Archive for the 'Diagnosis' Category

Student innovation in low cost diagnostics

My brother is amazing. For his senior design project as a biomedical engineer, he is developing an inexpensive platform for the diagnosis of infectious diseases (covered by the News & Observer). Pavak sought out technical and business development experts, put together a great team of students, and spent countless hours building an imaging cytometer – a device which can count cells in an automated fashion. By labeling cells of interest with a specific dye, its possible to detect and measure the presence of a specific organism. They are starting with an assay to detect tuberculosis, but the next step may be a malaria test. To be fair, the technology isn’t appropriate for all situations and there are many hurdles before the idea can even make it to the field. But for a group of undergraduate students its a tour de force demonstrating initiative, creativity, and engineering ability.

An addendum: how do we create the right environments to encourage and support students to take such risks?


Belgium and the globalization of malaria

A very interesting malaria case was reported in the CDC Emerging Infectious Diseases journal (open access). Theunissen et al. describe a patient who contracted Plasmodium falciparum malaria in Belgium despite not having  visited any malaria endemic area for nine years! What happened here? A number of possibilities exist. Relapse from a previous infection is not possible with falciparum, which unlike the vivax and ovale species of malaria parasites, does not have a “dormant” stage. However, there may have been chronic, low-grade infection acquired nine years ago which remained asymptomatic until now. A few cases of >1 year delay between initial exposure and clinical symptoms have been reported, but a nine year delay would be quite rare. A second explanation could be indigenous malaria transmission by local anopheline species – i.e. a Belgian mosquito bites an infected returning traveler and then bites our patient. Mini-outbreaks have occurred in Florida and Texas, where malaria used to be endemic and conditions are still ripe for transmission. In this case, which occurred in winter, the report claims it is too cold to have many mosquitoes flying around (and I would add too cold for P. falciparum to complete its life cycle in any mosquitoes which were present). Blood transfusion, intravenous drug use, or accidental needle stick injuries can also transmit P. falciparum, but none of these exposures were present here. One key detail is left: two weeks ago (a classic incubation period for malaria), a friend visiting from Guinea-Conakry stayed with the patient. Airport/luggage/container malaria describes the transmission of malaria from an infected mosquito which is accidentally imported during travel. In the end, none of the explanations can be proved definitively, though the authors believe “suitcase malaria” was probably responsible. They then conclude:

This case highlights the problem of diagnosing P. falciparum malaria in patients without a recent travel history to malaria-endemic areas.

A tangential rant – what is certainly not difficult though is diagnosing malaria when a recently returned traveler from West Africa presents with fever and malaise. Unfortunately,  the student health service at my university told a friend of mine that she had viral pneumonia and gave her ibuprofen. Luckily, someone else correctly diagnosed her later, and she lived. Barely.

Scaling lab diagnosis of malaria and the end of presumptive treatment in Africa?

PLOS Medicine (open access! – I enjoy supporting journals in this format) did it again. The journal has carried some great exchanges between scientific “clans” on contentious topics which tend to be both lively and informative. A previous debate included whether or not data from Demographic Surveillance Systems (DSS), a form of long term demographic and health data collection from the routine surveys of a defined population, should be openly accessible rather than only shared among researchers participating in a global DSS network.

The latest issue at hand is whether it is now appropriate to pursue a large scale expansion of laboratory confirmation of malaria through the use of rapid diagnostic tests (RDTs) and abandon the presumptive treatment of malaria based on clinical symptoms alone in sub-Saharan Africa. The geographic qualifier in this debate is important – in this region health systems are generally consider weak with little capacity for diagnosis. In addition, given the high burden of malaria, and health worker shortages the standard practice is to treat anyone with suspected malaria which is often simply the presence of fever and leads to a wastage of valuable drugs, promotion of drug resistance, and the under-treatment of other underlying causes of fever.

Of course, both sides support strengthening case management and the use of new tools like RDTs. The counterpoint is not so much a disagreement as it is a caution against rapid implementation. What we don’t know is how much attention scaling RDTs will take (i.e. do we have the capacity without losing focus on other interventions?), how many cases would be miss if presumptive treatment decreased, and when/what context such an effort should be executed. It is a complex scenario. To better understand how to interpret divergent opinions from the lens of program management and strategy, I asked a trusted malaria expert to share his views:

I agree with Blaise and others. However, the problem with the discussion is that Blaise et al. do not sufficiently think through how labour and time intensive the change process will be.  On the other hand, Mike et al. do not sufficiently understand that the process of introducing diagnostics – done properly with all thorough and full coverage of training and quality assurance of products and services – is in itself a health system strengthening activity.

Well, one way to succinctly summarize the debate. What are your thoughts?

The CellScope – mobile phone microscopes for malaria

This is cool. Often much research feels far removed from everyday applications and practical concerns. So it is terribly rewarding to see a skunk works type creation that has great potential for how we deliver care. The CellScope is a microscope attachment for cellular phones which is designed to allow field workers to take images of specimens and send them to an expert for diagnosis. Developed by engineers at the University of California at Berkeley, the CellScope was designed to handle a range of magnifications including the optical power neccessary to diagnose malaria (malaria slide image from the CellScope).

There are a number of obstacles for the designers to overcome before such a device could become field usable – though I believe all of them should be surmountable. For example, in many malaria infections only a small portion of red blood cells are infected (often <0.5%) which means an accurate diagnosis requires the examination of many different microscope fields. The device therefore needs to image multiple fields automatically and deciding which fields to send is important. Sending too few might result in misdiagnoses and sending all fields places a large workload for technicians at the receiving end. A screening software, in the phone or the receiving workstation, capable of rapidly screening fields and selecting for example 10 out of 100 imaged fields for expert verification could overcome this challenge.

Overdiagnosis of malaria hurts the patient (and you and me)

Much of the world still diagnoses malaria clinically (based on symptoms alone without testing for the presence of the parasite). Recently, a Liverpool team working in Mozambique examined the cost to individual patients resulting from the clinical diagnosis of malaria (Malaria Journal – open access). The findings were striking but certainly not surprising. 23 percent of children and 31 percent of adults were overdiagnosed with malaria which resulted in a greater number of healthcare visits and costs for the adult patients.

At a population level, overdiagnosis is expensive for the health system due to the increased wastage of antimalarials and increased demand on provider time. The former concern is more pronounced recently since many countries are now using expensive artemisinin-combination therapies. Increased drug pressure also facilities the emergence and spread of drug-resistant malaria. Drug-resistant malaria increases morbidity and mortality and in some regions of the world our therapeutic alternatives are alarmingly few. I research the epidemiology and mechanisms of antimalarial resistance, and thus the lack of emphasis on parasitogically confirmed treatment is particularly worrisome. A leading malaria researcher once wrote to me, “The problem is even key malaria scientists still have difficulty thinking about how to prevent drug resistance development and how important it is to improve diagnosis and health care infrastructure so that “rational drug use” can be reinforced. They only think about what alternative drugs should be now that this one fails….” Words to heed indeed.