Eosinophilia in Advanced HIV Infection with Hyperinfection Syndrome: A Case Report.

Strongyloides stercoralis is a soil-transmitted helminth that occurs almost worldwide, yet estimates about its prevalence are not well documented. The spectrum of clinical manifestations of strongyloidiasis is wide, ranging from asymptomatic disease to hyperinfection or dissemination of larvae involving multiple organ systems. Immunosuppression can increase the risk of hyperinfection syndrome in patients with strongyloidiasis. Strongyloidiasis continues to remain a neglected tropical disease, the diagnosis of which is often overlooked by clinicians and diagnosticians alike. The paucity of published literature from India further accentuates this problem. We hereby present a case report with the aim of elucidating this relatively underreported infection.

INTRODUCTION

Strongyloides stercoralis is a soil-transmitted helminth (STH) that occurs almost worldwide, yet estimates about its prevalence are not well documented. Compared to other major STHs such as Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, and Trichuris trichiura, the information on S. stercoralis is scarce.[1]

The spectrum of clinical manifestations of strongyloidiasis is wide, ranging from asymptomatic disease to hyperinfection or dissemination of larvae involving multiple organ systems. Asymptomatic strongyloidiasis is the most common form of the disease. Hyperinfection syndrome is estimated to occur in 1.5%–2.5% of the patients with strongyloidiasis.[2]

Immunosuppression, either iatrogenic (for example, because of use of systemic corticosteroids) or because of intercurrent illness such as Human T-cell Lymphotropic Virus-I (HTLV-1) and Human Immunodeficiency Virus (HIV) infection, and organ transplantation can increase the risk of hyperinfection syndrome in patients with strongyloidiasis.[2] Few previous reports from India have shown that the prevalence of strongyloidiasis in HIV-infected patients ranged from 0% to 5.3% with the exception of a study conducted in northeastern India, which showed a high prevalence of 27.3%.[3]

Strongyloidiasis continues to remain a neglected tropical disease, the diagnosis of which is often overlooked by clinicians and diagnosticians alike. The paucity of published literature from India further accentuates this problem.[4] We hereby present a case report with the aim of elucidating this relatively underreported infection.

CASE REPORT

A 40-year-old female patient presented in outpatient department of a tertiary care hospital in 2017 with complaints of intermittent, low-grade fever, malaise, nocturnal cough with mucoid expectoration, dyspnea on exertion and loss of appetite since 3 months. The patient also had a history of passing loose stools and abdominal pain since 4 days. There was no history of chest pain or hemoptysis. On further questioning, the patient revealed that her husband had expired recently with probable diagnosis of pulmonary tuberculosis. General physical examination revealed that the patient was febrile and had pallor. No abnormality was detected on systemic examination.

Investigations were carried out, the results of which are as follows: complete hemogram revealed anemia (hemoglobin, 8g/dL), normal total leucocyte count (5100/mm3) and eosinophilia (22% eosinophil in differential leukocyte count and absolute eosinophil count, 1122/µL). Erythrocyte sedimentation rate was 50mm/h. Urine analysis revealed grade 3 proteinuria. Liver and kidney function tests were within normal limits. Blood culture was sterile after 7 days of aerobic incubation. Microscopic examination of Gram-stained smears of sputum sample revealed the presence of normal throat flora, which was subsequently confirmed by aerobic culture. Keeping the likelihood of her spouse dying of pulmonary tuberculosis in mind, two consecutive sputum samples of this patient were subjected to Ziehl–Neelsen staining as per Revised National Tuberculosis Control guidelines. Serum samples of this patient were also tested for the presence of anti-HIV antibodies as per National AIDS Control Organization (NACO) guidelines. Although, no acid-fast bacilli were seen in both sputum samples, certain non-acid-fast structures morphologically resembling parasitic larvae were visible, and the patient was found to be seropositive for HIV. The CD4+ T-cell count of this patient was 39 cells/mm3. X-ray of the chest revealed infiltrates in the lower zone of right lung [Figure 1].

Figure 1

X-ray of the chest showing infiltrates in the lower zone of right lung

Subsequently, the sputum samples of this patient were screened again, keeping a parasitic infection in mind and to rule out Pneumocystis jirovecii infection. Giemsa-stained smears of sputum sample further revealed the presence of structures morphologically resembling eggs and larvae of Strongyloides spp. [Figure 2A and B]. Sputum wet mount examination revealed the presence of oval, transparent, thin-walled eggs approximately 55×30 µm in size along with motile rhabditiform larvae approximately 250–300 µm in length with short buccal cavity and double bulb esophagus suggestive of S. stercoralis [Figure 3]. Later on, stool samples obtained from this patient also revealed similar findings on wet mount examination. The aforementioned microscopic findings were further substantiated by performing agar plate culture method [Figure 4].

Figure 2

Giemsa-stained smears of sputum sample showing presence of structures morphologically resembling (A) eggs and (B) larvae of Strongyloides spp.

Figure 3

Sputum wet mount examination showing structures morphologically resembling rhabditiform larvae of Strongyloides stercoralis

Figure 4

Agar plate culture method for demonstrating the presence of rhabditiform larvae of Strongyloides stercoralis

In lieu of clinical background and laboratory evaluation results, a diagnosis of strongyloidiasis with hyperinfection syndrome was made. Antiretroviral therapy (ART) was started as per NACO guidelines. Ivermectin 200 µg/kg was given for 7 days. The patient was followed up for 6 months and she showed remarkable improvement.

DISCUSSION

The hallmark of hyperinfection syndrome is an increase in the number of larvae in stool and/or sputum along with manifestations confined to respiratory and gastrointestinal systems.[2] The manifestations of this syndrome are divided into intestinal and extraintestinal. The intestinal manifestations include severe cramping abdominal pain, watery diarrhea, weight loss, nausea, vomiting and occasional gastrointestinal bleeding. The extraintestinal manifestations include mainly asthma-like symptoms such as cough and wheezing, pneumonia and pulmonary hemorrhage with diffuse bilateral infiltrates as shown in the chest X-ray.[2]

Traditionally, advanced HIV infection has not been associated with disseminated strongyloidiasis, despite a 21-fold increased risk of intestinal infection in endemic areas. The absence of dissemination has been explained by the fact that Th2 immune function is preserved in the later stages of this infection. In 1987, the Center for Disease Control and Prevention and the World Health Organization removed disseminated strongyloidiasis in HIV from the list of Acquired Immunodeficiency Syndrome (AIDS) defining illnesses. This has resulted in reduced awareness of clinicians about disseminated strongyloidiasis in HIV-infected patients. Despite the apparent absence of disseminated strongyloidiasis in advanced HIV infection, four such cases have been reported after initiation of Antiretroviral Therapy (ART) supporting the existence of immune reconstitution disease towards S. stercoralis.[5]

Eosinophilia is not uncommon in patients infected with HIV and is encountered in 28% of such patients.[6] The presence of eosinophilia, regardless of the HIV status of the patient, has traditionally been associated with an underlying disease process. In developing countries, eosinophilia is most commonly associated with helminth and fungal infections.[6] Eosinophils are recruited to the site of parasitic infection and promote a Th2 immune response. Infections such as histoplasmosis and tuberculosis have also been associated with eosinophilia. HIV itself is thought to cause eosinophilia because of a Th1–Th2 shift and studies have shown an association between eosinophilia and advanced HIV infection with low CD4+ cell counts.[67] Interestingly, the lack of eosinophilia among HIV-infected individuals with hyperinfection syndrome has been associated with poor prognosis.[8]

In a study conducted by Skiest and Keiser,[9] it was concluded that eosinophilia in AIDS patients is associated with cutaneous disease. A study of patients with advanced HIV during the pre-Highly Active Anti-retroviral Therapy (HAART) era found that pruritic skin rashes, in particular, eosinophilic pustular folliculitis, were associated with eosinophilia.[6]

The patient under study had eosinophilia with pulmonary manifestations. There were no skin lesions. The patient was simultaneously evaluated for pulmonary tuberculosis and HIV infection, keeping the possibility of her husband dying of pulmonary tuberculosis in mind. The patient was found to be seropositive for HIV and the microscopic examination of sputum samples revealed neither acid-fast bacilli nor P. jirovecii. Microscopic examination of sputum and stool samples of the patient revealed the presence of eggs and rhabditiform larvae of S. stercoralis. The CD4+ count was subsequently found to be 39 cells/mm3, indicating a hyperinfection syndrome with an underlying severe immunosuppression.

Eggs of S. stercoralis may occasionally be found in sputum samples obtained from patients with hyperinfection syndrome.[10] Bava et al.[11] first reported the presence of adult female and eggs of S. stercoralis in respiratory secretions obtained from an HIV-negative patient who had polymyositis and was on a treatment with corticosteroids. The authors concluded that the presence of adult female S. stercoralis in clinical samples can be considered as an indirect marker of severe immunosuppression.[11] The presence of eggs of S. stercoralis in respiratory secretions obtained from an AIDS patient was also reported by Bava and Troncoso.[12]

Opportunistic lung infections such as those caused by Mycobacterium tuberculosis, M. avium-intracellulare, P. jirovecii, Herpes Simplex Virus, Cytomegalovirus and Candida and Aspergillus spp. have commonly been reported in HIV-infected patients with CD4+ T-cell count <200 cells/µL.[13] Parasites such as Paragonimus westermani, Capillaria aerophila, Entamoeba histolytica, and rarely migrating larvae of Strongyloides stercoralis, Ascaris lumbricoides, Ancylostoma duodenale and Necator americanus have also been isolated from sputum samples of these patients.[14]

In a study conducted by Chordia et al.,[3] it was found that CD4 cell counts were significantly lower in HIV-infected individuals with Strongyloides compared with those with no parasites in their stool samples (P < 0.001). The authors concluded that in HIV, an association with lower CD4 counts indicated the need for inclusion of Strongyloides as an opportunistic parasite.[3] A study from Thailand also reported an increased prevalence of strongyloidiasis in HIV-infected patients with CD4 counts <100 cells/µL.[15] The present case also highlights this point.

CONCLUSION

Eosinophilia in HIV-infected patients could be an important clue for diagnosing conditions such as hyperinfection syndrome due to S. stercoralis. This seemingly underreported association needs further evaluation.

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Conflicts of interest

There are no conflicts of interest.