Search

A major motivation for developing molecular methods for malaria surveillance is to measure the impact of control interventions on the population genetics of Plasmodium falciparum as a potential marker of progress towards elimination. Here we assess three established methods (i) single nucleotide polymorphism (SNP) barcoding (panel of 24-biallelic loci), (ii) microsatellite genotyping (panel of 12-multiallelic loci), and (iii) varcoding (fingerprinting var gene diversity, akin to microhaplotyping) to identify changes in parasite population genetics in response to a short-term indoor residual spraying (IRS) intervention. Typical of high seasonal transmission in Africa, multiclonal infections were found in 82.3% (median 3; range 1-18) and 57.8% (median 2; range 1-12) of asymptomatic individuals pre- and post-IRS, respectively, in Bongo District, Ghana. Since directly phasing multilocus haplotypes for population genetic analysis is not possible for biallelic SNPs and microsatellites, we chose ~200 low-complexity infections biased to single and double clone infections for analysis. Each genotyping method presented a different pattern of change in diversity and population structure as a consequence of variability in usable data and the relative polymorphism of the molecular markers (i.e., SNPs < microsatellites < var). Varcoding and microsatellite genotyping showed the overall failure of the IRS intervention to significantly change the population structure from pre-IRS characteristics (i.e., many diverse genomes of low genetic similarity). The 24-SNP barcode provided limited information for analysis, largely due to the biallelic nature of SNPs leading to a high proportion of double-allele calls and a view of more isolate relatedness compared to microsatellites and varcoding. Relative performance, suitability, and cost-effectiveness of the methods relevant to sample size and local malaria elimination in high-transmission endemic areas are discussed.

The global health community has targeted the elimination of neglected tropical diseases (NTDs) including soil-transmitted helminthiasis by 2030. The elimination strategy has not changed from that of control using regular mass drug administration (MDA) with albendazole, WASH and education. Already doubts have been expressed about this achievement, principally because drugs do not interrupt transmission. We report here the findings of a cohort study aimed to identify host modifiable and environmental factors associated with hookworm infection and reinfection in rural communities in Kintampo North Municipality, Ghana. Faecal samples of 564 consented participants were screened for intestinal parasites at baseline, 9 months and 24 months using the Kato-Katz method. At each time point, positive cases were treated with a single dose of albendazole (400 mg) and their samples were again screened 10-14 days post-treatment to record treatment failures. The hookworm prevalence at the three-time points was 16.7%, 9.22% and 5.3% respectively, whilst treatment failure rates were 17.25%, 29.03% and 40.9% respectively. The intensities of hookworm infection (in eggs per gram) at the time points were 138.3, 40.5 and 135, which showed a likely association with wet and dry seasons. We posit that the very low intensity of hookworm infections in humans during the dry season offers a window of opportunity for any intervention that could drastically reduce the community worm burden before the rainy season.

In the African region COVID-19 infection and death rates are increasing (writing in May 2020), most deaths have occurred among individuals with chronic conditions, and poor communities face higher risks of infection and socio-economic insecurities. We assessed the psychosocial needs of a chronic illness support group in Accra, Ghana, within the context of their broader community. The community lives in structural poverty and has a complex burden of infectious and chronic non-communicable diseases (NCDs). Between March and May 2020, we conducted interviews, group discussions, and surveys, with members of the support group and their caregivers, frontline healthcare workers, and religious and community leaders. Data was analysed through the social psychology of participation framework. Community members understood COVID-19 as a new public health threat and drew on eclectic sources of information to make sense of this. Members of the support group had psychosocial and material needs: they were anxious about infection risk as well as money, food and access to NCD treatment. Some community members received government food packages during the lockdown period. This support ended after lockdown in April and while anti-poverty COVID policies have been unveiled they have yet to be implemented. We discuss the impact of these representational, relational and power dynamics on the community’s access to COVID-19 and NCD support. We argue that strategies to address immediate and post-COVID needs of vulnerable communities have to focus on the politics and practicalities of implementing existing rights-based policies that intersect health, poverty reduction and social protection.

Influenza is known to cause severe respiratory illness in HIV-infected adults, but there are few data describing the relationship between HIV infection and influenza in West African countries such as Ghana. We conducted a prospective cohort study in the Shai-Osudoku and Ningo Prampram districts of Ghana from 2014 to 2016. Beginning May 2014, 266 HIV-infected and 510 HIV-uninfected participants age 18 to 73 years were enrolled and monitored for 12 months. We observed 4 and 11 laboratory-confirmed influenza cases among HIV-infected and HIV-uninfected persons, respectively. The overall rate of laboratory-confirmed influenza among HIV-infected participants was 15.0 per 1,000 person years (PY) (95% CI, 0.3–29.80 per 1,000 PY), whereas that among HIV-uninfected participants was 21.6 per 1,000 PY (95% CI, 8.8–34.3 per 1,000 PY) (incidence density ratio, 0.70; P = 0.56). Our study found no significant difference in the incidence of laboratory-confirmed influenza-associated illness among HIV-infected and HIV-uninfected individuals in Ghana.

To describe how early case detection, testing and contact tracing measures were deployed by stakeholders in response to the COVID-19 outbreak in Ghana - using three outbreak scenarios.A descriptive assessment of three case studies of COVID-19 outbreaks within three settings that occurred in Ghana from March 13 till the end of June 2020.A construction camp, a factory and a training institution in Ghana.Staff of a construction camp, a factory, workers and students of a training institution.We described and compared the three COVID-19 outbreak scenarios in Ghana, highlighting identification and diagnosis of cases, testing, contact tracing and stakeholder engagement for each scenario. We also outlined the challenges and lessons learnt in the management of these scenarios.Approach used for diagnosis, testing, contact tracing and stakeholder engagement.Index cases of the training institution and construction camp were screened the same day of reporting symptoms, whiles the factory index case required a second visit before the screening. All index cases were tested with RT-PCR. The training institution followed and tested all contacts, and an enhanced contact tracing approach was conducted for staff of the other two sites. Multi-sectorial engagement and collaboration with stakeholders enabled effective handling of the outbreak response in all sites.Comparing all three settings, early diagnosis and prompt actions taken through multi-sectorial collaborations played a major role in controlling the outbreak. Engaging stakeholders in the COVID-19 response is an effective way to mitigate the challenges in responding to the pandemic.The COVID-19 outbreak response and writing workshop by the Ghana Field Epidemiology and Laboratory Training Programme (GFELTP) was supported with funding from President Malaria Initiative - CDC, and Korea International Cooperation Agency (on CDC CoAg 6NU2GGH001876) through AFENET.

Among western African countries, the Republic of Ghana has maintained an economic growth rate of 5% since the 1980s and is now categorized as a middle-income country. However, as with other developing countries, Ghana still has challenges in the effective implementation of surveillance for infectious diseases. Facing public health emergencies of international concern (PHEIC), it is crucial to establish a reliable sample transportation system to the referral laboratory. Previously, surveillance capacity in Ghana was limited based on Integrated Disease Surveillance and Response, and therefore the “Surveillance and Laboratory Support for Emerging Pathogens of Public Health Importance in Ghana (SLEP)” was introduced to strengthen diarrhea surveillance. The SLEP project started with a sentinel diarrhea survey supported by SATREPS/JICA in collaboration with National Public Health Reference Laboratory (NHPRL) and Noguchi Memorial Institute of Medicine (NMIMR). The base-line survey revealed the limited capacity to detect diarrhea pathogens and to transfer samples from health centers to NHPRL. The involvement of private clinic/hospital facilities into the surveillance network is also crucial to strengthen surveillance in Ghana. The strong and interactive relationship between the two top referral laboratories, NHPRL under the Ministry of Health NMIMR and under the Ministry of Education, enables Ghana Health Services and is critical for the rapid response against PHEIC. In future, we hope that the outcome of the SLEP surveillance project could contribute to building a surveillance network with more timely investigation and transfer of samples to referral labs.

Here, we report the first population genetic study to examine the impact of indoor residual spraying (IRS) on Plasmodium falciparum in humans. This study was conducted in an area of high seasonal malaria transmission in Bongo District, Ghana. IRS was implemented during the dry season (November–May) in three consecutive years between 2013 and 2015 to reduce transmission and attempt to bottleneck the parasite population in humans towards lower diversity with greater linkage disequilibrium. The study was done against a background of widespread use of long‐lasting insecticidal nets, typical for contemporary malaria control in West Africa. Microsatellite genotyping with 10 loci was used to construct 392 P. falciparum multilocus infection haplotypes collected from two age‐stratified cross‐sectional surveys at the end of the wet seasons pre‐ and post‐IRS. Three‐rounds of IRS, under operational conditions, led to a >90% reduction in transmission intensity and a 35.7% reduction in the P. falciparum prevalence (p

Highlights • Unresolved previous infection as major cause of recurring tuberculosis (TB) in Ghana. • Genomic epidemiology identifies high relapse among recurrent TB cases in Ghana. • 15-locus MIRU-VNTR typing is sufficient to predict the cause of TB recurrence. • Evidence of recent household-related TB transmission in Ghana. • Need for increased education by national TB control program., Objective To retrospectively investigate the cause of recurring tuberculosis (rcTB) among participants with pulmonary TB recruited from a prospective population-based study conducted between July 2012 and December 2015. Methods Mycobacterium tuberculosis complex isolates obtained from rcTB cases were characterized by standard mycobacterial genotyping tools, whole-genome sequencing, and phylogenetic analysis carried out to assess strain relatedness. Results The majority (58.3%, 21/36) of study participants with rcTB episodes had TB recurrence within 12 months post treatment. TB strains with isoniazid (INH) resistance were found in 19.4% (7/36) of participants at the primary episode, of which 29% (2/7) were also rifampicin-resistant. On TB recurrence, an INH-resistant strain was found in a larger proportion of participants, 27.8% (10/36), of which 40% (4/10) were MDR-TB strains. rcTB was attributed to relapse (same strain) in 75.0% (27/36) of participants and 25.0% (9/36) to re-infection. Conclusion Our findings indicate that previous unresolved infectiondue to inadequate treatment, may be the major cause of rcTB.

Estimates of SARS-CoV-2 transmission rates have significant public health policy implications since they shed light on the severity of illness in various groups and aid in strategic deployment of diagnostics, treatment and vaccination. Population-based investigations have not been conducted in Ghana to identify the seroprevalence of SARS-CoV-2. We conducted an age stratified nationally representative household study to determine the seroprevalence of SARS-CoV-2 and identify risk factors between February and December 2021. Study participants, 5 years and older regardless of prior or current infection COVID-19 infection from across Ghana were included in the study. Data on sociodemographic characteristics, contact with an individual with COVID-19-related symptoms, history of COVID-19-related illness, and adherence to infection prevention measures were collected. Serum obtained was tested for total antibodies with the WANTAI ELISA kit. The presence of antibodies against SAR-COV-2 was detected in 3,476 of 5,348 participants, indicating a seroprevalence of 67.10% (95% CI: 63.71–66.26). Males had lower seroprevalence (65.8% [95% CI: 63.5–68.04]) than females (68.4% [95% CI: 66.10–69.92]). Seroprevalence was lowest in >20 years (64.8% [95% CI: 62.36–67.19]) and highest among young adults; 20–39 years (71.1% [95% CI 68.83,73.39]). Seropositivity was associated with education, employment status and geographic location. Vaccination status in the study population was 10%. Exposure is more likely in urban than rural areas thus infection prevention protocols must be encouraged and maintained. Also, promoting vaccination in target groups and in rural areas is necessary to curb transmission of the virus.

Michael Fokuo Ofori,1,* Emma E Kploanyi,1 Benedicta A Mensah,2 Emmanuel K Dickson,1 Eric Kyei-Baafour,1 Sampson Gyabaa,3 Mary Tetteh,4 Kwadwo A Koram,2 Benjamin K Abuaku,2,* Anita Ghansah1,5,* 1Immunology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra, Ghana; 2Epidemiology Department, Noguchi Memorial Institute for Medical Research,University of Ghana, Legon, Accra, Ghana; 3Ewim Polyclinic, Ghana Health Service, Cape Coast, Ghana; 4Begoro District Hospital, Ghana Health Service, Begoro, Ghana; 5Parasitology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra, Ghana*These authors contributed equally to this workCorrespondence: Michael Fokuo OforiImmunology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Post Office Box LG581, Legon, GhanaTel +233 244 715975Fax +233 302 502182Email mofori@noguchi.ug.edu.ghPurpose: Malaria continues to be a major health issue globally with almost 85% of the global burden and deaths borne by sub-Saharan Africa and India. Although the current artemisinin derived combination therapies in Ghana are still efficacious against the Plasmodium falciparum (Pf) parasite, compounding evidence of artemisinin and amodiaquine resistance establish the need for a full, up-to-date understanding and monitoring of antimalarial resistance to provide evidence for planning control strategies.Materials and Methods: The study was cross-sectional and was conducted during the peak malaria transmission seasons of 2015, 2016, and 2017 in two ecological zones of Ghana. Study participants included children aged 6 months to 14 years. Using ex vivo 4,6-diamidino-2-phenylindole (DAPI) drug sensitivity assay, 330 Pf isolates were used to investigate susceptibility to five antimalarial drugs: chloroquine (CQ), amodiaquine (AMD) dihydroartemisinin (DHA), artesunate (ART) and mefloquine (MFQ).Results: The pooled geometric mean IC50S (GMIC50) of the five drugs against the parasites from Cape Coast and Begoro were 15.5, 42.4, 18.9, 4.6 and 27.3nM for CQ, AMD, DHA, ART, and MFQ, respectively. The GMIC50 values for CQ (p< 0.001), ART (p< 0.011) and DHA (p< 0.018) were significantly higher for Cape Coast isolates as compared to Begoro isolates. However, GMIC50 estimates for MFQ (p< 0.022) were significantly higher for Begoro isolates. Positive correlations were found between each pair of drugs with the weakest found between MFQ and DHA (r = 0.34;p< 0.001), and the strongest between ART and DHA (r =0.66; p< 0.001).Conclusion: The parasites showed reduced sensitivities to three (AMD, DHA and MFQ) out of the five drugs assessed. The study also demonstrated the continual return of chloroquine-sensitive parasites after 13 years of its withdrawal as the first-line drug for the treatment of uncomplicated malaria in Ghana. The ex vivo DAPI assay is a reliable method for assessing antimalarial drug sensitivities of Pf field isolates under field settings.Keywords: malaria, Plasmodium falciparum, anti-malarial drugs, field isolates, DAPI, uncomplicated malaria

High-malaria burden countries in sub-Saharan Africa are shifting from malaria control towards elimination. Hence, there is need to gain a contemporary understanding of how indoor residual spraying (IRS) with non-pyrethroid insecticides when combined with long-lasting insecticidal nets (LLINs) impregnated with pyrethroid insecticides, contribute to the efforts of National Malaria Control Programmes to interrupt transmission and reduce the reservoir of Plasmodium falciparum infections across all ages. Using an interrupted time-series study design, four age-stratified malariometric surveys, each of ~2,000 participants, were undertaken pre- and post-IRS in Bongo District, Ghana. Following the application of three-rounds of IRS, P. falciparum transmission intensity declined, as measured by a >90% reduction in the monthly entomological inoculation rate. This decline was accompanied by reductions in parasitological parameters, with participants of all ages being significantly less likely to harbor P. falciparum infections at the end of the wet season post-IRS (aOR = 0.22 [95% CI: 0.19–0.26], p-value < 0.001). In addition, multiplicity of infection (MOI(var)) was measured using a parasite fingerprinting tool, designed to capture within-host genome diversity. At the end of the wet season post-IRS, the prevalence of multi-genome infections declined from 75.6% to 54.1%. This study demonstrates that in areas characterized by high seasonal malaria transmission, IRS in combination with LLINs can significantly reduce the reservoir of P. falciparum infection. Nonetheless despite this success, 41.6% of the population, especially older children and adolescents, still harboured multi-genome infections. Given the persistence of this diverse reservoir across all ages, these data highlight the importance of sustaining vector control in combination with targeted chemotherapy to move high-transmission settings towards pre-elimination. This study also points to the benefits of molecular surveillance to ensure that incremental achievements are not lost and that the goals advocated for in the WHO’s High Burden to High Impact strategy are realized.

The molecular determinants of Plasmodium falciparum artemisinin resistance are the single nucleotide polymorphisms in the parasite’s kelch propeller domain, pfk13. Validated and candidate markers are under surveillance in malaria endemic countries using artemisinin-based combination therapy. However, pfk13 mutations which may confer parasite artemisinin resistance in Africa remains elusive. It has therefore become imperative to report all observed pfk13 gene polymorphisms in malaria therapeutic efficacy studies for functional characterization. We herein report all novel pfk13 mutations observed only in the Ghanaian parasite population. In all, 977 archived samples from children aged 12 years and below with uncomplicated malaria from 2007 to 2017 were used. PCR/Sanger sequencing analysis revealed 78% (763/977) of the samples analyzed were wild type (WT) for pfk13 gene. Of the 214 (22%) mutants, 78 were novel mutations observed only in Ghana. The novel SNPs include R404G, P413H, N458D/H/I, C473W/S, R529I, M579T/Y, C580R/V, D584L, N585H/I, Q661G/L. Some of the mutations were sites and ecological zones specific. There was low nucleotide diversity and purifying selection at the pfk13 locus in Ghanaian parasite population. With increasing drug pressure and its consequent parasite resistance, documenting these mutations as baseline data is crucial for future molecular surveillance of P. falciparum resistance to artemisinin in Ghana.

Diarrheal disease remains a major global health problem particularly in children under 5 years and the emergence of antibiotic-resistant strains of causative pathogens could slow control efforts, particularly in settings where treatment options are limited. This surveillance study conducted in Ghana aimed to determine the prevalence and antimicrobial susceptibility profile of diarrhea-causing bacteria. This was a cross-sectional study carried out in five health facilities in the Ga West Municipality of Ghana between 2017 and 2021. Diarrheic stool samples from patients were collected and cultured on standard differential/selective media and isolates identified by standard biochemical tests, MALDI-TOF assay, and serological analysis. The antibiogram was determined using Kirby-Bauer disk diffusion and Microscan autoScan4 MIC panels which were used for extended-spectrum beta-lactamase (ESBL) detection. Bacteria were isolated from 97.5% (772/792) of stool samples, and 167 of the isolates were diarrheagenic and met our inclusion criteria for antimicrobial resistance (AMR) analysis. These included Escherichia coli (49.1%, 82/167), Salmonella species (23.9%, 40/167), Vibrio species (16.8%, 28/167), and Shigella species (10.2%, 17/167). Among 24 Vibrio species, we observed resistances to cefotaxime (21/24, 87.5%), ceftriaxone (20/24, 83.3%), and ciprofloxacin (6/24, 25%), including four multi-drug resistant isolates. All 13 Vibrio parahaemolyticus isolates were resistant to cefazolin. All 17 Shigella isolates were resistant to tetracycline with resistance to shigellosis drugs such as norfloxacin and ciprofloxacin. Salmonella isolates were highly susceptible to norfloxacin (40/40, 100%) and tetracycline (12/34, 35%). Two ESBL-producing E. coli were also identified with marked susceptibility to gentamicin (66/72, 91.7%) and amikacin (57/72, 79.2%) prescribed in the treatment of E. coli infections. This study showed the different bacteria implicated in diarrhea cases in Ghana and the need for differential diagnoses for better treatment outcomes. Escherichia coli, Shigella, Salmonella, and Vibrio have all been implicated in diarrhea cases in Ghana. The highest prevalence was E. coli and Salmonella with Shigella the least prevalent. Resistance to commonly used drugs found in these isolates may render bacteria infection treatment in the near future nearly impossible. Routine antimicrobial susceptibility testing, effective monitoring, and nationwide surveillance of AMR pathogens should be implemented to curb the increase of antimicrobial resistance in Ghana.

The COVID-19 pandemic caused by SARS-CoV-2 is an important subject for global health. Ghana experienced lowmoderate transmission of the disease when the first case was detected in March 12, 2020 until the middle of July when the number of cases begun to drop. By August 24, 2020, the country's total number of confirmed cases stood at 43,622, with 263 deaths. By the same time, the Noguchi Memorial Institute for Medical Research (NMIMR) of the University of Ghana, the primary testing centre for COVID-19, had tested 285,501 with 28,878 confirmed cases. Due to database gaps, there were initial challenges with timely reporting and feedback to stakeholders during the peak surveillance period. The gaps resulted from mismatches between samples and their accompanying case investigation forms, samples without case investigation forms and vice versa, huge data entry requirements, and delayed test results. However, a revamp in data management procedures, and systems helped to improve the turnaround time for reporting results to all interested parties and partners. Additionally, inconsistencies such as multiple entries and discrepant patient-sample information were resolved by introducing a barcoding electronic capture system. Here, we describe the main challenges with COVID-19 data management and analysis in the laboratory and recommend measures for improvement. © 2021 Clinical Archives of Communication Disorders. All rights reserved.

Background The majority of Plasmodium falciparum infections, constituting the reservoir in all ages, are asymptomatic in high-transmission settings in Africa. The role of this reservoir in the evolution and spread of drug resistance was explored. Methods Population genetic analyses of the key drug resistance–mediating polymorphisms were analyzed in a cross-sectional survey of asymptomatic P. falciparum infections across all ages in Bongo District, Ghana. Results Seven years after the policy change to artemisinin-based combination therapies in 2005, the pfcrt K76 and pfmdr1 N86 wild-type alleles have nearly reached fixation and have expanded via soft selective sweeps on multiple genetic backgrounds. By constructing the pfcrt-pfmdr1-pfdhfr-pfdhps multilocus haplotypes, we found that the alleles at these loci were in linkage equilibrium and that multidrug-resistant parasites have not expanded in this reservoir. For pfk13, 32 nonsynonymous mutations were identified; however, none were associated with artemisinin-based combination therapy resistance. Conclusions The prevalence and selection of alleles/haplotypes by antimalarials were similar to that observed among clinical cases in Ghana, indicating that they do not represent 2 subpopulations with respect to these markers. Thus, the P. falciparum reservoir in all ages can contribute to the maintenance and spread of antimalarial resistance.

A large body of evidence supports the role of antibodies directed against the Plasmodium spp. parasite in the development of naturally acquired immunity to malaria, however an antigen signature capable of predicting protective immunity against Plasmodium remains to be identified. Key challenges for the identification of a predictive immune signature include the high dimensionality of data produced by high-throughput technologies and the limitation of standard statistical tests in accounting for synergetic interactions between immune responses to multiple targets. In this study, using samples collected from young children in Ghana at multiple time points during a longitudinal study, we adapted a predictive modeling framework which combines feature selection and machine learning techniques to identify an antigen signature of clinical immunity to malaria. Our results show that an individual's immune status can be accurately predicted by measuring antibody responses to a small defined set of 15 target antigens. We further demonstrate that the identified immune signature is highly versatile and capable of providing precise and accurate estimates of clinical protection from malaria in an independent geographic community. Our findings pave the way for the development of a robust point-of-care test to identify individuals at high risk of disease and which could be applied to monitor the impact of vaccinations and other interventions. This approach could be also translated to biomarker discovery for other infectious diseases.

Background Access to healthcare is important in controlling malaria burden and, as a result, distance or travel time to health facilities is often a significant predictor in modelling malaria prevalence. Adding new health facilities may reduce overall travel time to health facilities and may decrease malaria transmission. To help guide local decision-makers as they scale up community-based accessibility, the influence of the spatial allocation of new health facilities on malaria prevalence is evaluated in Bunkpurugu-Yunyoo district in northern Ghana. A location-allocation analysis is performed to find optimal locations of new health facilities by separately minimizing three district-wide objectives: malaria prevalence, malaria incidence, and average travel time to health facilities. Methods Generalized additive models was used to estimate the relationship between malaria prevalence and travel time to the nearest health facility and other geospatial covariates. The model predictions are then used to calculate the optimisation criteria for the location-allocation analysis. This analysis was performed for two scenarios: adding new health facilities to the existing ones, and a hypothetical scenario in which the community-based healthcare facilities would be allocated anew. An interactive web application was created to facilitate efficient presentation of this analysis and allow users to experiment with their choice of health facility location and optimisation criteria. Results Using malaria prevalence and travel time as optimisation criteria, two locations that would benefit from new health facilities were identified, regardless of scenarios. Due to the non-linear relationship between malaria incidence and prevalence, the optimal locations chosen based on the incidence criterion tended to be inequitable and was different from those based on the other optimisation criteria. Conclusions This study findings underscore the importance of using multiple optimisation criteria in the decision-making process. This analysis and the interactive application can be repurposed for other regions and criteria, bridging the gap between science, models and decisions.

Background Since the introduction of artemisinin-based combination therapy (ACT) in Ghana in 2005 there has been a surveillance system by the National Malaria Control Programme (NMCP) and the University of Ghana Noguchi Memorial Institute for Medical Research (UG-NMIMR) to monitor the therapeutic efficacy of ACTs for the treatment of uncomplicated malaria in the country. We report trends and determinants of failure following treatment of Ghanaian children with artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) combinations. Methods Per protocol analyses as well as cumulative incidence of day 28 treatment failure from Kaplan Meier survival analyses were used to describe trends of failure over the surveillance period of 2005–2018. Univariable and multivariable cox regression analyses were used to assess the determinants of treatment failure over the period. Results Day 28 PCR-corrected failure, following treatment with ASAQ, significantly increased from 0.0% in 2005 to 2.0% (95% CI: 1.1–3.6) in 2015 (p = 0.013) but significantly decreased to 0.4% (95% CI: 0.1–1.6) in 2018 (p = 0.039). Failure, following treatment with AL, decreased from 4.5% (95% CI: 2.0–9.4) in 2010 to 2.7% (95% CI: 1.4–5.1) in 2018, though not statistically significant (p = 0.426). Risk of treatment failure, from multivariable cox regression analyses, was significantly lower among children receiving ASAQ compared with those receiving AL (HR = 0.24; 95% CI: 0.11–0.53; p Conclusions Treatment failures for both ASAQ and AL have remained less than 5% (below WHO’s threshold of 10%) in Ghana since 2005. Predictors of treatment failure that need to be considered in the management of uncomplicated malaria in the country should include type of ACT, day 3 parasitaemia, and day 1 axillary temperature of patients being treated.

Immunity to Plasmodium falciparum is non-sterilising, thus individuals residing in malaria-endemic areas are at risk of infection throughout their lifetime. Here we seek to find a genomic epidemiological explanation for why residents of all ages harbour blood stage infections despite lifelong exposure to P. falciparum in areas of high transmission. We do this by exploring, for the first known time, the age-specific patterns of diversity of variant antigen encoding (var) genes in the reservoir of infection. Microscopic and submicroscopic P. falciparum infections were analysed at the end of the wet and dry seasons in 2012-2013 for a cohort of 1541 residents aged from 1 to 91 years in an area characterised by high seasonal malaria transmission in Ghana. By sequencing the near ubiquitous Duffy-binding-like alpha domain (DBLα) that encodes immunogenic domains, we defined var gene diversity in an estimated 1096 genomes detected in sequential wet and dry season sampling of this cohort. Unprecedented var (DBLα) diversity was observed in all ages with 42,399 unique var types detected. There was a high degree of maintenance of types between seasons (40% seen more than once), with many of the same types, especially upsA, appearing multiple times in isolates from different individuals. Children and adolescents were found to be significant reservoirs of var DBLα diversity compared with adults. Var repertoires within individuals were highly variable, with children having more related var repertoires compared to adolescents and adults. Individuals of all ages harboured multiple genomes with var repertoires unrelated to those infecting other hosts. High turnover of parasites with diverse isolate var repertoires was also observed in all ages. These age-specific patterns are best explained by variant-specific immune selection. The observed level of var diversity for the population was then used to simulate the development of variant-specific immunity to the diverse var types under conservative assumptions. Simulations showed that the extent of observed var diversity with limited repertoire relatedness was sufficient to explain why adolescents and adults in this community remain susceptible to blood stage infection, even with multiple genomes.

Objectives: Oral health surveys aid in estimating the oral health of a population and provide a projection for future oral health care needs. We report the procedures and rationale of a survey carried out to assess the oral health status and risk factors for oral disease among adults in the Greater Accra Region (GAR) of Ghana. It’s objective was to provide prevalence estimates on dental diseases, oral health behaviour and risk factors, and to establish baseline epidemiological data on the population’s oral health for further research.Methods: This was a population-based cross-sectional study of adults aged 25 years and above. A random, stratified two-stage sampling method was used to select participants from rural and urban communities in three types of districts (Metropolitan, Municipal, Ordinary). A semi- structured questionnaire was used to collect data on socio-demographic characteristics, oral health behaviours and risk factors for oral disease. Anthropometric data and a full-mouth clinical examination was carried out including: soft tissue assessment, tooth count, prosthodontic status, dental caries assessment and periodontal assessment.Results: A total of 729 participants were included in the study with a mean age of 43.9 (±14.6). Majority 425 (61%) were females. Though the metropolitan districts had more dental clinics and personnel, along with better health insurance coverage, they had a higher prevalence of missing teeth, retained roots, severe periodontitis and poorer oral health coverage. The findings also show some significant differences in disease prevalence, within the different localities and districts.Conclusions: Availability and access to oral health services is not the most important determinant of good oral health outcomes in this region. We recommend exploring socio-behavioral and cultural factors as well. This study provides district level data to inform policy and guide further research.

Acute gastroenteritis associated with diarrhea is considered a serious disease in Africa and South Asia. In this study, we examined the trends in the causative pathogens of diarrhea and the corresponding gut microbiota in Ghana using microbiome analysis performed on diarrheic stools via 16S rRNA sequencing. In total, 80 patients with diarrhea and 34 healthy adults as controls, from 2017 to 2018, were enrolled in the study. Among the patients with diarrhea, 39 were norovirus-positive and 18 were rotavirus-positive. The analysis of species richness (Chao1) was lower in patients with diarrhea than that in controls. Beta-diversity analysis revealed significant differences between the two groups. Several diarrhea-related pathogens (e.g., Escherichia-Shigella, Klebsiella and Campylobacter) were detected in patients with diarrhea. Furthermore, co-infection with these pathogens and enteroviruses (e.g., norovirus and rotavirus) was observed in several cases. Levels of both Erysipelotrichaceae and Staphylococcaceae family markedly differed between norovirus-positive and -negative diarrheic stools, and the 10 predicted metabolic pathways, including the carbohydrate metabolism pathway, showed significant differences between rotavirus-positive patients with diarrhea and controls. This comparative study of diarrheal pathogens in Ghana revealed specific trends in the gut microbiota signature associated with diarrhea and that pathogen-dependent dysbiosis occurred in viral gastroenteritis.

Objective: Describe the epidemiology of COVID-19 cases detected in the first four months of the pandemic in Ghana by person, place and time to provide an understanding of the local epidemiology of the disease. Methods: We conducted an exploratory descriptive study of all confirmed COVID-19 cases in Ghana from March 12 to June 30, 2020. Data was merged from the country's electronic databases, cleaned and summarized using medians, proportions and geospatial analysis. Design: A cross-sectional study design. Setting: Ghana. Participants: All confirmed COVID-19 cases in Ghana from March 12 to June 30, 2020. Interventions: None. Main Outcome measures: Epidemiological characterization of all confirmed COVID-19 cases recorded from March 12 - June 30, 2020 in Ghana by person, place and time. Results: A total of 17,763 cases were recorded with median age (IQR) of 33years (One month to 85 years). Among the confirmed cases, 10,272 (57.8%) were males and 3,521 (19.8%) were symptomatic with cough recorded in 1,420 (40.3%) cases. The remaining 14,242 (80.2%) were asymptomatic. Greater Accra region recorded the highest number of confirmed cases 11,348 (63.9%). All 16 administrative regions had recorded cases of COVID-19 by June 30, 2020 due to internal migration between the hotspots and other regions. The epidemiological curve showed a propagated outbreak with 117 deaths (CFR= 0.67%) recorded. Conclusion: A propagated outbreak of COVID - 19 was confirmed in Ghana on March 12, 2020. Internal migration from hotspots to other regions led to the spread of the virus across the nation. Majority of cases were asymptomatic. Funding: The COVID-19 pandemic response and writing workshop by the Ghana Field Epidemiology and Laboratory Training Programme (GFELTP) was supported with funding from President Malaria Initiative - CDC, and Korea International Cooperation Agency (on CDC CoAg 6NU2GGH001876) through AFENET.

Background: Access to healthcare is important in controlling malaria burden and, as a result, distance or travel time to health facilities is often a significant predictor in modeling malaria prevalence. Adding new health facilities may reduce overall travel time to health facilities and may decrease malaria transmission. To help guide local decision makers as they scale up community-based accessibility, we explore how the allocation of new health facilities might influence malaria prevalence in Bunkpurugu-Yunyoo district in northern Ghana. We perform a location-allocation analysis to find optimal locations of new health facilities by minimizing three district-wide objectives separately: malaria prevalence, malaria incidence, and average travel time to health facilities. Methods: We used generalized additive model to model malaria prevalence as a function of travel time to health facility and other geospatial covariates. The model predictions are used to calculate the optimization criteria and to conduct spatial optimization. This analysis was performed for two scenarios: adding new health facilities to the existing ones, and a hypothetical scenario in which the community-based healthcare facilities would be allocated anew. We created an interactive web application to facilitate efficient presentation of this analysis and allow users to experiment with their choice of health facility location and optimization criteria. Results: Using malaria prevalence and travel time as optimization criteria, we found two locations that were not covered by existing community-based health services that would benefit from new health facilities, regardless of scenarios. Due to the non-linear relationship between malaria incidence and prevalence, the optimal locations chosen by using incidence criterion tend to be inequitable and are different from those based on the other optimization criteria. Conclusion: Our findings underscore the importance of using multiple optimization criteria in the decision-making process. We believe that our analysis and interactive application can be repurposed for other regions and criteria, bridging the gap between science, models and decisions.

Purpose Malaria continues to be a major health issue globally with almost 85% of the global burden and deaths borne by sub-Saharan Africa and India. Although the current artemisinin derived combination therapies in Ghana are still efficacious against the Plasmodium falciparum (Pf) parasite, compounding evidence of artemisinin and amodiaquine resistance establish the need for a full, up-to-date understanding and monitoring of antimalarial resistance to provide evidence for planning control strategies. Materials and Methods The study was cross-sectional and was conducted during the peak malaria transmission seasons of 2015, 2016, and 2017 in two ecological zones of Ghana. Study participants included children aged 6 months to 14 years. Using ex vivo 4,6-diamidino-2-phenylindole (DAPI) drug sensitivity assay, 330 Pf isolates were used to investigate susceptibility to five antimalarial drugs: chloroquine (CQ), amodiaquine (AMD) dihydroartemisinin (DHA), artesunate (ART) and mefloquine (MFQ). Results The pooled geometric mean IC50S (GMIC50) of the five drugs against the parasites from Cape Coast and Begoro were 15.5, 42.4, 18.9, 4.6 and 27.3nM for CQ, AMD, DHA, ART, and MFQ, respectively. The GMIC50 values for CQ (p

High-malaria burden countries in sub-Saharan Africa are shifting from malaria control towards elimination. Hence, there is need to gain a contemporary understanding of how indoor residual spraying (IRS) with non-pyrethroid insecticides when combined with long-lasting insecticidal nets (LLINs) impregnated with pyrethroid insecticides, contribute to the efforts of National Malaria Control Programmes to interrupt transmission and reduce the reservoir of Plasmodium falciparum infections across all ages. Using an interrupted time-series study design, four age-stratified malariometric surveys, each of ~2,000 participants, were undertaken pre- and post-IRS in Bongo District, Ghana. Following the application of three-rounds of IRS, P. falciparum transmission intensity declined, as measured by a >90% reduction in the monthly entomological inoculation rate. This decline was accompanied by reductions in parasitological parameters, with participants of all ages being significantly less likely to harbor P. falciparum infections at the end of the wet season post-IRS (aOR = 0.22 [95% CI: 0.19–0.26], p-value < 0.001). In addition, multiplicity of infection (MOIvar) was measured using a parasite fingerprinting tool, designed to capture within-host genome diversity. At the end of the wet season post-IRS, the prevalence of multi-genome infections declined from 75.6% to 54.1%. This study demonstrates that in areas characterized by high seasonal malaria transmission, IRS in combination with LLINs can significantly reduce the reservoir of P. falciparum infection. Nonetheless despite this success, 41.6% of the population, especially older children and adolescents, still harboured multi-genome infections. Given the persistence of this diverse reservoir across all ages, these data highlight the importance of sustaining vector control in combination with targeted chemotherapy to move high-transmission settings towards pre-elimination. This study also points to the benefits of molecular surveillance to ensure that incremental achievements are not lost and that the goals advocated for in the WHO’s High Burden to High Impact strategy are realized.

Background Recent studies from different malaria-endemic regions including western Africa have now shown that Plasmodium vivax can infect red blood cells (RBCs) and cause clinical disease in Duffy-negative people, though the Duffy-negative phenotype was thought to confer complete refractoriness against blood invasion with P. vivax. The actual prevalence of P. vivax in local populations in Ghana is unknown and little information is available about the distribution of Duffy genotypes. The aim of this study was to assess the prevalence of P. vivax in both asymptomatic and symptomatic outpatients and the distribution of Duffy genotypes in Ghana. Methods DNA was extracted from dried blood spots (DBS) collected from 952 subjects (845 malaria patients and 107 asymptomatic persons) from nine locations in Ghana. Plasmodium species identification was carried out by nested polymerase chain reaction (PCR) amplification of the small-subunit (SSU) rRNA genes. For P. vivax detection, a second PCR of the central region of the Pvcsp gene was carried out. Duffy blood group genotyping was performed by allele-specific PCR to detect the presence of the FYES allele. Results No cases of P. vivax were detected in any of the samples by both PCR methods used. Majority of infections (542, 94.8%) in the malaria patient samples were due to P. falciparum with only 1 infection (0.0017%) due to Plasmodium malariae, and 2 infections (0.0034%) due to Plasmodium ovale. No case of mixed infection was identified. Of the samples tested for the FYES allele from all the sites, 90.5% (862/952) had the FYES allele. All positive samples were genotyped as FY*B-33/FY*B-33 (Duffy-negative homozygous) and therefore classified as Fy(a−b−). Conclusions No cases of P. vivax were detected by both PCRs and majority of the subjects tested carried the FYES allele. The lack of P. vivax infections observed can be attributed to the high frequency of the FYES allele that silences erythroid expression of the Duffy. These results provide insights on the host susceptibility for P. vivax infections that had not been investigated in Ghana before.

BackgroundMisguided prescription of antibiotics is an important contributor towards the emergence and spread of antibiotic resistance. The absence of effective interventions to control antibiotic use leads to increased consumption beyond the needed requirements. Antibiotic stewardship interventions must be appropriately targeted and assessed to enhance the controlled use of antibiotics. The objective of this study was to determine the factors associated with antibiotic prescription to febrile outpatients who seek care in health facilities within the Greater Accra region of Ghana.MethodsSecondary data obtained from the medical records of 2519 febrile outpatients, consecutively sampled at the outpatient department of 6 health facilities in 3 municipalities during the baseline survey of a quasi-experiment in 2015 was used. The primary outcome was prescription of any antibiotic. Independent variables included patients’ demographics, symptoms, laboratory investigations (blood film microscopy, malaria rapid diagnostic test, full blood count, urine and stool routine examinations), diagnoses, and prescribers’ demographics. Crude and adjusted logistic regression analyses were used to determine the factors associated with antibiotic prescription.ResultsThe prevalence of antibiotic prescription was 70.1% (95% CI: 67.7–72.4). Prescribers with more years of practice (> 5 years) were more likely to prescribe antibiotics compared to those with less than 3 years of practice (p p p ConclusionPrescription of antibiotics to febrile outpatients was high. Promoting laboratory testing can potentially reduce irrational antibiotic prescription. Prescribing antibiotics for children under five and the prescribing practices of prescribers with longer years of practice should be targeted with interventions to reduce high use of antibiotics.

Background Artemisinin-based combination therapy (ACT) partner drugs, currently used in Ghana are lumefantrine, amodiaquine and piperaquine. Plasmodium falciparum isolates with reduced susceptibility to these partner drugs may affect treatment outcome. Mutations in pfmdr1 gene is linked to reduced parasite susceptibility to amodiaquine and lumefantrine. In addition, the potency of the partner drugs in vivo depends on the metabolism by the cytochrome P450 (CYP) enzyme in the host. Mutations in the CYP2C8 and CYP3A4 genes are linked to reduced metabolism of amodiaquine and lumefantrine in vitro, respectively. This study investigated the host and parasite genetic factors affecting the susceptibility of the malaria parasite to ACT partner drugs.Methods Archived samples from 240 patients age ≤9 years participating in anti-malarial drug resistance survey in Ghana, and given artemether with lumefantrine (AL) or artesunate with amodiaquine (AA), were selected and analysed. Polymerase chain reaction (PCR) followed by Sanger sequencing was used to determine the polymorphisms in CYP2C8, CYP3A4 and pfmdr1 genes. Results For CYP3A4, all had wild type alleles, suggesting that the hosts are good metabolizers of lumefantrine. For CYP2C8 60% had wild type alleles, 35% heterozygous and 5% homozygous recessive alleles suggesting efficient metabolism of amodiaquine by the hosts. For pfmdr1 gene, at codon 86, 95% were wild type (N86) and 5% mutant (Y86). For codon 184, 36% were wild type (Y184) and 64% mutant (F184) while for codons 1034, 1042 and 1246, 100% (all) were wild type. The high prevalence of N86-F184-D1246 haplotype (NFD) suggest presence of parasites with reduced susceptibility to lumefantrine and not amodiaquine. Delayed clearance was observed in individuals with mutations in the pfmdr1 gene and not cytochrome 450 gene. Both synonymous and non-synonymous mutations were observed in the Pfmdr1 at low prevalence. Conclusion The outcome of this study indicates that the parasite's genetic factors rather than the host’s are likely to drive resistance to ACT in Ghana.

Background: Artemisinin-based Combination Therapy (ACT), a combination of a fast-acting artemisinin derivative and a relatively slow-acting partner drug, is used for malaria treatment in disease-endemic areas. The ACT partner drugs, currently used in Ghana are lumefantrine, amodiaquine, and piperaquine. Plasmodium falciparum isolates with reduced susceptibility to these partner drugs may affect treatment outcome. Mutations in the parasite multidrug-resistant 1 (Pfmdr1) gene is linked to reduced susceptibility to amodiaquine and lumefantrine. In addition, the potency of the partner drugs in vivo depends on the metabolism by the cytochrome P450 (CYP) enzyme in the host. Mutations in the CYP2C8 gene are linked to reduced metabolism of amodiaquine in vitro while mutations in CYP3A4 may be linked to reduced metabolism to lumefantrine in vitro. Methods: This study investigated the host and parasite genetic factors affecting the susceptibility of the malaria parasite to ACT partner drugs. Archived samples from 240 patients (120 given AL and the other half given AA) aged ≤9years participating in antimalarial drug resistance survey in sites representing the three ecological areas of Ghana were used. Polymerase chain reaction (PCR) followed by Sanger sequencing was used to determine the polymorphisms in CYP2C8, CYP3A4, and Pfmdr1 genes. Results: Of the 93 samples successfully genotyped for CYP3A4, all had wild type alleles which suggest that the hosts are good metabolizers of lumefantrine. Ninety-four samples were successfully genotyped for CYP2C8 of which 60% had wild type alleles, 35% heterozygous and 5% homozygous recessive alleles. The high percentage of wild type alleles observed also suggests that amodiaquine was metabolized efficiently by the hosts. Ninety-five samples were successfully genotyped for the Pfmdr1 gene. At codon 86, 95% were wild type (N86), 5% mutant (Y86). For codon 184, 36% were wild type (Y184) and 64% mutant (F184) while for codons 1034, 1042 and 1246, 100% (all) were wild type. The high prevalence of N86, F184, and D1246 (NFD) suggest the presence of strains of the parasites with reduced susceptibility to lumefantrine and not amodiaquine. Delayed clearance was observed in individuals with mutations in the Pfmdr1 gene and not Cytochrome 450 gene. There were both synonymous and nonsynonymous mutations observed in the Pfmdr1 at low prevalence. Conclusion: The outcome of this study indicates that parasite's genetic factors rather than the hosts' are likely to drive resistance to ACTs in Ghana.

Aedes-borne viral diseases mainly Yellow Fever (YF), Dengue (DEN), Zika (ZIK) and Chikungunya (CHK) have contributed to many deaths’ in the world especially in Africa. There have been major outbreaks of these diseases in West Africa. YF outbreaks have occurred in Ghana. Although Ghana has not recorded any outbreak of DEN, ZIK and CHK, the risk is high due to its proximity to West African countries where outbreaks have been recently been recorded. This study assessed the risk of transmission of Yellow fever (YFV), Dengue (DENV), Chikungunya (CHKV) and Zika (ZIKV) viruses in Larabanga and Mole Game Reserve areas in Northern Ghana. The immature and adult stages of Aedes mosquitoes were collected from Larabanga and Mole Game Reserve area. There was a significant (P>0.001) number of mosquitoes collected during the rainy season than the dry season. A total of 1,930 Aedes mosquitoes were collected during the rainy season and morphologically identified. Of these, 1,915 (99.22%) were Aedes aegypti and 15 (0.22%) were Aedes vittatus. During the dry season, 27 Aedes aegypti mosquitoes were collected. A total of 415 Ae. aegypti mosquitoes were molecularly identified to subspecies level of which Aedes (Ae) aegypti aegypti was the predominant subspecies. Both Ae. aegypti aegypti and Ae aegypti formosus exist in sympatry in the area. All Aedes pools (75) were negative for DENV, ZIKV and CHKV when examined by RT-PCR. Three Larval indices namely House Index, HI (percentage of houses positive for Aedes larvae or pupae), Container Index, CI (the percentage of containers positive for Aedes larvae or pupae) and Breteau Index, BI (the number of positive containers (with larvae and/or pupae per 100 inspected houses) were assessed as a measure for risk of transmission. The HI, CI and BI for both sites were as follows; Mole game reserve (HI, 42.1%, CI, 23.5% and BI, 100 for rainy season and 0 for all indices for dry season) and Larabanga (39%, 15.5% and 61 for rainy season and 2.3%, 1.3% and 2.3 for dry season). The spatial distribution of Aedes breeding sites in both areas indicated that Aedes larvae were breeding in areas with close proximity to humans. Lorry tires were the main source of Aedes larvae in all the study areas. Information about the species composition and the potential role of Aedes mosquitoes in future outbreaks of the diseases that they transmit is needed to design efficient surveillance and vector control tools.

Background Drug resistance remains a concern for malaria control and elimination. The effect of interventions on its prevalence needs to be monitored to pre-empt further selection. We assessed the prevalence of Plasmodium falciparum gene mutations associated with resistance to the antimalarial drugs: sulfadoxine-pyrimethamine (SP), chloroquine (CQ) and artemisinin combination therapy (ACTs) after the scale-up of a vector control activity that reduced transmission. Methods A total of 400 P. falciparum isolates from children under five years were genotyped for seventeen single nucleotide polymorphisms (SNPs) in pfcrt, pfmdr1, pfdhfr, pfdhps and pfk13 genes using polymerase chain reaction (PCR) and high resolution melting (HRM) analysis. These included 80 isolates, each randomly selected from cross-sectional surveys of asymptomatic infections across 2010 (baseline), 2011, 2012, 2013 (midline: post-IRS) and 2014 (endline: post-IRS) during the peak transmission season, when IRS intervention was rolled out in Bunkpurugu Yunyoo (BY) District, Ghana. The proportions of isolates with drug resistant alleles were assessed over this period. Results There were significant decreases in the prevalence of pfdhfr- I51R59N108 haplotype from 2010 to 2014, while the decline in pfdhfr/pfdhps- I51R59N108G437 during the same period was not significant. The prevalence of lumefantrine (LM), mefloquine (MQ) and amodiaquine (AQ) resistance-associated haplotypes pfmdr1-N86F184D1246 and pfmdr1-Y86Y184Y1246 showed decreasing trends (z = -2.86, P = 0.004 and z = -2.71, P = 0.007, respectively). Each of pfcrt-T76 and pfmdr1-Y86 mutant alleles also showed a declining trend in the asymptomatic reservoir, after the IRS rollout in 2014 (z = -2.87, P = 0.004 and z = -2.65, P = 0.008, respectively). Similarly, Pyrimethamine resistance mediating polymorphisms pfdhfr-N108, pfdhfr-I51 and pfdhfr-R59 also declined (z = -2.03, P = 0.042, z = -3.54, Ppfdhps-G437 and pfdhps-F436 (z = -0.36, P = 0.715 and z = 0.41, P = 0.684, respectively). No mutant pfk13-Y580 were detected during the study period. Conclusion The study demonstrated declining trends in the prevalence of drug resistant mutations in asymptomatic P. falciparum infections following transmission reduction after an enhanced IRS intervention in Northern Ghana.

Background: Malaria continues to be a major health issue globally with nine out of ten cases reported in Africa. Although the current artemisinin derived combination therapies in Ghana are still efficacious against the Plasmodium falciparum parasite, compounding evidence of artemisinin and amodiaquine resistance in the African region establish the need for a full, up-to-date understanding and monitoring of antimalarial resistance to provide evidence for planning control strategies.Methods: The study was cross-sectional and was conducted during the peak transmission seasons of 2015, 2016, and 2017 in two study sites located in different ecological zones of Ghana involving children aged 0.5-14 years presenting with symptomatic uncomplicated Plasmodium falciparum (Pf) malaria with parasitaemia greater than 1000 parasites/µl of blood. Using in vitro 4-,6-diamidino-2-phenylindole (DAPI) drug sensitivity assays, 328 Pf parasites collected were used to investigate susceptibility to five selected antimalarial drugs: chloroquine, amodiaquine, dihydroartemisinin, artesunate and mefloquine.Results: The geometric mean B (GMIC50) of five drugs against the parasites collected from Cape Coast were 9.6, 23.6, 9.1, 3.5 and 8.1nM for chloroquine, amodiaquine, artemisinin, artesunate, and mefloquine respectively in 2015. There was a 2 fold increase in the GMIC50 levels of all the drugs against the isolates collected in 2016 as compared to the 2015 data from Cape Coast .The a of the five drugs against the parasites collected from Cape Coast were significantly higher than those isolates collected from Begoro in 2016 and 2017 (PConclusions: The study has assessed the antimalarial drug sensitivities of Ghanaian Pf isolates collected over 3 consecutive years. The parasites showed variable resistance levels to all the drugs used over the period. The study has demonstrated the continual return of chloroquine-sensitive parasites. The in vitro DAPI assay is a useful method for monitoring individual drugs used in combinations in Ghana for the generation of data on their sensitivities over time.

Whole genome sequencing (WGS) is progressively being used to investigate the transmission dynamics of; Mycobacterium tuberculosis; complex (MTBC). We used WGS analysis to resolve traditional genotype clusters and explored the spatial distribution of confirmed recent transmission clusters. Bacterial genomes from a total of 452 MTBC isolates belonging to large traditional clusters from a population-based study spanning July 2012 and December 2015 were obtained through short read next-generation sequencing using the illumina HiSeq2500 platform. We performed clustering and spatial analysis using specified R packages and ArcGIS. Of the 452 traditional genotype clustered genomes, 314 (69.5%) were confirmed clusters with a median cluster size of 7.5 genomes and an interquartile range of 4-12. Recent tuberculosis (TB) transmission was estimated as 24.7%. We confirmed the wide spread of a Cameroon sub-lineage clone with a cluster size of 78 genomes predominantly from the Ablekuma sub-district of Accra metropolis. More importantly, we identified a recent transmission cluster associated with isoniazid resistance belonging to the Ghana sub-lineage of lineage 4. WGS was useful in detecting unsuspected outbreaks; hence, we recommend its use not only as a research tool but as a surveillance tool to aid in providing the necessary guided steps to track, monitor, and control TB.

Edem MA Tette,1 Ben A Gyan,2 Kwadwo A Koram3 1Department of Community Health, University of Ghana Medical School, Accra, Greater Accra Region, Ghana; 2Department of Immunology, Noguchi Memorial Institute for Medical Research University of Ghana, Accra, Greater Accra Region, Ghana; 3Department of Epidemiology, Noguchi Memorial Institute for Medical Research University of Ghana, Accra, Greater Accra Region, GhanaCorrespondence: Edem MA Tette Email edemenator@googlemail.comAbstract: The corona virus pandemic undoubtedly demonstrates the growing need for research in medical science. However, with the decline in physician scientists world-wide, innovative ways are needed to engender interest in research among medical students and young doctors to replenish the stock of physician investigators. One way of doing this is to create compulsory and elective projects for them. We describe research internships created for medical students at the Noguchi Memorial Institute for Medical Research to expose them to the rudiments of biomedical research and proposal development. We also describe research internships for doctors waiting for house job postings or keen to do research who needed mentorship. Though the response has been positive, the full impact will be realized with time. The recognition that training should be backed with a supportive environment, mentorship and clear career paths for physician scientists is also mentioned.Keywords: research, internship, medical students, doctors, physician scientist, investigator, extracurricular research, medical education

Introduction: Frequent and/or misguided prescription of antibiotics are important facilitators of the emergence and spread of antibiotic resistance. In the absence of the implementation of effective interventions to control antibiotic use, its consumption may increase out of proportion to requirements. Antibiotic stewardship interventions must be appropriately targeted and assessed to enhance the proper use of antibiotics. The objective of this study was to determine the factors associated with of antibiotics prescription to febrile patients who seek care in health facilities within the Greater Accra region of Ghana. Methods: Secondary data obtained from a review of medical records of 2,519 febrile patients at the outpatient department of 6 health facilities in 3 municipalities during the baseline survey of a quasi-experiment in 2016 were used. The primary outcome was prescription of any antibiotic. Independent variables included patients’ demographics, symptoms, laboratory investigations (blood film microscopy, malaria rapid diagnostic test, full blood count, urine and stool routine examinations), diagnoses, and prescribers’ demographics. Crude and adjusted logistic regression analyses were used to determine the factors associated with antibiotics prescription. Results: The prevalence of antibiotics prescription was 70.1% (95% CI: 67.7-72.4). Prescribers with more years of practice (>5years) were more likely to prescribe antibiotics compared to those with less than 3 years of practice (p < 0.001). Integrated Management of Neonatal and Childhood Illnesses (IMNCI) training was associated with a 2.3 (95% CI: 1.54, 3.53, p < 0.001) times higher odds of antibiotic prescribing. Patients aged 5 years or more were 60% less likely to be prescribed antibiotics compared with those under 5 years (AOR=0.40, 95% CI: 0.32, 0.51; p

Trypanosomiasis, leishmaniasis, and malaria are protozoan infections of public health importance with thousands of new cases recorded annually. Control of these infection(s) with existing chemotherapy is limited by drug toxicity, lengthy parenteral treatment, affordability, and/or the emergence of resistant strains. Medicinal plants on the other hand are used in the treatment of various infectious diseases although their chemical properties are not fully evaluated. In this study, we screened 112 crude extracts from 72 selected Ghanaian medicinal plants for anti-Trypanosoma, anti-Leishmania, and anti-Plasmodium activities in vitro and investigated their mechanisms of action. Twenty-three extracts from 20 plants showed significant antiprotozoan activity against at least 1 of 3 protozoan parasites screened with IC50 values less than 20 μg/ml. Eleven extracts showed high anti-Trypanosoma activity with Bidens pilosa whole plant and Morinda lucida leaf extracts recording the highest activities. Their IC50 (selectivity index [SI]) values were 5.51 μg/ml (35.00) and 5.96 μg/ml (13.09), respectively. Nine extracts had high anti-Leishmania activity with Annona senegalensis and Cassia alata leaf extracts as the most active. Their IC50 (SI) values were 10.8 μg/ml (1.50) and 10.1 μg/ml (0.37), respectively. Six extracts had high anti-Plasmodium activity with the leaf and stem-bark extracts of Terminalia ivorensis recording the highest activity. Their IC50 (SI) values were 7.26 μg/ml (129.36) and 17.45 μg/ml (17.17), respectively. Only M. lucida at 25 μg/ml induced significant apoptosis-like cell death in Trypanosoma parasites. Anti-Leishmania active extracts induced varying morphological changes in Leishmania parasites such as multiple nuclei and/or kinetoplast, incomplete flagella division, or nuclear fragmentation. Active extracts may be potential sources for developing new chemotherapy against these infections.

The concept of niche partitioning has received considerable theoretical attention at the interface of ecology and evolution of infectious diseases. Strain theory postulates that pathogen populations can be structured into distinct nonoverlapping strains by frequency‐dependent selection in response to intraspecific competition for host immune space. The malaria parasite Plasmodium falciparum presents an opportunity to investigate this phenomenon in nature, under conditions of high recombination rate and extensive antigenic diversity. The parasite's major blood‐stage antigen, PfEMP1, is encoded by the hyperdiverse var genes. With a dataset that includes thousands of var DBLα sequence types sampled from asymptomatic cases within an area of high endemicity in Ghana, we address how var diversity is distributed within isolates and compare this to the distribution of microsatellite allelic diversity within isolates to test whether antigenic and neutral regions of the genome are structured differently. With respect to var DBLα sequence types, we find that on average isolates exhibit significantly lower overlap than expected randomly, but that there also exists frequent pairs of isolates that are highly related. Furthermore, the linkage network of var DBLα sequence types reveals a pattern of nonrandom modularity unique to these antigenic genes, and we find that modules of highly linked DBLα types are not explainable by neutral forces related to var recombination constraints, microsatellite diversity, sampling location, host age, or multiplicity of infection. These findings of reduced overlap and modularity among the var antigenic genes are consistent with a role for immune selection as proposed by strain theory. Identifying the evolutionary and ecological dynamics that are responsible for the nonrandom structure in P. falciparum antigenic diversity is important for designing effective intervention in endemic areas.

A new virus causing predominantly respiratory tract infection was described in China late 2019. The virus was subsequently named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes as COVID-19. Subsequently the virus spread to many parts of the world. This resulted in the World Health Organisation declaring COVID-19 a global pandemic on 11th March 2020.

Malaria control in West Africa is impeded by the large reservoir of chronic asymptomatic Plasmodium falciparum infections in the human population. This study aimed to assess the extent of diversity in the P. falciparum reservoir in Bongo District (BD), Ghana, at the end of the dry season, the lowest point in malaria transmission over the course of the year. Analysis of the variation in 12 microsatellite loci was completed for 200 P. falciparum isolates collected from a cross-sectional survey of residents of all ages from two catchment areas in BD. Analysis of the multilocus haplotypes showed high levels of genetic diversity (He = 0.74), no population differentiation yet significant linkage disequilibrium (LD) (ISA = 0.0127, P = 0.006) in BD. Multilocus LD was significant between and within catchment areas even though every haplotype in the population was unique and the majority of individuals (84.0%) harbored multiple-clone infections. The linkage structure among multilocus haplotypes was not associated with sampling location. These data provide the first study with deep sampling of the P. falciparum reservoir in an area of seasonal malaria transmission in West Africa. The co-occurrence of high multiplicity of infection (multiple-clone infections) with significant multilocus LD is surprising given the likelihood of high recombination rates in BD. The results suggest that the linkage structure among multilocus haplotypes has not been shaped by geographic separation of parasite populations. Furthermore, the observed LD levels provide a baseline population genetic metric with putatively neutral markers to evaluate the effects of seasonality and malaria control efforts in BD.

The declining efficacy of chloroquine in the early 2000s in Ghana led to its replacement with artesunate/amodiaquine (AS/AQ) combination as first-line drug for treating uncomplicated malaria in 2005. Since then efficacy studies have been ongoing in the country to provide continuous data on the efficacy of AS/AQ and other alternative antimalarials (artemether/lumefantrine and dihyroartemisinin/piperaquine combinations) introduced in 2008. In vivo AS/AQ efficacy studies were conducted between June and October 2014 among children aged 6 months to 14 years, in two sentinel sites representing the forest and coastal zones of the country. The 2009 World Health Organization protocol for monitoring antimalarial drug efficacy was used in these studies. The studies showed an overall cumulative polymerase chain reaction-corrected day 28 cure rate of 97.2% (95% confidence interval [CI]: 93.6–99.1): 97.7% (95% CI: 92.0–99.7) within the forest zone and 96.7% (95% CI: 90.7–99.3) within the coastal zone (P = 0.686). Prevalence of fever declined from 100% to < 4% after first day of treatment in both ecological zones. All children in the coastal zone had cleared parasites by day 2. Three children (3.2%) in the forest zone were parasitemic on day 2, whereas one child was parasitemic on day 3. Gametocytemia was absent in both zones after day 14, and mean hemoglobin concentration significantly increased from 10.3 g/dL (95% CI: 10.1–10.5) on day 0 to 11.8 g/dL (95% CI: 11.6–12.0) on day 28. We conclude that AS/AQ combination remains efficacious in the treatment of uncomplicated malaria in Ghana.

Understanding the epidemiology of asymptomatic Plasmodium falciparum infections is critical for countries to move toward malaria elimination. Using different methods for parasite detection, we evaluated how seasonality, spatial location, and other factors affect the age-specific epidemiology of asymptomatic malaria in Bongo District, Ghana. Asymptomatic prevalence by microscopy decreased significantly from 42.5% at the end of the wet to 27.5% at the end of the dry season (P 20 years of age, we found evidence of infection in 64.3% of the population in the wet and 27.0% in the dry season. Using both microscopy and PCR, the asymptomatic P. falciparum reservoir peaks at the end of the wet season and infections in all age groups constitute the reservoir of malaria infection. At the end of the wet season, spatial heterogeneity in the prevalence and density of P. falciparum infections was observed between the two catchment areas surveyed in Bongo District. These results indicate that if elimination is to succeed, interventions will need to target not just P. falciparum infections in children but also in adults, and be implemented toward the end of the dry season in this area of West Africa.

On 12 January 2020, the World Health Organization (WHO) confirmed that a novel coronavirus was the cause of a respiratory illness in a cluster of people in Wuhan City, Hubei Province, China. The disease was christened COVID-19 and the pathogen (an RNA virus) identified as SARS-Coronavirus-2 (SARS-CoV-2).1,2 The virus is primarily spread through contact with small droplets produced from coughing, sneezing, or talking by an infected person. While a substantial proportion of infected individuals may remain asymptomatic, the most common symptoms in clinical cases include, fever, cough, acute respiratory distress, fatigue, and failure to resolve over 3 to 5 days of antibiotic treatment. Complications may include pneumonia and acute respiratory distress syndrome.3 Over five million confirmed cases of COVID-19 has been recorded globally with more than 300,000 deaths as at 25th May 2020. The United States of America has recorded the highest number of cases with more than 1.5 million and over 100,000 deaths.4 In Africa, more than 90,0000 cases have been reported with about 3,000 deaths. South Africa has recorded the highest number of cases with 23,615 cases and 481 deaths. Ghana confirmed its first cases of COVID-19 on 12th March 2020 and had as at 25 May 2020 recorded over 7,000 cases with 34 deaths.5

Background Global efforts to scale-up malaria control interventions are gaining steam. These include the use of Long-Lasting Insecticide Nets, Indoor Residual Spraying, Intermittent Preventive Treatment and Test, Treat and Track. Despite these, the drive for malaria elimination is far from being realistic in endemic communities in Africa. This is partly due to the fact that asymptomatic parasite carriage, not specifically targeted by most interventions, remains the bedrock that fuels transmission. This has led to mass testing, treatment and tracking (MTTT) as an alternative strategy to target asymptomatic individuals. We report the impact of MTTT on the prevalence of asymptomatic malaria parasitaemia over a one-year period in Ghana, hypothesizing that implementing MTTT could reduce the rate of asymptomatic parasitaemia. Methods A population of about 5000 individuals in seven communities in the Pakro sub-district of Ghana participated in this study. A register was developed for each community following a census. MTTT engaged trained community-based health volunteers who conducted house-to-house testing using RDTs every 4 months and treated positive cases with Artemisinin–based Combination Therapy. Between interventions, community-based management of malaria was implemented for symptomatic cases. Results MTTT Coverage was 98.8% in July 2017 and 79.3% in July 2018. Of those tested, asymptomatic infection with malaria parasites reduced from 36.3% (1795/4941) in July 2017 to 32.9% (1303/3966) in July 2018 (p = 0.001). Prevalence of asymptomatic parasitaemia among children under 15 years declined from 52.6% (1043/1984) in July 2017 to 47.5% (820/1728) in July 2018 (p = 0.002). Implementing MTTT significantly reduced asymptomatic parasitaemia by 24% from July 2017 to July 2018 after adjusting for age, ITN use and axillary temperature (OR = 0.76, CI = 0.67, 0.85 p ≤ 0.001). Conclusion This study has demonstrated that implementing MTTT is feasible and could reduce the prevalence of asymptomatic malaria parasitaemia in children under 15 years of age. Furthermore, the use of community-based health volunteers could ensure high coverage at lower cost of implementation. Trial registration NCT04167566, Date 14/11/2019. Retrospective registration.

Introduction Frequent or/and misguided prescription of antibiotics are important facilitators of the emergence and spread of antibiotic resistance. In the absence of the implementation of effective interventions to control antibiotic use, its consumption may quadruple. Antibiotic stewardship interventions must be appropriately targeted to enhance the proper use of antibiotics. The objective of this study was to determine the predictors of prescribing antibiotics to febrile patients who seek care in health facilities within the Greater Accra region of Ghana. Methods Secondary data obtained from a review of medical records of 2,519 febrile patients at the outpatient department of 6 health facilities in 3 municipalities during the baseline survey of a quasi-experiment in 2016, were used. In addition, sociodemographic data on the prescribers who saw the patients were obtained. The primary outcome was prescription of any antibiotic. Predictor variables included patients’ demographics, symptoms, laboratory investigations, diagnoses and prescribed medicines. Binary and multivariable logistic regression analyses were used to determine the predictors of antibiotics prescription. Clustering was adjusted for in all the analyses. Results The prevalence of antibiotics prescription was 70.1% (95% CI: 67.7-72.4). Prescribers with 6 to 9 years and 10 or more years of practice experience were 3 (95% CI: 1.99, 4.44) and 1.6 (95% CI: 1.12, 2.27) times more likely to prescribe antibiotics, respectively (p < 0.001). IMCI training was associated with a 2.3 (95% CI: 1.54, 3.53, p < 0.001) times higher odds of antibiotic prescribing. Patients aged 5 years or more were 60% less likely to be prescribed antibiotics compared with those under 5 years (AOR=0.40, 95% CI: 0.32, 0.51; p

BackgroundFebrile children seen in malaria hypo-endemic settings, such as the Greater Accra region (GAR) of Ghana are more likely to be suffering from a non-malarial febrile illness compared to those seen in hyper-endemic settings. The need for prescribers to rely on malaria test results to guide treatment practices in the GAR is even greater. This study was designed to investigate the factors associated with inappropriate artemisinin-based combination therapy (ACT) prescription.MethodsA survey was conducted in six health facilities in the region in 2015. Treatment practices for febrile outpatient department (OPD) patients were obtained from their records. Prescribers were interviewed and availability of malaria commodities were assessed. The primary outcome was the proportion of patients prescribed ACT inappropriately. Independent variables included patient age and access to care, prescriber factors (professional category, work experience, access to guidelines, exposure to training). Data were analysed using Stata at 95% CI (α-value of 0.05). Frequencies and means were used to describe the characteristics of patients and prescribers. To identify the predictors of inappropriate ACT prescription, regression analyses were performed accounting for clustering.ResultsOverall, 2519 febrile OPD records were analysed; 45.6% (n = 1149) were younger than 5 years. Only 40.0% of patients were tested. The proportion of patients who were prescribed ACT inappropriately was 76.4% (n = 791 of 1036). Of these 791 patients, 141 (17.8%) were prescribed anti-malarial injections. Patients seen in facilities with rapid diagnostic tests (RDT) in stock were less likely to be prescribed ACT inappropriately, (AOR: 0.04, 95% CI 0.01–0.14, p ConclusionInappropriate ACT prescription to OPD febrile cases was high. Training and supervision of health workers appears not to be yielding the desired outcomes. Further research is needed to understand this observation.

Objective: This study examines explanatory models (EMs) of stroke and its complications among people living with stroke, and their caregivers, in two urban poor communities in Accra (Ga Mashie) and...