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Recent publications and statements have drawn attention to a sustainable system of managing malaria control interventions globally but especially on the Continent of Africa. Arbitrary and unstable governments often interfere with health programmes, causing upsurges in malaria transmission as well as other health issues. A well-run health infrastructure will deal with public health as a whole. This commentary follows historical conditions in Zimbabwe where much original work on malaria control was initiated and implemented and where unstable conditions happened through local politics. These periodic conditions of instability on the ground challenge the current philosophical thrust to eradication and stress the need and role of an established and well-staffed health infrastructure in each country. Such facilities should be well staffed and supplied with drugs and point-of care diagnostic tests to manage malaria and should be sustained to serve the community even after tools that can eradicate malaria are developed.

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OBJECTIVE: To determine household and health-care provider costs associated with Plasmodium vivax infection across a range of endemic settings. METHODS: We collected cost data alongside three multicentre clinical trials of P. vivax treatment in Afghanistan, Brazil, Colombia, Ethiopia, Indonesia, Philippines, Peru, Thailand and Viet Nam conducted between April 2014 to December 2017. We derived household costs from trial participant surveys administered at enrolment and again 2 weeks later to determine the costs of treatment and transportation, and the number of days that patients and their household caregivers were unable to undertake their usual activities. We determined costs of routine care by health-care providers by micro-costing the resources used to diagnose and treat P. vivax at the study sites. FINDINGS: The mean total household costs ranged from 8.7 United States dollars (US$; standard deviation, SD: 4.3) in Afghanistan to US$ 254.7 (SD: 148.4) in Colombia. Across all countries, productivity losses were the largest household cost component, resulting in mean indirect costs ranging from US$ 5.3 (SD: 3.0) to US$ 220.8 (SD: 158.40). The range of health-care provider costs for routine care was US$ 3.6-6.6. The cost of administering a glucose-6-phosphate-dehydrogenase rapid diagnostic test, ranged from US$ 0.9 to 13.5, consistently lower than the costs of the widely-used fluorescent spot test (US$ 6.3 to 17.4). CONCLUSION: An episode of P. vivax malaria results in high costs to households. The costs of diagnosing and treating P. vivax are important inputs for future cost-effectiveness analyses to ensure optimal allocation of resources for malaria elimination.

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Introduction: Historically, the global community has focused on the control of symptomatic malaria. However, interest in asymptomatic malaria has been growing, particularly in the context of malaria elimination.Areas covered: We undertook a comprehensive PubMed literature review on asymptomatic malaria as it relates to detection and elimination with emphasis between 2014 and 2019. Diagnostic tools with a low limit of detection (LOD) have allowed us to develop a more detailed understanding of asymptomatic malaria and its impact. These highly sensitive diagnostics have demonstrated that the prevalence of asymptomatic malaria is greater than previously thought. In addition, it is now possible to detect the malaria reservoir in the community, something that was previously not feasible. Asymptomatic malaria has previously not been treated, but research has begun to examine whether treating individuals with asymptomatic malaria may lead to health benefits. Finally, we have begun to understand the importance of asymptomatic malaria in ongoing transmission.Expert opinion: Therefore, with malaria elimination back on the agenda, asymptomatic malaria can no longer be ignored, especially in light of new ultra-sensitive diagnostic tools.

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A portion of the economics literature has long debated about the relative importance of historical, institutional, geographical, and health determinants of economic growth. In 2001, Gallup and Sachs quantified the association between malaria and the level and growth of per capita income over the period 1965-1995 in a cross-country regression framework. We took a contemporary look at Gallup and Sachs' seminal work in the context of significant progress in malaria control achieved globally since 2000. Focusing on the period 2000-2017, we used the latest data available on malaria case incidence and other determinants of economic growth, as well as macro-econometric methods that are now the professional norm. In our preferred specification using a fixed-effects model, a 10% decrease in malaria incidence was associated with an increase in income per capita of nearly 0.3% on average and a 0.11 percentage point faster per capita growth per annum. Greater average income gains were expected among higher burden countries and those with lower income. Growth of industries with the same level of labor intensity was found to be significantly slower in countries with higher malaria incidence. To analyze the causal impact of malaria on economic outcomes, we used malaria treatment failure and pyrethroid-only insecticide resistance as exogeneous instruments in two-stage least squares estimations. Despite several methodological challenges, as expected in these types of analyses, our findings confirm the intrinsic link between malaria and economic growth and underscore the importance of malaria control in the agenda for sustainable development.

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A resolution for eradicating malaria, if passed by the World Health Assembly (WHA), will have a distracting effect on all countries with malaria. The continued prevalence of malaria is indicative of weak public health infrastructure. True, smallpox was eradicated by international efforts following WHA resolution: the success factor was primary prevention using a safe and effective vaccine. A resolution to eradicate polio was passed in 1988, with a target year of 2000, but even in 2019 success is not within reach. Public health experts are hesitant to move forward with measles eradication before polio is eradicated. Country by country elimination of malaria is a better way, ensuring the strengthening of public health infrastructure, with many other health benefits.

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Several efforts are being made now for malaria elimination with a goal for eradication. New tools and strategies are being developed and there is currently renewed political engagement and interest. Several technical groups have produced a guide on elimination for policymakers and indicated different research questions to be addressed. The World Health Assembly resolution and the United Nations General Assembly convened a high-level roundtable "From High Burden to High Impact: Getting back on track to end Malaria". In Africa, the Head of states pronounced a vision for an Africa free of malaria and launched the slogan "Zero malaria starts with me". Massive efforts to sustain research capacity in the endemic countries will be critical. It will be important to both increase domestic financing, and advocate to sustain and increase funding from major donor countries. It is unethical to continue to observe deaths of so many children in malaria endemic countries, the most vulnerable populations. Considering malaria eradication as a vision and working with all the opportunities we now have could accelerate the process. Eliminating malaria with a country regional approach and progressing step by step will give us consistent information on our way towards eradication.

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BACKGROUND: Malaria is a huge global health burden due to its mortality, morbidity and cost to economies. It is necessary to eliminate the disease in all countries where possible to achieve the World Health Organization target of > 90% reduction by 2030. Successful previous campaigns suggest elimination is feasible in Peru. However, the incidence has recently been rising, focalized to the region of Loreto. Currently, the distribution of long-lasting insecticide-treated nets (LLINs) is a major part of Peru's malaria control strategy, however these may be having a limited effect in Loreto, because of the recent behavioural adaption of the mosquito vector, Anopheles darlingi, to earlier biting times, as well as local perceptions and practices towards LLINs. It was, therefore, necessary to investigate how perceptions, practices and lifestyle factors affect the efficacy of LLINs in Loreto. METHODS: Qualitative research was carried out in 5 rural communities along the Iquitos-Nauta Road in Loreto, which have increased exposure and have received nets in a distribution scheme prior to the study. Twenty semi-structured interviews as well as observations of the bed nets were conducted in participants' homes, using a topic guide. Thematic content analysis was used to produce the findings. RESULTS: All participants viewed malaria prevention as a high priority, and the use of bed nets was deeply embedded in the culture. They expressed preference for LLINs over traditional-type nets. However there were too few LLINs distributed, participants did not maintain the nets correctly, washed them too frequently and did not repair holes. The earlier mosquito biting times were also problematic. Additionally, poor housing construction and proximity to mosquito breeding sites further increased transmission. CONCLUSION: The positive findings in attitudes of the respondents can be used to improve malaria control in these communities. Interventions providing education on effective LLIN use should be implemented. A change in strategy away from vector control methods is also necessary, as these do not provide long-term protection due to the adaptability of An. darlingi. Interventions focusing on parasite control are recommended, and socio-economic factors which increase malaria risk should be addressed.

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Older travellers are at higher risk of malaria-related morbidity and mortality compared with younger people. Yet, prevention of malaria in this specific group of travellers is a long-standing issue in travel medicine. The aim of this research was to synthetize the existing evidence about this important topic, highlighting older travellers' attitudes and practises toward malaria prevention. Searches were performed on PubMed, Embase, EuropePMC, Web of Science, WHOLIS and LILACS databases for relevant studies reporting malaria prevention measures in older travellers. To measure malaria prevention in the older traveller population, the main information outcomes were obtained from the ABCD framework that included travellers' 'Awareness' towards pre-travel health advice, their utilisation of 'Bite-prevention measures' and adherence to 'Chemoprophylaxis'. Data on 'Diagnosis'-related outcomes were excluded for not being measures of malaria prevention. Three evaluators independently selected studies, extracted data and assessed the quality of the included articles. The research protocol was registered with PROSPERO (protocol number CRD42019124202). Out of the 899 titles and abstracts screened, 13 articles were included in this review synthesis. These studies included a wide range of interventions for malaria prevention: no relevant differences in pre-travel healthcare attendance were found depending on age; older travellers were found to be less likely to comply with bite-prevention measures; three high-quality studies reported that adherence to chemoprophylaxis significantly increased with age, while three studies did not find age-related differences in travellers' adherence. Overall, prevention of malaria in the older traveller has received limited attention from the scientific community. Older travellers seem to be less likely to comply with bite-prevention measures, but there was high heterogeneity across the reports. This population group demands particular attention and tailored health advice before travelling to malaria endemic areas. More research is required on how to improve malaria prevention in the older traveller.

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Malaria has infected and killed humans since long before history began recording evidence of the parasite's pernicious influence. The extraordinary discoveries of the Plasmodium parasite by Charles Louis Alphonse Laveran in 1880, and the role of the Anopheles mosquito in transmission of the parasite to humans by Sir Ronald Ross in 1897, led to an understanding of the parasite life cycle and ultimately to the development of interventions that would interrupt disease transmission. Almost as soon as the insecticidal properties of dichlorodiphenyltrichloroethane (DDT) were discovered in 1939, the public health profession began battling to achieve a world free of malaria. That vision persists as the aim of all malariologists and, increasingly, the goal of all nations that remain endemic for malaria. This chapter recounts the history of malaria eradication and elimination efforts throughout the world and focuses on the current status of country-led and country-driven malaria elimination programs, along with the technical strategies recommended by the World Health Organization (WHO) for achievement of malaria elimination.

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BACKGROUND: China has achieved zero indigenous malaria case report in 2017. However, along with the increasing of international cooperation development, there is an increasing number of imported malaria cases from Chinese nationals returning from malaria-affected countries. Previous studies have focused on malaria endemic areas in China. There is thus limited information on non-endemic areas in China, especially on the performance of malaria surveillance and response in health facilities. METHODS: A comparative retrospective study was carried out based on routine malaria surveillance data collected from 2013 to 2017. All imported malaria cases reported within the mainland of China were included. Variables used in the comparative analysis between cases in former endemic and former non-endemic areas, included age, gender and occupation, destination of overseas travel, Plasmodium species and patient health outcome. Monthly aggregated data was used to compare seasonal and spatial characteristics. Geographical distribution and spatial-temporal aggregation analyses were conducted. Time to diagnosis and report, method of diagnosis, and level of reporting/diagnosing health facilities were used to assess performance of health facilities. RESULTS: A total of 16 733 malaria cases, out of which 90 were fatal, were recorded in 31 provinces. The majority of cases (96.2%) were reported from former malaria endemic areas while 3.8% were reported from former non-malaria endemic areas. Patients in the age class from 19 to 59 years and males made the highest proportion of cases in both areas. There were significant differences between occupational categories in the two areas (P <  0.001). In former endemic areas, the largest proportion of cases was among outdoor workers (80%). Two peaks (June, January) and three peaks (June, September and January) were found in former endemic and former non-endemic areas, respectively. Time between the onset of symptoms and diagnosis at clinics was significantly different between the two areas at different level of health facilities (P <  0.05). CONCLUSIONS: All the former non-endemic areas are now reporting imported malaria cases. However, the largest proportion of imported cases is still reported from former endemic areas. Health facilities in former endemic areas outperformed those in former non-endemic areas. Information, treatment, and surveillance must be provided for expatriates while capacity building and continuous training must be implemented at health facilities in China.

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BACKGROUND: Primaquine is the only widely used drug that prevents Plasmodium vivax malaria relapses, but adherence to the standard 14-day regimen is poor. We aimed to assess the efficacy of a shorter course (7 days) of primaquine for radical cure of vivax malaria. METHODS: We did a randomised, double-blind, placebo-controlled, non-inferiority trial in eight health-care clinics (two each in Afghanistan, Ethiopia, Indonesia, and Vietnam). Patients (aged ≥6 months) with normal glucose-6-phosphate dehydrogenase (G6PD) and presenting with uncomplicated vivax malaria were enrolled. Patients were given standard blood schizontocidal treatment and randomly assigned (2:2:1) to receive 7 days of supervised primaquine (1·0 mg/kg per day), 14 days of supervised primaquine (0·5 mg/kg per day), or placebo. The primary endpoint was the incidence rate of symptomatic P vivax parasitaemia during the 12-month follow-up period, assessed in the intention-to-treat population. A margin of 0·07 recurrences per person-year was used to establish non-inferiority of the 7-day regimen compared with the 14-day regimen. This trial is registered at ClinicalTrials.gov (NCT01814683). FINDINGS: Between July 20, 2014, and Nov 25, 2017, 2336 patients were enrolled. The incidence rate of symptomatic recurrent P vivax malaria was 0·18 (95% CI 0·15 to 0·21) recurrences per person-year for 935 patients in the 7-day primaquine group and 0·16 (0·13 to 0·18) for 937 patients in the 14-day primaquine group, a difference of 0·02 (-0·02 to 0·05, p=0·3405). The incidence rate for 464 patients in the placebo group was 0·96 (95% CI 0·83 to 1·08) recurrences per person-year. Potentially drug-related serious adverse events within 42 days of starting treatment were reported in nine (1·0%) of 935 patients in the 7-day group, one (0·1%) of 937 in the 14-day group and none of 464 in the control arm. Four of the serious adverse events were significant haemolysis (three in the 7-day group and one in the 14-day group). INTERPRETATION: In patients with normal G6PD, 7-day primaquine was well tolerated and non-inferior to 14-day primaquine. The short-course regimen might improve adherence and therefore the effectiveness of primaquine for radical cure of P vivax malaria. FUNDING: UK Department for International Development, UK Medical Research Council, UK National Institute for Health Research, and the Wellcome Trust through the Joint Global Health Trials Scheme (MR/K007424/1) and the Bill & Melinda Gates Foundation (OPP1054404).

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BACKGROUND: The emergence and spread of resistance in Plasmodium falciparum malaria to artemisinin combination therapies in the Greater Mekong subregion poses a major threat to malaria control and elimination. The current study is part of a multi-country, open-label, randomised clinical trial (TRACII, 2015-18) evaluating the efficacy, safety, and tolerability of triple artemisinin combination therapies. A very high rate of treatment failure after treatment with dihydroartemisinin-piperaquine was observed in Thailand, Cambodia, and Vietnam. The immediate public health importance of our findings prompted us to report the efficacy data on dihydroartemisinin-piperaquine and its determinants ahead of the results of the overall trial, which will be published later this year. METHODS: Patients aged between 2 and 65 years presenting with uncomplicated P falciparum or mixed species malaria at seven sites in Thailand, Cambodia, and Vietnam were randomly assigned to receive dihydroartemisinin-piperaquine with or without mefloquine, as part of the TRACII trial. The primary outcome was the PCR-corrected efficacy at day 42. Next-generation sequencing was used to assess the prevalence of molecular markers associated with artemisinin resistance (kelch13 mutations, in particular Cys580Tyr) and piperaquine resistance (plasmepsin-2 and plasmepsin-3 amplifications and crt mutations). This study is registered with ClinicalTrials.gov, number NCT02453308. FINDINGS: Between Sept 28, 2015, and Jan 18, 2018, 539 patients with acute P falciparum malaria were screened for eligibility, 292 were enrolled, and 140 received dihydroartemisinin-piperaquine. The overall Kaplan-Meier estimate of PCR-corrected efficacy of dihydroartemisinin-piperaquine at day 42 was 50·0% (95% CI 41·1-58·3). PCR-corrected efficacies for individual sites were 12·7% (2·2-33·0) in northeastern Thailand, 38·2% (15·9-60·5) in western Cambodia, 73·4% (57·0-84·3) in Ratanakiri (northeastern Cambodia), and 47·1% (33·5-59·6) in Binh Phuoc (southwestern Vietnam). Treatment failure was associated independently with plasmepsin2/3 amplification status and four mutations in the crt gene (Thr93Ser, His97Tyr, Phe145Ile, and Ile218Phe). Compared with the results of our previous TRACI trial in 2011-13, the prevalence of molecular markers of artemisinin resistance (kelch13 Cys580Tyr mutations) and piperaquine resistance (plasmepsin2/3 amplifications and crt mutations) has increased substantially in the Greater Mekong subregion in the past decade. INTERPRETATION: Dihydroartemisinin-piperaquine is not treating malaria effectively across the eastern Greater Mekong subregion. A highly drug-resistant P falciparum co-lineage is evolving, acquiring new resistance mechanisms, and spreading. Accelerated elimination of P falciparum malaria in this region is needed urgently, to prevent further spread and avoid a potential global health emergency. FUNDING: UK Department for International Development, Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council, and National Institutes of Health.

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BACKGROUND: Biological rhythms allow organisms to compartmentalise and coordinate behaviours, physiologies, and cellular processes with the predictable daily rhythms of their environment. There is increasing recognition that the biological rhythms of mosquitoes that vector parasites are important for global health. For example, whether perturbations in blood foraging rhythms as a consequence of vector control measures can undermine disease control. To address this, we explore the impacts of altered timing of blood-feeding on mosquito life history traits and malaria transmission. METHODS: We present three experiments in which Anopheles stephensi mosquitoes were fed in the morning or evening on blood that had different qualities, including: (i) chemical-induced or (ii) Plasmodium chabaudi infection-induced anaemia; (iii) Plasmodium berghei infection but no anaemia; or (iv) stemming from hosts at different times of day. We then compared whether time-of-day variation in blood meal characteristics influences mosquito fitness proxies relating to survival and reproduction, and malaria transmission proxies. RESULTS: Mosquito lifespan is not influenced by the time-of-day they received a blood meal, but several reproductive metrics are affected, depending on other blood characteristics. Overall, our data suggest that receiving a blood meal in the morning makes mosquitoes more likely to lay eggs, lay slightly sooner and have a larger clutch size. In keeping with previous work, P. berghei infection reduces mosquito lifespan and the likelihood of laying eggs, but time-of-day of blood-feeding does not impact upon these metrics nor on transmission of this parasite. CONCLUSION: The time-of-day of blood-feeding does not appear to have major consequences for mosquito fitness or transmission of asynchronous malaria species. If our results from a laboratory colony of mosquitoes living in benign conditions hold for wild mosquitoes, it suggests that mosquitoes have sufficient flexibility in their physiology to cope with changes in biting time induced by evading insecticide-treated bed nets. Future work should consider the impact of multiple feeding cycles and the abiotic stresses imposed by the need to forage for blood during times of day when hosts are not protected by bed nets.

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BACKGROUND: In 2010, Uganda Malaria Control Programme distributed cost-free mosquito bed nets to households with children under-five years and pregnant women in selected sub-counties. We assessed the factors associated with sleeping under costfree mosquito nets among children under-five years in Nyakayojo sub-county, Mbarara District, Uganda. METHODS: 381 households with at least a child under-five years and benefited from cost-free bed nets in Nyakayojo were randomly selected. Caregivers of children were interviewed using a questionnaire. RESULTS: 74% children slept under bed nets a night before the study. Children from households with ≥2 nets [aOR=1.75; 95% CI: 1.09-2.81, p=0.02], female caregiver [aOR=2.11; 95% CI: 1.16-3.79, p=0.01] and children from households that did not face problems (skin irritation, torn nets, suffocation, night sweating, nasal congestion and candle fire) when sleeping under bed nets [aOR=1.81; 95% CI: 1.10-2.98, p=0.02] were more likely to use nets. Main reason for not sleeping under a net was damage to the net (47.1%). CONCLUSION: The proportion of children sleeping under nets was comparable to MDG target. Improvements in use of mosquito nets by children can be achieved through increasing number of nets in a household.

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Background: Malaria is one of the infectious diseases of greatest interest to the scientific community and of greatest concern to international health authorities. Traditionally, the focus has been on Plasmodium falciparum, the parasite that causes the most severe form of the disease in Africa. However, in the last twenty years, the Plasmodium vivax parasite, responsible for a large number of cases in Latin America, the Middle East, South and Southeast Asia, the Horn of Africa, and Oceania, has also generated enormous interest due, among other things, to the published evidence that it can cause severe malaria. Methods: In this paper, the international scientific publication on malaria and P. vivax has been analyzed using the Scopus database to try to define global trends in this field of study. Results: It has been shown that events such as the emergence of resistance to certain drugs can break a trend. The important role of non-malaria-endemic countries such as the USA or Switzerland in malaria research is also evident. Conclusions: International cooperation will be essential for the eradication of the disease. Moreover, in this sense, the general vision given by the bibliometric analysis of malaria caused by P. vivax is fundamental to paint the picture regarding the current situation and encourage international cooperation and control efforts.

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BACKGROUND: Sustaining achievements in malaria control and making progress toward malaria elimination requires coordinated funding. We estimated domestic malaria spending by source in 106 countries that were malaria-endemic in 2000-16 or became malaria-free after 2000. METHODS: We collected 36 038 datapoints reporting government, out-of-pocket (OOP), and prepaid private malaria spending, as well as malaria treatment-seeking, costs of patient care, and drug prices. We estimated government spending on patient care for malaria, which was added to government spending by national malaria control programmes. For OOP malaria spending, we used data reported in National Health Accounts and estimated OOP spending on treatment. Spatiotemporal Gaussian process regression was used to ensure estimates were complete and comparable across time and to generate uncertainty. FINDINGS: In 2016, US$4·3 billion (95% uncertainty interval [UI] 4·2-4·4) was spent on malaria worldwide, an 8·5% (95% UI 8·1-8·9) per year increase over spending in 2000. Since 2000, OOP spending increased 3·8% (3·3-4·2) per year, amounting to $556 million (487-634) or 13·0% (11·6-14·5) of all malaria spending in 2016. Governments spent $1·2 billion (1·1-1·3) or 28·2% (27·1-29·3) of all malaria spending in 2016, increasing 4·0% annually since 2000. The source of malaria spending varied depending on whether countries were in the malaria control or elimination stage. INTERPRETATION: Tracking global malaria spending provides insight into how far the world is from reaching the malaria funding target of $6·6 billion annually by 2020. Because most countries with a high burden of malaria are low income or lower-middle income, mobilising additional government resources for malaria might be challenging. FUNDING: The Bill & Melinda Gates Foundation.

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Ten countries have reported pfhrp2/pfhrp3 gene deletions since the first observation of pfhrp2-deleted parasites in 2012. In a previous study (Watson et al., 2017), we characterised the drivers selecting for pfhrp2/3 deletions and mapped the regions in Africa with the greatest selection pressure. In February 2018, the World Health Organization issued guidance on investigating suspected false-negative rapid diagnostic tests (RDTs) due to pfhrp2/3 deletions. However, no guidance is provided regarding the timing of investigations. Failure to consider seasonal variation could cause premature decisions to switch to alternative RDTs. In response, we have extended our methods and predict that the prevalence of false-negative RDTs due to pfhrp2/3 deletions is highest when sampling from younger individuals during the beginning of the rainy season. We conclude by producing a map of the regions impacted by seasonal fluctuations in pfhrp2/3 deletions and a database identifying optimum sampling intervals to support malaria control programmes.

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