Dataset Information

Assessment of antimalarial drug resistant markers in asymptomatic Plasmodium falciparum infections after 4 years of indoor residual spraying in Northern Ghana.

ABSTRACT: Background: Drug resistance remains a concern for malaria control and elimination. The effect of interventions on its prevalence needs to be monitored to pre-empt further selection. We assessed the prevalence of Plasmodium falciparum gene mutations associated with resistance to the antimalarial drugs: sulfadoxine-pyrimethamine (SP), chloroquine (CQ) and artemisinin combination therapy (ACTs) after the scale-up of a vector control activity that reduced transmission.

Methods: A total of 400 P. falciparum isolates from children under five years were genotyped for seventeen single nucleotide polymorphisms (SNPs) in pfcrt, pfmdr1, pfdhfr, pfdhps and pfk13 genes using polymerase chain reaction (PCR) and high resolution melting (HRM) analysis. These included 80 isolates, each randomly selected from cross-sectional surveys of asymptomatic infections across 2010 (baseline), 2011, 2012, 2013 (midline: post-IRS) and 2014 (endline: post-IRS) during the peak transmission season, when IRS intervention was rolled out in Bunkpurugu Yunyoo (BY) District, Ghana. The proportions of isolates with drug resistant alleles were assessed over this period.

Results: There were significant decreases in the prevalence of pfdhfr- I51R59N108 haplotype from 2010 to 2014, while the decline in pfdhfr/pfdhps- I51R59N108G437 during the same period was not significant. The prevalence of lumefantrine (LM), mefloquine (MQ) and amodiaquine (AQ) resistance-associated haplotypes pfmdr1-N86F184D1246 and pfmdr1-Y86Y184Y1246 showed decreasing trends (z = -2.86, P = 0.004 and z = -2.71, P = 0.007, respectively). Each of pfcrt-T76 and pfmdr1-Y86 mutant alleles also showed a declining trend in the asymptomatic reservoir, after the IRS rollout in 2014 (z = -2.87, P = 0.004 and z = -2.65, P = 0.008, respectively). Similarly, Pyrimethamine resistance mediating polymorphisms pfdhfr-N108, pfdhfr-I51 and pfdhfr-R59 also declined (z = -2.03, P = 0.042, z = -3.54, P<0.001 and z = -4.63, P<0.001, respectively), but not the sulphadoxine resistance mediating pfdhps-G437 and pfdhps-F436 (z = -0.36, P = 0.715 and z = 0.41, P = 0.684, respectively). No mutant pfk13-Y580 were detected during the study period.

Conclusion: The study demonstrated declining trends in the prevalence of drug resistant mutations in asymptomatic P. falciparum infections following transmission reduction after an enhanced IRS intervention in Northern Ghana.

SUBMITTER: Myers-Hansen JL

PROVIDER: S-EPMC7721464 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Assessment of antimalarial drug resistant markers in asymptomatic Plasmodium falciparum infections after 4 years of indoor residual spraying in Northern Ghana.

Myers-Hansen James L JL Abuaku Benjamin B Oyebola Muyiwa K MK Mensah Benedicta A BA Ahorlu Collins C Wilson Michael D MD Awandare Gordon G Koram Kwadwo A KA Ngwa Alfred Amambua AA Ghansah Anita A

PloS one 20201207 12

<h4>Background</h4>Drug resistance remains a concern for malaria control and elimination. The effect of interventions on its prevalence needs to be monitored to pre-empt further selection. We assessed the prevalence of Plasmodium falciparum gene mutations associated with resistance to the antimalarial drugs: sulfadoxine-pyrimethamine (SP), chloroquine (CQ) and artemisinin combination therapy (ACTs) after the scale-up of a vector control activity that reduced transmission.<h4>Methods</h4>A total ...[more]

PMID: 33284800

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Project description:Indoor residual spraying (IRS) is being implemented as one of the malaria prevention methods in the Northern Region of Ghana. Changes in longevity, sporozoite and entomological inoculation rates (EIRs) of major malaria vectors were monitored to assess the impact of IRS in selected districts.Monthly human landing catches (HLCs) were used to collect mosquitoes from sentinel sites in three adjacent districts between July 2009 and December 2014: Savelugu Nanton (SND) where IRS had been implemented from 2008 to 2014; Tolon Kumbungu (TKD) where IRS had been implemented between 2008 and 2012 and Tamale Metropolis (TML) with no history of IRS. Mosquitoes were morphologically identified to species level and into sibling species, using PCR. Samples of Anopheles gambiae sensu lato (s.l.) were examined for parity and infectivity. EIR was calculated from biting and infectivity rates of malaria vectors.Parity rates of An. gambiae s.l. decreased significantly (p < 0.0001) in SND from 44.8% in 2011 to 28.1% by 2014, and in TKD from 53.3% in 2011 to 46.6% in 2012 (p = 0.001). However 2 years after IRS was discontinued in TKD, the proportion of parous An. gambiae s.l. increased significantly to 68.5% in 2014 (p < 0.0001). Parity rates in the unsprayed district remained high throughout the study period, ranging between 68.6% in 2011 and 72.3% in 2014. The sum of monthly EIRs post-IRS season (July-December) in SND ranged between 2.1 and 6.3 infective bites/person/season (ib/p/s) during the 3 years that the district was sprayed with alphacypermethrin. EIR in SND was reduced to undetectable levels when the insecticide was switched to pirimiphos methyl CS in 2013 and 2014. Two years after IRS was withdrawn from TKD the sum of monthly EIRs (July-December) increased by about fourfold from 41.8 ib/p/s in 2012 to 154.4 ib/p/s in 2014. The EIR in the control area, TML, ranged between 35 ib/p/s in 2009 to 104.71 ib/p/s by 2014.This study demonstrates that IRS application did have a significant impact on entomological indicators of malaria transmission in the IRS project districts of Northern Ghana. Transmission indicators increased following the withdrawal of IRS from Tolon Kumbungu District.

Project description:In June 2015, a malaria epidemic was confirmed in ten districts of Northern Uganda; after cessation of indoor residual spraying (IRS). Epidemic was defined as an increase in incidence per month beyond one standard deviation above mean incidence of previous 5 years. Trends in malaria incidence among children-under-5-years were analysed so as to describe the extent of change in incidence prior to and after cessation of IRS.Secondary data on out-patient malaria case numbers for children-under-5-years July 2012 to June 2015 was electronically extracted from the district health management information software2 (DHIS2) for ten districts that had IRS and ten control districts that didn't have IRS. Data was adjusted by reporting rates, cleaned by smoothing and interpolation and incidence of malaria per 1000 population derived. Population data obtained from 2002 and 2014 census reports. Data on interventions obtained from malaria programme reports, rainfall data obtained from Uganda National Meteorological Authority. Three groups of districts were created; two based on when IRS ended, the third not having IRS. Line graphs were plotted showing malaria incidence vis-à-vis implementation of IRS, mass net distribution and rainfall. Changes in incidence after withdrawal of IRS were obtained using incidence rate ratios (IRR). IRR was calculated as incidence for each month after the last IRS divided by incidence of the IRS month. Poisson regression was used to test statistical significance.Incidence of malaria declined between spray activities in districts that had IRS. Decline in IRR for 4 months after last IRS month was greater in the sprayed than control districts. On the seventh month following cessation of IRS, incidence in sprayed districts rose above that of the last spray month [1.74: 95% CI (1.40-2.15); and 1.26: 95% CI (1.05-1.51)]. Rise in IRR continued from 1.26 to 2.62 (95% CI 2.21-3.12) in June 2015 for districts that ended IRS in April 2014. Peak in rainfall occurred in May 2015.There was sustained control of malaria incidence during IRS implementation. Following withdrawal and peak in rainfall, incidence rose to epidemic proportions. This suggests a plausible link between the malaria epidemic, peak in rainfall and cessation of IRS.

Project description:The scale up of indoor residual spraying (IRS) and insecticide treated nets have contributed significantly to global reductions in malaria prevalence over the last two decades. However, widespread pyrethroid resistance has necessitated the use of new and more expensive insecticides for IRS. Partial IRS with pirimiphos-methyl in experimental huts and houses in a village-wide trial was evaluated against Anopheles gambiae s.l. in northern Ghana. Four different scenarios in which either only the top or bottom half of the walls of experimental huts were sprayed, with or without also spraying the ceiling were compared. Mortality of An. gambiae s.l. on partially sprayed walls was compared with the standard procedures in which all walls and ceiling surfaces are sprayed. A small-scale trial was then conducted to assess the effectiveness, feasibility, and cost of spraying only the upper walls and ceiling as compared to full IRS and no spraying in northern Ghana. Human landing catches were conducted to estimate entomological indices and determine the effectiveness of partial IRS. An established transmission dynamics model was parameterized by an analysis of the experimental hut data and used to predict the epidemiological impact and cost effectiveness of partial IRS for malaria control in northern Ghana. In the experimental huts, partial IRS of the top (IRR 0.89, p = 0.13) or bottom (IRR 0.90, p = 0.15) half of walls and the ceiling was not significantly less effective than full IRS in terms of mosquito mortality. In the village trial, the annual entomological inoculation rate was higher for the unsprayed control (217 infective bites/person/year (ib/p/yr)) compared with the fully and partially sprayed sites, with 28 and 38 ib/p/yr, respectively. The transmission model predicts that the efficacy of partial IRS against all-age prevalence of malaria after six months would be broadly equivalent to a full IRS campaign in which 40% reduction is expected relative to no spray campaign. At scale, partial IRS in northern Ghana would have resulted in a 33% cost savings ($496,426) that would enable spraying of 36,000 additional rooms. These findings suggest that partial IRS is an effective, feasible, and cost saving approach to IRS that could be adopted to sustain and expand implementation of this key malaria control intervention.

Project description:BackgroundInsecticide-based tools remain critical for controlling vector-borne diseases in Uganda. Securing public support from targeted populations for such tools is an important component in sustaining their long-run effectiveness. Yet little quantitative evidence is available on the perceived benefits and costs of vector control programmes among targeted households.MethodsA survey was administered to a clustered random sample of 612 households in Gulu and Oyam districts of northern Uganda during a period of very high malaria transmission and following a pilot indoor residual spray (IRS) programme. A discrete choice experiment was conducted within the survey, in which respondents indicated their preferences for different IRS programmes relative to money compensation in a series of experimentally controlled, hypothetical choice sets. The data were analysed using conditional logit regression models to estimate respondents' willingness to accept (WTA) some amount of money compensation in lieu of foregone malaria risk reductions. Latent class models were used to analyse whether respondent characteristics predicted WTA.ResultsAverage WTA is estimated at $8.94 annually for a 10 % reduction in malaria risk, and additional co-benefits of IRS were estimated to be worth on average $54-$56 (depending on insecticide type) per round of IRS. Significant heterogeneity is observed: Four in five household heads in northern Uganda have high valuations for IRS programmes, while the remaining 20 % experience costly side effects of IRS (valued at between $2 and $3 per round). Statistically significant predictors of belonging to the high-value group include respondent gender, mean age of household members, participation in previous IRS, basic knowledge of mosquito reproduction, and the number of mosquito nets owned. Proxies for household income and wealth are not found to be statistically significant predictors of WTA.ConclusionsThis study suggests that the majority of people in areas of high malaria transmission like northern Uganda place a high value on vector control programmes using IRS. However, there is significant heterogeneity in terms of the perceived side effects (positive and negative). This has implications for sustaining public support for these programmes in the long-term.

Project description:Historically, mosquito control programs successfully helped contain malaria and yellow fever, but recent efforts have been unable to halt the spread of dengue, chikungunya, or Zika, all transmitted by Aedes mosquitoes. Using a dengue transmission model and results from indoor residual spraying (IRS) field experiments, we investigated how IRS-like campaign scenarios could effectively control dengue in an endemic setting.In our model, we found that high levels of household coverage (75% treated once per year), applied proactively before the typical dengue season could reduce symptomatic infections by 89.7% (median of 1000 simulations; interquartile range [IQR]:[83.0%, 94.8%]) in year one and 78.2% (IQR: [71.2%, 88.0%]) cumulatively over the first five years of an annual program. Lower coverage had correspondingly lower effectiveness, as did reactive campaigns. Though less effective than preventative campaigns, reactive and even post-epidemic interventions retain some effectiveness; these campaigns disrupt inter-seasonal transmission, highlighting an off-season control opportunity. Regardless, none of the campaign scenarios maintain their initial effectiveness beyond two seasons, instead stabilizing at much lower levels of benefit: in year 20, median effectiveness was only 27.3% (IQR: [-21.3%, 56.6%]). Furthermore, simply ceasing an initially successful program exposes a population with lowered herd immunity to the same historical threat, and we observed outbreaks more than four-fold larger than pre-intervention outbreaks. These results do not take into account evolving insecticide resistance, thus long-term effectiveness may be lower if new, efficacious insecticides are not developed.Using a detailed agent-based dengue transmission model for Yucatán State, Mexico, we predict that high coverage indoor residual spraying (IRS) interventions can largely eliminate transmission for a few years, when applied a few months before the typical seasonal epidemic peak. However, vector control succeeds by preventing infections, which precludes natural immunization. Thus, as a population benefits from mosquito control, it gradually loses naturally acquired herd immunity, and the control effectiveness declines; this occurs across all of our modeled scenarios, and is consistent with other empirical work. Long term control that maintains early effectiveness would require some combination of increasing investment, complementary interventions such as vaccination, and control programs across a broad region to diminish risk of importation.

Dataset Information

Assessment of antimalarial drug resistant markers in asymptomatic Plasmodium falciparum infections after 4 years of indoor residual spraying in Northern Ghana.

Publications

Assessment of antimalarial drug resistant markers in asymptomatic Plasmodium falciparum infections after 4 years of indoor residual spraying in Northern Ghana.

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