Skip to main content

Malaria elimination in Ghana: recommendations for reactive case detection strategy implementation in a low endemic area of Asutsuare, Ghana

Abstract

Background

Progress toward malaria elimination is increasing as many countries near zero indigenous malaria cases. In settings nearing elimination, interventions will be most effective at interrupting transmission when targeted at the residual foci of transmission. These foci may be missed due to asymptomatic infections. To solve this problem, the World Health Organization recommends reactive case detection (RACD). This case study was conducted to identify individuals with asymptomatic malaria, their predisposing risk factors and recommend RACD in Asutsuare, Ghana based on literature review and a cross sectional study.

Methods

The study involved a search on PubMed and Google Scholar of literature published between 1st January, 2009–14th August, 2023 using the search terms “malaria” in “Asutsuare”. Furthermore, structured questionnaires were administered to one hundred individuals without symptoms of malaria and screened using rapid diagnostic test (RDT) kits, microscopy and real-time polymerase chain reaction (rt-PCR). Malaria prevalence based on the three diagnostic techniques as well as potential malaria risk factors were assessed through questionnaires in a cross-sectional study.

Results

Cumulatively, sixty-four (64) studies (Google Scholar, 57 and PubMed, 7) were reviewed and 22 studies included in the literature on malaria in Asutsuare, Ghana. Significant risk factors were occupation, distance from a house to a waterbody, age group and educational level. Out of the 100 samples, 3 (3%) were positive by RDT, 6 (6%) by microscopy and 9 (9%) by rt-PCR. Ages 5–14.9 years had the highest mean malaria parasite densities of 560 parasites/µl with Plasmodium falciparum as the dominant species in 4 participants. Moreover, in the age group ≥ 15, 2 participants (1 each) harboured P. falciparum and Plasmodium malariae parasites. RDT had a higher sensitivity (76.54%; CI95 66.82–85.54) than rt-PCR (33.33%; CI95 4.33–77.72), while both rt-PCR and RDT were observed to have a higher specificity (92.55; CI95 85.26–96.95) and (97.30; CI95 93.87–99.13), respectively in the diagnosis of malaria.

Conclusion

In Asutsuare, Ghana, a low endemic area, the elimination of malaria may require finding individuals with asymptomatic infections. Given the low prevalence of asymptomatic individuals identified in this study and as repleted in the literature review, which favours RACD, Asutsuare is a possible setting receptive for RACD implementation.

Background

Malaria control efforts in Ghana have a long history preceding independence [1]. The global malaria elimination programme in 2016, classified Ghana as one of the nations in the control phase [2]. Subsequently, Ghana has made significant gains in reducing the disease burden [3]. Malaria parasite prevalence by microscopy in the age group 6 to 59 months decreased from 28 to 14% in 2011 and 2019, respectively [4]. In 2022, there was a further decline of 5% in the national prevalence from 14 to 9% [5]. All of these were made possible as a result of the development and implementation of numerous strategic plans of action, intervention policies, and increased financial assistance over the years [6]. Furthermore, effective 2024–2028, the National Malaria Control Programme proposes a shift in malaria control to malaria elimination with the implementation of the national malaria elimination strategic plan (NMESP) of Ghana, 2024–2028 as contained in the World Health Organization (WHO) global technical strategy (GTS) for malaria 2016–2030 [7].

In hypoendemic areas, prior to the actualization of malaria elimination, malaria programmes are confronted with the difficult task of a changing epidemiology. Such settings are characterized by an increased number of imported malaria and hence a shift in high-risk groups from young children and pregnant women to demographic and occupational risk factors [8]. Transmission also becomes more geographically focal and possibly spread by means of asymptomatic infections [9]. To deal with the problem of malaria transmission that is more demographically and geographically focal and depicted by asymptomatic infection, the WHO recommends the use of Reactive Case Detection (RACD), the screening of household members and neighbours of index cases reported in passive surveillance [10]. Studies reporting on RACD used a number of protocols to assess its effectiveness. Despite this, RACD was generally implemented in lower endemic settings [11]. According to the WHO, an annual parasite prevalence of 1–10% is considered low and ≥ 35% as high [12]. Aidoo et al. [11], in a systematic review of 55 published studies that reported on RACD from 25 countries, had no record of its implementation in Ghana. Malaria elimination is often first achieved in parts of the areas within a country and prevention of re-establishment started at the subnational level while countries are working on full interruption of transmission in all their regions [10]. For Ghana to achieve its Malaria Strategic Plan 2021–2025, of reducing malaria case incidence by 50%, malaria mortality by 90%, and achieving malaria elimination as envisaged by 2028, the first RACD strategy in Ghana, in a yet to be implemented area of Asutsuare based on a cross sectional study of preliminary findings, coupled with previous studies in the literature is proposed and recommendations made. A literature review will, therefore, synthesize experiences with malaria in Asutsuare at different time points while the cross sectional study provides additional data to collectively inform recommendations and future use of RACD in Asutsuare, Ghana. This case study aimed to identify individuals with asymptomatic malaria, their predisposing risk factors and recommendations for the feasibility of RACD in a low-endemic area of Asutsuare in future. Within this context, understanding the epidemiology of low-endemic malaria transmission is crucial to achieving and sustaining elimination.

Ghana and Asutsuare’s Malaria landscape

In Ghana, malaria is endemic and perennial. Children under five years and pregnant women are the most vulnerable. Malaria is marked by seasonal fluctuations which differ from region to region [4]. In the ecological zone of Northern Savannah area, parasite prevalence is highly seasonal and peaks in a single wet season (June–October). However, in both forest and coastal ecological areas, malaria parasite prevalence peaks twice in a year [13]. Members of the Anopheles gambiae species complex, such as An. gambiae, Anopheles coluzzii, and Anopheles arabiensis, are the main malaria vectors in Ghana. Anopheles gambiae predominate and transcends across the country. However, during the drier months at the start and end of the season, An. coluzzii is frequently more prevalent. Anopheles funestus is a minor vector present at low levels. The vector species tend to bite late at night and are more prevalent in rural and periurban locations. The majority of parasite species, more than 95.0%, are Plasmodium falciparum. Although Plasmodium vivax infections have not yet been recorded, low-level Plasmodium malariae and Plasmodium ovale infections have been observed, typically occurring as mixed infections with P. falciparum [4].

Asutsuare is in the Shai-Osudoku District, Greater Accra Region, Ghana. It has a low seasonal malaria transmission, which peaks slightly after the rainy season between April to July [14]. Parasite prevalence by light microscopy was 2.4% in February 2009, 2.7% in May 2009 and 2.4% in August 2009 during a third survey [15]. Also in 2009, microscopy prevalence was reported to be 8.9% [16]. Regarding age groups, parasite prevalence increased from 1.7% in < 5 years to 3.4% in the 5–14 year group and 0% in the adult group by microscopy [14]. Another study reported a microscopy prevalence of 3.5% [17]. Agbana et al. [18] recorded a parasite prevalence of 0%, 2.2%, 5.6%, 11.2% and 50.1% by RDT, microscopy, PET-PCR, HRP2 bead assay, nested PCR, respectively.

A survey in the Asutsuare community comprising 337 respondents also indicated universal awareness of malaria as a health problem coupled with high knowledge of some common malaria symptoms. However, 3% of such respondents visited a health facility with suspected malaria and the remainder (97%) visited following self-medicated treatment failure [19]. Lamptey et al. [20] reported a 96% parasite distribution of P. falciparum and less than 5% P. malariae and P. ovale single infection and mixed infections of P. falciparum and P. malariae/P. ovale. Comparatively, P. falciparum prevalence was 6.4%, 8.0% and 16.4% amongst adults, children and pregnant women respectively. While children recorded a gametocyte prevalence of 39.5% (15/38), adult and pregnant women had a gametocyte prevalence of 17.4% (4/23) and 29.7% (11/37) respectively. Following a baseline parasite prevalence of [2.9%, (6/209)], P. falciparum proportion of children with at least one episode of malaria at the end of a follow-up period was 8.6% (95% CI 5.5–13.3) [21]. In a study involving 57 children, 18 had asymptomatic P. falciparum infections, 22 with symptomatic malaria, and 17 devoid of P. falciparum by microscopy or rapid diagnostic test [22]. In another follow-up study, children with malaria (168/669; 25.1%) were identified as either febrile (101/669; 15.1%) or those with asymptomatic parasitaemia (67/669; 10.0%) [23]. In children with P. falciparum malaria (n = 25), malaria was diagnosed by microscopy as either febrile (> 37.5 °C) uncomplicated P. falciparum infection (n = 7) or asymptomatic parasitaemia (n = 18) [24].

Walker et al. [25], in a study involving 78 healthy adults (18–69 years) likely to have been exposed many times to P. falciparum, found none of them to be positive by rapid diagnostic test (RDT) and microscopy. Furthermore, in two longitudinal cohort surveys, the parasite prevalence was found to be 14.45% [26] and 13% (53/395 children) cumulative incidence in a prospective cohort study [27]. Overall asexual parasite prevalence by microscopy of 6.1% (11/180) and gametocyte prevalence of 0% (0/180) were recorded by Jones et al. [28]. Ravens et al. [29] in their study reported a malaria prevalence of 8.9%. In a study involving 115 participants, P. falciparum microscopy prevalence was found to be 17.2% at any point during the respective study periods [26]. Tiendrebeogo et al. [30] recorded a malaria incidence of 15.1%. Relative to younger children (1–5 year old), older children (6–12 year old) were protected from febrile malaria with no association in parasitaemia (P = 0.29). Moreover, using 18srRNA PCR for P. falciparum speciation, 59.1% of samples tested positive for malaria parasite with a microscopy prevalence of 3.3% and RDT of 1.7% [31].

Abukari et al. [32] also reported asymptomatic P. falciparum microscopy prevalence of 3.75% (3/80). During the dry and rainy seasons, Acquah et al. [33] using Pfs25 mRNA PCR reported a gametocyte prevalence of 3/230 (1.3) and 3/174 (1.7), respectively. Conversely, the same study had a microscopy asexual parasite prevalence of 8/230 (3.5) and 7/174 (4.0) respectively. Furthermore, out of 644 pregnant women evaluated for placental malaria, peripheral parasitaemia was detected in 104 of them [34]. Ononye et al. [35] observed higher proportion of An. gambiae biting indoors relative to outdoors, in addition to sporozoite rate of 0.24% and an overall annual Entomological Inoculation Rate (EIR) of 4.9 infective bites per man per year (ib/m/y).

Generally, as indicated in the literature, malaria is a problem in Asutsuare despite its low endemicity. Hence, the need to recommend RACD that is informed by 14 years of literature between 2009 and 2023 in the country’s efforts towards malaria elimination.

Study design

Between July, 2022 to August, 2022, a cross sectional community-based study of asymptomatic individuals of all age groups was conducted in Asutsuare. This was further complemented with a search on PubMed and Google Scholar of literature published between 1st January, 2009–14th August, 2023 (effective year for the synthesized experiences with malaria in Asutsuare to the end of the literature search that met the inclusion criteria detailed below) using the search terms “malaria” in “Asutsuare”.

Search results were assessed using the following inclusion criteria:

  1. 1.

    Studies on the immunology, entomology, ecology, or genetics of malaria.

  2. 2.

    Studies designed to determine prevalence based on the diagnostic testing method used or characterize transmission patterns in all age groups.

  3. 3.

    Studies other than malaria were excluded.

Sample size determination

The sample size with a 95% CI and 5% margin of error was estimated according to the formula and variables defined, N =  Z2pq/e2, Z − 1.96, assuming 6% malaria prevalence from previous study [18] and 15% expected refusal rate. Following these assumptions, the final sample size was determined to be 100.

Data collection and laboratory methods

Data collected on the structured questionnaire included whether the household has been sprayed with insecticide, bed net ownership and usage, gender, age, amongst others. A single finger prick was used to collect blood samples, which were then spotted on Whatman 903™ protein saver card for rt-PCR and processed into smears for both thin and thick films. Using standard procedures, asexual parasites in thick and thin blood films on the same slide were counted against a minimum of 200 white blood cells and multiplied by a white blood cell count of 8000 per microlitre for quantification of parasite density [36]. For rt-PCR, dried blood spots on Whatman 903™ protein saver cards were placed inside individually sealed zip locks containing desiccant and kept at − 20 °C. As previously described [37], DNA was extracted using the Chelex method and kept at − 20 °C. P. falciparum rt-PCR was performed per published protocols [38].

Statistical analyses

Data collected was entered into Microsoft Excel 2019 (Microsoft Corp., Washington, USA) and analysed using Statistical Package for the Social Sciences (SPSS) version 26 (IBM Corp., Armonk, NY, USA) and GraphPad Prism 9.0 (GraphPad Software Inc., Boston, USA). For categorical variables, frequencies and percentages were computed while descriptive statistics was done for continuous variables. Test of association between variables was done using t-test, chi-square and analysis of variance where appropriate. Risk factors associated with malaria infection amongst the cohort was explored using multivariate analysis. A p-value < 0.05 was considered statistically significant. MedCalc® Statistical Software version 22 (MedCalc Software Ltd, Ostend, Belgium) was used to evaluate the diagnostic performance of rt-PCR and RDT for the detection of Plasmodium species infection. Positive and negative predictive values of rt-PCR and RDT were computed taking into consideration the prevalence of disease. The level of agreement between the diagnostic tests and the gold standard was measured using the Cohen Kappa score as described by McHugh [39].Values between 0.0 and 0.20 were considered as poor agreement, 0.21–0.40 as fair, 0.41–0.60 as moderate, 0.61–0.80 as strong and 0.81 and 1.00 as nearly perfect.

Ethics

The study was approved by the Research and Ethical Review Committee of the Department of Medical Laboratory Technology, Accra Technical University (ATU/MLT/ET/01192135B/2021–2022). Informed consent was expressly sought from all adult participants. Also, participants below 18 years old were given an assent form to be completed by their parents or guardians on their behalf. During screening, participants who tested positive for malaria were sent to the Shai Osodoku Health Centre and treated according to current national malaria treatment guidelines (Fig. 1).

Fig. 1
figure 1

Map of Asutsuare in the Shai Osudoku District, Greater Accra Region, Ghana “adapted with permission from [ 20 ].

Results

Demographic characteristics of study participants

The study recruited a total of 100 participants who were asymptomatic of malaria. As shown in Table 1, many of the study participants were females, representing 55%. Study participants > 15 years were 53% representing the majority of the study population, while ages 5–14.9 years and ≥ 15years were 37% and 10% respectively. More than half, 52%, of participants were without bednets while 53 (53%) lived near water bodies.

Table 1 Characteristics of the study population

Prevalence of Plasmodium infection and distribution of parasite density

Plasmodium infection using three diagnostic techniques showed a prevalence of 3%, 6% and 9% by RDT, microscopy and rt-PCR, respectively (Fig. 2). The study found no Plasmodium infection in participants aged 0–4.9 years. However, the mean parasite density for participants aged 5-14.9 years was 560 parasite/µl of blood and participants ≥ 15 years had a mean parasite density of 242 parasite/µl of blood. Statistically, there was no significant difference (p = 0.294) in parasite density between participants aged 5-14.9 years and those ≥ 15 years (Fig. 3).

Fig. 2
figure 2

Distribution of Plasmodium infection by diagnostic tests

Fig. 3
figure 3

Distribution of parasite density amongst study participants by age

Distribution of Plasmodium infection amongst study participants using microscopy and rt-PCR

Regarding the 6 participants who had malaria, all 6 had a forest related job such as farming and all 6 had their houses not sprayed. Four did not own a bednet and all 6 travelled 2 weeks prior to the survey with a household member. Using microscopy, statistically occupation and distance of house to a water body were found to be significant (< 0.001 and 0.043), respectively (Table 2).

Table 2 Distribution of Plasmodium infection amongst study participants using microscopy

Out of the 9 participants, identified by rt-PCR to harbour malaria parasites, 8 were within the age group 5–14.9 and 1 was ≥ 15 years. Five did not own a bednet and lived near a waterbody. Age group and education were found to be statistically significant (0.003 and 0.032), respectively (Table 3).

Table 3 Distribution of Plasmodium infection amongst study participants using rt-PCR

Distribution of Plasmodium spp infection amongst study participants

As shown in Table 4, P. falciparum was the predominant species identified, followed by P. malariae. The study, however, did not find P. ovale and P. vivax. The highest prevalence of P. falciparum was seen in males 3(60%), primary students 4(80%), age group 5-14.9 years 4 (80%), forest related jobs 5(100%), workplace distance not near forest 5(100%), those who do not live near water body 3(60%) and do not own a bed net 3(60%).

Table 4 Distribution of Plasmodium spp infection amongst study participants

Clinical performance of rt-PCR and RDT for Malaria diagnosis

In Table 5, both rt-PCR and RDT showed higher specificity (92.55; CI95 85.26–96.95) and (97.30; CI95: 93.87–99.13) respectively. Also, rt-PCR had a higher negative predictive value (93.35% CI95 88.83–96.12) while RDT showed a positive predictive value (92.53% CI95 83.80-96.74). An accuracy of 91.05% (CI95 86.61–93.43) was reported for RDT and 87.22% (CI95 79.06–93.06) was reported as the accuracy of rt-PCR in diagnosing malaria parasites infection.

Table 5 Clinical performance of rt-PCR and RDT in the diagnosis of malaria using microscopy as the gold standard

Discussion

The study sought to identify asymptomatic malaria and the predisposing risk factors in a low-endemic area of Asutsuare using microscopy, RDT, and rt-PCR. Primarily, malaria risk factors were occupation, distance of a house to a water body, age group and educational level. All six individuals who tested positive by microscopy had forest-related occupation and hence possible exposure to mosquitoes in the course of work. This finding is consistent with other studies in which adult men in low-transmission settings were at risk due to forest-related occupation and behavioural factors [8, 9, 40]. In Swaziland, distance of a house to a water body was one of the most important variables for prediction of transmission risk [41].

Prevalence as found by RDT, microscopy and rt-PCR was 3%, 6% and 9% respectively. In a study at Asutsuare, Agbana et al. [18] reported a parasite prevalence of 0%, 2.2% and 5.6% by RDT, microscopy and PET-PCR, respectively. The differences in the prevalence results may possibly be because of the period both studies took place. Be that as it may, both studies pointed to a low malaria prevalence. According to Ajakaye and Ibukunoluwa [42], a high prevalence leads to a high positive predictive value and low negative predictive value. However, in the present study, using microscopy as the gold standard, RDT showed a low prevalence, high positive predictive value (92.53%) and high negative predictive value (90.56%).

Also, RDT had a sensitivity and specificity of 76.54% and 97.30% respectively. The high positive predictive value demonstrates the utility of RDT in resource limited settings for the diagnosis of malaria, with positive results able to be considered truly positive. Also, the high negative predictive value minimizes false negatives. The WHO recommends 95% sensitivity and 97% specificity for malaria RDT. This is worth considering when utilizing RDT for malaria control programmes or for the diagnosis of malaria. In this study, the RDT specificity of 97.30% fell within the recommendation of the WHO, while that of the 76.54% sensitivity fell short of the recommendation. Compared with the WHO recommendation, the low sensitivity could be as a result of low parasite density below the threshold of RDT positivity [43]. The prozone effect, hyperparasitaemia, deletion or mutation of the HRP-2 gene, and other factors have also been cited as possible causes of low sensitivity in other studies [44, 45].

In hypoendemic areas, a negative RDT result therefore calls for confirmation with more sensitive diagnostic techniques as demonstrated by the study’s low sensitivity. The high specificity in this study suggests that community health workers in primary healthcare centers may employ RDT to rule out the absence of malaria in situations where microscopes are uncommon or lacked trained microscopist. The use of PCR in the diagnosis of malaria has been explored in many studies and indicated as a sensitive tool [46, 47]. This study detected a rt-PCR sensitivity and specificity of 33.3% and 92.55%, respectively, when using microscopy as gold standard. In contrast to this study, Madkhali et al. [48] reported a higher PCR sensitivity and specificity of 97.6% and 95.5% respectively, than what was reported in this study. This variation could be attributed to differences in study area, sample size and the type of nucleic acid isolation and amplification kit used.

Asymptomatic Plasmodium infection was prevalent in males than in females. Similar to this study, Mensah et al. [49] found that males were more likely to have malaria than female. Males typically have a weaker immunological response than females [50] and this may have necessitated this observation [51]. Such immunological differences may find expression in oestradiol, testosterone and progesterone [50]. In the host, however, hormonal concentrations may also be generated and modified by parasites [51]. Moreover, males are more likely to stay late outside at night and at best sleep outside without a mosquito net or proper protective clothing. Therefore, a better understanding of how gender activities affect exposure to mosquitoes can help inform guidelines for reducing malaria infection, particularly in males.

Asymptomatic malaria carriage has been associated with age [52]. Age-wise, majority of the participants with Plasmodium infection in this study were between 5 and 14.9 years. Studies conducted in Northern Ghana by Kanwugu et al. [52], was not consistent with the findings of the present study. However, the findings of Aidoo et al. [53] was consistent with the present study. Age is regarded as one of the most significant factors influencing protective immunity. Comparatively, younger children are most susceptible, while young children and adults who have had frequent bouts of malaria and built up immunity are more likely to carry asymptomatic infection [54].

Recommendations for consideration of RACD

At the onset of RACD, awareness should be raised to achieve high coverage and to encourage community participation within the defined target area. It will be ideal to have community health workers at the forefront of this campaign to have the buy in of the community. Such an awareness drive should include malaria symptoms, preventive measures, and the importance of seeking early diagnosis and treatment.

There is the need for a dedicated research team comprising healthcare providers stationed at the recruiting medical facility, laboratories, and community health workers for swift notification and investigation of index cases. These personnels should have the capacity to conduct case investigations, perform rapid diagnostic tests (RDTs), and administer appropriate treatment based on national treatment guidelines. Furthermore, there should be active collaboration among these personnels at the various levels (primary healthcare centres and hospitals) and other stakeholders to coordinate efforts and leverage available resources. Partnerships can enhance the scope and impact of RACD.

There should be clear definition of the target area. Hence, in resource limited settings, RACD should be restricted to particular high-risk places, such as within known foci or in places with low coverage of indoor residual spraying (IRS) and/or insecticide-treated nets (ITN). In like manner, index case households and close neighbours of index cases should be given precedence. Where malaria risk may not be connected to place of residence but rather population characteristics such as occupation, RACD can be implemented demographically instead of geographically, reactively testing contacts of members with common risk factors.

During RACD, to optimize coverage, screening should be undertaken when there is a full house or majority of the household members are likely to be present (such as during vacation or days people do not go to the farm). Also, those absent should be noted and possibly followed up on and screened later to avoid missing those at highest risk of contracting malaria.

RACD should be enhanced by frequently monitoring and evaluating its effectiveness by treatment outcomes, the number of cases detected and challenges faced during implementation.

Conclusion

For targeted interventions, risk factor assessments in low-endemic areas with a goal of eliminating malaria are crucial. Routine data analysis as depicted by this study can be used to identify risk factors and further enhanced with RACD as recommended by the study in malaria investigations.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

EIR :

Entomological inoculation rate

GTS :

Global technical strategy

HRP2 :

Histidine rich protein 2

Mps :

Malaria parasites

mRNA :

Messenger ribonucleic acid

NMESP :

National malaria elimination strategic plan

PET-PCR :

Photo-induced electron transfer polymerase chain reaction

RACD :

Reactive case detection

RDT :

Rapid diagnostic test

rt-PCR :

Real time polymerase chain reaction

SPSS :

Statistical Package for the Social Sciences

WHO :

World Health Organization

References

  1. National Malaria Control. Programme An epidemiological profile of malaria and its control in Ghana. Accra, 2013.

  2. WHO. Eliminating malaria. Geneva: World Health Organization; 2016.

    Google Scholar 

  3. WHO. Action and investment to defeat malaria 2016–2030. For a malaria-free world. Geneva: World Health Organization; 2015.

    Google Scholar 

  4. U.S. President’s Malaria Initiative. Ghana Malaria Operational Plan FY; 2022.

  5. Ghana Statistical Service (GSS) and ICF. Ghana Demographic and Health Survey 2022: Key indicators Report. Accra, Ghana, and Rockville. Maryland, USA: GSS and ICF; 2023.

    Google Scholar 

  6. Ghana Health Service. Ghana malaria programme review final report. Accra: Ghana Health Service; 2013.

    Google Scholar 

  7. WHO. Global technical. Strategy for malaria 2016–2030. Geneva: World Health Organization; 2015.

    Google Scholar 

  8. Herdiana H, Cotter C, Coutrier FN, Zarlinda I, Zelman BW, Tirta YK, et al. Malaria risk factor assessment using active and passive surveillance data from Aceh Besar, Indonesia, a low endemic, Malaria elimination setting with Plasmodium Knowlesi, Plasmodium Vivax, and Plasmodium Falciparum. Malar J. 2016;15:468.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Cotter C, Sturrock HJ, Hsiang MS, Liu J, Phillips AA, Hwang J, et al. The changing epidemiology of Malaria elimination: new strategies for new challenges. Lancet. 2013;382:900–11.

    Article  PubMed  PubMed Central  Google Scholar 

  10. WHO. World Malaria report. Geneva: World Health Organization; 2022.

    Google Scholar 

  11. Aidoo EK, Aboagye FT, Botchway FA, Osei-Adjei G, Appiah M, Duku-Takyi R, et al. Reactive case detection strategy for Malaria control and elimination: a 12 year systematic review and meta-analysis from 25 malaria-endemic countries. Trop Med Infect Dis. 2023;8:180.

    Article  PubMed  PubMed Central  Google Scholar 

  12. WHO. World Malaria report 2015. Geneva: World Health Organization; 2016.

    Google Scholar 

  13. Nkrumah F, Klutse NA, Adukpo DC, Owusu K, Quagraine KA, Owusu A, et al. Rainfall variability over Ghana: model versus rain gauge observation. Int J Geosci. 2014;5:673–83.

    Article  Google Scholar 

  14. Badu K, Gyan B, Appawu M, Mensah D, Dodoo D, Yan G, et al. Serological evidence of vector and parasite exposure in Southern Ghana: the dynamics of malaria transmission intensity. Parasit Vectors. 2015;8:251.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kusi KA, Bosomprah S, Dodoo D, Kyei-Baafour E, Dickson EK, Mensah D, et al. Anti-sporozoite antibodies as alternative markers for Malaria transmission intensity estimation. Malar J. 2014;13:103.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Adu B, Dodoo D, Adukpo S, Hedley PL, Arthur FK, Gerds TA, et al. Fc gamma receptor IIIB (FcγRIIIB) polymorphisms are associated with clinical Malaria in Ghanaian children. PLoS ONE. 2012;7:e46197.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Amoah LE, Abagna HB, Akyea-Mensah K, Lo AC, Kusi KA, Gyan BA. Characterization of anti-EBA175RIII-V in asymptomatic adults and children living in communities in the Greater Accra Region of Ghana with varying Malaria transmission intensities. BMC Immunol. 2018;19:34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Agbana HB, Rogier E, Lo A, Abukari Z, Jones S, Gyan B, et al. Detecting asymptomatic carriage of Plasmodium Falciparum in southern Ghana: utility of molecular and serological diagnostic tools. Malar J. 2022;21:57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Attu H, Adjei JK. Local knowledge and practices towards Malaria in an irrigated farming community in Ghana. Malar J. 2018;17:150.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Lamptey H, Ofori MF, Kusi KA, Adu B, Owusu-Yeboa E, Kyei-Baafour E, et al. The prevalence of submicroscopic Plasmodium falciparum gametocyte carriage and multiplicity of Infection in children, pregnant women and adults in a low Malaria transmission area in Southern Ghana. Malar J. 2018;17:331.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Adu B, Cherif MK, Bosomprah S, Diarra A, Arthur FK, Dickson EK, et al. Antibody levels against GLURP R2, MSP1 block 2 hybrid and AS202. 11 and the risk of Malaria in children living in hyperendemic (Burkina Faso) and hypo-endemic (Ghana) areas. Malar J. 2016;15:123.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Frimpong A, Kusi KA, Tornyigah B, Ofori MF, Ndifon W. Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum Infection. Malar J. 2018;17:263.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Adu B, Jepsen MP, Gerds TA, Kyei-Baafour E, Christiansen M, Dodoo D, et al. Fc gamma receptor 3B (FCGR3B-c. 233 C > A-rs5030738) polymorphism modifies the protective effect of Malaria specific antibodies in Ghanaian children. J Infect Dis. 2014;209:285–9.

    Article  PubMed  CAS  Google Scholar 

  24. León-Lara X, Yang T, Fichtner AS, Bruni E, von Kaisenberg C, Eiz-Vesper B, et al. Evidence for an adult-like type 1-Immunity phenotype of Vδ1, Vδ2 and Vδ3 T cells in Ghanaian children with repeated exposure to Malaria. Front Immunol. 2022;13:807765.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Walker MR, Knudsen AS, Partey FD, Bassi MR, Frank AM, Castberg FC, et al. Acquisition and decay of IgM and IgG responses to merozoite antigens after Plasmodium Falciparum Malaria in Ghanaian children. PLoS ONE. 2020;15:e0243943.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Garcia-Senosiain A, Kana IH, Singh SK, Chourasia BK, Das MK, Dodoo D, et al. Peripheral merozoite surface proteins are targets of naturally acquired immunity against Malaria in both India and Ghana. Infect Immun. 2020;88:10–28.

    Article  Google Scholar 

  27. Dwomoh D, Adu B, Dodoo D, Theisen M, Iddi S, Gerds TA. Evaluating the predictive performance of Malaria antibodies and FCGR3B gene polymorphisms on Plasmodium falciparum Infection outcome: a prospective cohort study. Malar J. 2020;19:307.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Jones S, Grignard L, Nebie I, Chilongola J, Dodoo D, Sauerwein R, et al. Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates. J Infect. 2015;71:117–27.

    Article  PubMed  Google Scholar 

  29. Ravens S, Fichtner AS, Willers M, Torkornoo D, Pirr S, Schöning J, et al. Microbial exposure drives polyclonal expansion of innate γδ T cells immediately after birth. Proc Natl Acad Sci USA. 2020;117:18649–60.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Tiendrebeogo RW, Adu B, Singh SK, Dziegiel MH, Nébié I, Sirima SB, et al. Antibody-dependent cellular inhibition is associated with reduced risk against febrile Malaria in a longitudinal cohort study involving Ghanaian children. Open Forum Infect Dis. 2015;2:ofv044.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Nyarko SB. Identification of Plasmodium Falciparum histidine-rich protein II and III (PFHRP2/3) gene deletions in two communities in southern Ghana: implications on rapid diagnostic tests. Doctoral Dissertation, UCC. 2018.

  32. Abukari Z, Okonu R, Nyarko SB, Lo AC, Dieng CC, Salifu SP, et al. The diversity, multiplicity of Infection and population structure of P. falciparum parasites circulating in asymptomatic carriers living in high and low Malaria transmission settings of Ghana. Genes. 2019;10:434.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Acquah FK, Lo AC, Akyea-Mensah K, Abagna HB, Faye B, Theisen M, et al. Stage-specific Plasmodium falciparum immune responses in afebrile adults and children living in the Greater Accra Region of Ghana. Malar J. 2020;19:64.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Ofori MF, Lamptey H, Dickson EK, Kyei-Baafour E, Hviid L. Etiology of placental Plasmodium falciparum Malaria in African women. J Infect Dis. 2018;218:277–81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Ononye NC. Characterization of malaria transmission and insecticide susceptibility status of Anopheles gambiae sensu lato Gilles (Diptera: Culicidae). Shai-Osudoku District of Southern Ghana. Doctoral Dissertation, University of Ghana. 2015.

  36. WHO, UNICEF/UNDP/World Bank/WHO Special Programme for Research. and Training in Tropical Diseases. Microscopy for the detection, identification and quantification of Malaria parasites. Geneva, World Health Organization.

  37. Schwartz A, Baidjoe A, Rosenthal PJ, Dorsey G, Bousema T, Greenhouse B. The effect of storage and extraction methods on amplification of Plasmodium falciparum DNA from dried blood spots. Am J Trop Med Hyg. 2015;92:922–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Rougemont M, Van Saanen M, Sahli R, Hinrikson HP, Bille J, Jaton K. Detection of four Plasmodium species in blood from humans by 18S rRNA gene subunit-based and species-specific real-time PCR assays. J Clin Microbiol. 2004;42:5636–43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. McHugh ML. Interrater reliability: the kappa statistic. Biochem Med. 2012;22:276–82.

    Article  Google Scholar 

  40. Monteiro TH, Chaves TD, Matos HJ, Sofffiatti NF, Guimarães RJ, Guimarães LH, et al. Basic sanitation, socioeconomic conditions, and degree of risk for the presence and maintenance of Malaria in a low-transmission area in the Brazilian Amazon. Rev Soc Bras Med Trop. 2015;48:573–9.

    Article  PubMed  Google Scholar 

  41. Cohen JM, Dlamini S, Novotny JM, Kandula D, Kunene S, Tatem AJ. Rapid case-based mapping of seasonal Malaria transmission risk for strategic elimination planning in Swaziland. Malar J. 2013;12:61.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Ajakaye OG, Ibukunoluwa MR. Performance evaluation of a popular Malaria RDT in Nigeria compared with microscopy. J Parasit Dis. 2020;44:122–5.

    Article  PubMed  Google Scholar 

  43. Mouatcho JC, Goldring JD. Malaria rapid diagnostic tests: challenges and prospects. J Med Microbiol. 2013;62:1491–505.

    Article  PubMed  CAS  Google Scholar 

  44. Singh R, Abdullahi K, Bunza MD, Singh S, Kaitholia K. Comparative diagnosis of falciparum Malaria Infections by microscopy, two RDTs, and nested PCR in the three states of North-western Nigeria. J Biol Agric Healthc. 2013;3:31–9.

    Google Scholar 

  45. Koita OA, Doumbo OK, Ouattara A, Tall LK, Konaré A, Diakité M, et al. False-negative rapid diagnostic tests for Malaria and deletion of the histidine-rich repeat region of the hrp2 gene. Am J Trop Med Hyg. 2012;86:194–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Roth JM, Korevaar DA, Leeflang MM, Mens PF. Molecular Malaria diagnostics: a systematic review and meta-analysis. Crit Rev Clin Lab Sci. 2016;53:87–105.

    Article  PubMed  CAS  Google Scholar 

  47. Mfuh KO, Achonduh-Atijegbe OA, Bekindaka ON, Esemu LF, Mbakop CD, Gandhi K, et al. A comparison of thick-film microscopy, rapid diagnostic test, and polymerase chain reaction for accurate diagnosis of Plasmodium Falciparum Malaria. Malar J. 2019;18:73.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Madkhali AM, Ghzwani AH, Al-Mekhlafi HM. Comparison of rapid diagnostic test, microscopy, and polymerase chain reaction for the detection of Plasmodium Falciparum Malaria in a low-transmission area, Jazan region, southwestern Saudi Arabia. Diagnostics (Basel). 2022;12:1485.

    Article  PubMed  CAS  Google Scholar 

  49. Mensah BA, Myers-Hansen JL, Obeng Amoako E, Opoku M, Abuaku BK, Ghansah A. Prevalence and risk factors associated with asymptomatic Malaria among school children: repeated cross-sectional surveys of school children in two ecological zones in Ghana. BMC Public Health. 2021;21:1697.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Klein SL. Hormonal and immunological mechanisms mediating sex differences in parasite Infection. Parasite Immunol. 2004;26:247–64.

    Article  PubMed  CAS  Google Scholar 

  51. Klein PW, Easterbrook JD, Lalime EN, Klein SL. Estrogen and progesterone affect responses to Malaria Infection in female C57BL/6 mice. Gend Med. 2008;5:423–33.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Kanwugu ON, Helegbe GK, Aryee PA, Abdul-Karim A, Anaba F, Ziblim Z, et al. Prevalence of asymptomatic Malaria among children in the Tamale Metropolis: how does the PfHRP2 CareStart™ RDT perform against microscopy? J Trop Med. 2019;2019:6457628.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Aidoo EK, Afrane YA, Machani MG, Chebore W, Lawson BW, Atieli H, et al. Reactive case detection of Plasmodium Falciparum in western Kenya highlands: effective in identifying additional cases, yet limited effect on transmission. Malar J. 2018;17:111.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Zaw MT, Thant M, Hlaing TM, Aung NZ, Thu M, Phumchuea K, et al. Asymptomatic and sub-microscopic Malaria Infection in Kayah State, eastern Myanmar. Malar J. 2017;16:138.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank the study population for their participation and Dr Helena Lamptey, Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana for her consent to use the site map of Asutsuare.

Funding

Not applicable.

Author information

Authors and Affiliations

Authors

Contributions

EKA designed the study, literature review, coordinated data collection and management, performed molecular laboratory works, initial draft and writing final manuscript; FTA participated in microscopy, writing final manuscript, data management and analysis; GEA participated in study design, data management and writing final manuscript; FAB, GO-A, MA, RD-T, SAS, GA, BWL, RHA, LA, PB, OA, KAK helped in writing the final manuscript.

Corresponding author

Correspondence to Ebenezer Krampah Aidoo.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the Research and Ethical Review Committee of the Department of Medical Laboratory Technology, Accra Technical University (ATU/MLT/ET/01192135B/2021–2022).

Consent for publication

Map of Asutsuare in the Shai Osudoku District, Greater Accra Region, Ghana “adapted with permission.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aidoo, E.K., Aboagye, F.T., Agginie, G.E. et al. Malaria elimination in Ghana: recommendations for reactive case detection strategy implementation in a low endemic area of Asutsuare, Ghana. Malar J 23, 5 (2024). https://doi.org/10.1186/s12936-023-04792-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12936-023-04792-z

Keywords