Davis R. Mumbengegwi

Spatial clustering of patent and sub-patent malaria infections in northern Namibia: Implications for surveillance and response strategies for elimination.

Background Reactive case detection (RACD) around passively detected malaria cases is a strategy to identify and treat hotspots of malaria transmission. This study investigated the unproven assumption on which this approach is based, that in low transmission settings, infections cluster over small scales. Methods A prospective case-control study was conducted between January 2013 and August 2014 in Ohangwena and Omusati regions in north central Namibia. Patients attending health facilities who tested positive by malaria rapid diagnostic test (RDT) (index cases) were traced back to their home. All occupants of index case households (n = 116 households) and surrounding households (n = 225) were screened for Plasmodium infection with a rapid diagnostic test (RDT) and loop mediated isothermal amplification (LAMP) and interviewed to identify risk factors. A comparison group of 286 randomly-selected control households was also screened, to compare infection levels of RACD and non-RACD households and their neighbours. Logistic regression was used to investigate spatial clustering of patent and sub-patent infections around index cases and to identify potential risk factors that would inform screening approaches and identify risk groups. Estimates of the impact of RACD on onward transmission to mosquitoes was made using previously published figures of infection rates. Results Prevalence of Plasmodium falciparum infection by LAMP was 3.4%, 1.4% and 0.4% in index-case households, neighbors of index case households and control households respectively; adjusted odds ratio 6.1 [95%CI 1.9–19.5] comparing case households versus control households. Using data from Engela, neighbors of cases had higher odds of infection [adjusted OR 5.0 95%CI 1.3–18.9] compared to control households. All infections identified by RDTs were afebrile and RDTs identified only a small proportion of infections in case (n = 7; 17%) and control (0%) neighborhoods. Based on published estimates of patent and sub-patent infectiousness, these results suggest that infections missed by RDTs during RACD would allow 50–71% of infections to mosquitoes to occur in this setting. Conclusion Malaria infections cluster around passively detected cases. The majority of infections are asymptomatic and of densities below the limit of detection of current RDTs. RACD using standard RDTs are unlikely to detect enough malaria infections to dramatically reduce transmission. In low transmission settings such as Namibia more sensitive field diagnostics or forms of focal presumptive treatment should be tested as strategies to reduce malaria transmission.

Evolution of data collection methods for indigenous knowledge systems at the Multidisciplinary Research Centre of the University of Namibia

This paper describes the evolution of indigenous knowledge systems documentation at the Multidisciplinary Research Centre, University of Namibia. As awareness of the value of indigenous knowledge systems has increased it has become apparent that it is threatened with extinction and there is a need to document it. Documentation of indigenous knowledge systems is important to preserve indigenous knowledge so it continues to provide local solutions or alternatives to Western knowhow and instill pride in rural communities about their indigenous knowledge systems. There is no clearly defined approach to document indigenous knowledge systems accurately and in its entirety; such a process has to develop, evolve and improve over time. Documentation at the Multidisciplinary Research Centre at the University of Namibia has gone through several phases of refinement with lessons being learnt and efforts being made to improve the process of documentation to capture indigenous knowledge as accurately as possible. The aim of this paper is present development of the indigenous knowledge systems research at the Multidisciplinary Research Centre from the documentation of general indigenous knowledge systems practices; to data collection methods for indigenous knowledge systems baseline studies on the traditional use of medicinal plants, livestock movement, traditional food and beverages and validation of medicinal plants used to treat malaria.

Evaluation of loop-mediated isothermal amplification as a surveillance tool for malaria in reactive case detection moving towards elimination

BackgroundAs malaria transmission decreases, the proportion of infections that are asymptomatic at any given time increases. This poses a challenge for diagnosis as routinely used rapid diagnostic tests (RDTs) miss asymptomatic malaria cases with low parasite densities due to poor sensitivity. Yet, asymptomatic infections can contribute to onward transmission of malaria and therefore act as infectious reservoirs and perpetuate malaria transmission. This study compared the performance of RDTs to loop-mediated isothermal amplification (LAMP) in the diagnosis of malaria during reactive active case detection surveillance.MethodsAll reported malaria cases in the Engela Health District of Namibia were traced back to their place of residence and persons living within the four closest neighbouring houses to the index case (neighbourhood) were tested for malaria infection with RDTs and dried blood spots (DBS) were collected. LAMP and nested PCR (nPCR) were carried out on all RDTs and DBS. The same procedure was followed in randomly selected control neighbourhoods.ResultsSome 3151 individuals were tested by RDT, LAMP and nPCR. Sensitivity of RDTs and LAMP were 9.30 and 95.50%, respectively, and specificities were 99.27 and 99.92%, respectively, compared to nPCR. LAMP carried out on collected RDTs showed a sensitivity and specificity of 95.35 and 99.85% compared to nPCR carried out on DBS. There were 2 RDT samples that were negative by LAMP but the corresponding DBS samples were positive by PCR.ConclusionThe study showed that LAMP had the equivalent performance as nPCR for the identification of Plasmodium falciparum infection. Given its relative simplicity to implement over more complex and time-consuming methods, such as PCR, LAMP is particularly useful in elimination settings where high sensitivity and ease of operation are important.

FLASH: A next-generation CRISPR diagnostic for multiplexed detection of antimicrobial resistance sequences

The growing prevalence of deadly microbes with resistance to previously life-saving drug therapies is a dire threat to human health. Detection of low abundance pathogen sequences remains a challenge for metagenomic Next Generation Sequencing (NGS). We introduce FLASH (Finding Low Abundance Sequences by Hybridization), a next-generation CRISPR/Cas9 diagnostic method that takes advantage of the efficiency, specificity and flexibility of Cas9 to enrich for a programmed set of sequences. FLASH-NGS achieves up to 5 orders of magnitude of enrichment and sub-attomolar gene detection with minimal background. We provide an open-source software tool (FLASHit) for guide RNA design. Here we applied it to detection of antimicrobial resistance genes in respiratory fluid and dried blood spots, but FLASH-NGS is applicable to all areas that rely on multiplex PCR.

Is there a correlation between malaria incidence and IRS coverage in western Zambezi region, Namibia?

Setting: A comparison of routine Namibia National Malaria Programme data (reported) vs. household survey data (administrative) on indoor residual spraying (IRS) in western Zambezi region, Namibia, for the 2014-2015 malaria season. Objectives: To determine 1) IRS coverage (administrative and reported), 2) its effect on malaria incidence, and 3) reasons for non-uptake of IRS in western Zambezi region, Namibia, for the 2014-2015 malaria season. Design: This was a descriptive study. Results: IRS coverage in western Zambezi region was low, ranging from 42.3% to 52.2% for administrative coverage vs. 45.9-66.7% for reported coverage. There was no significant correlation between IRS coverage and malaria incidence for this region (r = -0.45, P = 0.22). The main reasons for households not being sprayed were that residents were not at home during spraying times or that spray operators did not visit the households. Conclusions: IRS coverage in western Zambezi region, Namibia, was low during the 2014-2015 malaria season because of poor community engagement and awareness of times for spray operations within communities. Higher IRS coverage could be achieved through improved community engagement. Better targeting of the highest risk areas by the use of malaria surveillance will be required to mitigate malaria transmission.

Study protocol for a cluster randomised controlled factorial design trial to assess the effectiveness and feasibility of reactive focal mass drug administration and vector control to reduce malaria transmission in the low endemic setting of Namibia

Introduction To interrupt malaria transmission, strategies must target the parasite reservoir in both humans and mosquitos. Testing of community members linked to an index case, termed reactive case detection (RACD), is commonly implemented in low transmission areas, though its impact may be limited by the sensitivity of current diagnostics. Indoor residual spraying (IRS) before malaria season is a cornerstone of vector control efforts. Despite their implementation in Namibia, a country approaching elimination, these methods have been met with recent plateaus in transmission reduction. This study evaluates the effectiveness and feasibility of two new targeted strategies, reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in Namibia. Methods and analysis This is an open-label cluster randomised controlled trial with 2×2 factorial design. The interventions include: rfMDA (presumptive treatment with artemether-lumefantrine (AL)) versus RACD (rapid diagnostic testing and treatment using AL) and RAVC (IRS with Acellic 300CS) versus no RAVC. Factorial design also enables comparison of the combined rfMDA+RAVC intervention to RACD. Participants living in 56 enumeration areas will be randomised to one of four arms: rfMDA, rfMDA+RAVC, RACD or RACD+RAVC. These interventions, triggered by index cases detected at health facilities, will be targeted to individuals residing within 500 m of an index. The primary outcome is cumulative incidence of locally acquired malaria detected at health facilities over 1 year. Secondary outcomes include seroprevalence, infection prevalence, intervention coverage, safety, acceptability, adherence, cost and cost-effectiveness. Ethics and dissemination Findings will be reported on clinicaltrials.gov, in peer-reviewed publications and through stakeholder meetings with MoHSS and community leaders in Namibia. Trial registration number NCT02610400; Pre-results.