V. Evaluation of Cross-Immunity against Type 1 Dengue Fever in Human Subjects Convalescent from Subclinical Natural Japanese Encephalitis Virus Infection and Vaccinated with 17D Strain Yellow Fever Vaccine
1 Division of Parasitic Diseases, National Center for Infectious Diseases, and International Health Program Office, Centers for Disease Control and Prevention, Atlanta, Georgia; University of Malawi School of Medicine and Ministry of Health, Blantyre, Malawi
In sub-Saharan Africa, women frequently report a variety of symptoms during pregnancy, some of which indicate possible illness. Given the adverse impact of malaria in pregnancy, these events may be important for at least two reasons: it may be possible to use reported fever illness as a determinant of which women need an antimalarial intervention, and, it is possible that adverse symptoms following the antimalarial intervention may be important determinants of continued adherence to the prevention regimen. In a cohort of pregnant women enrolled at first antenatal clinic visit in rural Malawi, we evaluated reported fever, determined parasitemia, and placed the women on antimalarial regimens containing chloroquine (CQ) or mefloquine (MQ). We then systematically evaluated reported symptoms following antimalarial drug use after initial therapeutic doses and subsequent prophylactic doses, and monitored women throughout their pregnancy and at delivery. Among 4,187 enrolled women, 1,048 (25%) reported at least one febrile episode during pregnancy before their first antenatal clinic visit. Factors associated with this reported fever included low parity, enrollment in the rainy season, human immunodeficiency virus seropositivity, use of antimalarial prophylaxis before enrollment, high socioeconomic status, normal (compared to low) maternal height and weight, and literacy. Fever before the first antenatal clinic visit was reported by 24.4% of parasitemic women and 25.4% of aparasitemic women; the sensitivity and specificity of fever to identify parasitemic women was 24% and 71%, respectively. In contrast, the sensitivity and specificity of first or second pregnancy to identify parasitemic women was 71% and 57%, respectively. Among women on a CQ or MQ regimen, approximately 60% reported side effects (e.g., itching, dizziness, and gastrointestinal disturbances) after a treatment dose and approximately 25% reported side effects after a prophylactic dose; rates and types of symptoms reported were similar in the CQ and MQ groups. Few serious side effects were observed and rates of fetal loss were low and similar in the groups. Reliance on fever illness will be wholly inadequate to identify parasitemic women; therefore, our findings support existing World Health Organization recommendations that presumptive treatment and prevention regimens should be offered to all pregnant women. When resources are inadequate to offer antimalarial prophylaxis to all pregnant women, women in their first or second pregnancy may be a more appropriate target group than pregnant women with reported fever. Education regarding expected minor side effects may reduce rates of poor compliance and improve the effectiveness of the prevention effort.
Authors’ addresses: Richard W. Steketee, Epidemiology Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, STD, and TB Prevention, Centers for Disease Control and Prevention, Mailstop E-45, 1600 Clifton Road, Atlanta, GA 30333. Jack J. Wirima and Charles O. Khoromana (deceased), University of Malawi School of Medicine and Ministry of Health, Blantyre, Malawi. Laurence Slutsker, Foodborne and Diarrheal Diseases Branch, Division of Bacterial and Mycotic Diseases, Centers for Disease Control and Prevention, Mailstop A-38, Atlanta, GA 30333. David L. Heymann, Emerging and Other Communicable Diseases Programme, World Health Organization, 1211 Geneva 27, Switzerland. Joel G. Breman, Division of International Training and Research, Fogarty International Center, National Institutes of Health, Building 31, Room B2C 39, Bethesda, MD 20892-2220.