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.

Early effects of COVID-19 on maternal and child health service disruption in Mozambique.

This article is part of the Research Topic 'Health Systems Recovery in the Context of COVID-19 and Protracted Conflict'. Introduction: After the World Health Organization declared COVID-19 a pandemic, more than 184 million cases and 4 million deaths had been recorded worldwide by July 2021. These are likely to be underestimates and do not distinguish between direct and indirect deaths resulting from disruptions in health care services. The purpose of our research was to assess the early impact of COVID-19 in 2020 and early 2021 on maternal and child healthcare service delivery at the district level in Mozambique using routine health information system data, and estimate associated excess maternal and child deaths. Methods: Using data from Mozambique's routine health information system (SISMA, Sistema de Informação em Saúde para Monitoria e Avaliação), we conducted a time-series analysis to assess changes in nine selected indicators representing the continuum of maternal and child health care service provision in 159 districts in Mozambique. The dataset was extracted as counts of services provided from January 2017 to March 2021. Descriptive statistics were used for district comparisons, and district-specific time-series plots were produced. We used absolute differences or ratios for comparisons between observed data and modeled predictions as a measure of the magnitude of loss in service provision. Mortality estimates were performed using the Lives Saved Tool (LiST). Results: All maternal and child health care service indicators that we assessed demonstrated service delivery disruptions (below 10% of the expected counts), with the number of new users of family planing and malaria treatment with Coartem (number of children under five treated) experiencing the largest disruptions. Immediate losses were observed in April 2020 for all indicators, with the exception of treatment of malaria with Coartem. The number of excess deaths estimated in 2020 due to loss of health service delivery were 11,337 (12.8%) children under five, 5,705 (11.3%) neonates, and 387 (7.6%) mothers. Conclusion: Findings from our study support existing research showing the negative impact of COVID-19 on maternal and child health services utilization in sub-Saharan Africa. This study offers subnational and granular estimates of service loss that can be useful for health system recovery planning. To our knowledge, it is the first study on the early impacts of COVID-19 on maternal and child health care service utilization conducted in an African Portuguese-speaking country.

Tropical infections as occupational diseases among young volunteers in social projects.

PURPOSE: The trend of volunteering overseas has increased tremendously over the last decade. Volunteers often go to regions where they are exposed to the risk of tropical infections like malaria, dengue, typhoid fever and schistosomiasis. Health assessments have shown a high occurrence of tropical infections among young volunteers. Such tropical infections are notifiable in Germany, as they are covered by a separate branch of the social insurance system. However, there is still limited data on systematical improvement of medical prevention and health care for volunteers. METHODS: This retrospective study included 457 cases with a diagnosis for a tropical infection or typhoid fever from January 2016 to December 2019. Data sets were anonymised and then analysed with descriptive statistics first. Cases of volunteers sent abroad by "Weltwärts" were compared to cases of aid workers sent to non-industrial countries. RESULTS: A high occurrence of tropical infections as occupational diseases has been shown for volunteers compared to other (mostly older) aid workers being sent to tropical regions. The risk of acquiring a tropical infection was significantly higher in Africa compared to other tropical regions. Cases of malaria were reported significantly more often among the group of volunteers than among aid workers during the period under review. Medical check-ups after travel were rare among volunteers. CONCLUSIONS: Data imply a disproportionate risk for malaria in Africa with a higher risk of acquiring malaria tropica in Sub-Saharan regions. Region-specific risks need to be addressed in training seminars in order to raise awareness among young volunteers before travel. Medical examinations after travel should be mandatory and specific to a particular region.

1-3-7 surveillance and response approach in malaria elimination: China's practice and global adaptions.

There has been a significant reduction in malaria morbidity and mortality worldwide from 2000 to 2019. However, the incidence and mortality increased again in 2020 due to the disruption to services during the COVID-19 pandemic. Surveillance to reduce the burden of malaria, eliminate the disease and prevent its retransmission is, therefore, crucial. The 1-3-7 approach proposed by China has played an important role in eliminating malaria, which has been internationally popularized and adopted in some countries to help eliminate malaria. This review summarizes the experience and lessons of 1-3-7 approach in China and its application in other malaria-endemic countries, so as to provide references for its role in eliminating malaria and preventing retransmission. This approach needs to be tailored and adapted according to the region condition, considering the completion, timeliness and limitation of case-based reactive surveillance and response. It is very important to popularize malaria knowledge, train staff, improve the capacity of health centres and monitor high-risk groups to improve the performance in eliminating settings. After all, remaining vigilance in detecting malaria cases and optimizing surveillance and response systems are critical to achieving and sustaining malaria elimination.

Attractive targeted sugar bait phase III trials in Kenya, Mali, and Zambia.

BACKGROUND: Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) target night-time indoor biting mosquitoes and effectively reduce malaria transmission in rural settings across Africa, but additional vector control tools are needed to interrupt transmission. Attractive targeted sugar baits (ATSBs) attract and kill mosquitoes, including those biting outdoors. Deployment of ATSBs incorporating the insecticide dinotefuran was associated with major reductions in mosquito density and longevity in Mali. The impact of this promising intervention on malaria transmission and morbidity now needs to be determined in a range of transmission settings. METHODS/DESIGN: We will conduct three similar stand-alone, open-label, two-arm, cluster-randomized, controlled trials (cRCTs) in Mali, Kenya, and Zambia to determine the impact of ATSB + universal vector control versus universal vector control alone on clinical malaria. The trials will use a "fried-egg" design, with primary outcomes measured in the core area of each cluster to reduce spill-over effects. All household structures in the ATSB clusters will receive two ATSBs, but the impact will be measured in the core of clusters. Restricted randomization will be used. The primary outcome is clinical malaria incidence among children aged 5-14 years in Mali and 1-14 years in Kenya and Zambia. A key secondary outcome is malaria parasite prevalence across all ages. The trials will include 76 clusters (38 per arm) in Mali and 70 (35 per arm) in each of Kenya and Zambia. The trials are powered to detect a 30% reduction in clinical malaria, requiring a total of 3850 person-years of follow-up in Mali, 1260 person-years in Kenya, and 1610 person-years in Zambia. These sample sizes will be ascertained using two seasonal 8-month cohorts in Mali and two 6-month seasonal cohorts in Zambia. In Kenya, which has year-round transmission, four 6-month cohorts will be used (total 24 months of follow-up). The design allows for one interim analysis in Mali and Zambia and two in Kenya. DISCUSSION: Strengths of the design include the use of multiple study sites with different transmission patterns and a range of vectors to improve external validity, a large number of clusters within each trial site, restricted randomization, between-cluster separation to minimize contamination between study arms, and an adaptive trial design. Noted threats to internal validity include open-label design, risk of contamination between study arms, risk of imbalance of covariates across study arms, variation in durability of ATSB stations, and potential disruption resulting from the COVID-19 pandemic. TRIAL REGISTRATION: Zambia: ClinicalTrials.gov NCT04800055 . Registered on March 15, 2021 Mali: ClinicalTrials.gov NCT04149119 . Registered on November 4, 2019 Kenya: ClinicalTrials.gov NCT05219565 . Registered on February 2, 2022.

Outcomes of childhood severe malaria: a comparative of study pre-COVID-19 and COVID-19 periods.

BACKGROUND: The collateral damages from measures adopted to mitigate the coronavirus disease 2019 (COVID-19) pandemic have been projected to negatively impact malaria in sub-Saharan Africa. Herein, we compare the prevalence and outcomes of childhood severe malaria during the pre-COVID-19 and COVID-19 periods at a tertiary health facility in Nigeria. METHODS: This was a retrospective review of cases of severe malaria admitted from 1st January to 31st December 2019 (pre-COVID-19 period) and 1st January to 31st December 2020 (COVID-19 period). We extracted relevant information, including demographics, the duration of symptoms before presentation, forms of severe malaria, and outcomes of hospitalization (discharged or death). RESULTS: In the pre-COVID-19 period, there were a total of 2312 admissions to the EPU and 1685 in the COVID-19 period, representing a decline of 27%. In contrast, there were 263 and 292 severe malaria admissions in the pre-COVID-19 and COVID-19 periods, respectively, representing an 11% increase in the absolute number of cases. The prevalence rates were 11.4% in the pre-COVID-19 period and 17.3% in the COVID-19 period, representing an increase of 52% in the percentage differences. The mortality rate in the COVID-19 period was higher than the pre-COVID-19 period ([10.3%; 30/292 vs. 2.3%; 6/263], p 0.001). The death rate increased by 350% during the COVID-19 period. The odds ratio (OR) of a child dying from severe malaria in the COVID-19 era was 4.9 [95% confidence interval (CI): 2.008 to 11.982]. In the COVID-19 era, presentation at a health facility was also delayed (p = 0.029), as were the odds of multiple features of severe malaria manifestations (OR-1.9, 95% CI, 1.107 to 3.269; p = 0.020). CONCLUSION: This study shows that the prevalence of severe childhood malaria increased by as much as 11.0%, with a disproportionate increase in mortality compared to the pre-pandemic level. Most children with severe malaria presented late with multiple features of severe malaria, probably contributing to the poor hospitalization outcomes (death) observed in this study.

Determinants of malaria infections among children in refugee settlements in Uganda during 2018-2019.

BACKGROUND: While 5% of 247 million global malaria cases are reported in Uganda, it is also a top refugee hosting country in Africa, with over 1.36 million refugees. Despite malaria being an emerging challenge for humanitarian response in refugee settlements, little is known about its risk factors. This study aimed to investigate the risk factors for malaria infections among children under 5 years of age in refugee settlements in Uganda. METHODS: We utilized data from Uganda's Malaria Indicator Survey which was conducted between December 2018 and February 2019 at the peak of malaria season. In this national survey, household level information was obtained using standardized questionnaires and a total of 7787 children under 5 years of age were tested for malaria using mainly the rapid diagnostic test. We focused on 675 malaria tested children under five in refugee settlements located in Yumbe, Arua, Adjumani, Moyo, Lamwo, Kiryadongo, Kyegegwa, Kamwenge and Isingiro districts. The extracted variables included prevalence of malaria, demographic, social-economic and environmental information. Multivariable logistic regression was used to identify and define the malaria associated risk factors. RESULTS: Overall, malaria prevalence in all refugee settlements across the nine hosting districts was 36.6%. Malaria infections were higher in refugee settlements located in Isingiro (98.7%), Kyegegwa (58.6%) and Arua (57.4%) districts. Several risk factors were significantly associated with acquisition of malaria including fetching water from open water sources [adjusted odds ratio (aOR) = 1.22, 95% CI: 0.08-0.59, P = 0.002], boreholes (aOR = 2.11, 95% CI: 0.91-4.89, P = 0.018) and water tanks (aOR = 4.47, 95% CI: 1.67-11.9, P = 0.002). Other factors included pit-latrines (aOR = 1.48, 95% CI: 1.03-2.13, P = 0.033), open defecation (aOR = 3.29, 95% CI: 1.54-7.05, P = 0.002), lack of insecticide treated bed nets (aOR = 1.15, 95% CI: 0.43-3.13, P = 0.003) and knowledge on the causes of malaria (aOR = 1.09, 95% CI: 0.79-1.51, P = 0.005). CONCLUSIONS: The persistence of the malaria infections were mainly due to open water sources, poor hygiene, and lack of preventive measures that enhanced mosquito survival and infection. Malaria elimination in refugee settlements requires an integrated control approach that combines environmental management with other complementary measures like insecticide treated bed nets, indoor residual spraying and awareness.

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.

Effect of large-scale mass drug administration for malaria on mortality and morbidity in Angumu health zone, Ituri, Democratic Republic of Congo.

BACKGROUND: Angumu health zone in Ituri, Democratic Republic of Congo, is a highly malaria-endemic area with an overburdened health system and hosting internally displaced persons (IDP). The World Health Organization recommends mass drug administration (MDA) for malaria in complex emergencies. Therefore, three MDA rounds were implemented by Ministry of Public Health and Médecins sans Frontières from September 2020 to January 2021 in four health areas selected for epidemiological (high malaria incidence) and logistic reasons. Reported mortality and morbidity were compared in locations where MDA has been performed and locations where it has not. METHODS: A non-randomized controlled population-based retrospective mortality survey was conducted in March 2021. Two-stage cluster sampling was used in villages; all IDP sites were surveyed with systematic random sampling. The main (mortality rates) and secondary (morbidity) outcomes were estimated and compared between locations where MDA had been conducted and where it had not, using mixed Poisson and binomial regression models respectively. RESULTS: Data was collected for 2554 households and 15470 individuals, of whom 721 died in the 18-month recall period. The under-five mortality rate (U5MR) decreased in the locations where MDA had been implemented from 2.32 [1.48-3.16] "before" the MDA to 1.10 [0.5-1.71] deaths/10,000 children under 5 years/day "after", whereas it remained stable from 2.74 [2.08-3.40] to 2.67 [1.84-3.50] deaths/10,000 children/day in the same time periods in locations where MDA had not been implemented. The U5MR and malaria-specific mortality was significantly higher in non-MDA locations after MDA was implemented (aRR = 2.17 [1.36-3.49] and 2.60 [1.56-4.33], respectively, for all-cause and malaria-specific mortality among children < 5 years). Morbidity (all age and < 5 years, all cause or malaria-specific) appeared lower in MDA locations 2.5 months after last round: reported malaria-specific morbidity was 14.7% [11-18] and 25.0% [19-31] in villages and IDP sites where MDA had been implemented, while it was 30.4% [27-33] and 49.3% [45-54] in villages and IDP sites with no MDA. CONCLUSIONS: Despite traditional limitations associated with non-randomized controlled retrospective surveys, the documented sharp decrease of under-5 mortality and morbidity shows that MDA has the potential to become an important malaria-control tool in emergency settings. Based on these results, new MDA rounds, along with indoor residual spraying campaigns, have been planned in the health zone in 2022. A set of surveys will be conducted before, during and after these rounds to confirm the effect observed in 2021 and assess its duration.

Spatio-Temporal Bayesian Models for Malaria Risk Using Survey and Health Facility Routine Data in Rwanda.

INTRODUCTION: Malaria is a life-threatening disease ocuring mainly in developing countries. Almost half of the world's population was at risk of malaria in 2020. Children under five years age are among the population groups at considerably higher risk of contracting malaria and developing severe disease. Most countries use Demographic and Health Survey (DHS) data for health programs and evaluation. However, malaria elimination strategies require a real-time, locally-tailored response based on malaria risk estimates at the lowest administrative levels. In this paper, we propose a two-step modeling framework using survey and routine data to improve estimates of malaria risk incidence in small areas and enable quantifying malaria trends. METHODS: To improve estimates, we suggest an alternative approach to modeling malaria relative risk by combining information from survey and routine data through Bayesian spatio-temporal models. We model malaria risk using two steps: (1) fitting a binomial model to the survey data, and (2) extracting fitted values and using them in the Poison model as nonlinear effects in the routine data. We modeled malaria relative risk among under-five-year old children in Rwanda. RESULTS: The estimation of malaria prevalence among children who are under five years old using Rwanda demographic and health survey data for the years 2019-2020 alone showed a higher prevalence in the southwest, central, and northeast of Rwanda than the rest of the country. Combining with routine health facility data, we detected clusters that were undetected based on the survey data alone. The proposed approach enabled spatial and temporal trend effect estimation of relative risk in local/small areas in Rwanda. CONCLUSIONS: The findings of this analysis suggest that using DHS combined with routine health services data for active malaria surveillance may provide provide more precise estimates of the malaria burden, which can be used toward malaria elimination targets. We compared findings from geostatistical modeling of malaria prevalence among under-five-year old children using DHS 2019-2020 and findings from malaria relative risk spatio-temporal modeling using both DHS survey 2019-2020 and health facility routine data. The strength of routinely collected data at small scales and high-quality data from the survey contributed to a better understanding of the malaria relative risk at the subnational level in Rwanda.

International modified Delphi study on malaria preventive behaviour: new themes, contexts and framework for future research on Plasmodium knowlesi malaria.

INTRODUCTION: Plasmodium knowlesi malaria is a non-human simian malaria that threatens Southeast Asian rural communities. Studies indicate that non-compliant bednet usage, travelling into the forest and working as farmers and rubber tappers put communities at risk for infection. Despite guidelines, malaria incidence increases yearly and has become a public health concern. In addition to research gaps addressing factors that influence malaria prevention behaviour in these communities, there are no specific guidelines to facilitate strategies against the threat of P. knowlesi malaria. METHOD: To examine potential factors that influence malaria-prevention behaviour in communities exposed to P. knowlesi malaria, 12 malaria experts participated in a modified Delphi study; every participant maintained their anonymity throughout the study. Three Delphi rounds were conducted via different online platforms between 15 November 2021 and 26 February 2022, and consensus was achieved when 70% of the participants agreed on a particular point with a 4-5 median. The results from the open-ended questions were then subjected to thematic analysis, and the dataset generated by this study was analysed using a deductive and inductive approach. RESULTS: After a systematic, iterative process, knowledge and belief, social support, cognitive and environmental factors, past experience as a malaria patient, and the affordability and feasibility of a given intervention were critical contributors to malaria-prevention behaviour. CONCLUSION: Future research on P. knowlesi malaria could adapt this study's findings for a more nuanced understanding of factors that influence malaria-prevention behaviour and improve P. knowlesi malaria programmes based on the expert consensus.

The effect of the COVID-19 lockdown on malaria transmission in South Africa.

BACKGROUND: For a country such as South Africa which is targeting malaria elimination, mobile and migrant populations pose a substantial risk to importation of malaria parasites. It has been hypothesized that halting cross-border movement of mobile and migrant populations will decrease the importation of malaria, however this option is not a politically, operationally, and financially viable prospect. It has social impacts as well, since families live on either side of the border and preventing travel will challenge family ties. Due to the COVID-19 pandemic and closure of ports of entry (land and air) for non-essential travel into South Africa, a unique opportunity arose to test the hypothesis. METHODOLOGY: An interrupted time series analysis was done to assess whether the post-lockdown trends (April-December 2020) in monthly reported imported and local cases differed from the pre-lockdown trends (January 2015-March 2020). The analysis was conducted separately for KwaZulu-Natal, Mpumalanga, and Limpopo provinces. RESULTS: On average, imported cases were lower in the post-intervention period in all three provinces, and local cases were lower in Mpumalanga and Limpopo, though no results were statistically significant. CONCLUSION: Since population movement continued after the travel restrictions were lifted, border screening with testing and treating should be considered for reducing parasite movement. Another option is reducing malaria cases at the source in neighbouring countries by implementing proven, effective vector and parasite control strategies and through a downstream effect reduce malaria entering South Africa.

Evaluation of the model malaria elimination strategy in Mandla district along with its neighbouring districts: a time series analysis from 2008 to 2020.

BACKGROUND: Compared to 2017, India achieved a significant reduction in malaria cases in 2020. Madhya Pradesh (MP) is a tribal dominated state of India with history of high malaria burden in some districts. District Mandla of MP state showed a considerable decline in malaria cases between 2000 and 2013, except in 2007. Subsequently, a resurgence of malaria cases was observed during 2014 and 2015. The Malaria Elimination Demonstration Project (MEDP) was launched in 2017 in Mandla with the goal to achieve zero indigenous malaria cases. This project used: (1) active surveillance and case management using T4 (Track fever, Test fever, Treat patient, and Track patient); (2) vector control using indoor residual sprays and long-lasting insecticidal nets; (3) information education communication and behaviour change communication; and (4) regular monitoring and evaluation with an emphasis on operational and management accountability. This study has investigated malaria prevalence trends from 2008 to 2020, and has predicted trends for the next 5 years for Mandla and its bordering districts. METHODS: The malaria prevalence data of the district Mandla for the period of January 2008 to August 2017 was obtained from District Malaria Office (DMO) Mandla and data for the period of September 2017 to December 2020 was taken from MEDP data repository. Further, the malaria prevalence data for the period of January 2008 to December 2020 was collected from DMOs of the neighbouring districts of Mandla. A univariate time series and forecast analysis was performed using seasonal autoregressive integrated moving average model. FINDINGS: Malaria prevalence in Mandla showed a sharp decline [- 87% (95% CI - 90%, - 84%)] from 2017 to 2020. The malaria forecast for Mandla predicts zero cases in the next 5 years (2021-2025), provided current interventions are sustained. By contrast, the model has forecasted a risk of resurgence of malaria in other districts in MP (Balaghat, Dindori, Jabalpur, Seoni, and Kawardha) that were not the part of MEDP. CONCLUSION: The interventions deployed as part of MEDP have resulted in a sustainable zero indigenous malaria cases in Mandla. Use of similar strategies in neighbouring and other malaria-endemic districts in India could achieve similar results. However, without adding extra cost to the existing intervention, sincere efforts are needed to sustain these interventions and their impact using accountability framework, data transparency, and programme ownership from state to district level.

Barriers against and strategies for malaria control during the COVID-19 pandemic in low- and middle-income countries: a systematic review.

BACKGROUND: The COVID-19 pandemic has disrupted malaria control activities globally. Notably, high levels of excess malaria morbidity and mortality in low- and middle-income countries (LMICs) were reported. Although it is crucial to systematically understand the main causes of the disruption to malaria control and synthesize strategies to prepare for future pandemics, such studies are scarce. Therefore, this study aims to better identify barriers against and strategies for malaria control. METHODS: Following the PRISMA guidelines and through searches of electronic databases and Google Scholar, a systematic literature review was conducted to identify studies pertaining to malaria control published between January 2020 and December 2021. Only studies that discussed reported barriers and/or strategies related to malaria were included for the review. The Mixed Methods Quality Appraisal Tool (MMAT) and the Authority, Accuracy, Coverage, Objectivity, Date and Significance (AACODS) checklist were used for quality appraisal. Key information such as literature type, study design, setting and population, interventions, outcomes, barriers, and strategies were extracted. With an existing framework of four dimensions (accessibility, affordability, availability, and acceptability) further subdivided by the supply and demand sides, this study synthesized information on barriers and strategies related to malaria control and further categorized the strategies based on the time frame. RESULTS: From the 30 selected studies, 27 barriers and 39 strategies were identified. The lockdown measures, which mainly threatened geographic accessibility and availability of malaria control services, were identified to be the main barrier hindering effective mobilization of community health workers and resources. Among the identified strategies, clear risk communication strategies would alleviate psychosocial barriers, which challenged acceptability. Some strategies that cross-cut points across all four dimensions would, require systems-level integration to enhance availability and affordability of malaria control. The strategies were distinguished between short-term, for instant response, and mid to long-term for future readiness. CONCLUSIONS: The pandemic resulted in complex barriers to malaria control, particularly imposing a double burden on LMICs. Identifying strategies to overcome said barriers provides useful insights in the decision-making processes for the current and future pandemic. Cross-cutting strategies that integrate all dimensions need to be considered. Health system strengthening and resilience strategy appropriate for country-specific context is fundamental.

Malaria and the incidence of COVID-19 in Africa: an ecological study.

BACKGROUND: It has been shown that stimulation of innate immunity may provide temporary protection against a variety of infectious diseases. Malaria has been shown to induce a robust innate immune response. This study was conducted to test the hypothesis that if the cumulative number of cases diagnosed with COVID-19 per 100,000 population was correlated with the prevalence of malaria in African countries where both malaria and COVID-19 were prevalent. METHODS: In this ecological study, the cumulative incidence of COVID-19 and the prevalence of malaria were compared in 53 African countries. A negative binomial regression analysis with the cumulative incidence of COVID-19 as the dependent variable, and the human development index (HDI) and the prevalence of malaria, as independent variables, were used. RESULTS: The mean cumulative incidence of COVID-19 was 522 cases per 100,000. Each 0.1 unit increase in HDI was associated with 2.4-fold (95% confidence interval 1.8-3.1) increase in the cumulative incidence of COVID-19. Prevalence of malaria was also independently associated with the cumulative incidence; each 10% increase in the prevalence was associated with 28% (10-41%) decrease in the cumulative incidence of COVID-19. CONCLUSIONS: Malaria might protect people against SARS-CoV-2 through the stimulation of innate immunity. Stimulation of the innate immune system could be the first line of defense in the pandemic preparedness arsenal.

Universal two-dimensional labelled probe-mediated melting curve analysis based on multiplex PCR for rapid typing of Plasmodium in a single closed tube.

Currently, malaria is still one of the major public health problems commonly caused by the four Plasmodium species. The similar symptoms of malaria and the COVID-19 epidemic of fever or fatigue lead to frequent misdiagnosis. The disadvantages of existing detection methods, such as time-consuming, costly, complicated operation, need for experienced technicians, and indistinguishable typing, lead to difficulties in meeting the clinical requirements of rapid, easy, and accurate typing of common Plasmodium species. In this study, we developed and optimized a universal two-dimensional labelled probe-mediated melting curve analysis (UP-MCA) assay based on multiplex and asymmetric PCR for rapid and accurate typing of five Plasmodium species, including novel human Plasmodium, Plasmodium knowlesi (Pk), in a single closed tube following genome extraction. The assay showed a limit of detection (LOD) of 10 copies per reaction and could accurately distinguish Plasmodium species from intra-plasmodium and other pathogens. Additionally, we proposed and validated different methods of fluorescence quenching and tag design for probes that are suitable for UP-MCA assays. Moreover, the clinical performance of the Plasmodium UP-MCA assay using a base-quenched universal probe was evaluated using 226 samples and showed a sensitivity of 100% (164/164) and specificity of 100% (62/62) at a 99% confidence interval, with the microscopy method as the gold standard. In summary, the UP-MCA assay showed excellent sensitivity, specificity, and accuracy for genotyping Plasmodium species spp. Additionally, it facilitates convenient and rapid Plasmodium detection in routine clinical practice and has great potential for clinical translation.

Millions of excess cases and thousands of excess deaths of malaria occurred globally in 2020 during the COVID-19 pandemic.

Background: The COVID-19 pandemic disrupted malaria-related health care services, leading to an excess burden of malaria. However, there is a lack of research on the indirect global impact of the COVID-19 pandemic on malaria. We aimed to assess the excess burden of malaria due to the COVID-19 pandemic in malaria-endemic countries in 2020. Methods: Based on data from the World Health Organization Global Observatory, we used estimated annual percentage changes (EAPCs) from 2000 to 2019 (model A) and from 2015 to 2019 (model B) to predict the malaria burden in 2020. We calculated the ratios between reported and predicted malaria incidence (incidence rate ratio (IRR)) and mortality rates (mortality rate ratio (MRR)). Results: In 2020, African countries suffered the most from malaria, with the largest number of malaria cases (64.7 million) and deaths (151 thousand) observed in Nigeria. Most countries showed a decrease in malaria incidence and mortality rates from 2000 to 2019, with the strongest decline in incidence rates in Bhutan (EAPC = -35.7%, 95% CI = -38.7 to -32.5%) and mortality rates Ecuador (EAPC = -40.6%, 95% confidence interval (CI) = -46.6 to -33.8%). During the COVID-19 pandemic in 2020, there was a total of 18 million excess malaria cases and 83 291 excess deaths per model A, and 7.4 million excess cases and 33 528 excess deaths per model B globally. Malaria incidence rates increased excessively in over 50% of the malaria-endemic countries, with the greatest increase in Costa Rica (IRR = 35.6) per model A and Bhutan (IRR = 15.6) per model B. Mortality rates had increased excessively in around 70% of the malaria-endemic countries, with the greatest increase in Ecuador in both model A (MRR = 580) and model B (MRR = 58). Conclusions: The emergence of the COVID-19 pandemic indirectly caused an increase in the prevalence of malaria and thwarted progress in malaria control. Global efforts to control the pandemic's impact should be balanced with malaria control to ensure that the goal for global malaria elimination is achieved on time.

Prevalence of SARS-CoV-2 and co-infection with malaria during the first wave of the pandemic (the Burkina Faso case).

Africa accounts for 1.5% of the global coronavirus disease 2019 (COVID-19) cases and 2.7% of deaths, but this low incidence has been partly attributed to the limited testing capacity in most countries. In addition, the population in many African countries is at high risk of infection with endemic infectious diseases such as malaria. Our aim is to determine the prevalence and circulation of SARS-CoV-2 variants, and the frequency of co-infection with the malaria parasite. We conducted serological tests and microscopy examinations on 998 volunteers of different ages and sexes in a random and stratified population sample in Burkina-Faso. In addition, nasopharyngeal samples were taken for RT-qPCR of SARS-CoV-2 and for whole viral genome sequencing. Our results show a 3.2 and a 2.5% of SARS-CoV-2 seroprevalence and PCR positivity; and 22% of malaria incidence, over the sampling period, with marked differences linked to age. Importantly, we found 8 cases of confirmed co-infection and 11 cases of suspected co-infection mostly in children and teenagers. Finally, we report the genome sequences of 13 SARS-CoV-2 isolates circulating in Burkina Faso at the time of analysis, assigned to lineages A.19, A.21, B.1.1.404, B.1.1.118, B.1 and grouped into clades; 19B, 20A, and 20B. This is the first population-based study about SARS-CoV-2 and malaria in Burkina Faso during the first wave of the pandemic, providing a relevant estimation of the real prevalence of SARS-CoV-2 and variants circulating in this Western African country. Besides, it highlights the non-negligible frequency of co-infection with malaria in African communities.

Malaria, HIV and Malnutrition among Internally Displaced People in Mozambique During COVID-19 Pandemic: Results from a Community-Based Intervention.

Background: The spread of COVID-19 poses an unprecedented challenge to care delivery in post-disaster and conflict situations. In Mozambique, the 2019 cyclone Idai and the violence by Non-State-Armed-Groups devastated the province of Sofala and Cabo Delgado respectively and led to the displacement of thousands of people living in poor and overcrowded conditions. The pandemic has further aggravated the situation. Doctors with Africa CUAMM (University college for aspiring missionary doctors) implemented surveillance activities in these regions between October 2020 and September 2021. The aim of this study is to give an overview of the prevalence of malaria, malnutrition, COVID-19 related symptoms and access to HIV testing. Methods: Data were collected in targeted internally displaced people (IDP) sites in Sofala and Cabo Delgado province between 31st January and 25th September 2021. The tool used enabled to assess COVID-19 symptoms, risk of HIV infection, malaria cases and malnutrition in children under five. Results: The project reached 93 503 people. During the study period, 13.6% people reported at least one symptom suggestive of COVID-19 infection. Malaria Rapid Diagnostic Tests (RDT) were administered to 86% of the recruited people (n = ?), with a positive diagnosis in the 4.5% of them (n = ?). Among the recruited Internally Displaced Persons (IDP), 23.1% were considered eligible for HIV screening, but only 1.4% were referred for testing. Acute malnutrition was found in 6.3% of children screened and, among these, a higher prevalence of concurrent COVID-19 symptoms was reported. Discussion: Our study highlights the importance of mass clinical screening for COVID-19 infection in this target population to enact prevention behavior, although this may not be enough, due to the pivotal role played by asymptomatic transmissions. Considering the overlap of the symptoms of COVID-19 and malaria, a combined diagnostic algorithm is urgently needed to avoid underdiagnosing malaria. Moreover, the high prevalence of respiratory symptoms in malnourished children confirmed the known correlation between malnutrition and respiratory infection. Finally, access to HIV screening needs to be implemented, given the high prevalence of people with HIV risk factors to avoid diagnostic delay. Conclusions: Population-specific needs make necessary to develop new screening methods that respond to the specific characteristics of the target population.