A 25-year-old man with no medical history living in Paris, France, went to the local emergency room in November 2018 with sudden onset of psychotic symptoms (paranoid delusions, auditory hallucinations and major anxiety) associated with fever, cough and general asthenia. He had no psychiatric history apart from an anxious personality and a mild tobacco and cannabis consumption and was not taking any medication. He had travelled in Greece for one week and had returned ten days before the first symptoms. He reported having unprotected sex with a man 2 months before and during his travel.
On admission, he had fever (38.5 C), pharyngitis, oral candidiasis and skin rash. Laboratory values revealed increased C-reactive protein (18 mg/L), mild anemia (10.5 g/dL) with low reticulocytes count (37 G/L), lymphopenia (500/mm3), neutropenia down to 600/mm3 and thrombocytopenia (90 G/L). HIV-1 serology returned positive, confirmed by immunoblot, with a viral load of 5.47 million copies/mL and a CD4+ T-cells count of 90/mm3. Neuroleptic drugs (cyamemazine, risperidone) and benzodiazepines were introduced to treat psychotic and anxious symptoms. He was transferred to our Infectious Diseases Department. HIV blood viral load at admission (2 weeks after first symptoms) was at 6.85 million copies/mL with a blood CD4+ T-cells count of 30/mm3 and a global lymphopenia (including CD8+ and NK cells). The immunoblot showed an uncommon band pattern (gp120 and gp41 reactivity, weak ambiguous reactivity to p24 and p31, no reactivity to other antigens), which could have been consistent with acute primary infection. He never had any HIV infection screening in the past. The research of past blood tests showed a normal lymphocytes count (1.4 G/L) a year ago. Of note, his recent partner was just diagnosed with HIV infection as well.
Lumbar puncture, electroencephalography and cerebral MRI showed no abnormality. Thoraco-abdominal and pelvic CT revealed homogenous hepatosplenomegaly and few parenchymatous interstitial pulmonary lesions (micronodules and reticulations). Sputum cultures and bronchoalveolar lavage showed no Pneumocystis nor tuberculosis infection. No co-infection with HAV, HBV, HCV, HEV, toxoplasmosis nor syphilis was found. EBV and CMV viral loads were undetectable. Genotypic testing found a CRF19-cpx strain. Combined anti-retroviral therapy (cART) was introduced 2 weeks after diagnosis, consisting in tenofovir, emtricitabine and raltegravir, and Pneumocystis pneumonia was prevented by cotrimoxazole.
Despite cART and neuroleptic drugs, psychotic symptoms and fever persisted associated with chills, sweats and a neurological disorder occurred with bilateral muscle rigidity. The worsening of his clinical state required intensive care. A neuroleptic malignant syndrome was diagnosed, and extrapyramidal syndrome recovered after stopping neuroleptic treatment, but fever, chills and night sweats persisted. At this time, blood tests showed worsening pancytopenia (anemia 7.0 g/dL, platelets count 50 G/L, neutropenia 600/mm3), hyperferritinemia, elevated liver enzymes and mild elevated triglyceridemia. We hypothesized that the patient had a hemophagocytic lymphohistiocytosis (HLH) triggered by an acute primary HIV infection. Sternal bone marrow aspiration was performed showing signs of macrophages activation without hemophagocytosis. No Leishmania was found on bone marrow aspirate smears and Mycobacterium tuberculosis complex PCR was negative. An empiric treatment with intravenous immunoglobulins 1 g/kg for 2 days was administered; no clinical response was observed.
Finally, a bone marrow biopsy was performed showing hemophagocytosis, confirming HLH, and moreover, revealing the presence of Leishmania spp ( Figure 1 ), with a low parasitic load. Serology was also positive for Leishmania infantum antibodies by immune-enzymatic screening technique, confirmed by Western-Blot assay. Molecular species identification confirmed a Leishmania infantum strand.
Intravenous liposomal amphotericin B was administered at 4 mg/kg/day on five consecutive days followed by five weekly administrations, allowing complete clinical recovery and pancytopenia recovery. Patient was discharged, no secondary prophylaxis against VL was prescribed. Viral load decreased to 75 copies/mL and CD4+ T-cells count increased to 213/mm3 two months after cART initiation and viral load was undetectable with CD4+ T-cells count at 345/mm3 after 6 months ( Figure 2 ), with no sign of VL relapse. After 24 months of follow-up, no VL relapse was observed.