Table 5.
Primary Immunodeficiencies reported in HIV-negative children with T. marneffei infection.
| Patients | Genetic defect | Mutation | Gender | Age | Residence | Detection methods | Extent of T.marneffei infection | Treatment and outcome |
|---|---|---|---|---|---|---|---|---|
| p1 (Lee et al., 2012) (Lee et al., 2019) (Lee et al., 2014) | STAT1, GOF | c.800C>T (p.A267V) | M | 15y | Hong Kong, China | Fine-needle aspiration of the cervical lymph node for culture yielded T. marneffei | Disseminated | Liposomal amphotericin B for 6 weeks, followed by itraconazole prophylaxis with good clinical response |
| p2 (Lee et al., 2012) (Lee et al., 2019) (Lee et al., 2014) | STAT1, GOF | c.1074G>T (p.L358F) | F | 7y | Hong Kong, China | BALF culture yielded T. marneffei | Disseminated | Lliposomal amphotericin B for 6 weeks, followed by itraconazole prophylaxis with good clinical response |
| p3 (Lee et al., 2012) (Lee et al., 2019) (Lee et al., 2014) | STAT1, GOF | c.863C>T (p.T288I) | F | 7y | Hong Kong, China | Lymph node biopsy yielded T. marneffei | Disseminated | Treated with itraconazole with good response, died of massive pulmonary hemorrhage at 16 years old |
| p4 (Lee et al., 2019) (Yuen et al., 1986) | STAT1, GOF | c.1170G>A (p.M390I) | M | 10y | Hong Kong, China | Tissue from the neck ulcer and axillary lymph node for culture yielded T. marneffei | Disseminated | Intravenous amphotericin B and oral flucytosine for 3 months with good response |
| p5 (Chen et al., 2020) | STAT1, GOF | c.193G>A (p.D65N) | M | 5y11m | China | NA | Lymphadenitis | Amphotericin B and voriconazole, alive |
| p6 (Chen et al., 2020) | STAT1, GOF | c.1053G>T(p.L351F) | F | 9y11m | China | NA | Pulmonary | Itraconazole and amphotericin B, alive |
| p7 (Fan et al., 2021) | STAT1 | NA | M | 2y | Hunan, China | Bone marrow culture yielded T. marneffei, Lymph node biopsy (Right inguinal hernia) fungal spore structure, PAS(+) | Disseminated | Intravenous voriconazole for 2 weeks, amphotericin B for 3 weeks, oral itraconazole for 1 year |
| p8 (Chen et al., 2021) | STAT1, GOF | nt.859T > A (Y287N) | M | 20y | China | Blood, bone marrow and sputum cultures yielded T. marneffei | Disseminated | Amphotericin B for 6 months, recovery |
| p9 (Lee et al., 2012) | STAT3, Hyper-IgE syndrome | c.1121A>G (p.D374G) | F | 12m | China | Blood and bone marrow cultures yielded T. marneffei | Disseminated | Treated with itraconazole with good response |
| p10 (Ma et al., 2009) | STAT3, Hyper-IgE syndrome | NA | M | 10y | Hong Kong, China | Sputum and abscess fluid cultures yielded T. marneffei | Pulmonary | Treated with amphotericin B, died of respiratory failure due to rapid disease progression |
| p11 (Fan et al., 2018) | STAT3, Hyper-IgE syndrome | c.1593A>T (p.K531N) | M | 13y | Guangzhou, China | BALF culture yielded T. marneffei | Disseminated | Treated with amphotericin B, voriconazole for 2 weeks and itraconazole orally for 2 months with good response |
| p12 (Pan et al., 2020) | STAT3, Hyper-IgE syndrome | c.1673G>A (p.G558D) | M | 37m | Guangxi, China | The colon biopsy showed a large number of fungal spores, liver tissue revealed numerous intracellular yeast-like or sausage-like cells, bone marrow culture confirmed T.marneffei | Disseminated | Intravenous voriconazole and antibiotics for 10 days and oral voriconazole for 7 months, recovery |
| p13 (Zhang et al., 2020) | STAT3, Hyper-IgE syndrome | c.92G>A (p.R31Q) | M | 34y | Zhejiang, China | mNGS of BALF confirmed T. marneffei (readers 566), cultures of BALF and the endobronchial biopsied tissue mass yielded T. marneffei | Pulmonary | Itraconazole, recovery |
| p14 (Fan et al., 2021) | STAT3, Hyper-IgE syndrome | NA | F | 2y | Hunan, China | Cultures of bone marrow, sputum and BALF yielded T. marneffei | Disseminated | Amphotericin B for 2 days (discontinued due to liver dysfunction), Intravenous voriconazole for 4 days, give up and died |
| p15 (Lee et al., 2019) (Du et al., 2019) | CD40L(TNFSF5) | g.IVS1+1G>A | M | 29m | China | Cervical lymph node and endobronchial biopsy yielded T. marneffei; cultures of blood, nasal secretions, throat swab and sputum yielded T. marneffei | Disseminated | Treated with voriconazole for 4 months and subsequent recurrence treated with voriconazole, with good response |
| p16 (Kamchaisatian et al., 2006) | CD40L deficiency | Complex mutation in exon 5 | M | 14m | Northeastern Thailand | Throat swab, sputum, blood and bone marrow cultures grew T. marneffei | Disseminated | Treated with amphotericin B for 21 days, followed by itraconzole for 10–12 weeks |
| p17 (Kamchaisatian et al., 2006) | CD40L deficiency | NA | M | 1y | Northern Thailand | Lymph node tissue culture yielded T. marneffei | Pulmonary disease and lymphadenopathy | Treated with amphotericin B for 21 days, followed by itraconzole for 10–12 weeks |
| p18 (Sripa et al., 2010) | CD40L deficiency | NA | M | 3y | Thailand | T. marneffei infection of the sputum | Pulmonary | Itraconazole, good response |
| p19 (Du et al., 2019) | CD40L deficiency | g.IVS1-3T>G | M | 2y | Hunan,China | Blood culture and hepatic biopsy showed T. marneffei | Disseminated | Treated with amphotericin B, died of multi-organ failure |
| p20 (Li et al., 2018) | CD40L deficiency | NA | M | 14m | Jiangxi,China | Blood culture yielded T. marneffei | Disseminated | Treated with itraconazole for 2 weeks and improved |
| p21 (Du et al., 2019) | CD40L deficiency | IVS3 + 1G>A | M | 2y11m | China | Bone marrow culture yielded T. marneffei | Disseminated | Responded effectively to anti-fungal therapy |
| p22 (Du et al., 2019) | CD40L deficiency | IVS1-1 G > A | M | 2y3m | China | Blood culture yielded T. marneffei | Disseminated | Lost to follow-up |
| p23 (Du et al., 2019) | CD40L deficiency | IVS4 + 1G>C | M | 3y | China | Bone marrow culture yielded T. marneffei | Disseminated | Responded effectively to anti-fungal therapy |
| p24 (Du et al., 2019) | CD40L deficiency | Large fragment deletion including exon 4 and 5 | M | 13y7m | China | Blood culture yielded T. marneffei | Disseminated | Responded effectively to anti-fungal therapy |
| p25 (Lee et al., 2019) | IFNGR1 | c.182dupT (p.V61fs69) | F | 5m | Northern Thailand | NA | Disseminated | Die |
| p26 (Lee et al., 2019) | IFNGR1 | c.182dupT (p.V61fs69) | M | 12m | Northern Thailand | Blood culture yielded T. marneffei | Disseminated | Treated with amphotericin B for 6 weeks with good response, followed by itraconazole prophylaxis |
| p27 (You et al., 2021) | CARD9, compound heterozygote | c.440T>C (p.L147P), c.586A>G (p.K196E) | M | 5y | Chongqing,China | Bone marrow smear identified T. marneffei infection, ascites culture yielded T. marneffei | Disseminated | Treated with amphotericin B and voriconazole, died of multiple organ failure |
| p28 (Ba et al., 2021) | CARD9, compound heterozygote | c.1118G>C (p.R373P), c.610C>T (p.R204C) | M | 7m | Guangzhou, China | Blood culture and mNGS of blood confirmed T. marneffei (readers 248) | Disseminated | Voriconazole, good response |
y, year; m, month; BALF, bronchoalveolar lavage fluid; mNGS, metagenomic next-generation sequencing; GOF, gain of function; M, male; F, female; NA, not available.