The cost of tsetse control using ‘Tiny Targets’ in the sleeping sickness endemic forest area of Bonon in Côte d’Ivoire: Implications for comparing costs across different settings

Background Work to control the gambiense form of human African trypanosomiasis (gHAT), or sleeping sickness, is now directed towards ending transmission of the parasite by 2030. In order to supplement gHAT case-finding and treatment, since 2011 tsetse control has been implemented using Tiny Targets in a number of gHAT foci. As this intervention is extended to new foci, it is vital to understand the costs involved. Costs have already been analysed for the foci of Arua in Uganda and Mandoul in Chad. This paper examines the costs of controlling Glossina palpalis palpalis in the focus of Bonon in Côte d’Ivoire from 2016 to 2017. Methodology/Principal findings Some 2000 targets were placed throughout the main gHAT transmission area of 130 km2 at a density of 14.9 per km2. The average annual cost was USD 0.5 per person protected, USD 31.6 per target deployed of which 12% was the cost of the target itself, or USD 471.2 per km2 protected. Broken down by activity, 54% was for deployment and maintenance of targets, 34% for tsetse surveys/monitoring and 12% for sensitising populations. Conclusions/Significance The cost of tsetse control per km2 of the gHAT focus protected in Bonon was more expensive than in Chad or Uganda, while the cost per km2 treated, that is the area where the targets were actually deployed, was cheaper. Per person protected, the Bonon cost fell between the two, with Uganda cheaper and Chad more expensive. In Bonon, targets were deployed throughout the protected area, because G. p. palpalis was present everywhere, whereas in Chad and Uganda G. fuscipes fuscipes was found only the riverine fringing vegetation. Thus, differences between gHAT foci, in terms of tsetse ecology and human geography, impact on the cost-effectiveness of tsetse control. It also demonstrates the need to take into account both the area treated and protected alongside other impact indicators, such as the cost per person protected.

Current Situation of Malaria and Resistance of Main Vectors to WHO Recommended Insecticides in an Endemic Area, Southeastern Iran

Although malaria is endemic in some areas of southeastern Iran, following the successful national malaria elimination plan, the local transmission area has been shrunk. The main cases in Iran are due to Plasmodium vivax followed by P. falciparum. This study was aimed to determine the current situation of malaria in Kerman Province of Iran and evaluate the insecticide resistance of main vectors. The field study was conducted in 2019. Data of new malaria cases were obtained from the health centers for the period of 2009–2018. Susceptibility status of Anopheles stephensi and An. dthali was evaluated against dichlorodiphenyltrichloroethane, Dieldrin, Malathion, Bendiocarb, Deltamethrin, and Temephos at the diagnostic dose. A total of 522 malaria cases were recorded and divided into indigenous (33.14%) and imported (66.86%) categories. The highest incidence of the disease was reported from the southern areas of the province, where all indigenous cases occurred. Adults of An. stephensi were resistant to dichlorodiphenyltrichloroethane while its resistance to be confirmed to dieldrin, bendiocarb and deltamethrin. As An. dthali had less than 98% mortality against bendiocarb, the resistance status should be confirmed with more tests. Our findings showed both species had less than 98% mortality against bendiocarb and deltamethrin insecticides which are used in malaria vector control program in Iran. Due to the susceptibility of these vectors to temephos, larviciding can be advised for vector control in this area.

Assessing the Relationship Between Gravidity and Placental Malaria Among Pregnant Women in a High Transmission Area in Ghana

Background Malaria infection during pregnancy can cause significant morbidity and mortality to a pregnant woman, her foetus and newborn. In areas of high endemic transmission, gravidity is an important risk factor for infection, but there is a complex relationship with other exposure-related factors, and use of protective measures. This study investigated the association between gravidity and placental malaria (PM), among pregnant women aged 14-49 in Kintampo, a high transmission area of Ghana. Methods Between 2008-2011, as part of a study investigating the association between PM and malaria in infancy, pregnant women attending antenatal care (ANC) clinics in the study area were enrolled and followed up until delivery. The outcome of PM was assessed at delivery by placental histopathology. Multivariable logistic regression analyses were used to investigate the association between gravidity and PM, identify other key risk factors, and control for potential confounders. Pre-specified effect modifiers including area of residence, socio-economic score (SES), ITN use and IPTp-SP use were explored. Results The prevalence of PM was 65.9% in primigravidae, and 26.5% in multigravidae. After adjusting for age, SES and relationship status, primigravidae were shown to have over three times the odds of PM compared to multigravidae, defined as women with 2 or more previous pregnancies (adjusted OR=3.36 (95% CI 2.39-4.71), N=1808, P<0.001). The association appeared stronger in rural areas (OR for PG vs. MG was 3.79 (95% CI: 3.61-5.51) in rural areas; 2.09 (95% CI: 1.17- 3.71) in urban areas; P for interaction =0.07), and among women with lower socio-economic scores (OR for PG vs. MG was 4.73 (95% CI 3.08-7.25) amongst women with lower SES; OR=2.14 (95% CI 1.38-3.35) among women with higher SES; P for interaction =0.008. There was also evidence of lower risk among primigravidae with better use of the current preventive measures IPTp and LLIN. Conclusions The burden of PM is most heavily focused on primigravidae of low SES living in rural areas of high transmission. Programmes should prioritize primigravidae and young women of child-bearing age for interventions such as LLIN distribution, educational initiatives and treatment to reduce the burden of malaria in first pregnancy.

Microbiota Variation Across Life Stages of European Field-Caught Anopheles atroparvus and During Laboratory Colonization: New Insights for Malaria Research

The potential use of bacteria for developing novel vector control approaches has awakened new interests in the study of the microbiota associated with vector species. To set a baseline for future malaria research, a high-throughput sequencing of the bacterial 16S ribosomal gene V3-V4 region was used to profile the microbiota associated with late-instar larvae, newly emerged females, and wild-caught females of a sylvan Anopheles atroparvus population from a former malaria transmission area of Spain. Field-acquired microbiota was then assessed in non-blood-fed laboratory-reared females from the second, sixth, and 10th generations. Diversity analyses revealed that bacterial communities varied and clustered differently according to origin with sylvan larvae and newly emerged females distributing closer to laboratory-reared females than to their field counterparts. Inter-sample variation was mostly observed throughout the different developmental stages in the sylvan population. Larvae harbored the most diverse bacterial communities; wild-caught females, the poorest. In the transition from the sylvan environment to the first time point of laboratory breeding, a significant increase in diversity was observed, although this did decline under laboratory conditions. Despite diversity differences between wild-caught and laboratory-reared females, a substantial fraction of the bacterial communities was transferred through transstadial transmission and these persisted over 10 laboratory generations. Differentially abundant bacteria were mostly identified between breeding water and late-instar larvae, and in the transition from wild-caught to laboratory-reared females from the second generation. Our findings confirmed the key role of the breeding environment in shaping the microbiota of An. atroparvus. Gram-negative bacteria governed the microbiota of An. atroparvus with the prevalence of proteobacteria. Pantoea, Thorsellia, Serratia, Asaia, and Pseudomonas dominating the microbiota associated with wild-caught females, with the latter two governing the communities of laboratory-reared females. A core microbiota was identified with Pseudomonas and Serratia being the most abundant core genera shared by all sylvan and laboratory specimens. Overall, understanding the microbiota composition of An. atroparvus and how this varies throughout the mosquito life cycle and laboratory colonization paves the way when selecting potential bacterial candidates for use in microbiota-based intervention strategies against mosquito vectors, thereby improving our knowledge of laboratory-reared An. atroparvus mosquitoes for research purposes.

In vivo efficacy and safety of artemether–lumefantrine and amodiaquine–artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018

Background Artemisinin-based combination therapy (ACT) has been the recommended first-line treatment for uncomplicated malaria in Mozambique since 2006, with artemether–lumefantrine (AL) and amodiaquine–artesunate (AS–AQ) as the first choice. To assess efficacy of currently used ACT, an in vivo therapeutic efficacy study was conducted. Methods The study was conducted in four sentinel sites: Montepuez, Moatize, Mopeia and Massinga. Patients between 6 and 59 months old with uncomplicated Plasmodium falciparum malaria (2000–200,000 parasites/µl) were enrolled between February and September of 2018, assigned to either an AL or AS–AQ treatment arm, and monitored for 28 days. A Bayesian algorithm was applied to differentiate recrudescence from new infection using genotyping data of seven neutral microsatellites. Uncorrected and PCR-corrected efficacy results at day 28 were calculated. Results Totals of 368 and 273 patients were enrolled in the AL and AS–AQ arms, respectively. Of these, 9.5% (35/368) and 5.1% (14/273) were lost to follow-up in the AL and AS–AQ arms, respectively. There were 48 and 3 recurrent malaria infections (late clinical and late parasitological failures) in the AL and AS–AQ arms, respectively. The day 28 uncorrected efficacy was 85.6% (95% confidence interval (CI) 81.3–89.2%) for AL and 98.8% (95% CI 96.7–99.8%) for AS–AQ, whereas day 28 PCR-corrected efficacy was 97.9% (95% CI 95.6–99.2%) for AL and 99.6% (95% CI 97.9–100%) for AS–AQ. Molecular testing confirmed that 87.4% (42/48) and 33.3% (1/3) of participants with a recurrent malaria infection in the AL and AS–AQ arms were new infections; an expected finding in a high malaria transmission area. Adverse events were documented in less than 2% of participants for both drugs. Conclusion Both AL and AS–AQ have therapeutic efficacies well above the 90% WHO recommended threshold and remain well-tolerated in Mozambique. Routine monitoring of therapeutic efficacy should continue to ensure the treatments remain efficacious. Trial registration Clinicaltrials.gov: NCT04370977

GENETIC ARCHITECTURE AND DYNAMICS OF PFKELCH13S PROPELLER DOMAIN IN SENEGALESE PLASMODIUM FALCIPARUMCLINICAL ISOLATES

Plasmodium resistance to Artemisinin Combination-based Therapies (ACT) in Southeast Asia is a major public health concern that is sporadically appearing in Africa. Senegal has shifted from malaria control to elimination plans. Given notable progresses obtained through robust strategic plans,it is still crucial to assess genetic variability of the Plasmodium falciparumartemisinin resistance gene marker Kelch13 (PfKelch13)in circulating field isolates.We herereportan analysis of PfKelch13-propeller polymorphism in clinical isolates collected nine years after ACT introduction in five Senegalese regions with different malaria transmission settings. Sequencing of PfKelch13-propeller domainfrom 280 clinicalisolates reveals that 16% (45/280) of the parasite population harboredvariants. Dynamics of PfKelch13 variants reveals emerging, persistent but also disappearing mutations over time. In addition to the malaria epidemiology, our survey also shows the dynamics of PfKelch13 variants in different malaria transmission settings in Senegal. Despite the absence of PfKelch13associatedartemisinin resistance mutations, a shift from 86% to 68% of PfKelch13WTwas observed when comparing parasites collected prior vs. post ACT intensive usage in Dakar a low malaria transmission area. All together,our data confirms the need to closely monitor PfKelch13 polymorphism to anticipate and or preventemergence ofP. falciparum resistancein Senegal.

Sensitive detection of Plasmodium vivax malaria by the rotating-crystal magneto-optical method in Thailand

The rotating-crystal magneto-optical detection (RMOD) method has been developed for the rapid and quantitative diagnosis of malaria and tested systematically on various malaria infection models. Very recently, an extended field trial in a high-transmission region of Papua New Guinea demonstrated its great potential for detecting malaria infections, in particular Plasmodium vivax. In the present small-scale field test, carried out in a low-transmission area of Thailand, RMOD confirmed malaria in all samples found to be infected with Plasmodium vivax by microscopy, our reference method. Moreover, the magneto-optical signal for this sample set was typically 1–3 orders of magnitude higher than the cut-off value of RMOD determined on uninfected samples. Based on the serial dilution of the original patient samples, we expect that the method can detect Plasmodium vivax malaria in blood samples with parasite densities as low as $$\sim$$ ∼ 5–10 parasites per microliter, a limit around the pyrogenic threshold of the infection. In addition, by investigating the correlation between the magnitude of the magneto-optical signal, the parasite density and the erythrocytic stage distribution, we estimate the relative hemozoin production rates of the ring and the trophozoite stages of in vivo Plasmodium vivax infections.

Comparison of the impact of allelic polymorphisms in PfAMA1 on the induction of T Cell responses in high and low malaria endemic communities in Ghana

Background Malaria eradication requires a combined effort involving all available control tools, and these efforts would be complemented by an effective vaccine. The antigen targets of immune responses may show polymorphisms that can undermine their recognition by immune effectors and hence render vaccines based on antigens from a single parasite variant ineffective against other variants. This study compared the influence of allelic polymorphisms in Plasmodium falciparum apical membrane antigen 1 (PfAMA1) peptide sequences from three strains of P. falciparum (3D7, 7G8 and FVO) on their function as immunodominant targets of T cell responses in high and low malaria transmission communities in Ghana. Methods Peripheral blood mononuclear cells (PBMCs) from 10 subjects from a high transmission area (Obom) and 10 subjects from a low transmission area (Legon) were tested against 15 predicted CD8 + T cell minimal epitopes within the PfAMA1 antigen of multiple parasite strains using IFN-γ ELISpot assay. The peptides were also tested in similar assays against CD8 + enriched PBMC fractions from the same subjects in an effort to characterize the responding T cell subsets. Results In assays using unfractionated PBMCs, two subjects from the high transmission area, Obom, responded positively to four (26.7%) of the 15 tested peptides. None of the Legon subject PBMCs yielded positive peptide responses using unfractionated PBMCs. In assays with CD8 + enriched PBMCs, three subjects from Obom made positive recall responses to six (40%) of the 15 tested peptides, while only one subject from Legon made a positive recall response to a single peptide. Overall, 5 of the 20 study subjects who had positive peptide-specific IFN-γ recall responses were from the high transmission area, Obom. Furthermore, while subjects from Obom responded to peptides in PfAMA1 from multiple parasite strains, one subject from Legon responded to a peptide from 3D7 strain only. Conclusions The current data demonstrate the possibility of a real effect of PfAMA1 polymorphisms on the induction of T cell responses in malaria exposed subjects, and this effect may be more pronounced in communities with higher parasite exposure.

Survival analysis and influence of the surgical aggression of a cohort of orthopedic and trauma patients in a non-controlled spread COVID-19 scenario

Background Determining the infection rate and mortality probability in healthy patients who have undergone orthopedic and trauma surgeries (OTS) during a period of uncontrolled COVID-19 transmission may help to inform preparations for future waves. This study performed a survival analysis in a cohort of non-infected OTS patients and determined the effect of COVID-19 on mortality. Methods This observational study included 184 patients who underwent OTS in the month before surgical activities ceased and before the implementation of special measures. Four groups of surgery (GS) were established based on the location of the surgery and the grade of inflammation produced. Crude risk of infection and infection rates were assessed. Survival and failure functions by GS were analyzed. Comparison of the Kaplan-Meier survival curves by GS was assessed. Cox regression and Fine-Gray models were used to determine the effect of different confounders on mortality. Results The crude risk of COVID-19 diagnosis was 14.13% (95% CI: 9.83–19.90%). The total incidence rate was 2.67 (1000 person-days, 95% CI: 1.74–3.91). At the end of follow-up, there was a 94.42% chance of surviving 76 days or more after OTS. The differences in K-M survivor curves by GS indicated that GS 4 presented a lower survival function (Mantel-Cox test, p = 0.024; Wilcoxon-Breslow test, p = 0.044; Tarone-Ware test, p = 0.032). One of the best models to determine the association with mortality was the age-adjusted model for GS, high blood pressure, and respiratory history, with a hazard ratio of 1.112 in Cox regression analysis (95% CI: 1.005–1.230) and a sub hazard ratio of 1.111 (95% CI: 1.046–1.177) in Fine-Gray regression analysis for competitive risk. Conclusions The infection risk after OTS was similar to that of the general population in a community transmission area; the grade of surgical aggression did not influence this rate. The survival probability was extremely high if patients had not previously been infected. With higher grades of surgical aggression, the risk of mortality was higher in OTS patients. Adjusting for age and other confounders (e.g., GS, high blood pressure and respiratory history) was associated with higher mortality rates.

Low MSP-1 haplotype diversity in the West Palearctic population of the avian malaria parasite Plasmodium relictum

Background Although avian Plasmodium species are widespread and common across the globe, limited data exist on how genetically variable their populations are. Here, the hypothesis that the avian blood parasite Plasmodium relictum exhibits very low genetic diversity in its Western Palearctic transmission area (from Morocco to Sweden in the north and Transcaucasia in the east) was tested. Methods The genetic diversity of Plasmodium relictum was investigated by sequencing a portion (block 14) of the fast-evolving merozoite surface protein 1 (MSP1) gene in 75 different P. relictum infections from 36 host species. Furthermore, the full-length MSP1 sequences representing the common block 14 allele was sequenced in order to investigate if additional variation could be found outside block 14. Results The majority (72 of 75) of the sequenced infections shared the same MSP1 allele. This common allele has previously been found to be the dominant allele transmitted in Europe. Conclusion The results corroborate earlier findings derived from a limited dataset that the globally transmitted malaria parasite P. relictum exhibits very low genetic diversity in its Western Palearctic transmission area. This is likely the result of a recent introduction event or a selective sweep.