Study findings are grouped below by major themes. To illustrate the technical aspects, a schematic outline of G6PD testing with the biosensor is shown in Figure 1.
1. Introducing the biosensor into routine laboratory and clinic practice
Technical aspects of the biosensor: Ease of use, sample preparation and storage requirements
The LTs appreciated the usefulness of the biosensor results, its portability and ease of use (FGD1, 3). However, compared to existing portable diagnostics, such as the glucometer and malaria RDT, some technicians found the sample preparation procedure complicated. A laboratory technician outlined the requirement of additional steps, as follows:
“for this we have to take blood then mix again then have to change the dropper and then again take the blood. It seems difficult to me. But for RDT, we put only buffer.” (IDI3 LT DH)
The technician also identified that errors may potentially arise in busy clinics, such as inadvertently using the same sample transfer device twice (IDI 3 LT DH). In one of the FGDs, the LTs discussed concerns over using incorrect buffer volumes or insufficient mixing with blood hence eliminating the buffer step could improve the quality of the results (FGD3). Challenges of using the SD Ezi Tube sample collector (a sample transfer device developed by SD Biosensor) instead of the more familiar and more accurate micro-pipette were also discussed, since this would fit better with users who routinely collect venous blood rather than finger prick (IDI2 LT UHC, IDI6 LT UHC). Some workshop participants found the sample collector to be fiddly to use, for example presenting risks of aspirating air bubbles when using it in a hurry in the context of a busy clinic. Such perceptions of the test’s ease of use might change with more routine use.
Concerns over electricity interruptions, battery replacements, humidity, storage conditions, maintaining cold chains and temperature (<30°C) when refrigerators or electricity are not always available also featured in the discussions (FGD1, FGD4, IDI7 nurse, IDI2 LT UHC, 3). They resulted in suggestions to allow for charging the device by direct connection to the main electricity (FGD1), and to provide a back-up device (FGD2, IDI15 LT UHC).
Supply chains and shelf life concerns
The LTs recounted experiences with poor quality and stock-outs of other testing supplies and expired drugs. This might explain concerns expressed regarding the 12 months shelf life of test strips and buffer of the biosensor (IDI6 LT UHC, IDI11 LT UHC, FGD2). The practical shelf life of a device is less than its official duration if time gets lost during the supply and distribution process:
“It happens that a device arrives at Dhaka and remains there for a long time. It then takes time to reach the District level at which point it becomes a "short duration" device.” (FGD2 participant)
Technicians are held accountable by their superiors for not using the device properly and are not able to provide timely care to patients. Technicians mentioned having been requested to overcome supply chain challenges, e.g. one technician was sent to the local market to buy missing items (IDI11 LT UHC), which would not be an option for the biosensor supplies. The participants of FGD2 recommended providing supplies prior to the malaria peak season (FGD2, IDI6 LT UHC) and to request accelerated shipping of supplies from the central level (FGD2).
Considerations over workload and training requirements
Various technicians expressed concerns that might arise from high clinic workloads, mentioning for example conducting around 100 tests daily (IDI11 LT UHC), being the only laboratory technician in a health centre, in some settings being only available twice a week, and having vacant posts not been filled for years (FGD2). Adding the biosensor therefore caused concerns, especially during the malaria season, and potentially causing delays in turn-around times and adding record keeping work (FGD1, 2, 3). Additional staff would be needed to provide results within 24 hours (IDI11 LT UHC). Easy monitoring and minimum reporting efforts for the biosensor would be appreciated, as noted by a nurse at a district hospital (IDI1 nurse DH).
The workshop participants emphasized that it would be important to ensure sufficient training on the biosensor and the implications of G6PDd to staff across the health system, not just to LTs, but also to doctors (who prescribe and order tests), fieldworkers (who conduct RDTs and can motivate patients to seek testing), and nurses (who are available outside laboratory opening hours) (IDI11 LT UHC, IDI2 LT UHC LT UHC, IDI3 LT DH LT DH, IDI5 doctor UHC; FGD3).
Laboratory technicians recommended conducting refresher trainings every six months or so, especially because patients with P. vivax malaria are few (IDI22 LT central laboratory, IDI16 LT UHC, IDI10 LT UHC).
Re-conceptualizing the risk associated with P. vivax in routine care
Health workers at the community level refer patients with high P. falciparum parasite counts or severe symptoms to UHCs for treatment. If the biosensor were implemented at UHC levels but not at community level, they would have to refer P. vivax patients in the absence of severe symptoms or high parasite counts, hence re-conceptualize both P. vivax relapses and malaria treatment (with radical cure drugs in this case) as risky (i.e. nothing is wrong, but it could be wrong in the future). This also means convincing patients to invest scarce time and resources for travelling and potentially facing transportation challenges, especially during the rainy season, even in the absence of severe symptoms (IDI17 programme officer).
2. The context of elimination complicates diagnosis and the introduction of a new technology
Remoteness, challenging weather and a constantly moving target require flexibility in response
In the context of malaria elimination, a medical officer detecting a malaria patient needs to perform case investigations (22), which sometimes involves travelling to very remote locations or through challenging weather conditions. Coordination between staff at different levels of the health system is required and the response is complicated by lack of resources and staff (IDI17 programme officer). Programme officers are caught in a cat and mouse game, responding to hot-spots that keep moving from one region to another (IDI17 programme officer). Eliminating malaria then is aiming at a constantly moving target. This heterogeneity makes it more difficult to introduce any new diagnostic including G6PD testing, and to budget for related supplies, human resources, or decide on deployment.
A programme officer outlined how donor funding is preplanned and not flexible enough to respond to such moving targets or changing needs. Government funding is more flexible but not necessarily available (IDI21 programme officer). In Bangladesh, 90% of malaria control is donor funded and both the NMEP and local NGOs struggle with ensuring funding for diagnostics in the context of decreasing patient numbers. A programme officer explains how ensuring funding by the Global Fund for very low numbers of malaria patients requires creative ways of presenting disaggregated data (IDI21 programme officer). It might even lead to undesired consequences, such as over diagnosing, to ensure funding continues (IDI15 LT UHD), and requires efficient use of limited resources to enable staff to travel to remote locations (IDI19 programme officer). Sometimes health care workers need other forms of (emotional) support or need to deviate from the WHO guidelines to make case investigation work:
“if we have heavy rains, your staff cannot go [to do case investigation], so you cannot force them (..) otherwise, in those places, if I am being posted there, I will not do any work after one year. (…) So you have to think about their side. (..) the care provider needs also some sort of... backup support, emotional support. (…) Some places we can tell them '(…) you don't need to go there. Form a local team.' Try to solve the problems by themselves. (…) Sometimes they find a way. Even if not fully appropriate, but at least they find a way.” (IDI19 programme officer)
Centralized or peripheral deployment of biosensor? Considering accessibility and meaning of diagnostics
According to the laboratory technicians, only a few patients are diagnosed with P. vivax and much of the malaria burden is concentrated in remote, border or conflict regions. This will complicate selecting the G6PD testing sites and managing the device, number of biosensors, expiry dates and packaging of the test strips which currently come in packs of 25 (FGD3, IDI10 LT UHC). Some UHCs diagnose about two P. vivax patients per month (IDI11 LT UHC) and others none:
“…since vivax cases are relatively rare, and in some places more or less present, in some places it is absent. Where it is not found, the devices will expire. Twenty-five [biosensor] devices will be provided but not a single one used.” (FGD3, participant 2)
Currently, government and NGO health workers conduct malaria RDTs, diagnose and treat patients at the community level. Most patients therefore do not reach the sub-district/district level laboratories where the LTs work. While PQ treatment is currently available at both community and UHC level, it could be more centralized alongside the biosensor at UHC level if treatment regimens were changed to shorter course PQ or single-dose TQ, requiring prior G6PD testing. However, FGD3 participants had concerns that patients usually diagnosed and treated at the community level might not be willing to travel for additional tests and treatment (FGD3), mirroring similar concerns expressed in interviews (see above).
The question of where the biosensor should be deployed is also related to the meaning that diagnostics have for health workers at different levels. A programme officer (IDI21) illustrated that for different health workers, diagnostics can represent different things, namely ensuring an NGO’s financial survival, while at the same time overburden NGO workers with workload, or representing just one task among many others for governmental community level staff (CHCP):
“…actually NGOs’ main focus is to detect these patients, and they have to show it - for getting their funds, so they are very focused on that. On the other hand, for the CHCP it is an added function because they have a lot of other activities. So they may not actually give due importance to diagnosing malaria. So maybe it is not working in the way that we actually thought. (IDI21 programme officer)
This has implications for who should be responsible for the biosensor diagnostic device (IDI17, 21). The NGO that prioritizes it as a matter of their survival but then might be overworked (IDI21) or fudge numbers if patient numbers go down (IDI15 LT UHC)? Or the government facilities with many competing priorities but also existing expertise? According to IDI21 programme officer, “ultimately, the community clinic [CHCP] should be the main center for management of malaria patients” because these settings are more sustainable, even though they would require strengthening (IDI21 programme officer).
Too many and too few patients to implement G6PD testing
Participants emphasized the benefit to patients of testing for G6PDd and its necessity to reach elimination targets in 2030 (FGD3; IDI15 LT UHC; IDI22 LT central laboratory):
“this [testing biosensor] is a new concept for our country. So, especially since primaquine has had that many, many contradictions with it, or that are involved in it, sometimes it is not known if there is severe anemia, even if someone dies. So it is a life-saving technology for us” (FGD3 participant)
However, it was reported that there are simultaneously too many and too few patients to implement a test for G6PD like the biosensor. Too many patients to be able to afford a focused case investigation approach involving G6PD testing and radical cure. As mentioned above, FGD participants were concerned about added workload (FGD1, 2, 3). A former member of the Malaria Technical Committee in Dhaka recounts the discussion to not track every patient for G6PD testing during the creation of the national malaria guidelines in 2016 due to cost:
“Bangladesh is not in that position now, to do G6PD for every patient. everywhere in Bangladesh. (..)... the case was so much... so high. (…). it is very costly also. (IDI17 programme officer)
Malaria is almost entirely donor funded and so funding for the biosensor and related costs including reagents is a concern (IDI17 programme officer).
Conversely there are too few P. vivax patients to acquire funding, justify staffing, storage space and the work required to create new policy with G6PD testing as a priority. Programme officers highlighted their challenges in keeping malaria visible and a priority in the face of declining patient numbers. A programme officer outlined that the significant reduction of positive tests resulted in the providers assuming that malaria was gone, and patients interpreting negative malaria RDT results as a failure to diagnose the disease, threatening the provider’s reputation and in turn resulting in less testing:
“...earlier, they [healthworkers at NGOs] tested 10, found 7 positive. So 70% positive. But gradually it happens that they did 100 tests, and found 1 positive. So very low. From 70% to 1%. So two things happened: one is that the worker thought that there is no more malaria. On the other hand people who used to come there, when they were found negative and didn't get anything, they said 'why you are testing? You cannot identify the disease. You cannot diagnose the disease. Then why do you take the blood? I don't like it.' So both from the recipient end and the provider end they started to become reluctant [to test and be tested] and probably they were not testing.” (IDI21 programme officer)
This dynamic led to an increased delay between the onset of symptoms and testing from 5 to 15 days at which point malaria-infected patients would have developed gametocytes that propel onwards transmission (IDI21).
A programme officer (IDI21) argued that currently P. vivax and G6PDd are not given much priority since there are fewer patients with P. vivax than with P. falciparum, and it is a more benign form of malaria. There is little follow up on PQ treatment adherence (IDI17 programme officer), and the last therapeutic efficacy study on CQ and PQ in Bangladesh that the programme officer was aware of was conducted in 1977 so essentially policymakers do not know how effective CQ and PQ are (IDI17 programme officer) and more recent evidence is not mentioned (23). Poor monitoring of PQ treatment adds to the uncertainty at policy level.
As a result, little evidence is collected routinely on P. vivax, G6PD, adherence and possible complications of PQ treatment (IDI23 programme officer), despite the importance of such evidence informing changes to routine policy and practice:
“… first challenge is that to collect information (...) evidence. To see what is the status of the vivax. Then you go for the status of G6PD.” (IDI18 programme officer).
Keeping malaria visible whilst proving malaria is eliminable
To align the implementation of the biosensor with the policy priority of referrals to higher health facility levels that are currently reserved for severe malaria cases, work would have to be undertaken to ensure that the burden of P. vivax relapses remains visible and the importance of implementing efficacious radical cure for P. vivax malaria elimination is understood. This strategy would involve work, but is essential to acquire donor funding, establish G6PD testing and radical cure treatment infrastructure, and uphold political will and leadership (IDI19 programme officer).
A programme officer illustrated the effort it took to change the status of malaria from controllable to eliminable and the national approach from focusing on endemic districts to hotspots. First, the programme officer had to make hotspots visible, i.e. produce data stratified by district, subdistrict, union and village to justify that elimination was possible and to generate funding (IDI21 programme officer). The programme officer developed interventions to prove that malaria could be eradicated; he mobilized health workers, involved communities and created partnerships with other communicable disease programmes, NGOs and military officers to prove the ‘eliminable’ character of malaria. Finally, he convinced local scientists and policy makers at the Ministry of Health and ultimately the Global Fund that Bangladesh should embark on the eliminating malaria.
According to the programme officer, the elimination approach also means that every malaria patient becomes a priority, whether P. vivax or P. falciparum, whether severe or not:
“malaria is malaria” (IDI21 programme officer).