Malaria Transmission at The Zimbabwe-Mozambique Border: An Observational Study of Parasitemia by Travel History and Household Location.

Cross-border human population movement contributes to malaria transmission in border regions, impeding national elimination. However, its impact in low-to-moderate transmission settings is not well characterized. This community-based study in Mutasa District, Zimbabwe, estimated the association of parasite prevalence with self-reported overnight travel to Mozambique and household distance to the border from 2012-2020. A fully adjusted Poisson regression model with robust variance estimation was fit using active surveillance data. The population attributable fraction of parasite prevalence from overnight travel was also estimated. The relative risk of testing positive for malaria by rapid diagnostic test declined 14% (prevalence ratio [PR] = 0.86, 95% CI = 0.81-0.92) per kilometer from the border up to 12 km away. Travel to Mozambique was associated with a 157% increased risk (PR = 2.57, 95% CI = 1.38-4.78), although only 5.8% of cases were attributable to overnight travel (95% CI = -1.1% to 12.7%), reflecting infrequent overnight trips (1.3% of visits). This study suggests that transmission in eastern Zimbabwe is driven by increasingly conducive social or environmental conditions approaching the border and low levels of importation from overnight travel. Although day trips to Mozambique during peak biting hours were not assessed, the contribution of such trips to ongoing transmission may be significant. Future malaria control efforts should prioritize high coverage of existing interventions and continued support for community health workers and health facilities at the border, which provide free case management.

Characterizing human movement patterns using GPS data loggers in an area of persistent malaria in Zimbabwe along the Mozambique border.

BACKGROUND: Human mobility is a driver for the reemergence or resurgence of malaria and has been identified as a source of cross-border transmission. However, movement patterns are difficult to measure in rural areas where malaria risk is high. In countries with malaria elimination goals, it is essential to determine the role of mobility on malaria transmission to implement appropriate interventions. METHODS: A study was conducted in Mutasa District, Zimbabwe, to investigate human movement patterns in an area of persistent transmission along the Mozambique border. Over 1 year, a convenience sample of 20 participants/month was recruited from active malaria surveillance cohorts to carry an IgotU® GT-600 global positioning system (GPS) data logger during all daily activities. Consenting participants were tested for malaria at data logger distribution using rapid antigen diagnostic tests and completed a survey questionnaire. GPS data were analyzed using a trajectory analysis tool, and participant movement patterns were characterized throughout the study area and across the border into Mozambique using movement intensity maps, activity space plots, and statistical analyses. RESULTS: From June 2016-May 2017, 184 participants provided movement tracks encompassing > 350,000 data points and nearly 8000 person-days. Malaria prevalence at logger distribution was 3.7%. Participants traveled a median of 2.8 km/day and spent a median of 4.6 h/day away from home. Movement was widespread within and outside the study area, with participants traveling up to 500 km from their homes. Indices of mobility were higher in the dry season than the rainy season (median km traveled/day = 3.5 vs. 2.2, P = 0.03), among male compared to female participants (median km traveled/day = 3.8 vs. 2.0, P = 0.0008), and among adults compared to adolescents (median total km traveled = 104.6 vs. 59.5, P = 0.05). Half of participants traveled outside the study area, and 30% traveled into Mozambique, including 15 who stayed in Mozambique overnight. CONCLUSIONS: Study participants in Mutasa District, Zimbabwe, were highly mobile throughout the year. Many participants traveled long distances from home, including overnight trips into Mozambique, with clear implications for malaria control. Interventions targeted at mobile populations and cross-border transmission may be effective in preventing malaria introductions in this region.

Scientific Findings of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe.

For a decade, the Southern and Central Africa International Center of Excellence for Malaria Research has operated with local partners across study sites in Zambia and Zimbabwe that range from hypo- to holoendemic and vary ecologically and entomologically. The burden of malaria and the impact of control measures were assessed in longitudinal cohorts, cross-sectional surveys, passive and reactive case detection, and other observational designs that incorporated multidisciplinary scientific approaches: classical epidemiology, geospatial science, serosurveillance, parasite and mosquito genetics, and vector bionomics. Findings to date have helped elaborate the patterns and possible causes of sustained low-to-moderate transmission in southern Zambia and eastern Zimbabwe and recalcitrant high transmission and fatality in northern Zambia. Cryptic and novel mosquito vectors, asymptomatic parasite reservoirs in older children, residual parasitemia and gametocytemia after treatment, indoor residual spraying timed dyssynchronously to vector abundance, and stockouts of essential malaria commodities, all in the context of intractable rural poverty, appear to explain the persistent malaria burden despite current interventions. Ongoing studies of high-resolution transmission chains, parasite population structures, long-term malaria periodicity, and molecular entomology are further helping to lay new avenues for malaria control in southern and central Africa and similar settings.

Policy Implications of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe.

The International Centers of Excellence for Malaria Research (ICEMR) were established by the National Institute of Allergy and Infectious Diseases more than a decade ago to provide multidisciplinary research support to malaria control programs worldwide, operating in endemic areas and contributing technology, expertise, and ultimately policy guidance for malaria control and elimination. The Southern and Central Africa ICEMR has conducted research across three main sites in Zambia and Zimbabwe that differ in ecology, entomology, transmission intensity, and control strategies. Scientific findings led to new policies and action by the national malaria control programs and their partners in the selection of methods, materials, timing, and locations of case management and vector control. Malaria risk maps and predictive models of case detection furnished by the ICEMR informed malaria elimination programming in southern Zambia, and time series analyses of entomological and parasitological data motivated several major changes to indoor residual spray campaigns in northern Zambia. Along the Zimbabwe-Mozambique border, temporal and geospatial data are currently informing investigations into a recent resurgence of malaria. Other ICEMR findings pertaining to parasite and mosquito genetics, human behavior, and clinical epidemiology have similarly yielded immediate and long-term policy implications at each of the sites, often with generalizable conclusions. The ICEMR programs thereby provide rigorous scientific investigations and analyses to national control and elimination programs, without which the impediments to malaria control and their potential solutions would remain understudied.

What Heterogeneities in Individual-level Mobility Are Lost During Aggregation? Leveraging GPS Logger Data to Understand Fine-scale and Aggregated Patterns of Mobility.

Human movement drives spatial transmission patterns of infectious diseases. Population-level mobility patterns are often quantified using aggregated data sets, such as census migration surveys or mobile phone data. These data are often unable to quantify individual-level travel patterns and lack the information needed to discern how mobility varies by demographic groups. Individual-level datasets can capture additional, more precise, aspects of mobility that may impact disease risk or transmission patterns and determine how mobility differs across cohorts; however, these data are rare, particularly in locations such as sub-Saharan Africa. Using detailed GPS logger data collected from three sites in southern Africa, we explore metrics of mobility such as percent time spent outside home, number of locations visited, distance of locations, and time spent at locations to determine whether they vary by demographic, geographic, or temporal factors. We further create a composite mobility score to identify how well aggregated summary measures would capture the full extent of mobility patterns. Although sites had significant differences in all mobility metrics, no site had the highest mobility for every metric, a distinction that was not captured by the composite mobility score. Further, the effects of sex, age, and season on mobility were all dependent on site. No factor significantly influenced the number of trips to locations, a common way to aggregate datasets. When collecting and analyzing human mobility data, it is difficult to account for all the nuances; however, these analyses can help determine which metrics are most helpful and what underlying differences may be present.

The role of bacteriological monitoring using culture and drug susceptibility tests (CDST) on treatment outcomes among MDR/RR-TB patients on treatment: a cohort analysis of patients enrolled on treatment 2010-2015 in Zimbabwe.

INTRODUCTION: an estimated 25% of the world population is infected with Mycobacterium tuberculosis. In 2017, new tuberculosis cases were estimated at 10 million, while 1.6 million tuberculosis related deaths were recorded, 25% residing in Africa. Treatment outcomes of multi drug resistant Tuberculosis patients in Zimbabwe has been well documented but the role of bacteriological monitoring on treatment outcomes has not been systematically evaluated. The objective of the study was to determine the role of bacteriological monitoring using culture and drug susceptibility tests on treatment outcomes among patients with multi drug resistant tuberculosis. METHODS: a retrospective, secondary data analysis was conducted using routinely collected data of patients with multi drug resistant TB in Zimbabwe. Frequencies were used to summarize categorical variables and a generalized linear model with a log-link function and a Poisson distribution was used to assess factors associated with unfavourable outcomes. The level of significance was set at P-Value<0.05. RESULTS: about the study collected data from 473 records of patients with an average age of 36.35 years. Forty-nine percent (49%) were male and 51% were female. Results showed that when a patient has baseline culture result missing, has no culture conversion result, regardless of having a follow up culture and drug susceptibility test result, the risk of developing unfavourable outcomes increase by 3.9 times compared to a patient who has received all the three (3) bacteriological monitoring tests. CONCLUSION: results highlights the need for consistent bacteriological monitoring of patients to avert unfavourable treatment outcomes.

Predictors of mortality and treatment success of multi-drug resistant and Rifampicin resistant tuberculosis in Zimbabwe: a retrospective cohort analysis of patients initiated on treatment during 2010 to 2015.

INTRODUCTION: Zimbabwe is one of the 30 countries globally with a high burden of multidrug-resistant TB or rifampicin-resistant TB. The World Health Organization recommended that patients diagnosed with multidrug-resistant TB be treated with 20-24 month standardized second-line drugs since 2010. However, factors associated with mortality and treatment success have not been systematically evaluated in Zimbabwe. The Objective of the study was to assess factors associated with Mortality and treatment success among multidrug-resistant-TB patients registered and treated under the National Tuberculosis programme in Zimbabwe. METHODS: the study was conducted using secondary data routinely collected from the National tuberculosis (TB) programme. Categorical variables were summarised using frequencies and a generalized linear model with a log-link function and a Poisson distribution was used to assess factors associated with mortality and treatment success. The level of significance was set at P-Value < 0.05. RESULTS: patient antiretroviral therapy (ART) status was a significant associated factor of treatment success or failure (RRR = 3.92, p < 0.001). Patients who were not on ART had a high risk of death by 3.92 times compared to patients who were on ART. In the age groups 45 - 54 years (relative risk ratios (RRR) = 1.41, p = 0.048), the risk of death was increased by 1.41 times compared to other age groups. Patients aged 55 years and above (RRR = 1.55, p = 0.017), had a risk of dying increased by 1.55 times compared to other age groups. Diagnosis time duration of 8 - 30 days (RRR = 0.62, p = 0.022) was found to be protective, a shorter diagnosis time duration between 8 to 30 days reduced the risk of TB deaths by 0.62 times compared to longer periods. Missed TB doses of > 10% (RRR = 2.03, p < 0.001) increased the risk of MDR/RR-TB deaths by 2.03 times compared to missing TB doses of ≤ 10%. CONCLUSION: not being on ART when HIV positive was a major significant predictor of mortality. Improving ART uptake among those ART-naïve and strategies aimed at improving treatment adherence are important in improving treatment success rates.

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.

Comprehensive investigation of sources of misclassification errors in routine HIV testing in Zimbabwe.

INTRODUCTION: Misclassification errors have been reported in rapid diagnostic HIV tests (RDTs) in sub-Saharan African countries. These errors can lead to missed opportunities for prevention-of-mother-to-child-transmission (PMTCT), early infant diagnosis and adult HIV-prevention, unnecessary lifelong antiretroviral treatment (ART) and wasted resources. Few national estimates or systematic quantifications of sources of errors have been produced. We conducted a comprehensive assessment of possible sources of misclassification errors in routine HIV testing in Zimbabwe. METHODS: RDT-based HIV test results were extracted from routine PMTCT programme records at 62 sites during national antenatal HIV surveillance in 2017. Positive- (PPA) and negative-percent agreement (NPA) for HIV RDT results and the false-HIV-positivity rate for people with previous HIV-positive results ("known-positives") were calculated using results from external quality assurance testing done for HIV surveillance purposes. Data on indicators of quality management systems, RDT kit performance under local climatic conditions and user/clerical errors were collected using HIV surveillance forms, data-loggers and a Smartphone camera application (7 sites). Proportions of cases with errors were compared for tests done in the presence/absence of potential sources of errors. RESULTS: NPA was 99.9% for both pregnant women (N = 17224) and male partners (N = 2173). PPA was 90.0% (N = 1187) and 93.4% (N = 136) for women and men respectively. 3.5% (N = 1921) of known-positive individuals on ART were HIV negative. Humidity and temperature exceeding manufacturers' recommendations, particularly in storerooms (88.6% and 97.3% respectively), and premature readings of RDT output (56.0%) were common. False-HIV-negative cases, including interpretation errors, occurred despite staff training and good algorithm compliance, and were not reduced by existing external or internal quality assurance procedures. PPA was lower when testing room humidity exceeded 60% (88.0% vs. 93.3%; p = 0.007). CONCLUSIONS: False-HIV-negative results were still common in Zimbabwe in 2017 and could be reduced with HIV testing algorithms that use RDTs with higher sensitivity under real-world conditions and greater practicality under busy clinic conditions, and by strengthening proficiency testing procedures in external quality assurance systems. New false-HIV-positive RDT results were infrequent but earlier errors in testing may have resulted in large numbers of uninfected individuals being on ART.

Sulfadoxine-pyrimethamine parasitological efficacy against Plasmodium falciparum among pregnant women and molecular markers of resistance in Zambia: an observational cohort study.

BACKGROUND: The World Health Organization recommends the provision of intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) at 4-week intervals from gestational week 13 to delivery in areas of moderate to high malaria transmission intensity. However, the effect of IPTp-SP has been compromised in some areas due to parasite resistance, raising the importance of parasitological and chemoprophylactic surveillance, and monitoring SP-resistance markers in the Plasmodium falciparum population. METHODS: Between November 2013 and April 2014 in Nchelenge, Zambia, 1086 pregnant women received IPTp-SP at antenatal-care bookings. Blood samples were collected on day 0, and on day 28 post-treatment to test for malaria parasites and to estimate SP parasitological efficacy in the treatment and prevention of parasitaemia. A random sample of 96, day 0 malaria-positive samples were analysed to estimate the prevalence of SP-resistance markers in the P. falciparum population. RESULTS: The overall parasitological and prophylactic failure among women who had paired day 0 and day 28 blood slides was 18.6% (95% CI 15.5, 21.8; 109 of 590). Among pregnant women who had asymptomatic parasitaemia on day 0, the day 28 PCR-uncorrected parasitological failure was 30.0% (95% CI 23.7, 36.2; 62 of 207) and the day 28 PCR-corrected parasitological failure was 15.6% (95% CI: 10.6, 20.6; 32 of 205). Among women who tested negative at day 0, 12.3% (95% CI: 9.0, 15.6; 47 of 383) developed parasitaemia at day 28. Among the 96 malaria-positive samples assayed from day 0, 70.8% (95% CI: 60.8, 79.2) contained the DHPS double (Gly-437 + Glu-540) mutation and 92.7% (95% CI: 85.3, 96.5) had the DHFR triple (Asn-108 + Ile-51 + Arg-59) mutation. The quintuple mutation (DHFR triple + DHPS double) and the sextuple mutant (DHFR triple + DHPS double + Arg-581) were found among 68.8% (95% CI: 58.6, 77.3) and 9.4% (95% CI: 4.2, 16.0) of samples, respectively. CONCLUSION: The parasitological and chemoprophylactic failure of SP, and the prevalence of resistance markers in Nchelenge is alarmingly high. Alternative therapies are urgently needed to safeguard pregnant women against malarial infection.

Detecting Plasmodium falciparum in community surveys: a comparison of Paracheck Pf® Test and ICT Malaria Pf® Cassette Test to polymerase chain reaction in Mutasa District, Zimbabwe.

BACKGROUND: Microscopy and rapid diagnostic tests (RDTs) are the main techniques used to diagnose malaria. While microscopy is considered the gold standard, RDTs have established popularity as they allow for rapid diagnosis with minimal technical skills. This study aimed to compare the diagnostic performance of two Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-based RDTs (Paracheck Pf® Test (Paracheck) and Malaria Pf™ ICT (ICT)) to polymerase chain reaction (PCR) in a community survey. METHODS: A cross-sectional study was conducted between October 2012 and December 2014 in Mutasa District, Manicaland Province, eastern Zimbabwe. Households were randomly selected using satellite imagery, and 224 households were visited. Residents present in the household on the date of the visit were recruited for the study. Participants of all age groups from the selected households were screened with Paracheck and ICT RDTs in parallel. Dried blood spots (DBS) and thin and thick smears were collected. Parasite DNA extracted from the DBS was subjected to nested PCR targeting the Plasmodium cytochrome b mitochondrial gene. Data analysis was performed using the Cohen's Kappa test to determine the interrater agreement and the sensitivity and specificity of the diagnostic test were reported. RESULTS: Results from a total of 702 participants were analysed. Most were females, 397 (57%), and the median age of participants was 21 years with an interquartile range of 9-39 years. Of those who were screened, 8 (1.1%), 35 (5.0%), and 21 (2.9%) were malaria parasite positive by microscopy, RDT and PCR, respectively. Paracheck and ICT RDTs had a 100% agreement. Comparing RDT and PCR results, 34 participants (4.8%) had discordant results. Most of the discordant cases were RDT positive but PCR negative (n = 24). Half of those RDT positive, but PCR negative individuals reported anti-malarials to use in the past month, which is significantly higher than reported anti-malarial drug use in the population (p < 0.001). The participant was febrile on the day of the visit, but relying on PfHRP2-based RDT would miss this case. Among the diagnostic methods evaluated, with reference to PCR, the sensitivity was higher with the RDT (52.4%) while specificity was higher with the microscopy (99.9%). The positive predictive value (PPV) was higher with the microscopy (87.5%), while the negative predictive values were similar for both microscopy and RDTs (98%). Overall, a strong correlated agreement with PCR was observed for the microscopy (97.9%) and the RDTs (95.2%). CONCLUSIONS: Paracheck and ICT RDTs showed 100% agreement and can be used interchangeably. As malaria transmission declines and Zimbabwe aims to reach malaria elimination, management of infected individuals with low parasitaemia as well as non-P. falciparum infection can be critical.

Steep Rebound of Chloroquine-Sensitive Plasmodium falciparum in Zimbabwe.

Removal of chloroquine from national malaria formularies can lead to the reversion of resistant Plasmodium falciparum to wild-type. We report a steep decline in chloroquine-resistant P falciparum within 10 years of national discontinuation of chloroquine monotherapy in Zimbabwe. Drug resistance surveillance is a vital component of malaria control programs, and the experience with chloroquine in Zimbabwe and elsewhere in sub-Saharan Africa is illustrative of the potentially rapid and dramatic impact of drug policy on antimalarial resistance.

Treatment outcomes of multi drug resistant and rifampicin resistant Tuberculosis in Zimbabwe: A cohort analysis of patients initiated on treatment during 2010 to 2015.

BACKGROUND: Zimbabwe is one of the thirty countries globally with a high burden of multidrug-resistant tuberculosis (TB) or rifampicin-resistant TB (MDR/RR-TB). Since 2010, patients diagnosed with MDR/RR-TB are being treated with 20-24 months of standardized second-line drugs (SLDs). The profile, management and factors associated with unfavourable treatment outcomes of MDR/RR TB have not been systematically evaluated in Zimbabwe. OBJECTIVE: To assess treatment outcomes and factors associated with unfavourable outcomes among MDR/RR-TB patients registered and treated under the National Tuberculosis Programme in all the district hospitals and urban healthcare facilities in Zimbabwe between January 2010 and December 2015. METHODS: A cohort study using routinely collected programme data. The 'death', 'loss to follow-up' (LTFU), 'failure' and 'not evaluated' were considered as "unfavourable outcome". A generalized linear model with a log-link and binomial distribution or a Poisson distribution with robust error variances were used to assess factors associated with "unfavourable outcome". The unadjusted and adjusted relative risks were calculated as a measure of association. A 𝑝value< 0.05 was considered statistically significant. RESULTS: Of the 473 patients in the study, the median age was 34 years [interquartile range, 29-42] and 230 (49%) were males. There were 352 (74%) patients co-infected with HIV, of whom 321 (91%) were on antiretroviral therapy (ART). Severe adverse events (SAEs) were recorded in 118 (25%) patients; mostly hearing impairments (70%) and psychosis (11%). Overall, 184 (39%) patients had 'unfavourable' treatment outcomes [125 (26%) were deaths, 39 (8%) were lost to follow-up, 4 (<1%) were failures and 16 (3%) not evaluated]. Being co-infected with HIV but not on ART [adjusted relative risk (aRR) = 2.60; 95% CI: 1.33-5.09] was independently associated with unfavourable treatment outcomes. CONCLUSION: The high unfavourable treatment outcomes among MDR/RR-TB patients on standardized SLDs were coupled with a high occurrence of SAEs in this predominantly HIV co-infected cohort. Switching to individualized all oral shorter treatment regimens should be considered to limit SAEs and improve treatment outcomes. Improving the ART uptake and timeliness of ART initiation can reduce unfavourable outcomes.

Distinct Antibody Signatures Associated with Different Malaria Transmission Intensities in Zambia and Zimbabwe.

Antibodies to Plasmodium falciparum are specific biomarkers that can be used to monitor parasite exposure over broader time frames than microscopy, rapid diagnostic tests, or molecular assays. Consequently, seroprevalence surveys can assist with monitoring the impact of malaria control interventions, particularly in the final stages of elimination, when parasite incidence is low. The protein array format to measure antibodies to diverse P. falciparum antigens requires only small sample volumes and is high throughput, permitting the monitoring of malaria transmission on large spatial and temporal scales. We expanded the use of a protein microarray to assess malaria transmission in settings beyond those with a low malaria incidence. Antibody responses in children and adults were profiled, using a P. falciparum protein microarray, through community-based surveys in three areas in Zambia and Zimbabwe at different stages of malaria control and elimination. These three epidemiological settings had distinct serological profiles reflective of their malaria transmission histories. While there was little correlation between transmission intensity and antibody signals (magnitude or breadth) in adults, there was a clear correlation in children younger than 5 years of age. Antibodies in adults appeared to be durable even in the absence of significant recent transmission, whereas antibodies in children provided a more accurate picture of recent levels of transmission intensity. Seroprevalence studies in children could provide a valuable marker of progress toward malaria elimination.IMPORTANCE As malaria approaches elimination in many areas of the world, monitoring the effect of control measures becomes more important but challenging. Low-level infections may go undetected by conventional tests that depend on parasitemia, particularly in immune individuals, who typically show no symptoms of malaria. In contrast, antibodies persist after parasitemia and may provide a more accurate picture of recent exposure. Only a few parasite antigens-mainly vaccine candidates-have been evaluated in seroepidemiological studies. We examined antibody responses to 500 different malaria proteins in blood samples collected through community-based surveillance from areas with low, medium, and high malaria transmission intensities. The breadth of the antibody responses in adults was broad in all three settings and was a poor correlate of recent exposure. In contrast, children represented a better sentinel population for monitoring recent malaria transmission. These data will help inform the use of multiplex serology for malaria surveillance.

Malaria knowledge and bed net use in three transmission settings in southern Africa.

BACKGROUND: Insecticide-treated nets (ITNs) reduce malaria morbidity and mortality in endemic areas. Despite increasing availability, the use of ITNs remains limited in some settings. Poor malaria knowledge is a barrier to the widespread use of ITNs. The goal of this study was to assess the levels of malaria knowledge and evaluate factors associated with bed net use among individuals residing in three regions of southern Africa with different levels of malaria transmission and control. METHODS: A cross-sectional study was conducted on a sample of 7535 residents recruited from 2066 households in Mutasa District, Zimbabwe (seasonal malaria transmission), Choma District, Zambia (low transmission) and Nchelenge District, Zambia (high transmission), between March 2012 and March 2017. A standardized questionnaire was used to collect data on demographics, malaria-related knowledge and use of preventive measures. Multivariate logistic regression analyses were used to assess determinants of bed net use. RESULTS: Most of the 3836 adult participants correctly linked mosquito bites to malaria (85.0%), mentioned at least one malaria symptom (95.5%) and knew of the benefit of sleeping under an ITN. Bed net ownership and use were highest in Choma and Nchelenge Districts and lowest in Mutasa District. In multivariate analyses, knowledge of ITNs was associated with a 30-40% increased likelihood of bed net use after adjusting for potential confounders across all sites. Other factors significantly associated with bed net use were age, household size and socioeconomic status, although the direction, strength and size of association varied by study site. Importantly, participants aged 5-14 years had reduced odds of sleeping under a bed net compared to children younger than 5 years. CONCLUSION: Relevant knowledge of ITNs translated into the expected preventive behaviour of sleeping under a bed net, underscoring the need for continued health messaging on malaria prevention. The implementation and delivery of malaria control and elimination interventions needs to consider socioeconomic equity gaps, and target school-age children to ensure access to and improve utilization of ITNs.

Distinct parasite populations infect individuals identified through passive and active case detection in a region of declining malaria transmission in southern Zambia.

BACKGROUND: Substantial reductions in the burden of malaria have been documented in parts of sub-Saharan Africa, with elimination strategies and goals being formulated in some regions. Within this context, understanding the epidemiology of low-level malaria transmission is crucial to achieving and sustaining elimination. A 24 single-nucleotide-polymorphism Plasmodium falciparum molecular barcode was used to characterize parasite populations from infected individuals identified through passive and active case detection in an area approaching malaria elimination in southern Zambia. METHODS: The study was conducted in the catchment area of Macha Hospital in Choma District, Southern Province, Zambia, where the parasite prevalence declined over the past decade, from 9.2% in 2008 to less than 1% in 2013. Parasite haplotypes from actively detected, P. falciparum-infected participants enrolled in a serial cross-sectional, community-based cohort study from 2008 to 2013 and from passively detected, P. falciparum-infected individuals enrolled at five rural health centres from 2012 to 2015 were compared. Changes in P. falciparum genetic relatedness, diversity and complexity were analysed as malaria transmission declined. RESULTS: Actively detected cases identified in the community were most commonly rapid diagnostic test negative, asymptomatic and had submicroscopic parasitaemia. Phylogenetic reconstruction using concatenated 24 SNP barcode revealed a separation of parasite haplotypes from passively and actively detected infections, consistent with two genetically distinct parasite populations. For passively detected infections identified at health centres, the proportion of detectable polyclonal infections was consistently low in all seasons, in contrast with actively detected infections in which the proportion of polyclonal infections was high. The mean genetic divergence for passively detected infections was 34.5% for the 2012-2013 transmission season, 37.8% for the 2013-2014 season, and 30.8% for the 2014-2015 season. The mean genetic divergence for actively detected infections was 22.3% in the 2008 season and 29.0% in the 2008-2009 season and 9.9% across the 2012-2014 seasons. CONCLUSIONS: Distinct parasite populations were identified among infected individuals identified through active and passive surveillance, suggesting that infected individuals detected through active surveillance may not have contributed substantially to ongoing transmission. As parasite prevalence and diversity within these individuals declined, resource-intensive efforts to identify the chronically infected reservoir may not be necessary to eliminate malaria in this setting.

Malarial Infection and Curable Sexually Transmitted and Reproductive Tract Infections Among Pregnant Women in a Rural District of Zambia.

Malarial infection and curable sexually transmitted and reproductive tract infections (STIs/RTIs) are important causes of adverse birth outcomes. Reducing the burden of these infections in pregnancy requires interventions that can be easily integrated into the antenatal care (ANC) package. However, efforts to integrate the control of malarial infection and curable STIs/RTIs in pregnancy have been hampered by a lack of evidence related to their coinfection. Thus, we investigated the prevalence of coinfection among pregnant women of rural Zambia. A prospective cohort study was conducted in Nchelenge District, Zambia, involving 1,086 first ANC attendees. We screened participants for peripheral malarial infection and curable STIs/RTIs (syphilis, Chlamydia, gonorrhea, trichomoniasis, and bacterial vaginosis), and collected relevant sociodemographic data at booking. Factors associated with malarial and STI/RTI coinfection were explored using univariate and multivariate regression models. Among participants with complete results (N = 1,071), 38.7% (95% confidence interval [CI] = 35.7-41.6) were coinfected with malaria parasites and at least one STI/RTI; 18.9% (95% CI = 16.5-21.2) were infected with malaria parasites only; 26.0% (95% CI = 23.5-28.8) were infected with at least one STI/RTI but no malaria parasites, and 16.4% (95% CI = 14.1-18.6) had no infection. Human immunodeficiency virus (HIV)-infected women had a higher risk of being coinfected than HIV-uninfected women (odds ratio [OR] = 3.59 [95% CI = 1.73-7.48], P < 0.001). The prevalence of malarial and STI/RTI coinfection was high in this population. An integrated approach to control malarial infection and STIs/RTIs is needed to reduce this dual burden in pregnancy.

Pilot testing of dipsticks as point-of-care assays for rapid diagnosis of poor-quality artemisinin drugs in endemic settings.

BACKGROUND: Good-quality artemisinin drugs are essential for malaria treatment, but increasing prevalence of poor-quality artemisinin drugs in many endemic countries hinders effective management of malaria cases. METHODS: To develop a point-of-care assay for rapid identification of counterfeit and substandard artemisinin drugs for resource-limited areas, we used specific monoclonal antibodies against artesunate and artemether, and developed prototypes of lateral flow dipstick assays. In this pilot test, we evaluated the feasibility of these dipsticks under different endemic settings and their performance in the hands of untrained personnel. RESULTS: The results showed that the dipstick tests can be successfully performed by different investigators with the included instruction sheet. None of the artemether and artesunate drugs collected from public pharmacies in different endemic countries failed the test. CONCLUSION: It is possible that the simple dipstick assays, with future optimization of test conditions and sensitivity, can be used as a qualitative and semi-quantitative assay for rapid screening of counterfeit artemisinin drugs in endemic settings.

Individual- and Household-Level Risk Factors Associated with Malaria in Mutasa District, Zimbabwe: A Serial Cross-Sectional Study.

Malaria constitutes a major public health problem in Zimbabwe, particularly in the north and east bordering Zambia and Mozambique. In Manicaland Province in eastern Zimbabwe, malaria transmission is seasonal and unstable. Over the past decade, Manicaland Province has reported increased malaria transmission due to limited funding, drug resistance and insecticide resistance. The aim of this study was to identify risk factors at the individual and household levels to better understand the epidemiology of malaria and guide malaria control strategies in eastern Zimbabwe. Between October 2012 and September 2014, individual demographic data and household characteristics were collected from cross-sectional surveys of 1,116 individuals residing in 316 households in Mutasa District, one of the worst affected districts. Factors associated with malaria, measured by rapid diagnostic test (RDT), were identified through multilevel logistic regression models. A total of 74 participants were RDT positive. Sleeping under a bed net had a protective effect against malaria despite pyrethroid resistance in the mosquito vector. Multivariate analysis showed that malaria risk was higher among individuals younger than 25 years, residing in households located at a lower household density and in closer proximity to the Mozambique border. The risk factors identified need to be considered in targeting malaria control interventions to reduce host-vector interactions.

High-Resolution Plasmodium falciparum Malaria Risk Mapping in Mutasa District, Zimbabwe: Implications for Regaining Control.

In Zimbabwe, more than half of malaria cases are concentrated in Manicaland Province, where seasonal malaria epidemics occur despite intensified control strategies. The objectives of this study were to develop a prediction model based on environmental risk factors and obtain seasonal malaria risk maps for Mutasa District, one of the worst affected districts in Manicaland Province. From October 2012 to September 2015, 483 households were surveyed, and 104 individuals residing within 69 households had positive rapid diagnostic test results. Logistic regression was used to model the probability of household positivity as a function of the environmental covariates extracted from high-resolution remote sensing data sources. Model predictions and prediction standard errors were generated for the rainy and dry seasons. The resulting maps predicted elevated risk during the rainy season, particularly in low-lying areas bordering Mozambique. In contrast, the risk of malaria was low across the study area during the dry season with foci of malaria risk scattered along the northern and western peripheries of the study area. These findings underscore the need for strong cross-border malaria control initiatives to complement country-specific interventions.