Mass Testing and Treatment to Accelerate Malaria Elimination: A Systematic Review and Meta-Analysis.

In regions where malaria transmission persists, the implementation of approaches aimed at eliminating parasites from the population can effectively decrease both burden of disease and transmission of infection. Thus, mass strategies that target symptomatic and asymptomatic infections at the same time may help countries to reduce transmission. This systematic review assessed the potential benefits and harms of mass testing and treatment (MTaT) to reduce malaria transmission.

Targeted Testing and Treatment To Reduce Human Malaria Transmission in High-Risk Populations: A Systematic Review.

As countries approach elimination of malaria, groups with increased exposure to malaria vectors or poor access to health services may serve as important human reservoirs of infection that help maintain transmission in the community. Parasitological testing and treatment targeted to these groups may reduce malaria transmission overall. This systematic review assessed the effectiveness of targeted testing and treatment (TTaT) to reduce malaria transmission, the contextual factors, and the results of modeling studies that estimated the intervention's potential impact.

Targeted Drug Administration to Reduce Malaria Transmission: A Systematic Review and Meta-Analysis.

In low- to very low-malaria transmission areas, most infections may be accrued within specific groups whose behaviors or occupations put them at increased risk of infection. If these infections comprise a large proportion of the reservoir of infection, targeting interventions to these groups could reduce transmission at the population level. We conducted a systematic review to assess the impact of providing antimalarials to groups of individuals at increased risk of malaria whose infections were considered to comprise a large proportion of the local reservoir of infections (targeted drug administration [TDA]).

Targeted Test and Treat at Point of Entry to Reduce Importation of Malaria Parasites: A Systematic Review.

As countries approach malaria elimination, imported cases of malaria make up a larger proportion of all cases and may drive malaria transmission. Targeted test and treat (TTaT) at points of entry (POEs) is a strategy that aims to reduce the number of imported infections in countries approaching elimination by testing and treating individuals at border crossings. No evidence has been systematically collected and evaluated to assess the impact and operational feasibility of this strategy.

A pilot evaluation of alternative procedures to simplify LAMP-based malaria diagnosis in field conditions.

Highly-sensitive and field-friendly diagnostic tools are needed for accurate detection of low-density malaria infections. Although loop-mediated isothermal amplification (LAMP) fulfills these conditions, operational challenges are still encountered during pilot population screenings in remote settings when employing Loopamp™ MALARIA Pan/Pf detection kit (Eiken Chemical Co.).

Loop-mediated isothermal DNA amplification for asymptomatic malaria detection in challenging field settings: Technical performance and pilot implementation in the Peruvian Amazon.

Background: Loop-mediated isothermal DNA amplification (LAMP) methodology offers an opportunity for point-of-care (POC) molecular detection of asymptomatic malaria infections. However, there is still little evidence on the feasibility of implementing this technique for population screenings in isolated field settings.

Methods: Overall, we recruited 1167 individuals from terrestrial ('road') and hydric ('riverine') communities of the Peruvian Amazon for a cross-sectional survey to detect asymptomatic malaria infections.

Diagnosing congenital malaria in a high-transmission setting: clinical relevance and usefulness of P. falciparum HRP2-based testing.

Congenital malaria diagnosis is challenging due to frequently observed low parasite density infections, while their clinical relevance during early infancy is not well characterized. In Nanoro health district (Burkina Faso), we determined the prevalence of congenital malaria by real-time quantitative PCR and we assessed the performance of rapid diagnosis test (RDT) and light microscopy (LM) to detect Plasmodium falciparum infections in cord-blood samples. In addition, we examined the usefulness of P.

Global survey of malaria rapid diagnostic test (RDT) sales, procurement and lot verification practices: assessing the use of the WHO-FIND Malaria RDT Evaluation Programme (2011-2014).

Background: Malaria rapid diagnostic tests (RDTs) play a critical role in malaria case management, and assurance of quality is a key factor to promote good adherence to test results. Since 2007, the World Health Organization (WHO) and the Foundation for Innovative New Diagnostics (FIND) have coordinated a Malaria RDT Evaluation Programme, comprising a pre-purchase performance evaluation (product testing, PT) and a pre-distribution quality control of lots (lot testing, LT), the former being the basis of WHO recommendations for RDT procurement. Comprehensive information on malaria RDTs sold worldwide based on manufacturers' data and linked to independent performance data is currently not available, and detailed knowledge of procurement practices remains limited.

Harmonization of malaria rapid diagnostic tests: best practices in labelling including instructions for use.

Background: Rapid diagnostic tests (RDTs) largely account for the scale-up of malaria diagnosis in endemic settings. However, diversity in labelling including the instructions for use (IFU) limits their interchangeability and user-friendliness. Uniform, easy to follow and consistent labelling, aligned with international standards and appropriate for the level of the end user's education and training, is crucial but a consolidated resource of information regarding best practices for IFU and labelling of RDT devices, packaging and accessories is not available.

Malaria and HIV infection in Mozambican pregnant women are associated with reduced transfer of antimalarial antibodies to their newborns.

Background: Malaria and human immunodeficiency virus (HIV) infection during pregnancy affect the transplacental transfer of antibodies against several pathogens from mother to fetus, although the effect of malaria and HIV infection on the transfer of antimalarial antibodies remains unclear.

Methods: Levels of total immunoglobulin G (IgG), immunoglobulin M (IgM), and IgG subtypes against the following Plasmodium falciparum antigens were measured in 187 pairs of mother-cord plasma specimens from Mozambique: 19-kDa fragment of merozoite surface protein 1 (MSP119), erythrocyte binding antigen 175 (EBA175), apical membrane antigen 1 (AMA1), and parasite lysate. Placental antibody transfer was defined as the cord-to-mother ratio (CMR) of antibody levels.

VAR2CSA signatures of high Plasmodium falciparum parasitemia in the placenta.

Plasmodium falciparum infected erythrocytes (IE) accumulate in the placenta through the interaction between Duffy-binding like (DBL) domains of parasite-encoded ligand VAR2CSA and chondroitin sulphate-A (CSA) receptor. Polymorphisms in these domains, including DBL2X and DBL3X, may affect their antigenicity or CSA-binding affinity, eventually increasing parasitemia and its adverse effects on pregnancy outcomes. A total of 373 DBL2X and 328 DBL3X sequences were obtained from transcripts of 20 placental isolates infecting Mozambican women, resulting in 176 DBL2X and 191 DBL3X unique sequences at the protein level.

Immunoglobulins against the surface of Plasmodium falciparum-infected erythrocytes increase one month after delivery.

Background: The risk of Plasmodium falciparum malaria increases during pregnancy and at early postpartum. Immunological and physiological alterations associated with pregnancy that persist after delivery may contribute to the susceptibility to P. falciparum during early postpartum period.

How hidden can malaria be in pregnant women? Diagnosis by microscopy, placental histology, polymerase chain reaction and detection of histidine-rich protein 2 in plasma.

Background: Accurate diagnosis of malaria infection during pregnancy remains challenging because of low parasite densities and placental sequestration of Plasmodium falciparum. The performance of different methods to detect P. falciparum in pregnancy and the clinical relevance of undetected infections were evaluated.

Intermittent preventive treatment with sulfadoxine-pyrimethamine does not modify plasma cytokines and chemokines or intracellular cytokine responses to Plasmodium falciparum in Mozambican children.

Background: Cytokines and chemokines are key mediators of anti-malarial immunity. We evaluated whether Intermittent Preventive Treatment in infants with Sulfadoxine-Pyrimethamine (IPTi-SP) had an effect on the acquisition of these cellular immune responses in Mozambican children. Multiple cytokines and chemokines were quantified in plasma by luminex, and antigen-specific cytokine production in whole blood was determined by intracellular cytokine staining and flow cytometry, at ages 5, 9, 12 and 24 months.

Reduction of antimalarial antibodies by HIV infection is associated with increased risk of Plasmodium falciparum cord blood infection.

Background: Plasmodium falciparum infection in pregnancy can lead to congenital malaria, which has detrimental health consequences for infants. Human immunodeficiency virus (HIV) might increase cord blood P. falciparum infection by decreasing maternal antimalarial-specific antibodies.

Age-dependent IgG subclass responses to Plasmodium falciparum EBA-175 are differentially associated with incidence of malaria in Mozambican children.

Plasmodium falciparum blood-stage antigens such as merozoite surface protein 1 (MSP-1), apical membrane antigen 1 (AMA-1), and the 175-kDa erythrocyte binding antigen (EBA-175) are considered important targets of naturally acquired immunity to malaria. However, it is not clear whether antibodies to these antigens are effectors in protection against clinical disease or mere markers of exposure. In the context of a randomized, placebo-controlled trial of intermittent preventive treatment in infants conducted between 2002 and 2004, antibody responses to Plasmodium falciparum blood-stage antigens in a cohort of 302 Mozambican children were evaluated by immunofluorescence antibody test and enzyme-linked immunosorbent assay at 5, 9, 12, and 24 months of age.

Transcription of var genes other than var2csa in Plasmodium falciparum parasites infecting Mozambican pregnant women.

Background: Increased susceptibility to Plasmodium falciparum infection during pregnancy has been attributed to the accumulation of infected erythrocytes in the placenta. This phenomenon is mediated by a var gene coding for VAR2CSA, which adheres to chondroitin sulphate A. However, the contribution of parasites transcribing other var genes to maternal infections has not been well characterized.

IgG against Plasmodium falciparum variant surface antigens and growth inhibitory antibodies in Mozambican children receiving intermittent preventive treatment with sulfadoxine-pyrimethamine.

This study aimed to evaluate whether intermittent preventive treatment in infants with sulfadoxine-pyrimethamine (IPTi-SP) had an effect on the acquisition of IgG against Plasmodium falciparum variant surface antigens (VSA) and growth-inhibitory antibodies in Manhiça, Mozambique. In addition, we assessed factors affecting the magnitude of these responses and the association between antibody levels and protection against malaria. IgG to VSA expressed by MOZ2, R29 and E8B parasite isolates were measured in plasma samples collected at 5, 9, 12 and 24 months of age by flow cytometry.

HIV and placental infection modulate the appearance of drug-resistant Plasmodium falciparum in pregnant women who receive intermittent preventive treatment.

Background: Factors involved in the development of resistance to sulphadoxine-pyrimethamine (SP) by Plasmodium falciparum, particularly in the context of intermittent preventive treatment during pregnancy (IPTp), are not well known. We aimed to determine the impact of IPTp and human immunodeficiency virus (HIV) infection on molecular markers of SP resistance and the clinical relevance of resistant infections.

Methods: SP resistance alleles were determined in peripheral (n = 125) and placental (n = 145) P.

Persistence of Plasmodium falciparum parasites in infected pregnant Mozambican women after delivery.

Pregnant women are susceptible to Plasmodium falciparum parasites that sequester in the placenta. The massive accumulation of infected erythrocytes in the placenta has been suggested to trigger the deleterious effects of malaria in pregnant women and their offspring. The risk of malaria is also high during the postpartum period, although mechanisms underlying this susceptibility are not known.

The effect of intermittent preventive treatment during pregnancy on malarial antibodies depends on HIV status and is not associated with poor delivery outcomes.

Background: Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in sub-Saharan Africa. However, studies reporting the effect of IPTp on malaria-specific immunity are scarce and are based on findings in human immunodeficiency virus (HIV)-negative primigravidae.

Methods: Plasma samples obtained from 302 pregnant women (177 who were HIV negative, 88 who were HIV positive, and 37 who were of unknown HIV status) participating in a placebo-controlled trial of IPTp with SP (IPTp-SP) were analyzed for the presence of antibodies against merozoite antigens, whole asexual parasites, and variant surface antigens from chondroitin sulfate A-binding and nonbinding lines.

Sub-microscopic infections and long-term recrudescence of Plasmodium falciparum in Mozambican pregnant women.

Background: Control of malaria in pregnancy remains a public health challenge. Improvements in its correct diagnosis and the adequacy of protocols to evaluate anti-malarial drug efficacy in pregnancy, are essential to achieve this goal.

Methods: The presence of Plasmodium falciparum was assessed by real-time (RT) PCR in 284 blood samples from pregnant women with clinical complaints suggestive of malaria, attending the maternity clinic of a Mozambican rural hospital.

Impact of intermittent preventive treatment with sulfadoxine-pyrimethamine on antibody responses to erythrocytic-stage Plasmodium falciparum antigens in infants in Mozambique.

We evaluated the impact of intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP), which was given at ages 3, 4, and 9 months through the Expanded Program on Immunization (EPI), on the development of antibody responses to Plasmodium falciparum in Mozambique. Immunoglobulin M (IgM) and IgG subclass antibodies specific to whole asexual parasites and to recombinant MSP-1(19), AMA-1, and EBA-175 were measured at ages 5, 9, 12, and 24 months for 302 children by immunofluorescence antibody tests and by enzyme-linked immunosorbent assays. Antibody responses did not significantly differ between children receiving IPTi with SP and those receiving a placebo at any time point measured, with the exception of the responses of IgG and IgG1 to AMA-1 and/or MSP-1(19), which were significantly higher in the SP-treated group than in the placebo group at ages 5, 9, and/or 24 months.

Molecular markers of resistance to sulfadoxine-pyrimethamine during intermittent preventive treatment for malaria in Mozambican infants.

Background: Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a potential malaria control strategy. There is concern about the impact that increasing in vivo resistance to SP has on the efficacy of IPTi, as well as about the potential contribution of IPTi to increases in resistance.

Methods: We compared the frequency of clinical episodes of malaria caused by P.