Clinical consequences of submicroscopic malaria parasitaemia in Uganda

Katrak, Shereen; Nayebare, Patience; Rek, John; Arinaitwe, Emmanuel; Nankabirwa, Joaniter I.; Kamya, Moses R.; Dorsey, Grant; Rosenthal, Philip J.; Greenhouse, Bryan

doi:10.1186/s12936-018-2221-9

Cited by 30 publications

(40 citation statements)

References 32 publications

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“…While the results in the rainy season confirm findings from another cross-sectional study of Rwandan school-going children (6 -10 years old) (20), they differ from a recent report from Uganda of a prospective cohort study of children and adults, which reported that children aged 2 -10 years old with submicroscopic P. falciparum infections had increased risk of fever compared to those with no parasitemia (19). That study used loop-mediated isothermal amplification to detect submicroscopic infection; our PCR-based approach is slightly more sensitive (25,26).…”

Section: Discussioncontrasting

confidence: 69%

“…Others have evaluated the association between submicroscopic P. falciparum infections and clinical malaria (12,(18)(19)(20)(21), but with varying study designs and inconsistent results. Most recently, a study from Uganda suggested that submicroscopic P. falciparum infections may be associated with symptoms (19). This report and other studies have focused on young children, who have not developed the acquired immunity to clinical malaria that is typical of older children and adults in high transmission settings.…”

Section: Introductionmentioning

confidence: 99%

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Submicroscopic malaria infection is not associated with fever in cross-sectional studies in Malawi

Vareta

Buchwald

Barrall

et al. 2020

Preprint

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Abstract Background: Submicroscopic Plasmodium falciparum infections are widespread in many areas. However, the contribution of these infections to symptomatic malaria is not well understood. In this study we evaluated whether participants with submicroscopic P. falciparum infections have higher prevalence of fever than uninfected participants in southern Malawi.Methods: We enrolled a total of 16,650 children and adults in the course of six cross-sectional surveys during the dry season (October - November) and after the rainy season (April - May) between 2012 - 2014 in three districts in southern Malawi. Demographic and socioeconomic data were collected in conjunction with data on clinical histories, use of malaria preventive measures, and antimalarial medication taken within two weeks of the survey. Axillary temperatures were measured, and blood samples were collected for P. falciparum detection by microscopy and PCR. Participants without malaria parasites detected on microscopy but with a positive PCR for P. falciparum were defined as having submicroscopic infection. Fever was defined as having any one of: reported fever in the past two weeks, reported fever in the past 48 hours, or a temperature of ≥37.5 °C measured at the time of interview.Results: Submicroscopic P. falciparum infections and fever were both detected in 9% of the study population. In the final analysis adjusted for clustering within household and enumeration area, having submicroscopic P. falciparum infection was associated with reduced odds of fever in the dry season (odds ratio = 0.52; 95% CI: 0.33 – 0.82); the association in the rainy season did not achieve statistical significance (odds ratio = 1.20; 95% CI: 0.91 – 1.59). The association between submicroscopic infection and fever was consistent across all age groups. When we limited the definition of fever to temperature of ≥37.5 °C measured at the time of interview, the association was not statistically significant in either the rainy or dry season.Conclusions: In this series of cross-sectional studies in southern Malawi, submicroscopic P. falciparum infection was not associated with increased risk of fever. Submicroscopic detection of the malaria parasite is important in efforts to decrease transmission but is not essential for the clinical recognition of malaria disease.

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Section: Discussioncontrasting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Submicroscopic malaria infection is not associated with fever in cross-sectional studies in Malawi

Vareta

Buchwald

Barrall

et al. 2020

Preprint

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“…Submicroscopic infections have been reported in high transmission regions as in Ghana and hypo-endemic areas as in Uganda [ 41 – 43 ], demonstrating a relationship between submicroscopic infections and clinical malaria in children. These findings highlight the importance of treat patients with low-density malaria parasitaemia, and support interventions addressed to eliminate submicroscopic infections [ 44 ]. The concept that submicroscopic infection has clinical consequences strengthens arguments for malaria control strategies designed to eliminate all malaria parasitaemia.…”

Section: Discussionmentioning

confidence: 84%

Comparison of three diagnostic methods (microscopy, RDT, and PCR) for the detection of malaria parasites in representative samples from Equatorial Guinea

Berzosa

Lucio

Romay‐Barja

et al. 2018

Malar J

219

207

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BackgroundMalaria in Equatorial Guinea remains a major public health problem. The country is a holo-endemic area with a year-round transmission pattern. In 2016, the prevalence of malaria was 12.09% and malaria caused 15% of deaths among children under 5 years. In the Continental Region, 95.2% of malaria infections were Plasmodium falciparum, 9.5% Plasmodium vivax, and eight cases mixed infection in 2011. The main strategy for malaria control is quick and accurate diagnosis followed by effective treatment. Early and accurate diagnosis of malaria is essential for both effective disease management and malaria surveillance. The quality of malaria diagnosis is important in all settings, as misdiagnosis can result in significant morbidity and mortality. Microscopy and RDTs are the primary choices for diagnosing malaria in the field. However, false-negative results may delay treatment and increase the number of persons capable of infecting mosquitoes in the community. The present study analysed the performance of microscopy and RDTs, the two main techniques used in Equatorial Guinea for the diagnosis of malaria, compared to semi-nested multiplex PCR (SnM-PCR).ResultsA total of 1724 samples tested by microscopy, RDT, and SnM-PCR were analysed. Among the negative samples detected by microscopy, 335 (19.4%) were false negatives. On the other hand, the negative samples detected by RDT, 128 (13.3%) were false negatives based on PCR. This finding is important, especially since it is a group of patients who did not receive antimalarial treatment.ConclusionsOwing to the high number of false negatives in microscopy, it is necessary to reinforce training in microscopy, the “Gold Standard” in endemic areas. A network of reference centres could potentially support ongoing diagnostic and control efforts made by malaria control programmes in the long term, as the National Centre of Tropical Medicine currently supports the National Programme against Malaria of Equatorial Guinea to perform all of the molecular studies necessary for disease control. Taking into account the results obtained with the RDTs, an exhaustive study of the deletion of the hrp2 gene must be done in EG to help choose the correct RDT for this area.

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“…Although rarely causative of severe symptoms, they have been associated with a number of adverse 9 outcomes during pregnancy 12,13 , as well as mild anaemia 14 and other symptoms (vomiting, jaundice 10 etc.) in children under 10 15 . In addition to their capacity to cause low-grade disease, these infections 11 may hold public health relevance due to their contribution to onwards transmission: though typically 12 characterised by lower parasite densities than microscopically detectable infections, individuals with 13 submicroscopic infections frequently harbour gametocytes (the transmissible form of the parasite) 14…”

mentioning

confidence: 97%

Global & Temporal Patterns of Submicroscopic Plasmodium falciparum Malaria Infection

Whittaker

Slater

Bousema

et al. 2019

Preprint

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Background: Adoption of molecular techniques to detect Plasmodium falciparum infection has revealed many 11 previously undetected (yet transmissible) low-density infections in areas of low malaria transmission. In a world 12 where numerous countries are approaching elimination, additional data from low transmission areas are 13 required to better understand the determinants of submicroscopic infection and their potential relevance in 14 these settings. 15Methods: We updated a systematic review of studies assessing asexual P. falciparum prevalence by microscopy 16 and PCR in the same population. PubMed and Web of Science databases were searched up to July 2017. Bayesian Research in Context:1 Evidence before this study: Cross-sectional studies of malaria prevalence in endemic populations have revealed 2 the widespread presence of infections with parasite densities lower than the threshold of detection by 3 microscopy. Previous systematic reviews of these surveys have highlighted that the fraction of P.falciparum 4 infections missed by microscopy can be substantial (~45% of all infections detected by PCR on average), that 5 submicroscopic infection is more likely in adults than in children (a phenomenon attributed to increased levels 6 of immunity), and that this missed fraction (the "submicroscopic reservoir") is typically highest in areas with low 7 transmission intensity. Although further work is required, a number of studies have also demonstrated the 8 capacity of these submicroscopic, low density infections to infect mosquitoes and therefore contribute to 9 onwards transmission. 10Added value of this study: Although previous studies have found that infections in older, more immune 11 individuals are more likely to be submicroscopic, in lower transmission settings where individuals generally 12 develop less immunity, a larger proportion of infections are also typically submicroscopic. Here we present an 13 updated systematic review to explore this apparent paradox across a range of transmission settings and define 14 contexts in which submicroscopic infections are likely to be most relevant to malaria control efforts. Leveraging 15 the substantial increase in the availability of malaria cross-sectional surveys reporting prevalence by molecular 16 methods, we explore the association of submicroscopic infection with a number of novel factors -these include

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Clinical consequences of submicroscopic malaria parasitaemia in Uganda

Cited by 30 publications

References 32 publications

Submicroscopic malaria infection is not associated with fever in cross-sectional studies in Malawi

Submicroscopic malaria infection is not associated with fever in cross-sectional studies in Malawi

Comparison of three diagnostic methods (microscopy, RDT, and PCR) for the detection of malaria parasites in representative samples from Equatorial Guinea

Global & Temporal Patterns of Submicroscopic Plasmodium falciparum Malaria Infection

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