No Evidence for Spread of Plasmodium falciparum Artemisinin Resistance to Savannakhet Province, Southern Laos

We conducted an open-label, randomized clinical trial to assess parasite clearance times (PCT) and the efficacy of 4 mg/kg (group 1, n = 22) and 2 mg/kg (group 2, n = 22) of oral artesunate for three days followed by artemether-lumefantrine in patients with uncomplicated Plasmodium falciparum malaria at Xepon Interdistrict Hospital, Savannakhet Province in southern Laos. Slides were read in duplicate. The overall mean (95% confidence interval; range) PCT in hours was 23.2 (21.2–25.3; 12–46) and 22.4 (20.3–24.5; 12–46) for the first and second microscopists, respectively (P = 0.57). Ten (23%) patients remained parasitemic on day 1 after treatment (4 [18%] in group 1 and 6 [27%] in group 2; P = 0.47). No patient had patent asexual parasitemia on the second and third days of treatment. The 42-day polymerase chain reaction–corrected cure rates were 100% in both treatment groups. Serious adverse events did not develop during or after treatment in any patients. In conclusion, no evidence of P. falciparum in vivo resistance to artesunate was found in southern Laos

Comparison of chloroquine, sulfadoxine/pyrimethamine, mefloquine and mefloquine-artesunate for the treatment of falciparum malaria in Kachin State, North Myanmar.

Multi-drug resistant falciparum malaria is widespread in Asia. In Thailand, Cambodia and Vietnam the national protocols have changed largely to artesunate combined treatment regimens but elsewhere in East and South Asia chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) are still widely recommended by national malaria control programmes. In Kachin State, northern Myanmar, an area of low seasonal malaria transmission, the efficacy of CQ (25 mg base/kg) and SP (1.25/25 mg/kg), the nationally recommended treatments at the time, were compared with mefloquine alone (M; 15 mg base/kg) and mefloquine combined with artesunate (MA; 15:4 mg/kg). An open randomized controlled trial enrolled 316 patients with uncomplicated Plasmodium falciparum malaria, stratified prospectively into three age-groups. Early treatment failures (ETF) occurred in 41% (32/78) of CQ treated patients and in 24% of patients treated with SP (18/75). In young children the ETF rates were 87% after CQ and 35% after SP. Four children (two CQ, two SP) developed symptoms of cerebral malaria within 3 days after treatment. By day 42, failure rates (uncorrected for reinfections) had increased to 79% for CQ and 81% for SP. ETF rates were 2.5% after treatment with M and 3.9% after treatment with MA (P > 0.2). Overall uncorrected treatment failure rates at day 42 following M and MA were 23% and 21%, respectively. Chloroquine and SP are completely ineffective for the treatment of falciparum malaria in northern Myanmar. Mefloquine treatment is much more effective, but three day combination regimens with artesunate will be needed for optimum efficacy and protection against resistance

Bowel obstruction from wild bananas: a neglected health problem in Laos

We investigated the significance and risk factors of bowel obstruction caused by the consumption of wild bananas (BOWB) in Laos. Of six patients with BOWB in Luang Namtha, North Laos, five required enterotomy for phytobezoars. All had eaten wild banana (WB) seeds

Geographical distribution of selected and putatively neutral SNPs in Southeast Asian malaria parasites.

Loci targeted by directional selection are expected to show elevated geographical population structure relative to neutral loci, and a flurry of recent papers have used this rationale to search for genome regions involved in adaptation. Studies of functional mutations that are known to be under selection are particularly useful for assessing the utility of this approach. Antimalarial drug treatment regimes vary considerably between countries in Southeast Asia selecting for local adaptation at parasite loci underlying resistance. We compared the population structure revealed by 10 nonsynonymous mutations (nonsynonymous single-nucleotide polymorphisms [nsSNPs]) in four loci that are known to be involved in antimalarial drug resistance, with patterns revealed by 10 synonymous mutations (synonymous single-nucleotide polymorphisms [sSNPs]) in housekeeping genes or genes of unknown function in 755 Plasmodium falciparum infections collected from 13 populations in six Southeast Asian countries. Allele frequencies at known nsSNPs underlying resistance varied markedly between locations (F(ST) = 0.18-0.66), with the highest frequencies on the Thailand-Burma border and the lowest frequencies in neighboring Lao PDR. In contrast, we found weak but significant geographic structure (F(ST) = 0-0.14) for 8 of 10 sSNPs. Importantly, all 10 nsSNPs showed significantly higher F(ST) (P < 8 x 10(-5)) than simulated neutral expectations based on observed F(ST) values in the putatively neutral sSNPs. This result was unaffected by the methods used to estimate allele frequencies or the number of populations used in the simulations. Given that dense single-nucleotide polymorphism (SNP) maps and rapid SNP assay methods are now available for P. falciparum, comparing genetic differentiation across the genome may provide a valuable aid to identifying parasite loci underlying local adaptation to drug treatment regimes or other selective forces. However, the high proportion of polymorphic sites that appear to be under balancing selection (or linked to selected sites) in the P. falciparum genome violates the central assumption that selected sites are rare, which complicates identification of outlier loci, and suggests that caution is needed when using this approach

The Impact of Preparedness in Defying COVID-19 Pandemic Expectations in the Lower Mekong Region: A Case Study

Dire COVID-19 expectations in the Lower Mekong Region (LMR) can be understood as Cambodia, the Lao PDR, Myanmar, Thailand, and Vietnam have stared down a succession of emerging infectious disease (EID) threats from neighboring China. Predictions that the LMR would be overwhelmed by a coming COVID-19 tsunami were felt well before the spread of the COVID-19 pandemic had been declared. And yet, the LMR, excepting Myanmar, has proved surprisingly resilient in keeping COVID-19 contained to mostly sporadic cases. Cumulative case rates (per one million population) for the LMR, including or excluding Myanmar, from January 1 to October 31 2020, are 1,184 and 237, respectively. More telling are the cumulative rates of COVID-19–attributable deaths for the same period of time, 28 per million with and six without Myanmar. Graphics demonstrate a flattening of pandemic curves in the LMR, minus Myanmar, after managing temporally and spatially isolated spikes in case counts, with negligible follow-on community spread. The comparable success of the LMR in averting pandemic disaster can likely be attributed to years of preparedness investments, triggered by avian influenza A (H5N1). Capacity building initiatives applied to COVID-19 containment included virological (influenza-driven) surveillance, laboratory diagnostics, field epidemiology training, and vaccine preparation. The notable achievement of the LMR in averting COVID-19 disaster through to October 31, 2020 can likely be credited to these preparedness measure

In vivo parasitological measures of artemisinin susceptibility

Parasite clearance data from 18,699 patients with falciparum malaria treated with an artemisinin derivative in areas of low (n=14,539), moderate (n=2077), and high (n=2083) levels of malaria transmission across the world were analyzed to determine the factors that affect clearance rates and identify a simple in vivo screening measure for artemisinin resistance. The main factor affecting parasite clearance time was parasite density on admission. Clearance rates were faster in high-transmission settings and with more effective partner drugs in artemisinin-based combination treatments (ACTs). The result of the malaria blood smear on day 3 (72 h) was a good predictor of subsequent treatment failure and provides a simple screening measure for artemisinin resistance. Artemisinin resistance is highly unlikely if the proportion of patients with parasite densities of <100,000 parasites/microL given the currently recommended 3-day ACT who have a positive smear result on day 3 is <3%; that is, for n patients the observed number with a positive smear result on day 3 does not exceed (n + 60)/24

Factors associated with a measles outbreak in children admitted at Mahosot Hospital, Vientiane, Laos

<p>Abstract</p> <p>Background</p> <p>In 2002 and 2003 there were large outbreaks of measles in many provinces of Laos, including in Vientiane. We therefore conducted a study to determine risk factors associated with measles amongst children admitted at Mahosot Hospital, Vientiane.</p> <p>Methods</p> <p>A retrospective case-control study was conducted in 50 children with clinical measles who were matched by age and sex with 50 healthy children (who had never had a febrile rash) living in the same villages as the cases.</p> <p>Results</p> <p>The proportion of children with complete immunizations was significantly lower in the group with clinical measles compared to the controls [13/50 (26%) vs 34/50 (68%), <it>P </it>< 0.001). The percentage of children who had received measles vaccine at 9–23 months of age was significantly lower in the group with clinical measles compared to the healthy controls [12/50 (24%) vs 24/50 (48%), <it>P </it>= 0.01). The family educational and socio-economic status did not differ significantly (<it>P </it>> 0.05) between cases and controls.</p> <p>Conclusion</p> <p>These results emphasize the importance of intensification of measles immunization coverage in Laos. The strengthening of campaigns with large, widespread high second dose coverage is likely to be a key measure to prevent further measles outbreaks in Laos (192 words).</p