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[Preprint]. 2023 Sep 10:2023.09.06.23295089.
doi: 10.1101/2023.09.06.23295089.

Micro-heterogeneity of transmission shapes the submicroscopic malaria reservoir in coastal Tanzania

Tyler Rapp  1 , Kano Amagai  2 , Cyrus Sinai  3 , Christopher Basham  1 , Mwajabu Loya  4 , Sifa Ngasala  4 , Hamza Said  4 , Meredith S Muller  1 , Srijana B Chhetri  1 , Guozheng Yang  1 , Ruthly François  2 , Melic Odas  4 , Derrick Mathias  5 , Jonathan J Juliano  1 , Feng-Chang Lin  3 , Billy Ngasala  4 , Jessica T Lin  1
Affiliations

Micro-heterogeneity of transmission shapes the submicroscopic malaria reservoir in coastal Tanzania

Tyler Rapp et al. medRxiv. .

Update in

Abstract

Background: Asymptomatic malaria may be patent (visible by microscopy) and detectable by rapid malaria diagnostic tests (RDTs), or it may be submicroscopic and only detectable by polymerase chain reaction (PCR).

Methods: To characterize the submicroscopic reservoir in an area of declining malaria transmission, asymptomatic persons >5 years of age in Bagamoyo District, Tanzania, were screened using RDT, microscopy, and PCR. We investigated the size of the submicroscopic reservoir across villages, determined factors associated with submicroscopic parasitemia, and assessed the natural history of submicroscopic malaria over four weeks.

Results: Among 6,076 participants, Plasmodium falciparum prevalence by RDT, microscopy, and PCR was 9%, 9%, and 28%, respectively, with roughly two-thirds of PCR-positive individuals harboring submicroscopic infection. Adult status, female gender, dry season months, screened windows, and bednet use were associated with submicroscopic carriage. Among 15 villages encompassing 80% of participants, the proportion of submicroscopic carriers increased with decreasing village-level malaria prevalence. Over four weeks, 23% (61/266) of submicroscopic carriers became RDT-positive and were treated, with half exhibiting symptoms. This occurred more frequently in villages with higher malaria prevalence.

Conclusions: Micro-heterogeneity in transmission impacts the size of the submicroscopic reservoir and the likelihood of submicroscopic carriers developing patent malaria in coastal Tanzania.

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Figures

Figure 1.
Figure 1.. RDT-positive and submicroscopic malaria prevalence in relation to rainfall and age in Bagamoyo, Tanzania.
Data are derived from screening 6,076 asymptomatic persons aged 6 and above between 2018–2021 using rapid diagnostic tests and 18S rRNA real-time PCR. Sampling was discontinuous. Dry season months based on lower rainfall (<33 mm) are indicated in gray in panel A. The distribution of parasite densities as determined by PCR in wet and dry season months is depicted in panel B. The proportion of participants who who tested positive by RDT vs PCR only for each age category is depicted in panel C.
Figure 2.
Figure 2.. Village-level characterization of the submicroscopic reservoir in rural Bagamoyo district.
A map of Bagamoyo district in eastern Tanzania depicts the size of the submicroscopic reservoir among 15 villages and the locations of the two clinics and two schools where study participants were recruited. The submicroscopic malaria ratio is the ratio of PCR+/RDT− cases to all PCR+ cases in the village. Zemba village is not included in the map, but is located nearby Mwavi proper village based on the Tanzania Regional Postcode list.
Figure 3.
Figure 3.. Village-level characterization of malaria prevalence and the size of the submicroscopic malaria.
Each data point represents a village, with size corresponding to the number participants reporting residence in that village. Microscopic malaria prevalence from the sampled villages correlated with PCR malaria prevalence (A). The size of the submicroscopic reservoir for each village, indicated by the submicroscopic ratio (PCR+ only cases/total PCR+ cases), increases with decreasing malaria prevalence (B).
Figure 4.
Figure 4.. The natural history of submicroscopic parasite carriers over 4 weeks follow-up.
The flow diagram depicts the parasite status (based on RDT and PCR) of those who screened positive for submicroscopic malaria (PCR+/RDT−), then followed without treatment and assessed 2 and 4 weeks later. Those who developed RDT+ malaria were treated and discharged. In total, of those enrolled and followed to week 4 (n=219) or became RDT+ before then (n=47) (total n=266), 23% of submicroscopic carriers developed RDT-positive malaria, 25% continued to have asymptomatic submicroscopic carriage, and the remaining had spontaneous resolution by week 4, though this last group may have continued to harbor low density infection not detected by PCR. LFTU indicates lost to follow-up.
Figure 5.
Figure 5.. Parasitologie outcomes for untreated submicroscopic parasitemia after 2 and 4 weeks of follow-up, stratified by village malaria prevalence.
The proportion of participants with asymptomatic submicroscopic malaria who became RDT-positive (red), continued to have asymptomatic submicroscopic infection (orange), or became PCR-negative (green) is depicted after 2 weeks and 4 weeks of follow-up, with cumulative outcomes depicted in the bottom panel. The minority of participants who developed RDT+ patent malaria were more likely to reside in villages with higher malaria prevalence.
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