Review of malaria situation in Cameroon: technical viewpoint on challenges and prospects for disease


Abstract

Malaria still has a devastating impact on public health and welfare in Cameroon. Despite the increasing number of studies conducted on disease prevalence, transmission patterns or treatment, there are to date, not enough studies summarising findings from previous works in order to identify gaps in knowledge and areas of interest where further evidence is needed to drive malaria elimination efforts. The present study seeks to address these gaps by providing a review of studies conducted so far on malaria in Cameroon since the 1940s to date. Over 250 scientific publications were consulted for this purpose. Although there has been increased scale-up of vector control interventions which significantly reduced the morbidity and mortality to malaria across the country from a prevalence of 41% of the population reporting at least one malaria case episode in 2000 to a prevalence of 24% in 2017, the situation is not yet under control. There is a high variability in disease endemicity between epidemiological settings with prevalence of Plasmodium parasitaemia varying from 7 to 85% in children aged 6 months to 15 years after long-lasting insecticidal nets (LLINs) scale-up. Four species of Plasmodium have been recorded across the country: Plasmodium falciparum, P. malariae, P. ovale and P. vivax. Several primate-infecting Plasmodium spp. are also circulating in Cameroon. A decline of artemisinin-based combinations therapeutic efficacy from 97% in 2006 to 90% in 2016 have been reported. Several mutations in the P. falciparum chloroquine resistance (Pfcrt) and P. falciparum multidrug resistance 1 (Pfmdr1) genes conferring resistance to either 4-amino-quinoleine, mefloquine, halofanthrine and quinine have been documented. Mutations in the Pfdhfr and Pfdhps genes involved in sulfadoxine-pyrimethamine are also on the rise. No mutation associated with artemisinin resistance has been recorded. Sixteen anopheline species contribute to malaria parasite transmission with six recognized as major vectors: An. gambiae, An. coluzzii, An. arabiensis, An. funestus, An. nili and An. moucheti. Studies conducted so far, indicated rapid expansion of DDT, pyrethroid and carbamate resistance in An. gambiae, An. coluzzii, An. arabiensis and An. funestus threatening the performance of LLINs. This review highlights the complex situation of malaria in Cameroon and the need to urgently implement and reinforce integrated control strategies in different epidemiological settings, as part of the substantial efforts to consolidate gains and advance towards malaria elimination in the country.


  1. Background Malaria is still an important public health threat in Cameroon with the whole country exposed to the risk of transmission [1, 2]. Although significant progress has been made in the recent past, the disease remains prevalent with a high number of suspected cases in health care facilities varying between 3.3–3.7 million per year [1]. Malaria parasite transmission is highly heterogeneous with high and perennial parasite transmission occurring in the forest, coastal and humid savanna areas and low parasite transmission in highlands and seasonal parasite transmission in sahelian and dry savanna areas [3]. Plasmodium falciparum is the main parasite responsible for over 95% of the cases [4]. Other human-infecting Plasmodium species circulating in the country include P. malariae, P. ovale and P vivax [5]. The latter parasite species which was thought to be absent from West and Central Africa in more recent evolutionary times, has now been reported in the country [6,7,8], highlighting the changing pattern of malaria in Cameroon. However, the epidemiological role of this species as well as local vector species competence for this parasite is still to be determined. Up to 52 anopheline species have been reported in the country so far, with 16 recognized as main or secondary vectors [9,10,11]. Six of the species are among the most efficient vectors in sub-Saharan Africa, namely, An. gambiae (s.s.), An. coluzzii, An. arabiensis, An. funestus, An. nili and An. moucheti [11, 12].Vector control has been a vital component of malaria prevention and control, relying mainly on the use of long-lasting insecticidal nets (LLINs). Since 2000, Cameroon has benefited from the support of various international partners to implement malaria control interventions [9, 13]. Over 20 million LLINs have so far been freely distributed to the population through several campaigns [1], with the support of partners (e.g. the Global Fund). Although the coverage rate of the population is still below the target of the Ministry of Health (> 80% of the households having one net for two persons), it is estimated that between 2000 and 2015, the scale-up of treated bednets across the country resulted in a significant decrease in the prevalence of malaria reported cases from 41% to 24.3%, and 54% decrease in malaria related mortality (from about 13,000 to 6000 per year) [1].In the northern regions of the country where malaria parasite transmission is seasonal and prone to frequent eruptions of epidemics, seasonal chemoprevention has been introduced and targets mostly children [1]. In 2017, Cameroon was selected as a US President’s Malaria Initiative (PMI) focus country. The PMI programme, which will focus essentially in the North and Far North regions, will support the procurement of over 250,000 LLINs for routine distribution to pregnant women during antenatal care and will undertake indoor residual spraying (IRS) trials to foster malaria elimination in this part of the country [14]. A third nationwide free distribution of over 15 million LLINs to the population is planned for 2019 [1]. Other interventions are being piloted in other epidemiological settings of the country such as larviciding in the city of Yaoundé and the PADY (Projet d’Assainissement de Yaoundé) programme focusing on hygiene and sanitation in Yaoundé [15, 16]. Concerning malaria treatment, several programmes including case management are undertaken regularly to improve the management of malaria cases and tracking of drug resistance [17,18,19,20,21,22,23]. All these efforts, if well-coordinated, could further improve malaria control in Cameroon. Thus, there is still a need to further probe into the understanding of malaria epidemiology and transmission ecology for informed decision-making and to better coordinate control intervention strategies across the country.Although there have been several studies on malaria epidemiology, case management, parasite prevalence, drug resistance, vectors distribution, bionomics, role in malaria parasite transmission or insecticide resistance since the 1950s, little has been done to assess the impact of control interventions on disease transmission. Also, there are still not enough reviews summarising previous data in order to identify gaps in knowledge or to document recent evolution and dynamics of the vectors or the parasites. Such information is essential for the management of control programmes and scale-up of new or supplemental intervention strategies.The objective of the present review is to collate information from previous studies in order to better appraise the complexity of malaria situation and evidence in order to guide efforts towards malaria elimination in Cameroon. Although strengthening the health care system is an important requirement to achieve malaria elimination this has not been included in the present review which limits itself to an assessment of technical challenges and interventions.

  2. Data retrieval Information on malaria in Cameroon were extracted from published reports. Online bibliographic databases including PubMed, Google and Google Scholar were used to search for information. Terms used to guide these searches included “malaria”, “parasite”, “drug resistance”, “vector control”, “Plasmodium”, “LLINs”, “insecticide resistance”, “Anopheles”, “Cameroon”, “susceptibility”, “case management” “Yaoundé” and “Douala”. The search period included 1940 to 2019. The search resulted in 1029 articles. Over 750 papers were excluded because they were not on malaria or not reporting data from Cameroon.Information extracted from each selected published study were entered into a Microsoft Excel spreadsheet for easy access and data analysis. Information registered included authors names, the year of the study, methods and main findings.

  3. Situation of malaria in Cameroon Cameroon is situated in central Africa, within the Gulf of Guinea at a latitude between 2–13°N and a longitude between 9–16°E. It has a surface area of approximately 475,000 km2 with a population of about 24 million [24]. It is bordered to the West by Nigeria, to the North and East by Chad, to the East by Central African Republic and to the South by Congo, Gabon and Equatorial Guinea [25]. The country also has a coastal border of about 400 km with the Atlantic Ocean. Administratively, Cameroon is divided into 10 administrative regions covering different ecological domains (Fig. 1). Data from the demographic and health survey (DHS) and from the malaria indicator survey (MIS), indicated vegetation and altitude as important predictors of the geographical distribution of malaria in Cameroon [2]. During the last decade an increase in temperature of 0.4 °C and decrease in rainfall of 10–20% have been reported, compared to the period 1951–1980 [26]. Across sub-Saharan Africa, similar projections have been reported with an increase in temperature of 1.5 °C above the 1951–1980 baseline level [27]. Although this situation coincided with a certain number of events such as frequent reports of dengue cases in the country [28, 29], outbreaks of chikungunya and yellow fever in Cameroon and neighbouring countries [30,31,32] or invasion of Cameroon by Aedes albopictus mosquitoes originating from Asia [33, 34], there have not been many studies assessing the direct relationship between vector-borne diseases dynamics and changing climate conditions in Cameroon. This deserves further investigation in the light of some recent reviews [35,36,37,38,39]. Fig. 1

    A map of Cameroon showing climatic and administrative divisionsFull size image The Far North region belongs to the sahelian domain characterized by hot and dry weather with annual rainfall never exceeding 700 mm/year. According to malaria stratification the Far North region belongs to a hyperendemic malaria stratum with seasonal malaria parasite transmission prone to cyclic outbreaks. The Far North region is one of the most densely populated regions in the country, with a population estimated at 3.9 million inhabitants occupying a surface area of 34,263 km2 (Table 1) [40]. The fast demographic growth of the area, deforestation and desertification, deeply affected the landscape of the area which is now witnessing extended dry seasons with a reduction in crops yields and livestock productivity [41]. Table 1 Population repartition and bed net coverage in the different regions of CameroonFull size table In this region, frequent malaria epidemics occur during the rainy season which last 2–3 months [42]. Surveys conducted before the implementation of LLINs in the sites of Koza, Yagoua and Maga, indicated the prevalence of P. falciparum parasitaemia in children (n = 924) aged between 2 and 9 years-old, varying from 8.5% at the end of the dry season to 40.8% during the rainy season [43, 44]. A similar pattern was recorded in other sites of the region in Mahouda, Simatou, Guividig and Farahoulou with malaria prevalence varying from 10% (62/616) to 17.2% (109/632) [44]. Following LLINs scale-up, a decrease in the prevalence in children to 7.3–9.2% (n = 341) was recorded in 2017 [45]. However, the region still reported the highest number of malaria cases in 2015 in the country according to the NMCP annual report [3]. Entomological inoculation rate (EIR) was not reported to vary much before and after LLINs scale-up it is estimated to range between 2.4–24.0 infective bites/person/month during the rainy season, with An. arabiensis as the main vector species [46, 47]. The difference between reported entomological and epidemiological data may be due to the fact that the studies cited in the present review were not conducted in the same sites.The North region is located within the dry savanna domain and is characterized by a rainy season lasting 3–5 months with annual rainfall reaching 1000 mm/year. According to malaria stratification, this area belongs to a hyperendemic malaria stratum with seasonal malaria parasite transmission prone to cyclic outbreaks (transmission period could be extended compare to the Far North region). The population in the area is estimated at 2.4 million inhabitants on a surface area of 66,090 km2. The region population more than doubled during the last decades due in part to migration of population affected by droughts or displaced by the Boko Haram insurgency. Before LLINs scale-up in the country, malaria parasite prevalence in children of 1–15 years-old, was estimated to vary between 6.5–30.7% (n = 655) during cross-sectional surveys in the health districts of Lagdo [46, 48]. The EIR was found to vary between 2.7–36.5 infected bites/person/month [49, 50]. After LLINs scale-up, average malaria parasite prevalence levels of 30.4% [varying significantly from 28.6% (798/2795) for net users and 35% (243/694) for non-net users] was recorded in the health districts of Garoua, Pitoa and Mayo-Oulo in children of 6 months to 5 years-old (Table 2) [51]. Intense transmission was found to occur during the rainy season with estimates varying from 24.5 to 60 infective bites/person/month in the health districts of Lagdo, Garoua, Pitoa, Mayo Mbocki and Mayo Oulo [49, 50, 52, 53]. The increase in the EIR rate recorded for this region could derive from the fact that entomological surveys were undertaken in different sites before and after LLINs scale-up. It is possible that localities scoring high EIR had much higher rate before LLINs scale-up. Main vectors species in the area are An. arabiensis, An. gambiae and An. funestus. Other species playing a role in malaria parasite transmission are An. pharoensis, An. coluzzii, An. rufipes and An. ziemanni [50, 52]. Table 2 Summary of entomological and epidemiological data according to regions before and after LLINs scale-upFull size table The Adamaoua region situated mid-way between the North and the Centre regions, is dominated by a landscape above 1000 m and is characterized by humid savannah with one rainy season lasting over 6 months with a moderate climate and precipitation which amounts to 1500 mm/year. In some parts of the region, daily average temperatures could be as low as 20 °C part of the year. The region could be classified as belonging to a mesoendemic stratum with perennial malaria parasite transmission due to the abundance of rivers and lakes. The population of the area is about 1.18 million inhabitants living on a surface area of 63,701 km2 [40]. The region as well as the North, Far-North and East regions have several displaced camps for refugees or displaced persons coming from neighbouring countries, such as, Nigeria, Chad or the Central African Republic [54]. Yet there is still not enough information on how this influx of people has influenced local disease epidemiology which still deserves further investigation. Before LLINs, scale-up malaria parasite prevalence in 2–9 year-old children was 17.5% (n = 724) [55] and entomological inoculation rate (EIR) was 100 infected bites/person/year [56, 57]. After LLINs scale-up in 2017, parasites rates in febrile children of 2–9 years-old were reported to vary from 8.1 to 10.6% (n = 315) [58]. High Plasmodium infections in mosquitoes varying from 5 to 20% were recorded in An. funestus and An. gambiae [59].The West and North-West regions are all situated in highland areas (> 1000 m above sea level) and characterized by a temperate climate with rainfall lasting up to 8 months and a vegetation dominated by grasslands. These areas are considered as hypoendemic with seasonal malaria parasite transmission occurring at very low level. Average annual rainfall is estimated at 1800 mm/year. The West and North-West region has each over 1.9 million inhabitants. The West region covers a surface area of 13,892 km2 whereas the North-West covers a surface area of 17,300 km2. A survey conducted in the 1990s before the scale-up of LLINs in these settings, indicated parasite prevalence reaching up to 25% in children of less than 15 years-old (n = 530) [44, 60]. Entomological inoculation rate in the West region was found to vary from 62.8 to 90.5 infective bites/person/year [61]. After LLINs scale-up, a parasite rate varying from 9.3 to 22.4% (n = 173) in febrile children of 2–15 years-old was reported in different health care units of the West region [8, 58]. Retrospective analysis conducted between 2006 and 2012, in the health care district of Mbakong (North-West), showed a decrease in the parasite rate in febrile patients from 53.2% to 18.2% (n = 4230) following LLINs scale-up and a usage rate of > 50% [62]. Current entomological investigations reported parasite inoculation rates varying from 4.9 to 11 infective bites/person/year in the highland areas of the North-West region [63], whereas 2.24 infective bites/person/month was recorded in the West region (Table 2) [61, 64]. Main vectors in the area are An. gambiae, An. coluzzii and An. funestus.The Littoral, Centre, South-West, East and South regions all belong to the forest domain. This domain extends from the Atlantic coast to the border with the Central African Republic and is characterized by a succession of vegetation, including mangrove, deep equatorial evergreen forest and humid savannah. The climate comprises four seasons, two rainy seasons and two dry seasons with annual rainfall varying between 1500 mm/year inland to 4000 mm/year on the sea coast. These regions are considered as belonging to a holoendemic stratum with high and perennial malaria parasite transmission. The Littoral, Centre and South-West regions are the most densely populated, with the population varying from 4.09 million for the Centre, 3.3 million for the Littoral and 1.5 million inhabitants for the South-West region. The East and South regions are the less densely populated with a population of 745,000 inhabitants in the South and 832,000 inhabitants in the East region (Table 1). Prior to LLINs scale-up, the prevalence rate in children aged 6 months to 15 years-old ranged from 35 to 85.4% (n = 109–1690) [44, 65,66,67,68,69]. Studies conducted in the South-West region after LLINs mass campaigns scale-up, on children aged one month to 14 years-old, indicated a prevalence varying from 9 to 41.5% (n = 454) during the rainy season in Tiko, Limbé, Idenau, Mutengene and Buéa [18, 68, 70,71,72,73,74,75]. High parasite prevalence varying from 41.7 to 56.2% (n = 828) along the slope of Mount Cameroon was also recorded [76, 77]. The social crisis affecting the North-West and South-West regions of the country with a displaced population, could be affecting malaria epidemiology in the area and this could constitute an enormous challenge that could impede malaria elimination or control efforts in these regions and neighbouring regions. In the South and Centre regions a decrease in malaria parasite prevalence was recorded in the majority of settings with estimates of 6.6–29.5% (n = 2525) [58, 78, 79]. However, high parasite prevalence estimates were still recorded in some places such as Nkolbisson (43.4%) (n = 315) and Mfou (77.2%) (n = 263) [80, 81]. In the Littoral region, malaria parasite prevalence ranged between 20.4–29.4% (n = 288) [58, 71]. Regarding malaria parasite transmission, different patterns of transmission were reported. Before the scale-up of vector control tools, in the coastal cities of Tiko, Limbé and Ideanu, transmission estimates varied from 149 to 287 infective bites/person/year and this was similar to transmission level in the forested or highland areas (161 infective bites/person/year) [82]. Decreases in the transmission level was recorded following the scale-up of LLINs with transmission estimates as low as 0.7 infective bites/person/month in Tiko, 1.4 infective bites/person/month in Mamfe [64]. In the Littoral, Centre and South regions, transmission was reported to vary between 100 and 350 infective bites/person/year before the scale-up of LLINs [49, 83,84,85,86,87,88,89,90,91]. After scale-up, EIR values ranging from 0 to 100 infective bites/person/year [92,93,94,95] were reported (Table 2).Because of the poor road state in the East region, there have not been many studies conducted in this part of the country. Yet this region is considered as one of the most affected by malaria in the country [1]. This region is also one of the most vulnerable in the country because of its proximity with the Central African Republic and receives regularly influx of population running the social crisis in Central African Republic. Because the East region could constitute a reservoir for malaria dissemination in Cameroon, it is urgent that more efforts to improve the treatment and disease prevention be undertaken to reduce the high endemicity of malaria in the area.The cities of Yaoundé and Douala with a population of about 3 million inhabitants each [96] are similar to most of sub-Saharan cities [97, 98]. They are characterised by a rapid demographic growth, unplanned urbanization, fast development of informal settlements, large-scale practice of urban agriculture and rapid evolution of insecticide resistance in vectors [96, 99,100,101], which all probably affect the dynamics and epidemiology of vector-borne diseases. Before LLINs scale-up, EIR varied between 0–33 infected bites/person/year. Parasite prevalence was reported at 35% (n = 965) in children of 0–15 years-old [66]. The parasite rate in febrile children of less than 15 years-old admitted in hospital was equal to 42.9% (n = 415) [102]. After LLINs scale-up, EIR levels of 0 to 90 infective bites/person/year and a prevalence of 35% in children aged 3–14 years-old in the general population (n = 236) were recorded [101, 103].

  4. Plasmodium species All four human Plasmodium species have been documented in Cameroon, including P falciparum, P. ovle, P. malariae and P. vivax [6, 8, 9]. Plasmodium falciparum is by far the predominant species recorded in up to 95% of all infection cases [104, 105]. Plasmodium malariae and P. ovale represent each 1 and 3% of infection cases, respectively [9]. However, the distribution of the different Plasmodium species across the country could be underestimated as suggested by recent studies using molecular tools which indicated P. malariae infection cases in 17% out of 236 blood samples analysed [95, 106]. The study suggested the need to associate molecular tools in diagnostics to improve species detection. Genetic structure studies of P. falciparum suggested high diversity of circulating strains in Cameroon [107, 108].Plasmodium vivax was recently reported from Cameroon [6,7,8]. Studies conducted so far suggested frequent occurrence of this parasite in Duffy-negative people in different epidemiological settings [6,7,8]. In the city of Dschang (West Cameroon), out of 484 blood samples collected consecutively from febrile outpatients attending the main hospital during a 3-month period, P. vivax infection was detected by PCR in 5.6% (27/484) patients, representing 38.6% (27/70) of all Plasmodium infection cases detected [8]. Another study conducted in Bolifamba (South-West Cameroon) indicated that 14.9% (13/87) of Plasmodium infection cases were caused either exclusively or concomitantly by P. vivax, in individuals both positive (50%) and negative (50%) for the Duffy receptor [6]. In a larger study conducted in five locations in the South region of Cameroon, out of 201 malaria positive cases detected, six P. vivax and two mixed parasite infections (P. falciparum + P. vivax), were detected corresponding to a prevalence of 4% [7]. Yet the true profile of species occurrence and distribution across the country is not well documented. It is possible that P. vivax could have been misdiagnosed as P. ovale in the past since distinction in routine microscopy is very difficult. In neighbouring Equatorial Guinea, cases of P vivax infection are also highly prevalent [109, 110]. It is thought that the influx of workers from countries where P. vivax is endemic (Indonesia, Philippines) following the discovery of oil reserves in Equatorial Guinea could have increased P. vivax reservoir and transmission [110]. It is not clear whether subsequent expansion of the parasite in Cameroon could have resulted from population migration between the two countries. The discovery of P. vivax in Cameroon offers new research avenues on this species distribution, pathogenicity, genetic variability, transmission by different vectors species, interaction with other Plasmodium species and distribution in regard to urbanisation, climatic changes or malaria treatment policy. The expansion of P. vivax in Cameroon could oppose important challenges for malaria elimination in the country. One of these challenges could be the adoption of primaquine for radical cure of P. vivax related cases. Plasmodium vivax infections differ from other Plasmodium species because the parasites can lie dormant in a person’s liver, and reawaken suddenly later to cause relapses of malaria. Primaquine is thus taken daily for 14 days to clear P. vivax parasites in the blood and liver to prevent subsequent relapses. However, this drug is considered to be associated to serious adverse effects (destruction of red blood cells), particularly for patients with hereditary deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD) [111,112,113] and might require specific case management strategies. Another challenge is the proper diagnostic and procurement of new RDT tests for the detection of P. vivax infections in patients.Great apes in Cameroon were also reported to harbour several Plasmodium species close to P. falciparum, P. vivax, P. malariae and P. ovale [114,115,116]. Six Plasmodium species closely related to human-infecting P. falciparum were reported in the central African equatorial forest region. These include P. reichnowi, P. gaboni and P. billcollinsi found in chimpanzees, and P. adleri, P. blacklocki and P. praefalciparum found in gorillas [117]. Anopheline species such as An. moucheti was considered to be a possible bridge vector between human and apes [118]. Plasmodium falciparum-like parasites infecting wild apes in southern Cameroon were not found to represent a recurrent source for human malaria [106]. In Malaysia, Southeast Asia, recurrent cases of human infections by Plasmodium knowlesi, an Asian simian malaria parasite, were regularly reported [119]. Although subsequent malaria control interventions induced a marked reduction in the incidence of P. falciparum and P. vivax malaria cases, an increase in the incidence of malaria cases from the simian parasite P. knowlesi was still recorded [120,121,122,123]. Given the potential for simian Plasmodium to be transmitted from human to human and the public health implications of this zoonosis, it becomes important that more surveillance activities be conducted on this end through frequent diagnostic of simian Plasmodium in blood donors or resident living close to primates in the forest regions. It is still not known whether primates could represent a reservoir for human-infecting Plasmodium. Moreover, in the context of malaria elimination, identifying sources for reinfection of mosquitoes or possibilities of parasite introgression could have implications for the successful implementation of vector control programmes.

  5. Malaria treatment and case management Following expansion of drug resistance, drug policy for malaria treatment in Cameroon gradually changed over the years from monotherapies with chloroquine and amodiaquine used as a first-line treatment for uncomplicated malaria to combination therapy [124]. Chloroquine was largely used from the 1970s through to 2002 [9]. From 1999 to 2004, following the adoption of an interim drug policy, amodiaquine was incorporated alongside chloroquine as an alternative first-line drug for uncomplicated malaria while sulfadoxine-pyrimethamine was used as a second line drug [9, 124]. In 2004, following recurrent treatment failure to amodiaquine and sulfadoxine-pyrimethamine, the Ministry of Health of Cameroon reconsidered its policy and shifted to artemisinin-based combination therapy (ACT) used as a first-line treatment for uncomplicated malaria. Common ACT used in the country include artesunate-lumefanthrine, artesunate-atovaquone-proguanyl, artesunate-amodiaquine, artesunate-mefloquine. Sulfadoxine-pyrimethamine is still recommended as an intermittent preventive treatment for malaria during pregnancy (IPTp) whereas injectable artemether or quinine are used in case of treatment failure or for severe malaria cases [9]. In the northern part of the country exposed to recurrent malaria outbreaks during the rainy season, the government introduced in 2016 seasonal malaria chemoprevention for children below 5 years-old [1, 14]. The combination artesunate-amodiaquine (ASAQ) which was used before for the treatment of uncomplicated malaria cases for children under 5 years-old was replaced by artemether-lumefantrine (AL) provided free of charge to all families for malaria prevention. This strategy permitted to take in charge over 80% of children in the target settings in the North and Far-North regions [1].Case management in Cameroon includes: diagnosis of suspected cases; treatment of confirmed cases at health facilities and community level; scale-up of integrated community case management; pharmacovigilance and supply chain strengthening. Since 2011 the Cameroon government adopted free treatment of uncomplicated malaria for children of less than five years-old [1, 14]. Malaria diagnosis in most health care units is done through microscopic and/or TDR [1, 14, 20]. Since 2014 treatment of severe malaria is also free for children under 5 years-old [1, 14]. Integrated community case management (iCCM) for diarrhoea, pneumonia and malaria using community health workers, was introduced in 2009 to target groups with difficult access to health care services [125]. ICCM include clinical diagnosis and treatment provided by trained and supervised community health workers (CHWs). The results of pilot programmes conducted in the East region of Cameroon (Doume and Nguelemendouka) with 456 trained community health workers indicated that this approach improve equitable access to treatment for malaria and diarrhoea in remote settings of Cameroon [125]. The implementation of modified iCCM programme with proactive screening of children of < 5years-old in high malaria transmission settings (Bare Bakem in the Littoral region) showed that it could increase the likelihood to find malaria parasite infections in children by > 67% [126]. In different settings where iCCM have been introduced it is reported to have increased the treatment rate for malaria, care seeking behaviour for fever, and has reduced the burden on health care facilities [127]. Yet this approach faces several challenges such as underutilisation or the attrition of trained CHWs, inadequate supervision and motivation of CHWs, prolonged and frequent unavailability of commodities for malaria diagnosis and treatment [126]. Concerning pharmacovigilance several studies have so far been conducted across the country to assess malaria drug efficacy. The efficacy and safety of artemisinin base combination have been evaluated in four sentinel sites, Garoua, Bamenda, Nkongsamba and Ebolowa [128, 129]. Also, eight generic artemisinin base combinations have been evaluated from 2005 to 2016 [24, 103, 124, 129, 130]. All these studies concluded to the continuous efficacy of artemisinin base combination in Cameroon [128, 129, 131]. For diagnostic and treatment of malaria cases, several programmes have been conducted across the country in order to strengthen health care workers practices [132,133,134]. Additional case management programmes conducted include seasonal malaria chemoprevention in the North and Far-North regions.In order to achieve disease elimination, proper detection and treatment of malaria cases is required and the contribution of case management could become even more determinant, particularly in settings selected for malaria elimination, where the objective will be to track all cases to avoid reintroduction of malaria infected patients in malaria free zones.

  6. Drug resistance Current therapeutic efficacy studies suggest continuous efficacy of artemisinin-based combinations (with complete parasite clearance on day 3) in the country despite slight decline from 97% in 2006 to 90.2% in 2016 for artesunate-amodiaquine (AS-AQ), a compound largely used for malaria treatment in Cameroon [14]. Although these values are still largely in favour of a high efficacy of this combination there is a need to remain vigilant to avoid rapid expansion of drug resistance which could threaten the successful elimination of malaria. Yet if AS-AQ continues to be used as the official first-line treatment, then a policy change would need to be considered in the years to come. Fortunately, the Ministry of Health has started adopting artemether-lumefantrine as a first-line treatment in some part of the country [1, 14]. In Cameroon as in most countries in sub-Saharan Africa, almost half of drugs sold on the market or in some private health care units are fake and counterfeit medication of low quality [135]. Over 50% of the population get recourse to these drugs for their treatment [136, 137]. It is considered that substandard or fake antimalarials cause the death of 64,000 to 158,000 people in Africa in the recent years [138]. Controlling the quality of drugs sold on the market for improved case management constitute an important requirement to further consider in the perspective of malaria elimination.Drug efficacy has been reported to be affected by mutations occurring in the Pfcrt and Pfmdr1 gene in P. falciparum [139,140,141,142]. Mutations in the Pfcrt gene in P. falciparum are known to be associated with chloroquine and amodiaquine resistance [140, 143], whereas mutations in the P. falciparum multidrug resistance 1 (Pfmdr1) are considered to confer resistance to a large set of compounds including chloroquine, mefloquine, halofanthrine and quinine [142, 144, 145]. Pfdhfr and Pfdhps alleles are considered to mediate resistance to sulfadoxine-pyrimethamine [146, 147]. Studies conducted between 2005 and 2009 indicated a high prevalence of Pfcrt 76T mutation in various sites across Cameroon [148, 149]. The Pfmdr1 86Y mutation was also recorded at high frequency [150] however, no mutations in the Pfcrt 72 and no duplication of the Pfmdr1 gene were detected [149, 151, 152]. A recent study assessing the evolution of resistance genes in P. falciparum in the South-West region of Cameroon in blood samples collected between 2003 and 2013, indicated rapid elimination of alleles conferring resistance to 4-aminoquinoline (chloroquine and amodiaquine) Pfcrt 76T, Pfmdr1, 86Y, 184F and 1246Y and return to chloroquine sensitive genotypes since the withdrawal of chloroquine [20, 153]. However different evolutionary patterns of mutations associated with Pfcrt gene have been reported across the country, with novel mutations still reported from different settings, notably the Centre and South regions [148, 154]. For pfdhfr/pfdhps genes, no reduction in SNPs associated with antifolate drug resistance was recorded [20]. A study on pregnant women in the city of Yaoundé confirmed the presence of an increasing number of mutations on the Pfdhfr/Pfdhps genes [147]. Apinjoh et al. [72], described the presence of triple mutants on the Pfdhfr, Pfcrt, Pfdhps and Pfmdr1 genes in the South-West region (Table 3). The increase in the prevalence of mutations could result from intense selective pressure still going on with the use of sulfadoxine-pyrimethamine for chemoprophylaxis by pregnant women and other vulnerable groups. For the Pfkelch 13 gene few random mutations have been recorded. However, none of the mutations associated with artemisinin resistance in Southeast Asia have so far been recorded [72, 155, 156]. Yet Cameroon remains extremely vulnerable to potential risk of introduction and spread of artemisinin resistant mutations originating from Southeast Asia with the United Nation peace keeping operations with soldiers from Asia (Bangladesh and Pakistan troops) in Central African Republic [157] or oils workers from Asia in the neighbouring Equatorial Guinea [110]. The following stresses the need for regular surveillance activities to avoid the rapid spreading of these new mutations in Cameroon and the sub-region. It should also be important to conduct regular monitoring of the therapeutic efficacy of artemether-lumefantrine now widely used across the country. Table 3 Most prevalent drug resistant mutations in Plasmodium falciparum reported during recent years across CameroonFull size table

  7. Vectors species distribution, bionomics and genetic variability Cameroon has one of the most diverse anopheline fauna in Africa with more than 50 species reported [10]. Sixteen of the species are recognised as main or secondary malaria vectors and are involved in malaria parasite transmission either permanently or occasionally [11, 53, 63]. Species considered as main malaria vectors include: An. gambiae (s.s.), An. coluzzii, An. arabiensis, An. funestus, An. nili and An. moucheti (Table 2). Recent progress in molecular biology and genomics has allowed in-depth studies on species distribution, bionomics, genetic variability and geographical distribution across the country. The distribution of these species is now well documented in favour of intensive field studies undertaken across the country [11, 158,159,160,161]. Secondary malaria vectors include species which are involved in malaria parasite transmission either occasionally or temporally. Up to 11 species have been classified in this group which comprises: An. ovengensis, An. paludis, An. ziemanni, An. coustani, An. pharoensis, An. marshallii, An. rufipes, An. carnevalei, An. hancocki, An. leesoni and An. wellcomei [11,