Intravenous artesunate plus oral dihydroartemisinin–piperaquine or intravenous quinine plus oral quinine for optimum treatment of severe malaria: lesson learnt from a field hospital in Timika, Papua, Indonesia

Abstract

BackgroundIntravenous artesunate and its follow on full course dihydroartemisinin–piperaquine are the standard treatment for severe malaria in Indonesia. The current policy suggests that intravenous and oral quinine could be used when standard therapy is not available. Its pragmatic use of both treatment combinations in a field hospital is evaluated.MethodsA retrospective study among hospitalized malaria patients receiving intravenous anti-malarial treatments at Mitra Masyarakat Hospital, Timika from April 2004 to December 2013 was conducted. The length of hospital stay (LoS) and the risk of malaria recurrence within 28 days after hospital admission were compared between patients receiving intravenous artesunate and oral dihydroartemisinin–piperaquine (Iv Art + DHP) and those receiving intravenous and oral quinine (Iv + Oral Qu).ResultsOf 10,514 patients requiring intravenous therapy, 2759 received Iv + Oral Qu and 7755 received Iv Art + DHP. Plasmodium falciparum infection accounted for 65.8% (6915), while Plasmodium vivax, Mixed infections, Plasmodium malariae and Plasmodium ovale were accounted for 17.0% (1789), 16.4% (1729), 0.8% (79) and 0.01% (2) of the infections, respectively. The majority of severe malaria hospital admissions were highland Papuans (78.0%, 8201/10,501). In total 49% (5158) of patients were older than 15 years and 3463 (32.9%) were children under 5 years old. The median LoS was shorter in patients receiving intravenous artesunate compared to those treated with intravenous quinine (median = 2 [IQR 1–3] versus 3 days [IQR 2–4], p < 0.0001). Patients treated with intravenous quinine had higher risk of being hospitalized longer than 2 days (aOR of 1.70 [95% CI 1.54–1.88], p < 0.0001). The risk of recurrences within 28 days after hospital admission was 1.94 times higher (95% CI aHR 1.57–2.39, p < 0.0001) in patients receiving intravenous quinine with follow on oral quinine treatment than in patients treated with DHP after intravenous artesunate therapy.ConclusionsIntravenous artesunate reduced the LoS of malaria patients and in combination with DHP reduced the risk of malaria recurrence within 28 days after hospital admission compared to those with Iv + Oral Qu treatment. Thus, ensuring continuous supply of intravenous artesunate and artemisinin-based combination therapy (ACT) should be a priority.

The high risk of malarial recurrence in patients with Plasmodium-mixed infection after treatment with antimalarial drugs: a systematic review and meta-analysis

“…Of the 11 included studies (Table 1 ), seven (63.6%) were conducted in the WHO South-East Asian Region, including Indonesia [ 30 , 31 , 33 , 34 ], Thailand [ 28 ], India [ 26 ], and Myanmar [ 35 ] during 1991–2015. Three studies were conducted in Papua New Guinea during 1994–2010 [ 29 , 32 , 36 ], and one was conducted in Ghana during 2010 [ 27 ].…”

“…Three studies were conducted in Papua New Guinea during 1994–2010 [ 29 , 32 , 36 ], and one was conducted in Ghana during 2010 [ 27 ]. Two studies [ 26 , 33 ] enrolled patients with severe malaria, while eight studies [ 27 – 30 , 32 , 34 – 36 ] enrolled patients with uncomplicated malaria. One study [ 31 ] enrolled patients with both severe and uncomplicated malaria in their study.…”

“…One study [ 31 ] enrolled patients with both severe and uncomplicated malaria in their study. The list of drugs for the treatment of malaria is shown in Table 1 : one study [ 26 ] with intravenous quinine and oral quinine, six studies [ 27 , 28 , 30 – 32 , 35 ] with ACTs, three studies [ 29 , 34 , 36 ] with chloroquine, and one study [ 33 ] with intravenous artesunate and dihydroartemisinin–piperaquine or intravenous and oral quinine. Most of the included studies (9/11, 81.8%) reported Plasmodium -mixed species after treatment of Plasmodium -mixed infection.…”

“…One study [ 32 ] reported P. falciparum or P. vivax mono-infection, while another study [ 35 ] reported P. vivax mono-infection after treatment of Plasmodium -mixed infection. Recurrence caused by clinical treatment failure (≤ 28 days) was demonstrated in six studies [ 26 , 27 , 29 , 33 , 34 , 36 ], while recurrence after treatment (> 28 days) was demonstrated in four studies [ 28 , 31 , 32 , 35 ]. One study demonstrated recurrence on both ≤ 28 and > 28 days after treatment [ 30 ].…”

Structural and biological survey of 7‐chloro‐4‐(piperazin‐1‐yl)quinoline and its derivatives

“…Again, in 1990s, piperaquine proved its efficacy as part of artemisinin‐based combination therapies (Davis et al, 2005). Since that time, piperaquine is used in combination with other antimalarials in treatment and prophylaxis protocols of malaria (Byakika‐Kibwika, Ssenyonga, Lamorde, Blessborn, & Tarning, 2019; Chotsiri et al, 2019; Chu et al, 2018; Funck‐Brentano et al, 2019; Pull et al, 2019; Sikora et al, 2019). In 1967, compound 3 was claimed to exhibit antimalarial potential against Plasmodium berghei , in addition to its activity against Trypanosoma cruzi for treatment of Chagas' disease (Stephen et al, 1967).…”