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

Abstract 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.

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Adding proactive and reactive case detection into the integrated community case management system to optimise diagnosis and treatment of malaria in a high transmission setting of Cameroon: an observational quality improvement study

BMJ Open ◽

10.1136/bmjopen-2018-026678 ◽

2019 ◽

Vol 9 (6) ◽

pp. e026678 ◽

Cited By ~ 2

Author(s):

Cavin Epie Bekolo ◽

Thomas D’Arcy Williams

Keyword(s):

Quality Improvement ◽

Case Management ◽

Diagnostic Testing ◽

Sub Saharan Africa ◽

Secondary Outcome ◽

Case Detection ◽

Community Case Management ◽

Reactive Case Detection ◽

Integrated Community Case Management ◽

Index Cases

ObjectiveIntegrated community case management (iCCM) of childhood illness is a powerful intervention to reduce mortality. Yet, only 29% and 59% of children with fever in sub-Saharan Africa had access to malaria testing and treatment between 2015 and 2017. We report how iCCM+ based on incorporating active case detection of malaria into iCCM could help improve testing and treatment.DesignA community-led observational quality improvement study.SettingThe rural community of Bare-Bakem in Cameroon.ParticipantsChildren and adults with fever between April and June 2018.InterventionA modified iCCM programme (iCCM+) comprising a proactive screening of febrile children <5 years old for malaria using rapid diagnostic testing to identify index cases and a reactive screening triggered by these index cases to detect secondary cases in the community.Primary and secondary outcome measuresThe proportion of additional malaria cases detected by iCCM+ over iCCM.ResultsWe screened 501 febrile patients of whomPlasmodiuminfection was confirmed in 425 (84.8%) cases. Of these cases, 102 (24.0%) were index cases identified in the community during routine iCCM activity and 36 (8.5%) cases detected passively in health facilities; 38 (8.9%) were index cases identified proactively in schools and 249 (58.6%) were additional cases detected by reactive case detection—computing to a total of 287 (67.5%) additional cases found by iCCM+ over iCCM. The likelihood of finding additional cases increased with increasing family size (adjusted odd ratio (aOR)=1.2, 95% CI: 1.1 to 1.3) and with increasing age (aOR=1.7, 95% CI: 1.5 to 1.9).ConclusionMost symptomatic cases of malaria remain undetected in the community despite the introduction of CCM of malaria. iCCM+ can be adopted to diagnose and treat more of these undiagnosed cases especially when targeted to schools, older children and larger households.

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Reactive Case Detection of Asymptomatic Malaria in Households and Neighbors of Laboratory Confirmed Cases in Raya Kobo District, Northeast Ethiopia

10.21203/rs.2.19723/v1 ◽

2019 ◽

Author(s):

Yimer Melese ◽

megbaru alemu abate ◽

Mulat Yimer ◽

Banchamlak Tegegne

Keyword(s):

Diagnostic Tests ◽

Multivariable Analysis ◽

High Morbidity ◽

Asymptomatic Malaria ◽

Case Detection ◽

Reactive Case Detection ◽

Cross Sectional ◽

Asymptomatic Carriage ◽

Northeast Ethiopia ◽

Asymptomatic Infections

Abstract Background Malaria is the leading vector borne parasitic disease causing enormously high morbidity and mortality worldwide. There have been huge efforts so far to control and eliminate malaria in the world. However, high prevalence of asymptomatic carriage poses a threat on malaria control and elimination programs. Since asymptomatic infections present no overt sign and symptoms, they do not get clinical attention. Moreover, asymptomatic cases are a potential source of infection in high and low transmission settings. Despite the presence of some pocket data, the prevalence of asymptomatic carriage has not yet been known nationally and the current study area as well. Therefore, we aimed to assess the prevalence of asymptomatic malaria cases and associated factors in households and neighbors of laboratory confirmed cases in Raya Kobo district, Northeast Ethiopia. Methods: A community based cross-sectional study was conducted from February to April, 2019 among 270 study participants selected by convenient sampling technique at the community where laboratory confirmed cases were found. A structured questionnaire was used to collect data on socio-demographic characteristics, individual and household level factors. The data were entered in Epi Data 3.1 version and analyzed by using SPSS version 20. Variables with P<0.25 in the bivariable analysis were taken to the multivariable analysis to control potential confounders, and p< 0.05 was considered statistically significant. Results: The overall prevalence of asymptomatic malaria was 7.0%, with 3.0%, 5.2% and 12.0%, respectively by Rapid diagnostic tests (RDT), Microscopy and Polymerase chain reaction (PCR). Majority of the infections (73.7%) were identified from index households. PCR detected asymptomatic infections about 2.7 and 2.3 folds higher than RDT and microscope, respectively. Previous malaria history (AOR: 4.030, 95% CI: 1.021-15.903), living with index cases (AOR: 3.880, 95% CI: 1.275-11.806) and family size > 6 members (AOR: 4.820, 95% CI: 1.260-18.437) were significant predictors of Plasmodium spp infection.Conclusion: Reactive case detection had identified considerably higher asymptomatic malaria cases at the community. Therefore, active case investigation should be established in the community by tracking the symptomatic cases at the health facilities. Diagnostic tests involving the PCR should be implemented in the surveillance of asymptomatic malaria. Active malaria cases should also be treated.

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

Malaria Journal ◽

10.1186/s12936-021-04025-1 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Humphrey R. Mkali ◽

Erik J. Reaves ◽

Shabbir M. Lalji ◽

Abdul-Wahid Al-mafazy ◽

Joseph J. Joseph ◽

...

Keyword(s):

Risk Factors ◽

Malaria Infection ◽

Universal Access ◽

Behavioural Change ◽

P Value ◽

Case Detection ◽

Reactive Case Detection ◽

Factors Associated ◽

Household Members ◽

Index Cases

Abstract 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.

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

10.21203/rs.3.rs-37048/v3 ◽

2020 ◽

Author(s):

Lenny Lia Ekawati ◽

Kelly C. Johnson ◽

Jerry O. Jacobson ◽

Carmen A. Cueto ◽

Iska Zarlinda ◽

...

Keyword(s):

Formative Assessment ◽

Plasmodium Knowlesi ◽

Malaria Prevention ◽

Traditional Healers ◽

Case Detection ◽

Willingness To Participate ◽

Health Seeking ◽

Reactive Case Detection ◽

Malaria Burden ◽

Forest Activities

Abstract 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.

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Active Case Finding for Malaria: A 3-Year National Evaluation of Optimal Approaches to Detect Infections and Hotspots Through Reactive Case Detection in the Low-transmission Setting of Eswatini

Clinical Infectious Diseases ◽

10.1093/cid/ciz403 ◽

2019 ◽

Vol 70 (7) ◽

pp. 1316-1325 ◽

Cited By ~ 7

Author(s):

Michelle S Hsiang ◽

Nyasatu Ntshalintshali ◽

Mi-Suk Kang Dufour ◽

Nomcebo Dlamini ◽

Nomcebo Nhlabathi ◽

...

Keyword(s):

Malaria Elimination ◽

Large Scale ◽

Response Times ◽

Index Case ◽

Diagnostic Testing ◽

Case Detection ◽

Hotspot Detection ◽

Operational Parameters ◽

Reactive Case Detection ◽

Index Cases

Abstract Background Reactive case detection (RACD) is a widely practiced malaria elimination intervention whereby close contacts of index cases receive malaria testing to inform treatment and other interventions. However, the optimal diagnostic and operational approaches for this resource-intensive strategy are not clear. Methods We conducted a 3-year prospective national evaluation of RACD in Eswatini, a malaria elimination setting. Loop-mediated isothermal amplification (LAMP) was compared to traditional rapid diagnostic testing (RDT) for the improved detection of infections and for hotspots (RACD events yielding ≥1 additional infection). The potential for index case–, RACD-, and individual-level factors to improve efficiencies was also evaluated. Results Among 377 RACD events, 10 890 participants residing within 500 m of index cases were tested. Compared to RDT, LAMP provided a 3-fold and 2.3-fold higher yield to detect infections (1.7% vs 0.6%) and hotspots (29.7% vs 12.7%), respectively. Hotspot detection improved with ≥80% target population coverage and response times within 7 days. Proximity to the index case was associated with a dose-dependent increased infection risk (up to 4-fold). Individual-, index case–, and other RACD-level factors were considered but the simple approach of restricting RACD to a 200-m radius maximized yield and efficiency. Conclusions We present the first large-scale national evaluation of optimal RACD approaches from a malaria elimination setting. To inform delivery of antimalarial drugs or other interventions, RACD, when conducted, should utilize more sensitive diagnostics and clear context-specific operational parameters. Future studies of RACD’s impact on transmission may still be needed.

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

Malaria Journal ◽

10.1186/s12936-020-03511-2 ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Lenny L. Ekawati ◽

Kelly C. Johnson ◽

Jerry O. Jacobson ◽

Carmen A. Cueto ◽

Iska Zarlinda ◽

...

Keyword(s):

Formative Assessment ◽

Plasmodium Knowlesi ◽

Malaria Prevention ◽

Traditional Healers ◽

Case Detection ◽

Willingness To Participate ◽

Health Seeking ◽

Reactive Case Detection ◽

Malaria Burden ◽

Forest Activities

Abstract 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.

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Contribution of Asymptomatic Plasmodium Infections to the Transmission of Malaria in Kayin State, Myanmar

The Journal of Infectious Diseases ◽

10.1093/infdis/jiy686 ◽

2018 ◽

Vol 219 (9) ◽

pp. 1499-1509 ◽

Cited By ~ 14

Author(s):

Victor Chaumeau ◽

Ladda Kajeechiwa ◽

Bénédicte Fustec ◽

Jordi Landier ◽

Saw Naw Nyo ◽

...

Keyword(s):

Malaria Transmission ◽

Entomological Inoculation Rate ◽

Fold Increase ◽

Estimating Equation ◽

Malaria Prevalence ◽

Pcr Analysis ◽

Asymptomatic Malaria ◽

Asymptomatic Infections ◽

Greater Mekong Subregion ◽

The Impact

Abstract Background The objective of mass antimalarial drug administration (MDA) is to eliminate malaria rapidly by eliminating the asymptomatic malaria parasite reservoirs and interrupting transmission. In the Greater Mekong Subregion, where artemisinin-resistant Plasmodium falciparum is now widespread, MDA has been proposed as an elimination accelerator, but the contribution of asymptomatic infections to malaria transmission has been questioned. The impact of MDA on entomological indices has not been characterized previously. Methods MDA was conducted in 4 villages in Kayin State (Myanmar). Malaria mosquito vectors were captured 3 months before, during, and 3 months after MDA, and their Plasmodium infections were detected by polymerase chain reaction (PCR) analysis. The relationship between the entomological inoculation rate, the malaria prevalence in humans determined by ultrasensitive PCR, and MDA was characterized by generalized estimating equation regression. Results Asymptomatic P. falciparum and Plasmodium vivax infections were cleared by MDA. The P. vivax entomological inoculation rate was reduced by 12.5-fold (95% confidence interval [CI], 1.6–100-fold), but the reservoir of asymptomatic P. vivax infections was reconstituted within 3 months, presumably because of relapses. This was coincident with a 5.3-fold (95% CI, 4.8–6.0-fold) increase in the vector infection rate. Conclusion Asymptomatic infections are a major source of malaria transmission in Southeast Asia.

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The impact of transfluthrin on the spatial repellency of the primary malaria mosquito vectors in Vietnam: Anopheles dirus and Anopheles minimus

Malaria Journal ◽

10.1186/s12936-019-3092-4 ◽

2020 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Nicholas J. Martin ◽

Vu S. Nam ◽

Andrew A. Lover ◽

Tran V. Phong ◽

Tran C. Tu ◽

...

Keyword(s):

Vector Control ◽

Large Scale ◽

Limit Of Detection ◽

Malaria Vectors ◽

Adult Mosquito ◽

Anopheles Dirus ◽

Anopheles Minimus ◽

Control Programmes ◽

The Impact ◽

Spatial Repellency

Abstract Background The complexity of mosquito-borne diseases poses a major challenge to global health efforts to mitigate their impact on people residing in sub-tropical and tropical regions, to travellers and deployed military personnel. To supplement drug- and vaccine-based disease control programmes, other strategies are urgently needed, including the direct control of disease vectors. Modern vector control research generally focuses on identifying novel active ingredients and/or innovative methods to reduce human-mosquito interactions. These efforts include the evaluation of spatial repellents, which are compounds capable of altering mosquito feeding behaviour without direct contact with the chemical source. Methods This project examined the impact of airborne transfluthrin from impregnated textile materials on two important malaria vectors, Anopheles dirus and Anopheles minimus. Repellency was measured by movement within taxis cages within a semi-field environment at the National Institute of Hygiene and Epidemiology in Hanoi, Vietnam. Knockdown and mortality were measured in adult mosquito bioassay cages. Metered-volume air samples were collected at a sub-set of points in the mosquito exposure trial. Results Significant differences in knockdown/mortality were observed along a gradient from the exposure source with higher rates of knockdown/mortality at 2 m and 4 m when compared with the furthest distance (16 m). Knockdown/mortality was also greater at floor level and 1.5 m when compared to 3 m above the floor. Repellency was not significantly different except when comparing 2 m and 16 m taxis cages. Importantly, the two species reacted differently to transfluthrin, with An. minimus being more susceptible to knockdown and mortality. The measured concentrations of airborne transfluthrin ranged from below the limit of detection to 1.32 ng/L, however there were a limited number of evaluable samples complicating interpretation of these results. Conclusions This study, measuring repellency, knockdown and mortality in two malaria vectors in Vietnam demonstrates that both species are sensitive to airborne transfluthrin. The differences in magnitude of response between the two species requires further study before use in large-scale vector control programmes to delineate how spatial repellency would impact the development of insecticide resistance and the disruption of biting behaviour.

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