Mass Screening and Treatment on the Basis of Results of a Plasmodium falciparum-Specific Rapid Diagnostic Test Did Not Reduce Malaria Incidence in Zanzibar

Background. Seasonal increases in malaria continue in hot spots in Zanzibar. Mass screening and treatment (MSAT) may help reduce the reservoir of infection; however, it is unclear whether rapid diagnostic tests (RDTs) detect a sufficient proportion of low-density infections to influence subsequent transmission. Methods. Two rounds of MSAT using Plasmodium falciparum-specific RDT were conducted in 5 hot spots (population, 12 000) in Zanzibar in 2012. In parallel, blood samples were collected on filter paper for polymerase chain reaction (PCR) analyses. Data on confirmed malarial parasite infections from health facilities in intervention and hot spot control areas were monitored as proxy for malaria transmission. Results. Approximately 64% of the population (7859) were screened at least once. P. falciparum prevalence, as measured by RDT, was 0.2% (95% confidence interval [CI], .1%-.3%) in both rounds, compared with PCR measured prevalences (for all species) of 2.5% (95% CI, 2.1%-2.9%) and 3.8% (95% CI, 3.2%-4.4%) in rounds 1 and 2, respectively. Two fifths (40%) of infections detected by PCR included non-falciparum species. Treatment of RDT-positive individuals (4% of the PCR-detected parasite carriers) did not reduce subsequent malaria incidence, compared with control areas. Conclusions. Highly sensitive point-of-care diagnostic tools for detection of all human malaria species are needed to make MSAT an effective strategy in settings where malaria elimination programs are in the pre-elimination phas

Efficacy, persistence and vector susceptibility to pirimiphos-methyl (Actellic® 300CS) insecticide for indoor residual spraying in Zanzibar

Background Indoor residual spraying (IRS) of households with insecticide is a principal malaria vector control intervention in Zanzibar. In 2006, IRS using the pyrethroid lambda-cyhalothrine was introduced in Zanzibar. Following detection of pyrethroid resistance in 2010, an insecticide resistance management plan was proposed, and IRS using bendiocarb was started in 2011. In 2014, bendiocarb was replaced by pirimiphos methyl. This study investigated the residual efficacy of pirimiphos methyl (Actellic® 300CS) sprayed on common surfaces of human dwellings in Zanzibar. Methods The residual activity of Actellic 300CS was determined over 9 months through bioassay tests that measured the mortality of female Anopheles mosquitoes, exposed to sprayed surfaces under a WHO cone. The wall surfaces included; mud wall, oil or water painted walls, lime washed wall, un-plastered cement block wall and stone blocks. Insecticide susceptibility testing was done to investigate the resistance status of local malaria vectors against Actellic 300CS using WHO protocols; Anopheline species were identified using PCR methods. Results Baseline tests conducted one-day post-IRS revealed 100 % mortality on all sprayed surfaces. The residual efficacy of Actellic 300CS was maintained on all sprayed surfaces up to 8 months post-IRS. However, the bioassay test conducted 9 months post-IRS showed the 24 h mortality rate to be ≤80 % for lime wash, mud wall, water paint and stone block surfaces. Only oil paint surface retained the recommended residual efficacy beyond 9 months post-IRS, with mortality maintained at ≥97 %. Results of susceptibility tests showed that malaria vectors in Zanzibar were fully (100 %) susceptible to Actellic 300CS. The predominant mosquito vector species was An. arabiensis (76.0 %) in Pemba and An. gambiae (83.5 %) in Unguja. Conclusion The microencapsulated formulation of pirimiphos methyl (Actellic 300CS) is a highly effective and appropriate insecticide for IRS use in Zanzibar as it showed a relatively prolonged residual activity compared to other products used for the same purpose. The insecticide extends the residual effect of IRS thereby making it possible to effectively protect communities with a single annual spray round reducing overall costs. The insecticide proved to be a useful alternative in insecticide resistance management plans

Potential Opportunities and Challenges of Deploying Next Generation Sequencing and CRISPR-Cas Systems to Support Diagnostics and Surveillance Towards Malaria Control and Elimination in Africa

Recent developments in molecular biology and genomics have revolutionized biology and medicine mainly in the developed world. The application of next generation sequencing (NGS) and CRISPR-Cas tools is now poised to support endemic countries in the detection, monitoring and control of endemic diseases and future epidemics, as well as with emerging and re-emerging pathogens. Most low and middle income countries (LMICs) with the highest burden of infectious diseases still largely lack the capacity to generate and perform bioinformatic analysis of genomic data. These countries have also not deployed tools based on CRISPR-Cas technologies. For LMICs including Tanzania, it is critical to focus not only on the process of generation and analysis of data generated using such tools, but also on the utilization of the findings for policy and decision making. Here we discuss the promise and challenges of NGS and CRISPR-Cas in the context of malaria as Africa moves towards malaria elimination. These innovative tools are urgently needed to strengthen the current diagnostic and surveillance systems. We discuss ongoing efforts to deploy these tools for malaria detection and molecular surveillance highlighting potential opportunities presented by these innovative technologies as well as challenges in adopting them. Their deployment will also offer an opportunity to broadly build in-country capacity in pathogen genomics and bioinformatics, and to effectively engage with multiple stakeholders as well as policy makers, overcoming current workforce and infrastructure challenges. Overall, these ongoing initiatives will build the malaria molecular surveillance capacity of African researchers and their institutions, and allow them to generate genomics data and perform bioinformatics analysis in-country in order to provide critical information that will be used for real-time policy and decision-making to support malaria elimination on the continent

Using Mobile Technology to Facilitate Reactive Case Detection of Malaria

ObjectiveThis presentation will share findings from more than three years ofusing mobile technology for reactive case detection (RACD) to helpeliminate malaria in a well-defined geographic area. It will reviewthe concepts of RACD, the application of mobile technology, lessonslearned from more than three years of application, and considerationsin applying this technology in other malaria elimination contexts.IntroductionZanzibar is comprised primarily of two large islands with apopulation of 1.3 million. Indoor Residual Spraying (IRS) campaigns,distribution of long-lasting insecticide treated bed nets (LLINs),and use of Rapid Diagnostic Tests (RDTs) have reduced Malariaprevalence from 39% in 2005 to less than 1% in 2011-2012. Asmalaria burden decreases, there is an increasing need to track andfollow up individual cases to contain transmission that could lead toresurgence. One method being used to achieve these aims is reactivecase detection (RACD).RACD is generally understood to be triggered whenever a case isidentified by passive case detection. The response involves visiting thehousehold of the newly reported case and screening family members.Depending on program protocol, it may also involve screeningneighbors within a defined radius. RACD has been used or testedin Cambodia, China, India, Peru, Senegal, Swaziland, Tanzania,and Zambia. RACD can be resource intensive. Several studies raisequestions concerning whether and how RACD can be prioritized andtargeted effectively as case numbers continue to decline.MethodsSince September 2012 Zanzibar Malaria Elimination Programme(ZAMEP) has used RACD to limit onward transmission, reduce thelocal parasite reservoir, and gather data needed improve programeffectiveness. Zanzibar is one of very few malaria eliminationcontexts using a mobile technology system to support RACD.1Thissystem, called the Malaria Case Notification system (MCN) usesmobile software called Coconut Surveillance.Coconut Surveillance is free and open source software designed formalaria elimination. It includes an interactive SMS system for casenotification, a mobile software application designed to guide mobilecase workers through RACD, and an analytics software applicationdesigned for surveillance and response program managers.Data were collected in the Coconut Surveillance database formore than three years, beginning in September 2012. Reports weremonitored in real time and periodically to assess RACD responsetimes against protocol targets, case trends, case locations, and otherdata. Geographical Information System (GIS) software was usedto produce detailed maps of case households. Three independentassessments were conducted of various aspects of the malariasurveillance system.ResultsFrom September 2012 to December 2015, Coconut Surveillancehas helped malaria surveillance officers in Zanzibar respond tomore than 8,617 (84%) reported cases of malaria, complete nearly10,245 household visits, test more than 36,185 household members,and identify and treat 2,032 previously unknown cases. The averagenumber of RACD activities occurring within 48 hours increased from72% in 2013 to 89% in 2015. The number of household membersscreened during RACD also increased from 7,589 in 2013 to 14,987in 2015. Challenges included incomplete registers at health carefacilities, lack of transport, inadequate training for clinicians andsurveillance officers, and insufficient communication to the affectedcommunities.ConclusionsIn Zanzibar twenty malaria surveillance officers equipped withinexpensive Android tablets and motorbikes are keeping malariaprevalence at less than 1%. The effectiveness of the system mightbe enhanced by improving training for clinicians and surveillanceofficers, ensuring the availability of transportation for surveillanceofficers, and improving communications to the affected communities.These results suggest key considerations for applying this and similarsystems in other malaria elimination contexts

Using Mobile Technology to Facilitate Reactive Case Detection of Malaria

ObjectiveThis presentation will share findings from more than three years ofusing mobile technology for reactive case detection (RACD) to helpeliminate malaria in a well-defined geographic area. It will reviewthe concepts of RACD, the application of mobile technology, lessonslearned from more than three years of application, and considerationsin applying this technology in other malaria elimination contexts.IntroductionZanzibar is comprised primarily of two large islands with apopulation of 1.3 million. Indoor Residual Spraying (IRS) campaigns,distribution of long-lasting insecticide treated bed nets (LLINs),and use of Rapid Diagnostic Tests (RDTs) have reduced Malariaprevalence from 39% in 2005 to less than 1% in 2011-2012. Asmalaria burden decreases, there is an increasing need to track andfollow up individual cases to contain transmission that could lead toresurgence. One method being used to achieve these aims is reactivecase detection (RACD).RACD is generally understood to be triggered whenever a case isidentified by passive case detection. The response involves visiting thehousehold of the newly reported case and screening family members.Depending on program protocol, it may also involve screeningneighbors within a defined radius. RACD has been used or testedin Cambodia, China, India, Peru, Senegal, Swaziland, Tanzania,and Zambia. RACD can be resource intensive. Several studies raisequestions concerning whether and how RACD can be prioritized andtargeted effectively as case numbers continue to decline.MethodsSince September 2012 Zanzibar Malaria Elimination Programme(ZAMEP) has used RACD to limit onward transmission, reduce thelocal parasite reservoir, and gather data needed improve programeffectiveness. Zanzibar is one of very few malaria eliminationcontexts using a mobile technology system to support RACD.1Thissystem, called the Malaria Case Notification system (MCN) usesmobile software called Coconut Surveillance.Coconut Surveillance is free and open source software designed formalaria elimination. It includes an interactive SMS system for casenotification, a mobile software application designed to guide mobilecase workers through RACD, and an analytics software applicationdesigned for surveillance and response program managers.Data were collected in the Coconut Surveillance database formore than three years, beginning in September 2012. Reports weremonitored in real time and periodically to assess RACD responsetimes against protocol targets, case trends, case locations, and otherdata. Geographical Information System (GIS) software was usedto produce detailed maps of case households. Three independentassessments were conducted of various aspects of the malariasurveillance system.ResultsFrom September 2012 to December 2015, Coconut Surveillancehas helped malaria surveillance officers in Zanzibar respond tomore than 8,617 (84%) reported cases of malaria, complete nearly10,245 household visits, test more than 36,185 household members,and identify and treat 2,032 previously unknown cases. The averagenumber of RACD activities occurring within 48 hours increased from72% in 2013 to 89% in 2015. The number of household membersscreened during RACD also increased from 7,589 in 2013 to 14,987in 2015. Challenges included incomplete registers at health carefacilities, lack of transport, inadequate training for clinicians andsurveillance officers, and insufficient communication to the affectedcommunities.ConclusionsIn Zanzibar twenty malaria surveillance officers equipped withinexpensive Android tablets and motorbikes are keeping malariaprevalence at less than 1%. The effectiveness of the system mightbe enhanced by improving training for clinicians and surveillanceofficers, ensuring the availability of transportation for surveillanceofficers, and improving communications to the affected communities.These results suggest key considerations for applying this and similarsystems in other malaria elimination contexts

Using Mobile Technology to Help Eliminate Malaria in Zanzibar

Decision support systems for malaria elimination must support rapid response to contain outbreaks. The integrated mobile system in Zanzibar has been recognized as one of the most advanced in the world. The system consists of a simple facility-based case notification system that uses common feature phones, and a mobile application for Android tablet computers. The resulting system enables rapid response to new cases, helps to rapidly diagnose and treat secondary case, and provides high-quality data for identifying hot spots, trends, and transmission patterns. This presentation will review the history, technology, results, lessons-learned, and applicability to other contexts

Mass screening and treatment on the basis of results of a Plasmodium falciparum-specific rapid diagnostic test did not reduce malaria incidence in Zanzibar

Seasonal increases in malaria continue in hot spots in Zanzibar. Mass screening and treatment (MSAT) may help reduce the reservoir of infection; however, it is unclear whether rapid diagnostic tests (RDTs) detect a sufficient proportion of low-density infections to influence subsequent transmission.; Two rounds of MSAT using Plasmodium falciparum-specific RDT were conducted in 5 hot spots (population, 12 000) in Zanzibar in 2012. In parallel, blood samples were collected on filter paper for polymerase chain reaction (PCR) analyses. Data on confirmed malarial parasite infections from health facilities in intervention and hot spot control areas were monitored as proxy for malaria transmission.; Approximately 64% of the population (7859) were screened at least once. P. falciparum prevalence, as measured by RDT, was 0.2% (95% confidence interval [CI], .1%-.3%) in both rounds, compared with PCR measured prevalences (for all species) of 2.5% (95% CI, 2.1%-2.9%) and 3.8% (95% CI, 3.2%-4.4%) in rounds 1 and 2, respectively. Two fifths (40%) of infections detected by PCR included non-falciparum species. Treatment of RDT-positive individuals (4% of the PCR-detected parasite carriers) did not reduce subsequent malaria incidence, compared with control areas.; Highly sensitive point-of-care diagnostic tools for detection of all human malaria species are needed to make MSAT an effective strategy in settings where malaria elimination programs are in the pre-elimination phase

Artemisinin combination therapy mass drug administration in a setting of low malaria endemicity: programmatic coverage and adherence during an observational study in Zanzibar

Abstract Background Mass drug administration (MDA) appears to be effective in reducing the risk of malaria parasitaemia. This study reports on programmatic coverage and compliance of MDA using artemisinin-based combination therapy (ACT) in four shehias (smallest administration unit) that had been identified as hotspots through Zanzibar’s malaria case notification surveillance system. Methods Mass drug administration was done in four shehias selected on the basis of: being an established malaria hot spot; having had mass screening and treatment (MSaT) 2–6 weeks previously; and exceeding the epidemic alert threshold of 5 cases within a week even after MSaT. Communities were sensitized and MDA was conducted using a house-to-house approach. All household members, except pregnant women and children aged less than 2 months, were provided with ACT medicine. Two weeks after the MDA campaign, a survey was undertaken to investigate completion of ACT doses. Results A total of 8816 [97.1% of eligible; 95% confidence interval (CI) 96.8–97.5] people received ACT. During post MDA surveys, 2009 people were interviewed: 90.2% reported having completed MDA doses; 1.9% started treatment but did not complete dosage; 4.7% did not take treatment; 2.0% were absent during MDA and 1.2% were ineligible (i.e. infants <2 months and pregnant women). Main reasons for failure to complete treatment were experience of side-effects and forgetting to take subsequent doses. Failure to take treatment was mainly due to fear of side-effects, reluctance due to lack of malaria symptoms and caregivers forgetting to give medication to children. Conclusion Mass drug administration for malaria was well accepted by communities at high risk of malaria in Zanzibar, with high participation and completion rates. Further work to investigate the potential of MDA in accelerating Zanzibar’s efforts towards malaria elimination should be pursued

Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions among patients enrolled at 100 health facilities throughout Tanzania: February to July 2021

Abstract Plasmodium falciparum with the histidine rich protein 2 gene (pfhrp2) deleted from its genome can escape diagnosis by HRP2-based rapid diagnostic tests (HRP2-RDTs). The World Health Organization (WHO) recommends switching to a non-HRP2 RDT for P. falciparum clinical case diagnosis when pfhrp2 deletion prevalence causes ≥ 5% of RDTs to return false negative results. Tanzania is a country of heterogenous P. falciparum transmission, with some regions approaching elimination and others at varying levels of control. In concordance with the current recommended WHO pfhrp2 deletion surveillance strategy, 100 health facilities encompassing 10 regions of Tanzania enrolled malaria-suspected patients between February and July 2021. Of 7863 persons of all ages enrolled and providing RDT result and blood sample, 3777 (48.0%) were positive by the national RDT testing for Plasmodium lactate dehydrogenase (pLDH) and/or HRP2. A second RDT testing specifically for the P. falciparum LDH (Pf-pLDH) antigen found 95 persons (2.5% of all RDT positives) were positive, though negative by the national RDT for HRP2, and were selected for pfhrp2 and pfhrp3 (pfhrp2/3) genotyping. Multiplex antigen detection by laboratory bead assay found 135/7847 (1.7%) of all blood samples positive for Plasmodium antigens but very low or no HRP2, and these were selected for genotyping as well. Of the samples selected for genotyping based on RDT or laboratory multiplex result, 158 were P. falciparum DNA positive, and 140 had sufficient DNA to be genotyped for pfhrp2/3. Most of these (125/140) were found to be pfhrp2+/pfhrp3+, with smaller numbers deleted for only pfhrp2 (n = 9) or only pfhrp3 (n = 6). No dual pfhrp2/3 deleted parasites were observed. This survey found that parasites with these gene deletions are rare in Tanzania, and estimated that 0.24% (95% confidence interval: 0.08% to 0.39%) of false-negative HRP2-RDTs for symptomatic persons were due to pfhrp2 deletions in this 2021 Tanzania survey. These data provide evidence for HRP2-based diagnostics as currently accurate for P. falciparum diagnosis in Tanzania