The effect of COVID-19 on malaria cases in Zambia: a mixed effect multilevel analysis.

BACKGROUND: The burden of Malaria in Zambia remains a challenge, with the entire population at risk of contracting this infectious disease. Despite concerted efforts by African countries, including Zambia, to implement malaria policies and strategies aimed at reducing case incidence, the region faces significant hurdles, especially with emerging pandemics such as COVID-19. The efforts to control malaria were impacted by the constraints imposed to curb its transmission during the COVID-19 pandemic. The aim of the study was to assess the effect of the COVID-19 pandemic on malaria cases in Zambia and the factors associated by comparing the COVID-19 period and the pre-COVID-19 era. METHODS: This was a cross-sectional panel study in which routinely collected programmatic data on malaria was used. The data were extracted from the Health Management Information System (HMIS) for the period January 2018 to January 2022. The period 2018 to 2022 was selected purely due to the availability of data and to avoid the problem of extrapolating too far away from the period of interest of the study. A summary of descriptive statistics was performed in which the number of cases were stratified by province, age group, and malaria cases. The association of these variables with the COVID-19 era was checked using the Wilcoxon rank-sum test and Kruskal‒Wallis test as applicable. In establishing the factors associated with the number of malaria cases, a mixed-effect multilevel model using the Poisson random intercept and random slope of the COVID-19 panel. The model was employed to deal with the possible correlation of the number of cases in the non-COVID-19 panel and the expected correlation of the number of cases in the COVID-19 panel. RESULTS: A total of 18,216 records were extracted from HMIS from January 2018 to January 2022. Stratifying this by the COVID-19 period/era, it was established that 8,852 malaria cases were recorded in the non-COVID-19 period, whereas 9,364 cases were recorded in the COVID-19 era. Most of the people with malaria were above the age of 15 years. Furthermore, the study found a significant increase in the relative incidence of the COVID-19 panel period compared to the non-COVID-19 panel period of 1.32, 95% CI (1.18, 1.48, p < 0.0001). The observed numbers, as well as the incident rate ratio, align with the hypothesis of this study, indicating an elevated incidence rate ratio of malaria during the COVID-19 period. CONCLUSION: This study found that there was an increase in confirmed malaria cases during the COVID-19 period compared to the non-COVID-19 period. The study also found Age, Province, and COVID-19 period to be significantly associated with malaria cases.

Residual bioefficacy of attractive targeted sugar bait stations targeting malaria vectors during seasonal deployment in Western Province of Zambia.

BACKGROUND: The primary vector control interventions in Zambia are long-lasting insecticidal nets and indoor residual spraying. Challenges with these interventions include insecticide resistance and the outdoor biting and resting behaviours of many Anopheles mosquitoes. Therefore, new vector control tools targeting additional mosquito behaviours are needed to interrupt transmission. Attractive targeted sugar bait (ATSB) stations, which exploit the sugar feeding behaviours of mosquitoes, may help in this role. This study evaluated the residual laboratory bioefficacy of Westham prototype ATSB® Sarabi v.1.2.1 Bait Station (Westham Ltd., Hod-Hasharon, Israel) in killing malaria vectors in Western Province, Zambia, during the first year of a large cluster randomized phase-III trial (Clinical Trials.gov Identifier: NCT04800055). METHODS: This was a repeat cross-sectional study conducted within three districts, Nkeyema, Kaoma, and Luampa, in Western Province, Zambia. The study was conducted in 12 intervention clusters among the 70 trial clusters (35 interventions, 35 controls) between December 2021 and June 2022. Twelve undamaged bait stations installed on the outer walls of households were collected monthly (one per cluster per month) for bioassays utilizing adult female and male Anopheles gambiae sensu stricto (Kisumu strain) mosquitoes from a laboratory colony. RESULTS: A total of 84 field-deployed ATSB stations were collected, and 71 ultimately met the study inclusion criteria for remaining in good condition. Field-deployed stations that remained in good condition (intact, non-depleted of bait, and free of dirt as well as mold) retained high levels of bioefficacy (mean induced mortality of 95.3% in males, 71.3% in females, 83.9% combined total) over seven months in the field but did induce lower mortality rates than non-deployed ATSB stations (mean induced mortality of 96.4% in males, 87.0% in females, 91.4% combined total). There was relatively little variation in corrected mortality rates between monthly rounds for those ATSB stations that had been deployed to the field. CONCLUSION: While field-deployed ATSB stations induced lower mortality rates than non-deployed ATSB stations, these stations nonetheless retained relatively high and stable levels of bioefficacy across the 7-month malaria transmission season. While overall mean mosquito mortality rates exceeded 80%, mean mortality rates for females were 24 percentage points lower than among males and these differences merit attention and further evaluation in future studies. The duration of deployment was not associated with lower bioefficacy. Westham prototype ATSB stations can still retain bioefficacy even after deployment in the field for 7 months, provided they do not meet predetermined criteria for replacement.

Characteristics of the Western Province, Zambia, trial site for evaluation of attractive targeted sugar baits for malaria vector control.

BACKGROUND: The attractive targeted sugar bait (ATSB) is a novel malaria vector control tool designed to attract and kill mosquitoes using a sugar-based bait, laced with oral toxicant. Western Province, Zambia, was one of three countries selected for a series of phase III cluster randomized controlled trials of the Westham ATSB Sarabi version 1.2. The trial sites in Kenya, Mali, and Zambia were selected to represent a range of different ecologies and malaria transmission settings across sub-Saharan Africa. This case study describes the key characteristics of the ATSB Zambia trial site to allow for interpretation of the results relative to the Kenya and Mali sites. METHODS: This study site characterization incorporates data from the trial baseline epidemiological and mosquito sugar feeding surveys conducted in 2021, as well as relevant literature on the study area. RESULTS: CHARACTERIZATION OF THE TRIAL SITE: The trial site in Zambia was comprised of 70 trial-designed clusters in Kaoma, Nkeyema, and Luampa districts. Population settlements in the trial site were dispersed across a large geographic area with sparsely populated villages. The overall population density in the 70 study clusters was 65.7 people per square kilometre with a total site population of 122,023 people living in a geographic area that covered 1858 square kilometres. However, the study clusters were distributed over a total area of approximately 11,728 square kilometres. The region was tropical with intense and seasonal malaria transmission. An abundance of trees and other plants in the trial site were potential sources of sugar meals for malaria vectors. Fourteen Anopheles species were endemic in the site and Anopheles funestus was the dominant vector, likely accounting for around 95% of all Plasmodium falciparum malaria infections. Despite high coverage of indoor residual spraying and insecticide-treated nets, the baseline malaria prevalence during the peak malaria transmission season was 50% among people ages six months and older. CONCLUSION: Malaria transmission remains high in Western Province, Zambia, despite coverage with vector control tools. New strategies are needed to address the drivers of malaria transmission in this region and other malaria-endemic areas in sub-Saharan Africa.

Community perceptions, acceptability, and the durability of house screening interventions against exposure to malaria vectors in Nyimba district, Zambia.

BACKGROUND: House screening remains conspicuously absent in national malaria programs despite its recognition by the World Health Organization as a supplementary malaria vector-control intervention. This may be attributed, in part, to the knowledge gap in screen durability or longevity in local climatic conditions and community acceptance under specific cultural practices and socio-economic contexts. The objectives of this study were to assess the durability of window and door wire mesh screens a year after full house screening and to assess the acceptability of the house screening intervention to the participants involved. METHODS: This study was conducted in Nyimba district, Zambia and used both quantitative and qualitative methods of data collection and analysis. Both direct observation and questionnaires were employed to assess the durability of the screens and the main reasons for damage. Findings on damage were summarized as percentages. Focus group discussions were used to assess people's knowledge, perceptions, and acceptability of the closing eaves and house screening intervention. Deductive coding and inductive coding were used to analyse the qualitative data. RESULTS: A total of 321 out of 400 (80.3%) household owners of screened houses were interviewed. Many window screens (90.3%) were intact. In sharp contrast, most door screens were torn (n = 150; 46.7%) or entirely removed (n = 55; 17.1%). Most doors (n = 114; 76%) had their wire mesh damaged or removed on the bottom half. Goats (25.4%), rust (17.6%) and children (17.1%) were cited most as the cause of damage to door screens. The focus group discussion elicited positive experiences from the participants following the closing of eaves and screening of their windows and doors, ranging from sleeping peacefully due to reduced mosquito biting and/or nuisance and having fewer insects in the house. Participants linked house screening to reduced malaria in their households and community. CONCLUSION: This study demonstrated that in rural south-east Zambia, closing eaves and screening windows and doors was widely accepted. Participants perceived that house screening reduced human-vector contact, reduced the malaria burden and nuisance biting from other potentially disease carrying insects. However, screened doors are prone to damage, mainly by children, domestic animals, rust, and termites.

Anopheles rufipes implicated in malaria transmission both indoors and outdoors alongside Anopheles funestus and Anopheles arabiensis in rural south-east Zambia.

BACKGROUND: The primary malaria vector-control interventions, indoor residual spraying and long-lasting insecticidal nets, are effective against indoor biting and resting mosquito species. Consequently, outdoor biting and resting malaria vectors might elude the primary interventions and sustain malaria transmission. Varied vector biting and resting behaviour calls for robust entomological surveillance. This study investigated the bionomics of malaria vectors in rural south-east Zambia, focusing on species composition, their resting and host-seeking behaviour and sporozoite infection rates. METHODS: The study was conducted in Nyimba District, Zambia. Randomly selected households served as sentinel houses for monthly collection of mosquitoes indoors using CDC-light traps (CDC-LTs) and pyrethrum spray catches (PSC), and outdoors using only CDC-LTs for 12 months. Mosquitoes were identified using morphological taxonomic keys. Specimens belonging to the Anopheles gambiae complex and Anopheles funestus group were further identified using molecular techniques. Plasmodium falciparum sporozoite infection was determined using sandwich enzyme-linked immunosorbent assays. RESULTS: From 304 indoor and 257 outdoor light trap-nights and 420 resting collection, 1409 female Anopheles species mosquitoes were collected and identified morphologically; An. funestus (n = 613; 43.5%), An. gambiae sensu lato (s.l.)(n = 293; 20.8%), Anopheles pretoriensis (n = 282; 20.0%), Anopheles maculipalpis (n = 130; 9.2%), Anopheles rufipes (n = 55; 3.9%), Anopheles coustani s.l. (n = 33; 2.3%), and Anopheles squamosus (n = 3, 0.2%). Anopheles funestus sensu stricto (s.s.) (n = 144; 91.1%) and Anopheles arabiensis (n = 77; 77.0%) were the dominant species within the An. funestus group and An. gambiae complex, respectively. Overall, outdoor CDC-LTs captured more Anopheles mosquitoes (mean = 2.25, 95% CI 1.22-3,28) than indoor CDC-LTs (mean = 2.13, 95% CI 1.54-2.73). Fewer resting mosquitoes were collected with PSC (mean = 0.44, 95% CI 0.24-0.63). Sporozoite infectivity rates for An. funestus, An. arabiensis and An. rufipes were 2.5%, 0.57% and 9.1%, respectively. Indoor entomological inoculation rates (EIRs) for An. funestus s.s, An. arabiensis and An. rufipes were estimated at 4.44, 1.15 and 1.20 infectious bites/person/year respectively. Outdoor EIRs for An. funestus s.s. and An. rufipes at 7.19 and 4.31 infectious bites/person/year, respectively. CONCLUSION: The findings of this study suggest that An. rufipes may play an important role in malaria transmission alongside An. funestus s.s. and An. arabiensis in the study location.

Effectiveness of community case management of malaria on severe malaria and inpatient malaria deaths in Zambia: a dose-response study using routine health information system data.

BACKGROUND: Community case management of malaria (CCM) has been expanded in many settings, but there are limited data describing the impact of these services in routine implementation settings or at large scale. Zambia has intensively expanded CCM since 2013, whereby trained volunteer community health workers (CHW) use rapid diagnostic tests and artemether-lumefantrine to diagnose and treat uncomplicated malaria. METHODS: This retrospective, observational study explored associations between changing malaria service point (health facility or CHW) density per 1000 people and severe malaria admissions or malaria inpatient deaths by district and month in a dose-response approach, using existing routine and programmatic data. Negative binomial generalized linear mixed-effect models were used to assess the impact of increasing one additional malaria service point per 1000 population, and of achieving Zambia's interim target of 1 service point per 750 population. Access to insecticide-treated nets, indoor-residual spraying, and rainfall anomaly were included in models to reduce potential confounding. RESULTS: The study captured 310,855 malaria admissions and 7158 inpatient malaria deaths over 83 districts (seven provinces) from January 2015 to May 2020. Total CHWs increased from 43 to 4503 during the study period, while health facilities increased from 1263 to 1765. After accounting for covariates, an increase of one malaria service point per 1000 was associated with a 19% reduction in severe malaria admissions among children under five (incidence rate ratio [IRR] 0.81, 95% confidence interval [CI] 0.75-0.87, p < 0.001) and 23% reduction in malaria deaths among under-fives (IRR 0.77, 95% CI 0.66-0.91). After categorizing the exposure of population per malaria service point, there was evidence for an effect on malaria admissions and inpatient malaria deaths among children under five only when reaching the target of one malaria service point per 750 population. CONCLUSIONS: CCM is an effective strategy for preventing severe malaria and deaths in areas such as Zambia where malaria diagnosis and treatment access remains challenging. These results support the continued investment in CCM scale-up in similar settings, to improve access to malaria diagnosis and treatment.

The provision of malaria services in border districts of four countries in Southern Africa: results from a cross-sectional community assessment of malaria border health posts.

BACKGROUND: The importation of parasites across borders remains a threat to malaria elimination. The Southern African Development Community Malaria Elimination Eight (E8) established 39 border health facilities on 5 key international borders between high and low-burden countries. These clinics aimed to improve access to prevention, diagnosis, and treatment of malaria for residents in border areas and for mobile and migrant populations who frequently cross borders. Studies were conducted in each of the four high-burden E8 countries (Angola, Mozambique, Zambia, and Zimbabwe) to evaluate malaria services in border areas. METHODS: Cross-sectional surveys were conducted within 30 km of recently established E8 Border Health Posts. Structured questionnaires were administered to randomly selected respondents to assess malaria-related knowledge and behavior, access to malaria prevention, diagnosis and treatment of malaria, and risk factors for malaria associated with local and cross-border travel. RESULTS: Results showed that most providers followed appropriate guidelines performing blood tests when individuals presented with fever, and that nearly all those who reported a positive blood test received medication. Lack of access to health care due to distance, cost or mistrust of the provider was rare. A minority of respondents reported not receiving timely diagnosis either because they did not seek help, or because they were not offered a blood test when presenting with fever. There was a high level of correct knowledge of causes, symptoms, and prevention of malaria. A majority, of border residents had access to primary prevention against malaria through either long-lasting insecticidal nets (LLINs) or indoor residual spraying (IRS). Cross border travel was common with travellers reporting sleeping outside without protection against malaria. CONCLUSIONS: The study demonstrated the importance of border health facilities in providing access to malaria services. Prevention needs to be improved for people who travel and sleep outdoors. Community health workers can play a key role in providing access to information, testing and treating malaria.

Assessing national vector control micro-planning in Zambia using the 2021 malaria indicator survey.

BACKGROUND: In 2020, the Zambia National Malaria Elimination Centre targeted the distribution of long-lasting insecticidal nets (LLINs) and indoor-residual spraying (IRS) campaigns based on sub-district micro-planning, where specified geographical areas at the health facility catchment level were assigned to receive either LLINs or IRS. Using data from the 2021 Malaria Indicator Survey (MIS), the objectives of this analysis were to (1) assess how well the micro-planning was followed in distributing LLINs and IRS, (2) investigate factors that contributed to whether households received what was planned, and (3) investigate how overall coverage observed in the 2021 MIS compared to the 2018 MIS conducted prior to micro-planning. METHODS: Households' receipt of ≥ 1 LLIN, and/or IRS within the past 12 months in the 2021 MIS, was compared against the micro-planning area under which the households fell. GPS points for 3,550 households were overlayed onto digitized micro-planning maps in order to determine what micro-plan the households fell under, and thus whether they received their planned intervention. Mixed-effects regression models were conducted to investigate what factors affected whether these households: (1) received their planned intervention, and (2) received any intervention. Finally, coverage indicators between the 2021 and 2018 MIS were compared. RESULTS: Overall, 60.0% (95%CI 55.4, 64.4) of households under a micro-plan received their assigned intervention, with significantly higher coverage of the planned intervention in LLIN-assigned areas (75.7% [95%CI 69.5, 80.9]) compared to IRS-assigned areas (49.4% [95%CI: 44.4, 54.4]). Regression analysis indicated that households falling under the IRS micro-plan had significantly reduced odds of receiving their planned intervention (OR: 0.34 [95%CI 0.24, 0.48]), and significantly reduced odds of receiving any intervention (OR: 0.51 [95%CI 0.37, 0.72] ), compared to households under the LLIN micro-plan. Comparison between the 2021 and 2018 MIS indicated a 27% reduction in LLIN coverage nationally in 2021, while IRS coverage was similar. Additionally, between 2018 and 2021, there was a 13% increase in households that received neither intervention. CONCLUSIONS: This analysis shows that although the micro-planning strategy adopted in 2020 worked much better for LLIN-assigned areas compared to IRS-assigned areas, there was reduced overall vector control coverage in 2021 compared to 2018 before micro-planning.

Evaluating the Impact of Programmatic Mass Drug Administration for Malaria in Zambia Using Routine Incidence Data.

BACKGROUND: In 2016, the Zambian National Malaria Elimination Centre started programmatic mass drug administration (pMDA) campaigns with dihydroartemisinin-piperaquine as a malaria elimination tool in Southern Province. Two rounds were administered, 2 months apart (coverage 70% and 57%, respectively). We evaluated the impact of 1 year of pMDA on malaria incidence using routine data. METHODS: We conducted an interrupted time series with comparison group analysis on monthly incidence data collected at the health facility catchment area (HFCA) level, with a negative binomial model using generalized estimating equations. Programmatic mass drug administration was conducted in HFCAs with greater than 50 cases/1000 people per year. Ten HFCAs with incidence rates marginally above this threshold (pMDA group) were compared with 20 HFCAs marginally below (comparison group). RESULTS: The pMDA HFCAs saw a 46% greater decrease in incidence at the time of intervention than the comparison areas (incidence rate ratio = 0.536; confidence interval = 0.337-0.852); however, incidence increased toward the end of the season. No HFCAs saw a transmission interruption. CONCLUSIONS: Programmatic mass drug administration, implemented during 1 year with imperfect coverage in low transmission areas with suboptimal vector control coverage, significantly reduced incidence. However, elimination will require additional tools. Routine data are important resources for programmatic impact evaluations and should be considered for future analyses.

Modelling of malaria risk, rates, and trends: A spatiotemporal approach for identifying and targeting sub-national areas of high and low burden.

While mortality from malaria continues to decline globally, incidence rates in many countries are rising. Within countries, spatial and temporal patterns of malaria vary across communities due to many different physical and social environmental factors. To identify those areas most suitable for malaria elimination or targeted control interventions, we used Bayesian models to estimate the spatiotemporal variation of malaria risk, rates, and trends to determine areas of high or low malaria burden compared to their geographical neighbours. We present a methodology using Bayesian hierarchical models with a Markov Chain Monte Carlo (MCMC) based inference to fit a generalised linear mixed model with a conditional autoregressive structure. We modelled clusters of similar spatiotemporal trends in malaria risk, using trend functions with constrained shapes and visualised high and low burden districts using a multi-criterion index derived by combining spatiotemporal risk, rates and trends of districts in Zambia. Our results indicate that over 3 million people in Zambia live in high-burden districts with either high mortality burden or high incidence burden coupled with an increasing trend over 16 years (2000 to 2015) for all age, under-five and over-five cohorts. Approximately 1.6 million people live in high-incidence burden areas alone. Using our method, we have developed a platform that can enable malaria programs in countries like Zambia to target those high-burden areas with intensive control measures while at the same time pursue malaria elimination efforts in all other areas. Our method enhances conventional approaches and measures to identify those districts which had higher rates and increasing trends and risk. This study provides a method and a means that can help policy makers evaluate intervention impact over time and adopt appropriate geographically targeted strategies that address the issues of both high-burden areas, through intensive control approaches, and low-burden areas, via specific elimination programs.

Decreased prevalence of the Plasmodium falciparum Pfcrt K76T and Pfmdr1 and N86Y mutations post-chloroquine treatment withdrawal in Katete District, Eastern Zambia.

BACKGROUND: In 2002, Zambia withdrew chloroquine as first-line treatment for Plasmodium falciparum malaria due to increased treatment failure and worldwide spread of chloroquine resistance. The artemisinin combination regimen, artemether-lumefantrine, replaced chloroquine (CQ) as first choice malaria treatment. The present study determined the prevalence of CQ resistance molecular markers in the Pfcrt and Pfmdr1 genes in Eastern Zambia at 9 and 13 years after the removal of drug pressure. METHODS: Samples collected from Katete District during the drug therapeutic efficacy assessments conducted in 2012 and 2016 were assayed by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) to determine the prevalence of genetic mutations, K76T on the Pfcrt gene and N86Y on the Pfmdr1 gene. A total of 204 P. falciparum-positive DBS samples collected at these two time points were further analysed. RESULTS: Among the samples analysed for Pfcrt K76T and Pfmdr1 N86Y in the present study, 112 (82.4%) P. falciparum-infected samples collected in 2012 were successfully amplified for Pfcrt and 94 (69.1%) for Pfmdr1, while 69 (65.7%) and 72 (68.6%) samples from 2016 were successfully amplified for Pfcrt and Pfmdr1, respectively. In 2012, the prevalence of Pfcrt 76K (sensitive) was 97.3%, 76T (resistant) was 1.8%, and 0.8% had both 76K and 76T codons (mixed). Similarly in 2012, the prevalence of Pfmdr1 86N (sensitive) was 97.9% and 86Y (resistant) was 2.1%. In the 2016 samples, the prevalence of the respective samples was 100% Pfcrt 76K and Pfmdr1 86N. CONCLUSION: This study shows that there was a complete recovery of chloroquine-sensitive parasites by 2016 in Katete District, Eastern Zambia, 13 years following the withdrawal of CQ in the country. These findings add to the body of evidence for a fitness cost in CQ-resistant P. falciparum in Zambia and elsewhere. Further studies are recommended to monitor resistance countrywide and explore the feasibility of integration of the former best anti-malarial in combination therapy in the future.

Retrospective evaluation of the effectiveness of indoor residual spray with pirimiphos-methyl (Actellic) on malaria transmission in Zambia.

BACKGROUND: Widespread insecticide resistance to pyrethroids could thwart progress towards elimination. Recently, the World Health Organization has encouraged the use of non-pyrethroid insecticides to reduce the spread of insecticide resistance. An electronic tool for implementing and tracking coverage of IRS campaigns has recently been tested (mSpray), using satellite imagery to improve the accuracy and efficiency of the enumeration process. The purpose of this paper is to retrospectively analyse cross-sectional observational data to provide evidence of the epidemiological effectiveness of having introduced Actellic 300CS and the mSpray platform into IRS programmes across Zambia. METHODS: Health facility catchment areas in 40 high burden districts in 5 selected provinces were initially targeted for spraying. The mSpray platform was used in 7 districts in Luapula Province. An observational study design was used to assess the relationship between IRS exposure and confirmed malaria case incidence. A random effects Poisson model was used to quantify the effect of IRS (with and without use of the mSpray platform) on confirmed malaria case incidence over the period 2013-2017; analysis was restricted to the 4 provinces where IRS was conducted in each year 2014-2016. RESULTS: IRS was conducted in 283 health facility catchment areas from 2014 to 2016; 198 health facilities from the same provinces, that received no IRS during this period, served as a comparison. IRS appears to be associated with reduced confirmed malaria incidence; the incidence rate ratio (IRR) was lower in areas with IRS but without mSpray, compared to areas with no IRS (IRR = 0.91, 95% CI 0.84-0.98). Receiving IRS with mSpray significantly lowered confirmed case incidence (IRR = 0.75, 95% CI 0.66-0.86) compared to no IRS. IRS with mSpray resulted in lower incidence compared to IRS without mSpray (IRR = 0.83, 95% CI 0.72-0.95). CONCLUSIONS: IRS using Actellic-CS appears to substantially reduce malaria incidence in Zambia. The use of the mSpray tool appears to improve the effectiveness of the IRS programme, possibly through improved population level coverage. The results of this study lend credence to the anecdotal evidence of the effectiveness of 3GIRS using Actellic, and the importance of exploring new platforms for improving effective population coverage of areas targeted for spraying.

Performance evaluation of RDT, light microscopy, and PET-PCR for detecting Plasmodium falciparum malaria infections in the 2018 Zambia National Malaria Indicator Survey.

BACKGROUND: Zambia continues to advance on the path to elimination with significant reductions in malaria morbidity and mortality. Crucial components that have contributed to progress thus far and are necessary for achieving the national malaria elimination goals include properly identifying and treating all malaria cases through accurate diagnosis. This study sought to compare and assess the diagnostic performance of Rapid Diagnostic Tests (RDT) and Light Microscopy (LM) with photo-induced electron transfer polymerase chain reaction (PET-PCR) as the gold standard using 2018 Malaria Indicator Survey (MIS) data across Zambia to better understand diagnostic accuracy metrics and how these vary across a transmission gradient. METHODS: Cross-sectional samples collected in a nationally representative survey from 7 provinces in Zambia were tested for the presence of malaria parasites by light microscopy (LM), rapid diagnostic test (RDT) and the gold standard PET-PCR. Diagnostic performance was assessed including sensitivity, specificity, negative- and positive-predictive values across a wide malaria transmission spectrum. Diagnostic accuracy metrics were measured, and statistically significant differences were calculated between test methods for different outcome variables. RESULTS: From the individuals included in the MIS, the overall prevalence of Plasmodium falciparum malaria was 32.9% by RDT, 19.4% by LM, and 23.2% by PET-PCR. Herein, RDT and LM diagnostic performance was compared against gold standard PET-PCR with LM displaying a higher diagnostic accuracy than RDTs (91.3% vs. 84.6% respectively) across the transmission spectrum in Zambia. However, the performance of both diagnostics was significantly reduced in low parasitaemia samples. Consistent with previous studies, RDT diagnostic accuracy was predominantly affected by a high rate of false positives. CONCLUSIONS: RDTs and LM both perform well across a range of transmission intensities within their respective target applications, i.e., in the community, for the former, where ease of use and speed of result is critical, and at the health facility, for the latter, where accuracy is prioritized. However, the performance of both diagnostic methods is adversely affected by low parasitaemia infections. As Zambia moves towards elimination more sensitive tools may be required to identify the last cases.

Climate change and the dynamics of age-related malaria incidence in Southern Africa.

In the last decade, many malaria-endemic countries, like Zambia, have achieved significant reductions in malaria incidence among children <5 years old but face ongoing challenges in achieving similar progress against malaria in older age groups. In parts of Zambia, changing climatic and environmental factors are among those suspectedly behind high malaria incidence. Changes and variations in these factors potentially interfere with intervention program effectiveness and alter the distribution and incidence patterns of malaria differentially between young children and the rest of the population. We used parametric and non-parametric statistics to model the effects of climatic and socio-demographic variables on age-specific malaria incidence vis-à-vis control interventions. Linear regressions, mixed models, and Mann-Kendall tests were implemented to explore trends, changes in trends, and regress malaria incidence against environmental and intervention variables. Our study shows that while climate parameters affect the whole population, their impacts are felt most by people aged ≥5 years. Climate variables influenced malaria substantially more than mosquito nets and indoor residual spraying interventions. We establish that climate parameters negatively impact malaria control efforts by exacerbating the transmission conditions via more conducive temperature and rainfall environments, which are augmented by cultural and socioeconomic exposure mechanisms. We argue that an intensified communications and education intervention strategy for behavioural change specifically targeted at ≥5 aged population where incidence rates are increasing, is urgently required and call for further malaria stratification among the ≥5 age groups in the routine collection, analysis and reporting of malaria mortality and incidence data.

Attrition, physical integrity and insecticidal activity of long-lasting insecticidal nets in sub-Saharan Africa and modelling of their impact on vectorial capacity.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are the primary malaria prevention and control intervention in many parts of sub-Saharan Africa. While LLINs are expected to last at least 3 years under normal use conditions, they can lose effectiveness because they fall out of use, are discarded, repurposed, physically damaged, or lose insecticidal activity. The contributions of these different interrelated factors to durability of nets and their protection against malaria have been unclear. METHODS: Starting in 2009, LLIN durability studies were conducted in seven countries in Africa over 5 years. WHO-recommended measures of attrition, LLIN use, insecticidal activity, and physical integrity were recorded for eight different net brands. These data were combined with analyses of experimental hut data on feeding inhibition and killing effects of LLINs on both susceptible and pyrethroid resistant malaria vectors to estimate the protection against malaria transmission-in terms of vectorial capacity (VC)-provided by each net cohort over time. Impact on VC was then compared in hypothetical scenarios where one durability outcome measure was set at the best possible level while keeping the others at the observed levels. RESULTS: There was more variability in decay of protection over time by country than by net brand for three measures of durability (ratios of variance components 4.6, 4.4, and 1.8 times for LLIN survival, use, and integrity, respectively). In some countries, LLIN attrition was slow, but use declined rapidly. Non-use of LLINs generally had more effect on LLIN impact on VC than did attrition, hole formation, or insecticide loss. CONCLUSIONS: There is much more variation in LLIN durability among countries than among net brands. Low levels of use may have a larger impact on effectiveness than does variation in attrition or LLIN degradation. The estimated entomological effects of chemical decay are relatively small, with physical decay probably more important as a driver of attrition and non-use than as a direct cause of loss of effect. Efforts to maximize LLIN impact in operational settings should focus on increasing LLIN usage, including through improvements in LLIN physical integrity. Further research is needed to understand household decisions related to LLIN use, including the influence of net durability and the presence of other nets in the household.

Knowledge, attitudes and practices assessment of malaria interventions in rural Zambia.

BACKGROUND: Despite rapid upscale of insecticide-treated nets (ITNs) and indoor residual spraying (IRS), malaria remains a major source of morbidity and mortality in Zambia. Uptake and utilization of these and novel interventions are often affected by knowledge, attitudes and practices (KAP) amongst persons living in malaria-endemic areas. The aims of this study were to assess malaria KAP of primary caregivers and explore trends in relation to ITN use, IRS acceptance and mosquito density in two endemic communities in Luangwa and Nyimba districts, Zambia. METHODS: A cohort of 75 primary caregivers were assessed using a cross-sectional, forced-choice malaria KAP survey on ITN use, IRS acceptance and initial perception of a novel spatial repellent (SR) product under investigation. Entomological sampling was performed in participant homes using CDC Miniature Light Traps to relate indoor mosquito density with participant responses. RESULTS: Ninety-nine percent of participants cited bites of infected mosquitoes as the route of malaria transmission although other routes were also reported including drinking dirty water (64%) and eating contaminated food (63%). All caregivers agreed that malaria was a life-threatening disease with the majority of caregivers having received malaria information from health centers (86%) and community health workers (51%). Cumulatively, self-reported mosquito net use was 67%. Respondents reportedly liked the SR prototype product but improvements on color, shape and size were suggested. Overall, 398 mosquitoes were captured from light-trap collections, including 49 anophelines and 349 culicines. Insecticide treated nets use was higher in households from which at least one mosquito was captured. CONCLUSIONS: The current study identified misconceptions in malaria transmission among primary caregivers indicating remaining knowledge gaps in educational campaigns. Participant responses also indicated a misalignment between a low perception of IRS efficacy and high stated acceptance of IRS, which should be further examined to better understand uptake and sustainability of other vector control strategies. While ITNs were found to be used in study households, misperceptions between presence of mosquitoes and bite protection practices did exist. This study highlights the importance of knowledge attitudes and practice surveys, with integration of entomological sampling, to better guide malaria vector control product development, strategy acceptance and compliance within endemic communities.

Theory of reactive interventions in the elimination and control of malaria.

BACKGROUND: Reactive case detection (RCD) is an integral part of many malaria control and elimination programmes and can be conceived of as a way of gradually decreasing transmission. However, it is unclear under what circumstances RCD may have a substantial impact on prevalence, how likely it is to lead to local elimination, or how effective it needs to be to prevent reintroduction after transmission has been interrupted. METHODS: Analyses and simulations of a discrete time compartmental susceptible-infectious-susceptible (SIS) model were used to understand the mechanisms of how RCD changes transmission dynamics and estimate the impact of RCD programmes in a range of settings with varying patterns of transmission potential and programme characteristics. Prevalence survey data from recent studies in Zambia were used to capture the effects of spatial clustering of patent infections. RESULTS: RCD proved most effective at low prevalence. Increasing the number of index cases followed was more important than increasing the number of neighbours tested per index case. Elimination was achieved only in simulations of situations with very low transmission intensity and following many index cases. However, RCD appears to be helpful in maintaining the disease-free state after achieving malaria elimination (through other interventions). CONCLUSION: RCD alone can eliminate malaria in only a very limited range of settings, where transmission potential is very low, and improving the coverage of RCD has little effect on this range. In other settings, it is likely to reduce disease burden. RCD may also help maintain the disease-free state in the face of imported infections. Prevalence survey data can be used to estimate a targeting ratio (the ratio of prevalence found through RCD to that in the general population) which is an important determinant of the effect of RCD.

Distribution of Plasmodium species and assessment of performance of diagnostic tools used during a malaria survey in Southern and Western Provinces of Zambia.

BACKGROUND: Zambia continues to make strides in reducing malaria burden through the use of proven malaria interventions and has recently pledged to eliminate malaria by 2021. Case management services have been scaled up at community level with rapid diagnostic tests (RDTs) providing antigen-based detection of falciparum malaria only. Key to national malaria elimination goals is the ability to identify, treat and eliminate all Plasmodium species. This study sought to determine the distribution of non-falciparum malaria and assess the performance of diagnostic tests for Plasmodium falciparum in Western and Southern Provinces of Zambia, two provinces planned for early malaria elimination. METHODS: A sub-set of individuals' data and samples from a cross-sectional household survey, conducted during peak malaria transmission season in April and May 2017, was used. The survey collected socio-demographic information on household members and coverage of malaria interventions. Malaria testing was done on respondents of all ages using blood smears and RDTs while dried blood spots were collected on filter papers for analysis using photo-induced electron transfer polymerase chain reaction (PET-PCR). Slides were stained using Giemsa stain and examined by microscopy for malaria parasites. RESULTS: From the 1567 individuals included, the overall prevalence of malaria was 19.4% (CI 17.5-21.4) by PCR, 19.3% (CI 17.4-21.4) by RDT and 12.9% (CI 11.3-14.7) by microscopy. Using PET-PCR as the gold standard, RDTs showed a sensitivity of 75.7% (CI 70.4-80.4) and specificity of 94.2% (CI 92.8-95.4). The positive predictive value (PPV) was 75.9% (CI 70.7-80.6) and negative predictive value (NPV) was 94.1% (CI 92.1-95.4). In contrast, microscopy for sensitivity, specificity, PPV, and NPV values were 56.9% (CI 51.1-62.5), 97.7% (CI 96.7-98.5), 85.6% (CI 80.0-90.2), 90.4% (CI 88.7-91.9), respectively. Non-falciparum infections were found only in Western Province, where 11.6% of P. falciparum infections were co-infections with Plasmodium ovale or Plasmodium malariae. CONCLUSION: From the sub-set of survey data analysed, non-falciparum species are present and occurred as mixed infections. As expected, PET-PCR was slightly more sensitive than both malaria RDTs and microscopy to detecting malaria infections.

Insecticide-treated nets mass distribution campaign: benefits and lessons in Zambia.

BACKGROUND: Zambia was an early adopter of insecticide-treated nets strategy in 2001, and policy for mass distribution with long-lasting insecticidal nets (LLINs) in 2005. Since then, the country has implemented mass distribution supplemented with routine delivery through antenatal care and under five clinics in health facilities. The national targets of universal (100%) coverage and 80% utilization of LLINs have not been attained. Free mass LLIN distribution campaign in Zambia offers important lessons to inform future campaigns in the African region. METHODS: This study reviewed LLIN free mass distribution campaign information derived from Zambia's national and World Health Organization Global Malaria Programme annual reports and strategic plans published between 2001 and 2016. RESULTS: In 2014, a nationwide mass distribution campaign in Zambia delivered all the 6.0 million LLINs in 6 out of 10 provinces in 4 months between June and September before the onset of the rainy season. Compared with 235,800 LLINs and 2.9 million LLINs distributed on a rolling basis in 2008 and 2013, respectively, the 2014 mass campaign, which distributed 6 million LLINs represented the largest one-time-nationwide LLIN distribution in Zambia. The province (Luapula) with highest malaria transmission, mostly with rural settings recorded 98-100% sleeping spaces in homes covered with LLINs. The percentage of households owning at least 1 LLIN increased from 50.9% in 2006 to 77.7% in 2015. The 2014 mass campaign involved a coordinated response with substantial investments into macro (central) and micro (district) level planning, capacity building, tracking and logistics management supported by a new non-health sector partnership landscape. Coordination of LLIN distribution and logistics benefited from the mobile phone technology to transmit "real time" data on commodity tracking that facilitated timely delivery to districts. CONCLUSION: Free mass distribution of LLINs policy was adopted in 2005 in Zambia. Consistently implemented, has not only contributed to increased coverage of LLINs, but has also produced the added value and lessons of strengthening joint planning, strategic coordination, partnerships with non-health sector institutions and community engagement with traditional leaders at community. Furthermore, the mass distribution, through improving coverage has indirect added (spin-off) value or impact on other arthropod-borne diseases, in addition to malaria.

Wash-resistance of pirimiphos-methyl insecticide treatments of window screens and eave baffles for killing indoor-feeding malaria vector mosquitoes: an experimental hut trial, South East of Zambia.

BACKGROUND: The effectiveness of long-lasting insecticidal-treated nets (LLINs) and indoor residual spraying (IRS) for malaria control is threatened by resistance to commonly used pyrethroid insecticides. Rotations, mosaics, combinations, or mixtures of insecticides from different complementary classes are recommended by the World Health Organization (WHO) for mitigating against resistance, but many of the alternatives to pyrethroids are prohibitively expensive to apply in large national IRS campaigns. Recent evaluations of window screens and eave baffles (WSEBs) treated with pirimiphos-methyl (PM), to selectively target insecticides inside houses, demonstrated malaria vector mortality rates equivalent or superior to IRS. However, the durability of efficacy when co-applied with polyacrylate-binding agents (BA) remains to be established. This study evaluated whether WSEBs, co-treated with PM and BA have comparable wash resistance to LLINs and might therefore remain insecticidal for years rather than months. METHODS: WHO-recommended wire ball assays of insecticidal efficacy were applied to polyester netting treated with or without BA plus 1 or 2 g/sq m PM. They were then tested for insecticidal efficacy using fully susceptible insectary-reared Anopheles gambiae mosquitoes, following 0, 5, 10, 15, then 20 washes as per WHO-recommended protocols for accelerated ageing of LLINs. This was followed by a small-scale field trial in experimental huts to measure malaria vector mortality achieved by polyester netting WSEBs treated with BA and 2 g/sq m PM after 0, 10 and then 20 standardized washes, alongside recently applied IRS using PM. RESULTS: Co-treatment with BA and either dosage of PM remained insecticidal over 20 washes in the laboratory. In experimental huts, WSEBs treated with PM plus BA consistently killed similar proportions of Anopheles arabiensis mosquitoes to PM-IRS (both consistently ≥ 94%), even after 20 washes. CONCLUSION: Co-treating WSEBs with both PM and BA results in wash-resistant insecticidal activity comparable with LLINs. Insecticide treatments for WSEBs may potentially last for years rather than months, therefore, reducing insecticide consumption by an order of magnitude relative to IRS. However, durability of WSEBs will still have to be assessed in real houses under representative field conditions of exposure to wear and tear, sunlight and rain.