CASE REPORT |
https://doi.org/10.5005/jacm-11020-0003 |
Pulmonary Infection due to Conidiobolus coronatus in a Patient with Crescentic Immunoglobulin A Nephropathy: Case Report and Literature Review
1–4Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India
Corresponding Author: Sujatha Sistla, Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India, Phone: +91 9894058062, e-mail: sujathasistla@gmail.com
Received: 10 April 2024; Accepted: 28 May 2024; Published on: 26 July 2024
ABSTRACT
Conidiobolomycosis, a rare chronic subcutaneous mycosis, is caused by filamentous fungi belonging to the phylum Entomophthoromycota. The most common form of conidiobolomycosis is the rhinofacial form involving sinuses, nasal passages, and the surrounding tissue. However, rare forms of invasive infection can occur in immunocompromised hosts. Here, we report a case of pulmonary conidiobolomycosis due to Conidiobolus coronatus in a patient with crescentic immunoglobulin A (IgA) nephropathy.
Keywords: Case report, Conidiobolomycosis, Crescentic immunoglobulin A nephropathy
How to cite this article: M MB, Darjees D, Ambati NLS, et al. Pulmonary Infection due to Conidiobolus coronatus in a Patient with Crescentic Immunoglobulin A Nephropathy: Case Report and Literature Review. J Acad Clin Microbiol 2024;26(1):23–26.
Source of support: Nil
Conflict of interest: None
Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.
INTRODUCTION
Conidiobolus species are filamentous fungi belonging to the phylum Entomophthoromycota, which are responsible for the disease conidiobolomycosis. These fungi are ubiquitous in the environment, especially in soil and decaying vegetation. It is a rare form of fungal infection typically found in tropical and subtropical countries.1,2 It usually occurs in individuals with underlying conditions that compromise the immune system, such as poorly controlled diabetes mellitus, human immunodeficiency virus (HIV), or malignancy. The most common form of conidiobolomycosis is the rhinofacial form involving sinuses, nasal passages, and the surrounding tissue.3 However, rare forms of invasive infection can occur in immunocompromised hosts.3,4 Here we report a case of pulmonary infection with Conidiobolus species in a woman with chronic kidney disease secondary to crescentic immunoglobulin A (IgA) nephropathy and primary hyperparathyroidism.
CASE DESCRIPTION
A 25-year-old woman, para-2, live-1, abortion-1, known case of chronic kidney disease secondary to crescentic IgA nephropathy, on maintenance hemodialysis twice weekly for the past 6 months, presented with complaints of breathlessness, cough with expectoration, abdominal distension, and decreased urine output 10 days prior to presentation. Breathlessness worsened on walking and lying down but improved upon sitting. She also reported bilateral leg swelling over the past 6 months. There was no history of fever, chest pain, abdominal pain, burning micturition, or altered sensorium. One month earlier, she had pyomyositis in her right calf for which incision and drainage was performed, followed by secondary suturing 6 days ago. She also mentioned experiencing pain in the right calf and difficulty walking for the past 10 days, along with discharge from the suture site.
On examination, she was well-built and moderately nourished, conscious, and oriented. Pallor was noted along with bilateral pitting pedal edema. Her pulse rate was 100 beats per minute, blood pressure was 180/100 mm Hg, respiratory rate was 32 breaths per minute with oxygen saturation of 88% on room air. Auscultation revealed decreased breath sounds on the right side and bilateral infrascapular and left infra-axillary fine crepitations. Abdominal examination showed a palpable liver 3 cm below the right costal margin with mild ascites. The jugular venous pulse was normal, and other systemic examinations were unremarkable. Local examination of the right calf revealed tenderness and mild serous discharge at the suture site, with surrounding skin induration but no pus discharge.
INVESTIGATIONS
Laboratory investigations revealed low hemoglobin (5.1 gm/dL), total leukocyte count of 10,750 cells/mm3 with neutrophilic predominance and a platelet count of 288 × 10 cells/L. Her serum urea and creatinine levels were elevated in concordance with chronic kidney disease as depicted in Table 1. Arterial blood gas analysis showed high anion gap metabolic acidosis. Dialysis was initiated due to chronic renal failure.
| Variable/unit | On admission | Reference values |
|---|---|---|
| Hemoglobin (gm/L) | 6.6 | Males: 14–18 Females: 12–16 |
| Hematocrit (%) | 17.1 | 38–50 |
| Leukocytes (cells × 109/L) | 10.630 | 4–11 |
| Neutrophils (%) | 72 | 40–75% |
| Lymphocytes (%) | 23 | 20–45% |
| Platelets (105/L) | 1.7 | 1.5–4 |
| Alanine aminotransferase (U/L) | 17 | 7–56 |
| Aspartate aminotransferase (U/L) | 19 | 10–36 |
| Gamma-glutamyl transferase (U/L) | 13 | 5–40 |
| Urea (mg/dL) | 58 | 20–40 |
| Creatinine (mg/dL) | 4.3 | 0.7–1.3 |
| Total protein (gm/L) | 60 | 66–83 |
| Albumin (gm/L) | 21 | 35–55 |
| Pleural fluid | ||
| White blood cells (cells/μL) | 140 | 1700 |
| Neutrophils (%) | 75 | 1 |
| Lymphocytes (%) | 25 | 23 |
Chest X-ray revealed right-sided pleural effusion. High-resolution computed tomography (HRCT) of the thorax showed moderate right-sided pleural effusion, cardiomegaly with mild pericardial effusion, and peribronchovascular consolidation in the right middle lobe and inferior lobe, as well as in the left lingular segment of the left lower lobe (Fig. 1). She was started empirically on injection piperacillin–tazobactam 2.25 gm IV every 6 hours after renal adjustment. Ultrasound examination of the right calf showed a heterogeneous hypoechoic collection measuring 5 × 2.1 × 9 cm in the intramuscular plane. Based on the clinical, laboratory, and radiological findings, a provisional diagnosis of pulmonary edema was made. Diagnostic pleural tapping was performed and the sample was sent for bacterial and fungal culture, as well as Cartridge-based nucleic acid amplification test (CBNAAT) for Mycobacterium tuberculosis complex. Gram staining of the pleural fluid showed the presence of pus cells and broad aseptate hyphae. The sample was inoculated onto 5% sheep blood agar, MacConkey agar, chocolate agar, and brain heart infusion (BHI) broth, and incubated aerobically at 37°C. After 48 hours of incubation, all three culture plates were examined for the presence of growth, and the sample was reported sterile. BHI broth became turbid with the presence of fungal balls on the 4th day of incubation. Subculture was performed on 5% sheep blood agar and Sabouraud Dextrose Agar (SDA), considering fungal etiology. Colonies grew rapidly within 2 days of incubation at 37°C. The colonies were flat, cream-colored, waxy, and folded with multiple satellite colonies. The walls of the SDA tube were covered with conidia forcibly discharged from the conidiophore, characteristic of Conidiobolus species (Fig. 2). Lactophenol cotton blue (LPCB) mount demonstrated, spherical conidia ranging in size from 10 to 20 µm in size, with prominent papillae characteristic of Conidiobolus species (Fig. 3). CBNAAT for M. tuberculosis complex was negative. Blood cultures were sterile.
Fig. 1: Chest X-ray showing right-sided pleural effusion
Fig. 2: Sabouraud Dextrose Agar tube showing walls of the tube with powdery colonies due to conidia forcibly discharged from the conidiophore
Fig. 3: Lactophenol cotton blue mount showing spherical conidia with prominent papillae (red arrow) and multiple villi (orange arrow)
TREATMENT
The patient was started on injection liposomal amphotericin B, and a total cumulative dose of 3 gm was administered over a 12-day period, with regular monitoring of serum potassium and magnesium levels. Symptoms improved dramatically, with clearing of the pleural effusion and no adverse drug reactions observed. She continued on maintenance hemodialysis for chronic kidney disease, and there was no recurrence of pleural effusion. The patient was discharged when she was afebrile and hemodynamically stable, with instructions for regular follow-ups in the nephrology department for chronic kidney disease.
DISCUSSION
Invasive fungal infections pose a significant risk of morbidity and mortality among immunocompromised individuals. Conidiobolus species are molds belonging to the order Entomophthorales. The name is derived from the Greek word ”Entomon,” meaning insect, reflecting their original identification as pathogens infecting insects. Originally, Basidiobolus and Conidiobolus were classified under the class Zygomycetes, but they now belong to a new order within the subphylum Entomophthoromycotina, known as Entomophthorales. Entomophthoromycota includes Basidiobolomycetes, Neozygitomycetes, and Entomophthoramycetes.5Entomophthoramycetes include Conidiobolus species. This fungus is ubiquitous, found in the environment in soil and decaying vegetation, and acts as a saprotroph on arthropod cadavers. Cases of conidiobolomycosis are typically restricted to their environmental niche, primarily in tropical countries where high humidity is necessary for the fungus to germinate. It is a cosmopolitan soil fungus, prevalent in tropical and subtropical regions such as Africa, Central America, and India.6 It usually causes localized infection and is known to cause infection both in humans and animals.
Though the genus contains around 27 species, Conidiobolus coronatus, C. incongruus, C. lamprauges, and rarely C. pachyzygosporus have been reported as causative agents of human and animal infections.7 The first well-documented human case of conidiobolomycosis was reported in 1965 in an 11-year-old boy residing on Grand Cayman, an island near Jamaica.8 The lesions were limited to the nose and paranasal sinuses, and C. coronatus was grown in pure culture. Conidiobolus species may utilize a variety of modes to enter the human host. Among immunocompetent individuals, infection with Conidiobolus species is typically restricted to the skin and subcutaneous tissue, causing rhinofacial disease and disfigurement. Inhalation of the conidia and subsequent implantation in the nasal mucosa is likely the mode of acquiring the disease. Later, enzymatic destruction can lead to spread into the subcutaneous tissue. Tracheobronchial erosions have been observed in some patients who were autopsied after acquiring the infection, suggesting the respiratory tract as a possible route of acquiring the disease.9 Atypical forms of conidiobolomycosis as described by Blumentrath et al.10 could be infection in the sites other than the nose and maxillary sinus or in other nonfascial cutaneous sites. Literature search revealed only seven cases of disseminated conidiobolomycosis reported worldwide: two cases due to C. coronatus—one in a 64-year-old male postkidney transplantation11 and another in a 10-year-old female with T-cell acute lymphoblastic leukemia12; and three cases due to C. incongruus—one in a 1-year-old male with no underlying conditions,13 a second in a 20-year-old female with no underlying conditions,4 and a third in a 32-year-old female with lymphocytic lymphoma with leukemic transformation.14 An unidentified Conidiobolus species was reported from a 15 months old boy with a hard mass invading the heart and roots of both the lungs15 and the last one due to C. lamprauges9 in a patient with malignant melanoma.
In immunocompromised individuals, conidiobolomycosis can rapidly disseminate to various organs such as the lungs, brain, liver, gastrointestinal tract, and heart. With an increasing number of immunocompromised individuals due to conditions like HIV, transplantation, or other medical conditions, human infections caused by these typically harmless saprophytic fungi are becoming more common. Initially thought to be restricted to tropical countries with farming as a common occupational risk factor, cases of conidiobolomycosis are now increasing globally due to changing climatic conditions and global migration. The requirement of Conidiobolus spp. for high humidity levels for growth and development may explain why their pathogenicity is typically limited to tropical areas.
Immunoglobulin A nephropathy is the most common type of glomerulonephritis worldwide, characterized by the deposition of IgA antibodies in the glomeruli. In our case, the compromised immune response associated with IgA nephropathy and immunosuppressive medications likely predisposed the patient to Conidiobolus infection. The impaired clearance of fungal spores from the respiratory tract and altered immune function may have contributed to the development and progression of the pulmonary infection in this case. The exact mode of transmission could not be established in the present case.
Definitive diagnosis depends on demonstrating fungal elements and characteristic culture findings. A distinctive feature in detecting Conidiobolus species is the presence of forcibly discharged conidia on the lid of the Petri dish. Our isolate was macroscopically and microscopically identical to C. coronatus as reported by others, using the characteristics described by Vilela et al.16,17 Although culture remains the gold standard for the definitive diagnosis of conidiobolomycosis, literature search has revealed many culture-negative cases, even in situations with strong clinical suspicion.18 This may be due to the following reasons: storing samples in the refrigerator, as these fungi typically do not survive at 4°C,19 and aggressive manipulation of the sample before culture, which may render fungi nonviable.3 In cases where cultures are negative, molecular identification of Entomophthoromycotina from fresh frozen or paraffin-embedded tissue can help confirm the diagnosis and identify the genus and species.
In the present case, the patient was treated with injection liposomal amphotericin B, with a total cumulative dose of 3 gm administered over a 12-day period. Treatment of conidiobolomycosis typically involves a combination of medical and surgical approaches. Systemic, prolonged antifungal therapy such as amphotericin B, along with surgical debridement in cases of localized infections, remains the cornerstone of treatment. The choice of the optimal therapeutic agent, its dosage, and duration for conidiobolomycosis remain unclear. There is no single antifungal agent with consistently reliable activity against conidiobolomycosis.20Conidiobolus species are known to exhibit in vitro resistance to many antifungal drugs, including the azole group. Cotrimoxazole, amphotericin B, and combinations of amphotericin B with flucytosine have been attempted against disseminated infections, but success has been limited.4,11,14
CONCLUSION
This case underscores the importance of considering Conidiobolus as a potential pathogen in patients with underlying immunocompromising conditions, such as IgA nephropathy on immunosuppressive therapy. Early diagnosis, appropriate antifungal therapy, and close collaboration between various specialties are crucial for optimal management and improved outcomes in patients with pulmonary conidiobolomycosis. Further research is necessary to enhance our understanding of the pathogenesis and to develop optimal management strategies for this rare fungal infection.
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