Epidemiology of malaria, schistosomiasis, geohelminths, anemia and malnutrition in the context of a demographic surveillance system in northern Angola

Background

Malaria, schistosomiasis and geohelminth infection are linked to maternal and child morbidity and mortality in sub-Saharan Africa. Knowing the prevalence levels of these infections is vital to guide governments towards the implementation of successful and cost-effective disease control initiatives.

Methodology/Principal Findings

A cross-sectional study of 1,237 preschool children (0–5 year olds), 1,142 school-aged children (6–15 year olds) and 960 women (>15 year olds) was conducted to understand the distribution of malnutrition, anemia, malaria, schistosomiasis (intestinal and urinary) and geohelminths in a north-western province of Angola. We used a recent demographic surveillance system (DSS) database to select and recruit suitable households. Malnutrition was common among children (23.3% under-weight, 9.9% wasting and 32.2% stunting), and anemia was found to be a severe public health problem (i.e., >40%). Malaria prevalence was highest among preschool children reaching 20.2%. Micro-hematuria prevalence levels reached 10.0% of preschool children, 16.6% of school-aged children and 21.7% of mothers. Geohelminth infections were common, affecting 22.3% of preschool children, 31.6% of school-aged children and 28.0% of mothers.

Conclusions

Here we report prevalence levels of malaria, schistosomiasis and geohelminths; all endemic in this poorly described area where a DSS has been recently established. Furthermore we found evidence that the studied infections are associated with the observed levels of anemia and malnutrition, which can justify the implementation of integrated interventions for the control of these diseases and morbidities.     

Mapping helminth co-infection and co-intensity: geostatistical prediction in ghana

Background

Morbidity due to Schistosoma haematobium and hookworm infections is marked in those with intense co-infections by these parasites. The development of a spatial predictive decision-support tool is crucial for targeting the delivery of integrated mass drug administration (MDA) to those most in need. We investigated the co-distribution of S. haematobium and hookworm infection, plus the spatial overlap of infection intensity of both parasites, in Ghana. The aim was to produce maps to assist the planning and evaluation of national parasitic disease control programs.

Methodology/Principal Findings

A national cross-sectional school-based parasitological survey was conducted in Ghana in 2008, using standardized sampling and parasitological methods. Bayesian geostatistical models were built, including a multinomial regression model for S. haematobium and hookworm mono- and co-infections and zero-inflated Poisson regression models for S. haematobium and hookworm infection intensity as measured by egg counts in urine and stool respectively. The resulting infection intensity maps were overlaid to determine the extent of geographical overlap of S. haematobium and hookworm infection intensity. In Ghana, prevalence of S. haematobium mono-infection was 14.4%, hookworm mono-infection was 3.2%, and S. haematobium and hookworm co-infection was 0.7%. Distance to water bodies was negatively associated with S. haematobium and hookworm co-infections, hookworm mono-infections and S. haematobium infection intensity. Land surface temperature was positively associated with hookworm mono-infections and S. haematobium infection intensity. While high-risk (prevalence >10–20%) of co-infection was predicted in an area around Lake Volta, co-intensity was predicted to be highest in foci within that area.

Conclusions/Significance

Our approach, based on the combination of co-infection and co-intensity maps allows the identification of communities at increased risk of severe morbidity and environmental contamination and provides a platform to evaluate progress of control efforts.     

Malaria and Helminth Co-Infections in School and Preschool Children: A Cross-Sectional Study in Magu District,North-Western Tanzania

Background

Malaria, schistosomiasis and soil transmitted helminth infections (STH) are important parasitic infections in Sub-Saharan Africa where a significant proportion of people are exposed to co-infections of more than one parasite. In Tanzania, these infections are a major public health problem particularly in school and pre-school children. The current study investigated malaria and helminth co-infections and anaemia in school and pre-school children in Magu district, Tanzania.

Methodology

School and pre-school children were enrolled in a cross-sectional study. Stool samples were examined for Schistosoma mansoni and STH infections using Kato Katz technique. Urine samples were examined for Schistosoma haematobium using the urine filtration method. Blood samples were examined for malaria parasites and haemoglobin concentrations using the Giemsa stain and Haemoque methods, respectively.

Principal Findings

Out of 1,546 children examined, 1,079 (69.8%) were infected with one or more parasites. Malaria-helminth co-infections were observed in 276 children (60% of all children with P. falciparum infection). Malaria parasites were significantly more prevalent in hookworm infected children than in hookworm free children (p = 0.046). However, this association was non-significant on multivariate logistic regression analysis (OR = 1.320, p = 0.064). Malaria parasite density decreased with increasing infection intensity of S. mansoni and with increasing number of co-infecting helminth species. Anaemia prevalence was 34.4% and was significantly associated with malaria infection, S. haematobium infection and with multiple parasite infections. Whereas S. mansoni infection was a significant predictor of malaria parasite density, P. falciparum and S. haematobium infections were significant predictors of anaemia.

Conclusions/Significance

These findings suggest that multiple parasite infections are common in school and pre-school children in Magu district. Concurrent P. falciparum, S. mansoni and S. haematobium infections increase the risk of lower Hb levels and anaemia, which in turn calls for integrated disease control interventions. The associations between malaria and helminth infections detected in this study need further investigation.     

State-space forecasting of Schistosoma haematobium time-series in Niono, Mali

Background

Much of the developing world, particularly sub-Saharan Africa, exhibits high levels of morbidity and mortality associated with infectious diseases. The incidence of Schistosoma sp.—which are neglected tropical diseases exposing and infecting more than 500 and 200 million individuals in 77 countries, respectively—is rising because of 1) numerous irrigation and hydro-electric projects, 2) steady shifts from nomadic to sedentary existence, and 3) ineffective control programs. Notwithstanding the colossal scope of these parasitic infections, less than 0.5% of Schistosoma sp. investigations have attempted to predict their spatial and or temporal distributions. Undoubtedly, public health programs in developing countries could benefit from parsimonious forecasting and early warning systems to enhance management of these parasitic diseases.

Methodology/Principal Findings

In this longitudinal retrospective (01/1996–06/2004) investigation, the Schistosoma haematobium time-series for the district of Niono, Mali, was fitted with general-purpose exponential smoothing methods to generate contemporaneous on-line forecasts. These methods, which are encapsulated within a state–space framework, accommodate seasonal and inter-annual time-series fluctuations. Mean absolute percentage error values were circa 25% for 1- to 5-month horizon forecasts.

Conclusions/Significance

The exponential smoothing state–space framework employed herein produced reasonably accurate forecasts for this time-series, which reflects the incidence of S. haematobium–induced terminal hematuria. It obliquely captured prior non-linear interactions between disease dynamics and exogenous covariates (e.g., climate, irrigation, and public health interventions), thus obviating the need for more complex forecasting methods in the district of Niono, Mali. Therefore, this framework could assist with managing and assessing S. haematobium transmission and intervention impact, respectively, in this district and potentially elsewhere in the Sahel.     

Complex Interactions between soil-transmitted helminths and malaria in pregnant women on the Thai-Burmese border

Background

Deworming is recommended by the WHO in girls and pregnant and lactating women to reduce anaemia in areas where hookworm and anaemia are common. There is conflicting evidence on the harm and the benefits of intestinal geohelminth infections on the incidence and severity of malaria, and consequently on the risks and benefits of deworming in malaria affected populations. We examined the association between geohelminths and malaria in pregnancy on the Thai-Burmese border.

Methodology

Routine antenatal care (ANC) included active detection of malaria (weekly blood smear) and anaemia (second weekly haematocrit) and systematic reporting of birth outcomes. In 1996 stool samples were collected in cross sectional surveys from women attending the ANCs. This was repeated in 2007 when malaria incidence had reduced considerably. The relationship between geohelminth infection and the progress and outcome of pregnancy was assessed.

Principal Findings

Stool sample examination (339 in 1996, 490 in 2007) detected a high prevalence of geohelminths 70% (578/829), including hookworm (42.8% (355)), A. lumbricoides (34.4% (285)) and T.trichuria (31.4% (250)) alone or in combination. A lower proportion of women (829) had mild (21.8% (181)) or severe (0.2% (2)) anaemia, or malaria 22.4% (186) (P.vivax monoinfection 53.3% (101/186)). A. lumbricoides infection was associated with a significantly decreased risk of malaria (any species) (AOR: 0.43, 95% CI: 0.23–0.84) and P.vivax malaria (AOR: 0.29, 95% CI: 0.11–0.79) whereas hookworm infection was associated with an increased risk of malaria (any species) (AOR: 1.66, 95% CI: 1.06–2.60) and anaemia (AOR: 2.41, 95% CI: 1.18–4.93). Hookworm was also associated with low birth weight (AOR: 1.81, 95% CI: 1.02–3.23).

Conclusion/Significance

A. lumbricoides and hookworm appear to have contrary associations with malaria in pregnancy.     

The synergistic effect of concomitant schistosomiasis, hookworm, and trichuris infections on children's anemia burden

Objective

To estimate the degree of synergism between helminth species in their combined effects on anemia.

Methods

Quantitative egg counts using the Kato–Katz method were determined for Ascaris lumbricoides, hookworm, Trichuris trichiura, and Schistosoma japonicum in 507 school-age children from helminth-endemic villages in The Philippines. Infection intensity was defined in three categories: uninfected, low, or moderate/high (M+). Anemia was defined as hemoglobin <11 g/dL. Logistic regression models were used to estimate odds ratios (OR), 95% confidence intervals (CI), and synergy index for pairs of concurrent infections.

Results

M+ co-infection of hookworm and S. japonicum (OR = 13.2, 95% CI: 3.82–45.5) and of hookworm and T. trichiura (OR = 5.34, 95% CI: 1.76–16.2) were associated with higher odds of anemia relative to children without respective M+ co-infections. For co-infections of hookworm and S. japonicum and of T. trichiura and hookworm, the estimated indices of synergy were 2.9 (95% CI: 1.1–4.6) and 1.4 (95% CI: 0.9–2.0), respectively.

Conclusion

Co-infections of hookworm and either S. japonicum or T. trichiura were associated with higher levels of anemia than would be expected if the effects of these species had only independent effects on anemia. This suggests that integrated anti-helminthic treatment programs with simultaneous deworming for S. japonicum and some geohelminths could yield a greater than additive benefit for reducing anemia in helminth-endemic regions.     

Effect of Schistosomiasis and Soil-Transmitted Helminth Infections on Physical Fitness of School Children in C?te d'Ivoire

Background

Schistosomiasis and soil-transmitted helminthiasis are important public health problems in sub-Saharan Africa causing malnutrition, anemia, and retardation of physical and cognitive development. However, the effect of these diseases on physical fitness remains to be determined.

Methodology

We investigated the relationship between schistosomiasis, soil-transmitted helminthiasis and physical performance of children, controlling for potential confounding of Plasmodium spp. infections and environmental parameters (i.e., ambient air temperature and humidity). A cross-sectional survey was carried out among 156 school children aged 7–15 years from Côte d''Ivoire. Each child had two stool and two urine samples examined for helminth eggs by microscopy. Additionally, children underwent a clinical examination, were tested for Plasmodium spp. infection with a rapid diagnostic test, and performed a maximal multistage 20 m shuttle run test to assess their maximal oxygen uptake (VO₂ max) as a proxy for physical fitness.

Principal Findings

The prevalence of Schistosoma haematobium, Plasmodium spp., Schistosoma mansoni, hookworm and Ascaris lumbricoides infections was 85.3%, 71.2%, 53.8%, 13.5% and 1.3%, respectively. Children with single, dual, triple, quadruple and quintuple species infections showed VO₂ max of 52.7, 53.1, 52.2, 52.6 and 55.6 ml kg⁻¹ min⁻¹, respectively. The VO₂ max of children with no parasite infections was 53.5 ml kg⁻¹ min⁻¹. No statistically significant difference was detected between any groups. Multivariable analysis revealed that VO₂ max was influenced by sex (reference: female, coef. = 4.02, p<0.001) and age (years, coef. = −1.23, p<0.001), but not by helminth infection and intensity, Plasmodium spp. infection, and environmental parameters.

Conclusion/Significance

School-aged children in Côte d''Ivoire showed good physical fitness, irrespective of their helminth infection status. Future studies on children''s physical fitness in settings where helminthiasis and malaria co-exist should include pre- and post-intervention evaluations and the measurement of hemoglobin and hematocrit levels and nutritional parameters as potential co-factors to determine whether interventions further improve upon fitness.     

Diagnostic accuracy of Kato-Katz and FLOTAC for assessing anthelmintic drug efficacy

Background

Sensitive diagnostic tools are required for an accurate assessment of prevalence and intensity of helminth infections in areas undergoing regular deworming, and for monitoring anthelmintic drug efficacy. We compared the diagnostic accuracy of the Kato-Katz and FLOTAC techniques in the frame of a drug efficacy trial.

Methodology/Principal Findings

Stool samples from 343 Zanzibari children were subjected to duplicate Kato-Katz thick smears and the FLOTAC basic technique in a baseline screening in early 2009. The FLOTAC showed a higher sensitivity than the Kato-Katz method for the diagnosis of Trichuris trichiura (95% vs. 88%, p = 0.012) and Ascaris lumbricoides (88% vs. 68%, p = 0.098), but a lower sensitivity for hookworm diagnosis (54% vs. 81%, p = 0.006). Considering the combined results from both methods as ‘gold’ standard, the prevalences of T. trichiura, hookworm and A. lumbricoides were 71% (95% confidence interval (CI): 66–75%), 22% (95% CI: 17–26%) and 12% (95% CI: 8–15%), respectively. At follow-up, 3–5 weeks after 174 among the 269 re-examined children were administered anthelmintic drugs, we observed cure rates (CRs) against A. lumbricoides, hookworm and T. trichiura of 91% (95% CI: 80–100%), 61% (95% CI: 48–75%) and 41% (95% CI: 34–49%), respectively, when using the Kato-Katz method. FLOTAC revealed lower CRs against A. lumbricoides (83%, 95% CI: 67–98%) and T. trichiura (36%, 95% CI: 29–43%), but a higher CR against hookworm (69%, 95% CI: 57–82%). These differences, however, lacked statistical significance. Considerable differences were observed in the geometric mean fecal egg counts between the two methods with lower egg reduction rates (ERRs) determined by FLOTAC.

Conclusion/Significance

Our results suggest that the FLOTAC technique, following further optimization, might become a viable alternative to the Kato-Katz method for anthelmintic drug efficacy studies and for monitoring and evaluation of deworming programs. The lower CRs and ERRs determined by FLOTAC warrant consideration and could strategically impact future helminth control programs.     

Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide-treated bednet in Mali: a randomised, double-blind, placebo-controlled trial

Background

Previous studies have shown that in areas of seasonal malaria transmission, intermittent preventive treatment of malaria in children (IPTc), targeting the transmission season, reduces the incidence of clinical malaria. However, these studies were conducted in communities with low coverage with insecticide-treated nets (ITNs). Whether IPTc provides additional protection to children sleeping under an ITN has not been established.

Methods and Findings

To assess whether IPTc provides additional protection to children sleeping under an ITN, we conducted a randomised, double-blind, placebo-controlled trial of IPTc with sulphadoxine pyrimethamine (SP) plus amodiaquine (AQ) in three localities in Kati, Mali. After screening, eligible children aged 3–59 mo were given a long-lasting insecticide-treated net (LLIN) and randomised to receive three rounds of active drugs or placebos. Treatments were administered under observation at monthly intervals during the high malaria transmission season in August, September, and October 2008. Adverse events were monitored immediately after the administration of each course of IPTc and throughout the follow-up period. The primary endpoint was clinical episodes of malaria recorded through passive surveillance by study clinicians available at all times during the follow-up. Cross-sectional surveys were conducted in 150 randomly selected children weekly and in all children at the end of the malaria transmission season to assess usage of ITNs and the impact of IPTc on the prevalence of malaria, anaemia, and malnutrition. Cox regression was used to compare incidence rates between intervention and control arms. The effects of IPTc on the prevalence of malaria infection and anaemia were estimated using logistic regression. 3,065 children were screened and 3,017 (1,508 in the control and 1,509 in the intervention arm) were enrolled in the study. 1,485 children (98.5%) in the control arm and 1,481 (98.1%) in the intervention arm completed follow-up. During the intervention period, the proportion of children reported to have slept under an ITN was 99.7% in the control and 99.3% in intervention arm (p = 0.45). A total of 672 episodes of clinical malaria defined as fever or a history of fever and the presence of at least 5,000 asexual forms of Plasmodium falciparum per microlitre (incidence rate of 1.90; 95% confidence interval [CI] 1.76–2.05 episodes per person year) were observed in the control arm versus 126 (incidence rate of 0.34; 95% CI 0.29–0.41 episodes per person year) in the intervention arm, indicating a protective effect (PE) of 82% (95% CI 78%–85%) (p<0.001) on the primary endpoint. There were 15 episodes of severe malaria in children in the control arm compared to two in children in the intervention group giving a PE of 87% (95% CI 42%–99%) (p = 0.001). IPTc reduced the prevalence of malaria infection by 85% (95% CI 73%–92%) (p<0.001) during the intervention period and by 46% (95% CI 31%–68%) (p<0.001) at the end of the intervention period. The prevalence of moderate anaemia (haemoglobin [Hb] <8 g/dl) was reduced by 47% (95% CI 15%–67%) (p<0.007) at the end of intervention period. The frequencies of adverse events were similar between the two arms. There was no drug-related serious adverse event.

Conclusions

IPTc given during the malaria transmission season provided substantial protection against clinical episodes of malaria, malaria infection, and anaemia in children using an LLIN. SP+AQ was safe and well tolerated. These findings indicate that IPTc could make a valuable contribution to malaria control in areas of seasonal malaria transmission alongside other interventions.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00738946","term_id":"NCT00738946"}}NCT00738946 Please see later in the article for the Editors'' Summary     

Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review

Background

Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities. In a systematic review of published studies, we examined evidence for incremental benefits from repeated praziquantel dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of Africa.

Methodology/Principal Findings

We performed systematic searches of electronic databases PubMed and EMBASE for relevant data using search terms ‘schistosomiasis’, ‘dosing’ and ‘praziquantel’ and hand searches of personal collections and bibliographies of recovered articles. In 10 reports meeting study criteria, improvements in parasitological treatment outcomes after two doses of praziquantel were greater for S. mansoni infection than for S. haematobium infection. Observed cure rates (positive to negative conversion in egg detection assays) were, for S. mansoni, 69–91% cure after two doses vs. 42–79% after one dose and, for S. haematobium, 46–99% cure after two doses vs. 37–93% after a single dose. Treatment benefits in terms of reduction in intensity (mean egg count) were also different for the two species—for S. mansoni, the 2-dose regimen yielded an weighted average 89% reduction in standardized egg counts compared to a 83% reduction after one dose; for S. haematobium, two doses gave a 93% reduction compared to a 94% reduction with a single dose. Cost-effectiveness analysis was performed based on Markov life path modeling.

Conclusions/Significance

Although schedules for repeated treatment with praziquantel require greater inputs in terms of direct costs and community participation, there are incremental benefits to this approach at an estimated cost of $153 (S. mansoni)–$211 (S. haematobium) per additional lifetime QALY gained by double treatment in school-based programs. More rapid reduction of infection-related disease may improve program adherence, and if, as an externality of the program, transmission can be reduced through more effective coverage, significant additional benefits are expected to accrue in the targeted communities.     

Associations between infection intensity categories and morbidity prevalence in school-age children are much stronger for Schistosoma haematobium than for S. mansoni

BackgroundWorld Health Organization (WHO) guidelines for measuring global progress in schistosomiasis control classify individuals with Schistosoma spp. infections based on the concentration of excreted eggs. We assessed the associations between WHO infection intensity categories and morbidity prevalence for selected S. haematobium and S. mansoni morbidities in school-age children.MethodologyA total of 22,488 children aged 6–15 years from monitoring and evaluation cohorts in Burkina Faso, Mali, Niger, Uganda, Tanzania, and Zambia from 2003–2008 were analyzed using Bayesian logistic regression. Models were utilized to evaluate associations between intensity categories and the prevalence of any urinary bladder lesion, any upper urinary tract lesion, microhematuria, and pain while urinating (for S. haematobium) and irregular hepatic ultrasound image pattern (C-F), enlarged portal vein, laboratory-confirmed diarrhea, and self-reported diarrhea (for S. mansoni) across participants with infection and morbidity data.Principal findingsS. haematobium infection intensity categories possessed consistent morbidity prevalence across surveys for multiple morbidities and participants with light infections had elevated morbidity levels, compared to negative participants. Conversely, S. mansoni infection intensity categories lacked association with prevalence of the morbidity measures assessed.Conclusions/significanceCurrent status infection intensity categories for S. haematobium were associated with morbidity levels in school-age children, suggesting urogenital schistosomiasis morbidity can be predicted by an individual’s intensity category. Conversely, S. mansoni infection intensity categories were not consistently indicative of childhood morbidity at baseline or during the first two years of a preventive chemotherapy control program.     

Epidemiological and genetic data supporting the transmission of Ancylostoma ceylanicum among human and domestic animals

Background

Currently, information on species-specific hookworm infection is unavailable in Malaysia and is restricted worldwide due to limited application of molecular diagnostic tools. Given the importance of accurate identification of hookworms, this study was conducted as part of an ongoing molecular epidemiological investigation aimed at providing the first documented data on species-specific hookworm infection, associated risk factors and the role of domestic animals as reservoirs for hookworm infections in endemic communities of Malaysia.

Methods/Findings

A total of 634 human and 105 domestic canine and feline fecal samples were randomly collected. The overall prevalence of hookworm in humans and animals determined via microscopy was 9.1% (95% CI = 7.0–11.7%) and 61.9% (95% CI = 51.2–71.2%), respectively. Multivariate analysis indicated that participants without the provision of proper latrine systems (OR = 3.5; 95% CI = 1.53–8.00; p = 0.003), walking barefooted (OR = 5.6; 95% CI = 2.91–10.73; p<0.001) and in close contact with pets or livestock (OR = 2.9; 95% CI = 1.19–7.15; p = 0.009) were more likely to be infected with hookworms. Molecular analysis revealed that while most hookworm-positive individuals were infected with Necator americanus, Ancylostoma ceylanicum constituted 12.8% of single infections and 10.6% mixed infections with N. americanus. As for cats and dogs, 52.0% were positive for A. ceylanicum, 46.0% for Ancylostoma caninum and 2.0% for Ancylostoma braziliense and all were single infections.

Conclusion

This present study provided evidence based on the combination of epidemiological, conventional diagnostic and molecular tools that A. ceylanicum infection is common and that its transmission dynamic in endemic areas in Malaysia is heightened by the close contact of human and domestic animal (i.e., dogs and cats) populations.     

Efficacy of single-dose and triple-dose albendazole and mebendazole against soil-transmitted helminths and Taenia spp.: a randomized controlled trial

Background

The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common STH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based randomized controlled trial in the People''s Republic of China.

Methodology/Principal findings

The hookworm CR and fecal ERR were assessed in 314 individuals aged ≥5 years who submitted two stool samples before and 3–4 weeks after administration of single-dose oral albendazole (400 mg) or mebendazole (500 mg) or triple-dose albendazole (3×400 mg over 3 consecutive days) or mebendazole (3×500 mg over 3 consecutive days). Efficacy against T. trichiura, Ascaris lumbricoides, and Taenia spp. was also assessed.Albendazole cured significantly more hookworm infections than mebendazole in both treatment regimens (single dose: respective CRs 69% (95% confidence interval [CI]: 55–81%) and 29% (95% CI: 20–45%); triple dose: respective CRs 92% (95% CI: 81–98%) and 54% (95% CI: 46–71%)). ERRs followed the same pattern (single dose: 97% versus 84%; triple dose: 99.7% versus 96%). Triple-dose regimens outperformed single doses against T. trichiura; three doses of mebendazole – the most efficacious treatment tested – cured 71% (95% CI: 57–82%). Both single and triple doses of either drug were highly efficacious against A. lumbricoides (CR: 93–97%; ERR: all >99.9%). Triple dose regimens cured all Taenia spp. infections, whereas single dose applications cured only half of them.

Conclusions/Significance

Single-dose oral albendazole is more efficacious against hookworm than mebendazole. To achieve high CRs against both hookworm and T. trichiura, triple-dose regimens are warranted.

Trial Registration

www.controlled-trials.com ISRCTN47375023     

Association between anaemia, iron deficiency anaemia, neglected parasitic infections and socioeconomic factors in rural children of West Malaysia

Background

Given that micronutrient deficiency, neglected intestinal parasitic infections (IPIs) and poor socioeconomic status are closely linked, we conducted a cross-sectional study to assess the relationship between IPIs and nutritional status of children living in remote and rural areas in West Malaysia.

Methods/Findings

A total of 550 children participated, comprising 520 (94.5%) school children aged 7 to 12 years old, 30 (5.5%) young children aged 1 to 6 years old, 254 (46.2%) boys and 296 (53.8%) girls. Of the 550 children, 26.2% were anaemic, 54.9% iron deficient and 16.9% had iron deficiency anaemia (IDA). The overall prevalence of helminths was 76.5% comprising Trichuris trichiura (71.5%), Ascaris lumbricoides (41.6%) and hookworm infection (13.5%). It was observed that iron deficiency was significantly higher in girls (p = 0.032) compared to boys. Univariate analysis demonstrated that low level of mother''s education (OR = 2.52; 95% CI = 1.38–4.60; p = 0.002), non working parents (OR = 2.18; 95% CI = 2.06–2.31; p = 0.013), low household income (OR = 2.02; 95% CI = 1.14–3.59; p = 0.015), T. trichiura (OR = 2.15; 95% CI = 1.21–3.81; p = 0.008) and A. lumbricoides infections (OR = 1.63; 95% CI = 1.04–2.55; p = 0.032) were significantly associated with the high prevalence of IDA. Multivariate analysis confirmed that low level of mother''s education (OR = 1.48; 95 CI% = 1.33–2.58; p<0.001) was a significant predictor for IDA in these children.

Conclusion

It is crucial that a comprehensive primary health care programme for these communities that includes periodic de-worming, nutrition supplement, improved household economy, education, sanitation status and personal hygiene are taken into consideration to improve the nutritional status of these children.     

Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide-treated bednet in Burkina Faso: a randomised, double-blind, placebo-controlled trial

Background

Intermittent preventive treatment of malaria in children (IPTc) is a promising new approach to the control of malaria in areas of seasonal malaria transmission but it is not known if IPTc adds to the protection provided by an insecticide-treated net (ITN).

Methods and Findings

An individually randomised, double-blind, placebo-controlled trial of seasonal IPTc was conducted in Burkina Faso in children aged 3 to 59 months who were provided with a long-lasting insecticide-treated bednet (LLIN). Three rounds of treatment with sulphadoxine pyrimethamine plus amodiaquine or placebos were given at monthly intervals during the malaria transmission season. Passive surveillance for malaria episodes was established, a cross-sectional survey was conducted at the end of the malaria transmission season, and use of ITNs was monitored during the intervention period. Incidence rates of malaria were compared using a Cox regression model and generalized linear models were fitted to examine the effect of IPTc on the prevalence of malaria infection, anaemia, and on anthropometric indicators. 3,052 children were screened and 3,014 were enrolled in the trial; 1,505 in the control arm and 1,509 in the intervention arm. Similar proportions of children in the two treatment arms were reported to sleep under an LLIN during the intervention period (93%). The incidence of malaria, defined as fever or history of fever with parasitaemia ≥5,000/µl, was 2.88 (95% confidence interval [CI] 2.70–3.06) per child during the intervention period in the control arm versus 0.87 (95% CI 0.78–0.97) in the intervention arm, a protective efficacy (PE) of 70% (95% CI 66%–74%) (p<0.001). There was a 69% (95% CI 6%–90%) reduction in incidence of severe malaria (p = 0.04) and a 46% (95% CI 7%–69%) (p = 0.03) reduction in the incidence of all-cause hospital admissions. IPTc reduced the prevalence of malaria infection at the end of the malaria transmission season by 73% (95% CI 68%–77%) (p<0.001) and that of moderately severe anaemia by 56% (95% CI 36%–70%) (p<0.001). IPTc reduced the risks of wasting (risk ratio [RR] = 0.79; 95% CI 0.65–1.00) (p = 0.05) and of being underweight (RR = 0.84; 95% CI 0.72–0.99) (p = 0.03). Children who received IPTc were 2.8 (95% CI 2.3–3.5) (p<0.001) times more likely to vomit than children who received placebo but no drug-related serious adverse event was recorded.

Conclusions

IPT of malaria provides substantial protection against malaria in children who sleep under an ITN. There is now strong evidence to support the integration of IPTc into malaria control strategies in areas of seasonal malaria transmission.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00738946","term_id":"NCT00738946"}}NCT00738946 Please see later in the article for the Editors'' Summary     

Hookworm-related anaemia among pregnant women: a systematic review

Background and Objectives

Hookworm infection is among the major causes of anaemia in poor communities, but its importance in causing maternal anaemia is poorly understood, and this has hampered effective lobbying for the inclusion of anthelmintic treatment in maternal health packages. We sought to review existing evidence on the role of hookworm as a risk factor for anaemia among pregnant women. We also estimate the number of hookworm infections in pregnant women in sub-Saharan Africa (SSA).

Methods

Structured searches using MEDLINE and EMBASE as well as manual searches of reference lists were conducted, and unpublished data were obtained by contacting authors. Papers were independently reviewed by two authors, and relevant data were extracted. We compared haemoglobin concentration (Hb) according to intensity of hookworm infection and calculated standardised mean differences and 95% confidence intervals. To estimate the number of pregnant women, we used population surfaces and a spatial model of hookworm prevalence.

Findings

One hundred and five reports were screened and 19 were eligible for inclusion: 13 cross-sectional studies, 2 randomised controlled trials, 2 non-randomised treatment trials and 2 observational studies. Comparing uninfected women and women lightly (1–1,999 eggs/gram [epg]) infected with hookworm, the standardised mean difference (SMD) was −0.24 (95% CI: −0.36 to −0.13). The SMD between women heavily (4000+ epg) infected and those lightly infected was −0.57 (95% CI: −0.87 to −0.26). All identified intervention studies showed a benefit of deworming for maternal or child health, but since a variety of outcomes measures were employed, quantitative evaluation was not possible. We estimate that 37.7 million women of reproductive age in SSA are infected with hookworm in 2005 and that approximately 6.9 million pregnant women are infected.

Conclusions

Evidence indicates that increasing hookworm infection intensity is associated with lower haemoglobin levels in pregnant women in poor countries. There are insufficient data to quantify the benefits of deworming, and further studies are warranted. Given that between a quarter and a third of pregnant women in SSA are infected with hookworm and at risk of preventable hookworm-related anaemia, efforts should be made to increase the coverage of anthelmintic treatment among pregnant women.     

Controlling Schistosomiasis: Significant Decrease of Anaemia Prevalence One Year after a Single Dose of Praziquantel in Nigerien Schoolchildren

Background

In the framework of the monitoring and evaluation of the Nigerien schistosomiasis and soil-transmitted helminth control programme, a follow-up of children took place in eight sentinel sites. The objective of the study was to assess the evolution of Schistosoma haematobium infection and anaemia in schoolchildren after a single administration of praziquantel (PZQ) and albendazole.

Methods/Principal Findings

Pre-treatment examination and follow-up at one year post-treatment of schoolchildren aged 7, 8, and 11 years, including interview, urine examination, ultrasound examination of the urinary tract, and measurement of haemoglobin. Before treatment, the overall prevalence of S. heamatobium infection was 75.4% of the 1,642 enrolled children, and 21.8% of children excreted more than 50 eggs/10 ml urine. Prevalence increased with age. The overall prevalence of anaemia (haemoglobin <11.5 g/dl) was 61.6%, decreasing significantly with increasing age. The mean haemoglobinemia was 11 g/dl. In bivariate analysis, anaemia was significantly more frequent in children infected with S. haematobium, although it was not correlated to the intensity of infection. Anaemia was also associated with micro-haematuria and to kidney distensions. In a sub-sample of 636 children tested for P. falciparum infection, anaemia was significantly more frequent in malaria-infected children. In multivariate analysis, significant predictors of anaemia were P. falciparum infection, kidney distension, and the village. One year after a single-dose praziquantel treatment (administered using the WHO PZQ dose pole) co-administered with albendazole (400 mg single dose) for de-worming, the prevalence of S. haematobium infection was 38%, while the prevalence of anaemia fell to 50.4%. The mean haemoglobinemia showed a statistically significant increase of 0.39 g/dl to reach 11.4 g/dl. Anaemia was no longer associated with S. haematobium or to P. falciparum infections, or to haematuria or ultrasound abnormalities of the urinary tract.

Conclusions

The high prevalence of anaemia in Nigerien children is clearly a result of many factors and not of schistosomiasis alone. Nevertheless, treatment of schistosomiasis and de-worming were followed by a partial, but significant, reduction of anaemia in schoolchildren, not explainable by any other obvious intervention.     

Morbidity from malaria in children in the year after they had received intermittent preventive treatment of malaria: a randomised trial

Background

Interventions that reduce exposure to malaria infection may lead to delayed malaria morbidity and mortality. We investigated whether intermittent preventive treatment of malaria in children (IPTc) was associated with an increase in the incidence of malaria after cessation of the intervention.

Methods

An individually randomised, trial of IPTc, comparing three courses of sulphadoxine pyrimethamine (SP) plus amodiaquine (AQ) with placebos was implemented in children aged 3–59 months during the 2008 malaria transmission season in Burkina Faso. All children in the trial were given a long lasting insecticide treated net; 1509 children received SP+AQ and 1505 received placebos. Passive surveillance for malaria was maintained until the end of the subsequent malaria transmission season in 2009, and active surveillance for malaria infection, anaemia and malnutrition was conducted.

Results

On thousand, four hundred and sixteen children (93.8%) and 1399 children (93.0%) initially enrolled in the intervention and control arms of the trial respectively were followed during the 2009 malaria transmission season. During the period July 2009 to November 2009, incidence rates of clinical malaria were 3.84 (95%CI; 3.67–4.02) and 3.45 (95%CI; 3.29–3.62) episodes per child during the follow up period in children who had previously received IPT or placebos, indicating a small increase in risk for children in the former intervention arm (IRR = 1.12; 95%CI 1.04–1.20) (P = 0.003). Children who had received SP+AQ had a lower prevalence of malaria infection (adjusted PR: 0.88 95%CI: 0.79–0.98) (P = 0.04) but they had a higher parasite density (P = 0.001) if they were infected. There was no evidence that the risks of moderately severe anaemia (Hb<8 g/dL), wasting, stunting, or of being underweight in children differed between treatment arms.

Conclusion

IPT with SP+AQ was associated with a small increase in the incidence of clinical malaria in the subsequent malaria transmission season.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00738946","term_id":"NCT00738946"}}NCT00738946     

Low efficacy of single-dose albendazole and mebendazole against hookworm and effect on concomitant helminth infection in Lao PDR

Background

Albendazole and mebendazole are increasingly deployed for preventive chemotherapy targeting soil-transmitted helminth (STH) infections. We assessed the efficacy of single oral doses of albendazole (400 mg) and mebendazole (500 mg) for the treatment of hookworm infection in school-aged children in Lao PDR. Since Opisthorchis viverrini is co-endemic in our study setting, the effect of the two drugs could also be determined against this liver fluke.

Methodology

We conducted a randomized, open-label, two-arm trial. In total, 200 children infected with hookworm (determined by quadruplicate Kato-Katz thick smears derived from two stool samples) were randomly assigned to albendazole (n = 100) and mebendazole (n = 100). Cure rate (CR; percentage of children who became egg-negative after treatment), and egg reduction rate (ERR; reduction in the geometric mean fecal egg count at treatment follow-up compared to baseline) at 21–23 days posttreatment were used as primary outcome measures. Adverse events were monitored 3 hours post treatment.

Principal Findings

Single-dose albendazole and mebendazole resulted in CRs of 36.0% and 17.6% (odds ratio: 0.4; 95% confidence interval: 0.2–0.8; P = 0.01), and ERRs of 86.7% and 76.3%, respectively. In children co-infected with O. viverrini, albendazole and mebendazole showed low CRs (33.3% and 24.2%, respectively) and moderate ERRs (82.1% and 78.2%, respectively).

Conclusions/Significance

Both albendazole and mebendazole showed disappointing CRs against hookworm, but albendazole cured infection and reduced intensity of infection with a higher efficacy than mebendazole. Single-dose administrations showed an effect against O. viverrini, and hence it will be interesting to monitor potential ancillary benefits of a preventive chemotherapy strategy that targets STHs in areas where opisthorchiasis is co-endemic.

Clinical Trial Registration

Current Controlled Trials ISRCTN29126001     

Plasmodium vivax and mixed infections are associated with severe malaria in children: a prospective cohort study from Papua New Guinea

Background

Severe malaria (SM) is classically associated with Plasmodium falciparum infection. Little information is available on the contribution of P. vivax to severe disease. There are some epidemiological indications that P. vivax or mixed infections protect against complications and deaths. A large morbidity surveillance conducted in an area where the four species coexist allowed us to estimate rates of SM among patients infected with one or several species.

Methods and Findings

This was a prospective cohort study conducted within the framework of the Malaria Vaccine Epidemiology and Evaluation Project. All presumptive malaria cases presenting at two rural health facilities over an 8-y period were investigated with history taking, clinical examination, and laboratory assessment. Case definition of SM was based on the World Health Organization (WHO) criteria adapted for the setting (i.e., clinical diagnosis of malaria associated with asexual blood stage parasitaemia and recent history of fits, or coma, or respiratory distress, or anaemia [haemoglobin < 5 g/dl]). Out of 17,201 presumptive malaria cases, 9,537 (55%) had a confirmed Plasmodium parasitaemia. Among those, 6.2% (95% confidence interval [CI] 5.7%–6.8%) fulfilled the case definition of SM, most of them in children <5 y. In this age group, the proportion of SM was 11.7% (10.4%–13.2%) for P. falciparum, 8.8% (7.1%–10.7%) for P. vivax, and 17.3% (11.7%–24.2%) for mixed P. falciparum and P. vivax infections. P. vivax SM presented more often with respiratory distress than did P. falciparum (60% versus 41%, p = 0.002), but less often with anaemia (19% versus 41%, p = 0.0001).

Conclusion

P. vivax monoinfections as well as mixed Plasmodium infections are associated with SM. There is no indication that mixed infections protected against SM. Interventions targeted toward P. falciparum only might be insufficient to eliminate the overall malaria burden, and especially severe disease, in areas where P. falciparum and P. vivax coexist.