Antimicrobial use of patients with sexually transmitted infection symptoms prior to presentation at five health facilities in Southern Ghana.

BACKGROUND: Unregulated and inappropriate antimicrobial use are major contributors to the evolution of antimicrobial resistance worldwide. It is important to monitor and collect data on the use of antibiotics at health facilities and in the general population in order to support antimicrobial stewardship programs. METHODS: As part of a gonorrhea surveillance study that was conducted from June 2012 to Jan 2018, we administered a questionnaire to elicit information on the types of antimicrobials used by individuals to treat symptoms of a gonorrhea infection prior to presenting at five health facilities in Southern Ghana. RESULTS: Almost one-third (383/1,349; 28%) of study participants admitted taking one or more antimicrobial types before hospital presentation, while 138/383 (36%) of those who took antimicrobials could not remember what they ingested. A greater percentage of individuals who reported prior antimicrobial use before presentation at a health facility tested positive for gonorrhea by NAAT (30%), in contrast to 24% for those without prior treatment (p = 0.004). Penicillin and its derivatives, as well as ciprofloxacin and doxycycline, were the most used, while a few individuals reported taking drugs such as kanamycin and rifampin. Males were more likely than females to take an antimicrobial prior to attending a health center. CONCLUSION: In order to curb excessive and inappropriate antimicrobial use, antibiotics used by patients before presenting at hospitals ought to be investigated by healthcare providers. It is recommended that health professionals receive continuing education on the consequences of unregulated antimicrobial use.

Comparison of molecular surveillance methods to assess changes in the population genetics of Plasmodium falciparum in high transmission.

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.

Measuring changes in Plasmodium falciparum census population size in response to sequential malaria control interventions.

Here we introduce a new endpoint "census population size" to evaluate the epidemiology and control of Plasmodium falciparum infections, where the parasite, rather than the infected human host, is the unit of measurement. To calculate census population size, we rely on a definition of parasite variation known as multiplicity of infection (MOIvar), based on the hyper-diversity of the var multigene family. We present a Bayesian approach to estimate MOIvar from sequencing and counting the number of unique DBLα tags (or DBLα types) of var genes, and derive from it census population size by summation of MOIvar in the human population. We track changes in this parasite population size and structure through sequential malaria interventions by indoor residual spraying (IRS) and seasonal malaria chemoprevention (SMC) from 2012 to 2017 in an area of high-seasonal malaria transmission in northern Ghana. Following IRS, which reduced transmission intensity by > 90% and decreased parasite prevalence by ~40-50%, significant reductions in var diversity, MOIvar, and population size were observed in ~2,000 humans across all ages. These changes, consistent with the loss of diverse parasite genomes, were short lived and 32-months after IRS was discontinued and SMC was introduced, var diversity and population size rebounded in all age groups except for the younger children (1-5 years) targeted by SMC. Despite major perturbations from IRS and SMC interventions, the parasite population remained very large and retained the var population genetic characteristics of a high-transmission system (high var diversity; low var repertoire similarity) demonstrating the resilience of P. falciparum to short-term interventions in high-burden countries of sub-Saharan Africa.

Performance of SNP barcodes to determine genetic diversity and population structure of Plasmodium falciparum in Africa.

Panels of informative biallelic single nucleotide polymorphisms (SNPs) have been proposed to be an economical method to fast-track the population genetic analysis of Plasmodium falciparum in malaria-endemic areas. Whilst used successfully in low-transmission areas where infections are monoclonal and highly related, we present the first study to evaluate the performance of these 24- and 96-SNP molecular barcodes in African countries, characterised by moderate-to-high transmission, where multiclonal infections are prevalent. For SNP barcodes it is generally recommended that the SNPs chosen i) are biallelic, ii) have a minor allele frequency greater than 0.10, and iii) are independently segregating, to minimise bias in the analysis of genetic diversity and population structure. Further, to be standardised and used in many population genetic studies, these barcodes should maintain characteristics i) to iii) across various iv) geographies and v) time points. Using haplotypes generated from the MalariaGEN P. falciparum Community Project version six database, we investigated the ability of these two barcodes to fulfil these criteria in moderate-to-high transmission African populations in 25 sites across 10 countries. Predominantly clinical infections were analysed, with 52.3% found to be multiclonal, generating high proportions of mixed-allele calls (MACs) per isolate thereby impeding haplotype construction. Of the 24- and 96-SNPs, loci were removed if they were not biallelic and had low minor allele frequencies in all study populations, resulting in 20- and 75-SNP barcodes respectively for downstream population genetics analysis. Both SNP barcodes had low expected heterozygosity estimates in these African settings and consequently biased analyses of similarity. Both minor and major allele frequencies were temporally unstable. These SNP barcodes were also shown to identify weak genetic differentiation across large geographic distances based on Mantel Test and DAPC. These results demonstrate that these SNP barcodes are vulnerable to ascertainment bias and as such cannot be used as a standardised approach for malaria surveillance in moderate-to-high transmission areas in Africa, where the greatest genomic diversity of P. falciparum exists at local, regional and country levels.

Health system adaptions to improve care for people living with non-communicable diseases during COVID-19 in low-middle income countries: A scoping review.

Background: During the COVID-19 pandemic, access to health care for people living with non-communicable diseases (NCDs) has been significantly disrupted. Calls have been made to adapt health systems and innovate service delivery models to improve access to care. We identified and summarized the health systems adaptions and interventions implemented to improve NCD care and their potential impact on low- and middle-income countries (LMICs). Methods: We comprehensively searched Medline/PubMed, Embase, CINAHL, Global Health, PsycINFO, Global Literature on coronavirus disease, and Web of Science for relevant literature published between January 2020 and December 2021. While we targeted articles written in English, we also included papers published in French with abstracts written in English. Results: After screening 1313 records, we included 14 papers from six countries. We identified four unique health systems adaptations/interventions for restoring, maintaining, and ensuring continuity of care for people living with NCDs: telemedicine or teleconsultation strategies, NCD medicine drop-off points, decentralization of hypertension follow-up services and provision of free medication to peripheral health centers, and diabetic retinopathy screening with a handheld smartphone-based retinal camera. We found that the adaptations/interventions enhanced continuity of NCD care during the pandemic and helped bring health care closer to patients using technology and easing access to medicines and routine visits. Telephonic aftercare services appear to have saved a significant amount of patients' time and funds. Hypertensive patients recorded better blood pressure controls over the follow-up period. Conclusions: Although the identified measures and interventions for adapting health systems resulted in potential improvements in access to NCD care and better clinical outcomes, further exploration is needed to establish the feasibility of these adaptations/interventions in different settings given the importance of context in their successful implementation. Insights from such implementation studies are critical for ongoing health systems strengthening efforts to mitigate the impact of COVID-19 and future global health security threats for people living with NCDs.

Regular deworming and seasonality are potential challenges but also offer opportunities for hookworm elimination.

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.

Indoor residual spraying with a non-pyrethroid insecticide reduces the reservoir of Plasmodium falciparum in a high-transmission area in northern Ghana.

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.

Age-specific patterns of DBLα var diversity can explain why residents of high malaria transmission areas remain susceptible to Plasmodium falciparum blood stage infection throughout life.

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.

The impact of indoor residual spraying on Plasmodium falciparum microsatellite variation in an area of high seasonal malaria transmission in Ghana, West Africa.

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 < .001). Despite these declines, population genetic analysis of the infection haplotypes revealed no dramatic changes with only a slight, but significant increase in genetic diversity (He : pre-IRS = 0.79 vs. post-IRS = 0.81, p = .048). Reduced relatedness of the parasite population (p < .001) was observed post-IRS, probably due to decreased opportunities for outcrossing. Spatiotemporal genetic differentiation between the pre- and post-IRS surveys (D = 0.0329 [95% CI: 0.0209 - 0.0473], p = .034) was identified. These data provide a genetic explanation for the resilience of P. falciparum to short-term IRS programmes in high-transmission settings in sub-Saharan Africa.

High frequency of the Duffy-negative genotype and absence of Plasmodium vivax infections in Ghana.

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.

Ex vivo Sensitivity Profile of Plasmodium falciparum Clinical Isolates to a Panel of Antimalarial Drugs in Ghana 13 Years After National Policy Change.

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<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.

Utility of early diagnosis, contact tracing and stakeholder engagement in outbreak response in three COVID-19 outbreak settings in Ghana.

OBJECTIVE: 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. DESIGN: 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. SETTING: A construction camp, a factory and a training institution in Ghana. PARTICIPANTS: Staff of a construction camp, a factory, workers and students of a training institution. INTERVENTIONS: 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. MAIN OUTCOME MEASURES: Approach used for diagnosis, testing, contact tracing and stakeholder engagement. RESULTS: 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. CONCLUSION: 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. FUNDING: 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.

Data management during COVID-19 outbreak response in Ghana: a reference laboratory perspective on key issues and measures.

The COVID-19 pandemic caused by SARS-CoV-2 is an important subject for global health. Ghana experienced low-moderate 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. FUNDING: The work was supported by the Government of Ghana.

Utility of early diagnosis, contact tracing and stakeholder engagement in outbreak response in three COVID-19 outbreak settings in Ghana

Objective: 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. Design: 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. Setting: A construction camp, a factory and a training institution in Ghana. Participants: Staff of a construction camp, a factory, workers and students of a training institution. Interventions: 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. Main outcome measures: Approach used for diagnosis, testing, contact tracing and stakeholder engagement. Results: 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 RTPCR. 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. Conclusion: 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.

Data management during COVID-19 outbreak response in Ghana: a reference laboratory perspective on key issues and measures

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

Assessment of antimalarial drug resistant markers in asymptomatic Plasmodium falciparum infections after 4 years of indoor residual spraying in Northern Ghana.

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, P<0.001 and z = -4.63, P<0.001, respectively), but not the sulphadoxine resistance mediating pfdhps-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.

Perspectives on Research Internships for Medical Students and Young Doctors in Ghana: An Opportunity to Replenish the Stock of Physician Investigators?

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.

Coverage of intermittent preventive treatment of malaria in pregnancy (IPTp) influences delivery outcomes among women with obstetric referrals at the district level in Ghana.

BACKGROUND: The aim of the study was to determine the coverage of intermittent preventive treatment of malaria in pregnancy (IPTp) and its relationship with delivery outcomes among obstetric referral cases at the district level of healthcare. METHODS: An implementation research within three districts of the Greater Accra region was conducted from May 2017 to February 2018, to assess the role of an enhanced inter-facility communication system on processes and outcomes of obstetric referrals. A cross-sectional analysis of the data on IPTp coverage as well as delivery outcomes for the period of study was conducted, for all the referrals ending up in deliveries. Primary outcomes were maternal and neonatal complications at delivery. IPTp coverage was determined as percentages and classified as adequate or inadequate. Associated factors were determined using Chi square. Odds ratios (OR, 95% CI) were estimated for predictors of adequate IPTp dose coverage for associations with delivery outcomes, with statistical significance set at p = 0.05. RESULTS: From a total of 460 obstetric referrals from 16 lower level facilities who delivered at the three district hospitals, only 223 (48.5%) received adequate (at least 3) doses of IPTp. The district, type of facility where ANC is attended, insurance status, marital status and number of antenatal clinic visits significantly affected IPTp doses received. Adjusted ORs show that adequate IPTp coverage was significantly associated with new-born complication [0.80 (0.65-0.98); p = 0.03], low birth weight [0.51 (0.38-0.68); p < 0.01], preterm delivery [0.71 (0.55-0.90); p = 0.01] and malaria as indication for referral [0.70 (0.56-0.87); p < 0.01]. Positive association with maternal complication at delivery was seen but was not significant. CONCLUSION: IPTp coverage remains low in the study setting and is affected by type of health facility that ANC is received at, access to health insurance and number of times a woman attends ANC during pregnancy. This study also confirmed earlier findings that, as an intervention IPTp prevents bad outcomes of pregnancy, even among women with obstetric referrals. It is important to facilitate IPTp service delivery to pregnant women across the country, improve coverage of required doses and maximize the benefits to both mothers and newborns.