Health itinerary-related survival of children under-five with severe malaria or bloodstream infection, DR Congo.

BACKGROUND: Prompt appropriate treatment reduces mortality of severe febrile illness in sub-Saharan Africa. We studied the health itinerary of children under-five admitted to the hospital with severe febrile illness in a setting endemic for Plasmodium falciparum (Pf) malaria and invasive non-typhoidal Salmonella infections, identified delaying factors and assessed their associations with in-hospital death. METHODOLOGY: Health itinerary data of this cohort study were collected during 6 months by interviewing caretakers of children (>28 days - <5 years) admitted with suspected bloodstream infection to Kisantu district hospital, DR Congo. The cohort was followed until discharge to assess in-hospital death. PRINCIPAL FINDINGS: From 784 enrolled children, 36.1% were admitted >3 days after fever onset. This long health itinerary was more frequent in children with bacterial bloodstream infection (52.9% (63/119)) than in children with severe Pf malaria (31.0% (97/313)). Long health itinerary was associated with in-hospital death (OR = 2.1, p = 0.007) and two thirds of deaths occurred during the first 3 days of admission. Case fatality was higher in bloodstream infection (22.8% (26/114)) compared to severe Pf malaria (2.6%, 8/309). Bloodstream infections were mainly (74.8% (89/119)) caused by non-typhoidal Salmonella. Bloodstream infections occurred in 20/43 children who died in-hospital before possible enrolment and non-typhoidal Salmonella caused 16 out of these 20 bloodstream infections. Delaying factors associated with in-hospital death were consulting traditional, private and/or multiple providers, rural residence, prehospital intravenous therapy, and prehospital overnight stays. Use of antibiotics reserved for hospital use, intravenous therapy and prehospital overnight stays were most frequent in the private sector. CONCLUSIONS: Long health itineraries delayed appropriate treatment of bloodstream infections in children under-five and were associated with increased in-hospital mortality. Non-typhoidal Salmonella were the main cause of bloodstream infection and had high case fatality. TRIAL REGISTRATION: NCT04289688.

Malaria diagnostic methods with the elimination goal in view.

Malaria control measures have been in use for years but have not completely curbed the spread of infection. Ultimately, global elimination is the goal. A major playmaker in the various approaches to reaching the goal is the issue of proper diagnosis. Various diagnostic techniques were adopted in different regions and geographical locations over the decades, and these have invariably produced diverse outcomes. In this review, we looked at the various approaches used in malaria diagnostics with a focus on methods favorably used during pre-elimination and elimination phases as well as in endemic regions. Microscopy, rapid diagnostic testing (RDT), loop-mediated isothermal amplification (LAMP), and polymerase chain reaction (PCR) are common methods applied depending on prevailing factors, each with its strengths and limitations. As the drive toward the elimination goal intensifies, the search for ideal, simple, fast, and reliable point-of-care diagnostic tools is needed more than ever before to be used in conjunction with a functional surveillance system supported by the ideal vaccine.

Seroprevalence of SARS-CoV-2 antibodies among children and adolescents recruited in a malariometric survey in north-eastern Tanzania July 2021.

BACKGROUND: African countries stand out globally as the region seemingly least affected by the COVID-19 pandemic, caused by the virus SARS-CoV-2. Besides a younger population and potential pre-existing immunity to a SARS-CoV-2-like virus, it has been hypothesized that co-infection or recent history of Plasmodium falciparum malaria may be protective of COVID-19 severity and mortality. The number of COVID-19 cases and deaths, however, may be vastly undercounted. Very little is known about the extent to which the Tanzanian population has been exposed to SARS-CoV-2. Here, we investigated the seroprevalence of IgG to SARS-CoV-2 spike protein in two Tanzanian rural communities 1½ years into the pandemic and the association of coinciding malaria infection and exposure. METHODS: During a malariometric survey in July 2021 in two villages in north-eastern Tanzania, blood samples were taken from 501 participants (0-19 years old). Malaria was detected by mRDT and microscopy. Levels of IgG against the spike protein of SARS-CoV-2 were measured by ELISA as well as IgG against five different antigens of P. falciparum; CIDRα1.1, CIDRα1.4 and CIDRα1.5 of PfEMP1 and GLURP and MSP3. RESULTS: The seroprevalence of SARS-CoV-2 IgG was 39.7% (106/267) in Kwamasimba and 32.5% (76/234) in Mkokola. In both villages the odds of being seropositive increased significantly with age (AOR = 1.12, 95% CI 1.07-1.17, p < 0.001). P. falciparum malaria prevalence by blood smear microscopy was 7.9% in Kwamasimba and 2.1% in Mkokola. 81.3% and 70.5% in Kwamasimba and Mkokola, respectively, showed recognition of minimum one malaria antigen. Residing in Kwamasimba was associated with a broader recognition (AOR = 1.91, 95% CI 1.34-2.71, p < 0.001). The recognition of malaria antigens increased significantly with age in both villages (AOR = 1.12; 95% CI 1.08-1.16, p < 0.001). Being SARS-CoV-2 seropositive did not associate with the breadth of malaria antigen recognition when adjusting for age (AOR = 0.99; 95% CI 0.83-1.18; p = 0.91). CONCLUSION: More than a third of the children and adolescents in two rural communities in Tanzania had antibodies to SARS-CoV-2. In particular, the adolescents were seropositive but being seropositive did not associate with the status of coinciding malaria infections or previous exposure. In Tanzania, natural immunity may have developed fast, potentially protecting a substantial part of the population from later variants.

A Comparative Study of Asymptomatic Malaria in a Forest Rural and Depleted Forest Urban Setting during a Low Malaria Transmission and COVID-19 Pandemic Period.

The global malaria morbidity and mortality witnessed an increase from 2019 to 2020 partly due to disruptions in control programs' activities imposed by the COVID-19 pandemic. Therefore, there is still a significant burden of malaria in Cameroon which needs attention from all fronts to attain elimination goals. It is normally expected that a typical forest ecology that has undergone urbanization and subjected to high rates of ecological instabilities should also have a shift from characteristic perennial malaria transmission and a shift in the type of malaria endemicity plaguing such distorted forest ecology. In this observational comparative study, we randomly enrolled participants from rural and urban settings of a forest zone during a low malaria transmission period, which coincided with the onset of COVID-19 pandemic. An optimized structured questionnaire was employed, to collect socio-demographic data and associated risk factors. The CareStart™ Malaria HRP2 antigen test was performed on participants from both settings to determine the prevalence of community asymptomatic malaria. Of 307 participants, 188 (61.0%) were from the rural, while 119 (38.8%) from the urban community. The overall prevalence of asymptomatic malaria (27.0%) detected Plasmodium falciparum antigen in 83 participants. The urban community's prevalence was 4.2% (5 positives) while the rural community's was 41.5% (78 positives). In simple logistic regression models, rural forest community and farm around the house were statistically significant predictors of testing positive (coefficient 2.8, 95% CI 1.8-3.7, p value<0.001) and (coefficient 3.1, 95% CI 1.1-5.1, p value =0.003), respectively. In the multivariate model, the strongest predictor of testing positive was living in a rural community, with p < 0.001 and odds ratio of 10.9 (95% CI, 3.8-31.8). These results indicate that during a low transmission period, the prevalence of asymptomatic malaria differs between depleted urban and rural forested settings, suggesting a need for strategic target intervention for the control of asymptomatic malaria.

Automated Recognition of Plasmodium falciparum Parasites from Portable Blood Levitation Imaging.

In many malaria-endemic regions, current detection tools are inadequate in diagnostic accuracy and accessibility. To meet the need for direct, phenotypic, and automated malaria parasite detection in field settings, a portable platform to process, image, and analyze whole blood to detect Plasmodium falciparum parasites, is developed. The liberated parasites from lysed red blood cells suspended in a magnetic field are accurately detected using this cellphone-interfaced, battery-operated imaging platform. A validation study is conducted at Ugandan clinics, processing 45 malaria-negative and 36 malaria-positive clinical samples without external infrastructure. Texture and morphology features are extracted from the sample images, and a random forest classifier is trained to assess infection status, achieving 100% sensitivity and 91% specificity against gold-standard measurements (microscopy and polymerase chain reaction), and limit of detection of 31 parasites per µL. This rapid and user-friendly platform enables portable parasite detection and can support malaria diagnostics, surveillance, and research in resource-constrained environments.

Impact of antimalarial resistance and COVID-19 pandemic on malaria care among pregnant women in Northern Uganda (ERASE): protocol of a prospective observational study.

BACKGROUND: Uganda accounts for 5% of all malaria cases and deaths reported globally and, in endemic countries, pregnancy is a risk factor for both acquisition of P. falciparum infection and development of severe malaria. In recent years, malaria control has been threatened by COVID-19 pandemic and by the emergence, in Northern Uganda, of both resistance to artemisinin derivatives and to sulfadoxine-pyrimethamine. METHODS: In this facility-based, prospective, observational study, pregnant women will be recruited at antenatal-care visits and followed-up until delivery. Collected data will explore the incidence of asymptomatic parasitemia and malaria-related outcomes, as well as the attitudes towards malaria prevention, administration of intermittent preventive treatment, healthcare seeking behavior and use of insecticide-treated nets. A subpopulation of women diagnosed with malaria will be recruited and their blood samples will be analyzed for detection of genetic markers of resistance to artemisinin derivatives and sulfadoxine-pyrimethamine. Also, to investigate the impact of COVID-19 on malaria care among pregnant women, a retrospective, interrupted-time series will be conducted on at the study sites for the period January 2018 to December 2021. DISCUSSION: The present study will explore the impact of COVID-19 pandemic on incidence of malaria and malaria-related adverse outcomes, along with the prevalence of resistance to artemisinin derivatives and to sulfadoxine-pyrimethamine. To our knowledge, this is the first study aiming to explore the combined effect of these factors on a cohort of pregnant women. TRIAL REGISTRATION: This study has been registered on the ClinicalTrials.gov public website on 26th April, 2022. CLINICALTRIALS: gov Identifier: NCT05348746.

Spend wisely to eliminate malaria.

The countries of the Greater Mekong subregion-Myanmar, Thailand, Laos, Cambodia, and Vietnam-have set a target of eliminating all Plasmodium falciparum malaria by 2025. Generous funding has been provided, principally by The Global Fund to Fight AIDS, Tuberculosis, and Malaria, to achieve this objective and thereby prevent the spread of artemisinin-resistant Plasmodium falciparum to India and Africa. As the remaining time to reach agreed targets is limited and future external funding is uncertain, it is important to be realistic about the future and spend what remaining funding is left, wisely. New, labour intensive, vertical approaches to malaria elimination (such as the 1-3-7 approach) should not be promoted as these are unproven, likely to be ineffective, costly, and unlikely to be sustainable in the most remote areas where malaria prevalence is highest. Instead, the focus should be on reducing the malaria burden more rapidly in the remaining localised high transmission foci with proven effective interventions, including mass drug administration. Well supported community-based health workers are the key operatives in controlling malaria, but their remit should be broadened to sustain the uptake of their services as malaria declines. This strategy is a sustainable evolution, which will improve rural health care while ensuring progress towards malaria elimination.

Development and On-Field Deployment of a Mobile-Based Application 'MoSQuIT' for Malaria Surveillance in International Border Districts of Northeast India-Challenges and Opportunities.

The conventional paper-based system for malaria surveillance is time-consuming, difficult to track and resource-intensive. Few digital platforms are in use but wide-scale deployment and acceptability remain to be seen. To address this issue, we created a malaria surveillance mobile app that offers real-time data to stakeholders and establishes a centralised data repository. The MoSQuIT app was designed to collect data from the field and was integrated with a web-based platform for data integration and analysis. The MoSQuIT app was deployed on mobile phones of accredited social health activists (ASHA) working in international border villages in the northeast (NE) Indian states of Assam, Tripura and Arunachal Pradesh for 20 months in a phased manner. This paper shares the challenges and opportunities associated with the use of MoSQuIT for malaria surveillance. MoSQuIT employs the same data entry formats as the NVBDCP's malaria surveillance programme. Using this app, a total of 8221 fever cases were recorded, which included 1192 (14.5%) cases of P. falciparum malaria, 280 (3.4%) cases of P. vivax malaria and 52 (0.6%) mixed infection cases. Depending on network availability, GPS coordinates of the fever cases were acquired by the app. The present study demonstrated that mobile-phone-based malaria surveillance facilitates the quick transmission of data from the field to decision makers. Geospatial tagging of cases helped with easy visualisation of the case distribution for the identification of malaria-prone areas and potential outbreaks, especially in hilly and remote regions of Northeast India. However, to achieve the full operational potential of the system, operational challenges have to be overcome.

Asymptomatic malaria infection at the China-Vietnam border: Knowledge and implications for the cross-border migrant population during the COVID-19 pandemic.

BACKGROUND: Eliminating malaria along the China-Vietnam border remains one of the greatest challenges in China, especially during the coronavirus disease 2019 (COVID-19) pandemic, which has disrupted the continuity of malaria control and elimination programs. Understanding the factors associated with asymptomatic malaria infection will inform control interventions aimed at elimination of the disease among migrants from Vietnam working in China, who constitute an at-risk population. METHODS: From March 2018 to September 2019, 108 migrants from Vietnam working in Ningming County, Guangxi, were enrolled in this study. Each person was interviewed using a structured questionnaire. Blood samples were collected and sent for PCR detection and sequencing. The obtained sequences were analyzed using the BLAST program and DNAMAN software. RESULTS: The proportion of participants with malaria knowledge was low, with 19.4% (21/108) reporting knowledge about transmission, 23.2% (25/108) reporting knowledge about clinical symptoms, 7.4% (8/108) reporting awareness of the risk of death and 14.8% (16/108) reporting awareness of prevention methods. No significant difference in the malaria knowledge rate was found among occupational groups, except in the migrant worker group, whose knowledge rate was higher than those in the other occupational groups (χ2 = 32.452, p < 0.001). Although most of the participants (80.6%, 87/108) owned mosquito nets, only approximately half of the participants (49.1%, 53/108) reported using bed nets. The parasitological analysis revealed that 5.6% (6/108) of all the participants were positive for malaria, including 5 participants with Plasmodium falciparum and 1 participant with Plasmodium vivax malaria. There were no statistically significant differences in the positivity rates among the different age, sex, family-size, nationality, occupational, and behavior groups. The positivity rates in individuals who did not use mosquito nets, did not use mosquito coils, and did not install mosquito nets were 4.8% (1/21), 6.8% (3/44), and 3.6% (2/55), respectively. CONCLUSION: Health education focused on high-risk populations, such as migrant workers and forest goers, should be strengthened. Verbal communication and information transmission via the internet, radio, and mobile phone platforms may be required during the COVID-19 pandemic. Further risk assessments and proactive case detection should also be performed in Ningming County and other border counties in Guangxi to detect active and asymptomatic infections in a timely manner and prevent re-establishment of the disease in these communities.

Less Severe Cases of COVID-19 in Sub-Saharan Africa: Could Co-infection or a Recent History of Plasmodium falciparum Infection Be Protective?

Sub-Saharan Africa has generally experienced few cases and deaths of coronavirus disease 2019 (COVID-19). In addition to other potential explanations for the few cases and deaths of COVID-19 such as the population socio-demographics, early lockdown measures and the possibility of under reporting, we hypothesize in this mini review that individuals with a recent history of malaria infection may be protected against infection or severe form of COVID-19. Given that both the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium falciparum (P. falciparum) merozoites bind to the cluster of differentiation 147 (CD147) immunoglobulin, we hypothesize that the immunological memory against P. falciparum merozoites primes SARS-CoV-2 infected cells for early phagocytosis, hence protecting individuals with a recent P. falciparum infection against COVID-19 infection or severity. This mini review therefore discusses the potential biological link between P. falciparum infection and COVID-19 infection or severity and further highlights the importance of CD147 immunoglobulin as an entry point for both SARS-CoV-2 and P. falciparum into host cells.

Malaria epidemiology and anti-malarial drug efficacy in Guinea: a review of clinical and molecular studies.

Malaria is one of the leading causes of mortality and morbidity in Guinea. The entire country is considered at risk of the disease. Transmission occurs all year round with peaks occurring from July through October with Plasmodium falciparum as the primary parasite species. Chloroquine (CQ) was the first-line drug against uncomplicated P. falciparum in Guinea until 2005, prior to the adoption of artemisinin-based combination therapy (ACT). In this review, data on therapeutic efficacy of CQ and artemisinin-based combinations reported in published literature is summarized. Against CQ, a failure rate of 27% (12/44) was reported in a study in 1992; a median failure rate of 15.6% [range: 7.7-28.3; 8 studies] was observed during 1996-2001, and 81% (17/21) of the patients failed to clear parasitaemia in a study conducted in 2007. For artemisinin-based combinations, three published studies were identified (1495 patients; 2004-2016); all three studies demonstrated day 28 polymerase chain reaction corrected efficacy > 95%. One study characterized kelch-13 mutations (389 tested; samples collected in 2016) with no evidence of mutations currently known to be associated with artemisinin resistance. The impact of the ongoing COVID-19 pandemic and widespread usage of counterfeit medicines are immediate challenges to malaria control activities in Guinea.

Failure of rapid diagnostic tests in Plasmodium falciparum malaria cases among travelers to the UK and Ireland: Identification and characterisation of the parasites.

OBJECTIVES: Our objective was to systematically investigate false-negative histidine-rich protein 2 rapid diagnostic tests (HRP2-RDT) in imported Plasmodium falciparum malaria cases from travelers to the UK and the Republic of Ireland (RoI). METHODS: Five imported malaria cases in travellers returning to the UK and RoI from East Africa were reported to the PHE Malaria Reference Laboratory as negative according to histidine-rich protein (HRP2)-RDT. The cases were systematically investigated using microscopic, RDT, molecular, genomic, and in in vitro approaches. RESULTS: In each case, HRP2-RDT was negative, whereas microscopy confirmed the presence of P. falciparum. Further analysis revealed that the genes encoding HRP2 and HRP3 were deleted in three of the five cases. Whole-genome sequencing in one of these isolates confirmed deletions in P. falciparum chromosomes 8 and 13. Our study produced evidence that the fourth case, which had high parasitemia at clinical presentation, was a rare example of antigen saturation ('prozone-like effect'), leading to a false negative in the HRP2-RDT, while the fifth case was due to low parasitemia. CONCLUSIONS: False-negative HRP2-RDT results with P. falciparum are concerning. Our findings emphasise the necessity of supporting the interpretation of RDT results with microscopy, in conjunction with clinical observations, and sets out a systematic approach to identifying parasites carrying pfhrp2 and pfhrp3 deletions.

Plasmodium falciparum outbreak in native communities of Condorcanqui, Amazonas, Perú.

BACKGROUND: Malaria remains a serious health threat in the Amazonas Region of Peru and approximately 95% of the cases, mainly Plasmodium vivax, are found in native communities of The Rio Santiago District, Condorcanqui Province. In 2019, more than one thousand malaria cases were reported, with an unusual number of Plasmodium falciparum autochthonous cases. The present study aims to report this P. falciparum outbreak while describing the epidemiology of malaria and the risk factors associated in the native communities of Amazonas, Peru. METHODS: The DIRESA-Amazonas in collaboration with the Condorcanqui Health Network and the Institute of Tropical Diseases of the UNTRM carried out a malaria Active Case Detection (ACD III) between January 31st and February 10th of 2020. A total of 2718 (47.4%) individuals from 21 native communities grouped in eight sanitary districts, were screened for malaria infections. Each participant was screened for malaria using microscopy. Follow-up surveys were conducted for all malaria positive individuals to collect socio-demographic data. Spatial clustering of infection risk was calculated using a generalized linear model (GLM). Analysis of risk considered factors such as gender, age, type of infection, symptomatology, and parasitaemia. RESULTS: The study suggests that the P. falciparum index case was imported from Loreto and later spread to other communities of Rio Santiago during 2019. The ACD III reported 220 (8.1%) malaria cases, 46 P. falciparum, 168 P. vivax and 6 mixed infections. SaTScan analysis detected a cluster of high infection risk in Middle Rio Santiago and a particular high P. falciparum infection risk cluster in Upper Rio Santiago. Interestingly, the evaluation of different risk factors showed significant associations between low parasitaemia and P. falciparum asymptomatic cases. CONCLUSION: This is the first report of a P. falciparum outbreak in native communities of Condorcanqui, Amazonas. Timely identification and treatment of symptomatic and asymptomatic cases are critical to achieve malaria control and possible elimination in this area. However, the current malaria situation in Condorcanqui is uncertain, given that malaria ACD activities have been postponed due to COVID-19.

Molecular detection of drug resistant polymorphisms in Plasmodium falciparum isolates from Southwest, Nigeria.

OBJECTIVE: Nigeria bears 25% of global malaria burden despite concerted efforts towards its control and elimination. The emergence of drug resistance to first line drugs, artemisinin combination therapies (ACTs), indicates an urgent need for continuous molecular surveillance of drug resistance especially in high burden countries where drug interventions are heavily relied on. This study describes mutations in Plasmodium falciparum genes associated with drug resistance in malaria; Pfk13, Pfmdr1, PfATPase6 and Pfcrt in isolates obtained from 83 symptomatic malaria patients collected in August 2014, aged 1-61 years old from South-west Nigeria. RESULTS: Two Pfmdr1, N86 and Y184 variants were present at a prevalence of 56% and 13.25% of isolates respectively. There was one synonymous (S679S) and two non-synonymous (M699V, S769M) mutations in the PATPase6 gene, while Pfcrt genotype (CVIET), had a prevalence of 45%. The Pfk13 C580Y mutant allele was suspected by allelic discrimination in two samples with mixed genotypes although this could not be validated with independent isolation or additional methods. Our findings call for robust molecular surveillance of antimalarial drug resistance markers in west Africa especially with increased use of antimalarial drugs as prophylaxis for Covid-19.

Emergence of Undetectable Malaria Parasites: A Threat under the Radar amid the COVID-19 Pandemic?

Rapid diagnostic tests (RDTs) play a critical role in malaria diagnosis and control. The emergence of Plasmodium falciparum parasites that can evade detection by RDTs threatens control and elimination efforts. These parasites lack or have altered genes encoding histidine-rich proteins (HRPs) 2 and 3, the antigens recognized by HRP2-based RDTs. Surveillance of such parasites is dependent on identifying false-negative RDT results among suspected malaria cases, a task made more challenging during the current pandemic because of the overlap of symptoms between malaria and COVID-19, particularly in areas of low malaria transmission. Here, we share our perspective on the emergence of P. falciparum parasites lacking HRP2 and HRP3, and the surveillance needed to identify them amid the COVID-19 pandemic.