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BackgroundIncreasing pyrethroid resistance has been an undesirable correlate of the rapid increase in coverage of insecticide-treated nets (ITNs) since 2000. Whilst monitoring of resistance levels has increased markedly over this period, longitudinal monitoring is still lacking, meaning the temporal and spatial dynamics of phenotypic resistance in the context of increasing ITN coverage are unclear.MethodsAs part of a large WHO-co-ordinated epidemiological study investigating the impact of resistance on malaria infection, longitudinal monitoring of phenotypic resistance to pyrethroids was undertaken in 290 clusters across Benin, Cameroon, India, Kenya and Sudan. Mortality in response to pyrethroids in the major anopheline vectors in each location was recorded during consecutive years using standard WHO test procedures. Trends in mosquito mortality were examined using generalised linear mixed-effect models.ResultsInsecticide resistance (using the WHO definition of mortality < 90%) was detected in clusters in all countries across the study period. The highest mosquito mortality (lowest resistance frequency) was consistently reported from India, in an area where ITNs had only recently been introduced. Substantial temporal and spatial variation was evident in mortality measures in all countries. Overall, a trend of decreasing mosquito mortality (increasing resistance frequency) was recorded (Odds Ratio per year: 0.79 per year (95% CI: 0.79-0.81, P < 0.001). There was also evidence that higher net usage was associated with lower mosquito mortality in some countries.DiscussionPyrethroid resistance increased over the study duration in four out of five countries. Insecticide-based vector control may be compromised as a result of ever higher resistance frequencies.

BACKGROUND\ud Chloroquine remains the mainstay of treatment for Plasmodium vivax malaria despite increasing reports of treatment failure. We did a systematic review and meta-analysis to investigate the effect of chloroquine dose and the addition of primaquine on the risk of recurrent vivax malaria across different settings.\ud \ud METHODS\ud A systematic review done in MEDLINE, Web of Science, Embase, and Cochrane Database of Systematic Reviews identified P vivax clinical trials published between Jan 1, 2000, and March 22, 2017. Principal investigators were invited to share individual patient data, which were pooled using standardised methods. Cox regression analyses with random effects for study site were used to investigate the roles of chloroquine dose and primaquine use on rate of recurrence between day 7 and day 42 (primary outcome). The review protocol is registered in PROSPERO, number CRD42016053310.\ud \ud FINDINGS\ud Of 134 identified chloroquine studies, 37 studies (from 17 countries) and 5240 patients were included. 2990 patients were treated with chloroquine alone, of whom 1041 (34·8%) received a dose below the target 25 mg/kg. The risk of recurrence was 32·4% (95% CI 29·8-35·1) by day 42. After controlling for confounders, a 5 mg/kg higher chloroquine dose reduced the rate of recurrence overall (adjusted hazard ratio [AHR] 0·82, 95% CI 0·69-0·97; p=0·021) and in children younger than 5 years (0·59, 0·41-0·86; p=0·0058). Adding primaquine reduced the risk of recurrence to 4·9% (95% CI 3·1-7·7) by day 42, which is lower than with chloroquine alone (AHR 0·10, 0·05-0·17; p

Background & objectives: India has switched over to artemisinin-based combination therapy (ACT) for the treatment of acute uncomplicated Plasmodium falciparum malaria and the ACT used in the national programme is artesunate + sulphadoxine-pyrimethamine. Since the efficacy of ACT is dependent also on the partner drug, there is a need to evaluate and deploy multiple ACTs. Methods: This multicentre, single-arm, open-label clinical trial was carried out to assess the efficacy, safety and population pharmacokinetics of a fixed dose combination (FDC) artesunate mefloquine (ASMQ) in P. falciparum infected, Indian adults at Panjim, Goa, and Mangalore, Karnataka between December 2007 and November 2008. Results: A total of 77 patients (males 74) were screened and enrolled: 42 at Goa and 35 at Mangalore with a median age of 25 yr (range 18-55 yr). One patient failed in treatment on D53, a PCR proven new infection, seven developed recurrent vivax parasitaemia and 11 did not have a parasitological endpoint. By per protocol analysis, the D63 cure rate was 58/59 (98.3; 95% C.I. 90.9-99.9%), and 58/58, with PCR correction. ASMQ was welltolerated and no serious adverse events were reported. Interpretation & conclusion: The study showed that the ASMQ FDC was efficacious and well-tolerated for the treatment of acute, uncomplicated P. falciparum malaria in highly endemic, chloroquine resistant areas of Goa and Mangalore. It is a viable option for India.

The Malaria Policy Advisory Committee to the World Health Organization met for the first time from 31 January to 2 February 2012 in Geneva, Switzerland. This article provides a summary of the discussions, conclusions and recommendations from that meeting, as part of the newly launched Malaria Journal thematic series “WHO Malaria Policy Advisory Committee: Reports and Recommendations”. Summaries are provided, referencing the relevant background documents, for the meeting sessions on global malaria control, drug resistance and containment, rapid diagnostic test procurement criteria, larviciding, classification of countries for elimination, estimating malaria cases and deaths, and seasonal malaria chemoprevention. Policy statements, position statements, and guidelines that will arise from the MPAC meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization member states by the World Health Organization Global Malaria Programme.

The Malaria Policy Advisory Committee to the World Health Organization held its fourth meeting in Geneva, Switzerland from 11 to 13 September, 2013. This article provides a summary of the discussions, conclusions and recommendations from that meeting. Meeting sessions included: recommendations for achieving universal coverage of long-lasting insecticide-treated nets; guidance on estimating the longevity of insecticide-treated nets; improving capacity in entomology and vector control; a review of the latest evidence on intermittent preventive treatment in pregnancy; improving dissemination of Malaria Policy Advisory Committee guidance; updates on the development of the global technical strategy for malaria control and elimination (2016–2025) and the global strategy for control and elimination of Plasmodium vivax; updates from the drug resistance and containment technical expert group, the evidence review group on malaria burden estimation, a consultation on malaria case management indicators, and the constitution of the surveillance, monitoring and evaluation technical expert group; subnational elimination criteria; and consideration for future evidence review groups, including diagnosis in low transmission settings and testing for Glucose-6-Phosphate Dehydrogenase Deficiency. Policy statements, position statements and guidelines that arise from the Malaria Policy Advisory Committee meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization Member States by the World Health Organization Global Malaria Programme.

Plasmodium DNA, in addition to being used for molecular diagnosis of malaria, find utility in monitoring patient responses to antimalarial drugs, drug resistance studies, genotyping and sequencing purposes. Over the years, numerous protocols have been proposed for extracting Plasmodium DNA from a variety of sources. Given that DNA isolation is fundamental to successful molecular studies, here we review the most commonly used methods for Plasmodium genomic DNA isolation, emphasizing their pros and cons. A comparison of these existing methods has been made, to evaluate their appropriateness for use in different applications and identify the method suitable for a particular laboratory based study. Selection of a suitable and accessible DNA extraction method for Plasmodium requires consideration of many factors, the most important being sensitivity, cost-effectiveness and, purity and stability of isolated DNA. Need of the hour is to accentuate on the development of a method that upholds well on all these parameters.

Background & objectives: Aedes mosquito control has gained much importance nowadays in view of rise in number of reported cases of dengue and chikungunya in India and other countries. In the present study, C21 attracticide (containing a pheromone and an insect growth regulator-IGR, developed by Defence Research and Development Establishment (DRDE), Gwalior, India was tested for its feasibility for surveillance and control of Aedes mosquito in a multicentric mode from October 2007 to June 2012 in urban (Delhi, and Bengaluru district, Karnataka) and suburban (Alappuzha district, Kerala) settings of the country in three phases. Methods: Across the randomly selected households in each study area, two to four containers treated with attracticide (experimental) and untreated (control) were placed and monitored by trained surveillance workers on weekly/ fortnightly basis for determining the presence of eggs, larvae and pupae. Container positivity, percent larvae, egg and pupae collected were determined during different phases and analyzed statistically using SPSS 18.0. Results: Container positivity was found statistically significant at Bengaluru and Alappuzha, Kerala while in Delhi, it was found non-significant. Eggs collected from experimental containers were significantly higher in comparison to control at all the locations except Delhi. Also larvae collected from control containers were significantly higher at all the locations except Bengaluru. Pupae collected from control containers remained significantly higher at all the locations as no pupal formation was recorded from experimental containers. Interpretation & conclusion: The use of C21 attracticide hampered pupal formation, thus inhibiting adult population in the study areas. The study established that C21 attracticide was efficacious in the field conditions and has potential for use in surveillance and management of dengue and chikungunya mosquitoes.

The Malaria Policy Advisory Committee to the World Health Organization met in Geneva, Switzerland from 13 to 15 March, 2013. This article provides a summary of the discussions, conclusions and recommendations from that meeting. Meeting sessions included: a review of the efficacy of artemisinin-based combination therapy in Guyana and Suriname; the outcomes from a consultation on non-malaria febrile illness; the outcomes from the second meeting of the Evidence Review Group on malaria burden estimation; an update on the review of the WHO Guidelines for the Treatment of Malaria; an update regarding progress on the constitution of the vector control Technical Expert Group; updates on the RTS, S/AS01 vaccine and the malaria vaccine technology roadmap; financing and resource allocation for malaria control; malaria surveillance and the need for a surveillance, monitoring and evaluation Technical Expert Group; criteria and classification related to malaria elimination; the next meeting of the Evidence Review Group on Intermittent Preventive Treatment in pregnancy; an update on the soon-to-be launched Elimination Scenario Planning Tool; and an update on the process for the Global Technical Strategy for Malaria Control and Elimination (2016–2025). Policy statements, position statements, and guidelines that arise from the MPAC meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization Member States by the World Health Organization Global Malaria Programme.

Background: Plasmodium falciparum the main causative agent of malaria is an important public health vector. With the use of PCR, its genetic diversity has been extensively studied with dearth information from Nigeria.Methods: In this study, 100 P. falciparum strains merozoite surface protein 1( msp-1), merozoite surface protein 2 (msp-2) and Glutamate rich protein (Glurp) from Ogun State General Hospitals were characterized. The genetic diversity of P. falciparum isolates was analyzed by restriction fragment length polymorphism following gel electrophoresis of DNA products from nested polymerase chain reactions (PCR) of their respective allelic families KI, MAD 20, RO33 (MSP-1);FC27, 3D7 (MSP-2) and Glutamate rich protein respectively.Results: Majority of the patients showed monoclonal infections while multiplicity of the infection for msp-1 and msp-2 were 1.1 and 1.2 respectively. The estimated number of genotypes was 8 msp-1 (4 KI; 3 MAD; 1 RO33) and 6 msp-2 (3 FC27; 3 3D7). 80% of the isolates coded for Glurp with allelic size ranged between 700 and 900 bp.Conclusion: The allelic distributions however were similar to those previously reported in other endemic malaria countries. Future studies will be designed to include other malaria endemic regions of Nigeria such as the oil exploration regions.Keywords: Genetic diversity; Plasmodium; Merozoite surface protein, monoclonal infection

Background & objectives: Delhi, the capital city of India, has so far witnessed several outbreaks of dengue fever since 1967 (last one reported in 2013). Improved virological and entomological surveillance are the only tools that can help in prevention of dengue as well as in the development of dengue control programmes. The aim of the study was to conduct a prospective field study to detect dengue virus in adult Aedes aegypti mosquitoes collected from various localities represented by different socioeconomic groups in Delhi. Methods: The study areas were selected and categorized into high, medium and low income groups on the basis of socioeconomical characteristics of the resident population, where dengue cases were reported during the past three years by MCD. Dengue viral infection was detected in the head squash of each adult mosquito by immunofluorescent assay (IFA) employing monoclonal antibodies against dengue virus (DENV). A total of 2408 females and 1206 males of Ae. aegypti were collected and tested by IFA. Results: Out of 2408 Ae. aegypti females, 14 were found positive, with minimum infection rate (MIR) of 5.8 per 1000 mosquitoes. Among the 18 study areas, 11 localities were found positive for dengue virus infection. Low income group (LIG) areas showed highest mosquito infectivity (9.8), followed by medium income group (MIG), i.e. 6.2; while least was observed in high income group (HIG), i.e. 1.3. No vertical transmission of dengue virus could be detected in 1206 Ae. aegypti males collected. Interpretation & conclusion: The study concludes that there was high MIR in the identified localities of low and medium income groups. Estimation of MIR in a female Aedes mosquito in the existing arsenals for dengue surveillance would be an added advantage for early warning of dengue outbreak. The presence of infected mosquitoes in identified localities of Delhi was alarming and require rigorous vector surveillance so that the severe outbreaks can be prevented.

Malaria parasite infections that are only detectable by molecular methods are highly prevalent and represent a potential transmission reservoir. The methods used to detect these infections are not standardized, and their operating characteristics are often unknown. We designed a proficiency panel of Plasmodium spp. in order to compare the accuracy of parasite detection of molecular protocols used by labs in a clinical trial consortium. Ten dried blood spots (DBSs) were assembled that contained P. falciparum, P. vivax, P. malariae, and P. ovale; DBSs contained either a single species or a species mixed with P. falciparum. DBS panels were tested in 9 participating laboratories in a masked fashion. Of 90 tests, 68 (75.6%) were correct; there were 20 false-negative results and 2 false positives. The detection rate was 77.8% (49/63) for P. falciparum, 91.7% (11/12) for P. vivax, 83.3% (10/12) for P. malariae, and 70% (7/10) for P. ovale. Most false-negative P. falciparum results were from samples with an estimated ≤5 parasites per μl of blood. Between labs, accuracy ranged from 100% to 50%. In one lab, the inability to detect species in mixed-species infections prompted a redesign and improvement of the assay. Most PCR-based protocols were able to detect P. falciparum and P. vivax at higher densities, but these assays may not reliably detect parasites in samples with low P. falciparum densities. Accordingly, formal quality assurance for PCR should be employed whenever this method is used for diagnosis or surveillance. Such efforts will be important if PCR is to be widely employed to assist malaria elimination efforts.