Quality issues with malaria rapid diagnostic test accessories and buffer packaging: findings from a 5-country private sector project in Africa.

BACKGROUND: Use of antigen-detecting malaria rapid diagnostic tests (RDTs) has increased exponentially over the last decade. WHO's Global Malaria Programme, FIND, and other collaborators have established a quality assurance scheme to guide product selection, lot verification, transport, storage, and training procedures. Recent concerns over the quality of buffer packaging and test accessories suggest a need to include these items in product assessments. This paper describes quality problems with buffer and accessories encountered in a project promoting private sector RDT use in five African countries and suggests steps to avoid or more rapidly identify and resolve such problems. METHODS: Private provider complaints about RDT buffer vials and kit accessories were collected during supervisory visits, and a standard assessment process was developed. Using 100 tests drawn from six different lots produced by two manufacturers, lab technicians visually assessed alcohol swab packaging, blood transfer device (BTD) usability, and buffer appearance, then calculated mean blood volume from 10 BTD transfers and mean buffer volume from 10 individual buffer vials. WHO guided complaint reporting and follow-up with manufacturers. RESULTS: Supervisory visits confirmed user reports of dry alcohol swabs, poorly functioning BTDs, and non-uniform volumes of buffer. Lot testing revealed further evidence of quality problems, leading one manufacturer to replace buffer vials and accessories for 40,000 RDTs. In December 2014, WHO issued an Information Notice for Users regarding variable buffer volumes in single-use vials and recommended against procurement of these products until defects were addressed. DISCUSSION: Though not necessarily comprehensive or generalizable, the findings presented here highlight the need for extending quality assessment to all malaria RDT test kit contents. Defects such as those described in this paper could reduce test accuracy and increase probability of invalid, false positive, or false negative results. Such deficiencies could undermine provider confidence in RDTs, prompting a return to presumptive treatment or reliance on poor quality microscopy. In partial response to this experience, WHO, FIND, and other project partners have developed guidance on documenting, troubleshooting, reporting, and resolving such problems when they occur.

Why do health workers give anti-malarials to patients with negative rapid test results? A qualitative study at rural health facilities in western Uganda.

BACKGROUND: The large-scale introduction of malaria rapid diagnostic tests (RDTs) promises to improve management of fever patients and the rational use of valuable anti-malarials. However, evidence on the impact of RDT introduction on the overprescription of anti-malarials has been mixed. This study explored determinants of provider decision-making to prescribe anti-malarials following a negative RDT result. METHODS: A qualitative study was conducted in a rural district in mid-western Uganda in 2011, ten months after RDT introduction. Prescriptions for all patients with negative RDT results were first audited from outpatient registers for a two month period at all facilities using RDTs (n = 30). Facilities were then ranked according to overall prescribing performance, defined as the proportion of patients with a negative RDT result prescribed any anti-malarial. Positive and negative deviant facilities were sampled for qualitative investigation; positive deviants (n = 5) were defined ex post facto as <0.75% and negative deviants (n = 7) as >5%. All prescribing clinicians were targeted for qualitative observation and in-depth interview; 55 fever cases were observed and 22 providers interviewed. Thematic analysis followed the 'framework' approach. RESULTS: 8344 RDT-negative patients were recorded at the 30 facilities (prescription audit); 339 (4.06%) were prescribed an anti-malarial. Of the 55 observed patients, 38 tested negative; one of these was prescribed an anti-malarial. Treatment decision-making was influenced by providers' clinical beliefs, capacity constraints, and perception of patient demands. Although providers generally trusted the accuracy of RDTs, anti-malarial prescription was driven by perceptions of treatment failure or undetectable malaria in patients who had already taken artemisinin-based combination therapy prior to facility arrival. Patient assessment and other diagnostic practices were minimal and providers demonstrated limited ability to identify alternative causes of fever. Provider perceptions of patient expectations sometimes appeared to influence treatment decisions. CONCLUSIONS: The study found high provider adherence to RDT results, but that providers believed in certain clinical exceptions and felt they lacked alternative options. Guidance on how the RDT works and testing following partial treatment, better methods for assisting providers in diagnostic decision-making, and a context-appropriate provider behaviour change intervention package are needed.

Can Outreach Training and Supportive Supervision Improve Competency in Malaria Service Delivery? An Evaluation in Cameroon, Ghana, Niger, and Zambia.

Outreach Training and Supportive Supervision (OTSS) of malaria services at health facilities has been adopted by numerous malaria-endemic countries. The OTSS model is characterized by a hands-on method to enhance national guidelines and supervision tools, train supervisors, and perform supervision visits. An independent evaluation was conducted to evaluate the effectiveness of OTSS on health worker competence in the clinical management of malaria, parasitological diagnosis, and prevention of malaria in pregnancy. From 2018 to 2021, health facilities in Cameroon, Ghana, Niger, and Zambia received OTSS visits during which health workers were observed directly during patient consultations, and supervisors completed standardized checklists to assess their performance. Mixed-effects logistic regression models were developed to assess the impact of increasing OTSS visit number on a set of eight program-generated outcome indicators, including overall competency and requesting a confirmatory malaria test appropriately. Seven of eight outcome indicators showed evidence of beneficial effects of increased OTSS visits. Odds of health workers reaching competency thresholds for the malaria-in-pregnancy checklist increased by more than four times for each additional OTSS visit (odds ratio [OR], 4.62; 95% CI, 3.62-5.88). Each additional OTSS visit was associated with almost four times the odds of the health worker foregoing antimalarial prescriptions for patients who tested negative for malaria (OR, 3.80; 95% CI, 2.35-6.16). This evaluation provides evidence that successive OTSS visits result in meaningful improvements in indicators linked to quality case management of patients attending facilities for malaria diagnosis and treatment, as well as quality malaria prevention services received by women attending antenatal services.

Outreach Training and Supportive Supervision for Quality Malaria Service Delivery: A Qualitative Evaluation in 11 Sub-Saharan African Countries.

Quality improvement of malaria services aims to ensure that more patients receive accurate diagnosis, appropriate treatment, and referral. The Outreach Training and Supportive Supervision Plus (OTSS+) approach seeks to improve health facility readiness and provider competency through onsite supportive supervision, troubleshooting, and on-the-job training. As part of a multicomponent evaluation, qualitative research was conducted to understand the value of the OTSS+ approach for malaria quality improvement. Semistructured key informant interviews, focus group discussions, and structured health facility-based interviews were used to gather stakeholder perspectives at subnational, national, and global levels. Data were collected globally and in 11 countries implementing OTSS+; in-depth data collection was done in four: Cameroon, Ghana, Niger, and Zambia. Study sites and participants were selected purposively. Verbatim transcripts were analyzed thematically, following the Framework approach. A total of 262 participants were included in the analysis; 98 (37.4%) were supervisees, 99 (37.8%) were supervisors, and 65 (24.8%) were other stakeholders. The OTSS+ approach was perceived to improve provider knowledge and skills in malaria service delivery and to improve data and supply management indirectly. Improvements were attributed to a combination of factors. Participants valued the relevance, adaptation, and digitization of supervision checklists; the quality and amount of contact with problem-solving supervisors; and the joint identification of problems and solutions, and development of action plans. Opportunities for improvement were digitized checklist refinement, assurance of a sufficient pool of supervisors, prioritization of health facilities, action plan dissemination and follow-up, and data review and use. The OTSS+ approach was perceived to be a useful quality improvement approach for malaria services.

Multiple origins and regional dispersal of resistant dhps in African Plasmodium falciparum malaria.

BACKGROUND: Although the molecular basis of resistance to a number of common antimalarial drugs is well known, a geographic description of the emergence and dispersal of resistance mutations across Africa has not been attempted. To that end we have characterised the evolutionary origins of antifolate resistance mutations in the dihydropteroate synthase (dhps) gene and mapped their contemporary distribution. METHODS AND FINDINGS: We used microsatellite polymorphism flanking the dhps gene to determine which resistance alleles shared common ancestry and found five major lineages each of which had a unique geographical distribution. The extent to which allelic lineages were shared among 20 African Plasmodium falciparum populations revealed five major geographical groupings. Resistance lineages were common to all sites within these regions. The most marked differentiation was between east and west African P. falciparum, in which resistance alleles were not only of different ancestry but also carried different resistance mutations. CONCLUSIONS: Resistant dhps has emerged independently in multiple sites in Africa during the past 10-20 years. Our data show the molecular basis of resistance differs between east and west Africa, which is likely to translate into differing antifolate sensitivity. We have also demonstrated that the dispersal patterns of resistance lineages give unique insights into recent parasite migration patterns.

Differential effect of regional drug pressure on dihydrofolate reductase and dihydropteroate synthetase mutations in southern Mozambique.

The prevalence and frequency of the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) mutations associated with sulfadoxine-pyrimethamine (SP) resistance at 13 sentinel surveillance sites in southern Mozambique were examined regularly between 1999 and 2004. Frequency of the dhfr triple mutation increased from 0.26 in 1999 to 0.96 in 2003, remaining high in 2004. The dhps double mutation frequency peaked in 2001 (0.22) but declined to baseline levels (0.07) by 2004. Similarly, parasites with both dhfr triple and dhps double mutations had increased in 2001 (0.18) but decreased by 2004 (0.05). The peaking of SP resistance markers in 2001 coincided with a SP-resistant malaria epidemic in neighboring KwaZulu-Natal, South Africa. The decline in dhps (but not dhfr) mutations corresponded with replacement of SP with artemether-lumefantrine as malaria treatment policy in KwaZulu-Natal. Our results show that drug pressure can exert its influence at a regional level rather than merely at a national level.

Household cost of malaria overdiagnosis in rural Mozambique.

BACKGROUND: It is estimated that over 70% of patients with suspected malaria in sub-Saharan Africa, diagnose and manage their illness at home without referral to a formal health clinic. Of those patients who do attend a formal health clinic, malaria overdiagnosis rates are estimated to range between 30-70%. METHODS: This paper details an observational cohort study documenting the number and cost of repeat consultations as a result of malaria overdiagnosis at two health care providers in a rural district of Mozambique. 535 adults and children with a clinical diagnosis of malaria were enrolled and followed over a 21 day period to assess treatment regimen, symptoms, number and cost of repeat visits to health providers in patients misdiagnosed with malaria compared to those with confirmed malaria (determined by positive bloodfilm reading). RESULTS: Diagnosis based solely on clinical symptoms overdiagnosed 23% of children (<16y) and 31% of adults with malaria. Symptoms persisted (p = 0.023) and new ones developed (p < 0.001) in more adults than children in the three weeks following initial presentation. Adults overdiagnosed with malaria had more repeat visits (67% v 46%, p = 0.01-0.06) compared to those with true malaria. There was no difference in costs between patients correctly or incorrectly diagnosed with malaria. Median costs over three weeks were $0.28 for those who had one visit and $0.76 for > or = 3 visits and were proportionally highest among the poorest (p < 0.001) CONCLUSION: Overdiagnosis of malaria results in a greater number of healthcare visits and associated cost for adult patients. Additionally, it is clear that the poorest individuals pay significantly more proportionally for their healthcare making it imperative that the treatment they receive is correct in order to prevent wastage of limited economic resources. Thus, investment in accurate malaria diagnosis and appropriate management at primary level is critical for improving health outcomes and reducing poverty.

Prototype Positive Control Wells for Malaria Rapid Diagnostic Tests: Prospective Evaluation of Implementation Among Health Workers in Lao People's Democratic Republic and Uganda.

Rapid diagnostic tests (RDTs) are widely used for malaria diagnosis, but lack of quality control at point of care restricts trust in test results. Prototype positive control wells (PCW) containing recombinant malaria antigens have been developed to identify poor-quality RDT lots. This study assessed community and facility health workers' (HW) ability to use PCWs to detect degraded RDTs, the impact of PCW availability on RDT use and prescribing, and preferred strategies for implementation in Lao People's Democratic Republic (Laos) and Uganda. A total of 557 HWs participated in Laos (267) and Uganda (290). After training, most (88% to ≥ 99%) participants correctly performed the six key individual PCW steps; performance was generally maintained during the 6-month study period. Nearly all (97%) reported a correct action based on PCW use at routine work sites. In Uganda, where data for 127,775 individual patients were available, PCW introduction in health facilities was followed by a decrease in antimalarial prescribing for RDT-negative patients ≥ 5 years of age (4.7-1.9%); among community-based HWs, the decrease was 12.2% (P < 0.05) for all patients. Qualitative data revealed PCWs as a way to confirm RDT quality and restore confidence in RDT results. HWs in malaria-endemic areas are able to use prototype PCWs for quality control of malaria RDTs. PCW availability can improve HWs' confidence in RDT results, and benefit malaria diagnostic programs. Lessons learned from this study may be valuable for introduction of other point-of-care diagnostic and quality-control tools. Future work should evaluate longer term impacts of PCWs on patient management.

Introducing malaria rapid diagnostic tests in private medicine retail outlets: A systematic literature review.

BACKGROUND: Many patients with malaria-like symptoms seek treatment in private medicine retail outlets (PMR) that distribute malaria medicines but do not traditionally provide diagnostic services, potentially leading to overtreatment with antimalarial drugs. To achieve universal access to prompt parasite-based diagnosis, many malaria-endemic countries are considering scaling up malaria rapid diagnostic tests (RDTs) in these outlets, an intervention that may require legislative changes and major investments in supporting programs and infrastructures. This review identifies studies that introduced malaria RDTs in PMRs and examines study outcomes and success factors to inform scale up decisions. METHODS: Published and unpublished studies that introduced malaria RDTs in PMRs were systematically identified and reviewed. Literature published before November 2016 was searched in six electronic databases, and unpublished studies were identified through personal contacts and stakeholder meetings. Outcomes were extracted from publications or provided by principal investigators. RESULTS: Six published and six unpublished studies were found. Most studies took place in sub-Saharan Africa and were small-scale pilots of RDT introduction in drug shops or pharmacies. None of the studies assessed large-scale implementation in PMRs. RDT uptake varied widely from 8%-100%. Provision of artemisinin-based combination therapy (ACT) for patients testing positive ranged from 30%-99%, and was more than 85% in five studies. Of those testing negative, provision of antimalarials varied from 2%-83% and was less than 20% in eight studies. Longer provider training, lower RDT retail prices and frequent supervision appeared to have a positive effect on RDT uptake and provider adherence to test results. Performance of RDTs by PMR vendors was generally good, but disposal of medical waste and referral of patients to public facilities were common challenges. CONCLUSIONS: Expanding services of PMRs to include malaria diagnostic services may hold great promise to improve malaria case management and curb overtreatment with antimalarials. However, doing so will require careful planning, investment and additional research to develop and sustain effective training, supervision, waste-management, referral and surveillance programs beyond the public sector.

How Do Patients and Health Workers Interact around Malaria Rapid Diagnostic Testing, and How Are the Tests Experienced by Patients in Practice? A Qualitative Study in Western Uganda.

BACKGROUND: Successful scale-up in the use of malaria rapid diagnostic tests (RDTs) requires that patients accept testing and treatment based on RDT results and that healthcare providers treat according to test results. Patient-provider communication is a key component of quality care, and leads to improved patient satisfaction, higher adherence to treatment and better health outcomes. Voiced or perceived patient expectations are also known to influence treatment decision-making among healthcare providers. While there has been a growth in literature on provider practices around rapid testing for malaria, there has been little analysis of inter-personal communication around the testing process. We investigated how healthcare providers and patients interact and engage throughout the diagnostic and treatment process, and how the testing service is experienced by patients in practice. METHODS: This research was conducted alongside a larger study which explored determinants of provider treatment decision-making following negative RDT results in a rural district (Kibaale) in mid-western Uganda, ten months after RDT introduction. Fifty-five patients presenting with fever were observed during routine outpatient visits at 12 low-level public health facilities. Observation captured communication practices relating to test purpose, results, diagnosis and treatment. All observed patients or caregivers were immediately followed up with in-depth interview. Analysis followed the 'framework' approach. A summative approach was also used to analyse observation data. RESULTS: Providers failed to consistently communicate the reasons for carrying out the test, and particularly to RDT-negative patients, a diagnostic outcome or the meaning of test results, also leading to confusion over what the test can detect. Patients appeared to value testing, but were frustrated by the lack of communication on outcomes. RDT-negative patients were dissatisfied by the absence of information on an alternative diagnosis and expressed uncertainty around adequacy of proposed treatment. CONCLUSIONS: Poor provider communication practices around the testing process, as well as limited inter-personal exchange between providers and patients, impacted on patients' perceptions of their proposed treatment. Patients have a right to health information and may be more likely to accept and adhere to treatment when they understand their diagnosis and treatment rationale in relation to their perceived health needs and visit expectations.

Prevalence of malaria among patients attending public health facilities in Maputo City, Mozambique.

We conducted a health facility-based survey to estimate the prevalence of malaria among febrile patients at health facilities (HFs) in Maputo City. Patients answered a questionnaire on malaria risk factors and underwent malaria testing. A malaria case was defined as a positive result for malaria by microscopy in a patient with fever or history of fever in the previous 24 hours. Among 706 patients with complete information, 111 (15.7%) cases were identified: 105 were positive for Plasmodium falciparum only, two for Plasmodium ovale only, and four for both P. falciparum and P. ovale. Fever documented at study enrollment, age ≥ 5 years, rural HF, and travel outside Maputo City were statistically significantly associated with malaria by multivariate analysis. We found a high prevalence of laboratory-confirmed malaria among febrile patients in Maputo City. Further studies are needed to relate these findings with mosquito density to better support malaria prevention and control.