Malaria infection prevalence and sensitivity of reactive case detection in Zanzibar

Abstract Background Molecular detection of low-density Plasmodium falciparum infections is essential for surveillance studies conducted to inform malaria control strategies in close-to-elimination settings. Molecular monitoring of residual malaria infections usually requires a large study size, therefore sampling and diagnostic processes need to be economical and optimized for high-throughput. A method comparison was undertaken to identify the most efficient diagnostic procedure for processing large collections of community samples with optimal test sensitivity, simplicity, and minimal costs. Methods In a reactive case detection study conducted on Zanzibar, parasitaemia of 4590 individuals of all ages was investigated by a highly sensitive quantitative (q) PCR that targets multiple var gene copies per parasite genome. To reduce cost, a first round of positivity screening was performed on pools of dried blood spots from five individuals. Ten cycles of a pre-PCR were performed directly on the filter paper punches, followed by qPCR. In a second round, samples of positive pools were individually analysed by pre-PCR and qPCR. Results Prevalence in household members and neighbors of index cases was 1.7% (78/4590) with a geometric mean parasite density of 58 parasites/µl blood. Using qPCR as gold standard, diagnostic sensitivity of rapid diagnostic tests (RDTs) was 37% (29/78). Infections positive by qPCR but negative by RDT had mean densities of 15 parasites/µl blood. Conclusion The approach of pre-screening reactive case detection samples in pools of five was ideal for a low prevalence setting such as in Zanzibar. Performing direct PCR on filter paper punches saves substantial time and justifies the higher cost for a polymerase suitable for amplifying DNA directly from whole blood. Molecular monitoring in community samples provided a more accurate picture of infection prevalence, as it identified a potential reservoir of infection that was largely missed by RDT. The developed qPCR-based methodology for screening large sample sets represents primarily a research tool that should inform the design of malaria elimination strategies. It may also prove beneficial for diagnostic tasks in surveillance-response activities.

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

10.21203/rs.3.rs-936591/v1 ◽

2021 ◽

Author(s):

Humphrey Raphael Mkali ◽

Erik J. Reaves ◽

Shabbir M. Lalji ◽

Abdul-wahid Al-mafazy ◽

Joseph J. Joseph ◽

...

Keyword(s):

Risk Factors ◽

Malaria Infection ◽

Universal Access ◽

Indoor Residual Spraying ◽

P Value ◽

Case Detection ◽

Reactive Case Detection ◽

Factors Associated ◽

Llin Use ◽

History Of

Abstract 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.

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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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Molecular methods for tracking residual P. falciparum transmission in a close-to-elimination setting in Zanzibar

10.21203/rs.2.17710/v1 ◽

2019 ◽

Author(s):

Benjamin Grossenbacher ◽

Aurel Holzschuh ◽

Natalie Hofmann ◽

Kali Abdullah Omar ◽

Logan Stuck ◽

...

Keyword(s):

Filter Paper ◽

Geometric Mean ◽

Method Comparison ◽

Dried Blood Spots ◽

Infection Prevalence ◽

Case Detection ◽

Molecular Monitoring ◽

Reactive Case Detection ◽

Direct Pcr ◽

Optimal Test

Abstract Background Molecular detection of low-density Plasmodium falciparum infections is essential for surveillance studies conducted to inform malaria control strategies in close-to-elimination settings. Molecular monitoring of residual malaria infections usually requires a large study size, therefore sampling and diagnostic processes need to be economical and optimized for high-throughput. In a method comparison, we aimed at identifying the most efficient diagnostic procedure for processing large collections of community samples with optimal test sensitivity, simplicity, and minimal costs.Methods In a reactive case detection study conducted on Zanzibar, parasitemia of 4590 individuals of all ages was investigated by a highly sensitive quantitative (q) PCR that targets multiple var gene copies per parasite genome. To reduce cost, a first round of positivity screening was performed on pools of dried blood spots from five individuals. Ten cycles of a pre-PCR were performed directly on the filter paper punches, followed by qPCR. In a second round, samples of positive pools were individually analyzed by pre-PCR and qPCR.Results Prevalence in household members and neighbors of index cases was 1.7% (78/4590) with a geometric mean parasite density of 58 parasites/µl blood. Using qPCR as gold standard, diagnostic sensitivity of rapid diagnostic tests (RDTs) was 37% (29/78). Infections positive by qPCR but negative by RDT had mean densities of 15 parasites/µl blood. Conclusion The approach of pre-screening reactive case detection samples in pools of five was ideal for a low prevalence setting such as in Zanzibar. Performing direct PCR on filter paper punches saves substantial time and justifies the higher cost for a polymerase suitable for amplifying DNA directly from whole blood. Molecular monitoring in community samples provided a more accurate picture of infection prevalence compared to RDT results alone, by identifying a reservoir of infection which is largely missed by RDT. qPCR as a research and surveillance tool can great benefits the evaluation of strategies or programs to eliminate malaria.

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Accuracy of Fever and Fraction of Fevers Attributable to Malaria among Under-fives under Reduced Malaria Infection Prevalence in District

Malaria Chemotherapy Control and Elimination ◽

10.4172/2090-2778.1000121 ◽

2014 ◽

Vol 03 (01) ◽

Author(s):

Donath S Tarimo

Keyword(s):

Malaria Infection ◽

Infection Prevalence

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Case investigation and reactive case detection for malaria elimination in northern Senegal

Malaria Journal ◽

10.1186/1475-2875-12-331 ◽

2013 ◽

Vol 12 (1) ◽

Cited By ~ 46

Author(s):

Megan Littrell ◽

Gnagna Dieng Sow ◽

Algaye Ngom ◽

Mady Ba ◽

Balla Mbacke Mboup ◽

...

Keyword(s):

Malaria Elimination ◽

Case Detection ◽

Reactive Case Detection ◽

Case Investigation

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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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