Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy

BACKGROUND: Pregnancy increases the risk of morbidity and mortality in sickle cell disease. We previously showed pregnant women with sickle cell disease to have a relatively low plasma renin concentration in late pregnancy, associated with a lack of the expected plasma volume expansion. We hypothesized this to be due to increased systemic vascular resistance through an imbalance between the vasodilator prostacyclin and vasoconstrictor thromboxane, associated with decreased glomerular filtration rate (GFR). OBJECTIVE: To compare estimated prostacyclin, thromboxane and GFR in non-pregnant and pregnant women with hemoglobin SS (HbSS) and AA (HbAA). STUDY DESIGN: Four groups of 20 normotensive, nulliparous women were studied in Lagos, Nigeria: pregnant HbSS or HbAA women at 36-40 weeks gestation; non-pregnant HbSS and HbAA controls. We measured stable metabolites of prostacyclin and thromboxane A2 by enzyme-linked immunosorbent assay; GFR using the Cockcroft-Gault equation. Data analysis was by independent (Student's) t-test or Mann-Whitney U test for comparisons between any two groups of continuous variables, univariate ANOVA for multiple groups and Pearson's correlation coefficient for degree of association between variables. RESULTS: HbSS women had lower serum 6-keto-PGF1α concentrations than HbAA, whether pregnant or non-pregnant (P<0.001; P<0.004 respectively). Conversely, pregnant HbSS women had higher serum TxB2 (P<0.001); non-pregnant HbSS women had non-significantly higher TxB2 concentrations. The 6-keto-PGF1α:TxB2 ratio was markedly increased (pro-vasodilatory) in HbAA pregnancy (P<0.001) but reduced in HbSS pregnancy (P = 0.037). GFRs (mL/min) were higher in non-pregnant HbSS than HbAA (P<0.008) but only marginally raised in HbSS women in late pregnancy (P = 0.019) while markedly raised in HbAA pregnancy (P<0.001). CONCLUSION: The lower ratio of prostacyclin-thromboxane metabolites in HbSS pregnancy may indicate endothelial damage and an increased tendency to vasoconstriction and clotting. If confirmed by subsequent longitudinal studies, interventions to increase prostacyclin and reduce thromboxane, such as low dose aspirin, may be potentially useful in their management

Prevalence and type of monoclonal gammopathy of undetermined significance in an apparently healthy Nigerian population: a cross sectional study

Background The prevalence of monoclonal gammopathy of undetermined significance (MGUS), a premalignant plasma-cell disorder has not been determined in our geographic area Nigeria. Methods A cross sectional survey was carried on apparently healthy Nigerians selected by multistage sampling technique from the cosmopolitan city of Lagos, Nigeria. Subjects enrolled into the study had 2-step screening for the presence, type and concentration of monoclonal band. Agarose-gel electrophoresis was performed on all serum samples, and any serum sample with a discrete band of monoclonal protein or thought to have a localized band was subjected to Immunofixation. Subjects were also evaluated for Bence jones proteinuria, haematological and biochemical parameters. Results Four hundred and ten subjects with a mean age of 45.68 ± 10.3 years, a median of 45.00 years and a range of 20 to 80 years were enrolled into the study. MGUS was identified in only one (0.24 percent) of the 410 study subject. This subject was demonstrated to have a double monoclonal gammopathy; IgGλ at 16.9 g/L and IgAκ at 8.5 g/L. None of them including the sole subject with MGUS had a monoclonal urinary light chain. Conclusion Among residents of Lagos, Nigeria, MGUS was found in only 0.24% percent of apparently normal persons with a median age of 45 years. This suggests that MGUS which represents the earliest stage of monoclonal plasma/lymphoid cell proliferation is not a common finding in the relatively young population of Nigeria. Future epidemiologic studies dealing with plasma cell disorders in older people are required to carefully examine the relationship between environmental factors and prevalence of MGUS and its ultimate progression to MM

Prevalence of HIV related oral lesions in people living with HIV and on combined antiretroviral therapy: a Nigerian experience

Introduction:&nbsp;oral lesions comprise significant clinical features of HIV infection and are often indicators of immune suppression. However, the advent of antiretroviral therapy has significantly reduced its prevalence. The aim of this study was to relate the prevalence of oral lesions of HIV to treatment outcome of Combined Antiretroviral Therapy (cART) in a Nigerian HIV adult population. Methods:&nbsp;a cross-sectional study was conducted on 491 People Living with HIV (PLWHIV) on cART from two HIV centres in Lagos state, Nigeria. The EC-clearing house guidelines were employed to categorise oral lesions. Presence or absence of these lesions was reconciled with CD4+ cell count as a measure of efficacy of cART treatment. Results:&nbsp;a total of 491 PLWHIV on cART were enrolled, 366 (74.5%) were females and 125 (25.5%) were males. Age ranged between 18-80 years, with a mean of 41.2 ± 9.1 years. On examination, 12 (2.4%) patients presented with HIV oral lesions. Oral hyperpigmentation (10, 2.0%) was the most common lesion seen, followed by oral ulcers (2,0.4%). Majority (75%) of the affected patients were on a Lamivudine containing regimen. 7 out of the 12 patients with oral lesions had CD4+ cell count between 200-500 cell/mm3&nbsp;prior to cART initiation. Eleven (92%) of the patients with oral lesions had significant improvement of their CD4+ cell count after cART administration. Conclusion:&nbsp;the prevalence of oral lesions in HIV patients on cART therapy in Lagos is low. Oral hyperpigmentation and oral ulcers are the most frequent lesions seen. The presence or absence of oral lesions were not associated with CD4+ cell count. Therefore, we conclude that the oral lesions seen in HIV patients on cART may not be a direct manifestation of the disease

Prevalence and Factors Associated with Parvovirus B19 Infection among Blood Donors: A Hospital‑Based Study in South‑West, Nigeria

Background: Parvovirus B19 (B19V) is a transfusion transmissible infection that can result in severe consequences in vulnerable population that includes pregnant women, immunocompromised and chronic hemolytic anemia patients. The aim of this study was to determine the prevalence and factors associated with B19V infection amongst blood donors in South–West Nigeria. Materials and Methods: We conducted a comparative cross‑sectional study to determine the seroprevalence of B19V immunoglobulin M (IgM) antibody among 183 blood donors at the blood bank of a tertiary hospital. The results were analyzed with SPSS 23 software, prevalence and associated factors were determined using frequencies and logistic regression, respectively. Results: The prevalence of B19V IgM was 7.1% (95% confidence interval: 4–11) with a higher prevalence among male donors compared to females (84.6% vs. 15.4%, P = 0.54). There was a statistically significant difference in the seropositivity of B19V IgM amongst the ethnic groups with the Yoruba ethnic group having a higher proportion of B19V IgM‑positive participants P = 0.04. Ethnicity, gender, and steady employment were also associated with increased odds of infection, while increasing age appeared to be protective; though none of these factors were statistically significant. Conclusion: This study has shown that there is still high exposure to transfusion transmissible B19V infection. Keywords: Blood donor, parvovirus immunoglobulin M antibody, sickle cell anaemi

Opportunistic fungal infections in persons living with advanced HIV disease in Lagos, Nigeria; a 12-year retrospective study

Introduction: Nigeria has a large estimated burden of AIDS-related mycoses. We aimed to determine the proportion of patients with AIDS-related opportunistic fungal infections (OFIs) at an urban antiretroviral treatment (ART) centre in Nigeria. Methods: A retrospective analysis of a cohort of ART-na\uefve, HIV-infected patients, assessed for ART eligibility and ART-experience at the PEPFAR outpatient clinic at Lagos University Teaching Hospital over a 12-year period (April 2004-February 2016) was conducted. Results: During this period, 7,034 patients visited the clinic: 4,797 (68.2%) were female; 6161 patients had a recorded baseline CD4 count, and the median CD4 count was 184 cells/\u3bcl (IQR, 84-328). A baseline HIV-1 viral load (VL) was recorded for 5,908 patients; the median VL was 51,194 RNA copies/ml (IQR, 2,316-283,508) and 6,179/7046(88%) had initiated ART. Some 2,456 (34.9%) had a documented opportunistic infections, of whom 1,306 (18.6%) had an opportunistic fungal infection. The total number of OFI episodes was 1,632: oral candidiasis (n=1,473, 90.3%), oesophageal candidiasis (n=118; 8%), superficial mycoses (n=23; 1.6%), Pneumocystis pneumonia (PJP) (n=13; 0.8%), and cryptococcal meningitis(CM) (n=5; 0.4%). 113 (1.6%) were known to have died in the cohort. Conclusion: Approximately 1 in 5 HIV-infected patients in this retrospective cohort, most of whom had initiated ART, were clinically diagnosed with an OFI. Improved access to simple accurate diagnostic tests for CM and PJP should be prioritised for this setting

A modified anthrax toxin-based enzyme-linked immunospot assay reveals robust T cell responses in symptomatic and asymptomatic Ebola virus exposed individuals

Background Ebola virus (EBOV) caused more than 11,000 deaths during the 2013–2016 epidemic in West Africa without approved vaccines or immunotherapeutics. Despite its high lethality in some individuals, EBOV infection can produce little to no symptoms in others. A better understanding of the immune responses in individuals who experienced minimally symptomatic and asymptomatic infection could aid the development of more effective vaccines and antivirals against EBOV and related filoviruses. Methodology/Principle findings Between August and November 2017, blood samples were collected from 19 study participants in Lagos, Nigeria, including 3 Ebola virus disease (EVD) survivors, 10 individuals with documented close contact with symptomatic EVD patients, and 6 control healthcare workers for a cross-sectional serosurvey and T cell analysis. The Lagos samples, as well as archived serum collected from healthy individuals living in surrounding areas of the 1976 Democratic Republic of Congo (DRC) epidemic, were tested for EBOV IgG using commercial enzyme-linked immunosorbent assays (ELISAs) and Western blots. We detected antibodies in 3 out of 3 Lagos survivors and identified 2 seropositive individuals not known to have ever been infected. Of the DRC samples tested, we detected antibodies in 9 out of 71 (12.7%). To characterize the T cell responses in the Lagos samples, we developed an anthrax toxin-based enzyme-linked immunospot (ELISPOT) assay. The seropositive asymptomatic individuals had T cell responses against EBOV nucleoprotein, matrix protein, and glycoprotein 1 that were stronger in magnitude compared to the survivors. Conclusion/Significance Our data provide further evidence of EBOV exposure in individuals without EVD-like illness and, for the first time, demonstrate that these individuals have T cell responses that are stronger in magnitude compared to severe cases. These findings suggest that T cell immunity may protect against severe EVD, which has important implications for vaccine development

Identification and Characterization of Microsporidia from Fecal Samples of HIV-Positive Patients from Lagos, Nigeria

BACKGROUND: Microsporidia are obligate intracellular parasites that infect a broad range of vertebrates and invertebrates. They have been increasingly recognized as human pathogens in AIDS patients, mainly associated with a life-threatening chronic diarrhea and systemic disease. However, to date the global epidemiology of human microsporidiosis is poorly understood, and recent data suggest that the incidence of these pathogens is much higher than previously reported and may represent a neglected etiological agent of more common diseases indeed in immunocompetent individuals. To contribute to the knowledge of microsporidia molecular epidemiology in HIV-positive patients in Nigeria, the authors tested stool samples proceeding from patients with and without diarrhea. METHODOLOGY/PRINCIPAL FINDINGS: Stool samples from 193 HIV-positive patients with and without diarrhea (67 and 126 respectively) from Lagos (Nigeria) were investigated for the presence of microsporidia and Cryptosporidium using Weber's Chromotrope-based stain, Kinyoun stain, IFAT and PCR. The Weber stain showed 45 fecal samples (23.3%) with characteristic microsporidia spores, and a significant association of microsporidia with diarrhea was observed (O.R. = 18.2; CI: 95%). A similar result was obtained using Kinyoun stain, showing 44 (31,8%) positive samples with structures morphologically compatible with Cryptosporidium sp, 14 (31.8%) of them with infection mixed with microsporidia. The characterization of microsporidia species by IFAT and PCR allowed identification of Enterocytozoon bieneusi, Encephalitozoon intestinalis and E. cuniculi in 5, 2 and 1 samples respectively. The partial sequencing of the ITS region of the rRNA genes showed that the three isolates of E.bieneusi studied are included in Group I, one of which bears the genotype B. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this is the first report of microsporidia characterization in fecal samples from HIV-positive patients from Lagos, Nigeria. These results focus attention on the need to include microsporidial diagnosis in the management of HIV/AIDS infection in Nigeria, at the very least when other more common pathogens have not been detected

The 8p12 myeloproliferative syndrome

The occurrence of a myeloproliferative disorder in association with an aggressive lymphoproliferative disorder is a distinctly unusual phenomenon. We report a case of concurrent leukaemia-lymphoma syndrome characterized by a BCR/ABL-negative myeloproliferative disease, eosinophilia and a lymphoma. The bone marrow chromosome analysis showed the karyotype 46, XY, t(8;9) (q12; p33), which indicated presence of FGFR1 gene translocations. 8p12 myeloproliferative syndrome (EMS) / stem cell leukaemia-lymphoma syndrome (SCLL) belongs to the tyrosine kinase fusion genes chronic myeloproliferative diseases. The patient was managed conservatively with hydroxyurea, allopurinol and blood component therapy. The patient eventually died of intracerebral haemorrhage due to severe thrombocytopaenia. Based on our experience the overlap in the clinical presentation of this disease with lymphomas, can lead to a delay in diagnosis of EMS/SCLL. Given the aggressive nature of this disease, an accurate clinical and molecular diagnosis of this entity has become increasingly important

Opportunistic fungal infections in persons living with advanced HIV disease in Lagos, Nigeria:a 12-year retrospective study

Introduction: Nigeria has a large estimated burden of AIDS-related mycoses. We aimed to determine the proportion of pa- tients with AIDS-related opportunistic fungal infections (OFIs) at an urban antiretroviral treatment (ART) centre in Nigeria. Methods: A retrospective analysis of a cohort of ART-naïve, HIV-infected patients, assessed for ART eligibility and ART- experience at the PEPFAR outpatient clinic at Lagos University Teaching Hospital over a 12-year period (April 2004-Feb- ruary 2016) was conducted. Results: During this period, 7,034 patients visited the clinic: 4,797 (68.2%) were female; 6161 patients had a recorded base- line CD4 count, and the median CD4 count was 184 cells/µl (IQR, 84-328). A baseline HIV-1 viral load (VL) was recorded for 5,908 patients; the median VL was 51,194 RNA copies/ml (IQR, 2,316-283,508) and 6,179/7046(88%) had initiated ART. Some 2,456 (34.9%) had a documented opportunistic infections, of whom 1,306 (18.6%) had an opportunistic fungal infection. The total number of OFI episodes was 1,632: oral candidiasis (n=1,473, 90.3%), oesophageal candidiasis (n=118; 8%), superficial mycoses (n=23; 1.6%), Pneumocystis pneumonia (PJP) (n=13; 0.8%), and cryptococcal meningitis(CM) (n=5; 0.4%). 113 (1.6%) were known to have died in the cohort. Conclusion: Approximately 1 in 5 HIV-infected patients in this retrospective cohort, most of whom had initiated ART, were clinically diagnosed with an OFI. Improved access to simple accurate diagnostic tests for CM and PJP should be pri- oritised for this setting. Keywords: Opportunistic fungal infections; ART Adherence; Advanced HIV disease