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.

Blackwater Fever Treated with Steroids in Nonimmune Patient, Italy.

Causes of blackwater fever, a complication of malaria treatment, are not completely clear, and immune mechanisms might be involved. Clinical management is not standardized. We describe an episode of blackwater fever in a nonimmune 12-year-old girl in Italy who was treated with steroids, resulting in a rapid clinical resolution.

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.

mRNA vaccines: a new opportunity for malaria, tuberculosis and HIV.

The success of the first licensed mRNA-based vaccines against COVID-19 has created a widespread interest on mRNA technology for vaccinology. As expected, the number of mRNA vaccines in preclinical and clinical development increased exponentially since 2020, including numerous improvements in mRNA formulation design, delivery methods and manufacturing processes. However, the technology faces challenges such as the cost of raw materials, the lack of standardization, and delivery optimization. MRNA technology may provide a solution to some of the emerging infectious diseases as well as the deadliest hard-to-treat infectious diseases malaria, tuberculosis, and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), for which an effective vaccine, easily deployable to endemic areas is urgently needed. In this review, we discuss the functional structure, design, manufacturing processes and delivery methods of mRNA vaccines. We provide an up-to-date overview of the preclinical and clinical development of mRNA vaccines against infectious diseases, and discuss the immunogenicity, efficacy and correlates of protection of mRNA vaccines, with particular focus on research and development of mRNA vaccines against malaria, tuberculosis and HIV.

Editorial: Special Issue on the "Molecular Biology of Disease Vectors".

Arthropod disease vectors not only transmit malaria but many other serious diseases, many of which are, to a greater or lesser degree, neglected [...].

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.

Association between inequalities in human resources for health and all cause and cause specific mortality in 172 countries and territories, 1990-2019: observational study.

OBJECTIVE: To explore inequalities in human resources for health (HRH) in relation to all cause and cause specific mortality globally in 1990-2019. DESIGN: Observational study. SETTING: 172 countries and territories. DATA SOURCES: Databases of the Global Burden of Disease Study 2019, United Nations Statistics, and Our World in Data. MAIN OUTCOME MEASURES: The main outcome was age standardized all cause mortality per 100 000 population in relation to HRH density per 10 000 population, and secondary outcome was age standardized cause specific mortality. The Lorenz curve and the concentration index (CCI) were used to assess trends and inequalities in HRH. RESULTS: Globally, the total HRH density per 10 000 population increased, from 56.0 in 1990 to 142.5 in 2019, whereas age standardized all cause mortality per 100 000 population decreased, from 995.5 in 1990 to 743.8 in 2019. The Lorenz curve lay below the equality line and CCI was 0.43 (P<0.05), indicating that the health workforce was more concentrated among countries and territories ranked high on the human development index. The CCI for HRH was stable, at about 0.42-0.43 between 1990 and 2001 and continued to decline (narrowed inequality), from 0.43 in 2001 to 0.38 in 2019 (P<0.001). In the multivariable generalized estimating equation model, a negative association was found between total HRH level and all cause mortality, with the highest levels of HRH as reference (low: incidence risk ratio 1.15, 95% confidence interval 1.00 to 1.32; middle: 1.14, 1.01 to 1.29; high: 1.18, 1.08 to 1.28). A negative association between total HRH density and mortality rate was more pronounced for some types of cause specific mortality, including neglected tropical diseases and malaria, enteric infections, maternal and neonatal disorders, and diabetes and kidney diseases. The risk of death was more likely to be higher in people from countries and territories with a lower density of doctors, dentistry staff, pharmaceutical staff, aides and emergency medical workers, optometrists, psychologists, personal care workers, physiotherapists, and radiographers. CONCLUSIONS: Inequalities in HRH have been decreasing over the past 30 years globally but persist. All cause mortality and most types of cause specific mortality were relatively higher in countries and territories with a limited health workforce, especially for several specific HRH types among priority diseases. The findings highlight the importance of strengthening political commitment to develop equity oriented health workforce policies, expanding health financing, and implementing targeted measures to reduce deaths related to inadequate HRH to achieve universal health coverage by 2030.

Autoantibodies during infectious diseases: Lessons from malaria applied to COVID-19 and other infections.

Autoimmunity is a common phenomenon reported in many globally relevant infections, including malaria and COVID-19. These and other highly inflammatory diseases have been associated with the presence of autoantibodies. The role that these autoantibodies play during infection has been an emerging topic of interest. The vast numbers of studies reporting a range of autoantibodies targeting cellular antigens, such as dsDNA and lipids, but also immune molecules, such as cytokines, during malaria, COVID-19 and other infections, underscore the importance that autoimmunity can play during infection. During both malaria and COVID-19, the presence of autoantibodies has been correlated with associated pathologies such as malarial anemia and severe COVID-19. Additionally, high levels of Atypical/Autoimmune B cells (ABCs and atypical B cells) have been observed in both diseases. The growing literature of autoimmune B cells, age-associated B cells and atypical B cells in Systemic Lupus erythematosus (SLE) and other autoimmune disorders has identified recent mechanistic and cellular targets that could explain the development of autoantibodies during infection. These new findings establish a link between immune responses during infection and autoimmune disorders, highlighting shared mechanistic insights. In this review, we focus on the recent evidence of autoantibody generation during malaria and other infectious diseases and their potential pathological role, exploring possible mechanisms that may explain the development of autoimmunity during infections.

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.

The CARAMAL study could not assess the effectiveness of rectal artesunate in treating suspected severe malaria.

CARAMAL was a large observational study which recorded mortality in children with suspected severe malaria before and after the roll-out of rectal artesunate in Nigeria, Uganda and the Democratic Republic of the Congo. The results of CARAMAL have had a huge impact on public health policy leading to a World Health Organization moratorium on the roll-out of rectal artesunate. The conclusion reported in the abstract uses strong causal language, stating that "pre-referral RAS [rectal artesunate suppositories] had no beneficial effect on child survival". We argue that this causal interpretation of the study results is not justified. Data from the CARAMAL study inform chiefly on the strengths and weaknesses of referral systems in these three countries and do not inform reliably as to the beneficial effect of providing access to a known life-saving treatment.

Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial.

BACKGROUND: Whole sporozoite immunization under chemoprophylaxis (CPS regime) induces long-lasting sterile homologous protection in the controlled human malaria infection model using Plasmodium falciparum strain NF54. The relative proficiency of liver-stage parasite development may be an important factor determining immunization efficacy. Previous studies show that Plasmodium falciparum strain NF135 produces relatively high numbers of large liver-stage schizonts in vitro. Here, we evaluate this strain for use in CPS immunization regimes. METHODS: In a partially randomized, open-label study conducted at the Radboudumc, Nijmegen, the Netherlands, healthy, malaria-naïve adults were immunized by three rounds of fifteen or five NF135-infected mosquito bites under mefloquine prophylaxis (cohort A) or fifteen NF135-infected mosquito bites and presumptive treatment with artemether/lumefantrine (cohort B). Cohort A participants were exposed to a homologous challenge 19 weeks after immunization. The primary objective of the study was to evaluate the safety and tolerability of CPS immunizations with NF135. RESULTS: Relatively high liver-to-blood inocula were observed during immunization with NF135 in both cohorts. Eighteen of 30 (60%) high-dose participants and 3/10 (30%) low-dose participants experienced grade 3 adverse events 7 to 21 days following their first immunization. All cohort A participants and two participants in cohort B developed breakthrough blood-stage malaria infections during immunizations requiring rescue treatment. The resulting compromised immunizations induced modest sterile protection against homologous challenge in cohort A (5/17; 29%). CONCLUSIONS: These CPS regimes using NF135 were relatively poorly tolerated and frequently required rescue treatment, thereby compromising immunization efficiency and protective efficacy. Consequently, the full potential of NF135 sporozoites for induction of immune protection remains inconclusive. Nonetheless, the high liver-stage burden achieved by this strain highlights it as an interesting potential candidate for novel whole sporozoite immunization approaches. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov under identifier NCT03813108.

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.

Two cases of COVID-19 presenting with severe malaria: a clinical challenge (case report).

The novel coronavirus (COVID-19) pandemic has stretched the medical resources of both developed and developing countries. The global focus on COVID-19 may lead to the neglect of other infectious diseases such as malaria which is still endemic in many African countries. Some similarities in malaria and COVID-19 disease presentations may also lead to late diagnosis of either disease which could complicate the effects. Here, we present two cases of a 6-year-old child and a 17-year-old female who presented to a primary care facility in Ghana with a clinical and microscopy-confirmed diagnosis of severe malaria complicated by thrombocytopenia. As their symptoms worsened with associated respiratory complications, nasopharyngeal samples were taken for real-time polymerase chain reaction (RT-PCR) and tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Clinicians, policymakers, and public health practitioners should be alert to the variety of presenting symptoms of COVID-19 and its similarity to malaria to mitigate the risk of mortality from either disease.

Superoxide Dismutase Inhibitors against Malaria, Leishmaniasis, and Chagas Disease: Systematic Review.

INTRODUCTION: Diseases caused by protozoa are one of the leading causes of death worldwide, especially in tropical regions such as Brazil. Chagas disease, leishmaniasis, and malaria are responsible for around 234 million cases and more than 400,000 deaths worldwide. Despite this scenario, drugs for these diseases have several limitations, which justifies the search for new treatments. Iron superoxide dismutase is a promising target for the drug design to treat patients with these diseases. It is a validated target and protects against oxidative stress. AIM: Thus, this systematic review aimed to synthesize evidence on the importance of superoxide dismutase in the drug design to treat patients with this protozoosis. METHODS: A search was performed for in vitro and in vivo studies, without publication and language restrictions, in MEDLINE (PubMed), LILACS (BVS), Science Direct, and EMBASE (Elsevier). Studies that pointed to the relationship between the reduction or increase in superoxide dismutase activity and the diseases were included. 23 studies were selected for the qualitative synthesis. RESULTS: The results showed that the inhibition or reduction of the enzyme activity decreases the degree of infection and reinfection and improves the results in treating these diseases. In contrast, the increase in activity caused a high degree of survival and resistance of the parasites. CONCLUSION: However, the overall quality of evidence is low and more studies with methodological rigor are provided.

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.

Factors associated with delay in seeking healthcare for imported malaria: a retrospective study in a French hospital.

BACKGROUND: Delayed treatment is associated with a higher risk of severe malaria. In malaria-endemic areas, the main factors associated with delay in seeking healthcare are low educational level and traditional beliefs. In imported malaria, determinants of delay in seeking healthcare are currently unknown. METHODS: We studied all patients presenting with malaria, from 1 January 2017 to 14 February 2022, in the hospital of Melun, France. Demographic and medical data were recorded for all patients, and socio-professional data were recorded for a subgroup of hospitalized adults. Relative-risks and 95% confidence intervals were determined using univariate analysis by cross-tabulation. RESULTS: There were 234 patients included, all travelling from Africa. Among them, 218 (93%) were infected with P. falciparum, 77 (33%) had severe malaria, 26 (11%) were <18 years old and 81 were included during the SARS-CoV-2 pandemic. There were 135 hospitalized adults (58% of all patients). The median time to hospital admission (THA) , defined by the period from onset of symptoms to arrival at hospital, was 3 days (IQR = 2-5). A THA ≥3 days tended to be more frequent in travellers visiting friends and relatives (VFR; RR = 1.44, 95% CI = [1.0-2.05], P = 0.06), while it was less frequent in children and teenagers (RR = 0.58, 95% CI = [0.39-0.84], P = 0.01). Gender, African background, unemployment, living alone and absence of referring physician were not associated with delay in seeking healthcare. Consulting during the SARS-CoV-2 pandemic was neither associated with a longer THA nor with a higher rate of severe malaria. CONCLUSION: In contrast to an endemic area, socio-economic factors did not impact on delay in seeking healthcare in imported malaria. Prevention should focus on VFR subjects, who tend to consult later than other travellers.

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.