Changes in central venous to arterial carbon dioxide gap (PCO 2 gap) in response to acute changes in ventilation

Background Early diagnosis of shock is a predetermining factor for a good prognosis in intensive care. An elevated central venous to arterial PCO2 difference (∆PCO2) over 0.8 kPa (6 mm Hg) is indicative of low blood flow states. Disturbances around the time of blood sampling could result in inaccurate calculations of ∆PCO2, thereby misrepresenting the patient status. This study aimed to determine the influences of acute changes in ventilation on ∆PCO2 and understand its clinical implications.Methods To investigate the isolated effects of changes in ventilation on ∆PCO2, eight pigs were studied in a prospective observational cohort. Arterial and central venous catheters were inserted following anaesthetisation. Baseline ventilator settings were titrated to achieve an EtCO2 of 5±0.5 kPa (VT = 8 mL/kg, Freq = 14 ± 2/min). Blood was sampled simultaneously from both catheters at baseline and 30, 60, 90, 120, 180 and 240 s after a change in ventilation. Pigs were subjected to both hyperventilation and hypoventilation, wherein the respiratory frequency was doubled or halved from baseline. ∆PCO2 changes from baseline were analysed using repeated measures ANOVA with post-hoc analysis using Bonferroni’s correction.Results ∆PCO2 at baseline for all pigs was 0.76±0.29 kPa (5.7±2.2 mm Hg). Following hyperventilation, there was a rapid increase in the ∆PCO2, increasing maximally to 1.35±0.29 kPa (10.1±2.2 mm Hg). A corresponding decrease in the ∆PCO2 was seen following hypoventilation, decreasing maximally to 0.23±0.31 kPa (1.7±2.3 mm Hg). These changes were statistically significant from baseline 30 s after the change in ventilation.Conclusion Disturbances around the time of blood sampling can rapidly affect the PCO2, leading to inaccurate calculations of the ∆PCO2, resulting in misinterpretation of patient status. Care should be taken when interpreting blood gases, if there is doubt as to the presence of acute and transient changes in ventilation

The effect of long-lasting insecticidal nets on the transmission of malaria and lymphatic filariasis in Papua New Guinea, and opportunities for accelerating lymphatic filariasis elimination through novel treatment strategies

Currently, programmatic interventions to combat vector-borne diseases are largely underpinned by the concept that strategies proven effective in one context will work in all contexts. However, areas with high vector diversity present a challenge because the traits targeted by an intervention may not exist in most of the population. Papua New Guinea (PNG) is endemic for both malaria and lymphatic filariasis (LF) and has a diverse vector population. Typical vector control measures, such as long-lasting insecticidal nets (LLINs), have been very successful in reducing malaria burden in sub-Saharan Africa, partly because these mosquitoes bite humans at night inside houses. However, it may be that this intervention is inappropriate in areas like PNG, where a wide range of biting behaviour is the status quo, and that deploying complementary strategies will be necessary. The aim of this thesis is to evaluate the efficacy of existing and emerging interventions to prevent malaria and LF transmission and eliminate filariasis in PNG. This will be achieved through studies which 1) evaluate the impact of a nationwide LLIN distribution on vector density, behaviour, and species composition, 2) evaluate the impact of LLINs on malaria and LF transmission and disease prevalence and 3) evaluate the efficacy of complementary, integrated control measures to increase the likelihood of LF elimination. The data from observational and cross-sectional studies and a controlled clinical trial, demonstrate that LLINs can decrease transmission intensity of both malaria and LF in PNG. However, the sustainability of this control measure may be compromised by an epidemiologically significant shift in the behaviour of mosquitoes to bite at earlier hours of the night. Modifying LF elimination efforts, which typically include a mass administration of two drugs to the at-risk population, to incorporate a novel 3-drug regimen, is shown to potentially increase the likelihood of eliminating the disease

Evaluation of a game-based training course to build capacity for insecticide resistance management in vector control programmes

Across Africa, malaria control programmes are increasingly challenged with the emergence of insecticide resistance among malaria vector populations. Confronted with this challenge, vector control staff must understand insecticide resistance management, think comprehensively and react positively when confronted with new problems. However, information on the subject is often only available through written guidelines that are difficult to put into practice. Based on the successes and strengths of educational games for health, we developed and evaluated a novel game-based course to fill the gap in training resources for insecticide resistance management. The training was evaluated by analysing results of pre- and post-course knowledge tests and self-efficacy surveys, as well as post-course interviews. At the start of the training, fundamental concepts of insecticide resistance were reviewed through Resistance101, a mobile app game. Subsequently, insecticide resistance management strategies were explored using the simulation game ResistanceSim, which was introduced by mini-lectures and complemented by class discussions and group work. The game-based training was conducted and evaluated in two African countries (Ethiopia and Zambia) using a mixed-methods approach. Quantitative outcome measures included knowledge acquisition and change in self-efficacy. We completed a qualitative inductive thematic analysis of participant interviews to explore the views and experiences of participants with the games and training, and the impact of the training on professional practices and attitudes. The game-based training increased knowledge in the short-term and improved self-efficacy scores. The training increased participants’ knowledge base, stimulated knowledge sharing and changed work practices. The game-based training offers scalable training opportunities that could nurture and capacitate the next generation of professionals in vector control

Plasticity of host selection by malaria vectors of Papua New Guinea

Background Host selection is an important determinant of vectorial capacity because malaria transmission increases when mosquitoes feed more on humans than non-humans. Host selection also affects the outcome of long-lasting insecticidal nets (LLIN). Despite the recent nationwide implementation of LLIN-based malaria control program in Papua New Guinea (PNG), little is known about the host selection of the local Anopheles vectors. This study investigated the host selection of Anopheles vectors in PNG. Methods Blood-engorged mosquitoes were sampled using the barrier screen method and blood meals analyzed for vertebrate host source with PCR-amplification of the mitochondrial cytochrome b gene. Abundance of common hosts was estimated in surveys. The test of homogeneity of proportions and the Manly resource selection ratio were used to determine if hosts were selected in proportion to their abundance. Results Two thousand four hundred and forty blood fed Anopheles females of seven species were sampled from five villages in Madang, PNG. Of 2,142 samples tested, 2,061 (96.2%) yielded a definitive host source; all were human, pig, or dog. Hosts were not selected in proportion to their abundance, but rather were under-selected or over-selected by the mosquitoes. Four species, Anopheles farauti (sensu stricto) (s.s.), Anopheles punctulatus (s.s.), Anopheles farauti no. 4 and Anopheles longirostris, over-selected humans in villages with low LLIN usage, but over-selected pigs in villages with high LLIN usage. Anopheles koliensis consistently over-selected humans despite high LLIN usage, and Anopheles bancroftii over-selected pigs. Conclusions The plasticity of host selection of an Anopheles species depends on its opportunistic, anthropophilic or zoophilic behavior, and on the extent of host availability and LLIN usage where the mosquitoes forage for hosts. The high anthropophily of An. koliensis increases the likelihood of contacting the LLIN inside houses. This allows its population size to be reduced to levels insufficient to support transmission. In contrast, by feeding on alternative hosts the likelihood of the opportunistic species to contact LLIN is lower, making them difficult to control. By maintaining high population size, the proportion that feed on humans outdoors can sustain residual transmission despite high LLIN usage in the village

Mosquito behavior change after distribution of bednets results in decreased protection against malaria exposure

Behavioral resilience in mosquitoes poses a significant challenge to mosquito control. Although behavior changes in anopheline vectors have been reported over the last decade, there are no empirical data to suggest they compromise the efficacy of vector control in reducing malaria transmission.; In this study, we quantified human exposure to both bites and infective bites of a major malaria vector in Papua New Guinea over the course of 4 years surrounding nationwide bednet distribution. We also quantified malaria infection prevalence in the human population during the same time period.; We observed a shift in mosquito biting to earlier hours of the evening, before individuals are indoors and protected by bednets, followed by a return to preintervention biting rates. As a result, net users and non-net users experienced higher levels of transmission than before the intervention. The personal protection provided by a bednet decreased over the study period and was lowest in the adult population, who may be an important reservoir for transmission. Malaria prevalence decreased in only 1 of 3 study villages after the distribution.; This study highlights the necessity of validating and deploying vector control measures targeting outdoor exposure to control and eliminate malaria