Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine.

Abstract Placental malaria is a public health burden particularly in Africa as it causes severe symptoms and results in stillbirths or maternal deaths. Plasmodium falciparum protein VAR2CSA drives placental malaria (PM) in pregnant women by adhering to chondroitin sulfate A (CSA) on the placenta. VAR2CSA is a primary vaccine candidate for PM with two vaccines based on it already under clinical trials. The first cryo-EM three-dimensional structure of Pf CSA-VAR2CSA complex revealed crucial interacting residues considered to be highly conserved across P. falciparum strains. In the current study, we have conducted a global sequence analysis of 1,114 VAR2CSA field isolate sequences from more than nine countries across three continents revealing numerous mutations in CSA-binding residues. Further, structural mapping has revealed significant polymorphisms on the ligand binding surfaces. The variants from this limited set of 1,114 sequences highlight the concerns that are vital in current considerations for development of vaccines based on VAR2CSA for placental malaria

Field and laboratory comparative evaluation of rapid malaria diagnostic tests versus traditional and molecular techniques in India

<p>Abstract</p> <p>Background</p> <p>Malaria presents a diagnostic challenge in most tropical countries. Microscopy remains the gold standard for diagnosing malaria infections in clinical practice and research. However, microscopy is labour intensive, requires significant skills and time, which causes therapeutic delays. The objective of obtaining result quickly from the examination of blood samples from patients with suspected malaria is now made possible with the introduction of rapid malaria diagnostic tests (RDTs). Several RDTs are available, which are fast, reliable and simple to use and can detect <it>Plasmodium falciparum </it>and non-falciparum infections or both. A study was conducted in tribal areas of central India to measure the overall performance of several RDTs for diagnosis of <it>P. falciparum </it>and non-falciparum infections in comparison with traditional and molecular techniques. Such data will be used to guide procurement decisions of policy makers and programme managers.</p> <p>Methods</p> <p>Five commercially available RDTs were tested simultaneously in field in parallel with peripheral blood smears in outbreak-affected areas. The evaluation is designed to provide comparative data on the performance of each RDT. In addition, molecular method i.e. polymerase chain reaction (PCR) was also carried out to compare all three methods.</p> <p>Results</p> <p>A total of 372 patients with a clinical suspicion of malaria from Bajag Primary Health Centre (PHC) of district Dindori and Satanwada PHC of district Shivpuri attending the field clinics of Regional Medical Research Centre were included in the study. The analysis revealed that the First Response Malaria Antigen pLDH/HRP2 combo test was 94.7% sensitive (95% CI 89.5-97.7) and 69.9% specific (95% CI 63.6-75.6) for <it>P. falciparum</it>. However, for non-falciparum infections (<it>Plasmodium vivax</it>) the test was 84.2% sensitive (95% CI 72.1-92.5) and 96.5% specific (95% CI 93.8-98.2). The Parascreen represented a good alternative. All other RDTs were relatively less sensitive for both <it>P. falciparum </it>and non-falciparum infections.</p> <p>Conclusions</p> <p>The results in this study show comparative performance between microscopy, various RDTs and PCR. Despite some inherent limitation in the five RDTs tested, First Response clearly has an advantage over other RDTs. The results suggest that RDTs could play and will play an important role in malaria diagnosis.</p

The usefulness of a new rapid diagnostic test, the First Response® Malaria Combo (pLDH/HRP2) card test, for malaria diagnosis in the forested belt of central India

<p>Abstract</p> <p>Background</p> <p>Malaria presents a diagnostic challenge in tribal belt of central India where two Plasmodium species, <it>Plasmodium falciparum </it>and <it>Plasmodium vivax</it>, are prevalent. In these areas, rapid detection of the malaria parasites and early treatment of infection remain the most important goals of disease management. Therefore, the usefulness of a new rapid diagnostic (RDT), the First Response^®Combo Malaria Ag (pLDH/HRP2) card test was assessed for differential diagnosis between <it>P. falciparum </it>with other Plasmodium species in remote villages of Jabalpur district.</p> <p>Methods</p> <p>A finger prick blood sample was collected to prepare blood smear and for testing with the RDT after taking informed consent. The figures for sensitivity, specificity, accuracy and predictive values were calculated using microscopy as gold standard.</p> <p>Results</p> <p>Analysis revealed that overall, the RDT was 93% sensitive, 85% specific with a positive predictive value (PPV) of 79%, and a negative predictive value (NPV) of 95%. The accuracy 88% and J-index was 0.74. For <it>P. falciparum</it>, the sensitivity and specificity of the test were 96% and 95% respectively, with a PPV of 85% and a NPV of 99%. The RDT accuracy 95% and J-index was 0.84. For non-falciparum malaria, the sensitivity, specificity and accuracy were 83%, 94% and 92% respectively with a PPV of 69% and a NPV of 97%.</p> <p>Conclusion</p> <p>The RDTs are easy to use, reliable and simple to interpret. RDTs are more suited to health workers in situations where health services are deficient or absent. Therefore, the test can be used as an epidemiological tool for the rapid screening of malaria.</p

Diagnostic and prognostic utility of an inexpensive rapid on site malaria diagnostic test (ParaHIT f) among ethnic tribal population in areas of high, low and no transmission in central India

BACKGROUND: Malaria presents a diagnostic challenge in most tropical countries. Rapid detection of the malaria parasite and early treatment of infection still remain the most important goals of disease management. Therefore, performance characteristics of the new indigenous ParaHIT f test (Span diagnostic Ltd, Surat, India) was determined among ethnic tribal population in four districts of different transmission potential in central India to assess whether this rapid diagnostic test (RDT) could be widely applied as a diagnostic tool to control malaria. Beyond diagnosis, the logical utilization of RDTs is to monitor treatment outcome. METHODS: A finger prick blood sample was collected from each clinically suspected case of malaria to prepare blood smear and for testing with the RDT after taking informed consent. The blood smears were read by an experienced technician blinded to the RDT results and clinical status of the subjects. The figures for specificity, sensitivity, accuracy and predictive values were calculated using microscopy as gold standard. RESULTS: The prevalence of malaria infection estimated by RDT in parallel with microscopy provide evidence of the type of high, low or no transmission in the study area. Analysis revealed (pooled data of all four epidemiological settings) that overall sensitivity, specificity and accuracy of the RDT were >90% in areas of different endemicity. While, RDT is useful to confirm the diagnosis of new symptomatic cases of suspected P. falciparum infection, the persistence of parasite antigen leading to false positives even after clearance of asexual parasitaemia has limited its utility as a prognostic tool. CONCLUSION: The study showed that the ParaHIT f test was easy to use, reliable and cheap. Thus this RDT is an appropriate test for the use in the field by paramedical staff when laboratory facilities are not available and thus likely to contribute greatly to an effective control of malaria in resource poor countries

Science of malaria elimination: using knowledge of bottlenecks and enablers from the Malaria Elimination Demonstration Project in Central India for eliminating malaria in the Asia Pacific region

Malaria poses a major public health challenge in the Asia Pacific. Malaria Elimination Demonstration Project was conducted as a public-private partnership initiative in Mandla between State government, ICMR, and FDEC India. The project employed controls for efficient operational and management decisions. IEC campaigns found crucial in schools and communities. Capacity building of local workers emphasized for better diagnosis and treatment. SOCH mobile app launched for complete digitalization. Better supervision for Indoor Residual Sprays and optimized Long Lasting Insecticidal Nets distribution. Significant malaria cases reduction in Mandla. Insights from MEDP crucial for malaria elimination strategies in other endemic regions of the Asia Pacific

Therapeutic efficacy of artemether–lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria from three highly malarious states in India

Additional file 1. Flowchart showing site-wise enrolment and follow-up profile