Estimating the hidden magnitude of the malaria community burden
Authors: Tsige Ketema, Quique Bassat
Journal: The Lancet Infectious Diseases (2020)

The second push for global malaria eradication, launched more than a decade ago,1Tanner M de Savigny D Malaria eradication back on the table.Bull World Health Organ. 2008; 86: 82Crossref PubMed Scopus (95) Google Scholar has motivated a renewed interest in the understanding of malaria transmission, and in the strategies required to interrupt it. In this respect, in order to eliminate malaria from a given geographical area, rapid detection and treatment of the clinical cases is rarely sufficient. In settings where transmission intensity is sufficiently high, populations exposed to continuous infective mosquito bites progressively develop a tolerance to malaria infections during the first few years of their life. This tolerance protects them against malaria disease, but not necessarily against the infection itself. This situation results in a varying frequency of asymptomatic carriage of malaria parasites. Indeed, the higher the transmission intensity, the earlier the acquisition of immunity and the larger the population capable of carrying malaria parasites in their blood without necessarily expressing clinical symptoms. To paraphrase the “iceberg” metaphor, some authors have described that the true burden of malaria infections lies “hidden beneath the surface”, and that clinical cases would only represent the so-called “ears of the hippopotamus”2Breman JG The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden.Am J Trop Med Hyg. 2001; 64: 1-11Crossref PubMed Scopus (678) Google Scholar of the total malaria burden. These symptomless infections, not motivating an active search for treatment, are invisible to the system, although they remain potentially transmissible to mosquitoes, thus acting as silent reservoirs of transmission.3Galatas B Bassat Q Mayor A Malaria parasites in the asymptomatic: looking for the hay in the haystack.Trends Parasitol. 2016; 32: 296-308Summary Full Text Full Text PDF PubMed Scopus (57) Google Scholar For this reason, estimating the true burden of malaria infections from the relatively small proportion of those that are clinically visible and detectable through the health system can provide an actionable idea of the magnitude of undercounting, and therefore of the efforts required to interrupt malaria transmission at the community level. In The Lancet Infectious Diseases, Gillian Stresman and colleagues,4Stresman G Sepúlveda N Fornace K et al.Association between the proportion of Plasmodium falciparum and Plasmodium vivax infections detected by passive surveillance and the magnitude of the asymptomatic reservoir in the community: a pooled analysis of paired health facility and community data.Lancet Infect Dis. 2020; (published online April 8.)https://doi.org/10.1016/S1473-3099(20)30059-1Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar representing a variety of malaria-endemic countries, propose a new approach to quantify, using a Bayesian model, the proportion of the total malaria infections in a given community detected through routine passive case surveillance. Such an indicator, termed P(Detect) and ranging from 0 to 100%, would use health system clinical data to derive an idea of the overall community transmission, by expressing the probability that an infection becomes symptomatic and potentially detected by the health system. Thus, theoretically, a very high value of P(Detect)—ie, a value approaching 100%—would suggest that the vast majority of infections are clinically manifest and therefore detectable by the health system, whereas a low value would indicate that most of the parasite reservoir remains undetected by the health system. As the authors suggest, and for elimination purposes, such an indicator could have an enormous potential to help to identify “the critical point at which programmes could scale back control activities and rely on the health system to identify all infections”.4Stresman G Sepúlveda N Fornace K et al.Association between the proportion of Plasmodium falciparum and Plasmodium vivax infections detected by passive surveillance and the magnitude of the asymptomatic reservoir in the community: a pooled analysis of paired health facility and community data.Lancet Infect Dis. 2020; (published online April 8.)https://doi.org/10.1016/S1473-3099(20)30059-1Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar The pooled analysis of paired health facility (passive case detection) and community survey data (household surveys) allows the study authors to explore the association between infection detection and transmission in malaria endemic areas. The analysis of such an impressive dataset (including 471 clusters in 13 countries for Plasmodium falciparum and 231 clusters in seven countries for Plasmodium vivax, for the period 2008–2017) shows low median estimated P(Detect) values (12·5% for P falciparum and 10·1% for P vivax). However, their more important finding is a negative association between the level of infection detection and the underlying intensity of transmission for both species (P falciparum adjusted odds ratio 0·63 [95% CI 0·57–0·69] and P vivax adjusted odds ratio 0·52 [0·47–0·57]). As a plausible explanation for these findings, the authors suggest that as disease transmission and repeated exposure to malaria infection decrease, population immunity to this deadly infection will start to wane, rendering the population vulnerable again and gradually non-immune.5Ghani AC Sutherland CJ Riley EM et al.Loss of population levels of immunity to malaria as a result of exposure-reducing interventions: consequences for interpretation of disease trends.PLoS One. 2009; 4e4383Crossref PubMed Scopus (67) Google Scholar As a result, the proportion of the infections that will become clinical (and as such, for which the affected individuals might seek health care and thus are detectable at the health system level) will also increase. Subgroup analyses done by the authors exploring the variability of P(Detect) according to age or seasonality further substantiate this hypothesis and help to validate their results, although such an association in the case of P vivax was less conclusive. In this respect, an important limitation of the work presented relates to the absence of data in their analyses from highly malaria-endemic areas in the Pacific (eg, Papua-Indonesia and Papua New Guinea), where P vivax is a major cause of infection and disease, and where immunity to this species builds up even faster than it does for P falciparum.6Koepfli C Colborn KL Kiniboro B et al.A high force of Plasmodium vivax blood-stage infection drives the rapid acquisition of immunity in Papua New Guinean children.PLoS Negl Trop Dis. 2013; 7e2403Crossref PubMed Scopus (40) Google Scholar, 7Poespoprodjo JR Fobia W Kenangalem E et al.Vivax malaria: a major cause of morbidity in early infancy.Clin Infect Dis. 2009; 48: 1704-1712Crossref PubMed Scopus (117) Google Scholar Generating estimates of P(Detect) in those regions could have further illustrated the association between transmission and clinical disease for a malaria species that clearly has its own particularities, and is extremely relevant if global eradication of malaria is to be achieved. Despite the aforementioned limitations, the authors should be praised for their proposed approach to quantifying the degree of hidden malaria transmission, which is an important indicator of the likelihood of success of all malaria control and elimination strategies worldwide. We declare no competing interests. Association between the proportion of Plasmodium falciparum and Plasmodium vivax infections detected by passive surveillance and the magnitude of the asymptomatic reservoir in the community: a pooled analysis of paired health facility and community dataThe proportion of all infections detected within health systems increases once transmission intensity is sufficiently low. The likely explanation for P falciparum is that reduced exposure to infection leads to lower levels of protective immunity in the population, increasing the likelihood that infected individuals will become symptomatic and seek care. These factors might also be true for P vivax but a better understanding of the transmission biology is needed to attribute likely reasons for the observed trend. Full-Text PDF Open Access