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Objective: The aim of this study was to determine the prevalence of hepatitis B surface antigen (HBsAg) among febrile individuals tested at Mercy Hospital Research Laboratory (MHRL) in Bo, Sierra Leone. Results: A total of 860 febrile individuals ages 5 years and older were tested by MHRL between July 2012 and June 2013 with a Standard Diagnostics Bioline HBsAg rapid diagnostic test. The overall HBsAg prevalence rate was 13.7%, including a rate of 15.5% among males and 12.6% among females. The HBsAg rate did not differ by child or adult age group (p > 0.5). The prevalence rate in Bo was similar to the 11-15% HBsAg prevalence rates reported in the past decade from other studies across West Africa. Scaling up the infant hepatitis B vaccination program in Sierra Leone will be important for reducing the future burden of disease and premature death attributable to chronic viral hepatitis B disease. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF) is a mosquito-borne filarial disease targeted for elimination by the year 2020. The Republic of Togo undertook mass treatment of entire endemic communities from 2000 to 2009 to eliminate the transmission of the disease and is currently the first sub-Saharan African country to be validated by WHO for the elimination of LF as a public health problem. However, post-validation surveillance activities are required to ensure the gains achieved are sustained. This survey assessed the mosquito vectors of the disease and determined the presence of infection in these vectors, testing the hypothesis that transmission has already been interrupted in Togo. Method: Mosquitoes were collected from 37 villages located in three districts in one of four evaluation units in the country. In each district, 30 villages were selected based on probability proportionate to size; eight villages (including one of the 30 villages already selected) where microfilaremia-positive cases had been identified during post-treatment surveillance activities were intentionally sampled. Mosquitoes were collected using pyrethrum spray collections (PSC) in households randomly selected in all villages for five months. In the purposefully selected communities, mosquitoes were also collected using human landing collections (HLC) and exit traps (ET). Collected mosquitoes were identified morphologically, and the identification of Wuchereria bancrofti DNA in the mosquitoes was based on the pool screening method, using the LAMP assay. Results: A total of 15,539 mosquitoes were collected during the study. Anopheles gambiae (72.6%) was the predominant LF vector collected using PSC. Pool screen analysis of 9191 An. gambiae in 629 pools revealed no mosquitoes infected with W. bancrofti (0%; CI: 0-0.021). Conclusions: These results confirm the findings of epidemiological transmission assessment surveys conducted in 2012 and 2015, which demonstrated the absence of LF transmission in Togo. The challenges of implementing molecular xenomonitoring are further discussed. [ABSTRACT FROM AUTHOR]

Background: Reliable mapping of soil-transmitted helminth (STH) parasites requires rigorous statistical and machine learning algorithms capable of integrating the combined influence of several determinants to predict distributions. This study tested whether combining edaphic predictors with relevant environmental predictors improves model performance when predicting the distribution of STH, Ascaris lumbricoides and hookworms at a national scale in Zimbabwe. Methods: Geo-referenced parasitological data obtained from a 2010/2011 national survey indicating a confirmed presence or absence of STH among school children aged 10-15 years was used to calibrate ten species distribution models (SDMs). The performance of SDMs calibrated with a set of environmental and edaphic variables was compared to that of SDMs calibrated with environmental variables only. Model performance was evaluated using the true skill statistic and receiver operating characteristic curve. Results: Results show a significant improvement in model performance for both A. lumbricoides and hookworms for all ten SDMs after edaphic variables were combined with environmental variables in the modelling of the geographical distribution of the two STHs at national scale. Using the top three performing models, a consensus prediction was developed to generate the first continuous maps of the potential distribution of the two STHs in Zimbabwe. Conclusions: The findings from this study demonstrate significant model improvement if relevant edaphic variables are included in model calibration resulting in more accurate mapping of STH. The results also provide spatially-explicit information to aid targeted control of STHs in Zimbabwe and other countries with STH burden. [ABSTRACT FROM AUTHOR]

Background: Community engagement (CE) models have provided much needed guidance for researchers to conceptualise and design engagement strategies for research projects. Most of the published strategies, however, still show very limited contribution of the community to the engagement process. One way of achieving this is to document experiences of community members in the CE processes during project implementation. The aim of our study was to explore the experiences of two research naïve communities, regarding a CE strategy collaboratively developed by researchers and study communities in a multicountry study.Methods: The study was carried out in two research naïve communities; Gwanda, Zimbabwe and uMkhanyakude, South Africa. The multicentre study was a community based participatory ecohealth multicentre study. A qualitative case study approach was used to explore the CE strategy. Data was collected through Focus Group Discussions, Key Informant Interviews and Direct Observations. Data presented in this paper was collected at three stages of the community engagement process; soon after community entry, soon after sensitisation and during study implementation. Data was analysed through thematic analysis.Results: The communities generally had positive experiences of the CE process. They felt that the continuous solicitation of their advice and preferences enabled them to significantly contribute to shaping the engagement process. Communities also perceived the CE process as having been flexible, and that the researchers had presented an open forum for sharing responsibilities in all decision making processes of the engagement process.Conclusions: This study has demonstrated that research naïve communities can significantly contribute to research processes if they are adequately engaged. The study also showed that if researchers put in maximum effort to demystify the research process, communities become empowered and participate as partners in research. [ABSTRACT FROM AUTHOR]

Background: Although there has been a decline in the number of malaria cases in Zimbabwe since 2010, the disease remains the biggest public health threat in the country. Gwanda district, located in Matabeleland South Province of Zimbabwe has progressed to the malaria pre-elimination phase. The aim of this study was to determine the spatial distribution of malaria incidence at ward level for improving the planning and implementation of malaria elimination in the district. Methods: The Poisson purely spatial model was used to detect malaria clusters and their properties, including relative risk and significance levels at ward level. The geographically weighted Poisson regression (GWPR) model was used to explore the potential role and significance of environmental variables [rainfall, minimum and maximum temperature, altitude, Enhanced Vegetation Index (EVI), Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI), rural/urban] and malaria control strategies [indoor residual spraying (IRS) and long-lasting insecticide-treated nets (LLINs)] on the spatial patterns of malaria incidence at ward level. Results: Two significant clusters (p < 0.05) of malaria cases were identified: (1) ward 24 south of Gwanda district and (2) ward 9 in the urban municipality, with relative risks of 5.583 and 4.316, respectively. The semiparametric-GWPR model with both local and global variables had higher performance based on AICc (70.882) compared to global regression (74.390) and GWPR which assumed that all variables varied locally (73.364). The semiparametric-GWPR captured the spatially non-stationary relationship between malaria cases and minimum temperature, NDVI, NDWI, and altitude at the ward level. The influence of LLINs, IRS and rural or urban did not vary and remained in the model as global terms. NDWI (positive coefficients) and NDVI (range from negative to positive coefficients) showed significant association with malaria cases in some of the wards. The IRS had a protection effect on malaria incidence as expected. Conclusions: Malaria incidence is heterogeneous even in low-transmission zones including those in pre-elimination phase. The relationship between malaria cases and NDWI, NDVI, altitude and minimum temperature may vary at local level. The results of this study can be used in planning and implementation of malaria control strategies at district and ward levels. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to examine the prevalence of HIV among febrile patients seeking care in Mercy Hospital, Bo, Sierra Leone, in 2012-2013. Results: A total of 1207 febrile persons were tested for HIV with DetermineTMand SD Bioline rapid diagnostic tests kits that detect the presence of HIV antibodies and HIV p24 antigens. The overall prevalence of HIV among the tested patients was 8.9%, which is considerably higher than the < 2% prevalence of HIV reported previously in the general population. While these results are not sufficient to prove a causal relationship, the obtained data imply that HIV positive individuals may be more likely to suffer from febrile infectious diseases than individuals without HIV infection. Increasing the availability and use of HIV testing services will allow antiretroviral therapy to be accessed in a timely manner and improve health status among people living with HIV. [ABSTRACT FROM AUTHOR]

Background: Given that increase in temperature may alter host-parasite relationships, the anticipated rise in temperature due to global warming might change transmission patterns of certain diseases. However, the extent to which this will happen is not well understood. Methods: Using a host-parasite system involving Bulinus globosus and Schistosoma haematobium, we assessed the effect of temperature on snail fecundity, growth, survival and parasite development under laboratory conditions. Results: Our results show that temperature may have a non-linear effect on snail fecundity and snail growth. Snails maintained at 15.5 °C and 36.0 °C did not produce egg masses while those maintained at 25.8 °C laid 344 and 105 more egg masses than snails at 31.0 °C and 21.2 °C, respectively. Attainment of patency led to a reduction in egg mass production among the snails. However, the reduction in fecundity for snails maintained at 21.2 °C occurred before snails started shedding cercariae. Parasite development was accelerated at high temperatures with snails maintained at 31.0 °C reaching patency after three weeks. Furthermore, snail growth rate was highest at 25.8 °C while it was inhibited at 15.5 °C and reduced at 31.0 °C. Increase in temperature increased snail mortality rates. Snails maintained at 36.0 °C had the shortest survival time while those maintained at 15.5 °C had the longest survival time. Conclusions: We concluded that temperature influences fecunxdity, growth, survival and parasite development in the snail and thus dictates the time it takes the parasite to complete the life cycle. This has implications on transmission of schistosomiasis in the context of global warming. [ABSTRACT FROM AUTHOR]

Background: Community Engagement (CE) in health research ensures that research is consistent with the sociocultural, political and economic contexts where the research is conducted. The greatest challenges for researchers are the practical aspects of CE in multicentre health research. This study describes the CE in an ecohealth community-based research project focusing on two vulnerable and research naive rural communities. Methods: A qualitative, longitudinal multiple case study approach was used. Data was collected through Participatory Rural Appraisals, Focus Group Discussions, In-depth Interviews, and observations. Results: The two sites had different cultural values, research literacy levels, and political and administrative structures. The engagement process included 1) introductions to the administrative and political leaders of the area; 2) establishing a community advisory mechanism; 3) community empowerment and 4) initiating sustainable post-study activities. In both sites the study employed community liaison officers to facilitate the community entry and obtaining letters of permission. Both sites opted to form Community Advisory Boards as their main advisory mechanism together with direct advice from community leaders. Empowerment was achieved through the education of ordinary community members at biannual meetings, employment of community research assistants and utilising citizen science. Through the research assistants and the citizen science group, the study has managed to initiate activities that the community will continue to utilise after the study ends. General strategies developed are similar in principle, but implementation and emphasis of various aspects differed in the two communities. Conclusions: We conclude that it is critical that community engagement be consistent with community values and attitudes, and considers community resources and capacity. A CE strategy fully involving the community is constrained by community research literacy levels, time and resources, but creates a conducive research environment. [ABSTRACT FROM AUTHOR]

Background: Over the past 15 years, mortality and morbidity due to malaria have been reduced substantially in sub-Saharan Africa and local elimination has been achieved in some settings. This study addresses the bio-ecology of larval and adult stages of malaria vectors, Plasmodium infection in Anopheles gambiae s.l. in the city of Conakry, Guinea, and discusses the prospect for malaria elimination. Methods: Water bodies were prospected to identify potential mosquito breeding sites for 6 days each in the dry season (January 2013) and in the rainy season (August 2013), using the dipping method. Adult mosquitoes were collected in 15 communities in the five districts of Conakry using exit traps and indoor spraying catches over a 1-year period (November 2012 to October 2013). Molecular approaches were employed for identification of Anopheles species, including An. coluzzii and An. gambiae s.s. Individual An. gambiae mosquitoes were tested for Plasmodium falciparum and P. vivax sporozoites using the VecTest™ malaria panel assay and an enzyme-linked immunosorbent assay. A systematic research of Ministry of Health statistical yearbooks was performed to determine malaria prevalence in children below the age of 5 years. Results: Culex larval breeding sites were observed in large numbers throughout Conakry in both seasons. While Anopheles larval breeding sites were less frequent than Culex breeding sites, there was a high odds of finding An. gambiae mosquito larvae in agricultural sites during the rainy season. Over the 1-year study period, a total of 14,334 adult mosquitoes were collected; 14,135 Culex (98.6 %) and 161 (1.1 %) from the An. gambiae complex. One-hundred and twelve Anopheles mosquitoes, mainly collected from rice fields and gardens, were subjected to molecular analysis. Most of the mosquitoes were An. gambiae s.s. (n = 102; 91.1 %) while the remaining 10 (8.9 %) were An. melas. The molecular M form of An. gambiae s.s. was predominant (n = 89; 79.5 %). The proportions of kdr genotype in the An. gambiae s.s. M and S form were 65.2 and 81.8 % (n = 9), respectively. No sporozoite infection were detected in any of the mosquitoes tested. The prevalence of Plasmodium recorded in children aged below 5 years was relatively low and varied between 2.2 and 7.6 % from 2009 to 2012. Conclusions: The low density of larval and adult stages of Anopheles mosquitoes, the absence of infected An. gambiae species and the low prevalence of Plasmodium in under 5-year-old children are important features that might facilitate malaria elimination in Conakry. The heterogeneity in species composition and resistance profiles call for vector control interventions that are tailored to the local bio-ecological setting. [ABSTRACT FROM AUTHOR]

Malaria is a global public health problem, with about 3.2 billion people at risk of infection. The populations at risk mainly reside in Africa, Asia and America, with African populations accounting for the largest burden of the disease. In 2013, close to 198 million malaria cases were reported, leading to 584,000 deaths. Much (90%) of the mortality rates were recorded from the World Health Organization (WHO) database in the African region and 78% of these occurred in children under the age of five. In Zimbabwe, approximately half of the population is at risk of infection with malaria. Insecticide residual spraying (IRS) has been documented as an effective way to control malaria and has been adopted globally by the WHO and national governments. However, both insecticide resistance and climate change threaten to reverse the progress made by IRS in malaria control. Resistance has been reported in all four classes of insecticides approved by the WHO for vector control intervention. Variability of environmental temperature is suspected to complicate the situation through alteration in the genetic structure, and enzyme and protein profiles of mosquitoes. In Zimbabwe, little research has been done on the interaction between climate change, temperature variability and insecticide resistance in malarial mosquitoes over time. Such information is important for informing policies on insecticide selection for IRS. We reviewed literature on insecticide sensitivity among malarial mosquitoes in Zimbabwe from 1972 to 2014. International peer-reviewed articles on insecticide sensitivity in Zimbabwe, published in English in this time period, were searched using MEDLINE® (PubMed), Google Scholar, Google and grey literature. Eight publications were eligible for the present study, with one of the articles being a review paper. Six articles covered insecticide resistance, while the other two articles, published in 2000, were about the absence of resistance. Contradicting resistance results were reported in 2014. The insecticide sensitivity status and distribution of insecticide resistance in mosquitoes are still under debate in Zimbabwe, as studies report differing results. The resistance trend in Zimbabwe is characterised by fluctuations in the status of the sensitivity of existing insecticides. Inconsistencies in data collection methods may be responsible for the inconsistencies in the results. None of the studies have determined a link between climate/temperature variability and insecticide resistance as yet. The current insecticide sensitivity status of mosquitoes still needs to be verified. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF) is one of the neglected tropical diseases targeted for global elimination. The ability to interrupt transmission is, partly, influenced by the underlying intensity of transmission and its geographical variation. This information can also help guide the design of targeted surveillance activities. The present study uses a combination of geostatistical and mathematical modelling to predict the prevalence and transmission intensity of LF prior to the implementation of large-scale control in sub-Saharan Africa. Methods: A systematic search of the literature was undertaken to identify surveys on the prevalence of Wuchereria bancrofti microfilaraemia (mf), based on blood smears, and on the prevalence of antigenaemia, based on the use of an immuno-chromatographic card test (ICT). Using a suite of environmental and demographic data, spatiotemporal multivariate models were fitted separately for mf prevalence and ICT-based prevalence within a Bayesian framework and used to make predictions for non-sampled areas. Maps of the dominant vector species of LF were also developed. The maps of predicted prevalence and vector distribution were linked to mathematical models of the transmission dynamics of LF to infer the intensity of transmission, quantified by the basic reproductive number (R0). Results: The literature search identified 1267 surveys that provide suitable data on the prevalence of mf and 2817 surveys that report the prevalence of antigenaemia. Distinct spatial predictions arose from the models for mf prevalence and ICT-based prevalence, with a wider geographical distribution when using ICT-based data. The vector distribution maps demonstrated the spatial variation of LF vector species. Mathematical modelling showed that the reproduction number (R0) estimates vary from 2.7 to 30, with large variations between and within regions. Conclusions: LF transmission is highly heterogeneous, and the developed maps can help guide intervention, monitoring and surveillance strategies as countries progress towards LF elimination. [ABSTRACT FROM AUTHOR]

Background: The Global Programme to Eliminate Lymphatic Filariasis was launched in 2000 with the goal of interrupting transmission of lymphatic filariasis (LF) through multiple rounds of mass drug administration (MDA). In Guinea, there is evidence of ongoing LF transmission, but little is known about the most densely populated parts of the country, including the capital Conakry. In order to guide the LF control and elimination efforts, serological and entomological surveys were carried out to determine whether or not LF transmission occurs in Conakry. Methods: The prevalence of circulating filarial antigen (CFA) of Wuchereria bancrofti was assessed by an immuno-chromatography test (ICT) in people recruited from all five districts of Conakry. Mosquitoes were collected over a 1-year period, in 195 households in 15 communities. A proportion of mosquitoes were analysed for W. bancrofti, using dissection, loop-mediated isothermal amplification (LAMP) assay and conventional polymerase chain reaction (PCR). Results: CFA test revealed no infection in the 611 individuals examined. A total of 14,334 mosquitoes were collected; 14,135 Culex (98.6 %), 161 Anopheles (1.1 %) and a few other species. Out of 1,312 Culex spp. (9.3 %) and 51 An. gambiae (31.7 %) dissected, none was infected with any stage of the W. bancrofti parasite. However, the LAMP assay revealed that 1.8 % of An. gambiae and 0.31 % of Culex spp. were positive, while PCR determined respective prevalences of 0 % and 0.19 %. Conclusions: This study revealed the presence of W. bancrofti DNA in mosquitoes, despite the apparent absence of infection in the human population. Although MDA interventions are not recommended where the prevalence of ICT is below 1 %, the entomological results are suggestive of the circulation of the parasite in the population of Conakry. Therefore, rigorous surveillance is still warranted so that LF transmission in Conakry would be identified rapidly and adequate responses being implemented. [ABSTRACT FROM AUTHOR]

Background: Many countries have made significant progress in the implementation of World Health Organization recommended preventive chemotherapy strategy, to eliminate lymphatic filariasis (LF). However, pertinent challenges such as the existence of areas of residual infections in disease endemic districts pose potential threats to the achievements made. Thus, this study was undertaken to assess the importance of these areas in implementation units (districts) where microfilaria (MF) positive individuals could not be found during the mid-term assessment after three rounds of mass drug administration. Methods: This study was undertaken in Bo and Pujehun, two LF endemic districts of Sierra Leone, with baseline MF prevalence of 2 % and 0 % respectively in sentinel sites for monitoring impact of the national programme. Study communities in the districts were purposefully selected and an assessment of LF infection prevalence was conducted together with entomological investigations undertaken to determine the existence of areas with residual MF that could enable transmission by local vectors. The transmission Assessment Survey (TAS) protocol described by WHO was applied in the two districts to determine infection of LF in 6-7 year old children who were born before MDA against LF started. Results: The results indicated the presence of MF infected children in Pujehun district. An. gambiae collected in the district were also positive for W. bancrofti, even though the prevalence of infection was below the threshold associated with active transmission. Conclusions: Residual infection was detected after three rounds of MDA in Pujehun - a district of 0 % Mf prevalence at the sentinel site. Nevertheless, our results showed that the transmission was contained in a small area. With the scale up of vector control in Anopheles transmission zones, some areas of residual infection may not pose a serious threat for the resurgence of LF if the prevalence of infections observed during TAS are below the threshold required for active transmission of the parasite. However, robust surveillance strategies capable of detecting residual infections must be implemented, together with entomological assessments to determine if ongoing vector control activities, biting rates and infection rates of the vectors can support the transmission of the disease. Furthermore, in areas where mid-term assessments reveal MF prevalence below 1 % or 2 % antigen level, in Anopheles transmission areas with active and effective malaria vector control efforts, the minimum 5 rounds of MDA may not be required before implementing TAS. Thus, we propose a modification of the WHO recommendation for the timing of sentinel and spot-check site assessments in national programs. [ABSTRACT FROM AUTHOR]

Mechanisms and outcomes of host-parasite interactions during malaria co-infections with gastrointestinal helminths are reasonably understood. In contrast, very little is known about such mechanisms in cases of malaria co-infections with tissue-dwelling parasites. This is lack of knowledge is exacerbated by misdiagnosis, lack of pathognomonic clinical signs and the chronic nature of tissue-dwelling helminthic infections. A good understanding of the implications of tissuedwelling parasitic co-infections with malaria will contribute towards the improvement of the control and management of such co-infections in endemic areas. This review summarises and discusses current information available and gaps in research on malaria co-infection with gastro-intestinal helminths and tissue-dwelling parasites with emphasis on helminthic infections, in terms of the effects of migrating larval stages and intra and extracellular localisations of protozoan parasites and helminths in organs, tissues, and vascular and lymphatic circulations. [ABSTRACT FROM AUTHOR]

Background Lymphatic filariasis (LF) is one of the neglected tropical diseases targeted for global elimination by 2020 and to guide elimination efforts countries have, in recent years, conducted extensive mapping surveys. Documenting the past and present distribution of LF and its environmental limits is important for a number of reasons. Here, we present an initiative to develop a global atlas of LF and present a new global map of the limits of LF transmission. Methods We undertook a systematic search and assembly of prevalence data worldwide and used a suite of environmental and climatic data and boosted regression trees (BRT) modelling to map the transmission limits of LF. Results Data were identified for 66 of the 72 countries currently endemic and for a further 17 countries where LF is no longer endemic. Our map highlights a restricted and highly heterogeneous distribution in sub-Saharan Africa, with transmission more widespread in West Africa compared to east, central and southern Africa where pockets of transmission occur. Contemporary transmission occurs across much of south and South-east Asia and the Pacific. Interestingly, the risk map reflects environmental conditions suitable for LF transmission across Central and South America, including the southern States of America, although active transmission is only known in a few isolated foci. In countries that have eliminated LF, our predictions of environmental suitability are consistent with historical distribution. Conclusions The global distribution of LF is highly heterogeneous and geographically targeted and sustained control will be required to achieve elimination. This first global map can help evaluate the progress of interventions and guide surveillance activities. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), international donors and partners have emphasized the importance of integrated control of neglected tropical diseases (NTDs). Integrated mapping of NTDs is a first step for integrated planning of programmes, proper resource allocation and monitoring progress of control. Integrated mapping has several advantages over disease specific mapping by reducing costs and enabling co-endemic areas to be more precisely identified. We designed and conducted integrated mapping of lymphatic filariasis (LF) and podoconiosis in Ethiopia; here we present the methods, challenges and lessons learnt. Methods: Integrated mapping of 1315 communities across Ethiopia was accomplished within three months. Within these communities, 129,959 individuals provided blood samples that were tested for circulating Wuchereria bancrofti antigen using immunochromatographic card tests (ICT). Wb123 antibody tests were used to further establish exposure to LF in areas where at least one ICT positive individual was detected. A clinical algorithm was used to reliably diagnose podoconiosis by excluding other potential causes of lymphoedema of the lower limb. Results: A total of 8110 individuals with leg swelling were interviewed and underwent physical examination. Smartphones linked to a central database were used to collect data, which facilitated real-time data entry and reduced costs compared to traditional paper-based data collection approach; their inbuilt Geographic Positioning System (GPS) function enabled simultaneous capture of geographical coordinates. The integrated approach led to efficient use of resources and rapid mapping of an enormous geographical area and was well received by survey staff and collaborators. Mobile based technology can be used for such large scale studies in resource constrained settings such as Ethiopia, with minimal challenges. Conclusions: This was the first integrated mapping of podoconiosis and LF globally. Integrated mapping of podoconiosis and LF is feasible and, if properly planned, can be quickly achieved at nationwide scale. [ABSTRACT FROM AUTHOR]

Background: The wide distribution of Loa loa infection (loiasis) throughout the Democratic Republic of Congo (DRC) is a major obstacle to the plans to eliminate onchocerciasis and lymphatic filariasis (LF) because the standard drug regime is dependent on ivermectin, which cannot be used in co-endemic areas due to the risk of severe adverse events (SAEs). A better understanding of the micro-epidemiology, overlapping low and high risk areas, and how they relate to SAEs is critical to ensure safe and effective treatment. Findings: Based on published data from the Bas Congo Province in DRC, this study used geographical information systems (GIS) to re-map and analyse onchocerciasis and loiasis prevalence (<20%, 20 to 40%, >40%) at 144 sites in relation to health district areas reporting SAEs. The new maps highlighted the contrasting patterns of the high prevalence sites, and significant geographical overlap between low onchocerciasis and high loiasis sites. Statistical analyses found that sites with medium to high loiasis prevalence were 10 to 16 times more likely to be in a SAE area than those with low prevalence of loiasis. Sites where both onchocerciasis and loiasis prevalence was >20% were also associated with SAE areas. Conclusions: Collaborative efforts between the national onchocerciasis and LF programmes are critical as plans to scale interventions are moving forward and thus, alternative strategies needed in loiasis co-endemic areas which may include the new L. loa test and treat strategy using the Cellscope, or interventions such as integrated vector management, or anti Wolbachia therapy using doxycycline. [ABSTRACT FROM AUTHOR]

Background Neglected tropical diseases (NTDs) predominantly occur in resource poor settings where they often present a serious public health burden. Sustained global advocacy has been important in raising awareness of NTDs and the relatively low cost for control of helminthic NTDs using preventive chemotherapy. This enthusiasm was recently boosted at the London declaration on NTDs through commitments by different partners to avail resources required for control of NTDs particularly those that employ preventive chemotherapy as the major intervention strategy. Subsequently, national NTD programmes are responding to these new opportunities by implementing preventive chemotherapy including school-based deworming (SBD). Further, with the availability of increased resources, both financial and pharma, the optimal strategies for implementing preventive chemotherapy in highly endemic settings are under debate and this paper goes some way to addressing this issue in a specific setting in coastal Kenya. Methods We conducted a repeated cross-sectional study in Matuga District, Kwale County, Kenya to evaluate the effect of school-based co-administration of praziquantel and albendazole against urogenital schistosomiasis and soil-transmitted helminth (STH) infections. A total of 1022 school children in 5 study schools were tested for the infections in urine and stool samples during a baseline survey in September 2009. The presence of Schistosoma haematobium infection was determined by the urine filtration method while STH infections were determined by Kato-Katz technique. Results Urogenital schistosomiasis and hookworm infection were the major parasitic infections among the children in the study area. There was significant decrease in both prevalence and intensity of S. haematobium infection after treatment but varying levels of rebound were observed during the period between the treatments. The school-based treatment, however, did not have any significant effect on both the prevalence and intensity of hookworm infection. Conclusions Once per year SBD programmes may not be adequate for controlling hookworm infection and urogenital schistosomiasis in rural areas of Kwale County. There is a need to consider expanded preventive chemotherapy strategies that will allow inclusion of the adult populations. Community-based health education campaigns focusing on increasing household latrine ownership and use, as a complementary measure to control STH and urogenital schistosomiasis in similar settings, may also be useful. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF) caused by Wuchereria bancrofti is present at high prevalence in some parts of Papua New Guinea. However, there has been no rigorous data-based representative assessment of nationwide prevalence of LF. The LF programme has been daunted by the scope of the problem, and progress on mass drug administration (MDA) has been slow and lacking in resources. Methods: A systematic literature review identified LF surveys in Papua New Guinea between 1980 and 2011. Results were extracted by location, time period and test used (blood slide, immunochromatographic test (ICT) or Og4C3 ELISA) and combined by district. Three criteria schemes based on the Global Programme to Eliminate Lymphatic Filariasis guidelines, with modifications, were developed to classify and prioritize districts by prevalence level. Results of repeated surveys in the same sites were used to investigate the impact of MDA on LF prevalence over the time period. Results: There were 312 distinct survey sites identified in 80 of the 89 districts over the 31-year period. The overall LF prevalence in the sites tested was estimated at 18.5 to 27.5% by blood slide for microfilariae (Mf), 10.1% to 12.9% by ICT and 45.4% to 48.8% by Og4C3. Biases in site selection towards areas with LF, and change in type of assay used, affected the prevalence estimates, but overall decline in prevalence over the time period was observed. Depending on the criteria used, 34 to 36 districts (population 2.7 to 2.9 million) were classed as high endemic (=5% prevalence), 15 to 25 districts (1.7 to 1.9 million) as low endemic (<5%) and 20 to 31 (1.3 to 2.2 million) as nonendemic. Nine districts (0.7 million) had no information. The strong impact of MDA, especially on microfilaria (Mf) prevalence, was noted in sites with repeat surveys. Conclusions: This analytical review of past surveys of LF in Papua New Guinea enables better estimation of the national burden, identifies gaps in knowledge, quantifies and locates the population at risk, and can be used to predict the likely impact of MDA and/or vector control. Better targeting of districts by level of prevalence will strengthen the control programme, facilitate monitoring of the disease trend and increase the likelihood of reaching the target of LF elimination by 2020. [ABSTRACT FROM AUTHOR]

Background: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000, and nearly all endemic countries in the Americas, Eastern Mediterranean and Asia-Pacific regions have now initiated the WHO recommended mass drug administration (MDA) campaign to interrupt transmission of the parasite. However, nearly 50% of the LF endemic countries in Africa are yet to implement the GPELF MDA strategy, which does not include vector control. Nevertheless, the recent scale up in insecticide treated /long lasting nets (ITNs/LLINs) and indoor residual spraying (IRS) for malaria control in Africa may significantly impact LF transmission because the parasite is transmitted mainly by Anopheles mosquitoes. This study examined the magnitude, geographical extent and potential impact of vector control in the 17 African countries that are yet to or have only recently started MDA. Methods: National data on mosquito bed nets, ITNs/LLINs and IRS were obtained from published literature, national reports, surveys and datasets from public sources such as Demographic Health Surveys, Malaria Indicator Surveys, Multiple Indicator Cluster Surveys, Malaria Report, Roll Back Malaria and President's Malaria Initiative websites. The type, number and distribution of interventions were summarised and mapped at sub-national level. and compared with known or potential LF distributions, and those which may be co-endemic with Loa loa and MDA is contraindicated. Results: Analyses found that vector control activities had increased significantly since 2005, with a three-fold increase in ITN ownership and IRS coverage. However, coverage varied dramatically across the 17 countries; some regions reported >70% ITNs ownership and regular IRS activity, while others had no coverage in remote rural populations where the risk of LF was potentially high and co-endemic with high risk L.loa. Conclusions: Despite many African countries being slow to initiate MDA for LF, the continued commitment and global financial support for NTDs, and the concurrent expansion of vector control activities for malaria, is promising. It is not beyond the capacity of GPELF to reach its target of global LF elimination by 2020, but monitoring and evaluating the impact of these activities over the next decade will be critical to its success. [ABSTRACT FROM AUTHOR]

Lymphatic Filariasis (LF) is targeted for elimination by the Global Programme for the Elimination of Lymphatic Filariasis (GPELF). The strategy adopted is based on the density dependent phenomenon of Facilitation, which hypothesizes that in an area where the vector species transmitting Wuchereria bancrofti are Anopheles mosquitoes, it is feasible to eliminate LF using Mass Drug Administration (MDA) because of the inability of Anopheles species to transmit low-density microfilaraemia. Even though earlier studies have shown Anopheles species can exhibit the process of Facilitation in West Africa, observations point towards the process of Limitation in certain areas, in which case vector control is recommended. Studies on Anopheles species in West Africa have also shown genetic differentiation, cryptic taxa and speciation, insecticide resistance and the existence of molecular and chromosomalforms, all of which could influence the vectorial capacity of the mosquitoes and ultimately the elimination goal. This paper outlines the uniqueness of LF vectors in West Africa and the challenges it poses to the 2020 elimination goal, based on the current MDA strategies. [ABSTRACT FROM AUTHOR]

Background: National mapping of lymphatic filariasis (LF) was conducted using Immunochromatographic tests (ICT) in 2005 to determine endemicity and geographic spread of the disease. A baseline microfilaria survey was then conducted to determine LF prevalence and microfilaria intensity. Methods: In 2005 1,982 persons of 15 years and over from 14 health districts were selected and fingertip blood samples were tested with ICT cards. In 2007-8 blood samples were taken between 10 p.m. and 2 a.m. and examined for microfilaria (mf) from 9,288 persons from 16 sentinel sites representing each district and 2 additional sites for districts with populations over 500,000 (Bo and Kenema). Results: The overall LF prevalence by ICT cards was 21% (males 28%, females 15%). All districts had a prevalence of Wuchereria bancrofti antigen > 1%. Distribution of LF prevalence showed a strong spatial correlation pattern with high prevalence in a large area in the northeast gradually decreasing to a relatively low prevalence in the southwest coast. High prevalence was found in the northeast, Bombali (52%), Koinadugu (46%), Tonkolili (37%) and Kono (30%). Low prevalence was found in the southwest, Bonthe (3%) and Pujehun (4%). The mf prevalence was higher in the northeast: Bombali, 6.7%, Koinadugu 5.7%, Port Loko 4.4% and Kono 2.4%. Overall there was a significant difference in mf prevalence by gender: males 2.9%, females 1.8% (p = 0.0002) and within districts in Kailahun, Kono, Port Loko, Moyamba and Koinadugu (all p < 0.05). The mf prevalence was higher in people > 20 years (2.5%) than in people ⩽ 20 years (1.7%) (p = 0.043). The overall arithmetic mean mf density was 50.30 mf/ml among mf-positive individuals and 1.19 mf/ml in the population examined which varied significantly between districts. Conclusions: The ICT results showed that LF was endemic nationwide and that preventive chemotherapy (PCT) was justified across the country. Both the ICT and microfilaraemia surveys found that prevalence was greater in males than females. The increase in microfilaraemia prevalence by age was evident when grouped as ⩽ 20 versus > 20 years demonstrating early exposure. Baseline LF microfilaria load will be used to monitor PCT program progress. [ABSTRACT FROM AUTHOR]

Background: The mosquito Aedes aegypti, vector of dengue fever, is a target for control by entomopathogenic fungi. Recent studies by our group have shown the susceptibility of adult A. aegypti to fungal infection by Metarhizium anisopliae. This fungus is currently being tested under field conditions. However, it is unknown whether blood-fed A. aegypti females are equally susceptible to infection by entomopathogenic fungi as sucrose fed females. Insect populations will be composed of females in a range of nutritional states. The fungus should be equally efficient at reducing survival of insects that rest on fungus impregnated surfaces following a blood meal as those coming into contact with fungi before host feeding. This could be an important factor when considering the behavior of A. aegypti females that can blood feed on multiple hosts over a short time period. Methods: Female A. aegypti of the Rockefeller strain and a wild strain were infected with two isolates of the entomopathogenic fungus M. anisopliae (LPP 133 and ESALQ 818) using an indirect contact bioassay at different times following blood feeding. Survival rates were monitored on a daily basis and one-way analysis of variance combined with Duncan's post-hoc test or Log-rank survival curve analysis were used for statistical comparisons of susceptibility to infection. Results: Blood feeding rapidly reduced susceptibility to infection, determined by the difference in survival rates and survival curves, when females were exposed to either of the two M. anisopliae isolates. Following a time lag which probably coincided with digestion of the blood meal (96-120 h post-feeding), host susceptibility to infection returned to pre-blood fed (sucrose fed) levels. Conclusions: Reduced susceptibility of A. aegypti to fungi following a blood meal is of concern. Furthermore, engorged females seeking out intra-domicile resting places post-blood feeding, would be predicted to rest for prolonged periods on fungus impregnated black cloths, thus optimizing infection rates. It should be remembered that lowered susceptibility was only a temporary phenomenon and this may not necessarily occur when mosquitoes are infected with other fungal isolates. These results may have implications for field testing of entomopathogenic fungi by our group and further studies should be carried out to better understand the insectfungus interaction. [ABSTRACT FROM AUTHOR]

Background: Toll-like receptors (TLR) and related downstream signaling pathways of innate immunity have been implicated in the pathogenesis of Plasmodium falciparum malaria. Because of their potential role in malaria pathogenesis, polymorphisms in these genes may be under selective pressure in populations where this infectious disease is endemic. Methods: A post-PCR Ligation Detection Reaction-Fluorescent Microsphere Assay (LDR-FMA) was developed to determine the frequencies of TLR2, TLR4, TLR9, MyD88-Adaptor Like Protein (MAL) single nucleotide polymorphisms (SNPs), and TLR2 length polymorphisms in 170 residents of two regions of Kenya where malaria transmission is stable and high (holoendemic) or episodic and low, 346 residents of a malaria holoendemic region of Papua New Guinea, and 261 residents of North America of self-identified ethnicity. Results: The difference in historical malaria exposure between the two Kenyan sites has significantly increased the frequency of malaria protective alleles glucose-6-phoshpate dehydrogenase (G6PD) and Hemoglobin S (HbS) in the holoendemic site compared to the episodic transmission site. However, this study detected no such difference in the TLR2, TLR4, TLR9, and MAL allele frequencies between the two study sites. All polymorphisms were in Hardy Weinberg Equilibrium in the Kenyan and Papua New Guinean populations. TLR9 SNPs and length polymorphisms within the TLR2 5' untranslated region were the only mutant alleles present at a frequency greater than 10% in all populations. Conclusion: Similar frequencies of TLR2, TLR4, TLR9, and MAL genetic polymorphisms in populations with different histories of malaria exposure suggest that these innate immune pathways have not been under strong selective pressure by malaria. Genotype frequencies are consistent with Hardy-Weinberg Equilibrium and the Neutral Theory, suggesting that genetic drift has influenced allele frequencies to a greater extent than selective pressure from malaria or any other infectious agents in these populations. [ABSTRACT FROM AUTHOR]

Background: The outcomes of insecticide-treated bednet (ITN) interventions for malaria control in Papua New Guinea tend to suggest a differential protective effect against Plasmodium falciparum and Plasmodium vivax. Little is known about the impact of ITNs on the relative abundance of mosquitoes infected with either P. falciparum or P. vivax. This paper describes the biting cycle of P. falciparum and P. vivax-infected mosquitoes and the impact of an ITN intervention on the proportion of mosquitoes infected with either parasite species. Methods: Entomological investigations were performed in East Sepik (ESP) and New Ireland Provinces (NIP) of PNG. Mosquitoes were collected using the all-night (18:00 - 06:00) landing catch and CDC light-trap methods and species specific malaria sporozoite rates were determined by ELISA. Results and discussion: The distribution of sporozoite positive mosquitoes in three four-hour periods (18:00-22:00, 22:00-02:00 & 02:00-06:00) showed that a higher proportion of P. vivaxinfected mosquitoes were biting before people retired to bed under the protection of bednets. In the intervention village, the 308 mosquitoes collected before ITNs were introduced included eight (2.0%) P. falciparum-positive and four (1.0%) P. vivax-positive specimens, giving a parasite ratio of 2:1. The sporozoite rate determined from 908 mosquitoes caught after ITNs were introduced showed a significant decrease for P. falciparum (0.7%) and a slight increase for P. vivax (1.3%), resulting in a post intervention parasite ratio of 1:2. In the East Sepik Province, where ITNs were not used, P. falciparum remained the dominant species in 12 monthly mosquito collections and monthly P. falciparum:P. vivax formula varied from 8:1 to 1.2:1. Conclusion: These findings suggest that people sleeping under treated bednets may be more exposed to P. vivax than P. falciparum-infected mosquitoes before going to sleep under the protection of bednets. This difference in the biting behaviour of mosquitoes infected with different malaria parasites may partly explain the change in the P. falciparum:P. vivax formula after the introduction of ITNs. [ABSTRACT FROM AUTHOR]

Most neglected tropical diseases (NTDs) have complex life cycles and are challenging to control. The "2020 goals" of control and elimination as a public health programme for a number of NTDs are the subject of significant international efforts and investments. Beyond 2020 there will be a drive to maintain these gains and to push for true local elimination of transmission. However, these diseases are affected by variations in vectors, human demography, access to water and sanitation, access to interventions and local health systems. We therefore argue that there will be a need to develop local quantitative expertise to support elimination efforts. If available now, quantitative analyses would provide updated estimates of the burden of disease, assist in the design of locally appropriate control programmes, estimate the effectiveness of current interventions and support 'real-time' updates to local operations. Such quantitative tools are increasingly available at an international scale for NTDs, but are rarely tailored to local scenarios. Localised expertise not only provides an opportunity for more relevant analyses, but also has a greater chance of developing positive feedback between data collection and analysis by demonstrating the value of data. This is essential as rational program design relies on good quality data collection. It is also likely that if such infrastructure is provided for NTDs there will be an additional impact on the health system more broadly. Locally tailored quantitative analyses can help achieve sustainable and effective control of NTDs, but also underpin the development of local health care systems.

Priorities for NTD control programmes will shift over the next 10-20 years as the elimination phase reaches the 'end game' for some NTDs, and the recognition that the control of other NTDs is much more problematic. The current goal of scaling up programmes based on preventive chemotherapy (PCT) will alter to sustaining NTD prevention, through sensitive surveillance and rapid response to resurgence. A new suite of tools and approaches will be required for both PCT and Intensive Disease Management (IDM) diseases in this timeframe to enable disease endemic countries to: 1. Sensitively and sustainably survey NTD transmission and prevalence in order to identify and respond quickly to resurgence. 2. Set relevant control targets based not only on epidemiological indicators but also entomological and ecological metrics and use decision support technology to help meet those targets. 3. Implement verified and cost-effective tools to prevent transmission throughout the elimination phase. Liverpool School of Tropical Medicine (LSTM) and partners propose to evaluate and implement existing tools from other disease systems as well as new tools in the pipeline in order to support endemic country ownership in NTD decision-making during the elimination phase and beyond.

Achieving the 2020 goals for Neglected Tropical Diseases (NTDs) requires scale-up of Mass Drug Administration (MDA) which will require long-term commitment of national and global financing partners, strengthening national capacity and, at the community level, systems to monitor and evaluate activities and impact. For some settings and diseases, MDA is not appropriate and alternative interventions are required. Operational research is necessary to identify how existing MDA networks can deliver this more complex range of interventions equitably. The final stages of the different global programmes to eliminate NTDs require eliminating foci of transmission which are likely to persist in complex and remote rural settings. Operational research is required to identify how current tools and practices might be adapted to locate and eliminate these hard-to-reach foci. Chronic disabilities caused by NTDs will persist after transmission of pathogens ceases. Development and delivery of sustainable services to reduce the NTD-related disability is an urgent public health priority. LSTM and its partners are world leaders in developing and delivering interventions to control vector-borne NTDs and malaria, particularly in hard-to-reach settings in Africa. Our experience, partnerships and research capacity allows us to serve as a hub for developing, supporting, monitoring and evaluating global programmes to eliminate NTDs.