Placental Plasmodium falciparum malaria infection: operational accuracy of HRP2 rapid diagnostic tests in a malaria endemic setting.

BACKGROUND: Malaria has a negative effect on the outcome of pregnancy. Pregnant women are at high risk of severe malaria and severe haemolytic anaemia, which contribute 60-70% of foetal and perinatal losses. Peripheral blood smear microscopy under-estimates sequestered placental infections, therefore malaria rapid diagnostic tests (RDTs) detecting histidine rich protein-2 antigen (HRP-2) in peripheral blood are a potential alternative. METHODS: HRP-2 RDTs accuracy in detecting malaria in pregnancy (MIP >28 weeks gestation) and placental Plasmodium falciparum malaria (after childbirth) were conducted using Giemsa microscopy and placental histopathology respectively as the reference standard. The study was conducted in Mbale Hospital, using the midwives to perform and interpret the RDT results. Discordant results samples were spot checked using PCR techniques. RESULTS: Among 433 febrile women tested, RDTs had a sensitivity of 96.8% (95% CI 92-98.8), specificity of 73.5% (95% CI 67.8-78.6), a positive predictive value (PPV) of 68.0% (95% CI 61.4-73.9), and negative predictive value (NPV) of 97.5% (95% CI 94.0-99.0) in detecting peripheral P. falciparum malaria during pregnancy. At delivery, in non-symptomatic women, RDTs had a 80.9% sensitivity (95% CI 57.4-93.7) and a 87.5% specificity (95%CI 80.9-92.1), PPV of 47.2% (95% CI 30.7-64.2) and NPV of 97.1% (95% CI 92.2-99.1) in detecting placental P. falciparum infections among 173 samples. At delivery, 41% of peripheral infections were detected by microscopy without concurrent placental infection. The combination of RDTs and microscopy improved the sensitivity to 90.5% and the specificity to 98.4% for detecting placental malaria infection (McNemar's X(2)> 3.84). RDTs were not superior to microscopy in detecting placental infection (McNemar's X(2)< 3.84). Presence of malaria in pregnancy and active placental malaria infection were 38% and 12% respectively. Placental infections were associated with poor pregnancy outcome [pre-term, still birth and low birth weight] (aOR = 37.9) and late pregnancy malaria infection (aOR = 20.9). Mosquito net use (aOR 2.1) and increasing parity (aOR 2.7) were associated with lower risk for malaria in pregnancy. CONCLUSION: Use of HRP-2 RDTs to detect malaria in pregnancy in symptomatic women was accurate when performed by midwives. A combination of RDTs and microscopy provided the best means of detecting placental malaria. RDTs were not superior to microscopy in detecting placental infection. With a high sensitivity and specificity, RDTs could be a useful tool for assessing malaria in pregnancy, with further (cost-) effectiveness studies.

The pre-B-cell receptor associated protein VpreB3 is a useful diagnostic marker for identifying c-MYC translocated lymphomas.

BACKGROUND: During B-cell development, precursor B cells transiently express the pre-B-cell receptor composed of µ heavy chain complexed with VpreB and λ5 surrogate light chain polypeptides. Recent profiling studies unexpectedly revealed abundant transcripts of one member of the VpreB family, VpreB3, in a subset of mature B cells and Burkitt lymphoma. DESIGN AND METHODS: Here we used a novel antibody to investigate the normal expression pattern of VpreB3 protein in human hematopoietic and lymphoid tissues, and to determine whether VpreB3 could serve as a useful diagnostic biomarker for select B-cell lymphomas. RESULTS: We found that VpreB3 protein is normally expressed by precursor B cells in bone marrow and by a subset of normal germinal center B cells in secondary lymphoid organs. Among lymphoid malignancies, we found an association between VpreB3 expression and B-cell tumors with c-MYC abnormalities. VpreB3 was highly expressed in all cases of Burkitt lymphoma, whether of endemic or sporadic origin (44/44 cases, 100%), all cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (5/5 cases, 100%), and the majority of diffuse large B-cell lymphomas harboring a c-MYC translocation (15/18 cases, 83%). The expression of VpreB3 in diffuse large B-cell lymphomas without a c-MYC translocation was associated with c-MYC polysomy in 25/75 cases (33%) but only rarely observed in diffuse large B-cell lymphomas lacking a c-MYC abnormality (9/98 cases, 9%). CONCLUSIONS: We conclude that for B-cell tumors with features suggesting a possible c-MYC translocation, such as intermediate to large cell size and high proliferation rate, the presence of VpreB3 should prompt subsequent confirmatory genetic testing, whereas the absence of VpreB3 is virtually always associated with wild-type c-MYC alleles.

EBV-Positive Grey Zone Lymphoma in an HIV Infected Man from Kampala, Uganda: Case Report.

AIM: We describe the clinical, histopathological and immunophenotypic characteristics of an HIV-infected adult man on antiretroviral therapy who presented with an EBV-positive grey zone lymphoma. CASE PRESENTATION: A 56-year-old HIV infected man from Uganda presented with a four month history of progressive abdominal swelling and B-symptoms. He was on highly active antiretroviral therapy (HAART) and cotrimoxazole. He was afebrile (36.9°C), severely wasted (BMI 14.8), and mildly anaemic. On physical examination, he had a 15 by 8 cm mass in the hypogastrium and umbilical region. The total white cell count was 8.3×103/µL; neutrophils, 5.72×103/µL; haemoglobin 11.1g/dL, platelets 528×103/µL, LDH 197 IU/L and CD4 367/µL. Abdominal ultrasound and CT scan showed a tumour involving the mesentery, jejunum and mid ileum. At laparotomy, a biopsy was taken, fixed, processed and stained with Haematoxylin & Eosin (H & E). Histopathology demonstrated large pleomorphic cells admixed with inflammatory smaller cells, Reed-Sternberg-like cell variants and frequent abnormal mitoses. Biomarkers CD20, PAX5, CD30 were positive but ALK negative (immunohistochemistry and strong EBER positivity in situ hybridization. The patient improved on modified CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy. DISCUSSION: The tumour had features intermediate between mediastinal large B cell lymphoma and classical Hodgkin lymphoma. CONCLUSION: We present a case of EBV-positive grey zone lymphoma in an HIV-infected man on HAART therapy diagnosed and treated in a resource constrained medical setting. The histological features are unusual and represent a low incidence lymphoma that is recognized by mixed features reminiscent of Hodgkin's lymphoma and mediastinal large B-cell lymphoma.