Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients.

BACKGROUND: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID patients is unknown. PATIENTS/METHODS: We studied the impact of anti-SARS-CoV-2 S antibodies levels on survival, viral RNA-load in plasma, and N-antigenaemia in 92 COVID-19 patients over ICU admission. RESULTS: Frequency of N-antigenaemia was >2.5-fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA-load in plasma, representing a protective factor against mortality (adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61], <0.001). Viral RNA-load in plasma and N-antigenaemia predicted increased mortality: (N1-viral load [≥2.156 copies/ml]: 2.25 [1.16; 4.36], 0.016); (N-antigenaemia: 2.45 [1.27; 4.69], 0.007). CONCLUSIONS: Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS-CoV-2.

Persistence of Plasmodium falciparum HRP-2 antigenaemia after artemisinin combination therapy is not associated with gametocytes.

BACKGROUND: In some settings, sensitive field diagnostic tools may be needed to achieve elimination of falciparum malaria. To this end, rapid diagnostic tests (RDTs) based on the detection of the Plasmodium falciparum protein HRP-2 are being developed with increasingly lower limits of detection. However, it is currently unclear how parasite stages that are unaffected by standard drug treatments may contribute to HRP-2 detectability and potentially confound RDT results even after clearance of blood stage infection. This study assessed the detectability of HRP-2 in periods of post-treatment residual gametocytaemia. METHODS: A cohort of 100 P. falciparum infected, gametocyte positive individuals were treated with or without the gametocytocidal drug primaquine (PQ), alongside standard artemisinin-based combination therapy (ACT), in the context of a randomised clinical trial in Ouelessebougou, Mali. A quantitative ELISA was used to measure levels of HRP-2, and compared time to test negativity using a standard and ultra-sensitive RDT (uRDT) between residual gametocyte positive and negative groups. RESULTS: Time to test negativity was longest by uRDT, followed by ELISA and then standard RDT. No significant difference in time to negativity was found between the treatment groups with and without residual gametocytes: uRDT (HR 0.79 [95% CI 0.52-1.21], p = 0.28), RDT (HR 0.77 [95% CI 0.51-1.15], p = 0.20) or ELISA (HR 0.88 [95% CI 0.59-1.32], p = 0.53). Similarly, no difference was observed when adjusting for baseline asexual parasite density. Quantified levels of HRP-2 over time were similar between groups, with differences attributable to asexual parasite densities. Furthermore, no difference in levels of HRP-2 was found between individuals who were or were not infectious to mosquitoes (OR 1.19 [95% CI 0.98-1.46], p = 0.077). CONCLUSIONS: Surviving sexual stage parasites after standard ACT treatment do not contribute to the persistence of HRP-2 antigenaemia, and appear to have little impact on RDT results.

Evaluation of Asymptomatic Malaria Antigenaemia and Parasitaemia in Human Immunodeficiency Virus-Infected Children in Benin City, Nigeria.

BACKGROUND: Malaria and HIV/AIDS are rampant in subSaharan Africa with prevalence of one reinforcing the other and control of one impactful on control of the other. Malaria parasitaemia (MP) prevalence is increased in HIV-infected individuals while certain drugs used in latter cause decline in MP but it is uncertain how they affect malaria antigenaemia (MA). How certain bio-social and disease characteristics affect MA and MP in this cohort is unknown. OBJECTIVES: To determine prevalence of asymptomatic MP and MA and their clinical and social determinants in HIV infected. METHODS: In a prospective cross-sectional study carried out at the University of Benin Teaching Hospital (April to June 2016), 221 HIV-infected children (aged 1-17years) asymptomatic for malaria and 221 apparently healthy HIV-negative controls were studied. MA was assessed using rapid diagnostic test while MP was evaluated using microscopy. Standard method was used to determine parasite count. RESULTS: Prevalence of asymptomatic MP was 24.4% in subjects and 17.6% in controls while MA prevalence in subjects and controls were comparable (20.8% vs 18.1%). Malaria parasitaemia rate (MPr) of 24.4% was higher than malaria antigenaemia rate (MAr) (20.8%). MP and MA rates were independent of socioeconomic status, access to anti-retroviral drugs, their duration of use and clinical disease stage. CONCLUSION: MA occurred frequently enough to warrant its use as malaria case definition surrogate in asymptomatic children with HIV/AIDS receiving trimethoprim-sulfamethoxazole prophylaxis and protease inhibitors.

CONTEXTE: Le paludisme et le VIH / SIDA sont endémiques en Afrique subsaharienne, la prévalence de l'un renforçant l'autre et le contrôle de l'un ayant un impact sur le contrôle de l'autre. La prévalence de la parasitémie du paludisme (MP) est augmentée chez les personnes infectées par le VIH, tandis que certains médicaments utilisés dans ces derniers entraînent une baisse de la MP, mais on ignore comment ils affectent l'antigénémie du paludisme (AM). On ne sait pas comment certaines caractéristiques biosociales et pathologiques affectent l'AMM et la MP dans cette cohorte. OBJECTIFS: Déterminer la prévalence de la MP et de l'AMM et leurs déterminants cliniques-sociaux chez les enfants infectés par le VIH. METHODES: Dans une étude transversale prospective menée à l'hôpital universitaire de l'Université du Bénin (avril et juin 2016), 221 enfants infectés par le VIH (âgés de 1 à 17 ans) asymptomatiques pour le paludisme et 221 témoins séronégatifs apparemment en bonne santé ont été étudiés. La MA a été évaluée à l'aide d'un test de diagnostic rapide tandis que la MP a été évaluée à l'aide de la microscopie à coloration de Giemsa. La méthode standard a été utilisée pour déterminer le nombre de parasites. RESULTATS: La prévalence de la MP asymptomatique était de 24,4% chez les sujets et de 17,6% chez les témoins, tandis que la prévalence de l'AM chez les sujets et les témoins était comparable (20,8% vs 18,1%). Le taux de parasitémie du paludisme (MPr) de 24,4% était plus élevé que le taux d'antigénémie du paludisme (MAr) (20,8%). Les taux de MP et d'AM étaient indépendants du statut socio-économique, de l'accès aux médicaments antirétroviraux, de leur durée d'utilisation et du stade clinique de la maladie. CONCLUSION: l'AMM est survenue suffisamment fréquemment pour justifier son utilisation comme substitut de la définition de cas dans la prise en charge de ces sujets, étant donné l'implication de la parasitémie dans la physiopathologie et la virulence du VIH. MOTS CLÉS: Paludisme, Antigénémie, Parasitémie, Enfants infectés par le VIH, Benin City.

Prevalence and mortality of cryptococcal disease in adults with advanced HIV in an urban tertiary hospital in Sierra Leone: a prospective study.

BACKGROUND: The global annual estimate for cryptococcal disease-related deaths exceeds 180,000, with three fourth occurring in sub-Saharan Africa. The World Health Organization (WHO) recommends cryptococcal antigen (CrAg) screening in all HIV patients with CD4 count < 100/µl. As there is no previous published study on the burden and impact of cryptococcal disease in Sierra Leone, research is needed to inform public health policies. We aimed to establish the seroprevalence and mortality of cryptococcal disease in adults with advanced HIV attending an urban tertiary hospital in Sierra Leone. METHODS: A prospective cohort study design was used to screen consecutive adult (18 years or older) HIV patients at Connaught Hospital in Freetown, Sierra Leone with CD4 count below 100 cells/mm3 from January to April 2018. Participants received a blood CrAg lateral flow assay (IMMY, Oklahoma, USA). All participants with a positive serum CrAg had lumbar puncture and cerebrospinal fluid (CSF) CrAg assay, and those with cryptococcal diseases had fluconazole monotherapy with 8 weeks followed up. Data were entered into Excel and analysed in Stata version 13.0. Proportions, median and interquartile ranges were used to summarise the data. Fisher's exact test was used to compare categorical variables. RESULTS: A total of 170 patients, with median age of 36 (IQR 30-43) and median CD4 count of 45 cells/mm3 (IQR 23-63) were screened. At the time of enrolment, 54% were inpatients, 51% were newly diagnosed with HIV, and 56% were either ART-naïve or newly initiated (≤ 30 days). Eight participants had a positive blood CrAg, giving a prevalence of 4.7% (95% CI: 2.4-9.2%). Of those with a positive CrAg, CSF CrAg was positive in five (62.5%). Five (62.5%) CrAg-positive participants died within the first month, while the remaining three were alive and established on ART at 8 weeks. CONCLUSION: A substantial prevalence of cryptococcal antigenaemia and poor outcome of cryptococcal disease were demonstrated in our study. The high mortality suggests a need for the HIV programme to formulate and implement policies on screening and pre-emptive fluconazole therapy for all adults with advanced HIV in Sierra Leone, and advocate for affordable access to effective antifungal therapies.

Pathogenesis and prevention of risk of cardiovascular events in patients with pneumococcal community-acquired pneumonia.

It is now well recognized that cardiovascular events (CVE) occur quite commonly, both in the acute phase and in the long-term, in patients with community-acquired pneumonia (CAP). CVE have been noted in up to 30% of patients hospitalized with all-cause CAP. One systematic review and meta-analysis of hospitalized patients with all-cause CAP noted that the incidence rates for overall cardiac events were 17.7%, for incident heart failure were 14.1%, for acute coronary syndromes were 5.3% and for incident cardiac arrhythmias were 4.7%. In the case of pneumococcal CAP, almost 20% of patients studied had one or more of these cardiac events. Recent research has provided insights into the pathogenesis of the acute cardiac events occurring in pneumococcal infections. With respect to the former, key involvements of the major pneumococcal protein virulence factor, pneumolysin, are now well documented, whilst systemic platelet-driven neutrophil activation may also contribute. However, events involved in the pathogenesis of the long-term cardiovascular sequelae remain largely unexplored. Emerging evidence suggests that persistent antigenaemia may predispose to the development of a systemic pro-inflammatory/prothrombotic phenotype underpinning the risk of future cardiovascular events. The current manuscript briefly reviews the occurrence of cardiovascular events in patients with all-cause CAP, as well as in pneumococcal and influenza infections. It highlights the close interaction between influenza and pneumococcal pneumonia. It also includes a brief discussion of mechanisms of the acute cardiac events in CAP. However, the primary focus is on the prevalence, pathogenesis and prevention of the longer-term cardiac sequelae of severe pneumococcal disease, particularly in the context of persistent antigenaemia and associated inflammation.

Circulating filarial antigen detection in brugian filariasis.

Human lymphatic filariasis (LF) is a major cause of disability globally. The success of global elimination programmes for LF depends upon effectiveness of tools for diagnosis and treatment. In this study on stage-specific antigen detection in brugian filariasis, L3, adult worm (AW) and microfilarial antigenaemia were detected in around 90-95% of microfilariae carriers (MF group), 50-70% of adenolymphangitis (ADL) patients, 10-25% of chronic pathology (CP) patients and 10-15% of endemic normal (EN) controls. The sensitivity of the circulating filarial antigen (CFA) detection in serum samples from MF group was up to 95%. In sera from ADL patients, unexpectedly, less antigen reactivity was observed. In CP group all the CFA positive individuals were from CP grade I and II only and none from grade III or IV, suggesting that with chronicity the AWs lose fecundity and start to disintegrate and die. Amongst EN subject, 10-15% had CFA indicating that few of them harbour filarial AWs, thus they might not be truly immune as has been conventionally believed. The specificity for antigen detection was 100% when tested with sera from various other protozoan and non-filarial helminthic infections.

Lymphatic Filariasis Elimination Status: Wuchereria bancrofti Infections in Human Populations after Five Effective Rounds of Mass Drug Administration in Zambia.

Lymphatic filariasis (LF), also commonly known as elephantiasis, is a neglected tropical disease (NTD) caused by filarial parasites. The disease is transmitted via a bite from infected mosquitoes. The bites of these infected mosquitoes deposit filarial parasites, Wuchereria or Brugia, whose predilection site is the lymphatic system. The damage to the lymph system causes swelling in the legs, arms, and genitalia. A mapping survey conducted between 2003 and 2011 determined LF as being endemic in Zambia in 96 out of 116 districts. Elimination of LF is known to be possible by stopping the spread of the infection through large-scale preventive chemotherapy. Therefore, mass drug administration (MDA) with diethylcarbamazine citrate (DEC) (6 mg/kg) and Albendazole (400 mg) for Zambia has been conducted and implemented in all endemic districts with five effective rounds. In order to determine whether LF prevalence has been sufficiently reduced to levels less than 2% antigenemia and less than 1% microfilaremia, a pre-transmission assessment survey (pre-TAS) was conducted. Therefore, post-MDA pre-TAS was conducted between 2021 and 2022 in 80 districts to determine the LF prevalence. We conducted a cross-sectional seroprevalence study involving 600 participants in each evaluation unit (EU) or each district. The study sites (sentinel and spot-check sites) were from districts that were the implementation units (IUs) of the LF MDA. These included 80 districts from the 9 provinces. A total of 47,235 people from sentinel and spot-check locations were tested. Of these, valid tests were 47,052, of which 27,762 (59%) were females and 19,290 (41%) were males. The survey revealed in the 79/80 endemic districts a prevalence of Wb antigens of 0.14% and 0.0% prevalence of microfilariae. All the surveyed districts had an optimum prevalence of less than 2% for antigenaemia, except for Chibombo district. The majority of participants that tested positive for Wuchereria bancrofti (Wb) Antigens (Ag) were those that had 2, 3, and 4 rounds of MDA. Surprisingly, individuals that had 1 round of MDA were not found to have circulating antigens of Wb. The study showed that all the surveyed districts, except for Chibombo, passed pre-TAS. This further implies that there is a need to conduct transmission assessment surveys (TASs) in these districts.

Prevalence of cryptococcal antigen (CrAg) among HIV-positive patients in Eswatini, 2014-2015.

BACKGROUND: Cryptococcal meningitis is a leading cause of death amongst people living with HIV. However, routine cryptococcal antigen (CrAg) screening was not in the national guidelines in Eswatini. OBJECTIVES: A cross-sectional study was conducted between August 2014 and March 2015 to examine CrAg prevalence at Mbabane Government Hospital in Eswatini. METHODS: We collected urine and whole blood from antiretroviral-therapy-naïve patients with HIV and a cluster of differentiation 4 (CD4) counts < 200 cells/mm3 for plasma and urine CrAg lateral flow assay (LFA) screening at the national HIV reference laboratory. Two CD4 cut-off points were used to estimate CrAg prevalence: CD4 < 100 and < 200 cells/mm3. Sensitivity and specificity of urine CrAg LFA was compared to plasma CrAg LFA. RESULTS: Plasma CrAg prevalence was 4% (8/182, 95% confidence interval [CI]: 2-8) amongst patients with CD4 counts of < 200 cells/mm3, and 8% (8/102, 95% CI: 3-15) amongst patients with CD4 counts of < 100 cells/mm3. Urine CrAg LFA had a sensitivity of 100% (95% CI: 59-100) and a specificity of 80% (95% CI: 72-86) compared with plasma CrAg LFA tests for patients with CD4 < 200 cells/mm3. Forty-three per cent of 99 patients with CD4 < 100 were at World Health Organization clinical stages I or II. CONCLUSION: The prevalence of CrAg in Eswatini was higher than the current global estimate of 6% amongst HIV-positive people with CD4 < 100 cell/mm3, indicating the importance of initiating a national screening programme. Mechanisms for CrAg testing, training, reporting, and drug and commodity supply issues are important considerations before national implementation.

Mapping the baseline prevalence of lymphatic filariasis across Nigeria.

INTRODUCTION: The baseline endemicity profile of lymphatic filariasis (LF) is a key benchmark for planning control programmes, monitoring their impact on transmission and assessing the feasibility of achieving elimination. Presented in this work is the modelled serological and parasitological prevalence of LF prior to the scale-up of mass drug administration (MDA) in Nigeria using a machine learning based approach. METHODS: LF prevalence data generated by the Nigeria Lymphatic Filariasis Control Programme during country-wide mapping surveys conducted between 2000 and 2013 were used to build the models. The dataset comprised of 1103 community-level surveys based on the detection of filarial antigenemia using rapid immunochromatographic card tests (ICT) and 184 prevalence surveys testing for the presence of microfilaria (Mf) in blood. Using a suite of climate and environmental continuous gridded variables and compiled site-level prevalence data, a quantile regression forest (QRF) model was fitted for both antigenemia and microfilaraemia LF prevalence. Model predictions were projected across a continuous 5 × 5 km gridded map of Nigeria. The number of individuals potentially infected by LF prior to MDA interventions was subsequently estimated. RESULTS: Maps presented predict a heterogeneous distribution of LF antigenemia and microfilaraemia in Nigeria. The North-Central, North-West, and South-East regions displayed the highest predicted LF seroprevalence, whereas predicted Mf prevalence was highest in the southern regions. Overall, 8.7 million and 3.3 million infections were predicted for ICT and Mf, respectively. CONCLUSIONS: QRF is a machine learning-based algorithm capable of handling high-dimensional data and fitting complex relationships between response and predictor variables. Our models provide a benchmark through which the progress of ongoing LF control efforts can be monitored.

Dengue virus non-structural Protein-1 expression and associated risk factors among febrile Patients attending University of Abuja Teaching Hospital, Nigeria.

BACKGROUND: Dengue is a mosquito-borne and neglected tropical viral disease that has been reported to be hyper-endemic in Nigeria. However, this is the first dengue study in Abuja. OBJECTIVE: This hospital-based cross-sectional study investigated the prevalence of Dengue virus (DENV) non-structural protein-1 (NS1) antigenaemia, anti-Dengue virus IgG and their associated risk factors among febrile patients attending the University of Abuja Teaching Hospital (UATH), Nigeria. MATERIALS AND METHODS: From May to August 2016, blood samples were individually collected from 171 consented participants. These samples were analyzed using DENV NS1 and anti-DENV IgG Enzyme Linked Immunosorbent Assay (ELISA) kits. Well-structured questionnaires was used to collect sociodemographic variables of participants. RESULTS: Out of the 171 participants, the prevalence of Dengue virus NS1 antigenaemia and IgG seropositivity were 8.8% and 43.3%, respectively. Three (1.8%) of the patients were NS1 (+) IgG (-), 12 (7.0%) had NS1 (+) IgG (+), 62 (36.3%) were NS1 (-) IgG (+), while 97 (56.7%) of the remaining patients were NS1 (-) IgG (-). There was statistical association between DENV NS1 antigenaemia with age of patients (p=0.034), residence in proximity to waste dumpsites (p<0.0001) but not with occupation of patients (p=0.166), use of indoor insecticide sprays (p=0.4910) and presence of household artificial water containers (p=0.3650). There was statistical association between the prevalence of anti-Dengue virus IgG with occupation (p=0.0034) and education level of patients (p<0.001). However, there was no statistical association between the prevalence of anti-Dengue virus IgG with gender (p=0.4060) and residential area of patients (p=0.3896). CONCLUSION: Findings from this study revealed that DENV infection is one of the etiological agents of acute febrile illnesses in Abuja. It's recommended that Dengue testing be considered during differential diagnosis of febrile patients.

Early abnormal liver enzyme levels may increase the prevalence of human cytomegalovirus antigenaemia after hematopoietic stem cell transplantation.

Objective Human cytomegalovirus (HCMV) infection is common after bone marrow transplantation (BMT), and it increases morbidity and mortality for transplant recipients. HCMV infection may cause hepatitis and elevate the liver enzymes aspartate transferase (AST) and alanine transferase (ALT). This study aimed to analyse the associations between liver enzyme levels and infection with HCMV antigenaemia after BMT. Methods Data from 30 patients after BMT were collected at different time points (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, and 6.0 months post-transplantation). The patients were divided into the HCMV antigenaemia-positive and HCMV antigenaemia-negative groups according to a peripheral blood pp65 antigen assay. Immunohistochemistry was used to identify HCMV pp65 antigen and conventional methods were used to detect liver enzyme levels. Results Twelve patients were pp65 antigenaemia-positive and 10 patients were positive in the first 3 months post-transplant. Liver enzyme levels were increased after positivity for HCMV antigenaemia (p = 0.034 and p = 0.018 for ALT and AST, respectively). One month before antigenaemia, AST levels were higher in the HCMV antigenaemia-positive group compared with the negative group (p = 0.006). Conclusion HCMV antigenaemia mostly occurs in the early stage of post-BMT and early abnormal liver enzyme levels may increase the chance of HCMV antigenaemia after BMT.

Understanding the relationship between prevalence of microfilariae and antigenaemia using a model of lymphatic filariasis infection.

BACKGROUND: Lymphatic filariasis is a debilitating neglected tropical disease that affects impoverished communities. Rapid diagnostic tests of antigenaemia are a practical alternative to parasitological tests of microfilaraemia for mapping and surveillance. However the relationship between these two methods of measuring burden has previously been difficult to interpret. METHODS: A statistical model of the distribution of worm burden and microfilariae (mf) and resulting antigenaemic and mf prevalence was developed and fitted to surveys of two contrasting sentinel sites undergoing interventions. The fitted model was then used to explore the relationship in various pre- and post-intervention scenarios. RESULTS: The model had good quantitative agreement with the data and provided estimates of the reduction in mf output due to treatment. When extrapolating the results to a range of prevalences there was good qualitative agreement with published data. CONCLUSIONS: The observed relationship between antigenamic and mf prevalence is a natural consequence of the relationship between prevalence and intensity of adult worms and mf production. The method described here allows the estimation of key epidemiological parameters and consequently gives insight into the efficacy of an intervention programme.

Cryptococcosis in HIV-infected hospitalized patients in Germany: Evidence for routine antigen testing.

OBJECTIVES: To investigate the diagnostic value of routine cryptococcal antigen (CRAG) testing in HIV-infected patients in a low prevalence setting. METHODS: Retrospective single centre cohort study of a 10-year period (2005-2014). RESULTS: 5461 patients tested for CRAG were included. Cryptococcal antigenaemia was found in 1.6% and 1.1% of patients with CD4 counts of ≤100/µl and 101-200/µl, respectively. The positive predictive values for identifying clinically relevant cryptococcal disease was 96% and 100%, respectively. Half of the patients had a non-specific presentation and median time-to-diagnosis was high (5 days, range 1-44 days). The median time-to-diagnosis in direct admissions to our centre with routine CRAG testing was significantly shorter: 1 day (range: 1-17) vs. 7 days (range: 2-44), p = 0.003. Prevalence of cryptococcal antigenaemia was 2.8% in patients with pneumocystis pneumonia and median time-to-diagnosis of cryptococcosis was significantly longer in this subgroup (15 days; range: 1-44 vs. 3 days; range: 1-17; p = 0.008). CRAG titres ≥1:512 were associated with disseminated disease (OR 21.3, p = 0.0008, 95% CI 1.64-277), however, 10% of patients with disseminated cryptococcosis had CRAG titres <1:16. CONCLUSION: Our data support routine CRAG testing in hospitalized HIV-infected patients with CD4 counts ≤200/µl, and/or pneumocystis pneumonia.

An investigation of the disparity in estimates of microfilaraemia and antigenaemia in lymphatic filariasis surveys.

BACKGROUND: The diagnosis of lymphatic filariasis (LF) is based typically on either microfilaraemia as assessed by microscopy or filarial antigenaemia using an immuno-chromatographic test. While it is known that estimates of antigenaemia are generally higher than estimates of microfilaraemia, the extent of the difference is not known. METHODS: This paper presents the results of an extensive literature search for surveys that estimated both microfilaraemia and antigenaemia in order to better understand the disparity between the two measures. RESULTS AND CONCLUSIONS: In some settings there was a very large disparity, up to 40-70%, between estimates of microfilaraemia and antigenaemia. Regression analysis was unable to identify any predictable relationship between the two measures. The implications of findings for risk mapping and surveillance of LF are discussed.

Cytomegalovirus load in whole blood is more reliable for predicting and assessing CMV disease than pp65 antigenaemia.

CMV is a common cause of disease in immunocompromised patients. Because sampling of the diseased organ can be invasive, markers of systemic CMV reactivation such as pp65 and CMV viral load are commonly used to monitor patients at risk of CMV disease. In this retrospective analysis, the performance of these markers was compared in solid organ transplant recipients, patients with haematological malignancies and HIV infection. Both assays were sensitive markers of reactivation, however, the predictive value for disease of a positive result for both was low. Compared to viral load, the pp65 assay was a less sensitive marker of CMV reactivation. It was only positive when the viral load was greater than 3 log (10) copies/ml whole blood and was negative in 10 instances when the viral load was between 3 and 5 logs. In concordantly positive samples, the number of pp65 positive cells varied widely relative to the viral load and the number of positive cells counted could not be used to predict disease likelihood with any certainty. To conclude, CMV viral load provides a more consistent guide to determine likelihood of disease than pp65 count and is a more sensitive marker of CMV reactivation.

Sero-epidemiology of Hepatitis B Surface Antigenaemia among Adult Nigerians with Clinical Features of Liver Diseases Attending a Primary-Care Clinic in a Resource-Constrained Setting of Eastern Nigeria.

BACKGROUND: Hepatitis-B infection is not commonly perceived as a serious medical problem in Nigeria. However, chronic hepatitis-B infection, which is a subject of global concern, may lead to lethal liver diseases. AIM: The study was to determine the sero-epidemiology of hepatitis-B surface antigenaemia among adult Nigerians with clinical features of liver diseases attending a primary-care clinic in a resource-constrained setting of Eastern Nigeria. MATERIALS AND METHODS: A cross-sectional study was carried out on 140 adult Nigerians with clinical features of liver diseases at the primary-care clinic of Federal Medical Centre, Owerri. They made up three groups: 44 patients, 62 patients and 34 patients with clinical features of hepatitis, liver cirrhosis and hepatocellular carcinoma, respectively. Hepatitis-B surface antigen (HBsAg) was assayed using an immunochromatographic method. Demographic variables were collected. RESULTS: The overall sero-positivity rate was 50.7%. The sero-positivity rates for these patients were 23.9%, 39.5% and 36.6% for hepatitis, liver cirrhosis and hepatocellular carcinoma, respectively. The age group 40-60 years (P = 0.048) and artisans (P = 0.019) were significantly infected. Abdominal swelling (86.4%) and ascites (67.1%) were the most common symptoms and signs, respectively. CONCLUSION: HBsAg prevalence was high and has significant association with age and occupation.

Evaluation of human cytomegalovirus-specific CD8+ T-cells in allogeneic haematopoietic stem cell transplant recipients using pentamer and interferon-γ-enzyme-linked immunospot assays.

BACKGROUND: Reactivation of latent human cytomegalovirus (HCMV) is a frequent complication following allogeneic haematopoietic stem cell transplantation (HSCT). Evaluation of the quantity and function of HCMV-specific CD8+ T-cell responses after HSCT may play a crucial role in the prevention of HCMV reactivation. OBJECTIVES: To investigate the mechanism of HCMV-specific T-cell immune responses after HSCT in HCMV-specific CD8+ T cells. STUDY DESIGN: HCMV-specific CD8+ T cells were quantified using human leucocyte antigen (HLA) pentamer staining and functionally analysed by interferon-γ-enzyme-linked immunospot (IFN-γ-ELISPOT) assay with a pp65495-503 peptide in recipients four years after HSCT. RESULTS: The absolute number of pp65495-503-specific CD8+ T cells did not differ significantly (p>0.05) between samples with antigenaemia and those without antigenaemia given a mean of 54.5/µl and 40.5/µl, respectively, in 21 HLA-A* 0201 patients after HSCT. The level of pp65495-503-specific CD8+ T cells>20/µl of peripheral blood was maintained 90 days after transplantation. There was a significant difference in the spot count of IFN-γ-secreting T cells between samples with antigenaemia (mean, 507/2.5×10(5)PBMCs) and those without antigenaemia (mean, 216/2.5×10(5)PBMCs; p<0.05). CONCLUSION: pp65495-503-specific CD8+ T cells may not be sufficient to control HCMV reactivation in recipients after HSCT. However, the combination of pentamer and IFN-γ-ELISPOT assays may be valuable for evaluating HCMV-specific CD8+ T cells. Further studies on HCMV-specific T-cell immune responses continue to be performed for the prevention of persistent HCMV reactivation.