The role of laboratory confirmations and molecular epidemiology in global eradication of measles

This review reports on the role of laboratory confirmation and molecular epidemiology in global eradication of measles. The role of laboratory confirmation and molecular epidemiology in defining the origins of measles outbreaks cannot be overemphasized. New serological tests based on recombinant proteins detect only a fraction of the total measles virus (MV) specific antibodies. Several assays based on recombinant MV-haemagglutinin (ELISA and flow cytometry) or MV-fusion protein (flow cytometry) as well as neutralization and haemagglutination test have been evaluated using a large panel of lowtitre and negative sera. Isolation of measles virus confirmed the diagnosis. Phylogenetic trees are invaluable tools for monitoring the progress of immunization activities. Recent advances in genomic sequencing technology have lent its support to the monitoring and evaluation of vaccination programmes. More so, indigenous prepared measles antigens has been advocated to be produced, refined further and reproduced massively. This will be highly cost effective especially in field for seromonitoring and surveillance of measles. There is therefore, continual need for simpler diagnostic tests in elimination and eventual eradication of measles

Changes in Parasite Virulence Induced by the Disruption of a Single Member of the 235 kDa Rhoptry Protein Multigene Family of Plasmodium yoelii

Invasion of the erythrocyte by the merozoites of the malaria parasite is a complex process involving a range of receptor-ligand interactions. Two protein families termed Erythrocyte Binding Like (EBL) proteins and Reticulocyte Binding Protein Homologues (RH) play an important role in host cell recognition by the merozoite. In the rodent malaria parasite, Plasmodium yoelii, the 235 kDa rhoptry proteins (Py235) are coded for by a multigene family and are members of the RH. In P. yoelii Py235 as well as a single member of EBL have been shown to be key mediators of virulence enabling the parasite to invade a wider range of host erythrocytes. One member of Py235, PY01365 is most abundantly transcribed in parasite populations and the protein specifically binds to erythrocytes and is recognized by the protective monoclonal antibody 25.77, suggesting a key role of this particular member in virulence. Recent studies have indicated that overall levels of Py235 expression are essential for parasite virulence. Here we show that disruption of PY01365 in the virulent YM line directly impacts parasite virulence. Furthermore the disruption of PY01365 leads to a reduction in the number of schizonts that express members of Py235 that react specifically with the mcAb 25.77. Erythrocyte binding assays show reduced binding of Py235 to red blood cells in the PY01365 knockout parasite as compared to YM. While our results identify PY01365 as a mediator of parasite virulence, they also confirm that other members of Py235 are able to substitute for PY01365

Mortality from HIV-associated meningitis in sub-Saharan Africa: a systematic review and meta-analysis.

INTRODUCTION: HIV-associated cryptococcal, TB and pneumococcal meningitis are the leading causes of adult meningitis in sub-Saharan Africa (SSA). We performed a systematic review and meta-analysis with the primary aim of estimating mortality from major causes of adult meningitis in routine care settings, and to contrast this with outcomes from clinical trial settings. METHODS: We searched PubMed, EMBASE and the Cochrane Library for published clinical trials (defined as randomized-controlled trials (RCTs) or investigator-managed prospective cohorts) and observational studies that evaluated outcomes of adult meningitis in SSA from 1 January 1990 through 15 September 2019. We performed random effects modelling to estimate pooled mortality, both in clinical trial and routine care settings. Outcomes were stratified as short-term (in-hospital or two weeks), medium-term (up to 10 weeks) and long-term (up to six months). RESULTS AND DISCUSSION: Seventy-nine studies met inclusion criteria. In routine care settings, pooled short-term mortality from cryptococcal meningitis was 44% (95% confidence interval (95% CI):39% to 49%, 40 studies), which did not differ between amphotericin (either alone or with fluconazole) and fluconazole-based induction regimens, and was twofold higher than pooled mortality in clinical trials using amphotericin based treatment (21% (95% CI:17% to 25%), 17 studies). Pooled short-term mortality of TB meningitis was 46% (95% CI: 33% to 59%, 11 studies, all routine care). For pneumococcal meningitis, pooled short-term mortality was 54% in routine care settings (95% CI:44% to 64%, nine studies), with similar mortality reported in two included randomized-controlled trials. Few studies evaluated long-term outcomes. CONCLUSIONS: Mortality rates from HIV-associated meningitis in SSA are very high under routine care conditions. Better strategies are needed to reduce mortality from HIV-associated meningitis in the region

Immunogenicity of Self-Associated Aggregates and Chemically Cross-Linked Conjugates of the 42 kDa Plasmodium falciparum Merozoite Surface Protein-1

Self-associated protein aggregates or cross-linked protein conjugates are, in general, more immunogenic than oligomeric or monomeric forms. In particular, the immunogenicity in mice of a recombinant malaria transmission blocking vaccine candidate, the ookinete specific Plasmodium falciparum 25 kDa protein (Pfs25), was increased more than 1000-fold when evaluated as a chemical cross-linked protein-protein conjugate as compared to a formulated monomer. Whether alternative approaches using protein complexes improve the immunogenicity of other recombinant malaria vaccine candidates is worth assessing. In this work, the immunogenicity of the recombinant 42 kDa processed form of the P. falciparum merozoite surface protein 1 (MSP142) was evaluated as a self-associated, non-covalent aggregate and as a chemical cross-linked protein-protein conjugate to ExoProtein A, which is a recombinant detoxified form of Pseudomonas aeruginosa exotoxin A. MSP142 conjugates were prepared and characterized biochemically and biophysically to determine their molar mass in solution and stoichiometry, when relevant. The immunogenicity of the MSP142 self-associated aggregates, cross-linked chemical conjugates and monomers were compared in BALB/c mice after adsorption to aluminum hydroxide adjuvant, and in one instance in association with the TLR9 agonist CPG7909 with an aluminum hydroxide formulation. Antibody titers were assessed by ELISA. Unlike observations made for Pfs25, no significant enhancement in MSP142 specific antibody titers was observed for any conjugate as compared to the formulated monomer or dimer, except for the addition of the TLR9 agonist CPG7909. Clearly, enhancing the immunogenicity of a recombinant protein vaccine candidate by the formation of protein complexes must be established on an empirical basis

Pattern and prevalence of TB among PLWHAS and the complementary roles of two NGOS in the management of TB/HIV co-infection in a Teaching Hospital in Nigeria

No Abstracts.Nigerian Medical Practitioner Vol.50(5)2006: pp.81-9

Atherosclerosis – A Review

Atherosclerosis although a normal concomitant of aging, is the major pathogenic factor in coronary and cerebral thrombosis. While coronary thrombosis is implicated in the development of ischaemic heart disease, cerebral thrombosis is implicated in the pathogenesis of stroke, a major cause of morbidity and mortality throughout the world. Furthermore, the microangiopathic changes resulting in diabetic nephropathy and retinopathy are due to atherosclerosis. The increasing incidence of each of these pathological conditions seems to cause fear to every knowledgeable person about fat consumption. It is misleading to link atherosclerosis to an abnormal lipid metabolism, although studies have shown that cholesterol ester is the major class of lipid that accumulates while triglycericles, phospholipids, sphingolipids and cholesterol are present in smaller amounts. Past studies have also indicated that essential fatty acid (EFA) and Vitamin E prevent atherogenesis. This review emphasizes the biochemical events of atherogenesis as well as the role of Chlamydia pneumoniae in atherosclerosis. Nigerian Medical Practitioner Vol. 48 (1), 2005: 22 - 2

Lymphoepitheloal-like carcinoma of the submandibular gland

Lymphoepithelial-like carcinoma (LELC) of the salivary gland is uncommon, with about 80% of these occurring In the parotid gland. Its occurrence In the submandlbular gland is very rare. It has a higher Incidence In Eskimos and Orientals. Apart from a report about a North-African woman with LELC of the submandibular gland, to the best of the authors' knowledge, there are no other African reports In the English literature. We therefore report the case of a 3-year painless right submandibular swelllng in a female Nigerian diagnosed as LELC. The patient was managed by submandibular salivary gland surgical excision with adjuvant chemotherapy and is currently disease free.Keywords: lymphoepithelial-like carcinoma, submandlbular salivary glan

Determinants of the disposition of patients attending a psychiatric emergency department in Nigeria

No Abstrac

Antigenic and sequence diversity at the C-terminus of the merozoite surface protein-1 from rodent malaria isolates, and the binding of protective monoclonal antibodies

Merozoite surface protein-1 (MSP-1) is a major candidate in the development of a vaccine against malaria. Immunisation with a recombinant fusion protein containing the two Plasmodium yoelii MSP-1 C-terminal epidermal growth factor-like domains (MSP-119) can protect mice against homologous but not heterologous challenge, and therefore, antigenic differences resulting from sequence diversity in MSP-119 may be crucial in determining the potential of this protein as a vaccine. Representative sequence variants from a number of distinct P. yoelii isolates were expressed in Escherichia coli and the resulting recombinant proteins were screened for binding to a panel of monoclonal antibodies (Mabs) capable of suppressing a P. yoelii YM challenge infection in passive immunisation experiments. The sequence polymorphisms affected the binding of the antibodies to the recombinant proteins. None of the Mabs recognised MSP-119 of P. yoelii yoelii 2CL or 33X or P. yoelii nigeriensis N67. The epitopes recognised by the Mabs were further distinguished by their reactivity with the other fusion proteins. The extent of sequence variation in MSP-119 among the isolates was extensive, with differences detected at 35 out of the 96 positions compared. Using the 3-dimensional structure of the Plasmodium falciparum MSP-119 as a model, the locations of the amino acid substitutions that may affect Mab binding were identified. The DNA sequence of MSP-119 from two Plasmodium vinckei isolates was also cloned and the deduced amino acid sequence compared with that in other species