Samuel Omokhodion

The Drakensberg Declaration on the Control of Rheumatic Fever and Rheumatic Heart Disease in Africa

Bongani Mayosi, Kate Robertson, Jimmy Volmink, Wole Adebo, Kingsley Akinyore, Albert Amoah, Charles Bannerman, Shan Biesman-Simons, Jonathan Carapetis, Antoinette Cilliers, Patrick Commerford, Anne Croasdale, Albertino Damasceno, Jenny Dean, Michael Dean, Robert de Souza, Antonio Filipe, Chris Hugo-Hamman, Sally-Ann JurgensClur, Pierre Kombila-Koumba, Christelle Kotzenberg, John Lawrenson, Pravin Manga, Jonathan Matenga, Tshimbi Mathivha, Phindile Mntla, Ana Mocumbi, Tiny Mokone, Elijah Ogola, Samuel Omokhodion, Chapman Palweni, Adrian Pearce, Avril Salo, Baby Thomas, Kathie Walker, Charles Wiysonge, Salah Zaher

Circulatory hepcidin is associated with the anti-inflammatory response but not with iron or anemic status in childhood malaria

Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore, it is important to understand the pathology underlying the development of CM and SMA as opposed to uncomplicated malaria (UM). Increased levels of hepcidin have been associated with UM, but its level and role in severe malarial disease remains to be investigated. Plasma and clinical data were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, Nigeria. Here, we report that hepcidin levels are lower in children with SMA or CM than in those with milder outcome (UM). While different profiles of pro- and anti-inflammatory cytokines were observed between the malaria syndromes, circulatory hepcidin levels remained associated with the levels of its regulatory cytokine interleukin-6 and of the anti-inflammatory cytokine inerleukin-10, irrespective of iron status, anemic status, and general acute-phase response. We propose a role for hepcidin in anti-inflammatory processes in childhood malaria.

Affinity Proteomics Reveals Elevated Muscle Proteins in Plasma of Children with Cerebral Malaria

Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria.

Tympanic thermometry in Nigerian children.

Summary Rectal and aural temperatures were recorded at the same time in 378 children aged ≤ 60 months and were found to be similar across the various age groups, correlation coefficients (r) ranging from 0.61 to 0.91. The mean differences between rectal and aural temperatures varied between -0.06 and 0.25°C. Concordance between the two methods ranged from 88.9% to 98% across the temperature range. Tympanic thermometry is simpler, safer and quicker than rectal thermometry and these findings justify the use of aural thermometry in any busy clinical facility for children.

Severe childhood malaria syndromes defined by plasma proteome profiles

Background Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore it is important to understand the pathology underlying the development of CM and SMA, as opposed to uncomplicated malaria (UM). Different host responses to infection are likely to be reflected in plasma proteome-patterns that associate with clinical status and therefore provide indicators of the pathogenesis of these syndromes. Methods and Findings Plasma and comprehensive clinical data for discovery and validation cohorts were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, an urban and densely populated holoendemic malaria area in Nigeria. A total of 946 children participated in this study. Plasma was subjected to high-throughput proteomic profiling. Statistical pattern-recognition methods were used to find proteome-patterns that defined disease groups. Plasma proteome-patterns accurately distinguished children with CM and with SMA from those with UM, and from healthy or severely ill malaria-negative children. Conclusions We report that an accurate definition of the major childhood malaria syndromes can be achieved using plasma proteome-patterns. Our proteomic data can be exploited to understand the pathogenesis of the different childhood severe malaria syndromes.

Health status of working and non-working school children in Ibadan, Nigeria.

Abstract Child labour continues to pose a challenge to national and international agencies. This study compares the health status of working and non-working school children in Ibadan, Nigeria. Altogether, 223 working and 230 non-working children were interviewed. Their ages ranged between 8 and 15 years. Fifty-nine (13%) reported fever, 36 (8%) visual problems, 28 (6%) skin lesions, 17 (4%) muscular and joint pains and 5 (1%) diarrhoea. Schistosoma ova were observed in 25 (6%) children. There was no difference in the occurrence of diseases between working and non-working children. Twenty-seven per cent of the children were underweight and 30% were stunted. Malnutrition was more prevalent among working children as 74 (33%) were underweight (p =0.001) and 76 (34%) were stunted. Public enlightenment about the effect of child labour might discourage parents from engaging their school-age children in work. Governments should address the socio-economic factors that promote child labour.

Klebsiella septicaemia, osteomyelitis and septic arthritis in neonates in Ibadan, Nigeria.

An outbreak of skeletal infections associated with neonatal Klebsiella septicaemia seen over a 6-month period at the Special Care Baby Unit, University College Hospital, Ibadan is reported. It involved 12 neonates, and the significant antecedent events included perinatal asphyxia, fetal distress and prolonged rupture of membranes. All the babies had septic arthritis and ten cases had osteomyelitis in addition: multiple joint involvement occurred in 50% of cases. All the babies exhibited severe systemic disturbance and the Klebsiella isolated demonstrated multiple antibiotic resistance. The epidemic coincided with a period of severe water shortage which affected the hospital. The probable nosocomial acquisition of the infection is highlighted.

Management of patients with rheumatic fever and rheumatic heart disease in Nigeria - need for a national system of primary, secondary and tertiary prevention

The burden of RF/RHD in the industrialised world began to decrease in the late 19th century, with a marked decrease after the 1950s. This decline coincided with an increase in the standard of living and improved access to medical care. 4

The IL17F and IL17RA Genetic Variants Increase Risk of Cerebral Malaria in Two African Populations

ABSTRACT Cerebral malaria (CM) is a neurological complication of infection with Plasmodium falciparum that is partly caused by cytokine-mediated inflammation. It is not known whether interleukin-17 (IL-17) cytokines, which regulate inflammation, control the development of CM. To evaluate the involvement of IL-17 cytokines in CM, we analyzed 46 common polymorphisms in IL17A, IL17F, and IL17RA (which encodes the common receptor chain of the members of the IL-17 family) in two independent African populations. A case-control study involving 115 Nigerian children with CM and 160 controls from the community (CC) showed that IL17F reference single nucleotide polymorphism (SNP) 6913472 (rs6913472) (P = 0.004; odds ratio [OR] = 3.12), IL17F rs4715291 (P = 0.004; OR = 2.82), IL17RA rs12159217 (P = 0.01; OR = 2.27), and IL17RA rs41396547 (P = 0.026; OR = 3.15) were independently associated with CM. A replication study was performed in 240 nuclear Malian family trios (two parents with one CM child). We replicated the association for 3 SNPs, IL17F rs6913472 (P = 0.03; OR = 1.39), IL17RA rs12159217 (P = 0.01; OR = 1.52), and IL17RA rs41396547 (P = 0.04; OR = 3.50). We also found that one additional SNP, IL17RA rs41433045, in linkage disequilibrium (LD) with rs41396547, was associated with CM in both Nigeria and Mali (P = 0.002; OR = 4.12 in the combined sample). We excluded the possibility that SNPs outside IL17F and IL17RA, in strong LD with the associated SNPs, could account for the observed associations. Furthermore, the results of a functional study indicated that the aggravating GA genotype of IL17F rs6913472 was associated with lower IL-17F concentrations. Our findings show for the first time that IL17F and IL17RA polymorphisms modulate susceptibility to CM and provide evidence that IL-17F protects against CM.

The Ibadan conjoined twins: a report of omphalopagus twins and a review of cases reported in Nigeria over 60 years.

Summary An omphalopagus set of female conjoined twins, undiagnosed prenatally, who presented as obstructed labour needing operative delivery is reported. Their anatomic characteristics and clinical features, including overwhelming sepsis in twin II which forced early separation, and those which led to their demise are described. Twelve other cases reported in Nigeria over the past 60 years are reviewed with reference to the aetiology and epidemiology of conjoined twinning and the determinants of successful surgical separation.