Risk factors associated with malaria infection identified through reactive case detection in Zanzibar, 2012–2019

Background Over the past two decades, Zanzibar substantially reduced malaria burden. As malaria decreases, sustainable improvements in control interventions may increasingly depend on accurate knowledge of malaria risk factors to further target interventions. This study aimed to investigate the risk factors associated with malaria infection in Zanzibar. Methods Surveillance data from Zanzibar’s Malaria Case Notification system from August 2012 and December 2019 were analyzed. This system collects data on malaria cases passively detected and reported by all health facilities (index cases), and household-based reactive case detection (RCD) activities linked to those primary cases. All members of households of the index cases were screened for malaria using a malaria rapid diagnostic test (RDT). Individuals with a positive RDT were treated with artemisinin-based combination therapy. Univariate and multivariate logistic regression analyses were done to investigate the association between RDT positivity among the household members and explanatory factors with adjustment for seasonality and clustering at Shehia level. Results A total of 30,647 cases were reported of whom household RCD was completed for 21,443 (63%) index case households and 85,318 household members tested for malaria. The findings show that younger age (p-value for trend [Ptrend] < 0.001), history of fever in the last 2 weeks (odds ratio [OR] = 35.7; 95% CI 32.3–39.5), travel outside Zanzibar in the last 30 days (OR = 2.5; 95% CI 2.3–2.8) and living in Unguja (OR = 1.2; 95% CI 1.0–1.5) were independently associated with increased odds of RDT positivity. In contrast, male gender (OR=0.8; 95% CI 0.7–0.9), sleeping under an LLIN the previous night (OR = 0.9; 95% CI 0.7–0.9), having higher household net access (Ptrend < 0.001), and living in a household that received IRS in the last 12 months (OR = 0.8; 95% CI 0.7–0.9) were independently associated with reduced odds of RDT positivity. A significant effect modification of combining IRS and LLIN was also noted (OR = 0.7; 95% CI 0.6–0.8). Conclusions The findings suggest that vector control remains an important malaria prevention intervention: they underscore the need to maintain universal access to LLINs, the persistent promotion of LLIN use, and application of IRS. Additionally, enhanced behavioural change and preventive strategies targeting children aged 5–14 years and travellers are needed.

Risk Factors Associated with Malaria Infection Identified through Reactive Case Detection in Zanzibar, 2012-2019

BackgroundOver the past two decades, Zanzibar substantially reduced malaria burden. As malaria decreases, sustainable improvements in prevention and control interventions may increasingly depend on accurate knowledge of malaria risk factors to further target interventions. This study aimed to investigate the risk factors associated with malaria infection in Zanzibar. MethodsWe analyzed surveillance data from Zanzibar’s Malaria Case Notification system collected between August 2012 and December 2019. This system collects data from all malaria cases passively detected and reported by public and private health facilities, from household-based follow-up and reactive case detection activities linked to those primary cases. All members of households of the passively detected malaria cases were screened for malaria using a malaria rapid diagnostic test (mRDT); individuals with a positive mRDT result were treated with artemisinin-based combination therapy. Univariate and multivariate logistic regression analyses were done to investigate the association between mRDT positivity among the household members and explanatory factors (i.e., age, sex, history of fever, history of travel, rainfall, long-lasting insecticidal net [LLIN] density, LLIN use, household indoor residual spraying [IRS], and household location) with adjustment for seasonality ResultsThe findings show that younger age (p-value for trend<0.001), history of fever in the last two weeks (odds ratio [OR]=32.0; 95% CI: 29.1-35.3), history of travel outside Zanzibar in the last 30 days (OR=2.3; 95% CI: 2.1-2.6) and living in Unguja (OR=1.2; 95% CI: 1.1-1.3) were independently associated with increased odds of mRDT positivity. In contrast, male sex (OR=0.8; 95% CI: 0.7-0.9), having higher household LLIN density (p-value for trend<0.001), sleeping under an LLIN the previous night (OR=0.8; 95% CI: 0.7-0.9), and living in a household that received IRS in the last 12 months (OR=0.9; 95% CI: 0.8-0.9) were independently associated with reduced odds of mRDT positivity. A significant effect modification of combining IRS and LLIN was also noted (OR=0.7; 95% CI:0.6-0.8).ConclusionsThe findings suggest that vector control remains an important malaria prevention intervention: they underscore the need to maintain universal access to LLINs, the persistent promotion of LLIN use, and application of IRS. Additionally, enhanced behavioral change and preventive strategies targeting children aged 5-14 years and travelers are needed.

Clustering of malaria in households in the Greater Mekong Subregion: operational implications for reactive case detection

Background Malaria reactive case detection is the testing and, if positive, treatment of close contacts of index cases. It is included in national malaria control programmes of countries in the Greater Mekong Subregion to accelerate malaria elimination. Yet the value of reactive case detection in the control and elimination of malaria remains controversial because of the low yield, limited evidence for impact, and high demands on resources. Methods Data from the epidemiological assessments of large mass drug administration (MDA) studies in Myanmar, Vietnam, Cambodia and Laos were analysed to explore malaria infection clustering in households. The proportion of malaria positive cases among contacts screened in a hypothetical reactive case detection programme was then determined. The parasite density thresholds for rapid diagnostic test (RDT) detection was assumed to be > 50/µL (50,000/mL), for dried-blood-spot (DBS) based PCR > 5/µL (5000/mL), and for ultrasensitive PCR (uPCR) with a validated limit of detection at 0.0022/µL (22/mL). Results At baseline, before MDA, 1223 Plasmodium infections were detected by uPCR in 693 households. There was clustering of Plasmodium infections. In 637 households with asymptomatic infections 44% (278/637) had more than one member with Plasmodium infections. In the 132 households with symptomatic infections, 65% (86/132) had more than one member with Plasmodium infections. At baseline 4% of households had more than one Plasmodium falciparum infection, but three months after MDA no household had more than one P. falciparum infected member. Reactive case detection using DBS PCR would have detected ten additional cases in six households, and an RDT screen would have detected five additional cases in three households among the 169 households with at least one RDT positive case. This translates to 19 and 9 additional cases identified per 1000 people screened, respectively. Overall, assuming all febrile RDT positive patients would seek treatment and provoke reactive case detection using RDTs, then 1047 of 1052 (99.5%) Plasmodium infections in these communities would have remained undetected. Conclusion Reactive case detection in the Greater Mekong subregion is predicted to have a negligible impact on the malaria burden, but it has substantial costs in terms of human and financial resources.

Epidemiology of Plasmodium falciparum Infections in a Semi-Arid Rural African Setting: Evidence of Reactive Case Detection in Northwestern Kenya

In northwestern Kenya, Turkana County has been historically considered unsuitable for stable malaria transmission because of its unfavorable climate and predominantly semi-nomadic population; consequently, it is overlooked during malaria control planning. However, the area is changing, with substantial development, an upsurge in travel associated with resource extraction, and more populated settlements forming. Recently, numerous malaria outbreaks have highlighted the need to characterize malaria transmission and its associated risk factors in the region to inform control strategies. Reactive case detection of confirmed malaria cases at six health facilities across central Turkana was conducted from 2018 to 2019. Infections in household members of index cases were detected by malaria rapid diagnostic tests (RDTs) and PCR tests, and they were grouped according household and individual characteristics. The relationships between putative risk factors and infection were quantified by multilevel logistic regression models. Of the 3,189 household members analyzed, 33.6% had positive RDT results and/or PCR test results. RDT-detected infections were more prevalent in children; however, PCR-detected infections were similarly prevalent across age groups. Recent travel was rarely reported and not significantly associated with infection. Bed net coverage was low and net crowding was associated with increased risks of household infections. Infections were present year-round, and fluctuations in prevalence were not associated with rainfall. These findings indicate year-round, endemic transmission with moderate population immunity. This is in stark contrast to recent estimates in this area. Therefore, further investigations to design effective intervention approaches to address malaria in this rapidly changing region and other similar settings across the Horn of Africa are warranted.

What is the yield of malaria reactive case detection in the Greater Mekong Sub-region? A review of published data and meta-analysis

Background Reactive malaria case detection involves the screening of those in contact with index cases and is used in countries in the Greater Mekong Sub-region. The yield of reactive case detection, defined here as the percentage of positive malaria cases among potential contacts who were screened, was assessed. Methods A literature search was conducted on PubMed to identify studies on reactive case detection in the Greater Mekong Sub-region. Eligible published articles were reviewed and pooled estimates from the studies were calculated, by type of malaria test used. Results Eighty-five publications were retrieved, of which 8 (9.4%) eligible articles were included in the analysis. The yield from reactive case detection ranged from 0.1 to 4.2%, with higher rates from PCR testing compared with microscopy and/or rapid diagnostic test. The overall yield from microscopy and/or rapid diagnostic test was 0.56% (95% CI 0.31–0.88%), while that from PCR was 2.35% (95% CI 1.19–3.87%). The two studies comparing different target groups showed higher yield from co-workers/co-travellers, compared with household contacts. Conclusion In low malaria transmission settings, the effectiveness of reactive case detection is diminishing. In the Greater Mekong Sub-region, modifying reactive case detection from household contacts to co-workers/co-travellers and from testing to presumptive treatment of targeted contacts, could increase the impact of this approach.

Defining malaria risks among forest workers in Aceh, Indonesia: a formative assessment

Background Following a dramatic decline of malaria cases in Aceh province, geographically-based reactive case detection (RACD) was recently evaluated as a tool to improve surveillance with the goal of malaria elimination. While RACD detected few cases in households surrounding index cases, engaging in forest work was identified as a risk factor for malaria and infections from Plasmodium knowlesi—a non-human primate malaria parasite—were more common than expected. This qualitative formative assessment was conducted to improve understanding of malaria risk from forest work and identify strategies for targeted surveillance among forest workers, including adapting reactive case detection. Methods Between June and August, 2016, five focus groups and 18 in-depth interviews with forest workers and key informants were conducted in each of four subdistricts in Aceh Besar and Aceh Jaya districts. Themes included: types of forest activities, mobility of workers, interactions with non-human primates, malaria prevention and treatment-seeking behaviours, and willingness to participate in malaria surveys at forest work sites and using peer-referral. Results Reported forest activities included mining, logging, and agriculture in the deep forest and along the forest fringe. Forest workers, particularly miners and loggers, described often spending weeks to months at work sites in makeshift housing, rarely utilizing mosquito prevention and, upon fever, self-medicating and seeking care from traditional healers or pharmacies rather than health facilities. Non-human primates are frequently observed near work sites, and most forest work locations are within a day’s journey of health clinics. Employers and workers expressed interest in undertaking malaria testing and in participating in survey recruitment by peer-referral and at work sites. Conclusions Diverse groups of forest workers in Aceh are potentially exposed to malaria through forest work. Passive surveillance and household-based screening may under-estimate malaria burden due to extended stays in the forest and health-seeking behaviours. Adapting active surveillance to specifically target forest workers through work-site screening and/or peer-referral appears promising for addressing currently undetected infections.

Defining malaria risks among forest workers in Aceh, Indonesia: a formative assessment

Background Following a dramatic decline of malaria cases in Aceh province, geographically-based reactive case detection (RACD) was recently evaluated as a tool to improve surveillance with the goal of malaria elimination. While RACD detected few cases in households surrounding index cases, engaging in forest work was identified as a risk factor for malaria and infections from Plasmodium knowlesi—a non-human primate malaria parasite—were more common than expected. This qualitative formative assessment was conducted to improve understanding of malaria risk from forest work and identify strategies for targeted surveillance among forest workers, including adapting reactive case detection. Methods Between June and August, 2016, five focus groups and 18 in-depth interviews with forest workers and key informants were conducted in each of four subdistricts in Aceh Besar and Aceh Jaya districts. Themes included: types of forest activities, mobility of workers, interactions with non-human primates, malaria prevention and treatment-seeking behaviours, and willingness to participate in malaria surveys at forest work sites and using peer-referral. Results Reported forest activities included mining, logging, and agriculture in the deep forest and along the forest fringe. Forest workers, particularly miners and loggers, described often spending weeks to months at work sites in makeshift housing, rarely utilizing mosquito prevention and, upon fever, self-medicating and seeking care from traditional healers or pharmacies rather than health facilities. Non-human primates are frequently observed near work sites, and most forest work locations are within a day’s journey of health clinics. Employers and workers expressed interest in undertaking malaria testing and in participating in survey recruitment by peer-referral and at work sites. Conclusions Diverse groups of forest workers in Aceh are potentially exposed to malaria through forest work. Passive surveillance and household-based screening may under-estimate malaria burden due to extended stays in the forest and health-seeking behaviours. Adapting active surveillance to specifically target forest workers through work-site screening and/or peer-referral appears promising for addressing currently undetected infections.

Spatial and genetic clustering of Plasmodium falciparum and Plasmodium vivax infections in a low-transmission area of Ethiopia

The distribution of malaria infections is heterogeneous in space and time, especially in low transmission settings. Understanding this clustering may allow identification and targeting of pockets of transmission. In Adama district, Ethiopia, Plasmodium falciparum and P. vivax malaria patients and controls were examined, together with household members and immediate neighbors. Rapid diagnostic test and quantitative PCR (qPCR) were used for the detection of infections that were genetically characterized by a panel of microsatellite loci for P. falciparum (26) and P. vivax (11), respectively. Individuals living in households of clinical P. falciparum patients were more likely to have qPCR detected P. falciparum infections (22.0%, 9/41) compared to individuals in control households (8.7%, 37/426; odds ratio, 2.9; 95% confidence interval, 1.3–6.4; P = .007). Genetically related P. falciparum, but not P. vivax infections showed strong clustering within households. Genotyping revealed a marked temporal cluster of P. falciparum infections, almost exclusively comprised of clinical cases. These findings uncover previously unappreciated transmission dynamics and support a rational approach to reactive case detection strategies for P. falciparum in Ethiopia.

Reactive Case Detection (RACD) and foci investigation strategies in malaria control and elimination: a review

Background Reactive case detection (RACD) and foci investigation are key strategies in malaria elimination and prevention of its re-establishment. They are a key part of surveillance that has been recommended by the World Health Organization (WHO) to be considered as a core intervention and as one of the three pillars of the Global Technical Strategy for Malaria 2016–2030. Methods A search using the key words “Reactive Case Detection”, “RACD”, “RCD” and “Malaria” was carried out in PubMed, Scopus, Taylor and Francis online databases for studies published until 31st July 2019. The inclusion criteria for selection of articles for review included (1) how RACD is implemented in each country; (2) challenges faced in RACD implementation; (3) suggestions on how the effectiveness of RACD process can be improved. Results 411 titles were identified, 41 full text articles were screened and 29 were found eligible for inclusion in the review. Published literature on RACD, and case and foci investigations has mostly assessed the process of the activity. Most studies have documented that the yield of positives in RACD has been highest in the index case’s household and the immediate neighbourhood of the index case. Microscopy and RDTs are the common tests used in RACD. The guidelines for case and foci investigation, and RACD and PACD, are not universally adopted and are country-specific. Some of the limitations and challenges identified include lack of proper guidelines, logistic issues and problems with public compliance. Conclusions Although there is no documented evidence that RACD is useful in malaria elimination settings, most authors have opined that RACD is necessary for malaria elimination. Lack of knowledge in the target populations, a target radius and how to carry out the RACD process is a major challenge in the decision-making process.

Defining malaria risks among forest workers in Aceh, Indonesia: A formative assessment

Background. Following a dramatic decline of malaria cases in Aceh province, geographically-based reactive case detection (RACD) was recently evaluated as a tool to improve surveillance with the goal of malaria elimination. While RACD detected few cases in households surrounding index cases, engaging in forest work was identified as a risk factor for malaria and infections from Plasmodium knowlesi—a non-human primate malaria parasite—were more common than expected. This qualitative formative assessment was conducted to improve understanding of malaria risk from forest work and identify strategies for targeted surveillance among forest workers, including adapting reactive case detection.Methods. Between June and August, 2016, five focus groups and 18 in-depth interviews with forest workers and key informants were conducted in each of four subdistricts in Aceh Besar and Aceh Jaya districts. Themes included: types of forest activities, mobility of workers, interactions with non-human primates, malaria prevention and treatment-seeking behaviors, and willingness to participate in malaria surveys at forest work sites and using peer-referral.Results. Reported forest activities included mining, logging, and agriculture in the deep forest and along the forest fringe. Forest workers, particularly miners and loggers, described often spending weeks to months at work sites in makeshift housing, rarely utilizing mosquito prevention and, upon fever, self-medicating and seeking care from traditional healers or pharmacies rather than health facilities. Non-human primates are frequently observed near work sites, and most forest work locations are within a day’s journey of health clinics. Employers and workers expressed interest in undertaking malaria testing and in participating in survey recruitment by peer-referral and at work sites.Conclusions. Diverse groups of forest workers in Aceh are potentially exposed to malaria through forest work. Passive surveillance and household-based screening may under-estimate malaria burden due to extended stays in the forest and health-seeking behaviors. Adapting active surveillance to specifically target forest workers through work-site screening and/or peer-referral appears promising for addressing currently undetected infections.