Modeling the effect of imported malaria on the elimination programme in KwaZulu-Natal province of South Africa.

Introduction: with imported malaria cases in a given population, the question arises as to what extent the local cases are a consequence of the imports or not. We perform a modeling analysis for a specific area, in a region aspiring for malaria-free status. Methods: data on malaria cases over ten years is subjected to a compartmental model which is assumed to be operating close to the equilibrium state. Two of the parameters of the model are fitted to the decadal data. The other parameters in the model are sourced from the literature. The model is utilized to simulate the malaria prevalence with or without imported cases. Results: in any given year the annual average of 460 imported cases, resulted in an end-of-year season malaria prevalence of 257 local active infectious cases, whereas without the imports the malaria prevalence at the end of the season would have been fewer than 10 active infectious cases. We calculate the numerical value of the basic reproduction number for the model, which reveals the extent to which the disease is being eliminated from the population or not. Conclusion: without the imported cases, over the ten seasons of malaria, 2008-2018, the KwaZulu-Natal province would have been malaria-free over at least the last 7 years of the decade indicated. This simple methodology works well even in situations where data is limited.

Field evaluation of the residual efficacy of new generation insecticides for potential use in indoor residual spray programmes in South Africa.

BACKGROUND: The decreasing residual efficacy of insecticides is an important factor when making decisions on insecticide choice for national malaria control programmes. The major challenge to using chemicals for vector control is the selection for the development of insecticide resistance. Since insecticide resistance has been recorded for most of the existing insecticides used for indoor residual spraying, namely, DDT, pyrethroids, organophosphates and carbamates, and new chemicals are necessary for the continued success of indoor residual spraying. The aim of this study was to assess the residual efficacy of Actellic 300CS, SumiShield™ 50WG and Fludora®Fusion by spraying on different wall surfaces. METHODS: One hundred and sixty-eight houses with different wall surface types (mud, cement, painted cement, and tin) which represented the rural house wall surface types in KwaZulu-Natal, South Africa were used to evaluate the residual efficacy of Actellic 300CS, SumiShield 50WG and Fludora®Fusion with DDT as the positive control. All houses were sprayed by experienced spray operators from the Malaria Control Programme. Efficacy of these insecticides were evaluated by contact bioassays against Anopheles arabiensis, a vector species. The residual efficacy of the insecticide formulations was evaluated against a susceptible insectary-reared population of An. arabiensis using WHO cone bioassays. RESULTS: Effectiveness of the three insecticides was observed up to 12 months post-spray. When assessing the achievement of 100% mortality over time, SumiShield performed significantly better than DDT on mud (OR 2.28, 95% CI 1.72-3.04) and painted cement wall types (OR 3.52, 95% CI 2.36-5.26). On cement wall types, Actellic was found to be less effective than DDT (OR 0.55, 95% CI 0.37-0.82) while Fludora®Fusion was less effective on tin wall types (OR 0.67, 95% CI 0.47-0.95). When compared to the combined efficacy of DDT on mud surfaces, SumiShield applied to each of the mud, cement and painted cement wall types and DDT applied to the cement wall types was found to be significantly more effective. These insecticides usually resulted in 100% mortality for up to 12 months with a delayed mortality period of 96-144 h, depending on the insecticide evaluated and the surface type sprayed. CONCLUSION: Field evaluation of these insecticides have shown that Actellic, SumiShield and Fludora®Fusion are suitable replacements for DDT. Each of these insecticides can be used for malaria vector control, requiring just one spray round. These insecticides can be used in rotation or as mosaic spraying.

A Comparative Study of Genetic Diversity and Multiplicity of Infection in Uncomplicated Plasmodium falciparum Infections in Selected Regions of Pre-Elimination and High Transmission Settings Using MSP1 and MSP2 Genes.

BACKGROUND: Understanding the genetic structure of P. falciparum population in different regions is pivotal to malaria elimination. Genetic diversity and the multiplicity of infection are indicators used for measuring malaria endemicity across different transmission settings. Therefore, this study characterized P. falciparum infections from selected areas constituting pre-elimination and high transmission settings in South Africa and Nigeria, respectively. METHODS: Parasite genomic DNA was extracted from 129 participants with uncomplicated P. falciparum infections. Isolates were collected from 78 participants in South Africa (southern Africa) and 51 in Nigeria (western Africa). Allelic typing of the msp1 and msp2 genes was carried out using nested PCR. RESULTS: In msp1, the K1 allele (39.7%) was the most common allele among the South African isolates, while the RO33 allele (90.2%) was the most common allele among the Nigerian isolates. In the msp2 gene, FC27 and IC3D7 showed almost the same percentage distribution (44.9% and 43.6%) in the South African isolates, whereas FC27 had the highest percentage distribution (60.8%) in the Nigerian isolates. The msp2 gene showed highly distinctive genotypes, indicating high genetic diversity in the South African isolates, whereas msp1 showed high genetic diversity in the Nigerian isolates. The RO33 allelic family displayed an inverse relationship with participants' age in the Nigerian isolates. The overall multiplicity of infection (MOI) was significantly higher in Nigeria (2.87) than in South Africa (2.44) (p < 0.000 *). In addition, heterozygosity was moderately higher in South Africa (1.46) than in Nigeria (1.13). CONCLUSIONS: The high genetic diversity and MOI in P. falciparum that were observed in this study could provide surveillance data, on the basis of which appropriate control strategies should be adopted.

Towards malaria elimination: analysis of travel history and case forecasting using the SARIMA model in Limpopo Province.

Despite various efforts and policy implementation aimed at controlling and eliminating malaria, imported malaria remains a major factor posing challenges in places that have made progress in malaria elimination. The persistence of malaria in Limpopo Province has largely been attributed to imported cases, thus reducing the pace of achieving the malaria-free target by 2025. Data from the Limpopo Malaria Surveillance Database System (2010-2020) was analyzed, and a seasonal auto-regressive integrated moving average (SARIMA) model was developed to forecast malaria incidence based on the incidence data's temporal autocorrelation. The study found that out of 57,288 people that were tested, 51,819 (90.5%) cases were local while 5469 (9.5%) cases were imported. Mozambique (44.9%), Zimbabwe (35.7%), and Ethiopia (8.5%) were the highest contributors of imported cases. The month of January recorded the highest incidence of cases while the least was in August. Analysis of the yearly figures showed an increasing trend and seasonal variation of recorded malaria cases. The SARIMA (3,1,1) X (3,1,0) [12] model used in predicting expected malaria case incidences for three consecutive years showed a decline in malaria incidences. The study demonstrated that imported malaria accounted for 9.5% of all cases. There is a need to re-focus on health education campaigns on malaria prevention methods and strengthening of indoor residual spray programs. Bodies collaborating toward malaria elimination in the Southern Africa region need to ensure a practical delivery of the objectives.

The effect of the COVID-19 lockdown on malaria transmission in South Africa.

BACKGROUND: For a country such as South Africa which is targeting malaria elimination, mobile and migrant populations pose a substantial risk to importation of malaria parasites. It has been hypothesized that halting cross-border movement of mobile and migrant populations will decrease the importation of malaria, however this option is not a politically, operationally, and financially viable prospect. It has social impacts as well, since families live on either side of the border and preventing travel will challenge family ties. Due to the COVID-19 pandemic and closure of ports of entry (land and air) for non-essential travel into South Africa, a unique opportunity arose to test the hypothesis. METHODOLOGY: An interrupted time series analysis was done to assess whether the post-lockdown trends (April-December 2020) in monthly reported imported and local cases differed from the pre-lockdown trends (January 2015-March 2020). The analysis was conducted separately for KwaZulu-Natal, Mpumalanga, and Limpopo provinces. RESULTS: On average, imported cases were lower in the post-intervention period in all three provinces, and local cases were lower in Mpumalanga and Limpopo, though no results were statistically significant. CONCLUSION: Since population movement continued after the travel restrictions were lifted, border screening with testing and treating should be considered for reducing parasite movement. Another option is reducing malaria cases at the source in neighbouring countries by implementing proven, effective vector and parasite control strategies and through a downstream effect reduce malaria entering South Africa.

A Systematic Review and Meta-Analysis of Malaria Test Positivity Outcomes and Programme Interventions in Low Transmission Settings in Southern Africa, 2000-2021.

Malaria is one of the most significant causes of mortality and morbidity globally, especially in sub-Saharan Africa (SSA) countries. It harmfully disturbs the public's health and the economic growth of many developing countries. Despite the massive effect of malaria transmission, the overall pooled proportion of malaria positivity rate in Southern Africa is still elusive. Therefore, the objective of this systematic review and meta-analysis is to pool estimates of the incidence of the malaria positivity rate, which is the first of its kind in South African countries. A literature search is performed to identify all published articles reporting the incidence of malaria positivity in Southern Africa. Out of the 3359 articles identified, 17 studies meet the inclusion for systematic review and meta-analysis. In addition, because substantial heterogeneity is expected due to the studies being extracted from the universal population, random-effects meta-analyses are carried out to pool the incidence of the malaria positivity rate from diverse diagnostic methods. The result reveals that between-study variability is high (τ2 = 0.003; heterogeneity I2 = 99.91% with heterogeneity chi-square χ2 = 18,143.95, degree of freedom = 16 and a p-value < 0.0001) with the overall random pooled incidence of 10% (95%CI: 8−13%, I2 = 99.91%) in the malaria positivity rate. According to the diagnostic method called pooled incidence estimate, the rapid diagnostic test (RDT) is the leading diagnostic method (17%, 95%CI: 11−24%, I2 = 99.95%), followed by RDT and qPCR and RDT and loop mediated isothermal amplification (LAMP), respectively, found to be (3%, 95%CI: 2−3%, I2 = 0%) and (2%, 95%CI: 1−3%, I2 = 97.94%).Findings of the present study suggest high malaria positive incidence in the region. This implies that malaria control and elimination programmes towards malaria elimination could be negatively impacted and cause delays in actualising malaria elimination set dates. Further studies consisting of larger samples and continuous evaluation of malaria control programmes are recommended.

Whole Genome Sequencing Contributions and Challenges in Disease Reduction Focused on Malaria.

Malaria elimination remains an important goal that requires the adoption of sophisticated science and management strategies in the era of the COVID-19 pandemic. The advent of next generation sequencing (NGS) is making whole genome sequencing (WGS) a standard today in the field of life sciences, as PCR genotyping and targeted sequencing provide insufficient information compared to the whole genome. Thus, adapting WGS approaches to malaria parasites is pertinent to studying the epidemiology of the disease, as different regions are at different phases in their malaria elimination agenda. Therefore, this review highlights the applications of WGS in disease management, challenges of WGS in controlling malaria parasites, and in furtherance, provides the roles of WGS in pursuit of malaria reduction and elimination. WGS has invaluable impacts in malaria research and has helped countries to reach elimination phase rapidly by providing required information needed to thwart transmission, pathology, and drug resistance. However, to eliminate malaria in sub-Saharan Africa (SSA), with high malaria transmission, we recommend that WGS machines should be readily available and affordable in the region.

Malaria diagnostic methods with the elimination goal in view.

Malaria control measures have been in use for years but have not completely curbed the spread of infection. Ultimately, global elimination is the goal. A major playmaker in the various approaches to reaching the goal is the issue of proper diagnosis. Various diagnostic techniques were adopted in different regions and geographical locations over the decades, and these have invariably produced diverse outcomes. In this review, we looked at the various approaches used in malaria diagnostics with a focus on methods favorably used during pre-elimination and elimination phases as well as in endemic regions. Microscopy, rapid diagnostic testing (RDT), loop-mediated isothermal amplification (LAMP), and polymerase chain reaction (PCR) are common methods applied depending on prevailing factors, each with its strengths and limitations. As the drive toward the elimination goal intensifies, the search for ideal, simple, fast, and reliable point-of-care diagnostic tools is needed more than ever before to be used in conjunction with a functional surveillance system supported by the ideal vaccine.

Chloroquine and Sulfadoxine-Pyrimethamine Resistance in Sub-Saharan Africa-A Review.

Malaria is a great concern for global health and accounts for a large amount of morbidity and mortality, particularly in Africa, with sub-Saharan Africa carrying the greatest burden of the disease. Malaria control tools such as insecticide-treated bed nets, indoor residual spraying, and antimalarial drugs have been relatively successful in reducing the burden of malaria; however, sub-Saharan African countries encounter great challenges, the greatest being antimalarial drug resistance. Chloroquine (CQ) was the first-line drug in the 20th century until it was replaced by sulfadoxine-pyrimethamine (SP) as a consequence of resistance. The extensive use of these antimalarials intensified the spread of resistance throughout sub-Saharan Africa, thus resulting in a loss of efficacy for the treatment of malaria. SP was replaced by artemisinin-based combination therapy (ACT) after the emergence of resistance toward SP; however, the use of ACTs is now threatened by the emergence of resistant parasites. The decreased selective pressure on CQ and SP allowed for the reintroduction of sensitivity toward those antimalarials in regions of sub-Saharan Africa where they were not the primary drug for treatment. Therefore, the emergence and spread of antimalarial drug resistance should be tracked to prevent further spread of the resistant parasites, and the re-emergence of sensitivity should be monitored to detect the possible reappearance of sensitivity in sub-Saharan Africa.

Exploring rural hospital admissions for diarrhoeal disease, malaria, pneumonia, and asthma in relation to temperature, rainfall and air pollution using wavelet transform analysis.

BACKGROUND: Climate variables impact human health and in an era of climate change, there is a pressing need to understand these relationships to best inform how such impacts are likely to change. OBJECTIVES: This study sought to investigate time series of daily admissions from two public hospitals in Limpopo province in South Africa with climate variability and air quality. METHODS: We used wavelet transform cross-correlation analysis to monitor coincidences in changes of meteorological (temperature and rainfall) and air quality (concentrations of PM2.5 and NO2) variables with admissions to hospitals for gastrointestinal illnesses including diarrhoea, pneumonia-related diagnosis, malaria and asthma cases. We were interested to disentangle meteorological or environmental variables that might be associated with underlying temporal variations of disease prevalence measured through visits to hospitals. RESULTS: We found preconditioning of prevalence of pneumonia by changes in air quality and showed that malaria in South Africa is a multivariate event, initiated by co-occurrence of heat and rainfall. We provided new statistical estimates of time delays between the change of weather or air pollution and increase of hospital admissions for pneumonia and malaria that are addition to already known seasonal variations. We found that increase of prevalence of pneumonia follows changes in air quality after a time period of 10 to 15 days, while the increase of incidence of malaria follows the co-occurrence of high temperature and rainfall after a 30-day interval. DISCUSSION: Our findings have relevance for early warning system development and climate change adaptation planning to protect human health and well-being.

Immunoinformatics approach for multi-epitope vaccine design against P. falciparum malaria.

Plasmodium falciparum (P. falciparum) is a leading causative agent of malaria, an infectious disease that can be fatal. Unfortunately, control measures are becoming less effective over time. A vaccine is needed to effectively control malaria and lead towards the total elimination of the disease. There have been multiple attempts to develop a vaccine, but to date, none have been certified as appropriate for wide-scale use. In this study, an immunoinformatics method is presented to design a multi-epitope vaccine construct predicted to be effective against P. falciparum malaria. This was done through the prediction of 12 CD4+ T-cell, 10 CD8+ T-cell epitopes and, 1 B-cell epitope which were assessed for predicted high antigenicity, immunogenicity, and non-allergenicity through in silico methods. The Human Leukocyte Antigen (HLA) population coverage showed that the alleles associated with the epitopes accounted for 78.48% of the global population. The CD4+ and CD8+ T-cell epitopes were docked to HLA-DRB1*07:01 and HLA-A*32:01 successfully. Therefore, the epitopes were deemed to be suitable as components of a multi-epitope vaccine construct. Adjuvant RS09 was added to the construct to generate a stronger immune response, as confirmed by an immune system simulation. Finally, the structural stability of the predicted multi-epitope vaccine was assessed using molecular dynamics simulations. The results show a promising vaccine design that should be further synthesised and assessed for its efficacy in an experimental laboratory setting.

Effectiveness and cost-effectiveness of reactive, targeted indoor residual spraying for malaria control in low-transmission settings: a cluster-randomised, non-inferiority trial in South Africa.

BACKGROUND: Increasing insecticide costs and constrained malaria budgets could make universal vector control strategies, such as indoor residual spraying (IRS), unsustainable in low-transmission settings. We investigated the effectiveness and cost-effectiveness of a reactive, targeted IRS strategy. METHODS: This cluster-randomised, open-label, non-inferiority trial compared reactive, targeted IRS with standard IRS practice in northeastern South Africa over two malaria seasons (2015-17). In standard IRS clusters, programme managers conducted annual mass spray campaigns prioritising areas using historical data, expert opinion, and other factors. In targeted IRS clusters, only houses of index cases (identified through passive surveillance) and their immediate neighbours were sprayed. The non-inferiority margin was 1 case per 1000 person-years. Health service costs of real-world implementation were modelled from primary and secondary data. Incremental costs per disability-adjusted life-year (DALY) were estimated and deterministic and probabilistic sensitivity analyses conducted. This study is registered with ClinicalTrials.gov, NCT02556242. FINDINGS: Malaria incidence was 0·95 per 1000 person-years (95% CI 0·58 to 1·32) in the standard IRS group and 1·05 per 1000 person-years (0·72 to 1·38) in the targeted IRS group, corresponding to a rate difference of 0·10 per 1000 person-years (-0·38 to 0·59), demonstrating non-inferiority for targeted IRS (p<0·0001). Per additional DALY incurred, targeted IRS saved US$7845 (2902 to 64 907), giving a 94-98% probability that switching to targeted IRS would be cost-effective relative to plausible cost-effectiveness thresholds for South Africa ($2637 to $3557 per DALY averted). Depending on the threshold used, targeted IRS would remain cost-effective at incidences of less than 2·0-2·7 per 1000 person-years. Findings were robust to plausible variation in other parameters. INTERPRETATION: Targeted IRS was non-inferior, safe, less costly, and cost-effective compared with standard IRS in this very-low-transmission setting. Saved resources could be reallocated to other malaria control and elimination activities. FUNDING: Joint Global Health Trials.

High levels of imported asymptomatic malaria but limited local transmission in KwaZulu-Natal, a South African malaria-endemic province nearing malaria elimination.

BACKGROUND: KwaZulu-Natal, one of South Africa's three malaria endemic provinces, is nearing malaria elimination, reporting fewer than 100 locally-acquired cases annually since 2010. Despite sustained implementation of essential interventions, including annual indoor residual spraying, prompt case detection using malaria rapid diagnostics tests and treatment with effective artemisinin-based combination therapy, low-level focal transmission persists in the province. This malaria prevalence and entomological survey was therefore undertaken to identify the drivers of this residual transmission. METHODS: Malaria prevalence as well as malaria knowledge, attitudes and practices among community members and mobile migrant populations within uMkhanyakude district, KwaZulu-Natal were assessed during a community-based malaria prevalence survey. All consenting participants were tested for malaria by both conventional and highly-sensitive falciparum-specific rapid diagnostic tests. Finger-prick filter-paper blood spots were also collected from all participants for downstream parasite genotyping analysis. Entomological investigations were conducted around the surveyed households, with potential breeding sites geolocated and larvae collected for species identification and insecticide susceptibility testing. A random selection of households were assessed for indoor residual spray quality by cone bioassay. RESULTS: A low malaria prevalence was confirmed in the study area, with only 2% (67/2979) of the participants found to be malaria positive by both conventional and highly-sensitive falciparum-specific rapid diagnostic tests. Malaria prevalence however differed markedly between the border market and community (p < 0001), with the majority of the detected malaria carriers (65/67) identified as asymptomatic Mozambican nationals transiting through the informal border market from Mozambique to economic hubs within South Africa. Genomic analysis of the malaria isolates revealed a high degree of heterozygosity and limited genetic relatedness between the isolates supporting the hypothesis of limited local malaria transmission within the province. New potential vector breeding sites, potential vector populations with reduced insecticide susceptibility and areas with sub-optimal vector intervention coverage were identified during the entomological investigations. CONCLUSION: If KwaZulu-Natal is to successfully halt local malaria transmission and prevent the re-introduction of malaria, greater efforts need to be placed on detecting and treating malaria carriers at both formal and informal border crossings with transmission blocking anti-malarials, while ensuring optimal coverage of vector control interventions is achieved.

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.

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.

Decadal epidemiology of malaria in KwaZulu-Natal, a province in South Africa targeting elimination.

BACKGROUND: Although malaria remains a noteworthy disease in South Africa, the provinces are at differing stages of the malaria elimination continuum. KwaZulu-Natal has consistently reported the lowest number of cases over the past 5 years and it is expected that the goal of elimination will be achieved in this province over the next few years. The study reports on few key indicators that realistically represents the provinces progress over the past decade. Local and imported morbidity and mortality is seen as the key indicator as is malaria in children under the age of five and pregnant women. The only vector control intervention in the province is indoor residual spraying (IRS) and this gives an estimate of the population protected by this intervention. METHODS: Trend analysis was used to examine the changing epidemiology in KwaZulu-Natal over the past decade from 2008 to 2018. The data used in this decadal analysis was obtained from the provincial Department of Health. Since malaria is a medically notifiable disease, all malaria cases diagnosed in the province are reported from health facilities and are captured in the malaria information system in the province. RESULTS: The results have shown that imported cases are on the increase whilst local cases are decreasing, in keeping with an elimination objective. Preventing secondary cases is the key to reaching elimination. Only 10% of the cases reported occur in children under 5 years whereas the cases in pregnant women account for about 1% of the reported cases. Over 85% of the houses receive IRS and this is also the same proportion of the population protected by the intervention. CONCLUSION: Several challenges to elimination have been identified but these are not insurmountable. Although there are major impediments to achieving elimination, the changing epidemiology suggests that major strides have been made in the past 10 years and KwaZulu-Natal is on track to achieving this milestone in the next few years.

Assessing Kwa-Zulu-Natal's progress towards malaria elimination and its readiness for sub-national verification.

BACKGROUND: The South African province of KwaZulu-Natal is rapidly approaching elimination status for malaria with a steady decline in local cases. With the possibility of achieving elimination in reach, the KZN malaria control programme conducted a critical evaluation of its practices and protocols to identify potential challenges and priorities to achieving elimination. Three fundamental questions were addressed: (1) How close is KZN to malaria elimination; (2) Are all systems required to pursue subnational verification of elimination in place; and (3) What priority interventions must be implemented to reduce local cases to zero? METHODS: Based on the 2017 World Health Organization Framework for Elimination, twenty-eight requirements were identified, from which forty-nine indicators to grade elimination progress were further stratified. Malaria data were extracted from the surveillance system and other programme data sources to calculate each indicator and semi-quantitatively rate performance into one of four categories to assess the provinces elimination preparedness. RESULTS: Across the key components a number of gaps were elucidated based on specific indicators. Out of the 49 indicators across these key components, 10 indicators (20%) were rated as fully implemented/well implemented, 11 indicators (22%) were rated as partially done/somewhat implemented/activity needs to be strengthened, and 12 indicators (24%) were rated as not done at all/not implemented/poor performance. Sixteen indicators (33%) could not be calculated due to lack of data or missing data. CONCLUSIONS: The critical self-evaluation of programme performance has allowed the KZN malaria programme to plan to address key issues moving forward. Based on the findings from the checklist review process, planning exercises were conducted to improve lower-rating indicators, and a monitoring and evaluation framework was created to assess progress on a monthly basis. This is scheduled to be reviewed annually to ensure continued progress toward meeting the elimination goal. In addition, multiple dissemination meetings were held with both provincial senior management and operational staff to ensure ownership of the checklist and its action plan at all levels.

Exploring the Impact of Climate Variability on Malaria Transmission Using a Dynamic Mosquito-Human Malaria Model.

INTRODUCTION: The reasons for malaria resurgence mostly in Africa are yet to be well understood. Although the causes are often linked to regional climate change, it is important to understand the impact of climate variability on the dynamics of the disease. However, this is almost impossible without adequate long-term malaria data over the study areas. METHODS: In this study, we develop a climate-based mosquito-human malaria model to study malaria dynamics in the human population over KwaZulu-Natal, one of the epidemic provinces in South Africa, from 1970-2005. We compare the model output with available observed monthly malaria cases over the province from September 1999 to December 2003. We further use the model outputs to explore the relationship between the climate variables (rainfall and temperature) and malaria incidence over the province using principal component analysis, wavelet power spectrum and wavelet coherence analysis. The model produces a reasonable fit with the observed data and in particular, it captures all the spikes in malaria prevalence. RESULTS: Our results highlight the importance of climate factors on malaria transmission and show the seasonality of malaria epidemics over the province. Results from the principal component analyses further suggest that, there are two principal factors associated with climates variables and the model outputs. One of the factors indicate high loadings on Susceptible, Exposed and Infected human, while the other is more correlated with Susceptible and Recovered humans. However, both factors reveal the inverse correlation between Susceptible-Infected and Susceptible-Recovered humans respectively. Through the spectrum analysis, we notice a strong annual cycle of malaria incidence over the province and ascertain a dominant of one year periodicity. Consequently, our findings indicate that an average of 0 to 120-day lag is generally noted over the study period, but the 120-day lag is more associated with temperature than rainfall. This is consistence with other results obtained from our analyses that malaria transmission is more tightly coupled with temperature than with rainfall in KwaZulu-Natal province.

A promising azeotrope-like mosquito repellent blend.

Topical repellents play a key role in reducing the outdoor transmission of mosquito-borne diseases by reducing human-vector contact. Excellent repellents are available, but there is always room for improvement. This article reports on a particularly effective binary repellent blend of ethyl butylacetylaminopropionate and nonanoic acid. A composition containing 25 mol% of the acid exhibits negative pseudo-azeotrope behaviour at 50 °C, meaning that the liquid vapour pressure is lower than that of the parent compounds and evaporation occurs without a change in the liquid composition. In tests performed using the South African Medical Research Council's cup-on-arm procedure, this mixture provided better protection for a longer time than the "gold standard of mosquito repellents", namely N,N-diethyl-m-toluamide, commonly known as DEET.

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.