Field expansion of DNA polymerase chain reaction for early infant diagnosis of HIV-1: The Ethiopian experience

Background: Early diagnosis of infants infected with HIV (EID) and early initiation of treatment significantly reduces the rate of disease progression and mortality. One of the challengesto identification of HIV-1-infected infants is availability and/or access to quality molecular laboratory facilities which perform molecular virologic assays suitable for accurate identificationof the HIV status of infants. Method: We conducted a joint site assessment and designed laboratories for the expansion of DNA polymerase chain reaction (PCR) testing based on dried blood spot (DBS) for EID insix regions of Ethiopia. Training of appropriate laboratory technologists and development of required documentation including standard operating procedures (SOPs) was carried out. The impact of the expansion of EID laboratories was assessed by the number of tests performed as well as the turn-around time. Results: DNA PCR for EID was introduced in 2008 in six regions. From April 2006 to April 2008, a total of 2848 infants had been tested centrally at the Ethiopian Health and Nutrition Research Institute (EHNRI) in Addis Ababa, and which was then the only laboratory with the capability to perform EID; 546 (19.2%) of the samples were positive. By November 2010, EHNRI and the six laboratories had tested an additional 16 985 HIV-exposed infants, of which 1915 (11.3%) were positive. The median turn-around time for test results was 14 days (range 14−21 days). Conclusion: Expansion of HIV DNA PCR testing facilities that can provide quality and reliable results is feasible in resource-limited settings. Regular supervision and monitoring for quality assurance of these laboratories is essential to maintain accuracy of testing

Therapeutic efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum and chloroquine and dihydroartemisinin-piperaquine for uncomplicated Plasmodium vivax infection in Ethiopia

Abstract Background Routine monitoring of anti-malarial drugs is recommended for early detection of drug resistance and to inform national malaria treatment guidelines. In Ethiopia, the national treatment guidelines employ a species-specific approach. Artemether-lumefantrine (AL) and chloroquine (CQ) are the first-line schizonticidal treatments for Plasmodium falciparum and Plasmodium vivax, respectively. The National Malaria Control and Elimination Programme in Ethiopia is considering dihydroartemisinin-piperaquine (DHA/PPQ) as an alternative regimen for P. falciparum and P. vivax. Methods The study assessed the clinical and parasitological efficacy of AL, CQ, and DHA/PPQ in four arms. Patients over 6 months and less than 18 years of age with uncomplicated malaria mono-infection were recruited and allocated to AL against P. falciparum and CQ against P. vivax. Patients 18 years or older with uncomplicated malaria mono-infection were recruited and randomized to AL or dihydroartemisinin-piperaquine (DHA/PPQ) against P. falciparum and CQ or DHA/PPQ for P. vivax. Patients were followed up for 28 (for CQ and AL) or 42 days (for DHA/PPQ) according to the WHO recommendations. Polymerase chain reaction (PCR)-corrected and uncorrected estimates were analysed by Kaplan Meier survival analysis and per protocol methods. Results A total of 379 patients were enroled in four arms (n = 106, AL-P. falciparum; n = 75, DHA/PPQ- P. falciparum; n = 142, CQ-P. vivax; n = 56, DHA/PPQ-P. vivax). High PCR-corrected adequate clinical and parasitological response (ACPR) rates were observed at the primary end points of 28 days for AL and CQ and 42 days for DHA/PPQ. ACPR rates were 100% in AL-Pf (95% CI: 96–100), 98% in CQ-P. vivax (95% CI: 95–100) at 28 days, and 100% in the DHA/PPQ arms for both P. falciparum and P. vivax at 42 days. For secondary endpoints, by day three 99% of AL-P. falciparum patients (n = 101) cleared parasites and 100% were afebrile. For all other arms, 100% of patients cleared parasites and were afebrile by day three. No serious adverse events were reported. Conclusion This study demonstrated high therapeutic efficacy for the anti-malarial drugs currently used by the malaria control programme in Ethiopia and provides information on the efficacy of DHA/PPQ for the treatment of P. falciparum and P. vivax as an alternative option

Correction: Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: A randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pmed.1002299.]

Hazard ratios and incidence rate ratios.

<p>Hazard ratios and incidence rate ratios.</p

Cumulative risk of <i>P</i>. <i>vivax</i> recurrence in all four treatment arms over the entire follow-up time.

<p>AL, artemether-lumefantrine; AL+PQ, artemether-lumefantrine + primaquine; CQ, chloroquine; CQ+PQ, chloroquine + primaquine.</p

Baseline characteristics of the study population.

<p>Baseline characteristics of the study population.</p

Treatment failure and risk and incidence of recurrent parasitaemia.

<p>Treatment failure and risk and incidence of recurrent parasitaemia.</p

Parasite and fever clearance by treatment arm.

<p>Parasite and fever clearance by treatment arm.</p

Histogram of the distribution of the number of recurrent <i>P</i>. <i>vivax</i> infections occurring during the 1-y follow-up period.

<p>AL, artemether-lumefantrine; AL+PQ, artemether-lumefantrine + primaquine; CQ, chloroquine; CQ+PQ, chloroquine + primaquine.</p

CONSORT flowchart of patient allocation for the day 42 outcome.

<p>AL, artemether-lumefantrine; AL+PQ, artemether-lumefantrine + primaquine; CQ, chloroquine; CQ+PQ, chloroquine + primaquine; G6PD, glucose-6-phosphate dehydrogenase; Lost, lost to follow-up.</p