When all other tests failed, NGS made the diagnosis

A 56-year old man presented with transient coma, nausea, and vomiting when he visited the local hospital. There were no visible abnormalities observed in the MRI and his CSF pressure on the second day of illness was 275mmH₂O. Despite receiving symptomatic treatment, the patient developed drowsiness and a severe headache. A neurological examination showed hypersomnia (excessive sleepiness), stiff neck, a positive Kernig sign (not being able to extend the knees beyond 90 degrees without pain), and normal muscle strength in the limbs. Further, he had dark red lesions located on both forearms. He had not been on any recent travel, and had no history of freshwater swimming. There was also no report that he had consumed undercooked meat or unpasteurized dairy products. He had worked in a garbage dump for about two years prior to his illness. Bacterial and fungal cultures as well as cytology of the CSF were all negative.

Ultimately, the patient was diagnosed with CNS infection and treated accordingly but his condition worsened on day 14 of onset with development of lethargy, urinary and fecal dysfunction, and weakness of both lower limbs. MRI of both brain and several spinal cord segments showed abnormal signals (MRI from a different patient with Balamuthia is shown above). It took consultation with infectious disease specialists and two NGS (Next-generation Sequencing, pictured below) results to finally diagnose the man with encephalomyelomeningitis caused by Balamuthia mandrillaris. After receiving a combination of various antimicrobials, his prognosis worsened and he died 30 days after the disease onset. (1)

Balamuthia mandrillaris is a free living ameba naturally found in the environment (photo above). It lives freely in soil around the world and may also be present in fresh water. Gardening, playing with dirt, or breathing in soil carried by the wind might increase the risk of infection. It is able to infect anyone, including healthy people. Since its first discovery in 1986, about 200 cases of infection have been reported worldwide, making B. mandrillaris infections extremely rare. (2) This organism can cause a rare and serious infection of the brain called granulomatous amebic encephalitis (GAE) which is fatal in 90% of cases. Balamuthia amebas are thought to enter the body when soil containing the organism comes in contact with skin wounds and cuts, or when dust containing Balamuthia is breathed into the lungs. After initial exposure, the amebas can travel to the brain and cause GAE. It can take weeks to months to develop the first symptoms of Balamuthia GAE after initial exposure.

According to reports, B. mandrillaris infections can manifest in two main ways. The first is more common in the United States and presents as encephalitis without skin lesions. The second is more commonly seen in China and Peru where the skin is usually involved first and then encephalitis develops gradually. The skin lesions usually appear as painless plaques or ulcers and are commonly seen in the center of the face but may also appear on the trunk, hands, and feet. (1) In the case of the 56 year old patient, a pathological examination of the lesions on his forearms was not done and therefore it is not confirmed if this case was a cutaneous manifestation of B. mandrillaris infection.

Non-specific symptoms are the main reason that diagnosis of B. mandrillaris can be very difficult. NGS technology can provide a rapid, early etiologic diagnosis without the need for a local brain biopsy. Although the mortality rate is high for B. mandrillaris infections, early diagnosis and treatment will offer the best chances of survival.

By Alani Vasquez, R&D Manager, Hardy Diagnostics

References: 1, 2

Super Shigella on the Rise

Bacteria of the genus Shigella are clinically-significant pathogens which may cause mild to severe illness. Shigella comprises four species which include Shigella sonnei, Shigella flexneri, Shigella boydii, and Shigella dysenteriae. These bacteria cause an infection coined shigellosis, which infect an estimated 450,000 people in the United States each year.(1)

Shigellosis is characterized by symptoms of abdominal pain, fever, tenesmus (A painfully urgent but ineffectual attempt to urinate or defecate) and diarrhea that may be bloody and/or prolonged.(2) Shigella dysenteriae produces shiga toxin which may cause severe symptoms and can be deadly. However, in many cases, people will not exhibit any symptoms of Shigella infection. At this time, the mortality rate by shigellosis is considered low in the United States. There are an estimated 40 deaths in the United States per year citing shigellosis as the cause.(3)

Shigella bacteria are easily transmissible via the fecal-oral route through food, water, and sexual contact. Shigella has an extremely low infectious dose of approximately 10-100 organisms. Young children, homeless people, travelers, those living with human immunodeficiency virus (HIV), as well as gay or bisexual men are most at risk for infection.(4) A photomicrograph of infected stool is shown below with the gram negative rods of Shigella and characteristic red blood cells.

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Early this year, the CDC issued an urgent

health advisory regarding XDR Shigella

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In late February 2023, the Centers for Disease Control and Prevention (CDC) issued a health advisory due to an increase in cases of extensively drug-resistant (XDR) Shigella species.(4) XDR Shigella are strains that are resistant to azithromycin, ciprofloxacin, ceftriaxone, trimethoprim-sulfamethoxazole, and ampicillin. There are currently no CDC recommendations for treating XDR shigellosis. Alternate antibiotics are limited by US availability, lack of clinical data, as well as poor efficacy for infections in the gut lining.(5) The incidence of XDR Shigella infections has increased from 0% in 2015 to 5% in 2022. The National Antimicrobial Resistance Monitoring System (NARMS) serves to track XDR Shigella.(6)

An infection by Shigella is effectively diagnosed by stool culture on a culture medium such as HardyCHROM SS NoPRO Agar (shown above as teal colored colonies), or alternately, a PCR test. Antimicrobial susceptibility testing (AST) is ordered for positive stool cultures to guide antibiotic treatment for severe cases. Antibiotic treatment typically allows patients to recover faster, however, most people suffering from shigellosis will recover without antibiotic treatment within a week of infection.(1)

In order to reduce the chances of becoming infected with or transmitting Shigella, the CDC recommends: hand washing, avoiding food handling for others, staying home, not swimming, and abstaining from sex.

By Trey Jensen, Technical Service Microbiologist, Hardy Diagnostics

References: 1, 2, 3, 4, 5, 6