Clinical laboratory reference values amongst children aged 4 weeks to 17 months in Kilifi, Kenya: A cross sectional observational study

Reference intervals for clinical laboratory parameters are important for assessing eligibility, toxicity grading and management of adverse events in clinical trials. Nonetheless, haematological and biochemical parameters used for clinical trials in sub-Saharan Africa are typically derived from industrialized countries, or from WHO references that are not region-specific. We set out to establish community reference values for haematological and biochemical parameters amongst children aged 4 weeks to 17 months in Kilifi, Kenya. We conducted a cross sectional study nested within phase II and III trials of RTS, S malaria vaccine candidate. We analysed 10 haematological and 2 biochemical parameters from 1,070 and 423 community children without illness prior to experimental vaccine administration. Statistical analysis followed Clinical and Laboratory Standards Institute EP28-A3c guidelines. 95% reference ranges and their respective 90% confidence intervals were determined using non-parametric methods. Findings were compared with published ranges from Tanzania, Europe and The United States. We determined the reference ranges within the following age partitions: 4 weeks to <6 months, 6 months to less than <12 months, and 12 months to 17 months for the haematological parameters; and 4 weeks to 17 months for the biochemical parameters. There were no gender differences for all haematological and biochemical parameters in all age groups. Hb, MCV and platelets 95% reference ranges in infants largely overlapped with those from United States or Europe, except for the lower limit for Hb, Hct and platelets (lower); and upper limit for platelets (higher) and haematocrit(lower). Community norms for common haematological and biochemical parameters differ from developed countries. This reaffirms the need in clinical trials for locally derived reference values to detect deviation from what is usual in typical children in low and middle income countries

A Primal-Dual Augmented Lagrangian Method for Optimal Control of Linear-Quadratic Problem with Time Varying Systems

In this paper we are concerned with time-varying optimal control problems whose cost is quadratic and whose state is a differential equation and with general boundary conditions. The basic new idea of this paper is to propose a primal-dual augmented Lagrangian method, embedded with a sequential quadratic programming(SQP) for the solution of such problems.The benefit of this approach is that the quality of the dual variables is monitored explicitly during the solution of the subproblem. Moreover, the formulation of a penalized matrix in the primal-dual variables with mesh-refinement strategy guarantees the reliability of the algorithm. Numerical experiments verify the efficiency of the proposed method.Keywords: Optimal control,primal-dual methods, augmented Lagrangian methods, conjugate gradient method, sequential quadratic programmingJournal of the Nigerian Association of Mathematical Physics, Volume 20 (March, 2012), pp 165 – 17

A Primal-Dual Augmented Lagrangian Method for Optimal Control of Linear-Quadratic Problem with Time Varying Systems

In this paper we are concerned with time-varying optimal control problems whose cost is quadratic and whose state is a differential equation and with general boundary conditions. The basic new idea of this paper is to propose a primal-dual augmented Lagrangian method, embedded with a sequential quadratic programming(SQP) for the solution of such problems.The benefit of this approach is that the quality of the dual variables is monitored explicitly during the solution of the subproblem. Moreover, the formulation of a penalized matrix in the primal-dual variables with mesh-refinement strategy guarantees the reliability of the algorithm. Numerical experiments verify the efficiency of the proposed method.Keywords: Optimal control,primal-dual methods, augmented Lagrangian methods, conjugate gradient method, sequential quadratic programming

Haemolytic uraemic syndrome in children admitted to a rural district hospital in Kenya.

We studied children admitted to Kilifi District Hospital, Kenya, between 1997 and 2005 with haemolytic uraemic syndrome (HUS) and reviewed their records in order to determine the clinical features and outcomes of the disease. Thirty-one children fulfilled the criteria: 21 (68%) had diarrhoea-associated HUS (D + HUS), the remainder did not (D-HUS); five had involvement of the central nervous system. Those with D-HUS had lower haemoglobin and platelet counts when compared with those with D + HUS. The overall mortality rate was 55% (17/31) with no significant difference between the two groups. Severe hyponatraemia ([Na(+)] &lt;120 mmol/L) predicted a poor outcome. Shigella dysenteriae was the most common isolated organism in the stool and Escherichia coli and S. dysenteriae were the most common blood isolates. HUS carries a high mortality rate and D-HUS is as common as D + HUS

The relationship between RTS,S vaccine-induced antibodies, CD4⁺ T cell responses and protection against Plasmodium falciparum infection.

Vaccination with the pre-erythrocytic malaria vaccine RTS,S induces high levels of antibodies and CD4(+) T cells specific for the circumsporozoite protein (CSP). Using a biologically-motivated mathematical model of sporozoite infection fitted to data from malaria-naive adults vaccinated with RTS,S and subjected to experimental P. falciparum challenge, we characterised the relationship between antibodies, CD4(+) T cell responses and protection from infection. Both anti-CSP antibody titres and CSP-specific CD4(+) T cells were identified as immunological surrogates of protection, with RTS,S induced anti-CSP antibodies estimated to prevent 32% (95% confidence interval (CI) 24%-41%) of infections. The addition of RTS,S-induced CSP-specific CD4(+) T cells was estimated to increase vaccine efficacy against infection to 40% (95% CI, 34%-48%). This protective efficacy is estimated to result from a 96.1% (95% CI, 93.4%-97.8%) reduction in the liver-to-blood parasite inoculum, indicating that in volunteers who developed P. falciparum infection, a small number of parasites (often the progeny of a single surviving sporozoite) are responsible for breakthrough blood-stage infections