Application of a High-Resolution Melt Assay for Monitoring SARS-CoV-2 Variants in Burkina Faso and Kenya (preprint)

The rapid emergence and global dissemination of SARS-CoV-2 highlighted a need for robust, adaptable surveillance systems. However, financial and infrastructure requirements for whole genome sequencing (WGS) mean most surveillance data have come from higher-resource geographies, despite unprecedented investment in sequencing in low-middle income countries (LMICs) throughout the SARS-CoV-2 pandemic. Consequently, the molecular epidemiology of SARS-CoV-2 in some LMICs is limited, and there is a need for more cost-accessible technologies to help close data gaps for surveillance of SARS-CoV-2 variants. To address this, we have developed two high-resolution melt curve (HRM) assays that target key variant-defining mutations in the SARS-CoV-2 genome, which give unique signature profiles that define different SARS-CoV-2 variants of concern (VOCs). Extracted RNA from SARS-CoV-2 positive samples collected from 205 participants (112 in Burkina Faso, 93 in Kenya) on the day of enrolment in the MALCOV study (Malaria as a Risk Factor for COVID-19) between February 2021 and February 2022 were analysed using our optimised HRM assays and compared to Next Generation Sequencing (NGS) on Oxford Nanopore MinION . With NGS as a reference, two HRM assays, HRM-VOC-1 and HRM-VOC-2, demonstrated sensitivity/specificity of 100%/99.29% and 92.86/99.39%, respectively, for detecting Alpha, 90.08%/100% and 92.31%/100% for Delta and 93.75%/100% and 100%/99.38% for Omicron. The assays described here provide a lower-cost approach (<$1 per sample) to conducting molecular epidemiology, capable of high-throughput testing. We successfully scaled up the HRM-VOC-2 assay to screen a total of 506 samples from which we were able to show the replacement of Alpha with the introduction of Delta and the replacement of Delta by the Omicron variant in this community in Kisumu, Kenya. These assays are readily adaptable and can focus on local epidemiological surveillance questions or be updated quickly to accommodate the emergence of a novel variant or adapt to novel and emerging pathogens.

A mechanism that transduces lysosomal damage signals to stress granule formation for cell survival (preprint)

Lysosomal damage poses a significant threat to cell survival. Our previous work has reported that lysosomal damage induces stress granule (SG) formation. However, the importance of SG formation in determining cell fate and the precise mechanisms through which lysosomal damage triggers SG formation remains unclear. Here, we show that SG formation is initiated via a novel calcium-dependent pathway and plays a protective role in promoting cell survival in response to lysosomal damage. Mechanistically, we demonstrate that during lysosomal damage, ALIX, a calcium-activated protein, transduces lysosomal damage signals by sensing calcium leakage to induce SG formation by controlling the phosphorylation of eIF2α. ALIX modulates eIF2α phosphorylation by regulating the association between PKR and its activator PACT, with galectin-3 exerting a negative effect on this process. We also found this regulatory event of SG formation occur on damaged lysosomes. Collectively, these investigations reveal novel insights into the precise regulation of SG formation triggered by lysosomal damage, and shed light on the interaction between damaged lysosomes and SGs. Importantly, SG formation is significant for promoting cell survival in the physiological context of lysosomal damage inflicted by SARS-CoV-2 ORF3a, adenovirus infection, Malaria hemozoin, proteopathic tau as well as environmental hazard silica.

Impact of a six-month COVID-19 travel moratorium on Plasmodium falciparum malaria prevalence on Bioko Island, Equatorial Guinea (preprint)

Importation of malaria infections has long been suspected as a driver of sustained malaria prevalence on areas of Bioko Island, Equatorial Guinea. However, quantifying the impact of imported infections is difficult because of the dynamic nature of the disease and the complexity of designing a randomized trial. Here, we leverage a six-month travel moratorium in and out of Bioko Island during the initial COVID-19 pandemic response to evaluate the contribution of imported infections to Pf prevalence on Bioko Island. Using a difference in differences design and data from island wide household surveys conducted before (2019) and after (2020) the travel moratorium, we compared the change in prevalence between areas of low historical travel to those with high historical travel. We found that prevalence increased in low travel areas after the moratorium compared to before, while prevalence decreased in high travel areas. In the absence of a travel moratorium, the prevalence of infection in high travel areas was expected to be 5% higher than what was observed. The observed decrease in prevalence can be directly attributed to the lack of imported cases, highlighting the importance of control measures that target these types of infections.

Using the role model approach to optimise caregiver administration of sulfadoxine- pyrimethamine amodiaquine to children aged 3–59 months in Burkina Faso, Chad and Togo: findings from an evaluation (preprint)

Background Seasonal malaria chemoprevention (SMC) is a World Health Organization-recommended intervention for the prevention of malaria among children at high risk in areas with seasonal transmission. During the coronavirus disease 2019 (COVID-19) pandemic, SMC drug distribution was rapidly adapted to reduce contact and mitigate the risk of transmission between communities and community distributors, with caregivers administering doses. To address the challenges and find local solutions to improve administration and adherence, the role model approach was designed, implemented and evaluated in selected communities of Burkina Faso, Chad and Togo. This paper describes the results of this evaluation.Methods Focus group discussions were held with primary caregivers in all three countries to understand their perceptions of the approach’s acceptability and feasibility. In Burkina Faso and Togo, household surveys assessed the characteristics of caregivers reached by role model activities. Key indicators on SMC coverage and adherence allowed for an assessment of caregiver engagement outcomes related to participation in activities. We tested statistical associations between participation in role model activities and caregiver beliefs related to SMC.Results The majority of caregivers believed the approach to have a positive effect on drug administration, with most adopting the promoted strategies. Greater involvement of fathers in drug administration and acknowledgement of their joint responsibility was a notable positive outcome. However, several barriers to participation were noted and there was criticism of the group approach. In Burkina Faso and Togo, end-of-round survey results revealed that 98.4% of respondents agreed the approach improved their knowledge and skills in malaria prevention, while 100% expressed a desire to continue practicing the behaviours learned. However, there was a relatively low level of awareness of the approach among communities. Participation was strongly associated with participants’ self-reported belief in ease of remembering to administer, and ease of administering, SMC medicines.Conclusion Caregivers perceived the role model approach to be beneficial in aiding drug administration, with other positive impacts also reported. Replication and scale-up should utilise the most popular communication channels and existing community structures to ensure activities are promoted effectively. A mixture of group and one-on-one approaches should be used where appropriate and feasible.

Prior exposure to malaria decreases SARS-CoV-2 mediated mortality in K18-hACE2 mice without influencing viral load in lungs (preprint)

Abstract: Background: Epidemiological evidence for decreased prevalence and/or mortality due to SARS-CoV-2 infections in countries endemic for malaria have been reported. However, such associational studies in human population are limited by known and several unknown confounding factors. The current study, the first of its kind, was designed to seek experimental evidence to test the hypothesis if prior exposure to Plasmodial infections cross-protect against SARS-CoV-2 challenge infection in a murine model, K-18 human ACE2 transgenic mice. Methods: Mice that had recovered from Plasmodium chabaudi infection 40 days earlier were challenged with a virulent strain of SARS-CoV-2 and viral load in lungs as well as mortality were scored and compared with K18 hACE2 mice that had not experienced prior malaria. Results: The viral load in lungs 6 days post challenge were comparable in malaria recovered mice and controls suggesting no significant generation of anti-viral immunity. However, mice with prior malaria exposure were significantly protected against SARS-CoV-2 induced mortality. Significant differences were observed in several host immune responses between the two groups when cytokines, chemokines and transcription factors were quantified in lungs. The plasma levels of several cytokines and chemokines were also significantly different between the two groups. Conclusion: The results of the study suggest that prior exposure to malaria protects mice against viral induced mortality in K18 hACE2 transgenic mice challenged with a virulent isolate of SARS- CoV-2 in the absence of demonstrable host immunity inhibiting viral growth in lungs.

A recent history of disease outbreaks in Kenya, 2007-2022: Findings from routine surveillance data (preprint)

Background Africa reports the highest number of outbreaks in the world, accounting for 39% of all outbreaks in 2022. The Integrated Disease Surveillance and Response strategy in Kenya ensures the reporting of outbreaks at the national level. We present a summary of the burden of reported disease outbreaks in Kenya, 2007–2022.Methods We reviewed historical surveillance data, 2007–2022. We summarized the annual caseload and deaths of the reported outbreaks per county. We classified the outbreaks into 3 categories i.e., high, moderate, and low burden. We conducted the Mann-Kendall test to detect trends in the number of outbreaks and counties reporting over time.Results Twenty-three outbreaks were reported. COVID-19, cholera, epidemic malaria, leishmaniasis, and measles were associated with high disease burden. The highest number of outbreaks reported in a single year was 10. Garissa, Nairobi, Nakuru, Wajir, Mandera, and Mombasa, had the majority of the outbreaks and caseload.Conclusion There was an increase in the frequency and magnitude of outbreaks. This highlights the complex public health landscape and the vulnerability of the country to epidemics. The differences in outbreak occurrence among counties necessitate targeted and enhanced preventive, preparedness, and response interventions at the sub-national level to reduce the burden of outbreaks.

Societal Factors Constraining the Control of COVID-19 and Mosquito and Tick-Borne Diseases (preprint)

Advances in biological sciences have been applied in medicine, agriculture and industry with great benefit. Some recent trends in society, governance structures and communications, however, appear to be hampering the use of new scientific findings for controlling infectious diseases. These limitations are illustrated with examples related to (i) the adaptation of fresh water mosquito vectors of major arboviral diseases to salinity in coastal areas with consequences for disease transmission, (ii) understanding the implications of reduced dengue transmission during the COVID-19 lockdown for dengue control, (iii) causes underlying the rapid spread of the malaria vector Anopheles stephensi in South Asia and Africa, (iv) the application of serodiagnostic techniques for Lyme disease and tick-borne relapsing fever caused by tick-borne bacteria of the genus Borrelia, and (v) COVID-19 prevention.

A blended learning approach for capacity strengthening to improve the quality of integrated HIV, TB, and Malaria services during antenatal and postnatal care in LMICs: A feasibility study (preprint)

Background The blended learning (BL) approach to training health care professionals is increasingly adopted in many countries because of high costs and disruption to service delivery in the light of severe human resource shortage in low resource settings. The Covid-19 pandemic increased the urgency to identify alternatives to traditional face-to-face (f2f) education approach. A four-day f2f antenatal care (ANC) and postnatal care (PNC) continuous professional development course (CPD) was repackaged into a 3-part BL course; 1) self-directed learning (16 hours) 2) facilitated virtual sessions (2.5 hours over 3 days) and 3) 2-day f2f sessions.Methods This study assessed the feasibility, change in healthcare providers' knowledge and costs of the BL package in Nigeria, Tanzania, and Kenya. A mixed methods design was used. A total of 89 healthcare professionals, were purposively selected. Quantitative data was collected through an online questionnaire and skills assessments, analyzed using STATA 12 software. Qualitative data was collected through key informant interviews and focus group discussions, analysed using thematic analysis.Results Majority of participants (86%) accessed the online sessions using a mobile phone from home and health facilities. The median (IQR) time of completing the self-directed component was 16 hours, IQR (8, 30). A multi-disciplinary team comprising of 42% nurse-midwives, 28% doctors, 20% clinical officers and 10% other healthcare professionals completed the BL course. Participants liked the BL approach due to its flexibility in learning, highly educative/relevant content, mixing of health worker cadres and CPD points. Aspects that were noted as challenging were related to personal log-in details and network connectivity issues during the self-directed learning and facilitated virtual sessions respectively.Conclusion The blended learning approach to ANC-PNC in-service training was found to be feasible, cost saving compared to the face-to-face approach and acceptable to health care professionals in LMICs.

Impact of COVID-19 Lockdown Measures on Mother and Child Health – The case of Ghana (preprint)

Background  The lockdown measures in response to the coronavirus disease (COVID-19) have led to a wide range of unintended consequences for women and children. Until the outbreak of COVID-19, attention was on reducing maternal and infant mortality due to pregnancy and delivery complications. The aim of this study was to interrogate the impact of lockdown measures on women and children in two contrasting districts in Ghana – Krobo Odumase and Ayawaso West Wuogon. Methods This study adopted the mixed-method approach using both qualitative and quantitative data. The qualitative study relied on two data collection methods to explore the impacts of COVID-19 control measures on women and children in Ghana. These were: Focus Group Discussions (FGDs; n=12) and Key Informant Interviews (KIIs; n = 18).The study complemented the qualitative data with survey data - household surveys (n = 78) and policy data gathered from government websites consisting of government responses to COVID-19. Results  Engagements with participants in the study revealed that the lockdown measures implemented in Ghana had consequences on child and maternal health, and the health care system as a whole. Our study revealed, for example, that there was a decrease in antenatal and postnatal attendance in hospitals. Childhood vaccinations also came to a halt. Obesity and malnutrition were found to be common among children depending on the location of our study participants (urban and rural areas respectively). Our study also revealed that TB, Malaria and HIV treatment seeking reduced due to the fear of going to health facilities since those ailments manifest similar symptoms as COVID 19. Conclusion  Government responded to COVID-19 using different strategies however the policy response resulted in both intended and unintended consequences especially for women and children in Ghana.  It is recommended that national policy directions should ensure the continuous provision of child and maternal healthcare services which are essential health services during lockdowns.

Discovery of anthelmintic small molecules in the Medicines for Malaria Ventures COVID and Global Health Priority Boxes using an infrared-based assay for Caenorhabditis elegans motility (preprint)

Background: Parasitic nematodes are a public health problem globally, and an economic burden on animal and plant agricultural industries. With their ability to generate drug resistance, new anthelmintic compounds must be constantly sourced. Methods: Using the free-living nematode, Caenorhabditis elegans, in an infrared-based motility assay, we screened 400 compounds from two open-source, small-molecule collections distributed by the Medicines for Malaria Venture, namely, the COVID Box and Global Health Priority Box. The screening assay was first validated for worm number, DMSO concentration and final volume. Results: Primary and secondary (time- and concentration-dependent) screens of both boxes, identified twelve compounds as hits; nine of which were known anthelmintics. Three novel anthelmintic hits, flufenerim, flucofuron and indomethacin were identified with EC50 values ranging from 0.211 to 23.174 M. Counter toxicity screens with HEK293 cells indicated varying degrees of toxicity with EC50 values ranging from 0.453 to >100 M. Conclusions: A C. elegans motility assay was optimized and used to screen two recently-released, small molecule libraries. One or more of these three novel active compounds might serve as starting points for the development of new anthelmintics.

Epidemiological overlaps in COVID-19 and malaria within healthcare and community settings of Southern Ghana (preprint)

Background: COVID-19 disruptions in Africa in 2020-2022 contributed to reductions in malaria control activities including antimalarial surveillance programs. This study investigated the malaria burden and distribution on the background of active transmission of SARS-CoV-2 in Southern Ghana. Specifically, it aimed to identify epidemiological factors that can maximise programmatic control for both diseases, utilising community health education and medical screening (CHEMS). Methods: Between October-December 2022, prospective cross-sectional surveys, with CHEMS were conducted in Greater Accra and Central regions, where 994 participants enrolled either at a hospital or community setting provided demographic and clinical data including history of clinical malaria infection and antimalarial treatment in the past two weeks. Of this study population, 953 provided nasal/throat swabs for COVID-19 RT-PCR testing, with a subset of 136 participants also providing finger-prick blood for malaria RDT testing. Results: The study population comprised of 73.6% adults, with 54.6% COVID-19 vaccination rate. Overall, 18.1% of participants had a history of clinical malaria, which was associated (adjusted odds ratio > 1.50, P-value [≤] 0.022) with COVID-19 symptoms and positivity, study area and hospital setting, suggestive of overlaps in the epidemiological risk for malaria. On a background of widespread SARS-CoV-2 infections (12-37%), malaria parasitaemia was detected in 6%, with 2% being co-infections. Among the malaria positives, 9.5% had a history of antimalarial treatment, which suggested that their infections were recrudescent parasitaemia. Conclusion: The overlaps in the epidemiological risk for malaria and COVID-19 indicate that innovative surveillance programs, with community engagement are needed to maximise control interventions including treatment of asymptomatic malaria infections.

Circulation of SARS-CoV-2 and co-infection with Plasmodium falciparum in Equatorial Guinea (preprint)

The impact of COVID-19 in Africa has been a big concern since the beginning of the pandemic. However, low incidence of COVID-19 case severity and mortality has been reported in many African countries, although data are highly heterogeneous and, in some regions, like Sub-Saharan Africa, very scarce. Many of these regions are also the cradle of endemic infectious diseases like malaria. The aim of this study was to determine the prevalence of SARS-CoV-2, the diversity and origin of circulating variants as well as the frequency of co-infections with malaria in Equatorial Guinea. For this purpose, we conducted antigen diagnostic tests for SARS-CoV-2, and microscopy examinations for malaria of 1,556 volunteers at six health centres in Bioko and Bata from June to October 2021. Nasopharyngeal swab samples were also taken for molecular detection of SARS-CoV-2 by RT-qPCR and whole genome viral sequencing. We report 3.0% of SARS-CoV-2 and 24.4% of malaria prevalence over the sampling in Equatorial Guinea. SARS-CoV-2 cases were found at a similar frequency in all age groups, whereas the age groups most frequently affected by malaria were children (36.8% [95% CI 30.9-42.7]) and teenagers (34.7% [95% CI 29.5-39.9]). We found six cases of confirmed co-infection of malaria and SARS-CoV-2 distributed among all age groups, representing a 0.4% frequency of co-infection in the whole sampled population. Interestingly, the majority of malaria and SARS-CoV-2 co-infections were mild. We obtained the genome sequences of 43 SARS-CoV-2 isolates, most of which belong to the lineage Delta (AY.43) and that according to our pandemic-scale phylogenies were introduced from Europe in multiple occasions (7 transmission groups and 17 unique introductions). This study is relevant in providing first-time estimates of the actual prevalence of SARS-CoV-2 in this malaria-endemic country, with the identification of circulating variants, their origin, and the occurrence of SARS-CoV-2 and malaria co-infection.

Why some countries but not others? Urbanisation, GDP and endemic disease predict global SARS-CoV-2 excess mortality patterns. (preprint)

The global impact of the SARS-CoV-2 pandemic has been uneven, with some regions experiencing significant excess mortality while others have been relatively unaffected. Yet factors which predict this variation remain enigmatic, particularly at large spatial scales. We used spatially explicit Bayesian models that integrate socio-demographic and endemic disease data at the country level to provide robust global estimates of excess SARS-CoV-2 mortality (P scores) for the years 2020 and 2021. We find that gross domestic product (GDP), spatial patterns and urbanization are strong predictors of excess mortality, with countries characterized by low GDP but high urbanization experiencing the highest levels of excess mortality. Intriguingly, we also observed that the prevalence of malaria and human immunodeficiency virus (HIV) are associated with country-level SARS-CoV-2 excess mortality in Africa and the Western Pacific, whereby countries with low HIV prevalence but high malaria prevalence tend to have lower levels of excess mortality. While these associations are correlative in nature at the macro-scale, they emphasize that patterns of endemic disease and socio-demographic factors are needed to understand the global dynamics of SARS-CoV-2.

High rates of SARS-CoV-2 infection in pregnant Ugandan women and association with stunting in infancy (preprint)

Background: SARS-CoV-2 has been well studied in resource-rich areas but many questions remain about effects of infection in African populations, particularly in vulnerable groups such as pregnant women. Methods: We describe SARS-CoV-2 immunoglobulin (Ig) G and IgM antibody responses and clinical outcomes in mother-infant dyads enrolled in malaria chemoprevention trials in Uganda. Results: From December 2020 to February 2022, among 400 unvaccinated pregnant women, serologic assessments revealed that 128 (32%) were seronegative for anti-SARS-CoV-2 IgG and IgM at enrollment and delivery, 80 (20%) were infected either prior to or early in pregnancy, and 192 (48%) were infected or re-infected with SARS-CoV-2 during pregnancy. We observed preferential binding of plasma IgG to Wuhan-Hu-1-like antigens in individuals seroconverting up to early 2021, and to Delta variant antigens in a subset of individuals in mid-2021. Breadth of IgG binding to all variants improved over time. No participants experienced severe respiratory illness during the study. SARS-CoV-2 infection in early pregnancy was associated with lower median length-for-age Z-score at age 3 months compared with no infection or late pregnancy infection (-1.54 versus -0.37 and -0.51, p=0.009). Conclusion: Pregnant Ugandan women experienced high levels of SARS-CoV-2 infection without severe respiratory illness. Variant-specific serology testing demonstrated evidence of antibody affinity maturation at the population level. Early gestational SARS-CoV-2 infection was associated with shorter stature in early infancy.

Malaria and COVID-19 coinfection in a non-malaria-endemic area in Brazil.

Differential diagnosis of coronavirus disease 2019 (COVID-19) from other febrile diseases is one of several challenges imposed by the pandemic. We present a case of severe malaria and COVID-19 coinfection in a non-malaria-endemic region. A 44-year-old female with malaise, fever, hypotension, jaundice, and enlarged liver and spleen was admitted to the intensive care unit. Reverse transcription-quantitative PCR results for severe acute respiratory syndrome coronavirus 2 were positive. Rapid tests, microscopy, and quantitative PCR were positive for Plasmodium vivax. Cytokine storm profiles were identified. We could not determine whether the severe vivax malaria in our patient was triggered by COVID-19 coinfection.

Imported malaria from land bordering countries in China: A challenge in preventing the reestablishment of malaria transmission.

OBJECTIVE: No indigenous malaria cases have been reported since 2017 in China, but a large number of imported cases are still reported every year, including those from the land bordering countries. To characterize their epidemiological profiles will provide evidence for the development of appropriate strategies to effectively address the challenges of border malaria in the post-elimination phase. METHODS: Individual-level data of imported malaria cases from the land bordering countries were collected from 2017 to 2021 in China via the web-based surveillance systems, and analyzed by SPSS, ArcGIS and WPS software, to explore their epidemiological profiles. RESULTS: A total of 1170 malaria cases imported into China from six of the fourteen land bordering countries were reported between 2017 and 2021 with a decline trend. Overall, cases were widely distributed in 31-97 counties from 11 to 21 provinces but mainly in Yunnan. Moreover, these imported cases were mainly infected with P. vivax (94.8%), and a total of 68 recurrent cases were reported in 6-14 counties from 4 to 8 provinces. In addition, nearly 57.1% of the total reported cases could seek healthcare within 2 days of getting sick, and 71.3% of the reported cases could be confirmed as malaria on the day they sought medical care. CONCLUSIONS: China still needs to attach great importance to the risk and challenge of the imported malaria from bordering countries particularly from Myanmar in preventing reestablishment of malaria transmission in the post-elimination phase. It is necessary not only to strengthen collaboration and cooperation with the bordering countries, but also coordinate multiple departments at home to improve malaria surveillance and response system and prevent the reestablishment of malaria transmission in China.

Effect of voluntary human mobility restrictions on vector-borne diseases during the COVID-19 pandemic in Japan: A descriptive epidemiological study using a national database (2016 to 2021).

The coronavirus disease 2019 (COVID-19) pandemic not only encouraged people to practice good hygiene but also caused behavioral inhibitions and resulted reduction in both endemic and imported infectious diseases. However, the changing patterns of vector-borne diseases under human mobility restrictions remain unclear. Hence, we aimed to investigate the impact of transborder and local mobility restrictions on vector-borne diseases through a descriptive epidemiological study. The analysis was conducted using data from the National Epidemiological Surveillance of Infectious Diseases system in Japan. We defined the pre-pandemic period as the period between the 1st week of 2016 to the 52nd week of 2019 and defined the pandemic period as from the 1st week of 2020 to the 52nd week of 2021, with the assumption that human mobility was limited throughout the pandemic period. This study addressed 24 diseases among notifiable vector borne diseases. Datasets were obtained from weekly reports from the National Epidemiological Surveillance of Infectious Diseases, and the incidence of each vector-borne disease was examined. Interrupted time series analysis was conducted on the epidemic curves for the two periods. Between the pre- and post-pandemic periods, the incidence of dengue fever and malaria significantly decreased, which may be related to limited human transboundary mobility (p = 0.003/0.002). The incidence of severe fever with thrombocytopenia syndrome, scrub typhus, and Japanese spotted fever did not show changes between the two periods or no association with human mobility. This study suggests that behavioral control may reduce the incidence of new mosquito-borne diseases from endemic areas but may not affect tick-borne disease epidemics within an endemic area.

Rectal artesunate for severe malaria, implementation research, Zambia.

Objective: To determine whether the positive results of a single-district pilot project focused on rectal artesunate administration at the community level in Zambia could be replicated on a larger scale. Methods: In partnership with government, in 10 rural districts during 2018-2021 we: (i) trained community health volunteers to administer rectal artesunate to children with suspected severe malaria and refer them to a health facility; (ii) supported communities to establish emergency transport, food banks and emergency savings to reduce referral delays; (iii) ensured adequate drug supplies; (iv) trained health workers to treat severe malaria with injectable artesunate; and (v) monitored severe malaria cases and associated deaths via surveys, health facility data and a community monitoring system. Results: Intervention communities accessed quality-assured rectal artesunate from trained community health volunteers, and follow-on treatment for severe malaria from health workers. Based on formal data from the health management information system, reported deaths from severe malaria reduced significantly from 3.1% (22/699; 95% confidence interval, CI: 2.0-4.2) to 0.5% (2/365; 95% CI: 0.0-1.1) in two demonstration districts, and from 6.2% (14/225; 95% CI: 3.6-8.8) to 0.6% (2/321; 95% CI: 0.0-1.3) in eight scale-up districts. Conclusion: Despite the effects of the coronavirus disease, our results confirmed that pre-referral rectal artesunate administered by community health volunteers can be an effective intervention for severe malaria among young children. Our results strengthen the case for wider expansion of the pre-referral treatment in Zambia and elsewhere when combined with supporting interventions.

COVID-19 Coinfection with Malaria and Its Presentation with Bilateral Pleural Effusion: A Case Report and Literature Review (preprint)

Background There could be misdiagnosis of COVID 19 for malaria and vice versa because of their similar presentation, particularly when clinician relies mainly on symptoms. Coinfection with COVID-19 and malaria is associated with increased all-cause in-hospital mortality compared to isolated infection with SARS-CoV-2. Presentation with pleural effusion adds another challenge in the diagnosis of COVID-19.Case summary: This is a 57-year-old woman who presented with symptoms of acute febrile illness associated with shortness of breath and cough. Physical examination was remarkable for fever, hypotension, tachycardia, tachypnea, desaturation, decreased air entry and dullness over bilateral lower 1/3rd of the chest. Upon investigations, she was found to have ring-form trophozoites of plasmodium falciparum and bilateral ground glass opacities, bilateral consolidations and bilateral pleural effusions. She was managed with supportive treatments, antimalarial agents and antibiotics. COVID-19 was diagnosed late due to the initial high diagnostic inertia.Conclusion Clinicians should be aware of the possibility of COVID-19 in any patient who presents with acute febrile illness or respiratory complaints like shortness of breath and cough. In patients with symptoms such as fever, fatigue, and headache, both malaria and COVID-19 tests should always be performed. Though pleural effusion is rarely reported in COVID-19 patients, viral etiologies like COVID-19 should be considered if alternative diagnoses are lacking.

Is TNF alpha a mediator in the co-existence of malaria and type 2 diabetes in a malaria endemic population?

Malaria remains a disease of public health importance globally, especially in sub-Saharan Africa. Malaria deaths reduced globally steadily between 2000-2019, however there was a 10% increase in 2020 due to disruptions in medical service during the COVID-19 pandemic. Globally, about 96% of malaria deaths occurred in 29 countries; out of which, four countries (Nigeria, the Democratic Republic of the Congo, the Niger, and the United Republic of Tanzania) accounted for just over half of the malaria deaths. Nigeria leads the four countries with the highest malaria deaths (accounting for 31% globally). Parallelly, sub-Saharan Africa is faced with a rise in the incidence of Type 2 diabetes (T2D). Until recently, T2D was a disease of adulthood and old age. However, this is changing as T2D in children and adolescents is becoming an increasingly important public health problem. Nigeria has been reported to have the highest burden of diabetes in Africa with a prevalence of 5.77% in the country. Several studies conducted in the last decade investigating the interaction between malaria and T2D in developing countries have led to the emergence of the intra-uterine hypothesis. The hypothesis has arisen as a possible explanation for the rise of T2D in malaria endemic areas; malaria in pregnancy could lead to intra-uterine stress which could contribute to low birth weight and may be a potential cause of T2D later in life. Hence, previous, and continuous exposure to malaria infection leads to a higher risk of T2D. Current and emerging evidence suggests that an inflammation-mediated link exists between malaria and eventual T2D emergence. The inflammatory process thus, is an important link for the co-existence of malaria and T2D because these two diseases are inflammatory-related. A key feature of T2D is systemic inflammation, characterized by the upregulation of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) which leads to impaired insulin signaling. Malaria infection is an inflammatory disease in which TNF-α also plays a major role. TNF-α plays an important role in the pathogenesis and development of malaria and T2D. We therefore hypothesize that TNF-α is an important link in the increasing co-existence of T2D.