Introduction and acceptability of the Surveillance Outbreak Response Management and Analysis System (SORMAS) during the COVID-19 pandemic in Côte d'Ivoire.

BACKGROUND: The Surveillance Outbreak Response Management and Analysis System (SORMAS) has been implemented for various infectious diseases since 2015. 2020, at the beginning of the COVID-19 pandemic, SORMAS was adapted to SARS-CoV2. METHODS: We assessed the acceptability and usability of SORMAS and accompanied its implementation in two pilot regions of Côte d'Ivoire (Abidjan 2 and Gbêkê) from July/August 2021 to March 2022. We conducted 136 semi-structured interviews to cover knowledge on COVID-19, information on conventional surveillance systems for disease monitoring including COVID-19, acceptability of SORMAS, and impact of SORMAS on epidemic preparedness and surveillance. Scores before and 6-8 months after implementation were compared. RESULTS: SORMAS was implemented in two pilot regions in Côte d'Ivoire. The conventional software for the surveillance of the COVID-19 pandemic by the company MAGPI was maintained in parallel; the additional time needs to enter and manage the data in SORMAS were the main concern. SORMAS acceptance and satisfaction scores were high after the user training, which was prior to implementation, and after 6-8 months of use. The ability of SORMAS to improve COVID-19 preparedness and early detection of cases and contacts was widely acknowledged. To keep the understanding and skills of users up-to-date, regular refresher trainings were requested. The expectation to be able to make decisions based on data produced by SORMAS was high at baseline and the perceived experience after several months of use of the software was very positive. Unfortunately, the link with the laboratories could not be established in the pilot regions, but it is an existing feature of SORMAS that many users were asking for. Following the positive experience using SORMAS for COVID-19, the pilot regions expanded its use for monitoring and management of measles, yellow fever, meningitis, and cholera. CONCLUSION: SORMAS was very well accepted by users and decision makers in the two pilot regions of Côte d'Ivoire and its ability to improve epidemic preparedness and surveillance was acknowledged. If the hurdles of maintenance (tablets, server, and maintaining user skills) are handled sustainably, it can serve as a valid tool to identify, surveil and manage future outbreaks of various infectious diseases in Côte d'Ivoire.

Nutritional status of Tajik children and women: Transition towards a double burden of malnutrition.

The double burden of malnutrition, an emerging concern in developing countries, can exist at various levels: individual, household, and population. Here, we explore the nutritional status of Tajik women (15-49 years) and children (5-59 months) focusing on overweight/obesity along with undernutrition (underweight, stunting, and micronutrient deficiencies). For this, nutritional markers (haemoglobin (Hb), transferrin receptor (TfR), serum ferritin (Sf), retinol binding protein (RBP), vitamin D, serum folate, and urinary iodine), height, and weight were assessed from 2,145 women and 2,149 children. Dietary intake, weaning, and breastfeeding habits were recorded using a 24-hr recall and a questionnaire. Overweight (24.5%) and obesity (13.0%) are increasing among Tajik women compared with previous national surveys (2003 and 2009). Prevalence of iron deficiency and anaemia was 38.0% and 25.8%, respectively; 64.5% of women were iodine deficient, 46.5% vitamin A deficient, and 20.5% had insufficient folate levels. Women in rural areas had significantly lower iron status and body mass index and higher iodine intake compared with urban areas; 20.9% of children were stunted, 2.8% wasted, 6.2% underweight, 52.4% iron deficient, and 25.8% anaemic; all more prominent in rural areas. Dietary diversity was higher among urban women. Intraindividual or household double burden was not seen. In summary, double burden of malnutrition constituted an increase in overweight among women, especially in urban areas, and persisting levels of undernutrition (stunting, iron, and vitamin A deficiency), predominately in rural areas. A holistic, innovative approach is needed to improve infant and young children feeding and advise mothers to maintain an adequate diet.

The Leprosy Post-Exposure Prophylaxis (LPEP) programme: update and interim analysis.

Innovative approaches are required to further enhance leprosy control, reduce the number of people developing leprosy, and curb transmission. Early case detection, contact screening, and chemoprophylaxis currently is the most promising approach to achieve this goal. The Leprosy Post-Exposure Prophylaxis (LPEP) programme generates evidence on the feasibility of integrating contact tracing and single-dose rifampicin (SDR) administration into routine leprosy control activities in different settings. The LPEP programme is implemented within the leprosy control programmes of Brazil, Cambodia, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Focus is on three key interventions: tracing the contacts of newly diagnosed leprosy patients; screening the contacts for leprosy; and administering SDR to eligible contacts. Country-specific protocol adaptations refer to contact definition, minimal age for SDR, and staff involved. Central coordination, detailed documentation and rigorous supervision ensure quality evidence. Around 2 years of field work had been completed in seven countries by July 2017. The 5,941 enrolled index patients (89·4% of the registered) identified a total of 123,311 contacts, of which 99·1% were traced and screened. Among them, 406 new leprosy patients were identified (329/100,000), and 10,883 (8·9%) were excluded from SDR for various reasons. Also, 785 contacts (0·7%) refused the prophylactic treatment with SDR. Overall, SDR was administered to 89·0% of the listed contacts. Post-exposure prophylaxis with SDR is safe; can be integrated into the routines of different leprosy control programmes; and is generally well accepted by index patients, their contacts and the health workforce. The programme has also invigorated local leprosy control.

Prebiotic galacto-oligosaccharides mitigate the adverse effects of iron fortification on the gut microbiome: a randomised controlled study in Kenyan infants.

OBJECTIVE: Iron-containing micronutrient powders (MNPs) reduce anaemia in African infants, but the current high iron dose (12.5 mg/day) may decrease gut Bifidobacteriaceae and Lactobacillaceae, and increase enteropathogens, diarrhoea and respiratory tract infections (RTIs). We evaluated the efficacy and safety of a new MNP formula with prebiotic galacto-oligosaccharides (GOS) combined with a low dose (5 mg/day) of highly bioavailable iron. DESIGN: In a 4-month, controlled, double-blind trial, we randomised Kenyan infants aged 6.5-9.5 months (n=155) to receive daily (1) a MNP without iron (control); (2) the identical MNP but with 5 mg iron (2.5 mg as sodium iron ethylenediaminetetraacetate and 2.5 mg as ferrous fumarate) (Fe group); or (3) the identical MNP as the Fe group but with 7.5 g GOS (FeGOS group). RESULTS: Anaemia decreased by ≈50% in the Fe and FeGOS groups (p<0.001). Compared with the control or FeGOS group, in the Fe group there were (1) lower abundances of Bifidobacterium and Lactobacillus and higher abundances of Clostridiales (p<0.01); (2) higher abundances of virulence and toxin genes (VTGs) of pathogens (p<0.01); (3) higher plasma intestinal fatty acid-binding protein (a biomarker of enterocyte damage) (p<0.05); and (4) a higher incidence of treated RTIs (p<0.05). In contrast, there were no significant differences in these variables comparing the control and FeGOS groups, with the exception that the abundance of VTGs of all pathogens was significantly lower in the FeGOS group compared with the control and Fe groups (p<0.01). CONCLUSION: A MNP containing a low dose of highly bioavailable iron reduces anaemia, and the addition of GOS mitigates most of the adverse effects of iron on the gut microbiome and morbidity in African infants. TRIAL REGISTRATION NUMBER: NCT02118402.

Operational and implementation research within Global Fund to Fight AIDS, Tuberculosis and Malaria grants: a situation analysis in six countries.

BACKGROUND: Operational/implementation research (OR/IR) is a key activity to improve disease control programme performance. We assessed the extent to which malaria and tuberculosis (TB) grants from the Global Fund to Fight AIDS, Tuberculosis and Malaria ("Global Fund") include support for OR/IR, and discuss the implications of the current Global Fund operating mechanisms for OR/IR support. METHODS: The situation analysis focussed on malaria and TB, while HIV was excluded. Stakeholder interviews were conducted at the Global Fund secretariat and in six purposefully selected high disease burden countries, namely the Democratic Republic of the Congo, Ethiopia, India, Indonesia, Myanmar and Zimbabwe. Interviewed in-country stakeholders included the relevant disease control programme managers, project implementation partners, representatives from international organisations with a stake in global health, academic and governmental research institutions, and other relevant individuals such as members of the country coordination mechanism. Additionally, documentation of grants and OR/IR obtained from the Global Fund was reviewed. RESULTS: The Global Fund provides substantial resources for malaria and TB surveys, and supports OR/IR if such support is requested and the application is well justified. We observed considerable variations from one country to another and between programmes with regards to need, demand, absorption capacity and funding for OR/IR related to malaria and TB. Important determinants for the extent of such funding are the involvement of national research coordination bodies, established research agendas and priorities, human and technical research capacity, and involvement of relevant stakeholders in concept note development. Efforts to disseminate OR/IR findings were generally weak, and the Global Fund does not maintain a central OR/IR database. When faced with a need to choose between procurement of commodities for disease control and supporting research, countries tend to seek research funding from other donors. The Global Fund is expected to issue more specific guidance on the conditions under which it supports OR/IR, and to adapt administrative procedures to facilitate research. CONCLUSIONS: The importance of OR/IR for optimising disease control programmes is generally accepted but countries vary in their capacity to demand and implement studies. Countries expect guidance on OR/IR from the Global Fund. Administrative procedures specifically related to the budget planning should be modified to facilitate ad-hoc OR/IR funding. More generally, several countries expressed a need to strengthen capacity for planning, negotiating and implementing research.

Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants.

BACKGROUND: In-home iron fortification for infants in developing countries is recommended for control of anaemia, but low absorption typically results in >80% of the iron passing into the colon. Iron is essential for growth and virulence of many pathogenic enterobacteria. We determined the effect of high and low dose in-home iron fortification on the infant gut microbiome and intestinal inflammation. METHODS: We performed two double-blind randomised controlled trials in 6-month-old Kenyan infants (n=115) consuming home-fortified maize porridge daily for 4 months. In the first, infants received a micronutrient powder (MNP) containing 2.5 mg iron as NaFeEDTA or the MNP without iron. In the second, they received a different MNP containing 12.5 mg iron as ferrous fumarate or the MNP without the iron. The primary outcome was gut microbiome composition analysed by 16S pyrosequencing and targeted real-time PCR (qPCR). Secondary outcomes included faecal calprotectin (marker of intestinal inflammation) and incidence of diarrhoea. We analysed the trials separately and combined. RESULTS: At baseline, 63% of the total microbial 16S rRNA could be assigned to Bifidobacteriaceae but there were high prevalences of pathogens, including Salmonella Clostridium difficile, Clostridium perfringens, and pathogenic Escherichia coli. Using pyrosequencing, +FeMNPs increased enterobacteria, particularly Escherichia/Shigella (p=0.048), the enterobacteria/bifidobacteria ratio (p=0.020), and Clostridium (p=0.030). Most of these effects were confirmed using qPCR; for example, +FeMNPs increased pathogenic E. coli strains (p=0.029). +FeMNPs also increased faecal calprotectin (p=0.002). During the trial, 27.3% of infants in +12.5 mgFeMNP required treatment for diarrhoea versus 8.3% in -12.5 mgFeMNP (p=0.092). There were no study-related serious adverse events in either group. CONCLUSIONS: In this setting, provision of iron-containing MNPs to weaning infants adversely affects the gut microbiome, increasing pathogen abundance and causing intestinal inflammation. TRIAL REGISTRATION NUMBER: NCT01111864.

Bifidobacteria strains isolated from stools of iron deficient infants can efficiently sequester iron.

BACKGROUND: Bifidobacteria is one of the major gut commensal groups found in infants. Their colonization is commonly associated with beneficial effects to the host through mechanisms like niche occupation and nutrient competition against pathogenic bacteria. Iron is an essential element necessary for most microorganisms, including bifidobacteria and efficient competition for this micronutrient is linked to proliferation and persistence. For this research we hypothesized that bifidobacteria in the gut of iron deficient infants can efficiently sequester iron. The aim of the present study was to isolate bifidobacteria in fecal samples of iron deficient Kenyan infants and to characterize siderophore production and iron internalization capacity. RESULTS: Fifty-six bifidobacterial strains were isolated by streaking twenty-eight stool samples from Kenyan infants, in enrichment media. To target strains with high iron sequestration mechanisms, a strong iron chelator 2,2-dipyridyl was supplemented to the agar media. Bifidobacterial isolates were first identified to species level by 16S rRNA sequencing, yielding B. bifidum (19 isolates), B. longum (15), B. breve (11), B. kashiwanohense (7), B. pseudolongum (3) and B. pseudocatenulatum (1). While most isolated bifidobacterial species are commonly encountered in the infantile gut, B. kashiwanohense was not frequently reported in infant feces. Thirty strains from culture collections and 56 isolates were characterized for their siderophore production, tested by the CAS assay. Siderophore activity ranged from 3 to 89% siderophore units, with 35 strains (41%) exhibiting high siderophore activity, and 31 (36%) and 20 (23%) showing intermediate or low activity. The amount of internalized iron of 60 bifidobacteria strains selected for their siderophore activity, was in a broad range from 8 to118 µM Fe. Four strains, B. pseudolongum PV8-2, B. kashiwanohense PV20-2, B. bifidum PV28-2a and B. longum PV5-1 isolated from infant stool samples were selected for both high siderophore activity and iron internalization. CONCLUSIONS: A broad diversity of bifidobacteria were isolated in infant stools using iron limited conditions, with some strains exhibiting high iron sequestration properties. The ability of bifidobacteria to efficiently utilize iron sequestration mechanism such as siderophore production and iron internalization may confer an ecological advantage and be the basis for enhanced competition against enteropathogens.

Iron interventions in children from low-income and middle-income populations: benefits and risks.

PURPOSE OF REVIEW: Children from low- and middle-income countries are particularly vulnerable to develop iron deficiency and iron deficiency anaemia (IDA), which can be prevented or controlled with different iron intervention strategies. However, there is a debate on the efficacy and safety of iron interventions, especially in children from areas with a high infectious disease burden. This review provides an overview of recent trials that investigated the benefits and potential risks of iron interventions in children from low and middle-income countries. RECENT FINDINGS: Recent studies showed that intermittent iron supplementation is a promising strategy in reducing iron deficiency and IDA. Only a few studies investigated the effect of iron interventions on developmental outcomes, such as growth and cognition, and provided mixed results. An increasing number of studies reported that iron intervention increases morbidity and causes unfavourable shifts in the gut microbial composition along with increases in intestinal inflammation, particularly in children with a high infectious disease burden. SUMMARY: More studies in children from low and middle-income populations are needed that provide evidence for the beneficial effects of iron interventions on functional outcomes beyond alleviating iron deficiency and IDA, and that explore potential mechanisms underlying the negative effects of iron reported in recent trials.

In-home fortification with 2.5 mg iron as NaFeEDTA does not reduce anaemia but increases weight gain: a randomised controlled trial in Kenyan infants.

In-home fortification of infants with micronutrient powders (MNPs) containing 12.5 mg iron may increase morbidity from infections; therefore, an efficacious low-dose iron-containing MNP might be advantageous. Effects of iron-containing MNPs on infant growth are unclear. We assessed the efficacy of a low-iron MNP on iron status and growth and monitored safety in a randomised, controlled, double-blind 1-year trial in 6-month-old infants (n = 287) consuming daily a maize porridge fortified with either a MNP including 2.5 mg iron as NaFeEDTA (MNP + Fe) or the same MNP without iron (MNP - Fe). At baseline, after 6 and 12 months, we determined haemoglobin (Hb), iron status [serum ferritin (SF), soluble transferrin receptor (sTfR) and zinc protoporphyrin (ZPP)], inflammation [C-reactive protein (CRP)] and anthropometrics. We investigated safety using weekly morbidity questionnaires asking for diarrhoea, cough, flu, bloody or mucus-containing stool and dyspnoea, and recorded any other illness. Furthermore, feeding history and compliance were assessed weekly. At baseline, 71% of the infants were anaemic and 22% iron deficient; prevalence of inflammation was high (31% had an elevated CRP). Over the 1 year, Hb increased and SF decreased in both groups, without significant treatment effects of the iron fortification. At end point, the weight of infants consuming MNP + Fe was greater than in the MNP - Fe group (9.9 vs. 9.5 kg, P = 0.038). Mothers of infants in the MNP + Fe group reported more infant days spent with cough (P = 0.003) and dyspnoea (P = 0.0002); there were no significant differences on any other of the weekly morbidity measures. In this study, low-dose iron-containing MNP did not improve infant's iron status or reduce anaemia prevalence, likely because absorption was inadequate due to the high prevalence of infections and the low-iron dose.

Key Characteristics and Perception of Different Outbreak Surveillance Systems in Côte d'Ivoire: Cross-Sectional Survey Among Users.

Background: Accurate and timely infectious disease surveillance is pivotal for effective public health responses. An important component of this is the disease surveillance tools used. Understanding views and experiences of users is crucial for informing policy decisions and ensuring the seamless functioning of surveillance systems. Objective: In this study, we aimed to assess the user perceptions of 3 disease surveillance tools used in Côte d'Ivoire, namely, MAGPI, District Health Information Software 2 (DHIS2), and Surveillance Outbreak Response Management and Analysis System (SORMAS), the latter was implemented in 2021 within a pilot scheme. Methods: We conducted interviews and a web-based survey distributed to users of the 3 surveillance tools. The survey assessed users' views of the surveillance tools' usefulness, ease of use, feelings toward the tool, conditions that may influence the use, and other characteristics. The descriptive analysis compared responses from SORMAS, MAGPI, and DHIS2 users, providing a comprehensive evaluation of their experiences. Results: Among the 159 respondents who actively use one of the systems, MAGPI was the most widely used surveillance tool among respondents (n=127, 79.9%), followed by DHIS2 (n=108, 67.9%), and SORMAS (n=25, 15.7%). In terms of users' perceptions, SORMAS, despite its limited implementation, emerged as a tool that allows for data analysis and had the most comprehensive set of functionalities. DHIS2 was appreciated for its frequency of report provision, although users reported occasional IT system failures. MAGPI was recognized for its ease of use but was reported to lack certain functionalities offered by the other surveillance systems. Conclusions: This study offers valuable insights into the perceptions of disease surveillance tools users in Côte d'Ivoire. While all systems were positively regarded, each exhibited strengths and weaknesses addressing different needs and functionalities. Policy makers and health officials can use these findings to enhance existing tools or consider a unified approach for infectious disease surveillance systems. Understanding users' perspectives allows them to optimize the choice of surveillance tools, ultimately strengthening public health responses in Côte d'Ivoire and potentially serving as a model for other countries facing similar decisions in their health care systems.

Nutrition transition, double burden of malnutrition, and urbanization patterns in secondary cities of Bangladesh, Kenya and Rwanda.

BACKGROUND: By 2050, approximately 68% of the global population will live in cities, but nutrition data on urban populations of low- and middle-income countries are scarce. Fast growing secondary cities, combining characteristics and hurdles of urban and rural settings, are hotspots for the double burden of malnutrition. The Nutrition in City Ecosystems (NICE) project focuses on 6 secondary cities in Bangladesh, Kenya and Rwanda, to improve health and nutrition, and reduce poverty. To assess the baseline situation and guide future interventions, food insecurity, dietary diversity, nutrition status, and food production and purchasing patterns were explored. METHODS: In a cross-sectional study design, data were collected from urban and peri-urban households of Dinajpur and Rangpur in Bangladesh, Bungoma and Busia in Kenya, and Rubavu and Rusizi in Rwanda. Approximately 1200 households, in neighborhoods prone to malnutrition, were involved from April to June 2021. We assessed Household Food Insecurity Access Score (HFIAS), both current and before COVID-19, Household Dietary Diversity Score (HDDS), Minimum Dietary Diversity for Women (MDD-W), anthropometric measurements, household and socioeconomic information, and questions related to food production and consumer behavior. Further we collected secondary data on low birthweight and anemia during pregnancy. RESULTS: All cities experienced a substantial increase in food insecurity during the COVID-19 pandemic. Stunting rates in children under 5 years varied among the cities and ranged from 7.8% in Busia to 46.6% in Rubavu, while half of adult women were overweight (between 42.1% in Rusizi and 55.8% in Bungoma). Furthermore, many women did not consume an adequately diverse diet (MDD-W < 5 for 29.3% in Bangladesh, 47.5% in Kenya, and 67.0% in Rwanda), however many of the urban and peri-urban households were engaged in farming (58-78%). CONCLUSIONS: The double burden of malnutrition is high in secondary cities and the COVID-19 pandemic has exacerbated levels of food insecurity. Demand for, and access to, an affordable healthy diverse diet that comprises local, nutritious, and agroecologically produced foods present a pathway for overcoming the complex challenges of malnutrition.

Nutrition in City Ecosystems (NICE): Protocol of a multi-sectoral development project to improve food and nutrition security of secondary city populations in Bangladesh, Kenya and Rwanda.

Background: Secondary cities tend to be better linked with local food systems than primate cities, acting as important platforms to trade agricultural produce with rural surrounding. COVID-19, conflicts and climate change continue to expose inefficiencies in food systems and have further exacerbated malnutrition, calling for substantial food systems transformations. However, tackling current food systems' challenges requires new approaches to ensure food and nutrition security. Nutritious and agroecologically produced food offer the potential to transform food systems by improving diets and alleviating pressure on the environment, as well as by creating jobs and reducing poverty. This paper describes the design of a project by a Swiss public-private consortium to improve food and nutrition security and to reduce poverty in city ecosystems in six secondary cities in Bangladesh, Kenya and Rwanda through governance/policy and supply and demand side interventions. Methods: The Nutrition in City Ecosystems (NICE) project promotes well-balanced nutrition for city populations through interdisciplinary agricultural, food, and health sector collaborations along city-specific value chains. Adopting a transdiciplinary systems approach, the main interventions of NICE are (i) advocacy and policy dialogue, (ii) building of decentralized institutional capacity in multi-sectoral collaborations, (iii) support of data-driven planning, coordination and resource mobilization, (iv) anchoring of innovations and new approaches in city-level partnerships, (v) capacity building in the agricultural, retail, health and education sectors, as well as (vi) evidence generation from putting policies into practice at the local level. NICE is coordinated by in-country partners and local offices of the Swiss public-private consortium partners. Discussion: The NICE project seeks to contribute to urban food system resilience and enhanced sustainable nutrition for city populations by (A) strengthening urban governance structures involving key stakeholders including women and youth, (B) generating income for producers along the supply chain, (C) triggering change in producers' and consumers' behavior such that nutritious and agroecologically produced foods are both in demand as well as available and affordable in urban markets, and (D) allowing a scale up of successful approaches to other national and international cities and city networks.

Iron depletion and repletion with ferrous sulfate or electrolytic iron modifies the composition and metabolic activity of the gut microbiota in rats.

Iron (Fe) deficiency anemia is a global health concern and Fe fortification and supplementation are common corrective strategies. Fe is essential not only for the human host but also for nearly all gut bacteria. We studied the impact of Fe deficiency and Fe repletion on the gut microbiota in rats. Weanling rats were fed an Fe-deficient diet for 24 d and then repleted for 13 d with FeSO4 (n = 15) or electrolytic Fe (n = 14) at 10 and 20 mg Fe · kg diet⁻¹. In addition, one group of rats (n = 8) received the Fe-deficient diet and one group (n = 3) received a Fe-sufficient control diet for all 37 d. Fecal samples were collected at baseline and after the depletion and repletion periods, and colonic tissues were examined histologically. Microbial metabolite composition in cecal water was measured and fecal samples were analyzed for microbial composition with temporal temperature gradient gel electrophoresis and qPCR. Compared to Fe-sufficient rats, Fe-deficient rats had significantly lower concentrations of cecal butyrate (-87%) and propionate (-72%) and the abundance of dominant species was strongly modified, including greater numbers of lactobacilli and Enterobacteriaceae and a large significant decrease of the Roseburia spp./E. rectale group, a major butyrate producer. Repletion with 20 mg FeSO4 · kg diet⁻¹ significantly increased cecal butyrate concentrations and partially restored bacterial populations compared to Fe-deficient rats at endpoint. The effects on the gut microbiota were stronger in rats repleted with FeSO4 than in rats repleted with electrolytic Fe, suggesting ferrous Fe may be more available for utilization by the gut microbiota than elemental Fe. Repletion with FeSO4 significantly increased neutrophilic infiltration of the colonic mucosa compared to Fe-deficient rats. In conclusion, Fe depletion and repletion strongly affect the composition and metabolic activity of rat gut microbiota.

The long-term impact of the Leprosy Post-Exposure Prophylaxis (LPEP) program on leprosy incidence: A modelling study.

BACKGROUND: The Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of single dose rifampicin (SDR) to eligible contacts of newly diagnosed leprosy patients in Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. As the impact of the programme is difficult to establish in the short term, we apply mathematical modelling to predict its long-term impact on the leprosy incidence. METHODOLOGY: The individual-based model SIMCOLEP was calibrated and validated to the historic leprosy incidence data in the study areas. For each area, we assessed two scenarios: 1) continuation of existing routine activities as in 2014; and 2) routine activities combined with LPEP starting in 2015. The number of contacts per index patient screened varied from 1 to 36 between areas. Projections were made until 2040. PRINCIPAL FINDINGS: In all areas, the LPEP program increased the number of detected cases in the first year(s) of the programme as compared to the routine programme, followed by a faster reduction afterwards with increasing benefit over time. LPEP could accelerate the reduction of the leprosy incidence by up to six years as compared to the routine programme. The impact of LPEP varied by area due to differences in the number of contacts per index patient included and differences in leprosy epidemiology and routine control programme. CONCLUSIONS: The LPEP program contributes significantly to the reduction of the leprosy incidence and could potentially accelerate the interruption of transmission. It would be advisable to include contact tracing/screening and SDR in routine leprosy programmes.

Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP): an international feasibility programme.

BACKGROUND: Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities. METHODS: The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates. FINDINGS: Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174 782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported. INTERPRETATION: Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established. FUNDING: Novartis Foundation.

Core components, concepts and strategies for parasitic and vector-borne disease elimination with a focus on schistosomiasis: A landscape analysis.

Efforts to control and eliminate human schistosomiasis have accelerated over the past decade. In a number of endemic countries and settings, interruption of schistosome transmission has been achieved. In others, Schistosoma infections continue to challenge program managers at different levels, from the complexity of the transmission cycle, over limited treatment options and lack of field-friendly accurate diagnostics, to controversy around adequate intervention strategies. We conducted a landscape analysis on parasitic and vector-borne disease elimination approaches with the aim to identify evidence-based strategies, core components and key concepts for achieving and sustaining schistosomiasis control and for progressing elimination efforts towards interruption of transmission in sub-Saharan Africa. A total of 118 relevant publications were identified from Web of Science, Pubmed and the grey literature and reviewed for their content. In addition, we conducted in-depth interviews with 23 epidemiologists, program managers, policymakers, donors and field researchers. Available evidence emphasizes the need for comprehensive, multipronged and long-term strategies consisting of multiple complementary interventions that must be sustained over time by political commitment and adequate funding in order to reach interruption of transmission. Based on the findings of this landscape analysis, we propose a comprehensive set of intervention strategies for schistosomiasis control and elimination. Before deployment, the proposed interventions will require review, evaluation and validation in the frame of an expert consultation as a step towards adaptation to specific contexts, conditions and settings. Field testing to ensure local relevance and effectiveness is paramount given the diversity of socio-ecological and epidemiological contexts.

Retrospective active case finding in Cambodia: An innovative approach to leprosy control in a low-endemic country.

Currently, leprosy control relies on the clinical diagnosis of leprosy and the subsequent administration of multidrug therapy (MDT). However, many health workers are not familiar with the cardinal signs of leprosy, particularly in low-endemic settings including Cambodia. In response, a new approach to early diagnosis was developed in the country, namely retrospective active case finding (RACF) through small mobile teams. In the frame of RACF, previously diagnosed leprosy patients are traced and their contacts screened through "drives". According to the available records, 984 of the 1,463 (67.3%) index patients diagnosed between 2001 and 2010 and registered in the national leprosy database were successfully traced in the period 2012-2015. Migration (8.4%), death (6.7%), operational issues (1.6%) and unidentified other issues (16.0%) were the main reasons for non-traceability. A total of 17,134 contacts of traced index patients (average: 2.2 household members and 15.2 neighbors) and another 7,469 contacts of the untraced index patients could be screened. Among them, 264 new leprosy patients were diagnosed. In the same period, 1,097 patients were diagnosed through the routine passive case detection system. No change was observed in the relation between the rate at which new patients were identified and the number of years since the diagnosis of the index patient. Similar to leprosy patients diagnosed through passive case detection, the leprosy patients detected through RACF were predominantly adult males. However, the fraction of PB leprosy patients was higher among the patients diagnosed through RACF, suggesting relatively earlier diagnosis. It appears that RACF is a feasible option and effective in detecting new leprosy patients among contacts of previously registered patients. However, a well-maintained national leprosy database is essential for successful contact tracing. Hence, passive case detection in the frame of routine leprosy surveillance is a precondition for efficient RACF as the two systems are mutually enhancing. Together, the two approaches may offer an interesting option for countries with low numbers of leprosy patients but evidence of ongoing transmission. The impact on leprosy transmission could be further increased by the administration of single dose rifampicin as post-exposure prophylaxis to eligible contacts.

Leprosy Post-Exposure Prophylaxis (LPEP) programme: study protocol for evaluating the feasibility and impact on case detection rates of contact tracing and single dose rifampicin.

INTRODUCTION: The reported number of new leprosy patients has barely changed in recent years. Thus, additional approaches or modifications to the current standard of passive case detection are needed to interrupt leprosy transmission. Large-scale clinical trials with single dose rifampicin (SDR) given as post-exposure prophylaxis (PEP) to contacts of newly diagnosed patients with leprosy have shown a 50-60% reduction of the risk of developing leprosy over the following 2 years. To accelerate the uptake of this evidence and introduction of PEP into national leprosy programmes, data on the effectiveness, impact and feasibility of contact tracing and PEP for leprosy are required. The leprosy post-exposure prophylaxis (LPEP) programme was designed to obtain those data. METHODS AND ANALYSIS: The LPEP programme evaluates feasibility, effectiveness and impact of PEP with SDR in pilot areas situated in several leprosy endemic countries: India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Complementary sites are located in Brazil and Cambodia. From 2015 to 2018, contact persons of patients with leprosy are traced, screened for symptoms and assessed for eligibility to receive SDR. The intervention is implemented by the national leprosy programmes, tailored to local conditions and capacities, and relying on available human and material resources. It is coordinated on the ground with the help of the in-country partners of the International Federation of Anti-Leprosy Associations (ILEP). A robust data collection and reporting system is established in the pilot areas with regular monitoring and quality control, contributing to the strengthening of the national surveillance systems to become more action-oriented. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the relevant ethics committees in the countries. Results and lessons learnt from the LPEP programme will be published in peer-reviewed journals and should provide important evidence and guidance for national and global policymakers to strengthen current leprosy elimination strategies.

Iron status and systemic inflammation, but not gut inflammation, strongly predict gender-specific concentrations of serum hepcidin in infants in rural Kenya.

Hepcidin regulation by competing stimuli such as infection and iron deficiency has not been studied in infants and it's yet unknown whether hepcidin regulatory pathways are fully functional in infants. In this cross-sectional study including 339 Kenyan infants aged 6.0±1.1 months (mean±SD), we assessed serum hepcidin-25, biomarkers of iron status and inflammation, and fecal calprotectin. Prevalence of inflammation, anemia, and iron deficiency was 31%, 71%, 26%, respectively. Geometric mean (±SD) serum hepcidin was 6.0 (±3.4) ng/mL, and was significantly lower in males than females. Inflammation (C-reactive protein and interleukin-6) and iron status (serum ferritin, zinc protoporphyrin and soluble transferrin receptor) were significant predictors of serum hepcidin, explaining nearly 60% of its variance. There were small, but significant differences in serum hepcidin comparing iron deficient anemic (IDA) infants without inflammation to iron-deficient anemic infants with inflammation (1.2 (±4.9) vs. 3.4 (±4.9) ng/mL; P<0.001). Fecal calprotectin correlated with blood/mucus in the stool but not with hepcidin. Similarly, the gut-linked cytokines IL-12 and IL-17 did not correlate with hepcidin. We conclude that hepcidin regulatory pathways are already functional in infancy, but serum hepcidin alone may not clearly discriminate between iron-deficient anemic infants with and without infection. We propose gender-specific reference values for serum hepcidin in iron-replete infants without inflammation.