WHO target product profiles to shape global research and development.

Research and development leading to new and improved health products is essential for achieving healthier lives for populations worldwide. However, new products in development do not always match the global need for products for neglected diseases and populations. To promote research, provide an incentive for investment and align products with the needs of end-users, research needs to be better coordinated and prioritized. The World Health Organization (WHO) has developed target product profiles that define the characteristics required in new health products to address the greatest public health needs. A WHO target product profile document presents a need and provides guidance on what to include to consider access and equity as part of the research and development plan from the outset. WHO has also set up the Target Product Profile Directory, a free-to-use online database of characteristics used to describe desired health products, including medicines, vaccines, diagnostic tools and medical equipment. Here we describe the process of developing a WHO target product profile, and the benefits of this type of guidance. We urge product developers to share product profiles addressing unmet needs in public health, to help in progress towards global targets for better health and well-being.

Promouvoir la santé des populations à travers le monde va de pair avec la recherche-développement responsable de la conception et de l'optimisation de produits sanitaires. Pourtant, les nouveaux produits à l'étude ne répondent pas toujours aux exigences mondiales des populations et maladies négligées. En vue de promouvoir la recherche, de favoriser les investissements et d'aligner les produits sur les besoins des utilisateurs finaux, les travaux doivent être mieux coordonnés et leurs priorités, mieux définies. L'Organisation mondiale de la Santé (OMS) a donc élaboré des profils de produits cibles qui déterminent les caractéristiques requises pour les nouveaux produits sanitaires, afin qu'ils correspondent davantage aux besoins les plus criants en matière de santé publique. Un profil de produit cible établi par l'OMS est un document qui met en évidence un besoin et fournit des indications sur les aspects à prendre en compte pour garantir l'accès et l'équité dès le départ dans le plan de recherche-développement. L'OMS a également publié un Répertoire des profils de produits cibles, une base de données en ligne consultable gratuitement qui reprend les caractéristiques employées pour décrire les produits sanitaires souhaités (médicaments, vaccins, outils diagnostiques et équipements médicaux). Dans le présent document, nous détaillons le processus de développement d'un profil de produit cible par l'OMS, mais aussi les avantages que comportent de telles indications. Nous encourageons vivement les laboratoires à partager les profils de produits qui répondent à des besoins non satisfaits en matière de santé publique, afin de contribuer à avancer vers les objectifs mondiaux de santé et de bien-être.

La investigación y el desarrollo de productos sanitarios nuevos y mejorados son esenciales para que las poblaciones de todo el mundo vivan más sanas. Sin embargo, los productos nuevos en desarrollo no siempre se ajustan a las necesidades mundiales de productos para enfermedades y poblaciones desatendidas. Para promover la investigación, incentivar la inversión y adaptar los productos a las necesidades de los usuarios finales, es necesario coordinar mejor la investigación y establecer prioridades. La Organización Mundial de la Salud (OMS) ha elaborado perfiles de productos específicos que definen las características que deben reunir los productos sanitarios nuevos para satisfacer las principales necesidades de salud pública. Un documento de perfil de producto específico de la OMS presenta una necesidad y ofrece orientación sobre lo que debe incluirse para tener en cuenta el acceso y la equidad como parte del plan de investigación y desarrollo desde el principio. La OMS también ha creado el Directorio de Perfiles de Productos Específicos, una base de datos en línea de uso gratuito con las características utilizadas para describir los productos sanitarios deseados, incluidos medicamentos, vacunas, herramientas de diagnóstico y equipos médicos. En el presente documento, describimos el proceso de elaboración de un perfil de producto específico de la OMS y las ventajas de este tipo de orientación. Instamos a los desarrolladores de productos a compartir perfiles de productos que aborden necesidades no cubiertas en salud pública para contribuir al avance hacia los objetivos mundiales de mejora de la salud y el bienestar.

Tracking global resources and capacity for health research: time to reassess strategies and investment decisions.

The COVID-19 pandemic and more recently the Monkeypox outbreak emphasize the urgency and importance of improving the availability and equitable distribution of resources for health research across rich and poor countries. Discussions about the persistent imbalances in resource allocation for health research between rich and poor countries are not new, but little or no progress has been made in redressing these imbalances over the years. This is critical not only for emergency preparedness, but for the worlds' ability to improve population health in an equitable manner. Concerned with the lack of progress in this area, Member States of the World Health Organization requested the establishment of a Global Observatory on Health Research and Development, with the aim of consolidating, monitoring and analyzing relevant information on health research and development, with a view to informing the coordination and prioritization of new investments. In this commentary, we highlight some of the striking disparities from the Observatory's analysis over the 5 years since its establishment and reflect on what is needed to overturn stagnant progress.

Dancing With Algorithms: Interaction Creates Greater Preference and Trust in Machine-Learned Behavior.

OBJECTIVE: We examined a method of machine learning (ML) to evaluate its potential to develop more trustworthy control of unmanned vehicle area search behaviors. BACKGROUND: ML typically lacks interaction with the user. Novel interactive machine learning (IML) techniques incorporate user feedback, enabling observation of emerging ML behaviors, and human collaboration during ML of a task. This may enable trust and recognition of these algorithms. METHOD: Participants judged and selected behaviors in a low and a high interaction condition (IML) over the course of behavior evolution using ML. User trust in the outputs, as well as preference, and ability to discriminate and recognize the behaviors were measured. RESULTS: Compared to noninteractive techniques, IML behaviors were more trusted and preferred, as well as recognizable, separate from non-IML behaviors, and approached similar performance as pure ML models. CONCLUSION: IML shows promise for creating behaviors by involving the user; this is the first extension of this technique for vehicle behavior model development targeting user satisfaction and is unique in its multifaceted evaluation of how users perceived, trusted, and implemented these learned controllers. APPLICATION: There are many contexts where the brittleness of ML cannot be trusted, but the advantage of ML over traditional programmed behaviors may be large, as in some military operations where they could be scaled. IML in this early form appears to generate satisfactory behaviors without sacrificing performance, use, or trust in the behavior, but more work is necessary.

Towards harmonization of microscopy methods for malaria clinical research studies.

Microscopy performed on stained films of peripheral blood for detection, identification and quantification of malaria parasites is an essential reference standard for clinical trials of drugs, vaccines and diagnostic tests for malaria. The value of data from such research is greatly enhanced if this reference standard is consistent across time and geography. Adherence to common standards and practices is a prerequisite to achieve this. The rationale for proposed research standards and procedures for the preparation, staining and microscopic examination of blood films for malaria parasites is presented here with the aim of improving the consistency and reliability of malaria microscopy performed in such studies. These standards constitute the core of a quality management system for clinical research studies employing microscopy as a reference standard. They can be used as the basis for the design of training and proficiency testing programmes as well as for procedures and quality assurance of malaria microscopy in clinical research.

Phylogeography of var gene repertoires reveals fine-scale geospatial clustering of Plasmodium falciparum populations in a highly endemic area.

Plasmodium falciparum malaria is a major global health problem that is being targeted for progressive elimination. Knowledge of local disease transmission patterns in endemic countries is critical to these elimination efforts. To investigate fine-scale patterns of malaria transmission, we have compared repertoires of rapidly evolving var genes in a highly endemic area. A total of 3680 high-quality DBLα-sequences were obtained from 68 P. falciparum isolates from ten villages spread over two distinct catchment areas on the north coast of Papua New Guinea (PNG). Modelling of the extent of var gene diversity in the two parasite populations predicts more than twice as many var gene alleles circulating within each catchment (Mugil = 906; Wosera = 1094) than previously recognized in PNG (Amele = 369). In addition, there were limited levels of var gene sharing between populations, consistent with local parasite population structure. Phylogeographic analyses demonstrate that while neutrally evolving microsatellite markers identified population structure only at the catchment level, var gene repertoires reveal further fine-scale geospatial clustering of parasite isolates. The clustering of parasite isolates by village in Mugil, but not in Wosera was consistent with the physical and cultural isolation of the human populations in the two catchments. The study highlights the microheterogeneity of P. falciparum transmission in highly endemic areas and demonstrates the potential of var genes as markers of local patterns of parasite population structure.

Significant geographical differences in prevalence of mutations associated with Plasmodium falciparum and Plasmodium vivax drug resistance in two regions from Papua New Guinea.

BACKGROUND: Drug resistance remains a major obstacle to malaria treatment and control. It can arise and spread rapidly, and vary substantially even at sub-national level. National malaria programmes require cost-effective and timely ways of characterizing drug-resistance at multiple sites within their countries. METHODS: An improved multiplexed post-PCR ligase detection reaction-fluorescent microsphere assay (LDR-FMA) was used to simultaneously determine the presence of mutations in chloroquine resistance transporter (crt), multidrug resistance 1 (mdr1), dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes in Plasmodium falciparum (n = 727) and Plasmodium vivax (n = 574) isolates collected in 2006 from cross-sectional community population surveys in two geographically distinct regions (Madang and East Sepik) of Papua New Guinea (PNG) where strong regional differences in in vivo aminoquinoline and antifolate therapeutic efficacy had previously been observed. Data were compared to those of a follow-up survey conducted in 2010. RESULTS: Despite some very low parasite densities, the assay successfully amplified all P. falciparum and P. vivax loci in 77 and 69 % of samples, respectively. In 2006, prevalences of pfdhfr (59R-108 N) double mutation/wild type pfdhps haplotype, pfcrt SVMNT haplotype (72S-76T double mutation), and 86Y pfmdr1 mutation all exceeded 90 %. For P. vivax, 65 % carried at least two pvdhfr mutations, 97 % the 647P pvdhps mutation and 54 % the 976F pvmdr1 mutation. Prevalence of mutant haplotypes was higher in Madang than East Sepik for pfcrt SVMNT (97.4 vs 83.3 %, p = 0.001), pfdhfr (59R-108 N) (100 vs 90.6 %, p = 0.001), pvdhfr haplotypes (75.8 vs 47.6 %, p = 0.001) and pvmdr1 976F (71.2 vs 26.2 %, p < 0.001). Data from a subsequent Madang survey in 2010 showed that the prevalence of pfdhps mutations increased significantly from <5 % to >30 % (p < 0.001) as did the prevalence of pvdhfr mutant haplotypes (from 75.8 to 97.4 %, p = 0.012). CONCLUSIONS: This LDR-FMA multiplex platform shows feasibility for low-cost, high-throughput, rapid characterization of a broad range of drug-resistance markers in low parasitaemia infections. Significant geographical differences in mutation prevalence correlate with previous genotyping surveys and in vivo trials and may reflect variable drug pressure and differences in health-care access in these two PNG populations.

Streptococcus pneumoniae and Haemophilus influenzae in paediatric meningitis patients at Goroka General Hospital, Papua New Guinea: serotype distribution and antimicrobial susceptibility in the pre-vaccine era.

BACKGROUND: Bacterial meningitis remains an important infection globally, with the greatest burden in children in low-income settings, including Papua New Guinea (PNG). We present serotype, antimicrobial susceptibility and outcome data from paediatric meningitis patients prior to introduction of Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines (PCVs) in PNG, providing a baseline for evaluation of immunisation programs. METHODS: Cerebrospinal fluid (CSF) was collected from children admitted to Goroka General Hospital with suspected meningitis between 1996 and 2005. Culture and sensitivity was conducted, and pneumococci and H. influenzae were serotyped. Laboratory findings were linked to clinical outcomes. RESULTS: We enrolled 1884 children. A recognised pathogen was identified in 375 children (19.9%). Streptococcus pneumoniae (n = 180) and Hib (n = 153) accounted for 88.8% of pathogens isolated. 24 different pneumococcal serogroups were identified; non-PCV types 2, 24 and 46 accounted for 31.6% of pneumococcal meningitis. 10- and 13-valent PCVs would cover 44.1% and 45.4% of pneumococcal meningitis respectively. Pneumococcal isolates were commonly resistant to penicillin (21.5%) and 23% of Hib isolates were simultaneously resistant to ampicillin, co-trimoxazole and chloramphenicol. The case fatality rate in patients with a recognised bacterial pathogen was 13.4% compared to 8.5% in culture-negative patients. CONCLUSIONS: If implemented in routine expanded programme of immunisation (EPI) with high coverage, current PCVs could prevent almost half of pneumococcal meningitis cases. Given the diversity of circulating serotypes in PNG serotype replacement is of concern. Ongoing surveillance is imperative to monitor the impact of vaccines. In the longer term vaccines providing broader protection against pneumococcal meningitis will be needed.

Building coherence and synergy among global health initiatives.

BACKGROUND: The fast growth of global health initiatives (GHIs) has raised concerns regarding achievement of coherence and synergy among distinct, complementary and sometimes competing activities. Herein, we propose an approach to compare GHIs with regard to their main purpose and operational aspects, using the Special Programme for Research and Training in Tropical Diseases (TDR/WHO) as a case study. The overall goal is to identify synergies and optimize efforts to provide solutions to reduce the burden of diseases. METHODS: Twenty-six long-established GHIs were identified from among initiatives previously associated/partnered with TDR/WHO. All GHIs had working streams that would benefit from linking to the capacity building or implementation research focus of TDR. Individual profiles were created using a common template to collect information on relevant parameters. For analytical purposes, GHIs were simultaneously clustered in five and eight groups according to their 'intended outcome' and 'operational framework', respectively. A set of specific questions was defined to assess coherence/alignment against a TDR reference profile by attributing a score, which was subsequently averaged per GHI cluster. GHI alignment scores for intended outcome were plotted against scores for operational framework; based on the analysis of coherence/alignment with TDR functions and operations, a risk level (high, medium or low) of engagement was attributed to each GHI. RESULTS: The process allowed a bi-dimensional ranking of GHIs with regards to how adequately they fit with or match TDR features and perspectives. Overall, more consistence was observed with regard to the GHIs' main goals and expected outcomes than with their operational aspects, reflecting the diversity of GHI business models. Analysis of coherence indicated an increasing common trend for enhancing the engagement of developing country stakeholders, building research capacity and optimization of knowledge management platforms in support of improved access to healthcare. CONCLUSIONS: The process used offers a broader approach that could be adapted by other GHIs to build coherence and synergy with peer organizations and helps highlight the potential contribution of each GHI in the new era of sustainable development goals. Emerging opportunities and new trends suggest that engagement between GHIs should be selective and tailored to ensure efficient collaborations.

Plasmodium falciparum and Plasmodium vivax genotypes and efficacy of intermittent preventive treatment in Papua New Guinea.

Intermittent preventive treatment of infants (IPTi) reduces early childhood malaria-related morbidity. While genotypic drug resistance markers have proven useful in predicting the efficacy of antimalarial drugs in case management, there are few equivalent data relating to their protective efficacy when used as IPTi. The present data from an IPTi trial in Papua New Guinea demonstrate how these markers can predict protective efficacy of IPTi for both Plasmodium falciparum and Plasmodium vivax.

Research to policy and practice change: is capacity building in operational research delivering the goods?

OBJECTIVES: Between 2009 and 2012, eight operational research capacity building courses were completed in Paris (3), Luxembourg (1), India (1), Nepal (1), Kenya (1) and Fiji (1). Courses had strict milestones that were subsequently adopted by the Structured Operational Research and Training InitiaTive (SORT IT) of the World Health Organization. We report on the numbers of enrolled participants who successfully completed courses, the number of papers published and their reported effect on policy and/or practice. DESIGN: Retrospective cohort study including a survey. METHODS: Participant selection criteria ensured that only those proposing specific programme-related and relevant operational research questions were selected. Effects on policy and/or practice were assessed in a standardised manner by two independent reviewers. RESULTS: Of 93 enrolled participants from 31 countries (14 in Africa, 13 in Asia, two in Latin America and two in South Pacific), 83 (89%) completed their courses. A total of 96 papers were submitted to scientific journals of which 89 (93%) were published and 88 assessed for effect on policy and practice. There was a reported effect in 65 (74%) studies including changes to programme implementation (27), adaptation of monitoring tools (24) and changes to existing guidelines (20). CONCLUSION: Three quarters of published operational research studies from these structured courses had reported effects on policy and/or practice. It is important that this type of tracking becomes a standard component of operational research and research in general.

Distinct patterns of diversity, population structure and evolution in the AMA1 genes of sympatric Plasmodium falciparum and Plasmodium vivax populations of Papua New Guinea from an area of similarly high transmission.

BACKGROUND: As Plasmodium falciparum and Plasmodium vivax co-exist in most malaria-endemic regions outside sub-Saharan Africa, malaria control strategies in these areas must target both species in order to succeed. Population genetic analyses can predict the effectiveness of interventions including vaccines, by providing insight into patterns of diversity and evolution. The aim of this study was to investigate the population genetics of leading malaria vaccine candidate AMA1 in sympatric P. falciparum and P. vivax populations of Papua New Guinea (PNG), an area of similarly high prevalence (Pf = 22.3 to 38.8%, Pv = 15.3 to 31.8%). METHODS: A total of 72 Pfama1 and 102 Pvama1 sequences were collected from two distinct areas, Madang and Wosera, on the highly endemic PNG north coast. RESULTS: Despite a greater number of polymorphic sites in the AMA1 genes of P. falciparum (Madang = 52; Wosera = 56) compared to P. vivax (Madang = 36, Wosera = 34), the number of AMA1 haplotypes, haplotype diversity (Hd) and recombination (R) was far lower for P. falciparum (Madang = 12, Wosera = 20; Hd ≤0.92, R ≤45.8) than for P. vivax (Madang = 50, Wosera = 38; Hd = 0.99, R = ≤70.9). Balancing selection was detected only within domain I of AMA1 for P. vivax, and in both domains I and III for P. falciparum. CONCLUSIONS: Higher diversity in the genes encoding P. vivax AMA1 than in P. falciparum AMA1 in this highly endemic area has important implications for development of AMA1-based vaccines in PNG and beyond. These results also suggest a smaller effective population size of P. falciparum compared to P. vivax, a finding that warrants further investigation. Differing patterns of selection on the AMA1 genes indicate that critical antigenic sites may differ between the species, highlighting the need for independent investigations of these two leading vaccine candidates.

Effectiveness of artemether/lumefantrine for the treatment of uncomplicated Plasmodium vivax and P. falciparum malaria in young children in Papua New Guinea.

BACKGROUND: Artemisinin combination therapy is recommended as treatment for uncomplicated Plasmodium falciparum (Pf) malaria, whereas chloroquine is still widely used for non-Pf infections. A common treatment for both vivax and falciparum malaria would be welcome. METHODS: A longitudinal prospective effectiveness study of 1682 children aged 3-27 months in outpatient clinics in Papua New Guinea. The main outcome was clinical treatment failure rate following treatment with artemether/lumefantrine (AL). RESULTS: Among 5670 febrile episodes, 1682 (28%) had positive rapid diagnostic test (RDT) results and were treated with AL. A total of 1261 (22%) had an infection confirmed by blood slide examination. Of these, 594 Pv and 332 Pf clinical malaria cases were included in the primary effectiveness analysis. Clinical treatment failure rates at 7, 28, and 42 days were 0.2%, 2.2%, and 12.0%, respectively, for Pv and 0.3%, 1.2%, and 3.6%, respectively, for Pf. A single malaria-unrelated death occurred within 42 days following treatment with AL, in a child who was aparasitemic by blood slide at reattendance. CONCLUSIONS: AL provides a rapid clinical response against both Pf and Pv malaria, but is associated with a high rate of Pv recurrent clinical episodes between days 28 and 42. In order to prevent relapsing infections from long-lasting hypnozoites, AL should ideally be complemented with a course of primaquine. In the absence of better treatment and diagnostic options, the use of AL in young children in routine practice is an acceptable, interim option in coendemic areas where Pv is resistant to chloroquine and specific treatment for Pv hypnozoites not feasible.

Assessment of the impact of implementation research on the Visceral Leishmaniasis (VL) elimination efforts in Nepal.

Nepal, Bangladesh, and India signed a Memorandum of Understanding (MoU) in 2005 to eliminate visceral leishmaniasis (VL) as a public health problem from the Indian subcontinent by 2015. By 2021, the number of reported VL cases in these countries had declined by over 95% compared to 2007. This dramatic success was achieved through an elimination programme that implemented early case detection and effective treatment, vector control, disease surveillance, community participation, and operational research that underpinned these strategies. The experience offered an opportunity to assess the contribution of implementation research (IR) to VL elimination in Nepal. Desk review and a stakeholder workshop was conducted to analyse the relationship between key research outputs, major strategic decisions in the national VL elimination programme, and annual number of reported new cases over time between 2005 and 2023. The results indicated that the key decisions across the strategic elements, throughout the course of the elimination programme (such as on the most appropriate tools for diganostics and treatment, and on best strategies for case finding and vector management), were IR informed. IR itself responded dynamically to changes that resulted from interventions, addressing new questions that emerged from the field. Close collaboration between researchers, programme managers, and implementers in priority setting, design, conduct, and review of studies facilitated uptake of evidence into policy and programmatic activities. VL case numbers in Nepal are now reduced by 90% compared to 2005. Although direct attribution of disease decline to research outputs is difficult to establish, the Nepal experience demonstrates that IR can be a critical enabler for disease elimination. The lessons can potentially inform IR strategies in other countries with diseases targeted for elimination.

Rapid diagnostic test-based management of malaria: an effectiveness study in Papua New Guinean infants with Plasmodium falciparum and Plasmodium vivax malaria.

BACKGROUND: In malaria-endemic areas it is recommended that febrile children be tested for malaria by rapid diagnostic test (RDT) or blood slide (BS) and receive effective malaria treatment only if results are positive. However, RDTs are known to perform less well for Plasmodium vivax. We evaluated the safety of withholding antimalarial drugs from young Papua New Guinean children with negative RDT results in areas with high levels of both Plasmodium falciparum and P. vivax infections. METHODS: Longitudinal prospective study of children aged 3-27 months visiting outpatient clinics for fever. RDT was administered at first visit. RDT and microscopy were performed if children returned because of persistent symptoms. Outcomes were rates of reattendance and occurrence of severe illnesses. RESULTS: Of 5670 febrile episodes, 3942 (70%) involved a negative RDT result. In 133 cases (3.4%), the children reattended the clinic within 7 days for fever, of whom 29 (0.7%) were parasitemic by RDT or microscopy. Of children who reattended, 24 (0.7%) presented with a severe illness: 2 had lower respiratory tract infections (LRTIs) with low-density P. vivax on BS; 2 received a diagnosis of P. vivax malaria on the basis of RDT but BSs were negative; 16 had LRTIs; 3 had alternative diagnoses. Of these 24, 22 were cured at day 28. Two children died of illnesses other than malaria and were RDT and BS negative at the initial and subsequent visits. CONCLUSION: Treatment for malaria based on RDT results is safe and feasible even in infants living in areas with moderate to high endemicity for both P. falciparum and P. vivax infections.

Intermittent preventive treatment for malaria in Papua New Guinean infants exposed to Plasmodium falciparum and P. vivax: a randomized controlled trial.

BACKGROUND: Intermittent preventive treatment in infants (IPTi) has been shown in randomized trials to reduce malaria-related morbidity in African infants living in areas of high Plasmodium falciparum (Pf) transmission. It remains unclear whether IPTi is an appropriate prevention strategy in non-African settings or those co-endemic for P. vivax (Pv). METHODS AND FINDINGS: In this study, 1,121 Papua New Guinean infants were enrolled into a three-arm placebo-controlled randomized trial and assigned to sulfadoxine-pyrimethamine (SP) (25 mg/kg and 1.25 mg/kg) plus amodiaquine (AQ) (10 mg/kg, 3 d, n = 374), SP plus artesunate (AS) (4 mg/kg, 3 d, n = 374), or placebo (n = 373), given at 3, 6, 9 and 12 mo. Both participants and study teams were blinded to treatment allocation. The primary end point was protective efficacy (PE) against all episodes of clinical malaria from 3 to 15 mo of age. Analysis was by modified intention to treat. The PE (compared to placebo) against clinical malaria episodes (caused by all species) was 29% (95% CI, 10-43, p ≤ 0.001) in children receiving SP-AQ and 12% (95% CI, -11 to 30, p = 0.12) in those receiving SP-AS. Efficacy was higher against Pf than Pv. In the SP-AQ group, Pf incidence was 35% (95% CI, 9-54, p = 0.012) and Pv incidence was 23% (95% CI, 0-41, p = 0.048) lower than in the placebo group. IPTi with SP-AS protected only against Pf episodes (PE = 31%, 95% CI, 4-51, p = 0.027), not against Pv episodes (PE = 6%, 95% CI, -24 to 26, p = 0.759). Number of observed adverse events/serious adverse events did not differ between treatment arms (p > 0.55). None of the serious adverse events were thought to be treatment-related, and the vomiting rate was low in both treatment groups (1.4%-2.0%). No rebound in malaria morbidity was observed for 6 mo following the intervention. CONCLUSIONS: IPTi using a long half-life drug combination is efficacious for the prevention of malaria and anemia in infants living in a region highly endemic for both Pf and Pv.