Stratification of malaria incidence in Papua New Guinea (2011-2019): contribution towards a sub-national control policy

Malaria risk in Papua New Guinea (PNG) is highly heterogeneous, between and within geographical regions, which is operationally challenging for control. To enhance targeting of malaria interventions in PNG, we investigated risk factors and stratified malaria incidence at the level of health facility catchment areas. Catchment areas and populations of 808 health facilities were delineated using a travel-time accessibility approach and linked to reported malaria cases (2011-2019). Zonal statistics tools were used to calculate average altitude and air temperature in catchment areas before they were spatially joined with incidence rates. In addition, empirical Bayesian kriging (EBK) was employed to interpolate incidence risk strata across PNG. Malaria annual incidence rates are, on average, 186.3 per 1000 population in catchment areas up to 600 m, dropped to 98.8 at (800-1400) m, and to 24.1 cases above 1400 m altitude. In areas above the two altitudinal thresholds 600m and 1400m, the average annual temperature drops below 22°C and 17°C, respectively. EBK models show very low- to low-risk strata ( 200 per 1000) strata are modelled mainly in Momase and Islands Regions. Besides, strata with moderate risk (100-200) predominate throughout the coastal areas. While 35.7% of the PNG population (estimated 3.33 million in 2019) lives in places at high or moderate risk of malaria, 52.2% (estimated 4.88 million) resides in very low-risk areas. In five provinces, relatively large proportions of populations (> 50%) inhabit high-risk areas: New Ireland, East and West New Britain, Sandaun and Milne Bay. Incidence maps show a contrast in malaria risk between coastal and inland areas influenced by altitude. However, the risk is highly variable in low-lying areas. Malaria interventions should be guided by sub-national risk levels in PNG

A novel FAM20C

Raine syndrome is a rare, autosomal recessive, osteosclerotic bone dysplasia due to pathogenic variants in FAM20C. The clinical phenotype is characterized by generalized osteosclerosis affecting all bones, cerebral calcifications, and craniofacial dysmorphism. Most cases present during the neonatal period with early lethality due to pulmonary hypoplasia and respiratory compromise while only few affected individuals have been reported to survive into adulthood. FAM20C is a ubiquitously expressed protein kinase that contains five functional domains including a catalytic domain, a binding pocket for FAM20A and three distinct N-glycosylation sites. We report a newborn infant with a history of prenatal onset fractures, generalized osteosclerosis, and craniofacial dysmorphism and early lethality. The clinical presentation was highly suggestive of Raine syndrome. A homozygous, novel missense variant in exon 5 of FAM20C (c.1007T>G ; p.Met336Arg) was identified by targeted Sanger sequencing. Following in silico analysis and mapping of the variant on a three-dimensional (3D) model of FAM20C it is predicted to be deleterious and to affect N-glycosylation, protein folding, and subsequent secretion of FAM20C. In addition, we reviewed all published FAM20C mutations and observed that most pathogenic variants affect functional regions within the protein establishing evidence for an emerging genotype-phenotype correlation

Common Childhood Epilepsy Mimics

Unusual movements in children frequently generate concern of underlying seizures from parents and lead to professional review. Stigma associated with epilepsy heightens anxiety and a wish to confirm or exclude the diagnosis as soon as possible. These considerations could lead to a wrong diagnosis of epilepsy being given with unwarranted exposure to medications with potential side effects and cost burden to families. This chapter seeks to provide practitioners in pediatric epilepsy with an exploration of practical differential diagnoses for epilepsy in children, particularly for convulsive seizures. Evaluation of all epilepsy mimics requires a precise and relevant history to help arrive at a diagnosis. Epilepsy mimics across various ages will be reviewed, with the most common differential diagnoses presented first. Examples of common potential epilepsy mimics include benign sleep myoclonus, which is frequently observed in infants and may be a challenge to differentiate from myoclonic seizures in infants. It is a very common phenomenon in pre-term infants with an incidence of 57–132 per 1000 live births. Breath-holding spells among toddlers are common and may be mistaken for epilepsy, as can reflex anoxic seizures. Self-gratification phenomena have been observed from infancy onward and may resemble clonic seizures. Inattention in school-going children is a differential diagnosis for absence seizures and both conditions may co-exist. Stressed or traumatized children may present with non-epileptic psychogenic seizures, as can children with established seizures. Lack of concurrent electrophysiological correlates and absence of stereotypic presentation help differentiate inattention and non-epileptic seizures from childhood epilepsy. Sleep-related activity such as hallucinations, parasomnias, and hypnagogic jerks could also be mistaken for epilepsy in children. Video electroencephalogram (video-EEG) telemetry evaluation is invaluable in such cases. Lack of video-EEG services, simple videos, or EEG studies in resource-poor settings makes diagnosis of epilepsy imitators challenging. The differences between epilepsy and common differential diagnoses for practitioners in resource-limited settings who may lack access to requisite investigative tools will be addressed in the following text. The outcome for most epilepsy mimics is excellent with minimal morbidity and mortality. The potential danger posed by unnecessary medical interventions caused by misdiagnosis of epilepsy makes it imperative that this possibility is minimized

Current challenges and implications for dengue, chikungunya and Zika seroprevalence studies worldwide: A scoping review.

BACKGROUND:Arboviral infections are a public health concern and an escalating problem worldwide. Estimating the burden of these diseases represents a major challenge that is complicated by the large number of unapparent infections, especially those of dengue fever. Serological surveys are thus required to identify the distribution of these diseases and measure their impact. Therefore, we undertook a scoping review of the literature to describe and summarize epidemiological practices, findings and insights related to seroprevalence studies of dengue, chikungunya and Zika virus, which have rapidly expanded across the globe in recent years. METHODOLOGY/PRINCIPAL FINDINGS:Relevant studies were retrieved through a literature search of MEDLINE, WHOLIS, Lilacs, SciELO and Scopus (2000 to 2018). In total, 1389 publications were identified. Studies addressing the seroprevalence of dengue, chikungunya and/or Zika written in English or French and meeting the inclusion and exclusion criteria were included. In total, 147 studies were included, from which 185 data points were retrieved, as some studies used several different samples. Most of the studies were exclusively conducted on dengue (66.5%), but 16% were exclusively conducted on chikungunya, and 7 were exclusively conducted on Zika; the remainder were conducted on multiple arboviruses. A wide range of designs were applied, but most studies were conducted in the general population (39%) and in households (41%). Although several assays were used, enzyme-linked immunosorbent assays (ELISAs) were the predominant test used (77%). The temporal distribution of chikungunya studies followed the virus during its rapid expansion since 2004. The results revealed heterogeneity of arboviruses seroprevalence between continents and within a given country for dengue, chikungunya and Zika viruses, ranging from 0 to 100%, 76% and 73% respectively. CONCLUSIONS/SIGNIFICANCE:Serological surveys provide the most direct measurement for defining the immunity landscape for infectious diseases, but the methodology remains difficult to implement. Overall, dengue, chikungunya and Zika serosurveys followed the expansion of these arboviruses, but there remain gaps in their geographic distribution. This review addresses the challenges for researchers regarding study design biases. Moreover, the development of reliable, rapid and affordable diagnosis tools represents a significant issue concerning the ability of seroprevalence surveys to differentiate infections when multiple viruses co-circulate