Global outreach and networking promotion to accelerate tropical diseases elimination.

Cooperation and networking are powerful tools in the combating against tropical diseases. Cooperation on a global scale is essential due to the transboundary nature of tropical diseases. Networking plays a pivotal role in facilitating such cooperation. Both cooperation and networking can foster innovation in disease control programmes. Collaborative research can lead to the development of new drugs and vaccines, while shared surveillance data can enable the early detection and control of disease epidemics. Therefore, consensus of cooperation and networking has been reached during the 7th Symposium on Surveillance-Response Systems Leading to Tropical Diseases Elimination, which reflected in the two documents, i.e., Consensus for Transboundary Tropical Diseases Control, and Action Consensus of the Network of WHO Collaborating Centres Related to NTDs. These documents will improve the efforts in the fighting against tropical diseases through collective actions to achieve the United Nations' Sustainable Development Goals (SDGs).

Multi-criteria decision analysis method for differential diagnosis of tropical febrile diseases.

This paper employs the Analytical Hierarchy Process (AHP) to enhance the accuracy of differential diagnosis for febrile diseases, particularly prevalent in tropical regions where misdiagnosis may have severe consequences. The migration of health workers from developing countries has resulted in frontline health workers (FHWs) using inadequate protocols for the diagnosis of complex health conditions. The study introduces an innovative AHP-based Medical Decision Support System (MDSS) incorporating disease risk factors derived from physicians' experiential knowledge to address this challenge. The system's aggregate diagnostic factor index determines the likelihood of febrile illnesses. Compared to existing literature, AHP models with risk factors demonstrate superior prediction accuracy, closely aligning with physicians' suspected diagnoses. The model's accuracy ranges from 85.4% to 96.9% for various diseases, surpassing physicians' predictions for Lassa, Dengue, and Yellow Fevers. The MDSS is recommended for use by FHWs in communities lacking medical experts, facilitating timely and precise diagnoses, efficient application of diagnostic test kits, and reducing overhead expenses for administrators.

Protocol for the crowdsourced image-based morbidity hotspot surveillance for neglected tropical diseases (CIMS-NTDs).

INTRODUCTION: Efficient NTDs elimination strategies require effective surveillance and targeted interventions. Traditional methods are costly and time-consuming, often failing to cover entire populations in case of movement restrictions. To address these challenges, a morbidity image-based surveillance system is being developed. This innovative approach which leverages the smartphone technology aims at simultaneous surveillance of multiple NTDs, enhancing cost-efficiency, reliability, and community involvement, particularly in areas with movement constraints. Moreover, it holds promise for post-elimination surveillance. METHODOLOGY: The pilot of this method will be conducted across three states in southern Nigeria. It will target people affected by Neglected Tropical Diseases and members of their communities. The new surveillance method will be introduced to target communities in the selected states through community stakeholder's advocacy meetings and awareness campaigns. The pilot which is set to span eighteen months, entails sensitizing NTDs-affected individuals and community members using signposts, posters, and handbills, to capture photos of NTDs manifestations upon notice using smartphones. These images, along with pertinent demographic information, will be transmitted to a dedicated server through WhatsApp or Telegram accounts. The received images will be reviewed and organized at backend and then forwarded to a panel of experts for identification and annotation to specific NTDs. Data generated, along with geocoordinate information, will be used to create NTDs morbidity hotspot maps using ArcGIS. Accompanying metadata will be used to generate geographic and demographic distributions of various NTDs identified. To protect privacy, people will be encouraged to send manifestation photos of the affected body part only without any identifiable features. EVALUATION PROTOCOL: NTDs prevalence data obtained using conventional surveillance methods from both the pilot and selected control states during the pilot period will be compared with data from the CIMS-NTDs method to determine its effectiveness. EXPECTED RESULTS AND CONCLUSION: It is expected that an effective, privacy-conscious, population inclusive new method for NTDs surveillance, with the potential to yield real-time data for the identification of morbidity hotspots and distribution patterns of NTDs will be established. The results will provide insights into the effectiveness of the new surveillance method in comparison to traditional approaches, potentially advancing NTDs elimination strategies.

Evaluating the World Health Organization's SkinNTDs App as a Training Tool for Skin Neglected Tropical Diseases in Ghana and Kenya: Cross-Sectional Study.

BACKGROUND: Neglected tropical diseases (NTDs) affect over 1.5 billion people worldwide, primarily impoverished populations in low- and middle-income countries. Skin NTDs, a significant subgroup, manifest primarily as skin lesions and require extensive diagnosis and treatment resources, including trained personnel and financial backing. The World Health Organization has introduced the SkinNTDs app, a mobile health tool designed to train and be used as a decision support tool for frontline health care workers. As most digital health guidelines prioritize the thorough evaluation of mobile health interventions, it is essential to conduct a rigorous and validated assessment of this app. OBJECTIVE: This study aims to assess the usability and user experience of World Health Organization SkinNTDs app (version 3) as a capacity-building tool and decision-support tool for frontline health care workers. METHODS: A cross-sectional study was conducted in Ghana and Kenya. Frontline health care workers dealing with skin NTDs were recruited through snowball sampling. They used the SkinNTDs app for at least 5 days before completing a web-based survey containing demographic variables and the user version of the Mobile Application Rating Scale (uMARS), a validated scale for assessing health apps. A smaller group of participants took part in semistructured interviews and one focus group. Quantitative data were analyzed using SPSS with a 95% CI and P≤.05 for statistical significance and qualitative data using ATLAS.ti to identify attributes, cluster themes, and code various dimensions that were explored. RESULTS: Overall, 60 participants participated in the quantitative phase and 17 in the qualitative phase. The SkinNTDs app scored highly on the uMARS questionnaire, with an app quality mean score of 4.02 (SD 0.47) of 5, a subjective quality score of 3.82 (SD 0.61) of 5, and a perceived impact of 4.47 (SD 0.56) of 5. There was no significant association between the app quality mean score and any of the categorical variables examined, according to Pearson correlation analysis; app quality mean score vs age (P=.37), sex (P=.70), type of health worker (P=.35), country (P=.94), work context (P=.17), frequency of dealing with skin NTDs (P=.09), and dermatology experience (P=.63). Qualitative results echoed the quantitative outcomes, highlighting the ease of use, the offline functionality, and the potential utility for frontline health care workers in remote and resource-constrained settings. Areas for improvement were identified, such as enhancing the signs and symptoms section. CONCLUSIONS: The SkinNTDs app demonstrates notable usability and user-friendliness. The results indicate that the app could play a crucial role in improving capacity building of frontline health care workers dealing with skin NTDs. It could be improved in the future by including new features such as epidemiological context and direct contact with experts. The possibility of using the app as a diagnostic tool should be considered. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/39393.

Burden of neglected tropical diseases and access to medicine and diagnostics in Ethiopia: a scoping review.

BACKGROUND: More than 1.7 billion people are affected by neglected tropical diseases (NTDs) worldwide. Forty percent of the NTD-affected people live in Africa with the poorest, most vulnerable, and hard to reach geographical areas. The NTDs cause significant social and economic burden and deepen marginalization and stigmatization. The World Health Organization's current roadmap for NTD aims to prevent, control, eliminate, or eradicate 20 tropical diseases. Ethiopia experiences a high burden of these diseases, but current access to diagnostics, medicine, and/or care has been little explored to inform the country's NTD strategic plan. The overall purpose of the scoping review was to map and characterize the burden of NTDs and challenges in access to diagnostics, medicine, and/or care in Ethiopia. METHODS: A systematic search of evidence was conducted in PubMed, Cochrane Library, and Google Scholar from January 2000 until May 2022, without restrictions of language or study design. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review was followed for screening of studies. Key findings were extracted and narrated qualitatively. RESULTS: The search resulted in 4532 articles, of which 105 met the inclusion criteria and were included in the scoping review under three themes: burden of NTDs, access to diagnostics, medicine and/or care, and key barriers. Although gains have been made in the prevention and control of NTDs in Ethiopia, the burden remains high, and progress in access to diagnostics, medicine/drugs, and/or care is very slow. Poverty, poor quality of life, and underfunding of NTD programs decelerate the process of NTD elimination program in the country. CONCLUSIONS: The scoping review identified a considerable number of studies on the burden of NTDs in Ethiopia and strategies for diagnosis, treatment, and/or care; however, there is a paucity of evidence on the suitability and potential benefits of novel diagnostic technologies and medicines in the country. A regular review and analysis of such country-level evidence is important to inform the country NTDs roadmap and local implementation strategies.

Safely resuming neglected tropical disease control activities during COVID-19: Perspectives from Nigeria and Guinea.

Since its early spread in early 2020, the disease caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus Disease 2019 (COVID-19) has caused mass disruptions to health services. These have included interruptions to programs that aimed to prevent, control, and eliminate neglected tropical diseases (NTDs). In March 2020, the World Health Organization (WHO) released interim guidelines recommending the temporary cessation of mass drug administration (MDA), community-based surveys, and case detection, while encouraging continuation of morbidity management and vector control where possible. Over the course of the following months, national programs and implementing partners contributed to COVID-19 response efforts, while also beginning to plan for resumption of NTD control activities. To understand the challenges, opportunities, and recommendations for maximizing continuity of disease control during public health emergencies, we sought perspectives from Nigeria and Guinea on the process of restarting NTD control efforts during the COVID-19 pandemic. Through semistructured interviews with individuals involved with NTD control at the local and national levels, we identified key themes and common perspectives between the 2 countries, as well as observations that were specific to each. Overall, interviewees stressed the challenges posed by COVID-19 interruptions, particularly with respect to delays to activities and related knock-on impacts, such as drug expiry and prolonged elimination timelines, as well as concerns related to funding. However, respondents in both countries also highlighted the benefits of a formal risk assessment approach, particularly in terms of encouraging information sharing and increasing coordination and advocacy. Recommendations included ensuring greater availability of historical data to allow better monitoring of how future emergencies affect NTD control progress; continuing to use risk assessment approaches in the future; and identifying mechanisms for sharing lessons learned and innovations between countries as a means of advancing postpandemic health systems and disease control capacity strengthening.

Health-related vulnerability to climate extremes in homoclimatic zones of Amazonia and Northeast region of Brazil.

Amazonia and the Northeast region of Brazil exhibit the highest levels of climate vulnerability in the country. While Amazonia is characterized by an extremely hot and humid climate and hosts the world largest rainforest, the Northeast is home to sharp climatic contrasts, ranging from rainy areas along the coast to semiarid regions that are often affected by droughts. Both regions are subject to extremely high temperatures and are susceptible to many tropical diseases. This study develops a multidimensional Extreme Climate Vulnerability Index (ECVI) for Brazilian Amazonia and the Northeast region based on the Alkire-Foster method. Vulnerability is defined by three components, encompassing exposure (proxied by seven climate extreme indicators), susceptibility (proxied by sociodemographic indicators), and adaptive capacity (proxied by sanitation conditions, urbanization rate, and healthcare provision). In addition to the estimated vulnerability levels and intensity, we break down the ECVI by indicators, dimensions, and regions, in order to explore how the incidence levels of climate-sensitive infectious and parasitic diseases correlate with regional vulnerability. We use the Grade of Membership method to reclassify the mesoregions into homoclimatic zones based on extreme climatic events, so climate and population/health data can be analyzed at comparable resolutions. We find two homoclimatic zones: Extreme Rain (ER) and Extreme Drought and High Temperature (ED-HT). Vulnerability is higher in the ED-HT areas than in the ER. The contribution of each dimension to overall vulnerability levels varies by homoclimatic zone. In the ER zone, adaptive capacity (39%) prevails as the main driver of vulnerability among the three dimensions, in contrast with the approximately even dimensional contribution in the ED-HT. When we compare areas by disease incidence levels, exposure emerges as the most influential dimension. Our results suggest that climate can exacerbate existing infrastructure deficiencies and socioeconomic conditions that are correlated with tropical disease incidence in impoverished areas.

Determining seropositivity-A review of approaches to define population seroprevalence when using multiplex bead assays to assess burden of tropical diseases.

BACKGROUND: Serological surveys with multiplex bead assays can be used to assess seroprevalence to multiple pathogens simultaneously. However, multiple methods have been used to generate cut-off values for seropositivity and these may lead to inconsistent interpretation of results. A literature review was conducted to describe the methods used to determine cut-off values for data generated by multiplex bead assays. METHODOLOGY/PRINCIPAL FINDINGS: A search was conducted in PubMed that included articles published from January 2010 to January 2020, and 308 relevant articles were identified that included the terms "serology", "cut-offs", and "multiplex bead assays". After application of exclusion of articles not relevant to neglected tropical diseases (NTD), vaccine preventable diseases (VPD), or malaria, 55 articles were examined based on their relevance to NTD or VPD. The most frequently applied approaches to determine seropositivity included the use of presumed unexposed populations, mixture models, receiver operating curves (ROC), and international standards. Other methods included the use of quantiles, pre-exposed endemic cohorts, and visual inflection points. CONCLUSIONS/SIGNIFICANCE: For disease control programmes, seropositivity is a practical and easily interpretable health metric but determining appropriate cut-offs for positivity can be challenging. Considerations for optimal cut-off approaches should include factors such as methods recommended by previous research, transmission dynamics, and the immunological backgrounds of the population. In the absence of international standards for estimating seropositivity in a population, the use of consistent methods that align with individual disease epidemiological data will improve comparability between settings and enable the assessment of changes over time.

New global targets for NTDs in the WHO roadmap 2021-2030.

The second World Neglected Tropical Diseases (NTDs) Day was celebrated on 30 January 2021. To mark the occasion, the World Health Organization (WHO) launched its roadmap for NTDs for the period 2021 to 2030, which is aimed at increasing prevention and control of these too-long neglected diseases. Described here is a global overview on past achievements, current challenges, and future prospects for the WHO NTDs roadmap 2021-2030.

Strengthening data collection for neglected tropical diseases: What data are needed for models to better inform tailored intervention programmes?

Locally tailored interventions for neglected tropical diseases (NTDs) are becoming increasingly important for ensuring that the World Health Organization (WHO) goals for control and elimination are reached. Mathematical models, such as those developed by the NTD Modelling Consortium, are able to offer recommendations on interventions but remain constrained by the data currently available. Data collection for NTDs needs to be strengthened as better data are required to indirectly inform transmission in an area. Addressing specific data needs will improve our modelling recommendations, enabling more accurate tailoring of interventions and assessment of their progress. In this collection, we discuss the data needs for several NTDs, specifically gambiense human African trypanosomiasis, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), trachoma, and visceral leishmaniasis. Similarities in the data needs for these NTDs highlight the potential for integration across these diseases and where possible, a wider spectrum of diseases.

Actives from MMV Open Access Boxes? A suggested way forward.

It is estimated that more than 1 billion people across the world are affected by a neglected tropical disease (NTD) that requires medical intervention. These diseases tend to afflict people in areas with high rates of poverty and cost economies billions of dollars every year. Collaborative drug discovery efforts are required to reduce the burden of these diseases in endemic regions. The release of "Open Access Boxes" is an initiative launched by Medicines for Malaria Venture (MMV) in collaboration with its partners to catalyze new drug discovery in neglected diseases. These boxes are mainly requested by biology researchers across the globe who may not otherwise have access to compounds to screen nor knowledge of the workflow that needs to be followed after identification of actives from their screening campaigns. Here, we present guidelines on how to move such actives beyond the hit identification stage, to help in capacity strengthening and enable a greater impact of the initiative.

Optimising passive surveillance of a neglected tropical disease in the era of elimination: A modelling study.

BACKGROUND: Surveillance is an essential component of global programs to eliminate infectious diseases and avert epidemics of (re-)emerging diseases. As the numbers of cases decline, costs of treatment and control diminish but those for surveillance remain high even after the 'last' case. Reducing surveillance may risk missing persistent or (re-)emerging foci of disease. Here, we use a simulation-based approach to determine the minimal number of passive surveillance sites required to ensure maximum coverage of a population at-risk (PAR) of an infectious disease. METHODOLOGY AND PRINCIPAL FINDINGS: For this study, we use Gambian human African trypanosomiasis (g-HAT) in north-western Uganda, a neglected tropical disease (NTD) which has been reduced to historically low levels (<1000 cases/year globally), as an example. To quantify travel time to diagnostic facilities, a proxy for surveillance coverage, we produced a high spatial-resolution resistance surface and performed cost-distance analyses. We simulated travel time for the PAR with different numbers (1-170) and locations (170,000 total placement combinations) of diagnostic facilities, quantifying the percentage of the PAR within 1h and 5h travel of the facilities, as per in-country targets. Our simulations indicate that a 70% reduction (51/170) in diagnostic centres still exceeded minimal targets of coverage even for remote populations, with >95% of a total PAR of ~3million individuals living ≤1h from a diagnostic centre, and we demonstrate an approach to best place these facilities, informing a minimal impact scale back. CONCLUSIONS: Our results highlight that surveillance of g-HAT in north-western Uganda can be scaled back without substantially reducing coverage of the PAR. The methodology described can contribute to cost-effective and equable strategies for the surveillance of NTDs and other infectious diseases approaching elimination or (re-)emergence.

A Cautionary Tale Regarding the Use of Causal Inference to Study How Environmental Change Influences Tropical Diseases.

There has been substantial interest on the effect of large-scale environmental change, such as deforestation, on human health. An important and relatively recent development has been the use of causal-inference approaches (e.g., instrumental variables [IVs]) to more properly analyze this type of observational data. Here, we discuss an important study that attempted to disentangle the effect of malaria on deforestation from the effect of deforestation on malaria using an IV approach. The authors found that deforestation increases malaria (e.g., they estimate that a 10% increase in deforestation leads to a 3.3% increase in malaria incidence) through ecological mechanisms, whereas malaria reduces deforestation through socioeconomic mechanisms. An important characteristic of causal-inference approaches is that they are critically dependent on the plausibility of the underlying assumptions and that, differently from standard statistical models, many of these assumptions are not testable. In particular, we show how important assumptions of the IV approach adopted in the study described earlier were not met and that, as a result, it is possible that the correct conclusion could have been the opposite of that reported by the authors (e.g., deforestation decreases, rather than increasing, malaria through ecological mechanisms). Causal-inference approaches may be critical to characterize the relationship between environmental change and disease risk, but conclusions based on these methods can be even more unreliable than those from traditional methods if careful attention is not given to the plausibility of the underlying assumptions.

Adapting an integrated neglected tropical disease programme in response to COVID-19.

The COVID-19 pandemic hit at a time when the Ascend West and Central Africa programme was nearing the end of its first year of a 3-y programme. This article reflects on key lessons learnt from the rapid adaptation of an integrated neglected tropical disease (NTD) programme to support COVID-19 responses in 11 countries. It shares the experiences of adopting a flexible and directive approach, leveraging the NTD network and relationships, and working in collaboration with multiple ministry departments, commercial sector partners and the UK Foreign Commonwealth Development Office to repurpose over £6 million of budget.

Adaptation and performance of a mobile application for early detection of cutaneous leishmaniasis.

BACKGROUND: Detection and management of neglected tropical diseases such as cutaneous leishmaniasis present unmet challenges stemming from their prevalence in remote, rural, resource constrained areas having limited access to health services. These challenges are frequently compounded by armed conflict or illicit extractive industries. The use of mobile health technologies has shown promise in such settings, yet data on outcomes in the field remain scarce. METHODS: We adapted a validated prediction rule for the presumptive diagnosis of CL to create a mobile application for use by community health volunteers. We used human-centered design practices and agile development for app iteration. We tested the application in three rural areas where cutaneous leishmaniasis is endemic and an urban setting where patients seek medical attention in the municipality of Tumaco, Colombia. The application was assessed for usability, sensitivity and inter-rater reliability (kappa) when used by community health volunteers (CHV), health workers and a general practitioner, study physician. RESULTS: The application was readily used and understood. Among 122 screened cases with cutaneous ulcers, sensitivity to detect parasitologically proven CL was >95%. The proportion of participants with parasitologically confirmed CL was high (88%), precluding evaluation of specificity, and driving a high level of crude agreement between the app and parasitological diagnosis. The chance-adjusted agreement (kappa) varied across the components of the risk score. Time to diagnosis was reduced significantly, from 8 to 4 weeks on average when CHV conducted active case detection using the application, compared to passive case detection by health facility-based personnel. CONCLUSIONS: Translating a validated prediction rule to a mHealth technology has shown the potential to improve the capacity of community health workers and healthcare personnel to provide opportune care, and access to health services for underserved populations. These findings support the use of mHealth tools for NTD research and healthcare.

Neglected tropical diseases activities in Africa in the COVID-19 era: the need for a "hybrid" approach in COVID-endemic times.

With the coronavirus disease 2019 (COVID-19) pandemic showing no signs of abating, resuming neglected tropical disease (NTD) activities, particularly mass drug administration (MDA), is vital. Failure to resume activities will not only enhance the risk of NTD transmission, but will fail to leverage behaviour change messaging on the importance of hand and face washing and improved sanitation-a common strategy for several NTDs that also reduces the risk of COVID-19 spread. This so-called "hybrid approach" will demonstrate best practices for mitigating the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by incorporating physical distancing, use of masks, and frequent hand-washing in the delivery of medicines to endemic communities and support action against the transmission of the virus through water, sanitation and hygiene interventions promoted by NTD programmes. Unless MDA and morbidity management activities resume, achievement of NTD targets as projected in the WHO/NTD Roadmap (2021-2030) will be deferred, the aspirational goal of NTD programmes to enhance universal health coverage jeopardised and the call to 'leave no one behind' a hollow one. We outline what implementing this hybrid approach, which aims to strengthen health systems, and facilitate integration and cross-sector collaboration, can achieve based on work undertaken in several African countries.

Integration of Management Strategies for Skin-Related Neglected Tropical Diseases.

The concept of skin neglected tropical diseases has been widely adopted into the policy and strategy of various organizations, governments, nongovernmental organizations, and health agencies. By pooling information and resources across different diseases, whose primary manifestations affect the skin, it is possible to deliver integrated surveillance and control programs and promote advocacy and reduction of disability and stigma. A further key part of the skin neglected tropical diseases program is the development and validation of training methods for front-line health workers. Networks that allow those involved in this work to share and compare expertise are being developed through various organizations.

Mass administration of medicines in changing contexts: Acceptability, adaptability and community directed approaches in Kaduna and Ogun States, Nigeria.

Nigeria has the highest burden of NTDs in sub-Saharan Africa. Commitments to reach the control and elimination of many Neglected Tropical Diseases (NTDs), particularly those amenable to preventive chemotherapy (onchocerciasis, schistosomiasis, soil transmitted helminths, lymphatic filariasis and trachoma) by 2020 are detailed in the London declaration. Strategies to reach targets build on existing approaches, one of which is the use of community directed intervention (CDI) methods to deliver the mass administration of medicines (MAM). However, treatment using this approach has been inconsistent and there are questions about the acceptability and adaptability of these interventions during periods of programmatic, social, and political change. This paper explores the current strengths and weaknesses of CDI approaches in MAM delivery. We consider the acceptability and adaptability of existing MAM approaches to ensure equity in access to essential treatments. Using qualitative methods, we explore implementer perspectives of MAM delivery. We purposively selected programme implementers to ensure good programmatic knowledge and representation from the different levels of health governance in Nigeria. Data collection took place across two States (Kaduna and Ogun). Our results indicate that CDI approaches have underpinned many historic successes in NTD programme acceptance in Nigeria, specifically in Kaduna and Ogun State. However, our results also show that in some contexts, factors that underpin the success of CDI have become disrupted presenting new challenges for programme implementers. Capturing the tacit knowledge of health implementers at varying levels of the health system, we present the current and changing context of MAM delivery in Kaduna and Ogun States and consolidate a platform of evidence to guide future programme delivery and research studies. We situate our findings within the broader NTD literature, specifically, in identifying how our findings align to existing reviews focused on factors that shape individual acceptance of MAM.

Aetiology of fever in returning travellers and migrants: a systematic review and meta-analysis.

BACKGROUND: Numerous publications focus on fever in returning travellers, but there is no known systematic review considering all diseases, or all tropical diseases causing fever. Such a review is necessary in order to develop appropriate practice guidelines. OBJECTIVES: Primary objectives of this review were (i) to determine the aetiology of fever in travellers/migrants returning from (sub) tropical countries as well as the proportion of patients with specific diagnoses, and (ii) to assess the predictors for specific tropical diseases. METHOD: Embase, MEDLINE and Cochrane Library were searched with terms combining fever and travel/migrants. All studies focusing on causes of fever in returning travellers and/or clinical and laboratory predictors of tropical diseases were included. Meta-analyses were performed on frequencies of etiological diagnoses. RESULTS: 10 064 studies were identified; 541 underwent full-text review; 30 met criteria for data extraction. Tropical infections accounted for 33% of fever diagnoses, with malaria causing 22%, dengue 5% and enteric fever 2%. Non-tropical infections accounted for 36% of febrile cases, with acute gastroenteritis causing 14% and respiratory tract infections 13%. Positive likelihood ratios demonstrated that splenomegaly, thrombocytopenia and hyperbilirubinemia were respectively 5-14, 3-11 and 5-7 times more likely in malaria than non-malaria patients. High variability of results between studies reflects heterogeneity in study design, regions visited, participants' characteristics, setting, laboratory investigations performed and diseases included. CONCLUSION: Malaria accounted for one-fifth of febrile cases, highlighting the importance of rapid malaria testing in febrile returning travellers, followed by other rapid tests for common tropical diseases. High variability between studies highlights the need to harmonize study designs and to promote multi-centre studies investigating predictors of diseases, including of lower incidence, which may help to develop evidence-based guidelines. The use of clinical decision support algorithms by health workers which incorporate clinical predictors, could help standardize studies as well as improve quality of recommendations.