Gulf War and Health Volume 5: Infectious Diseases (2007) / Chapter Skim
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5 Levels of Association Between Select Diseases and Long-Term Adverse Health Outcomes
5 Levels of Association Between Select Diseases and Long-Term Adverse Health Outcomes
Pages 101-180
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From page 101... ...
For every health outcome discussed in this chapter, there is limited or suggestive evidence of an association, sufficient evidence of an association, or sufficient evidence of a causal relationship with the infectious disease. Several delayed long-term adverse health outcomes of the nine diseases are listed in Chapter 3 but not reviewed here; the committee determined that there is inadequate or insufficient evidence of an association between these health outcomes and the infectious diseases.
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From page 102... ...
Reactive arthritis infection Shigella infection Hemolytic uremic syndrome Reactive arthritis Tuberculosisb Activation of latent tuberculosis infection Late manifestations of pulmonary and extrapulmonary tuberculosis West Nile virus infectionc Persistent deficits in cognition, movement, and daily functioning aViscerotropic leishmaniasis is considered a subset of VL for the purposes of this discussion. bTuberculosis (TB)
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From page 103... ...
. The committee examined three potential long-term adverse health outcomes of Campylobacter infection: Guillain-Barré syndrome, reactive arthritis, and uveitis.
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From page 104... ...
After 2 months have elapsed, there is no reliable diagnostic test for exposure to Campylobacter in people who manifest diseases that could be late adverse health outcomes of a Campylobacter infection. Treatment of Acute Illness Fluid and electrolyte replacement is the treatment of choice for diarrheal illnesses.
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From page 105... ...
. The committee concludes that there is sufficient evidence of an association between Campylobacter jejuni infection and GBS, if the GBS is manifested within 2 months of the infection.
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From page 106... ...
Population-based studies have provided the most convincing evidence of an association between Campylobacter infection and ReA. Two such studies found that 7% and 1.8% of patients with laboratory-confirmed Campylobacter infection later developed ReA (Hannu et al.
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From page 107... ...
later develop ReA. The committee concludes that there is sufficient evidence of an association between Campylobacter infection and reactive arthritis (ReA)
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From page 108... ...
. In contrast, uncomplicated infection with nontyphoidal salmonellae causes an array of generally milder illnesses that appear similar to other diarrheal diseases and usually resolve without medical attention.
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From page 109... ...
. Coinfection with Nontyphoidal Salmonellae and Human Immunodeficiency Virus Salmonellosis is sometimes the first manifestation of HIV infection.
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From page 110... ...
The committee concludes that there is sufficient evidence of an association between nontyphoidal Salmonella infection and reactive arthritis (ReA) if the ReA is manifested within 3 months of the infection.
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From page 111... ...
Long-Term Adverse Health Outcomes of Shigella Infection Reactive Arthritis As discussed above, ReA is an acute nonpurulent form of arthritis that complicates infections at other sites of the body. If ReA follows an acute episode of shigellosis, it is usually manifested 2-3 weeks after the gastrointestinal illness (Calin and Fries 1976; Chen et al.
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From page 112... ...
. The committee concludes that there is sufficient evidence of an association between Shigella infection and reactive arthritis (ReA)
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From page 113... ...
. Human brucellosis occurs sporadically in many developed or industrialized countries, including the United States, but most cases occur in three distinct endemic zones: the Near East and Middle East, including Iran, Iraq, Kuwait, Saudi Arabia, Israel, Jordan, and Turkey; the Mediterranean region, including Spain, Portugal, Italy, and Greece; and Latin American countries, including Peru, Argentina, and Mexico (Abo-Shehada et al.
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From page 114... ...
. If microbiologic cultures are negative, diagnosis of human brucellosis usually involves serologic analysis.
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From page 115... ...
Clinical manifestations due to relapsing or chronic brucellosis usually are evident within 2-6 months of acute illness and if untreated can persist for years or decades (Spink 1951)
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From page 116... ...
Arthritis is usually manifested within 12 months of the acute illness; spondylitis might be manifested later. Hepatic Involvement Human brucellosis is often associated with changes in liver function and has been associated with granulomatous hepatitis (Harrington et al.
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From page 117... ...
. The committee concludes that there is sufficient evidence of an association between brucellosis and chronic meningitis and meningoencephalitis and between brucellosis and infection of the nervous system.
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From page 118... ...
TABLE 5.3 Clinical Syndromes Caused by Leishmania Species and Their Geographic Distribution Clinical Syndromes Leishmania species Location Visceral leishmaniasis: Kala-azar; generalized L donovani Indian subcontinent, northern and involvement of eastern China, Pakistan, Nepal reticuloendothelial system (spleen, bone marrow, liver)
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From page 119... ...
However, a handful of US soldiers deployed to the Gulf War developed a mild visceral form of leishmaniasis caused by L tropica (termed viscerotropic disease)
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From page 120... ...
Only 31 cases of leishmaniasis were diagnosed among 697,000 troops deployed during the Gulf War, and deployment to the open desert during cooler weather was thought to be a partial reason for the low incidence of the disease (Cope et al.
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From page 121... ...
Serum antibody testing, often used in assessment of persons with suspected VL, is most commonly performed with the direct agglutination test. However, the performance of this test is highly variable; in fact, serology was negative in a number of the viscerotropic cases identified in Gulf War soldiers.
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From page 122... ...
, reduced rates of treatment response, progression from cutaneous to visceral disease, higher rates of death, and reduced sensitivity of serologic tests. Long-Term Adverse Health Outcomes of Leishmaniasis Cutaneous Leishmaniasis Infections with L
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From page 123... ...
. However, intensive evaluation among 150 Gulf War veterans with complaints was unable to identify prior or current infection with Leishmania spp.
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From page 124... ...
ovale is limited mostly to tropical Africa, the Middle East, southeast Asia, and the western Pacific. Transmission of Malaria Malaria infection occurs when a Plasmodium-infected Anopheles mosquito feeds on a susceptible human host, delivering sporozoites that initially invade hepatocytes and mature into merozoites that then invade erythrocytes.
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From page 125... ...
. Antimalarial drugs have well-documented acute adverse effects on the skin, gastrointestinal tract, central nervous system, and other organ systems, but evidence of long-term adverse health outcomes is sparse (Taylor and White 2004)
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From page 126... ...
falciparum predominates in Saudi Arabia, only seven cases of malaria were reported in US troops during the Persian Gulf War, as described in Chapter 4.
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From page 127... ...
highlight the relative rarity of the retinal complications and the need for long-term administration of the drugs. The committee concludes that there is sufficient evidence of a causal relationship between malaria infection and ophthalmologic manifestations, particularly retinal hemorrhage and scarring, recognized for the first time months or years after the infection.
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From page 128... ...
The committee concludes that there is sufficient evidence of a causal relationship between malaria infection and renal disease, especially the nephrotic syndrome that may occur weeks to months after acute infection. Relapse and Recrudescence of Malaria Some P
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From page 129... ...
months to years after acute infection. The committee concludes that there is sufficient evidence of an association between infection by Plasmodium falciparum and recrudescence weeks to months after the primary infection, but only in the case of inadequate therapy.
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From page 130... ...
The acute phase usually lasts 1-3 weeks and resolves without specific therapy or adverse health outcomes. Coxiella burnetii Pneumonia The symptoms of Q fever pneumonia include prominent headache, cough, pleuritic chest pain, and fever (Tissot-Dupont et al.
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From page 131... ...
. Coinfection with Coxiella burnetii and Human Immunodeficiency Virus Relatively little is known about C
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From page 132... ...
burnetii persists in circulating monoctyes and bone marrow of healthy people who had a diagnosis of Q fever and recovered from the acute illness. Complications of Acute Q Fever About 2% of patients with acute Q fever manifest neurologic involvement.
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From page 133... ...
. The committee concludes that there is sufficient evidence of an association between infection by Coxiella burnetii and endocarditis years after primary infection.
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From page 134... ...
burnetii infection. The committee concludes that there is sufficient evidence of an association between infection by Coxiella burnetii and chronic hepatitis years after primary infection.
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From page 135... ...
Second, TB has a long history of occurrence and transmission in military settings and remains a cause of potential delayed adverse health outcomes in US troops and veterans of the Gulf War, OEF, and OIF -- especially those who are or were deployed to regions where TB is highly endemic. The committee discusses TB in the military at the end of this section.
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From page 136... ...
Risk Factors for Transmission TB is not a highly infectious disease, so most transmission occurs in such places where people have close and frequent contact such as households and closed community settings. Occasionally, however, infection follows brief, casual contact in airplanes, buses, hospitals, or prisons.
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From page 137... ...
. Thus, for US military personnel, the risk of exposure to TB is much greater in southcentral and southwest Asia than domestically.
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From page 138... ...
138 GULF WAR AND HEALTH 1.000 Risk Relative 0.410 0.130 0.086 0.028 1 2 3 4 5 Years Since "Conversion" FIGURE 5.1 Relationship between rate at which people experience their first episode of active TB in each year following infection or reinfection and rate at which people experience their first episode of active TB during first year after infection or reinfection. Estimated from distribution of interval between TST conversion and onset of active TB in those who were tuberculin-negative at start of UK Medical Research Council's trial of BCG vaccine in 1950-1952 (Hart and Sutherland 1977)
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From page 139... ...
Tuberculin reactors whose induration measured 5 mm at enlistment and who had a history of household exposure to TB were more likely to progress to active TB than sailors who lacked such a history. HIV infection dramatically increases the risk of both primary TB and reactivation TB (Davies 2005)
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From page 140... ...
Treatment for Latent Tuberculosis Infection to Prevent Active Tuberculosis To mitigate the risk of LTBI's becoming active TB, such infections are treated with isoniazid for 9 months. Completing the treatment regimen reduces the risk of active TB by 7090% (CDC 2000b)
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From page 141... ...
TB may present atypically in some patients, particularly diabetics, immunocompromised people, and people with HIV infection. In such cases, chest radiographic findings are variable, ranging from dense lobar or segmental consolidation to atelectasis, large-mass lesions, or cavities.
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From page 142... ...
Although pleural fluid is exudative, it usually tests negative with an AFB smear and, in 75% of cases, in cultures. The committee concludes that there is sufficient evidence of a causal relationship between infection with Mycobacterium tuberculosis and occurrence of active tuberculosis months to decades after infection.
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From page 143... ...
Tuberculosis Meningitis and Long-Term Neurologic Disability It is well accepted in the biomedical community that TB meningitis is associated with long-term neurologic outcomes. The extent of disability depends on the duration and severity of acute symptoms, the age of the patient, and the neurologic deficits (Dube et al.
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From page 144... ...
. The committee concludes that there is sufficient evidence of an association between severe forms of pulmonary and extrapulmonary tuberculosis and long-term adverse health outcomes due to irreversible tissue damage.
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From page 145... ...
. No case of active TB has been recognized in troops deployed to the Persian Gulf during Operation Desert Shield or Operation Desert Storm (Hyams et al.
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From page 146... ...
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From page 147... ...
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From page 148... ...
148 ;s ev I; te LTB osiulrc Effecti Da ubeT 06; Force TB re fense; = 20y Air ncee valrep-hghiaot toerusopxefo weelp 3niht TB; the Arm of wi eless- het ry peor hom riskr heethweni ce rveillan TSTaevie Defotne ary-care Secreta; lation, prim Departm TestnikSniul of ntemrt = 06 pa 20 ngitaco theig rme Su rece popu byd berc De ter opl DOD; Tu = 5; rel reo assessinr ealthH beflen fo detotlenno Pe italp Cen )
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From page 149... ...
Those reports could help the military to estimate the likelihood that a person who acquires a TB infection harbors a drug-resistant strain. WEST NILE VIRUS INFECTION First isolated in 1937 from a febrile woman in the West Nile Province of Uganda, West Nile virus (WNV)
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From page 150... ...
Transmission of West Nile Virus Infection Although WNV is found in several species of mosquitoes, the vast majority of infections are transmitted by Culex spp. (Campbell et al.
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From page 151... ...
. Patients with West Nile fever who do not have neurologic manifestations might have residual fatigue, muscle weakness, and headache that can persist for months after resolution of the acute febrile illness (Watson et al.
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From page 152... ...
Long-Term Adverse Health Outcomes of Infection with West Nile Virus The scientific community is just beginning to unveil the long-term adverse health outcomes of WNV infection. Two teams of investigators have conducted long-term followup studies of the self-reported health outcomes of people who suffered acute episodes of W est Nile fever, WNM, WNE, or West Nile meningoencephalitis (Gottfried et al.
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From page 153... ...
study, two of the five patients whose acute illness lacked neurologic involvement reported a full recovery during the 1-year followup interview; the degree of recovery of the other three patients, who moved to nursing facilities after their WNV infection, was not ascertained. Unlike the retrospective case-series studies based on self-reported symptoms, a prospective, clinical case series of long-term morbidity associated with WNND was conducted with 39 suspect cases of acute WNV infection in Louisiana (Sejvar et al.
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From page 154... ...
The committee concludes that there is sufficient evidence of an association between acute West Nile virus infection and variable levels of physical, functional, or cognitive disability that may persist for months, years, or permanently.
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From page 155... ...
Future investigators will be able to conduct more robust studies on the long-term adverse health outcomes of patients who suffer acute infection by WNV, and create a broader foundation for conclusions about the acute illness and its long-term adverse health outcomes. The committee recommends that the Department of Veterans Affairs (VA)
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From page 156... ...
Clinical Infectious Diseases 22(3)
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From page 157... ...
American Journal of Tropical Medicine and Hygiene 64(1-2 Suppl)
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From page 158... ...
2002. Update: Investigations of West Nile virus infections in recipients of organ transplantation and blood transfusion.
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From page 159... ...
2005e. West Nile Virus Activity -- United States, January 1 -- December 1, 2005.
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From page 160... ...
2004. Differential diagnosis of West Nile encephalitis.
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From page 161... ...
1993. Q fever meningoencephalitis in a soldier returning from the Persian Gulf War.
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From page 162... ...
2005. Clinical description and follow-up investigation of human West Nile virus cases.
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From page 163... ...
2004. West Nile virus: A growing concern?
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From page 164... ...
1999. West Nile fever -- A reemerging mosquito-borne viral disease in Europe.
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From page 165... ...
2000. Ribavirin inhibits West Nile virus replication and cytopathic effect in neural cells.
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From page 166... ...
2004. Long term prognosis for clinical West Nile virus infection.
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From page 167... ...
Clinical Infectious Diseases 19(4)
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From page 168... ...
Clinical Infectious Diseases 15(4)
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From page 169... ...
2001. The outbreak of West Nile virus infection in the New York City area in 1999.
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From page 170... ...
Clinical Infectious Diseases 39(7)
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From page 171... ...
2001. West Nile virus: A reemerging global pathogen.
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From page 172... ...
Clinical Infectious Diseases 38(3 Suppl)
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From page 173... ...
2005. Acute flaccid paralysis: The spectrum of a newly recognized complication of West Nile virus infection.
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From page 174... ...
2003. Neurologic manifestations and outcome of West Nile virus infection.
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From page 175... ...
1988. Seroepidemiological study of infection with West Nile virus in Karachi, Pakistan, in 1983 and 1985.
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From page 176... ...
and IgG enzyme immunoassays in serologic diagnosis of West Nile Virus infection. Journal of Clinical Microbiology 38(6)
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From page 177... ...
Clinical Infectious Diseases 22(3)
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From page 178... ...
2004. Clinical characteristics and functional outcomes of West Nile Fever.
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From page 179... ...
Clinical Infectious Diseases 31(4)
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