Search

Background: Pyronaridine-artesunate is an artemisinin-based combination therapy under evaluation for the treatment of Plasmodium falciparum and P. vivax malaria.Methods: We conducted a phase 3, open-label, multicenter, noninferiority trial that included 1271 patients between 3 and 60 years of age from Asia (81.3%) or Africa (18.7%) with microscopically confirmed, uncomplicated P. falciparum malaria. Patients underwent randomization for treatment with a fixed-dose combination of 180 mg of pyronaridine and 60 mg of artesunate or with 250 mg of mefloquine plus 100 mg of artesunate. Doses were calculated according to body weight and administered once daily for 3 days.Results: Pyronaridine-artesunate was noninferior to mefloquine plus artesunate for the primary outcome: adequate clinical and parasitologic response in the per-protocol population on day 28, corrected for reinfection with the use of polymerase-chain-reaction (PCR) genotyping. For this outcome, efficacy in the group receiving pyronaridine-artesunate was 99.2% (743 of 749 patients; 95% confidence interval [CI], 98.3 to 99.7) and that in the group receiving mefloquine plus artesunate was 97.8% (360 of 368 patients; 95% CI, 95.8 to 99.1), with a treatment difference of 1.4 percentage points (95% CI, 0.0 to 3.5; P=0.05). In the intention-to-treat population, efficacy on day 42 in the group receiving pyronaridine-artesunate was 83.1% (705 of 848 patients; 95% CI, 80.4 to 85.6) and that in the group receiving mefloquine plus artesunate was 83.9% (355 of 423 patients; 95% CI, 80.1 to 87.3). In Cambodia, where there were 211 study patients, the median parasite clearance time was prolonged for both treatments: 64 hours versus 16.0 to 38.9 hours in other countries (P<0.001, on the basis of Kaplan-Meier estimates). Kaplan-Meier estimates of the recrudescence rate in the intention-to-treat population in Cambodia until day 42 were higher with pyronaridine-artesunate than with mefloquine plus artesunate (10.2% [95% CI, 5.4 to 18.6] vs. 0%; P=0.04 as calculated with the log-rank test), but similar for the other countries combined (4.7% [95% CI, 3.3 to 6.7] and 2.8% [95% CI, 1.5 to 5.3], respectively; P=0.24). Elevated levels of aminotransferases were observed in those receiving pyronaridine-artesunate. Two patients receiving mefloquine plus artesunate had seizures.Conclusions: Fixed-dose pyronaridine-artesunate was efficacious in the treatment of uncomplicated P. falciparum malaria. In Cambodia, extended parasite clearance times were suggestive of in vivo resistance to artemisinin. (Funded by Shin Poong Pharmaceutical Company and the Medicines for Malaria Venture; ClinicalTrials.gov number, NCT00403260.). [ABSTRACT FROM AUTHOR]

Despite treatment advances, head and neck squamous cell carcinoma (HNSCC) still poses a significant global health challenge. Combination therapies have emerged as more effective strategies than traditional chemotherapy in clinical practice by improving tumor response rates and patient survival while minimizing treatment-related toxicity. This study investigates the anticancer effects of metformin and verteporfin (Yes-associated protein 1 [YAP1] inhibitor) alone or in combination in HNSCC using vitro and in vivo approaches. Quantitative RT-PCR analysis of HNSCC cell lines reveals upregulation of YAP1 and related genes in the Hippo signaling pathway. Cell viability assays demonstrate a beneficial synergistic effect between metformin and verteporfin in inhibiting HNSCC tumor growth. In male BALB/cAJcl-nu/nu mice harboring HNSCC tumor xenografts, intraperitoneal administration of metformin and verteporfin enhances the inhibitory effect on tumor growth and suppresses YAP1 nuclear translocation when compared to vehicle or monotherapies. Furthermore, combination of these drugs reduces tumor cell proliferation (marked by Ki-67) and inhibits phosphoS6 ribosomal protein, as observed through immunofluorescent and immunohistochemical (IHC) analyses. The in vivo study underscores the therapeutic potential of the dual targeting approach with metformin and verteporfin in treating HNSCC, with minimal toxicity., (© 2025 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

Background: The countries within the Greater Mekong Region of Southeast Asia have pledged to eliminate malaria by 2030. Elimination of Plasmodium vivax malaria is challenging as it requires radical cure to prevent relapse. Understanding and facilitating adherence to primaquine radical cure regimens is necessary for malaria elimination., Methods: A convergent parallel mixed methods study was conducted to investigate the barriers to and facilitators for completing primaquine treatment of P. vivax infection among mobile migrant communities on the Myanmar-Thailand border. Quantative data were derived from routine malaria consultations. Qualitative data, informed by the social cognitive theory and health belief model, were collected through in-depth interviews with patients and focus group discussions with local health providers and community leaders., Results: Of 729 adult patients with primaquine treatment outcomes, 45% did not complete the follow-up of 28 days and were assumed to be non-adherent to primaquine treatment. Patients of Karen ethnicity (OR 1.7, 95% CI 1.2-2.3; p = 0.001) or having a previous episode of malaria from any species (OR 1.6, 95% CI 1.1-2.3; p = 0.007) were more likely to report completing the 14-day primaquine radical cure regimen. Five focus group discussions with front-line healthcare workers and community members and 16 in-depth interviews with patients who were prescribed P. vivax radical cure were conducted. Key themes related to the social cognitive theory included behavioral factors where work outweighed the choice to complete treatment; environmental factors where access to care determined primaquine treatment completion; and cognitive factors having a positive but limited influence on treatment completion. According to the health belief model, prioritizaton of work reduced seeking diagnosis and completing treatment, and often outweighed facilitating factors such as malaria literacy, health education, and social norms; and affected the perceived susceptibility and severity of P. vivax infections., Discussion: Work and productivity were identified as primary behavioral factors affecting adherence to primaquine radical cure and follow up in a migrant population. Community support and cultural cues may overcome these barriers. Understanding the rationale of patient adherence to primaquine may help guide programming for P. vivax elimination among migrant populations in resource-constrained settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Ansari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Upon infection with the virus, cells increase the expression of cytidine deaminase APOBEC3 family genes. This leads to the accumulation of C-to-T mutations in the replicating viral genome and suppresses viral propagation. In contrast, herpesviruses, including Epstein-Barr virus (EBV), express genes that counteract APOBEC3 during lytic infection. However, because viral resistance factors are not expressed during EBV latent infection, it is unknown how APOBEC3 functions during latent infection. We observed that in gastric epithelial cells persistently infected with EBV, the expression of APOBEC3 family genes increased, C-to-T mutations in the D-loop genome of mitochondrial DNA (mtDNA) increased, and mtDNA copy number decreased. By introducing and expressing individual APOBEC3 family genes, APOBEC3C was particularly expressed in the cytoplasm, increasing C-to-T mutations in mtDNA and decreasing mtDNA copy number. Furthermore, we confirmed that APOBEC3C co-localized with mitochondria in EBV-infected cells. Expression of the EBV latent gene LMP2A increased APOBEC3C expression. Conversely, APOBEC3C expression was reduced in LMP2A-deficient EBV-infected cells compared to wild-type EBV-infected cells. These results indicate that persistent infection of EBV in gastric epithelial cells reduces the number of mitochondria through mtDNA mutations induced by APOBEC3C expression., (© 2024 The Societies and John Wiley & Sons Australia, Ltd.)

Epstein-Barr virus (EBV) is linked to lymphoma and epithelioma but lacks drugs specifically targeting EBV-positive tumors. BamHI A Rightward Transcript (BART) miRNAs are expressed in all EBV-positive tumors, suppressing both lytic infection and host cell apoptosis. We identified suberoylanilide hydroxamic acid (SAHA), an inhibitor of histone deacetylase enzymes, as an agent that suppresses BART promoter activity and transcription of BART miRNAs. SAHA treatment demonstrated a more pronounced inhibition of cell proliferation in EBV-positive cells compared to EBV-negative cells, affecting both p53 wild-type and mutant gastric epithelial cells. SAHA treatment enhanced lytic infection in wild-type EBV-infected cells, while also enhancing cell death in BZLF1-deficient EBV-infected cells. It reduced BART gene expression by 85% and increased the expression of proapoptotic factors targeted by BART miRNAs. These findings suggest that SAHA not only induces lytic infection but also leads to cell death by suppressing BART miRNA transcription and promoting the apoptotic program., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Giardiasis   is one of the major causes of diarrhea among children. To determine the prevalence, risk factors, and genotype of Giardia intestinalis , a cross-sectional descriptive study was done on stool samples of 462 children attending three monastery primary schools from North Okkalapa Township in Yangon, Myanmar from January 2016 to February 2019. Socioeconomic data were collected using a pre-tested questionnaire after obtaining informed consent. Direct wet mount, formalin-ether sedimentation, and trichrome staining techniques were used for the primary identification and then molecular identification was carried out by conventional polymerase chain reaction (PCR)-sequencing assay. G. intestinalis was identified in 11.7% (54/462) of students. There was no significant association with water source (p=0.948) and drinking untreated water (p=0.595). The infection was more common in children with low-educated parents, unsanitary garbage disposal practices, and no restrooms. All isolates were G. intestinalis assemblage B. This is the first study characterizing human isolates in a lower region of Myanmar, at the molecular level [MOU1]. These findings pointed out the high prevalence of G. intestinalis among primary school children from densely populated and low-resource settings., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Ethical and Research Committee of the University of Medicine 2, Yangon issued approval 16/ERC-3 (12-2016. This research was done after obtaining ethical clearance from the Ethical and Research Committee of the University of Medicine 2, Yangon (16/ERC-3 (12-2016) on 9.12.2016. Written informed consent was obtained from the parents/guardians of participant children after a thorough explanation of the procedures of this study. Official approval was obtained from the Department of Education in the North Okkalapa Township for obtaining samples from school children. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Myint et al.)

Background: To fight the current coronavirus disease (COVID-19) pandemic, many countries have implemented various mitigation measures to contain the spread of the disease. By engaging with health service providers, the community's participation in adherence to preventive measures is certainly required in the implementation of COVID-19 mitigation strategies. Therefore, this study aimed to assess the level of adherence to COVID-19 preventive measures and its associated factors among the residents, Yangon Region, Myanmar., Methods: A community-based cross-sectional study was carried out among 636 residents in Yangon Region, Myanmar, from October to December 2021. A multistage non-probability sampling method, purposively selected for three townships in Yangon Region and convenience sampling for 212 participants from each township, was applied and the data were collected by face-to-face interviews using structured and pretested questionnaires. Data were entered, coded, and analyzed using IBM SPSS version 25.0. Simple and multiple logistic regression analysis were performed to identify the significant variables of adherence to COVID-19 preventive measures., Results: As a level of adherence to COVID-19 preventive measures, the proportion of residents who had good adherence was 39.3% (95% CI 35.5-43.2%), moderate adherence was 37.6% (95% CI 33.8-41.5%), and poor adherence was 23.1% (95% CI 19.9-26.6%). The age group of 31-40 years (AOR: 3.13, 95% CI 1.62-6.05), 30 years and younger (AOR: 3.22, 95% CI 1.75-5.92), Burmese ethnicity (AOR: 2.52, 95% CI 1.44-4.39), own business (AOR: 3.19, 95% CI 1.15-8.87), high school education level and below (AOR: 1.64, 95% CI 1.02-2.69), less than 280.90 USD of monthly family income (AOR: 1.51, 95% CI 1.01-2.29), low knowledge about COVID-19 (AOR: 1.90, 95% CI 1.26-2.88) were significantly associated with poor adherence to COVID-19 preventive measures., Conclusions: In this study, nearly one-fourth of the residents were experiencing poor adherence to COVID-19 preventive measures. Therefore, building up the risk communication through the community using widely used mainstream media, the continuation of disease surveillance and announcement of updated information or advice for the public to increase awareness towards COVID-19, and enforcement to follow the recommended directions and regulations of health institutions are vital to consider for improving the adherence to preventive measures against COVID-19 among the residents., (© 2024. The Author(s).)

Background: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013-2019) was characterized., Methods: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13-a molecular marker of artemisinin resistance., Result: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p < 0.001). In the MDA villages there was no significant change in the K13 proportions before and after MDA. The distribution of different K13 mutations changed substantially; F446I and P441L mutations increased in both MDA and non-MDA villages, while most other K13 mutations decreased. The proportion of C580Y mutations fell from 9.2% (43/467) before MDA to 2.3% (19/813) after MDA (p < 0.001). Similar changes occurred in the 487 villages where MDA was not conducted., Conclusion: The malaria elimination program in Kayin state, eastern Myanmar, led to a substantial reduction in falciparum malaria. Despite the intense use of artemisinin-based combination therapies, both in treatment and MDA, this did not select for artemisinin resistance., (© 2024. The Author(s).)

Introduction: Causes of deaths often go unrecorded in lower income countries, yet this information is critical. Verbal autopsy is a questionnaire interview with a family member or caregiver to elicit the symptoms and circumstances preceding a death and assign a probable cause. The social and cultural aspects of verbal autopsy have gotten less attention than the technical aspects and have not been widely explored in South and Southeast Asia settings., Methods: Between October 2021 and March 2023, prior to implementing a verbal autopsy study at rural sites in Bangladesh, Cambodia, Laos, Myanmar and Thailand, focus group discussions were conducted with village heads, religious leaders and community members from varied demographic backgrounds. Thematic analysis elucidated customs and traditional views surrounding death to understand local ethnocultural sensitivities., Results: We found that death rituals varied greatly among religions, ethnicities and by socioeconomic status. Mourning periods were reported to last 3-100 days and related to the cause of death, age and how close the deceased person was to the family. Participants advised that interviews should happen after mourning periods to avoid emotional distress, but not long after so as to avoid recall bias. Interviewers should be introduced to respondents by a trusted local person. To provide reassurance and confidentiality, a family's residence is the preferred interview location. Interview questions require careful local language translation, and community sensitisation is important before data collection., Conclusion: Verbal autopsy is acceptable across a wide range of cultural settings in Southeast Asia, provided that local norms are preidentified and followed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Neglected tropical diseases (NTDs) affect most impoverished communities in developing countries, like Myanmar in Southeast Asia. NTDs have been understudied and underreported in Myanmar., Methods: A systematic review of published and grey literature (1900-2023) on neglected tropical diseases (NTDs) in Myanmar was conducted. The literature search included five international databases: PubMed, EMBASE, Ovid Global Health, and Web of Science Core Collection and one national database: the Myanmar Central Biomedical Library (locally published papers and grey literature). The selection criteria included articles with all types of study designs of current or previous infections conducted in humans, that reported NTDs, recognised by WHO, US CDC, and listed in PLoS NTDs. We included melioidosis and rickettsioses which we consider also meet the definition of an NTD., Results: A total of 5941 records were retrieved and screened, of which, 672 (11%) met the selection criteria and were included in this review. Of the included articles, 449 (65%) were published after 2000 and 369 (55%) were from two regions (Yangon and Mandalay) of Myanmar. Of the included articles, 238 (35%) reported bacterial NTDs, 212 (32%) viral NTDs, 153 (23%) helminth NTDs, 25 (4%) protozoal NTDs and 39 (6%) reported more than one aetiology. Based on reported frequency in descending order, the bacterial NTDs were leprosy, Escherichia coli enteritis, salmonellosis, cholera, shigellosis, melioidosis, leptospirosis and rickettsioses; the viral NTDs were dengue, chikungunya and Japanese encephalitis virus (JEV) infection; the protozoal NTDs were amoebiasis, giardiasis and leishmaniasis, and the helminth NTDs were ascariasis, trichuriasis, hookworm disease, filariasis and strongyloidiasis., Conclusion: This review summarises NTDs reported in Myanmar over the past 100 years. The findings suggest that most NTDs are likely to be under reported, especially from the majority of the country which is far from academic centres. Research capacity building together with strengthening of laboratory systems would lead to better understanding of the true burden of NTDs in Myanmar., Trial Registration: PROSPERO registration ID: CRD42018092627., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Swe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The northwestern border of Thailand is an area of low seasonal malaria transmission. Until recent successful malaria elimination activities, malaria was a major cause of disease and death. Historically the incidences of symptomatic Plasmodium falciparum and Plasmodium vivax malaria were approximately similar., Methods: All malaria cases managed in the Shoklo Malaria Research Unit along the Thailand-Myanmar border between 2000 and 2016 were reviewed., Results: There were 80 841 consultations for symptomatic P. vivax and 94 467 for symptomatic P. falciparum malaria. Overall, 4844 (5.1%) patients with P. falciparum malaria were admitted to field hospitals, of whom 66 died, compared with 278 (0.34%) with P. vivax malaria, of whom 4 died (3 had diagnoses of sepsis, so the contribution of malaria to their fatal outcomes is uncertain). Applying the 2015 World Health Organization severe malaria criteria, 68 of 80 841 P. vivax admissions (0.08%) and 1482 of 94 467 P. falciparum admissions (1.6%) were classified as severe. Overall, patients with P. falciparum malaria were 15 (95% confidence interval, 13.2-16.8) times more likely than those with P. vivax malaria to require hospital admission, 19 (14.6-23.8) times more likely to develop severe malaria, and ≥14 (5.1-38.7) times more likely to die., Conclusions: In this area, both P. falciparum and P. vivax infections were important causes of hospitalization, but life-threatening P. vivax illness was rare., Competing Interests: Potential conflicts of interest. M. Stolbrink reports a Clinical PhD fellowship from Wellcome Trust, unrelated to this manuscript or the topic. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Severe malaria in pregnancy causes maternal mortality, morbidity, and adverse foetal outcomes. The factors contributing to adverse maternal and foetal outcomes are not well defined. We aimed to identify the factors predicting higher maternal mortality and to describe the foetal mortality and morbidity associated with severe falciparum malaria in pregnancy., Methods: A retrospective cohort study was conducted of severe falciparum malaria in pregnancy, as defined by the World Health Organization severe malaria criteria. The patients were managed prospectively by the Shoklo Malaria Research Unit (SMRU) on the Thailand-Myanmar border or were included in hospital-based clinical trials in six Southeast Asian countries. Fixed-effects multivariable penalised logistic regression was used for analysing maternal mortality., Results: We included 213 (123 SMRU and 90 hospital-based) episodes of severe falciparum malaria in pregnancy managed between 1980 and 2020. The mean maternal age was 25.7 (SD 6.8) years, and the mean gestational age was 25.6 (SD 8.9) weeks. The overall maternal mortality was 12.2% (26/213). Coma (adjusted odds ratio [aOR], 7.18, 95% CI 2.01-25.57, p = 0.0002), hypotension (aOR 11.21, 95%CI 1.27-98.92, p = 0.03) and respiratory failure (aOR 4.98, 95%CI 1.13-22.01, p = 0.03) were associated with maternal mortality. Pregnant women with one or more of these three criteria had a mortality of 29.1% (25/86) (95%CI 19.5 to 38.7%) whereas there were no deaths in 88 pregnant women with hyperparasitaemia (> 10% parasitised erythrocytes) only or severe anaemia (haematocrit < 20%) only. In the SMRU prospective cohort, in which the pregnant women were followed up until delivery, the risks of foetal loss (23.3% by Kaplan-Meier estimator, 25/117) and small-for-gestational-age (38.3%, 23/60) after severe malaria were high. Maternal death, foetal loss and preterm birth occurred commonly within a week of diagnosis of severe malaria., Conclusions: Vital organ dysfunction in pregnant women with severe malaria was associated with a very high maternal and foetal mortality whereas severe anaemia or hyperparasitaemia alone were not associated with poor prognosis, which may explain the variation of reported mortality from severe malaria in pregnancy. Access to antenatal care must be promoted to reduce barriers to early diagnosis and treatment of both malaria and anaemia., (© 2023. BioMed Central Ltd., part of Springer Nature.)

A major threat to the goal of eliminating malaria, particularly in Southeast Asia, is the spread of Plasmodium falciparum resistant to artemisinin-based combination therapies. P218 is a drug candidate designed to combat antifolate-sensitive and -resistant parasites. However, there is no evidence that P218 is effective against artemisinin-resistant P. falciparum. This report investigated the susceptibilities of 10 parasite isolates from Southeast Asia to P218 and other antimalarial drugs. All isolates with different levels of artemisinin resistance were genetically distinct from one another, although common haplotypes associated with antimalarial resistance were identified. All isolates were highly resistant to pyrimethamine, and none of them were significantly less sensitive to P218 than the pyrimethamine-resistant laboratory strain V1/S. Significant differences in sensitivity to other types of antimalarials (mefloquine, atovaquone and chloroquine) compared with V1/S were found for some isolates, although the differences were not clinically relevant. P218 is thus efficacious against multi-drug (including artemisinin-resistant P. falciparum., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Smokers are not the only ones who suffer the effects of tobacco; those around them are also harmed, particularly vulnerable groups such as pregnant women. This study aimed to describe the prevalence of secondhand smoke (SHS) among pregnant women and the factors associated with SHS exposure. This study was a cross-sectional descriptive study conducted at Central Women's Hospital in the Yangon Region in 2022. The prevalence of SHS exposure was described, and multivariate analyses were conducted to determine the associated factors. Out of 407 participants, the prevalence of SHS exposure was 65.4%. Education level, religion, smoking rules at home, visiting public places, and avoidance of SHS during pregnancy were significantly associated with SHS exposure. The findings highlighted the need for community guidance programs, policies, and interventions to establish smoke-free environments. It is also important to conduct behavioral interventions for smokers, especially to avoid SHS for pregnant women.

Background: Preterm birth is a major public health concern with the largest burden of morbidity and mortality falling within low- and middle-income countries (LMIC)., Materials and Methods: This sequential explanatory mixed methods study was conducted in special care baby units (SCBUs) serving migrants and refugees along the Myanmar-Thailand border. It included a retrospective medical records review, qualitative interviews with mothers receiving care within SCBUs, and focus group discussions with health workers. Changes in neonatal mortality and four clinical outcomes were described. A mix of ethnographic phenomenology and implementation frameworks focused on cultural aspects, the lived experience of participants, and implementation outcomes related to SCBU care., Results: From 2008-2017, mortality was reduced by 68% and 53% in very (EGA 28-32 weeks) and moderate (EGA 33-36 weeks) preterm neonates, respectively. Median SCBU stay was longer in very compared to moderate preterm neonates: 35 (IQR 22, 48 days) vs. 10 days (IQR 5, 16). Duration of treatments was also longer in very preterm neonates: nasogastric feeding lasted 82% (IQR 74, 89) vs. 61% (IQR 40, 76) of the stay, and oxygen therapy was used a median of 14 (IQR 7, 27) vs. 2 (IQR 1, 6) days respectively. Nine interviews were conducted with mothers currently receiving care in the SCBU and four focus group discussions with a total of 27 local SCBU staff. Analysis corroborated quantitative analysis of newborn care services in this setting and incorporated pertinent implementation constructs including coverage, acceptability, appropriateness, feasibility, and fidelity. Coverage, acceptability, and appropriateness were often overlapping outcomes of interest highlighting financial issues prior to or while admitted to the SCBU and social issues and support systems adversely impacting SCBU stays. Interview and FGD findings highlight the barriers in this resource-limited setting as they impact the feasibility and fidelity of providing evidence-based SCBU care that often required adaptation to fit the financial and environmental constraints imposed by this setting., Discussion: This study provides an in-depth look at the nature of providing preterm neonatal interventions in a SCBU for a vulnerable population in a resource-limited setting. These findings support implementation of basic evidence-based interventions for preterm and newborn care globally, particularly in LMICs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hashmi, Darakamon, Aung, Mu, Misa, Jittamala, Chu, Phyo, Turner, Nosten, McGready and Carrara.)

Introduction: Acute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) patients affects their health outcomes. Incidence and outcomes varied in the literature, particularly with different population and epidemiological demographics. Data remain scarce in the Southeast Asia region. We report the incidence, outcomes, pattern, types of AKI, and factors that influence AKI patient outcomes in Brunei Darussalam., Methods: All patients (N = 930) with COVID-19 who were admitted to the National Isolation Center (between 7th August 2021 and 30thSeptember 2021) were included in the study. The confirmation of AKI was based on the KDIGO (Kidney Disease Improving Global Outcomes) criteria., Results: The mean age of the patients was 41.9 ± 14.4 years with diabetes mellitus (DM), hypertension (HT), and chronic kidney disease (CKD) accounting for 11.7%, 29.1%, and 4.8% of comorbidities, respectively. Overall, 109 (11.7%) had AKI (KDIGO Stage 1 [67.9%], 2 [13.8%], and 3 [18.3%]), while 75.2% of the cases occurred pre-admission and 26.6% were cases of acute exacerbation of CKD. Univariate analysis identified age (odd ratio [OR] 1.06), male gender (OR 1.63), local nationality (OR 8.03), DM (OR 4.44), HT (OR 5.29), vascular disease (OR 6.08), presence of gastrointestinal symptoms (OR 2.08), antibiotic (OR 3.70) and nephrotoxins exposures (OR 8.57) as significant variables. Multivariate analysis showed age (adjusted OR [AOR] 1.04), male gender (AOR 1.67), gastrointestinal symptoms (AOR 1.61), antibiotic (AOR 2.34), and nephrotoxins exposure (AOR 4.73) as significant., Conclusions: Our study showed that one in nine patients with COVID-19 developed AKI with almost a third having stages 2 and 3 AKI. Older age, male gender, presence of GI symptoms, and antibiotic and nephrotoxin exposures were significant predictors of AKI. Patients with these factors should be prioritized for admission and treatment. Even though manifestations are generally now less severe, findings from this study can guide the management of COVID-19 as the disease enters the endemic stage. Furthermore, lessons learned from the COVID-19 pandemic will provide useful information and knowledge for future viral outbreaks or pandemics., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Oo et al.)

Recent years have demonstrated an increase in caesarean section (CS) in most countries worldwide with considerable concern for the potential consequences. In 2015, WHO proposed the use of Robson classification as a global standard for assessing, monitoring and comparing CS rates. Currently, there is no standardized method to assess CS in Myanmar. The aim of this study was to explore health provider's perceptions about the feasibility, acceptability and readiness to implement the Robson classification in public hospitals across Myanmar. Ten maternities were purposively chosen, including all five teaching hospitals (tertiary referral hospital-level) affiliated to each medical university in Myanmar, which provide maternal and newborn care services, and district/township hospitals. Face-to-face in-depth interviews (IDI) with healthcare providers and facility administrators were conducted using semi-structured discussion guides. Facility and medical records systems were also assessed. We used the thematic analysis approach and Atlas.ti qualitative analysis software. A total of 67 IDIs were conducted. Most participants had willingness to implement Robson classification if there were sufficient human resources and training. Limited human resources, heavy workloads, and infrastructure resources were the major challenges described that may hinder implementation. The focal person for data entry, analysis, or reporting could be differed according to the level of facility, availability of human resources, and ability to understand medical terms and statistics. The respondents mentioned the important role of policy enforcement for the sustainability of data collection, interpretation and feedback. The optimal review interval period could therefore differ according to the availability of responsible persons, and the number of births. However, setting a fixed schedule according to the specific hospital for continuous monitoring of CS rate is required. In Myanmar, implementation of Robson classification is feasible while key barriers mainly related to human resource and training must be addressed to sustain., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Show et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network.  It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented.  For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations.  We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent.  We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines.  Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 MalariaGEN et al.)

DNA methylation of both viral and host DNA is one of the major mechanisms involved in the development of Epstein-Barr virus-associated gastric carcinoma (EBVaGC); thus, epigenetic treatment using demethylating agents would seem to be promising. We have verified the effect of MC180295, which was discovered by screening for demethylating agents. MC180295 inhibited cell growth of the EBVaGC cell lines YCCEL1 and SNU719 in a dose-dependent manner. In a cell cycle analysis, growth arrest and apoptosis were observed in both YCCEL1 and SNU719 cells treated with MC180295. MKN28 cells infected with EBV were sensitive to MC180295 and showed more significant inhibition of cell growth compared to controls without EBV infection. Serial analysis of gene expression analysis showed the expression of genes belonging to the role of BRCA1 in DNA damage response and cell cycle control chromosomal replication to be significantly reduced after MC180295 treatment. We confirmed with quantitative PCR that the expression levels of BRCA2, FANCM, RAD51, TOP2A , and CDC45 were significantly decreased by MC180295. LMP1 and BZLF1 are EBV genes with expression that is epigenetically regulated, and MC180295 could up-regulate their expression. In conclusion, MC180295 inhibited the growth of EBVaGC cells by suppressing DNA repair and the cell cycle.

Background: Understanding the effect of immunity on Plasmodium falciparum clearance is essential for interpreting therapeutic efficacy studies designed to monitor emergence of artemisinin drug resistance. In low-transmission areas of Southeast Asia, where resistance has emerged, P. falciparum antibodies confound parasite clearance measures. However, variation in naturally acquired antibodies across Asian and sub-Saharan African epidemiological contexts and their impact on parasite clearance re yet to be quantified., Methods: In an artemisinin therapeutic efficacy study, antibodies to 12 pre-erythrocytic and erythrocytic P. falciparum antigens were measured in 118 children with uncomplicated P. falciparum malaria in the Democratic Republic of Congo (DRC) and compared with responses in patients from Asian sites, described elsewhere., Results: Parasite clearance half-life was shorter in DRC patients (median, 2 hours) compared with most Asian sites (median, 2-7 hours), but P. falciparum antibody levels and seroprevalences were similar. There was no evidence for an association between antibody seropositivity and parasite clearance half-life (mean difference between seronegative and seropositive, -0.14 to +0.40 hour) in DRC patients., Conclusions: In DRC, where artemisinin remains highly effective, the substantially shorter parasite clearance time compared with Asia was not explained by differences in the P. falciparum antibody responses studied., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 samples of Plasmodium vivax collected at 88 worldwide locations between 2001 and 2017. It includes 1,370 new samples contributed by MalariaGEN and VivaxGEN partner studies in addition to previously published samples from these and other sources. We provide genotype calls at over 4.5 million variable positions including over 3 million single nucleotide polymorphisms (SNPs), as well as short indels and tandem duplications. This enlarged dataset highlights major compartments of parasite population structure, with clear differentiation between Africa, Latin America, Oceania, Western Asia and different parts of Southeast Asia. Each sample has been classified for drug resistance to sulfadoxine, pyrimethamine and mefloquine based on known markers at the dhfr , dhps and mdr1 loci. The prevalence of all of these resistance markers was much higher in Southeast Asia and Oceania than elsewhere. This open resource of analysis-ready genome variation data from the MalariaGEN and VivaxGEN networks is driven by our collective goal to advance research into the complex biology of P. vivax and to accelerate genomic surveillance for malaria control and elimination., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 MalariaGEN et al.)

Myiasis is an infestation of maggot, which is frequently associated with poor personal hygiene and environmental sanitation. A 78-year-old female breast cancer patient visited clinic complaining of irritation, itching, and pain within the ulcerous cancer lesion for 3 weeks. Many maggots were found in the lesion. A total of 30 maggots were removed and identified to be 3rd stage of larvae of metallic fly. This is the first case of wound myiasis in advanced breast carcinoma as a complication of untreated or drug-induced ulcer.

The emergence and spread of artemisinin-resistant Plasmodium falciparum, first in the Greater Mekong Subregion (GMS), and now in East Africa, is a major threat to global malaria elimination ambitions. To investigate the artemisinin resistance mechanism, transcriptome analysis was conducted of 577 P. falciparum isolates collected in the GMS between 2016-2018. A specific artemisinin resistance-associated transcriptional profile was identified that involves a broad but discrete set of biological functions related to proteotoxic stress, host cytoplasm remodelling, and REDOX metabolism. The artemisinin resistance-associated transcriptional profile evolved from initial transcriptional responses of susceptible parasites to artemisinin. The genetic basis for this adapted response is likely to be complex., (© 2022. The Author(s).)

Background: Plasmodium vivax infects an estimated 7 million people every year. Previously, vivax malaria was perceived as a benign condition, particularly when compared to falciparum malaria. Reports of the severe clinical impacts of vivax malaria have been increasing over the last decade., Methods and Findings: We describe the main clinical impacts of vivax malaria, incorporating a rapid systematic review of severe disease with meta-analysis of data from studies with clearly defined denominators, stratified by hospitalization status. Severe anemia is a serious consequence of relapsing infections in children in endemic areas, in whom vivax malaria causes increased morbidity and mortality and impaired school performance. P. vivax infection in pregnancy is associated with maternal anemia, prematurity, fetal loss, and low birth weight. More than 11,658 patients with severe vivax malaria have been reported since 1929, with 15,954 manifestations of severe malaria, of which only 7,157 (45%) conformed to the World Health Organization (WHO) diagnostic criteria. Out of 423 articles, 311 (74%) were published since 2010. In a random-effects meta-analysis of 85 studies, 68 of which were in hospitalized patients with vivax malaria, we estimated the proportion of patients with WHO-defined severe disease as 0.7% [95% confidence interval (CI) 0.19% to 2.57%] in all patients with vivax malaria and 7.11% [95% CI 4.30% to 11.55%] in hospitalized patients. We estimated the mortality from vivax malaria as 0.01% [95% CI 0.00% to 0.07%] in all patients and 0.56% [95% CI 0.35% to 0.92%] in hospital settings. WHO-defined cerebral, respiratory, and renal severe complications were generally estimated to occur in fewer than 0.5% patients in all included studies. Limitations of this review include the observational nature and small size of most of the studies of severe vivax malaria, high heterogeneity of included studies which were predominantly in hospitalized patients (who were therefore more likely to be severely unwell), and high risk of bias including small study effects., Conclusions: Young children and pregnant women are particularly vulnerable to adverse clinical impacts of vivax malaria, and preventing infections and relapse in this groups is a priority. Substantial evidence of severe presentations of vivax malaria has accrued over the last 10 years, but reporting is inconsistent. There are major knowledge gaps, for example, limited understanding of the underlying pathophysiology and the reason for the heterogenous geographical distribution of reported complications. An adapted case definition of severe vivax malaria would facilitate surveillance and future research to better understand this condition., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: EA is a member of the Editorial Board of PLOS Medicine.