Strongyloidosis Hyperinfection Syndrome in an HIV-Infected …downloads.hindawi.com/journals/criid/2018/6870768.pdf · 2019-07-30 · CaseReport Strongyloidosis Hyperinfection Syndrome

Case ReportStrongyloidosis Hyperinfection Syndrome in an HIV-InfectedPatient: A Rare Manifestation of Immune ReconstitutionInflammatory Syndrome

Kartik Natrajan,1 Mahenderkumar Medisetty,1 Raviraj Gawali,1 Ajit Tambolkar,1

Divya Patel,2 Vinay Thorat,3 Nachiket Dubale,3 Vrushali Khirid,4 Chinmay Saraf,5

and Ameet Dravid 1

1Department of Medicine, Poona Hospital and Research Center, Pune, Maharashtra, India2Department of Pathology, Poona Hospital and Research Center, Pune, Maharashtra, India3Department of Gastroenterology, Poona Hospital and Research Center, Pune, Maharashtra, India4Department of Pulmonology, Poona Hospital and Research Center, Pune, Maharashtra, India5Precision Diagnostics and Biosciences, Pune, Maharashtra, India

Correspondence should be addressed to Ameet Dravid; [email protected]

Received 14 August 2018; Accepted 16 October 2018; Published 28 October 2018

Academic Editor: Larry M. Bush

Copyright © 2018 Kartik Natrajan et al. ,is is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

Parasitic infections such as Strongyloides stercoralis and HIV have been reported to coexist, particularly in resource-limitedsettings such as India. In an immunocompromised host, S. stercoralis can progress to strongyloidiasis hyperinfection syndrome(SHS). However, SHS is not common in patients with advanced HIV disease. Immune reconstitution inflammatory syndrome(IRIS) developing after initiation of antiretroviral therapy (ART) can target multiple pathogens including S. stercoralis. ,eauthors present here a 46-year-old HIV-infected female who was recently diagnosed with HIV-1 infection, started ART, anddeveloped SHS. Her upper GI endoscopy revealed severe gastroduodenitis, and X-ray chest showed extensive bilateral pneu-monitis. We could identify S. stercoralis in induced sputum and duodenal biopsy. We could also identify gut inflammation torestrict invading parasites. After receiving antihelminthic therapy, she showed improvement, a course of events that fit thediagnosis of unmasking S. stercoralis IRIS.

1. Background

Strongyloides stercoralis typically infects the small bowel(duodenum and jejunum) of human hosts and is endemic totropical and subtropical regions. ,e helminth enters thebody through the skin and initially migrates through thevenous peripheral blood system to the lung parenchyma. Itascends the tracheobronchial tree and is swallowed to reachthe small intestine. After initial infection, mature females inthe duodenum produce rhabditiform larvae that can developinto infective filariform larvae and reinfect the host throughpenetration of intestinal mucosa. ,is unique autoinfectivecapability facilitates chronic infection in a single host for

decades [1]. Most immunocompetent hosts are asymp-tomatic. Strongyloidiasis hyperinfection syndrome (SHS) isa manifestation of accelerated autoinfection in an immu-nocompromised host (chronic steroid users and HTLV-1-infected individuals) involving multiple organs (dissemi-nated disease) and extensive gastrointestinal (GI) in-volvement. ,e massive dissemination of filariform larvae tothe lungs, liver, heart, central nervous system, and endocrineglands induces inflammation that may result in symptomaticdysfunction of these organs and even septic shock. SHS isestimated to occur in 1.5%–2.5% of the patients withstrongyloidiasis [2]. S. stercoralis remains a neglectedtropical disease, and its association with HIV coinfection is

HindawiCase Reports in Infectious DiseasesVolume 2018, Article ID 6870768, 4 pageshttps://doi.org/10.1155/2018/6870768

sparsely studied in resource-limited settings such as India. Itis reflected by the paucity of the published literature onHIV/S. stercoralis coinfection [3–5]. Since 2005, there havebeen reports of seven patients presenting with SHS afterantiretroviral therapy (ART) initiation [6–12]. ART-associated immune reconstitution inflammatory syndrome(IRIS) to S. stercoralis may be responsible for it. We herebyreport a case of SHS as a component of IRIS in an HIV-positive individual recently initiated on ART in Pune, India.

2. Case Report

A 46-year-old female presented with complaints of fever,breathlessness on minimal exertion, vomiting, abdominalpain, and reduced appetite since 10 days. She also com-plained of weight loss of 10 kilograms in the last 6 months.She was diagnosed with HIV-1 infection, 1 month prior, andwas prescribed tenofovir, lamivudine, and efavirenz fixed-dose combination single-pill regimen. Her baseline CD4count was 68 cells/mm3, and plasma HIV-1 viral load was867,000 copies/ml. She had no comorbidities or prior sig-nificant medical history. On examination, she was febrile(temperature: 100 degrees Fahrenheit) with pulse (100/min),blood pressure (110/60mm Hg), and respiratory rate(24/min). Respiratory examination revealed crepitations inbilateral inframammary, infraaxillary, and infrascapularareas. ,ere was diffuse abdominal tenderness but noorganomegaly. Rest of the examination including fundo-scopy was unremarkable. Hemoglobin was 8.3 g/dl while restof the biochemical investigations was normal. CD4 countand plasma HIV-1 viral load after 1 month of ART was 190cells/mm3 and 9,500 copies/ml, respectively, suggestingsatisfactory immune reconstitution. ,e arterial blood gas(ABG) was suggestive of hypoxia (pO2-63mm Hg) on roomair. Chest X-ray was suggestive of bilateral, extensive, andpatchy consolidation suggestive of infective etiology (Fig-ure 1). Sonography of abdomen showed multiple mesentericnodes with the largest size of 21mm by 17mm, grade 2 fattyliver, and dilated portal vein. ,e CT scan of chest revealedbilateral ground glass haziness suggestive of pneumocystiscarinii pneumonia (PCP). CT abdomen showed biliary di-latation due to distal CBD stricture, mesenteric lymph-adenopathy and mild diffuse thickening of the caecum, andascending and transverse colon. 2D echocardiography of theheart was normal. Blood culture was sterile, and serumprocalcitonin was normal. Keeping a provisional diagnosisof IRIS to Pneumocystis jirovecii or Mycobacterium tuber-culosis in mind, she was started on high-dose trimethoprim-sulphamethoxazole (TMP-SMX), oral steroids, and empir-ical antitubercular therapy (ATT) in addition to ART. Shehad diarrhea on admission, which subsided in 2 days aftertaking loperamide. Stool routine and modified Ziehl–Neelsen (ZN) examination was unremarkable. Due toa suspicion of CMV enterocolitis, she was also started onempirical oral valgancyclovir. Bronchoscopy with BAL wasattempted but had to be aborted in view of worseninghypoxia during procedure. For establishing diagnosis, upperGI endoscopy and colonoscopy were attempted. Upper GI

endoscopy revealed diffuse gastroduodenitis. Colonoscopyshowed patchy colitis. Duodenal biopsy revealed focalblunting, ulceration, and neutrophilic exudates (Figure 2).,e surface epithelium showed several eggs, larvae, andadult forms of S. stercoralis (Figure 3). Lamina propriashowed moderate mononuclear inflammatory infiltrate withlymphoid follicle formation and many admixed eosinophils(Figures 2 and 3). ,ere was no evidence of tuberculosis ormalignancy. Induced sputum also demonstrated larvae of S.stercoralis. As a result, diagnosis of SHS as a manifestation ofIRIS was made, and she was started on an oral combinationof albendazole (400mg twice a day) and ivermectin(200 µg/kg). Inspite of antihelminthic treatment, her dyspneaworsened. Her repeat ABG showed hypoxia (PO2 –47mmHg, Spo2 89%) and respiratory alkalosis. She developed hy-potension (blood pressure 80/60mm Hg) and alteredsensorium in the form of increasing drowsiness (GlasgowComa Scale 12/15). She was shifted to the Intensive CareUnit (ICU) for the same. MRI brain and CSF examinationwere normal while serum sodium level had dropped to125mEq/L. Noradrenaline infusion and noninvasiveBIPAP ventilation were started. She was initiated on in-travenous (i.v.) meropenem, i.v. teicoplanin, and i.v. flu-conazole in addition to antihelminthic agents, steroids (intapering doses), and ART. ATT and valganciclovir werewithdrawn while TMP-SMX was reduced to prophylacticdose. She gradually started improving over the next 7 dayswith improvement in sensorium and reduction inbreathlessness. She was shifted out of the ICU by day 21 ofadmission. Her CXR showed complete resolution ofpneumonic consolidation. She was discharged on oralantihelminthic treatment which she continued for another8 weeks. Follow-up endoscopy studies showed completeclearance of S. stercoralis.

Figure 1: Chest X-ray of patient with SHS showing bilateral ex-tensive pneumonic consolidation.

2 Case Reports in Infectious Diseases

3. Discussion

Our case report is the eighth reported case of IRIS to S.stercoralis worldwide and the first from India. AdvancedHIV has not been linked with disseminated strongyloidiasisdespite a 21-fold increased risk of intestinal infection inendemic areas [3]. Few previous reports from India haveshown that the prevalence of S. stercoralis in HIV-infectedpatients ranged from 0% to 27.3% [3]. However, cases of SHShave been rarely described in HIV-infected patients in India[4, 5]. ,e absence is explained by the fact that in HIV-positive patients with higher CD4+ cell counts, direct de-velopment of infective filariform larvae in the gut (auto-infection) is favored, compared with those with lesserimmune function (low CD4 count or advanced HIV dis-ease), in whom, indirect development is favored. Indirectdevelopment of filariform larvae in individuals with ad-vanced HIV disease reduces the opportunity for dissemi-nation to occur [13]. T helper cell type 2 (,2) immunefunction is well preserved in advanced HIV which alsoprevents SHS or dissemination [13, 14]. As a result, dis-seminated strongyloidiasis in HIV was removed from theCenter for Disease Control (CDC) and World Health Or-ganization (WHO) lists of HIV specific infections in 1987.Since then, physician awareness of SHS in HIV has reduced[11]. ,is might change in future due to cases of SHS beingreported after initiating ART, supporting the existence

of immune reconstitution inflammatory syndrome(IRIS)towards S. stercoralis [6–12]. Two distinct patterns of IRISare described in the literature and are now recognized as“paradoxical IRIS” and “unmasking IRIS.” In paradoxicalforms of IRIS, symptoms and signs associated with a knownopportunistic infection (OI), for which treatment is underway, recur or become acutely worse, despite an earlier fa-vorable response to therapy prior to ART. In unmaskingIRIS, a new OI presents with a pronounced inflammatorycomponent following ART initiation [15]. Although S.stercoralis is listed as an immune reconstitution in-flammatory syndrome- (IRIS-) related pathogen, this con-dition is scarcely reported in the literature [14]. In the sevenprevious reports of IRIS to S. stercoralis, unmasking IRIS wasseen in five cases [6–10] while paradoxical IRIS was seen inthe other two [11, 12]. IRIS was seen approximately 19–150days after ART initiation.

In our patient, unmasking IRIS occurred 30 days afterART initiation and manifested as severe gastroduodenitisand patchy colitis leading to severe abdominal pain, vom-iting, and intermittent diarrhea. In addition, pulmonaryinvolvement was evidenced by dyspnea and bilateralpneumonitis on CXR leading to acute respiratory distresssyndrome (ARDS). ,e presence of immune reconstitutionwas indicated by an increased CD4+ count and decreasedviral load comparable to baseline. ,e temporal relationshipbetween ART initiation and SHS in this case suggestsa causal association between the two events.,ere are severalpossible explanations for this rapid clinical deterioration.First, a high parasite burden was present prior to ART, andthe development of symptoms was a result of a renewedimmune response to the pathogen that is typical ofunmasking IRIS. Post-ART duodenal biopsy showed heavyparasite load coupled with moderate mononuclear infiltrate,eosinophil infiltration, and granuloma formation (Figures 2and 3). Second, addition of steroids for treatment of IRIScould have also contributed to clinical deterioration duringadmission. However, our patient was not exposed to steroidsprior to diagnosis of SHS, unlike other case reports [6, 9].Our patient of SHS did not show eosinophilia on peripheralblood smear [6, 7] or haematogenous spread of gut coliforms[6]. Our histopathology findings were also not consistentwith earlier case reports which showed no significant in-flammatory response in the postmortem histopathology inpatients with SHS after immune reconstitution [10, 11].Temporary withdrawal of ART in view of life-threateningIRIS was not done unlike earlier instances [11]. We usedantihelminthic drug regimens for extended duration asshown in previous cases of SHS. Our case is the eighth-reported patient with progressive strongyloidiasis afterimmune reconstitution, lending additional support for therecognition of IRIS to S. stercoralis. We believe that theprevalence of this phenomenon is much higher in resource-limited settings such as India which is coendemic to HIVand S. stercoralis and has seen rapid scale up of ARTin recentyears. However, lack of awareness of health care personnel orlack of facilities in resource-limited settings to establishdiagnoses leads to underreporting [14].

Figure 2: Duodenal histopathology showing gut inflammationwith mucosal disruption.

Figure 3: Duodenal histopathology showing eggs, larvae, and adultforms of Strongyloides stercoralis.

Case Reports in Infectious Diseases 3

4. Conclusions

In conclusion, physicians working in resource-limited set-tings such as India should consider parasitic infections asa differential diagnosis while evaluating cases of IRIS inHIV-infected patients starting ART.

Conflicts of Interest

,e authors declare that there are no conflicts of interestregarding the publication of this paper.

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[12] H. Bar-Yoseph, Y. Zohar, and M. Lorber, “Strongyloidiasis-related IRIS,” Journal of the International Association ofProviders of AIDS Care, vol. 16, no. 1, pp. 8–10, 2017.

[13] M. E. Viney, M. Brown, N. E. Omoding et al., “Why does HIVinfection not lead to disseminated strongyloidiasis?,” Journalof Infectious Diseases, vol. 190, no. 12, pp. 2175–2180, 2004.

[14] S. D. Lawn and R. J. Wilkinson, “Immune reconstitutiondisease associated with parasitic infections following anti-retroviral treatment,” Parasite Immunology, vol. 28, no. 11,pp. 625–633, 2006.

[15] N. F. Walker, J. Scriven, G. Meintjes, and R. J. Wilkinson,“Immune reconstitution inflammatory syndrome in HIVinfected patients,” HIV Aids (Auckl), vol. 7, pp. 49–64, 2015.

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