High Prevalence of Low-Level Parasitemia With Plasmodium vivax in Makira-Ulawa Province Presents a Challenge for the Diagnosis and Eradication of Malaria in Solomon Islands

DISCUSSION

Our study confirmed the suspicion of the local nursing staff that the RDTs were not effective for diagnosing malaria in Kirakira. This result is at odds with the reported sensitivities of RDTs that range between 75% and 90%. However, the studies of RDT sensitivities have principally been conducted in the sub-Saharan region of Africa where P falciparum is the main species, the average parasite loads are usually much greater than 1,000 parasites per μL, and levels can be as high as 30,000 parasites per μL.¹⁴ The WHO recommends the use of quality RDTs as standard diagnostic tools for routine malaria case management, but evidence is insufficient to assess if RDTs are useful in low-transmission settings where submicroscopic infections, often not associated with febrile illness, have been shown to have efficient gametocyte production that serves as an ongoing reservoir of potential transmission.¹⁵ Further research into the sensitivity of the RDTs confirms that a parasite load of >500 parasites per μL is often required to trigger a positive result, so RDTs are frequently unable to detect malaria in patients with low parasite loads. In our study, 4 patients had parasite loads >500 parasites per μL, but all had negative RDT results.

The failure of the RDTs in this study could have several explanations. The kits may have been defective, the staff may not have used them correctly, and the low parasite loads may have contributed to the ineffectiveness of the RDTs. Because we only performed RDTs on patients with positive malaria parasite smears, we could not confirm a false-positive rate for this particular RDT that has been noted by Swiss researchers conducting fieldwork in Eswatini, formerly known as Swaziland.¹⁶ RDTs are an important tool for the detection of malaria in resource-poor communities without access to microscopy; however, we had no success with the RDT that was available. Kirakira Hospital had no access to other RDTs that can distinguish between P falciparum and P vivax strains and potentially might have been more effective than the CareStart Malaria HRP2/pLDH (Pf/pan) Combo RDT.¹⁷ The total budget for all health care in Makira-Ulawa Province is only $1.3 million US dollars per annum or the equivalent of $26 US dollars per annum per capita, so health care resources are extremely limited.¹⁸

Our study results demonstrate what appears to be a dramatic change in the epidemiology of malaria in Makira-Ulawa Province. P falciparum in this audit was rare and accounted for only 5.2% of identified cases vs the WHO estimate of approximately 60%.⁵ A possible reason for this change is the introduction of ACT protocols that are highly effective against P falciparum and have been first-line treatment for all cases of malaria in Solomon Islands since 2009. The staff in the Kirakira Hospital malaria laboratory provided anecdotal evidence that the clinics where P falciparum was detected were remote and did not have access to ACT. The introduction of ACT in 2009 proved hugely successful in eradicating P falciparum in Solomon Islands. In Makira-Ulawa Province, however, the situation with P vivax is quite different.

P vivax malaria requires treatment with primaquine for 2 weeks to prevent recurrent infection. However, primaquine can cause acute hemolytic anemia in patients with G6PD deficiency. In Solomon Islands, research indicates that approximately 7% of the population has a deficiency of G6PD and would be at risk of developing a severe hemolytic reaction when exposed to primaquine.¹⁹ Consequently, since 2009, the Ministry of Health for Solomon Islands has appropriately recommended that all patients with P vivax malaria be screened for G6PD deficiency, and if safe, to proceed with primaquine treatment.²⁰

Implementing this treatment protocol across Makira-Ulawa Province has been challenging on many levels. First, health literacy in the community is low, and the need for primaquine treatment when the patient has recovered from the acute febrile episode is often poorly understood by the nursing staff and the patients. Second, adherence with outpatient medication is a particularly challenging problem in Solomon Islands. One strategy to overcome lack of adherence would be to directly observe patients taking their primaquine medication each day to ensure compliance, but resources to implement such a policy are limited. Third, the G6PD screening test is not available at all health centers in Makira-Ulawa Province, and the community and health workforce do not have a clear understanding of why the test is important.²¹

An important issue raised by the study data is how the diagnosis of acute malaria is made. The presence of a fever and a positive malaria parasite smear have been considered sufficient to establish a diagnosis of malaria. What we cannot extract from this audit is whether the low-level parasitemia was the cause of the fever or if patients had other common causes of fever such as acute viral infection. The patients diagnosed with malaria in this study were not sick enough to require inpatient treatment and were effectively managed on an outpatient basis. The highest parasite load among the 45 patients in this study was 640 parasites per μL (16 parasites per 200 white blood cells). This number is below the level likely to cause symptoms of severe malaria (defined as >1,000 parasites per μL or >25 parasites per 200 white blood cells) and explains why all patients could be successfully managed as outpatients.

Whether the low-level parasitemia identified in this study was sign of a chronic underlying illness and not the cause of the fever is a vexing question because no agreed-upon levels of parasitemia that indicate a definite diagnosis have been established.²² Further, what constitutes symptomatic vs asymptomatic malaria has not been firmly established. Chronic or recurrent malaria has long been recognized to cause long-term health problems such as chronic anemia and splenomegaly.²³

To answer the question of whether the low-level parasitemia identified in this study is a sign of a chronic underlying illness and not the cause of the fever would require screening the population to determine the prevalence of low-grade parasitemia, anemia, and clinical splenomegaly in asymptomatic patients. Such population screening is not part of the current national strategy to address malaria in Solomon Islands.¹¹ The number of cases of malaria detected in the province would have likely been higher if polymerase chain reaction (PCR) had been used to screen for malaria because this technology is more sensitive in identifying malaria than microscopy or RDT.²⁴ Asymptomatic malaria is being recognized with increasing frequency in Southeast Asia, with research using PCR technology revealing that 3 to 4 times as many patients with malaria may be detected with PCR screening alone.

Developing an implementable combination of diagnostic testing and treatment to try to eradicate malaria from Makira-Ulawa Province will be an ongoing challenge.²⁵ Malaria is a complex infection; the challenge is to understand the nature of the illness and how that nature might change as the epidemiology changes. Therefore, developing a better understanding of low parasite level and asymptomatic disease is necessary for eradication programs to be successful.