Arthropod borne disease: the leading cause of fever in pregnancy on the Thai-Burmese border

Rose McGready, Elizabeth A Ashley, Vanaporn Wuthiekanun, Saw Oo Tan, Mupawjay Pimanpanarak, Samuel Jacher Viladpai-Nguen, Wilarat Jesadapanpong, Stuart D Blacksell, Sharon J Peacock, Daniel H Paris, Nicholas P Day, Pratap Singhasivanon, Nicholas J White, François Nosten, Rose McGready, Elizabeth A Ashley, Vanaporn Wuthiekanun, Saw Oo Tan, Mupawjay Pimanpanarak, Samuel Jacher Viladpai-Nguen, Wilarat Jesadapanpong, Stuart D Blacksell, Sharon J Peacock, Daniel H Paris, Nicholas P Day, Pratap Singhasivanon, Nicholas J White, François Nosten

Abstract

Background: Fever in pregnancy is dangerous for both mother and foetus. In the 1980's malaria was the leading cause of death in pregnant women in refugee camps on the Thai-Burmese border. Artemisinin combination therapy has significantly reduced the incidence of malaria in the population. The remaining causes of fever in pregnancy are not well documented.

Methodology: Pregnant women attending antenatal care, where weekly screening for malaria is routine, were invited to have a comprehensive clinical and laboratory screen if they had fever. Women were admitted to hospital, treated and followed up weekly until delivery. A convalescent serum was collected on day 21. Delivery outcomes were recorded.

Principal findings: Febrile episodes (n = 438) occurred in 5.0% (409/8,117) of pregnant women attending antenatal clinics from 7-Jan-2004 to 17-May-2006. The main cause was malaria in 55.5% (227/409). A cohort of 203 (49.6% of 409) women had detailed fever investigations and follow up. Arthropod-borne (malaria, rickettsial infections, and dengue) and zoonotic disease (leptospirosis) accounted for nearly half of all febrile illnesses, 47.3% (96/203). Coinfection was observed in 3.9% (8/203) of women, mostly malaria and rickettsia. Pyelonephritis, 19.7% (40/203), was also a common cause of fever. Once malaria, pyelonephritis and acute respiratory illness are excluded by microscopy and/or clinical findings, one-third of the remaining febrile infections will be caused by rickettsia or leptospirosis. Scrub and murine typhus were associated with poor pregnancy outcomes including stillbirth and low birth weight. One woman died (no positive laboratory tests).

Conclusion/significance: Malaria remains the leading cause of fever in pregnancy on the Thai-Burmese border. Scrub and murine typhus were also important causes of fever associated with poor pregnancy outcomes. Febrile pregnant women on the Thai-Burmese border who do not have malaria, pyelonephritis or respiratory tract infection should be treated with azithromycin, effective for typhus and leptospirosis.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1. Map of the study area…
Figure 1. Map of the study area including Maela Refugee camp and migrant clinic sites.
Figure 2. Patient flow.
Figure 2. Patient flow.
Figure 3. Complete blood count results (mean…
Figure 3. Complete blood count results (mean and 95% CI) by diagnostic group.
WBC – white blood cells, PLT – platelet, Mal. – malaria. Number at base of platelet column is the sample size for each diagnostic group.

References

    1. WHO. Geneva: 1999. Reduction of maternal mortality: a joint WHO/UNFPA/UNICEF/World Bank Statement.
    1. Nosten F, ter Kuile F, Maelankirri L, Decludt B, White NJ. Malaria during pregnancy in an area of unstable endemicity. Trans R Soc Trop Med Hyg. 1991;85:424–429.
    1. Brockman A, Price RN, van Vugt M, Heppner DG, Walsh D, et al. Plasmodium falciparum antimalarial drug susceptibility on the north- western border of Thailand during five years of extensive use of artesunate-mefloquine. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2000;94:537–544.
    1. Luxemburger C, McGready R, Kham A, Morison L, Cho T, et al. Effects of malaria during pregnancy on infant mortality in an area of low malaria transmission. Am J Epidemiol. 2001;154:459–465.
    1. Plewes K, Lee T, Kajeechewa L, Thwin MM, Lee SJ, et al. Low seroprevalence of HIV and syphilis in pregnant women in refugee camps on the Thai-Burma border. Int J STD AIDS. 2008;19:833–837.
    1. McGready R, Tan SO, Ashley EA, Pimanpanarak M, Viladpai-Nguen J, et al. A randomised controlled trial of artemether-lumefantrine versus artesunate for uncomplicated plasmodium falciparum treatment in pregnancy. PLoS Med. 2008;5:e253.
    1. WHO. Severe and complicated malaria. World Health Organization, Division of Control of Tropical Diseases. Trans R Soc Trop Med Hyg. 1990;84:1–65.
    1. Coleman RE, Sangkasuwan V, Suwanabun N, Eamsila C, Mungviriya S, et al. Comparative evaluation of selected diagnostic assays for the detection of IgG and IgM antibody to Orientia tsutsugamushi in Thailand. Am J Trop Med Hyg. 2002;67:497–503.
    1. Robinson DM, Brown G, Gan E, Huxsoll DL. Adaptation of a microimmunofluorescence test to the study of human Rickettsia tsutsugamuskh antibody. Am J Trop Med Hyg. 1976;25:900–905.
    1. Luksameetanasan R, Blacksell SD, Kalambaheti T, Wuthiekanun V, Chierakul W, et al. Patient and sample-related factors that effect the success of in vitro isolation of Orientia tsutsugamushi. Southeast Asian J Trop Med Public Health. 2007;38:91–96.
    1. Jiang J, Chan TC, Temenak JJ, Dasch GA, Ching WM, et al. Development of a quantitative real-time polymerase chain reaction assay specific for Orientia tsutsugamushi. Am J Trop Med Hyg. 2004;70:351–356.
    1. Paris DH, Blacksell SD, Stenos J, Graves SR, Unsworth NB, et al. Real-time multiplex PCR assay for detection and differentiation of rickettsiae and orientiae. Trans R Soc Trop Med Hyg. 2008;102:186–193.
    1. Paris DH, Aukkanit N, Jenjaroen K, Blacksell SD, Day NP. A highly sensitive quantitative real-time PCR assay based on the groEL gene of contemporary Thai strains of Orientia tsutsugamushi. Clin Microbiol Infect. 2009;15:488–495.
    1. Henry KM, Jiang J, Rozmajzl PJ, Azad AF, Macaluso KR, et al. Development of quantitative real-time PCR assays to detect Rickettsia typhi and Rickettsia felis, the causative agents of murine typhus and flea-borne spotted fever. Mol Cell Probes. 2007;21:17–23.
    1. Faine S, Adler B, Bolin C, Perolat P. Melbourne, Australia: MedSci; 1999. Leptospires and Leptospirosis.
    1. Palmer MF, Zochowski WJ. Survival of leptospires in commercial blood culture systems revisited. J Clin Pathol. 2000;53:713–714.
    1. Blacksell SD, Mammen MP, Jr, Thongpaseuth S, Gibbons RV, Jarman RG, et al. Evaluation of the Panbio dengue virus nonstructural 1 antigen detection and immunoglobulin M antibody enzyme-linked immunosorbent assays for the diagnosis of acute dengue infections in Laos. Diagn Microbiol Infect Dis. 2008;60:43–49.
    1. Dubowitz LM, Dubowitz V, Goldberg C. Clinical assessment of gestational age in the newborn infant. Journal of Pediatrics. 1970;77:1–10.
    1. Carrara VI, Zwang J, Ashley EA, Price RN, Stepniewska K, et al. Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. PLoS One. 2009;4:e4551.
    1. Nosten F, Luxemburger C, Kyle DE, Ballou WR, Wittes J, et al. Randomised double-blind placebo-controlled trial of SPf66 malaria vaccine in children in northwestern Thailand. Shoklo SPf66 Malaria Vaccine Trial Group. Lancet. 1996;348:701–707.
    1. Ellis RD, Fukuda MM, McDaniel P, Welch K, Nisalak A, et al. Causes of fever in adults on the Thai-Myanmar border. Am J Trop Med Hyg. 2006;74:108–113.
    1. Parola P, Miller RS, McDaniel P, Telford SR, 3rd, Rolain JM, et al. Emerging rickettsioses of the Thai-Myanmar border. Emerg Infect Dis. 2003;9:592–595.
    1. Perkins MD, Bell DR. Working without a blindfold: the critical role of diagnostics in malaria control. Malar J. 2008;7(Suppl 1):S5.
    1. Choi EK, Pai H. Azithromycin therapy for scrub typhus during pregnancy. Clin Infect Dis. 1998;27:1538–1539.
    1. Watt G, Kantipong P, Jongsakul K, Watcharapichat P, Phulsuksombati D, et al. Doxycycline and rifampicin for mild scrub-typhus infections in northern Thailand: a randomised trial. Lancet. 2000;356:1057–1061.
    1. Watt G, Chouriyagune C, Ruangweerayud R, Watcharapichat P, Phulsuksombati D, et al. Scrub typhus infections poorly responsive to antibiotics in northern Thailand. Lancet. 1996;348:86–89.
    1. Phimda K, Hoontrakul S, Suttinont C, Chareonwat S, Losuwanaluk K, et al. Doxycycline versus azithromycin for treatment of leptospirosis and scrub typhus. Antimicrob Agents Chemother. 2007;51:3259–3263.
    1. Murakami M, Deguchi H, Masuzaki H, Yamabe T. [Clinical studies on ceftriaxone in the field of obstetrics and gynecology]. Jpn J Antibiot. 1985;38:13–17.
    1. Popovic J, Grujic Z, Sabo A. Influence of pregnancy on ceftriaxone, cefazolin and gentamicin pharmacokinetics in caesarean vs. non-pregnant sectioned women. J Clin Pharm Ther. 2007;32:595–602.
    1. Tessari S, Michelon E. [Experience with ceftriaxone in the antimicrobial chemoprophylaxis in obstetric-gynecologic surgery]. Minerva Ginecol. 1992;44:451–455.
    1. de Pont AC, Wolf H, van Delden OM, de Reijke TM. [Pyelonephritis during pregnancy: a threat to mother and child]. Ned Tijdschr Geneeskd. 2007;151:1813–1816.
    1. Sirisanthana V, Puthanakit T, Sirisanthana T. Epidemiologic, clinical and laboratory features of scrub typhus in thirty Thai children. Pediatr Infect Dis J. 2003;22:341–345.
    1. Dolan G, ter Kuile FO, Jacoutot V, White NJ, Luxemburger C, et al. Bed nets for the prevention of malaria and anaemia in pregnancy. Trans R Soc Trop Med Hyg. 1993;87:620–626.
    1. Watt G, Kantipong P, Jongsakul K, Watcharapichat P, Phulsuksombati D. Azithromycin activities against Orientia tsutsugamushi strains isolated in cases of scrub typhus in Northern Thailand. Antimicrob Agents Chemother. 1999;43:2817–2818.
    1. Phupong V, Srettakraikul K. Scrub typhus during pregnancy: a case report and review of the literature. Southeast Asian J Trop Med Public Health. 2004;35:358–360.
    1. Mathai E, Rolain JM, Verghese L, Mathai M, Jasper P, et al. Case reports: scrub typhus during pregnancy in India. Trans R Soc Trop Med Hyg. 2003;97:570–572.
    1. Koliou M, Christoforou C, Soteriades ES. Murine typhus in pregnancy: a case report from Cyprus. Scand J Infect Dis. 2007;39:625–628.
    1. Kim YS, Lee HJ, Chang M, Son SK, Rhee YE, et al. Scrub typhus during pregnancy and its treatment: a case series and review of the literature. Am J Trop Med Hyg. 2006;75:955–959.
    1. Kiereini EM. [The consequences of AIDS for women and children in Africa]. Tvz. 1991:382–385.
    1. Ziraba AK, Madise N, Mills S, Kyobutungi C, Ezeh A. Maternal mortality in the informal settlements of Nairobi city: what do we know? Reprod Health. 2009;6:6.

Source: PubMed

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