Sarah Auburn and co-authors discuss the unique biology and epidemiology of P. vivax and current evidence on conventional and new approaches to surveillance.
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In The Lancet Infectious Diseases, the investigators provide an additional retrospective analysis of data from the same study to determine the effectiveness of tafenoquine and unsupervised primaquine ...in preventing recurrent P vivax malaria.4 Recurrent infections were detected 24 days earlier in patients treated with 7-day primaquine compared with those treated with tafenoquine, and at 3 months there was a modest reduction in recurrence-free effectiveness (83·5% in the 7-day primaquine group vs 88·6% in the tafenoquine group). By 6 months, the survival curves had converged, with an overall risk of recurrence of 24–27%, almost three times lower than that reported previously in patients at the same location who did not receive radical cure.1 Thus, the revised radical cure treatment strategy proved feasible and safe, with potential for substantial public health benefit. ...tafenoquine might delay rather than reduce the total number of recurrences.
Plasmodium vivax is an important cause of malaria, associated with a significant public health burden. Whilst enhanced malaria-control activities have successfully reduced the incidence of Plasmodium ...falciparum malaria in many areas, there has been a consistent increase in the proportion of malaria due to P. vivax in regions where both parasites coexist. This article reviews the epidemiology and biology of P. vivax, how the parasite differs from P. falciparum, and the key features that render it more difficult to control and eliminate. Since transmission of the parasite is driven largely by relapses from dormant liver stages, its timely elimination will require widespread access to safe and effective radical cure.
Plasmodium vivax infection is present across most of the malaria-endemic world.P. vivax relapses, arising from dormant liver stages, cause recurrent episodes of malaria that are the main determinant of significant morbidity, mortality, and ongoing transmission.In coendemic areas, where intense malaria-control activities have reduced the burden of P. falciparum, there has been a rise in the proportion of malaria attributable to P. vivax.There is an increased risk of P. vivax after the treatment of P. falciparum in coendemic regions, suggesting potential benefit of universal radical cure for both parasites in some areas.Novel host and parasite diagnostics, single-dose tafenoquine, and short-course primaquine regimens offer hope for safer and more effective radical cure to eliminate the parasite.
Roland Gosling and colleagues argue that "asymptomatic" malaria infections have significant health and societal consequences, and propose that they should be renamed "chronic" malaria infections.
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Bold measures to accelerate malaria elimination Price, Ric N
Lancet. Infectious diseases/The Lancet. Infectious diseases,
November 2021, 2021-11-00, 20211101, Letnik:
21, Številka:
11
Journal Article
Recenzirano
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...ultrasensitive molecular diagnostics highlight a high burden of low-density infections in asymptomatic individuals, below the threshold of detection of conventional diagnostic tests; this hidden ...reservoir undermines the effectiveness of mass screen and treat strategies.2 An alternative approach is mass drug administration (MDA), in which antimalarial treatment is offered to high-risk populations irrespective of confirmed parasitaemia.3 In The Lancet Infectious Diseases, Alistair McLean and colleagues present findings of a cluster-randomised control trial done in remote, rural Myanmar.4 Routine malaria case management was provided by community health workers, who also distributed long-lasting insecticidal bed-nets. The study confirms that in remote communities, deployment of community health workers, early diagnosis and treatment of malaria, and distribution of long-lasting insecticidal bed-nets can reduce the burden of malaria substantially.5 MDA accelerated the reduction in P falciparum infections but the intervention was intense, involving extensive community engagement, three rounds of a supervised 3-day regimen, active case detection, and screening of newcomers to the community. Regional implementation of MDA with high levels of coverage have a more profound and longer lasting benefit, as has been shown in Vanuatu, Comoros, and China.6–8 The key decision now is whether the results of recent large MDA trials, including the one by McLean and colleagues, warrant larger scale interventions.9,10 The approach will need to be tailored to specific settings, including targeting high-risk populations and isolated communities, repeating MDA at regular intervals, and consideration of the radical cure of Plasmodium vivax.
and
form dormant liver hypnozoites that can reactivate weeks to months following initial infection. Malaria recurrences caused by relapses are an important cause of morbidity and source of ...transmission. To estimate the proportions of
malaria recurrences caused by relapses in different geographical locations, we systematically reviewed clinical efficacy studies of uncomplicated
malaria, in which patients were randomized to treatment with or without radical cure primaquine regimens and were followed up for 1 year. The minimum proportion of recurrences caused by relapses was estimated for each study site by assuming primaquine prevented all relapses and did not augment blood-stage efficacy. Of the 261 studies identified, six were eligible enrolling 4,092 patients from 14 treatment arm comparisons across seven countries. Of the 2,735 patients treated with primaquine, 24.3% received low dose (2.5 to < 5.0 mg/kg total) and 75.7% received high-dose primaquine (≥ 5.0 mg/kg total). The overall pooled incidence rate ratio of
relapses for patients treated with primaquine versus no primaquine was 0.15 (95% CI: 0.10-0.21;
= 83.3%), equating to a minimum of 79% of recurrences attributable to relapse. Country-specific incidence rate ratios ranged from 0.05 (95% CI: 0.01-0.34; one estimate) in Pakistan to 0.34 in Nepal (95% CI: 0.12-0.83; one estimate) and Afghanistan (95% CI: 0.22-0.51; three estimates). Relapses account for a very high proportion of recurrent infections following schizontocidal treatment of acute
malaria across diverse geographic locations. This emphasizes the importance of implementing hypnozoitocidal treatment.
Summary Background Chloroquine is the first-line treatment for Plasmodium vivax malaria in most endemic countries, but resistance is increasing. Monitoring of antimalarial efficacy is essential, but ...in P vivax infections the assessment of treatment efficacy is confounded by relapse from the dormant liver stages. We systematically reviewed P vivax malaria treatment efficacy studies to establish the global extent of chloroquine resistance. Methods We searched Medline, Web of Science, Embase, and the Cochrane Database of Systematic Reviews to identify studies published in English between Jan 1, 1960, and April 30, 2014, which investigated antimalarial treatment efficacy in P vivax malaria. We excluded studies that did not include supervised schizonticidal treatment without primaquine. We determined rates of chloroquine resistance according to P vivax malaria recurrence rates by day 28 whole-blood chloroquine concentrations at the time of recurrence and study enrolment criteria. Findings We identified 129 eligible clinical trials involving 21 694 patients at 179 study sites and 26 case reports describing 54 patients. Chloroquine resistance was present in 58 (53%) of 113 assessable study sites, spread across most countries that are endemic for P vivax . Clearance of parasitaemia assessed by microscopy in 95% of patients by day 2, or all patients by day 3, was 100% predictive of chloroquine sensitivity. Interpretation Heterogeneity of study design and analysis has confounded global surveillance of chloroquine-resistant P vivax , which is now present across most countries endemic for P vivax . Improved methods for monitoring of drug resistance are needed to inform antimalarial policy in these regions. Funding Wellcome Trust (UK).
The COVID-19 pandemic has resulted in millions of infections, hundreds of thousands of deaths and major societal disruption due to lockdowns and other restrictions introduced to limit disease spread. ...Relatively little attention has been paid to understanding how the pandemic has affected treatment, prevention and control of malaria, which is a major cause of death and disease and predominantly affects people in less well-resourced settings.
Recent successes in malaria control and elimination have reduced the global malaria burden, but these gains are fragile and progress has stalled in the past 5 years. Withdrawing successful interventions often results in rapid malaria resurgence, primarily threatening vulnerable young children and pregnant women. Malaria programmes are being affected in many ways by COVID-19. For prevention of malaria, insecticide-treated nets need regular renewal, but distribution campaigns have been delayed or cancelled. For detection and treatment of malaria, individuals may stop attending health facilities, out of fear of exposure to COVID-19, or because they cannot afford transport, and health care workers require additional resources to protect themselves from COVID-19. Supplies of diagnostics and drugs are being interrupted, which is compounded by production of substandard and falsified medicines and diagnostics. These disruptions are predicted to double the number of young African children dying of malaria in the coming year and may impact efforts to control the spread of drug resistance. Using examples from successful malaria control and elimination campaigns, we propose strategies to re-establish malaria control activities and maintain elimination efforts in the context of the COVID-19 pandemic, which is likely to be a long-term challenge. All sectors of society, including governments, donors, private sector and civil society organisations, have crucial roles to play to prevent malaria resurgence. Sparse resources must be allocated efficiently to ensure integrated health care systems that can sustain control activities against COVID-19 as well as malaria and other priority infectious diseases.
As we deal with the COVID-19 pandemic, it is crucial that other major killers such as malaria are not ignored. History tells us that if we do, the consequences will be dire, particularly in vulnerable populations.
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Effective malaria control strategies require an accurate understanding of the epidemiology of locally transmitted Plasmodium species. Compared to Plasmodium falciparum infection, Plasmodium vivax has ...a lower asexual parasitaemia, forms dormant liver-stages (hypnozoites), and is more transmissible. Hence, treatment and diagnostic policies aimed exclusively at P. falciparum are far less efficient against endemic P. vivax. Within sub-Saharan Africa, malaria control programmes justly focus on reducing the morbidity and mortality associated with P. falciparum. However, the recent emphasis on malaria elimination and increased accessibility of more sensitive diagnostic tools have revealed greater intricacies in malaria epidemiology across the continent. Since 2010, the number of studies identifying P. vivax endemic to Africa has expanded considerably, with 88 new scientific reports published since a review of evidence in 2015, approximately doubling the available data. There is evidence of P. vivax in all regions of Africa, apparent from infected vectors, clinical cases, serological indicators, parasite prevalence, exported infections, and P. vivax-infected Duffy-negative individuals. Where the prevalence of microscopic parasitaemia is low, a greater proportion of P. vivax infections were observed relative to P. falciparum. This evidence highlights an underlying widespread presence of P. vivax across all malaria-endemic regions of Africa, further complicating the current practical understanding of malaria epidemiology in this region. Thus, ultimate elimination of malaria in Africa will require national malaria control programmes to adopt policy and practice aimed at all human species of malaria.
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To reduce the risk of drug-induced haemolysis, all patients should be tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) prior to prescribing primaquine (PQ)-based radical cure ...for the treatment of vivax malaria. This systematic review and individual patient meta-analysis assessed the utility of a qualitative lateral flow assay from Access Bio/CareStart (Somerset, NJ) (CareStart Screening test for G6PD deficiency) for the diagnosis of G6PDd compared to the gold standard spectrophotometry (International Prospective Register of Systematic Reviews PROSPERO: CRD42019110994).
Articles published on PubMed between 1 January 2011 and 27 September 2019 were screened. Articles reporting performance of the standard CSG from venous or capillary blood samples collected prospectively and considering spectrophotometry as gold standard (using kits from Trinity Biotech PLC, Wicklow, Ireland) were included. Authors of articles fulfilling the inclusion criteria were contacted to contribute anonymized individual data. Minimal data requested were sex of the participant, CSG result, spectrophotometry result in U/gHb, and haemoglobin (Hb) reading. The adjusted male median (AMM) was calculated per site and defined as 100% G6PD activity. G6PDd was defined as an enzyme activity of less than 30%. Pooled estimates for sensitivity and specificity, unconditional negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) were calculated comparing CSG results to spectrophotometry using a random-effects bivariate model. Of 11 eligible published articles, individual data were available from 8 studies, 6 from Southeast Asia, 1 from Africa, and 1 from the Americas. A total of 5,815 individual participant data (IPD) were available, of which 5,777 results (99.3%) were considered for analysis, including data from 3,095 (53.6%) females. Overall, the CSG had a pooled sensitivity of 0.96 (95% CI 0.90-0.99) and a specificity of 0.95 (95% CI 0.92-0.96). When the prevalence of G6PDd was varied from 5% to 30%, the unconditional NPV was 0.99 (95% CI 0.94-1.00), with an LR+ and an LR- of 18.23 (95% CI 13.04-25.48) and 0.05 (95% CI 0.02-0.12), respectively. Performance was significantly better in males compared to females (p = 0.027) but did not differ significantly between samples collected from capillary or venous blood (p = 0.547). Limitations of the study include the lack of wide geographical representation of the included data and that the CSG results were generated under research conditions, and therefore may not reflect performance in routine settings.
The CSG performed well at the 30% threshold. Its high NPV suggests that the test is suitable to guide PQ treatment, and the high LR+ and low LR- render the test suitable to confirm and exclude G6PDd. Further operational studies are needed to confirm the utility of the test in remote endemic settings.
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