Constructing a continuous hemodiafiltration-type circulatory model of acute kidney injury in pigs.

INTRODUCTION: Animal-model experimental systems capable of reflecting the effects of devices for continuous renal replacement therapy (CRRT) on living organisms are limited; thus, aimed to construct an animal model of AKI-CRRT using pigs. METHODS: Pigs were subjected to renal artery ischemia-reperfusion injury (IRI) and then to a maximum of 24 h of continuous hemodiafiltration (CHDF)-type CRRT. RESULTS: Post-IRI, pigs' creatinine levels rose threefold, and they exhibited 24 h of anuria and clear aggravation of oxidative stress, demonstrating successful induction of AKI for CRRT. Post-CRRT, no significant changes in their vital signs or hematological parameters were observed. Creatinine and blood urea nitrogen clearance, as well as suppression of increases in oxidative stress, were also confirmed. CONCLUSION: We believe that the use of our model can enable the preclinical evaluation of the effects of under-development CRRT devices on living organisms under conditions similar to those encountered in an actual clinical setting.

Prevalence of G6PD Viangchan variant in malaria endemic areas in Lao PDR: an implication for malaria elimination by 2030.

BACKGROUND: Primaquine is effective against the latent liver stage of Plasmodium vivax. Eliminating the latent liver stage of P. vivax is one of the necessary conditions to achieve the goal of malaria elimination in Lao People's Democratic Republic (PDR) by 2030. However, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk of haemolysis when ingesting primaquine. The aim of this study was to detect the prevalence of the G6PD Viangchan variant, which is said to be common in Lao PDR and which can result in severe haemolysis in patients exposed to primaquine. METHODS: Blood samples were collected from villagers in three malaria endemic provinces: Champasak and Savannakhet in the south, and Phongsaly in the north. Each blood sample was semi-quantitatively assayed for G6PD enzyme activity using the G6PD Assay Kit-WST Lyophilized (DOJINDO Laboratories, Japan). Blood samples that were found to be G6PD deficient were sequenced to detect G6PD Viangchan mutation. RESULTS: In total, 2043 blood samples were collected from Phongsaly (n = 426, 20.9%), Savannakhet (n = 924, 45.2%), and Champasak (n = 693, 33.9%) provinces in Lao PDR from 2016 to 2017. Of these, 964 (47.2%) were taken from male villagers and 1079 (52.8%) were taken from female villagers. G6PD Viangchan mutation was not detected in Phongsaly province in this study. In Savannakhet province, 48 of the 924 samples (45 males, 3 females) had the G6PD Viangchan mutation (n = 48, 5.2%). In Champasak province, 42 of the 693 samples (18 males, 24 females) had the G6PD Viangchan mutation (n = 42, 6.1%). CONCLUSIONS: G6PD Viangchan variant, which can cause severe haemolysis in the carrier when exposed to primaquine, was detected among 6.1% of the villagers in Champasak and 5.2% in Savannakhet but not in Phongsaly in this study. G6PD Viangchan variant might be common in the south of Laos but not so in the north. In the north, other G6PD deficiency variants might be more prevalent. However, in order not to overlook anyone and ensure a safe primaquine therapy for people living in malaria endemic areas in Lao PDR, G6PD testing is necessary.

Mothers' Opisthorchis viverrini infection status and raw fish dish consumption in Lao People's Democratic Republic: determinants of child infection status.

BACKGROUND: Opisthorchis viverrini (Ov) infection is one of the foodborne trematodiases, which is highly endemic in Lao People's Democratic Republic (PDR). The infection occurs especially when people eat raw fish containing Ov metacercariae. As eating raw fish is a traditional culture in Lao PDR, changing this behavior is difficult. A new approach is necessary to control Ov infection because people easily get re-infected even after taking praziquantel unless they change their behaviors. This study aimed to explore factors associated with Ov infection among children and to identify the existing behaviors and perception that might contribute to the control of Ov infection in Lao PDR. We conducted a cross-sectional study in Yommalath district, Khammouane province, in Lao PDR in August and September 2015. In this cross-sectional study, we used a semi-structured questionnaire and interviewed 348 mothers who had a child aged 5-15 years. We also collected the fecal samples from each mother-child pair and used the Kato-Katz method (three slides/sample) to detect Ov eggs. RESULTS: Of 284 children, 82.8% were infected with Ov. The children were more likely to be infected with Ov when their mothers were infected with Ov (adjusted odds ratio [AOR] 10.45, 95% confidence interval [CI] 3.13-34.86) or when their mothers liked raw fish dishes (AOR 2.47, 95% CI 1.07-5.69). Even though most mothers are primarily in charge of cooking family meals, fathers were also involved in the preparation of raw fish dishes. CONCLUSION: This study suggests that a new approach to control Ov infection should target families or communities, rather than children only. Cooking or food preparation behaviors should be investigated in more depth.

Systematic review of the clinical manifestations of glucose-6-phosphate dehydrogenase deficiency in the Greater Mekong Subregion: implications for malaria elimination and beyond.

INTRODUCTION: To achieve malaria elimination in the Greater Mekong Subregion (GMS) by 2030, proper case management is necessary. 8-aminoquinolines, such as primaquine, are the only available medicines effective in preventing relapse of the hypnozoite stage of Plasmodium vivax, as well as the onward transmission of Plasmodium falciparum. However, primaquine can cause haemolysis in individuals who have glucose-6-phosphate dehydrogenase deficiency (G6PDd). We conducted a systematic review on the reported clinical manifestations of G6PDd to provide a comprehensive overview of the situation in the GMS. METHODS: The protocol for this systematic review was registered on PROSPERO: International prospective register of systematic reviews (CRD42016043146). We searched the PubMed/MEDLINE, CINAHL, and Web of Science databases for published articles describing the clinical manifestations of G6PDd in the GMS. We included articles of all study designs from inception until 31 July 2016, reporting the clinical manifestations of G6PDd. We then performed a narrative synthesis of these articles. RESULTS: We included 56 articles in this review, 45 of which were from Thailand. Haemolysis in G6PD-deficient individuals was caused not only by primaquine but also by other medicines and infections. Other clinical manifestations of G6PDd that were found were favism, neonatal jaundice and chronic non-spherocytic haemolytic anaemia. G6PDd also influenced the clinical presentations of genetic disorders and infections, such as thalassemia and typhoid fever. CONCLUSION: As G6PDd also affects the clinical presentations of other infections, the benefits of G6PD testing and proper record keeping transcend those of malaria case management. Therefore, healthcare workers at the community level should be made familiar with complications resulting from G6PDd as these complications extend beyond the scope of malaria.

The potential of positive deviance approach for the sustainable control of neglected tropical diseases.

Neglected tropical diseases (NTDs) have gained much attention in recent years due to the support from various agencies. However, the main approach to combat NTDs has been to cure rather than to prevent. As many NTD infections are closely linked with human behaviors such as hygienic practices and tradition, behavior change is also very crucial to prevent relapse or reinfection. Therefore, we would like to suggest a potential new approach-the positive deviance approach-to tackle NTDs by focusing on the preventive phase. What makes this approach unique is that the solution comes from the affected population themselves and not from the expert outsiders. Preventive chemotherapy that relies on outside aid has serious sustainability issues as reinfection is also high after the aid program has ended. Learning from the success story in Vietnam on preventing childhood malnutrition, the positive deviance approach could end the spread of NTDs once and for all by making full use of the available local solutions.

Plasmodium berghei circumvents immune responses induced by merozoite surface protein 1- and apical membrane antigen 1-based vaccines.

BACKGROUND: Two current leading malaria blood-stage vaccine candidate antigens for Plasmodium falciparum, the C-terminal region of merozoite surface protein 1 (MSP1(19)) and apical membrane antigen 1 (AMA1), have been prioritized because of outstanding protective efficacies achieved in a rodent malaria Plasmodium yoelii model. However, P. falciparum vaccines based on these antigens have had disappointing outcomes in clinical trials. Discrepancies in the vaccine efficacies observed between the P. yoelii model and human clinical trials still remain problematic. METHODOLOGY AND RESULTS: In this study, we assessed the protective efficacies of a series of MSP1(19)- and AMA1-based vaccines using the P. berghei rodent malarial parasite and its transgenic models. Immunization of mice with a baculoviral-based vaccine (BBV) expressing P. falciparum MSP1(19) induced high titers of PfMSP1(19)-specific antibodies that strongly reacted with P. falciparum blood-stage parasites. However, no protection was achieved following lethal challenge with transgenic P. berghei expressing PfMSP1(19) in place of native PbMSP1(19). Similarly, neither P. berghei MSP1(19)- nor AMA1-BBV was effective against P. berghei. In contrast, immunization with P. yoelii MSP1(19)- and AMA1-BBVs provided 100% and 40% protection, respectively, against P. yoelii lethal challenge. Mice that naturally acquired sterile immunity against P. berghei became cross-resistant to P. yoelii, but not vice versa. CONCLUSION: This is the first study to address blood-stage vaccine efficacies using both P. berghei and P. yoelii models at the same time. P. berghei completely circumvents immune responses induced by MSP1(19)- and AMA1-based vaccines, suggesting that P. berghei possesses additional molecules and/or mechanisms that circumvent the host's immune responses to MSP1(19) and AMA1, which are lacking in P. yoelii. Although it is not known whether P. falciparum shares these escape mechanisms with P. berghei, P. berghei and its transgenic models may have potential as useful tools for identifying and evaluating new blood-stage vaccine candidate antigens for P. falciparum.

Baculovirus-based nasal drop vaccine confers complete protection against malaria by natural boosting of vaccine-induced antibodies in mice.

Blood-stage malaria parasites ablate memory B cells generated by vaccination in mice, resulting in diminishing natural boosting of vaccine-induced antibody responses to infection. Here we show the development of a new vaccine comprising a baculovirus-based Plasmodium yoelii 19-kDa carboxyl terminus of merozoite surface protein 1 (PyMSP1(19)) capable of circumventing the tactics of parasites in a murine model. The baculovirus-based vaccine displayed PyMSP1(19) on the surface of the virus envelope in its native three-dimensional structure. Needle-free intranasal immunization of mice with the baculovirus-based vaccine induced strong systemic humoral immune responses with high titers of PyMSP1(19)-specific antibodies. Most importantly, this vaccine conferred complete protection by natural boosting of vaccine-induced PyMSP1(19)-specific antibody responses shortly after challenge. The protective mechanism is a mixed Th1/Th2-type immunity, which is associated with the Toll-like receptor 9 (TLR9)-dependent pathway. The present study offers a novel strategy for the development of malaria blood-stage vaccines capable of naturally boosting vaccine-induced antibody responses to infection.