Impact of aerial humidity on seasonal malaria: an ecological study in Zambia.

BACKGROUND: Seasonal patterns of malaria cases in many parts of Africa are generally associated with rainfall, yet in the dry seasons, malaria transmission declines but does not always cease. It is important to understand what conditions support these periodic cases. Aerial moisture is thought to be important for mosquito survival and ability to forage, but its role during the dry seasons has not been well studied. During the dry season aerial moisture is minimal, but intermittent periods may arise from the transpiration of peri-domestic trees or from some other sources in the environment. These periods may provide conditions to sustain pockets of mosquitoes that become active and forage, thereby transmitting malaria. In this work, humidity along with other ecological variables that may impact malaria transmission have been examined. METHODS: Negative binomial regression models were used to explore the association between peri-domestic tree humidity and local malaria incidence. This was done using sensitive temperature and humidity loggers in the rural Southern Province of Zambia over three consecutive years. Additional variables including rainfall, temperature and elevation were also explored. RESULTS: A negative binomial model with no lag was found to best fit the malaria cases for the full year in the evaluated sites of the Southern Province of Zambia. Local tree and granary night-time humidity and temperature were found to be associated with local health centre-reported incidence of malaria, while rainfall and elevation did not significantly contribute to this model. A no lag and one week lag model for the dry season alone also showed a significant effect of humidity, but not temperature, elevation, or rainfall. CONCLUSION: The study has shown that throughout the dry season, periodic conditions of sustained humidity occur that may permit foraging by resting mosquitoes, and these periods are associated with increased incidence of malaria cases. These results shed a light on conditions that impact the survival of the common malaria vector species, Anopheles arabiensis, in arid seasons and suggests how they emerge to forage when conditions permit.

How far is the journey before malaria is knocked out of Zimbabwe? (or Africa): a commentary.

Recent publications and statements have drawn attention to a sustainable system of managing malaria control interventions globally but especially on the Continent of Africa. Arbitrary and unstable governments often interfere with health programmes, causing upsurges in malaria transmission as well as other health issues. A well-run health infrastructure will deal with public health as a whole. This commentary follows historical conditions in Zimbabwe where much original work on malaria control was initiated and implemented and where unstable conditions happened through local politics. These periodic conditions of instability on the ground challenge the current philosophical thrust to eradication and stress the need and role of an established and well-staffed health infrastructure in each country. Such facilities should be well staffed and supplied with drugs and point-of care diagnostic tests to manage malaria and should be sustained to serve the community even after tools that can eradicate malaria are developed.

Comparison of a PfHRP2-based rapid diagnostic test and PCR for malaria in a low prevalence setting in rural southern Zambia: implications for elimination.

BACKGROUND: Rapid diagnostic tests (RDTs) detecting histidine-rich protein 2 (PfHRP2) antigen are used to identify individuals with Plasmodium falciparum infection even in low transmission settings seeking to achieve elimination. However, these RDTs lack sensitivity to detect low-density infections, produce false negatives for P. falciparum strains lacking pfhrp2 gene and do not detect species other than P. falciparum. METHODS: Results of a PfHRP2-based RDT and Plasmodium nested PCR were compared in a region of declining malaria transmission in southern Zambia using samples from community-based, cross-sectional surveys from 2008 to 2012. Participants were tested with a PfHRP2-based RDT and a finger prick blood sample was spotted onto filter paper for PCR analysis and used to prepare blood smears for microscopy. Species-specific, real-time, quantitative PCR (q-PCR) was performed on samples that tested positive either by microscopy, RDT or nested PCR. RESULTS: Of 3,292 total participants enrolled, 12 (0.4%) tested positive by microscopy and 42 (1.3%) by RDT. Of 3,213 (98%) samples tested by nested PCR, 57 (1.8%) were positive, resulting in 87 participants positive by at least one of the three tests. Of these, 61 tested positive for P. falciparum by q-PCR with copy numbers ≤ 2 x 10(3) copies/µL, 5 were positive for both P. falciparum and Plasmodium malariae and 2 were positive for P. malariae alone. RDT detected 32 (53%) of P. falciparum positives, failing to detect three of the dual infections with P. malariae. Among 2,975 participants enrolled during a low transmission period between 2009 and 2012, sensitivity of the PfHRP2-based RDT compared to nested PCR was only 17%, with specificity of >99%. The pfhrp gene was detected in 80% of P. falciparum positives; however, comparison of copy number between RDT negative and RDT positive samples suggested that RDT negatives resulted from low parasitaemia and not pfhrp2 gene deletion. CONCLUSIONS: Low-density P. falciparum infections not identified by currently used PfHRP2-based RDTs and the inability to detect non-falciparum malaria will hinder progress to further reduce malaria in low transmission settings of Zambia. More sensitive and specific diagnostic tests will likely be necessary to identify parasite reservoirs and achieve malaria elimination.

Rapid diagnostic tests for malaria and health workers' adherence to test results at health facilities in Zambia.

BACKGROUND: In Zambia, there has been a large scaling up of interventions to control malaria in recent years including the deployment of rapid diagnostic tests (RDTs) to improve malaria surveillance data as well as guide malaria treatment in health facilities. The practical challenge is the impact of RDT results on subsequent management of patients. This study explored the role of RDTs in malaria diagnosis and the health workers' adherence to test results. METHODS: An observational prospective study was carried out at health centres in four districts, namely Chibombo, Chingola, Chipata, and Choma. Children under the age of five years with history of fever were recruited and the clinicians' use of RDT results was observed to establish whether prescriptions were issued prior to the availability of parasitological results or after, and whether RDT results influenced their prescriptions. RESULTS: Of the 2, 393 recruited children, 2, 264 had both RDT and microscopic results. Two in three (68.6%) children were treated with anti-malarials despite negative RDT results and almost half (46.2%) of these were prescribed Coartem®. Only 465 (19.4%) of the 2,393 children were prescribed drugs before receiving laboratory results. A total of 76.5% children were prescribed drugs after laboratory results. Children with RDT positive results were 2.66 (95% CI (2.00, 3.55)) times more likely to be prescribed anti-malarial drugs. Children who presented with fever at admission (although history of fever or presence of fever at admission was an entry criterion) were 42% less likely to be prescribed an anti-malarial drug compared to children who had no fever (AOR = 0.58; 95% CI (0.52, 0.65)). It was noted that proportions of children who were RDT- and microscopy-positive significantly declined over the years from 2005 to 2008. CONCLUSIONS: RDTs may contribute to treatment of febrile illness by confirming malaria cases from non-malaria cases in children under the age of five. However, the adherence of the health workers to prescribing anti-malarials to only RDT-positive cases at health facility level will still require to be explored further as their role is crucial in more precise reporting of malaria cases in this era towards malaria elimination as the target.

Evaluating local vegetation cover as a risk factor for malaria transmission: a new analytical approach using ImageJ.

BACKGROUND: In places where malaria transmission is unstable or is transmitted under hypoendemic conditions, there are periods where limited foci of cases still occur and people become infected. These residual "hot spots" are likely reservoirs of the parasite population and so are fundamental to the seasonal spread and decline of malaria. It is, therefore, important to understand the ecological conditions that permit vector mosquitoes to survive and forage in these specific areas. Features such as local waterways and vegetation, as well as local ecology, particularly nocturnal temperature, humidity, and vegetative sustainability, are important for modeling local mosquito behavior. Vegetation around a homestead likely provides refuge for outdoor resting of these insects and may be a risk factor for malaria transmission. Analysis of this vegetation can be done using satellite information and mapping programs, such as Google Earth, but manual quantification is difficult and can be tedious and subjective. A more objective method is required. METHODS: Vegetation cover in the environment is reasonably static, particularly in and around homesteads. In order to evaluate and enumerate such information, ImageJ, an image processing software, was used to analyse Google Earth satellite imagery. The number of plants, total amount of vegetation around a homestead and its percentage of the total area were calculated and related to homesteads where cases of malaria were recorded. RESULTS: Preliminary results were obtained from a series of field trials carried out in South East Zambia in the Choma and Namwala districts from a base at the Macha District Hospital. CONCLUSIONS: This technique is objective, clear and simple to manipulate and has potential application to determine the role that vegetation proximal to houses may play in affecting mosquito behaviour, foraging and subsequent malaria incidence.

Remotely-sensed, nocturnal, dew point correlates with malaria transmission in Southern Province, Zambia: a time-series study.

BACKGROUND: Plasmodium falciparum transmission has decreased significantly in Zambia in the last decade. The malaria transmission is influenced by environmental variables. Incorporation of environmental variables in models of malaria transmission likely improves model fit and predicts probable trends in malaria disease. This work is based on the hypothesis that remotely-sensed environmental factors, including nocturnal dew point, are associated with malaria transmission and sustain foci of transmission during the low transmission season in the Southern Province of Zambia. METHODS: Thirty-eight rural health centres in Southern Province, Zambia were divided into three zones based on transmission patterns. Correlations between weekly malaria cases and remotely-sensed nocturnal dew point, nocturnal land surface temperature as well as vegetation indices and rainfall were evaluated in time-series analyses from 2012 week 19 to 2013 week 36. Zonal as well as clinic-based, multivariate, autoregressive, integrated, moving average (ARIMAX) models implementing environmental variables were developed to model transmission in 2011 week 19 to 2012 week 18 and forecast transmission in 2013 week 37 to week 41. RESULTS: During the dry, low transmission season significantly higher vegetation indices, nocturnal land surface temperature and nocturnal dew point were associated with the areas of higher transmission. Environmental variables improved ARIMAX models. Dew point and normalized differentiated vegetation index were significant predictors and improved all zonal transmission models. In the high-transmission zone, this was also seen for land surface temperature. Clinic models were improved by adding dew point and land surface temperature as well as normalized differentiated vegetation index. The mean average error of prediction for ARIMAX models ranged from 0.7 to 33.5%. Forecasts of malaria incidence were valid for three out of five rural health centres; however, with poor results at the zonal level. CONCLUSIONS: In this study, the fit of ARIMAX models improves when environmental variables are included. There is a significant association of remotely-sensed nocturnal dew point with malaria transmission. Interestingly, dew point might be one of the factors sustaining malaria transmission in areas of general aridity during the dry season.

Malaria antifolate resistance with contrasting Plasmodium falciparum dihydrofolate reductase (DHFR) polymorphisms in humans and Anopheles mosquitoes.

Surveillance for drug-resistant parasites in human blood is a major effort in malaria control. Here we report contrasting antifolate resistance polymorphisms in Plasmodium falciparum when parasites in human blood were compared with parasites in Anopheles vector mosquitoes from sleeping huts in rural Zambia. DNA encoding P. falciparum dihydrofolate reductase (EC 1.5.1.3) was amplified by PCR with allele-specific restriction enzyme digestions. Markedly prevalent pyrimethamine-resistant mutants were evident in human P. falciparum infections--S108N (>90%), with N51I, C59R, and 108N+51I+59R triple mutants (30-80%). This resistance level may be from selection pressure due to decades of sulfadoxine/pyrimethamine use in the region. In contrast, cycloguanil-resistant mutants were detected in very low frequency in parasites from human blood samples-S108T (13%), with A16V and 108T+16V double mutants (∼4%). Surprisingly, pyrimethamine-resistant mutants were of very low prevalence (2-12%) in the midguts of Anopheles arabiensis vector mosquitoes, but cycloguanil-resistant mutants were highly prevalent-S108T (90%), with A16V and the 108T+16V double mutant (49-57%). Structural analysis of the dihydrofolate reductase by in silico modeling revealed a key difference in the enzyme within the NADPH binding pocket, predicting the S108N enzyme to have reduced stability but the S108T enzyme to have increased stability. We conclude that P. falciparum can bear highly host-specific drug-resistant polymorphisms, most likely reflecting different selective pressures found in humans and mosquitoes. Thus, it may be useful to sample both human and mosquito vector infections to accurately ascertain the epidemiological status of drug-resistant alleles.

Measuring malaria by passive case detection: a new perspective based on Zambian experience.

Most measurements of malaria are based on cross-sectional data and do not reflect the dynamic nature of transmission, particularly when interventions require timely data for planning strategies. Such data can be collected from local rural health centres (RHCs) where the infrastructure is sufficiently developed and where rapid diagnostics are in use. Because in rural areas, the population served by RHC is reasonably static, the regular use of malaria rapid diagnosis in RHCs can provide data to assess local weekly incidence rates, and such data are easily dispersed by cell phones. Essentially each RHC is a potential sentinel site that can deliver critical information to programme planners. Data collected during this process of passive case detection over a five-year period in the Macha area of Zambia show the importance of ecological zones and refugia in the seasonal fluctuation of malaria cases. If this process is implemented nationally it can assist in planning efficient use of resources and may contribute to local management and even elimination of malaria in this region.

Malaria research challenges in low prevalence settings.

The prevalence of malaria has reduced significantly in some areas over the past decade. These reductions have made local elimination possible and the research agenda has shifted to this new priority. However, there are critical issues that arise when studying malaria in low transmission settings, particularly identifying asymptomatic infections, accurate detection of individuals with microparasitaemic infections, and achieving a sufficient sample size to have an adequately powered study. These challenges could adversely impact the study of malaria elimination if they remain unanswered.

Scientific Findings of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe.

For a decade, the Southern and Central Africa International Center of Excellence for Malaria Research has operated with local partners across study sites in Zambia and Zimbabwe that range from hypo- to holoendemic and vary ecologically and entomologically. The burden of malaria and the impact of control measures were assessed in longitudinal cohorts, cross-sectional surveys, passive and reactive case detection, and other observational designs that incorporated multidisciplinary scientific approaches: classical epidemiology, geospatial science, serosurveillance, parasite and mosquito genetics, and vector bionomics. Findings to date have helped elaborate the patterns and possible causes of sustained low-to-moderate transmission in southern Zambia and eastern Zimbabwe and recalcitrant high transmission and fatality in northern Zambia. Cryptic and novel mosquito vectors, asymptomatic parasite reservoirs in older children, residual parasitemia and gametocytemia after treatment, indoor residual spraying timed dyssynchronously to vector abundance, and stockouts of essential malaria commodities, all in the context of intractable rural poverty, appear to explain the persistent malaria burden despite current interventions. Ongoing studies of high-resolution transmission chains, parasite population structures, long-term malaria periodicity, and molecular entomology are further helping to lay new avenues for malaria control in southern and central Africa and similar settings.

Policy Implications of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe.

The International Centers of Excellence for Malaria Research (ICEMR) were established by the National Institute of Allergy and Infectious Diseases more than a decade ago to provide multidisciplinary research support to malaria control programs worldwide, operating in endemic areas and contributing technology, expertise, and ultimately policy guidance for malaria control and elimination. The Southern and Central Africa ICEMR has conducted research across three main sites in Zambia and Zimbabwe that differ in ecology, entomology, transmission intensity, and control strategies. Scientific findings led to new policies and action by the national malaria control programs and their partners in the selection of methods, materials, timing, and locations of case management and vector control. Malaria risk maps and predictive models of case detection furnished by the ICEMR informed malaria elimination programming in southern Zambia, and time series analyses of entomological and parasitological data motivated several major changes to indoor residual spray campaigns in northern Zambia. Along the Zimbabwe-Mozambique border, temporal and geospatial data are currently informing investigations into a recent resurgence of malaria. Other ICEMR findings pertaining to parasite and mosquito genetics, human behavior, and clinical epidemiology have similarly yielded immediate and long-term policy implications at each of the sites, often with generalizable conclusions. The ICEMR programs thereby provide rigorous scientific investigations and analyses to national control and elimination programs, without which the impediments to malaria control and their potential solutions would remain understudied.

Designing a sustainable strategy for malaria control?

Malaria in the 21st century is showing signs of declining over much of its distribution, including several countries in Africa where previously this was not thought to be feasible. Yet for the most part the strategies to attack the infection are similar to those of the 1950s. Three major Journals have recently drawn attention to the situation, stressing the importance of research, describing the successes and defining semantics related to control. But there is a need to stress the importance of local sustainability, and consider somewhat urgently how individual endemic countries can plan and implement the programmes that are currently financed, for the most part, by donor institutions. On an immediate basis research should be more focused on a data driven approach to control. This will entail new thinking on the role of local infrastructure and in training of local scientists in local universities in epidemiology and field malariology so that expanded control programmes can become operational. Donor agencies should encourage and facilitate development of career opportunities for such personnel so that local expertise is available to contribute appropriately.

Early detection of malaria foci for targeted interventions in endemic southern Zambia.

BACKGROUND: Zambia has achieved significant reductions in the burden of malaria through a strategy of "scaling-up" effective interventions. Progress toward ultimate malaria elimination will require sustained prevention coverage and further interruption of transmission through active strategies to identify and treat asymptomatic malaria reservoirs. A surveillance system in Zambia's Southern Province has begun to implement such an approach. An early detection system could be an additional tool to identify foci of elevated incidence for targeted intervention. METHODS: Based on surveillance data collected weekly from 13 rural health centres (RHCs) divided into three transmission zones, early warning thresholds were created following a technique successfully implemented in Thailand. Alert levels were graphed for all 52 weeks of a year using the mean and 95% confidence interval upper limit of a Poisson distribution of the weekly diagnosed malaria cases for every available week of historic data (beginning in Aug, 2008) at each of the sites within a zone. Annually adjusted population estimates for the RHC catchment areas served as person-time of weekly exposure. The zonal threshold levels were validated against the incidence data from each of the 13 respective RHCs. RESULTS: Graphed threshold levels for the three zones generally conformed to observed seasonal incidence patterns. Comparing thresholds with historic weekly incidence values, the overall percentage of aberrant weeks ranged from 1.7% in Mbabala to 36.1% in Kamwanu. For most RHCs, the percentage of weeks above threshold was greater during the high transmission season and during the 2009 year compared to 2010. 39% of weeks breaching alert levels were part of a series of three or more consecutive aberrant weeks. CONCLUSIONS: The inconsistent sensitivity of the zonal threshold levels impugns the reliability of the alert system. With more years of surveillance data available, individual thresholds for each RHC could be calculated and compared to the technique outlined here. Until then, "aberrant" weeks during low transmission seasons, and during high transmission seasons at sites where the threshold level is less sensitive, could feasibly be followed up for household screening. Communities with disproportionate numbers of aberrant weeks could be reviewed for defaults in the scaling-up intervention coverage.

Latent Class Analysis: Insights about design and analysis of schistosomiasis diagnostic studies.

Various global health initiatives are currently advocating the elimination of schistosomiasis within the next decade. Schistosomiasis is a highly debilitating tropical infectious disease with severe burden of morbidity and thus operational research accurately evaluating diagnostics that quantify the epidemic status for guiding effective strategies is essential. Latent class models (LCMs) have been generally considered in epidemiology and in particular in recent schistosomiasis diagnostic studies as a flexible tool for evaluating diagnostics because assessing the true infection status (via a gold standard) is not possible. However, within the biostatistics literature, classical LCM have already been criticised for real-life problems under violation of the conditional independence (CI) assumption and when applied to a small number of diagnostics (i.e. most often 3-5 diagnostic tests). Solutions of relaxing the CI assumption and accounting for zero-inflation, as well as collecting partial gold standard information, have been proposed, offering the potential for more robust model estimates. In the current article, we examined such approaches in the context of schistosomiasis via analysis of two real datasets and extensive simulation studies. Our main conclusions highlighted poor model fit in low prevalence settings and the necessity of collecting partial gold standard information in such settings in order to improve the accuracy and reduce bias of sensitivity and specificity estimates.

Rural health centres, communities and malaria case detection in Zambia using mobile telephones: a means to detect potential reservoirs of infection in unstable transmission conditions.

BACKGROUND: Effective malaria control depends on timely acquisition of information on new cases, their location and their frequency so as to deploy supplies, plan interventions or focus attention on specific locations appropriately to intervene and prevent an upsurge in transmission. The process is known as active case detection, but because the information is time sensitive, it is difficult to carry out. In Zambia, the rural health services are operating effectively and for the most part are provided with adequate supplies of rapid diagnostic tests (RDT) as well as effective drugs for the diagnosis and treatment of malaria. The tests are administered to all prior to treatment and appropriate records are kept. Data are obtained in a timely manner and distribution of this information is important for the effective management of malaria control operations. The work reported here involves combining the process of positive diagnoses in rural health centres (passive case detection) to help detect potential outbreaks of malaria and target interventions to foci where parasite reservoirs are likely to occur. METHODS: Twelve rural health centres in the Choma and Namwala Districts were recruited to send weekly information of rapid malaria tests used and number of positive diagnoses to the Malaria Institute at Macha using mobile telephone SMS. Data were entered in excel, expressed as number of cases per rural health centre and distributed weekly to interested parties. RESULTS: These data from each of the health centres which were mapped using geographical positioning system (GPS) coordinates were used in a time sensitive manner to plot the patterns of malaria case detection in the vicinity of each location. The data were passed on to the appropriate authorities. The seasonal pattern of malaria transmission associated with local ecological conditions can be seen in the distribution of cases diagnosed. CONCLUSIONS: Adequate supplies of RDT are essential in health centres and the system can be expanded throughout the country to support strategic targeting of interventions by the National Malaria Control Programme. Participation by the health centre staff was excellent.

A method of active case detection to target reservoirs of asymptomatic malaria and gametocyte carriers in a rural area in Southern Province, Zambia.

BACKGROUND: Asymptomatic reservoirs of malaria parasites are common yet are difficult to detect, posing a problem for malaria control. If control programmes focus on mosquito control and treatment of symptomatic individuals only, malaria can quickly resurge if interventions are scaled back. Foci of parasite populations must be identified and treated. Therefore, an active case detection system that facilitates detection of asymptomatic parasitaemia and gametocyte carriers was developed and tested in the Macha region in southern Zambia. METHODS: Each week, nurses at participating rural health centres (RHC) communicated the number of rapid diagnostic test (RDT) positive malaria cases to a central research team. During the dry season when malaria transmission was lowest, the research team followed up each positive case reported by the RHC by a visit to the homestead. The coordinates of the location were obtained by GPS and all consenting residents completed a questionnaire and were screened for malaria using thick blood film, RDT, nested-PCR, and RT-PCR for asexual and sexual stage parasites. Persons who tested positive by RDT were treated with artemether/lumefantrine (Coartem). Data were compared with a community-based study of randomly selected households to assess the prevalence of asymptomatic parasitaemia in the same localities in September 2009. RESULTS: In total, 186 and 141 participants residing in 23 case and 24 control homesteads, respectively, were screened. In the case homesteads for which a control population was available (10 of the 23), household members of clinically diagnosed cases had a 8.0% prevalence of malaria using PCR compared to 0.7% PCR positive individuals in the control group (p = 0.006). The case and control groups had a gametocyte prevalence of 2.3% and 0%, respectively but the difference was not significant (p = 0.145). CONCLUSIONS: This pilot project showed that active case detection is feasible and can identify reservoirs of asymptomatic infection. A larger sample size, data over multiple low transmission seasons, and in areas with different transmission dynamics are needed to further validate this approach.

Identifying malaria vector breeding habitats with remote sensing data and terrain-based landscape indices in Zambia.

BACKGROUND: Malaria, caused by the parasite Plasmodium falciparum, is a significant source of morbidity and mortality in southern Zambia. In the Mapanza Chiefdom, where transmission is seasonal, Anopheles arabiensis is the dominant malaria vector. The ability to predict larval habitats can help focus control measures. METHODS: A survey was conducted in March-April 2007, at the end of the rainy season, to identify and map locations of water pooling and the occurrence anopheline larval habitats; this was repeated in October 2007 at the end of the dry season and in March-April 2008 during the next rainy season. Logistic regression and generalized linear mixed modeling were applied to assess the predictive value of terrain-based landscape indices along with LandSat imagery to identify aquatic habitats and, especially, those with anopheline mosquito larvae. RESULTS: Approximately two hundred aquatic habitat sites were identified with 69 percent positive for anopheline mosquitoes. Nine species of anopheline mosquitoes were identified, of which, 19% were An. arabiensis. Terrain-based landscape indices combined with LandSat predicted sites with water, sites with anopheline mosquitoes and sites specifically with An. arabiensis. These models were especially successful at ruling out potential locations, but had limited ability in predicting which anopheline species inhabited aquatic sites. Terrain indices derived from 90 meter Shuttle Radar Topography Mission (SRTM) digital elevation data (DEM) were better at predicting water drainage patterns and characterizing the landscape than those derived from 30 m Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) DEM. CONCLUSIONS: The low number of aquatic habitats available and the ability to locate the limited number of aquatic habitat locations for surveillance, especially those containing anopheline larvae, suggest that larval control maybe a cost-effective control measure in the fight against malaria in Zambia and other regions with seasonal transmission. This work shows that, in areas of seasonal malaria transmission, incorporating terrain-based landscape models to the planning stages of vector control allows for the exclusion of significant portions of landscape that would be unsuitable for water to accumulate and for mosquito larvae occupation. With increasing free availability of satellite imagery such as SRTM and LandSat, the development of satellite imagery-based prediction models is becoming more accessible to vector management coordinators.

Diagnostic urinary cfDNA detected in human cystic echinococcosis.

Cystic echinococcosis (CE) is a major neglected tropical zoonotic disease caused by the tissue-dwelling larval stage of the cestode parasite Echinococcus granulosus. For individuals suspected of CE, the diagnostic standard is imaging using ultrasonography, X rays, or computed tomography. These resource-demanding and expensive procedures are rarely available in endemic rural areas where CE is most prevalent. There is a critical need for a new approach to identify CE patients so that they can be managed early in the course of their infection. This study reports on the results of a diagnostic approach that identifies E. granulosus-derived cell-free DNA (cfDNA) in the urine of CE patients. Utilizing PCR to amplify a fragment of a major tandem repeat element found in E. granulosus nuclear DNA, urine samples from all seven imaging-confirmed CE patients who harbored active liver cysts were positive. In addition, the urine samples from 2/4 patients who presented with non-viable/calcified liver cysts were also PCR positive for the repeat fragment. To our knowledge, this is the first report of using parasite cfDNA from urine to diagnose CE. This approach provides an easy to implement and cost-effective method to survey for the prevalence of E. granulosus in humans populations.

Plasmodium yoelii: adverse outcome of non-lethal P. yoelii malaria during co-infection with Schistosoma mansoni in BALB/c mouse model.

Plasmodium yoelii and Schistosoma mansoni co-infections were studied in female BALB/c mice aged 4-6 weeks to determine the effect of time and stage of concomitant infections on malaria disease outcome. Patent S. mansoni infection in BALB/c mice increased malaria peak parasitemia and caused death from an otherwise non-lethal, self-resolving P. yoelii malaria infection. Exacerbation of malaria parasitemia occurred during both pre-patent and patent S. mansoni infection resulting in a delay of 4-8 days in malaria parasite resolution in co-infected mice. Praziquantel administered to mice with patent schistosome infection protected from fatal outcome during co-infection. However, this treatment did not completely clear the worm infestation, nor did it reduce the peak malaria parasitemia reached, which was nonetheless resolved completely. Hepatosplenomegaly was more marked in schistosome and malaria co-infected mice compared to either infection separately. The results suggest a complex relationship between schistosome co-infection and malaria disease outcome in which the timing of malaria infection in relation to schistosome acquisition is critical to disease outcome and pathology.

Detection of Taenia solium DNA in the Urine of Neurocysticercosis Patients.

Neurocysticercosis (NCC), caused by Taenia solium larvae that reside in the central nervous system, results in serious public health and medical issues in many regions of the world. Current diagnosis of NCC is complex requiring both serology and costly neuroimaging of parasitic cysts in the brain. This diagnostic pipeline can be problematic in resource-constrained settings. There is an unmet need for a highly sensitive and clinically informative diagnostic test to complement the present diagnostic approaches. Here, we report that T. solium-derived cell-free DNA is readily detectable in the urine of patients with the subarachnoid and parenchymal forms of NCC, and discuss the potential utility of this approach in enhancing and refining T. solium diagnostics.