Infectious diseases often lead to death among children under 5 years in many underdeveloped and developing countries. One of the main reasons behind this is an unawareness of disease symptoms among mothers and child caregivers. To overcome this, we propose the EasyDetectDisease mobile health app to educate mothers about the early symptoms of pediatric diseases and to provide them with practical advice for preventing the spread of such diseases in children under 5 years. The EasyDetectDisease app includes detailed knowledge of infectious diseases, including the corresponding symptoms, causes, incubation period, preventive measures, nutritional guidelines such as breastfeeding, video tutorials of child patients, and video guidelines by pediatric health experts to promote child health. It also provides information on the diagnosis of the infectious diseases based on symptoms.The objective of this study was to evaluate the usability  of the EasyDetectDisease app among mothers of children under 5 years of age.Two health sessions, held in Pakistan, were used to evaluate the usability of EasyDetectDisease by 30 mothers of children under 5 years. The app was evaluated based on various quantitative and qualitative measures.The participating mothers confirmed that they were able to diagnose diseases accurately and that after following the instructions provided, their children recovered rapidly without any nutritional deficiency. All participating mothers showed an interest in using the EasyDetectDisease app if made available by governmental public health agencies, and they suggested its inclusion in all mobile phones as a built-in health app in the future.EasyDetectDisease was modified into a user-friendly app based on feedback collected during the usability sessions. All participants found it acceptable and easy to use, especially illiterate mothers. The EasyDetectDisease app proved to be a useful tool for child health care at home and for the treatment of infectious diseases and is expected to reduce the mortality rate of children under 5 years of age. Child health care is one of the foremost priorities in the world. However, it is an undeniable truth that millions of children’s lives are affected each year by disease. Infectious diseases have been regarded as a major cause of morbidity and mortality in children under 5 years of age, according to a recent report by the World Health Organization (WHO) , 83% of A mother is considered to be a sick child's first health care provider at home. Various studies have been conducted in Pakistan to show a strong correlation between maternal education and lower child mortality . These sIn Pakistan, however, to the best of our knowledge, very little effort is being made to educate mothers about pediatric infectious and noninfectious diseases. It has been found that a lack of child health awareness, inadequate maternal education, improper access to medical facilities, and a lack of exposure to smart technology and mobile health  tools are some of the key causes behind child mortality in Pakistan -8. In thThis subsection provides the estimated statistics of global deaths by cause and sex of children under 5 years while focusing on the statistics for Pakistan. Updated data of children under 5 years has been retrieved from the WHO and United Nations International Children’s Emergency Fund (UNICEF) websites; specific information has been extracted and presented in tables.According to the WHO’s Global Health Observatory, globally, 15,000 children died every day in 2016 (5.6 million per year)  and 16,0It can be observed from Globally, most countries achieved remarkable progress in the reduction of deaths among children under 5 years during the period of 2000 to 2015. However, it is still expected to reach 5 million deaths by 2025 , accordiPakistan is ranked sixth among 22 high disease–burden countries and is facing the challenge of high communicable diseases with a 40% ratio .In According to the WHO, deaths among children under 5 years of age in Pakistan because of contagious diseases are higher than those linked to noncontagious diseases . In PakiWe can see from Reduce Child Mortality) of Millennium Development Goals, 4.6 million child deaths per year is projected for the period of 2016 to 2030, and Pakistan is expected to be responsible for 8% of these deaths [Pakistan has achieved remarkable progress in the reduction of deaths among children under 5 years during the period of 2000 to 2015, as shown in mHealth is an area of electronic health that deals with health aids via mobile phones -16. The It has been observed that most Pakistani mothers are not aware of diseases, their prevention, and child care at home . MothersAll the awareness efforts and education programs mentioned above were time limited to a few days or weeks. Similarly, online child health awareness and health promotion sessions are held globally, but they are of limited duration and participants usually have to pay for attending these sessions. The proposed EasyDetectDisease app, conversely, provides a long-term solution based on the following features:Symptoms detectionDiseases awarenessNutrition awarenessPromotion of breastfeedingExplanatory tutorials of live patientsVideo guidelines about diseases by pediatric health experts.EasyDetectDisease provides a means to mothers for diagnosing the early symptoms of infectious diseases in their children. This kind of early detection of symptoms can prevent serious attacks of diseases. The app provides complete awareness about the most frequently occurring diseases in children under the age of 5 years. The EasyDetectDisease app would be a free-of-cost service, made available through governmental health agencies and app stores.This section describes the main design stages of the EasyDetectDisease app development. We started off by collecting health care–related data from different websites and local health institutes. The app was designed and developed based of the collected data. Next, its usage was evaluated by a sample group of end users. Here, we explain these stages one by one.We gathered data on the diseases highlighted in the WHO and UNICEF websites and by The Children’s Hospital (CH) and the Institute of Child Health Multan (ICHM) in Pakistan. After gathering the data, 3 pediatric health experts from CH and ICHM examined the data for coherency and accuracy. The collected data were then sorted according to the instructions of experts and inserted into the app after final approval of the doctors.The EasyDetectDisease app consists of 7 modules: diagnostic test, diseases, prevention, nutrition, video guidelines, video tutorials, and report, as depicted in According to the UNESCO data, Pakistan ranked 135th (out of 150) in literacy in 2016 . AccordiThe diagnostic test module allows the mother to detect the disease from its early symptoms. The module detects the symptoms of the sick child by asking some questions from the mother while showing her pictures of sick children.The text of these questions is also read by the TTS. This module provides easy navigation between interfaces, and the foremost task for the mother is to select the language, and then, the user interface guides her to further navigate the app. The diagnostic test interface in Urdu and English is shown in This module provides a detailed description of infectious diseases and some noninfectious diseases, their spread, incubation period, causes, child care at home, and medical advices. For example, if a child is suffering from anaphylaxis and his/her mother chooses anaphylaxis from the list of diseases as shown in The prevention module provides the mother with guidelines on how to prevent common diseases such as acute hepatitis, anaphylaxis, asthma, chicken pox, diarrhea, diphtheria, febrile fits, iron deficiency anemia (IDA), malaria, measles, meningitis, mumps, pertussis, tetanus, and urinary tract infection; the do’s and don’ts when the child is suffering from a certain disease; guidelines on how to maintain cleanliness; and information on the kinds of medicine that should be avoided during specific infectious diseases and can result in emergency situations . For example, This module provides the nutritional guidelines to mothers. It contains dietary instructions for pregnant mothers and a nutritional guide for breastfeeding mothers . It provides details on complementary feeding, traditional infant foods, instant infant foods, protective foods, and energy-dense foods, and it instructs to monitor the growth of the child by using measuring scales. The topics of nutritional guidelines are listed in The video guidelines module consists of instructional videos recorded by pediatric health experts from CH and ICHM. In these videos, doctors educate mothers about the symptoms and prevention of diseases and provide clinical advice. For example, if a child is suffering from acute hepatitis, the pediatrician highlights the signs and symptoms of acute hepatitis before disease attack and after disease attack, causes and risk factors of acute hepatitis, its incubation period, nutrition during the disease period, prevention methods, care at home, and medical advice see .This module contains the recorded videos of actual patients affected by various diseases to practically teach mothers about the symptoms of diseases. This module also contains videos on how to make oral rehydration solution and samoji, how to use a nebulizer, etc. This module allows mothers to report all those diseases that are not described well in the app or are difficult to understand. This module is primarily based on an algorithm that monitors the reports from users about diseases. If the algorithm gets 3 reports about a specific disease, then it automatically replaces the content of that disease with easier to understand material to facilitate enhanced comprehension.Overall, 2 health sessions were conducted in 2 different communities with the help of LHWs to evaluate the app’s usability see .A total of 30 mothers were recruited from 2 different communities since the recommended number of participants for a usability evaluation is at least 10 . AccordiAfter all the mothers became familiar with the diseases and their symptoms, which they could find in their children, they were provided a questionnaire see . The facDoes the user interface provide easy navigation?Does the diseases module provide detailed knowledge of infectious diseases?Does the prevention module provide necessary preventive measures to avoid diseases?Does the nutrition module provide useful nutritional guidelines to mothers?Does the video guidelines module provide complete details about diseases?Do video tutorials contain useful information?What is the app’s best feature?Which feature of the app needs improvement?This section provides details of the evaluation outcomes of the EasyDetectDisease app and the participants’ feedback.The mothers of 30 ill children used the app and diagnosed the disease their child had. The ratio of the most and least common diseases was derived from the diagnostic test. The percentage of disease occurrence is shown in The highest number of cases were reported for diarrhea; this was diagnosed in 30% (9/30) of the children. The second major disease was chicken pox . Similarly, pertussis  and typhoid  were diagnosed as the third major diseases. The least common diseases were febrile fits and mumps .After diagnosing the diseases, mothers were advised to explore the details of the disease and to follow the guidelines. They read about the symptoms and preventive measures of the disease, nutritional guidelines, and medical advice, and followed the video guidelines of the pediatric health expert. In the next meeting, each mother was asked, “What kind of health improvement did you notice in your child after using the EasyDetectDisease App?”. Most of the mothers answered that they followed all of the instructions of the app, and that they noticed that their child recovered quickly without any visible signs of weakness in the body. They did not find any dietary deficiency in their children after following the nutritional instructions.This subsection provides the results of the diagnostic module usability questionnaire and qualitative feedback from the mothers.The diagnostic module questionnaire results were very positive. All participants diagnosed diseases accurately based on the symptoms. Most responses were recorded as 1 (strongly agreed). All participants strongly agreed to the statement “I liked using the EasyDetectDisease App.” All mothers found the app to be easily navigable, easy to use, and easy to understand. Very few mothers faced navigation errors because of their unfamiliarity with the app and touchscreen phones, but in the second health session, they were all able to navigate through the app.When asked about the positive and qualitative aspects of the EasyDetectDisease app, mothers generally liked its simplicity and ease of use. One mother commented that using the app required no training as it was really easy to use. Most of the mothers reported that the app provides easy health guidelines. One mother said:App does not need any skill to start, as I just started the app and it itself guided me what to do.Many mothers were of the view that the disease diagnosis does not require much time as the app quickly diagnoses the disease after getting the symptoms. One mother said:I liked the reporting feature as it automatically converts the text into easy to understand visuals.One mother suggested that this app should be available as an built-in feature in all smartphones.Development of a mobile app that can be used in a cross-cultural environment with low resources is challenging, as it requires iterative testing and adaptation. The EasyDetectDisease app has been developed and updated iteratively based on feedback from end users.The EasyDetectDisease app provides a user-friendly approach for disease diagnosis, description, symptoms, prevention, and nutrition, medical advices, tutorials featuring ill patients, and video guidelines by the pediatric health experts to promote in-home child health care. Our goal of teaching illiterate mothers about infectious diseases common in children under the age of 5 years was achieved successfully since their progress can be judged from the 2 pilot health sessions during which they used the app without any assistance. All mothers appreciated easy navigation, effectiveness, free-of-cost availability, and usefulness of EasyDetectDisease. Moreover, all mothers found the app to be very useful for their child care, and all of them agreed to use it if made publicly available.To support the varying levels of education among mothers, many ideas were discussed  that would be helpful for future implementations. Mothers with a low level of education preferred to have the app in the local languages of Pakistan. Awareness among mothers can play a vital role in reducing the mortality rate of children under 5 years. If EasyDetectDisease is made available at governmental public health agencies across Pakistan, there would be a need to educate and train mothers on some of its functionalities via governmental mHealth sessions or mHealth programs for its adaptation.The EasyDetectDisease app’s current version is in its initial state, and it only contains limited and the most common infectious diseases that each child may face in his/her childhood. This app does not contain directions on dosage or medicine that may lead to death. This app is not an alternative for any medical procedure. In fact, this is an educational app that can be used to train mothers to diagnose the illness of their child at home and to immediately provide first aid by reading or listening to the guidance instructions. The awareness among mothers can prove to be the best contribution to reducing the mortality rate of children under 5 years.Information on more diseases and additional education topics related to breastfeeding promotion, pregnancy guidelines for safe and healthy births, and noninfectious diseases will be added in the next version of the app. This app is bilingual, but in future implementations, more local languages will be added to enhance the acceptance of EasyDetectDisease in all parts of Pakistan.


This paper compares land use patterns of mestizo colonists and indigenous populations in the central Ecuadorian Amazon, based on data from a household survey covering mestizo colonist, Kichwa and Shuar households. As expected, colonists mostly engage in commercial agriculture and cattle ranching, but there are substantial differences in land use patterns between the Shuar and the Kichwa. The Shuar engage in cash cropping and cattle ranching, and on average, devote even more land to agricultural uses than mestizo colonists in this sample. In contrast, the Kichwa engage more in subsistence crop production and less in commercial agriculture. Such different patterns appear related to local conditions, earlier migratory and settlement patterns, and the level of exposure to markets. The implications of this for policy are explored in the conclusions. As with most environmental problems, deforestation is closely linked to human activities, especially agriculture , 2. In fMuch has been written on the determinants of land use decisions in the tropics. The literature makes a clear distinction between the land use patterns of migrant colonists and those of the traditional inhabitants. Colonists are generally reported to use unsustainable production systems featured by extensive clearing of land with continuous incorporation over time of additional forest areas into agricultural production , 6. ThisIn the case of the Amazon rainforest, one of the world’s biodiversity hotspots , 22, fewnaranjilla–a citrus fruit which accounted for most of the income of both ethnic groups: Colonists responded by converting infested fields to pasture, while the Shuar allowed secondary forest to develop in former naranjilla fields and engaged in the cultivation of customary garden crops and small areas of cash crops (coffee and cacao). But do these patterns still apply in a context of high rates of population growth and urbanization [Finally, several studies have been conducted on the Ecuadorian Amazon, generally concluding that indigenous practices have a much lower environmental impact than colonists , 26, 27.nization , 19, scanization , increasnization , and incnization ?This research addresses this and related questions using data from a household survey covering both colonist and indigenous (Kichwa and Shuar) households in the province of Pastaza, in the central Ecuadorian Amazon. Following this introduction, the rest of this paper is structured as follows: the next section describes the socio-economic-cultural context of the migrant colonists, the Kichwa and the Shuar in the Ecuadorian Amazon. Then the theoretical framework is presented, data collection explained and the statistical estimation methodology described. Finally, the results are presented and discussed, followed by concluding remarks and policy implications.In the 1960s, following the enactment of Ecuador’s major land reform legislation in 1964 and the first discovery of significant oil reserves in the northern Amazon in 1967, roads were constructed by oil companies to lay pipelines to pump petroleum from the Amazon to the Pacific port of Esmeraldas for export. This led to a large migration of mostly poor farmers with little or no land, principally from the Sierra or highlands region, to the Amazon in search of land. Although in the case of Ecuador -in contrast to Brazil, for example , this wanaranjilla, cacao and sugar cane) as well as some cattle ranching [yuca”, plantain, taro, and maize), the collection of forest products, hunting and fishing. Nevertheless, others report that some Kichwa have adopted colonist-style agricultural systems and nowadays also engage in commercial agriculture, cattle ranching, timber logging and off-farm wage employment in areas close to roads and urban centers [In terms of the main land use practices of the three study populations in Pastaza, first, mestizo colonists number about 46,000 and are settled in the westernmost part of the province, near Puyo, the provincial capital see . They spranching . In contranching . The Kicranching , 39. Somranching  describe centers , 41. AltThe so-called “jíbaros” or Shuar are the traditional inhabitants of the tropical forests of southeastern Ecuador, numbering about 78,000 persons, 80% in the province of Morona Santiago . During The rural livelihood model and the microeconomic model of the agricultural household , 45 togeThis framework has been previously used in other studies analyzing land use patterns among colonist , 46 and The data came from a household survey conducted in May-October 2013 in Pastaza . A questHouseholds were selected a two-stage approach, in which the first stage was to select communities following criteria of ethnicity, distance to the nearest accessible road, distance to the nearest town of more than 10,000 inhabitants -which in all cases was Puyo- and population size and density. Variation in these conditions across communities ensures a fair representation of the diversity of communities, contributing to the robustness of the study .In the second stage of the sample, households in each sample community were randomly selected from a list provided by community’s leaders, with large proportions of households selected from small communities and small proportions from large ones, yielding 8–30 households per community. The final result is that a total of 304 households  were successfully interviewed in 17 communities  see . The suryuca, taro and maize), area in cash crops , and area in pasture, all expressed as fractions of the total area available for use. These are estimated from the values reported by respondents as collected by interviewers. Previous research in the Amazon [We use a multivariate regression approach to model land use patterns of indigenous and colonist households. The dependent variables of interest are the total cultivated area, area in staples  of household i in community j, X is a vector of household and community-level covariates (described below), β is a vector of household and community coefficients, εij is the household-level error term, and vj is the community-level error term.A methodological issue should be addressed before proceeding. Household decisions regarding land use may be influenced by contextual (community) variables, which are distinctive for each community, because households within a community may exhibit similar land use patterns based on a common background in terms of ethnicity, economic well-being, market integration and environmental endowments , 46. Faicorner solution outcomes [yij is the fraction of the total area devoted to cash crops or the fraction of the total area in pasture of household i in community j, β is a vector of household-level coefficients, X a vector of household and community-level predictors The observable dependent variable y equals 0 if the latent variable y*≤0 and will take the value of y* if y*>0. The results of a Tobit model cannot be directly interpreted since the coefficients show to what extent a change of one unit in X has on the latent variable y*. As we are interested in the effects of X on y rather than y*, we calculate the marginal effects for the unconditional value of y.For the fractions of land in cash crops and in pasture, another issue must be addressed. Each of these dependent variables is continuous, taking on the value of zero for a large part of the sample . Using a linear regression approach under such circumstances would result in inconsistent estimators. Instead, this kind of outcomes  can be mDefinitions and descriptive statistics are presented in Financial capital variables include household spouse. A wealth index was derived as the first principal component of the possession of a radio, television, cell phone, computer, gas stove, refrigerator, chainsaw, spray pump, car, motorcycle, solar panel, boat and rifle This accounted for 29% of the variation in the data. The methodology above referred to is preferred since, in contrast to simple count indices, which assign equal values to every asset, it gives higher weight to the assets which provide more information about household wealth . There imingas) during the preceding 12 months provides an indicator of social capital, which may affect the dependent variables. The time the household head has resided in the community may influence the cultivated area since it reflects the “household life cycle”, with longer-term residents having more time to clear larger areas [We include the natural logarithm of distance to the closest road in the list of predictors since this variable reflects the ease of marketing agricultural products and hence should be an important determinant of land use decisions, as found in previous work , 54. Theer areas . Thus, iasamblea . In this sense, it is worth noting that all indigenous communities in our sample had recognized collective usufruct rights over their lands, while all colonist households declared having legal rights over the land they possessed. This means they can freely use those lands for agriculture and hunting, but cannot sell any part of the land or extract trees without permission of the asamblea, though unauthorized felling of trees is not uncommon.The household’s natural capital endowment is taken to be the natural logarithm of the amount of land owned or controlled via common property allocation. Additionally, we add a dummy variable to the model to indicate if the plot is reported by the respondent to have fertile soil. Finally, while the type of land tenure may be an important determinant of land use , 56, we Bono de Desarrollo Humano); and on whether the household had received credit from a bank or other source. Finally, distance from the dwelling to the household’s largest agricultural plot was examined on the hypothesis that a longer distance would lead to less intense use of that plot. These predictors were dropped from the final model specification, however, as they did not contribute to the model fit.At the community-level, the natural logarithm of the time required to reach Puyo  is used to control for the level of market access, which is likely linked to larger areas in crops . Additionally, as the availability of natural resources including land may be limited by population pressure , 43, popIn With respect to the remaining household-level variables in the model. The Shuar and the colonists live much nearer to roads than the Kichwa. This is probably related to colonists living closer urban areas, where road density is higher, and the Shuar tendency to settle near roads rather than fruit orchards . On averFinally comparing the values at the community-level, colonist households live much closer to Puyo, the provincial capital, with Kichwa households farthest away (more than six times as far), and Shuar villages in between. It is also worth noting that population density is much larger in colonist areas than in the sample Kichwa and Shuar communities.This section presents the main empirical findings of this research, based on pooling data for all interviewed households of the three ethnicities and controlling for ethnicity by the use of dummy variables. The results are presented in In terms of the key effects focused on in this paper, ethnicity is observed to have no effect on either the overall fraction of land devoted to agriculture and the fraction of land dedicated to staple crops. In the first case, this finding is not consistent with the descriptive evidence presented in Continuing with other variables, at the household level, wealth (assets) is negatively correlated with the fraction of land dedicated to staple crops. A probable explanation is that wealthier households can purchase staple foods (plantains and cassava) as well as a broad variety of other foods in the market whereas poorer households need to rely more on what they can produce themselves. Off-farm employment also plays a significant role in agricultural land use: Receiving off-farm income reduces the fraction of land devoted to cash crops and pasture by 1% and 7%, correspondingly. There are two likely explanations: First, off-farm earnings in the Ecuadorian Amazon tend to be higher than those from agriculture , so thatThe distance to the closest road is linked to a lower fraction of land devoted to agriculture, specifically to less land in cash crops and pasture. Establishing cash crop plots near roads facilitates the transport of inputs to the field and taking the produce to the road to transport to markets . This fiasamblea in the cases of the Shuar and Kichwa) and its perceived soil quality. One expects natural capital to be positively linked to the area in use, since a larger area or quantity of land available facilitates a larger area in use, and land of better quality produces more for a given labor effort. Indeed, in the study population, we see from quantity of land owned or available to a household is indeed linked to a smaller share of land used for agriculture and for staple crops. This reflects that households with less land tend to use it more intensively [The final two household-level variables refer to the role of natural resource endowments or natural capital—the area of land perceived as one’s own  nature of the response, or perhaps the wide variability of soil qualities observed on Amazonian farms in Ecuador. But in the case of migrant colonists in the northern Ecuadorian Amazon, a positive statistically significant relationship was found between (perceptions of) soil quality and area of land cleared and in agricultural use [On the other hand, we did not find any significant correlation of perceived land ural use , 46. Thunegative relationship to the fraction of land devoted to agriculture, which may reflect farm sizes shrinking over time near Puyo as a result of high rates of population growth and resulting subdivision of plots among heirs, as has occurred among both colonists and indigenous populations elsewhere in the Ecuadorian Amazon [In concluding with respect to the community level factors, once other factors have been controlled for, it was surprising that distance along the road to the main city and market (Puyo) is not negatively related to the area in agricultural use as expected. One possible explanation is that other predictors  already capture this effect. However, the effect of distance to Puyo remains non-significant even when these three predictors are removed, which leads us to think that distance to markets does not play a role in shaping land use decisions. Finally, population density in the community/vicinity has a statistically significant n Amazon , 30. It This paper is unusual in documenting differences in land use and investigating the factors responsible for these differences among both migrant settlers and indigenous populations based on collecting identical data on both types of populations in a single survey. The results are generally consistent with prior research showing that some indigenous peoples  are becoming increasingly integrated in the market economy, engaging in cattle ranching and commercial agriculture, and becoming more like migrant colonists –12, 14. Our findings thus empirically confirm that there are important differences in land use among indigenous groups in the Amazon, with the Shuar sharing several key characteristics of colonists, first, in establishing communities near roads, facilitating diversifying income sources, and engaging in commercial cash crop production and cattle ranching. Furthermore, most Shuar are also migrants, moving to Pastaza, pushed by population growth, land scarcity and livelihood risks in their original territories in the southern Amazon. it is therefore not surprising that the Shuar and colonists exhibit somewhat similar land use patterns. However, prior research  depictednaranjilla) and in pasture are larger in the proximity of roads. This suggests that, in this Ecuadorian Amazon context, the distance to a road matters more than the distance to markets in shaping land use decisions.In this context, it is also worth revisiting the role of accessibility, as it appears more complex than has been understood before. First, it has several dimensions, including distance of the farm household to the nearest road and distance from that point to the major urban cynosure or market in the region. While no significant effect of the latter is found here, the areas cultivated in cash crops Click here for additional data file.S2 FileConfirmation that the survey model used for this manuscript was approved by the Ethics Committee at Universidad Estatal Amazónica.(PDF)Click here for additional data file.


One hypothesis that could explain the beneficial effects of physical exercise on cognitive function is the cardiorespiratory hypothesis. This hypothesis proposes that improved cognitive functioning may be in part a result of the physiological processes that occur after physical exercise such as: Increased cerebral perfusion and regional cerebral blood flow. These processes ensure increased oxygenation and glucose transportation to the brain, which together can improve cognitive function. The objective of this narrative review is to examine the contribution of this hypothesis in the care of African older adults with neurodegenerative conditions ) or with mild cognitive impairments. Although studies in developed countries have examined people of African descent , only the limited findings presented in this review reflect how these conditions are also important for the African continent. This review revealed that no studies have examined the effects of cardiorespiratory fitness on neurodegenerative disease in Africa. African nations, like many other developing countries, have an aging population that is growing and will face an increased risk of neurodegenerative declines. It is therefore imperative that new research projects be developed to explore the role of the cardiorespiratory fitness in neurodegenerative disease prevention in African nations.  Africa is considered a continent with a young population. It is estimated that the percentage of people under 25 years will be 59.43% by 2020 . DespiteAging has been defined as the gradual decline of biological functions caused by progressive dysfunction of different cellular systems responsible for repairing and maintaining the homeostasis . This gr2), depressive symptoms, and a low level of education [The few studies addressing these issues have focused on determining the risk factors and the prevalence rate of MCI and age-related cognitive pathologies (dementia and AD) ,12,13,14ducation . Howeverducation . Apart fducation ,16.In summary, the prevalence of dementia in Africa is growing and is moving towards rates seen in developed countries. This prevalence, which seems low in comparison to developed countries, will increase in the coming years because the population is living longer. Indeed, it is predicted that by 2050, 71% of people with dementia will live in low- and middle-income countries . FinallyThese findings of cognitive impairment, dementia, and AD are important because physical exercise might be the answer to improving or maintaining cognitive health in this population. Physical exercise remains one of the most robust strategies that contribute to improving the functioning of the brain, helps to prevent cognitive impairment, and reduces the incidence of AD . FindingThe aims of this narrative review are first to present the cardiorespiratory hypothesis. The second aim of this review is to discuss studies examining the effects of cardiorespiratory fitness on MCI, dementia, and Alzheimer’s disease. Finally, we aimed to explore how the cardiorespiratory hypothesis may apply to neurodegenerative diseases in Africa.This hypothesis, which was proposed for the first time by Dustman and collaborators , suggestIn humans, the work of Bullitt and collaborators clarified the role of physical exercise in angiogenesis . The autr = 0.44). This positive correlation demonstrates that compliance and cardiorespiratory fitness move in the same direction for older adults. In their second, interventional study, the same authors found that after a 13-week training program, the compliance of blood vessels of older adults increased significantly. The characteristics of this program were: 73% of maximal heart rate (Intensity) for 42 min/day; 5 day/week for 13 weeks. It is clear from this work that improving the compliance of the blood vessels likely contributes to the increase in cerebral blood flow following the practice of physical exercise, partially supporting the cardiorespiratory hypothesis. However, this study did not examine the relationship between increased cerebral blood flow and cognitive performance. Vascular plasticity can be defined as the ability of the blood vessel to recover its compliance under the effect of a stimulus such as physical exercise. The process by which physical exercise induces better arterial compliance has been investigated by a recent study done in rodents . The aut−1) in the stiffness of the arteries [Similar to rodent findings, the increase in blood vessel compliance observed in humans can also be explained by the better availability of NO. The effect of NO on blood vessels in humans is a function of the acute or chronic nature of exercise . Indeed,arteries . This haarteries .Finally, the last mechanism associated with the cardiorespiratory hypothesis is the improvement of vascular health. In addition to the impacts of physical exercise on arterial stiffness, exercise can also reduce vascular dysfunctions that can occur with advancing age . Among tendogenous proteins  that support brain plasticity likely mediate the beneficial effects of exercise on the brain” p. 236 [In addition to aerobic training, other studies have shown the effects of resistance training on the mechanisms underlying the cardiorespiratory hypothesis. For example, recent studies have demonstrated that resistance training increases vascular structure and function , vascula” p. 236 .The studies described above, which focused on the explanatory mechanisms of the cardiorespiratory hypothesis, were based on microscopic processes. However, given the complexity of cognitive and cardiorespiratory functions, it is now suggested that the exploration of these mechanisms should be carried out using other approaches, such as the non-linear model (see ) or the Our review revealed that there is no research examining the effect of cardiorespiratory fitness on MCI, dementia, and Alzheimer’s disease in the African continent. However, some relevant cross-sectional and interventional studies with older adults living in industrialised countries exist. The cross-sectional studies examined correlations between cardiorespiratory fitness and other variables such as brain health ,60,61,62Apart from these cross-sectional studies, other interventional studies have examined the prophylactic effects of a higher level of cardiorespiratory fitness following aerobic exercise in patients with MCI and AD. In the case of MCI, the results of these studies demonstrate that six-months of high-intensity aerobic exercise improves executive control processes  in older women with MCI . SimilarOther studies have investigated the effect of resistance training in patients with cognitive decline and showed mixed results. Some studies have demonstrated improvements in cognition after resistance training without explaining the underlying mechanisms ,74. Conv2peak) or maximal oxygen uptake (VO2max). These physiological markers of cardiorespiratory fitness, which measure metabolic, cardiorespiratory, and pulmonary responses during exercise, provide little information on the coordination between these three subsystems [2, expired fraction of CO2, ventilation, systolic blood pressure, diastolic blood pressure, and heart rate) measured during an exertion test. The principal component analysis allows for the identification of the component that explains the greatest variation in the physiological parameters included in the analysis [However, it is worth noting a limitation in relation to the research reviewed in this section. Indeed, whether in cross-sectional or interventional studies, cardiorespiratory fitness was measured with aerobic physiological markers like peak oxygen uptake . fNIRS is a relatively low-cost optical imaging technique that allows for the investigation of hemodynamic changes associated with brain activity and has been successfully used to examine activations of the cerebral cortex in normal aging  and in phow diverse physiological systems and organs coordinate their functions over a broad range of space and time scales and horizontally integrate to generate distinct physiologic states at the organism level” p. 1 [Finally, following the same rationale as the limitations outlined at the end of el” p. 1 . A last el” p. 1 , chap. IThis review highlights the absence of studies on the effects of cardiorespiratory fitness on cognitive performance in patients with MCI or AD in the African continent. However, there are some studies in industrialized countries on Caucasians and African Americans that highlight the possible beneficial effects of cardiorespiratory fitness on the physical and cognitive performances of older individuals with cognitive decline or pathological aging. Based on these results, we have proposed some potential avenues of research that should be developed for the African continent. Future studies examining these avenues of research could lead to a better strategy for the prevention of MCI, dementia, and AD in Africa prior to a major increase in the older population. To adopt these strategies, it seems essential that the area of geriatric medicine develops and fosters research into the cardiorespiratory hypothesis in aging and disease as an important area of inquiry, as aging is becoming widespread in all the countries of the continent.


It is with great pride and a strong feeling of accomplishment, we now transition the editorship of Respiratory Research to our capable and accomplished colleagues Kelan Tantisira and Oliver Schildgen. After having served as Co-Editors for over 15 years, we wish to reflect on the legacy of the journal and heartily thank all those who worked so diligently as associate editors, editorial board members and dedicated reviewers, as well as the BioMedCentral staff.The initial vision for RR was created by the founding editor Professor Peter J. Barnes who saw an unmet need to bridge basic and clinical respiratory research. He therefore helped start this journal as an exclusively web-based publications, almost unheard off at the time. The journal was created in the year 2000, a time when significant challenges existed in the scientific literary world dominated by printed matter, complicated search processes, and inaccessibility to science for anyone outside of a large academic or commercial institution. The concept of open access was totally novel. As editors, the first years were challenging, and in 2003 only 15 papers were published. The scientific community was not familiar with the fundamental changes that Open Access publishing required, such as authors paying for publishing the work. Initially, the journal had no impact factor. However, when the initial impact factor was issued in 2004 the interest from peers suddenly exploded, and in the following year the number of publications increased ten-fold, and has steadily grown with approximately 200 papers now published by RR per year. In parallel, submissions have increased and are approaching 1,000 per year.When we assumed the Co-Editorship of RR in the spring of 2003 we embraced the contemporary concept of translational medicine and science that focused on fundamental studies using human cells, tissues or model systems that would translate basic observations into clinical studies. This approach was intrinsically bidirectional in nature; the insights from RR articles could generate novel questions that could be pursued by studies focused on the discovery of molecular mechanisms of disease. Most importantly, the open access of RR offered a global audience the rapid dissemination of scientific knowledge into clinical practice. The Journal boasts of a global focus with a consistent recruitment of international editors, associate editors and reviewers who provide the critical vision to publish cutting-edge, interdisciplinary work.We challenge the new Co-editors Kelan and Oliver to sustain the RR legacy and wish them the best in propelling RR to new heights. Providing respiratory scientists and clinicians with the highest quality translational research in a timely and easily accessible manner, remains the critical RR mission.Last, but not least, we wish to thank all the authors of the 2126 papers that have been published in Respiratory Research since we took on the editorship 15 years ago, as we could not have done this without your relentless support. Thank you also to all readers of the journal, who bring progress to science and translate basic science to clinical practice. We are both grateful and humbled for having had the opportunity to harness Respiratory Research for such a significant period of time, and wish the best of luck to Kelan and Oliver!Reynold Panettieri and Jan Lötvall.


Vibrio cholerae O1 were confirmed by bacterial culture. Average time to culture result was 3 days. On average, the CTI Rapid Response Team (RRT) was able to visit households 1.7 days after the culture result was received from the hospital . Coverage of WASH and health behavior messaging campaigns were 30.2% in the target areas. Recipients of the intervention were more likely to have knowledge of cholera symptoms, treatment, and prevention than non-recipients. Although the RRT were able to investigate cases at the household within 2 days of a positive culture result, the study identified several constraints that limited a truly rapid response.A comprehensive targeted intervention (CTI) was designed and deployed in the neighborhoods of cholera cases in the Kathmandu Valley with the intent of reducing rates among the neighbors of the case. This was a feasibility study to determine whether clinical centers, laboratories, and field teams were able to mount a rapid, community-based response to a case within 2 days of hospital admission. Daily line listings were requested from 15 participating hospitals during the monsoon season, and a single case initiated the CTI. A standard case definition was used: acute watery diarrhea, with or without vomiting, in a patient aged 1 year or older. Rapid diagnostic tests and bacterial culture were used for confirmation. The strategy included household investigation of cases; water testing; water, sanitation, and hygiene (WASH) intervention; and health education. A CTI coverage survey was conducted 8 months postintervention. From June to December of 2016, 169 cases of  Vibrio cholerae, presents clinically as the rapid onset of acute watery diarrhea (AWD) and vomiting. Without treatment, the disease can progress rapidly and lead to death from severe dehydration in as little as 4 hours from the onset of symptoms.1 During an outbreak in Guinea-Bissau, researchers found that cholera cases tended to cluster spatially with at least 30% of households in each cluster having at least one case.2 A later study in Matlab, Bangladesh,  showed that those living closest to a case (within 50 meters) had 36-fold higher chance of becoming infected with cholera than those living in other areas of the community.3 This risk was highest during the first 3 days after the index case was identified. Similar results were seen in urban Kolkata, India, where an increased risk for cholera was seen within 25–50 m of a case and persisted for a month, and up to 200 m for 5 days in Chad and D.R. Congo.6 These observations highlight that rapid detection of cholera cases and rapid response is needed to control the spread of disease.Cholera, caused by ingestion of the bacterium 7 Although the disease occurs nearly every year in the Kathmandu Valley and is detected sporadically in other parts of the country, exactly where it will occur is unpredictable.Cholera is endemic in Nepal, with a model-estimated 30,000 cases and 911 deaths per year during the monsoon months of May through September.8 By designing an intervention that focuses on halting an outbreak early rather than preventing one entirely, it may be possible to limit the transmission from index cases and reduce the overall rates of disease by targeting the high-risk groups who live near a case. A reactive vaccination strategy, when partnered with other important cholera prevention measures, forms the backbone of a comprehensive targeted intervention (CTI) approach to cholera control and has the potential to halt the spread of cases if deployed rapidly. Founded on a strengthened surveillance system, the CTI approach combines pointed health behavior messaging with traditional water, sanitation, and hygiene (WASH) interventions and a single-dose OCV campaign (estimated to have a short term effectiveness of 87%) to prevent the spread of cholera once it strikes.9 Delivery of a single dose of OCV to case households and neighbors after a case is detected has been previously been shown to be feasible in an urban setting in South Sudan.10 A single dose of OCV using a reactive ring strategy was included in the CTI plan, but the vaccine could not be obtained in time for the summer 2016 outbreak. Although preventing an outbreak by vaccinating a defined “hotspot” is preferable, this strategy is only successful when outbreaks occur consistently in an area. Outbreaks tend to occur sporadically during the monsoon season in varying areas of the city; thus, a preventive hotspot campaign for a large urban area such as Kathmandu is not feasible. By designing an intervention that focuses on halting an outbreak early, it may be possible to reduce transmission and lower morbidity and mortality significantly in Nepal and other countries in high-risk situations.Despite much progress, the global supply of oral cholera vaccine (OCV) remains limited as compared with the global at-risk population.11 This study was designed as a feasibility study to determine whether clinical centers, laboratories, and field teams were able to facilitate rapid, multi-sectoral response within 2 days of a case being admitted to the hospital.Following a major earthquake, the Epidemiology and Disease Control Division (EDCD) of the Department of Health Services in Nepal adopted a CTI approach to cholera control for the 2016 monsoon season, expanding the role of the country’s existing rapid response team (RRT) network. This study was designed to assess the feasibility of that response. We hypothesized that a CTI strategy for controlling cholera in the Kathmandu Valley would facilitate a cooperative and unifying method for cholera control and could potentially reduce transmission in this area. Deploying an early warning system and RRT for cholera in post-earthquake Nepal faced many challenges—poor disease surveillance, limited laboratory capacity, and loss of health infrastructure to name a few.Enhanced hospital-based surveillance for cholera cases took place at 15 sites throughout the Kathmandu Valley, consisting of Kathmandu, Lalitpur, and Bhaktapur districts. Focal persons  were identified at each hospital to be responsible for reporting suspected cases of cholera to the EDCD RRT. Physicians at the sentinel sites identified patients suspected of having cholera using a standard case definition: AWD, with or without vomiting, in a patient aged 1 year or older. Daily line listings of AWD cases were requested from each hospital, including zero-reporting, and a single suspected case of cholera triggered the CTI cascade. When such a patient was identified, a laboratory technician at the hospital was expected to perform both a rapid diagnostic test (RDT) and culture for cholera, in addition to sending a stool specimen to the National Public Health Laboratory (NPHL), for culture confirmation and serotyping. Within the same day (approximately 6 hours), any positive RDT result was reported to the EDCD by the appointed hospital focal person. Once notified, the RRT was expected to travel to the neighborhood of the index case the same day (or no more than 2 days) to initiate the CTI intervention. As this response was taking place at a time when the country was still recovering from the 2015 earthquakes, the country was still especially vulnerable to disease outbreaks. To limit the burden on the existing RRTs, an additional team was hired to assist specifically with the cholera response efforts. This six-person team consisted of microbiologists, health scientists, a geographic information system (GIS) specialist, and a data manager.1. Hospital and household investigations of each case2. An intensive WASH intervention to the case household and the first-degree neighbors3. Community-level WASH activities and health education messaging in the neighborhood surrounding the case to encourage safe water, safe food, and hand-washingV. cholerae at each index household4. Water testing for The CTI intervention included  and 2:1.Patients meeting the case definition for cholera were expected to have their clinical information recorded at the hospital by the RRT in what was termed the hospital investigation. Data collected here focus solely on the index case and included a summary of demographic characteristics, signs and symptoms, and approximate address. These data were aggregated and used to generate daily situation reports for the ministry and other relevant stakeholders.The RRT was then to be deployed to the home of the index case within 2 days to conduct the household investigation. GIS locations of the homes were recorded to map the geographic distribution of the outbreak. If a family did not consent to a home visit, or if the RRT was unable to contact the family, the approximate location of the household was mapped based on the patients’ neighborhood. Household investigation data included information on water sources, water treatment, history of diarrhea within the household over the last 2 weeks, history of food consumption and travel, and sanitation and hygiene behaviors of the entire household.The family of the index case and their immediate neighbors  were theFemale community health volunteers (FCHVs) and volunteers from local non-governmental organizations (NGOs) were trained by members of the cholera-specific RRT to deliver messages to the broader community surrounding the index case on various cholera prevention strategies. These messages included boiling, filtering, or treating water with chlorine, basic hygienic food preparation, parasite prevention methods, and the importance of vitamin A supplementation. Messages were to be delivered in a variety of ways to maximize coverage. Booths were set up in community areas with high foot traffic and the volunteers handed out flyers and answered questions. Awareness rallies were held with banners displaying prevention methods. Schools and food vendors were also targeted if they were within the target area. Presentations were given at meetings of community groups and schools, and radio messaging was projected from a vehicle (miking).12 The NPHL then performed culture analysis to preserve any V. cholerae isolates on thiosulfate citrate bile salt sucrose agar. Rapid response teams and FCHVs used a coliform presence/absence (H2S) test kit  as a visual demonstration of water unfit for drinking.13 These test kits were used at households and in the community on all water sources. The NPHL also performed a quantitative test for coliforms, the Idexx colilert-18 test.14Surface water samples (3 L each) were collected from primary and secondary drinking water sources for the index case households, filtered through sterile gauze, and incubated in alkaline peptone water for 24 hours.15 Results of testing at the community level were shared with that community and solutions to any water quality issues identified. If V. cholerae was found in any water source, families and the community were notified. Interventions for positive sources were dependent on the nature of the water source and were handled on a case by case basis.Total chorine tests were performed on household water sources and for tankers supplying water to the community.16 The survey asked residents whether their home was visited by a volunteer, whether they heard the health messaging in their neighborhood, whether they received specific information on health promotion from the volunteers, and whether they received water purification materials. It also included an assessment of their ability to answer basic hygiene promotion, water purification, and cholera prevention questions. Residents were consented to participate and had the option to refuse to answer a question if they desired.As part of the post-CTI program monitoring and evaluation, a survey was conducted in each of the areas targeted for a community-level WASH intervention. A field team visited each of the intervention areas and administered a simple questionnaire to households using a multistage cluster sampling method. A total of 400 households were targeted for the survey. First-stage clusters were the targeted wards, the lowest administrative unit used for planning and governance in Nepal, and the number of households sampled was proportionate to population size. For first-stage clusters larger than 20 households, an additional cluster was added within that ward, resulting in 30 total clusters. Second-stage clusters were chosen according to the WHO vaccine coverage survey guidelines.Detailed records on timeliness of the intervention were kept electronically by specific members of the RRTs for each phase of the response, and these were reviewed with the goal of answering questions regarding time to response. The number of cases over the course of the outbreak was graphed and cases were mapped by location of household using ArcGIS . Basic demographic characteristics of AWD cases, cholera cases, and survey respondents were described. Feasibility was measured through indicators of timeliness and quality of implementation . Survey Institutional Review Board (IRB) approval was obtained from the Johns Hopkins University IRB and the Nepal Health Research Counsel for the use of de-identified data collected during the campaign.V. cholerae O1 Ogawa (N = 194) and resulted in a sensitivity and specificity of 90% and 70%, respectively. Male–female ratio was similar between cholera and non-cholera diarrhea patients, but cholera patients were younger on average. Mostcases were detected from the Kathmandu Valley. The geographic distribution of cholera cases can be seen in A total of 2,207 cases of AWD were reported from the sentinel sites to the EDCD between June and November 2016 . Of thosO1 Ogawa . Rapid dAn evaluation of the speed with which the CTI was implemented can be seen in V. cholerae O1 Ogawa. Only 8.5% of drinking water samples tested had detectable levels of chlorine (10/118).Water samples were collected from all case households that were investigated and 90.7% (117/129) of those household water samples were found unsuitable for drinking based on coliform count (more than one coliform per 100 mL). Three household water sources were positive for Water, sanitation, and hygiene and health behavior messaging campaigns were conducted in 18 areas of Lalitpur and Kathmandu districts. On average, these campaigns happened 9.0 days after the initial case in that area was admitted to the hospital . A total of 394 households were surveyed , of whicThe initial pilot of the CTI program in the Kathmandu Valley suggests that this type of cholera-control approach is feasible in an urban, developing country setting. Traditionally, divides between clinicians, laboratory staff, and government responders have existed in Nepal as they do in many other countries. Clinicians treat patients based on clinical symptoms and they are often discharged before laboratory results are available. Combined with little to no contact information collected on these cases at admission , this scenario has made it very difficult to follow-up on cases in the past. This implementation of the CTI approach shows the potential to alleviate these issues, as participants at every level were required to communicate results quickly to remain within the established guidelines. Flow of information was evident from hospital admission as RRTs were able to interview 78% of patients before discharge, and this information was successfully translated into household-level, and in some areas, community-level responses. This program was also being implemented at a time when the health system was stressed post-earthquake, making the successes of the program even more promising.Despite this being the first time such an approach has been used to control cholera in the country and the absence of a vaccine to fully implement the intervention, the program contributed to a heightened awareness of cholera and AWD in the Kathmandu Valley among government officials, hospital staff, and local NGOs. The creation of a cholera task force within the ministry’s enteric disease steering committee during the CTI project further engaged these key players and the designation of focal points at sentinel site hospitals empowered hospital staff to report cases daily. This increased awareness is further evidenced by the subsequent workshops held among these stakeholders to discuss the lessons learned from the CTI program and the resulting creation and endorsement of the country’s first national cholera control strategy following the 2016 cholera season. This increased awareness also played a large role in the ability of the RRTs to mount a comprehensive response, rather than compartmentalized responses at each level of the health system.In addition to ensuring communication between historically disparate stakeholders, the evaluation of the CTI approach assists in the identification of bottlenecks for time-to-response. Diagnostic capacity is largely lacking at the hospital level, and although a few hospitals do have the capacity to perform culture confirmation of cholera, the time required to receive culture results diminishes the effectiveness of a response. Rapid response teams were able to respond to cases within an average of 4 days from hospital admission, but three of those days were typically spent waiting for a culture result. This highlights the need for an expansion of RDT at the hospital level for surveillance and response purposes, as well as the need for a reliable rapid test. The use of point-of-care RDTs would simplify all levels of the cholera surveillance and accelerate the response system by allowing the laboratory staff to provide clinicians with a rapid diagnosis, and the medical recorder with a diagnosis that warrants immediate report to the EDCD response team. An intervention could be implemented in the affected area within hours, as opposed to days, potentially preventing additional cases.In many cases, daily reports came from the large government hospitals, but for other health care providers, timely reporting remains a major issue. Staff reported being overburdened at the Ministry of Health and in the health facilities, making it difficult to encourage hospital reporting and government follow-up when the reports were not presented. With an at-risk population of 18.5 million people, one potential solution could be to increase or re-route manpower to specifically work on AWD and cholera surveillance at the district level during the monsoon season to ensure all cases are being identified, reported, and responded to. Lessons could also be taken from hospitals that consistently reported daily even when no cases were seen to create trainings for the less-responsive hospitals.The bar set for a “rapid” response under the CTI approach was to respond to the home within 2 days of a case presenting to the facility. Rapid response teams were able to perform thorough investigations at the homes of just over half of the confirmed cholera cases, but it took twice as long as planned. Several issues were at play here that can ultimately be traced back to the hospital-based surveillance. First, the vast majority of cases that could not be followed-up with household investigation were because of a lack of, or incorrect, contact information for the patient in the medical record. This is often a direct result of an overburdened and understaffed hospital where the accuracy and completeness of patient information is not a top priority. The EDCD officials’ uncertainty around the effectiveness of RDTs for case confirmation was a second time-limiting factor. Their preference to wait to initiate the household intervention until the case had been confirmed by culture led to major delays in response. To alleviate this hesitancy, culture was performed in parallel with the RDTs, resulting in a sensitivity and specificity of 90% and 70%, respectively. These results indicate that a system in which a response can be initiated by RDT result would lead to improved performance; culture can still be used at the national level as gold standard confirmation for official reporting. Especially in cases where an outbreak has already been detected and confirmed by culture, RDTs are a very efficient surveillance tool. Although false positives may lead to an increase in case load, these instances can be reduced by adding an enrichment step for 6 hours before testing. Last, it took as many as 6 days to respond after culture confirmation. There were only two central-level RRTs devoted to cholera response during the CTI implementation and as the outbreak progressed and daily case count increased, it was more difficult to keep up with household investigations. Manpower issues are a common constraint in Nepal, and one that will need serious commitment from the government to overcome.At the time of this intervention, there was no straightforward mechanism for initiating rapid interventions in Nepal’s health system. Before implementing WASH interventions, planning meetings needed to be held at the district level, even when the same intervention had already been carried out in another area of the same district weeks earlier. On average, it took teams 9 days to agree on a location to perform an intervention and obtain the necessary approval to carry it out. Although ensuring a quality response is important, there is a need for standard interventions to be agreed on and planning meetings and trainings to be held before the cholera season. This recommendation was presented to Ministry of Health officials, and discussions on how to implement this change are ongoing.The WASH program was designed to target those households immediately surrounding a case, however, interventions were planned and implemented more broadly. The intention was to reach more people at risk, but the result was low coverage of the intervention in the target population (neighbors of a case). In addition to needing a more rapid response, these results highlight the need to narrow the population target for the interventions. It is also notable that among those who recall receiving a WASH intervention, few cited receiving specific education on cholera, which shows a need for better training in the delivery of this important messaging. However, recall of the interventions themselves was associated with higher cholera-related knowledge.V. cholerae O1 during the household investigations. This sheds light on the state of the water system in Nepal, and the vulnerability of the nation’s poor. It is no surprise that improvements are needed in the water and sanitation infrastructure around the country, and steps are being taken, especially in light of these new data. Interventions such as WASH and OCV should be leveraged to prevent morbidity and mortality while those improvements are made.A key element of the CTI response was the monitoring of water sources. Nearly all sources were contaminated beyond levels safe for human consumption; however, only three water sources were found to be positive for The inability to obtain OCV within the program period was a significant obstacle, but it led to a discussion of the need for a small national vaccine stockpile. Without adequate knowledge of disease burden on which to base a pre-emptive vaccination campaign, the proposed reactive strategy provides an efficient alternative. To overcome this, a small stockpile would allow the Ministry of Health to respond quickly to seasonal outbreaks, but would also provide a safety net in the event of a large outbreak while more resources are being requested and obtained. Using vaccine within this approach would also require the targeted response that was lacking in this implementation of the CTI WASH intervention. The approach was designed to target the neighbors of cases, those living within approximately 100 m of a case household. This distance was chosen by experts at the ministry of health based on their knowledge of the population density of the Kathmandu Valley and a goal of vaccinating approximately 1,000 people per ring. The logistics of targeting OCV to a small population, and how large that population should be, are complicated and will require further study. It is clear that the selection of ring size is both population and resource dependent, and will likely need to conform to administrative boundaries (such as a ward) for ease of implementation at scale.17 Although the results here show an association between recall of the intervention and cholera knowledge, a true assessment of the intervention will require a tightly controlled, randomized study design and is planned for the future.In 2016, the CTI intervention was implemented as a program, not a research study, by the ministry of health, leaving many options open to interpretation by the implementers rather than being tightly controlled by study staff. Although this allowed for the feasibility assessment to be more true to life, it limits the ability to draw certain conclusions, especially in terms of the WASH response. Evidence surrounding effective WASH activities and implementation strategies is lacking.18Another potential limitation was the 6- to 8-month lag between the implementation of the WASH interventions and conducting the household survey. It is possible that individuals who recall the intervention are also more likely to recall the cholera-related knowledge, leading to inflation of the estimated ORs. Despite the implications for recall and therefore the reliability of the coverage estimate, the results of the knowledge portion of the survey are informative. Whether or not the family received or remembered the intervention itself, the results reveal the proportion of the population that has the knowledge necessary to protect themselves and their family from cholera. It has also been argued that surveys are inadequate for collecting data on the personal issues targeted here, such as hand-washing, food hygiene, and proper sanitation practices, because rates of such behaviors are often overestimated.Finally, timeliness and practicality were the main criteria used to determine feasibility of the CTI approach, however, cost is also a large determinant of the feasibility of any public health program that was not considered in this analysis.The CTI shows promise as a feasible strategy to unify effective cholera control procedures. We understood that this approach would represent a major change in the present procedures for cholera management, because case management, laboratory assays, and public health response are not generally tightly coordinated. The clinician would need to identify the case quickly and arrange for a rapid test to be carried out. The technician carrying out the test would notify the EDCD of the positive case, and the CTI RRT could quickly (within 2 days of the case coming for treatment) visit the neighborhood and implement within this neighborhood an integrated intervention package including WASH, health education, community mobilization, and vaccination. On its first implementation, this timeline has been extended, but through this evaluation we have revealed the current weaknesses in the cholera surveillance system and identified concrete areas for improvement seen in