Pascal Magnussen

Strongyloidiasis - the most neglected of the neglected tropical diseases?

Soil-transmitted helminths of the genus Strongyloides (S. fuelleborni and the more prevalent S. stercoralis) are currently believed to infect an estimated 30-100 million people worldwide. The health consequences of S. stercoralis infections range from asymptomatic light infections to chronic symptomatic strongyloidiasis. Uncontrolled multiplication of the parasite (hyperinfection) and potentially life-threatening dissemination of larvae to all internal organs is found among individuals with compromised immune system functions. This paper provides an overview of the current state of the art in relation to diagnostic methods for detecting the infection, the morbidity caused by the infection and the recommended treatment. It further discusses some of the reasons why this infection is so neglected and the consequence of this for the estimated global prevalence. The paper finally points to the gaps in our knowledge and future research needs related to this infection. As Strongyloides infections have the potential to develop into severe disease in certain population subgroups, untreated infections could cause serious problems in the community. Therefore, we need to carefully investigate this parasite in order to develop and implement effective control programmes.

Spatial clustering of malaria and associated risk factors during an epidemic in a highland area of western Kenya

The epidemiology of malaria over small areas remains poorly understood, and this is particularly true for malaria during epidemics in highland areas of Africa, where transmission intensity is low and characterized by acute within and between year variations. We report an analysis of the spatial distribution of clinical malaria during an epidemic and investigate putative risk factors. Active case surveillance was undertaken in three schools in Nandi District, Western Kenya for 10 weeks during a malaria outbreak in May–July 2002. Household surveys of cases and age‐matched controls were conducted to collect information on household construction, exposure factors and socio‐economic status. Household geographical location and altitude were determined using a hand‐held geographical positioning system and landcover types were determined using high spatial resolution satellite sensor data. Among 129 cases identified during the surveillance, which were matched to 155 controls, we identified significant spatial clusters of malaria cases as determined using the spatial scan statistic. Conditional multiple logistic regression analysis showed that the risk of malaria was higher in children who were underweight, who lived at lower altitudes, and who lived in households where drugs were not kept at home.

The contribution of hookworm and other parasitic infections to haemoglobin and iron status among children and adults in western Kenya

A cross-sectional study of 729 children and adults in western Kenya investigated the impact of infection with hookworm, Ascaris lumbricoides, Trichuris trichiura, Schistosoma mansoni and malaria on iron status. In bivariate analyses, hookworm intensities as low as 300 eggs/g of faeces were negatively related to levels of haemoglobin (Hb) and serum ferritin (SF). Malaria parasitaemia was negatively related to Hb and positively related to SF, while S. mansoni intensities were negatively related to SF. Multivariate regression analysis was done to identify predictors of Hb and SF levels. In children, age (in years) was the only predictor for Hb (B = 1.7 g/L) and only malaria parasitaemia (negative, light, moderate, heavy) was retained in the model for log10 SF (B = 0.097 microgram/L). In adults, hookworm infection and malaria parasitaemia together with age, sex, pregnancy, SF levels < 12 micrograms/L and elevated body temperature were significant predictors of low Hb. The regression coefficient for hookworm egg count (for increments of 100 eggs/g) was -1.3 g/L. Significant interactions between sex and age and between sex and malaria parasitaemia were revealed. Age and malaria parasitaemia were significant predictors only among females, with a regression coefficient for malaria parasitaemia of -6.9 g/L. The regression coefficient for hookworm did not change when SF < 12 micrograms/L was taken out of the model, indicating that the effect of hookworm cannot be explained by low iron stores alone. Using SF as the dependent variable, hookworm and S. mansoni intensities together with age and sex were retained in the model. The regression coefficients for hookworm egg count (increments of 100 eggs/g) and S. mansoni egg count (increments of 10 eggs/g) were -0.011 microgram/L and -0.012 microgram/L, respectively. Iron deficiency was a problem in this population and hookworm infections contributed significantly to this situation.

Management of Patients with Lymphoedema Caused by Filariasis in North-eastern Tanzania

Summary Background Lymphatic filariasis is a widely distributed tropical disease with around 120 million people infected worldwide. It is caused by the organism Wuchereria bancrofti, a worm that lives in and causes malfunction of the human lymphatic system and is transmitted by mosquitoes in warm and humid climates. Most infected individuals have no symptoms, but some 44 million people have lymphoedema of the upper or lower limb, breast, scrotum or genitals, or hydrocele, the latter being the most common chronic manifestation. In most countries, there is no available treatment for chronic lymphoedema. Method In the north-eastern part of Tanzania a lymphoedema clinic was established. A subset of patients received either complex decongestive physiotherapy carried out either by a physiotherapist or by the patients themselves under supervision of the physiotherapist. Forty-six patients (with 59 lymphoedematous legs) were treated and followed for nine months. All patients were instructed in hygiene, elevation and exercises for the affected limb. Results Both groups had significant reduction in leg volumes (P Conclusion Giving more responsibility to patients in the handling of lymph drainage and bandaging resulted in a greater sustained reduction in leg volume than in the group where the patients were not taught to do the treatment themselves. Following initial treatment, adherence to the programme and follow-up was limited by the impracticality of the compressive stockings and their tendency to deteriorate rapidly due to harsh environments.

Earth-eating and reinfection with intestinal helminths among pregnant and lactating women in western Kenya

We conducted a longitudinal study among 827 pregnant women in Nyanza Province, western Kenya, to determine the effect of earth‐eating on geohelminth reinfection after treatment. The women were recruited at a gestational age of 14–24 weeks (median: 17) and followed up to 6 months postpartum. The median age was 23 (range: 14–47) years, the median parity 2 (range: 0–11). After deworming with mebendazole (500 mg, single dose) of those found infected at 32 weeks gestation, 700 women were uninfected with Ascaris lumbricoides, 670 with Trichuris trichiura and 479 with hookworm. At delivery, 11.2%, 4.6% and 3.8% of these women were reinfected with hookworm, T. trichiura and A. lumbricoides respectively. The reinfection rate for hookworm was 14.8%, for T. trichiura 6.65, and for A. lumbricoides 5.2% at 3 months postpartum, and 16.0, 5.9 and 9.4% at 6 months postpartum. There was a significant difference in hookworm intensity at delivery between geophagous and non‐geophagous women (P = 0.03). Women who ate termite mound earth were more often and more intensely infected with hookworm at delivery than those eating other types of earth (P = 0.07 and P = 0.02 respectively). There were significant differences in the prevalence of A. lumbricoides between geophagous and non‐geophagous women at 3 (P = 0.001) and at 6 months postpartum (P = 0.001). Women who ate termite mound earth had a higher prevalence of A. lumbricoides, compared with those eating other kinds of earth, at delivery (P = 0.02), 3 months postpartum (P = 0.001) and at 6 months postpartum (P = 0.001). The intensity of infections with T. trichiura at 6 months postpartum was significantly different between geophagous and non‐geophagous women (P = 0.005). Our study shows that geophagy is associated with A. lumbricoides reinfection among pregnant and lactating women and that intensities built up more rapidly among geophagous women. Geophagy might be associated with reinfection with hookworm and T. trichiura, although these results were less unequivocal. These findings call for increased emphasis, in antenatal care, on the potential risks of earth‐eating, and for deworming of women after delivery.

Efficacy of chloroquine, amodiaquine, sulphadoxine–pyrimethamine and combination therapy with artesunate in Mozambican children with non‐complicated malaria

This paper reports a two‐phase study in Manhiça district, Mozambique: first we assessed the clinical efficacy and parasitological response of Plasmodium falciparum to chloroquine (CQ), sulphadoxine–pyrimethamine (SP) and amodiaquine (AQ), then we tested the safety and efficacy in the treatment of uncomplicated malaria, of three combinations: AQ + SP, artesunate (AR) + SP and AQ + AR. Based on the WHO (1996, WHO/MAL/96.1077) in vivo protocol, we conducted two open, randomized, clinical trials. Children aged 6–59 months with axillary body temperature ≥37.5 °C and non‐complicated malaria were randomly allocated to treatment groups and followed up for 21 days (first and second trial) and 28 days (first trial). The therapeutic efficacy of AQ (91.6%) was better than that of SP (82.7%) and CQ (47.1%). After 14 days, 69% of the strains were parasitologically resistant to CQ, 21.4% to SP and 26% to AQ. Co‐administration of AQ + SP, AR + SP and AQ + AR was safe and had 100% clinical efficacy at 14‐day follow‐up. The combination therapies affected rapid fever clearance time and reduced the incidence of gametocytaemia during follow‐up.

Prevention of anaemia in pregnancy using insecticide-treated bednets and sulfadoxine-pyrimethamine in a highly malarious area of Kenya: a randomized controlled trial

To compare the effects of intermittent treatment with sulfadoxine-pyrimethamine (SP) given during the second and third trimester of pregnancy, the use of insecticide-treated nets (ITN), or the combination of both on haemoglobin (Hb) levels during pregnancy, a randomized, placebo-controlled intervention trial was conducted in a malaria-endemic area of western Kenya from July 1997 to September 1999. Primigravidae and secundigravidae were enrolled into the study and randomized into 4 intervention groups: (i) ITNs and SP, (ii) ITNs and placebo SP, (iii) SP alone, and (iv) placebo SP. All groups were offered case management and iron and folic acid supplementation. Seven hundred and fifty-two women were followed until delivery (53.2% were primigravidae and 46.8% secundigravidae). Among primigravidae in all the groups there was a significant improvement in Hb levels at delivery (107.6 g/L) compared with recruitment (101.9 g/L) (P < 0.006) with the greatest improvement in the combination ITNs + SP group. The protective efficacy of ITNs + SP on anaemia was 55.8% (95% CI 30.6-71.8), of SP alone 50.9% (95% CI 22.2-69.0), and of ITNs 41.6% (95% CI 9.8-62.3). Among secundigravidae, Hb levels were slightly lower at delivery compared with recruitment (P = 0.03). It was concluded that malaria is a major cause of anaemia in primigravidae but that other causes play a more significant role in secundigravidae, and that intermittent treatment with SP or use of ITNs benefits primigravidae more than secundigravidae.

Patterns of Schistosoma haematobium infection, impact of praziquantel treatment and re-infection after treatment in a cohort of schoolchildren from rural KwaZulu-Natal/South Africa

BackgroundSchistosomiasis is one of the major health problems in tropical and sub-tropical countries, with school age children usually being the most affected group. In 1998 the Department of Health of the province of KwaZulu-Natal established a pilot programme for helminth control that aimed at regularly treating primary school children for schistosome and intestinal helminth infections. This article describes the baseline situation and the impact of treatment on S. haematobium infection in a cohort of schoolchildren attending grade 3 in a rural part of the province.MethodsPrimary schoolchildren from Maputaland in northern KwaZulu-Natal were examined for Schistosoma haematobium infection, treated with praziquantel and re-examined four times over one year after treatment in order to assess the impact of treatment and patterns of infection and re-infection.ResultsPraziquantel treatment was highly efficacious at three weeks after treatment when judged by egg reduction rate (95.3%) and cure rate of heavy infections (94.1%). The apparent overall cure rate three weeks after treatment (57.9%) was much lower but improved to 80.7% at 41 weeks after treatment. Re-infection with S. haematobium was low and appeared to be limited to the hot and rainy summer. Analysis of only one urine specimen per child considerably underestimated prevalence when compared to the analysis of two specimens, but both approaches provided similar estimates of the proportion of heavy infections and of average infection intensity in the population.ConclusionAccording to WHO guidelines the high prevalence and intensity of S. haematobium infection necessitate regular treatment of schoolchildren in the area. The seasonal transmission pattern together with the slow pace of re-infection suggest that one treatment per year, applied after the end of summer, is sufficient to keep S. haematobium infection in the area at low levels.

Are rapid diagnostic tests more accurate in diagnosis of plasmodium falciparum malaria compared to microscopy at rural health centres

BackgroundPrompt, accurate diagnosis and treatment with artemisinin combination therapy remains vital to current malaria control. Blood film microscopy the current standard test for diagnosis of malaria has several limitations that necessitate field evaluation of alternative diagnostic methods especially in low income countries of sub-Saharan Africa where malaria is endemic.MethodsThe accuracy of axillary temperature, health centre (HC) microscopy, expert microscopy and a HRP2-based rapid diagnostic test (Paracheck) was compared in predicting malaria infection using polymerase chain reaction (PCR) as the gold standard. Three hundred patients with a clinical suspicion of malaria based on fever and or history of fever from a low and high transmission setting in Uganda were consecutively enrolled and provided blood samples for all tests. Accuracy of each test was calculated overall with 95% confidence interval and then adjusted for age-groups and level of transmission intensity using a stratified analysis. The endpoints were: sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). This study is registered with Clinicaltrials.gov, NCT00565071.ResultsOf the 300 patients, 88(29.3%) had fever, 56(18.7%) were positive by HC microscopy, 47(15.7%) by expert microscopy, 110(36.7%) by Paracheck and 89(29.7%) by PCR. The overall sensitivity >90% was only shown by Paracheck 91.0% [95%CI: 83.1-96.0]. The sensitivity of expert microscopy was 46%, similar to HC microscopy. The superior sensitivity of Paracheck compared to microscopy was maintained when data was stratified for transmission intensity and age. The overall specificity rates were: Paracheck 86.3% [95%CI: 80.9-90.6], HC microscopy 93.4% [95%CI: 89.1-96.3] and expert microscopy 97.2% [95%CI: 93.9-98.9]. The NPV >90% was shown by Paracheck 95.8% [95%CI: 91.9-98.2]. The overall PPV was <88% for all methods.ConclusionThe HRP2-based RDT has shown superior sensitivity compared to microscopy in diagnosis of malaria and may be more suitable for screening of malaria infection.

Effects on serum retinol of multi-micronutrient supplementation and multi-helminth chemotherapy: a randomised, controlled trial in Kenyan school children.

Objective: To assess the effects of multi-micronutrient supplementation and multi-helminth chemotherapy on haemoglobin concentration (Hb), using schools as a health delivery system.Study area and population: Nine hundred seventy-seven children between 9 and 18 y of age from 19 primary schools in Bondo District, western Kenya, were included in the trial. The 746 (76.4%) children on whom baseline Hb was available were included in this study.Design: The study was a randomized, placebo-controlled, double-blind, two-by-two factorial trial of the effects of multi-micronutrient supplementation and multi-helminth chemotherapy on Hb after 8 months.Interventions: Single treatment of infected children with albendazole (600 mg) for geohelminths and praziquantel (40 mg/kg) for Schistosoma mansoni and daily supplementation with 13 micronutrients.Results: Multi-micronutrient supplementation (3.5 g/l, 95% CI 1.7, 5.3; P=0.0002) and anthelminthic treatment (2.0 g/l, 95% CI 0.2, 3.9; P=0.03) increased Hb independently (interaction, P=0.33). The effects were also independent of baseline Hb and general nutritional status. The treatment effect was due to reductions in S. mansoni and hookworm intensities of infection, in that Hb increased by 0.4 and 0.2 g/l, respectively, per 100 epg reductions in egg output. Interestingly, among S. mansoni-infected children, the effect of treatment seemed stronger in those with compared to those without co-existing malaria parasitaemia (interaction, P=0.09).Conclusion: Multi-micronutrient supplementation and multi-helminth chemotherapy increased Hb among school children, irrespective of initial Hb and nutritional status.Sponsorship: The Danish International Development Assistance.