Malaria microscopy was requested in 77% of inpatients with an admitting malaria diagnosis, similar to estimates for the public sector (80%) in moderate- to high-transmission countries in sub-Saharan Africa (SSA) [1]. Unfortunately, only half the microscopy results were available to guide appropriate antimalarial treatment. Thus, despite decent microscopy rates, healthcare professionals still rely on clinical judgement to treat half the suspected malaria cases. Clinical judgement increases the risk of unnecessary antimalarial treatment and, in turn, depletes antimalarial stocks for inpatients who truly need them; and increases the incidence of associated adverse drug reactions and drug resistance [2]. Seven in ten inpatients with suspected non-pregnancy-related malaria tested negative for malaria and would therefore not need antimalarials; compared with only two in ten inpatients with suspected malaria-in-pregnancy. The value of a confirmed malaria diagnosis depends on prompt availability of parasitology results and whether the clinician uses the results to decide how to manage the patient. Malaria negative test-results as confirmed by microscopy - the gold standard - should prompt clinicians to examine patients for other causes of illness and treat them accordingly [2]. However, the interpretation of negative microscopy results should take into account the high rates of antimalarial pre-treatment, which was as high as one in three admitted patients with suspected malaria in this patient cohort. A rapid diagnostic test (RDT), in addition to microscopy, could be used to detect the HRP2 malaria antigen in patients who recently received antimalarials and whose blood films are, thus, likely to show no malaria parasitaemia [2]. RDTs can give positive results for up to 1-month after parasite clearance [2].
One in six cases of confirmed malaria did not receive antimalarials during the current hospitalization, which raises concern over the safety of inpatient care at this tertiary care hospital. Poor coordination between the laboratory and clinicians is likely, which is exacerbated by high inpatient loads of up to 80 admissions in wards with official bed capacity of 54 [3]. Introducing an integrated electronic health record (EHR) system to track inpatient care could significantly improve the flow of information between different hospital departments and, in so doing, promote efficient clinical management of inpatients [12].
One in four inpatients who received at least one in-hospital dose of prescribed antimalarials missed the first day of their antimalarials, which is relatively frequent. Also, monotherapy and incomplete dosing primarily associated with injectable AS and Q were common, possibly fuelled by observed disparities in prescribed, dispensed and administered antimalarials –similar to observations made elsewhere [8, 10]. Possible reasons for these system lapses include; i) drug stock-outs, ii) poor communication between clinician and patient/caregiver and, iii) work overload [3]. The hospital should improve its stock forecasting for in-demand antimalarials, continue to promote intern-pharmacist-led bedside dispensing to reduce the clinicians’ workload during drug administration and improve supervision of junior and mid-level clinicians to promote accountability to inpatients and the hospital [3].
Each additional admitting diagnosis increases by more than two-fold the odds of missed Day 1 dosing of prescribed antimalarials, which underlines the need for prompt availability of malaria test-results to promote the timely initiation of antimalarials. Prompt and complete antimalarial treatment rapidly eliminates malaria parasites from a patient’s bloodstream [13]. Patients with severe malaria should access timely appropriate antimalarials, avoid antimalarial monotherapy and complete full courses of prescribed antimalarials to promote therapeutic success, reduce malaria-related morbidity and mortality, and prevent the emergence and spread of drug resistance [7–9].
Inpatients with an admitting malaria-in-pregnancy diagnosis seemed more likely to have a microscopically-confirmed malaria diagnosis than inpatients with other admitting malaria diagnoses. This comparative advantage at diagnosis did not translate into better antimalarial treatment because no pregnancy-related difference was observed in the prescription, dispensing and administration of antimalarials. Improvement in the antimalarial medication-use-cycle should target systemic weaknesses.
Unlike Q, the hospital frequently encounters drug stock-outs of in-demand, free-of-charge AS and AL, which inpatients must purchase from private community pharmacies to prevent lapses in prescribed treatment. Drugs bought from private community pharmacies are not recorded as dispensed in the hospital register [3], which explains why the reported number of inpatients with administered AS and AL exceeds the number of inpatients to whom these two drugs are dispensed. AS and AL are more in demand than Q because; i) AS is the drug of choice for its faster parasite clearance, less tedious administration regime, and safer profile and, ii) AL is administered after both injectable AS and Q as the continuation of antimalarial treatment in severe malaria [2].
Death could be attributed to severe malaria and/or quinine-related treatment in the 88-year-old female with a single admitting severe malaria diagnosis. The caveat to this malaria-related attribution is malaria based on clinical judgement only (in the absence of microscopy results), unknown HIV-serostatus, advanced age, unknown random blood sugar levels and other comorbidities – especially cardiovascular comorbidities. That notwithstanding, Q was poorly administered at intervals of 25 hours (between first and second doses) and 11 hours (between second and third doses). Yet, 8-hourly intervals of injectable Q administration for at least 24 hours are recommended until the patient is able to take oral medication [2]. The unconsciousness manifested in this inpatient is a known key sign of hypoglycaemia in severe falciparum malaria and carries a high risk of mortality [2]. Unfortunately, hypoglycaemia can result from both severe malaria and quinine-induced hyperinsulinaemia. Thus, blood sugar levels should be checked frequently in severe malaria inpatients who receive Q [2]. Also, this inpatient had tachycardia which could have resulted from Q use and/or hypoglyaemia. With hindsight, this elderly inpatient should have been treated with injectable AS instead, although the frequent unavailability of in-demand AS, and its associated higher cost, often dictates treatment with Q. This fatal case of suspected severe malaria underpins the need for the rapid turnaround of microscopy test-results and the hospital’s investment in routine random blood sugar testing to improve the clinical management of inpatients with severe malaria.
In conclusion, half the malaria microscopy results were not available to guide the clinical management of malaria despite that the rate of testing was high. Laboratory services should improve to promote the treatment of malaria based on confirmed diagnosis as opposed to clinical judgement only, which could reduce the unnecessary use of antimalarials. System-level improvement is required in the procurement, prescription, dispensing and administration of antimalarials to curb the rampant missed opportunities for antimalarial treatment, monotherapy especially with injectable antimalarials and delayed/missed antimalarial doses.
The study’s limitations have been reported elsewhere [3]. Briefly, the study was conducted at Uganda’s National Referral and Teaching Hospital and the results might not be generalizable to facilities with lower calibres of inpatient care. Also, antimalarials that were purchased from private community pharmacies were not documented as dispensed in the hospital register so we obtained this dispensing information by interviewing the inpatients and/or their caregivers [3].