Multidrug-Resistant Plasmodium vivax Associated with Severe and Fatal Malaria

A Prospective Study in Papua, Indonesia

Emiliana Tijitra, Nicholas Anstey, Paulus Sugiarto, N WARIKAR, Enny Kenangalem, M Karyana, D LAMPAH, Ric Price

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background Multidrug-resistant Plasmodium vivax (Pv) is widespread in eastern Indonesia, and emerging elsewhere in Asia-Pacific and South America, but is generally regarded as a benign disease. The aim of the study was to review the spectrum of disease associated with malaria due to Pv and P. falciparum (Pf) in patients presenting to a hospital in Timika, southern Papua, Indonesia. Methods and Findings Data were prospectively collected from all patients attending the outpatient and inpatient departments of the only hospital in the region using systematic data forms and hospital computerised records. Between January 2004 and December 2007, clinical malaria was present in 16% (60,226/373,450) of hospital outpatients and 32% (12,171/37,800) of inpatients. Among patients admitted with slide-confirmed malaria, 64% of patients had Pf, 24% Pv, and 10.5% mixed infections. The proportion of malarial admissions attributable to Pv rose to 47% (415/ 887) in children under 1 y of age. Severe disease was present in 2,634 (22%) inpatients with malaria, with the risk greater among Pv (23% [675/2,937]) infections compared to Pf (20% [1,570/7,817]; odds ratio [OR] = 1.19 [95% confidence interval (CI) 1.08-1.32], p = 0.001), and greatest in patients with mixed infections (31% [389/1,273]); overall p < 0.0001. Severe anaemia (haemoglobin < 5 g/dl) was the major complication associated with Pv, accounting for 87% (589/675) of severe disease compared to 73% (1,144/1,570) of severe manifestations with Pf(p < 0.001). Pure Pv infection was also present in 78 patients with respiratory distress and 42 patients with coma. In total 242 (2.0%) patients with malaria died during admission: 2.2% (167/ 7,722) with Pf, 1.6% (46/2,916) with Pv, and 2.3% (29/1260) with mixed infections (p = 0.126). Conclusions In this region with established high-grade chloroquine resistance to both Pv and Pf, Pv is associated with severe and fatal malaria particularly in young children. The epidemiology of P. vivax needs to be re-examined elsewhere where chloroquine resistance is increasing.
    Original languageEnglish
    Pages (from-to)890-899
    Number of pages10
    JournalPLoS Medicine
    Volume5
    Publication statusPublished - 2008

    Fingerprint

    Plasmodium vivax
    Indonesia
    Malaria
    Prospective Studies
    Coinfection
    Inpatients
    Chloroquine
    Outpatients
    Hospital Records
    South America
    Hospital Departments
    Coma
    Anemia
    Hemoglobins
    Epidemiology
    Odds Ratio

    Cite this

    Tijitra, Emiliana ; Anstey, Nicholas ; Sugiarto, Paulus ; WARIKAR, N ; Kenangalem, Enny ; Karyana, M ; LAMPAH, D ; Price, Ric. / Multidrug-Resistant Plasmodium vivax Associated with Severe and Fatal Malaria : A Prospective Study in Papua, Indonesia. In: PLoS Medicine. 2008 ; Vol. 5. pp. 890-899.
    @article{65bda1aaa73d481785bbffbe564a69b3,
    title = "Multidrug-Resistant Plasmodium vivax Associated with Severe and Fatal Malaria: A Prospective Study in Papua, Indonesia",
    abstract = "Background Multidrug-resistant Plasmodium vivax (Pv) is widespread in eastern Indonesia, and emerging elsewhere in Asia-Pacific and South America, but is generally regarded as a benign disease. The aim of the study was to review the spectrum of disease associated with malaria due to Pv and P. falciparum (Pf) in patients presenting to a hospital in Timika, southern Papua, Indonesia. Methods and Findings Data were prospectively collected from all patients attending the outpatient and inpatient departments of the only hospital in the region using systematic data forms and hospital computerised records. Between January 2004 and December 2007, clinical malaria was present in 16{\%} (60,226/373,450) of hospital outpatients and 32{\%} (12,171/37,800) of inpatients. Among patients admitted with slide-confirmed malaria, 64{\%} of patients had Pf, 24{\%} Pv, and 10.5{\%} mixed infections. The proportion of malarial admissions attributable to Pv rose to 47{\%} (415/ 887) in children under 1 y of age. Severe disease was present in 2,634 (22{\%}) inpatients with malaria, with the risk greater among Pv (23{\%} [675/2,937]) infections compared to Pf (20{\%} [1,570/7,817]; odds ratio [OR] = 1.19 [95{\%} confidence interval (CI) 1.08-1.32], p = 0.001), and greatest in patients with mixed infections (31{\%} [389/1,273]); overall p < 0.0001. Severe anaemia (haemoglobin < 5 g/dl) was the major complication associated with Pv, accounting for 87{\%} (589/675) of severe disease compared to 73{\%} (1,144/1,570) of severe manifestations with Pf(p < 0.001). Pure Pv infection was also present in 78 patients with respiratory distress and 42 patients with coma. In total 242 (2.0{\%}) patients with malaria died during admission: 2.2{\%} (167/ 7,722) with Pf, 1.6{\%} (46/2,916) with Pv, and 2.3{\%} (29/1260) with mixed infections (p = 0.126). Conclusions In this region with established high-grade chloroquine resistance to both Pv and Pf, Pv is associated with severe and fatal malaria particularly in young children. The epidemiology of P. vivax needs to be re-examined elsewhere where chloroquine resistance is increasing.",
    keywords = "chloroquine, hemoglobin, adolescent, adult, child, coma, disease severity, fatality, female, hemoglobin blood level, hospital admission, hospital patient, human, Indonesia, infant, major clinical study, malaria, male, mixed infection, multidrug resistance, nonhuman, outpatient department, Papua New Guinea, Plasmodium falciparum, Plasmodium vivax, prospective study, respiratory distress, review, age distribution, aged, animal, article, drug effect, health survey, middle aged, morbidity, mortality, newborn, pathology, physiology, preschool child, prevalence, severity of illness index, Adolescent, Adult, Age Distribution, Aged, Aged, 80 and over, Animals, Child, Child, Preschool, Drug Resistance, Multiple, Humans, Infant, Infant, Newborn, Malaria, Middle Aged, Morbidity, Population Surveillance, Prevalence, Prospective Studies, Severity of Illness Index",
    author = "Emiliana Tijitra and Nicholas Anstey and Paulus Sugiarto and N WARIKAR and Enny Kenangalem and M Karyana and D LAMPAH and Ric Price",
    year = "2008",
    language = "English",
    volume = "5",
    pages = "890--899",
    journal = "PLoS Medicine",
    issn = "1549-1277",
    publisher = "Public Library of Science (PLoS)",

    }

    Tijitra, E, Anstey, N, Sugiarto, P, WARIKAR, N, Kenangalem, E, Karyana, M, LAMPAH, D & Price, R 2008, 'Multidrug-Resistant Plasmodium vivax Associated with Severe and Fatal Malaria: A Prospective Study in Papua, Indonesia', PLoS Medicine, vol. 5, pp. 890-899.

    Multidrug-Resistant Plasmodium vivax Associated with Severe and Fatal Malaria : A Prospective Study in Papua, Indonesia. / Tijitra, Emiliana; Anstey, Nicholas; Sugiarto, Paulus; WARIKAR, N; Kenangalem, Enny; Karyana, M; LAMPAH, D; Price, Ric.

    In: PLoS Medicine, Vol. 5, 2008, p. 890-899.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Multidrug-Resistant Plasmodium vivax Associated with Severe and Fatal Malaria

    T2 - A Prospective Study in Papua, Indonesia

    AU - Tijitra, Emiliana

    AU - Anstey, Nicholas

    AU - Sugiarto, Paulus

    AU - WARIKAR, N

    AU - Kenangalem, Enny

    AU - Karyana, M

    AU - LAMPAH, D

    AU - Price, Ric

    PY - 2008

    Y1 - 2008

    N2 - Background Multidrug-resistant Plasmodium vivax (Pv) is widespread in eastern Indonesia, and emerging elsewhere in Asia-Pacific and South America, but is generally regarded as a benign disease. The aim of the study was to review the spectrum of disease associated with malaria due to Pv and P. falciparum (Pf) in patients presenting to a hospital in Timika, southern Papua, Indonesia. Methods and Findings Data were prospectively collected from all patients attending the outpatient and inpatient departments of the only hospital in the region using systematic data forms and hospital computerised records. Between January 2004 and December 2007, clinical malaria was present in 16% (60,226/373,450) of hospital outpatients and 32% (12,171/37,800) of inpatients. Among patients admitted with slide-confirmed malaria, 64% of patients had Pf, 24% Pv, and 10.5% mixed infections. The proportion of malarial admissions attributable to Pv rose to 47% (415/ 887) in children under 1 y of age. Severe disease was present in 2,634 (22%) inpatients with malaria, with the risk greater among Pv (23% [675/2,937]) infections compared to Pf (20% [1,570/7,817]; odds ratio [OR] = 1.19 [95% confidence interval (CI) 1.08-1.32], p = 0.001), and greatest in patients with mixed infections (31% [389/1,273]); overall p < 0.0001. Severe anaemia (haemoglobin < 5 g/dl) was the major complication associated with Pv, accounting for 87% (589/675) of severe disease compared to 73% (1,144/1,570) of severe manifestations with Pf(p < 0.001). Pure Pv infection was also present in 78 patients with respiratory distress and 42 patients with coma. In total 242 (2.0%) patients with malaria died during admission: 2.2% (167/ 7,722) with Pf, 1.6% (46/2,916) with Pv, and 2.3% (29/1260) with mixed infections (p = 0.126). Conclusions In this region with established high-grade chloroquine resistance to both Pv and Pf, Pv is associated with severe and fatal malaria particularly in young children. The epidemiology of P. vivax needs to be re-examined elsewhere where chloroquine resistance is increasing.

    AB - Background Multidrug-resistant Plasmodium vivax (Pv) is widespread in eastern Indonesia, and emerging elsewhere in Asia-Pacific and South America, but is generally regarded as a benign disease. The aim of the study was to review the spectrum of disease associated with malaria due to Pv and P. falciparum (Pf) in patients presenting to a hospital in Timika, southern Papua, Indonesia. Methods and Findings Data were prospectively collected from all patients attending the outpatient and inpatient departments of the only hospital in the region using systematic data forms and hospital computerised records. Between January 2004 and December 2007, clinical malaria was present in 16% (60,226/373,450) of hospital outpatients and 32% (12,171/37,800) of inpatients. Among patients admitted with slide-confirmed malaria, 64% of patients had Pf, 24% Pv, and 10.5% mixed infections. The proportion of malarial admissions attributable to Pv rose to 47% (415/ 887) in children under 1 y of age. Severe disease was present in 2,634 (22%) inpatients with malaria, with the risk greater among Pv (23% [675/2,937]) infections compared to Pf (20% [1,570/7,817]; odds ratio [OR] = 1.19 [95% confidence interval (CI) 1.08-1.32], p = 0.001), and greatest in patients with mixed infections (31% [389/1,273]); overall p < 0.0001. Severe anaemia (haemoglobin < 5 g/dl) was the major complication associated with Pv, accounting for 87% (589/675) of severe disease compared to 73% (1,144/1,570) of severe manifestations with Pf(p < 0.001). Pure Pv infection was also present in 78 patients with respiratory distress and 42 patients with coma. In total 242 (2.0%) patients with malaria died during admission: 2.2% (167/ 7,722) with Pf, 1.6% (46/2,916) with Pv, and 2.3% (29/1260) with mixed infections (p = 0.126). Conclusions In this region with established high-grade chloroquine resistance to both Pv and Pf, Pv is associated with severe and fatal malaria particularly in young children. The epidemiology of P. vivax needs to be re-examined elsewhere where chloroquine resistance is increasing.

    KW - chloroquine

    KW - hemoglobin

    KW - adolescent

    KW - adult

    KW - child

    KW - coma

    KW - disease severity

    KW - fatality

    KW - female

    KW - hemoglobin blood level

    KW - hospital admission

    KW - hospital patient

    KW - human

    KW - Indonesia

    KW - infant

    KW - major clinical study

    KW - malaria

    KW - male

    KW - mixed infection

    KW - multidrug resistance

    KW - nonhuman

    KW - outpatient department

    KW - Papua New Guinea

    KW - Plasmodium falciparum

    KW - Plasmodium vivax

    KW - prospective study

    KW - respiratory distress

    KW - review

    KW - age distribution

    KW - aged

    KW - animal

    KW - article

    KW - drug effect

    KW - health survey

    KW - middle aged

    KW - morbidity

    KW - mortality

    KW - newborn

    KW - pathology

    KW - physiology

    KW - preschool child

    KW - prevalence

    KW - severity of illness index

    KW - Adolescent

    KW - Adult

    KW - Age Distribution

    KW - Aged

    KW - Aged, 80 and over

    KW - Animals

    KW - Child

    KW - Child, Preschool

    KW - Drug Resistance, Multiple

    KW - Humans

    KW - Infant

    KW - Infant, Newborn

    KW - Malaria

    KW - Middle Aged

    KW - Morbidity

    KW - Population Surveillance

    KW - Prevalence

    KW - Prospective Studies

    KW - Severity of Illness Index

    UR - http://www.scopus.com/inward/record.url?scp=46349102897&partnerID=8YFLogxK

    M3 - Article

    VL - 5

    SP - 890

    EP - 899

    JO - PLoS Medicine

    JF - PLoS Medicine

    SN - 1549-1277

    ER -