Mapping the endemicity and seasonality of clinical malaria for intervention targeting in Haiti using routine case data

Towards the goal of malaria elimination on Hispaniola, the National Malaria Control Program of Haiti and its international partner organisations are conducting a campaign of interventions targeted to high-risk communities prioritised through evidence-based planning. Here we present a key piece of this planning: an up-to-date, fine-scale endemicity map and seasonality profile for Haiti informed by monthly case counts from 771 health facilities reporting from across the country throughout the 6-year period from January 2014 to December 2019. To this end, a novel hierarchical Bayesian modelling framework was developed in which a latent, pixel-level incidence surface with spatio-temporal innovations is linked to the observed case data via a flexible catchment sub-model designed to account for the absence of data on case household locations. These maps have focussed the delivery of indoor residual spraying and focal mass drug administration in the Grand’Anse Department in South-Western Haiti.

Evaluation of the Effect of Supervised Antimalarial Treatment on P. Vivax Malaria Recurrences

BackgroundRelapses in vivax malaria have posed great challenges to malaria control, accounting for a great proportion of reported cases. Knowing the real effectiveness of 7 day primaquine (PQ) scheme is crucial to understand not only the cost-effectiveness of implementing new anti-hypnozoite drugs but how health education strategies can guarantee better compliance and be reinforced. This study aimed the evaluation of the daily supervised treatment effect with chloroquine and PQ (in consented patients) versus prescription without supervision (non-consented patients), and the outcome was the passive detection of new positive thick blood smears until 180 days, based on the official data records from the National Malaria Control Program. The recurrences seen in the real life were therefore used as a surrogate for true relapses. Patients under supervised treatment had a lower risk of recurrence until day 180 when compared to the unsupervised treatment (17.9% vs 36.1%; p=0.027). The lack of consent in the non-supervised group (which followed standard of care in the real life) enabled proper comparison, as consent itself could lead to better compliance in this group. Future studies should scale such analysis to different settings in the Brazilian Amazon.

Therapeutic efficacy of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali, 2015–2016

Background The current first-line treatments for uncomplicated malaria recommended by the National Malaria Control Program in Mali are artemether–lumefantrine (AL) and artesunate–amodiaquine (ASAQ). From 2015–2016, we conducted an in vivo study to assess the clinical and parasitological responses to AL and ASAQ in Sélingué, Mali. Methods Children between 6 and 59 months of age with uncomplicated Plasmodium falciparum infection and 2,000–200,000 asexual parasites/µL of blood were enrolled, randomly assigned to either AL or ASAQ, and followed up for 42 days. Uncorrected and PCR-corrected efficacy results at days 28 and 42 were calculated. Known markers of resistance in the Pfk13, Pfmdr1, and Pfcrt genes were assessed using Sanger sequencing. Results A total of 449 patients were enrolled: 225 in the AL group and 224 in the ASAQ group. Uncorrected efficacy at day 28 was 83.4% (95% CI: 78.5–88.4%) in the AL arm and 93.1% (95% CI: 89.7–96.5%) in the ASAQ arm. The per protocol PCR-corrected efficacy at day 28 was 91.0% (86.0–95.9%) in the AL arm and 97.1% (93.6–100%) in the ASAQ arm. ASAQ was significantly (p < 0.05) better than AL for each of the aforementioned efficacy outcomes. No mutations associated with artemisinin resistance were identified in the Pfk13 gene. Overall, for Pfmdr1, the N86 allele and the NFD haplotype were the most common. The NFD haplotype was significantly more prevalent in the post-treatment than in the pre-treatment isolates in the AL arm (p < 0.01) but not in the ASAQ arm. For Pfcrt, the CVIET haplotype was the most common. Conclusions Our findings indicate that both AL and ASAQ remain effective for the treatment of uncomplicated malaria in Sélingué, Mali.

Genomic investigation of atypical malaria cases in Kanel, northern Senegal

BackgroundDiagnosis of malaria cases in regions where the malaria burden has decreased significantly and prevalence is very low becomes more challenging, in part because of reduced clinical presumption of malaria. The appearance of a cluster of malaria cases with atypical symptoms in Mbounguiel, a village in northern Senegal where malaria transmission is low, in September 2018 exemplifies this scenario. The collaboration between the national malaria control program (NMCP) at the Senegal ministry of health and the laboratory of parasitology mycology at Cheikh Anta Diop University worked together to evaluate this cluster of malaria cases using molecular and serology tools.ResultsNine of the fifteen patients were evaluated, and all nine samples were found to be positive for P. falciparum only. The 24 SNP molecular barcode showed the predominance of polygenomic infections, with identifiable strains being different from one another. All patients tested positive for the P. falciparum antigens. No other pathogenic infection was detected by either the serological panel or metagenomic sequencing. ConclusionsThis work undertaken locally within Senegal as a collaboration between the NMCP and a research malaria laboratory at University of Cheikh Anta Diop (UCAD) revealed that a cluster of malaria cases were caused by different strains of P. falciparum. The public health response in real time demonstrates the value of local molecular and genomics capacity in affected countries disease control and elimination.

Performance of pirimiphos-methyl based Indoor Residual Spraying on entomological parameters of malaria transmission in the pyrethroid resistance region of Koulikoro, Mali.

Background:Vector control relies heavily on Long-lasting insecticidal nets ( (LLINs) and Indoor Residual Spraying (IRS) in selected districts in Mali including Koulikoro district. As part of strengthening vector control strategies in the district, IRS was initiated by the National Malaria Control Program (NMCP) with the support of the US President's Malaria Initiative (PMI) since 2008. LLINs coverage was 93.3% and 98.2% for IRS in Koulikoro, the only district of the region where IRS was supported by PMI. Following mosquito vector resistance to both pyrethroid and carbamates, organophosphate (pirimiphos-methyl) was used for the IRS campaigns of 2015 and 2016 in the district of Koulikoro. In this study, we assessed the effect of IRS on malaria transmission by comparing entomological indices in of the district of Koulikoro, where IRS was implemented and its neighbored district of Banamba, where IRS had never been implemented. Methods:The study was conducted in two villages of each district (Koulikoro and Banamba). Pyrethrum spray catches and entry window trapping were used to collect mosquitoes on a monthly basis. WHO tube tests were carried out to assess mosquito susceptibility to insecticides. Mosquitoes were identified to species level by PCR and their infection to P. falciparum was detected by ELISA.Results:Of the 527 specimens identified, An. coluzzii was the most frequent species (95%) followed by An. gambiae (4%) and An. arabiensis (1%). Its density was rainfall dependent in the no-IRS area, and almost independent in the IRS area. The infection rate (IR) in the no-IRS area was 0.96%, while it was null in the IRS area. In the no-IRS area, the entomological inoculation rates (EIR) was 0.21 infective bites /person month with a peak in September. High resistance to pyrethroids and carbamates and susceptibility to organophosphates was observed at all sites.Conclusion:The introduction of pirimiphos-methyl based IRS in the area resulted in a significant decrease in malaria transmission. An.gambiae s.l., the main malaria vector of the area, was resistant to pyrethroids and carbamates, and remained susceptible to the organophosphates.

Susceptibility of Plasmodium falciparum isolates to antimalarial drugs in a highly seasonal malaria endemic village in Mali

Background: In 2006, the National Malaria Control Program (NMCP) in Mali recommended artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. Since the introduction of ACT, few reports are available on the level of resistance of Plasmodium falciparum (P. falciparum) to antimalarial drugs in Mali. Dihydroartermisinin is the active metabolite of artemisinin derivatives. Here, we conducted an ex-vivo drug sensitivity testing in a rural area of southern Mali, namely the Kéniéroba village from 2016 to 2017. Methods: Seventy-five (75) isolates of P. falciparum were successfully evaluated for ex-vivo sensitivity to key anti-malarial drugs, namely chloroquine (CQ), quinine (QN), amodiaquine (AQ), mefloquine (MQ), lumefantrine (LUM), dihydroartermisinin (DHA) , and piperaquine (PPQ). P. falciparum sensitivity to these drugs was assessed using the World Wide Antimalarial Resistance Network (WWARN) SYBR-GREEN method of inhibitory concentration of 50% (IC50) determination. Reduced sensitivity to antimalarial drugs was defined as IC50 less than the WWARN standard IC50. Results: The proportion of resistant P. falciparum isolates was 20.2% for CQ, 40.5% for QN, 6.8% for AQ, and 1.3% for MQ. All tested P. falciparum isolates were sensitive to LUM, DHA, and PPQ. A statistically significant correlation was found between QN and AQ IC50 values (r = 0.80; r2 = 0.64, P<0.0001). Conclusions: P. falciparum isolates were sensitive to all ACT derivates tested in Kenieroba in Mali. In contrast, P. falciparum isolates were resistant to, CQ, QN, and AQ as evidenced by high IC50 to these drugs.

A rapid, low-cost methodology for longitudinal evaluation of insecticide treated bednet distributions: a pilot survey coupling bednet usage with malaria prevalence at the household level

Tanzania’s National Malaria Control Program distributed 23.3 million insecticidetreated bed nets (ITNs) between 2009 and 2011. Annual randomized household surveys were conducted from 2009 to 2011 to assess the incremental effects of the distribution campaign on malaria prevalence and bednet usage in Kijumbura village in Kagera, Tanzania. Data was collected about household ITN ownership and individual use, and each household member was given a rapid malaria diagnostic test (RDT). In total, 1247 individuals from 285 households participated. From 2009 to 2011, household ITN ownership increased from 50.6 to 95.3% and individual usage increased from 9.7 to 55.3% in 2011. Malaria point prevalence decreased from 15.8% in 2009 to 6.5% in 2010, and increased from 6.5% in 2010 to 10.7% in 2011. The survey cost in 2011 was 23.50 USD per household; major expenses were transportation, personnel payment, and the purchase of the RDTs. Evaluations of bednet distribution programs generally rely on distribution data and selfreported net ownership, but it is important to also assess the goal endpoint of reduction in malaria prevalence. We show that this can be achieved quickly and cost-effectively through randomized surveys measuring bednet usage coupled with malaria prevalence at the household level.