Malaria rapid diagnostic tests (RDTs) play a critical role in malaria case management, surveillance and case investigations. Test performance is largely determined by design and quality characteristics, such as detection sensitivity, specificity, and thermal stability. However, parasite characteristics such as variable or absent expression of antigens targeted by RDTs can also affect RDT performance. Plasmodium falciparum parasites lacking the PfHRP2 protein, the most common target antigen for detection of P. falciparum, have been reported in some regions. Therefore, accurately mapping the presence and prevalence of P. falciparum parasites lacking pfhrp2 would be an important step so that RDTs targeting alternative antigens, or microscopy, can be preferentially selected for use in such regions. Herein the available evidence and molecular basis for identifying malaria parasites lacking PfHRP2 is reviewed, and a set of recommended procedures to apply for future investigations for parasites lacking PfHRP2, is proposed.

Malaria rapid diagnostic tests (RDTs) emerged in the early 1990s into largely unregulated markets, and uncertain field performance was a major concern for the acceptance of tests for malaria case management. This, combined with the need to guide procurement decisions of UN agencies and WHO Member States, led to the creation of an independent, internationally coordinated RDT evaluation programme aiming to provide comparative performance data of commercially available RDTs. Products were assessed against Plasmodium falciparum and Plasmodium vivax samples diluted to two densities, along with malaria-negative samples from healthy individuals, and from people with immunological abnormalities or non-malarial infections. Three measures were established as indicators of performance, (i) panel detection score (PDS) determined against low density panels prepared from P. falciparum and P. vivax wild-type samples, (ii) false positive rate, and (iii) invalid rate, and minimum criteria defined. Over eight rounds of the programme, 332 products were tested. Between Rounds 1 and 8, substantial improvements were seen in all performance measures. The number of products meeting all criteria increased from 26.8% (11/41) in Round 1, to 79.4% (27/34) in Round 8. While products submitted to further evaluation rounds under compulsory re-testing did not show improvement, those voluntarily resubmitted showed significant increases in P. falciparum (p = 0.002) and P. vivax PDS (p < 0.001), with more products meeting the criteria upon re-testing. Through this programme, the differentiation of products based on comparative performance, combined with policy changes has been influential in the acceptance of malaria RDTs as a case-management tool, enabling a policy of parasite-based diagnosis prior to treatment. Publication of product testing results has produced a transparent market allowing users and procurers to clearly identify appropriate products for their situation, and could form a model for introduction of other, broad-scale diagnostics.

Asymptomatic, low parasite density malaria infections are difficult to detect with currently available point-of-care diagnostics. This study piloted a loop-mediated isothermal amplification (LAMP) kit for field-friendly, high-throughput detection of asymptomatic malaria infections during mass screening and treatment (MSAT) in Zanzibar, a malaria pre-elimination setting. Screening took place in three known hotspot areas prior to the short rains in November. Finger-prick blood was taken for screening by rapid diagnostic test (RDT) and LAMP and collected on filter paper for subsequent polymerase chain reaction (PCR) analyses. LAMP results were compared to RDT and to PCR using McNemar’s test. Approximately 1,000 people were screened. RDT detected ten infections (1.0% (95% CI 0.3-1.6)) whilst both LAMP and PCR detected 18 (1.8% (95% CI 0.9-2.6)) infections. However, PCR identified three infections that LAMP did not detect and vice versa. LAMP testing was easy to scale-up in field conditions requiring minimal training and equipment, with results ready one to three hours after screening. Despite lower than expected prevalence, LAMP detected a higher number of infections than the currently used diagnostic, RDT. LAMP is a field-friendly, sensitive diagnostic test that could be useful for MSAT malaria campaigns which require quick results to enable prompt treatment.

The COVID-19 pandemic and public health “lockdown” responses in sub-Saharan Africa, including Uganda, are now widely reported. Although the impact of COVID-19 on African populations has been relatively light, it is feared that redirecting focus and prioritization of health systems to fight COVID-19 may have an impact on access to non–COVID-19 diseases. We applied age-based COVID-19 mortality data from China to the population structures of Uganda and non-African countries with previously established outbreaks, comparing theoretical mortality and disability-adjusted life years (DALYs) lost. We then predicted the impact of possible scenarios of the COVID-19 public health response on morbidity and mortality for HIV/AIDS, malaria, and maternal health in Uganda. Based on population age structure alone, Uganda is predicted to have a relatively low COVID-19 burden compared with an equivalent transmission in comparison countries, with 12% of the mortality and 19% of the lost DALYs predicted for an equivalent transmission in Italy. By contrast, scenarios of the impact of the public health response on malaria and HIV/AIDS predict additional disease burdens outweighing that predicted from extensive SARS-CoV-2 transmission. Emerging disease data from Uganda suggest that such deterioration may already be occurring. The results predict a relatively low COVID-19 impact on Uganda associated with its young population, with a high risk of negative impact on non–COVID-19 disease burden from a prolonged lockdown response. This may reverse hard-won gains in addressing fundamental vulnerabilities in women and children’s health, and underlines the importance of tailoring COVID-19 responses according to population structure and local disease vulnerabilities.

Background: In the absence of definitive diagnosis, healthcare providers are likely to prescribe empirical antibacterials to those who test negative for malaria. This problem is of critical importance in Southern Asia (SA) and South-eastern Asia (SEA) where high levels of antimicrobial consumption and high prevalence of antimicrobial resistance have been reported. To improve management and guide further diagnostic test development, better understanding is needed of the true causative agents of fever and their geographical variability. Methods: We conducted a systematic review of published literature (1980–2015) to characterise the spectrum of pathogens causing non-malarial febrile illness in SA and SEA. We searched six databases in English and French languages: MEDLINE, EMBASE, Global Health (CABI) database, WHO Global Health Library, PASCAL, and Bulletin de la Société Française de Parasitologie (BDSP). Selection criteria included reporting on an infection or infections with a confirmed diagnosis, defined as pathogens detected in or cultured from samples from normally sterile sites, or serological evidence of current or past infection. Results: A total of 29,558 records from 19 countries in SA and SEA were screened, of which 2410 (8.1%) met the selection criteria. Bacterial aetiologies were reported in 1235 (51.2%) articles, viral in 846 (35.1%), parasitic in 132 (5.5%), and fungal in 54 (2.2%), and 143 (6.0%) articles reported more than one pathogen group. In descending order of frequency, Salmonella Typhi, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and coagulase negative Staphylococcus were the commonly reported bacteria, while dengue virus, chikungunya virus, Japanese encephalitis virus, hepatitis B virus, and hepatitis C virus were common viral pathogens reported. Reports of rarely reported or emerging pathogens included a case report of Borrelia burgdorferi (Lyme disease) in India in 2010 and reports of Nipah virus in Singapore and India. Conclusions: This review summarises the reported non-malaria pathogens that may cause febrile illness in SA and SEA. The findings emphasise the need of standardising the reporting of aetiological studies to develop effective, evidence-based fever management and improved surveillance. Research and development of diagnostic tools would benefit from up-to-date epidemiological reporting of the regional diversities of non-malaria fever aetiologies. Trial registration: PROSPERO registration, CRD42016049281

: COVID-19 has had considerable global impact; however, in sub-Saharan Africa, it is one of several infectious disease priorities. Prioritization is normally guided by disease burden, but the highly age-dependent nature of COVID-19 and that of other infectious diseases make comparisons challenging unless considered through metrics that incorporate life-years lost and time lived with adverse health. Therefore, we compared the 2020 mortality and disability-adjusted life-years (DALYs) lost estimates for malaria, tuberculosis, and HIV/AIDS in sub-Saharan African populations with more than 12 months of COVID-19 burden (until the end of March 2021) by applying known age-related mortality to United Nations estimates of the age structure. We further compared exacerbations of disease burden predicted from the COVID-19 public health response. Data were derived from public sources and predicted exacerbations were derived from those published by international agencies. For sub-Saharan African populations north of South Africa, the estimated recorded COVID-19 DALYs lost in 2020 were 3.7%, 2.3%, and 2.4% of those for tuberculosis, HIV/AIDS, and malaria, respectively. Predicted exacerbations of these diseases were greater than the estimated COVID-19 burden. Including South Africa and Lesotho, COVID-19 DALYs lost were < 12% of those for other compared diseases; furthermore, the mortality of compared diseases were dominant in all age groups younger than 65 years. This analysis suggests the relatively low impact of COVID-19. Although all four epidemics continue, tuberculosis, HIV/AIDS, and malaria remain far greater health priorities based on their disease burdens. Therefore, resource diversion to COVID-19 poses a high risk of increasing the overall disease burden and causing net harm, thereby further increasing global inequities in health and life expectancy.