Public health-relevant consequences of the COVID-19 pandemic on malaria in sub-Saharan Africa: a scoping review

Background The COVID-19 pandemic has resulted in unprecedented challenges to health systems worldwide, including the control of non-COVID-19 diseases. Malaria cases and deaths may increase due to the direct and indirect effects of the pandemic in malaria-endemic countries, particularly in sub-Saharan Africa (SSA). This scoping review aims to summarize information on public health-relevant effects of the COVID-19 pandemic on the malaria situation in SSA. Methods Review of publications and manuscripts on preprint servers, in peer-reviewed journals and in grey literature documents from 1 December, 2019 to 9 June, 2021. A structured search was conducted on different databases using predefined eligibility criteria for the selection of articles. Results A total of 51 papers have been included in the analysis. Modelling papers have predicted a significant increase in malaria cases and malaria deaths in SSA due to the effects of the COVID-19 pandemic. Many papers provided potential explanations for expected COVID-19 effects on the malaria burden; these ranged from relevant diagnostical and clinical aspects to reduced access to health care services, impaired availability of curative and preventive commodities and medications, and effects on malaria prevention campaigns. Compared to previous years, fewer country reports provided data on the actual number of malaria cases and deaths in 2020, with mixed results. While highly endemic countries reported evidence of decreased malaria cases in health facilities, low endemic countries reported overall higher numbers of malaria cases and deaths in 2020. Conclusions The findings from this review provide evidence for a significant but diverse impact of the COVID-19 pandemic on malaria in SSA. There is the need to further investigate the public health consequences of the COVID-19 pandemic on the malaria burden. Protocol registered on Open Science Framework: https://doi.org/10.17605/OSF.IO/STQ9D

variable dynamics in the different WHO Regions, with the highest burden in the American, European and Southeast Asian Regions [3,4]. The latter has recently shown particularly high incidence rates, and India is now reporting the second highest number of confirmed cases after the USA [3]. In contrast, the African and the Western Pacific WHO Regions continue to report only relatively low numbers of cases and deaths [3,4].
It was initially predicted that Africa would be the worst affected region by the COVID-19 pandemic because of its weak health systems, prevailing poverty and the high burden of other infectious diseases [5,6]. However, by the end of 2020 about 3.5% of the global number of COVID-19 cases and deaths were reported from this continent, which is home to 17% of the world's population [3,7]. Overall, the epidemiology of COVID-19 in Africa remains puzzling [5]. By 14 June, 2021, there were some 3.6 million COVID-19 cases and 89,000 deaths reported from the entire continent, and most of these were from its northern and southern regions [8,9]. Potential explanations for such a situation are incomplete data due to much lower testing capacities, a significantly younger population, overall lower population mobility, crossreactive immunity or immunomodulation due to high prevalence of other infectious agents, and effects of public health responses [5,7,10]. First findings from SARS-CoV-2 seroprevalence surveys support the evidence for significant under-reporting and for a predominance of asymptomatic and mild cases [11,12]. Nevertheless, it appears that the second epidemic wave has hit the African continent more severely than the first one, possibly explained by the emergence of more transmissible SARS-CoV-2 variants [7,13].
Globally, malaria is still the most important parasitic disease and responsible for a quarter of all deaths among children under 5 years old in sub-Saharan Africa (SSA) [14,15]. The efforts for global malaria control and elimination have achieved large successes during the last two decades, but progress has stalled in recent years, and the COVID-19 pandemic could largely reverse the overall trend [16,17]. This review aims to summarize currently available data and understanding of the direct and indirect effects of the COVID-19 pandemic on the malaria burden in SSA.

Search strategy and selection criteria
Due to the complex topic and the different type of studies available, a scoping review methodology was chosen [18]. The study protocol (published on OFS, https:// doi. org/ 10. 17605/ OSF. IO/ STQ9D) complies with the 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) checklist' [19]. The following inclusion criteria were applied: papers needed to respect the categories of the PICoframework (Problem: malaria situation; Interest: the public health impact of the COVID-19 pandemic; Context: sub-Saharan Africa) [20]. No restrictions regarding the study type and the publication status were applied. Possible languages were English, French and German; papers published between 1 December, 2019 and 9 June, 2021 were included. In line with the protocol, the search strategy was developed, and the following databases were searched: PubMed; Ovid MEDLINE(R); Web of Science; Biosis Previews; MedRxiv, and The Lancet. Grey literature was included using WHO database and Google Scholar. Three broad blocks of search terms were used: (1) COVID-19; (2) malaria; (3) sub-Saharan Africa. The detailed search strategy is available in Appendix 1.
For the extracted findings, two researchers (OM and AH) conducted independently the title screening, then the abstract screening and finally the full text review. The papers selected for full-text reading were assessed for eligibility; ineligible papers did not include information on public health-relevant consequences of the COVID-19 pandemic on malaria in SSA. Inclusion decisions depended on whether the paper agreed to the PICo-framework and the formal eligibility criteria. Results were compared after each step for discussion and for reaching a consensus. For the analysis of the finally included papers, a data extraction table was constructed (Appendix 2).
The following information was extracted from the papers: authors, title, study place, study population, study design, and outcome. Moreover, the papers were categorized by study type: modelling study, report (country report, general report, case report), review, opinion paper, and policy guideline. The information content was structured and analysed around the following themes: • Modelled impact of COVID-19 on malaria. • Diagnostical and clinical aspects. • Access to health care services. • Availability of curative and preventive malaria commodities. • Impact on malaria programmes. • Epidemiologic data from countries.
Based on these findings, a conceptual framework was created, with input from all co-authors (Fig. 1). Figure 2 visualizes the study selection process. The initial search produced 851 documents. After removal of 203 duplicates, 648 documents underwent title and abstract screening. After exclusion of 535 documents, which did not meet the inclusion criteria, 113 papers were included for full text review. Nine papers were added from reference screening; 71 were excluded as they also did not meet the inclusion criteria. Thus, a total of 51 papers were reviewed (6 modelling studies, 10 country reports, 6 general reports, 1 case report, 9 review papers, 18 opinion papers, and 1 policy guideline).

Modelled impact of COVID-19 on malaria
Five papers predicted the evolution of the malaria burden in SSA based on different potential scenarios. Considering primarily a reduced access to effective anti-malarial treatment and reduced insecticide-treated mosquito net (ITN) distribution, Weiss et al. predicted in their worst-case scenario (75% fewer anti-malarial drugs and ITNs) and for the year 2020 that in SSA countries, malaria cases would increase by 22% (from 215 to 262 million) and malaria deaths by 99% (from 386,000 to 769,000); the lower access to anti-malarial treatment had a larger effect than reduced ITN distribution [21]. These estimates mirror those by the WHO, but the authors described the effects of nine different scenarios compared to the effects of three scenarios by Weiss et al. [22]. Comparable estimates were published by Sherrard-Smith et al. for the scenario of complete interruption of ITN distribution and 50% decreased access to anti-malarials, they predicted malaria deaths would increase in SSA to 779,000 for the year 2020 [23]. A further analysis by WHO predicted up to 100,000 additional deaths in 2020 with a 50% lower access to anti-malarials [17]. However, all these authors emphasized that the projected effects on malaria services and mortality are highly uncertain because these estimates are heavily dependent on how countries respond to the COVID-19 pandemic. Regarding the relative burden of COVID-19 in Africa, one study concluded that the excess disability-adjusted life years (DALYs) lost by malaria due to COVID-19 may exceed those directly lost due to COVID-19 [24].

Diagnostical and clinical aspects
The clinical manifestations of COVID-19 and malaria largely overlap; fever, headache, joint pain, respiratory symptoms, and general weakness are frequently seen with both diseases [25][26][27]. Thus, diagnosis based on symptoms alone can result in inadequate treatment, with potentially harmful consequences. Untreated malaria can be rapidly fatal and COVID-19 patients must be quarantined to interrupt community transmission [14,28]. Despite increasing availability of rapid diagnostic tests (RDTs) for malaria in all endemic areas, presumptive diagnosis of malaria is still common in SSA, and the WHO Malaria Technical Guidelines adapted to COVID-19 confirm this situation [29,30]. Initial information available for 2020 suggests major disruptions in malaria diagnosis and treatment due to COVID-19 [31,32].
Human travel history is important for SARS-CoV-2 and malaria, as for both of them asymptomatic persons can spread and/or maintain transmission of the infectious agent [26]. Malaria might have been reduced by the COVID-19 movement restrictions, especially in heterogenous malaria-endemic settings where transmission frequently results from migration flows of infected individuals across different regions [33]. Moreover, malaria and SARS-CoV-2 co-infections may be associated with clinical disease modification, although data on this are limited [27,[34][35][36].
While symptomatic malaria affects mainly children and younger age groups in endemic areas, COVID-19 affects all age groups but is more frequently symptomatic and severe with increasing age [34]. However, in areas of low malaria transmission, the age groups affected by the two diseases largely overlap [37]. RDTs are essential for malaria diagnosis in rural SSA and may also become important for COVID-19, as the PCR test capacity is very limited [32]. However, the impact of rather low sensitivity and specificity of COVID-19 RDTs is still under intense discussion [27,38]. An additional challenge for differential diagnosis is the increasing frequency of gene-mutated Plasmodium parasites, especially in the Horn of Africa, that escape detection by standard RDTs [37].
The role of anti-malarials, e.g. artemisinin derivates and chloroquine (CQ), in the COVID-19 pandemic is complex. Various artemisinin derivates, artemisinin-based combination therapy (ACT) as well as CQ have been shown to be effective against SARS-CoV-1 and SARS-CoV-2 in vitro [39][40][41][42]. However, such beneficial effect was not confirmed by several clinical trials [43][44][45][46]. The wide use of these treatments in highly malaria-endemic countries has been suggested to be responsible for the reported low COVID-19 burden in SSA [36,47]. On the other hand, the increased usage of these drugs for COVID-19 prevention and treatment in some malariaendemic countries might have reduced malaria [25]. A frequent off-label use of artemisinin-based drugs may also increase the likelihood of emerging drug resistance and thus threatens the most important of the remaining effective anti-malarials [33,[48][49][50].

Access to health care services
The COVID-19 pandemic in SSA endangers access to health care services due to several factors. Direct factors include restricted services and closures of health facilities because of reduced health care worker (HCW) capacity due to lack of personal protective equipment (PPE), stigmatization, fear of getting infected, or absence due to COVID-19 quarantine, disease or death [27,32,50,51]. Delayed treatment results in prolonged gametocyte carriage and additional opportunities for transmission.
Moreover, because of overload of COVID-19 patients and consequently reduced time to manage other diseases, or due to movement and travel restrictions and for fear of becoming infected with COVID-19, sick individuals with diseases other than COVID-19 no longer attend health facilities [33,48,52]. As older people fear severe COVID-19 disease and may thus avoid visiting health facilities, this might affect children the most as they depend on their care givers if sick, including for malaria [35,49]. Stay-at-home advice for febrile diseases, especially at the beginning of the pandemic, enhanced such behaviour [17,33].
Indirect factors include reduced income during lockdowns due to inability to perform informal work, and subsequently reduced purchasing power [52]. The resulting increase in poverty leads to challenges for paying the costs for routine care, drugs or transportation fees [51]. Lockdowns, movement restrictions and border closures further complicate access to health facilities and have also threatened the functioning of malaria surveillance systems [16,28,33,51]. Institutional mistrust and lack of valid information further reduced visits to health care facilities and reduced uptake of preventive measures; as an example, myths about the spread of COVID-19 via ITNs led to a reduced usage of this essential intervention in Sierra Leone [25].

Availability of curative and preventive commodities and medicines
Increased material costs, reluctance of producers to invest, travel restrictions, border closures, and lockdowns resulted in a lower availability of medical malaria products [26,28,48]. Low-and middle-income countries (LMICs) are disproportionately affected as they essentially rely on importation of these commodities [52]. Excessive use of anti-malarials for COVID-19 prevention and treatment in some regions has led to shortages for their original purpose [17,30]. Some international companies switched from the production of malaria products to COVID-19 products [48,49,51]. Difficult access to health facilities lowered the availability of essential drugs and increased their price, with subsequent increases in purchase and usage of sub-standard drugs and alternative medicines [28,[51][52][53]. In addition, PPE needed for the implementation of different malaria services [e.g., indoor residual spraying of insecticides (IRS)] has become scarce and expensive on global markets [17,54].

Impact of the pandemic on malaria programmes
The extent of the pandemic's impact on malaria depends on the timing of its waves. The largest effects may occur if the COVID-19 transmission peaks and the planned malaria campaigns overlap [21,23,53,55]. About threequarters of malaria-affected countries reported disruptions of malaria services and programmes [17,32,33,50,53,[56][57][58]. Re-allocation of funds from other disease control programmes to the control of COVID-19 have been common and pose great problems for malaria control [30,32,35,59,60]. Ongoing malaria programmes (e.g., IRS, ITN interventions) need to be adapted to the restrictions associated with COVID-19 control measures, which requires additional financial resources [32,33,36]. Programmes for vulnerable populations living in remote areas are particularly at risk as they strongly depend on logistics and external financing [33,48]. Disrupted ITN programmes will lead to increased malaria transmission as 80% of the nets are distributed through mass campaigns [22,48,53,55]. IRS campaigns face many challenges as they require direct household contact [33,50,57].
Nevertheless, these challenges have led to new approaches: Benin digitalized its ITN mass distribution campaign using a 'no touch' payment for campaign workers. The national strategy was changed from a fixed-point to a door-to-door-distribution procedure, which enabled health workers to provide additional community health education on COVID-19 and other aspects; other countries followed the Benin model and by the end of 2020, 90% of all globally planned malaria prevention campaigns had been implemented [17,28,54,57,59].

Epidemiologic data from countries
Compared to previous years, fewer papers provided data from African countries on the actual number of malaria cases and deaths in 2020. A small study from Sierra Leone reported a significantly lower number of malaria outpatient visits in one health facility during the March/ April 2020 lockdown period compared to the same period in 2019 [29]. In addition, preliminary national data from Uganda point to a reduction of malaria cases diagnosed in health facilities during the first quarter of 2020 compared to the same period in 2019 [61]. Another study from Uganda reported a 54% decrease in visits for malaria treatment of febrile children; visits for antenatal care declined by 26%, restricting the delivery of intermittent preventive malaria treatment in pregnancy (IPTp) [62]. In the Democratic Republic of the Congo (DRC), lower attendance to health facilities for malaria treatment ranged from 20 to 90%, depending on local lockdown measures [63]. In contrast, a study from one rural district in Zimbabwe reported a large increase in malaria cases in 2020 compared to previous years, which was associated with delayed IRS in 2020 [50]. These findings were confirmed by national data from Zimbabwe, which compared the number of malaria cases and deaths in 2020 with those in previous years; in 2020, there was a large excess of reported malaria cases and deaths [27,64]. Moreover, national data from Zambia showed an increase of malaria cases between August 2019 and June 2020; however, no data from control periods were provided [65].

Discussion
The COVID-19 pandemic has a massive impact on nearly all countries across the world. While the initial spread of SARS-CoV-2 to Africa has been slow and the COVID-19 burden appears to be much lower than in other continents, the pandemic carries a high potential to negatively affect the control of other diseases, such as malaria [7]. It has already been shown, that the pandemic has resulted in major reductions of incidence of other respiratory diseases due to various effects [66]. Moreover, it has been predicted that the pandemic will result in major disruptions of routine childhood vaccinations, which may cause an increase in vaccine-preventable infectious diseases in SSA [67]. Both malaria and COVID-19 affect disproportionally the low socio-economic classes [28,32,68]. It is possible that the COVID-19 pandemic and its indirect effects, including the measures to contain it, may produce collateral damage similar to those seen 6 years ago during the West African Ebola epidemic, i.e., a sharp increase of malaria deaths which finally exceeded the direct Ebola mortality [17,36,69]. Thus, understanding how the COVID-19 pandemic affects malaria control measures is of extreme importance for SSA [17,59].
Accelerated malaria control efforts since the early twenty-first century have significantly reduced the malaria burden in Africa and worldwide [17]. Control strategies include ITN and IRS interventions, early diagnosis and rapid treatment with ACT, and intermittent preventive treatment for infants, children and pregnant women [14]. However, the rate of reduction in malaria morbidity and mortality in SSA has recently stalled, and the initial overall positive trend could be seriously reversed due to the effects of the COVID-19 pandemic as shown in several modelling studies [17,[21][22][23].
In accordance with the conceptual framework, four major themes likely play an important role for the effects of the COVID-19 pandemic on malaria in SSA: (1) diagnostical and clinical aspects; (2) access to health care services; (3) availability of curative and preventive malaria commodities; and, (4) impact on malaria prevention programmes. While diagnostical and clinical aspects will play an obvious role due to the overlapping symptoms of both diseases [27,70,71], therapeutic aspects related to initial misperceptions regarding the efficacy of certain anti-malarials against COVID-19 may have been overemphasized [25,36]. Co-infection with malaria may complicate COVID-19, while immunomodulation caused by previous malaria exposure may result in less severe COVID-19, as was previously also shown in other respiratory diseases [72][73][74][75]. Reduced access to health care services due to direct and indirect effects of the pandemic has a negative impact on access to anti-malarial treatment, thus it would likely have a major effect on the malaria burden in endemic countries [17,49,53]. This will be compounded by the clear negative impact of the pandemic on global supply chains for curative and preventive malaria commodities [48,52]. The consequences of the pandemic for preventive malaria control programmes have been much emphasized by many of the reviewed papers and particularly in modelling papers. However, as an effect of such early warnings, country programmes and funding for malaria have probably adapted rapidly to the pandemic as early as 2020, which may have reduced the modelled impact [28,59]. International actors such as WHO may have contributed to the prevention of some worst-case scenarios by providing adapted malaria strategies and keeping malaria in their priorities [17,30].
Until June 2021, only a few reports provided actual epidemiological data on malaria in SSA during the first wave of the pandemic in 2020, thus drawing conclusions on these data might be premature. However, these reports showed that the number of reported malaria cases in Sierra Leone, Uganda and the DRC, that are more highly malaria-endemic countries, was much lower than expected [29,[61][62][63], while the number of reported malaria cases in Zimbabwe and Zambia, that are countries of low endemicity, was higher than in previous years [27,29,64,65]. It could be speculated that possibly lower access to health care services in combination with impaired malaria surveillance systems may have led to a lower number of reported malaria cases and deaths in these selected highly endemic countries. In the two low-endemic southern SSA countries, disruption of malaria control activities within relatively well-functioning health systems, including surveillance activities, may have resulted in a higher number of reported malaria cases and deaths. More information from other African endemic countries is needed to fully assess such developments [59,76]. As the COVID-19 pandemic is far from being under control in most low-and middle-income countries, as new and more infectious SARS-CoV-2 variants are emerging, and as SSA countries have limited access to COVID-19 vaccines, dramatic increases in the malaria burden may occur [59,77,78]. Although the findings of existing modelling studies are already alarming, the final impact of the pandemic on the malaria burden could be even more devasting [21,51]. Better education, sensitization and de-stigmatization of both diseases is essential, including emphasis on early careseeking behaviour, which also needs more community participation [25,29]. Community health workers should be encouraged to treat all uncomplicated malaria cases in the community and to refer to health facilities only severe cases [51,79]. As 2020 was a year with many planned malaria prevention campaigns, the negative effects of disrupted programmes would probably last for some years [21,23]. Fortunately, the international community, including WHO, acted fast to counteract such developments [17]. However, there is the need for more support for SSA countries from the international community and from high-income countries [32]. Malaria, one of Africa's deadliest diseases, which disproportionally affects the most vulnerable population groups, must be kept under control [16,35,59].

Conclusion
The findings from this review provide evidence for a significant but diverse impact of the COVID-19 pandemic on the malaria burden in SSA. Only results of further studies will enable a full understanding of these developments and its public health consequences. In the meantime, SSA countries need more support from the international community including the urgent delivery of COVID-19 vaccines for high-risk groups.