Pyrethroid and Carbamate Resistance in Anopheles funestus Giles along Lake Kariba in Southern Zambia.

Whereas data on insecticide resistance and its underlying mechanisms exist for parts of Zambia, data remain limited in the southern part of the country. This study investigated the status of insecticide resistance, metabolic mechanisms, and parasite infection in Anopheles funestus along Lake Kariba in southern Zambia. Indoor-resting mosquitoes were collected from 20 randomly selected houses within clusters where a mass drug administration trial was conducted and raised to F1 progeny. Non-blood-fed 2- to 5-day-old female An. funestus were exposed to WHO insecticide-impregnated papers with 0.05% deltamethrin, 0.1% bendiocarb, 0.25% pirimiphos-methyl, or 4% dichloro-diphenyl-trichloroethane (DDT). In separate assays, An. funestus were pre-exposed to piperonyl butoxide (PBO) to determine the presence of monooxygenases. Wild-caught An. funestus that had laid eggs for susceptibility assays were screened for circumsporozoite protein of Plasmodium falciparum by ELISA, and sibling species were identified by polymerase chain reaction. Anopheles funestus showed resistance to deltamethrin and bendiocarb but remained susceptible to pirimiphos-methyl and DDT. The pre-exposure of An. funestus to PBO restored full susceptibility to deltamethrin but not to bendiocarb. The overall sporozoite infection rate in An. funestus populations was 5.8%. Detection of pyrethroid and carbamate resistance in An. funestus calls for increased insecticide resistance monitoring to guide planning and selection of effective insecticide resistance management strategies. To prevent the development of resistance and reduce the underlying vectorial capacity of mosquitoes in areas targeted for malaria elimination, an effective integrated vector management strategy is needed.

Impact of Four Rounds of Mass Drug Administration with Dihydroartemisinin-Piperaquine Implemented in Southern Province, Zambia.

Over the past decade, Zambia has made substantial progress against malaria and has recently set the ambitious goal of eliminating by 2021. In the context of very high vector control and improved access to malaria diagnosis and treatment in Southern Province, we implemented a community-randomized controlled trial to assess the impact of four rounds of community-wide mass drug administration (MDA) and household-level MDA (focal MDA) with dihydroartemisinin-piperaquine (DHAP) implemented between December 2014 and February 2016. The mass treatment campaigns achieved relatively good household coverage (63-79%), were widely accepted by the community (ranging from 87% to 94%), and achieved very high adherence to the DHAP regimen (81-96%). Significant declines in all malaria study end points were observed, irrespective of the exposure group, with the overall parasite prevalence during the peak transmission season declining by 87.2% from 31.3% at baseline to 4.0% in 2016 at the end of the trial. Children in areas of lower transmission (< 10% prevalence at baseline) that received four MDA rounds had a 72% (95% CI = 12-91%) reduction in malaria parasite prevalence as compared with those with the standard of care without any mass treatment. Mass drug administration consistently had the largest short-term effect size across study end points in areas of lower transmission following the first two MDA rounds. In the context of achieving very high vector control coverage and improved access to diagnosis and treatment for malaria, our results suggest that MDA should be considered for implementation in African settings for rapidly reducing malaria outcomes in lower transmission settings.

Shifting the burden or expanding access to care? Assessing malaria trends following scale-up of community health worker malaria case management and reactive case detection.

BACKGROUND: Malaria is a significant burden to health systems and is responsible for a large proportion of outpatient cases at health facilities in endemic regions. The scale-up of community management of malaria and reactive case detection likely affect both malaria cases and outpatient attendance at health facilities. Using health management information data from 2012 to 2013 this article examines health trends before and after the training of volunteer community health workers to test and treat malaria cases in Southern Province, Zambia. RESULTS: An estimated 50% increase in monthly reported malaria infections was found when community health workers were involved with malaria testing and treating in the community (incidence rate ratio 1.52, p < 0.001). Furthermore, an estimated 6% decrease in outpatient attendance at the health facility was found when community health workers were involved with malaria testing and treating in the community. CONCLUSIONS: These results suggest a large public health benefit to both community case management of malaria and reactive case detection. First, the capacity of the malaria surveillance system to identify malaria infections was increased by nearly one-third. Second, the outpatient attendance at health facilities was modestly decreased. Expanding the capacity of the malaria surveillance programme through systems such as community case management and reactive case detection is an important step toward malaria elimination.

Short-term Impact of Mass Drug Administration With Dihydroartemisinin Plus Piperaquine on Malaria in Southern Province Zambia: A Cluster-Randomized Controlled Trial.

BACKGROUND: Mass drug administration (MDA) using dihydroartemisinin plus piperaquine (DHAp) represents a potential strategy to clear Plasmodium falciparum infections and reduce the human parasite reservoir. METHODS: A cluster-randomized controlled trial in Southern Province, Zambia, was used to assess the short-term impact of 2 rounds of community-wide MDA and household-level (focal) MDA with DHAp compared with no mass treatment. Study end points included parasite prevalence in children, infection incidence, and confirmed malaria case incidence. RESULTS: All end points significantly decreased after intervention, irrespective of treatment group. Parasite prevalence from 7.71% at baseline to 0.54% after MDA in lower-transmission areas, resulting in an 87% reduction compared with control (adjusted odds ratio, 0.13; 95% confidence interval, .02-.92; P = .04). No difference between treatment groups was observed in areas of high transmission. The 5-month cumulative infection incidence was 70% lower (crude incidence rate ratio, 0.30; 95% confidence interval, .06-1.49; P = .14) and 58% lower (0.42; .18-.98; P = .046) after MDA compared with control in lower- and higher-transmission areas, respectively. No significant impact of focal MDA was observed for any end point. CONCLUSIONS: Two rounds of MDA with DHAp rapidly reduced infection prevalence, infection incidence, and confirmed case incidence rates, especially in low-transmission areas. CLINICAL TRIALS REGISTRATION: NCT02329301.

A qualitative review of implementer perceptions of the national community-level malaria surveillance system in Southern Province, Zambia.

BACKGROUND: Parts of Zambia with very low malaria parasite prevalence and high coverage of vector control interventions are targeted for malaria elimination through a series of interventions including reactive case detection (RCD) at community level. When a symptomatic individual presenting to a community health worker (CHW) or government clinic is diagnostically confirmed as an incident malaria case an RCD response is initiated. This consists of a CHW screening the community around the incident case with rapid diagnostic tests (RDT) and treating positive cases with artemether-lumefantrine (AL, Coartem™) in accordance with national policy. Since its inception in 2011, Zambia's RCD programme has relied on anecdotal feedback from staff to identify issues and possible solutions. In 2014, a systematic qualitative programme review was conducted to determine perceptions around malaria rates, incentives, operational challenges and solutions according to CHWs, their supervisors and district-level managers. METHODS: A criterion-based sampling framework based on training regime and performance level was used to select nine rural health posts in four districts of Southern Province. Twenty-two staff interviews were completed to produce English or bilingual (CiTonga or Silozi + English) verbatim transcripts, which were then analysed using thematic framework analysis. RESULTS: CHWs, their supervisors and district-level managers strongly credited the system with improving access to malaria services and significantly reducing the number of cases in their area. The main implementation barriers included access (e.g., lack of rain gear, broken bicycles), insufficient number of CHWs for programme coverage, communication (e.g. difficulties maintaining cell phones and "talk time" to transmit data by phone), and inconsistent supply chain (e.g., inadequate numbers of RDT kits and anti-malarial drugs to test and treat uncomplicated cases). CONCLUSIONS: This review highlights the importance of a community surveillance system like RCD in shaping Zambia's malaria elimination campaign by identifying community-based infections that might otherwise remain undetected. At this stage the system must ensure it can meet growing public demand by providing CHWs the tools and materials they need to consistently carry out their work and expand programme reach to more isolated communities. Results from this review will be used to plan programme scale-up into other parts of Zambia.

The relative contribution of climate variability and vector control coverage to changes in malaria parasite prevalence in Zambia 2006-2012.

BACKGROUND: Four malaria indicator surveys (MIS) were conducted in Zambia between 2006 and 2012 to evaluate malaria control scale-up. Nationally, coverage of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) increased over this period, while parasite prevalence in children 1-59 months decreased dramatically between 2006 and 2008, but then increased from 2008 to 2010. We assessed the relative effects of vector control coverage and climate variability on malaria parasite prevalence over this period. METHODS: Nationally-representative MISs were conducted in April-June of 2006, 2008, 2010 and 2012 to collect household-level information on malaria control interventions such as IRS, ITN ownership and use, and child parasite prevalence by microscopic examination of blood smears. We fitted Bayesian geostatistical models to assess the association between IRS and ITN coverage and climate variability and malaria parasite prevalence. We created predictions of the spatial distribution of malaria prevalence at each time point and compared results of varying IRS, ITN, and climate inputs to assess their relative contributions to changes in prevalence. RESULTS: Nationally, the proportion of households owning an ITN increased from 37.8 % in 2006 to 64.3 % in 2010 and 68.1 % in 2012, with substantial heterogeneity sub-nationally. The population-adjusted predicted child malaria parasite prevalence decreased from 19.6 % in 2006 to 10.4 % in 2008, but rose to 15.3 % in 2010 and 13.5 % in 2012. We estimated that the majority of this prevalence increase at the national level between 2008 and 2010 was due to climate effects on transmission, although there was substantial heterogeneity at the provincial level in the relative contribution of changing climate and ITN availability. We predict that if climate factors preceding the 2010 survey were the same as in 2008, the population-adjusted prevalence would have fallen to 9.9 % nationally. CONCLUSIONS: These results suggest that a combination of climate factors and reduced intervention coverage in parts of the country contributed to both the reduction and rebound in malaria parasite prevalence. Unusual rainfall patterns, perhaps related to moderate El Niño conditions, may have contributed to this variation. Zambia has demonstrated considerable success in scaling up vector control. This analysis highlights the importance of accounting for climate variability when using cross-sectional data for evaluation of malaria control efforts.

An Operational Framework for Insecticide Resistance Management Planning.

Arthropod vectors transmit organisms that cause many emerging and reemerging diseases, and their control is reliant mainly on the use of chemical insecticides. Only a few classes of insecticides are available for public health use, and the increased spread of insecticide resistance is a major threat to sustainable disease control. The primary strategy for mitigating the detrimental effects of insecticide resistance is the development of an insecticide resistance management plan. However, few examples exist to show how to implement such plans programmatically. We describe the formulation and implementation of a resistance management plan for mosquito vectors of human disease in Zambia. We also discuss challenges, steps taken to address the challenges, and directions for the future.

Incremental impact upon malaria transmission of supplementing pyrethroid-impregnated long-lasting insecticidal nets with indoor residual spraying using pyrethroids or the organophosphate, pirimiphos methyl.

BACKGROUND: Long-lasting, insecticidal nets (LLINs) and indoor residual spraying (IRS) are the most widely accepted and applied malaria vector control methods. However, evidence that incremental impact is achieved when they are combined remains limited and inconsistent. METHODS: Fourteen population clusters of approximately 1000 residents each in Zambia's Luangwa and Nyimba districts, which had high pre-existing usage rates (81.7 %) of pyrethroid-impregnated LLINs were quasi-randomly assigned to receive IRS with either of two pyrethroids, namely deltamethrin [Wetable granules (WG)] and lambdacyhalothrin [capsule suspension (CS)], with an emulsifiable concentrate (EC) or CS formulation of the organophosphate pirimiphos methyl (PM), or with no supplementary vector control measure. Diagnostic positivity of patients tested for malaria by community health workers in these clusters was surveyed longitudinally over pre- and post-treatment periods spanning 29 months, over which the treatments were allocated and re-allocated in advance of three sequential rainy seasons. RESULTS: Supplementation of LLINs with PM CS offered the greatest initial level of protection against malaria in the first 3 months of application (incremental protective efficacy (IPE) [95 % confidence interval (CI)] = 0.63 [CI 0.57, 0.69], P < 0.001), followed by lambdacyhalothrin (IPE [95 % CI] = 0.31 [0.10, 0.47], P = 0.006) and PM EC (IPE, 0.23 [CI 0.15, 0.31], P < 0.001) and then by deltamethrin (IPE [95 % CI] = 0.19 [-0.01, 0.35], P = 0.064). Neither pyrethroid formulation provided protection beyond 3 months after spraying, but the protection provided by both PM formulations persisted undiminished for longer periods: 6 months for CS and 12 months for EC. The CS formulation of PM provided greater protection than the combined pyrethroid IRS formulations throughout its effective life IPE [95 % CI] = 0.79 [0.75, 0.83] over 6 months. The EC formulation of PM provided incremental protection for the first 3 months (IPE [95 % CI] = 0.23 [0.15, 0.31]) that was approximately equivalent to the two pyrethroid formulations (lambdacyhalothrin, IPE [95 % CI] = 0.31 [0.10, 0.47] and deltamethrin, IPE [95 % CI] = 0.19 [-0.01, 0.35]) but the additional protection provided by the former, apparently lasted an entire year. CONCLUSION: Where universal coverage targets for LLIN utilization has been achieved, supplementing LLINs with IRS using pyrethroids may reduce malaria transmission below levels achieved by LLIN use alone, even in settings where pyrethroid resistance occurs in the vector population. However, far greater reduction of transmission can be achieved under such conditions by supplementing LLINs with IRS using non-pyrethroid insecticide classes, such as organophosphates, so this is a viable approach to mitigating and managing pyrethroid resistance.

A longitudinal study of the durability of long-lasting insecticidal nets in Zambia.

BACKGROUND: A key goal of malaria control is to achieve universal access to, and use of, long-lasting insecticidal nets (LLINs) among people at risk for malaria. Quantifying the number of LLINs needed to achieve and maintain universal coverage requires knowing when nets need replacement. Longitudinal studies have observed physical deterioration in LLINs well before the assumed net lifespan of 3 years. The objective of this study was to describe attrition, physical integrity and insecticide persistence of LLINs over time to assist with better quantification of nets needing replacement. METHODS: 999 LLINs distributed in 2011 in two highly endemic provinces in Zambia were randomly selected, and were enrolled at 12 months old. LLINs were followed every 6 months up to 30 months of age. Holes were counted and measured (finger, fist, and head method) and a proportional hole index (pHI) was calculated. Households were surveyed about net care and repair and if applicable, reasons for attrition. Functional survival was defined as nets with a pHI <643 and present for follow-up. At 12 and 24 months of age, 74 LLINs were randomly selected for examination of insecticidal activity and content using bioassay and chemical analysis methods previously described by the World Health Organization (WHO). RESULTS: A total of 999 LLINs were enrolled; 505 deltamethrin-treated polyester nets and 494 permethrin-treated polyethylene nets. With 74 used to examine insecticide activity, 925 were available for full follow-up. At 30 months, 325 (33 %) LLINs remained. Net attrition was primarily due to disposal (29 %). Presence of repairs and use over a reed mat were significantly associated with larger pHIs. By 30 months, only 56 % of remaining nets met criteria for functional survival. A shorter functional survival was associated with having been washed. At 24 months, nets had reduced insecticidal activity (57 % met WHO minimal criteria) and content (5 % met WHO target insecticide content). CONCLUSIONS: The median functional survival time for LLINs observed the study was 2.5-3 years and insecticide activity and content were markedly decreased by 2 years. A better measure of net survival incorporating insecticidal field effectiveness, net physical integrity, and attrition is needed.

Impact of Sulfadoxine-Pyrimethamine Resistance on Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy at Clearing Infections and Preventing Low Birth Weight.

BACKGROUND: Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial. METHODS: Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus-uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted. RESULTS: Among 1222 parasitemic pregnant women, overall polymerase chain reaction-uncorrected and -corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69-.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67-.97; P = .02). CONCLUSIONS: The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.

Malaria surveillance in low-transmission areas of Zambia using reactive case detection.

BACKGROUND: Repeat national household surveys suggest highly variable malaria transmission and increasing coverage of high-impact malaria interventions throughout Zambia. Many areas of very low malaria transmission, especially across southern and central regions, are driving efforts towards sub-national elimination. CASE DESCRIPTION: Reactive case detection (RCD) is conducted in Southern Province and urban areas of Lusaka in connection with confirmed incident malaria cases presenting to a community health worker (CHW) or clinic and suspected of being the result of local transmission. CHWs travel to the household of the incident malaria case and screen individuals living in adjacent houses in urban Lusaka and within 140 m in Southern Province for malaria infection using a rapid diagnostic test, treating those testing positive with artemether-lumefantrine. DISCUSSION: Reactive case detection improves access to health care and increases the capacity for the health system to identify malaria infections. The system is useful for targeting malaria interventions, and was instrumental for guiding focal indoor residual spraying in Lusaka during the 2014/2015 spray season. Variations to maximize impact of the current RCD protocol are being considered, including the use of anti-malarials with a longer lasting, post-treatment prophylaxis. CONCLUSION: The RCD system in Zambia is one example of a malaria elimination surveillance system which has increased access to health care within rural communities while leveraging community members to build malaria surveillance capacity.

Spatial patterns and determinants of malaria infection during pregnancy in Zambia.

BACKGROUND: Malaria in pregnancy (MiP) is a major concern in Zambia. Here we aim to determine the burden and risk factors of MiP. METHODS: Monthly reported district-level malaria cases among pregnant women (count data) from January 2009 to December 2014 were obtained from the Zambian District Health Information System. Negative binomial regression model was used to investigate the associations between vector control tools, coverage of health care facilities, transportation networks and population density. Data on MiP treatment were obtained from the 2012 Zambian Malaria Indicator Survey. Yearly clusters of MiP were investigated using spatial statistics in ArcGIS v 10.1. RESULTS: The results indicated that MiP decreased in Zambia between 2010 and 2013. MiP was observed throughout the year, but showed a strong seasonal pattern. Persistent hotspots of MiP were reported in the southeast and northeast regions of Zambia, with districts that had better access to rail road and presence of water bodies associated with decreased prevalence of MiP. Better indoor residual spraying and long-lasting insecticide-treated nets coverage was demonstrated to be protective against MiP. CONCLUSIONS: Mapping the distribution of MiP to track the future requirements for scaling up essential disease-prevention efforts in stable hotspots can help the Zambian National Malaria Control Center to further develop strategies to reduce malaria prevalence in this vulnerable sub-population.

Diagnostic approaches to malaria in Zambia, 2009-2014.

Malaria is an important health burden in Zambia with proper diagnosis remaining as one of the biggest challenges. The need for reliable diagnostics is being addressed through the introduction of rapid diagnostic tests (RDTs). However, without sufficient laboratory amenities in many parts of the country, diagnosis often still relies on non-specific, clinical symptoms. In this study, geographical information systems were used to both visualize and analyze the spatial distribution and the risk factors related to the diagnosis of malaria. The monthly reported, district-level number of malaria cases from January 2009 to December 2014 were collected from the National Malaria Control Center (NMCC). Spatial statistics were used to reveal cluster tendencies that were subsequently linked to possible risk factors, using a non-spatial regression model. Significant, spatio-temporal clusters of malaria were spotted while the introduction of RDTs made the number of clinically diagnosed malaria cases decrease by 33% from 2009 to 2014. The limited access to road network(s) was found to be associated with higher levels of malaria, which can be traced by the expansion of health promotion interventions by the NMCC, indicating enhanced diagnostic capability. The capacity of health facilities has been strengthened with the increased availability of proper diagnostic tools and through retraining of community health workers. To further enhance spatial decision support systems, a multifaceted approach is required to ensure mobilization and availability of human, infrastructural and technological resources. Surveillance based on standardized geospatial or other analytical methods should be used by program managers to design, target, monitor and assess the spatio-temporal dynamics of malaria diagnostic resources country-wide.

Enhanced surveillance and data feedback loop associated with improved malaria data in Lusaka, Zambia.

BACKGROUND: Accurate and timely malaria data are crucial to monitor the progress towards and attainment of elimination. Lusaka, the capital city of Zambia, has reported very low malaria prevalence in Malaria Indicator Surveys. Issues of low malaria testing rates, high numbers of unconfirmed malaria cases and over consumption of anti-malarials were common at clinics within Lusaka, however. The Government of Zambia (GRZ) and its partners sought to address these issues through an enhanced surveillance and feedback programme at clinic level. METHODS: The enhanced malaria surveillance programme began in 2011 to verify trends in reported malaria, as well as to implement a data feedback loop to improve data uptake, use, and quality. A process of monthly data collection and provision of feedback was implemented within all GRZ health clinics in Lusaka District. During clinic visits, clinic registers were accessed to record the number of reported malaria cases, malaria test positivity rate, malaria testing rate, and proportion of total suspected malaria that was confirmed with a diagnostic test. RESULTS AND DISCUSSION: Following the enhanced surveillance programme, the odds of receiving a diagnostic test for a suspected malaria case increased (OR = 1.54, 95 % CI = 0.96-2.49) followed by an upward monthly trend (OR = 1.05, 95 % CI = 1.01-1.09). The odds of a reported malaria case being diagnostically confirmed also increased monthly (1.09, 95 % CI 1.04-1.15). After an initial 140 % increase (95 % CI = 91-183 %), costs fell by 11 % each month (95 % CI = 5.7-10.9 %). Although the mean testing rate increased from 18.9 to 64.4 % over the time period, the proportion of reported malaria unconfirmed by diagnostic remained high at 76 %. CONCLUSIONS: Enhanced surveillance and implementation of a data feedback loop have substantially increased malaria testing rates and decreased the number of unconfirmed malaria cases and courses of ACT consumed in Lusaka District within just two years. Continued support of enhanced surveillance in Lusaka as well as national scale-up of the system is recommended to reinforce good case management and to ensure timely, reliable data are available to guide targeting of limited malaria prevention and control resources in Zambia.

Costs and cost-effectiveness of a large-scale mass testing and treatment intervention for malaria in Southern Province, Zambia.

BACKGROUND: A cluster, randomized, control trial of three dry-season rounds of a mass testing and treatment intervention (MTAT) using rapid diagnostic tests (RDTs) and artemether-lumefantrine (AL) was conducted in four districts in Southern Province, Zambia. METHODS: Data were collected on the costs and logistics of the intervention and paired with effectiveness estimated from a community randomized control trial for the purpose of conducting a provider perspective cost-effectiveness analysis of MTAT vs no MTAT (Standard of Care). RESULTS: Dry-season MTAT in this setting did not reduce malaria transmission sufficiently to permit transition to a case-investigation strategy to then pursue malaria elimination, however, the intervention did substantially reduce malaria illness and was a highly cost-effective intervention for malaria burden reduction in this moderate transmission area. The cost per RDT administered was estimated to be USD4.39 (range: USD1.62-13.96) while the cost per AL treatment administered was estimated to be USD34.74 (range: USD3.87-3,835). The net cost per disability adjusted life year averted (incremental cost-effectiveness ratio) was estimated to be USD804. CONCLUSIONS: The intervention appears to be highly cost-effective relative to World Health Organization thresholds for malaria burden reduction in Zambia as compared to no MTAT. However, it was estimated that population-wide mass drug administration is likely to be more cost-effective for burden reduction and for transmission reduction compared to MTAT.

A qualitative study of perceptions of a mass test and treat campaign in Southern Zambia and potential barriers to effectiveness.

BACKGROUND: A mass test and treat campaign (MTAT) using rapid diagnostic tests (RDTs) and artemether-lumefantrine (AL) was conducted in Southern Zambia in 2012 and 2013 to reduce the parasite reservoir and progress towards malaria elimination. Through this intervention, community health workers (CHWs) tested all household members with rapid diagnostic tests (RDTs) and provided treatment to those that tested positive. METHODS: A qualitative study was undertaken to understand CHW and community perceptions regarding the MTAT campaign. A total of eight focus groups and 33 in-depth and key informant interviews were conducted with CHWs, community members and health centre staff that participated in the MTAT. RESULTS: Interviews and focus groups with CHWs and community members revealed that increased knowledge of malaria prevention, the ability to reach people who live far from health centres, and the ability of the MTAT campaign to reduce the malaria burden were the greatest perceived benefits of the campaign. Conversely, the primary potential barriers to effectiveness included refusals to be tested, limited adherence to drug regimens, and inadequate commodity supply. Study respondents generally agreed that MTAT services were scalable outside of the study area but would require greater involvement from district and provincial medical staff. CONCLUSIONS: These findings highlight the importance of increased community sensitization as part of mass treatment campaigns for improving campaign coverage and acceptance. Further, they suggest that communication channels between the Ministry of Health, National Malaria Control Centre and Medical Stores Limited may need to be improved so as to ensure there is consistent supply and management of commodities. Continued capacity building of CHWs and health facility supervisors is critical for a more effective programme and sustained progress towards malaria elimination.

Evaluation of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy: a retrospective birth outcomes study in Mansa, Zambia.

BACKGROUND: Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) decreases placental parasitaemia, thus improving birth outcomes. Zambian policy recommends monthly SP-IPTp doses given presumptively during pregnancy at each antenatal examination, spaced one month apart after 16 weeks of gestation. The effectiveness of SP-IPTp was evaluated in Zambia where a recent study showed moderate prevalence of Plasmodium falciparum parasites with genetic mutations that confer SP resistance. METHODS: HIV-negative women were enrolled at the time of delivery at two facilities in Mansa, Zambia, an area of high malaria transmission. Women were interviewed and SP exposure was determined by antenatal card documentation or self-reports. Using Poisson regression modelling, the effectiveness of SP-IPTp was evaluated for outcomes of parasitaemia (microscopic examination of maternal peripheral, cord, and placental blood films), maternal anaemia (Hb < 11 g/dl), placental infection (histopathology), and infant outcomes (low birth weight (LBW), preterm delivery, and small for gestational age) in women who took 0-4 doses of SP-IPTp. RESULTS: Participants included 435 women, with a median age of 23 years (range 16-44). Thirty-four women took zero doses of SP-IPTp, while 115, 142 and 144 women took one, two, or ≥ three doses, respectively. Multivariate Poisson regression models considering age, mosquito net usage, indoor residual spraying, urban home, gravidity, facility, wet season delivery, and marital status showed that among paucigravid women ≥ two doses of SP-ITPp compared to one or less doses was associated with a protective effect on LBW (prevalence ratio (PR) 0.33, 95% confidence interval (CI) 0.12-0.91) and any infection (PR 0.76, CI 0.58-0.99). Multivariate models considering SP-IPTp as a continuous variable showed a protective dose-response association with LBW (paucigravid women: PR 0.54, CI 0.33-0.90, multigravid women: PR 0.63, CI 0.41-0.97). CONCLUSIONS: In Mansa, Zambia, an area of moderate SP resistance, ≥ two doses of SP-IPTp were associated with a protective effect from malaria in pregnancy, especially among paucigravid women. Each dose of SP-IPTp contributed to a 46 and 37% decrease in the frequency of LBW among paucigravid and multigravid women, respectively. SP-IPTp remains a viable strategy in this context.

Comparison of a mobile phone-based malaria reporting system with source participant register data for capturing spatial and temporal trends in epidemiological indicators of malaria transmission collected by community health workers in rural Zambia.

BACKGROUND: Timeliness, completeness, and accuracy are key requirements for any surveillance system to reliably monitor disease burden and guide efficient resource prioritization. Evidence that electronic reporting of malaria cases by community health workers (CHWs) meet these requirements remains limited. METHODOLOGY: Residents of two adjacent rural districts in Zambia were provided with both passive and active malaria testing and treatment services with malaria rapid diagnostic tests (RDTs) and artemisinin-based combination therapy by 42 CHWs serving 14 population clusters centred around public sector health facilities. Reference data describing total numbers of RDT-detected infections and diagnostic positivity (DP) were extracted from detailed participant register books kept by CHWs. These were compared with equivalent weekly summaries relayed directly by the CHWs themselves through a mobile phone short messaging system (SMS) reporting platform. RESULTS: Slightly more RDT-detected malaria infections were recorded in extracted participant registers than were reported in weekly mobile phone summaries but the difference was equivalent to only 19.2% (31,665 versus 25,583, respectively). The majority (81%) of weekly SMS reports were received within one week and the remainder within one month. Overall mean [95% confidence limits] difference between the numbers of register-recorded and SMS-reported RDT-detected malaria infections per CHW per week, as estimated by the Bland Altman method, was only -2.3 [-21.9, 17.2]. The mean [range] for both the number of RDT-detected malaria infections (86 [0, 463] versus 73.6 [0, 519], respectively)) and DP (22.8% [0.0 to 96.3%] versus 23.2% [0.4 to 75.8%], respectively) reported by SMS were generally very consistent with those recorded in the reference paper-based register data and exhibited similar seasonality patterns across all study clusters. Overall, mean relative differences in the SMS reports and reference register data were more consistent with each other for DP than for absolute numbers of RDT-detected infections, presumably because this indicator is robust to variations in patient reporting rates by location, weather, season and calendar event because these are included in both the nominator and denominator. DISCUSSION/CONCLUSION: The SMS reports captured malaria transmission trends with adequate accuracy and could be used for population-wide, continuous, longitudinal monitoring of malaria transmission.

Therapeutic efficacy of artemether-lumefantrine on treatment of uncomplicated Plasmodium falciparum mono-infection in an area of high malaria transmission in Zambia.

BACKGROUND: Anti-malarial drug resistance continues to be a leading threat to ongoing malaria control efforts and calls for continued monitoring of the efficacy of these drugs in order to inform national anti-malarial drug policy decision-making. This study assessed the therapeutic efficacy and safety of artemether-lumefantrine (AL)(Coartem®) for the treatment of uncomplicated Plasmodium falciparum malaria in two sentinel high malaria transmission districts in the Eastern Province of Zambia in persons aged six months and above, excluding women aged 12 to 18 years. METHODS: This was an observational cohort of 176 symptomatic patients diagnosed with uncomplicated Plasmodium falciparum mono-infection. A World Health Organization (WHO)-standardized 28-day assessment protocol was used to assess clinical and parasitological responses to directly observed AL treatment of uncomplicated malaria. DNA polymerase chain reaction (PCR) analysis for molecular markers of AL resistance was conducted on positive blood samples and differentiated recrudescence from re-infections of the malaria parasites. RESULTS: All patients (CI 97.6-100) had adequate clinical and parasitological responses to treatment with AL. At the time of enrolment, mean slide positivity among study participants was 71.8% and 55.2% in Katete and Chipata, respectively. From a mean parasite density of 55,087, 98% of the study participants presented with zero parasitaemia by day 3 of the study. Fever clearance occurred within 24 hours of treatment with AL. However mean parasite density declines were most dramatic in participants in the older age. No adverse reactions to AL treatment were observed during the study. CONCLUSION: AL remains a safe and efficacious drug for the treatment of uncomplicated Plasmodium falciparum malaria in Zambia, endemic for malaria, with some provinces experiencing high transmission intensity. However, the delayed parasite clearance in younger patients calls for further sentinel and periodical monitoring of AL efficacy in different areas of the country.

Distribution of yellow fever vectors in Northwestern and Western Provinces, Zambia.

OBJECTIVE: To determine the distribution of yellow fever (YF) vectors species in Northwestern and Western of Zambia, which sampled mosquitoes inside and outside houses in rural, urban, peri-urban and forest areas. METHODS: Back-pack aspirators spray catches and CDC light traps collected adult mosquitoes including 405 Aedes, 518 Anopheles, 471 Culex and 71 Mansonia. Morphological vector identification and PCR viral determination were done at a WHO Regional Reference Centre (Institute Pasteur Dakar), Senegal. RESULTS: The two main YF vectors were Aedes (Stegomyia) aegypti (Ae. aegypti) and Aedes (Stegomyia) africanus. The first was collected in peri-urban areas and the later was in forest areas, both sparsely distributed in Northwestern Province, where the 0.43 Breteau and 1.92 container indexes, respectively implied low risk to YF. Aedes (Aedimorphus) mutilus; Aedes (Aedimorphus) minutus and Aedes (Finlaya) wellmani were also found in Northwestern, not in Western Province. No Aedes were collected from rural peri-domestic areas. Significantly more Aedes species (90.7%, n=398) than Anopheles (9.1%, n=40) were collected in forest areas (P<0.001) or Culex species (0.2%, n=2) (P<0.001). Ae. aegypti was found only in a discarded container but not in flower pots, old tyres, plant axils, discarded shallow wells, disused container bottles and canoes inspected. CONCLUSIONS: Ae. aegypti and Aedes africanus YF vectors were found in the study sites in the Northwestern Province of Zambia, where densities were low and distribution was sparse. The low Breteau index suggests low risk of YF in the Northwestern Province. The presence of Aedes in Northwestern Province and its absence in the Western Province could be due to differing ecological factors in the sampled areas. Universal coverage of vector control interventions could help to reduce YF vector population and the risk to arthropod-borne virus infections.