Estimating epidemiological parameters from experiments in vector access to host plants, the method of matching gradients.

Estimation of pathogenic life-history values, for instance the duration a pathogen is retained in an insect vector (i.e., retention period) is of particular importance for understanding plant disease epidemiology. How can we extract values for these epidemiological parameters from conventional small-scale laboratory experiments in which transmission success is measured in relation to durations of vector access to host plants? We provide a solution to this problem by deriving formulae for the empirical curves that these experiments produce, called access period response curves (i.e., transmission success vs access period). We do this by writing simple equations for the fundamental life-cycle components of insect vectors in the laboratory. We then infer values of epidemiological parameters by matching the theoretical and empirical gradients of access period response curves. Using the example of Cassava brown streak virus (CBSV), which has emerged in sub-Saharan Africa and now threatens regional food security, we illustrate the method of matching gradients. We show how applying the method to published data produces a new understanding of CBSV through the inference of retention period, acquisition period and inoculation period parameters. We found that CBSV is retained for a far shorter duration in its insect vector (Bemisia tabaci whitefly) than had previously been assumed. Our results shed light on a number of critical factors that may be responsible for the transition of CBSV from sub- to super-threshold R0 in sub-Saharan Africa. The method is applicable to plant pathogens in general, to supply epidemiological parameter estimates that are crucial for practical management of epidemics and prediction of pandemic risk

CLEANED documentation: Conceptual overview of CLEANED and parameterisation of a CLEANED tool for Lushoto, Tanzania

This companion document provides supporting information about the “Comprehensive Livestock Environmental Assessment for improved Nutrition, a secured Environment and sustainable Development along livestock value chains” (CLEANED) tool and how it has been parameterised for use in Tanzania, including a description of the study area. CLEANED is a spatial multi-dimensional and rapid environmental impact assessment framework of livestock value chains. It was developed to identify potential positive and negative environmental impacts of proposed practices or development interventions, and a ddresses the current gap in environmental assessment methods by being a rapid, multi-dimensional assessment tool including various spatial and temporal scales. For the “Researchand Learning for Sustainable Intensification of Smallholder Livestock Value Chains”(ResLeSS) project, CLEANED has been applied in Burkina Faso, Ethiopia and Tanzania. The CLEANED model focuses on environmental impact of livestock value chains associated with feed production, which constitutes the major source of environmental impacts related to livestock value chains.Environmental impact is categorized into four key impact dimensions that are used as proxies to assess environmental change. Three dimensions, I) water, II) land/soil and III) biodiversity, are impacting the local environment, while the fourth, IV) greenhouse gas (GHG) emissions, is used to assess the contribution to global climate change (CC). The tool uses pixel based modelling with spatial input data to generate output maps showing the distribution of environmental change in relation to baseline conditions. As such the CLEANED tool can be seen as a way to give meaning to the many openly available but difficult to interpret GIS data for the context of transforming livestock value chains. In Tanzania, the focus is smallscale dairy production in the district of Lushoto, Tanga Region, Tanzania. Lushoto is located is in the mountains near to the Kenyan boarder. The reconnaissance work has shown that smallholders keep cattle for dairy in three different systems: extensive in the lowland, semi-intensive and intensive in the highlands. Yet, discussion about future developments in the first ResLess workshop have pointed out that in all three systems smallholders are trying to improve the breeds. This is why the CLEANED Tanzania works with breeds, namely preliminary local breeds, cross breeds (with 65-85% exotic genes), almost pure breed (more than 85% exotic breed). Local breeds are mainly found in t he lowlands and are mainly fed on natural grasses and some crop residue. The cross-breeds are found in the highlands and are mainly fed on a mix of natural grass, crop residues and a bit of concentrate. In this system the main issue is the feed shortage in the dry season, which can be addressed with the production of hay and silage. Also planted feed, which has higher nutritional value than crop residues could be used to improve milk productivity per cow. The almost pure breed is a category is only marginal ly existent in Lushoto in the current situation. These animals needs much more care and hardly feed on natural grasses and crop residues, but mainly on planted fodder and concentrates. Initial livestock population numbers to parameterise the ‘base run’ in CLEANED (a scenario that represent the present day situation) are calculated for the three categories using a triangulation between the participatory GIS activities in the first workshop, freely accessible spatial data layers and household survey and verified against provincial livestock population statistics from FAO and data available from the district office and Demographic Health Surveys (DHS). To make it easy and fast for users to build scenarios of livestock production in Lushoto (how to produce in each category and how many animals per category) in a workshop setting, a set of ‘vignettes’ was produced that describe credible combinations of feed baskets with animal productivity for each animal category representing two or three different livestock management options within each production category. These vignettes are pre- set within the CLEANED tool code, so that the non-expert can develop credible scenarios. This document accompanies the report of the second ResLeSS workshop in Lushoto, Tanzania, titled “ Exploring alternatives for livestock production in Lushoto, Tanzania: Playing the Transformation Game” , which presents the design and results of the workshop

Skin Cancers Among Albinos at a University Teaching Hospital in Northwestern Tanzania: A Retrospective Review of 64 Cases.

Skin cancers are a major risk associated with albinism and are thought to be a major cause of death in African albinos. The challenges associated with the care of these patients are numerous and need to be addressed. The aim of this study was to outline the pattern and treatment outcome of skin cancers among albinos treated at our centre and to highlight challenges associated with the care of these patients and proffer solutions for improved outcome. This was a retrospective study of all albinos with a histopathological diagnosis of skin cancer seen at Bugando Medical Centre from March 2001 to February 2010. Data collected were analyzed using descriptive statistics. A total of 64 patients were studied. The male to female ratio was 1.5:1. The median age of patients was 30 years. The median duration of illness at presentation was 24 months. The commonest reason for late presentation was financial problem. Head and the neck was the most frequent site afflicted in 46(71.8%) patients. Squamous cell carcinoma was the most common histopathological type in 75% of cases. Surgical operation was the commonest modality of treatment in 60 (93.8%) patients. Radiotherapy was given in 24(37.5%) patients. Twenty-seven (42.2%) of the patients did not complete their treatment due to lack of funds. Local recurrence following surgical treatment was recorded in 6 (30.0%) patients. Only thirty-seven (61.7%) patients were available for follow-up at 6-12 months and the remaining patients were lost to follow-up. Skin cancers are the most common cancers among albinos in our environment. Albinism and exposure to ultraviolet light appears to be the most important risk factor in the development of these cancers. Late presentation and failure to complete treatment due to financial difficulties and lack of radiotherapy services at our centre are major challenges in the care of these patients. Early institution of preventive measures, early presentation and treatment, and follow-up should be encouraged in this population for better outcome

Trends in the clinical characteristics of HIV-infected patients initiating antiretroviral therapy in Kenya, Uganda and Tanzania between 2002 and 2009

East Africa has experienced a rapid expansion in access to antiretroviral therapy (ART) for HIV-infected patients. Regionally representative socio-demographic, laboratory and clinical characteristics of patients accessing ART over time and across sites have not been well described. We conducted a cross-sectional analysis of characteristics of HIV-infected adults initiating ART between 2002 and 2009 in Kenya, Uganda and Tanzania and in the International Epidemiologic Databases to Evaluate AIDS Consortium. Characteristics associated with advanced disease (defined as either a CD4 cell count level of less than 50 cells/mm3 or a WHO Stage 4 condition) at the time of ART initiation and use of stavudine (D4T) or nevirapine (NVP) were identified using a log-link Poisson model with robust standard errors. Among 48,658 patients (69% from Kenya, 22% from Uganda and 9% from Tanzania) accessing ART at 30 clinic sites, the median age at the time of ART initiation was 37 years (IQR: 31-43) and 65% were women. Pre-therapy CD4 counts rose from 87 cells/mm3 (IQR: 26-161) in 2002-03 to 154 cells/mm3 (IQR: 71-233) in 2008-09 (p<0.001). Accessing ART at advanced disease peaked at 35% in 2005-06 and fell to 27% in 2008-09. D4T use in the initial regimen fell from a peak of 88% in 2004-05 to 59% in 2008-09, and a greater extent of decline was observed in Uganda than in Kenya and Tanzania. Self-pay for ART peaked at 18% in 2003, but fell to less than 1% by 2005. In multivariable analyses, accessing ART at advanced immunosuppression was associated with male sex, women without a history of treatment for prevention of mother to child transmission (both as compared with women with such a history) and younger age after adjusting for year of ART initiation and country of residence. Receipt of D4T in the initial regimen was associated with female sex, earlier year of ART initiation, higher WHO stage, and lower CD4 levels at ART initiation and the absence of co-prevalent tuberculosis. Public health ART services in east Africa have improved over time, but the fraction of patients accessing ART with advanced immunosuppression is still high, men consistently access ART with more advanced disease, and D4T continues to be common in most settings. Strategies to facilitate access to ART, overcome barriers among men and reduce D4T use are needed

Perceptions, attitudes, and willingness of healthcare and frontline workers to participate in an Ebola vaccine trial in Uganda.

BACKGROUND: Understanding the knowledge, perception and attitudes towards Ebola vaccines is an important factor in ensuring future use of these vaccines. A qualitative methods study embedded in an Ebola vaccine immunogenicity and safety trial (NCT04028349) was conducted to explore the knowledge and perceptions of healthcare (HCWs) and frontline workers (FLWs), about Ebola vaccines and their willingness to participate or recommend participation in Uganda. METHOD: We carried out focus group discussions and semi-structured interviews before and after vaccination, with 70 HCWs and FLWs who consented to participate in the trial, and in the qualitative component, from August to September 2019. Data were analysed using thematic content analysis. RESULTS: Respondents showed good knowledge about Ebola and the vaccines in general, and had wide access to information through several channels, including the study team. On prevention, particular attention was given to effective communication within health facilities. Misconceptions were mainly around route of transmission, animal origin and types of vaccines. Previous fears were based on rumours circulating in the community, mainly about the presence of the virus in the vaccine, side effects and intention to harm (e.g. by "the whites"), ultimately insisting on transparency, trust and involvement of local leaders. Acceptability of participation was motivated by the need to protect self and others, and the willingness to advance research. Majority were willing to recommend participation to their community. CONCLUSIONS: Overall, information sharing leads to a better understanding and acceptance of vaccine trials and a positive vaccination experience can be a deciding factor in the acceptance of others. Particular attention should be paid to involving the community in addressing misconceptions and fears, while ensuring that participants have access to vaccination sites in terms of transport, and that they are properly accommodated at the study site including staying for a reasonable period of time

Distribution of causes of maternal mortality among different socio-demographic groups in Ghana; a descriptive study

BACKGROUND: Ghana's maternal mortality ratio remains high despite efforts made to meet Millennium Development Goal 5. A number of studies have been conducted on maternal mortality in Ghana; however, little is known about how the causes of maternal mortality are distributed in different socio-demographic subgroups. Therefore the aim of this study was to assess and analyse the causes of maternal mortality according to socio-demographic factors in Ghana.METHODS: The causes of maternal deaths were assessed with respect to age, educational level, rural/urban residence status and marital status. Data from a five year retrospective survey was used. The data was obtained from Ghana Maternal Health Survey 2007 acquired from the database of Ghana Statistical Service. A total of 605 maternal deaths within the age group 12-49 years were analysed using frequency tables, cross-tabulations and logistic regression.RESULTS: Haemorrhage was the highest cause of maternal mortality (22.8%). Married women had a significantly higher risk of dying from haemorrhage, compared with single women (adjusted OR = 2.7, 95%CI = 1.2-5.7). On the contrary, married women showed a significantly reduced risk of dying from abortion compared to single women (adjusted OR = 0.2, 95%CI = 0.1-0.4). Women aged 35-39 years had a significantly higher risk of dying from haemorrhage (aOR 2.6, 95%CI = 1.4-4.9), whereas they were at a lower risk of dying from abortion (aOR 0.3, 95% CI = 0.1-0.7) compared to their younger counterparts. The risk of maternal death from infectious diseases decreased with increasing maternal age, whereas the risk of dying from miscellaneous causes increased with increasing age.CONCLUSIONS: The study shows evidence of variations in the causes of maternal mortality among different socio-demographic subgroups in Ghana that should not be overlooked. It is therefore recommended that interventions aimed at combating the high maternal mortality in Ghana should be both cause-specific as well as target-specific

Effect of malaria transmission reduction by insecticide-treated bed nets (ITNs) on the genetic diversity of Plasmodium falciparum merozoite surface protein (MSP-1) and circumsporozoite (CSP) in western Kenya

Abstract Background: Although several studies have investigated the impact of reduced malaria transmission due to insecticide-treated bed nets (ITNs) on the patterns of morbidity and mortality, there is limited information on their effect on parasite diversity. Methods: Sequencing was used to investigate the effect of ITNs on polymorphisms in two genes encoding leading Plasmodium falciparum vaccine candidate antigens, the 19 kilodalton blood stage merozoite surface protein-1 (MSP-1 19kDa ) and the Th2R and Th3R T-cell epitopes of the pre-erythrocytic stage circumsporozoite protein (CSP) in a large community-based ITN trial site in western Kenya. The number and frequency of haplotypes as well as nucleotide and haplotype diversity were compared among parasites obtained from children &lt;5 years old prior to the introduction of ITNs (1996) and after 5 years of high coverage ITN use (2001). Results: A total of 12 MSP-1 19kDa haplotypes were detected in 1996 and 2001. The Q-KSNG-L and E-KSNG-L haplotypes corresponding to the FVO and FUP strains of P. falciparum were the most prevalent (range 32-37%), with an overall haplotype diversity of &gt; 0.7. No MSP-1 19kDa 3D7 sequence-types were detected in 1996 and the frequency was less than 4% in 2001. The CSP Th2R and Th3R domains were highly polymorphic with a total of 26 and 14 haplotypes, respectively detected in 1996 and 34 and 13 haplotypes in 2001, with an overall haplotype diversity of &gt; 0.9 and 0.75 respectively. The frequency of the most predominant Th2R and Th3R haplotypes was 14 and 36%, respectively. The frequency of Th2R and Th3R haplotypes corresponding to the 3D7 parasite strain was less than 4% at both time points. There was no significant difference in nucleotide and haplotype diversity in parasite isolates collected at both time points

The Effectiveness of Non-pyrethroid Insecticide-treated Durable Wall Lining to Control Malaria in Rural Tanzania: Study Protocol for a Two-armed Cluster Randomized Trial.

Despite considerable reductions in malaria achieved by scaling-up long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), maintaining sustained community protection remains operationally challenging. Increasing insecticide resistance also threatens to jeopardize the future of both strategies. Non-pyrethroid insecticide-treated wall lining (ITWL) may represent an alternate or complementary control method and a potential tool to manage insecticide resistance. To date no study has demonstrated whether ITWL can reduce malaria transmission nor provide additional protection beyond the current best practice of universal coverage (UC) of LLINs and prompt case management. A two-arm cluster randomized controlled trial will be conducted in rural Tanzania to assess whether non-pyrethroid ITWL and UC of LLINs provide added protection against malaria infection in children, compared to UC of LLINs alone. Stratified randomization based on malaria prevalence will be used to select 22 village clusters per arm. All 44 clusters will receive LLINs and half will also have ITWL installed on interior house walls. Study children, aged 6 months to 11 years old, will be enrolled from each cluster and followed monthly to estimate cumulative incidence of malaria parasitaemia (primary endpoint), time to first malaria episode and prevalence of anaemia before and after intervention. Entomological inoculation rate will be estimated using indoor CDC light traps and outdoor tent traps followed by detection of Anopheles gambiae species, sporozoite infection, insecticide resistance and blood meal source. ITWL bioefficacy and durability will be monitored using WHO cone bioassays and household surveys, respectively. Social and cultural factors influencing community and household ITWL acceptability will be explored through focus-group discussions and in-depth interviews. Cost-effectiveness, compared between study arms, will be estimated per malaria case averted. This protocol describes the large-scale evaluation of a novel vector control product, designed to overcome some of the known limitations of existing methods. If ITWL is proven to be effective and durable under field conditions, it may warrant consideration for programmatic implementation, particularly in areas with long transmission seasons and where pyrethroid-resistant vectors predominate. Trial findings will provide crucial information for policy makers in Tanzania and other malaria-endemic countries to guide resource allocations for future control efforts

Functional Connectivity fMRI of the Rodent Brain: Comparison of Functional Connectivity Networks in Rat and Mouse

At present, resting state functional MRI (rsfMRI) is increasingly used in human neuropathological research. The present study aims at implementing rsfMRI in mice, a species that holds the widest variety of neurological disease models. Moreover, by acquiring rsfMRI data with a comparable protocol for anesthesia, scanning and analysis, in both rats and mice we were able to compare findings obtained in both species. The outcome of rsfMRI is different for rats and mice and depends strongly on the applied number of components in the Independent Component Analysis (ICA). The most important difference was the appearance of unilateral cortical components for the mouse resting state data compared to bilateral rat cortical networks. Furthermore, a higher number of components was needed for the ICA analysis to separate different cortical regions in mice as compared to rats