Timothy Planche

Severe falciparum malaria in Gabonese children: clinical and laboratory features.

BackgroundMalaria continues to claim one to two million lives a year, mainly those of children in sub-Saharan Africa. Reduction in mortality depends, in part, on improving the quality of hospital care, the training of healthcare workers and improvements in public health. This study examined the prognostic indicators of severe falciparum malaria in Gabonese children.MethodsAn observational study examining the clinical presentations and laboratory features of severe malaria was conducted at the Centre Hospitalier de Libreville, Gabon over two years. Febrile children aged from 0 to 10 years with Plasmodium falciparum infection and one or more features of severe malaria were enrolled.ResultsMost children presenting with severe falciparum malaria were less than 5 years (92.3% of 583 cases). Anaemia was the most frequent feature of severe malaria (67.8% of cases), followed by respiratory distress (31%), cerebral malaria (24%) hyperlactataemia (16%) and then hypoglycaemia (10%). Anaemia was more common in children under 18 months old, while cerebral malaria usually occurred in those over 18 months. The overall case fatality rate was 9%. The prognostic indicators with the highest case fatality rates were coma/seizures, hyperlactataemia and hypoglycaemia, and the highest case fatality rate was in children with all three of these features.ConclusionsPrompt and appropriate, classification and treatment of malaria helps identify the most severely ill children and aids early and appropriate management of the severely ill child.

A novel and accurate diagnostic test for human African trypanosomiasis

INTRODUCTION Human African trypanosomiasis (sleeping sickness) affects up to half a million people every year in sub-Saharan Africa. Because current diagnostic tests for the disease have low accuracy, we sought to develop a novel test that can diagnose human African trypanosomiasis with high sensitivity and specificity. METHODS We applied serum samples from 85 patients with African trypanosomiasis and 146 control patients who had other parasitic and non-parasitic infections to a weak cation exchange chip, and analysed with surface-enhanced laser desorption-ionisation time-of-flight mass spectrometry. Mass spectra were then assessed with three powerful data-mining tools: a tree classifier, a neural network, and a genetic algorithm. FINDINGS Spectra (2-100 kDa) were grouped into training (n=122) and testing (n=109) sets. The training set enabled data-mining software to identify distinct serum proteomic signatures characteristic of human African trypanosomiasis among 206 protein clusters. Sensitivity and specificity, determined with the testing set, were 100% and 98.6%, respectively, when the majority opinion of the three algorithms was considered. This novel approach is much more accurate than any other diagnostic test. INTERPRETATION Our report of the accurate diagnosis of an infection by use of proteomic signature analysis could form the basis for diagnostic tests for the disease, monitoring of response to treatment, and for improving the accuracy of patient recruitment in large-scale epidemiological studies.

Evidence of decline of malaria in the general hospital of Libreville, Gabon from 2000 to 2008

BackgroundSubstantial decline in malaria transmission, morbidity and mortality has been reported in several countries where new malaria control strategies have been implemented. In Gabon, the national malaria policy changed in 2003, according to the WHO recommendations. The trend in malaria morbidity was evaluated among febrile children before and after their implementation in Libreville, the capital city of Gabon.MethodsFrom August 2000 to December 2008, febrile paediatric outpatients and inpatients, under 11 years of age, were screened for malaria by microscopic examination at the Malaria Clinical Research Unit (MCRU) located in the largest public hospital in Gabon. Climatic data were also collected.ResultsIn total, 28,092 febrile children were examined; those under five years always represented more than 70%. The proportion of malaria-positive slides was 45% in 2000, and declined to 15% in 2008. The median age of children with a positive blood smear increased from 24(15-48) to 41(21-72) months over the study period (p < 0.01). Rainfall patterns had no impact on the decline observed throughout the study period.ConclusionThe decrease of malaria prevalence among febrile children during the last nine years is observed following the introduction of new strategies of malaria cases management, and may announce epidemiological changes. Moreover, preventive measures must be extended to children older than five years.

Population kinetics, efficacy, and safety of dichloroacetate for lactic acidosis due to severe malaria in children.

The authors conducted a randomized, double‐blind, placebo‐controlled trial of intravenous dichloroacetate (DCA) for the purpose of treating lactic acidosis in 124 West African children with severe Plasmodium falciparum malaria. Lactic acidosis independently predicts mortality in severe malaria, and DCA stimulates the oxidative removal of lactate in vivo. A single infusion of 50 mg/kg DCA was well tolerated. When administered at the same time as a dose of intravenous quinine, DCA significantly increased the initial rate and magnitude of fall in blood lactate levels and did not interfere with the plasma kinetics of quinine. The authors developed a novel population pharmacokinetic‐pharmacodynamic indirect‐response model for DCA that incorporated characteristics associated with disease reversal. The model describes the complex relationships among antimalarial treatment procedures, plasma DCA concentrations, and the drugs lactate‐lowering effect. DCA significantly reduces the concentration of blood lactate, an independent predictor of mortality in malaria. Its prospective evaluation in affecting mortality in this disorder appears warranted.

Cervicofacial nontuberculous mycobacterium lymphadenitis in children: Is surgery always necessary?

INTRODUCTION The optimal treatment of cervicofacial nontuberculous mycobacterium lymphadenitis (CFNTB) in children is yet to be established. There is a general consensus that surgical excision results in a definitive resolution of the disease. The main aim of surgery is to remove affected nodes so that they do not discharge through the skin. Recently there are some investigators who are reporting successful antibiotic treatment and advocating medical therapy as the first line treatment. METHODS 16 children consecutively presenting to otolaryngology in a tertiary referral centre over an 8-year period with CFNTB. Inclusion criteria were chronic cervicofacial lymphadenitis with either: (1) a culture positive for atypical mycobacteria (from either a lymph node or fine needle aspirate (FNA) specimen); or (2) acid-fast bacilli identified (from either a lymph node or FNA specimen); or (3) post excision histological findings consistent with mycobacterial infection (i.e. non-caseating granulomas) in the absence of other clinical features suggestive of other granulomatous conditions. Lesions with superficial skin change were treated preferentially with surgery. Children presenting with lymph nodes contained deep to sternocleidmastoid were assessed with FNA cytological and microbiological analysis and MRI or CT, and treated preferentially with antibiotics or watchful waiting. RESULTS 4 children (2 culture positive, 2 with acid-fast bacilli on needle aspirate) presented with lymphadenopathy deep to sternocleidmastoid and were managed non-surgically. All 4 resolved without cutaneous involvement. 11 children with a clinical presentation of CFNTB underwent complete excision of all involved nodes for superficial lesions (6 were culture positive, and all had granulomatous histology). None recurred. 1 patient presented late with a mature, discharging parotid sinus, which was managed with watchful waiting as the lesion was clinically close to natural resolution. CONCLUSIONS Depth at presentation may help decide which patients with CFNTB can be treated non-surgically without cutaneous sequelae. We propose that a watch and wait management is an option for deep nodes.

Diagnostic Pitfalls in Clostridium difficile Infection

Accurate diagnosis of Clostridium difficile infection (CDI) is important not only for patient care but also for epidemiology and disease research. As it is not possible clinically to reliably differentiate CDI from other causes of health care-associated diarrhea, the laboratory confirmation of CDI is essential. Rapid commercial assays, including nucleic acid amplification tests and immunoassays for C difficile toxin and glutamate dehydrogenase, have largely superseded the use of older assays. Although assays that detect the presence of free C difficile toxin in feces are less frequently positive than tests for organism, they are preferable for the detection of CDI.

Impact of Plasmodium falciparum infection on the frequency of moderate to severe anaemia in children below 10 years of age in Gabon

BackgroundImproving the understanding of childhood malarial anaemia may help in the design of appropriate management strategies.MethodsA prospective observational study over a two-year period to assess the burden of anaemia and its relationship to Plasmodium falciparum infection and age was conducted in 8,195 febrile Gabonese children.ResultsThe proportion of children with anaemia was 83.6% (n = 6830), higher in children between the ages of six and 23 months. Those under three years old were more likely to develop moderate to severe anaemia (68%). The prevalence of malaria was 42.7% and P. falciparum infection was more frequent in children aged 36–47 months (54.5%). The proportion of anaemic children increased with parasite density (p < 0.01). Most of infected children were moderately to severely anaemic (69.5%, p < 0.01). Infants aged from one to 11 months had a higher risk of developing severe malarial anaemia. In children over six years of age, anaemia occurrence was high (>60%), but was unrelated to P. falciparum parasitaemia.ConclusionMalaria is one of the main risk factors for childhood anaemia which represents a public health problem in Gabon. The risk of severe malarial anaemia increases up the age of three years. Efforts to improve strategies for controlling anaemia and malaria are needed.

Plasma glutamine levels and falciparum malaria

Glutamine deficiency is associated with increased rates of sepsis and mortality, which can be prevented by glutamine supplementation. Changes in glutamine concentration were examined in Ghanaian children with acute falciparum malaria and control cases. The mean (SD) plasma glutamine concentration was lower in patients with acute malaria (401 (82) mumol/L, n = 50) than in control patients (623 (67) mumol/L, n = 7; P < 0.001). Plasma glutamine concentrations all rose in convalescence. The mean (SD) increase in plasma glutamine was 202 (123) mumol/L (n = 18; P < 0.001) compared with acute infection. We conclude that acute falciparum malaria is associated with large decreases in plasma glutamine and these falls may increase susceptibility to sepsis and dyserythropoeisis.

Neonatal sepsis – many blood samples, few positive cultures: implications for improving antibiotic prescribing

The National Institute for Health and Clinical Excellence is finalising the clinical practice guideline on antibiotics use for early-onset neonatal infection.1 The draft guideline compliments the national Antibiotic Stewardship Programme– Start Smart – then Focus2 by promoting stopping antibiotics at 36 h in infants without signs of infection and negative blood culture results, and switching from the recommended empiric broad-spectrum antibiotic treatment to a narrower-spectrum antibiotic regimen in consultation with microbiologists in those patients with infection. Prudent antibiotic prescribing …

Trends in paediatric nosocomial bacteraemia in a London tertiary hospital

To describe the incidence and microbiological characteristics of nosocomial bloodstream infections in childhood over a 9‐year period at a South London tertiary hospital.