Optimal health and disease management using spatial uncertainty: a geographic characterization of emergent artemisinin-resistant Plasmodium falciparum distributions in Southeast Asia.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum malaria parasites are now present across much of mainland Southeast Asia, where ongoing surveys are measuring and mapping their spatial distribution. These efforts require substantial resources. Here we propose a generic 'smart surveillance' methodology to identify optimal candidate sites for future sampling and thus map the distribution of artemisinin resistance most efficiently. METHODS: The approach uses the 'uncertainty' map generated iteratively by a geostatistical model to determine optimal locations for subsequent sampling. RESULTS: The methodology is illustrated using recent data on the prevalence of the K13-propeller polymorphism (a genetic marker of artemisinin resistance) in the Greater Mekong Subregion. CONCLUSION: This methodology, which has broader application to geostatistical mapping in general, could improve the quality and efficiency of drug resistance mapping and thereby guide practical operations to eliminate malaria in affected areas.

Intensive care unit presentation of central corneal descemetocele secondary to Methicillin-Resistant staphylococcal infection superimposed by a hypopyon: a case report.

A descemetocele is a rare type of keratopathy that occurs when an intact descemet's membrane of the eye undergoes a herniation through an overlying stroma. Previous literature has documented corneal damage via bacterial enzymes, especially, Pseudomonas and Neisseria species. Most recent prospective interventional studies showed treatment of these infections. Case presentation: This report presents the first instance of a methicillin-resistant Staphylococcus aureus descemetocele presentation in a 51-year-old African American male, with co-presenting hypopyon sequelae successfully managed conservatively in an intensive care unit setting. Clinical discussion: An instance of a methicillin-resistant Staphylococcus aureus has not yet been documented in the literature. Likewise, a co-presentation with a hypopyon, which is known as a formation of inflammatory debris rich in white blood cells has not been studied. Conclusion: The presence of a hypopyon in the instances of bacterial descemetocele herniation should be further evaluated to see if there are associations with conservative, nonsurgical intervention outcomes.

A Case of Collet-Sicard Syndrome Caused by Otitis Externa.

Collet-Sicard syndrome is a unilateral palsy of the lower cranial nerves IX, X, XI, and XII, resulting from lesions at the skull base that affect the jugular foramen and hypoglossal canal. Common causes of the lesions include basilar skull fractures, carotid artery dissections, and malignancy. Infectious and inflammatory etiologies have also been reported. A 63-year-old male with a history of uncontrolled diabetes was admitted for dysphagia, right ear pain, drainage, and right-sided facial droop after recent local trauma and surgical instrumentation of the right ear. Culture of the external auditory canal grew Pseudomonas aeruginosa. Triple phase bone scan demonstrated osteomyelitis at the skull base due to complications from otitis externa. The patient's presentation was consistent with Collet-Sicard syndrome, and he was subsequently treated with a six-week course of ciprofloxacin. This patient demonstrates a unique case since his malignant otitis externa spread locally and led to skull base osteomyelitis and subsequently developed Collet-Sicard syndrome. His uncontrolled diabetes likely played a role in his disease progression.

Oculomotor Nerve Palsy as a Manifestation of Immune Thrombocytopenic Purpura: A Case Report.

Immune thrombocytopenic purpura (ITP) is caused by alterations in the immune system resulting in platelet destruction. It often manifests clinically with bleeding or on routine lab work revealing thrombocytopenia in asymptomatic individuals. Neurologic manifestations of this condition are sparsely documented in the literature. Among the symptoms reported were case reports of ischemic strokes, transient ischemic attacks, mononeuropathy multiplex, and polyneuropathy as neurological complications from immune thrombocytopenic purpura. Isolated cranial nerve palsies are uncommon. The following case describes a patient with immune thrombocytopenic purpura who presented with an isolated cranial nerve III palsy. A 55-year-old presented with pain in the right eye that was found in a downward and lateral gaze paralysis. There was no evidence of central or peripheral neurovascular etiology on imaging. However, workup revealed isolated thrombocytopenia with platelets <2000/ml3. Other possible etiologies, such as human immunodeficiency virus (HIV) and infectious etiologies, were evaluated and excluded. Thrombotic thrombocytopenia purpura was excluded with the results from ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity. The patient was appropriately transfused with platelets and was treated with methylprednisolone, which improved his platelets. At the time of discharge, the patient continued to have cranial nerve III palsy and was referred to follow up with hematology on an outpatient basis. In prior case reports where ITP presented as neurological deficits, there was evidence of intraneural microhemorrhage. Our case is unique in that the primary neurologic presentation without central nervous system pathology eventually led to the diagnosis of ITP. The symptoms were attributed to microhemorrhages that were not detected in imaging studies. Further studies are warranted to explore any correlation or causative association between ITP and neurological symptoms. This case report highlights the need to consider uncommon but possible manifestations of conditions that may initially appear seemingly irrelevant to the patient's chief complaint.

Assessment of Noise Exposure and Hearing Loss Among Workers in Textile Mill (Thamine), Myanmar: A Cross-Sectional Study.

BACKGROUND: In a wide range of industries, noise-induced hearing loss remains one of the most prevalent occupational problems. This study aimed to assess the noise exposure level and associated factors of hearing loss among textile workers in Yangon Region, Myanmar. METHODS: A cross-sectional study was conducted at a Textile mill (Thamine), Yangon Region, from April to December 2018. In total, 226 workers who were randomly selected from 3 weaving sections participated in face-to-face interviews using a structured questionnaire. A digital sound level meter and pure-tone audiometer were used for the assessment of noise exposure level and hearing loss, respectively. Logistic regression analysis was performed to assess the associated factors of hearing loss. RESULTS: In total workers, 66.4% were exposed to ≥85 dB(A) of noise exposure, and the prevalence of hearing loss was 25.7%. Age ≥35 years, below high school education, hearing difficulty, tinnitus, hypertension, > 9 years of service duration in a textile mill were positively associated with hearing loss. After adjusting confounding factors, age ≥35 years (adjusted odds ratio = 6.90, 95% confidence interval = 3.45-13.82) and tinnitus (adjusted odds ratio = 2.88, 95% confidence interval = 1.13-7.37) were persistently associated with hearing loss. CONCLUSION: Providing occupational hazard education and enforcement of occupational safety regulations should be taken to decrease the noise exposure level. The regular audiometry test should be conducted for assessment of hearing threshold shift. The employer needs to implement a hearing conservation program in workplace when noise exposure reaches or exceeds 85 dB(A) for 8 hours.

The spread of artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion: a molecular epidemiology observational study.

BACKGROUND: Evidence suggests that the PfKelch13 mutations that confer artemisinin resistance in falciparum malaria have multiple independent origins across the Greater Mekong subregion, which has motivated a regional malaria elimination agenda. We aimed to use molecular genotyping to assess antimalarial drug resistance selection and spread in the Greater Mekong subregion. METHODS: In this observational study, we tested Plasmodium falciparum isolates from Myanmar, northeastern Thailand, southern Laos, and western Cambodia for PfKelch13 mutations and for Pfplasmepsin2 gene amplification (indicating piperaquine resistance). We collected blood spots from patients with microscopy or rapid test confirmed uncomplicated falciparum malaria. We used microsatellite genotyping to assess genetic relatedness. FINDINGS: As part of studies on the epidemiology of artemisinin-resistant malaria between Jan 1, 2008, and Dec 31, 2015, we collected 434 isolates. In 2014-15, a single long PfKelch13 C580Y haplotype (-50 to +31·5 kb) lineage, which emerged in western Cambodia in 2008, was detected in 65 of 88 isolates from northeastern Thailand, 86 of 111 isolates from southern Laos, and 14 of 14 isolates from western Cambodia, signifying a hard transnational selective sweep. Pfplasmepsin2 amplification occurred only within this lineage, and by 2015 these closely related parasites were found in ten of the 14 isolates from Cambodia and 15 of 15 isolates from northeastern Thailand. C580Y mutated parasites from Myanmar had a different genetic origin. INTERPRETATION: Our results suggest that the dominant artemisinin-resistant P falciparum C580Y lineage probably arose in western Cambodia and then spread to Thailand and Laos, outcompeting other parasites and acquiring piperaquine resistance. The emergence and spread of fit artemisinin-resistant P falciparum parasite lineages, which then acquire partner drug resistance across the Greater Mekong subregion, threatens regional malaria control and elimination goals. Elimination of falciparum malaria from this region should be accelerated while available antimalarial drugs still remain effective. FUNDING: The Wellcome Trust and the Bill and Melinda Gates Foundation.

Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker.

BACKGROUND: Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations. METHODS: We did this cross-sectional survey at malaria treatment centres at 55 sites in ten administrative regions in Myanmar, and in relevant border regions in Thailand and Bangladesh, between January, 2013, and September, 2014. K13 sequences from P falciparum infections were obtained mainly by passive case detection. We entered data into two geostatistical models to produce predictive maps of the estimated prevalence of mutations of the K13 propeller region across Myanmar. FINDINGS: Overall, 371 (39%) of 940 samples carried a K13-propeller mutation. We recorded 26 different mutations, including nine mutations not described previously in southeast Asia. In seven (70%) of the ten administrative regions of Myanmar, the combined K13-mutation prevalence was more than 20%. Geospatial mapping showed that the overall prevalence of K13 mutations exceeded 10% in much of the east and north of the country. In Homalin, Sagaing Region, 25 km from the Indian border, 21 (47%) of 45 parasite samples carried K13-propeller mutations. INTERPRETATION: Artemisinin resistance extends across much of Myanmar. We recorded P falciparum parasites carrying K13-propeller mutations at high prevalence next to the northwestern border with India. Appropriate therapeutic regimens should be tested urgently and implemented comprehensively if spread of artemisinin resistance to other regions is to be avoided. FUNDING: Wellcome Trust-Mahidol University-Oxford Tropical Medicine Research Programme and the Bill & Melinda Gates Foundation.