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Successful treatment of recurrent visceral leishmaniasis relapse in an immunocompetent adult female with functional hypopituitarism in Bangladesh [1]

['Tabiha Binte Hannan', 'Department Of Internal Medicine', 'Bangabandhu Sheikh Mujib Medical University', 'Bsmmu', 'Dhaka', 'Zazeba Hossain', 'Utshab Roy', 'S. M. Mahbubur Rahman', 'Md Sadiqur Rahman', 'Sadia Sabah']

Date: 2024-05

In 2021, a total of 11,743 cases of visceral leishmaniasis (VL) have been reported from WHO region. It is an endemic disease in four eco-epidemiological regions- Americas, East Africa, North Africa, West and South-east Asia. 1464 (13%) cases of new VL have been reported from South-east Asia in 2021 and 35 cases have been reported from Bangladesh with a case fatality rate of 6.9% [1, 2].

Several cases of frequent relapses of VL have been reported after optimal treatment regimen in immunosuppressed hosts (i.e., people living with HIV, patients with organ transplant etc.) around the world [3–5]. However, very few cases of recurrent VL in immunocompetent hosts have been reported to date [6]. Unfortunately, there is no definite treatment regimen available to treat these cases. To the best of our knowledge, here we report the first case of recurrent relapses of VL in an immunocompetent host with functional hypopituitarism from Bangladesh, who was treated successfully with a treatment regimen combining liposomal amphotericin B (LAmB) and miltefosine. We followed a treatment regimen reported by Lagadinou et. al., who treated a case of recurrent relapses of visceral leishmaniasis in a Greek immunocompetent male [6].

Case presentation

A 19-year-old female, hailing from Narsingdi, Bangladesh, was admitted into our hospital as a diagnosed case of recurrent visceral leishmaniasis relapse (VL) with the complaints of prolonged fever, weight loss, short stature and gradual swelling of abdomen. On background history, she had a long period of suffering due to her illness. She first developed irregular bouts of fever in 2012, along with progressive unintentional weight and gradual distension of abdomen. She sought medical consultation from local physicians, with no clinical improvement. In November 2018, she was first diagnosed as a case of new kala-azar on the basis of clinical presentations and positive rk-39 test in a district hospital. She was treated with single dose of 10 mg/kg body weight liposomal amphotericin-B (LAmB) with no improvement. In July 2019, she presented with high grade irregular fever, epistaxis, gum bleeding, weight loss, and was diagnosed as a case of relapse VL. She was treated with 15 mg/kg body weight LAmB in three divided doses (5 mg/kg body weight on every alternate day for three doses). Unfortunately, her symptoms did not improve this time either, and was re-admitted after two months. She was tagged as a case of recurrent relapse of VL and was treated with single dose LAmB 5 mg/kg body weight, followed by miltefosine 60 mg in two divided doses for seven days with no clinical improvement thereafter. She was lost to follow-up between 2019–2021 and in October 2021, the patient was referred to our hospital by national kala azar elimination programme (NKEP) Bangladesh.

On admission, the patient was febrile, severely malnourished evidenced by sparse, thin hair, gross muscle wasting. Her height was 130 cm (below 5th percentile), weight 20 kg (below 5th percentile) and BMI 11.8 kg/m2(below 5th percentile). She had hepatomegaly (12 cm), and massive splenomegaly (25 cm). Our patient was also amenorrheic, and there was no evidence of secondary sex characteristic development (Stage 1 breast development, and absence of axillary and pubic hair). We investigated her as much possible to exclude possible causes of immunosuppression. Her random blood sugar (RBS) and Chest X Ray were normal, and Anti-HIV (1+2), Mantoux test were also negative. Her serum albumin was low (22 gm/L). Her other investigation profile is summarized in Table 1.

The patient was treated with four units of fresh whole blood transfusion before starting anti-leishmania treatment. As she got multiple doses of the two most potent drugs available in our country, it was very challenging to establish a suitable treatment regimen for her. We treated our patient with a loading dose of high concentration LAmB (10 mg/kg body weight for two consecutive days) followed by oral miltefosine (2.5 mg/kg body weight daily) for seven days. To prevent the risk of recurrence, monthly secondary prophylaxis with LAmB at a dose of 3 mg/kg body weight followed by oral miltefosine (2.5 mg/kg body weight daily) for seven days for the next five months was planned. We also planned for a splenectomy if her thrombocytopenia and massive splenomegaly persisted after treatment. On her subsequent visits, clinical and laboratory improvements were monitored. To our relief, significant clinical improvement was noticed after the loading dose of LAmB evidenced by absence of fever, gradual weight gain, and decreasing size of liver and spleen. PCR for Leishmania DNA was done every month and it became negative after the 1st dose of secondary prophylaxis. During her course of treatment, she occasionally developed hypokalemia due to LAmB toxicity, which was treated with oral potassium chloride replacement. After six months of her treatment completion, she did not have any febrile episode, weight was 27 kg, she had splenomegaly (4 cm) but no hepatomegaly, platelet count was increased to 100,000/mm3, rK-39 was positive, however PCR for Leishmania DNA was negative. Her physical improvements during and after treatment is depicted in Fig 1A and 1B.

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TIFF original image Download: Fig 1. Patient’s physical improvement during and after treatment completion. Patient’s physical appearance during 2nd month of treatment showing gross muscle wasting, short stature, and abdominal distension and physical improvement after 6 months of treatment completion showing marked improvement in general physical appearance (N.B. picture taken by the first author and used with informed written consent from the patient). https://doi.org/10.1371/journal.pntd.0012134.g001

Alongside her treatment for visceral leishmaniasis, she was evaluated thoroughly by the department of endocrinology for short stature and primary amenorrhea in June 2021. She had low serum estradiol, free T 4 along with normal serum LH, FSH, TSH (Table 2) and normal pituitary gland on MRI shown in Fig 2.

She was diagnosed as a case of functional panhypopituitarism (hypogonadotropic hypogonadism with central hypothyroidism). Her hormone profile is given in Table 1. She was treated with conjugated estrogen and levothyroxine 50 mcg. In October 2022, after six months treatment with 0.3125 mg conjugated estrogen, her height increased to 140 cm, weight 27 kg, and she had stage 3 breast development. In her last follow-up visit in February 2023, after four months of treatment with 0.625 mg conjugated estrogen, her height was 146 cm, weight was 29 kg, and BMI was 13.6 kg/m2. She had stage 4 breast development, and adequate uterus size (Table 1). She was started on cyclical estrogen and progesterone and has been having regular withdrawal bleeds since then. After 18 months of hormone replacement therapy, estrogen and progesterone therapy was withhold to evaluate establishment of her natural menstrual cycle. During her most recent follow up in March 2024, she stated that she has been having regular menstrual cycle for the last 4 months.

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[1] Url: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0012134

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