Economic evaluation of a cluster randomized trial of interventions to improve health workers' practice in diagnosing and treating uncomplicated malaria in Cameroon.

BACKGROUND: Malaria rapid diagnostic tests (RDTs) are a valid alternative to malaria testing with microscopy and are recommended for the testing of febrile patients before prescribing an antimalarial. There is a need for interventions to support the uptake of RDTs by health workers. OBJECTIVE: To evaluate the cost-effectiveness of introducing RDTs with basic or enhanced training in health facilities in which microscopy was available, compared with current practice. METHODS: A three-arm cluster randomized trial was conducted in 46 facilities in central and northwest Cameroon. Basic training had a practical session on RDTs and lectures on malaria treatment guidelines. Enhanced training included small-group activities designed to change health workers' practice and reduce the consumption of antimalarials among test-negative patients. The primary outcome was the proportion of febrile patients correctly treated: febrile patients should be tested for malaria, artemisinin combination therapy should be prescribed for confirmed cases, and no antimalarial should be prescribed for patients who are test-negative. Individual patient data were obtained from facility records and an exit survey. Costs were estimated from a societal perspective using project reports and patient exit data. The analysis used bivariate multilevel modeling and adjusted for imbalance in baseline covariates. RESULTS: Incremental cost per febrile patient correctly treated was $8.40 for the basic arm and$3.71 for the enhanced arm. On scale-up, it was estimated that RDTs with enhanced training would save $0.75 per additional febrile patient correctly treated. CONCLUSIONS: Introducing RDTs with enhanced training was more cost-effective than RDTs with basic training when each was compared with current practice

Predominance of N-acetyl transferase 2 slow acetylator alleles in children less than ten years experiencing adverse treatment events following artemisinin-based combination therapy in North and South West Regions of Cameroon

The human N-acetyltransferase II (NAT2) gene may vary between individuals resulting in variability in the incidence of adverse drug reactions. We set out in this adhoc analysis to determine the distribution of allele frequencies of NAT2 gene variants among children less than ten years treated with artemisinin-based combinations in Cameroon. Children with uncomplicated malaria were deparasitized with artemisinin based combination therapy (artesunate amodiaquine, dihydroartemisinin-piperaquine and artemether-lumefantrine) and followed up for 42 days and adverse events recorded. Blood was spotted on filter paper prior to drug administration for DNA extraction by chelex method. Standard nested PCR followed by restriction enzyme analysis with KpnI, TaqI, and BamHI for detection of polymorphisms in the NAT2 was performed. Allelic frequencies and acetylator phenotypes were compared between participants with or without adverse drug events. The prevalence of slow, intermediate and fast acetylators was 54, 34 and 12% respectively. Significant clustering of mutant alleles (NAT2*5, NAT2*6 and NAT2*7) occurred among those who experienced skin rash and tiredness (OR = 5.765, P = 0.046) (OR = 13.280, P = 0.020). No significant difference was observed between fast and slow acetylators with respect to the development of other recorded adverse events. Overall, producers of the slow acetylator alleles were more likely to develop any adverse events (OR = 8.286, P = 0.017) during the study period. Mutant alleles of the wild type NAT2*4 associated with the slow acetylator phenotype were the most predominant NAT2 allelic type and individuals with the phenotype were more likely to develop adverse events to ACTs.Keywords: N-Acetyltransferase 2, Artemisinin based combination therapy, adverse events, slow acetylators, allel

Basic or enhanced clinician training to improve adherence to malaria treatment guidelines: a cluster-randomised trial in two areas of Cameroon

Background The scale-up of malaria rapid diagnostic tests (RDTs) is intended to improve case management of fever and targeting of artemisinin-based combination therapy. Habitual presumptive treatment has hampered these intentions, suggesting a need for strategies to support behaviour change. We aimed to assess the introduction of RDTs when packaged with basic or enhanced clinician training interventions in Cameroon. Methods We did a three-arm, stratifi ed, cluster-randomised trial at 46 public and mission health facilities at two study sites in Cameroon to compare three approaches to malaria diagnosis. Facilities were randomly assigned by a computer program in a 9:19:19 ratio to current practice with microscopy (widely available, used as a control group); RDTs with a basic (1 day) clinician training intervention; or RDTs with an enhanced (3 days) clinician training intervention. Patients (or their carers) and fi eldworkers who administered surveys to obtain outcome data were masked to study group assignment. The primary outcome was the proportion of patients treated in accordance with WHO malaria treatment guidelines, which is a composite indicator of whether patients were tested for malaria and given appropriate treatment consistent with the test result. All analyses were by intention to treat. This study is registered at ClinicalTrials. gov, number NCT01350752. Findings The study took place between June 7 and Dec 14, 2011. The analysis included 681 patients from nine facilities in the control group, 1632 patients from 18 facilities in the basic-training group, and 1669 from 19 facilities in the enhanced-training group. The proportion of patients treated in accordance with malaria guidelines did not improve with either intervention; the adjusted risk ratio (RR) for basic training compared with control was 1·04 (95% CI 0·53–2·07; p=0·90), and for enhanced training compared with control was 1·17 (0·61–2·25; p=0·62). Inappropriate use of antimalarial drugs after a negative test was reduced from 84% (201/239) in the control group to 52% (413/796) in the basic-training group (unadjusted RR 0·63, 0·28–1·43; p=0·25) and to 31% (232/759) in the enhanced-training group (0·29, 0·11–0·77; p=0·02). Interpretation Enhanced clinician training, designed to translate knowledge into prescribing practice and improve quality of care, has the potential to halve overtreatment in public and mission health facilities in Cameroon. Basic training is unlikely to be suffi cient to support the behaviour change required for the introduction of RDTs

Designing and implementing interventions to change clinicians' practice in the management of uncomplicated malaria: lessons from Cameroon.

BACKGROUND: Effective case management of uncomplicated malaria is a fundamental pillar of malaria control. Little is known about the various steps in designing interventions to accompany the roll out of rapid diagnostic tests (RDTs) and artemisinin-based combination therapy (ACT). This study documents the process of designing and implementing interventions to change clinicians' practice in the management of uncomplicated malaria. METHODS: A literature review combined with formative quantitative and qualitative research were carried out to determine patterns of malaria diagnosis and treatment and to understand how malaria and its treatment are enacted by clinicians. These findings were used, alongside a comprehensive review of previous interventions, to identify possible strategies for changing the behaviour of clinicians when diagnosing and treating uncomplicated malaria. These strategies were discussed with ministry of health representatives and other stakeholders. Two intervention packages - a basic and an enhanced training were outlined, together with logic model to show how each was hypothesized to increase testing for malaria, improve adherence to test results and increase appropriate use of ACT. The basic training targeted clinicians' knowledge of malaria diagnosis, rapid diagnostic testing and malaria treatment. The enhanced training included additional modules on adapting to change, professionalism and communicating effectively. Modules were delivered using small-group work, card games, drama and role play. Interventions were piloted, adapted and trainers were trained before final implementation. RESULTS: Ninety-six clinicians from 37 health facilities in Bamenda and Yaounde sites attended either 1-day basic or 3-day enhanced training. The trained clinicians then trained 632 of their peers at their health facilities. Evaluation of the training revealed that 68% of participants receiving the basic and 92% of those receiving the enhanced training strongly agreed that it is not appropriate to prescribe anti-malarials to a patient if they have a negative RDT result. CONCLUSION: Formative research was an important first step, and it was valuable to engage stakeholders early in the process. A logic model and literature reviews were useful to identify key elements and mechanisms for behaviour change intervention. An iterative process with feedback loops allowed appropriate development and implementation of the intervention. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01350752

A cost-effectiveness analysis of provider interventions to improve health worker practice in providing treatment for uncomplicated malaria in Cameroon: a study protocol for a randomized controlled trial

BACKGROUND: Governments and donors all over Africa are searching for sustainable, affordable and cost-effective ways to improve the quality of malaria case management. Widespread deficiencies have been reported in the prescribing and counselling practices of health care providers treating febrile patients in both public and private health facilities. Cameroon is no exception with low levels of adherence to national guidelines, the frequent selection of non-recommended antimalarials and the use of incorrect dosages. This study evaluates the effectiveness and cost-effectiveness of introducing two different provider training packages, alongside rapid diagnostic tests (RDTs), designed to equip providers with the knowledge and practical skills needed to effectively diagnose and treat febrile patients. The overall aim is to target antimalarial treatment better and to facilitate optimal use of malaria treatment guidelines. METHODS/DESIGN: A 3-arm stratified, cluster randomized trial will be conducted to assess whether introducing RDTs with provider training (basic or enhanced) is more cost-effective than current practice without RDTs, and whether there is a difference in the cost effectiveness of the provider training interventions. The primary outcome is the proportion of patients attending facilities that report a fever or suspected malaria and receive treatment according to malaria guidelines. This will be measured by surveying patients (or caregivers) as they exit public and mission health facilities. Cost-effectiveness will be presented in terms of the primary outcome and a range of secondary outcomes, including changes in provider knowledge. Costs will be estimated from a societal and provider perspective using standard economic evaluation methodologies. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00981877

Host candidate gene polymorphisms and clearance of drug-resistant Plasmodium falciparum parasites

Resistance to anti-malarial drugs is a widespread problem for control programmes for this devastating disease. Molecular tests are available for many anti-malarial drugs and are useful tools for the surveillance of drug resistance. However, the correlation of treatment outcome and molecular tests with particular parasite markers is not perfect, due in part to individuals who are able to clear genotypically drug-resistant parasites. This study aimed to identify molecular markers in the human genome that correlate with the clearance of malaria parasites after drug treatment, despite the drug resistance profile of the protozoan as predicted by molecular approaches

Immunological insights into COVID-19 in Southern Nigeria

Introduction: One of the unexpected outcomes of the COVID-19 pandemic was the relatively low levels of morbidity and mortality in Africa compared to the rest of the world. Nigeria, Africa's most populous nation, accounted for less than 0.01% of the global COVID-19 fatalities. The factors responsible for Nigeria's relatively low loss of life due to COVID-19 are unknown. Also, the correlates of protective immunity to SARS-CoV-2 and the impact of pre-existing immunity on the outcome of the COVID-19 pandemic in Africa are yet to be elucidated. Here, we evaluated the natural and vaccine-induced immune responses from vaccinated, non-vaccinated and convalescent individuals in Southern Nigeria throughout the three waves of the COVID-19 pandemic in Nigeria. We also examined the pre-existing immune responses to SARS-CoV-2 from samples collected prior to the COVID-19 pandemic. Methods: We used spike RBD and N- IgG antibody ELISA to measure binding antibody responses, SARS-CoV-2 pseudotype assay protocol expressing the spike protein of different variants (D614G, Delta, Beta, Omicron BA1) to measure neutralizing antibody responses and nucleoprotein (N) and spike (S1, S2) direct ex vivo interferon gamma (IFNγ) T cell ELISpot to measure T cell responses. Result: Our study demonstrated a similar magnitude of both binding (N-IgG (74% and 62%), S-RBD IgG (70% and 53%) and neutralizing (D614G (49% and 29%), Delta (56% and 47%), Beta (48% and 24%), Omicron BA1 (41% and 21%)) antibody responses from symptomatic and asymptomatic survivors in Nigeria. A similar magnitude was also seen among vaccinated participants. Interestingly, we revealed the presence of preexisting binding antibodies (N-IgG (60%) and S-RBD IgG (44%)) but no neutralizing antibodies from samples collected prior to the pandemic. Discussion: These findings revealed that both vaccinated, non-vaccinated and convalescent individuals in Southern Nigeria make similar magnitude of both binding and cross-reactive neutralizing antibody responses. It supported the presence of preexisting binding antibody responses among some Nigerians prior to the COVID-19 pandemic. Lastly, hybrid immunity and heterologous vaccine boosting induced the strongest binding and broadly neutralizing antibody responses compared to vaccine or infection-acquired immunity alone

Prevalence of malaria, typhoid, toxoplasmosis and rubella among febrile children in Cameroon

Abstract Background The current roll-out of rapid diagnostic tests (RDTs) in many endemic countries has resulted in the reporting of fewer cases of malaria-attributed illnesses. However, lack of knowledge of the prevalence of other febrile illnesses and affordable diagnostic tests means that febrile patients are not managed optimally. This study assessed the prevalence of commonly treatable or preventable febrile illnesses in children between 6 months and 15 years using rapid diagnostic tests at the point-of-care. Methods Febrile children were enrolled between February-April 2014 at a health facility after obtaining informed consent from parent. Eligible participants were aged 6 months-15 years with a history of fever in the last 24 h or axillary temperature ≥38 °C at consultation. All participants were tested using RDTs for malaria, typhoid, toxoplasmosis and rubella. Malaria parasites were further identified by microscopy and PCR. Clinical and household characteristics were recorded and association with pathogens determined. Results Of the 315 children enrolled, the mean age was 5.8 ± 3.8 years. Stomach pain (41.2 %) was the most reported symptom. Prior to attending the health facility, 70.8 % had taken antipyretics, 27.9 % antimalarials, 11.4 % antibiotics and 13.3 % antifungal drugs. Among 315 children with fever, based on RDTs, 56.8 % were infected with malaria, 4.4 % with typhoid, 3.2 % with acute toxoplasmosis, and 1.3 % with rubella (all positive for rubella were in the same family and not vaccinated). All non-malarial infections were co-infections and approximately 30 % of the fever cases went un-diagnosed. Malaria prevalence by microscopy and PCR was 43.4 and 70.2 % respectively. The sensitivity and specificity of RDTs for the diagnosis of malaria were 75.98 and 100 % respectively, with 0.73 measurement agreement between RDTs and microscopy while that of RDT and PCR were 81 and 100 % respectively with a K value of 0.72. The use of Insecticide Treated Bednets was 44 %. There was a significant association between ITN non-usage and malaria (p = 0. 029) as well as drinking water and presence of typhoid (p = 0.047). No association was observed between type of housing and malaria, or toxoplasmosis and raising cats. Conclusion Though malaria still remains the major cause of fever in children, using RDTs for other treatable febrile illnesses like typhoid and toxoplasmosis could facilitate the optimal management of febrile illnesses in children especially when these occur as co-infections with malari

A comparison of thick-film microscopy, rapid diagnostic test, and polymerase chain reaction for accurate diagnosis of Plasmodium falciparum malaria

Abstract Background Accurate diagnosis of malaria is important for effective disease management and control. In Cameroon, presumptive clinical diagnosis, thick-film microscopy (TFM), and rapid diagnostic tests (RDT) are commonly used to diagnose cases of Plasmodium falciparum malaria. However, these methods lack sensitivity to detect low parasitaemia. Polymerase chain reaction (PCR), on the other hand, enhances the detection of sub-microscopic parasitaemia making it a much-needed tool for epidemiological surveys, mass screening, and the assessment of interventions for malaria elimination. Therefore, this study sought to determine the frequency of cases missed by traditional methods that are detected by PCR. Methods Blood samples, collected from 551 febrile Cameroonian patients between February 2014 and February 2015, were tested for P. falciparum by microscopy, RDT and PCR. The hospital records of participants were reviewed to obtain data on the clinical diagnosis made by the health care worker. Results The prevalence of malaria by microscopy, RDT and PCR was 31%, 45%, and 54%, respectively. However, of the 92% of participants diagnosed as having clinical cases of malaria by the health care worker, 38% were malaria-negative by PCR. PCR detected 23% and 12% more malaria infections than microscopy and RDT, respectively. A total of 128 (23%) individuals had sub-microscopic infections in the study population. The sensitivity of microscopy, RDT, and clinical diagnosis was 57%, 78% and 100%; the specificity was 99%, 94%, and 17%; the positive predictive values were 99%, 94%, and 59%; the negative predictive values were 66%, 78%, and 100%, respectively. Thus, 41% of the participants clinically diagnosed as having malaria had fever caused by other pathogens. Conclusions Malaria diagnostic methods, such as TFM and RDT missed 12–23% of malaria cases detected by PCR. Therefore, traditional diagnostic approaches (TFM, RDT and clinical diagnosis) are not adequate when accurate epidemiological data are needed for monitoring malaria control and elimination interventions