Heterogeneity in the prevalence of subclinical malaria, other co-infections and anemia among pregnant women in rural areas of Myanmar: a community-based longitudinal study.

BACKGROUND: Due to the low prevalence of clinically suspected malaria among pregnant women in Myanmar, little is known about its impact on mothers and newborns. Helminth and Human Immuno-deficiency Virus (HIV) co-infections cause anemia in pregnant women. This study assessed the prevalence of subclinical malaria and co-infections among pregnant women, and its association with adverse outcomes of pregnancy in the presence of infection. METHODS: A prospective longitudinal study was conducted in 12 villages in two townships in Myanmar between 2013 to 2015. A total of 752 pregnant women, with a mean age of 27 years, were enrolled and followed up once a month until six weeks after childbirth. Prevalence ratio was calculated in the multivariable analysis. RESULTS: The prevalence of subclinical malaria as measured by nested PCR was 5.7% for either P. falciparum or P. vivax, 2.7% prevalence of P. falciparum and 2.8% prevalence of P. vivax. Helminth infections were prevalent in 17% of women, and one woman with an HIV infection was found in our study. The burden of anemia was high, with an overall prevalence of 37% with or without helminth infection, 42% of the women were malaria positive and 43% had dual infections (both malaria and helminth). Only 11 abnormal pregnancy outcomes (7 stillbirths, 2 premature, 2 twins) were identified. Poisson regression showed that women in their first trimester had a 2.9 times higher rate of subclinical malaria compared to women in the third trimester (PR:2.9, 95%CI 1.19, 7.31, p = 0.019), women who were enrolled during the wet season were 2.5 times more likely to be malaria positive than the women enrolled in the dry season (PR: 2.5, 95%CI 1.27, 4.88, p = 0.008), and the malaria positivity rate decreased by 5% when increased in one year of woman's age (PR:0.95, 95%CI 0.91, 0.99, p = 0.02). In the multivariable regression, the age of respondents was the only significant factor associated with subclinical malaria in pregnancy. CONCLUSIONS: A comprehensive approach of integrating interventions for malaria, anemia, and helminths should be delivered during antenatal care services for pregnant women in rural areas of Myanmar.

Finishing the task of eliminating neglected tropical diseases (NTDs) in WHO South-East Asia Region: promises kept, challenges, and the way forward.

Globally 20 Neglected tropical diseases (NTDs) are prioritized by World Health Organization (WHO), of which 15 are present in the South-East Asia Region (SEAR) with all 11 countries being affected. As the region bears 54% of the global burden, "Finishing the task of eliminating neglected tropical diseases and other diseases on the verge of elimination" was identified as a regional flagship priority in 2014 with focus on lymphatic filariasis (LF), kala-azar, yaws, trachoma, and leprosy. Intensified efforts have been made to raise and sustain political commitment and momentum among partners innovate tools, interventions and strategies to accelerate elimination, and establish the process and support countries to accelerate and validate achievement of elimination targets. Seven countries have verified or validated for having eliminated at least one NTD since 2016, including yaws, LF and trachoma. Between 2010 and 2020, the number of people requiring interventions against NTDs in the South-East Asia Region reduced by 20%. The priorities in the next decade are to strengthen last-mile efforts to eliminate identified NTDs, sustain it and to use the lessons learnt to eliminate other NTDs. Funding: None.

Dengue in Myanmar: Spatiotemporal epidemiology, association with climate and short-term prediction.

Dengue is a major public health problem in Myanmar. The country aims to reduce morbidity by 50% and mortality by 90% by 2025 based on 2015 data. To support efforts to reach these goals it is important to have a detailed picture of the epidemiology of dengue, its relationship to meteorological factors and ideally to predict ahead of time numbers of cases to plan resource allocations and control efforts. Health facility-level data on numbers of dengue cases from 2012 to 2017 were obtained from the Vector Borne Disease Control Unit, Department of Public Health, Myanmar. A detailed analysis of routine dengue and dengue hemorrhagic fever (DHF) incidence was conducted to examine the spatial and temporal epidemiology. Incidence was compared to climate data over the same period. Dengue was found to be widespread across the country with an increase in spatial extent over time. The temporal pattern of dengue cases and fatalities was episodic with annual outbreaks and no clear longitudinal trend. There were 127,912 reported cases and 632 deaths from 2012 and 2017 with peaks in 2013, 2015 and 2017. The case fatality rate was around 0.5% throughout. The peak season of dengue cases was from May to August in the wet season but in 2014 peak dengue season continued until November. The strength of correlation of dengue incidence with different climate factors (total rainfall, maximum, mean and minimum temperature and absolute humidity) varied between different States and Regions. Monthly incidence was forecasted 1 month ahead using the Auto Regressive Integrated Moving Average (ARIMA) method at country and subnational levels. With further development and validation, this may be a simple way to quickly generate short-term predictions at subnational scales with sufficient certainty to use for intervention planning.

Evaluation of the effects of three designs of oxygenators with integrated filters on clinical and haematological outcomes at an Australasian cardiothoracic unit.

INTRODUCTION: Cardiopulmonary bypass (CPB) machines have oxygenators with integrated filters and unique biocompatible coatings to combat systemic inflammatory response syndrome (SIRS) and mitigate coagulopathy. Contemporary oxygenators have undergone comparative studies; however, our study aimed to identify the most appropriate oxygenator for our regional Cardiothoracic unit in Australasia. METHODS: A prospective audit consecutively recruited one-hundred and fifty patients undergoing cardiac surgery at Waikato Hospital, New Zealand between the periods of 29th January 2018 and 31st July 2018. Fifty patients were recruited for each oxygenator arm: Sorin INSPIRE' (Group-S); Terumo CAPIOX'FX (Group-T); and Medtronic Affinity Fusion' (Group-M). The clinical outcomes were transfusions, chest drain output, reoperation and length of hospital stay (LOHS). Routine blood testing protocol included: haemoglobin, protein, albumin, white cell count (WCC), C-reactive protein (CRP), platelet count and coagulations tests including international normalized ratio (INR). RESULTS: Comparing Groups S, T and M there was no statistical difference in chest drain output (650 vs. 500 vs. 595 ml respectively, p = 0.45), transfusions (61 vs. 117 vs. 70 units, p = 0.67), reoperation (6 vs. 8 vs. 12%, p = 0.99) and LOHS (median 7.4 vs. 7.6 vs. 9.5 days, p = 0.42). Group-T had fewer SIRS cases but similar increase in CRP (p = 0.12) and WCC (p = 0.35). Group-M had a significant rise in post-op INR (p = 0.005) but no associated increase in chest drain output (p = 0.62). Group-S and -M required more 4%-albumin and Group-T had more transfusions. Only fresh frozen plasma (FFP) and red blood cell (RBC) transfusion had a significant relationship with LOHS (p < 0.05). CONCLUSION: Biochemically, there was slight difference among the oxygenators which did not translate into clinical difference in outcomes. The oxygenator design and perfusionist choice aided in our decision-making process.

Early diagnosis of surgically curable lung cancer is commonly serendipitous.

AIMS: Lung cancer is the largest cause of cancer death in New Zealand, accounting for 18.3% of cancer-related deaths.[[1,2]] There is limited literature on how patients with lung cancer clinically present in New Zealand. The aim of this cohort study was to identify the rate of incidentally diagnosed lung cancer in the Midland Region, the common symptomatology and route of diagnosis. METHODS: This retrospective cohort study included patients with lung cancer who underwent potentially curative thoracic surgery between January 2011 to June 2018 at Waikato Hospital, New Zealand. Symptoms or signs recorded were cough, dyspnoea, haemoptysis, lymphadenopathy, chest pain, hoarseness, fatigue, weight loss and finger clubbing. The lung cancer cases were grouped into incidental finding, symptomatic general practitioner, symptomatic emergency department and surveillance. RESULTS: Three hundred and ten patients with lung cancer had thoracic surgery with curative intent at Waikato Hospital. Two hundred and fourteen (69%) patients had symptoms which prompted presentation to a treating physician and 96 (31%) patients were asymptomatic. Incidental diagnosis was demonstrated in 121 (39.4%) patients. Of the patients diagnosed incidentally, 36.4% (n=44) had symptoms of lung cancer with the main symptoms including 45% with cough (n=20), 28% with dyspnoea (n=12) and 28% chest pain (n=12). CONCLUSIONS: In New Zealand, a large amount of lung cancer is still diagnosed incidentally with symptoms of cough, dyspnoea and chest pain. Further research into the development of a lung cancer screening program in New Zealand for a high-risk population is warranted.

Cardiac surgery simulation: a low-cost feasible option in an Australasian setting.

BACKGROUND: Simulation training is a useful adjunct to surgical training and education (SET) in Cardiothoracic Surgery yet training opportunities outside the Royal Australasian College of Surgery or industry-sponsored workshops are rare due to high cost and limited training faculty, time, assessment tools or structured curricula. We describe our experience in establishing a low-cost cardiac simulation programme. METHODS: We created low-cost models using hospital facilities, hardware stores, abattoirs and donations from industry. Three workshops were conducted on coronary anastomoses, aortic and mitral valve replacement. RESULTS: Whole porcine hearts were sourced from local farms. Industry donations of obsolete stock were used for suture and valve material-stations constructed using ironing-board, 2-L buckets and kebab-skewers. Suture ring holders were fashioned from recycled cardboard or donated. All participants were asked to complete pre and post simulation self-assessment forms. Across three workshops, 45 participants (57.8% female) with a median age 27 (interquartile range 24-31) attended. Training level consisted of nurses (8, 17.8%), medical students (17, 37.8%), residents/house officers (6, 13.3%) and registrars (14, 31.1%). There were improvements in knowledge of anatomy (mean difference 18%; 95% confidence interval 12%-24%), imaging (16%; 10%-22%) and procedural components (34%; 28%-42%); and practical ability to describe steps (30%; 24%-38%), partially (32%; 26%-38%) or fully complete (32%; 28%-38%) the procedure. CONCLUSIONS: Simulation-based training in cardiac surgery is feasible in a hospital setting with low overhead costs. It can benefit participants at all training levels and has the potential to be implemented in training hospitals as an adjunct to the SET programme.

Prevalence and seroprevalence of Plasmodium infection in Myanmar reveals highly heterogeneous transmission and a large hidden reservoir of infection.

Malaria incidence in Myanmar has significantly reduced over recent years, however, completeness and timeliness of incidence data remain a challenge. The first ever nationwide malaria infection and seroprevalence survey was conducted in Myanmar in 2015 to better understand malaria epidemiology and highlight gaps in Annual Parasite Index (API) data. The survey was a cross-sectional two-stage stratified cluster-randomised household survey conducted from July-October 2015. Blood samples were collected from household members for ultra-sensitive PCR and serology testing for P. falciparum and P. vivax. Data was gathered on demography and a priori risk factors of participants. Data was analysed nationally and within each of four domains defined by API data. Prevalence and seroprevalence of malaria were 0.74% and 16.01% nationwide, respectively. Prevalent infection was primarily asymptomatic P. vivax, while P. falciparum was predominant in serology. There was large heterogeneity between villages and by domain. At the township level, API showed moderate correlation with P. falciparum seroprevalence. Risk factors for infection included socioeconomic status, domain, and household ownership of nets. Three K13 P. falciparum mutants were found in highly prevalent villages. There results highlight high heterogeneity of both P. falciparum and P. vivax transmission between villages, accentuated by a large hidden reservoir of asymptomatic P. vivax infection not captured by incidence data, and representing challenges for malaria elimination. Village-level surveillance and stratification to guide interventions to suit local context and targeting of transmission foci with evidence of drug resistance would aid elimination efforts.

Performance of the AusSCORE II and STS Score for Coronary Artery Bypass Grafting in a New Zealand Population.

BACKGROUND: The updated Australian System for Cardiac Operative Risk Evaluation (AusSCORE II) and the Society of Thoracic Surgeons (STS) Score are well-established tools in cardiac surgery for estimating operative mortality risk. No validation analysis of both risk models has been undertaken for a contemporary New Zealand population undergoing isolated coronary bypass surgery. We therefore aimed to assess the efficacy of these models in predicting mortality for New Zealand patients receiving isolated coronary artery bypass grafting (CABG). MATERIAL AND METHODS: A prospective database was maintained of patients undergoing isolated CABG at a major tertiary referral centre in New Zealand between September 2014 and September 2017. This database collected the patients' demographic, clinical, biochemical, operative and mortality data. The primary outcome measure was the correlation between the predicted AusSCORE II and STS Score mortality risks and the observed 30-day mortality events for all patients in the database using discrimination and calibration statistics. Discrimination and calibration were assessed using receiver operating characteristic (ROC) curves and the Hosmer-Lemeshow test respectively. RESULTS: A total of 933 patients underwent isolated CABG during the 3-year study period. There were seven deaths in the study cohort occurring within 30 days of surgery. Discrimination analysis demonstrated the area under the ROC curve (AUC) of the AusSCORE II and STS Score as 88.2% (95% CI: 85.9-90.2, p<0.0001) and 92.1% (95% CI: 90.2-93.7, p<0.0001) respectively. Calibration analysis revealed Hosmer-Lemeshow test p-values for the AusSCORE II and STS Score as 0.696 and 0.294 respectively. DISCUSSION: ROC curve analysis produced very high and statistically significant AUC values for the AusSCORE II and STS Score. Hosmer-Lemeshow test analysis revealed that both risk scoring tools are well calibrated for our study cohort. Therefore, the AusSCORE II and STS Score are both strongly predictive of 30-day mortality for isolated coronary artery bypass grafting surgery in our New Zealand patient population. Both risk models have performed with excellent discrimination and calibration. There is, however, a need to consider the performance of these risk stratification models in other cardiac surgical procedures outside isolated coronary bypass surgery where appropriate.

What are the endovascular options and outcomes for repair of ascending aortic or aortic arch pathology?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'in patients with ascending aortic or aortic arch disease what are the outcomes with endovascular repair in terms of survival, complications and reintervention?' Altogether 585 papers were found using the reported search, of which 9 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We found that the endovascular operative techniques with the greatest evidence were ascending aortic chimney grafts (AACs), branched thoracic endovascular aortic repair (bTEVAR) aortic grafts and fenestrated TEVAR (fTEVAR) aortic grafts. The best evidence available were small case-series or retrospective cohort studies (n < 100), with 1 systematic review, at a short follow-up period (range 0-5 years). Intraoperatively, these techniques have a high technical success rate (84-100%). We found rates of endoleak comparable between AAC (7.4-16%) and bTEVAR/fenestrated TEVAR (11.1-21.4%). Stroke rates are higher in bTEVAR (3.1-42% vs 1-26% in AACs), attributed to more proximal pathology and technically challenging procedures. Following the immediate postoperative period, the 30-day mortality is 0-10.8% and patency is 97-100%. Stroke and reintervention rates remain higher in the bTEVAR group (3.1-42.0% and 0.5-33.3%) compared to the AAC group (1.0-11.1% and 6.7-16.7%). The 3- and 5-year survival ranges from 59% to 90%, but is driven by non-aortic pathology in a high-risk population; 3-year freedom from aortic death is 93-97%. Patency is 97-100% at up to 3 years, conformation and supra-aortic occlusions thereafter remain unknown. We conclude that AACs, bTEVARs and fenestrated TEVARs are safe endovascular options in high-risk elective patients, with results comparable to open or hybrid repair. They remain unverified in acute settings or in patients fit for open intervention.

Notified dengue deaths in Myanmar (2017-18): profile and diagnosis delays.

Background: Complications in dengue usually occur between day four and day six after fever onset. Hence, early diagnosis and haematological monitoring are vital. Among all hospital reported dengue deaths in Myanmar in 2017-18, we assessed the i) patient profile, ii) proportion of patients who arrived with a dengue diagnosis at admission and iii) delays in diagnosis after fever onset. Methods: This was a descriptive study involving secondary data. For all the notified deaths, death investigation forms were not available in prescribed format and therefore, data were extracted from hospital case records.  Results: Of 304 deaths, 184 (60.5%) were female and 233 (76.6%) were less than 10 years old. Township level hospitals or below reported 36 deaths (11.8%) and the remaining deaths were from higher level facilities. Dengue was diagnosed before admission in 26 (8.5%) people and 169 (55.6%) were in shock at admission. Of 208 with date of fever onset recorded, the median diagnosis delay was four (interquartile range-IQR: 3, 5) days. Patient level delay (median three days) was a major contributor to the diagnosis delay. Conclusions: Most of the patients who died did not have a diagnosis of dengue before admission. This calls for an urgent review of health system preparedness in peripheral health facilities to suspect, diagnose, monitor, refer and treat dengue in children and patient level factors for better understanding of the reasons of delay. Timely filling of death investigation forms in a prescribed format and quarterly death reviews based on these is recommended.

The burden of Japanese encephalitis, the catch-up vaccination campaign, and health service providers' perceptions in Myanmar: 2012-2017.

BACKGROUND: Myanmar is endemic for Japanese encephalitis (JE) and has experienced several outbreaks in recent years. The vector-borne disease control (VBDC) program has collected hospital-based surveillance data since 1974. There is an urgent need to collate, analyze, and interpret the most recent information. The study aimed to describe (i) hospital-based JE cases and deaths between 2012 and 2017, (ii) a catch-up vaccination campaign in children in 2017, and (iii) health service provider perceptions about JE in one township in 2018. METHODS: This was a cross-sectional study of cases, deaths, and catch-up childhood vaccinations using secondary data from program records and a survey database of health service provider perceptions. RESULTS: Between 2012 and 2017, there were 872 JE cases and 79 deaths with a case fatality rate of 91 per 1000; 2016 was the year with most cases and deaths. Most cases (n = 324) and deaths (n = 37) occurred in children aged 5-9 years. Large case numbers were reported in delta and lowland regions (n = 550) and during the wet season (n = 580). The highest case fatality rates were observed in the hills and coastal regions (120 and 112 per 1000, respectively). Nationwide coverage of the catch-up JE vaccination campaign among 13.7 million eligible children was 92%, with coverage lower in the hills and coastal regions (84%) compared with delta and lowland regions and plains (94%). More vaccinations (65%) occurred through school-based campaigns with the remainder (35%) vaccinated through community-based campaigns. Structured interviews in one township showed that service providers (n = 47) had good perceptions about various aspects of JE, although perceived benefits of specific vector control measures were poor: spraying/fumigation (38%), garbage removal (36%), larvicide use (36%), and drainage of standing/stagnant water (32%). CONCLUSION: The catch-up vaccination campaign was a successful response to high JE case numbers and deaths in children. However, ongoing surveillance for JE needs to continue and be strengthened to ensure comprehensive reporting of all cases, more knowledge is needed on disability in JE survivors, and all attempts must be made to ensure high percentage coverage of vaccination through routine and catch-up campaigns.

Utilization of insecticide-treated bed nets and care-seeking for fever and its associated socio-demographic and geographical factors among under-five children in different regions: evidence from the Myanmar Demographic and Health Survey, 2015-2016.

BACKGROUND: Malaria is one of the top-five contributors to under-5 deaths in Myanmar. Use of insecticide-treated nets (ITN) and receiving early appropriate care in case of fever are the core interventions to prevent malaria and its complications and thereby deaths. This study aimed to assess among the under-five children, (a) utilization of ITNs and its associated factors, (b) care-seeking behaviour among their caregivers and its associated factors and uptake of malaria testing among those with fever in the last 2 weeks. METHODS: This was a cross sectional study using secondary analysis of Myanmar Demographic and Health Survey (MDHS) conducted in 2015-2016. Multivariable logistic regression was used to explore the factors associated with non-utilization of ITNs and not seeking care for fever. Effect sizes have been presented using odds ratios with 95% confidence intervals. Data analysis was done using svyset command in STATA to account for the multi-stage sampling design of the survey. RESULTS: Of 4597 alive under-five children, 80.5% did not sleep under an ITN last night. The factors significantly associated with non-utilization of ITNs were residing in malaria elimination regions (aOR = 2.0, 1.3-3.2), urban residence (aOR = 1.8, 1.2-2.9), staying in delta region (aOR = 8.7, 4.7-12.2), hilly region (aOR = 3.0, 2.0-4.6, and having highest wealth quintile (aOR = 1.8, 1.1-3.0). Around 16% had fever in the last 2 weeks, of whom 66.7% sought care for fever and 3% got tested for malaria. Nearly half (50.9%) of the caregivers sought care from a government health facility, followed by private hospital/doctor (27.8%), shop (8.0%), village health worker (4.4%) and pharmacy (3.1%). The factors associated with not seeking care for fever were residing in specific geographical locations (hilly, delta and central plains compared to coastal region) and having lowest wealth quintile (aOR = 2.3, 1.1-5.7). CONCLUSIONS: This study highlighted that ownership and utilization of ITNs was very poor among under-5children. Care-seeking behaviour of the caregivers of under-5 children in case of fever was dismal with two-thirds not seeking care. The programme should seriously consider addressing these barriers if Myanmar is to achieve zero malaria deaths by 2030.

Importance of kelch 13 C580Y mutation in the studies of artemisinin resistance in Plasmodium falciparum in Greater Mekong Subregion.

The mortality caused by Plasmodium falciparum was reduced by Artemisinin (ART) and ART combination therapy (ACT). However, Artemisinin resistance (ART-R) emerge during 2008 in Cambodia and spread to Greater Mekong Subregion (GMS). ART-R was confirmed not to spread to India, a gateway to whole Africa. The whole genome sequencing approach of P. falciparum assumed the k13 gene encoded Kelch protein was discovered to be associated with ART-R. Of the single nucleotide polymorphisms (SNPs) of k13 gene, C580Y mutant was commonly dominant in Cambodia, Myanmar, Thailand, Laos and Vietnam and assumed to be one of strong molecular markers for ART-R in P. falciparum isolates in GMS. Literatures published between 2017 and 2018 were reviewed in this work. F446I is observed to be doubtful molecular marker as ART-R marker. Transgenic experiment showed that parasite with F446I mutation displayed prolonged clearance in respond to ART while C580Y was applied as positive control mutant. Furthermore, study of C580Y allele in four countries Cambodia, Thailand, Laos resulted in single origin whereas the parasite with this allele showed multi-origin in three Provinces of Vietnam. As artemisinin was short acting drug, the role of long acting partner drug was studied by using transgenic C580Y mutant and C580 to leave recrudescent P. falciparum. Recently, there was treatment failure with ACT in some countries in GMS. In this review, the importance of C580Y mutation in the study of ART-R was discussed.

Human Plasmodium knowlesi infections in South-East Asian countries.

Plasmodium knowlesi is now regarded as the fifth malaria parasite causing human malaria as it is widely distributed in South-East Asian countries especially east Malaysia where two Malaysian states namely Sabah and Sarawak are situated. In 2004, Polymerase Chain Reaction (PCR) was applied for diagnosing knowlesi malaria in the Kapit Division of Sarawak, Malaysia, so that human P. knowlesi infections could be detected correctly while blood film microscopy diagnosed incorrectly as Plasmodium malariae. This parasite is transmitted from simian hosts to humans via Anopheles vectors. Indonesia is the another country in South East Asia where knowlesi malaria is moderately prevalent. In the last decade, Sarawak and Sabah, the two states of east Malaysia became the target of P. knowlesi research due to prevalence of cases with occasional fatal infections. The host species of P. knowlesi are three macaque species namely Macaca fascicularis, Macaca nemestrina and Macaca leonina while the vector species are the Leucosphyrus Complex and the Dirus Complex of the Leucophyrus Group of Anopheles mosquitoes. Rapid diagnostic tests (RDT) are non-existent for knowlesi malaria although timely treatment is necessary for preventing complications, fatality and drug resistance. Development of RDT is essential in dealing with P. knowlesi infections in poor rural healthcare services. Genetic studies of the parasite on possibility of human-to-human transmission of P. knowlesi were recommended for further studies.

Acute shortness of breath due to reoccurrence of an intrapericardial bronchogenic cyst.

A 71-year-old woman presented with dysphagia and acute shortness of breath. Surgical history included a prior thoracotomy overseas for a bronchogenic mesothelial cyst 19 years before. Computed tomography demonstrated a mass within the posterior mediastinum measuring 69 × 70 × 74 mm. A median sternotomy was performed, and after removal of the cyst, repair of the left atrium and pulmonary vessels was undertaken due to the invading nature of the cyst. Intrapericardial bronchogenic cysts are a rare form of congenital cysts arising from the primitive foregut. The cardiac primordia are in close proximity to the foregut and primitive tracheobronchial tree, and thus, abnormal budding of the tracheobronchial tree can arise in a myocardial location. Irrespective of the method of approach in redo surgery, complete resection must be performed in order to minimize the chance of recurrence, relieve symptoms, eliminate risk of infection, and prevent malignant degeneration.

Genetic diversity of toxigenic Vibrio cholerae O1 from Sabah, Malaysia 2015.

BACKGROUND: Cholera is an important health problem in Sabah, a Malaysian state in northern Borneo; however, Vibrio cholerae in Sabah have never been characterized. Since 2002, serogroup O1 strains having the traits of both classical and El Tor biotype, designated as atypical El Tor biotype, have been increasingly reported as the cause of cholera worldwide. These variants are believed to produce clinically more severe disease like classical strains. PURPOSE: The purpose of this study is to investigate the genetic diversity of V.cholerae in Sabah and whether V.cholerae in Sabah belong to atypical El Tor biotype. METHODS: ERIC-PCR, a DNA fingerprinting method for bacterial pathogens based on the enterobacterial repetitive intergenic consensus sequence, was used to study the genetic diversity of 65 clinical V.cholerae O1 isolates from 3 districts (Kudat, Beluran, Sandakan) in Sabah and one environmental isolate from coastal sea water in Kudat district. In addition, we studied the biotype-specific genetic traits in these isolates to establish their biotype. RESULTS: Different fingerprint patterns were seen in isolates from these three districts but one of the patterns was seen in more than one district. Clinical isolates and environmental isolate have different patterns. In addition, Sabah isolates harbor genetic traits specific to both classical biotype (ctxB-1, rstRCla) and El Tor biotype (rstRET, rstC, tcpAET, rtxC, VC2346). CONCLUSION: This study revealed that V.cholerae in Sabah were genetically diverse and were atypical El Tor strains. Fingerprint patterns of these isolates will be useful in tracing the origin of this pathogen in the future.

Antibody Targets on the Surface of Plasmodium falciparum-Infected Erythrocytes That Are Associated With Immunity to Severe Malaria in Young Children.

BACKGROUND: Sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the microvasculature contributes to pathogenesis of severe malaria in children. This mechanism is mediated by antigens expressed on the IE surface. However, knowledge of specific targets and functions of antibodies to IE surface antigens that protect against severe malaria is limited. METHODS: Antibodies to IE surface antigens were examined in a case-control study of young children in Papua New Guinea presenting with severe or uncomplicated malaria (n = 448), using isolates with a virulent phenotype associated with severe malaria, and functional opsonic phagocytosis assays. We used genetically modified isolates and recombinant P. falciparum erythrocyte membrane protein 1 (PfEMP1) domains to quantify PfEMP1 as a target of antibodies associated with disease severity. RESULTS: Antibodies to the IE surface and recombinant PfEMP1 domains were significantly higher in uncomplicated vs severe malaria and were boosted following infection. The use of genetically modified P. falciparum revealed that PfEMP1 was a major target of antibodies and that PfEMP1-specific antibodies were associated with reduced odds of severe malaria. Furthermore, antibodies promoting the opsonic phagocytosis of IEs by monocytes were lower in those with severe malaria. CONCLUSIONS: Findings suggest that PfEMP1 is a dominant target of antibodies associated with reduced risk of severe malaria, and function in part by promoting opsonic phagocytosis.