A Retrospective Analysis of 7 Human Immunodeficiency Virus-Negative Infants Infected by Penicillium marneffei

Abstract

Infection with Penicillium marneffei has rarely been reported in human immunodeficiency virus (HIV)-negative infants. We aimed to determine the epidemiological, clinical, pathological, and immunological characteristics of 7 HIV-negative infants infected by P. marneffei, and to provide insights into its diagnosis and treatment.We retrospectively reviewed the cases of 7 HIV-negative infants infected by P. marneffei who presented to the First Affiliated Hospital of Guangxi Medical University between January 1, 2003 and December 1, 2014. The infants' median age was 23.43 months (SD = 8.34), and all lived in Guangxi Province in China, where P. marneffei is endemic. The median time from disease onset to diagnosis was 2.29 months (SD = 2.12). Of the cases studied, 5 (71.43%) had medical histories that included frequent pneumonia or bronchopneumonia, thrush, congenital megacolon, glucose-6-phosphate dehydrogenase deficiency, and hemophagocytic syndrome. The most common symptoms were fever, cough, and anemia, followed by lymphadenopathy, hepatosplenomegaly, and being underweight. Four patients had slightly elevated white blood cell counts. The lymphocyte and CD4 T-cell counts were normal. The CD8 T-cell counts, serum immunoglobulin (Ig) G titer, and serum IgA titer were low in 5 patients, and the serum IgM titers were high in 3 infants. Caseous necrosis was observed in 3 patients whose lymph nodes were affected. One case who received intravenous amphotericin B and 3 cases who received intravenous voriconazole improved, and these patients were cured after continual treatment with oral voriconazole for 6 or 12 months. The remaining patients died before they received antifungal treatment.P. marneffei causes severe disease and disseminated infections, and it has high mortality rates in HIV-negative infants in endemic areas. P. marneffei susceptibility may be associated with immunodeficiencies or immune disorders. In endemic areas, clinicians should aware of disseminated P. marneffei infections when infants present with serious or recurrent infections, even if they are HIV negative. P. marneffei is highly susceptible to amphotericin B and voriconazole. Timely diagnosis and treatment can improve patients' prognoses. Intravenous voriconazole could be recommended as the initial antifungal agent for HIV-negative infants infected by P. marneffei, because of its low nephrotoxicity, high sensitivity, and high efficacy levels.

FIGURE 1

Images from the high-resolution computed tomography of the infants’ chests indicated pulmonary involvement, which included (A) the pleural cavity and (B) nodular infiltrates.

FIGURE 2

Positive cultures, pathogen morphology, and histopathology of the infants’ clinical specimens indicated that (A) at 25°C on Sabouraud dextrose agar (SDA), the mold from cultured lymph nodes produced a red pigment on the SDA, (B) the mold was stained with lactophenol cotton blue, and the conidiophores of this mold were smooth and had 3 to 5 metulae, each of which had several phialides and produced smooth, spherical conidia in chains, (C) a pattern of necrosis was observed in lymph nodes stained with hematoxylin and eosin (×100), (D) the yeast form of Penicillium marneffei was confirmed by the histopathological analysis of the lymph nodes using Periodic Acid-Schiff staining (×400). The yeast showed a characteristic morphology, including a transverse septum, and (E) numerous intracellular yeast-like or sausage-like cells measuring 2 to 3 μm in diameter with a transverse septum were observed when specimens obtained from bone marrow were stained with the Wright stain (×1000).