Scientific title: An examination of ACT strategy in south-central Asia on P. falciparum malaria in a context where P. vivax is the major species.
What did we know before this research?
With the exception of Sub-Saharan Africa, most areas that are endemic for malaria have a combination of two species: Plasmodium falciparum and P. vivax. P. vivax is often the dominant species, accounting for a greater proportion of malaria cases.
Each of these species has a different level of severity and reaction to common drugs, therefore it’s crucial to diagnose patients and treat them accordingly. For example, P. falciparum is often resistant to cheap malaria drugs (monotherapies like Chloroquine), whereas P. vivax is still sensitive to those drugs. Recommended drugs for P. falciparum (ACT) can be more than ten times as expensive as those that are effective against P.vivax. Therefore, if a case of falciparum is mistakenly diagnosed as vivax, there is a danger of prescribing ineffective drugs which puts the patient at risk, and if a case of vivax is mistakenly diagnosed as falciparum, expensive ACT drugs are wasted unnecessarily.
Moreover, malaria transmission levels are much lower in south-central Asia than in Africa. For this reason, most people who go to clinics with fever do not, in fact, have malaria. Consequently, without accurate diagnosis and treatment, many patients are treated with a malaria drug when they do not, in fact, have malaria. This wastes drugs and neglects the treatment of the true cause of fever.
What does this study add?
Diagnosis is unavailable in most places where fever is common. Community health workers are often the main source of healthcare and are able to provide malaria drugs. However, without diagnosis that is reliable, clinicians and community health workers cannot distinguish the symptoms of malaria from other causes of fever. This results in huge overtreatment of malaria. Even when microscopy is available, many patients who are negative for malaria still receive an antimalarial drug.
One solution is the use of rapid diagnostic tests (RDT). The tests are seen as relatively cost-effective in diagnosing patients in areas where malaria transmission is low or mixed, but this only applies if health workers trust their result.
We conducted a series of studies to test how effective different diagnostic and treatment methods are under field conditions, and measured their impact in effectively treating malaria.
First, we tested the accuracy of a rapid test that can distinguish the two malaria species and accurately identify negative patients. We found that one brand was the most accurate, and this was subsequently introduced as the national standard in Afghanistan.
We then conducted two randomised trials, one in clinics and one amongst community health workers, comparing the use of rapid diagnostic tests and microscopy. These studies will provide robust evidence for the most effective diagnostic tool, and allow both clinicians and community health workers to apply malaria treatments according to diagnostic results.
The research team
Prof. Mark Rowland, London School of Hygiene & Tropical Medicine
Dr Toby Leslie - The Global Fund (previous: London School of Hygiene & Tropical Medicine)
Prof Chris Whitty - London School of Hygiene & Tropical Medicine
Dr. Ismail Mayan, Health Protection and Research Organization, Kabul, Afghanistan
Ms Amy Mikhail - London School of Hygiene & Tropical Medicine
Dr Ismail Mayan - Health Protection and Research Organization (HPRO), Kabul
Dr Nader Mohammed - HealthNet-TPO, Kabul
Dr Anwar Hasanzai – HealthNet-TPO, Jalalabad, Nangaher
Dr Sayed Habib Baktash - Medical Emergency Relief International (Merlin), Kunduz
Latest on this research
The patient-randomised trial involved 5,794 patients in 22 clinics. Malaria rapid diagnostic tests were compared to clinical diagnosis where no parasite diagnostic test was available, established field microscopy, and microscopy that had recently been introduced.
In the low transmission area, comparing rapid diagnostic tests to clinical diagnosis, 65.2% (212/325) vs. 12.5% (40/321) of febrile patients were appropriately treated for malaria, (p<0.001). The proportion of malaria negative patients receiving an antibiotic was 56.9% (185/325) in the rapid diagnostic test vs. 14.3% (46/321) in the clinical diagnosis arm, (p<0.001). In the comparison of rapid diagnostic test to microscopy in the moderate transmission area, 83.6% (1696/2028) vs. 76.3% (1512/1983) were appropriately treated for malaria (p<0.001). A higher proportion of P. falciparum cases received appropriate treatment with artemisinin combination therapy when diagnosed by rapid diagnostic test (81.7% vs. 31.5%, p<0.001).
We conclude that in South Asian regions of low to moderate malaria transmission where clinics lack capacity for diagnosis with rapid diagnostic tests or microscopy, the introduction of the tests should be considered to improve clinical care, reduce the overuse of antimalarials, and improve disease surveillance.
The results of a large cluster randomized trial which compared RDTs with clinical diagnosis amongst about 200 community health workers is forthcoming.