Strengthen Village Malaria Reporting to Better Target Reservoirs of Persistent Infections in Southeast Asia

References 1. Sekaggya-Wiltshire C, von Braun A, Lamorde M, et al. Delayed sputum culture conversion in tuberculosis-human immunodeficiency virus-coinfected patients with low isoniazid and rifampicin concentrations. Clin Infect Dis 2018; 67:708–16. 2. Heysell SK, Mtabho C, Mpagama S, et al. Plasma drug activity assay for treatment optimization in tuberculosis patients. Antimicrob Agents Chemother 2011; 55:5819–25. 3. Pasipanodya JG, Gumbo T. Individualizing tuberculosis (TB) treatment: are TB programs in high burden settings ready for prime time therapeutic drug monitoring? Clin Infect Dis 2018; 67:717–8. 4. Peloquin CA. Therapeutic drug monitoring in the treatment of tuberculosis. Drugs 2002; 62:2169–83. 5. Alffenaar JC, Tiberi S, Verbeeck RK, Heysell SK, Grobusch MP. Therapeutic drug monitoring in tuberculosis: practical application for physicians. Clin Infect Dis 2017; 64:104–5. 6. World Health Organization. Rapid communication: key changes to treatment of multidrugand rifampicin-resistant tuberculosis (MDR/RR-TB). Geneva, Switzerland: WHO, 2018. 7. Zentner I, Schlecht HP, Khensouvann L, et al. Urine colorimetry to detect low rifampin exposure during tuberculosis therapy: a proof-of-concept study. BMC Infect Dis 2016; 16:242. 8. van den Elsen SHJ, Oostenbrink LM, Heysell SK, et al. Systematic review of salivary versus blood concentrations of antituberculosis drugs and their potential for salivary therapeutic drug monitoring. Ther Drug Monit 2018; 40:17–37. 9. Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis 2016; 63:e147–95. 10. Alkabab Y, Keller S, Dodge D, Houpt E, Staley D, Heysell S. Early interventions for diabetes related tuberculosis associate with hastened sputum microbiological clearance in Virginia, USA. BMC Infect Dis 2017; 17:125. 11. World Health Organization. Technical report on the pharmacokinetics and pharmacodynamics (PK/PD) of medicines used in the treatment of drug-resistant tuberculosis. 2018. Available at: http://apps.who.int/iris/bitstream/handle/10665/ 260440/WHO-CDS-TB-2018.6-eng.pdf. Accessed 23 August 2018.


Strengthen Village Malaria Reporting to Better Target Reservoirs of Persistent Infections in Southeast Asia
To the Editor-The recent World Health Organization malaria surveillance, monitoring, and evaluation manual highlights the importance that strengthened community health worker (CHW) programs and their ability to report accurate and timely data hold for the elimination of malaria [1]. Mass Drug Administration (MDA) is proposed as a means of interrupting Plasmodium falciparum transmission in areas of emergent, multidrug-resistant parasites [2,3]. The 2017 World Health Organization recommendations on MDA inform control programs how to implement this strategy, but there is no specific advice on how to target suitable populations in Southeast Asia [4,5].
Since 2013, we have conducted population-based surveys to define the micro-epidemiology of asymptomatic malaria infections and have piloted MDA in Southeast Asia [6]. Asymptomatic P. falciparum infections persist, on average, for several months, with varying parasite densities that are periodically capable of transmission [7]. Our experience is that prevalence surveys are an expensive and time-consuming means of identifying foci of transmission in pre-elimination (low-transmission) settings, particularly where highly-sensitive molecular techniques are used to detect asymptomatic infections. Currently, CHWs are active in many more villages than could be practicably included in a baseline prevalence survey, but are well positioned-with strengthening of the reporting system where needed-to routinely collect travel and residency data to determine whether individual locations are sources where transmission occurs or sinks where cases are reported but not acquired.
If of sufficient quality, CHW data could be used to identify locations for targeted MDA, such as village clusters where the P. falciparum incidence is above a locally-defined threshold. High-quality incidence data has been shown to be predictive of asymptomatic carriage rates in low-transmission settings, thus potentially obviating the need to screen populations using more expensive molecular methods to define targets for MDA [8]. Incidence data determined from reliable case reporting could also be the preferred metric to evaluate the impact of MDA. For example, a recent elimination program in Myanmar demonstrated a rapid decline in the incidence of malaria following the implementation of a strong village malaria worker network, demonstrating the effectiveness of conducting an MDA in a transmission hotspot [9].
In Southeast Asia, asymptomatic Plasmodium vivax infections are even more under-detected and undertreated than P. falciparum [10]. In our studies, a history of clinical malaria was a consistently strong risk factor for persistent asymptomatic infection. In a prior survey, we matched participants to treatment records and found that approximately a third of people with a history of clinical P. vivax were parasitaemic [11]. Therefore, local health services already have recorded the names and locations of thousands of people harboring P. vivax infections that contribute to ongoing transmission. These people could be screened for G6PD deficiencies and offered safe treatment with primaquine for radical cures of liver-stage parasites. Targeting persistent P. vivax from treatment records alone would neither catch all carriers nor interrupt transmission, but could treat an important fraction of extant P. vivax infections and represent a move from P. vivax control towards elimination.
As countries progress towards elimination, investments in strengthening and expanding the coverage of CHW programs and case reporting are vital. Making better use of this data could identify persistent infections at both the community and individual levels, allowing for the targeting of elimination strategies that address the asymptomatic reservoir and for new screen-and-treat strategies, which may become viable with the deployment of highly-sensitive rapid diagnostics.

Potential conflicts of interest. All authors:
No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.