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Background Malaria transmission modelling has demonstrated the potential impact of semiquantitative glucose-6-phosphate dehydrogenase (G6PD) testing and treatment with single-dose tafenoquine for Plasmodium vivax radical cure but has not investigated the associated costs. This study evaluated the cost-effectiveness of P. vivax treatment with tafenoquine after G6PD testing using a transmission model. Methods and findings We explored the cost-effectiveness of using tafenoquine after G6PD screening as compared to usual practice (7-day low-dose primaquine (0.5 mg/kg/day) without G6PD screening) in Brazil using a 10-year time horizon with 5% discounting considering 4 scenarios: (1) tafenoquine for adults only assuming 66.7% primaquine treatment adherence; (2) tafenoquine for adults and children aged >2 years assuming 66.7% primaquine adherence; (3) tafenoquine for adults only assuming 90% primaquine adherence; and (4) tafenoquine for adults only assuming 30% primaquine adherence. The incremental cost-effectiveness ratios (ICERs) were estimated by dividing the incremental costs by the disability-adjusted life years (DALYs) averted. These were compared to a willingness to pay (WTP) threshold of US$7,800 for Brazil, and one-way and probabilistic sensitivity analyses were performed. All 4 scenarios were cost-effective in the base case analysis using this WTP threshold with ICERs ranging from US$154 to US$1,836. One-way sensitivity analyses showed that the results were most sensitive to severity and mortality due to vivax malaria, the lifetime and number of semiquantitative G6PD analysers needed, cost per malaria episode and per G6PD test strips, and life expectancy. All scenarios had a 100% likelihood of being cost-effective at the WTP threshold. The main limitations of this study are due to parameter uncertainty around our cost estimates for low transmission settings, the costs of G6PD screening, and the severity of vivax malaria Conclusions In our modelling study that incorporated impact on transmission, tafenoquine prescribed after a semiquantitative G6PD testing was highly likely to be cost-effective in Brazil. These results demonstrate the potential health and economic importance of ensuring safe and effective radical cure., Author(s): David J. Price 1,2, Narimane Nekkab 3,4, Wuelton M. Monteiro 5,6, Daniel A. M. Villela 7, Julie A. Simpson 2, Marcus V. G. Lacerda 5,8, Michael T. White 9, [...]

In malaria-endemic regions, Plasmodium vivax and Plasmodium falciparum coexist and may interact. For instance, fevers induced by P. falciparum might activate dormant P. vivax parasites and concurrent radical cure of both species has been proposed to prevent relapses. Heterogeneous mosquito exposure may contribute to the dependence of both parasites. We conducted a literature review on their respective prevalence and that of co-infections. The data revealed a positive correlation between P. vivax and P. falciparum prevalence, and co-infection prevalences exceeding expectations assuming infections occur independently. We used the review data to fit a compartmental model of co-infections that features heterogenous mosquito exposure. The fit suggests that heterogeneous exposure sufficiently explains the observed departure from independence. Finally, we performed simulations under the model assessing the impact on P. vivax prevalence of the activation-by-fever hypothesis and the radical cure proposition. We demonstrated a moderate impact of allowing P. falciparum fevers to reactivate P. vivax and a substantial impact of treating P. falciparum cases with radical cure. Our model highlights dependence between P. falciparum and P. vivax and emphasizes the influence of heterogeneous mosquito exposure. This simple framework can inform the design of more complex models assessing integrated malaria control strategies in coendemic regions. [ABSTRACT FROM AUTHOR]

Robust surveillance methods are needed for trachoma control and recrudescence monitoring, but existing methods have limitations. Here, we analyse data from nine trachoma-endemic populations and provide operational thresholds for interpretation of serological data in low-transmission and post-elimination settings. Analyses with sero-catalytic and antibody acquisition models provide insights into transmission history within each population. To accurately estimate sero-conversion rates (SCR) for trachoma in populations with high-seroprevalence in adults, the model accounts for secondary exposure to Chlamydia trachomatis due to urogenital infection. We estimate the population half-life of sero-reversion for anti-Pgp3 antibodies to be 26 (95% credible interval (CrI): 21-34) years. We show SCRs below 0.015 (95% confidence interval (CI): 0.0-0.049) per year correspond to a prevalence of trachomatous inflammation-follicular below 5%, the current threshold for elimination of active trachoma as a public health problem. As global trachoma prevalence declines, we may need cross-sectional serological survey data to inform programmatic decisions.

A major gap in the Plasmodium vivax elimination toolkit is the identification of individuals carrying clinically silent and undetectable liver-stage parasites, called hypnozoites. This study developed a panel of serological exposure markers capable of classifying individuals with recent P. vivax infections who have a high likelihood of harboring hypnozoites. We measured IgG antibody responses to 342 P. vivax proteins in longitudinal clinical cohorts conducted in Thailand and Brazil and identified candidate serological markers of exposure. Candidate markers were validated using samples from year-long observational cohorts conducted in Thailand, Brazil and the Solomon Islands and antibody responses to eight P. vivax proteins classified P. vivax infections in the previous 9 months with 80% sensitivity and specificity. Mathematical models demonstrate that a serological testing and treatment strategy could reduce P. vivax prevalence by 59-69%. These eight antibody responses can serve as a biomarker, identifying individuals who should be targeted with anti-hypnozoite therapy. Plasmodium vivax can cause a clinically silent liver-stage infection that can reactivate, triggering blood-stage disease. A new test measuring antibody responses can identify P. vivax carriers for targeted treatment intervention., Author(s): Rhea J. Longley [sup.1] [sup.2] [sup.3] , Michael T. White [sup.4] , Eizo Takashima [sup.5] , Jessica Brewster [sup.1] , Masayuki Morita [sup.5] , Matthias Harbers [sup.6] [sup.7] , [...]

Insecticide-treated nets and indoor residual spray programs for malaria control are entirely dependent on pyrethroid insecticides. The ubiquitous exposure of Anopheles mosquitoes to this chemistry has selected for resistance in a number of populations. This threatens the sustainability of our most effective interventions but no operationally practicable way of resolving the problem currently exists. One innovative solution involves the co-application of a powerful chemosterilant (pyriproxyfen or PPF) to bed nets that are usually treated only with pyrethroids. Resistant mosquitoes that are unaffected by the pyrethroid component of a PPF/pyrethroid co-treatment remain vulnerable to PPF. There is a differential impact of PPF on pyrethroid-resistant and susceptible mosquitoes that is modulated by the mosquito's behavioural response at co-treated surfaces. This imposes a specific fitness cost on pyrethroid-resistant phenotypes and can reverse selection. The concept is demonstrated using a mathematical model.

BackgroundCurrent vector control strategies focus largely on indoor measures, such as long-lasting insecticide treated nets (LLINs) and indoor residual spraying (IRS); however mosquitoes frequently feed on sugar sources outdoors, inviting the possibility of novel control strategies. Attractive toxic sugar baits (ATSB), either sprayed on vegetation or provided in outdoor bait stations, have been shown to significantly reduce mosquito densities in these settings.MethodsSimple models of mosquito sugar-feeding behaviour were fitted to data from an ATSB field trial in Mali and used to estimate sugar-feeding rates and the potential of ATSB to control mosquito populations. The model and fitted parameters were then incorporated into a larger integrated vector management (IVM) model to assess the potential contribution of ATSB to future IVM programmes.ResultsIn the Mali experimental setting, the model suggests that about half of female mosquitoes fed on ATSB solution per day, dying within several hours of ingesting the toxin. Using a model incorporating the number of gonotrophic cycles completed by female mosquitoes, a higher sugar-feeding rate was estimated for younger mosquitoes than for older mosquitoes. Extending this model to incorporate other vector control interventions suggests that an IVM programme based on both ATSB and LLINs may substantially reduce mosquito density and survival rates in this setting, thereby substantially reducing parasite transmission. This is predicted to exceed the impact of LLINs in combination with IRS provided ATSB feeding rates are 50% or more of Mali experimental levels. In addition, ATSB is predicted to be particularly effective against Anopheles arabiensis, which is relatively exophilic and therefore less affected by IRS and LLINs.ConclusionsThese results suggest that high coverage with a combination of LLINs and ATSB could result in substantial reductions in malaria transmission in this setting. Further field studies of ATSB in other settings are needed to assess the potential of ATSB as a component in future IVM malaria control strategies.

As progress towards malaria elimination continues, the challenge posed by the parasite species Plasmodium vivax has become more evident. In many regions co-endemic for P. vivax and Plasmodium falciparum, as transmission has declined the proportion of cases due to P. vivax has increased. Novel tools that directly target P. vivax are thus warranted for accelerated elimination. There is currently no advanced vaccine for P. vivax and only a limited number of potential candidates in the pipeline. In this study we aimed to identify promising P. vivax proteins that could be used as part of a subunit vaccination approach. We screened 342 P. vivax protein constructs for their ability to induce IgG antibody responses associated with protection from clinical disease in a cohort of children from Papua New Guinea. This approach has previously been used to successfully identify novel candidates. We were able to confirm previous results from our laboratory identifying the proteins reticulocyte binding protein 2b and StAR-related lipid transfer protein, as well as at least four novel candidates with similar levels of predicted protective efficacy. Assessment of these P. vivax proteins in further studies to confirm their potential and identify functional mechanisms of protection against clinical disease are warranted. [ABSTRACT FROM AUTHOR]