The patient is a chronically ill 8-year-old boy from Limpopo province in South Africa, living with his adoptive parents. He was born prematurely at 7 months' gestation, weighing 1.9 kg. There was a history of recent travel to the Kruger National Park, and to India 6 months prior to admission. All his vaccinations were up to date on history, but this was never confirmed. He was markedly underweight for his age (with weight-for-age and height-for-age z scores of -2 and -1, respectively, and body mass index of 13) with a 2-year history of abdominal distension, diarrhoea, failure to thrive and drenching night sweats. There was no history of chronic cough. His treatment up to the time of admission included nutritional and iron supplements and repeated courses of antibiotics. No clinical improvement was achieved with this management.
The patient was referred to a paediatric gastroenterologist in October 2016. He was acutely ill, severely wasted (17 kg) and pyrexial (39  C). He was clinically pale with a tachycardia and mild oedema of his lower limbs. Hepatosplenomegaly was detected, although there was no peripheral lymphadenopathy. His abdomen was severely distended, and he had recurrent diarrhoea and vomiting with marked intolerance of all foods.
Abdominal computed tomography (CT) scan and ultrasound revealed massively enlarged intra-abdominal lymph nodes (see Figure 1) with a moth-eaten appearance of the spleen. Prominent collateral circulation was seen, which was suggestive of portal hypertension.
Laboratory investigations confirmed that the patient was HIV-infected with a CD4 count of 59 cells/muL (7%) and HIV viral load of 453 780 copies/mL (log10 5.66). Further testing revealed mildly elevated liver enzymes. Moderate proteinuria was present and the faecal alpha-1 antitrypsin result was in keeping with a protein-losing enteropathy. His blood count showed microcytic hypochromic anaemia, with the iron function studies reflecting a pattern of reticuloendothelial iron blockade (see Table 1).
The differential diagnosis included tuberculosis or lymphoma. Over a period of 7 months, endoscopically and surgically obtained biopsy material was submitted for histology (see Table 2). Histological images of the duodenum and a lymph node are shown in Figure 2. The findings were consistent with non-tuberculous mycobacterial infection.
Further testing of the biopsy specimens included mycobacterial cultures, all of which showed no growth. Acid-fast bacilli (AFB) were noted during the processing of the tissue samples obtained from the intra-abdominal lymph nodes on 12 October 2016, and again in biopsy material obtained on 08 March 2017. Microscopy performed on a stool sample on 26 March 2017 also showed acid-fast organisms with a coccoid appearance. The polymerase chain reaction (PCR) assay for Mycobacterium avium complex was negative (artus  Mycobac. diff. LC PCR from Qiagen, Germany). Numerous PCR assays for Mycobacterium tuberculosis complex were negative, which include Nanogen (Nanogen Inc., San Diego, CA, USA), BD MAX (BD Diagnostics, Sparks, MD) and the Xpert  MTB/RIF assay (Cepheid Inc., CA, USA). The urinary lipoarabinomannan test conducted on 22 March 2017 was positive.
A cytomegalovirus (CMV) viraemia of 3974 copies/mL (log10 3.60) was measured in March 2017 together with a colon biopsy that was PCR positive for CMV. The Epstein Barr viral load at the time was 9318 copies/mL (log10 3.97).
Anti-mycobacterial treatment was started (rifampicin, isoniazid, ethambutol, pyrazinamide and clarithromycin) followed 4 weeks later with antiretroviral therapy (abacavir, lamivudine and efavirenz). The patient's HIV viral load was undetectable at 3 months, and his CD4 count at that stage was 101 cells/muL (6%). Clinically and radiologically, however, there was no improvement in his abdominal signs and symptoms. Malabsorption and refeeding syndrome was considered, and all treatment, including ganciclovir, was given intravenously. His antiretroviral medication was temporarily suspended until oral feeding could be tolerated. Immune reconstitution inflammatory syndrome (IRIS) was considered, and methylprednisone was initiated (1 mg/kg/dose) for 4 weeks, after which the dosage was tapered and stopped. The patient was given a period of bowel rest and free drainage, after which he was placed on an elemental diet. There was no clinical improvement and liver dysfunction worsened (see Table 1), and hence a decision was made to stop rifampicin, isoniazid and pyrazinamide.
In May 2017, a diagnosis of Mycobacterium genavense was made, based on sequencing of a mycobacterial 16S rRNA PCR product. This identity was subsequently confirmed using the HAIN Lifescience GenoType (Nehren, Germany) Mycobacterium AS assay that was performed directly on a histology specimen from May 2017. As a result of this finding, and in consultation with an infectious disease specialist and microbiologist, treatment was changed to include moxifloxacin, azithromycin and rifabutin for 2 years, with amikacin for the first 3 months. Methylprednisone was also restarted. Antiretroviral therapy, together with cotrimoxazole prophylaxis, was continued.
The patient's response to the new regimen was slow, and initially he was unable to tolerate food. Insertion of a nasogastric tube was required for continuous feeds together with total parenteral nutrition. At the time of writing this article (17 months of treatment completed), his clinical response had improved. He was able to tolerate small regular meals with no nausea, vomiting or diarrhoea. His weight gain had been slow (now up to 20 kg) despite nutritional supplementation. The hepatosplenomegaly and abdominal distension had improved markedly, and his HIV remains virologically suppressed.
Dr R. de Gama obtained consent from the patient's parents to publish this case report.