In the Journals

Rapid diagnostic tests detect malaria in pregnant women when used early

Rapid diagnostic tests may be an effective tool to detect malaria among pregnant women in endemic regions, according to data from a recently published trial.

Due to waning sensitivity upon subsequent visits to antenatal care facilities, however, researchers proposed limiting the use of these diagnostics to initial visits to maintain cost efficiency.

New approaches needed as preventive treatments lose strength

For pregnant women living in malaria-endemic African countries, WHO guidance recommends preventive treatments of sulfadoxine-pyrimethamine at each antenatal clinic visit after the first trimester of pregnancy. According to WHO, these treatments have been shown to prevent peripheral parasitemia, maternal anemia and clinical malaria during pregnancy, and are also capable of reducing overall neonatal mortality.

However, Plasmodium falciparum resistant to sulfadoxine-pyrimethamine are becoming more prevalent in many of these affected regions, the researchers wrote, increasing the need for new strategies to limit malaria during pregnancy.

“Intermittent screening and treatment provides a possible approach to the management of malaria in pregnancy in certain epidemiological situations,” the researchers wrote. “There are, however, concerns that infections present at too low a density to be detected with a [rapid diagnostic test (RDT)] could have an adverse effect on the outcome of pregnancy.”

To gauge the sensitivity of Histidine-Rich Protein 2/parasite lactate dehydrogenase (HRP2/pLDH) RDT screening, researchers examined samples and data obtained from a large multicenter trial comparing preventive sulfadoxine-pyrimethamine treatment to screening and treatment. Participating primigravidae and secundigravidae from four West African countries were screened with the HRP2/pLDH RDT during multiple antenatal clinic visits, and treated with artemether-lumefantrine if positive. The researchers re-examined finger prick blood samples collected during each visit for malaria infection using microscopy and PCR assay, and compared these findings to RDT results reported during the primary study. Researchers also reviewed birth outcomes to identify any association between missed infections and consequences including low birth weight, hemoglobin concentration and active malaria infection of the placenta.

RDTs demonstrate improved specificity upon first clinic visit

Malaria prevalence at enrollment as determined by microscopy or PCR was 70% in Burkina Faso, 58.6% in Ghana, 35.9% in Mali and 15.1% in The Gambia, the researchers wrote. The overall sensitivity of the RDT was 87.4% (95% CI, 85.3%-89.4%), and 55.6% of all RDT detections occurred during the first visit to an antenatal clinic. Sensitivity ranged from 90.9% in Burkina Faso to 59.3% in The Gambia, which the researchers wrote may suggest a potential relationship between parasite density and RDT specificity. Among Ghanaian women alone, P. falciparum prevalence was highest at enrollment and RDT sensitivity was 88.8% at the first antenatal clinic, 83.7% at the second, 77.4% at the third and 48.6% at delivery.

The researchers saw no association between RDT results and any of the measured birth outcomes. After adjusting for covariates, the only identifiable risk factor of missed infection was pregnancy with a woman’s second child as opposed to her first (OR = 1.85; 95% CI, 1-3.43).

Taken together, these results led researchers to suggest RDT screening and treatment upon a pregnant woman’s first clinic visit as a cost-effective means to detect and treat many infections with no serious repercussions for the child. However, the diminished test accuracy in less affected regions is a major shortcoming in need of more investigation.

“The lowest sensitivity of the RDT seen in this study was at the site with the lowest transmission; it is not clear if this is a causal association due to lower average parasite densities but this is a possible explanation for this observation,” the researchers wrote. “It is also unclear if sensitivity would decline further over the course of pregnancy in lower transmission settings and this needs to be investigated. As the incidence of malaria falls in many previously highly endemic areas, new approaches to the control of malaria in pregnancy need to be developed and evaluated.”

RDT screening curbs overprescription

Previous data have also shown the potential of RDTs to reduce costs in other areas of malaria care.

In another recently published trial, researchers provided 10 geographic clusters of registered Ugandan drug shops with RDTs instruction to only provide artemisinin-based combination therapy (ACT) upon positive results. The control arm, which also consisted of 10 clusters, treated febrile patients with ACT presumptively. In total, 15,517 eligible patients with fever sought treatment from these 59 enrolled drug shops and were included in the study.

Nearly 60% of patients who purchased an RDT had positive test results, which were verified by the researchers to be 95% accurate. All but 1.5% of patients with negative RDT results adhered to the results and did not receive ACT.

When compared with controls, ACT prescriptions were greatly reduced within the intervention arm (99.8% vs. 62.5%) and resulted in a 72.6% reduction in overprescription.

“Our findings show that it is feasible to collaborate with the private health sector and introduce malaria rapid diagnostic tests in drug shops,” Anthony K. Mbonye, PhD, commissioner of health services at the Ugandan Ministry of Health, said in a press release. “The next step is to refine the strategy and understand the cost implications of scaling it up in Uganda. Our long-term aim is to provide evidence to help [WHO] develop guidance to improve malaria treatment in the private sector.” – by Dave Muoio

References:

Mbonye AK, et al. PLoS One. 2015;doi:10.1371/journal.pone.0129545.

WHO. WHO Evidence Review Group: Intermittent Preventive Treatment of malaria in pregnancy with Sulfadoxine-Pyrimethamine. 2012. www.who.int/malaria/mpac/sep2012/iptp_sp_erg_meeting_report_july2012.pdf. Accessed January 8, 2016.

Williams JE, et al. Clin Infect Dis. 2015;doi:10.1093/cid/civ1198.

Disclosure: The researchers report no relevant financial disclosures.

Rapid diagnostic tests may be an effective tool to detect malaria among pregnant women in endemic regions, according to data from a recently published trial.

Due to waning sensitivity upon subsequent visits to antenatal care facilities, however, researchers proposed limiting the use of these diagnostics to initial visits to maintain cost efficiency.

New approaches needed as preventive treatments lose strength

For pregnant women living in malaria-endemic African countries, WHO guidance recommends preventive treatments of sulfadoxine-pyrimethamine at each antenatal clinic visit after the first trimester of pregnancy. According to WHO, these treatments have been shown to prevent peripheral parasitemia, maternal anemia and clinical malaria during pregnancy, and are also capable of reducing overall neonatal mortality.

However, Plasmodium falciparum resistant to sulfadoxine-pyrimethamine are becoming more prevalent in many of these affected regions, the researchers wrote, increasing the need for new strategies to limit malaria during pregnancy.

“Intermittent screening and treatment provides a possible approach to the management of malaria in pregnancy in certain epidemiological situations,” the researchers wrote. “There are, however, concerns that infections present at too low a density to be detected with a [rapid diagnostic test (RDT)] could have an adverse effect on the outcome of pregnancy.”

To gauge the sensitivity of Histidine-Rich Protein 2/parasite lactate dehydrogenase (HRP2/pLDH) RDT screening, researchers examined samples and data obtained from a large multicenter trial comparing preventive sulfadoxine-pyrimethamine treatment to screening and treatment. Participating primigravidae and secundigravidae from four West African countries were screened with the HRP2/pLDH RDT during multiple antenatal clinic visits, and treated with artemether-lumefantrine if positive. The researchers re-examined finger prick blood samples collected during each visit for malaria infection using microscopy and PCR assay, and compared these findings to RDT results reported during the primary study. Researchers also reviewed birth outcomes to identify any association between missed infections and consequences including low birth weight, hemoglobin concentration and active malaria infection of the placenta.

RDTs demonstrate improved specificity upon first clinic visit

Malaria prevalence at enrollment as determined by microscopy or PCR was 70% in Burkina Faso, 58.6% in Ghana, 35.9% in Mali and 15.1% in The Gambia, the researchers wrote. The overall sensitivity of the RDT was 87.4% (95% CI, 85.3%-89.4%), and 55.6% of all RDT detections occurred during the first visit to an antenatal clinic. Sensitivity ranged from 90.9% in Burkina Faso to 59.3% in The Gambia, which the researchers wrote may suggest a potential relationship between parasite density and RDT specificity. Among Ghanaian women alone, P. falciparum prevalence was highest at enrollment and RDT sensitivity was 88.8% at the first antenatal clinic, 83.7% at the second, 77.4% at the third and 48.6% at delivery.

The researchers saw no association between RDT results and any of the measured birth outcomes. After adjusting for covariates, the only identifiable risk factor of missed infection was pregnancy with a woman’s second child as opposed to her first (OR = 1.85; 95% CI, 1-3.43).

Taken together, these results led researchers to suggest RDT screening and treatment upon a pregnant woman’s first clinic visit as a cost-effective means to detect and treat many infections with no serious repercussions for the child. However, the diminished test accuracy in less affected regions is a major shortcoming in need of more investigation.

“The lowest sensitivity of the RDT seen in this study was at the site with the lowest transmission; it is not clear if this is a causal association due to lower average parasite densities but this is a possible explanation for this observation,” the researchers wrote. “It is also unclear if sensitivity would decline further over the course of pregnancy in lower transmission settings and this needs to be investigated. As the incidence of malaria falls in many previously highly endemic areas, new approaches to the control of malaria in pregnancy need to be developed and evaluated.”

RDT screening curbs overprescription

Previous data have also shown the potential of RDTs to reduce costs in other areas of malaria care.

In another recently published trial, researchers provided 10 geographic clusters of registered Ugandan drug shops with RDTs instruction to only provide artemisinin-based combination therapy (ACT) upon positive results. The control arm, which also consisted of 10 clusters, treated febrile patients with ACT presumptively. In total, 15,517 eligible patients with fever sought treatment from these 59 enrolled drug shops and were included in the study.

Nearly 60% of patients who purchased an RDT had positive test results, which were verified by the researchers to be 95% accurate. All but 1.5% of patients with negative RDT results adhered to the results and did not receive ACT.

When compared with controls, ACT prescriptions were greatly reduced within the intervention arm (99.8% vs. 62.5%) and resulted in a 72.6% reduction in overprescription.

“Our findings show that it is feasible to collaborate with the private health sector and introduce malaria rapid diagnostic tests in drug shops,” Anthony K. Mbonye, PhD, commissioner of health services at the Ugandan Ministry of Health, said in a press release. “The next step is to refine the strategy and understand the cost implications of scaling it up in Uganda. Our long-term aim is to provide evidence to help [WHO] develop guidance to improve malaria treatment in the private sector.” – by Dave Muoio

References:

Mbonye AK, et al. PLoS One. 2015;doi:10.1371/journal.pone.0129545.

WHO. WHO Evidence Review Group: Intermittent Preventive Treatment of malaria in pregnancy with Sulfadoxine-Pyrimethamine. 2012. www.who.int/malaria/mpac/sep2012/iptp_sp_erg_meeting_report_july2012.pdf. Accessed January 8, 2016.

Williams JE, et al. Clin Infect Dis. 2015;doi:10.1093/cid/civ1198.

Disclosure: The researchers report no relevant financial disclosures.