Predation efficiency of Anopheles gambiae larvae by aquatic predators in western Kenya highlands

Abstract Background The current status of insecticide resistance in mosquitoes and the effects of insecticides on non-target insect species have raised the need for alternative control methods for malaria vectors. Predation has been suggested as one of the important regulation mechanisms for malaria vectors in long-lasting aquatic habitats, but the predation efficiency of the potential predators is largely unknown in the highlands of western Kenya. In the current study, we examined the predation efficiency of five predators on Anopheles gambiae s.s larvae in 24 hour and semi- field evaluations. Methods Predators were collected from natural habitats and starved for 12 hours prior to starting experiments. Preliminary experiments were conducted to ascertain the larval stage most predated by each predator species. When each larval instar was subjected to predation, third instar larvae were predated at the highest rate. Third instar larvae of An. gambiae were introduced into artificial habitats with and without refugia at various larval densities. The numbers of surviving larvae were counted after 24 hours in 24. In semi-field experiments, the larvae were counted daily until they were all either consumed or had developed to the pupal stage. Polymerase chain reaction was used to confirm the presence of An. gambiae DNA in predator guts. Results Experiments found that habitat type (P < 0.0001) and predator species (P < 0.0001) had a significant impact on the predation rate in the 24 hour evaluations. In semi-field experiments, predator species (P < 0.0001) and habitat type (P < 0.0001) were significant factors in both the daily survival and the overall developmental time of larvae. Pupation rates took significantly longer in habitats with refugia. An. gambiae DNA was found in at least three out of ten midguts for all predator species. Gambusia affins was the most efficient, being three times more efficient than tadpoles. Conclusion These experiments provide insight into the efficiency of specific natural predators against mosquito larvae. These naturally occurring predators may be useful in biocontrol strategies for aquatic stage An. gambiae mosquitoes. Further investigations should be done in complex natural habitats for these predators

Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya

Abstract Background: Malarial anaemia is characterized by destruction of malaria infected red blood cells and suppression of erythropoiesis. Interleukin 12 (IL12) significantly boosts erythropoietic responses in murine models of malarial anaemia and decreased IL12 levels are associated with severe malarial anaemia (SMA) in children. Based on the biological relevance of IL12 in malaria anaemia, the relationship between genetic polymorphisms of IL12 and its receptors and SMA was examined. Methods: Fifty-five tagging single nucleotide polymorphisms covering genes encoding two IL12 subunits, IL12A and IL12B, and its receptors, IL12RB1 and IL12RB2, were examined in a cohort of 913 children residing in Asembo Bay region of western Kenya. Results: An increasing copy number of minor variant (C) in IL12A (rs2243140) was significantly associated with a decreased risk of SMA (P = 0.006; risk ratio, 0.52 for carrying one copy of allele C and 0.28 for two copies). Individuals possessing two copies of a rare variant (C) in IL12RB1 (rs429774) also appeared to be strongly protective against SMA (P = 0.00005; risk ratio, 0.18). In addition, children homozygous for another rare allele (T) in IL12A (rs22431348) were associated with reduced risk of severe anaemia (SA) (P = 0.004; risk ratio, 0.69) and of severe anaemia with any parasitaemia (SAP) (P = 0.004; risk ratio, 0.66). In contrast, AG genotype for another variant in IL12RB1 (rs383483) was associated with susceptibility to high-density parasitaemia (HDP) (P = 0.003; risk ratio, 1.21). Conclusions: This study has shown strong associations between polymorphisms in the genes of IL12A and IL12RB1 and protection from SMA in Kenyan children, suggesting that human genetic variants of IL12 related genes may significantly contribute to the development of anaemia in malaria patients

Effect of malaria transmission reduction by insecticide-treated bed nets (ITNs) on the genetic diversity of Plasmodium falciparum merozoite surface protein (MSP-1) and circumsporozoite (CSP) in western Kenya

Background Although several studies have investigated the impact of reduced malaria transmission due to insecticide-treated bed nets (ITNs) on the patterns of morbidity and mortality, there is limited information on their effect on parasite diversity. Methods Sequencing was used to investigate the effect of ITNs on polymorphisms in two genes encoding leading Plasmodium falciparum vaccine candidate antigens, the 19 kilodalton blood stage merozoite surface protein-1 (MSP-119kDa) and the Th2R and Th3R T-cell epitopes of the pre-erythrocytic stage circumsporozoite protein (CSP) in a large community-based ITN trial site in western Kenya. The number and frequency of haplotypes as well as nucleotide and haplotype diversity were compared among parasites obtained from children <5 years old prior to the introduction of ITNs (1996) and after 5 years of high coverage ITN use (2001). Results A total of 12 MSP-119kDa haplotypes were detected in 1996 and 2001. The Q-KSNG-L and E-KSNG-L haplotypes corresponding to the FVO and FUP strains of P. falciparum were the most prevalent (range 32–37%), with an overall haplotype diversity of > 0.7. No MSP-119kDa 3D7 sequence-types were detected in 1996 and the frequency was less than 4% in 2001. The CSP Th2R and Th3R domains were highly polymorphic with a total of 26 and 14 haplotypes, respectively detected in 1996 and 34 and 13 haplotypes in 2001, with an overall haplotype diversity of > 0.9 and 0.75 respectively. The frequency of the most predominant Th2R and Th3R haplotypes was 14 and 36%, respectively. The frequency of Th2R and Th3R haplotypes corresponding to the 3D7 parasite strain was less than 4% at both time points. There was no significant difference in nucleotide and haplotype diversity in parasite isolates collected at both time points. Conclusion High diversity in these two genes has been maintained overtime despite marked reductions in malaria transmission due to ITNs use. The frequency of 3D7 sequence-types was very low in this area. These findings provide information that could be useful in the design of future malaria vaccines for deployment in endemic areas with high ITN coverage and in interpretation of efficacy data for malaria vaccines based on 3D7 parasite strains

Perceptions and utilization of the anti-malarials artemether-lumefantrine and dihydroartemisinin-piperaquine in young children in the Chikhwawa District of Malawi: a mixed methods study

Background Adherence to anti-malarial dosing schedules is essential to ensure effective treatment. Measuring adherence is challenging due to recall issues and the participants’ awareness of the desired behaviour influencing their actions or responses. This study used qualitative methods, which allow for rapport building, to explore issues around anti-malarial utilization in young children, and used the results to guide the development of a context specific questionnaire on perceptions and adherence to artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ). Methods Qualitative data collection included 12 focus group discussions which explored community perceptions of anti-malarials and experiences of administering medications to children. Critical incidence interviews were conducted with 22 caregivers to explore experiences of administering the dispersible or original formulation of AL to young children during recent febrile episodes. A structured questionnaire was used to gather data on experience of recent treatment and adherence to anti-malarials during follow-up visits with 218 caregivers whose child was recently treated with either dispersible AL or DHA-PPQ. Discussion/Conclusion Caregivers experience great difficulty in administering medication to children. While the sweet taste of dispersible AL may have reduced conflict between the child and caregiver, sub-optimal dosing due to medication loss remained a problem and overall adherence was greater among those receiving DHA-PPQ, which requires fewer doses. Some caregivers were found to deliberately alter the dosing schedule according to whether they perceived the medication to be too weak or strong. They also developed theories for poor treatment outcomes, such as attributing this to lack of compatibility between the medication and the child. Health education messages should be strengthened to ensure a combination of clear pictorial and verbal instructions are used during dispensing, and consequences of under and over-dosing are explained alongside appropriate responses to possible adverse events. Further optimizing of anti-malarial adherence among children requires the development of anti-malarials with pharmacological properties that allow user-friendly administration and simplified dosing schedules

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種別: 実習報

Uncertainties in the measurement of blood glucose in paediatric intensive care: implications for clinical trials of tight glycaemic control

Abstract Purpose: In preparation for a tight glycaemic control (TGC) clinical trial we assessed the agreement between methods used to measure blood glucose in critically ill children. Methods: Service evaluation comparing blood gas and main laboratory analysers with point-ofcare (POC) devices PCX, ACCUChek and Hemocue. Results: Two hundred forty-five samples from 157 children measured on 2–4 devices provided 790 values. Marked variation was evident in glucose values between devices, time between tests, sample (whole blood/plasma) and source; 39% of paired values had [20% difference. The decision to start insulin at 7 mmol/L differed depending on the device used for 33% of samples. At low glucose values (\4 mmol/L), differences up to 1.8 mmol/L were evident. The blood gas analyser read lower than all POC models and the laboratory analyser (less risk of undetected hypoglycaemia). An inverse relationship was evident between haematocrit (Hct) and glucose error using POC devices. PCX values for samples with Hct \30% were higher (85%), whereas those for Hct values[38% were lower (66%). Glycolysis occurred during transfer of samples to the laboratory. Using the PCX at the bedside resulted in 0.5 mmol/L mean difference higher than laboratory values; locating the PCX in the laboratory reduced this to 0.2 mmol/L. Conclusions: Discrepancies between measurements may mask hypoglycaemia, and the potential benefits of controlling hyperglycaemia may not be achieved. Variation introduced by different devices, sample or source may have led to misclassification of treatment decisions contributing to the conflicting results of TGC studies