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Non-communicable diseases (NCDs) represent the primary cause of morbidity and mortality worldwide. Specific attention needs to be given in fragile and crisis-affected contexts, where health systems have even more difficulties in addressing and managing these diseases. Humanitarian actors intervening in crisis situations increasingly include NCD management in the services they support and provide. This review aims at presenting a series of questions that humanitarian agencies could consider when addressing NCDs in humanitarian crises. They include, among others, what conditions to address and for which target population, how to ensure continuity of care, which guidelines and medications to use, and what can be done beyond classical management of NCDs. Research and evidence are lacking on how to address care effectively for NCDs in emergencies. Therefore, advocacy is needed for NCD-oriented research so as to make interventions more effective and sustainable. No government or single agency can address NCDs in humanitarian crises alone. Strong leadership and partnerships between humanitarian actors, health providers, government bodies, research and academic institutions are required. Only a coordinated multidisciplinary and multi-stakeholder approach will achieve the required impact for affected populations. [ABSTRACT FROM AUTHOR]

Background: Strongyloidiasis is an infectious disease that can be fatal in immunocompromised patients. Patients with end-stage renal failure who are on dialysis have a considerably weakened immune system, and organ transplantation is a major risk factor for severe strongyloidiasis. Knowledge of the local epidemiology in tropical and subtropical areas is an essential prerequisite for designing an appropriate strategy to prevent this potentially lethal complication. In this study, we aimed to estimate the prevalence and associated risk factors of S. stercoralis infection in patients on dialysis in Cochabamba, Bolivia., Methods: A cross-sectional study was carried out among patients undergoing haemodialysis in Cochabamba (elevation 2,500 m, temperate climate), collecting information on socio-demographic, lifestyle, and clinical variables, and using one coproparasitological technique (the modified Baermann technique) and one serological (ELISA) test for S.stercoralis diagnosis., Results: In total, 149 patients participated in the study (mean age = 51.4 years, 48.3% male). End-stage renal disease was predominantly (59%) of hypertensive and/or diabetic origin. The positive serological prevalence was 18.8% (95% CI: 13.3%-25.9%). Based on the sensitivity and specificity of the ELISA test, the estimate of the actual prevalence was 15.1% (95% CI: 9.4%-20.7%). Stool samples of 105 patients (70.5%) showed a coproparasitological prevalence of 1.9% (95% CI: 0.52%-6.68%). No potential risk factors were significantly associated with S. stercoralis infection., Conclusions: We found a high seroprevalence of S. stercoralis in Bolivian patients undergoing haemodialysis in Cochabamba. We recommend presumptive antiparasitic treatment at regular intervals to avoid the potentially fatal complications of severe strongyloidiasis., (© 2023. The Author(s).)

Background: Persistent fever, defined as fever lasting for 7 days or more at first medical evaluation, has been hardly investigated as a separate clinical entity in the tropics. This study aimed at exploring the frequencies and diagnostic predictors of the ubiquitous priority (i.e., severe and treatable) infections causing persistent fever in the tropics., Methods: In six different health settings across four countries in Africa and Asia (Sudan, Democratic Republic of Congo [DRC], Nepal, and Cambodia), consecutive patients aged 5 years or older with persistent fever were prospectively recruited from January 2013 to October 2014. Participants underwent a reference diagnostic workup targeting a pre-established list of 12 epidemiologically relevant priority infections (i.e., malaria, tuberculosis, HIV, enteric fever, leptospirosis, rickettsiosis, brucellosis, melioidosis, relapsing fever, visceral leishmaniasis, human African trypanosomiasis, amebic liver abscess). The likelihood ratios (LRs) of clinical and basic laboratory features were determined by pooling all cases of each identified ubiquitous infection (i.e., found in all countries). In addition, we assessed the diagnostic accuracy of five antibody-based rapid diagnostic tests (RDTs): Typhidot Rapid IgM, Test-it TM Typhoid IgM Lateral Flow Assay, and SD Bioline Salmonella typhi IgG/IgM for Salmonella Typhi infection, and Test-it TM Leptospira IgM Lateral Flow Assay and SD Bioline Leptospira IgG/IgM for leptospirosis., Results: A total of 1922 patients (median age: 35 years; female: 51%) were enrolled (Sudan, n = 667; DRC, n = 300; Nepal, n = 577; Cambodia, n = 378). Ubiquitous priority infections were diagnosed in 452 (23.5%) participants and included malaria 8.0% (n = 154), tuberculosis 6.7% (n = 129), leptospirosis 4.0% (n = 77), rickettsiosis 2.3% (n = 44), enteric fever 1.8% (n = 34), and new HIV diagnosis 0.7% (n = 14). The other priority infections were limited to one or two countries. The only features with a positive LR ≥ 3 were diarrhea for enteric fever and elevated alanine aminotransferase level for enteric fever and rickettsiosis. Sensitivities ranged from 29 to 67% for the three RDTs targeting S. Typhi and were 9% and 16% for the two RDTs targeting leptospirosis. Specificities ranged from 86 to 99% for S. Typhi detecting RDTs and were 96% and 97% for leptospirosis RDTs., Conclusions: Leptospirosis, rickettsiosis, and enteric fever accounted each for a substantial proportion of the persistent fever caseload across all tropical areas, in addition to malaria, tuberculosis, and HIV. Very few discriminative features were however identified, and RDTs for leptospirosis and Salmonella Typhi infection performed poorly. Improved field diagnostics are urgently needed for these challenging infections., Trial Registration: NCT01766830 at ClinicalTrials.gov., (© 2022. The Author(s).)

Background: Microscopic examination of Giemsa-stained blood films remains the reference standard for malaria parasite detection and quantification, but is undermined by difficulties in ensuring high-quality manual reading and inter-reader reliability. Automated parasite detection and quantification may address this issue., Methods: A multi-centre, observational study was conducted during 2018 and 2019 at 11 sites to assess the performance of the EasyScan Go, a microscopy device employing machine-learning-based image analysis. Sensitivity, specificity, accuracy of species detection and parasite density estimation were assessed with expert microscopy as the reference. Intra- and inter-device reliability of the device was also evaluated by comparing results from repeat reads on the same and two different devices. This study has been reported in accordance with the Standards for Reporting Diagnostic accuracy studies (STARD) checklist., Results: In total, 2250 Giemsa-stained blood films were prepared and read independently by expert microscopists and the EasyScan Go device. The diagnostic sensitivity of EasyScan Go was 91.1% (95% CI 88.9-92.7), and specificity 75.6% (95% CI 73.1-78.0). With good quality slides sensitivity was similar (89.1%, 95%CI 86.2-91.5), but specificity increased to 85.1% (95%CI 82.6-87.4). Sensitivity increased with parasitaemia rising from 57% at < 200 parasite/µL, to ≥ 90% at > 200-200,000 parasite/µL. Species were identified accurately in 93% of Plasmodium falciparum samples (kappa = 0.76, 95% CI 0.69-0.83), and in 92% of Plasmodium vivax samples (kappa = 0.73, 95% CI 0.66-0.80). Parasite density estimates by the EasyScan Go were within ± 25% of the microscopic reference counts in 23% of slides., Conclusions: The performance of the EasyScan Go in parasite detection and species identification accuracy fulfil WHO-TDR Research Malaria Microscopy competence level 2 criteria. In terms of parasite quantification and false positive rate, it meets the level 4 WHO-TDR Research Malaria Microscopy criteria. All performance parameters were significantly affected by slide quality. Further software improvement is required to improve sensitivity at low parasitaemia and parasite density estimations. Trial registration ClinicalTrials.gov number NCT03512678., (© 2022. The Author(s).)

Background: The use of process evaluations is a growing area of interest in research groups working on complex interventions. This methodology tries to understand how the intervention was implemented to inform policy and practice. A recent systematic review by Liu et al. on process evaluations of complex interventions addressing non-communicable diseases found few studies in low- and middle- income countries (LMIC) because it was restricted to randomized controlled trials, primary healthcare level and non-communicable diseases. Yet, LMICs face different barriers to implement interventions in comparison to high-income countries such as limited human resources, access to health care and skills of health workers to treat chronic conditions especially at primary health care level. Therefore, understanding the challenges of interventions for non-communicable diseases and neglected tropical diseases (diseases that affect poor populations and have chronic sequelae) will be important to improve how process evaluation is designed, conducted and used in research projects in LMICs. For these reasons, in comparison to the study of Liu et al., the current study will expand the search strategy to include different study designs, languages and settings., Objective: Map research using process evaluation in the areas of non-communicable diseases and neglected tropical diseases to inform the gaps in the design and conduct of this type of research in LMICs., Methods: Scoping review of process evaluation studies of randomized controlled trials (RCTs) and non-RCTs of complex interventions implemented in LMICs including participants with non-communicable diseases or neglected tropical diseases and their health care providers (physicians, nurses, technicians and others) related to achieve better health for all through reforms in universal coverage, public policy, service delivery and leadership. The aspects that will be evaluated are as follows: (i) available evidence of process evaluation in the areas of non-communicable diseases and neglected tropical diseases such as frameworks and theories, (ii) methods applied to conduct process evaluations and (iii) gaps between the design of the intervention and its implementation that were identified through the process evaluation. Studies published from January 2008. Exclusion criteria are as follows: not peer reviewed articles, not a report based on empirical research, not reported in English or Spanish or Portuguese or French, reviews and non-human research., Discussion: This scoping review will map the evidence of process evaluations conducted in LMICs. It will also identify the methods they used to collect and interpret data, how different theories and frameworks were used and lessons from the implementation of complex interventions. This information will allow researchers to conduct better process evaluations considering special characteristics from countries with limited human resources, scarce data available and limited access to health care., (© 2021. The Author(s).)

Background: The epidemiology of human cysticercosis and neurocysticercosis, caused by the larval stage of the pork tapeworm Taenia solium, is not well known in the Democratic Republic of Congo (DRC). Within a multicenter etiological and diagnostic study conducted by the NIDIAG consortium ("Better Diagnosis for Neglected Infections") and investigating several challenging syndromes, we consecutively evaluated from 2012 to 2015 all patients older than 5 years presenting with neurological disorders (neurology cohort) and with fever > 7 days (persistent fever cohort) at the rural hospital of Mosango, province of Kwilu, DRC. In both cohorts, etiological diagnosis relied on a systematic set of reference laboratory assays and on pre-established clinical case definitions. No neuroimaging was available in the study hospital. In this study, we determined the frequency of T. solium infection in both cohorts and explored in the neurology cohort its association with specific neurological presentations and final etiological diagnoses., Methods: We conducted a post-hoc descriptive and analytic study on cysticercosis in the neurology and persistent fever cohorts, based on the presence in serum samples of circulating T. solium antigen using the B158/B60 enzyme-linked immunosorbent assay (ELISA) and of cysticercosis IgG using the LDBIO Cysticercosis Western Blot IgG assay., Results: For the neurology cohort, 340 samples (of 351 enrolled patients) were available for analysis (males: 46.8%; mean age: 38.9 years). T. solium antigen positivity was found in 43 participants (12.6%; 95% confidence interval [CI] 9.3-16.7%), including 9 of 60 (15%) patients with epilepsy. Among the 148 samples available from the persistent fever cohort (males: 39.9%; mean age: 19.9 years), 7 were positive in the T. solium antigen ELISA (4.7%; 95% CI 1.9-9.5%; P = 0.009 when compared to the neurology cohort). No significant association was found within the neurology cohort between positivity and clinical presentation or final diagnoses. Of note, the IgG antibody-detecting assay was found positive in only four (1.3%) of the participants of the neurology cohort and in none of the persistent fever cohort., Conclusions: T. solium antigen positivity was found in at least 10% of patients admitted with neurological disorders in the Kwilu province, DRC, with no specific pattern of presentation. Further neuroimaging studies should be used to confirm whether neurocysticercosis is prevalent in this region.

Background: Hypertension (HTN) and diabetes mellitus (DM) are highly prevalent in low- and middle-income countries (LMIC) and a leading cause of morbidity and mortality. Recent evidence on effectiveness of primary care interventions has attracted renewed calls for their implementation. This review aims to synthesize evidence pertaining to primary care interventions on these two diseases, evaluated and tested in LMICs., Methods: Two reviewers conducted an electronic search of three databases (Pubmed, EMBASE and Web of Science) and screened for eligible articles. Interventions covering health promotion, prevention, treatment, or rehabilitation activities at the PHC or community level were included. Studies published in English, French, Portuguese and Spanish, from January 2007 to January 2017, were included. Key extraction variables included the 12 criteria identified by the Template for Intervention Description and Replication (TIDieR) checklist and guide. The Innovative Care for Chronic Conditions Framework (ICCCF) was used to guide analysis and reporting of results., Results: 198 articles were analyzed. The strategies focused on healthcare service organization (76.5%), community level (9.7 %), creating a positive policy environment (3.6%) and strategies covering multiple domains (10.2%). Studies included related to the following topics: description or testing of interventions (n=81; 41.3%), implementation or evaluation projects (n=42; 21.4%), quality improvement initiatives (n=15; 7.7%), screening and prevention efforts (n=26; 13.2%), management of HTN or DM (n=13; 6.6%), integrated health services (n=10; 5.1%), knowledge and attitude surveys (n=5; 2.5%), cost-effective lab tests (n=2; 1%) and policy making efforts (n=2; 1%). Most studies reported interventions by non-specialists (n=86; 43.4%) and multidisciplinary teams (n=49; 25.5%)., Conclusion: Only 198 articles were found over a 10 year period which demonstrates the limited published research on highly prevalent diseases in LMIC. This review shows the variety and complexity of approaches that have been tested to address HTN and DM in LMICs and highlights the elements of interventions needed to be addressed in order to strengthen delivery of care. Most studies reported little information regarding implementation processes to allow replication. Given the need for multi-component complex interventions, study designs and evaluation techniques will need to be adapted by including process evaluations versus simply effectiveness or outcome evaluations.

Background: More than 30,000 malaria cases are reported annually among international travellers. Despite improvements in malaria control, malaria continues to threaten travellers due to inaccurate perception of risk and sub-optimal pre-travel preparation., Methods: Records with a confirmed malaria diagnosis after travel from January 2003 to July 2016 were obtained from GeoSentinel, a global surveillance network of travel and tropical medicine providers that monitors travel-related morbidity. Records were excluded if exposure country was missing or unascertainable or if there was a concomitant acute diagnosis unrelated to malaria. Records were analyzed to describe the demographic and clinical characteristics of international travellers with malaria., Results: There were 5689 travellers included; 325 were children <18 years. More than half (53%) were visiting friends and relatives (VFRs). Most (83%) were exposed in sub-Saharan Africa. The median trip duration was 32 days (interquartile range 20-75); 53% did not have a pre-travel visit. More than half (62%) were hospitalized; children were hospitalized more frequently than adults (73 and 62%, respectively). Ninety-two per cent had a single Plasmodium species diagnosis, most frequently Plasmodium falciparum (4011; 76%). Travellers with P. falciparum were most frequently VFRs (60%). More than 40% of travellers with a trip duration ≤7 days had Plasmodium vivax. There were 444 (8%) travellers with severe malaria; 31 children had severe malaria. Twelve travellers died., Conclusion: Malaria remains a serious threat to international travellers. Efforts must focus on preventive strategies aimed on children and VFRs, and chemoprophylaxis access and preventive measure adherence should be emphasized.

Background: Alveolar echinococcosis is a potentially lethal zoonosis caused by larval forms of the tapeworm Echinococcus multilocularis. Humans are aberrant intermediate hosts who become infected by ingestion of egg-contaminated food or water or via physical contact with domestic or wild animals that carry the parasite in their small intestine. In humans, the disease usually affects the liver and can spread to other organs causing metastatic infiltration. In this report, we describe an advanced presentation of human alveolar echinococcosis mimicking metastatic malignancy., Case Presentation: A 62-year-old white woman was evaluated for fever, jaundice, and abdominal pain, associated with significant weight loss. She lived in a rural area in Switzerland and used to eat wild forest fruits and mushrooms. She owned cats that used to hunt rodents. On physical examination, she appeared severely ill with cachexia, altered mental status, jaundice, and massive hepatomegaly. Laboratory tests showed cholestasis with preserved liver function. An abdominal computed tomography scan showed an enlarged liver with a huge cystic mass in the right lobe extending into the left lobe, infiltrating her hepatic hilum, causing intrahepatic bile duct dilation and occlusion of her right portal vein. A chest computed tomography scan showed multiple calcified bilateral pulmonary nodules. Her clinical and radiological presentation resembled an advanced neoplastic disease. Serologic tests for Echinococcus multilocularis were positive. The diagnosis of alveolar echinococcosis was established on her past history of exposure, imaging, and serology results., Conclusions: Clinical presentation and radiologic imaging findings of disseminated alveolar echinococcosis can mimic metastatic malignancy, and diagnosis can be challenging in atypically advanced cases. As the incidence of human alveolar echinococcosis appears to be increasing in Europe and Switzerland, physicians should be aware of alveolar echinococcosis, its epidemiology, and its clinical features.

Background: Large numbers of Latin American immigrants recently arrived in Western Europe. Curative and preventive programmes need to take account of their risk of suffering and transmitting imported chronic infections and of their susceptibility to cosmopolitan infections. We aimed to assess the prevalence and co-occurrence of imported chronic infections among Latin American immigrants, and their susceptibility to highly prevalent cosmopolitan infections., Methods: Adult participants were recruited in the community and in a primary health centre in Geneva in 2008. Serological tests were performed on stored sera for HIV, HBV, syphilis, Strongyloides stercoralis, Trypanosoma cruzi, varicella and measles. We considered only chronic active infections in the analysis., Results and Discussion: The 1 012 participants, aged 37.2 (SD 11.3) years, were mostly female (82.5 %) and Bolivians (48 %). Overall, 209 (20.7 %) had at least one and 27 (2.7 %) two or more chronic infections. T. cruzi (12.8 %) and S. stercoralis (8.4 %) were the most prevalent chronic active infections compared to syphilis (0.4 %), HBV (0.4 %) and HIV (1.4 %). Concomitant infections affected 28.2 and 18.5 % of T. cruzi and S. stercoralis infected cases. Bolivian origin (aOR: 13.6; 95 % CI: 3.2-57.9) was associated with risk of multiple infections. Susceptibilities for VZV and measles were 0.7 and 1.4 %, respectively. Latin American immigrants are at risk of complications and possible reactivation of chronic parasitic infections but have overall low risks of chronic viral and syphilitic active infections., Conclusions: Systematic screening for chronic active parasitic infections is therefore necessary especially among Bolivians. The high protection rate against measles and VZV doesn't require specific preventive interventions.

Background: In 2007 the "Crisp Report" on international partnerships increased interest in Northern countries on the way their links with Southern partners operated. Since its establishment in 2007 the Division of Tropical and Humanitarian Medicine at the Geneva University Hospitals has developed a variety of partnerships. Frameworks to assess these partnerships are needed and recent attention in the field of public management on collaborative governance may provide a useful approach for analyzing international collaborations., Methods: Projects of the Division of Tropical and Humanitarian Medicine were analyzed by collaborators within the Division using the model proposed by Emerson and colleagues for collaborative governance, which comprises different components that assess the collaborative process., Results: International projects within the Division of Tropical and Humanitarian Medicine can be divided into four categories: Human resource development; Humanitarian response; Neglected Tropical Diseases and Noncommunicable diseases. For each of these projects there was a clear leader from the Division of Tropical and Humanitarian Medicine as well as a local counterpart. These individuals were seen as leaders both due to their role in establishing the collaboration as well as their technical expertise. Across these projects the actual partners vary greatly. This diversity means a wide range of contributions to the collaboration, but also complexity in managing different interests. A common definition of the collaborative aims in each of the projects is both a formal and informal process. Legal, financial and administrative aspects of the collaboration are the formal elements. These can be a challenge based on different administrative requirements. Friendship is part of the informal aspects and helps contribute to a relationship that is not exclusively professional., Conclusion: Using collaborative governance allows the complexity of managing partnerships to be presented. The framework used highlights the process of establishing collaborations, which is an element often negated by other more traditional models used in international partnerships. Applying the framework to the projects of the Division of Tropical and Humanitarian Medicine highlights the importance of shared values and interests, credibility of partners, formal and informal methods of management as well as friendship.

Background: Diarrhoea still accounts for considerable mortality and morbidity worldwide. The highest burden is concentrated in tropical areas where populations lack access to clean water, adequate sanitation and hygiene. In contrast to acute diarrhoea (<14 days), the spectrum of pathogens that may give rise to persistent diarrhoea (≥14 days) and persistent abdominal pain is poorly understood. It is conceivable that pathogens causing neglected tropical diseases play a major role, but few studies investigated this issue. Clinical management and diagnostic work-up of persistent digestive disorders in the tropics therefore remain inadequate. Hence, important aspects regarding the pathogenesis, epidemiology, clinical symptomatology and treatment options for patients presenting with persistent diarrhoea and persistent abdominal pain should be investigated in multi-centric clinical studies., Methods/design: This multi-country, prospective, non-experimental case-control study will assess persistent diarrhoea (≥14 days; in individuals aged ≥1 year) and persistent abdominal pain (≥14 days; in children/adolescents aged 1-18 years) in up to 2000 symptomatic patients and 2000 matched controls. Subjects from Côte d'Ivoire, Indonesia, Mali and Nepal will be clinically examined and interviewed using a detailed case report form. Additionally, each participant will provide a stool sample that will be examined using a suite of diagnostic methods (i.e., microscopic techniques, rapid diagnostic tests, stool culture and polymerase chain reaction) for the presence of bacterial and parasitic pathogens. Treatment will be offered to all infected participants and the clinical treatment response will be recorded. Data obtained will be utilised to develop patient-centred clinical algorithms that will be validated in primary health care centres in the four study countries in subsequent studies., Discussion: Our research will deepen the understanding of the importance of persistent diarrhoea and related digestive disorders in the tropics. A diversity of intestinal pathogens will be assessed for potential associations with persistent diarrhoea and persistent abdominal pain. Different diagnostic methods will be compared, clinical symptoms investigated and diagnosis-treatment algorithms developed for validation in selected primary health care centres. The findings from this study will improve differential diagnosis and evidence-based clinical management of digestive syndromes in the tropics., Trial Registration: ClinicalTrials.gov; identifier: NCT02105714 .

Background: The duration of the stages of HAT is an important factor in epidemiological studies and intervention planning. Previously, we published estimates of the duration of the haemo-lymphatic stage 1 and meningo-encephalitic stage 2 of the gambiense form of human African trypanosomiasis (HAT), in the absence of treatment. Here we revise the estimate of stage 2 duration, computed based on data from Uganda and South Sudan, by adjusting observed infection prevalence for incomplete case detection coverage and diagnostic inaccuracy., Findings: The revised best estimate for the mean duration of stage 2 is 252 days (95% CI 171-399), about half of our initial best estimate, giving a total mean duration of untreated gambiense HAT infection of approximately 2 years and 2 months., Conclusions: Our new estimate provides improved information on the transmission dynamics of this neglected tropical disease in Uganda and South Sudan. We stress that there remains considerable variability around the estimated mean values, and that one must be cautious in applying these results to other foci.

Background: The World Health Organization proposes 6 building blocks for health systems. These are vulnerable to challenges in many contexts. Findings from a 2004 assessment of the health system in Mali for diabetes care found many barriers were present for the management and care of this condition. Following this assessment different projects to strengthen the healthcare system for people living with diabetes were undertaken by a local NGO, Santé Diabète., Case Description: In March 2012, following a Coup in Bamako, the northern part of Mali was occupied and cut-off from the rest of the country. This had a major impact on the health system throughout the country. Due to the lack of response by humanitarian actors, Santé Diabète in close collaboration with other local stakeholders developed a humanitarian response for patients with diabetes. This response included evacuation of children with Type 1 diabetes from northern regions to Bamako; supplies of medicines and tools for management of diabetes; and support to people with diabetes who moved from the north to the south of the country., Discussion: It has been argued that diabetes is a good tracer for health systems and based on Santé Diabète's experience in Mali, diabetes could also be used as a tracer in the context of emergencies. One lesson from this experience is that although people with diabetes should be included as a vulnerable part of the population they are not considered as such. Also within a complex emergency different "diabetes populations" may exist with different needs requiring tailored responses, such as internally displaced people versus those still in conflict areas. From Santé Diabète's perspective, the challenge was changing the ways it operated from a development NGO to an emergency NGO. In this role it could rely on its knowledge of the local situation and its function as part of the post-conflict situation., Conclusion: The lessons learnt from this experience by Santé Diabète in Mali may be useful for other NGOs and the humanitarian response in general in addressing the challenge of managing non communicable diseases and diabetes in conflict and disaster situations in countries with weak health systems.

Background: Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, remains an important public health issue in many Central and South American countries, as well as non-endemic areas with high rates of immigration from these countries. Existing treatment options for CD are limited and often unsatisfactory. Moreover the lack of post-treatment tests of cure limits the development of new drugs. To address this issue, we sought to identify serum biomarkers following nifurtimox (Nfx) treatment that could be used as an early test of cure and/or markers of a therapeutic response., Methods: Human sera from Chagas patients pre- and post-treatment with Nfx (n = 37) were compared to samples from healthy subjects (n = 37) using a range of proteomic and immunologic techniques. Biomarker peaks with the best discriminatory power were further characterized., Results: Using serum samples (n = 111), we validated the presence of five key biomarkers identified in our previous study, namely human apolipoprotein A-I (APOA1) and specific fragments thereof and one fragment of human fibronectin (FN1). In chagasic serum samples all biomarkers except full-length APOA1 were upregulated. These five biomarkers returned to normal in 43% (16/37) of the patients treated with Nfx at three years after treatment., Conclusions: The normalization of biomarker patterns strongly associated with CD suggests that these markers can be used to identify patients in whom Nfx treatment is successful. We believe that these are the first biomarkers predictive of cure in CD patients.

Background: With declining vectorial transmission, Chagas disease predominantly affects adults nowadays. The efficacy of nifurtimox in the chronic phase in adult patients is poorly known, particularly in regions where there is no risk of reinfection. Recommendations for treatment outcome assessment rely on serological follow-up. We evaluated the serological and parasitological response to nifurtimox in a cohort of adult patients three years post-treatment in Switzerland., Methods: Patients treated with nifurtimox in 2008 during a cross-sectional study in Geneva, Switzerland, were contacted for follow-up in 2011. Two ELISAs and a rapid immunochromatographic test were used to test 2008 and 2011 serum samples simultaneously. In addition, conventional and real-time PCR were performed on 2011 samples., Results: Thirty-seven (84.1%) of 44 eligible patients, predominantly female, middle-aged, Bolivians at the indeterminate stage, were enrolled. All 2011 ELISA and immunochromatographic tests were positive. Twenty-eight (75.7%) patients presented a lower optical density (OD) in 2011 compared to 2008. This OD difference was significant in both commercial (P < 0.001) and in-house (P = 0.002) ELISAs. Agreement between the two ELISAs was low (Kappa = 0.469). All patients had negative conventional PCR results but one (2.7%) was positive with real-time PCR., Conclusion: Our results highlight the inadequacy of serology for assessing response in adults, three years after treatment. In our cohort, 97.3% had results that could either indicate treatment failure or persistant humoral response despite treatment. The lack of accurate early post-treatment tests of cure prevents appropriate patients information and councelling. New follow-up tests are needed to assess treatments efficacy given the large adult population in need of antiparasitic therapy.

Background: Persistent digestive disorders account for considerable disease burden in the tropics. Despite advances in understanding acute gastrointestinal infections, important issues concerning epidemiology, diagnosis, treatment and control of most persistent digestive symptomatologies remain to be elucidated. Helminths and intestinal protozoa are considered to play major roles, but the full extent of the aetiologic spectrum is still unclear. We provide an overview of pathogens causing digestive disorders in the tropics and evaluate available reference tests., Methods: We searched the literature to identify pathogens that might give rise to persistent diarrhoea, chronic abdominal pain and/or blood in the stool. We reviewed existing laboratory diagnostic methods for each pathogen and stratified them by (i) microscopy; (ii) culture techniques; (iii) immunological tests; and (iv) molecular methods. Pathogen-specific reference tests providing highest diagnostic accuracy are described in greater detail., Results: Over 30 pathogens may cause persistent digestive disorders. Bacteria, viruses and parasites are important aetiologic agents of acute and long-lasting symptomatologies. An integrated approach, consisting of stool culture, microscopy and/or specific immunological techniques for toxin, antigen and antibody detection, is required for accurate diagnosis of bacteria and parasites. Molecular techniques are essential for sensitive diagnosis of many viruses, bacteria and intestinal protozoa, and are increasingly utilised as adjuncts for helminth identification., Conclusions: Diagnosis of the broad spectrum of intestinal pathogens is often cumbersome. There is a need for rapid diagnostic tests that are simple and affordable for resource-constrained settings, so that the management of patients suffering from persistent digestive disorders can be improved.

Background: Alcohol problems are a major health issue in Nepal and remain under diagnosed. Increase in consumption are due to many factors, including advertising, pricing and availability, but accurate information is lacking on the prevalence of current alcohol use disorders. The AUDIT (Alcohol Use Disorder Identification Test) questionnaire developed by WHO identifies individuals along the full spectrum of alcohol misuse and hence provides an opportunity for early intervention in non-specialty settings. This study aims to validate a Nepali version of AUDIT among patients attending a university hospital and assess the prevalence of alcohol use disorders along the full spectrum of alcohol misuse., Methods: This cross-sectional study was conducted in patients attending the medicine out-patient department of a university hospital. DSM-IV diagnostic categories (alcohol abuse and alcohol dependence) were used as the gold standard to calculate the diagnostic parameters of the AUDIT. Hazardous drinking was defined as self reported consumption of ≥21 standard drink units per week for males and ≥14 standard drink units per week for females., Results: A total of 1068 individuals successfully completed the study. According to DSM-IV, drinkers were classified as follows: No alcohol problem (n=562; 59.5%), alcohol abusers (n= 78; 8.3%) and alcohol dependent (n=304; 32.2%). The prevalence of hazardous drinker was 67.1%. The Nepali version of AUDIT is a reliable and valid screening tool to identify individuals with alcohol use disorders in the Nepalese population. AUDIT showed a good capacity to discriminate dependent patients (with AUDIT ≥11 for both the gender) and hazardous drinkers (with AUDIT ≥5 for males and ≥4 for females). For alcohol dependence/abuse the cut off values was ≥9 for both males and females., Conclusion: The AUDIT questionnaire is a good screening instrument for detecting alcohol use disorders in patients attending a university hospital. This study also reveals a very high prevalence of alcohol use disorders in Nepal.

Background: Active case detection through mass community screening is a major control strategy against human African trypanosomiasis (HAT, sleeping sickness) caused by T. brucei gambiense. However, its impact can be limited by incomplete attendance at screening sessions (screening coverage) and diagnostic inaccuracy., Methods: We developed a model-based approach to estimate the true prevalence and the fraction of cases detected during mass screening, based on observed prevalence, and adjusting for incomplete screening coverage and inaccuracy of diagnostic algorithms for screening, confirmation and HAT stage classification. We applied the model to data from three Médecins Sans Frontières projects in Uganda (Adjumani, Arua-Yumbe) and Southern Sudan (Kiri)., Results: We analysed 604 screening sessions, targeting about 710,000 people. Cases were about twice as likely to attend screening as non-cases, with no apparent difference by stage. Past incidence, population size and repeat screening rounds were strongly associated with observed prevalence. The estimated true prevalence was 0.46% to 0.90% in Kiri depending on the analysis approach, compared to an observed prevalence of 0.45%; 0.59% to 0.87% in Adjumani, compared to 0.92%; and 0.18% to 0.24% in Arua-Yumbe, compared to 0.21%. The true ratio of stage 1 to stage 2 cases was around two-three times higher than that observed, due to stage misclassification. The estimated detected fraction was between 42.2% and 84.0% in Kiri, 52.5% to 79.9% in Adjumani and 59.3% to 88.0% in Arua-Yumbe., Conclusions: In these well-resourced projects, a moderate to high fraction of cases appeared to be detected through mass screening. True prevalence differed little from observed prevalence for monitoring purposes. We discuss some limitations to our model that illustrate several difficulties of estimating the unseen burden of neglected tropical diseases.

Background: Human African trypanosomiasis (HAT), or sleeping sickness, is a fatal neglected tropical disease if left untreated. HAT primarily affects people living in rural sub-Saharan Africa, often in regions afflicted by violent conflict. Screening and treatment of HAT is complex and resource-intensive, and especially difficult in insecure, resource-constrained settings. The country with the highest endemicity of HAT is the Democratic Republic of Congo (DRC), which has a number of foci of high disease prevalence. We present here the challenges of carrying out HAT control programmes in general and in a conflict-affected region of DRC. We discuss the difficulties of measuring disease burden, medical care complexities, waning international support, and research and development barriers for HAT., Discussion: In 2007, Médecins Sans Frontières (MSF) began screening for HAT in the Haut-Uélé and Bas-Uélé districts of Orientale Province in northeastern DRC, an area of high prevalence affected by armed conflict. Through early 2009, HAT prevalence rate of 3.4% was found, reaching 10% in some villages. More than 46,000 patients were screened and 1,570 treated for HAT during this time. In March 2009, two treatment centres were forced to close due to insecurity, disrupting patient treatment, follow-up, and transmission-control efforts. One project was reopened in December 2009 when the security situation improved, and another in late 2010 based on concerns that population displacement might reactivate historic foci. In all of 2010, 770 patients were treated at these sites, despite a limited geographical range of action for the mobile teams., Summary: In conflict settings where HAT is prevalent, targeted medical interventions are needed to provide care to the patients caught in these areas. Strategies of integrating care into existing health systems may be unfeasible since such infrastructure is often absent in resource-poor contexts. HAT care in conflict areas must balance logistical and medical capacity with security considerations, and community networks and international-response coordination should be maintained. Research and development for less complicated, field-adapted tools for diagnosis and treatment, and international support for funding and program implementation, are urgently needed to facilitate HAT control in these remote and insecure areas.

Background: The durations of untreated stage 1 (early stage, haemo-lymphatic) and stage 2 (late stage, meningo-encephalitic) human African trypanosomiasis (sleeping sickness) due to Trypanosoma brucei gambiense are poorly quantified, but key to predicting the impact of screening on transmission. Here, we outline a method to estimate these parameters., Methods: We first model the duration of stage 1 through survival analysis of untreated serological suspects detected during Médecins Sans Frontières interventions in Uganda and Sudan. We then deduce the duration of stage 2 based on the stage 1 to stage 2 ratio observed during active case detection in villages within the same sites., Results: Survival in stage 1 appears to decay exponentially (daily rate = 0.0019; mean stage 1 duration = 526 days [95%CI 357 to 833]), possibly explaining past reports of abnormally long duration. Assuming epidemiological equilibrium, we estimate a similar duration of stage 2 (500 days [95%CI 345 to 769]), for a total of nearly three years in the absence of treatment., Conclusion: Robust estimates of these basic epidemiological parameters are essential to formulating a quantitative understanding of sleeping sickness dynamics, and will facilitate the evaluation of different possible control strategies.

Background: Artemisinin-containing therapies are highly effective against Plasmodium falciparum malaria. Insufficient numbers of tablets and inadequate package inserts result in sub-optimal dosing and possible treatment failure. This study reports the case of three, non-immune, expatriate workers with P. falciparum acquired in Africa, who failed to respond to artemisinin-based therapy. Sub-therapeutic dosing in accordance with the manufacturers' recommendations was the probable cause., Method: Manufacturers information and drug content included in twenty-five artemisinin-containing specialities were reviewed., Results: A substantial number of manufacturers do not follow current WHO recommendations regarding treatment duration and doses., Conclusion: This study shows that drug packaging and their inserts should be improved.