Pregnancy outcomes and risk of placental malaria after artemisinin-based and quinine-based treatment for uncomplicated falciparum malaria in pregnancy: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.

BACKGROUND: Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Individual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of uncomplicated falciparum malaria infection. METHODS: A systematic review and one-stage IPD meta-analysis of studies assessing the efficacy of artemisinin-based and quinine-based treatments for patent microscopic uncomplicated falciparum malaria infection (hereinafter uncomplicated falciparum malaria) in pregnancy was conducted. The risks of stillbirth (pregnancy loss at ≥ 28.0 weeks of gestation), moderate to late preterm birth (PTB, live birth between 32.0 and < 37.0 weeks), small for gestational age (SGA, birthweight of < 10th percentile), and placental malaria (defined as deposition of malaria pigment in the placenta with or without parasites) after different treatments of uncomplicated falciparum malaria were assessed by mixed-effects logistic regression, using artemether-lumefantrine, the most used antimalarial, as the reference standard. Registration PROSPERO: CRD42018104013. RESULTS: Of the 22 eligible studies (n = 5015), IPD from16 studies were shared, representing 95.0% (n = 4765) of the women enrolled in literature. Malaria treatment in this pooled analysis mostly occurred in the second (68.4%, 3064/4501) or third trimester (31.6%, 1421/4501), with gestational age confirmed by ultrasound in 91.5% (4120/4503). Quinine (n = 184) and five commonly used artemisinin-based combination therapies (ACTs) were included: artemether-lumefantrine (n = 1087), artesunate-amodiaquine (n = 775), artesunate-mefloquine (n = 965), and dihydroartemisinin-piperaquine (n = 837). The overall pooled proportion of stillbirth was 1.1% (84/4361), PTB 10.0% (619/4131), SGA 32.3% (1007/3707), and placental malaria 80.1% (2543/3035), and there were no significant differences of considered outcomes by ACT. Higher parasitaemia before treatment was associated with a higher risk of SGA (adjusted odds ratio [aOR] 1.14 per 10-fold increase, 95% confidence interval [CI] 1.03 to 1.26, p = 0.009) and deposition of malaria pigment in the placenta (aOR 1.67 per 10-fold increase, 95% CI 1.42 to 1.96, p < 0.001). CONCLUSIONS: The risks of stillbirth, PTB, SGA, and placental malaria were not different between the commonly used ACTs. The risk of SGA was high among pregnant women infected with falciparum malaria despite treatment with highly effective drugs. Reduction of malaria-associated adverse birth outcomes requires effective prevention in pregnant women.

Preparedness for severe malaria.

BACKGROUND: About 60 patients with malaria are admitted to Norwegian hospitals every year. The prescription figures for malaria medication may suggest that Norwegians are increasingly exposed to malaria infection. MATERIAL AND METHOD: All Norwegian hospitals with a department of internal medicine were sent an electronic questionnaire for reporting the available methods for diagnosing and treating malaria. RESULTS: There was a 100% response (48/48). Microscopy for malaria diagnosis was available at 92% (44/48) and a rapid test for detecting malaria antigen at 67% (32/48), while 6% (3/48) had no malaria detection test available. Artesunate and quinine for intravenous treatment were both available at 6% (3/48), only artesunate at 27% (13/48) and only quinine at 27% (13/48) of the hospitals. Drugs for intravenous treatment of severe malaria were not available at 40% (19/48) of the hospitals. INTERPRETATION: More than a third of Norwegian hospitals lack preparedness for treating severe malaria, and some hospitals lack diagnostic procedures. Severe malaria is a condition that may rapidly become life-threatening and is treated with artesunate or quinine intravenously. All Norwegian hospitals should have procedures for emergency treatment of the disease.

SMS for Life: a pilot project to improve anti-malarial drug supply management in rural Tanzania using standard technology.

BACKGROUND: Maintaining adequate supplies of anti-malarial medicines at the health facility level in rural sub-Saharan Africa is a major barrier to effective management of the disease. Lack of visibility of anti-malarial stock levels at the health facility level is an important contributor to this problem. METHODS: A 21-week pilot study, 'SMS for Life', was undertaken during 2009-2010 in three districts of rural Tanzania, involving 129 health facilities. Undertaken through a collaborative partnership of public and private institutions, SMS for Life used mobile telephones, SMS messages and electronic mapping technology to facilitate provision of comprehensive and accurate stock counts from all health facilities to each district management team on a weekly basis. The system covered stocks of the four different dosage packs of artemether-lumefantrine (AL) and quinine injectable. RESULTS: Stock count data was provided in 95% of cases, on average. A high response rate (≥ 93%) was maintained throughout the pilot. The error rate for composition of SMS responses averaged 7.5% throughout the study; almost all errors were corrected and messages re-sent. Data accuracy, based on surveillance visits to health facilities, was 94%. District stock reports were accessed on average once a day. The proportion of health facilities with no stock of one or more anti-malarial medicine (i.e. any of the four dosages of AL or quinine injectable) fell from 78% at week 1 to 26% at week 21. In Lindi Rural district, stock-outs were eliminated by week 8 with virtually no stock-outs thereafter. During the study, AL stocks increased by 64% and quinine stock increased 36% across the three districts. CONCLUSIONS: The SMS for Life pilot provided visibility of anti-malarial stock levels to support more efficient stock management using simple and widely available SMS technology, via a public-private partnership model that worked highly effectively. The SMS for Life system has the potential to alleviate restricted availability of anti-malarial drugs or other medicines in rural or under-resourced areas.

[Availability of antimalarial agents in Dutch hospitals]. / Beschikbaarheid van malariamiddelen in Nederlandse ziekenhuizen.

OBJECTIVE: To investigate the availability of antimalarial agents for the treatment of falciparum malaria in all Dutch hospital pharmacies, including changes in the situation over a period of two years. DESIGN: Descriptive. METHOD: In the period October 2006 to March 2007 all Dutch hospital pharmacies were questioned about the availability of antimalarial agents, by means of a telephone survey. The survey was repeated at the end of 2008. RESULTS: The percentage of hospitals that had quinine in stock increased from 72 (62 of the 86 hospitals responding) to 80 (73 of 91 hospitals). In 2008 artesunate was in stock in 7 hospitals. At the end of 2008 18 Dutch hospitals had no medication available for the treatment of severe malaria tropica; 6 hospitals had no agents for the treatment of malaria at all. CONCLUSION: The ideal situation, in which every hospital in the Netherlands has a supply of adequate agents for the treatment of severe malaria, has not yet been achieved.

Retail supply of malaria-related drugs in rural Tanzania: risks and opportunities.

OBJECTIVES: To characterize availability of fever and malaria medicines within the retail sector in rural Tanzania, assess the likely public health implications, and identify opportunities for policy interventions to increase the coverage of effective treatment. METHODS: A census of retailers selling drugs was undertaken in the areas under demographic surveillance in four Tanzanian districts, using a structured questionnaire. RESULTS: Drugs were stocked by two types of retailer: a large number of general retailers (n = 675) and a relatively small number of drug shops (n = 43). Almost all outlets stocked antipyretics/painkillers. One-third of general retailers stocking drugs had antimalarials, usually chloroquine alone. Almost all drug shops stocked antimalarials (98%): nearly all had chloroquine, 42% stocked quinine, 37% sulphadoxine-pyrimethamine and 30% amodiaquine. A large number of antimalarial brands were available. Population ratios indicate the relative accessibility of retail drug providers compared with health facilities. Drug shop staff generally travelled long distances to buy from drugs wholesalers or pharmacies. General retailers bought mainly from local general wholesalers, with a few general wholesalers accounting for a high proportion of all sources cited. CONCLUSIONS: Drugs were widely available from a large number of retail outlets. Potential negative implications include provision of ineffective drugs, confusion over brand names, uncontrolled use of antimalarials, and the availability of components of potential combination therapy regimens as monotherapies. On the other hand, this active and highly accessible retail market provides opportunities for improving the coverage of effective antimalarial treatment. Interventions targeted at all drug retailers are likely to be costly to deliver and difficult to sustain, but two promising points for targeted intervention are drug shops and selected general wholesalers. Retail quality may also be improved through consumer education, and modification of the chemical quality, packaging and price of products entering the retail distribution chain.