The role of indigenous knowledge and local knowledge in water sector adaptation to climate change in Africa: a structured assessment

Evidence is increasing of human responses to the impacts of climate change in Africa. However, understanding of the effectiveness of these responses for adaptation to climate change across the diversity of African contexts is still limited. Despite high reliance on indigenous knowledge (IK) and local knowledge (LK) for climate adaptation by African communities, potential of IK and LK to contribute to adaptation through reducing climate risk or supporting transformative adaptation responses is yet to be established. Here, we assess the influence of IK and LK for the implementation of water sector adaptation responses in Africa to better understand the relationship between responses to climate change and indigenous and local knowledge systems. Eighteen (18) water adaptation response types were identified from the academic literature through the Global Adaptation Mapping Initiative (GAMI) and intended nationally determined contributions (iNDCs) for selected African countries. Southern, West, and East Africa show relatively high evidence of the influence of IK and LK on the implementation of water adaptation responses, while North and Central Africa show lower evidence. At country level, Zimbabwe displays the highest evidence (77.8%) followed by Ghana (53.6%), Kenya (46.2%), and South Africa (31.3%). Irrigation, rainwater harvesting, water conservation, and ecosystem-based measures, mainly agroforestry, were the most implemented measures across Africa. These were mainly household and individual measures influenced by local and indigenous knowledge. Adaptation responses with IK and LK influence recorded higher evidence of risk reduction compared to responses without IK and LK. Analysis of iNDCs shows the most implemented water adaptation actions in academic literature are consistent with water sector adaptation targets set by most African governments. Yet only 10.4% of the African governments included IK and LK in adaptation planning in the iNDCs. This study recommends a coordinated approach to adaptation that integrates multiple knowledge sources, including IK and LK, to ensure sustainability of both current and potential water adaptation measures in Africa

Determining the Impact of a School-Based Health Education Package for Prevention of Intestinal Worm Infections in the Philippines: Protocol for a Cluster Randomized Intervention Trial

Repeated mass drug administration (MDA) of antihelminthics to at-risk populations is still the main strategy for the control of soil-transmitted helminth (STH) infections. However, MDA, as a stand-alone intervention, does not prevent reinfection. Accordingly, complementary measures to prevent STH reinfection, such as health education and improved sanitation, as part of an integrated control approach, are required to augment the effectiveness of MDA for optimal efficiency and sustainabilitythe UBS-Optimus Foundation, Switzerlan

Carbapenem Resistance in Klebsiella pneumoniae Not Detected by Automated Susceptibility Testing

Detecting β-lactamase–mediated carbapenem resistance among Klebsiella pneumoniae isolates and other Enterobacteriaceae is an emerging problem. In this study, 15 blaKPC-positive Klebsiella pneumoniae that showed discrepant results for imipenem and meropenem from 4 New York City hospitals were characterized by isoelectric focusing; broth microdilution (BMD); disk diffusion (DD); and MicroScan, Phoenix, Sensititre, VITEK, and VITEK 2 automated systems. All 15 isolates were either intermediate or resistant to imipenem and meropenem by BMD; 1 was susceptible to imipenem by DD. MicroScan and Phoenix reported 1 (6.7%) and 2 (13.3%) isolates, respectively, as imipenem susceptible. VITEK and VITEK 2 reported 10 (67%) and 5 (33%) isolates, respectively, as imipenem susceptible. By Sensititre, 13 (87%) isolates were susceptible to imipenem, and 12 (80%) were susceptible to meropenem. The VITEK 2 Advanced Expert System changed 2 imipenem MIC results from >16 μg/mL to <2 μg/mL but kept the interpretation as resistant. The recognition of carbapenem-resistant K. pneumoniae continues to challenge automated susceptibility systems

Status of soil-transmitted helminth infections in schoolchildren in Laguna Province, the Philippines: Determined by parasitological and molecular diagnostic techniques

Background Soil-transmitted helminths (STH) are the most common parasitic infections in impoverished communities, particularly among children. Current STH control is through school-based mass drug administration (MDA), which in the Philippines is done twice annually. As expected, MDA has decreased the intensity and prevalence of STH over time. As a result, the common Kato Katz (KK) thick smear method of detecting STH is less effective because it lacks sensitivity in low intensity infections, making it difficult to measure the impact of deworming programs. Methodology/Principal findings A cross-sectional study was carried out over a four-week period from October 27, 2014 until November 20, 2014 in Laguna province, the Philippines. Stool samples were collected from 263 schoolchildren, to determine the prevalence of STH and compare diagnostic accuracy of multiplex quantitative polymerase chain reaction (qPCR) with the KK. A large discrepancy in the prevalence between the two techniques was noted for the detection of at least one type of STH infection (33.8% by KK vs. 78.3% by qPCR), Ascaris lumbricoides (20.5% by KK vs. 60.8% by qPCR) and Trichuris trichiura (23.6% by KK vs. 38.8% by qPCR). Considering the combined results of both methods, the prevalence of at least one type of helminth infection, A. lumbricoides, and T. trichiura were 83.3%, 67.7%, and 53.6%, respectively. Sensitivity of the qPCR for detecting at least one type of STH infection, A. lumbricoides, and T. trichiura were 94.1%, 89.9%, and 72.3% respectively; whereas KK sensitivity was 40.6%, 30.3%, and 44.0%, respectively. The qPCR method also detected infections with Ancylostoma spp. (4.6%), Necator americanus (2.3%), and Strongyloides stercoralis (0.8%) that were missed by KK. Conclusion/Significance qPCR may provide new and important diagnostic information to improve assessment of the effectiveness and impact of integrated control strategies particularly in areas where large-scale STH control has led to low prevalence and/or intensity of infection.This work is funded by a National Health and Medical Research Council (NHMRC) Australia, project grant (1046901); and the UBS-Optimus Foundation Switzerland. DJG is an Australian NHMRC Career Development Fellow; ACAC is an Australian NHMRC Senior Research Fellow; DPM is an Australian NHMRC Senior Principal Research Fellow

Research priorities for climate mobility

The escalating impacts of climate change on the movement and immobility of people, coupled with false but influential narratives of mobility, highlight an urgent need for nuanced and synthetic research around climate mobility. Synthesis of evidence and gaps across the Intergovernmental Panel on Climate Change (IPCC) Sixth Assessment Report highlight a need to clarify the understanding of what conditions make human mobility an effective adaptation option and its nuanced outcomes, including simultaneous losses, damages, and benefits. Priorities include integration of adaptation and development planning; involuntary immobility and vulnerability; gender; data for cities; risk from responses and maladaptation; public understanding of climate risk; transboundary, compound, and cascading risks; nature-based approaches; and planned retreat, relocation, and heritage. Cutting across these priorities, research modalities need to better position climate mobility as type of mobility, as process, and as praxis. Policies and practices need to reflect the diverse needs, priorities, and experiences of climate mobility, emphasizing capability, choice, and freedom of movement

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

2003. In vitro activities of daptomycin, linezolid, and quinupristin-dalfopristin against a challenge panel of staphylococci and enterococci, including vancomycin-intermediate S. aureus and vancomycin-resistant E. faecium. Microb. Drug Resist

ABSTRACT We assessed the in vitro activities of daptomycin, linezolid, and quinupristin-dalfopristin (QD) against a contemporary challenge panel of 88 staphylococcal and 90 enterococcal isolates. The staphylococci selected included vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant S. aureus, and coagulasenegative staphylococci. Enterococcal isolates included vancomycin-resistant Enterococcus faecium (VREF) containing either vanA, vanB1, or vanD. The MICs of daptomycin, linezolid, and QD were determined using commercial broth microdilution panels. All three VISA isolates were susceptible to daptomycin, linezolid, and QD. QD was the most active agent against staphylococcal isolates (MIC 50 # 0.5 mg/ml and MIC 90 5 1 mg/ml), including those with decreased susceptibility to vancomycin. QD was also the most active agent against VREF (MIC 90 # 0.5 mg/ml). No differences were seen for susceptibility of vanA, vanB1, and vanD VREF strains for daptomycin, linezolid, or QD. Daptomycin was the most effective against E. faecalis. On the basis of manufacturer-suggested interpretive criteria, 92% of isolates were susceptible (MIC 90 5 4 mg/ml). All isolates tested were susceptible to at least one antimicrobial agent for which interpretive criteria have been defined. Population analysis of three S. aureus isolates for which the daptomycin MICs were 8 mg/ml showed a pattern of homogeneous resistance. 38

Antimicrobial Susceptibility Testing of Carbapenems: Multicenter Validity Testing and Accuracy Levels of Five Antimicrobial Test Methods for Detecting Resistance in Enterobacteriaceae and Pseudomonas aeruginosa Isolates

From January 1996 to May 1999, Project ICARE (Intensive Care Antimicrobial Resistance Epidemiology) received 448 nonduplicate clinical isolates of Enterobacteriaceae and Pseudomonas aeruginosa that were reported to be imipenem intermediate or resistant. However, broth microdilution (BMD) confirmatory testing at the Project ICARE central laboratory confirmed this result in only 11 of 123 (8.9%) Enterobacteriaceae isolates and 241 of 325 (74.2%) P. aeruginosa isolates. To investigate this overdetection of imipenem resistance, we tested 204 selected isolates from the Project ICARE collection plus five imipenem-resistant challenge strains at the Centers for Disease Control and Prevention against imipenem and meropenem by agar dilution, disk diffusion, Etest (AB BIODISK North America, Inc., Piscataway, N.J.), two MicroScan WalkAway conventional panels (Neg MIC Plus 3 and Neg Urine Combo 3) (Dade MicroScan, Inc., West Sacramento, Calif.), and two Vitek cards (GNS-116 containing meropenem and GNS-F7 containing imipenem) (bioMérieux Vitek, Inc., Durham, N.C.). The results of each test method were compared to the results of BMD testing using in-house-prepared panels. Seven imipenem-resistant and five meropenem-resistant isolates of Enterobacteriaceae and 43 imipenem-resistant and 21 meropenem-resistant isolates of P. aeruginosa were identified by BMD. For Enterobacteriaceae, the imipenem and meropenem test methods produced low numbers of very major and major errors. All test systems in the study produced low numbers of very major and major errors when P. aeruginosa was tested against imipenem and meropenem, except for Vitek testing (major error rate for imipenem, 20%). Further testing conducted in 11 of the participating ICARE hospital laboratories failed to pinpoint the factors responsible for the initial overdetection of imipenem resistance. However, this study demonstrated that carbapenem testing difficulties do exist and that laboratories should consider using a second, independent antimicrobial susceptibility testing method to validate carbapenem-intermediate and -resistant results