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Background: The unprecedented influx of Rohingya refugees into Cox's Bazar, Bangladesh, in 2017 led to a humanitarian emergency requiring large numbers of humanitarian workers to be deployed to the region. The World Health Organization (WHO) contributed to this effort through well-established deployment mechanisms: the Global Outbreak Alert and Response Network (GOARN) and the Standby Partnerships (SBP). The study captures the views and experiences of those humanitarian workers deployed by WHO through operational partnerships between December 2017 and February 2019 with the purpose of identifying challenges and good practice during the deployment process, and steps to their improvement.Methods: A mixed methods design was used. A desktop review was conducted to describe the demographics of the humanitarian workers deployed to Cox's Bazar and the work that was undertaken. Interviews were conducted with a subset of the respondents to elicit their views relating to their experiences of working as part of the humanitarian response. Thematic analysis was used to identify key themes.Results: We identified sixty-five deployments during the study period. Respondents' previous experience ranged between 3 and 28 years (mean 9.7 years). The duration of deployment ranged from 8 to 278 days (mean 67 days) and there was a higher representation of workers from Western Pacific and European regions. Forty-one interviews were conducted with people who experienced differing aspects of the deployment process. Key themes elicited from interviews related to staffing, the deployment process, the office environment and capacity building. Various issues raised have since been addressed, including the establishment of a sub-office structure, introduction of online training prior to deployment, and a staff wellbeing committee.Conclusions: This study identified successes and areas for improvement for deployments during emergencies. The themes and subthemes elicited can be used to inform policy and practice changes, as well as the development of performance indicators. Common findings between this study and previous literature indicate the pivotal role of staff deployments through partnership agreements during health emergency response operations and a need for continuous improvements of processes to ensure maximum effectiveness. [ABSTRACT FROM AUTHOR]

On August 25 2017, an unprecedented influx of Rohingya refugees began from Rakhine State in Myanmar into Bangladesh's district of Cox's Bazar. The scale and acuteness of this humanitarian crisis was unprecedented and unique globally, requiring strong coordination of a multitude of actors. This paper reflects on the health sector coordination from August 2017 to October 2019, focusing on selected achievements and persisting challenges of the health sector strategic advisory group (HSSAG), and the health sector working groups including epidemiology and case management, sexual and reproductive health, community health, mental health and psychosocial support, and emergency preparedness. In the early days of the response, minimum service standards for primary health care were established, a fundamental initial step which enabled the standardization of services based on critical needs. Similarly, establishing standards for community health outreach was the backbone for capitalizing on this important health workforce. Novel approaches were adopted for infectious disease responses for acute watery diarrhoea and varicella, drawing on inter-sectoral collaborations. Sexual and reproductive health services were prioritized from the initial onset of the crisis and improvements in skilled delivery attendance, gender-based violence services, abortion care and family planning were recorded. Mental health service provision was strengthened through community-based approaches although integration of mental health programmes into primary health care has been limited by availability of specialist psychiatrists. Strong, collaborative and legitimate leadership by the health sector strategic advisory group, drawing on inter-sectoral collaborations and the technical expertise of the different technical working groups, were critical in the response and proved effective, despite the remaining challenges to be addressed. Anticipated reductions in funding as the crisis moves into protracted status threatens the achievements of the health sector in provision of health services to the Rohingya refugees. [ABSTRACT FROM AUTHOR]

In the summer of 2017, an estimated 745,000 Rohingya fled to Bangladesh in what has been described as one of the largest and fastest growing refugee crises in the world. Among numerous health concerns, an outbreak of acute jaundice syndrome (AJS) was detected by the disease surveillance system in early 2018 among the refugee population. This paper describes the investigation into the increase in AJS cases, the process and results of the investigation, which were strongly suggestive of a large outbreak due to hepatitis A virus (HAV). An enhanced serological investigation was conducted between 28 February to 26 March 2018 to determine the etiologies and risk factors associated with the outbreak. A total of 275 samples were collected from 18 health facilities reporting AJS cases. Blood samples were collected from all patients fulfilling the study specific case definition and inclusion criteria, and tested for antibody responses using enzyme-linked immunosorbent assay (ELISA). Out of the 275 samples, 206 were positive for one of the agents tested. The laboratory results confirmed multiple etiologies including 154 (56%) samples tested positive for hepatitis A, 1 (0.4%) positive for hepatitis E, 36 (13%) positive for hepatitis B, 25 (9%) positive for hepatitis C, and 14 (5%) positive for leptospirosis. Among all specimens tested 24 (9%) showed evidence of co-infections with multiple etiologies. Hepatitis A and E are commonly found in refugee camps and have similar clinical presentations. In the absence of robust testing capacity when the epidemic was identified through syndromic reporting, a particular concern was that of a hepatitis E outbreak, for which immunity tends to be limited, and which may be particularly severe among pregnant women. This report highlights the challenges of identifying causative agents in such settings and the resources required to do so. Results from the month-long enhanced investigation did not point out widespread hepatitis E virus (HEV) transmission, but instead strongly suggested a large-scale hepatitis A outbreak of milder consequences, and highlighted a number of other concomitant causes of AJS (acute hepatitis B, hepatitis C, Leptospirosis), albeit most likely at sporadic level. Results strengthen the need for further water and sanitation interventions and are a stark reminder of the risk of other epidemics transmitted through similar routes in such settings, particularly dysentery and cholera. It also highlights the need to ensure clinical management capacity for potentially chronic conditions in this vulnerable population. [ABSTRACT FROM AUTHOR]

Background: Unrest in Myanmar in August 2017 resulted in the movement of over 700,000 Rohingya refugees to overcrowded camps in Cox's Bazar, Bangladesh. A large outbreak of diphtheria subsequently began in this population.Methods and Findings: Data were collected during mass vaccination campaigns (MVCs), contact tracing activities, and from 9 Diphtheria Treatment Centers (DTCs) operated by national and international organizations. These data were used to describe the epidemiological and clinical features and the control measures to prevent transmission, during the first 2 years of the outbreak. Between November 10, 2017 and November 9, 2019, 7,064 cases were reported: 285 (4.0%) laboratory-confirmed, 3,610 (51.1%) probable, and 3,169 (44.9%) suspected cases. The crude attack rate was 51.5 cases per 10,000 person-years, and epidemic doubling time was 4.4 days (95% confidence interval [CI] 4.2-4.7) during the exponential growth phase. The median age was 10 years (range 0-85), and 3,126 (44.3%) were male. The typical symptoms were sore throat (93.5%), fever (86.0%), pseudomembrane (34.7%), and gross cervical lymphadenopathy (GCL; 30.6%). Diphtheria antitoxin (DAT) was administered to 1,062 (89.0%) out of 1,193 eligible patients, with adverse reactions following among 229 (21.6%). There were 45 deaths (case fatality ratio [CFR] 0.6%). Household contacts for 5,702 (80.7%) of 7,064 cases were successfully traced. A total of 41,452 contacts were identified, of whom 40,364 (97.4%) consented to begin chemoprophylaxis; adherence was 55.0% (N = 22,218) at 3-day follow-up. Unvaccinated household contacts were vaccinated with 3 doses (with 4-week interval), while a booster dose was administered if the primary vaccination schedule had been completed. The proportion of contacts vaccinated was 64.7% overall. Three MVC rounds were conducted, with administrative coverage varying between 88.5% and 110.4%. Pentavalent vaccine was administered to those aged 6 weeks to 6 years, while tetanus and diphtheria (Td) vaccine was administered to those aged 7 years and older. Lack of adequate diagnostic capacity to confirm cases was the main limitation, with a majority of cases unconfirmed and the proportion of true diphtheria cases unknown.Conclusions: To our knowledge, this is the largest reported diphtheria outbreak in refugee settings. We observed that high population density, poor living conditions, and fast growth rate were associated with explosive expansion of the outbreak during the initial exponential growth phase. Three rounds of mass vaccinations targeting those aged 6 weeks to 14 years were associated with only modestly reduced transmission, and additional public health measures were necessary to end the outbreak. This outbreak has a long-lasting tail, with Rt oscillating at around 1 for an extended period. An adequate global DAT stockpile needs to be maintained. All populations must have access to health services and routine vaccination, and this access must be maintained during humanitarian crises. [ABSTRACT FROM AUTHOR]

Despite continued efforts to improve health systems worldwide, emerging pathogen epidemics remain a major public health concern. Effective response to such outbreaks relies on timely intervention, ideally informed by all available sources of data. The collection, visualization and analysis of outbreak data are becomingincreasingly complex, owing to the diversity in types of data, questions and available methods to address them. Recent advances have led to the rise of outbreak analytics, an emerging data science focused on the technological and methodological aspects of the outbreak data pipeline, fromcollection to analysis, modelling and reporting to inform outbreak response. In this article, we assess the current state of the field. After laying out the context of outbreak response, we critically review the most common analytics components, their interdependencies, data requirements and the type of information they can provide to informoperations in real time. We discuss some challenges and opportunities and conclude on the potential role of outbreak analytics for improving our understanding of, and response to outbreaks of emerging pathogens. [ABSTRACT FROM AUTHOR]

Background Malaria transmission in African highland areas can be prone to epidemics, with minor fluctuations in temperature or altitude resulting in highly heterogeneous transmission. In the Kenyan Highlands, where malaria prevalence has been increasing, characterising malaria incidence and identifying risk factors for infection is complicated by asymptomatic infection. Methods This all-age cohort study, one element of the Malaria Transmission Consortium, involved monthly follow-up of 3155 residents of the Kisii and Rachuonyo South districts during June 2009–June 2010. Participants were tested for malaria using rapid diagnostic testing at every visit, regardless of symptoms. Results The incidence of Plasmodium falciparum infection was 0.2 cases per person, although infections were clustered within individuals and over time, with the majority of infections detected in the last month of the cohort study. Overall, incidence was higher in the Rachuonyo district and infections were detected most frequently in 5–10-year-olds. The majority of infections were asymptomatic (58%). Travel away from the study area was a notable risk factor for infection. Conclusions Identifying risk factors for malaria infection can help to guide targeting of interventions to populations most likely to be exposed to malaria. [ABSTRACT FROM AUTHOR]

Background: The East African highlands are fringe regions between stable and unstable malaria transmission. What factors contribute to the heterogeneity of malaria exposure on different spatial scales within larger foci has not been extensively studied. In a comprehensive, community-based cross-sectional survey an attempt was made to identify factors that drive the macro- and micro epidemiology of malaria in a fringe region using parasitological and serological outcomes. Methods: A large cross-sectional survey including 17,503 individuals was conducted across all age groups in a 100 km2 area in the Western Kenyan highlands of Rachuonyo South district. Households were geo-located and prevalence of malaria parasites and malaria-specific antibodies were determined by PCR and ELISA. Household and individual risk-factors were recorded. Geographical characteristics of the study area were digitally derived using high-resolution satellite images. Results: Malaria antibody prevalence strongly related to altitude (1350-1600 m, p < 0.001). A strong negative association with increasing altitude and PCR parasite prevalence was found. Parasite carriage was detected at all altitudes and in all age groups; 93.2 % (2481/2663) of malaria infections were apparently asymptomatic. Malaria parasite prevalence was associated with age, bed net use, house construction features, altitude and topographical wetness index. Antibody prevalence was associated with all these factors and distance to the nearest water body. Conclusion: Altitude was a major driver of malaria transmission in this study area, even across narrow altitude bands. The large proportion of asymptomatic parasite carriers at all altitudes and the age-dependent acquisition of malaria antibodies indicate stable malaria transmission; the strong correlation between current parasite carriage and serological markers of malaria exposure indicate temporal stability of spatially heterogeneous transmission. [ABSTRACT FROM AUTHOR]

Background: Malaria transmission is highly heterogeneous, generating malaria hotspots that can fuel malaria transmission across a wider area. Targeting hotspots may represent an efficacious strategy for reducing malaria transmission. We determined the impact of interventions targeted to serologically defined malaria hotspots on malaria transmission both inside hotspots and in surrounding communities.Methods and Findings: Twenty-seven serologically defined malaria hotspots were detected in a survey conducted from 24 June to 31 July 2011 that included 17,503 individuals from 3,213 compounds in a 100-km2 area in Rachuonyo South District, Kenya. In a cluster-randomized trial from 22 March to 15 April 2012, we randomly allocated five clusters to hotspot-targeted interventions with larviciding, distribution of long-lasting insecticide-treated nets, indoor residual spraying, and focal mass drug administration (2,082 individuals in 432 compounds); five control clusters received malaria control following Kenyan national policy (2,468 individuals in 512 compounds). Our primary outcome measure was parasite prevalence in evaluation zones up to 500 m outside hotspots, determined by nested PCR (nPCR) at baseline and 8 wk (16 June-6 July 2012) and 16 wk (21 August-10 September 2012) post-intervention by technicians blinded to the intervention arm. Secondary outcome measures were parasite prevalence inside hotpots, parasite prevalence in the evaluation zone as a function of distance from the hotspot boundary, Anopheles mosquito density, mosquito breeding site productivity, malaria incidence by passive case detection, and the safety and acceptability of the interventions. Intervention coverage exceeded 87% for all interventions. Hotspot-targeted interventions did not result in a change in nPCR parasite prevalence outside hotspot boundaries (p ≥ 0.187). We observed an average reduction in nPCR parasite prevalence of 10.2% (95% CI -1.3 to 21.7%) inside hotspots 8 wk post-intervention that was statistically significant after adjustment for covariates (p = 0.024), but not 16 wk post-intervention (p = 0.265). We observed no statistically significant trend in the effect of the intervention on nPCR parasite prevalence in the evaluation zone in relation to distance from the hotspot boundary 8 wk (p = 0.27) or 16 wk post-intervention (p = 0.75). Thirty-six patients with clinical malaria confirmed by rapid diagnostic test could be located to intervention or control clusters, with no apparent difference between the study arms. In intervention clusters we caught an average of 1.14 female anophelines inside hotspots and 0.47 in evaluation zones; in control clusters we caught an average of 0.90 female anophelines inside hotspots and 0.50 in evaluation zones, with no apparent difference between study arms. Our trial was not powered to detect subtle effects of hotspot-targeted interventions nor designed to detect effects of interventions over multiple transmission seasons.Conclusions: Despite high coverage, the impact of interventions targeting malaria vectors and human infections on nPCR parasite prevalence was modest, transient, and restricted to the targeted hotspot areas. Our findings suggest that transmission may not primarily occur from hotspots to the surrounding areas and that areas with highly heterogeneous but widespread malaria transmission may currently benefit most from an untargeted community-wide approach. Hotspot-targeted approaches may have more validity in settings where human settlement is more nuclear.Trial Registration: ClinicalTrials.gov NCT01575613. [ABSTRACT FROM AUTHOR]

Background: Mass screening and treatment currently fails to identify a considerable fraction of low parasite density infections, while mass treatment exposes many uninfected individuals to antimalarial drugs. Here we test a hybrid approach to screen a sentinel population to identify clusters of subpatent infections in the Kenya highlands with low, heterogeneous malaria transmission.Methods: Two thousand eighty-two inhabitants were screened for parasitemia by nested polymerase chain reaction (nPCR). Children aged ≤ 15 years and febrile adults were also tested for malaria by rapid diagnostic test (RDT) and served as sentinel members to identify subpatent infections within the household. All parasitemic individuals were assessed for multiplicity of infections by nPCR and gametocyte carriage by nucleic acid sequence-based amplification.Results: Households with RDT-positive individuals in the sentinel population were more likely to have nPCR-positive individuals (odds ratio: 1.71, 95% confidence interval, 1.60-1.84). The sentinel population identified 64.5% (locality range: 31.6%-81.2%) of nPCR-positive households and 77.3% (locality range: 24.2%-91.0%) of nPCR-positive individuals. The sensitivity of the sentinel screening approach was positively associated with transmission intensity (P = .037).Conclusions: In this low endemic area, a focal screening approach with RDTs prior to the high transmission season was able to identify the majority of the subpatent parasite reservoirs. [ABSTRACT FROM AUTHOR]

Background: Monitoring and evaluation of malaria programmes may require a combination of approaches to detect any effects of control. This is particularly true at lower transmission levels where detecting both infection and exposure to infection will provide additional evidence of any change. This paper describes use of three transmission metrics to explore the malaria epidemiology in the highlands of western Kenya. Methods: A malariometric survey was conducted in June 2009 in two highland districts, Kisii and Rachuonyo South, Nyanza Province, Kenya using a cluster design. Enumeration areas were used to sample 46 clusters from which 12 compounds were randomly sampled. Individuals provided a finger-blood sample to assess malaria infection (rapid diagnostic test, PCR) and exposure (anti-Plasmodium falciparum MSP-1 antibodies) and a questionnaire was administered to record household factors and assess use of vector control interventions. Results: Malaria prevalence infection rates were 3.0 % (95 % CI 2.2–4.2 %) by rapid diagnostic test (RDT) and 8.5 % (95 % CI 7.0–10.4 %) by PCR and these ranged from 0–13.1 to 0–14.8 % between clusters for RDT and PCR, respectively. Seroprevalence was 36.8 % (95 % CI 33.9–39.8) ranging from 18.6 to 65.8 %. Both RDT and PCR prevalences were highest in children aged 5–10 years but the proportion of infections that were sub-patent was highest in those between 15 and 20 years of age (78.1 %, 95 % CI 63.0–93.3 %) and those greater than 20 years (73.3 %, 95 % CI 64.5– 81.9 %). Those reporting both indoor residual spraying (IRS) in their home and use of bed nets had lower exposure to malaria compared to those who reported using IRS or bed nets alone. Conclusions: In this highland site in western Kenya malaria transmission was low, but highly heterogeneous. To accurately characterize the true extent of malaria transmission, more sensitive and complementary metrics such as PCR or serology are required in addition to the standard microscopy and/or RDTs that are routinely used. This is likely to be the case in other low endemicity settings. [ABSTRACT FROM AUTHOR]

Background: Motivated by the success in malaria control that was documented over the last decade Ethiopia is aiming at malaria elimination by 2020 in selected districts. It is currently unknown if asymptomatic, submicroscopic malaria parasite carriage may form a hurdle to achieve elimination. The elimination effort may further be complicated by possible glucose-6 phosphate dehydrogenase (G6PD) deficiency which would hinder the use of 8-aminoquinolines in the elimination efforts. Method: In February 2014 a community-based cross-sectional survey was conducted in Malo, southwest Ethiopia. Finger-prick blood samples (n = 555) were tested for presence of Plasmodium falciparum and Plasmodium vivax with microscopy, rapid diagnostic test (RDT), and nested polymerase chain reaction (nPCR). Multiplicity of P. falciparum infections was determined based on genotyping the polymorphic merozoite surface protein-2 (MSP-2) gene. Individuals were also genotyped for mutations in the gene that produces G6PD. Results: All study participants were malaria infection negative by microscopy and RDT. Nested PCR revealed P. falciparum mono-infection in 5.2% (29/555), P. vivax mono-infection in 4.3% (24/555) and mixed infection in 0.2% (1/555) of individuals. All parasitemic individuals were afebrile (axillary temperature <37.5°C). None of the study participants carried mutations for the G6PD African A-(202GA) and Mediterranean (563CT) variants. All infections, except one, were single-clone infection by MSP-2 genotyping. Conclusion: The detection of a substantial number of subpatent malaria infections in an apparently asymptomatic population without evidence for malaria transmission by conventional diagnostics raises questions about the path to malaria elimination. It is currently unknown how important these infections are for sustaining malaria transmission in the study sites. The absence of G6PD deficiency indicates that 8-aminoquinolines may be safely deployed to accelerate elimination initiatives. [ABSTRACT FROM AUTHOR]

Introduction: Tools that allow for in silico optimization of available malaria control strategies can assist the decision-making process for prioritizing interventions. The OpenMalaria stochastic simulation modeling platform can be applied to simulate the impact of interventions singly and in combination as implemented in Rachuonyo South District, western Kenya, to support this goal. Methods: Combinations of malaria interventions were simulated using a previously-published, validated model of malaria epidemiology and control in the study area. An economic model of the costs of case management and malaria control interventions in Kenya was applied to simulation results and cost-effectiveness of each intervention combination compared to the corresponding simulated outputs of a scenario without interventions. Uncertainty was evaluated by varying health system and intervention delivery parameters. Results: The intervention strategy with the greatest simulated health impact employed long lasting insecticide treated net (LLIN) use by 80% of the population, 90% of households covered by indoor residual spraying (IRS) with deployment starting in April, and intermittent screen and treat (IST) of school children using Artemether lumefantrine (AL) with 80% coverage twice per term. However, the current malaria control strategy in the study area including LLIN use of 56% and IRS coverage of 70% was the most cost effective at reducing disability-adjusted life years (DALYs) over a five year period. Conclusions: All the simulated intervention combinations can be considered cost effective in the context of available resources for health in Kenya. Increasing coverage of vector control interventions has a larger simulated impact compared to adding IST to the current implementation strategy, suggesting that transmission in the study area is not at a level to warrant replacing vector control to a school-based screen and treat program. These results have the potential to assist malaria control program managers in the study area in adding new or changing implementation of current interventions. [ABSTRACT FROM AUTHOR]

Background: Informing and evaluating malaria control efforts relies on knowledge of local transmission dynamics. Serological and molecular tools have demonstrated great sensitivity to quantify transmission intensity in low endemic settings where the sensitivity of traditional methods is limited. Filter paper blood spots are commonly used a source of both DNA and antibodies. To enhance the operational practicability of malaria surveys, a method is presented for combined DNA extraction and antibody elution. Methods: Filter paper blood spots were collected as part of a large cross-sectional survey in the Kenyan highlands. DNA was extracted using a saponin/chelex method. The eluate of the first wash during the DNA extraction process was used for antibody detection and compared with previously validated antibody elution procedures. Antibody elution efficiency was assessed by total IgG ELISA for malaria antigens apical membrane antigen-1 (AMA-1) and merozoite-surface protein-1 (MSP-142). The sensitivity of nested 18S rRNA and cytochrome b PCR assays and the impact of doubling filter paper material for PCR sensitivity were determined. The distribution of cell material and antibodies throughout filter paper blood spots were examined using luminescent and fluorescent reporter assays. Results: Antibody levels measured after the combined antibody/DNA extraction technique were strongly correlated to those measured after standard antibody elution (p < 0.0001). Antibody levels for both AMA-1 and MSP-142 were generally slightly lower (11.3-21.4%) but age-seroprevalence patterns were indistinguishable. The proportion of parasite positive samples ranged from 12.9% to 19.2% in the different PCR assays. Despite strong agreement between outcomes of different PCR assays, none of the assays detected all parasite-positive individuals. For all assays doubling filter paper material for DNA extraction increased sensitivity. The concentration of cell and antibody material was not homogenously distributed throughout blood spots. Conclusion: Combined DNA extraction and antibody elution is an operationally attractive approach for high throughput assessment of cumulative malaria exposure and current infection prevalence in endemic settings. Estimates of antibody prevalence are unaffected by the combined extraction and elution procedure. The choice of target gene and the amount and source of filter paper material for DNA extraction can have a marked impact on PCR sensitivity. [ABSTRACT FROM AUTHOR]

Background. Artemisinin-based combination therapy (ACT) reduces the potential for malaria transmission, compared with non-ACTs. It is unclear whether this effect differs between ACTs.Methods. A total of 298 children (age, 6 months to 10 years) with uncomplicated falciparum malaria were randomized to artemether-lumefantrine (AL; n = 153) or dihydroartemisinin-piperaquine (DP; n = 145) in Mbita, a community in western Kenya. Gametocyte carriage was determined by molecular methods on days 0, 1, 2, 3, 7, 14, 28, and 42 after treatment initiation. The gametocyte infectiousness to mosquitoes was determined by mosquito-feeding assays on day 7 after beginning therapy.Results. The cumulative risk of recurrent parasitemia on day 42 after initiation of treatment, unadjusted by polymerase chain reaction findings, was 20.7% (95% confidence interval [CI], 14.4–28.2) for AL, compared with 3.7% (95% CI, 1.2–8.5) for DP (P < .001). The mean duration of gametocyte carriage was 5.5 days (95% CI, 3.6–8.5) for AL and 15.3 days (95% CI, 9.7–24.2) for DP (P = .001). The proportion of mosquitoes that became infected after feeding on blood from AL-treated children was 1.88% (43 of 2293), compared with 3.50% (83 of 2371) for those that fed on blood from DP-treated children (P = .06); the oocyst burden among mosquitoes was lower among those that fed on blood from AL-treated children (P = .005)Conclusions. While DP was associated with a longer prophylactic time after treatment, gametocyte carriage and malaria transmission to mosquitoes was lower after AL treatment.Clinical Trials Registration: NCT00868465. [ABSTRACT FROM AUTHOR]

Background: Malaria transmission is highly heterogeneous in most settings, resulting in the formation of recognizable malaria hotspots. Targeting these hotspots might represent a highly efficacious way of controlling or eliminating malaria if the hotspots fuel malaria transmission to the wider community. Methods/design: Hotspots of malaria will be determined based on spatial patterns in age-adjusted prevalence and density of antibodies against malaria antigens apical membrane antigen-1 and merozoite surface protein-1. The community effect of interventions targeted at these hotspots will be determined. The intervention will comprise larviciding, focal screening and treatment of the human population, distribution of long-lasting insecticide-treated nets and indoor residual spraying. The impact of the intervention will be determined inside and up to 500 m outside the targeted hotspots by PCR-based parasite prevalence in cross-sectional surveys, malaria morbidity by passive case detection in selected facilities and entomological monitoring of larval and adult Anopheles populations. Discussion: This study aims to provide direct evidence for a community effect of hotspot-targeted interventions. The trial is powered to detect large effects on malaria transmission in the context of ongoing malaria interventions. Follow-up studies will be needed to determine the effect of individual components of the interventions and the cost-effectiveness of a hotspot-targeted approach, where savings made by reducing the number of compounds that need to receive interventions should outweigh the costs of hotspot-detection. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic carriage of Giardia intestinalis is highly prevalent among children in developing countries, and evidence regarding its role as a diarrhea-causing agent in these settings is controversial. Impaired linear growth and cognition have been associated with giardiasis, presumably mediated by malabsorption of nutrients. In a prospective cohort study, we aim to compare diarrhea rates in pre-school children with and without Giardia infection. Because the study was conducted in the context of an intervention trial assessing the effects of multi-nutrients on morbidity, we also assessed how supplementation influenced the relationship between Giardia and diarrhoea rates, and to what extent Giardia modifies the intervention effect on nutritional status. Methods and Findings: Data were collected in the context of a randomized placebo-controlled efficacy trial with 2×2 factorial design assessing the effects of zinc and/or multi-micronutrients on morbidity (n = 612; height-for-age z-score <−1.5 SD). Outcomes measures were episodes of diarrhea (any reported, or with ≥3 stools in the last 24 h) and fever without localizing signs, as detected with health-facility based surveillance. Giardia was detected in stool by enzyme-linked immunosorbent assay. Among children who did not receive multi-nutrients, asymptomatic Giardia infection at baseline was associated with a substantial reduction in the rate of diarrhea (HR 0.32; 0.15–0.66) and fever without localizing signs (HR 0.56; 0.36–0.87), whereas no such effect was observed among children who received multi-nutrients (p-values for interaction 0.03 for both outcomes). This interaction was independent of age, HAZ-scores and distance to the research dispensary. There was no evidence that Giardia modified the intervention effect on nutritional status. Conclusion: Although causality of the Giardia-associated reduction in morbidity cannot be established, multi-nutrient supplementation results in a loss of this protection and thus seems to influence the proliferation or virulence of Giardia or associated intestinal pathogens. Author Summary: Giardia intestinalis is a well-known cause of diarrhea in industrialized countries. In children in developing countries, asymptomatic infections are common and their role as cause of diarrhea has been questioned. In a cohort of rural Tanzanian pre-school children, we assessed the association between the presence of Giardia at baseline and subsequent diarrhea risk. The study was conducted in the context of a randomised trial assessing the effect of supplementation with zinc and other micro-nutrients on malaria, and half of the children daily received a multi-nutrient supplement. Surprisingly, we found that the presence of Giardia at baseline was associated with a substantial reduction in diarrhea risk. Multivariate statistical analysis showed that this protection could not be explained by differences in age or walking distance to the dispensary between children with and without Giardia. Because we cannot exclude that children differed in other (unmeasured) characteristics, we cannot draw firm conclusions about the causality of the observed association, but our findings support the view that the parasite is not an important cause of diarrhea in highly endemic settings. Striking was that the Giardia-associated protection was lost when children received multi-nutrients. Our data do not provide information about the mechanisms involved, but suggest that multi-nutrients may influence the compositionor pathogenicity of intestinal biota. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic carriage of Giardia intestinalis is highly prevalent among children in developing countries, and evidence regarding its role as a diarrhea-causing agent in these settings is controversial. Impaired linear growth and cognition have been associated with giardiasis, presumably mediated by malabsorption of nutrients. In a prospective cohort study, we aim to compare diarrhea rates in pre-school children with and without Giardia infection. Because the study was conducted in the context of an intervention trial assessing the effects of multi-nutrients on morbidity, we also assessed how supplementation influenced the relationship between Giardia and diarrhoea rates, and to what extent Giardia modifies the intervention effect on nutritional status. Methods and Findings: Data were collected in the context of a randomized placebo-controlled efficacy trial with 2x2 factorial design assessing the effects of zinc and/or multi-micronutrients on morbidity (n = 612; height-for-age z-score <-1.5 SD). Outcomes measures were episodes of diarrhea (any reported, or with ⩾3 stools in the last 24 h) and fever without localizing signs, as detected with health-facility based surveillance. Giardia was detected in stool by enzyme-linked immunosorbent assay. Among children who did not receive multi-nutrients, asymptomatic Giardia infection at baseline was associated with a substantial reduction in the rate of diarrhea (HR 0.32; 0.15-0.66) and fever without localizing signs (HR 0.56; 0.36-0.87), whereas no such effect was observed among children who received multi-nutrients (p-values for interaction 0.03 for both outcomes). This interaction was independent of age, HAZ-scores and distance to the research dispensary. There was no evidence that Giardia modified the intervention effect on nutritional status. Conclusion: Although causality of the Giardia-associated reduction in morbidity cannot be established, multi-nutrient supplementation results in a loss of this protection and thus seems to influence the proliferation or virulence of Giardia or associated intestinal pathogens. [ABSTRACT FROM AUTHOR]

The spatial heterogeneity of malaria suggests that interventions may be targeted for maximum impact. It is unclear to what extent different metrics lead to consistent delineation of hotspot boundaries. Using data from a large community-based malaria survey in the western Kenyan highlands, we assessed the agreement between a model-based geostatistical (MBG) approach to detect hotspots using Plasmodium falciparum parasite prevalence and serological evidence for exposure. Malaria transmission was widespread and highly heterogeneous with one third of the total population living in hotspots regardless of metric tested. Moderate agreement (Kappa = 0.424) was observed between hotspots defined based on parasite prevalence by polymerase chain reaction (PCR)- and the prevalence of antibodies to two P. falciparum antigens (MSP-1, AMA-1). While numerous biologically plausible hotspots were identified, their detection strongly relied on the proportion of the population sampled. When only 3% of the population was sampled, no PCR derived hotspots were reliably detected and at least 21% of the population was needed for reliable results. Similar results were observed for hotspots of seroprevalence. Hotspot boundaries are driven by the malaria diagnostic and sample size used to inform the model. These findings warn against the simplistic use of spatial analysis on available data to target malaria interventions in areas where hotspot boundaries are uncertain. [ABSTRACT FROM AUTHOR]

An abstract of the article "Extended malaria parasite clearance time in African children following artemisinincombination therapy enhances transmission to Anopheles mosquitoes," by Khalid B. Beshir, Patrick Sawa, Chris J. Drakeley, Amrish Y. Baidjoe and colleagues is presented.

Background: Malaria transmission is highly heterogeneous in most settings, resulting in the formation of recognizable malaria hotspots. Targeting these hotspots might represent a highly efficacious way of controlling or eliminating malaria if the hotspots fuel malaria transmission to the wider community.Methods/design: Hotspots of malaria will be determined based on spatial patterns in age-adjusted prevalence and density of antibodies against malaria antigens apical membrane antigen-1 and merozoite surface protein-1. The community effect of interventions targeted at these hotspots will be determined. The intervention will comprise larviciding, focal screening and treatment of the human population, distribution of long-lasting insecticide-treated nets and indoor residual spraying. The impact of the intervention will be determined inside and up to 500 m outside the targeted hotspots by PCR-based parasite prevalence in cross-sectional surveys, malaria morbidity by passive case detection in selected facilities and entomological monitoring of larval and adult Anopheles populations.Discussion: This study aims to provide direct evidence for a community effect of hotspot-targeted interventions. The trial is powered to detect large effects on malaria transmission in the context of ongoing malaria interventions. Follow-up studies will be needed to determine the effect of individual components of the interventions and the cost-effectiveness of a hotspot-targeted approach, where savings made by reducing the number of compounds that need to receive interventions should outweigh the costs of hotspot-detection.Trial Registration: NCT01575613. The protocol was registered online on 20 March 2012; the first community was randomized on 26 March 2012. [ABSTRACT FROM AUTHOR]