Natacha Protopopoff, Jacklin F Mosha, Eliud Lukole, Jacques D Charlwood, Alexandra Wright, Charles D Mwalimu, Alphaxard Manjurano, Franklin W Mosha, William Kisinza, Immo Kleinschmidt, Mark Rowland

The PBO long-lasting insecticidal net and non-pyrethroid indoor residual spraying interventions showed improved control of malaria transmission compared with standard long-lasting insecticidal nets where pyrethroid resistance is prevalent and either intervention could be deployed to good effect. As a result, WHO has since recommended to increase coverage of PBO long-lasting insecticidal nets. Combining indoor residual spraying with pirimiphos-methyl and PBO long-lasting insecticidal nets provided no additional benefit compared with PBO long-lasting insecticidal nets alone or standard long-lasting insecticidal nets plus indoor residual spraying.

Immo Kleinschmidt, John Bradley, Tessa Bellamy Knox, Abraham Peter Mnzava, Hmooda Toto Kafy, Charles Mbogo, Bashir Adam Ismail, Jude D Bigoga, Alioun Adechoubou, Kamaraju Raghavendra, Jackie Cook, Elfatih M Malik, Zinga José Nkuni, Michael Macdonald, Nabie Bayoh, Eric Ochomo, Etienne Fondjo, Herman Parfait Awono-Ambene, Josiane Etang, Martin Akogbeto, Rajendra M Bhatt, Mehul Kumar Chourasia, Dipak K Swain, Teresa Kinyari, Krishanthi Subramaniam, Achille Massougbodji, Mariam Okê-Sopoh, Aurore Ogouyemi-Hounto

Irrespective of resistance, populations in malaria endemic areas should continue to use long-lasting insecticidal nets to reduce their risk of infection. As nets provide only partial protection, the development of additional vector control tools should be prioritised to reduce the unacceptably high malaria burden.

Roberto Amato, Richard D Pearson, Jacob Almagro-Garcia, Chanaki Amaratunga, Pharath Lim, Seila Suon, Sokunthea Sreng, Eleanor Drury, Jim Stalker, Olivo Miotto, Rick M Fairhurst, Dominic P Kwiatkowski

The KEL1/PLA1 co-lineage emerged in the same year that dihydroartemisinin–piperaquine became the first-line antimalarial drug in western Cambodia and spread rapidly thereafter, displacing other artemisinin-resistant parasite lineages. These findings have important implications for management of the global health risk associated with the current outbreak of multidrug-resistant malaria in southeast Asia.

The West African Network for Clinical Trials of Antimalarial Drugs (WANECAM)

Pyronaridine–artesunate and dihydroartemisinin–piperaquine treatment and retreatment of malaria were well tolerated with efficacy that was non-inferior to first-line ACTs. Greater access to these efficacious treatments in west Africa is justified.

Thuy-Nhien Nguyen, Lorenz von Seidlein, Tuong-Vy Nguyen, Phuc-Nhi Truong, Son Do Hung, Huong-Thu Pham, Tam-Uyen Nguyen, Thanh Dong Le, Van Hue Dao, Mavuto Mukaka, Nicholas PJ Day, Nicholas J White, Arjen M Dondorp, Guy E Thwaites, Tran Tinh Hien

Persistent largely asymptomatic P vivax and P falciparum infections are common in this area of low seasonal malaria transmission. Infections with low-density parasitaemias can develop into much higher density infections at a later time, which are likely to sustain malaria endemicity.

Anders B Björkman

Malaria parasitaemias are usually suppressed or eliminated in the human host by the immune system and antimalarial drugs. Low-density asymptomatic infections are therefore expected to be common in high-endemic areas with high herd immunity and premunition in the population. However, it is becoming increasingly apparent, with sensitive molecular PCR-based diagnostics, that submicroscopical asymptomatic infections are also common in low-endemic areas,1 despite residents having little protective or suppressive immunity.

Ric N Price, Nicholas J White

Substantial gains have been made in reducing the global burden of malaria, much of which can be attributed to greater access to prompt diagnosis and highly effective treatment. However, as endemic countries commit to eliminating malaria, more aggressive interventions are needed to target the large number of apparently healthy individuals who harbour transmissible malaria parasites. Although most national antimalarial guidelines recommend artemisinin combination therapy for the management of uncomplicated falciparum malaria, chemopreventive strategies have generally adopted non-artemisinin combination therapy regimens such as sulfadoxine-pyrimethamine and amodiaquine.

Didier Ménard, Jérôme Clain, Frédéric Ariey

Over the past decade, the burden of malaria has been greatly reduced in the Greater Mekong subregion, although artemisinin-resistant parasites have emerged,1,2 and high rates of treatment failure on dihydroartemisinin–piperaquine have been reported in Cambodia since 2012.3–7 Unsurprisingly, this situation is linked to the aggressive strategies implemented in this region to eliminate malaria and the inevitable massive reduction in the Plasmodium falciparum parasite population, leading to selection of best-adapted, multidrug-resistant parasites.

Onisillos Sekkides

In 2007 The Lancet Infectious Diseases published a special issue focussing on malaria in pregnancy. This highlighted that slow progress on prevention was being made at the time and that there were many research gaps needing to be addressed. A decade later we update readers with a new Series of three reports covering the burden, pathology, costs, prevention, and treatment of uncomplicated and severe malaria during pregnancy.

Elizabeth A Ashley, Aung Pyae Phyo, Charles J Woodrow

Following unsuccessful eradication attempts there was a resurgence of malaria towards the end of the 20th century. Renewed control efforts using a range of improved tools, such as long-lasting insecticide-treated bednets and artemisinin-based combination therapies, have more than halved the global burden of disease, but it remains high with 445 000 deaths and more than 200 million cases in 2016. Pitfalls in individual patient management are delayed diagnosis and overzealous fluid resuscitation in severe malaria.

Stephen J Rogerson, Meghna Desai, Alfredo Mayor, Elisa Sicuri, Steve M Taylor, Anna M van Eijk

Over the past 10 years, knowledge of the burden, economic costs, and consequences of malaria in pregnancy has improved, and the prevalence of malaria caused by Plasmodium falciparum has declined substantially in some geographical areas. In particular, studies outside of Africa have increased the evidence base of Plasmodium vivax in pregnancy. Rapid diagnostic tests have been poor at detecting malaria in pregnant women, while PCR has shown a high prevalence of low density infection, the clinical importance of which is unknown.

Meghna Desai, Jenny Hill, Silke Fernandes, Patrick Walker, Christopher Pell, Julie Gutman, Kassoum Kayentao, Raquel Gonzalez, Jayne Webster, Brian Greenwood, Michel Cot, Feiko O ter Kuile

Malaria remains one of the most preventable causes of adverse birth outcomes. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine–pyrimethamine is used to prevent malaria, but resistance to this drug combination has decreased its efficacy and new alternatives are needed. In Africa, a meta-analysis showed three-course or monthly IPTp with sulfadoxine–pyrimethamine to be safe and more effective than the original two-course sulfadoxine–pyrimethamine strategy, prompting WHO to update its policy in 2012.

Paul Joseph Brown

I arrived at the Kasungu District Hospital in the morning and found the grounds outside filled with hundreds of people waiting in the hot sun to be seen by the nurses and doctors. Many had walked for hours from villages in the surrounding rural area to attend the clinic and to be screened for tuberculosis, malaria, and other infectious diseases. Some families were camped next to the hospital. One of the nurses remarked that most of the folks in the waiting area would test positive for malaria, but there were no medications available for them.

The American Journal of Tropical Medicine and Hygiene

Authors: Potchen MJ, Kampondeni SD, Seydel KB, Haacke EM, Sinyangwe SS, Mwenechanya M, Glover SJ, Milner DA, Zeli E, Hammond CA, Utriainen D, Lishimpi K, Taylor TE, Birbeck GL Abstract The hallmark of pediatric cerebral malaria (CM) is sequestration of parasitized red blood cells in the cerebral microvasculature. Malawi-based research using 0.35 Tesla (T) magnetic resonance imaging (MRI) established that severe brain swelling is associated with fatal CM, but swelling etiology remains unclear. Autopsy and clinical studies suggest several potential etiologies, but limitations of 0.35 T MRI precluded optimal investigations into swelling pathophysiology. A 1.5 T MRI in Zambia allowed for further investigations including susceptibility-weighted imaging (SWI). SWI is an ideal sequence fo...

Abstract Background Malaria is one of the leading causes of death worldwide. This study aimed to determine the trend of malaria among febrile patients seeking treatment over 17 year (1997–2013) at Adi Arkay, Northwest Ethiopia. Methods A 17-year malaria microscopy data were extracted retrospectively at Adi Arkay health centre. Time series and curve estimation analysis were used to evaluate trends in the data. Pearson’s Chi square test was also used to describe associations of variables. Results Over 17 years, 20,483 blood films were requested for malaria diagnosis at the health centre. Out of this, 7428 (36.1%) were microscopically confirmed malaria cases. Plasmodium falciparum, Plasmodium vivax, and their mixed infection accounted for 68.85, 28.79, and 2.34% of all malaria cases, respectively. There was a remarkable reduction of overall malaria during the 17 years. Malaria was reported in all age groups of both sexes, but its positivity rate was significantly higher in males and in the 15–24 years than their counterparts. Conclusion In relative terms, the overall positivity rate of malaria in the area over 17 years showed a significant reduction, but its magnitude as a public health problem is still alarming. Plasmodium falciparum played a significant role in the remarkable drop of overall malaria in the area, whereas vivax malaria remained unchanged. Therefore, control measures should continue to strengthen targeting both predominant malaria parasites in the area.

Fidock D.

Plasmodium falciparummalariavolatile organic compoundsbreath metabolitesbiomarkersdiagnostic teststerpenesmosquito attractants…

Vaughan, A. M., Sack, B. K., Dankwa, D., Minkah, N., Nguyen, T., Cardamone, H., Kappe, S. H. I.

Genetically attenuated malaria parasites (GAP) that arrest during liver stage development are powerful immunogens and afford complete and durable protection against sporozoite infection. Late liver stage-arresting GAP provide superior protection against sporozoite challenge in mice when compared to early live stage-arresting attenuated parasites. However, very few late liver stage-arresting GAP have been generated to date. Therefore, identification of additional loci that are critical for late liver stage development and can be used to generate novel late liver stage-arresting GAPs are of importance. We further explored genetic attenuation in Plasmodium yoelii by combining two gene deletions, PlasMei2 and Liver-Specific Protein 2 (LISP2), that each cause late liver stage arrest with varying degrees of infrequent breakthrough to blood stage infection. The dual gene deletion resulted in a synthetic lethal phenotype that caused complete attenuation in a highly susceptible mouse strain. P. yoelii plasmei2–/lisp2– arrested late in liver stage development and did not persist in livers beyond three days after infection. Immunization with this GAP elicited robust protective antibody responses in outbred and inbred mice against sporozoites, liver stages and blood stages as well as eliciting protective liver resident T cells. The immunization afforded protection against both sporozoite challenge and blood stage challenge. These findings provide evidence that completely attenuated late liver stage-arresting GAP are achievable via the synthetic lethal approach and might enable a path forward for the creation of a completely attenuated late liver stage-arresting P. falciparum GAP.

Sabine Dittrich, Latsaniphone Boutthasavong, Dala Keokhamhoung, Weerawat Phuklia, Scott B. Craig, Suhella M. Tulsiani, Mary-Anne Burns, Steven L. Weier, David A. B. Dance, Viengmon Davong, Manivanh Vongsouvath, Mayfong Mayxay, Rattanaphone Phetsouvanh, Paul N. Newton and Kate Woods

Abstract. Leptospirosis is a globally important cause of acute febrile illness, and a common cause of non-malarial fever in Asia, Africa, and Latin America. Simple rapid diagnostic tests (RDTs) are needed to enable health-care workers, particularly in low resource settings, to diagnose leptospirosis early and give timely targeted treatment. This study compared four commercially available RDTs to detect human IgM against Leptospira spp. in a head-to-head prospective evaluation in Mahosot Hospital, Lao PDR. Patients with an acute febrile illness consistent with leptospirosis (N = 695) were included in the study during the 2014 rainy season. Samples were tested with four RDTs: (“Test-it” [Life Assay, Cape Town, South Africa; N = 418]; “Leptorapide” [Linnodee, Ballyclare, Northern Ireland; N = 492]; “Dual Path Platform” [DPP] [Chembio, Medford, NY; N = 530]; and “SD-IgM” [Standard Diagnostics, Yongin, South Korea; N = 481]). Diagnostic performance characteristics were calculated and compared with a composite reference standard combining polymerase chain reaction (PCR) (rrs), microscopic agglutination tests (MATs), and culture. Of all patients investigated, 39/695 (5.6%) were positive by culture, PCR, or MAT. The sensitivity and specificity of the RDTs ranged greatly from 17.9% to 63.6% and 62.1% to 96.8%, respectively. None of the investigated RDTs reached a sensitivity or specificity of > 90% for detecting Leptospira infections on admission. In conclusion, our investigation highlights the challenges associated with Leptospira diagnostics, particularly in populations with multiple exposures. These findings emphasize the need for extensive prospective evaluations in multiple endemic settings to establish the value of rapid tools for diagnosing fevers to allow targeting of antibiotics.

Abstract Background While China is a major manufacturer of artemisinin and its derivatives, it lags as a global leader in terms of the total export value of anti-malarial drugs as finished pharmaceutical products ready for marketing and use by patients. This may be due to the limited number of World Health Organization (WHO) prequalified anti-malarial drugs from China. Understanding the reasons for the slow progress of WHO prequalification (PQ) in China can help improve the current situation and may lead to greater efforts in malaria eradication by Chinese manufacturers. Methods In-depth interviews were conducted in China between November 2014 and December 2016. A total of 26 key informants from central government agencies, pharmaceutical companies, universities, and research institutes were interviewed, all of which had current or previous experience overseeing or implementing anti-malarial research and development in China. Results Chinese anti-malarial drugs that lack WHO PQ are mainly exported for use in the African private market. High upfront costs with unpredictable benefits, as well as limited information and limited technical support on WHO PQ, were reported as the main barriers to obtain WHO PQ for anti-malarial drugs by respondents from Chinese pharmaceutical companies. Potential incentives identified by respondents included tax relief, human resource training and consultation, as well as other incentives related to drug approval, such as China’s Fast Track Channel. Conclusions Government support, as well as innovative incentives and collaboration mechanisms are needed for further adoption of WHO PQ for anti-malarial drugs in China.

Abstract Background Malaria remains a public health problem in Zimbabwe. However, malaria elimination has become a foreseeable prospect with Matabeleland South Province making significant gains towards halting local malaria transmission. This study reviews malaria elimination progress and challenges to date utilizing the World Health Organization’s Malaria Programme Review framework. Results Between 2011 and 2015, malaria incidence was less than one case per 1000 population at risk in all districts save for Beitbridge and Gwanda. The majority of cases were from Beitbridge with local transmission in the same. Incidence declined in Bulilima (p = 0.01), Gwanda (p = 0.72) and Umzingwane (p = 0.44), increasing in Beitbridge (p = 0.35), Insiza (p = 0.79) and Mangwe (p = 0.60). Overall provincial incidence declined although this was not statistically significant. Malaria transmission was bimodal, with a major peak in April and a minor peak in October. A case based malaria surveillance system existed but was not real-time. Foci response guidelines were not domesticated. Artemisinin formed the backbone of case management regimens with primaquine for gametocyte clearance. Indoor residual spraying coverages were below the national target of 95% for rooms targeted for spraying. Conclusion Matabeleland South province has set precedence for targeting sub-national malaria elimination in Zimbabwe. This experience may prove useful for national scale up. There is need to improve surveillance, foci response and intensification of activities to halt residual malaria transmission in Beitbridge District.

The American Journal of Tropical Medicine and Hygiene

Authors: Killeen GF Abstract The term epidemiological entomology was first coined by Garrett-Jones over half a century ago1 but has been out of fashion for far too long.2 In this issue, Sougoufara et al.3 illustrate clearly just how insightful such an approach can be when applied to characterizing key properties of a dynamic malaria transmission system before and after the scale-up of vector control with long-lasting insecticidal nets in Dielmo, Senegal. Using simple analytical models first pioneered by Garrett-Jones himself,4 these authors illustrate how not all may be as it appears based on direct interpretation of entomological data alone. Allowing for the fact that malaria transmission requires both humans and mosquitoes to meet at the same time and place, they show that insect...

The morbidity and mortality that are associated with hepatitis B virus (HBV) infection have been overshadowed by the public health prominence of other infectious diseases, including human immunodeficiency virus (HIV) infection, tuberculosis, and malaria. There is a dawning realization that the……

Abstract Background Nearly half of the world’s population (3.2 billion people) were at risk of malaria in 2015, and resistance to current therapies is a major concern. While the standard of care includes drug combinations, there is a pressing need to identify new combinations that can bypass current resistance mechanisms. In the work presented here, a combined transcriptional drug repositioning/discovery and machine learning approach is proposed. Methods The integrated approach utilizes gene expression data from patient-derived samples, in combination with large-scale anti-malarial combination screening data, to predict synergistic compound combinations for three Plasmodium falciparum strains (3D7, DD2 and HB3). Both single compounds and combinations predicted to be active were prospectively tested in experiment. Results One of the predicted single agents, apicidin, was active with the AC50 values of 74.9, 84.1 and 74.9 nM in 3D7, DD2 and HB3 P. falciparum strains while its maximal safe plasma concentration in human is 547.6 ± 136.6 nM. Apicidin at the safe dose of 500 nM kills on average 97% of the parasite. The synergy prediction algorithm exhibited overall precision and recall of 83.5 and 65.1% for mild-to-strong, 48.8 and 75.5% for moderate-to-strong and 12.0 and 62.7% for strong synergies. Some of the prospectively predicted combinations, such as tacrolimus-hydroxyzine and raloxifene-thioridazine, exhibited significant synergy across the three P. falciparum strains included in the study. Conclusions Systematic approaches can play an important role in accelerating discovering novel combinational therapies for malaria as it enables selecting novel synergistic compound pairs in a more informed and cost-effective manner.

Yerlikaya S, Campillo A, Gonzalez I.

AbstractDespite the increased use and worldwide distribution of malaria rapid diagnostic tests (RDTs) which distinguish between Plasmodium falciparum and non-falciparum species, little is known about their performance for detecting Plasmodium knowlesi (Pk), Plasmodium malariae (Pm), and Plasmodium ovale (Po). The objective of this review is to analyze results of published studies evaluating the diagnostic accuracy of malaria RDTs in detecting Pk, Pm and Po mono-infections.MEDLINE, EMBASE, Web of Science and CENTRAL databases were systematically searched to identify studies which reported on the performance of RDTs in detecting Pk, Pm,Po mono-infections.Among 40 studies included in the review, three reported on Pk, eight on Pm, five on Po, one on Pk and Pm, and 23 on Pm and Po infections. In the meta-analysis, estimates of sensitivities of RDTs in detecting Pk infections ranged from 2% to 48%. Test performances for Pm and Po infections were less accurate and highly heterogeneous, mainly due to the small number of samples tested.Limited data available suggest that malaria RDTs show suboptimal performance for detecting Pk, Pm,Po infections. New improved RDTs as well as appropriately designed, cross-sectional studies to demonstrate their usefulness in the detection of neglected Plasmodium species, are urgently needed.

Ross Boyce, Raquel Reyes, Corinna Keeler, Michael Matte, Moses Ntaro, Edgar Mulogo and Mark J. Siedner

Abstract. The clinical epidemiology of severe malaria among patients presenting to peripheral health centers has not been well described. We conducted a prospective, observational cohort study to describe the epidemiology and clinical manifestations of severe malaria in a highland area of declining transmission intensity in Western Uganda. Individuals presenting with a history of fever were screened with a malaria rapid diagnostic test (RDT). We prepared blood smears and conducted clinical and laboratory testing for those with a positive RDT. We defined severe malaria in accordance with World Health Organization guidelines for research and epidemiological studies. A total of 6,641 individuals underwent testing for malaria. Ninety-six of 1,462 (6.6%) participants with confirmed parasitemia satisfied the criteria for severe malaria. The incidence of severe malaria peaked between 2 and 3 years of age (incidence rate ratio = 17.1, 95% confidence interval = 8.4–34.9, P < 0.001) and then declined steadily until age 10. However, we also found a second peak among those ≥ 50 years of age. Severe anemia was uncommon, detected in only 5.3% of cases. Instead, shock (22.2%) and lactic acidosis (19.4%) were most frequently encountered. Our results suggest that the clinical characteristics of severe malaria presenting to rural, peripheral health centers may be different than previously observed in referral centers. These findings merit further investigation into the optimal methods for identification and management of severe malaria in rural health centers in the region.

Abstract Background Malaria is an infectious disease caused by parasites of the genus Plasmodium, of which Plasmodium vivax and Plasmodium falciparum are the major species that cause the disease in humans. As there are relatively few alternatives for malaria treatment, it is necessary to search for new chemotherapeutic options. Colombia possesses a great diversity of plants, which are potential sources of new compounds of medical interest. Thus, in this study the antiplasmodial effect of extracts from two species of plants from the families Simaroubaceae and Picramniaceae (Picramnia latifolia and Picrolemma huberi) was evaluated in vitro and in vivo. These plants were chosen because they contain secondary metabolites with interesting medicinal effects. Results The ethanolic extracts of both species were highly active with IC50: 1.2 ± 0.19 µg/mL for P. latifolia and IC50: 0.05 ± 0.005 µg/mL for P. huberi. The P. latifolia extract had a stage specific effect on trophozoites and inhibited parasite growth in vivo by 52.1 ± 3.4%, evaluated at 1000 mg/kg in Balb/c mice infected with Plasmodium berghei. On the other hand, evaluated at 150 mg/kg body weight in the same murine model, the ethanolic extract from P. huberi had an antiplasmodial effect in all the asexual intraerythrocytic stages of P. falciparum FCR3 and inhibited the parasitic growth in 93 ± 32.9%. Conclusions This is the first report of anti-malarial activity for these two species of plants. Thus, P. latifolia and P. huberi are potential candidates for the development of new drugs for treating malaria.

Abstract Background The erythrocytic stage, where malaria parasites proliferate in human blood, is clinically significant as this causes the symptoms and illness of malaria. Experimental rodent models of malaria at the erythrocytic stage are used for the development of anti-malarial drugs and for biological analysis. An automated haematology analyzer XN-30 was developed for detection of infected red blood cells (iRBCs) in human blood samples and measurement of their parasitaemia in approximately 1 min through flow cytometry analysis. Additionally, the analyzer simultaneously measured other haematological parameters in these samples. It is inferred that the analyzer would also allow easy and rapid measurement of parasitaemia in mice and provide important clues on the mouse haematological state during infection and treatment. Results The XN-30 analyzer is a simple and rapid tool to detect iRBCs in mouse blood samples infected with rodent malarial parasites, with three-dimensional analysis permitting the precise measurement of parasitaemia (referred herein as the ‘XN-30 system’). The XN-30 analyzer allowed not only the detection of iRBCs but also the monitoring of RBC, white blood cell, and platelet counts, as well as haematocrit, mean corpuscular volume and mean platelet volume values in the mouse blood sample. For anti-malarial drug development, aside from demonstrating possible efficacy in mouse models, XN-30 analyzer could provide a first glimpse of the safety profile of the drug. Conclusions The XN-30 system is a powerful tool that can be utilized for the in vivo screening, development, and evaluation of anti-malarial drugs as well as for pre-clinical pharmacology and/or toxicity tests in rodent models.

Cinta Moraleda, Regina N. Rabinovich and Clara Menéndez

Abstract. Anemia is a major public health problem that affects mainly children, predominantly in low-income countries and most often due to iron deficiency (ID). Administration of iron supplements to prevent and treat ID anemia in malaria endemic areas has been controversial for decades; however, recent World Health Organization guidelines recommend universal iron supplementation for children in highly prevalent anemia settings, including those where malaria is endemic. However, infants younger than 6 months of age have been exempted from this recommendation because ID is not considered prevalent at this age and because of assumptions—without evidence—that they are protected from ID through breast milk. To achieve full impact of anemia prevention targeting infants less than 6 months of age who are at highest risk of ID, operational studies that conclusively demonstrate the effectiveness and safety of delivering iron supplements to young infants in settings with a high burden of infectious diseases, including malaria, are needed.

Schaber C, Katta N, Bollinger L, et al.

AbstractCurrent evidence suggests that malaria infection could alter patient breath metabolites, a phenomenon that could be exploited to create a breath-based diagnostic test. However, no study has explored this in a clinical setting. To investigate whether natural human malaria infection leads to a characteristic breath profile, we performed a field study in Malawi. Breath volatiles from children with and without uncomplicated falciparum malaria were analyzed by thermal desorption-gas chromatography/mass spectrometry. Using an unbiased, correlation-based analysis, we find that children with malaria have a distinct shift in overall breath composition. Highly accurate classification of infection status was achieved with a suite of six compounds. In addition, we find infection correlates with significantly higher breath levels of two mosquito-attractant terpenes, α-pinene and 3-carene. These findings attest to the viability of breath analysis for malaria diagnosis, identifies candidate biomarkers, and identifies plausible chemical mediators for increased mosquito attraction to malaria-infected patients.

Solomon Kibret, G. Glenn Wilson, Darren Ryder, Habte Tekie, Beyene Petros

by Solomon Kibret, G. Glenn Wilson, Darren Ryder, Habte Tekie, Beyene Petros Background Water level management has been suggested as a potential tool to reduce malaria around large reservoirs. However, no field-based test has been conducted to assess the effect of water level management on mosquito larval abundance in African settings. The objective of the present study is to evaluate the effects of water level drawdown rates on mosquito larval abundance. Methods Twelve experimental dams were constructed on the foreshore of the Koka Dam in Ethiopia. These were grouped into four daily water drawdown treatments, each with three replicates: no water-level drawdown (Group 1; Control), 10 mm.d-1 (Group 2), 15 mm.d-1 (Group 3) and 20 mm.d-1 (Group 4). Larval sampling was conducted weekly for a period of 6 weeks each in the main malaria transmission season (October to November 2013) and subsequent dry season (February to March 2014). Larval densities were compared among treatments over time using repeated measures Analysis of Variance (ANOVA). Results A total of 284 Anopheles mosquito larvae were collected from the experimental dams during the study period. Most (63.4%; n = 180) were collected during the main malaria transmission season while the remaining (36.6%; n = 104) were collected during the dry season. Larvae comprised four Anopheles species, dominated by Anopheles arabiensis (48.1% of total larval samples; n = 136) and An. pharoensis (33.2%; n = 94). Mean larval density was highest in control treatment dams with stable water levels throughout the study, and decreased significantly (P < 0.05) with increasing water drawdown rates in both seasons. During the main transmission season, anopheline larval density was generally lower by 30%, 70% and 84% in Groups 2, Group 3 and Group 4, respectively, compared with the control dams (Group 1). In the dry season, larval density was reduced by 45%, 70% and 84% in Groups 2, Group 3 and Group 4, respectively, when compared to the control dams. Conclusion Increased water drawdown rates were associated with lower mosquito larval abundance. Water level management could thus serve as a potential control measure for malaria vectors around reservoirs by regulating the persistence of shallow shoreline breeding habitats. Dam operators and water resource managers should consider incorporating water level management as a malaria control mechanism into routine dam operations to manage the risk of malaria transmission to human populations around reservoirs.

The American Journal of Tropical Medicine and Hygiene

In this report, we present a case of CM with associated severe brain edema that was successfully managed using a unique combination of therapeutic hypothermia, hypertonic saline, mannitol, and hyperventilation along with the antimalarial drugs quinidine and doxycycline. Our use of hypothermia was based on its proven benefit for improving neurological outcomes in post-cardiac arrest patients and previous in vitro research, suggesting its potential inhibitory role on malaria growth. PMID: 29405103 [PubMed - as supplied by publisher] (Source: The American Journal of Tropical Medicine and Hygiene)…

Nicolas Dauby, Mariana Figueiredo Ferreira, Deborah Konopnicki, Vo Thanh Phuong Nguyen, Brigitte Cantinieaux and Charlotte Martin

Abstract. Emerging evidence indicates that migrants from Plasmodium falciparum endemic regions are at risk of delayed presentation of P. falciparum malaria. We report three cases of P. falciparum malaria occurring years after arrival in Europe. All patients were originally from Sub-Saharan Africa. Two subjects had controlled human immunodeficiency virus infection and one was a pregnant woman. We performed a literature review of all published cases of delayed presentation of P. falciparum in migrants and identified 32 additional cases. All cases but one originate from sub-Saharan Africa. There was a median time of 36 months between the last visit to a malaria-endemic country and clinical malaria (range: 3 months to 10 years). Pregnancy was the most frequently reported risk factor (11/35 or 31.4%). Parasitemia was ≤ 0.1% in 38% of cases (11/29 reported), and no death was reported. The underlying possible mechanisms for this delayed presentation in migrants from an endemic area probably include the persistence of submicroscopic parasitemia combined with decaying P. falciparum–specific immunity. Suspicion of P. falciparum delayed malaria should remain high in migrants, mainly from sub-Saharan Africa, even without a recent travel history, especially in those presenting risk factors for impaired parasite clearance or distinct immune responses such as pregnancy and HIV infection. In these patients, new prevention and screening strategies should be studied and blood safety policies adapted.

The American Journal of Tropical Medicine and Hygiene

We report three cases of P. falciparum malaria occurring years after arrival in Europe. All patients were originally from Sub-Saharan Africa. Two subjects had controlled HIV infection and one was a pregnant woman. We performed a literature review of all published cases of delayed presentation of P. falciparum in migrants and identified 32 additional cases. All cases but one originate from sub-Saharan Africa. There was a median time of 36 months between the last visit to a malaria-endemic country and clinical malaria (range: 3 months to 10 years). Pregnancy was the most frequently reported risk factor (11/35 or 31.4%). Parasitemia was ≤ 0.1% in 38% of cases (11/29 reported), and no death was reported. The underlying possible mechanisms for this delayed presentation in migrants from an end...

Suryadi N. N. Tatura, Elizabeth Clarissa Wowor, Jose M. Mandei, Rocky Wilar, Sarah M. Warouw, Johnny Rompis, Priscilla Kalensang and Joseph Tuda

Abstract. Severe congenital malaria associated with Plasmodium vivax is uncommon. In Indonesia, most congenital malaria cases are due to Plasmodium falciparum infections. Most cases of congenital or neonatal malaria in endemic areas are diagnosed from peripheral smear as part of routine sepsis workup. Differentiating congenital and acquired neonatal malaria is very difficult. The case presented in this study describes severe P. vivax malaria with cholestatic jaundice and sepsis-like signs and symptoms in neonates. The mother was asymptomatic and the neonate was successfully treated with intravenous artesunate. Severe P. vivax malaria with cholestatic jaundice in neonates is an uncommon condition that should be included in the differential diagnosis of infants displaying hemolytic anemia, thrombocytopenia, cholestatic jaundice, and hepatosplenomegaly in malaria-endemic zones. Early diagnosis can prevent the use of unnecessary antibiotics and mortality of neonates.

The American Journal of Tropical Medicine and Hygiene

Authors: Tatura SNN, Wowor EC, Mandei JM, Wilar R, Warouw SM, Rompis J, Kalensang P, Tuda J Abstract Severe congenital malaria associated with Plasmodium vivax is uncommon. In Indonesia, most congenital malaria cases are due to Plasmodium falciparum infections. Most cases of congenital or neonatal malaria in endemic areas are diagnosed from peripheral smear as part of routine sepsis workup. Differentiating congenital and acquired neonatal malaria is very difficult. The case presented in this study describes severe P. vivax malaria with cholestatic jaundice and sepsis-like signs and symptoms in neonates. The mother was asymptomatic and the neonate was successfully treated with intravenous artesunate. Severe P. vivax malaria with cholestatic jaundice in neonates is an uncommon condit...

Dennis, A. S. M., Lehane, A. M., Ridgway, M. C., Holleran, J. P., Kirk, K.

For an increasing number of antimalarial agents identified in high throughput phenotypic screens there is evidence that they target PfATP4, a putative Na+ efflux transporter on the plasma membrane of the human malaria parasite, Plasmodium falciparum. For several such ‘PfATP4-associated’ compounds it has been noted that their addition to parasitised erythrocytes results in cell swelling. Here we show that six structurally diverse PfATP4-associated compounds, including the clinical candidate KAE609 (cipargamin), induce swelling both of isolated blood-stage parasites and of intact parasitised erythrocytes. The swelling of isolated parasites is dependent on the presence of Na+ in the external environment and may be attributed to the osmotic consequences of Na+ uptake. The swelling of the parasitised erythrocyte results in an increase in its osmotic fragility. Countering cell swelling by increasing the osmolarity of the extracellular medium reduces the antiplasmodial efficacy of PfATP4-associated compounds, consistent with cell swelling playing a role in the antimalarial activity of this class of compounds.

Abstract Background In 2011, the demographic and health survey (DHS) in Cameroon was combined with the multiple indicator cluster survey. Malaria parasitological data were collected, but the survey period did not overlap with the high malaria transmission season. A malaria indicator survey (MIS) was also conducted during the same year, within the malaria peak transmission season. This study compares estimates of the geographical distribution of malaria parasite risk and of the effects of interventions obtained from the DHS and MIS survey data. Methods Bayesian geostatistical models were applied on DHS and MIS data to obtain georeferenced estimates of the malaria parasite prevalence and to assess the effects of interventions. Climatic predictors were retrieved from satellite sources. Geostatistical variable selection was used to identify the most important climatic predictors and indicators of malaria interventions. Results The overall observed malaria parasite risk among children was 33 and 30% in the DHS and MIS data, respectively. Both datasets identified the Normalized Difference Vegetation Index and the altitude as important predictors of the geographical distribution of the disease. However, MIS selected additional climatic factors as important disease predictors. The magnitude of the estimated malaria parasite risk at national level was similar in both surveys. Nevertheless, DHS estimates lower risk in the North and Coastal areas. MIS did not find any important intervention effects, although DHS revealed that the proportion of population with an insecticide-treated nets access in their household was statistically important. An important negative relationship between malaria parasitaemia and socioeconomic factors, such as the level of mother’s education, place of residence and the household welfare were captured by both surveys. Conclusion Timing of the malaria survey influences estimates of the geographical distribution of disease risk, especially in settings with seasonal transmission. In countries with different ecological zones and thus different seasonal patterns, a single survey may not be able to identify all high risk areas. A continuous MIS or a combination of MIS, health information system data and data from sentinel sites may be able to capture the disease risk distribution in space across different seasons.

Watson, J., Chu, C. S., Tarning, J., White, N. J.

The minimum inhibitory concentration (MIC) is an essential quantitative measure of the asexual blood stage effect of an antimalarial drug. In areas of high malaria transmission, and thus frequent individual infection, patients who are treated with slowly eliminated antimalarials become reinfected as drug concentrations decline. In the frequent relapse forms of P. vivax and in P. ovale malaria, recurrent infection occurs from relapses which begin to emerge from the liver approximately two weeks after the primary illness. An important determinant of the interval from starting treatment of a symptomatic infection to the patency of these recurrent infections is the in vivo concentration-response relationship and thus the in vivo MIC. Using mechanistic knowledge of parasite asexual replication and the pharmacokinetic and pharmacodynamic properties of the antimalarial drugs, a generative statistical model was derived which relates the concentration-response relationship to time of reinfection patency. This model was used to estimate the in vivo MIC of chloroquine in the treatment of Plasmodium vivax malaria.

Gavina, K., Gnidehou, S., Arango, E., Hamel-Martineau, C., Mitran, C., Agudelo, O., Lopez, C., Karidio, A., Banman, S., Carmona-Fonseca, J., Salanti, A., Ndam, N., Hawkes, M., Maestre, A., Yanow, S. K.

BackgroundMalaria in pregnancy can cause serious adverse outcomes for the mother and the fetus. However, little is known about the effects of submicroscopic infections (SMIs) in pregnancy, particularly in areas where Plasmodium (P.) falciparum and P. vivax co-circulate.MethodsA cohort of 187 pregnant women living in Puerto Libertador in Northwest Colombia was followed longitudinally from recruitment to delivery. Malaria was diagnosed by microscopy, RT-qPCR, and placental histopathology. Gestational age, hemoglobin concentration, VAR2CSA-specific IgG levels and adhesion-blocking antibodies were measured during pregnancy. Statistical analyses were performed to evaluate the impact of SMIs on birth weight and other delivery outcomes.ResultsTwenty-five percent of women (45/180) were positive for SMIs during pregnancy. Forty-seven percent of infections (21/45) were caused by P. falciparum, 33% by P. vivax, and 20% by mixed Plasmodium spp. Mixed infections of P. falciparum and P. vivax were associated with lower gestational age at delivery (p=0.0033), while other outcomes were normal. Over 60% of women had antibodies to VAR2CSA and there was no difference in antibody levels between those with SMIs or not. The anti-adhesion function of these antibodies was associated with protection from SMI-related anemia at delivery (p=0.0086).ConclusionsSMIs occur frequently during pregnancy and while they were not associated with a decrease in birth weight, mixed infections of both P. falciparum and P. vivax were associated with significant risk of pre-term birth. We propose that the lack of adverse delivery outcomes is due to functional VAR2CSA antibodies that can protect pregnant women from SMI-related anemia.

Rossi G, Vernaeve L, Van den Bergh R, et al.

AbstractBackgroundIn the frame of elimination strategies of Plasmodium falciparum (Pf), active case detection has been recommended as complementary approach to the existing passive case detection programs. We trialed a polymerase chain reaction (PCR)–based active detection strategy targeting asymptomatic individuals, named proactive case detection (PACD), with the aim of assessing its feasibility, the extra yield of Pf infections, and the at-risk population for Pf carriage status.MethodsA pilot of PACD was conducted in 3 villages in Chey Saen district (Preah Vihear province, Cambodia), from December 2015 to March 2016. Voluntary screening and treatment, following health promotion sensitization, was used as mobilization strategy.ResultsA total of 2802 persons were tested, representing 54% of the population. PACD (n = 30) and the respective reactive case detection (RACD) (n = 3) identified 33 Pf carriers, approximately twice as many as the Pf infections (n = 17) diagnosed in passive case detection and respective RACD, by health centers and village malaria workers using PCR, in the same villages/period. Final positivity rate was 1.07% (30/2802). People spending nighttime in forests and plantations were found to be at increased risk for Pf infection (odds ratio [OR], 3.4 [95% CI, 1.6–7.2], P = .002 and OR, 2.3 [95% CI, 1.1–4.9], P = .03, respectively).ConclusionsWe demonstrated the usefulness of the PACD component in identifying Pf asymptomatic carriers. Social mobilization and promotion led to good attendance of specific risk groups, identified to be, in the Cambodian context, individuals spending nighttime in forest and plantations.

Vantaux A, Samreth R, Piv E, et al.

AbstractBackgroundEliminating falciparum malaria in Cambodia is a top priority, requiring the implementation of novel tools and strategies to interrupt its transmission. To date, few data are available regarding the contributions to malaria transmission of symptomatic and asymptomatic carriers.MethodsDirect-membrane and skin feeding assays (DMFA, SFA) were performed, using Anopheles minimus and An. dirus, to determine infectivity of symptomatic falciparum-infected patients and malaria asymptomatic carriers; a subset of the latter were followed for two months to assess their transmission potential.ResultsBy microscopy and RT-PCR, P. falciparum gametocyte prevalence rates were, respectively, 19.3% (21/109) and 44% (47/109) on Day (D) 0 and 17.9% (5/28) and 89.3% (25/28) in recrudescent patients (Drec) (RT-PCR Drec vs. D0 P=0.0015). Falciparum malaria patient infectivity was low on D0, 6.2% (3/48), and Drec, 8.3% (1/12). DFMA and SFA gave similar results. None of the falciparum (0/19) and 3/28 P. vivax asymptomatic carriers were infectious to mosquitoes, including those that were followed up for two months. Overall, P. falciparum gametocytemias were low except in a few symptomatic carriers.ConclusionsOnly symptomatic falciparum malaria patients were infectious to mosquito vectors at baseline and recrudescence, highlighting the need to detect promptly and treat effectively P. falciparum patients.

Malhotra I, LaBeaud A, Morris N, et al.

AbstractBackgroundAntenatal exposure to parasites can affect infants’ subsequent responses to vaccination. The present study investigated how maternal prenatal infections and newborns’ anti-parasite cytokine profiles relate to IgG responses to standard vaccination during infancy.Methods450 Kenyan women were tested for parasitic infections during pregnancy. Their newborns’ responses to malaria, schistosome, and filaria antigens were assessed in cord blood (CB) lymphocytes. Following standard neonatal vaccination, this infant cohort was followed biannually to age 30 months for circulating IgG levels against Haemophilus influenzae b (Hib), diphtheria toxoid (DT), hepatitis B, and tetanus.ResultsTrajectories of post-vaccination IgG levels were classified by functional principal component (PC) analysis to assess each child’s response profile. Two main components, PC1, reflecting height of response over time, and PC2, reflecting crossover from high to low or low to high, were identified. CB cytokine responses to schistosome and filarial antigens showed a significant association between augmented anti-helminth IL-10 and reduced antibody levels, particularly to DT and hepatitis B, and a more rapid post-vaccination decline in circulating IgG against Hib.ConclusionAntenatal sensitization to schistosomiasis or filariasis, and related production of anti-parasite IL-10 at birth, are associated with reduced anti-vaccine IgG levels in infancy, with possibly impaired protection.

H. Iqbal, H. Aziz

Mosquito-borne diseases such as dengue and malaria have caused much damage to the Pakistani population in the past years; suspected chikungunya thus requires the utmost governmental attention in order to be addressed in a timely manner and prevent harm to the population.

The American Journal of Tropical Medicine and Hygiene

This study showed a LAMP assay to be a rapid and very sensitive method for the early diagnosis of both complicated and uncomplicated P. vivax malaria. PMID: 29557335 [PubMed - as supplied by publisher] (Source: The American Journal of Tropical Medicine and Hygiene)…

Abstract Background In the context of malaria elimination/eradication, drugs that are effective against the different developmental stages of the parasite are highly desirable. The oldest synthetic anti-malarial drug, the thiazine dye methylene blue (MB), is known for its activity against Plasmodium blood stages, including gametocytes. The aim of the present study was to investigate a possible effect of MB against malaria parasite liver stages. Methods MB activity was investigated using both in vitro and in vivo models. In vitro assays consisted of testing MB activity on Plasmodium falciparum, Plasmodium cynomolgi and Plasmodium yoelii parasites in human, simian or murine primary hepatocytes, respectively. MB in vivo activity was evaluated using intravital imaging in BALB/c mice infected with a transgenic bioluminescent P. yoelii parasite line. The transmission-blocking activity of MB was also addressed using mosquitoes fed on MB-treated mice. Results MB shows no activity on Plasmodium liver stages, including hypnozoites, in vitro in primary hepatocytes. In BALB/c mice, MB has moderate effect on P. yoelii hepatic development but is highly effective against blood stage growth. MB is active against gametocytes and abrogates parasite transmission from mice to mosquitoes. Conclusion While confirming activity of MB against both sexual and asexual blood stages, the results indicate that MB has only little activity on the development of the hepatic stages of malaria parasites.

Abstract Background Vector control is a crucial element of anti-malaria campaigns and works best when there is a thorough knowledge of the biology and behaviour of the Anopheles vector species responsible for transmitting malaria within a given locale. With the push to eradicate malaria stronger than ever, there is a growing need to develop and deploy control strategies that exploit the behavioural attributes of local vector species. This is especially true in regions where the vectors are exophagic (i.e., prefer to bite outdoors), exophilic (i.e., prefer to remain outdoors), and zoophagic (i.e., as likely to feed on non-humans as humans). One promising strategy targeting vectors with these behavioural traits is the administration of avermectin-based endectocides, such as ivermectin, to humans and livestock. When ingested in a blood meal, ivermectin has been shown to reduce mosquito survivorship and fecundity in a number of Anopheles species. In this study, the relative toxicity of ivermectin was compared between two zoophagic, exophilic malaria vectors—Anopheles albimanus and Anopheles stephensi. Results Toxicity of ivermectin was assessed using membrane feedings, intrathoracic injections, and mosquito feedings on treated mice. When ingested in a blood meal, ivermectin was much less toxic to An. albimanus (4-day oral LC50 = 1468 ng/ml) than to An. stephensi (4-day oral LC50 = 7 ng/ml). However when injected into the haemocoel of An. albimanus, ivermectin was much more toxic (3-day parenteral LC50 = 188 ng/ml). Because the molecular targets of ivermectin (i.e., glutamate-gated chloride channels) reside outside the midgut in nerves and muscles, this suggests that ingested ivermectin was not readily absorbed across the midgut of An. albimanus. In contrast, ivermectin was considerably more toxic to An. stephensi when ingested (4-day oral LC50 = 7 ng/ml) than when injected (3-day parenteral LC50 = 49 ng/ml). This suggests that metabolic by-products from the digestion of ivermectin may play a role in the oral toxicity of ivermectin to An. stephensi. Blood meal digestion and subsequent oviposition rates were significantly hindered in both species by ingested ivermectin but only at concentrations at or above their respective oral LC50 concentrations. To test mosquitocidal activity of ivermectin in a live host system, two groups of three mice each received subcutaneous injections of either ivermectin (600 µg/kg BW) or saline (control). One day after injection, the ivermectin-treated mice (n = 3) exhibited significant mosquitocidal activity against both An. stephensi (85% mortality vs 0% in control-fed) and, to a lesser degree, An. albimanus (44% mortality vs 11% in control-fed). At 3 days, the mosquitocidal activity of ivermectin-treated mice waned and was effective only against An. stephensi (31% mortality vs 3% in control-fed). Conclusions Ivermectin was not uniformly toxic to both Anopheles species. Previous studies indicate that ivermectin is a good choice of endectocide to use against malaria vectors in southeast Asia and Africa. However, these data suggest that ivermectin may not be the optimal endectocide to use in Central America or the Caribbean where An. albimanus is a major malaria vector species. If endectocides are to be used to help eradicate malaria, then additional efficacy data will be needed to define the activity of specific endectocides against the major malaria vector species of the world.

Cruz M, Sánchez I, Diaz J, et al.

Bei A, Niang M, Deme A, et al.

AbstractDramatic changes in transmission intensity can impact Plasmodium population diversity. Using samples from 2 distant time-points in the Dielmo/Ndiop longitudinal cohorts from Senegal, we applied a molecular barcode tool to detect changes in parasite genotypes and complexity of infection that corresponded to changes in transmission intensity. We observed a striking statistically significant difference in genetic diversity between the 2 parasite populations. Furthermore, we identified a genotype in Dielmo and Ndiop previously observed in Thiès, potentially implicating imported malaria. This genetic surveillance study validates the molecular barcode as a tool to assess parasite population diversity changes and track parasite genotypes.

Abstract Background The Angolan government recommends three artemisinin-based combinations for the treatment of uncomplicated Plasmodium falciparum malaria: artemether–lumefantrine (AL), artesunate–amodiaquine (ASAQ), and dihydroartemisinin–piperaquine (DP). Due to the threat of emerging anti-malarial drug resistance, it is important to periodically monitor the efficacy of artemisinin-based combination therapy (ACT). This study evaluated these medications’ therapeutic efficacy in Benguela, Lunda Sul, and Zaire Provinces. Methods Enrollment occurred between March and July 2017. Study participants were children with P. falciparum monoinfection from each provincial capital. Participants received a 3-day course of a quality-assured artemisinin-based combination and were monitored for 28 (AL and ASAQ arms) or 42 days (DP arm). Each ACT was assessed in two provinces. The primary study endpoints were: (1) follow-up without complications and (2) failure to respond to treatment or development of recurrent P. falciparum infection. Parasites from each patient experiencing recurrent infection were genotyped to differentiate new infection from recrudescence of persistent parasitaemia. These parasites were also analysed for molecular markers associated with ACT resistance. Results Of 608 children enrolled in the study, 540 (89%) reached a primary study endpoint. Parasitaemia was cleared within 3 days of medication administration in all participants, and no early treatment failures were observed. After exclusion of reinfections, the corrected efficacy of AL was 96% (91–100%, 95% confidence interval) in Zaire and 97% (93–100%) in Lunda Sul. The corrected efficacy of ASAQ was 100% (97–100%) in Benguela and 93% (88–99%) in Zaire. The corrected efficacy of DP was 100% (96–100%) in Benguela and 100% in Lunda Sul. No mutations associated with artemisinin resistance were identified in the pfk13 gene in the 38 cases of recurrent P. falciparum infection. All 33 treatment failures in the AL and ASAQ arms carried pfmdr1 or pfcrt mutations associated with lumefantrine and amodiaquine resistance, respectively, on day of failure. Conclusions AL, ASAQ, and DP continue to be efficacious against P. falciparum malaria in these provinces of Angola. Rapid parasite clearance and the absence of genetic evidence of artemisinin resistance are consistent with full susceptibility to artemisinin derivatives. Periodic monitoring of in vivo drug efficacy remains a priority routine activity for Angola.

The American Journal of Tropical Medicine and Hygiene

This study evaluated the efficiency of this reactive test-and-treat strategy by characterizing infected individuals missed by the RDT and the current screening radius. The radius was expanded to 250 m, and a quantitative polymerase chain reaction (qPCR) test was performed on dried blood spot specimens. From January 2015 through March 2016, 145 index cases were identified at health centers and health posts. A total of 3,333 individuals residing in 525 households were screened. Excluding index cases, the parasite prevalence was 1.1% by RDT (33 positives of 3,016 participants) and 2.4% by qPCR (73 positives of 3,016 participants). Of the qPCR-positive cases, 62% of 73 individuals tested negative by RDT. Approximately half of the infected individuals resided within the index case household (58...