatological outcomes
among travellers’ diarrhoea cases are limited, an
increased risk of reactive arthritidies and arthro-
pathies following infection with Campylobacter,
Shigella, Yersinia and nontyphoidal Salmonella is well
established [56]. Given the proportion of travellers’
diarrhoea caused by these pathogens, it is fair to
assume an increased risk among deployed military
populations. This is supported by Curry et al. [73]
who not only showed an increased risk of reactive
arthritis diagnoses following acute enteric infection,
but also reported a two-fold increased risk sub-
sequent to deployment to regions with high travel-
lers’ diarrhoea rates.
CONCLUSION
In summary, evidence for the impact of acute infec-
tious diarrhoea on military deployments accumu-
lates and is multiplied by the emerging evidence
finding chronic health consequences as important
causes of increased direct medical costs and disabil-
ity among those returning from deployment and
leaving the military. Additional data are needed to
understand the ac ute effects of travellers’ diarrhoea,
including the impact of these infections on the
individual performance (physical and cognitive)
of those deployed. With respect to chronic health
consequences, areas of research include further
investigation on pathogen-specific mechanisms in
human and animal models which may explore the
interactions between genomics, microbiome and
immune mech anisms behind infection and chronic
health consequences, and evaluation of early
Table 1. Studies of postinfectious irritable bowel syndrome among military and other traveller populations
(alphabetical order)
Study Year
Study
size
Follow-up
(months)
Origin of
traveller
IBS
diagnosis
Study
type
IBS risk in exposed/
unexposed (%)
Effect estimate
(P value)
Ilnyckyj et al. [62] 2003 110 3 Canada Rome I Cohort 4.2/1.6 RR 2.5 (0.41)
Okhuysen et al. [61] 2004 101 6 US Rome II Cohort 12.7/2.6 OR 5.5 (0.09)
Pitzurra et al. [64] 2011 2476 6 Switzerland Rome III Cohort 3.1/0.7 OR 3.0 (<0.05)
Porter et al. [60] 2011 527 NA US ICD-9 Casecontrol 17.4/3.6 OR 6.3 (<0.001)
Stermer et al. [59] 2006 405 6 Israel Rome II Cohort 13.6/2.4 RR 5.2 (<0.0001)
Trivedi et al. [63] 2011 120 6 US Rome II Cohort 17.2/3.7 OR 5.4 (0.12)
ICD-9, International Classification of Disease; NA, not applicable; NOS, not otherwise specified; OR, odds ratio; RR, relative risk.
Gastrointestinal infections
552 www.co-infectiousdiseases.com
Volume 25 Number 5 October 2012
treatment on the effectiveness of acute morbidity
reduction and long-term disease outcome preven-
tion [74].
The value of sensitive and specific assays to
determine the cause of travellers’ diarrhoea may
have important implicatio ns for understanding
the epidemiology surrounding these infections,
not least of which is to support the assessment
and value of novel enteric vaccines on the horizon
(e.g. ETEC, Campylobacter, Shigella and norovirus)
[75]. Furthermore, the identification of outbreak-
associated causes in a field deployment setting
would significantly help public health efforts on
the ground, as well as clinical management strat-
egies. This critical need for field-deployable diagnos-
tics cannot be over emphasized.
Finally, mitigative strategies of primary and sec-
ondary prevention of both the acute and chronic
consequences of travellers’ diarrhoea in deployed
settings are known and need to be rapidly deployed.
A randomized controlled trial evaluating the effec-
tiveness of antimicrobial or probiotic chemo-
prophylaxis for prevention of acute travellers’
diarrhoea and the chronic consequences is quite
feasible given the known high attack rates of trav-
ellers’ diarrhoea and associated risk of sequelae.
Military service members of all nations have and
will continue to deploy to austere areas in support of
combat and humanitarian assistance and disaster-
relief missions. The maintenance of effectiveness of
these forces is critical to achieve the mission, and
the reduction of disease impact (both acute and
chronic) is also important given the fiscal impact
and global economic constraints.
Acknowledgements
None.
Conflicts of interest
Disclaimer: The opinions and assertions herein should
not be construed as official or representing the views of
the UK Ministry of Defence, the UK Defence Medical
Services, the US Department of the Navy, the US Depart-
ment of Defense or the US Government. This is a
collaborative work by members of the UK and US Govern-
ments, and as such there are no restrictions on its use.
There were no financial conflicts of interests among any
of the authors.
Copyright statement: Three of the authors (M.S.R.,
C.K.P., B.S.) are employees of the US Government and
a military service member. This work was prepared as
part of official duties. Title 17 U.S.C. §105 provides that
‘Copyright protection under this title is not available for
any work of the US Government.’ Title 17 U.S.C. §101
defines a US Government work as a work prepared by a
military service member or employee of the US Govern-
ment as part of that person’s official duties.
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554 www.co-infectiousdiseases.com
Volume 25 Number 5 October 2012
    • "The U.S. Centers for Disease Control and Prevention estimates that approximately 10 million people develop TD every year [1], and U.S. military estimates report an attack rate of 29 TD cases per every 100 person-months.[2] The most significant risk factor for TD is travel destination and type of travel, with Asia, the Middle East, Africa, Mexico, and Central and South America being the highest-risk regions, and backpackers, trekkers and visitors of friends and relatives being the highest at-risk populations.[3] From the sailing vessel and military perspectives, risk is associated with dwelling within densely populated living conditions and exposure to contaminated food and water sources.[4][5][6][7][8][9][10][11][12][13][14] The hospital ship and humanitarian assistance/disaster response (HA/DR) missions represent a unique deployment environment in terms of exposures (intensive interaction with local populations) and occupation (health care providers). "
    [Show abstract] [Hide abstract] ABSTRACT: Travelers' diarrhea (TD) is the most common ailment affecting travelers, including deployed U.S. military. Continuing Promise 2011 was a 5-month humanitarian assistance/disaster response (HA/DR) military and non-governmental organization training mission aboard the hospital ship USNS Comfort, which deployed to Central and South America and the Caribbean between April and September 2011. Enhanced TD surveillance was undertaken during this mission for public health purposes. Passive surveillance (clinic visits), active surveillance (self-reported questionnaires), and stool samples were collected weekly from shipboard personnel. Descriptive statistics and multivariate-logistic regression methods were used to estimate disease burden and risk factor identification. Two polymerase chain reaction methods on frozen stool were used for microbiological identification. TD was the primary complaint for all clinic visits (20%) and the leading cause of lost duties days due to bed rest confinement (62%), though underreported, as the active self-reported incidence was 3.5 times higher than the passive clinic-reported incidence. Vomiting (p = 0.002), feeling lightheaded or weak (p = 0.005), and being a food handler (p = 0.017) were associated with increased odds of lost duty days. Thirty-eight percent of self-reported cases reported some amount of performance impact. Based on the epidemiological curve, country of exercise and liberty appeared to be temporally associated with increased risk. From the weekly self-reported questionnaire risk factor analysis, eating off ship in the prior week was strongly associated (adjusted odds ratio [OR] 2.4, p
    Full-text · Article · May 2016
    • "Knowledge about the local antimicrobial-resistance situation in diarrhea-associated bacteria is crucial to allow for a tailored antimicrobial therapy. Next to standard recommendations regarding the therapy of acute gastroenteritis [47] and traveler's diarrhea4849505152, the British and U.S. military medical services also intend studies on the optimization of single-dose antibiotic treatment regimens [19]. High rates of colonization with atypically resistant or even multidrug-resistant bacteria in returnees from tropical settings have recently been described535455. "
    [Show abstract] [Hide abstract] ABSTRACT: . Since 2013, European soldiers have been deployed on the European Union Training Mission (EUTM) in Mali. From the beginning, diarrhea has been among the most “urgent” concerns. Diarrhea surveillance based on deployable real-time PCR equipment was conducted between December 2013 and August 2014. Material and Methods . In total, 53 stool samples were obtained from 51 soldiers with acute diarrhea. Multiplex PCR panels comprised enteroinvasive bacteria, diarrhea-associated Escherichia coli (EPEC, ETEC, EAEC, and EIEC), enteropathogenic viruses, and protozoa. Noroviruses were characterized by sequencing. Cultural screening for Enterobacteriaceae with extended-spectrum beta-lactamases (ESBL) with subsequent repetitive sequence-based PCR (rep-PCR) typing was performed. Clinical information was assessed. Results . Positive PCR results for diarrhea-associated pathogens were detected in 43/53 samples, comprising EPEC ( n = 21 ), ETEC ( n = 19 ), EAEC ( n = 15 ), Norovirus ( n = 10 ), Shigella spp./EIEC ( n = 6 ), Cryptosporidium parvum ( n = 3 ), Giardia duodenalis ( n = 2 ), Salmonella spp. ( n = 1 ), Astrovirus ( n = 1 ), Rotavirus ( n = 1 ), and Sapovirus ( n = 1 ). ESBL-positive Enterobacteriaceae were grown from 13 out of 48 samples. Simultaneous infections with several enteropathogenic agents were observed in 23 instances. Symptoms were mild to moderate. There were hints of autochthonous transmission. Conclusions . Multiplex real-time PCR proved to be suitable for diarrhea surveillance on deployment. Etiological attribution is challenging in cases of detection of multiple pathogens.
    Full-text · Article · Oct 2015
    • "In order to inhibit disease transmission, patients with diarrhea are isolated at medical centers upon admission. Based on the patient's medical and epidemiological history, a wide range of tests and examinations may be performed before a definite diagnosis is made [1]. Subsequent treatment may include fluid and electrolyte replacement plus antibiotic treatment for patients with fever and stomach pain. "
    [Show abstract] [Hide abstract] ABSTRACT: There are no rapid tests that can distinguish contagious gastroenteritis, which requires isolation at its onset, from exacerbation of chronic inflammatory bowel disease (IBD) or bowel engagement in the course of systemic inflammatory response syndrome (SIRS). Hepatocyte growth factor (HGF) is an acute phase cytokine that is produced at the site of injury. It has high affinity to sulfated glycan, and this binding affinity is lost during chronic inflammation. The fecal pH strongly impacts the prognosis for severe bowel disease. We developed a strip test to evaluate HGF as a local acute phase response marker in the bowel. This test assessed the binding affinity of HGF to sulfated glycans in fecal samples and determined fecal pH as an indicator of illness severity.
    Full-text · Article · Aug 2014
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