Prevalence and characteristics of malaria among COVID-19 individuals: A systematic review,meta-analysis,and analysis of case reports

BackgroundThe world population is currently at a very high risk of Coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). People who live in malaria-endemic areas and get infected by SARS-CoV-2 may be at increased risk of severe COVID-19 or unfavorable disease outcomes if they ignore their malaria status. Therefore, the present study aimed to synthesize, qualitatively and quantitatively, information on the prevalence and characteristics of malaria infection among COVID-19-infected individuals. The findings will help us better understand this particular comorbidity during the COVID-19 pandemic.MethodsThe systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) with the identification number: CRD42021247521. We searched for studies reporting on the coinfection of COVID-19 and malaria in PubMed, Web of Science, and Scopus from inception to March 27, 2021 using Medical Subject Headings (MeSH) terms. The study’s methodological quality in the search output was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Tools for cross-sectional study. The pooled prevalence of Plasmodium spp. infection among patients infected with COVID-19 was estimated using the random effect model and then graphically presented as forest plots. The heterogeneity among the included studies was assessed using Cochrane Q and I² statistics. The characteristics of patients co-infected with COVID-19 and malaria were derived from case reports and series and were formally analyzed using simple statistics.ResultsTwelve of 1,207 studies reporting the coinfection of COVID-19 and malaria were selected for further analysis. Results of quantitative synthesis show that the pooled prevalence of Plasmodium spp. infection (364 cases) among COVID–19 individuals (1,126 cases) is 11%, with a high degree of heterogeneity (95% CI: 4%–18%, I²: 97.07%, 5 studies). Most of the coinfections were reported in Nigeria (336 cases), India (27 cases), and the Democratic Republic of Congo (1 case). Results of qualitative synthesis indicate that patients with coinfection are typically symptomatic at presentation with mild or moderate parasitemia. An analysis of case reports and series indicates that co-infected individuals often display thrombocytopenia, lymphopenia, and elevated bilirubin levels. Among four patients (30%) who required treatment with intravenous artesunate, one experienced worsened clinical status after administering the drug. One serious outcome of coinfection involved a pregnant woman who experienced fetal abortion due to the initial misdiagnosis of malaria.ConclusionsAll individuals in malaria-endemic regions who are febrile or display symptoms of COVID-19 should be evaluated for malaria to avoid serious complications. Further prospective studies are required to investigate the burden and outcomes of COVID-19 in malaria-endemic regions. Prompt management is required to prevent serious outcomes in individuals co-infected with COVID-19 and malaria.     

Efficacy and safety of atovaquone-proguanil in treating imported malaria in Japan: the second report from the research group

Malaria remains an important health risk among travelers to tropical/subtropical regions. However, in Japan, only 2 antimalarials are licensed for clinical use - oral quinine and mefloquine. The Research Group on Chemotherapy of Tropical Diseases introduced atovaquone-proguanil in 1999, and reported on its excellent antimalarial efficacy and safety for treating non-immune patients with uncomplicated Plasmodium falciparum malaria (20 adult and 3 pediatric cases) in 2006. In the present study, additional cases of malaria were analyzed to confirm the efficacy and safety of this antimalarial drug. Fourteen adult and 2 pediatric cases of P. falciparum malaria and 13 adult cases and 1 pediatric case of P. vivax/ovale malaria were successfully treated with atovaquone-proguanil, including 3 P. falciparum cases in which the antecedent treatment failed. Two patients with P. vivax malaria were treated twice due to primaquine treatment failure as opposed to atovaquone-proguanil treatment failure. Except for 1 patient with P. falciparum malaria who developed a moderate liver function disturbance, no significant adverse effects were observed. Despite the intrinsic limitations of this study, which was not a formal clinical trial, the data showed that atovaquone-proguanil was an effective and well-tolerated therapeutic option; licensure of this drug in Japan could greatly contribute to individually appropriate treatment options.     

Malaria in India: Challenges and opportunities

India contributes about 70% of malaria in the South East Asian Region of WHO. Although annually India reports about two million cases and 1000 deaths attributable to malaria, there is an increasing trend in the proportion of Plasmodium falciparum as the agent. There exists heterogeneity and variability in the risk of malaria transmission between and within the states of the country as many ecotypes/paradigms of malaria have been recognized. The pattern of clinical presentation of severe malaria has also changed and while multi-organ failure is more frequently observed in falciparum malaria, there are reports of vivax malaria presenting with severe manifestations. The high burden populations are ethnic tribes living in the forested pockets of the states like Orissa, Jharkhand, Madhya Pradesh, Chhattisgarh and the North Eastern states which contribute bulk of morbidity and mortality due to malaria in the country. Drug resistance, insecticide resistance, lack of knowledge of actual disease burden along with new paradigms of malaria pose a challenge for malaria control in the country. Considering the existing gaps in reported and estimated morbidity and mortality, need for estimation of true burden of malaria has been stressed. Administrative, financial, technical and operational challenges faced by the national programme have been elucidated. Approaches and priorities that may be helpful in tackling serious issues confronting malaria programme have been outlined.     

Exploring the Seasonality of Reported Treated Malaria Cases in Mpumalanga,South Africa

South Africa, having met the World Health Organisation''s pre-elimination criteria, has set a goal to achieve malaria elimination by 2018. Mpumalanga, one of three provinces where malaria transmission still occurs, has a malaria season subject to unstable transmission that is prone to sporadic outbreaks. As South Africa prepares to intensify efforts towards malaria elimination, there is a need to understand patterns in malaria transmission so that efforts may be targeted appropriately. This paper describes the seasonality of transmission by exploring the relationship between malaria cases and three potential drivers: rainfall, geography (physical location) and the source of infection (local/imported). Seasonal decomposition of the time series by Locally estimated scatterplot smoothing is applied to the case data for the geographical and source of infection sub-groups. The relationship between cases and rainfall is assessed using a cross-correlation analysis. The malaria season was found to have a short period of no/low level of reported cases and a triple peak in reported cases between September and May; the three peaks occurring in October, January and May. The seasonal pattern of locally-sourced infection mimics the triple-peak characteristic of the total series while imported infections contribute mostly to the second and third peak of the season (Christmas and Easter respectively). Geographically, Bushbuckridge municipality, which exhibits a different pattern of cases, contributed mostly to the first and second peaks in cases while Maputo province (Mozambique) experienced a similar pattern in transmission to the imported cases. Though rainfall lagged at 4 weeks was significantly correlated with malaria cases, this effect was dampened due to the growing proportion of imported cases since 2006. These findings may be useful as they enhance the understanding of the current incidence pattern and may inform mathematical models that enable one to predict the impact changes in these drivers will have on malaria transmission.     

Congenital Malaria in China

Abstract

Background

Congenital malaria, in which infants are directly infected with malaria parasites from their mother prior to or during birth, is a potentially life-threatening condition that occurs at relatively low rates in malaria-endemic regions. It is recognized as a serious problem in Plasmodium falciparum–endemic sub-Saharan Africa, where recent data suggests that it is more common than previously believed. In such regions where malaria transmission is high, neonates may be protected from disease caused by congenital malaria through the transfer of maternal antibodies against the parasite. However, in low P. vivax–endemic regions, immunity to vivax malaria is low; thus, there is the likelihood that congenital vivax malaria poses a more significant threat to newborn health. Malaria had previously been a major parasitic disease in China, and congenital malaria case reports in Chinese offer valuable information for understanding the risks posed by congenital malaria to neonatal health. As most of the literature documenting congenital malaria cases in China are written in Chinese and therefore are not easily accessible to the global malaria research community, we have undertaken an extensive review of the Chinese literature on this subject.

Methods/Principal Findings

Here, we reviewed congenital malaria cases from three major searchable Chinese journal databases, concentrating on data from 1915 through 2011. Following extensive screening, a total of 104 cases of congenital malaria were identified. These cases were distributed mainly in the eastern, central, and southern regions of China, as well as in the low-lying region of southwest China. The dominant species was P. vivax (92.50%), reflecting the malaria parasite species distribution in China. The leading clinical presentation was fever, and other clinical presentations were anaemia, jaundice, paleness, diarrhoea, vomiting, and general weakness. With the exception of two cases, all patients were cured with antimalarial drugs such as chloroquine, quinine, artemether, and artesunate.

Conclusions

The symptoms of congenital malaria vary significantly between cases, so clear and early diagnosis is difficult. We suggest that active surveillance might be necessary for neonates born to mothers with a history of malaria.     

Polymorphism and epitope sharing between the alleles of merozoite surface protein-1 of Plasmodium falciparum among Indian isolates

A comparison was made between local malaria transmission and malaria imported by travellers to identify the utility of national and regional annual parasite index (API) in predicting malaria risk and its value in generating recommendations on malaria prophylaxis for travellers. Regional malaria transmission data was correlated with malaria acquired in Latin America and imported into the USA and nine European countries. Between 2000 and 2004, most countries reported declining malaria transmission. Highest API's in 2003/4 were in Surinam (287.4) Guyana (209.2) and French Guiana (147.4). The major source of travel associated malaria was Honduras, French Guiana, Guatemala, Mexico and Ecuador. During 2004 there were 6.3 million visits from the ten study countries and in 2005, 209 cases of malaria of which 22 (11%) were Plasmodium falciparum. The risk of adverse events are high and the benefit of avoided benign vivax malaria is very low under current policy, which may be causing more harm than benefit.     

Association of adhesion molecule PECAM-1/CD31 polymorphism with susceptibility to cerebral malaria in Thais

Adhesion molecules on endothelial cells are known to be important ligands for malaria infected red blood cells (PRBC) [Mol Biochem Parasitol, 76, (1996) 1], and may be involved in the pathogenic process of cerebral malaria (CM) which is the most serious complication of falciparum malaria, through enhancing micro embolism or sequestration in the capillaries of the brain. PECAM-1/CD31 is one of these candidate ligands and is coded by a polymorphic gene. Two hundred and ten Thai malaria patients (43 cerebral, 89 severe and 78 uncomplicated) were analyzed for their genetic polymorphism of CD31 to examine the clinical relationship between the disease and specific genotypes. Four alleles were defined 125 valine (V)-563 asparagine (N); 125V-563 serine (S); 125 leucine (L)-563N; and 125L-563S. We found that the frequency of the 125 V/V 563 N/N genotype was significantly high in CM patients as compared with severe cases without CM (P<0.01, OR=2.92), suggesting that this genotype is one of the risk factors for CM.     

Report of the clinical donor case workshop of the European Association of Tissue Banks annual meeting 2014

The European Association of Tissue Banks (EATB) donor case workshop is a forum held within the program of the EATB annual congress. The workshop offers an opportunity to discuss and evaluate possible approaches taken to challenging situations regarding donor selection. Donor case workshops actively engage participants with diverging background and experience in an informal, secure and enjoyable setting. The resulting discussion with peers promotes consensus development in deciding tissue donor acceptability, especially when donor health issues are not conclusively addressed in standards and regulations. Finally the workshop serves to strengthen the professional tissue banking networks across Europe and beyond. This report reflects some of the discussion at the workshop during the annual congress in Lund, Sweden, in 2014. The cases presented demonstrate that the implications of various donor illnesses, physical findings and behaviours on the safety of tissue transplantation, may be interpreted in a different way by medical directors and other professionals of different tissue facilities. This will also result in diverging preventive measures and decisions taken by the tissue facilities. Some of the donor cases illustrate varied responses from participants and demonstrate that operating procedures, regulations and standards cannot comprehensively cover all tissue donor illnesses, medical histories and circumstances surrounding the cause of death. For many of the issues raised, there is a lack of published scientific evidence. In those cases, tissue bank medical director judgement is critical to guarantee transplantation safety. This judgement should be based on a proper and documented risk assessment case by case. Conditions or parameters taken into account for risk assessment are amongst others, the type of tissue, the type of processing, the characteristics of the final product, and the availability of an adequate sterilisation methodology. By publishing these difficult donor suitability cases, and the resulting discussions, we provide information for future similar cases and we identify needs for future literature review and scientific research. In this way the donor case workshops play a role in optimizing the quality and security of tissue donation.     

Prevalence and risk factors for Plasmodium falciparum malaria in pregnant women of eastern Sudan

Background

Pregnant women are more susceptible to malaria, which is associated with serious adverse effects on pregnancy. The presentation of malaria during pregnancy varies according to the level of transmission in the area. Our study aimed to demonstrate the prevalence and risk factors for malaria (age, parity and gestational age) among pregnant women of eastern Sudan, which is characterized by unstable malaria transmission.

Methods

The prevalence and possible risk factors for Plasmodium falciparum malaria were investigated in 744 pregnant Sudanese women attending the antenatal clinic of New Haifa Teaching Hospital, eastern Sudan, during October 2003-April 2004.

Results

A total 102 (13.7%) had P. falciparum malaria, 18(17.6%) of these were severe cases (jaundice and severe anaemia). Univariate and multivariate analysis showed that, age and parity were not associated with malaria. Women who attended the antenatal clinic in the third trimester were at highest risk for malaria (OR = 1.58, 95% CI = 1.02–2.4; P < 0.05). Women with malaria had significantly lower mean haemoglobin (9.4 g/dl, 95% CI 9.1–9.7 versus 10.7, CI 10.6–10.8, P < 0.05). A significantly lower haemoglobin was observed in those with severe falciparum malaria compared to non-severe form (8.3 g/dl, 95% CI 7.6–9.1 versus 9.4, 95% CI 9.1–9.7, P = < 0.05).

Conclusion

The results suggest that P. falciparum malaria is common in pregnant women attending antenatal care and that anaemia is an important complication. Preventive measures (chemoprophylaxis and insecticide-treated bednets) may be beneficial in this area for all women irrespective of age or parity.     

Malaria Prevalence,Spatial Clustering and Risk Factors in a Low Endemic Area of Eastern Rwanda: A Cross Sectional Study

Background

Rwanda reported significant reductions in malaria burden following scale up of control intervention from 2005 to 2010. This study sought to; measure malaria prevalence, describe spatial malaria clustering and investigate for malaria risk factors among health-centre-presumed malaria cases and their household members in Eastern Rwanda.

Methods

A two-stage health centre and household-based survey was conducted in Ruhuha sector, Eastern Rwanda from April to October 2011. At the health centre, data, including malaria diagnosis and individual level malaria risk factors, was collected. At households of these Index cases, a follow-up survey, including malaria screening for all household members and collecting household level malaria risk factor data, was conducted.

Results

Malaria prevalence among health centre attendees was 22.8%. At the household level, 90 households (out of 520) had at least one malaria-infected member and the overall malaria prevalence for the 2634 household members screened was 5.1%. Among health centre attendees, the age group 5–15 years was significantly associated with an increased malaria risk and a reported ownership of ≥4 bednets was significantly associated with a reduced malaria risk. At the household level, age groups 5–15 and >15 years and being associated with a malaria positive index case were associated with an increased malaria risk, while an observed ownership of ≥4 bednets was associated with a malaria risk-protective effect. Significant spatial malaria clustering among household cases with clusters located close to water- based agro-ecosystems was observed.

Conclusions

Malaria prevalence was significantly higher among health centre attendees and their household members in an area with significant household spatial malaria clustering. Circle surveillance involving passive case finding at health centres and proactive case detection in households can be a powerful tool for identifying household level malaria burden, risk factors and clustering.     

Malaria morbidity and temperature variation in a low risk Kenyan district: a case of overdiagnosis?

Diagnosis of malaria using only clinical means leads to overdiagnosis. This has implications due to safety concerns and the recent introduction of more expensive drugs. Temperature is a major climatic factor influencing the transmission dynamics of malaria. This study looked at trends in malaria morbidity in the low risk Kenyan district of Nyandarua, coupled with data on temperature and precipitation for the years 2003–2006. July had the highest number of cases (12.2% of all cases) followed by August (10.2% of all cases). July and August also had the lowest mean maximum temperatures, 20.1 and 20.2 °C respectively. April, July and August had the highest rainfall, with daily means of 4.0, 4.3 and 4.9 mm, respectively. Observation showed that the coldest months experienced the highest number of cases of malaria. Despite the high rainfall, transmission of malaria tends to be limited by low temperatures due to the long duration required for sporogony, with fewer vectors surviving. These cold months also tend to have the highest number of cases of respiratory infections. There is a possibility that some of these were misdiagnosed as malaria based on the fact that only a small proportion of malaria cases were diagnosed using microscopy or rapid diagnostic tests. We conclude that overdiagnosis may be prevalent in this district and there may be a need to design an intervention to minimise it.     

Malaria: medical and surgical complications

The resurgence of malaria in Venezuela as an epidemic has caused an increase in the number of cases of this disease. 898 cases were registered in 1962 in contrast to 46,279 cases in 1988. This reality implies that all hospitals will have to face the increase of patients with this disease. Ten cases of malaria have been described and analyzed. These have been chosen for their medical and surgical complications, for which they were admitted to the "Hospital Universitario de Caracas" and "Hospital de Clínicas Caracas". Of these ten cases, eight were acquired in a natural way and two in an induced form. In six cases, the agent was P. falciparum; in three, P. vivax; in one, P. ovale and P.vivax combined. Five of the cases by P.falciparum were resistant to chloroquine, being necessary to treat them with a combination of quinine and other antimalaric drugs. Among the 10 described patients, there were: one case of splenic rupture in malaria by P. vivax, a severe case of anemia in a child with malaria by this same species and a case of relapse produced by P.vivax in another child with an insufficient radical treatment. The usual mistakes are observed in the management of malaria, such as a delay in the diagnosis and inappropriate radical treatment. As conclusion, publication of epidemiological, clinical and parasitological problems which are causing the actual epidemic, is recommended. This will be a guide in the fight against malaria, that must be considered again a national emergency.     

Deficiency of two red-cell flavin enzymes in a population in Sardinia: was glutathione reductase deficiency specifically selected for by malaria?

In two areas in Italy where malaria was endemic--in the Po delta and Maremma on the west coast--we have found a high prevalence of an inherited flavin-deficient red cell in the normal population, suggesting selection by malaria. This study in Sardinia enabled a direct comparison of red-cell activities of FAD-dependent glutathione reductase (EGR) and FMN-dependent pyridoxine phosphate (PNP) oxidase in an ethnically homogeneous population, between two coastal villages where malaria was endemic from 300 B.C. and two mountain villages with no history of malaria. Both enzyme activities were significantly lower on the coast, and it did not seem that this could be explained by possible small differences in dietary riboflavin. As was thought to be the case in Ferrara and Grosseto, it is probable that a genetically controlled flavin-deficient red cell was selected for by malaria. Low EGR apoenzyme activity was more common on the coast, usually explaining the accompanying low basic EGR activity, and may also have been selected for by malaria. This adds to evidence from others that the mechanism of defence of a flavin-deficient red cell against malaria may be through EGR deficiency. It could also play a part in the protection given by heterozygous beta-thalassemia. The multifactorial protection of the population against malaria is discussed.     

Malaria in Brazil: what happens outside the Amazonian endemic region

Brazil, a country of continental proportions, presents three profiles of malaria transmission. The first and most important numerically, occurs inside the Amazon. The Amazon accounts for approximately 60% of the nation’s territory and approximately 13% of the Brazilian population. This region hosts 99.5% of the nation’s malaria cases, which are predominantly caused by Plasmodium vivax (i.e., 82% of cases in 2013). The second involves imported malaria, which corresponds to malaria cases acquired outside the region where the individuals live or the diagnosis was made. These cases are imported from endemic regions of Brazil (i.e., the Amazon) or from other countries in South and Central America, Africa and Asia. Imported malaria comprised 89% of the cases found outside the area of active transmission in Brazil in 2013. These cases highlight an important question with respect to both therapeutic and epidemiological issues because patients, especially those with falciparum malaria, arriving in a region where the health professionals may not have experience with the clinical manifestations of malaria and its diagnosis could suffer dramatic consequences associated with a potential delay in treatment. Additionally, because the Anopheles vectors exist in most of the country, even a single case of malaria, if not diagnosed and treated immediately, may result in introduced cases, causing outbreaks and even introducing or reintroducing the disease to a non-endemic, receptive region. Cases introduced outside the Amazon usually occur in areas in which malaria was formerly endemic and are transmitted by competent vectors belonging to the subgenus Nyssorhynchus (i.e., Anopheles darlingi, Anopheles aquasalis and species of the Albitarsis complex). The third type of transmission accounts for only 0.05% of all cases and is caused by autochthonous malaria in the Atlantic Forest, located primarily along the southeastern Atlantic Coast. They are caused by parasites that seem to be (or to be very close to) P. vivax and, in a less extent, by Plasmodium malariae and it is transmitted by the bromeliad mosquito Anopheles (Kerteszia) cruzii. This paper deals mainly with the two profiles of malaria found outside the Amazon: the imported and ensuing introduced cases and the autochthonous cases. We also provide an update regarding the situation in Brazil and the Brazilian endemic Amazon.     

Molecular surveillance and temporal monitoring of malaria parasites in focal Vietnamese provinces

In the past decade substantial reduction in malaria morbidity and mortality has been observed through well-implemented case management and vector control strategies. India has also achieved a significant reduction in malaria burden in 2018 and has committed to eliminate malaria by 2030. The Mandla Malaria Elimination Demonstration Project (MEDP) was started in 2017 in 1233 villages of District Mandla to demonstrate malaria elimination in a tribal district with hard-to-reach areas was possible using active and passive surveillance, case management, vector control, and targeted information, education and communication campaigns. An operational plan was developed to strengthen the existing surveillance and malaria elimination systems, through fortnightly active case detection to ensure that all cases including those that are introduced into the communities are rapidly identified and treated promptly. The plan also focused on the reduction of human-mosquito contact through the use of Long-Lasting Insecticial Nets (LLINs) and Indoor Residual Spray (IRS). The operational plan was modified in view of the present COVID-19 pandemic by creating systems of assistance for the local administration for COVID-related work while ensuring the operational integrity of malaria elimination efforts. The use of MEDP study design and operational plan, with its built-in management control systems, has yielded significant (91%) reduction of indigenous cases of malaria during the period from June 2017 to May 2020. The malaria positivity rate was 0.33% in 2017–18, 0.13% in 2018–19, and 0.06% in 2019–20. Mass screening revealed 0.18% malaria positivity in September–October 2018, followed by 0.06% in June 2019, and 0.03% in December 2019, and these were mostly asymptomatic cases in the community. The project has been able to sustain the gains of the past three years during the ongoing COVID-19 pandemic. This paper provides the study design and the operational plan for malaria elimination in a high-burden district of Central India, which presented difficulties of hard to reach areas, forest malaria, and complex epidemiology of urban and rural malaria. The lessons learned could be used for malaria elimination efforts in rest of the country and other parts of South Asia with comparable demography and epidemiology.     

Characterizing the spatial and temporal variation of malaria incidence in Bangladesh, 2007

ABSTRACT: BACKGROUND: Malaria remains a significant health problem in Bangladesh affecting 13 of 64 districts. The risk of malaria is variable across the endemic areas and throughout the year. A better understanding of the spatial and temporal patterns in malaria risk and the determinants driving the variation are crucial for the appropriate targeting of interventions under the National Malaria Control and Prevention Programme. METHODS: Numbers of Plasmodium falciparum and Plasmodium vivax malaria cases reported by month in 2007, across the 70 endemic thanas (sub-districts) in Bangladesh, were assembled from health centre surveillance reports. Bayesian Poisson regression models of incidence were constructed, with fixed effects for monthly rainfall, maximum temperature and elevation, and random effects for thanas, with a conditional autoregressive prior spatial structure. RESULTS: The annual incidence of reported cases was 34.0 and 9.6 cases/10,000 population for P. falciparum and P. vivax respectively and the population of the 70 malaria-endemic thanas was approximately 13.5 million in 2007. Incidence of reported cases for both types of malaria was highest in the mountainous south-east of the country (the Chittagong Hill Tracts). Models revealed statistically significant positive associations between the incidence of reported P. vivax and P. falciparum cases and rainfall and maximum temperature. CONCLUSIONS: The risk of P. falciparum and P. vivax was spatially variable across the endemic thanas of Bangladesh and also highly seasonal, suggesting that interventions should be targeted and timed according to the risk profile of the endemic areas. Rainfall, temperature and elevation are major factors driving the spatiotemporal patterns of malaria in Bangladesh.     

Social and environmental determinants of malaria in space and time in Viet Nam

The malaria burden in Viet Nam has been in decline in recent decades, but localised areas of high transmission remain. We used spatiotemporal analytical tools to determine the social and environmental drivers of malaria risk and to identify residual high-risk areas where control and surveillance resources can be targeted. Counts of reported Plasmodium falciparum and Plasmodium vivax malaria cases by month (January 2007-December 2008) and by district were assembled. Zero-inflated Poisson regression models were developed in a Bayesian framework. Models had the percentage of the district’s population living below the poverty line, percent of the district covered by forest, median elevation, median long-term average precipitation, and minimum temperature included as fixed effects, and terms for temporal trend and residual district-level spatial autocorrelation. Strong temporal and spatial heterogeneity in counts of malaria cases was apparent. Poverty and forest cover were significantly associated with an increased count of malaria cases but the magnitude and direction of associations between climate and malaria varied by socio-ecological zone. There was a declining trend in counts of malaria cases during the study period. After accounting for the social and environmental fixed effects, substantial spatial heterogeneity was still evident. Unmeasured factors which may contribute to this residual variation include malaria control activities, population migration and accessibility to health care. Forest-related activities and factors encompassed by poverty indicators are major drivers of malaria incidence in Viet Nam.     

Coronavirus Disease (Covid-19) Associated Mucormycosis (CAM): Case Report and Systematic Review of Literature

Severe coronavirus disease (COVID-19) is currently managed with systemic glucocorticoids. Opportunistic fungal infections are of concern in such patients. While COVID-19 associated pulmonary aspergillosis is increasingly recognized, mucormycosis is rare. We describe a case of probable pulmonary mucormycosis in a 55-year-old man with diabetes, end-stage kidney disease, and COVID-19. The index case was diagnosed with pulmonary mucormycosis 21 days following admission for severe COVID-19. He received 5 g of liposomal amphotericin B and was discharged after 54 days from the hospital. We also performed a systematic review of the literature and identified seven additional cases of COVID-19 associated mucormycosis (CAM). Of the eight cases included in our review, diabetes mellitus was the most common risk factor. Three subjects had no risk factor other than glucocorticoids for COVID-19. Mucormycosis usually developed 10–14 days after hospitalization. All except the index case died. In two subjects, CAM was diagnosed postmortem. Mucormycosis is an uncommon but serious infection that complicates the course of severe COVID-19. Subjects with diabetes mellitus and multiple risk factors may be at a higher risk for developing mucormycosis. Concurrent glucocorticoid therapy probably heightens the risk of mucormycosis. A high index of suspicion and aggressive management is required to improve outcomes.

     

The Role of Climate Variability in the Spread of Malaria in Bangladeshi Highlands

Background

Malaria is a major public health problem in Bangladesh, frequently occurring as epidemics since the 1990s. Many factors affect increases in malaria cases, including changes in land use, drug resistance, malaria control programs, socioeconomic issues, and climatic factors. No study has examined the relationship between malaria epidemics and climatic factors in Bangladesh. Here, we investigate the relationship between climatic parameters [rainfall, temperature, humidity, sea surface temperature (SST), El Niño-Southern Oscillation (ENSO), the normalized difference vegetation index (NDVI)], and malaria cases over the last 20 years in the malaria endemic district of Chittagong Hill Tracts (CHT).

Methods and Principal Findings

Monthly malaria case data from January 1989 to December 2008, monthly rainfall, temperature, humidity sea surface temperature in the Bay of Bengal and ENSO index at the Niño Region 3 (NIÑO3) were used. A generalized linear negative binomial regression model was developed using the number of monthly malaria cases and each of the climatic parameters. After adjusting for potential mutual confounding between climatic factors there was no evidence for any association between the number of malaria cases and temperature, rainfall and humidity. Only a low NDVI was associated with an increase in the number of malaria cases. There was no evidence of an association between malaria cases and SST in the Bay of Bengal and NIÑO3.

Conclusion and Significance

It seems counterintuitive that a low NDVI, an indicator of low vegetation greenness, is associated with increases in malaria cases, since the primary vectors in Bangladesh, such as An. dirus, are associated with forests. This relationship can be explained by the drying up of rivers and streams creating suitable breeding sites for the vector fauna. Bangladesh has very high vector species diversity and vectors suited to these habitats may be responsible for the observed results.