Evaluation of Plasmodium vivax malaria recurrence in Brazil.

BACKGROUND: Control of vivax malaria in endemic areas requires management of recurrence. The Brazilian National Malaria Surveillance System (SIVEP-Malária) records every case of malaria in Brazil, but is not designed to differentiate between primary and recurrent infections. The aim of this study was to explore whether the information provided by SIVEP-Malária could be used to identify Plasmodium vivax recurrences, its risk factors and evaluate the effectiveness of short course primaquine (7-9 days: total dose 3-4.2 mg/kg) in preventing relapses. METHODS: In this observational retrospective cohort study, data matching of SIVEP-Malária records was undertaken using bloom filters to identify potential recurrences defined as microscopically-confirmed P. vivax episodes from the same individual occurring within a year. Generalized Estimation Equation (GEE) models were used to determine predictors of recurrence. Extended Cox-based conditional Prentice-Williams-Peterson models (PWP) models were used to evaluate time to recurrence. RESULTS: Between June 1, 2014 and May 31, 2015, 26,295 episodes fulfilled the criteria of potential recurrence among 154,970 reported malaria episodes. Age ≤ 3 years, being male, literate, not-indigenous and having domestic working activities were identified as risk factors for recurrence. There was no difference in time to recurrence or recurrence frequency between patients treated with 14-day or 7-9 day primaquine regimens (HR = 1.02, 0.96-1.09) and RR = 0.97 (0.90-1.04), respectively. The use of chloroquine alone was associated with a 1.43 (1.29-1.58, p < 0.0001) increased risk of P. vivax recurrence compared to patients who used chloroquine combined with short-course primaquine, the Brazilian standard of care. This was RR = 2.06 (1.48-2.86, p < 0.0001), RR = 1.90 (1.60-2.25, p = 0.0001) and RR = 1.14 (1.00-1.29, p = 0.05) for recurrences occurring between 3-28, 29-60 and > 60 days, respectively. PWP models showed that the time to recurrence was longer in recipients of both primaquine and artemisinin-based combination therapy (ACT) compared to patients treated with chloroquine alone or with concomitant primaquine, HR = 2.2 (1.62-2.99, p < 0.0001), HR = 1.27 (0.97-1.66, p = 0.08), respectively. CONCLUSION: Short course primaquine was as effective as 14-day regimens and associated with a halving of the risk and delay in time to recurrence of P. vivax infections in comparison to chloroquine alone. The study demonstrates the feasibility of using record linkage on routine surveillance data to identify potential P. vivax recurrences, associated risk factors and impact of treatment.

Impact of sustained use of insecticide-treated bednets on malaria vector species distribution and culicine mosquitoes.

Insecticide-treated bednets (ITNs) significantly reduce malaria vector populations. Susceptibility to ITNs differs by vector species, and culicine mosquitoes have not been shown to be significantly affected by the use of ITNs. We examined the impact of 2-4 yr of ITN use on malaria vector species distribution and culicine mosquitoes. Routine entomological surveillance was conducted in adjacent areas with and without ITNs from November 1999 to January 2002. Use of ITNs reduced the proportion of Anopheles gambiae Giles relative to Anopheles arabiensis Giles. The number of culicines per house was significantly lower in the ITN area than in the neighboring area. Changes in the An. gambiae sibling species distribution may help to explain apparent mosquito behavioral changes attributed to ITNs. Reductions in culicines by ITNs may have implications for community perceptions of ITN effectiveness and for control of other diseases such as lymphatic filariasis.

Insecticide-treated nets for preventing malaria in pregnancy.

BACKGROUND: Malaria in pregnancy is associated with adverse consequences for mother and fetus. Protection with insecticide-treated nets (ITNs) during pregnancy is widely advocated, but evidence of their benefit has been inconsistent. OBJECTIVES: To compare the impact of ITNs with no nets or untreated nets on preventing malaria in pregnancy. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (January 2006), CENTRAL (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to January 2006), EMBASE (1974 to January 2006), LILACS (1982 to January 2006), and reference lists. We also contacted researchers working in the field. SELECTION CRITERIA: Individual and cluster randomized controlled trials of ITNs in pregnant women. DATA COLLECTION AND ANALYSIS: Three authors independently assessed trials for methodological quality and extracted data. Data were combined using the generic inverse variance method. MAIN RESULTS: Six randomized controlled trials were identified, five of which met the inclusion criteria: four trials from sub-Saharan Africa compared ITNs with no nets, and one trial from Asia compared ITNs with untreated nets. Two trials randomized individual women and three trials randomized communities. In Africa, ITNs, compared with no nets, reduced placental malaria in all pregnancies (relative risk (RR) 0.79, 95% confidence interval (CI) 0.63 to 0.98). They also reduced low birthweight (RR 0.77, 95% CI 0.61 to 0.98) and stillbirths/abortions in the first to fourth pregnancy (RR 0.67, 95% CI 0.47 to 0.97), but not in women with more than four previous pregnancies. For anaemia and clinical malaria, results tended to favour ITNs, but the effects were not significant. In Thailand, one trial randomizing individuals to ITNs or untreated nets showed a significant reduction in anaemia and stillbirths/abortions in all pregnancies but not for clinical malaria or low birthweight. AUTHORS' CONCLUSIONS: ITNs have a beneficial impact on pregnancy outcome in malaria-endemic regions of Africa when used by communities or by individual women. No further trials of ITNs in pregnancy are required in sub-Saharan Africa. Further evaluation of the potential impact of ITNs is required in areas with less intense and Plasmodium vivax transmission in Asia and Latin America.

Prevalence and severity of malnutrition and age at menarche; cross-sectional studies in adolescent schoolgirls in western Kenya.

OBJECTIVE: Nutritional status is an important marker of overall health and linear growth retardation has serious long-term physiological and economic consequences. Approximately 35 and 29% of preschool children in sub-Saharan Africa are stunted and underweight, respectively. There is relatively little information available about the nutritional status in adolescents, the age group with the highest growth velocity after infancy. We conducted a series of cross-sectional surveys to determine the prevalence and main risk groups for malnutrition and to describe the associations between age, sexual maturation and nutritional status in adolescent schoolgirls in western Kenya. DESIGN: Three cross-sectional surveys; one in Mumias, using random sampling in all schools, and two surveys in Asembo, using a multi-stage random sample design. SETTING: Public primary schools in two different rural malaria endemic areas in western Kenya with high levels of malnutrition in preschool children. SUBJECTS: In all, 928 randomly selected adolescent schoolgirls aged 12-18 y. RESULTS: Overall prevalence of stunting and thinness was 12.1 and 15.6%, respectively. Of the total, 2% were severely stunted. Menarche and start of puberty were delayed by approximately 1.5-2 y compared to a US reference population. The prevalence of stunting and thinness decreased with age and mean height for age z-scores converged towards the median of the US reference curve. Girls who had not yet started menstruating were more likely to be stunted than the girls of the same age who were post-menarche. CONCLUSIONS: Stunting and thinness are common in young adolescent schoolgirls in these poor rural settings in western Kenya, but the prevalence decreases with age, providing observational support that children catch up on incomplete growth attained earlier in life due to a maturational delay of 1.5-2 y allowing prolonged growth.

Comparison of capillary whole blood, venous whole blood, and plasma concentrations of mefloquine, halofantrine, and desbutyl-halofantrine measured by high-performance liquid chromatography.

Whole blood mefloquine, halofantrine, and desbutyl-halofantrine concentrations were measured by high-performance liquid chromatography in capillary blood, venous blood, and venous plasma samples from patients along the Thai/Burmese border with falciparum malaria who were treated with either mefloquine (25 mg/kg) or halofantrine (24 mg/kg or 72 mg/kg). The limits of detection for mefloquine, halofantrine, and desbutyl-halofantrine were 50, 15, and 10 ng/ml, respectively, with 200 microliters whole blood samples. There was a good linear correlation (r > 0.9) between capillary and venous blood and between whole blood and plasma for all three compounds. Mefloquine concentrations in venous and capillary blood were very similar (mean ratio 1.02, 95% confidence intervals [CI] 0.95-1.09, n = 60), but were 1.15 times higher (95% CI 1.03-1.29) in whole blood than in plasma (n = 22). The halofantrine and desbutyl-halofantrine concentrations were 1.27 (1.12-1.45, n = 23) and 1.34 (1.16-1.55, n = 24) times higher in venous compared to capillary blood, while halofantrine but not desbutyl-halofantrine concentrations were lower in whole blood than in plasma (mean ratios: halofantrine: 0.83 [0.72, 0.94], n = 39 and desbutyl-halofantrine: 1.05 [0.96-1.15], n = 41). Measurement of mefloquine, halofantrine, or desbutyl-halofantrine in capillary blood is an accurate and practical alternative to venous blood sampling, and is particularly useful for sampling with children, and under field conditions when technical facilities are limited.

Effect of Plasmodium falciparum parasitemia density on hemoglobin concentrations among full-term, normal birth weight children in western Kenya, IV. The Asembo Bay Cohort Project.

The relative importance of acute high-density versus persistent low-density Plasmodium falciparum parasitemia in contributing to the public health problem of malarial anemia remains unclear. The Asembo Bay Cohort Project in western Kenya collected monthly hemoglobin (Hb) and parasitologic measurements and biweekly assessments of antimalarial drug use among 942 singleton live births between 1992 and 1996. A mixed-model analysis appropriate for repeated measures data was used to study how time-varying parasitemia and antimalarial drug exposures influenced mean Hb profiles. Incidence of World Health Organization-defined severe malarial anemia was 28.1 per 1,000 person-years. Among children aged less than 24 months, concurrent parasitemia was significantly associated with lower mean Hb, especially when compared to children with no concurrent parasitemia. Increased densities of the 90-day history of parasitemia preceding Hb measurement was more strongly associated with mean Hb levels than concurrent parasitemia density. While the highest quartile of 90-day parasitemia history was associated with lowest mean Hb levels, children in the lowest 90-day exposure quartile still experienced significantly lower Hb levels when compared to children who remained parasitemia-free for the same 90-day period. The results highlight the importance of collecting and analyzing longitudinal Hb and parasitologic data when studying the natural history of malarial anemia.

Human immunodeficiency virus seropositivity and malaria as risk factors for third-trimester anemia in asymptomatic pregnant women in western Kenya.

To assess risk factors for anemia in late pregnancy, we studied healthy pregnant women with a singleton uncomplicated pregnancy of > or = 32 weeks attending the prenatal clinic in the Provincial Hospital in Kisumu, Kenya. Between June 1996 and December 1998, 4,608 pregnant women had a blood sample collected for hemoglobin (Hb) measurement, malaria smear, and testing for human immunodeficiency virus (HIV). The mean +/- standard deviation of Hb was 9.58 +/- 1.8 g/dL; 21% had malaria in their blood; and 25% of the women were HIV seropositive. Plasmodium falciparum parasitemia was more common among HIV-seropositive women in all gravidities compared with HIV-seronegative women (risk ratio, 1.71; 95% confidence interval, 1.53-1.92). In a multivariate analysis, for primi- and secundigravidae women, the factors malaria, belonging to the Luo tribe, and HIV seropositivity were significantly associated with any anemia (Hb < 11 g/dL), and HIV seropositivity and documented fever were associated with severe anemia (Hb < 7 g/dL). In women of higher gravidities, HIV seropositivity was the only statistically significant factor associated with any anemia or with severe anemia. Asymptomatic HIV seropositivity is an important risk factor to be considered in the differential diagnosis of maternal anemia, independent of P. falciparum parasitemia.

All-cause mortality among young children in western Kenya. VI: the Asembo Bay Cohort Project.

Although all-cause mortality has been used as an indicator of the health status of childhood populations, such data are sparse for most rural areas of sub-Saharan Africa, particularly community-based estimates of infant mortality rates. The longitudinal follow-up of more than 1,500 children enrolled at birth into the Asembo Bay Cohort Project (ABCP) in western Kenya between 1992 and 1996 has provided a fixed birth cohort for estimating all-cause mortality over the first 5 yr of life. We surveyed mothers and guardians of cohort children in early 1999 to determine survival status. A total of 1,260 households were surveyed to determine the survival status of 1,556 live births (99.2% of original cohort, n = 1,570). Most mothers (66%) still resided but 27.5% had migrated, and 5.5% had died. In early 1999, the overall cumulative incidence of all-cause mortality for the entire 1992-1996 birth cohort was 26.5% (95% confidence interval, 24.1-28.9%). Neonatal and infant mortality were 32 and 176 per 1,000 live births, respectively. These community-based estimates of mortality in the ABCP area are substantially higher than for Kenya overall (nationally, infant mortality is 75 per 1,000 live births). The results provide a baseline description of all-cause mortality among children in an area with intense Plasmodium falciparum transmission and will be useful in future efforts to monitor changes in death rates attributable to control programs for specific diseases (e.g., malaria and HIV/AIDS) in Africa.

CNS adverse events associated with antimalarial agents. Fact or fiction?

CNS adverse drug events are dramatic, and case reports have influenced clinical opinion on the use of antimalarials. Malaria also causes CNS symptoms, thus establishing causality is difficult. CNS events are associated with the quinoline and artemisinin derivatives. Chloroquine, once considered too toxic for humans, has been the antimalarial of choice for 40 years. While a range of serious CNS effects have been documented during chloroquine therapy, the incidence is unclear (extrapyramidal symptoms occur with an incidence of 1 in 5000). Amodiaquine has a higher incidence of mild CNS effects than chloroquine. Mefloquine therapy causes dose-related transient dizziness. Serious CNS events during mefloquine therapy occur in 1:1200 Asians and 1:200 Caucasians/Africans. Risk factors include dosage, concomitant drug use/interactions, previous history of a CNS event and disease severity. Retreatment (within a month) increases the risk in Asians 7-fold. Studies indicate that the frequency of serious CNS events with mefloquine prophylaxis (1:10,000) is similar to that with chloroquine (1:13,600). Quinine causes cinchonism at standard therapeutic doses. High-tone hearing loss occurs, but irreversible auditory or ocular effects are very rare. The artemisinin derivatives are associated with dose-dependent brain lesions in rodent, canine and nonhuman primates. At low doses, histological injury has been demonstrated, without clinical neurological signs. No significant toxicity has been reported in humans. Other antimalarial drugs are seldom associated with CNS adverse events. Data do not suggest a need to diminish the correct use of the quinoline derivatives. Irreversible effects are extremely rare and usually associated with overdosing or prior history of a serious CNS event. Concomitant therapeutic use of 2 drugs from the same family, or retreatment with the same drug, should be avoided. Onset of drug-associated serious CNS events requires drug discontinuation and future avoidance of the drug.

Predictors of mefloquine treatment failure: a prospective study of 1590 patients with uncomplicated falciparum malaria.

The factors which identify patients at risk of treatment failure were characterized in 1590 children and adults with uncomplicated falciparum malaria treated with 15 or 25 mg/kg of mefloquine on the borders of Thailand. Six independent predictors of failure were identified using multiple logistic regression. Age < or = 2 years (odds ratio [OR] 4.54), 3-15 years (OR 4.4), vomiting < 30 min after a single dose of 25 mg/kg (despite re-administration of the dose) (OR 2.5) and diarrhoea after treatment (OR 3.6) were the strongest predictors of failure by day 7. Parasitaemias > 10 000/mm3 (OR 1.4), and fever with a history of recent vomiting (OR 1.6) were risk factors for recrudescence of the infection between days 10 and 28. Patients treated with mefloquine in the previous 2 months were also at increased risk of failure (OR 2.38), particularly if they were anaemic (haematocrit < 30%) (OR 5.96), which suggested that they had recrudescent infections at presentation. Combined, these 6 factors identified half of all treatment failures. Vomiting and diarrhoea accounted for 24% of the early failures in children. Patients at increased risk of treatment failure should be monitored closely and given early alternative treatment if fever and parasites persist for > or = 3 d.

Single day mefloquine-artesunate combination in the treatment of multi-drug resistant falciparum malaria.

The therapeutic efficacy and toxicity of a combination of low dose mefloquine (15 mg/kg) plus artesunate 10 mg/kg in one day (MA) was compared with the currently used regimen of high dose mefloquine (25 mg/kg) (MQ) in 552 patients with uncomplicated falciparum malaria in an area of multi-drug resistance on the Thai-Burmese border. MA gave faster clinical and parasitological responses and prevented early treatment failure; 15 patients in the MQ group (6%) were early failures (< 9 d) compared with none receiving MA (P = 0.0001). Overall failure rates by day 28 were 19% in the MA group and 24% in with MQ group (relative risk (RR) = 0.78, 95% confidence interval (CI) 0.54-1.12). In the subgroup of patients who required re-treatment, MA proved significantly more effective than MQ; failure rates were 25% and 52% respectively (RR = 0.49, 95% CI = 0.29-0.83). Treatment failures were associated with mefloquine treatment in the previous month (RR = 1.72, 95% CI = 1.09-2.70) and diarrhoea (RR = 1.55, 95% CI = 1.05-2.28). Gastrointestinal side-effects and dizziness were more likely in the MQ group. There was no evident adverse effect associated with artesunate. A single day's treatment with artesunate augments the antimalarial efficacy of mefloquine.

Bed nets for the prevention of malaria and anaemia in pregnancy.

A prospective comparison of the antimalarial efficacy of bed nets was conducted with 341 pregnant women living in a mesoendemic malarious area of the Thai-Burmese border. Women in 3 adjacent study sites were allocated at random to receive either a single size permethrin-impregnated bed net (PIB), a non-impregnated bed net (NIB), or to a control group who used either their own family size non-impregnated bed net (FNIB) or no net. In one study site, but not the other 2, PIB significantly reduced parasite densities and, together with FNIB, reduced the incidence of malaria in pregnancy from 56% to 33% (relative risk = 1.67, confidence interval = 1.07-2.61, P = 0.03, allowing for parity). Anaemia proved a more sensitive marker of bed net antimalarial efficacy than parasite rates. The incidence of anaemia (haematocrit < 30%) at all study sites was significantly lower at delivery in the PIB (27%) and FNIB groups (21%) than in the NIB group (41%) or those using no net (56%). This suggests that a significant proportion of the malaria in pregnancy in this mesoendemic area was sub-patent. Both patent Plasmodium falciparum parasitaemia and anaemia were associated with a reduction in birth weight. Infant mortality was high (16%) and strongly associated with prematurity, low birth weight and maternal anaemia. PIB were well tolerated and had no apparent adverse effect on the pregnancy or infant development. Although the overall effect of bed nets on patent parasitaemia was marginal, they were associated with a significant reduction in maternal malaria-associated anaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence and severity of anemia and iron deficiency: cross-sectional studies in adolescent schoolgirls in western Kenya.

OBJECTIVE: Anemia is a major public health concern in preschool children and pregnant women in the developing world. While many studies have examined these two at-risk groups, there is a paucity of data on anemia in adolescents living in developing countries in the complex ecologic context of poverty, parasitism, and malnutrition. We evaluated the prevalence, severity, and risk factors of anemia in adolescent schoolgirls in an area with intense malaria transmission in western Kenya. DESIGN: Two cross-sectional surveys were conducted, using a multistage random sample design. SETTING: Public primary schools in an area with intense malaria transmission in western Kenya. SUBJECTS: A total of 648 randomly selected adolescent schoolgirls aged 12-18 y. RESULTS: The prevalence of anemia (Hb <120 g/l) was 21.1%; only one girl had an Hb less than 70 g/l. Ferritin levels were available from a subsample of 206 girls. The prevalence of iron deficiency (ferritin <12 microg/l) was 19.8, and 30.4% of anemic girls were iron deficient. Malaria and schistosomiasis were the main risk factors for anemia in younger girls (12-13 y), while menstruation was the principal risk factor in older girls (14-18 y). CONCLUSIONS: Iron deficiency and anemia in school-attending girls in western Kenya were more prevalent than in developed countries, but considerably less prevalent than in preschool children and pregnant women from the same study area. Our findings are consistent with other recent school-based surveys from western Kenya, but not with recent community- and school-based cross-sectional surveys from other parts of sub-Saharan Africa. It deserves further study to determine if adolescent girls not attending school are at higher risk of anemia.

Does infection with Human Immunodeficiency Virus affect the antibody responses to Plasmodium falciparum antigenic determinants in asymptomatic pregnant women?

OBJECTIVES: HIV-seropositive pregnant women are more susceptible to malaria than HIV-seronegative women. We assessed whether HIV infection alters maternal and cord plasma malarial antibody responses and the mother-to-infant transfer of malaria antibodies. METHODS: We determined plasma levels of maternal and cord antibodies [Immunoglobulin (IgG)] to recombinant malarial proteins [merozoite surface protein 1 (MSP-1(19kD)), the erythrocyte binding antigen (EBA-175)], the synthetic peptides [MSP-2, MSP-3, rhoptry associated protein 1 (RAP-1), and the pre-erythrocytic stage, circumsporozoite protein (NANP)(5)] antigenic determinants of Plasmodium falciparum; and tetanus toxoid (TT) by ELISA among samples of 99 HIV-seropositive mothers, 69 of their infants, 102 HIV-seronegative mothers and 62 of their infants. RESULTS: The prevalence of maternal antibodies to the malarial antigenic determinants ranged from 18% on MSP3 to 91% on EBA-175; in cord plasma it ranged from 13% to 91%, respectively. More than 97% of maternal and cord samples had antibodies to TT. In multivariate analysis, HIV infection was only associated with reduced antibodies to (NANP)(5) in maternal (P=0.001) and cord plasma (P=0.001); and reduced mother-to-infant antibody transfer to (NANP)(5) (P=0.012). This effect of HIV was independent of maternal age, gravidity and placental malaria. No consistent HIV-associated differences were observed for other antigenic determinants. CONCLUSION: An effect of HIV infection was only observed on one malarial antigenic determinant, suggesting that the increased susceptibility to malaria among HIV-infected pregnant women may not be explained on the basis of their reduced antibody response to malaria antigens.

Risk factors for HIV infection among asymptomatic pregnant women attending an antenatal clinic in western Kenya.

Our objective was to evaluate HIV prevalence and identify risk factors for HIV infection among women attending the antenatal clinic (ANC) at a large public hospital in Kisumu town, western Kenya. Between June 1996 and November 1997, in the context of a study to determine the effect of placental malaria on mother-to-child transmission of HIV in western Kenya, HIV-1 antibody testing was offered to women with a singleton uncomplicated pregnancy of > or =32 weeks' gestation attending the ANC. Women were interviewed using a structured questionnaire and had a fingerstick blood sample collected for haemoglobin (Hb), malaria smears, and HIV antibody testing. Overall HIV seroprevalence was 26.1% (743/2844) (95% confidence interval (CI): 24.5-27.7) and in bivariate evaluation was significantly associated with anaemia (Hb <11 g/dl) (risk ratio (RR) 1.8), malarial parasitaemia (RR 1.6), fever (axillary temperature > or =37.5 degrees C at screening) (RR 1.6), a history of being treated for either vaginal discharge (RR 1.5) or tuberculosis (RR 1.6), reported alcohol consumption (RR 1.6), being an unmarried multigravida (RR 2.2) or a history of the most recent child having died (RR 2.0). Poisson regression analysis for all women identified 5 significant factors independently associated with HIV seropositivity: anaemia (adjusted RR 1.7; 95% CI 1.3-2.0), malarial parasitaemia (adjusted RR 1.7; 95% CI 1.4-2.0), a history of being treated for vaginal discharge (adjusted RR 1.5; 95% CI 1.1-2.0), fever (adjusted RR 2.0; 95% CI 1.3-3.2) and reported alcohol consumption (adjusted RR 1.6; 95% CI 1.1-2.5). Multigravidae women whose most recent child had died were also more likely to be HIV seropositive (adjusted RR 1.9; 95% CI 1.7-2.8). Only 5.5% (156/2844) of the women had none of these risk factors, of whom 12% (18/156) were HIV(+). Even though the model containing the 5 identified factors fitted the data well (goodness-of-fit chi2=18.41, P=0.10), its collective capacity to predict HIV infection was poor; while 74% of the truly positive women were correctly predicted positive by the model, 52% of the truly negative women were misclassified. Among pregnant women attending the ANC in western Kenya, we were unable to identify a subgroup at risk of HIV infection using non-serological information, indicating that wherever possible universal access to voluntary HIV counselling and testing would be preferable to targeted screening.

PIP: This study evaluated the HIV prevalence and identified the risk factors for HIV infection among women attending the antenatal clinic at a public hospital in Kisumu, western Kenya. Also, the effect of placental malaria on vertical HIV transmission were determined using structured interviews and HIV-1 antibody testing and hemoglobin malaria smears were offered to the respondents. Overall, HIV seroprevalence was 26.1% (743/2844) (95% confidence interval [CI]: 24.5-27.7) and in bivariate evaluation was significantly associated with anemia (risk ratio [RR] 1.8), malarial parasitemia (RR 1.6), fever (RR 1.6), a history of being treated for either vaginal discharge (RR 1.5) or tuberculosis (RR 1.6), alcohol consumption (RR 1.6), being an unmarried multigravida (RR 2.2), or a history of the most recent child having died (RR 2.0). Using the Poisson regression analysis, 5 significant factors associated with HIV seropositivity were identified: anemia, malarial parasitemia, and history of being treated for vaginal discharge, fever, and reported alcohol consumption. Among the pregnant women, the researchers were unable to identify a subgroup at risk of HIV infection using nonserological information, indicating that universal access to voluntary HIV counseling and testing would be preferable to targeted screening.

The effect of weekly iron and vitamin A supplementation on hemoglobin levels and iron status in adolescent schoolgirls in western Kenya.

BACKGROUND/OBJECTIVES: Iron deficiency anemia is a major public health problem in developing countries and may affect school performance and physical work capacity in nonpregnant adolescents, and may increase the risk of anemia during subsequent teenage pregnancies. We assessed the effect of weekly iron (120 mg elemental iron) and vitamin A (25 000 IU) supplementation on hemoglobin, iron status and malaria and nonmalaria morbidity in adolescent schoolgirls. SUBJECTS/METHODS: A total of 279 schoolgirls aged 12-18 years from public primary schools in Kisumu, western Kenya. Double-blind randomized placebo-controlled trial using a factorial design. RESULTS: Five months of iron supplementation was associated with a 0.52 g dl(-1) (0.21, 0.82) greater increase in hemoglobin relative to iron placebo. The effect was only observed in girls with iron deficiency on enrollment (1.34 g dl(-1) (0.79, 1.88)), but not in iron-replete girls (-0.20 g dl(-1) (-0.59, 0.18)). Similar differences in treatment effect were seen between menstruating and nonmenstruating girls. The effect of iron was independent of vitamin A. The baseline prevalence of vitamin A deficiency was low (6.7%) and no sustained increase in hemoglobin was seen with weekly vitamin A (-0.07 g dl(-1) (-0.38, 0.25)). Incidence of malaria parasitemia was higher in the iron than iron-placebo groups (Rate ratio 1.33 (0.94, 1.88)). CONCLUSIONS: Weekly iron supplementation results in substantial increases in hemoglobin concentration in adolescent schoolgirls in western Kenya, which may outweigh possible risks caused by malaria, but only in iron-deficient or menstruating girls and not in iron-replete and nonmenstruating girls.

Comparison of two mefloquine regimens for treatment of Plasmodium falciparum malaria on the northeastern Thai-Cambodian border.

In 1991 and 1992, a prospective randomized trial was conducted on the northern Thai-Cambodian border. That trial compared the efficacy and tolerance of two mefloquine regimens for the treatment of uncomplicated Plasmodium falciparum malaria in an area with multi-drug-resistant P. falciparum. The resolution of fever and other symptoms was faster with high-dose mefloquine (25 mg/kg of body weight [M25 group; n = 68]) than with the conventional 15-mg/kg dose (M15 group; n = 71). There were no early treatment failures (days 7 to 9) in the M25 group, but there were 5 (7%) treatment failures in the M15 group (P = 0.03). The incidences of treatment failures by day 28 were 40% with the M15 group and 11% with the M25 group (P = 0.0004). By day 42, these values had risen to 50 and 27%, respectively (P = 0.01). The risk of treatment failure was highest in children (relative risk, 2.1; 95% confidence interval, 1.3 to 3.4) and patients with posttreatment diarrhea (relative risk, 2.0; 95% confidence interval, 1.3 to 3.1). Over half of the recrudescences in the M25 group occurred between days 28 and 42, whereas 17% of the recrudescences in the M15 group occurred between days 28 and 42 (P = 0.02). Thus, the sensitivity of assessment was significantly increased with longer follow-up. Treatment failure was associated with a delayed parasite clearance and an inadequate hematological recovery. Upper gastrointestinal side effects and dizziness were significantly more common in the M25 group, but overall, the high dose was relatively well tolerated, in particular by children. An increase in the dose to 25 mg/kg can prolong the therapeutic use of mefloquine in areas with multi-drug-resistant P.falciparum malaria where high-grade resistance to mefloquine is still rare.

Cardiac effects of antimalarial treatment with halofantrine.

In a prospective electrocardiographic study of Karen patients with acute uncomplicated falciparum malaria, mefloquine (25 mg/kg) had no cardiac effects (n = 53), but halofantrine (72 mg/kg) induced consistent dose-related lengthening of the PR and QT intervals in all 61 patients treated. The likelihood of significant QTc prolongation (by more than 25% or a QTc of 0.55 s1/2 or more) was greater after halofantrine as retreatment following mefloquine failure than as primary treatment (7/10 vs 18/51; relative risk 2.0 [95% Cl 1.1-3.4], p = 0.04). More than 60% of the effect occurred with three doses of halofantrine (24 mg/kg). The arrhythmogenic potential of halofantrine should now be investigated.

Mefloquine in infants and young children.

In an area where multi-drug resistance in Plasmodium falciparum is a particular problem, more than 500 children under 5 years of age weighing > 5 kg were treated with mefloquine, either alone or combined with an artemisinin derivative, and followed up for a minimum of 28 days. The principal adverse effect was vomiting and this was associated with reduced efficacy of treatment (even when treatment was repeated). Later adverse effects occurred less frequently than in adults. There was no serious toxicity and, in particular, there were no neuropsychiatric side-effects. The high dose of mefloquine (25 mg/kg) required in this area is well tolerated by young children. It should be given in a divided dose of 15 mg/kg initially, followed by 10 mg/kg > or = 12 hours later.

Treatment of multidrug-resistant Plasmodium falciparum malaria with 3-day artesunate-mefloquine combination.

Studies of 652 adults and children with acute uncomplicated falciparum malaria were done to determine the optimum treatment of multidrug-resistant Plasmodium falciparum malaria on the Thai-Burmese border. Single-dose artesunate (4 mg/kg) plus mefloquine (25 mg of base/kg) gave more rapid symptomatic and parasitologic responses than high-dose mefloquine alone but did not improve cure rates. Three days of artesunate (total dose, 10 mg/kg) plus mefloquine was 98% effective compared with a 28-day failure rate of 31% with high-dose mefloquine alone (relative risk [RR], 0.06; 95% confidence interval [CI], 0.02-0.2; P < .0001). By day 63, the reinfection adjusted failure rates were 2% and 44%, respectively (P < .0001). Artesunate also prevented high-grade failures. Both drugs were well tolerated. No adverse effects were attributable to artesunate. Vomiting was reduced significantly by giving mefloquine on day 2 of treatment (RR, 0.40; 95% CI, 0.20-0.79; P = .009. Artesunate (10 mg/kg over 3 days) plus mefloquine (25 mg/kg) is currently the most effective treatment for falciparum malaria in this area of increasing mefloquine resistance.