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Background In March 2020, the government of Uganda implemented a strict lockdown policy in response to the COVID-19 pandemic. Interrupted time series analysis (ITSA) was performed to assess whether major changes in outpatient attendance, malaria burden, and case management occurred after the onset of the COVID-19 epidemic in rural Uganda. Methods Individual level data from all outpatient visits collected from April 2017 to March 2021 at 17 facilities were analysed. Outcomes included total outpatient visits, malaria cases, non-malarial visits, proportion of patients with suspected malaria, proportion of patients tested using rapid diagnostic tests (RDTs), and proportion of malaria cases prescribed artemether-lumefantrine (AL). Poisson regression with generalized estimating equations and fractional regression was used to model count and proportion outcomes, respectively. Pre-COVID trends (April 2017-March 2020) were used to predict the’expected’ trend in the absence of COVID-19 introduction. Effects of COVID-19 were estimated over two six-month COVID-19 time periods (April 2020-September 2020 and October 2020–March 2021) by dividing observed values by expected values, and expressed as ratios. Results A total of 1,442,737 outpatient visits were recorded. Malaria was suspected in 55.3% of visits and 98.8% of these had a malaria diagnostic test performed. ITSA showed no differences between observed and expected total outpatient visits, malaria cases, non-malarial visits, or proportion of visits with suspected malaria after COVID-19 onset. However, in the second six months of the COVID-19 time period, there was a smaller mean proportion of patients tested with RDTs compared to expected (relative prevalence ratio (RPR) = 0.87, CI (0.78–0.97)) and a smaller mean proportion of malaria cases prescribed AL (RPR = 0.94, CI (0.90–0.99)). Conclusions In the first year after the COVID-19 pandemic arrived in Uganda, there were no major effects on malaria disease burden and indicators of case management at these 17 rural health facilities, except for a modest decrease in the proportion of RDTs used for malaria diagnosis and the mean proportion of malaria cases prescribed AL in the second half of the COVID-19 pandemic year. Continued surveillance will be essential to monitor for changes in trends in malaria indicators so that Uganda can quickly and flexibly respond to challenges imposed by COVID-19.

The coronavirus disease (COVID-19) pandemic, which started in the late 2019 in China, has become an unforeseen challenge to the health care system of all the countries in the world. Establishment of a mass specific diagnostics of emergent infection caused by the coronavirus SARS-CoV-2 was one of the problems that needed immediate solution. This review presents the technologies used for the specific diagnostics of COVID-19. The advantages and limitations of the most common methodologies for detection of the pathogen or virus-specific antibodies are discussed. Detection of the virus genome fragments by reverse transcription and real-time polymerase chain reaction (rRT-PCR) allowed to achieve high accuracy of diagnosis. From the beginning of the pandemic, this method has been considered as the "gold" standard, despite the limitations associated with its high cost, complexity and the need for testing in specialized laboratories. Cheaper immunological methods have insufficient diagnostic efficiency and can be used only as complements to molecular testing. The review also presents promising methods of specific diagnostics of COVID-19 which are based on molecular genetic technologies, characterized by simplicity and rapidity, do not require expensive equipment and can be performed in points of care., Пандемия коронавирусной болезни (COVID-19), которая стартовала в конце 2019 года в Китае, стала непредсказуемым вызовом для системы здравоохранения абсолютно всех стран мира. Среди проблем, которые требовали немедленного решения, стало налаживание массовой специфической диа гностики эмерджентной инфекции, вызванной коронавирусом SARS-CoV-2. В данном обзоре представлены технологии, применяемые для специфической диагностики COVID-19. Обсуждаются преимущества и ограничения наиболее распространенных методологий, направленных на выявление возбудителя или специфических к нему антител. Выявление фрагментов генома вируса с помощью полимеразной цепной реакции с обратной транскрипцией в реальном времени (рОТ-ПЦР) позволило достичь высокой точности диагностики. С самого начала пандемии и до сих пор этот метод считается «золотым» стандартом, несмотря на ограничения, связанные с его высокой стоимостью, трудоемкостью и необходимостью проведения исследований в специализированных лабораториях. Более дешевые иммунологические методы имеют недостаточную диагностическую эффективность и могут использоваться только как дополнение к молекулярному тестированию. В обзоре также представлены перспективные методы специфической диагностики COVID-19, которые основаны на молекулярно-генетических технологиях, характеризуются простотой и быстротой выполнения, не требуют дорогостоящего оборудования и могут выполняться в пунктах оказания медицинской помощи., Пандемія коронавірусної хвороби (COVID-19), яка стартувала наприкінці 2019 року в Китаї, стала непередбаченим викликом для системи охорони здоров’я абсолютно усіх країн світу. Серед проблем, які потребували негайного вирішення, стало налагодження масової специфічної діагностики емерджентної інфекції, спричиненої коронавірусом SARS-CoV-2. У даному огляді представлені технології, які застосовуються для специфічної діагностики COVID-19. Обговорено переваги та обмеження найбільш поширених методологій, спрямованих на виявлення збудника або специфічних до нього антитіл. Виявлення фрагментів геному вірусу за допомогою полімеразної ланцюгової реакції зі зворотною транскрипцією в реальному часі (рЗТ-ПЛР) дозволило досягти високої точності діагностики. З самого початку пандемії та дотепер цей метод вважається «золотим» стандартом, незважаючи на обмеження, пов’язані з його високою вартістю, трудомісткістю та необхідністю проведення досліджень в спеціалізованих лабораторіях. Більш дешеві імунологічні методи мають недостатню діагностичну ефективність і можуть використовуватися лише як додаткові до молекулярного тестування. В огляді також представлені перспективні методи специфічної діагностики COVID-19, які засновані на молекулярно-генетичних технологіях, характеризуються простотою та швидкістю виконання, не потребують дорогого обладнання і можуть виконуватись в пунктах надання медичної допомоги.

This study was supported by the National Council for Scientific and Technological Development?Brazil (CNPq)?Grant 302292/2017-9 as well as by the Evandro Chagas Institute?s own budget resource Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Programa de P?s-Gradua??o em epidemiologia e Vigil?ncia em Sa?de. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. State Health Department of Acre. Hemon?cleo Cruzeiro do Sul. Cruzeiro do Sul, AC, Brazil. Central Public Health Laboratory of Amazonas. Manaus, AM, Brazil. Heitor Vieira Dourado Tropical Medicine Foundation. Manaus, AM, Brazil / Funda??o Oswaldo cruz. Le?nidas and Maria Deane Institute. Manaus, AM, Brazil. Ministry of Health. Health Surveillance Secretariat. Department of Immunization and Communicable Diseases. General Coordination for the Monitoring of Zoonoses and Malaria Vector Transmission Diseases. Malaria Technical Group. Bras?lia, DF, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / National Council for Scientific and Technological Development. Bras?lia, DF, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Histidine-rich proteins 2 and 3 gene (pfhrp2 and pfhrp3) deletions affect the efficacy of rapid diagnostic tests (RDTs) based on the histidine-rich protein 2 (HRP2), compromising the correct identification of the Plasmodium falciparum species. Therefore, molecular surveillance is necessary for the investigation of the actual prevalence of this phenomenon and the extent of the disappearance of these genes in these areas and other South American countries, thus guiding national malaria control programs on the appropriate use of RDTs. This study aimed to evaluate the pfhrp2 and pfhrp3 gene deletion in P. falciparum in endemic areas of the Brazilian Amazon. Aliquots of DNA from the biorepository of the Laboratory of Basic Research in Malaria, Evandro Chagas Institute, with a positive diagnosis for P. falciparum infection as determined by microscopy and molecular assays, were included. Monoinfection was confirmed by nested-polymerase chain reaction assay, and DNA quality was assessed by amplification of the merozoite surface protein-2 gene (msp2). The pfhrp2 and pfhrp3 genes were amplified using primers for the region between exons 1 and 2 and for all extension of exon 2. Aliquots of DNA from 192 P. falciparum isolates were included in the study, with 68.7% (132/192) from the municipality of Cruzeiro do Sul (Acre) and 31.3% (60/192) from Manaus (Amazonas). Of this total, 82.8% (159/192) of the samples were considered of good quality. In the state of Acre, 71.7% (71/99) showed pfhrp2 gene deletion and 94.9% (94/99) showed pfhrp3 gene deletion, while in the state of Amazonas, 100.0% (60/60) of the samples showed pfhrp2 gene deletion and 98.3% (59/60) showed pfhrp3 gene deletion. Moreover, 79.8% (127/159) of isolates displayed gene deletion. Our findings confirm the presence of a parasite population with high frequencies of pfhrp2 and pfhrp3 gene deletions in the Brazilian Amazon region. This suggests reconsidering the use of HRP2-based RDTs in the Acre and Amazonas states and calls attention to the importance of molecular surveillance and mapping of pfhrp2/pfhrp3 deletions in this area and in other locations in the Amazon region to guarantee appropriate patient care, control and ultimately contribute to achieving P. falciparum malaria elimination

Background Rapid diagnostic Tests (RDTs) for malaria enable diagnostic testing at primary care facilities in resource-limited settings, where weak infrastructure limits the use of microscopy. In 2010, Ghana adopted a test-before-treat guideline for malaria, with RDT use promoted to facilitate diagnosis. Yet healthcare practitioners still treat febrile patients without testing, or despite negative malaria test results. Few studies have explored RDT implementation beyond the notions of provider or patient acceptability. The aim of this study was to identify the factors directly influencing malaria RDT implementation at primary care facilities in a Ghanaian district. Methods Qualitative interviews, focus groups and direct observations were conducted with 50 providers at six purposively selected primary care facilities in the Atwima–Nwabiagya district. Data were analysed thematically. Results RDT implementation was hampered by: (1) healthcare delivery constraints (weak supply chain, limited quality assurance and control, inadequate guideline emphasis, staffing limitations); (2) provider perceptions (entrenched case-management paradigms, limited preparedness for change); (3) social dynamics of care delivery (expected norms of provider-patient interaction, test affordability); and (4) limited provider engagement in policy processes leading to fragmented implementation of health sector reform. Conclusion Limited health system capacity, socio-economic, political, and historical factors hampered malaria RDT implementation at primary care facilities in the study district. For effective RDT implementation providers must be: (1) adequately enabled through efficient allocation and management of essential healthcare commodities; (2) appropriately empowered with the requisite knowledge and skill through ongoing, effective professional development; and (3) actively engaged in policy dialogue to demystify socio-political misconceptions that hinder health sector reform policies from improving care delivery. Clear, consistent guideline emphasis, with complementary action to address deep-rooted provider concerns will build their confidence in, and promote uptake of recommended policies, practices, and technology for diagnosing malaria.

The idea of a private sector subsidy programme of artemisinin-based combination therapies (ACTs) was first proposed in 2004. Since then, several countries around the world have hosted pilot projects or programmes on subsidized ACTs and/or the Affordable Medicines Facility-malaria programme (AMFm). Overall the private sector subsidy programmes of ACTs have been effective in increasing availability of ACTs in the private sector and driving down average prices but struggled to crowd out antimalarial monotherapies. The results obtained from this ambitious strategy should inform policy makers in the designing of future interventions aimed to control malaria morbidity and mortality. Among the interventions recently proposed, a subsidy of rapid diagnostic tests (RDTs) in the private sector has been recommended by governments and international donors to cope with over-treatment with ACTs and to delay the emergence of resistance to artemisinin. In order to improve the cost-effectiveness of co-paid RDTs, we should build on the lessons we learned from almost 10 years of private sector subsidy programmes of ACTs in malaria-endemic countries.

Background Rapid diagnostic tests (RDTs) have become an essential tool in the contemporary malaria control and management programmes in the world. This study aims to evaluate the performance of two commonly used RDTs for malaria diagnosis in the China-Myanmar border area. Methods A total 606 febrile patients in the China-Myanmar border were recruited to this study and were diagnosed for malaria infections by microscopy, two RDTs tests (Pf/Pan device, and Pv/Pf device) and nested PCR. Results Malaria parasites were found in 143 patients by microscopy, of which 51, 73, and 19 were Plasmodium falciparum, Plasmodium vivax and P. falciparum/P. vivax mixed infections, respectively. Compared to microscopy, the sensitivity of the Pf/Pan device was 88.6% for P. falciparum and 69.9% for P. vivax with the specificity of 90.4%. For a subset of 350 patients, the sensitivity of the Pf/Pan device and Pv/Pf device for detection of P. falciparum was 87.5% and 91.7%, respectively; and for detection of P. vivax was 72.0% and 73.8%, respectively. The specificity of the Pf/Pan device and Pv/Pf device was 94.3% and 96.5%, respectively. Nested PCR detected malaria parasites in 174 of 606 samples, of which 67, 79, two and 26 were P. falciparum, P. vivax, P. ovale and P. falciparum/P. vivax mixed infections, respectively. Compared to nested PCR, all other methods had sensitivity below 80%, suggesting that a significant number of cases were missed. Conclusions Compared to PCR, both microscopy and RDTs had lower sensitivities. RDTs had similar performance to microscopy for P. falciparum diagnosis, but performed worse for P. vivax diagnosis. Other RDT products should be selected with higher sensitivity (and good specificity) for both P. falciparum and P. vivax diagnosis.

Background Accurate diagnosis and prompt treatment of pregnancy-associated malaria (PAM) are key aspects in averting adverse pregnancy outcomes. Microscopy is the gold standard in malaria diagnosis, but it has limited detection and availability. When used appropriately, rapid diagnostic tests (RDTs) could be an ideal diagnostic complement to microscopy, due to their ease of use and adequate sensitivity in detecting even sub-microscopic infections. Polymerase chain reaction (PCR) is even more sensitive, but it is mainly used for research purposes. The accuracy and reliability of RDTs in diagnosing PAM was evaluated using microscopy and PCR. Methods A cohort of pregnant women in north-eastern Tanzania was followed throughout pregnancy for detection of plasmodial infection using venous and placental blood samples evaluated by histidine rich protein 2 (HRP-2) and parasite lactate dehydrogenase (pLDH) based RDTs (Parascreen™) or HRP-2 only (Paracheck Pf® and ParaHIT®f), microscopy and nested Plasmodium species diagnostic PCR. Results From a cohort of 924 pregnant women who completed the follow up, complete RDT and microscopy data was available for 5,555 blood samples and of these 442 samples were analysed by PCR. Of the 5,555 blood samples, 49 ((proportion and 95% confidence interval) 0.9% [0.7 -1.1]) samples were positive by microscopy and 91 (1.6% [1.3-2.0]) by RDT. Forty-six (50.5% [40.5 - 60.6]) and 45 (49.5% [39.4 – 59.5]) of the RDT positive samples were positive and negative by microscopy, respectively, whereas nineteen (42.2% [29.0 - 56.7]) of the microscopy negative, but RDT positive, samples were positive by PCR. Three (0.05% [0.02 - 0.2]) samples were positive by microscopy but negative by RDT. 351 of the 5,461 samples negative by both RDT and microscopy were tested by PCR and found negative. There was no statistically significant difference between the performances of the different RDTs. Conclusions Microscopy underestimated the real burden of malaria during pregnancy and RDTs performed better than microscopy in diagnosing PAM. In areas where intermittent preventive treatment during pregnancy may be abandoned due to low and decreasing malaria risk and instead replaced with active case management, screening with RDT is likely to identify most infections in pregnant women and out-performs microscopy as a diagnostic tool.

Background: In Zambia, there has been a large scaling up of interventions to control malaria in recent years including the deployment of rapid diagnostic tests (RDTs) to improve malaria surveillance data as well as guide malaria treatment in health facilities. The practical challenge is the impact of RDT results on subsequent management of patients. This study explored the role of RDTs in malaria diagnosis and the health workers’ adherence to test results. Methods: An observational prospective study was carried out at health centres in four districts, namely Chibombo, Chingola, Chipata, and Choma. Children under the age of five years with history of fever were recruited and the clinicians’ use of RDT results was observed to establish whether prescriptions were issued prior to the availability of parasitological results or after, and whether RDT results influenced their prescriptions. Results: Of the 2, 393 recruited children, 2, 264 had both RDT and microscopic results. Two in three (68.6%) children were treated with anti-malarials despite negative RDT results and almost half (46.2%) of these were prescribed Coartem®. Only 465 (19.4%) of the 2,393 children were prescribed drugs before receiving laboratory results. A total of 76.5% children were prescribed drugs after laboratory results. Children with RDT positive results were 2.66 (95% CI (2.00, 3.55)) times more likely to be prescribed anti-malarial drugs. Children who presented with fever at admission (although history of fever or presence of fever at admission was an entry criterion) were 42% less likely to be prescribed an anti-malarial drug compared to children who had no fever (AOR = 0.58; 95% CI (0.52, 0.65)). It was noted that proportions of children who were RDT- and microscopy-positive significantly declined over the years from 2005 to 2008. Conclusions: RDTs may contribute to treatment of febrile illness by confirming malaria cases from non-malaria cases in children under the age of five. However, the adherence of the health workers to prescribing anti-malarials to only RDT-positive cases at health facility level will still require to be explored further as their role is crucial in more precise reporting of malaria cases in this era towards malaria elimination as the target.

Background During pregnancy, malaria infection with Plasmodium falciparum or Plasmodium vivax is related to adverse maternal health and poor birth outcomes. Diagnosis of malaria, during pregnancy, is complicated by the absence or low parasite densities in peripheral blood. Diagnostic methods, other than microscopy, are needed for detection of placental malaria. Therefore, the diagnostic accuracy of rapid diagnostic tests (RDTs), detecting antigen, and molecular techniques (PCR), detecting DNA, for the diagnosis of Plasmodium infections in pregnancy was systematically reviewed. Methods MEDLINE, EMBASE and Web of Science were searched for studies assessing the diagnostic accuracy of RDTs, PCR, microscopy of peripheral and placental blood and placental histology for the detection of malaria infection (all species) in pregnant women. Results The results of 49 studies were analysed in metandi (Stata), of which the majority described P. falciparum infections. Although both placental and peripheral blood microscopy cannot reliably replace histology as a reference standard for placental P. falciparum infection, many studies compared RDTs and PCR to these tests. The proportion of microscopy positives in placental blood (sensitivity) detected by peripheral blood microscopy, RDTs and PCR are respectively 72% [95% CI 62-80], 81% [95% CI 55-93] and 94% [95% CI 86-98]. The proportion of placental blood microscopy negative women that were negative in peripheral blood microscopy, RDTs and PCR (specificity) are 98% [95% CI 95-99], 94% [95% CI 76-99] and 77% [95% CI 71-82]. Based on the current data, it was not possible to determine if the false positives in RDTs and PCR are caused by sequestered parasites in the placenta that are not detected by placental microscopy. Conclusion The findings suggest that RDTs and PCR may have good performance characteristics to serve as alternatives for the diagnosis of malaria in pregnancy, besides any other limitations and practical considerations concerning the use of these tests. Nevertheless, more studies with placental histology as reference test are urgently required to reliably determine the accuracy of RDTs and PCR for the diagnosis of placental malaria. P. vivax-infections have been neglected in diagnostic test accuracy studies of malaria in pregnancy.

Background Rural populations experience several barriers to accessing clinical facilities for malaria diagnosis. Increasing penetration of ICT and mobile-phones and subsequent m-Health applications can contribute overcoming such obstacles. Methods GIS is used to evaluate the feasibility of m-Health technologies as part of anti-malaria strategies. This study investigates where in Uganda: (1) malaria affects the largest number of people; (2) the application of m-Health protocol based on the mobile network has the highest potential impact. Results About 75% of the population affected by Plasmodium falciparum malaria have scarce access to healthcare facilities. The introduction of m-Health technologies should be based on the 2G protocol, as 3G mobile network coverage is still limited. The western border and the central-Southeast are the regions where m-Health could reach the largest percentage of the remote population. Six districts (Arua, Apac, Lira, Kamuli, Iganga, and Mubende) could have the largest benefit because they account for about 28% of the remote population affected by falciparum malaria with access to the 2G mobile network. Conclusions The application of m-Health technologies could improve access to medical services for distant populations. Affordable remote malaria diagnosis could help to decongest health facilities, reducing costs and contagion. The combination of m-Health and GIS could provide real-time and geo-localized data transmission, improving anti-malarial strategies in Uganda. Scalability to other countries and diseases looks promising.