Helminth infections in the US military: from strongyloidiasis to schistosomiasis

Abstract

Background

Helminths, a group of parasitic worms encompassing cestodes (tapeworms), trematodes (flukes or flatworms) and nematodes (roundworms), are widely distributed in the tropical and subtropical regions. It is estimated that over 1 billion people globally are infected with at least one helminth.¹ In 2010, helminth infections contributed to more than 14 million disability-adjusted life-years.²

Helminth infection presentation in travellers can differ from the symptoms classically seen in endemic populations, resulting in delays in diagnosis or misdiagnosis if a travel history is not taken.^3–6 Left untreated, some of these parasites can cause chronic symptoms and lead to severe clinical outcomes. High burdens of intestinal roundworms and tapeworms can frequently cause abdominal pain, diarrhoea and anaemia in endemic populations.⁷ The extent to which this is seen in military populations, which likely have a lower burden of infection, is unclear and will be the subject of future studies. Strongyloides stercoralis is of particular concern as this roundworm can cause a potentially fatal hyper-infection syndrome if individuals become immunocompromised.⁸ Flatworms can cause chronic inflammation in the liver, intestines, genitourinary tract and hepatobiliary system, which can lead to cancer.^9,10 Currently, there are little data on the extent to which these helminths cause disease in the US military.

The US military represents a unique and high-risk group of travellers. Service members are deployed for overseas operations for 3–15 months at a time, and they may have longer term assignments abroad with their immediate family. Duration of travel has been shown to correspond with a higher risk for travel-related illnesses.¹¹ Additionally, the military frequently conducts activities in helminth-endemic regions. Separate from operational deployments, in 2015, over 95 000 active duty members were stationed in East Asian, North African, Caribbean or Central and South American nations.¹²

In the past several years, the US military has also conducted training and assistance missions in numerous countries in the Indo-Pacific region, Central Africa and Western Africa regions, all areas which are highly endemic for helminths.¹³ A 2018 report showed that between 2001 and 2014, more than 2.77 million service members served over 5.4 million deployments in conflict zones, principally Iraq and Afghanistan, and also in the Philippines and multiple African nations, with a peak at more than 567 000 unique individuals deployed during 2003.¹⁴ Large, though harder, to define numbers of service members have also taken part in short-term training or humanitarian assistance missions in helminth-endemic regions.

Helminth infections have long been recognized as a threat to US military personnel deployed overseas.^15–19 Thousands of soldiers during World War II and the Vietnam War were affected by lymphatic filariasis, and over 23 000 were hospitalized for hookworm infection in World War II.^20,21 Strongyloidiasis infection and fatality has also been reported in soldiers deployed to Vietnam.^17,22 More recently, a number of case reports have been published about service members who contracted helminth infections abroad, including diphyllobothriasis, schistosomiasis and echinococcosis.^22–25 However, there are no recent comprehensive reports of the prevalence of helminth infections in the US Military Health System (MHS). As such, this study sought to determine the burden of helminth infections in the US military service members, retirees and dependents over a 7-year period.

Methods

Results

Estimated helminth diagnoses

Calculated PPV of each diagnosis code was applied to raw totals to determine an adjusted diagnosis burden, resulting in 34 425 estimated helminth infections between FY 2012–2018, with a 95% confidence interval (CI) between 32 889 and 35 962 total diagnoses (Table 3). Excluding the estimated 30 429 pinworm cases, there were an estimated 3996 helminth diagnoses in the study period, with a 95% CI of 2460–5533 diagnoses. Across all helminth categories, dependents and retirees made up the majority of diagnoses (84.5% of total) (Table 4), proportionate to the demographics of TRICARE beneficiaries. Active duty and National Guard/Reserve beneficiaries had similar representation, with 7.7 and 6.2% of all estimated helminth diagnoses, respectively.

Table 3

Total estimated ‘actual’ unique subject diagnoses in the MDR using the calculated PPV from chart review for each helminth diagnosis

Helminth diagnosis	Total diagnoses	PPV-adjusted diagnoses	95% CI (range)
Intestinal nematodes	34 510	32 753	31 899—33 607
Enterobiasis (pinworm)	30 429	30 429	30 429—30 429
Strongyloidiasis	414	351	301–402
Ascariasis	783	470	298–642
Hookworm (any or unspecified)	1056	581	351–811
Trichuriasis	106	61	38–85
Intestinal helminth other/mixed/unsp.	1722	861	484–1238
Tissue-invasive nematodes	447	40	0–101
Loiasis	30	13	2–24
Lymphatic filariasis	91	15	0–42
Filariasis (other/unspecified)	179	12	0–35
Onchocerciasis	147	0	0–0
Trematodes	1481	846	635–1058
Cutaneous schistosomiasis	638	510	399–622
Schistosomiasis, any sp.	184	145	121–169
Schistosomiasis, other/unspecified	276	172	129–214
Opisthorchiasis/clonorchiasis	95	19	0–52
Fluke, other/unspecified	288	0	0–0
Cestodes	2007	786	375–1197
Cysticercosis	381	191	107–274
Cestode infection, unspecified	545	273	153–392
Diphyllobothriasis	157	74	39–110
Taeniasis	256	115	59–171
Echinococcosis	668	134	17–251
All total	38 445	34 425	32 889—35 962

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Table 4

Estimated actual helminth diagnoses for each military beneficiary category, using calculated PPV from chart review

	Intestinal nematodes	Tissue-invasive nematodes	Trematodes	Cestodes
Beneficiary status	N (Column %)	N (Col. %)	N (Col. %)	N (Col. %)
Active duty	1773 (7.3)	3 (5.2)	82 (12.5)	113 (13.4)
Dependent	19 863 (82.2)	32 (55.2)	415 (63.8)	531 (63.0)
Retiree	649 (2.7)	18 (31.0)	93 (14.2)	122 (14.5)
Guard/reserve	1467 (6.1)	4 (6.9)	56 (8.5)	64 (7.6)
Other	404 (1.7)	1 (1.7)	5 (<1.0)	13 (1.5)

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The annual incidence of helminth infection diagnoses ranged from 31 to 38 diagnoses per 100 000 TRICARE enrollees per FY (Figure 1A). Of these, non-pinworm helminth diagnoses accounted for 5.1 to 6.1 diagnoses per 100 000 per FY. Whilst incidence of tissue-invasive nematode and trematode diagnoses stayed relatively stable, the incidence of intestinal nematode diagnoses showed an upward trend, increasing from 3.33 to 4.48 per 100 000 during the study period (Figure 1B). By contrast, diagnoses of cestode infections showed a consistent decrease, from 1.60 per 100 000 enrollees in FY 2012 to 0.70 per 100 000 in FY 2018.

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Figure 1

(A) Estimated incidence of helminth diagnoses amongst all TRICARE enrollees, with pinworm diagnoses and all other helminth diagnoses excluding pinworm. (B) Estimated incidence of helminth diagnoses by helminth type

Discussion

Our analysis found 38 445 unique subjects diagnosed with helminth infections between FY 2012 and FY 2018, an average of 5428 diagnoses per FY. We undertook a validation of these diagnoses by medical record review in order to determine the reliability of diagnostic codes and how frequently lab tests provided confirmatory diagnoses. Using this methodology, we estimated 34 425 of these diagnoses to be actual helminth infections. Incidence of helminth diagnoses were relatively steady over the 7-year study period, indicating that these results are not an incidental finding, and military personnel, veterans and their families are consistently at risk for helminth infections.

Enterobiasis (pinworm) represented over 30 000 of these diagnoses. Pinworm is a relatively common yet fairly benign worm infection endemic throughout the world, with estimates of more than 20 million individuals infected annually in the USA alone.²⁷ Because most cases were empirically diagnosed based on symptoms or close contact status of known cases, it is possible this burden may be an overestimate. Whilst amongst the helminth infections not generally considered a travel-acquired or tropical disease, it is clear that the US MHS allocates significant resources to the treatment of pinworm.

For intestinal nematodes, diagnosis was commonly made on the basis of corresponding symptoms or self-reports of observing a worm and treated without further testing. Apart from pinworms, the most common intestinal nematodes diagnosis codes included ‘unspecified intestinal helminths’, hookworm, ascariasis and strongyloidiasis. Chart review demonstrated that the PPV of ICD codes for these intestinal nematodes ranged from 50 (for unspecified intestinal helminths) to 85% (for strongyloidiasis). These estimates may be low, as we considered a negative lab result to be indicative of a false diagnosis. However, the sensitivity of stool ova and parasite tests can be poor, particularly in populations with low parasite burdens.²⁸ Further, an unknown number of cases do not present for care and are not diagnosed.

Diagnosis codes for infections where serological testing was available (strongyloidiasis and schistosomiasis) typically had high PPVs. This is likely due to the ease of collecting a blood sample (rather than stool sample) and the availability of these serological tests. However, a positive serological result does not necessarily indicate an active infection, and as such, these diagnoses were considered probable rather than confirmed.

Many helminth infections, including strongyloidiasis, often have vague symptoms or no apparent symptoms at all, and practitioners in the USA unfamiliar with these infections may not include them in the differential diagnosis or select suboptimal tests to make the diagnosis. This is especially concerning as strongyloidiasis can persist for years if untreated and can lead to a potentially life-threatening hyper-infection syndrome if the patient is treated with corticosteroids or other immunosuppressive medications.

Schistosomiasis diagnosis rates were similar to strongyloidiasis. If left untreated, schistosomiasis can cause chronic granulomatous inflammation and scarring of the liver, colon and urogenital tract. Additionally, in some cases, eggs can migrate to aberrant locations, including the central nervous system.²⁹ We suspect that a large number of schistosomiasis infections are missed in this patient population, as a high percentage (44.8%) of the diagnoses reviewed in our analysis were made by biopsy specimen, indicating the infection may have progressed to a state that caused sufficient clinical symptoms to warrant endoscopic evaluation and biopsy. Thus, it is possible that many individuals with milder cases of intestinal or bladder inflammation caused by Schistosoma remain undiagnosed. Future studies will conduct manual chart reviews of larger numbers of schistosomiasis cases to determine the frequency with which symptoms led to endoscopic procedures as well as the duration of clinical symptoms prior to diagnosis.

Cestodes, particularly cysticercosis, occurred in relatively high numbers. Tapeworm infections do not typically have a high associated mortality rate but can cause clinical symptoms such as abdominal pain, anaemia and gastrointestinal issues. These can be mistaken for other gastrointestinal conditions and an accurate diagnosis may be delayed. By contrast, cysticercosis, and particularly neurocysticercosis, can lead to severe complications such as seizures and require complex specialty care to manage appropriately.³⁰

Hepatobiliary flukes (Clonorchis, Fasciola and Opisthorchis) have recently gained attention as a concern for Vietnam War veterans due to their prevalence in the East Asia.^31,32 Left untreated, these flukes can persist for decades and are known to cause cholangiocarcinoma in endemic areas. We saw few diagnoses in our population. This suggests that this may not be a priority issue for the current service personnel. However, it should be noted that the serological test for these flukes is neither highly accurate nor specific; the infection has a long latency period until hepatic complications are seen, and the US military does not currently conduct systematic screening for flukes or other helminth infections post-deployment. Low numbers of filarial infections were seen in this study. This is unsurprising, as filarial transmission is inefficient, and long-term exposure to mosquitos in an endemic area is typically required to acquire a significant infection.³³

The main limitation of the study is the low sample size of the chart reviews for some diagnoses, which could impact the precision of PPV estimates. However, these results provide important context for reliance on EMRs as a surveillance tool. Chart reviews should be standard practice for surveillance of conditions that are infrequently occurring and potentially subject to miscoding. Additionally, because we were limited to reviewing records in the MHS, it is possible that PPV will vary in other contexts. However, we hypothesize that military physicians, on the whole, would be as or more experienced than civilian physicians in recognizing and testing for travel-related illnesses. Finally, the military’s high uptake of pre-travel counselling and other countermeasures may lower the risk to contract a helminth infection compared with some civilian populations. However, military personnel are also more likely to travel to high-risk areas, where helminths and vector-borne diseases are not well controlled, and have longer durations of travel. Reviews have found similar rates of traveller’s diarrhoea in military personnel and civilian long-term travellers, indicating that the risk for travel-related illness is similar.³⁴

Conclusion

In summary, we found nearly 4000 non-pinworm unique subject helminth diagnoses estimated to have occurred in the US military personnel and dependents over a 7-year period. As helminth infections are often asymptomatic or misdiagnosed, these results may be underestimating the true incidence of helminth infections in US military personnel. Helminths are relatively low cost and easy to treat if diagnosed early, but they can persist for several years, and in some cases for decades, if undiagnosed. Many helminths cause severe and often chronic clinical issues. In addition to the complications from schistosomiasis, strongyloidiasis and hepatobiliary flukes discussed previously, enteric parasite infection (including helminthic parasites) has been shown to increase the risk of developing chronic gastrointestinal disorders, such as irritable bowel syndrome and gastroesophageal reflux disease (GERD).³⁵ Further, as the proportion of women in the military increases, it should be recognized that helminth infections can cause adverse outcomes during pregnancy, but treatment has been shown to be safe and effective.³⁶ Given sustained military presence in endemic regions, these results suggest that prospective studies of US military personnel deployed to helminth-endemic areas and post-deployment screening may be warranted to further elucidate the prevalence and risk of infection.

Supplementary Material

Notes

Data presented at the American Society of Tropical Medicine and Hygiene Annual Meeting, 2019.

Contributor Information

Alyssa R Lindrose, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA. Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

Indrani Mitra, Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

Jamie Fraser, Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

Edward Mitre, Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

Patrick W Hickey, Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

References