Rise in Malaria Incidence Rates in South Africa: A Small-Area Spatial Analysis of Variation in Time Trends

Using Bayesian statistical models, the authors investigated spatial and temporal variations in small-area malaria incidence rates for the period mid-1986 to mid-1999 for two districts in northern KwaZulu Natal, South Africa. Maps of spatially smoothed incidence rates at different time points and spatially smoothed time trends in incidence gave a visual impression of the highest increase in incidence occurring where incidence rates previously had been lowest. This was confirmed by conditional autoregressive models, which showed that there was a significant negative association between time trends and smoothed baseline incidence before the steady rise in caseloads began. Growth rates also appeared to be higher in the areas close to the Mozambican border. The main findings of this analysis were that: 1) the spatial distribution of the rise in malaria incidence is uneven and strongly suggests a geographic expansion of high-malaria-risk areas; 2) there is evidence of a stabilization of incidence in areas that had the highest rates before the current escalation of rates began; and 3) areas immediately adjoining the Mozambican border appear to have undergone larger increases in incidence, in contrast to the general pattern of low growth in the more northern, high-baseline-incidence areas, but this was not confirmed by modeling. Smoothing of small-area maps of incidence and growth in incidence (trend) is important for interpretation of the spatial distribution of disease incidence and the spatial distribution of rapid changes in disease incidenc

Estimating the numbers of malaria infections in blood samples using high-resolution genotyping data

People living in endemic areas often habour several malaria infections at once. High-resolution genotyping can distinguish between infections by detecting the presence of different alleles at a polymorphic locus. However the number of infections may not be accurately counted since parasites from multiple infections may carry the same allele. We use simulation to determine the circumstances under which the number of observed genotypes are likely to be substantially less than the number of infections present and investigate the performance of two methods for estimating the numbers of infections from high-resolution genotyping data.THE SIMULATIONS SUGGEST THAT THE PROBLEM IS NOT SUBSTANTIAL IN MOST DATASETS: the disparity between the mean numbers of infections and of observed genotypes was small when there was 20 or more alleles, 20 or more blood samples, a mean number of infections of 6 or less and where the frequency of the most common allele was no greater than 20%. The issue of multiple infections carrying the same allele is unlikely to be a major component of the errors in PCR-based genotyping.Simulations also showed that, with heterogeneity in allele frequencies, the observed frequencies are not a good approximation of the true allele frequencies. The first method that we proposed to estimate the numbers of infections assumes that they are a good approximation and hence did poorly in the presence of heterogeneity. In contrast, the second method by Li et al estimates both the numbers of infections and the true allele frequencies simultaneously and produced accurate estimates of the mean number of infections

Health Worker Compliance with a 'Test And Treat' Malaria Case Management Protocol in Papua New Guinea

The Papua New Guinea (PNG) Department of Health introduced a 'test and treat' malaria case management protocol in 2011. This study assesses health worker compliance with the test and treat protocol on a wide range of measures, examines self-reported barriers to health worker compliance as well as health worker attitudes towards the test and treat protocol. Data were collected by cross-sectional survey conducted in randomly selected primary health care facilities in 2012 and repeated in 2014. The combined survey data included passive observation of current or recently febrile patients (N = 771) and interviewer administered questionnaires completed with health workers (N = 265). Across the two surveys, 77.6% of patients were tested for malaria infection by rapid diagnostic test (RDT) or microscopy, 65.6% of confirmed malaria cases were prescribed the correct antimalarials and 15.3% of febrile patients who tested negative for malaria infection were incorrectly prescribed an antimalarial. Overall compliance with a strictly defined test and treat protocol was 62.8%. A reluctance to test current/recently febrile patients for malaria infection by RDT or microscopy in the absence of acute malaria symptoms, reserving recommended antimalarials for confirmed malaria cases only and choosing to clinically diagnose a malaria infection, despite a negative RDT result were the most frequently reported barriers to protocol compliance. Attitudinal support for the test and treat protocol, as assessed by a nine-item measure, improved across time. In conclusion, health worker compliance with the full test and treat malaria protocol requires improvement in PNG and additional health worker support will likely be required to achieve this. The broader evidence base would suggest any such support should be delivered over a longer period of time, be multi-dimensional and multi-modal

Taking Sharper Pictures of Malaria with CAMERAs: Combined Antibodies to Measure Exposure Recency Assays.

Antibodies directed against malaria parasites are easy and inexpensive to measure but remain an underused surveillance tool because of a lack of consensus on what to measure and how to interpret results. High-throughput screening of antibodies from well-characterized cohorts offers a means to substantially improve existing assays by rationally choosing the most informative sets of responses and analytical methods. Recent data suggest that high-resolution information on malaria exposure can be obtained from a small number of samples by measuring a handful of properly chosen antibody responses. In this review, we discuss how standardized multi-antibody assays can be developed and efficiently integrated into existing surveillance activities, with potential to greatly augment the breadth and quality of information available to direct and monitor malaria control and elimination efforts

Population genetic analysis of the Plasmodium falciparum 6-cys protein Pf38 in Papua New Guinea reveals domain-specific balancing selection

<p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>merozoite surface protein Pf38 is targeted by antibodies of malaria immune adults and has been shown to be under balancing (immune) selection in a Gambian parasite population, indicating potential as a malaria vaccine candidate. This study explores the population genetics of <it>Pf</it>38 in Papua New Guinea, to determine the extent and geographic distribution of diversity and to measure selective pressure along the length of the gene.</p> <p>Methods</p> <p>Using samples collected during community-based cross-sectional surveys in the Mugil and Wosera regions, the <it>Pf38 </it>genes of 59 <it>P. falciparum </it>isolates were amplified and sequenced. These sequences, along with previously sequenced Gambian and laboratory isolates, were then subjected to an array of population genetic analyses, examining polymorphisms, haplotype diversity and balancing selection. In addition to whole-gene analysis, the two 6-cys domains were considered separately, to investigate domain specific polymorphism and selection.</p> <p>Results</p> <p>Nineteen polymorphic sites were identified in the <it>Pf </it>38 gene. Of these, 13 were found in the Gambia, 10 in Mugil and 8 in Wosera. Notably, the majority of common polymorphisms were confined to domain I. Although only moderate levels of nucleotide diversity were observed, the haplotype diversity was high in all populations, suggesting extensive recombination. Analyses of the full-length sequence provided only modest evidence for balancing selection. However, there was a strong contrast between domain I, which showed strong evidence for positive balancing selection, and domain II which was neutral. Analyses of the geographic distribution of Pf38 haplotypes showed that four haplotypes accounted for the majority of sequences found world-wide, but there were many more haplotypes unique to the African than the PNG populations.</p> <p>Conclusion</p> <p>This study confirmed previous findings that <it>Pf38 </it>is a polymorphic gene under balancing selection. However, analysing polymorphism and selection across the length of the gene painted a considerably different picture. Domain I is highly polymorphic and the target of significant balancing selection. In contrast, domain II is relatively conserved and does not show evidence of immune selective pressure. The findings have implications for future population genetic studies on vaccine candidates, showing that the biological context must also be considered as a framework for analysis.</p

Key Knowledge Gaps for Plasmodium vivax Control and Elimination

There is inadequate understanding of the biology, pathology, transmission, and control of Plasmodium vivax, the geographically most widespread cause of human malaria. During the last decades, study of this species was neglected, in part due to the erroneous belief that it is intrinsically benign. In addition, many technical challenges in culturing the parasite also hampered understanding its fundamental biology and molecular and cellular responses to chemotherapeutics. Research on vivax malaria needs to be substantially expanded over the next decade to accelerate its elimination and eradication. This article summarizes key knowledge gaps identified by researchers, national malaria control programs, and other stakeholders assembled by the World Health Organization to develop strategies for controlling and eliminating vivax malaria. The priorities presented in this article emerged in these technical discussions, and were adopted by expert consensus of the authors. All involved understood the priority placed upon pragmatism in this research agenda, that is, focus upon tools delivering better prevention, diagnosis, treatment, and surveillance of P. vivax

Estimating the Burden of Malaria: The Need for Improved Surveillance

Ivo Mueller, Laurence Slutsker, and Marcel Tanner highlight the importance of using complementary methods to estimate the burden of malaria and call for a renewed focus on efficient malaria surveillance

The economic cost to households of childhood malaria in Papua New Guinea: a focus on intra-country variation

Background We compare direct and indirect household costs associated with malaria treatment for children <3 years in two provinces of Papua New Guinea. In particular, we explore the role of uncertainty around mean household costs and whether assuming a normal distribution for household costs limits the accuracy of any direct cost comparisons. Methods Exit surveys were undertaken at inpatient and outpatient health facilities. In order to handle uncertainty and facilitate comparisons, parametric and non-parametric bootstrap methods were used to estimate direct and indirect costs at the individual data level. The inpatient and outpatient incremental costs from Madang and Maprik health facilities were compared and significant differences between provinces were identified. Results Differences were noted between provinces for both inpatient and outpatient household costs. Total arithmetic mean costs for an outpatient malaria episode were US$7.54 in Madang and US$9.20 in Maprik. Total mean inpatient malaria episode costs were US$25.20 in Madang and US$14.08 in Maprik. As cost distributions were not normal, non-parametric bootstrap techniques were used for cost comparisons. Total household costs per outpatient episode of malaria were lower, although not significantly, in Maprik than in Madang (incremental cost of US$−1.67; 95$11.16; 95% CI 5.47, 25.33). A difference was noted between provinces in the proportion of indirect costs in total household costs for an outpatient visit: 76% in Madang vs 94% in Maprik. The proportion for indirect costs associated with inpatient visits varied less: 63% in Madang vs 68% in Maprik. Conclusions Intra-country differences need to be considered in estimating household costs for both outpatient and inpatient malaria treatment. Our findings suggest that it is important to recognize the impact of both direct and indirect costs on individuals' capacity to afford treatment. Certain indirect costs are difficult to measure accurately, particularly respondents' interpretations of their productive versus non-productive time. Despite this, exploring intra-country cost variation can provide important information to health policy maker