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Severe disease in children hospitalized with a diagnosis of Plasmodium vivax in south-eastern Pakistan.

ABSTRACT: Infection by Plasmodium vivax has been considered rarely threatening to life, but recent studies challenge this notion. This study documented the frequency and character of severe illness in paediatric patients admitted to a hospital in south-eastern Pakistan with a laboratory-confirmed diagnosis of vivax malaria.An observational study of all 180 paediatric patients admitted with any diagnosis of malaria during 2010 was conducted: 128 P. vivax; 48 Plasmodium falciparum; and four mixed infections of these species. Patients were classified as having severe illness with any of the following indicators: Glascow coma scale <11; ?2 convulsions; haemoglobin <5g/dL; thrombocytes <50,000/mL; blood glucose <45mg%; >70 breaths/min; or intravenous anti-malarial therapy. Additionally, 64 patients with a diagnosis of vivax malaria were treated during 2009, and the 21 of these having severe illness were included in analyses of the frequency and character of severe illness with that diagnosis.During 2010, 39 (31%) or 37 (77%) patients with a diagnosis of P. vivax or P. falciparum were classified as having severe disease. Including the 2009 records of 64 patients having vivax malaria, a total of 60 (31%) patients with severe illness and a diagnosis of P. vivax were available. Altered mental status (Glascow coma scale score <11; or ?2 convulsions) dominated at 54% of the 83 indicators of severe illness manifest among the patients with vivax malaria, as was true among the 37 children with a diagnosis of falciparum malaria and being severely ill; 58% of the 72 indicators of severe disease documented among them. No statistically significant difference appeared in frequencies of any other severe disease indicators between patients diagnosed with vivax or falciparum malaria. Despite such similarities, a diagnosis of falciparum malaria nonetheless came with 3.8-fold (95% CI = 1.8-8.1) higher risk of presenting with severe illness, and 8.0-fold (95% CI = 2.1-31) greater likelihood of presenting with three or more severe disease indicators. Two patients did not survive hospitalization, one each with a diagnosis of falciparum or vivax malaria.Vivax malaria caused a substantial burden of potentially life-threatening morbidity on a paediatric ward in a hospital in south-eastern Pakistan.

SUBMITTER: Shaikh S

PROVIDER: S-EPMC3480837 | biostudies-other | 2012 May

REPOSITORIES: biostudies-other

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Severe disease in children hospitalized with a diagnosis of Plasmodium vivax in south-eastern Pakistan.

Shaikh Salma S Memon Hafeezullah H Iohano Bhagchand B Shaikh Amna A Ahmed Imran I Baird J Kevin JK

Malaria journal 20120502

<h4>Background</h4>Infection by Plasmodium vivax has been considered rarely threatening to life, but recent studies challenge this notion. This study documented the frequency and character of severe illness in paediatric patients admitted to a hospital in south-eastern Pakistan with a laboratory-confirmed diagnosis of vivax malaria.<h4>Methods</h4>An observational study of all 180 paediatric patients admitted with any diagnosis of malaria during 2010 was conducted: 128 P. vivax; 48 Plasmodium fa ...[more]

PMID: 22551061

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Project description:BackgroundBetter understanding of the distribution of Plasmodium vivax and its risk factors could be used to prevent and control malaria infection. Therefore, the aim of this study was to characterize the distribution and risk factors of P. vivax, and to compare them with Plasmodium falciparum occurrence in south-central Ethiopia.MethodsA cohort of 34,548 individuals were followed for 121 weeks between 2014 and 2016 as part of larger cluster randomized controlled trial to evaluate the effect of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) on malaria prevention in Ethiopia. Weekly home visit (active search) and patient self- report to health post (passive search) between the weekly home visits were used to register malaria cases. A blood sample was collected by finger prick and malaria was diagnosed using rapid diagnostic test (RDT). Generalized estimating equation (GEE) Poisson model that accounts for repeated measure of malaria episodes was applied to assess the risk factors of P. vivax episode.ResultsThe overall incidence rate of P. vivax was 7.4 episodes per 1000 person-years of observation. The study showed households closer to the lake Zeway and Bulbula river (potential mosquito breeding sites) were more at risk of P. vivax infection (incidence rate ratio (IRR): 1.33; 95% CI = 1.23-1.45). Furthermore, the age group under 5 years (IRR: 1.40, 95% CI = 1.10-1.79), the age group 5-14 years (IRR: 1.27, 95% CI = 1.03-1.57), households with less educated household head (IRR: 1.63, 95% CI = 1.10-2.44) and house roof made of thatch/leaf (IRR: 1.35, 95% CI = 1.11-1.65) were at higher risk for P. vivax. Similar explanatory variables such as distance from the breeding sites, age group (under 5 years but not 5-14 years old), educational status and type of housing were also found to be the predictors of P. falciparum incidence.ConclusionHouseholds living closer to a mosquito breeding site, age group under 15 years, less educated household heads and thatch/leaf roof housing were the risk factor for P. vivax. The result of this study can be used for tailored interventions for malaria control and prevention by prioritizing those living close to potential mosquito breeding site, enhancing bed net use of children less than 15 years of age, and improving housing.

Project description:BackgroundPlasmodium vivax is the second most important cause of human malaria worldwide, and accounts for the majority of malaria cases in South America. A high-quality reference genome exists for Papua Indonesia (PvP01) and Thailand (PvW1), but is lacking for South America. A reference genome specifically for South America would be beneficial though, as P. vivax is a genetically diverse parasite with geographical clustering.ResultsThis study presents a new high-quality assembly of a South American P. vivax isolate, referred to as PvPAM (P. vivax Peruvian AMazon). The genome was obtained from a low input patient sample from the Peruvian Amazon and sequenced using PacBio technology, resulting in a highly complete assembly with 6497 functional genes. Telomeric ends were present in 17 out of 28 chromosomal ends, and additional (sub)telomeric regions are present in 12 unassigned contigs. A comparison of multigene families between PvPAM and the PvP01 genome revealed remarkable variation in vir genes, and the presence of merozoite surface proteins (MSP) 3.6 and 3.7. Three dhfr and dhps drug resistance associated mutations are present in PvPAM, similar to those found in other Peruvian isolates. Mapping of publicly available South American whole genome sequencing (WGS) data to PvPAM resulted in significantly fewer variants and truncated reads compared to the use of PvP01 or PvW1 as reference genomes. To minimize the number of core genome variants in non-South American samples, PvW1 is most suited for Southeast Asian isolates, both PvPAM and PvW1 are suited for South Asian isolates, and PvPAM is recommended for African isolates. Interestingly, non-South American samples still contained the least subtelomeric variants when mapped to PvPAM, indicating high quality of the PvPAM subtelomeric regions.ConclusionsOur findings show that the PvPAM reference genome more accurately represents South American P. vivax isolates in comparison to PvP01 and PvW1. In addition, PvPAM has a high level of completeness, and contains a similar number of annotated genes as PvP01 or PvW1. The PvPAM genome therefore will be a valuable resource to improve future genomic analyses on P. vivax isolates from the South American continent.

Project description:Plasmodium vivax is the most prevalent malaria species in Pakistan, with a distribution that coincides with Plasmodium falciparum in many parts of the country. Both species are likely exposed to drug pressure from a number of anti-malarials including chloroquine, sulphadoxine-pyrimethamine (SP), and artemisinin combination therapy, yet little is known regarding the effects of drug pressure on parasite genes associated with drug resistance. The aims of this study were to determine the prevalence of polymorphisms in the SP resistance-associated genes pvdhfr, pvdhps and chloroquine resistance-associated gene pvmdr1 in P. vivax isolates collected from across the country.In 2011, 801 microscopically confirmed malaria-parasite positive filter paper blood samples were collected at 14 sites representing four provinces and the capital city of Islamabad. Species-specific polymerase chain reaction (PCR) was used to identify human Plasmodium species infection. PCR-positive P. vivax isolates were subjected to sequencing of pvdhfr, pvdhps and pvmdr1 and to real-time PCR analysis to assess pvmdr1 copy number variation.Of the 801 samples, 536 were determined to be P. vivax, 128 were P. falciparum, 43 were mixed vivax/falciparum infections and 94 were PCR-negative for Plasmodium infection. Of PCR-positive P. vivax samples, 372 were selected for sequence analysis. Seventy-six of the isolates (23%) were double mutant at positions S58R and S117N in pvdhfr. Additionally, two mutations at positions N50I and S93H were observed in 55 (15%) and 24 (7%) of samples, respectively. Three 18 base pair insertion-deletions (indels) were observed in pvdhfr, with two insertions at different nucleotide positions in 36 isolates and deletions in 10. Ninety-two percent of samples contained the pvdhps (S382/A383G/K512/A553/V585) SAKAV wild type haplotype. For pvmdr1, all isolates were wild type at position Y976F and 335 (98%) carried the mutation at codon F1076L. All isolates harboured single copies of the pvmdr1 gene.The prevalence of mutations associated with SP resistance in P. vivax is low in Pakistan. The high prevalence of P. vivax mutant pvmdr1 codon F1076L indicates that efficacy of chloroquine plus primaquine could be in danger of being compromised, but further studies are required to assess the clinical relevance of this observation. These findings will serve as a baseline for further monitoring of drug-resistant P. vivax malaria in Pakistan.

Dataset Information

Severe disease in children hospitalized with a diagnosis of Plasmodium vivax in south-eastern Pakistan.

Publications

Severe disease in children hospitalized with a diagnosis of Plasmodium vivax in south-eastern Pakistan.

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