Long-Term Zidovudine Therapy and Whether It is a Trigger of Vitamin B12 Deficiency: A Case Study of Megaloblastic Anemia at the University of Zambia Teaching Hospital.

Macrocytic anemia is frequently observed in adult HIV-infected patients treated with nucleoside reverse transcriptase inhibitors and with vitamin B12 and folate deficiency. In this case report, we discuss a 52-year-old nonvegetarian male on long-term antiretroviral therapy for 5 years, presenting with severe macrocytic anemia (hemoglobin, 3.7 g/dL; mean corpuscular volume, 119.6 fL) and leukopenia (2.71∗109/L), who was diagnosed with megaloblastic anemia caused by vitamin B12 deficiency following laboratory investigations. Parenteral vitamin B12 replacement therapy was initiated, with an early response observed. Notwithstanding, the treatment response was not sustained as the patient later presented with refractory anemia and persistence of macrocytosis. Discontinuation of zidovudine with concurrent vitamin B12 administration promptly improved the patient's clinical deficiency symptoms. At the end of 3 months, the patient had a complete hematological recovery. The deficiency of vitamin B12 disrupts DNA synthesis inhibiting effective hematopoiesis in all cell lines, particularly erythroid precursors and further promotes reversible bone marrow failure. Long-term ART therapy with zidovudine causes cytotoxicity in myeloid and erythroid precursors and induces bone marrow suppression. Whether long-term zidovudine consumption induced lower levels of vitamin B12 and subsequent megaloblastic anemia requires in-depth research and exploration.

Molecular Detection of Fusion Oncogenes in Zambian Patients with Acute Lymphoblastic Leukemia.

INTRODUCTION: Chromosomal aberrations play a significant role in the pathogenesis of acute lymphoblastic leukemia (ALL) with prognostic and therapeutic implications. Despite the availability of molecular tools, low-resource settings struggle to diagnose the disease due to limited diagnostic capacity. The objective of this study was to detect common chromosomal aberrations in patients with ALL attending the University Teaching Hospital (UTH) in Lusaka, Zambia. MATERIALS AND METHODS: In this prospective study, 19 blood samples from patients with ALL were screened for the presence of BCR-ABL, E2A-PBX1, MLL-AF4, and ETV6-RUNX1 fusion oncogenes using reverse transcriptase-polymerase chain reaction assay. Blood counts and clinical characteristics of patients were also assessed. RESULTS: The age of patients ranged from 1½ to 72 years and comprised 57.9% of males and 42.1% of females. The majority of these patients were children (68%), and adults only comprised 32%. Only BCR-ABL and E2A-PBX1 oncogenes were detected in 3/19 of cases. The BCR-ABL gene was detected in a 4-year-old female child and a 15-year-old child. Both cases were associated with hepatomegaly and anemia coupled with low hemoglobin, white blood cell, and platelet counts. E2A-PBX1 was detected in a 12-year-old child with lymphadenopathy and splenomegaly, coupled with low hemoglobin, white blood cell, and platelet counts. All the three patients who harbored these fusion oncogenes died. CONCLUSION: This is the first study from Zambia to investigate the presence of fusion oncogenes in leukemia patients, which were found only among the older children population. Based on these findings, we recommend that molecular diagnosis be made a priority for the younger leukemia patient population at UTH.

Leucocytosis and Asymptomatic Urinary Tract Infections in Sickle Cell Patients at a Tertiary Hospital in Zambia.

Sickle cell anaemia (SCA) is an inherited disease resulting from mutations in the ß-globin chain of adult haemoglobin that results in the formation of homozygous sickle haemoglobin. It is associated with several complications including an altered blood picture and damage in multiple organs, including the kidneys. Kidney disease is seen in most patients with SCA and may affect glomerular and/or tubular function, thereby putting these patients at risk of urinary tract infections. However, there is a paucity of data on the prevalence of urinary tract infections (UTIs) among SCA patients in Zambia. This study aimed to determine the prevalence of UTIs and haematological and kidney function profiles among SCA patients at the University Teaching Hospitals, Lusaka, Zambia. This was a cross-sectional study conducted between April and July 2019 involving 78 SCA patients who presented at the UTH. Blood and midstream urine samples were collected from each participant using the standard specimen collection procedures. Full blood counts and kidney function tests were determined using Sysmex XT-4000i haematology analyser and the Pentra C200 by Horiba, respectively. Bacterial profiles of the urine samples were determined using conventional microbiological methods. We found that all the measured patients' haemoglobin (Hb) levels fell below the WHO-recommended reference range with a minimum of 5 g/dl, a maximum of 10.5 g/dl, and a mean of 8 ± 1 g/dl. Fifty percent of the participants had moderate anaemia, while the other 50% had severe anaemia. The minimum WBC count of the participants was 0.02 × 109/L with a maximum of 23.36 × 109/L and a mean of 13.48 ± 3.87 × 109/L. Using the one-way analysis of variance test, we found no significant difference in mean WBC count and Hb concentration across various age-group categories that we defined. Bacteriuria was found in 25% of participants. The most common bacterial isolates were Staphylococcus aureus (32%) and coagulase-negative Staphylococci (32%). Klebsiella pneumoniae was 16%. We found no significant association between bacterial isolates and white blood cell count, age groups, sex, and anaemia severity p = 0.41. None of the participants were diagnosed with kidney disease. There was a high prevalence of asymptomatic UTIs among SCA patients at UTH, which, when coupled with the marked leukocytosis and anaemia, may negatively impact the clinical outcome of the patients. Therefore, we recommend close monitoring of sickle cell patients in Zambia for such conditions to improve patients' outcomes.

The Use of Dried Blood Spots: A Potential Tool for the Introduction of a Neonatal Screening Program for Sickle Cell Anemia in Zambia.

CONTEXT: Sickle cell disease is a group of hemoglobin (Hb) disorders resulting from the inheritance of the sickle ß-globin gene. It is the most common pathological Hb mutation worldwide with 75% being born in Sub-Saharan Africa. AIMS: This study aims to determine if dried blood spots (DBSs) can be used for diagnosis of sickle cell in newborns. In Zambia, there is no neonatal screening program for sickle cell anemia (SCA), yet it has been proved that early diagnosis by newborn screening (NBS) using DBSs and access to comprehensive care results in survival to adulthood of over 96% of sickle cell patients. SETTINGS AND DESIGN: A cross-sectional study was carried out at the University Teaching Hospital to determine whether DBSs can be used to diagnose sickle cell using Hb electrophoresis. SUBJECTS AND METHODS: Results from DBSs stored for 2 weeks were then compared to those obtained using freshly collected whole blood. STATISTICAL ANALYSIS USED: To evaluate performance characteristics, the following values were used: true positive, false positive, true negative, and false negative. RESULTS: Ninety-seven participants were included in this study. DBSs had a sensitivity of 100%, a specificity of 94.7%, positive predictive value of 96.7%, negative predictive value of 100%, overall efficiency of 97.9%, and a Kappa r2, P < 0.0001 in comparison to fresh whole blood which we used as the gold standard. CONCLUSIONS: The use of DBSs can be recommended for NBS of SCA in Zambia due to its high sensitivity, specificity, and stability of hemoglobin.

Evaluation of a density-based rapid diagnostic test for sickle cell disease in a clinical setting in Zambia.

Although simple and low-cost interventions for sickle cell disease (SCD) exist in many developing countries, child mortality associated with SCD remains high, in part, because of the lack of access to diagnostic tests for SCD. A density-based test using aqueous multiphase systems (SCD-AMPS) is a candidate for a low-cost, point-of-care diagnostic for SCD. In this paper, the field evaluation of SCD-AMPS in a large (n = 505) case-control study in Zambia is described. Of the two variations of the SCD-AMPS used, the best system (SCD-AMPS-2) demonstrated a sensitivity of 86% (82-90%) and a specificity of 60% (53-67%). Subsequent analysis identified potential sources of false positives that include clotting, variation between batches of SCD-AMPS, and shipping conditions. Importantly, SCD-AMPS-2 was 84% (62-94%) sensitive in detecting SCD in children between 6 months and 1 year old. In addition to an evaluation of performance, an assessment of end-user operability was done with health workers in rural clinics in Zambia. These health workers rated the SCD-AMPS tests to be as simple to use as lateral flow tests for malaria and HIV.

Changing pattern of lymphoma subgroups at a tertiary academic complex in a high-prevalence HIV setting: a South African perspective.

BACKGROUND: HIV infection has been associated with an increased risk of non-Hodgkin lymphoma, particularly in the first world. Despite the high burden of HIV infection in sub-Saharan regions, published data on HIV and malignancies are sparse from these areas. MATERIALS AND METHODS: We recently published data on lymphomas diagnosed from January 2004 to December 2006, at a single center in Johannesburg, to serve as a baseline for long-term comparison during the period of highly active antiretroviral therapy rollout. We report a retrospective analysis of the follow-up data collected from January 2007 to December 2009 at the Johannesburg academic hospital complex (Gauteng, South Africa). RESULTS: There were 2225 new diagnoses of lymphoproliferative disorders made during 2007-2009 as compared with 1897 cases diagnosed during 2004-2006. A significant increase in both high-grade B-cell lymphomas and Hodgkin lymphoma was documented during 2007-2009. This was associated with a statistically significant increase in HIV prevalence in those tested (from 44.3% in 2004-2006 to 62.0% in 2007-2009). HIV-positive patients presented at a statistically significantly younger median age and showed a relative overrepresentation of females when compared with HIV-negative patients. HIV-positive patients were diagnosed at later stages of HIV infection when compared with patients in the first world. CONCLUSIONS: The pattern of lymphoma subtypes and the demographics of the patients diagnosed have altered in association with significantly increased HIV prevalence. These changes have important public health implications. In particular, scale-up and earlier access to highly active antiretroviral therapy is essential with continued monitoring as access to therapy improves.

Characterization of Lymphomas in a high prevalence HIV setting.

BACKGROUND: HIV infection has been associated with an increased risk of malignancy, both AIDS defining and non-AIDS defining. METHODS: This study presents a detailed pathological description of newly diagnosed lymphomas in Johannesburg, South Africa (January 2004 and December 2006). The review coincides with introduction of combination antiretroviral therapy. RESULTS: One thousand eight hundred and ninety-seven new lymphoproliferative disorders were referred to the Charlotte Maxeke Johannesburg Academic Hospital. B-cell non-Hodgkin lymphoma accounted for 83%, T-cell non-Hodgkin lymphoma 3.5%, and Hodgkin lymphoma 7% of cases. The overall prevalence of HIV infection was 37% (n = 709). Diffuse large B-cell lymphoma (21%; n = 401) was the most common lymphoma. HIV prevalence ranged from an absence in follicular or mantle cell lymphoma to a low prevalence in diseases like small lymphocytic lymphoma/chronic lymphocytic leukemia (4%) and pre-B/common ALL (5%) to a high prevalence in diffuse large B-cell lymphoma (80%), Burkitt lymphoma/leukemia (86%), and primary effusion lymphoma (100%). CONCLUSIONS: This study provides a baseline for monitoring the impact of HIV and management thereof on lymphoma trends. The high prevalence of HIV in certain lymphoma categories emphasizes the need for capacity to diagnose and manage dual conditions. This study highlights the need for strengthening of cancer registries within South Africa and the region.

Postnatal human herpesvirus 8 and human immunodeficiency virus type 1 infection in mothers and infants from Zambia.

The specific route and timing of human herpesvirus (HHV) 8 infection in regions where Kaposi sarcoma is endemic are not known. HHV-8 infection and any risk factors that may be associated with HHV-8, including human immunodeficiency virus (HIV) type 1 infection, were monitored during the 12-month postdelivery period for 416 mothers and 485 infants from Lusaka, Zambia. HHV-8 incident infection rates during this period were 3.2 and 5.3 infections/100 person-years for infants and mothers, respectively. HHV-8 infection among infants was not associated with HHV-8 or HIV-1 infection in the mother. Among the HHV-8-positive infants, 2 of 12 tested were found to have HHV-8 DNA in their peripheral blood mononuclear cells at birth, which suggests that in utero infection is possible. However, most HHV-8-positive infants appeared to have acquired infection either intrapartum or postpartum. The present study indicates that transmission of HHV-8 to infants can occur early and is likely via multiple routes.

Human herpesvirus 8 can be transmitted through blood in drug addicts

Human Herpes virus type-8 (HHV-8) seroprevalence was studied in a population of HIV positive intravenous drug users (IVDUs) from Argentina. Analysis of this population also indirectly made it possible to study HHV-8 blood transmission, because these individuals frequently engage in needle sharing behavior and are capable of acquiring a broad array of blood borne pathogens, including Hepatitis B/C virus. The seroprevalence of HHV-8 in IVDUs was compared to a group of non-IVDUs and HIV negative individuals. Of the 223 individuals tested, 13.45 percent were HHV-8 positive, 16.99 percent in the IVDUs group, and 5.71 percent in the non-IVDUs. Among HIV positive IVDUs, 25/144 (17.36 percent) were also HHV-8 seropositive. The seropositivity rate of HHV-8 in HIV negative IVDUs was 11.1 percent. In contrast, HHV-8 seroprevalence in HIV negative heterosexual individuals without drug usage behavior was even lower (5.71 percent). The rate of HHV-8 infection in HIV positive IVDUs was three times as high compared to the non IVDU HIV negative individuals, suggesting that IVDU is a risk for HHV-8 infection. Furthermore, it was found that IVDUs showed a very high rate of Hepatitis B/C (52.77 percent), which also correlate with HHV-8 infection in this population (23.68 percent). All Hepatitis B/C positive individuals were also HIV positive. Our data confirm other studies showing that individuals who share needles are at risk for acquiring Hepatitis B/C and HIV infections. In addition, our results suggest that they are also at risk to acquiring HHV-8 infection by the same route.

Human herpesvirus 8 can be transmitted through blood in drug addicts

Human Herpes virus type-8 (HHV-8) seroprevalence was studied in a population of HIV positive intravenous drug users (IVDUs) from Argentina. Analysis of this population also indirectly made it possible to study HHV-8 blood transmission, because these individuals frequently engage in needle sharing behavior and are capable of acquiring a broad array of blood borne pathogens, including Hepatitis B/C virus. The seroprevalence of HHV-8 in IVDUs was compared to a group of non-IVDUs and HIV negative individuals. Of the 223 individuals tested, 13.45 percent were HHV-8 positive, 16.99 percent in the IVDUs group, and 5.71 percent in the non-IVDUs. Among HIV positive IVDUs, 25/144 (17.36 percent) were also HHV-8 seropositive. The seropositivity rate of HHV-8 in HIV negative IVDUs was 11.1 percent. In contrast, HHV-8 seroprevalence in HIV negative heterosexual individuals without drug usage behavior was even lower (5.71 percent). The rate of HHV-8 infection in HIV positive IVDUs was three times as high compared to the non IVDU HIV negative individuals, suggesting that IVDU is a risk for HHV-8 infection. Furthermore, it was found that IVDUs showed a very high rate of Hepatitis B/C (52.77 percent), which also correlate with HHV-8 infection in this population (23.68 percent). All Hepatitis B/C positive individuals were also HIV positive. Our data confirm other studies showing that individuals who share needles are at risk for acquiring Hepatitis B/C and HIV infections. In addition, our results suggest that they are also at risk to acquiring HHV-8 infection by the same route. (Au)