Evaluation of acute flaccid paralysis surveillance performance before and during the 2014-2015 Ebola virus disease outbreak in Guinea and Liberia.

Introduction: the number of wild poliomyelitis cases, worldwide, dropped from 350,000 cases in 1988 to 33 in 2018. Acute flaccid paralysis (AFP) surveillance is a key strategy toward achieving global polio eradication. The 2014 Ebola virus disease (EVD) epidemic in West Africa infected over 28,000 people and had devastating effects on health systems in Guinea, Liberia, and Sierra Leone. We sought to assess the effects of the 2014 Ebola outbreak on AFP surveillance in Guinea and Liberia. Methods: a retrospective cross-sectional analysis was performed for Guinea and Liberia to evaluate EVD´s impact on World Health Organization (WHO) AFP surveillance performance indicators during 2012-2015. Results: both Guinea and Liberia met the WHO target non-polio AFP incidence rate nationally, and generally sub-nationally, prior to the EVD outbreak; rates decreased substantially during the outbreak in seven of eight regions in Guinea and 11 of 15 counties in Liberia. Throughout the study period, both Guinea and Liberia attained appropriate overall targets nationally for "notification" and "stool adequacy" indicators, but each country experienced periods of poor regional/county-specific indicator performance. Conclusion: these findings mirrored the negative effect of the Ebola outbreak on polio elimination activities in both countries and highlights the need to reinforce this surveillance system during times of crisis.

Reduced length of nodes of Ranvier and altered proteoglycan immunoreactivity in prefrontal white matter in major depressive disorder and chronically stressed rats.

Major depressive disorder (MDD) and chronic unpredictable stress (CUS) in animals feature comparable cellular and molecular disturbances that involve neurons and glial cells in gray and white matter (WM) in prefrontal brain areas. These same areas demonstrate disturbed connectivity with other brain regions in MDD and stress-related disorders. Functional connectivity ultimately depends on signal propagation along WM myelinated axons, and thus on the integrity of nodes of Ranvier (NRs) and their environment. Various glia-derived proteoglycans interact with NR axonal proteins to sustain NR function. It is unclear whether NR length and the content of associated proteoglycans is altered in prefrontal cortex (PFC) WM of human subjects with MDD and in experimentally stressed animals. The length of WM NRs in histological sections from the PFC of 10 controls and 10 MDD subjects, and from the PFC of control and CUS rats was measured. In addition, in WM of the same brain region, five proteoglycans, tenascin-R and NR protein neurofascin were immunostained or their levels measured with western blots. Analysis of covariance and t-tests were used for group comparisons. There was dramatic reduction of NR length in PFC WM in both MDD and CUS rats. Proteoglycan BRAL1 immunostaining was reduced at NRs and in overall WM of MDD subjects, as was versican in overall WM. Phosphacan immunostaining and levels were increased in both in MDD and CUS. Neurofascin immunostaining at NRs and in overall WM was significantly increased in MDD. Reduced length of NRs and increased phosphacan and neurocan in MDD and stressed animals suggest that morphological and proteoglycan changes at NRs in depression may be related to stress exposure and contribute to connectivity alterations. However, differences between MDD and CUS for some NR related markers may point to other mechanisms affecting the structure and function of NRs in MDD.

Perioperative Outcomes in Patients Who Underwent Fibula, Osteocutaneous Radial Forearm, and Scapula Free Flaps: A Multicenter Study.

Importance: Studies comparing perioperative outcomes of fibula free flaps (FFFs), osteocutaneous radial forearm free flaps (OCRFFFs), and scapula free flaps (SFFs) have been limited by insufficient sample size. Objective: To compare the perioperative outcomes of patients who underwent FFFs, OCRFFFs, and SFFs. Design, Setting, and Participants: This cohort study assessed the outcomes of 1022 patients who underwent FFFs, OCRFFFs, or SFFs for head and neck reconstruction performed at 1 of 6 academic medical centers between January 2005 and December 2019. Data were analyzed from September 17, 2021, to June 9, 2022. Main Outcomes and Measures: Patients were stratified based on the flap performed. Evaluated perioperative outcomes included complications (overall acute wound complications, acute surgical site infection [SSI], fistula, hematoma, and flap failure), 30-day readmissions, operative time, and prolonged hospital length of stay (75th percentile, >13 days). Patients were excluded if data on flap type or clinical demographic characteristics were missing. Associations between flap type and perioperative outcomes were analyzed using logistic regression, after controlling for other clinically relevant variables. Adjusted odds ratios (aORs) with 95% CIs were generated. Results: Perioperative outcomes of 1022 patients (mean [SD] age, 60.7 [14.5] years; 676 [66.1%] men) who underwent major osseous head and neck reconstruction were analyzed; 510 FFFs (49.9%), 376 OCRFFFs (36.8%), and 136 SFFs (13.3%) were performed. Median (IQR) operative time differed among flap types (OCRFFF, 527 [467-591] minutes; FFF, 592 [507-714] minutes; SFF, 691 [610-816] minutes). When controlling for SSI, FFFs (aOR, 2.47; 95% CI, 1.36-4.51) and SFFs (aOR, 2.95; 95% CI, 1.37-6.34) were associated with a higher risk of flap loss than OCRFFFs. Compared with OCRFFFs, FFFs (aOR, 1.77; 95% CI, 1.07-2.91) were associated with a greater risk of fistula after controlling for the number of bone segments and SSI. Both FFFs (aOR, 1.77; 95% CI, 1.27-2.46) and SFFs (aOR, 1.68; 95% CI, 1.05-2.69) were associated with an increased risk of 30-day readmission compared with OCRFFFs after controlling for Charlson-Deyo comorbidity score and acute wound complications. Compared with OCRFFFs, FFFs (aOR, 1.78; 95% CI, 1.25-2.54) and SFFs (aOR, 1.96; 95% CI, 1.22-3.13) were associated with a higher risk of prolonged hospital length of stay after controlling for age and flap loss. Conclusions and Relevance: Findings of this cohort study suggest that perioperative outcomes associated with OCRFFFs compare favorably with those of FFFs and SFFs, with shorter operative times and lower rates of flap loss, 30-day readmissions, and prolonged hospital length of stay. However, patients undergoing SFFs represented a more medically and surgically complex population than those undergoing OCRFFFs or FFFs.

Rapid Community Innovation: a Small Urban Liberal Arts Community Response to COVID-19.

Stories of community resilience and rapid innovation have emerged during the global pandemic caused by COVID-19. As communities, organizations, and individuals have had to shift modalities during the pandemic, they have identified ways to sustain community well-being. Prior to COVID-19, colleges and universities were hailed as anchors of economic and social resilience and well-being for communities of place. In this light, this commentary highlights stories of rapid community innovation occurring at Hobart & William Smith Colleges in the Finger Lakes region of New York. A series of vignettes are presented showcasing lessons and on-going questions regarding rapid pivots, community values, and diversity and inclusion during (and after) the pandemic. Overall, these insights can inform future local collaborative development efforts post-COVID-19 between colleges/universities and their local community.

Genetic Regulation of Avian Testis Development.

As in other vertebrates, avian testes are the site of spermatogenesis and androgen production. The paired testes of birds differentiate during embryogenesis, first marked by the development of pre-Sertoli cells in the gonadal primordium and their condensation into seminiferous cords. Germ cells become enclosed in these cords and enter mitotic arrest, while steroidogenic Leydig cells subsequently differentiate around the cords. This review describes our current understanding of avian testis development at the cell biology and genetic levels. Most of this knowledge has come from studies on the chicken embryo, though other species are increasingly being examined. In chicken, testis development is governed by the Z-chromosome-linked DMRT1 gene, which directly or indirectly activates the male factors, HEMGN, SOX9 and AMH. Recent single cell RNA-seq has defined cell lineage specification during chicken testis development, while comparative studies point to deep conservation of avian testis formation. Lastly, we identify areas of future research on the genetics of avian testis development.

The homeobox gene TGIF1 is required for chicken ovarian cortical development and generation of the juxtacortical medulla.

During early embryogenesis in amniotic vertebrates, the gonads differentiate into either ovaries or testes. The first cell lineage to differentiate gives rise to the supporting cells: Sertoli cells in males and pre-granulosa cells in females. These key cell types direct the differentiation of the other cell types in the gonad, including steroidogenic cells. The gonadal surface epithelium and the interstitial cell populations are less well studied, and little is known about their sexual differentiation programs. Here, we show the requirement of the homeobox transcription factor gene TGIF1 for ovarian development in the chicken embryo. TGIF1 is expressed in the two principal ovarian somatic cell populations: the cortex and the pre-granulosa cells of the medulla. TGIF1 expression is associated with an ovarian phenotype in estrogen-mediated sex reversal experiments. Targeted misexpression and gene knockdown indicate that TGIF1 is required, but not sufficient, for proper ovarian cortex formation. In addition, TGIF1 is identified as the first known regulator of juxtacortical medulla development. These findings provide new insights into chicken ovarian differentiation and development, specifically cortical and juxtacortical medulla formation.

COVID-19 mitigation measures to maintain access to essential health services: new opportunities with long-term benefits.

The coronavirus disease 2019 (COVID-19) pandemic has substantially impacted health systems globally. To highlight potential opportunities to improve health service delivery in low- and middle-income countries, we describe lessons learned from published literature and experiences responding to the pandemic. The benefits of healthcare service measures implemented during the pandemic with potential for lasting benefits for strengthening health systems are highlighted: 1) innovative pharmaceutical dispensing methods; 2) appointment-based systems in health facilities; 3) telehealth to provide patient care; 4) task shifting to redistribute healthcare workloads; and 5) home-based pulse oximetry to monitor oxygen levels. These measures can reduce unnecessary contact with healthcare staff while maintaining critical health service delivery and may be of value to continue after the pandemic subsides.

Attrition, physical integrity and insecticidal activity of long-lasting insecticidal nets in sub-Saharan Africa and modelling of their impact on vectorial capacity.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are the primary malaria prevention and control intervention in many parts of sub-Saharan Africa. While LLINs are expected to last at least 3 years under normal use conditions, they can lose effectiveness because they fall out of use, are discarded, repurposed, physically damaged, or lose insecticidal activity. The contributions of these different interrelated factors to durability of nets and their protection against malaria have been unclear. METHODS: Starting in 2009, LLIN durability studies were conducted in seven countries in Africa over 5 years. WHO-recommended measures of attrition, LLIN use, insecticidal activity, and physical integrity were recorded for eight different net brands. These data were combined with analyses of experimental hut data on feeding inhibition and killing effects of LLINs on both susceptible and pyrethroid resistant malaria vectors to estimate the protection against malaria transmission-in terms of vectorial capacity (VC)-provided by each net cohort over time. Impact on VC was then compared in hypothetical scenarios where one durability outcome measure was set at the best possible level while keeping the others at the observed levels. RESULTS: There was more variability in decay of protection over time by country than by net brand for three measures of durability (ratios of variance components 4.6, 4.4, and 1.8 times for LLIN survival, use, and integrity, respectively). In some countries, LLIN attrition was slow, but use declined rapidly. Non-use of LLINs generally had more effect on LLIN impact on VC than did attrition, hole formation, or insecticide loss. CONCLUSIONS: There is much more variation in LLIN durability among countries than among net brands. Low levels of use may have a larger impact on effectiveness than does variation in attrition or LLIN degradation. The estimated entomological effects of chemical decay are relatively small, with physical decay probably more important as a driver of attrition and non-use than as a direct cause of loss of effect. Efforts to maximize LLIN impact in operational settings should focus on increasing LLIN usage, including through improvements in LLIN physical integrity. Further research is needed to understand household decisions related to LLIN use, including the influence of net durability and the presence of other nets in the household.

Insights into Gonadal Sex Differentiation Provided by Single-Cell Transcriptomics in the Chicken Embryo.

Although the genetic triggers for gonadal sex differentiation vary across species, the cell biology of gonadal development was long thought to be largely conserved. Here, we present a comprehensive analysis of gonadal sex differentiation, using single-cell sequencing in the embryonic chicken gonad during sexual differentiation. The data show that chicken embryonic-supporting cells do not derive from the coelomic epithelium, in contrast to other vertebrates studied. Instead, they derive from a DMRT1+/PAX2+/WNT4+/OSR1+ mesenchymal cell population. We find a greater complexity of gonadal cell types than previously thought, including the identification of two distinct sub-populations of Sertoli cells in developing testes and derivation of embryonic steroidogenic cells from a differentiated supporting-cell lineage. Altogether, these results indicate that, just as the genetic trigger for sex differs across vertebrate groups, cell lineage specification in the gonad may also vary substantially.

Well-Differentiated Liposarcoma Localized to the Thyroid Gland.

Liposarcoma of the thyroid gland is a pathology that is rarely encountered in clinical practice, given the paucity of these cases. For the same reason, a definite treatment protocol has not been established for these cases. We present a case of a 49-year-old man who presented with a thyroid mass that was found to be a well-differentiated liposarcoma and was treated surgically with no adjuvant therapy other than close surveillance with clinical examination and MRI scans. On his most recent clinical visit, 9 months after surgery, there was no clinical or radiologic evidence of recurrence and the patient is doing well with good speech and swallow functions and no new symptoms. We also summarize all the cases of this rare pathology presented thus far to the best of our knowledge.

US Centers for Disease Control and Prevention and Its Partners' Contributions to Global Health Security.

To achieve compliance with the revised World Health Organization International Health Regulations (IHR 2005), countries must be able to rapidly prevent, detect, and respond to public health threats. Most nations, however, remain unprepared to manage and control complex health emergencies, whether due to natural disasters, emerging infectious disease outbreaks, or the inadvertent or intentional release of highly pathogenic organisms. The US Centers for Disease Control and Prevention (CDC) works with countries and partners to build and strengthen global health security preparedness so they can quickly respond to public health crises. This report highlights selected CDC global health protection platform accomplishments that help mitigate global health threats and build core, cross-cutting capacity to identify and contain disease outbreaks at their source. CDC contributions support country efforts to achieve IHR 2005 compliance, contribute to the international framework for countering infectious disease crises, and enhance health security for Americans and populations around the world.

The Public Health Legacy of Polio Eradication in Africa.

The legacy of polio in Africa goes far beyond the tragedies of millions of children with permanent paralysis. It has a positive side, which includes the many well-trained polio staff who have vaccinated children, conducted surveillance, tested stool specimens in the laboratories, engaged with communities, and taken care of polio patients. This legacy also includes support for routine immunization services and vaccine introductions and campaigns for other diseases. As polio funding declines, it is time to take stock of the resources made available with polio funding in Africa and begin to find ways to keep some of the talented staff, infrastructure, and systems in place to work on new public health challenges. The partnerships that helped support polio eradication will need to consider funding to maintain and to strengthen routine immunization services and other maternal, neonatal, and child health programs in Africa that have benefitted from the polio eradication infrastructure.

Role of Food Insecurity in Outbreak of Anthrax Infections among Humans and Hippopotamuses Living in a Game Reserve Area, Rural Zambia.

In September 2011, a total of 511 human cases of anthrax (Bacillus anthracis) infection and 5 deaths were reported in a game management area in the district of Chama, Zambia, near where 85 hippopotamuses (Hippopotamus amphibious) had recently died of suspected anthrax. The human infections generally responded to antibiotics. To clarify transmission, we conducted a cross-sectional, interviewer-administered household survey in villages where human anthrax cases and hippopotamuses deaths were reported. Among 284 respondents, 84% ate hippopotamus meat before the outbreak. Eating, carrying, and preparing meat were associated with anthrax infection. Despite the risk, 23% of respondents reported they would eat meat from hippopotamuses found dead again because of food shortage (73%), lack of meat (12%), hunger (7%), and protein shortage (5%). Chronic food insecurity can lead to consumption of unsafe foods, leaving communities susceptible to zoonotic infection. Interagency cooperation is necessary to prevent outbreaks by addressing the root cause of exposure, such as food insecurity.

An Operational Framework for Insecticide Resistance Management Planning.

Arthropod vectors transmit organisms that cause many emerging and reemerging diseases, and their control is reliant mainly on the use of chemical insecticides. Only a few classes of insecticides are available for public health use, and the increased spread of insecticide resistance is a major threat to sustainable disease control. The primary strategy for mitigating the detrimental effects of insecticide resistance is the development of an insecticide resistance management plan. However, few examples exist to show how to implement such plans programmatically. We describe the formulation and implementation of a resistance management plan for mosquito vectors of human disease in Zambia. We also discuss challenges, steps taken to address the challenges, and directions for the future.

A longitudinal study of the durability of long-lasting insecticidal nets in Zambia.

BACKGROUND: A key goal of malaria control is to achieve universal access to, and use of, long-lasting insecticidal nets (LLINs) among people at risk for malaria. Quantifying the number of LLINs needed to achieve and maintain universal coverage requires knowing when nets need replacement. Longitudinal studies have observed physical deterioration in LLINs well before the assumed net lifespan of 3 years. The objective of this study was to describe attrition, physical integrity and insecticide persistence of LLINs over time to assist with better quantification of nets needing replacement. METHODS: 999 LLINs distributed in 2011 in two highly endemic provinces in Zambia were randomly selected, and were enrolled at 12 months old. LLINs were followed every 6 months up to 30 months of age. Holes were counted and measured (finger, fist, and head method) and a proportional hole index (pHI) was calculated. Households were surveyed about net care and repair and if applicable, reasons for attrition. Functional survival was defined as nets with a pHI <643 and present for follow-up. At 12 and 24 months of age, 74 LLINs were randomly selected for examination of insecticidal activity and content using bioassay and chemical analysis methods previously described by the World Health Organization (WHO). RESULTS: A total of 999 LLINs were enrolled; 505 deltamethrin-treated polyester nets and 494 permethrin-treated polyethylene nets. With 74 used to examine insecticide activity, 925 were available for full follow-up. At 30 months, 325 (33 %) LLINs remained. Net attrition was primarily due to disposal (29 %). Presence of repairs and use over a reed mat were significantly associated with larger pHIs. By 30 months, only 56 % of remaining nets met criteria for functional survival. A shorter functional survival was associated with having been washed. At 24 months, nets had reduced insecticidal activity (57 % met WHO minimal criteria) and content (5 % met WHO target insecticide content). CONCLUSIONS: The median functional survival time for LLINs observed the study was 2.5-3 years and insecticide activity and content were markedly decreased by 2 years. A better measure of net survival incorporating insecticidal field effectiveness, net physical integrity, and attrition is needed.

Malaria surveillance in low-transmission areas of Zambia using reactive case detection.

BACKGROUND: Repeat national household surveys suggest highly variable malaria transmission and increasing coverage of high-impact malaria interventions throughout Zambia. Many areas of very low malaria transmission, especially across southern and central regions, are driving efforts towards sub-national elimination. CASE DESCRIPTION: Reactive case detection (RCD) is conducted in Southern Province and urban areas of Lusaka in connection with confirmed incident malaria cases presenting to a community health worker (CHW) or clinic and suspected of being the result of local transmission. CHWs travel to the household of the incident malaria case and screen individuals living in adjacent houses in urban Lusaka and within 140 m in Southern Province for malaria infection using a rapid diagnostic test, treating those testing positive with artemether-lumefantrine. DISCUSSION: Reactive case detection improves access to health care and increases the capacity for the health system to identify malaria infections. The system is useful for targeting malaria interventions, and was instrumental for guiding focal indoor residual spraying in Lusaka during the 2014/2015 spray season. Variations to maximize impact of the current RCD protocol are being considered, including the use of anti-malarials with a longer lasting, post-treatment prophylaxis. CONCLUSION: The RCD system in Zambia is one example of a malaria elimination surveillance system which has increased access to health care within rural communities while leveraging community members to build malaria surveillance capacity.

Long-lasting insecticidal nets in Zambia: a cross-sectional analysis of net integrity and insecticide content.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are a mainstay of malaria prevention in Africa. More LLINs are available now than in any time previously due to increases in funding for malaria control. LLINs are expected to last three to five years before they need to be replaced. Reports of nets lasting less than three years are frequent in Zambia, which, if true, will increase the number of LLINs needed to maintain universal coverage. METHODS: This study collected nets distributed during mass distribution campaigns. One net was collected from each participating home in 12 districts in 2010 and all nets were examined for holes. One household member was surveyed about net use and care. RESULTS: The study collected 713 polyester nets with a median age of 31 months (range 27-44 months, interquartile (IQR) range: 29-36 months), median number of holes was 17 (IQR: 5-33), and median total hole size was 88.3 sq cm (IQR: 14.5-360.4). The median total number of holes did differ by age of the net, from 27-44 months, but not in a linear fashion. The difference in the number of holes in the newest and oldest nets was not statistically significant. The mean deltamethrin level for all nets was 23 mg/sq m (≥8 mg/sq m is considered effective). There was a larger total hole area in the lower half of the nets (repeat measures ANOVA, F=228.43, df=2, p<0.0001) compared to the upper half and roof of the net. Only 8.7% of nets had evidence of repairs. CONCLUSIONS: At 27-30 months, LLINs already had a large total hole surface area that was equivalent to the oldest nets observed. Nets were often tucked under reed mats which may explain the finding that the largest hole area was found in the lower half of the net. Studies need to be conducted prospectively to determine when physical deterioration occurs and why nets are discarded. Re-enforcing the lower half of the sides of LLINs may help decrease holes.

Enhanced surveillance and data feedback loop associated with improved malaria data in Lusaka, Zambia.

BACKGROUND: Accurate and timely malaria data are crucial to monitor the progress towards and attainment of elimination. Lusaka, the capital city of Zambia, has reported very low malaria prevalence in Malaria Indicator Surveys. Issues of low malaria testing rates, high numbers of unconfirmed malaria cases and over consumption of anti-malarials were common at clinics within Lusaka, however. The Government of Zambia (GRZ) and its partners sought to address these issues through an enhanced surveillance and feedback programme at clinic level. METHODS: The enhanced malaria surveillance programme began in 2011 to verify trends in reported malaria, as well as to implement a data feedback loop to improve data uptake, use, and quality. A process of monthly data collection and provision of feedback was implemented within all GRZ health clinics in Lusaka District. During clinic visits, clinic registers were accessed to record the number of reported malaria cases, malaria test positivity rate, malaria testing rate, and proportion of total suspected malaria that was confirmed with a diagnostic test. RESULTS AND DISCUSSION: Following the enhanced surveillance programme, the odds of receiving a diagnostic test for a suspected malaria case increased (OR = 1.54, 95 % CI = 0.96-2.49) followed by an upward monthly trend (OR = 1.05, 95 % CI = 1.01-1.09). The odds of a reported malaria case being diagnostically confirmed also increased monthly (1.09, 95 % CI 1.04-1.15). After an initial 140 % increase (95 % CI = 91-183 %), costs fell by 11 % each month (95 % CI = 5.7-10.9 %). Although the mean testing rate increased from 18.9 to 64.4 % over the time period, the proportion of reported malaria unconfirmed by diagnostic remained high at 76 %. CONCLUSIONS: Enhanced surveillance and implementation of a data feedback loop have substantially increased malaria testing rates and decreased the number of unconfirmed malaria cases and courses of ACT consumed in Lusaka District within just two years. Continued support of enhanced surveillance in Lusaka as well as national scale-up of the system is recommended to reinforce good case management and to ensure timely, reliable data are available to guide targeting of limited malaria prevention and control resources in Zambia.

Progress toward polio eradication - worldwide, 2014-2015.

In 1988, the World Health Assembly of the World Health Organization (WHO) resolved to eradicate polio worldwide. Wild poliovirus (WPV) transmission has been interrupted in all but three countries (Afghanistan, Nigeria, and Pakistan). No WPV type 2 cases have been detected worldwide since 1999, and the last WPV type 3 case was detected in Nigeria in November 2012; since 2012, only WPV type 1 has been detected. Circulating vaccine-derived poliovirus (cVDPV), usually type 2, continues to cause cases of paralytic polio in communities with low population immunity. In 2012, the World Health Assembly declared global polio eradication "a programmatic emergency for global public health", and in 2014, WHO declared the international spread of WPV to previously polio-free countries to be "a public health emergency of international concern". This report summarizes global progress toward polio eradication during 2014-2015 and updates previous reports. In 2014, a total of 359 WPV cases were reported in nine countries worldwide. Although reported WPV cases increased in Pakistan and Afghanistan, cases in Nigeria decreased substantially in 2014, and encouraging progress toward global WPV transmission interruption has occurred. Overcoming ongoing challenges to interruption of WPV transmission globally will require sustained programmatic enhancements, including improving the quality of supplementary immunization activities (SIAs) to interrupt transmission in Afghanistan and Pakistan and to prevent WPV exportation to polio-free countries.