Predicting malaria outbreaks from sea surface temperature variability up to 9 months ahead in Limpopo, South Africa, using machine learning.

Malaria is the cause of nearly half a million deaths worldwide each year, posing a great socioeconomic burden. Despite recent progress in understanding the influence of climate on malaria infection rates, climatic sources of predictability remain poorly understood and underexploited. Local weather variability alone provides predictive power at short lead times of 1-2 months, too short to adequately plan intervention measures. Here, we show that tropical climatic variability and associated sea surface temperature over the Pacific and Indian Oceans are valuable for predicting malaria in Limpopo, South Africa, up to three seasons ahead. Climatic precursors of malaria outbreaks are first identified via lag-regression analysis of climate data obtained from reanalysis and observational datasets with respect to the monthly malaria case count data provided from 1998-2020 by the Malaria Institute in Tzaneen, South Africa. Out of 11 sea surface temperature sectors analyzed, two regions, the Indian Ocean and western Pacific Ocean regions, emerge as the most robust precursors. The predictive value of these precursors is demonstrated by training a suite of machine-learning classification models to predict whether malaria case counts are above or below the median historical levels and assessing their skills in providing early warning predictions of malaria incidence with lead times ranging from 1 month to a year. Through the development of this prediction system, we find that past information about SST over the western Pacific Ocean offers impressive prediction skills (~80% accuracy) for up to three seasons (9 months) ahead. SST variability over the tropical Indian Ocean is also found to provide good skills up to two seasons (6 months) ahead. This outcome represents an extension of the effective prediction lead time by about one to two seasons compared to previous prediction systems that were more computationally costly compared to the machine learning techniques used in the current study. It also demonstrates the value of climatic information and the prediction framework developed herein for the early planning of interventions against malaria outbreaks.

Publisher Correction: Malaria predictions based on seasonal climate forecasts in South Africa: A time series distributed lag nonlinear model.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Aberrations and accommodation.

Modern methods of measuring the refractive state of the eye include wavefront sensors which make it possible to monitor both static and dynamic changes of the ocular wavefront while the eye observes a target positioned at different distances away from the eye. In addition to monitoring the ocular aberrations, wavefront refraction methods allow measurement of the accommodative response while viewing with the eye's habitual chromatic and monochromatic aberrations present, with these aberrations removed, and with specific aberrations added or removed. A large number of experiments describing the effects of accommodation on aberrations and vice versa are reviewed, pointing out the implications for fundamental questions related to the mechanism of accommodation.

Malaria predictions based on seasonal climate forecasts in South Africa: A time series distributed lag nonlinear model.

Although there have been enormous demands and efforts to develop an early warning system for malaria, no sustainable system has remained. Well-organized malaria surveillance and high-quality climate forecasts are required to sustain a malaria early warning system in conjunction with an effective malaria prediction model. We aimed to develop a weather-based malaria prediction model using a weekly time-series data including temperature, precipitation, and malaria cases from 1998 to 2015 in Vhembe, Limpopo, South Africa and apply it to seasonal climate forecasts. The malaria prediction model performed well for short-term predictions (correlation coefficient, r > 0.8 for 1- and 2-week ahead forecasts). The prediction accuracy decreased as the lead time increased but retained fairly good performance (r > 0.7) up to the 16-week ahead prediction. The demonstration of the malaria prediction process based on the seasonal climate forecasts showed the short-term predictions coincided closely with the observed malaria cases. The weather-based malaria prediction model we developed could be applicable in practice together with skillful seasonal climate forecasts and existing malaria surveillance data. Establishing an automated operating system based on real-time data inputs will be beneficial for the malaria early warning system, and can be an instructive example for other malaria-endemic areas.

Effect of phenylephrine on static and dynamic accommodation / Efecto de la fenilefrina sobre la acomodación estática y dinámica

Purpose: We tested the hypothesis that changes in accommodation after instillation of Phenylephrine Hydrochloride (PHCl) observed in some studies could be caused by changes in optics. Methods: We performed two experiments to test the effects of PHCl on static and on dynamic accommodation in 8 and 6 subjects, respectively. Objective wavefront measurements were recorded of the static accommodation response to a stimulus at different distances or dynamic accommodation response to a sinusoidally moving stimulus (between 1 and 3 D of accommodative demand at 0.2 Hz). The responses were characterized using two methods: one that takes into account the mydriatic optical effects on the accommodation produced by higher-order aberrations of the eye and another that takes into account only power changes paraxially due to the action of the ciliary muscle and regardless of the pupil size. Results: When mydriatic optical effects were taken into account, differences in responses before and after PHCl instillation were 0.51 ± 0.53 D, and 0.12 ± 0.15, for static and dynamic accommodation, respectively, and were statistically significant (p < 0.039). When mydriatic optical effects were not taken into account, the differences in responses before and after PHCl instillation were -0.20 ± 0.51 D, and -0.05 ± 0.14, for static and dynamic accommodation, respectively, and were not statistically significant (p > 0.313). Conclusions: The mydriatic effect of the PHCl causes optical changes in the eye that can reduce the objective and subjective measurement of accommodation

Objetivo: Probamos la hipótesis de que los cambios de la acomodación tras la instilación de Hidrocloruro de Fenilefrina (PHCl) observados en algunos estudios podrían estar originados por los cambios en la óptica. Métodos: Realizamos dos experimentos para probar los efectos de PHCl sobre la acomodación estática y dinámica en 8 y 6 sujetos, respectivamente. Se registraron las mediciones objetivas de frente de onda de la respuesta acomodativa estática a un estímulo a diferentes distancias, o la respuesta acomodativa dinámica a un estímulo con movimiento sinusoidal (entre 1 y 3 D de demanda acomodativa a 0,2Hz). Las respuestas se caracterizaron utilizando dos métodos: uno que tiene en cuenta los efectos ópticos midriáticos sobre la acomodación producida por aberraciones de alto orden, y otro que considera únicamente los cambios de potencia paraxialmente, debido a la acción del músculo ciliar, independientemente del tamaño de la pupila. Resultados: Al tenerse en cuenta los efectos ópticos midriáticos, las diferencias de las respuestas antes y después de la instilación de PHCl fueron de 0,51 ± 0,53 D, y 0,12 ± 0,15, para la acomodación estática y dinámica, respectivamente, siendo estadísticamente significativas (p < 0,039). Al no considerarse los efectos ópticos midriáticos, las diferencias en cuanto a las respuestas antes y después de la instilación de PHCl fueron de -0,2 ± 0,51 D, y -0,05 ± 0,14, para la acomodación estática y dinámica, respectivamente, no siendo estadísticamente significativas (p > 0,313). Conclusiones: El efecto midriático de PHCl origina cambios ópticos en el ojo que pueden reducir la medición objetiva y subjetiva de la acomodación

Effect of phenylephrine on static and dynamic accommodation.

PURPOSE: We tested the hypothesis that changes in accommodation after instillation of Phenylephrine Hydrochloride (PHCl) observed in some studies could be caused by changes in optics. METHODS: We performed two experiments to test the effects of PHCl on static and on dynamic accommodation in 8 and 6 subjects, respectively. Objective wavefront measurements were recorded of the static accommodation response to a stimulus at different distances or dynamic accommodation response to a sinusoidally moving stimulus (between 1 and 3 D of accommodative demand at 0.2Hz). The responses were characterized using two methods: one that takes into account the mydriatic optical effects on the accommodation produced by higher-order aberrations of the eye and another that takes into account only power changes paraxially due to the action of the ciliary muscle and regardless of the pupil size. RESULTS: When mydriatic optical effects were taken into account, differences in responses before and after PHCl instillation were 0.51±0.53 D, and 0.12±0.15, for static and dynamic accommodation, respectively, and were statistically significant (p<0.039). When mydriatic optical effects were not taken into account, the differences in responses before and after PHCl instillation were -0.20±0.51 D, and -0.05±0.14, for static and dynamic accommodation, respectively, and were not statistically significant (p>0.313). CONCLUSIONS: The mydriatic effect of the PHCl causes optical changes in the eye that can reduce the objective and subjective measurement of accommodation.

Understanding human genetic factors influencing primaquine safety and efficacy to guide primaquine roll-out in a pre-elimination setting in southern Africa.

BACKGROUND: Primaquine (PQ) is recommended as an addition to standard malaria treatments in pre-elimination settings due to its pronounced activity against mature Plasmodium falciparum gametocytes, the parasite stage responsible for onward transmission to mosquitoes. However, PQ may trigger haemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. Additional human genetic factors, including polymorphisms in the human cytochrome P450 2D6 (CYP2D6) complex, may negatively influence the efficacy of PQ. This study assessed the prevalence of G6PD deficiency and two important CYP2D6 variants in representative pre-elimination settings in South Africa, to inform malaria elimination strategies. METHODS: Volunteers (n = 248) attending six primary health care facilities in a malaria-endemic region of South Africa were enrolled between October and November 2015. G6PD status was determined phenotypically, using a CareStart™ G6PD rapid diagnostic test (RDT), and genotypically for two common African G6PD variants, namely A+ (A376G) and A- (G202A, A542T, G680T & T968C) by PCR, restriction fragment length polymorphisms (RFLP) and DNA sequencing. CYP2D6*4 and CYP2D6*17 variants were determined with PCR and RFLP. RESULTS: A prevalence of 13% (33/248) G6PD deficiency was observed in the cohort by G6PD RDT whilst by genotypic assessment, 32% (79/248) were A+ and 3.2% were A-, respectively. Among the male participants, 11% (6/55) were G6PD A- hemizygous; among females 1% (2/193) were G6PD A- homozygous and 16% (32/193) G6PD A- heterozygous. The strength of agreement between phenotyping and genotyping result was fair (Cohens Kappa κ = 0.310). The negative predictive value for the G6PD RDT for detecting hemizygous, homozygous and heterozygous individuals was 0.88 (95% CI 0.85-0.91), compared to the more sensitive genotyping. The CYP2D6*4 allele frequencies for CYP2D6*4 (inferred poor metabolizer phenotype) and CYP2D6*17 (inferred intermediate metabolizer phenotype) were 3.2 and 19.5%, respectively. CONCLUSIONS: Phenotypic and genotypic analyses both detected low prevalence of G6PD deficiency and the CYP2D6*4 variants. These findings, combined with increasing data confirming safety of single low-dose PQ in individuals with African variants of G6PD deficiency, supports the deployment of single low-dose PQ as a gametocytocidal drug. PQ would pose minimal risks to the study populations and could be a useful elimination strategy in the study area.

Human eyes do not need monochromatic aberrations for dynamic accommodation.

PURPOSE: To determine if human accommodation uses the eye's own monochromatic aberrations to track dynamic accommodative stimuli. METHODS: Wavefront aberrations were measured while subjects monocularly viewed a monochromatic Maltese cross moving sinusoidally around 2D of accommodative demand with 1D amplitude at 0.2 Hz. The amplitude and phase (delay) of the accommodation response were compared to the actual vergence of the stimulus to obtain gain and temporal phase, calculated from wavefront aberrations recorded over time during experimental trials. The tested conditions were as follows: Correction of all the subject's aberrations except defocus (C); Correction of all the subject's aberrations except defocus and habitual second-order astigmatism (AS); Correction of all the subject's aberrations except defocus and odd higher-order aberrations (HOAs); Correction of all the subject's aberrations except defocus and even HOAs (E); Natural aberrations of the subject's eye, i.e., the adaptive-optics system only corrected the optical system's aberrations (N); Correction of all the subject's aberrations except defocus and fourth-order spherical aberration (SA). The correction was performed at 20 Hz and each condition was repeated six times in randomised order. RESULTS: Average gain (±2 standard errors of the mean) varied little across conditions; between 0.55 ± 0.06 (SA), and 0.62 ± 0.06 (AS). Average phase (±2 standard errors of the mean) also varied little; between 0.41 ± 0.02 s (E), and 0.47 ± 0.02 s (O). After Bonferroni correction, no statistically significant differences in gain or phase were found in the presence of specific monochromatic aberrations or in their absence. CONCLUSIONS: These results show that the eye's monochromatic aberrations are not necessary for accommodation to track dynamic accommodative stimuli.

Dynamic accommodation without feedback does not respond to isolated blur cues.

The aim of this study was to determine whether dynamic accommodation responds to isolated blur cues without feedback, and without changes in the distance of the object. Nine healthy subjects aged 21-40years were recruited. Four different aberration patterns were used as stimuli to induce blur with (1) the eye's natural, uncorrected, optical aberrations, (2) all aberrations corrected, (3) spherical aberration only, or (4) astigmatism only. The stimulus was a video animation based on computer-generated images of a monochromatic Maltese cross. Each individual video was generated for each subject off-line, after measuring individual aberrations at different accommodation levels. The video simulated sinusoidal changes in defocus at 0.2Hz. Dynamic images were observed through a 0.8mm pinhole placed at a plane conjugated with the eye's pupil, thus effectively removing potential feedback stemming from accommodation changes. Accommodation responses were measured with a Hartmann-Shack aberrometer for the four different aberration patterns. The results showed that seven out of nine subjects did not respond to any stimuli, whereas the response of the other two subjects was erratic and they seemed to be searching rather than following the stimulus. A significant reduction in average accommodative gain (from 0.52 to 0.11) was obtained when the dioptric demand cue was removed. No statistically significant differences were found among the experimental conditions used. We conclude that aberration related blur does not drive the accommodation response in the absence of feedback from accommodation.

Seasonally lagged effects of climatic factors on malaria incidence in South Africa.

Globally, malaria cases have drastically dropped in recent years. However, a high incidence of malaria remains in some sub-Saharan African countries. South Africa is mostly malaria-free, but northeastern provinces continue to experience seasonal outbreaks. Here we investigate the association between malaria incidence and spatio-temporal climate variations in Limpopo. First, dominant spatial patterns in malaria incidence anomalies were identified using self-organizing maps. Composite analysis found significant associations among incidence anomalies and climate patterns. A high incidence of malaria during the pre-peak season (Sep-Nov) was associated with the climate phenomenon La Niña and cool air temperatures over southern Africa. There was also high precipitation over neighbouring countries two to six months prior to malaria incidence. During the peak season (Dec-Feb), high incidence was associated with positive phase of Indian Ocean Subtropical Dipole. Warm temperatures and high precipitation in neighbouring countries were also observed two months prior to increased malaria incidence. This lagged association between regional climate and malaria incidence suggests that in areas at high risk for malaria, such as Limpopo, management plans should consider not only local climate patterns but those of neighbouring countries as well. These findings highlight the need to strengthen cross-border control of malaria to minimize its spread.

Accommodation Responds to Optical Vergence and Not Defocus Blur Alone.

Purpose: To determine whether changes in wavefront spherical curvature (optical vergence) are a directional cue for accommodation. Methods: Nine subjects participated in this experiment. The accommodation response to a monochromatic target was measured continuously with a custom-made adaptive optics system while astigmatism and higher-order aberrations were corrected in real time. There were two experimental open-loop conditions: vergence-driven condition, where the deformable mirror provided sinusoidal changes in defocus at the retina between -1 and +1 diopters (D) at 0.2 Hz; and blur-driven condition, in which the level of defocus at the retina was always 0 D, but a sinusoidal defocus blur between -1 and +1 D at 0.2 Hz was simulated in the target. Right before the beginning of each trial, the target was moved to an accommodative demand of 2 D. Results: Eight out of nine subjects showed sinusoidal responses for the vergence-driven condition but not for the blur-driven condition. Their average (±SD) gain for the vergence-driven condition was 0.50 (±0.28). For the blur-driven condition, average gain was much smaller at 0.07 (±0.03). The ninth subject showed little to no response for both conditions, with average gain <0.08. Vergence-driven condition gain was significantly different from blur-driven condition gain (P = 0.004). Conclusions: Accommodation responds to optical vergence, even without feedback, and not to changes in defocus blur alone. These results suggest the presence of a retinal mechanism that provides a directional cue for accommodation from optical vergence.

Serology reveals heterogeneity of Plasmodium falciparum transmission in northeastern South Africa: implications for malaria elimination.

BACKGROUND: It is widely acknowledged that modifications to existing control interventions are required if South Africa is to achieve malaria elimination. Targeting indoor residual spraying (IRS) to areas where cases have been detected is one strategy currently under investigation in northeastern South Africa. This seroprevalence baseline study, nested within a targeted IRS trial, was undertaken to provide insights into malaria transmission dynamics in South Africa and evaluate whether sero-epidemiological practices have the potential to be routinely incorporated into elimination programmes. METHODS: Filter-paper blood spots, demographic and household survey data were collected from 2710 randomly selected households in 56 study wards located in the municipalities of Ba-Phalaborwa and Bushbuckridge. Blood spots were assayed for Plasmodium falciparum apical membrane antigen-1 and merozoite surface protein-119 blood-stage antigens using an enzyme linked immunosorbent assay. Seroprevalence data were analysed using a reverse catalytic model to determine malaria seroconversion rates (SCR). Geospatial cluster analysis was used to investigate transmission heterogeneity while random effects logistic regression identified risk factors associated with malaria exposure. RESULTS: The overall SCR across the entire study site was 0.012 (95% CI 0.008-0.017) per year. Contrasting SCRs, corresponding to distinct geographical regions across the study site, ranging from <0.001 (95% CI <0.001-0.005) to 0.022 (95% CI 0.008-0.062) per annum revealed prominent transmission heterogeneity. Geospatial cluster analysis of household seroprevalence and age-adjusted antibody responses detected statistically significant (p < 0.05) spatial clusters of P. falciparum exposure. Formal secondary education was associated with lower malaria exposure in the sampled population (AOR 0.72, 95% CI 0.56-0.95, p = 0.018). CONCLUSIONS: Although overall transmission intensity and exposure to malaria was low across both study sites, malaria transmission intensity was highly heterogeneous and associated with low socio-economic status in the region. Findings suggest focal targeting of interventions has the potential to be an appropriate strategy to deploy in South Africa. Furthermore, routinely incorporating sero-epidemiological practices into elimination programmes may prove useful in monitoring malaria transmission intensity in South Africa, and other countries striving for malaria elimination.

Reviewing South Africa's malaria elimination strategy (2012-2018): progress, challenges and priorities.

BACKGROUND: With a sustained national malaria incidence of fewer than one case per 1000 population at risk, in 2012 South Africa officially transitioned from controlling malaria to the ambitious goal of eliminating malaria within its borders by 2018. This review assesses the progress made in the 3 years since programme re-orientation while highlighting challenges and suggesting priorities for moving the malaria programme towards elimination. METHODS: National malaria case data and annual spray coverage data from 2010 until 2014 were assessed for trends. Information on surveillance, monitoring and evaluation systems, human and infrastructure needs and community malaria knowledge was sourced from the national programme mid-term review. RESULTS: Malaria cases increased markedly from 6811 in 2013 to 11,711 in 2014, with Mpumalanga and Limpopo provinces most affected. Enhanced local transmission appeared to drive malaria transmission in Limpopo Province, while imported malaria cases accounted for the majority of cases reported in Mpumalanga Province. Despite these increases only Vhembe and Mopani districts in Limpopo Province reported malaria incidences more than one case per 1000 population at risk by 2014. Over the review period annual spray coverage did not reach the recommended target of 90 % coverage, with information gaps identified in parasite prevalence, artemether-lumefantrine therapeutic utilization, asymptomatic/sub-patent carriage, drug efficacy, vector distribution and insecticide resistance. CONCLUSIONS: Although South Africa has made steady progress since adopting an elimination agenda, a number of challenges have been identified. The heterogeneity of malaria transmission suggests interventions in Vhembe and Mopani districts should focus on control, while in KwaZulu-Natal Province eliminating transmission foci should be prioritized. Cross-border initiatives with neighbouring countries should be established/strengthened as a matter of urgency since malaria importation poses a real threat to the country's elimination efforts. It is also critical that provincial programmes are adequately resourced to effectively conduct the necessary targeted elimination activities, informed by current vector/parasite distribution and resistance data. More sensitive methods to detect sub-patent infections, primaquine as a transmission-blocking drug, and alternative vector control methods need to be investigated. Knowledge gaps among malaria health workers and affected communities should be identified and addressed.

mSpray: a mobile phone technology to improve malaria control efforts and monitor human exposure to malaria control pesticides in Limpopo, South Africa.

Recent estimates indicate that malaria has led to over half a million deaths worldwide, mostly to African children. Indoor residual spraying (IRS) of insecticides is one of the primary vector control interventions. However, current reporting systems do not obtain precise location of IRS events in relation to malaria cases, which poses challenges for effective and efficient malaria control. This information is also critical to avoid unnecessary human exposure to IRS insecticides. We developed and piloted a mobile-based application (mSpray) to collect comprehensive information on IRS spray events. We assessed the utility, acceptability and feasibility of using mSpray to gather improved homestead- and chemical-level IRS coverage data. We installed mSpray on 10 cell phones with data bundles, and pilot tested it with 13 users in Limpopo, South Africa. Users completed basic information (number of rooms/shelters sprayed; chemical used, etc.) on spray events. Upon submission, this information as well as geographic positioning system coordinates and time/date stamp were uploaded to a Google Drive Spreadsheet to be viewed in real time. We administered questionnaires, conducted focus groups, and interviewed key informants to evaluate the utility of the app. The low-cost, cell phone-based "mSpray" app was learned quickly by users, well accepted and preferred to the current paper-based method. We recorded 2865 entries (99.1% had a GPS accuracy of 20 m or less) and identified areas of improvement including increased battery life. We also identified a number of logistic and user problems (e.g., cost of cell phones and cellular bundles, battery life, obtaining accurate GPS measures, user errors, etc.) that would need to be overcome before full deployment. Use of cell phone technology could increase the efficiency of IRS malaria control efforts by mapping spray events in relation to malaria cases, resulting in more judicious use of chemicals that are potentially harmful to humans and the environment.

The feasibility of malaria elimination in South Africa.

BACKGROUND: Following the last major malaria epidemic in 2000, malaria incidence in South Africa has declined markedly. The decrease has been so emphatic that South Africa now meets the World Health Organization (WHO) threshold for malaria elimination. Given the Millennium Development Goal of reversing the spread of malaria by 2015, South Africa is being urged to adopt an elimination agenda. This study aimed to determine the appropriateness of implementing a malaria elimination programme in present day South Africa. METHODS: An assessment of the progress made by South Africa in terms of implementing an integrated malaria control programme across the three malaria-endemic provinces was undertaken. Vector control and case management data were analysed from the period of 2000 until 2011. RESULTS: Both malaria-related morbidity and mortality have decreased significantly across all three malaria-endemic provinces since 2000. The greatest decline was seen in KwaZulu-Natal where cases decreased from 42,276 in 2000 to 380 in 2010 and deaths dropped from 122 in 2000 to six in 2010. Although there has been a 49.2 % (8,553 vs 4,214) decrease in the malaria cases reported in Limpopo Province, currently it is the largest contributor to the malaria incidence in South Africa. Despite all three provinces reporting average insecticide spray coverage of over 80%, malaria incidence in both Mpumalanga and Limpopo remains above the elimination threshold. Locally transmitted case numbers have declined in all three malaria provinces but imported case numbers have been increasing. Knowledge gaps in vector distribution, insecticide resistance status and drug usage were also identified. CONCLUSIONS: Malaria elimination in South Africa is a realistic possibility if certain criteria are met. Firstly, there must be continued support for the existing malaria control programmes to ensure the gains made are sustained. Secondly, cross border malaria control initiatives with neighbouring countries must be strongly encouraged and supported to reduce malaria in the region and the importation of malaria into South Africa. Thirdly, operational research, particularly on vector distribution and insecticide resistance status must be conducted as a matter of urgency, and finally, the surveillance systems must be refined to ensure the information required to inform an elimination agenda are routinely collected.

Malaria control in South Africa 2000-2010: beyond MDG6.

BACKGROUND: Malaria is one of the key targets within Goal 6 of the Millennium Development Goals (MDGs), whereby the disease needs to be halted and reversed by the year 2015. Several other international targets have been set, however the MDGs are universally accepted, hence it is the focus of this manuscript. METHODS: An assessment was undertaken to determine the progress South Africa has made against the malaria target of MDG Goal 6. Data were analyzed for the period 2000 until 2010 and verified after municipal boundary changes in some of South Africa's districts and subsequent to verifying actual residence of malaria positive cases. RESULTS: South Africa has made significant progress in controlling malaria transmission over the past decade; malaria cases declined by 89.41% (63663 in 2000 vs 6741 in 2010) and deaths decreased by 85.4% (453 vs 66) in the year 2000 compared to the year 2010. Coupled with this, malaria cases among children under five years of age have also declined by 93% (6791 in 2000 vs 451 in 2010). This has resulted in South Africa achieving and exceeding the malaria target of the MDGs. A series of interventions have attributed to this decrease, these include: drug policy change from monotherapy to artemisinin combination therapy, insecticide change from pyrethroids back to DDT; cross border collaboration (South Africa with Mozambique and Swaziland through the Lubombo Spatial Development Initiative- LSDI) and financial investment in malaria control. The KwaZulu-Natal Province has seen the largest reduction in malaria cases and deaths (99.1% cases- 41786 vs 380; and 98.5% deaths 340 vs 5), when comparing the year 2000 with 2010. The Limpopo Province recorded the lowest reduction in malaria cases compared to the other malaria endemic provinces (56.1% reduction- 9487 vs 4174; when comparing 2000 to 2010). CONCLUSIONS: South Africa is well positioned to move beyond the malaria target of the MDGs and progress towards elimination. However, in addition to its existing interventions, the country will need to sustain its financing for malaria control and support programmed reorientation towards elimination and scale up active surveillance coupled with treatment at the community level. Moreover cross-border malaria collaboration needs to be sustained and scaled up to prevent the re-introduction of malaria into the country.

Accommodation to wavefront vergence and chromatic aberration.

PURPOSE: Longitudinal chromatic aberration (LCA) provides a cue to accommodation with small pupils. However, large pupils increase monochromatic aberrations, which may obscure chromatic blur. In this study, we examined the effect of pupil size and LCA on accommodation. METHODS: Accommodation was recorded by infrared optometer while observers (nine normal trichromats) viewed a sinusoidally moving Maltese cross target in a Badal stimulus system. There were two illumination conditions: white (3000 K; 20 cd/m) and monochromatic (550 nm with 10 nm bandwidth; 20 cd/m) and two artificial pupil conditions (3 and 5.7 mm). Separately, static measurements of wavefront aberration were made with the eye accommodating to targets between 0 and 4 D (COAS, Wavefront Sciences). RESULTS: Large individual differences in accommodation to wavefront vergence and to LCA are a hallmark of accommodation. LCA continues to provide a signal at large pupil sizes despite higher levels of monochromatic aberrations. CONCLUSIONS: Monochromatic aberrations may defend against chromatic blur at high spatial frequencies, but accommodation responds best to optical vergence and to LCA at 3 c/deg where blur from higher order aberrations is less.

Dynamic accommodation with simulated targets blurred with high order aberrations.

High order aberrations have been suggested to play a role in determining the direction of accommodation. We have explored the effect of retinal blur induced by high order aberrations on dynamic accommodation by measuring the accommodative response to sinusoidal variations in accommodative demand (1-3D). The targets were blurred with 0.3 and 1mum (for a 3-mm pupil) of defocus, coma, trefoil and spherical aberration. Accommodative gain decreased significantly when 1-mum of aberration was induced. We found a strong correlation between the relative accommodative gain (and phase lag) and the contrast degradation imposed on the target at relevant spatial frequencies.

Potential signal to accommodation from the Stiles-Crawford effect and ocular monochromatic aberrations.

The purpose of this study is to determine if cues within the blurred retinal image due to the Stiles-Crawford (SC) effect and the eye's monochromatic aberrations can drive accommodation with a small pupil (3 mm) that is typical of bright photopic conditions.The foveal, psychophysical SC function (17 min arc) and ocular monochromatic aberrations were measured in 21 visually normal adults. The retinal image of a 10.2 min arc disc was simulated for spherical defocus levels of -1 D, 0 D and +1 D in each of four conditions consisting of combinations of the presence or absence of the individual SC function and monochromatic aberrations with a 3 mm pupil. Accommodation was recorded in eleven participants as each viewed the simulations through a 0.75-mm pinhole.The SC effect alone did not provide a significant cue to accommodation. Monochromatic aberrations provided a statistically significant but rather small cue to monocular accommodation.