Comparative Assessment of Health Benefits of Praziquantel Treatment of Urogenital Schistosomiasis in Preschool and Primary School-Aged Children

Schistosomiasis is a major public health problem in Africa. However, it is only recently that its burden has become recognised as a significant component impacting on the health and development of preschool-aged children. A longitudinal study was conducted in Zimbabwean children to determine the effect of single praziquantel treatment on Schistosoma haematobium-related morbidity markers: microhaematuria, proteinuria, and albuminuria. Changes in these indicators were compared in 1–5 years versus 6–10 years age groups to determine if treatment outcomes differed by age. Praziquantel was efficacious at reducing infection 12 weeks after treatment: cure rate = 94.6% (95% CI: 87.9–97.7%). Infection rates remained lower at 12 months after treatment compared to baseline in both age groups. Among treated children, the odds of morbidity at 12 weeks were significantly lower compared to baseline for proteinuria: odds ratio (OR) = 0.54 (95% CI: 0.31–0.95) and albuminuria: OR = 0.05 (95% CI: 0.02–0.14). Microhaematuria significantly reduced 12 months after treatment, and the effect of treatment did not differ by age group: OR = 0.97 (95% CI: 0.50–1.87). In conclusion, praziquantel treatment has health benefits in preschool-aged children exposed to S. haematobium and its efficacy on infection and morbidity is not age-dependent

Drastic reduction in density of Blattella germanica and Periplaneta americana cockroaches after the application of fenitrothion and lindane in Dema, Zimbabwe

Field studies were conducted in villages near the peri urban Dema area, Seke district, Zimbabwe, in order to understand the effect of the insecticides fenitrothion and lindane on Periplaneta americana and Blattella germanica cockroaches. A total of 63, 72 and 71 rooms were used for control, fenitrothion and lindane respectively. The mean density per room for P. americana before spraying was 43.5, 42.7 and 44.1 for the control, fenitrothion and lindane respectively. The mean density per room for B. germanica before spraying was 51.4, 50.2 and 47.1 for the control, fenitrothion and lindane respectively. A reduction in population density of P. americana was 3.2%, 83.8% and 99.3% in the control, fenitrothion and lindane rooms respectively. A reduction in population density of B. germanica was 87.8% and 82.8% in fenitrothion and lindane rooms respectively. An increase of 9.9% in the control rooms was observed. The majority of P. americana cockroaches died one month post spray with fenitrothion killing 78.2% and lindane 37.4% of all cockroach collections. However, the number of dead B. germanica cockroaches was almost of the same order for fenitrothion (71.9%) and lindane (74.5%). The residual effect of fenitrothion was 3 months on both cockroach nymph species and that of lindane was 1 month. In conclusion, both fenitrothion and lindane had impact on cockroach density, and fenitrothion showed a residual effect of 3 months

Knock down and insecticidal activity of the plants Tagetes minuta, Lippia javanica, Lantana camara, Tagetes erecta and Eucalyptus grandis on Anopheles arabiensis mosquitoes

The knock down and insecticidal effects of the plants Tagetes minuta, Lippia javanica, Lantana camara, Tagetes erecta and Eucalyptus grandis were evaluated against Anopheles arabiensis mosquitoes in thatched round huts in Mumurwi village. Leaves from these plants were smouldered in order to provide mosquito repellent smoke. Complete knock down was provided 40 minutes after mosquitoes were exposed to smoke of T. erecta, 60 minutes to smoke of T. minuta and E. grandis and 120 minutes to smoke of L. javanica. Complete knock down of mosquitoes could not be provided by L. camara within the 140-minute exposure period. The KT50 (time required to knock down 50% of the mosquitoes) values were 24.985 minutes (T. minuta), 34.473 minutes (T. erecta), 59.119 minutes (L. javanica), 59.828 minutes (L. camara) and 25.245 minutes (E. grandis). The KT90 (time required to knock down 90% of the mosquitoes) values were 48.060 minutes (T. minuta), 50.169 minutes (T. erecta), 178.341 minutes (L. javanica), 140.220 minutes (L. camara) and 47.998 minutes (E. grandis). Mortality rates 24h after exposure were 40% (T. minuta), 100% (T. erecta), 75% (L. javanica), 90% (L. camara) and 100% (E. grandis). In conclusion, smoke from the plants T. erecta, T. minuta and E. grandis had very fast knock down rates with T. erecta, L. camara and E. grandis killing over 90% of the An. arabiensis mosquitoes. Plant smoke is important in mosquito control

Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity

Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way through infection prior to pregnancy can alter their immune response, with major consequences for offspring health and survival. In untreated maternal infections, maternally transferred protection suppressed parasitaemia and reduced pup mortality by 75 per cent compared with pups from naïve dams. However, when dams were treated with anti-malarial drugs, pups received fewer maternal antibodies, parasitaemia was only marginally suppressed, and mortality risk was 25 per cent higher than for pups from dams with full infections. We observed the same qualitative patterns across three different host strains and two parasite genotypes. This study reveals the role that within-host infection dynamics play in the fitness consequences of maternally transferred immunity. Furthermore, it highlights a potential trade-off between the health of mothers and offspring suggesting that anti-parasite treatment may significantly affect the outcome of infection in newborns

Identifying and evaluating field indicators of urogenital schistosomiasis-related morbidity in preschool-aged children

BACKGROUND:Several studies have been conducted quantifying the impact of schistosome infections on health and development in school-aged children. In contrast, relatively little is known about morbidity levels in preschool-aged children (≤ 5 years) who have been neglected in terms of schistosome research and control. The aim of this study was to compare the utility of available point-of-care (POC) morbidity diagnostic tools in preschool versus primary school-aged children (6-10 years) and determine markers which can be used in the field to identify and quantify Schistosoma haematobium-related morbidity. METHODS/PRINCIPAL FINDINGS:A comparative cross-sectional study was conducted to evaluate the performance of currently available POC morbidity diagnostic tools on Zimbabwean children aged 1-5 years (n=104) and 6-10 years (n=194). Morbidity was determined using the POC diagnostics questionnaire-based reporting of haematuria and dysuria, clinical examination, urinalysis by dipsticks, and urine albumin-to-creatinine ratio (UACR). Attributable fractions were used to quantify the proportion of morbidity attributable to S. haematobium infection. Based on results of attributable fractions, UACR was identified as the most reliable tool for detecting schistosome-related morbidity, followed by dipsticks, visual urine inspection, questionnaires, and lastly clinical examination. The results of urine dipstick attributes showed that proteinuria and microhaematuria accounted for most differences between schistosome egg-positive and negative children (T=-50.1; p<0.001). These observations were consistent in preschool vs. primary school-aged children. CONCLUSIONS/SIGNIFICANCE:Preschool-aged children in endemic areas can be effectively screened for schistosome-related morbidity using the same currently available diagnostic tools applicable to older children. UACR for detecting albuminuria is recommended as the best choice for rapid assessment of morbidity attributed to S. haematobium infection in children in the field. The use of dipstick microhaematuria and proteinuria as additional indicators of schistosome-related morbidity would improve the estimation of disease burden in young children

Characterisation of tetraspanins from Schistosoma haematobium and evaluation of their potential as novel diagnostic markers

Schistosoma haematobium is the leading cause of urogenital schistosomiasis and it is recognised as a class 1 carcinogen due to the robust association of infection with bladder cancer. In schistosomes, tetraspanins (TSPs) are abundantly present in different parasite proteomes and could be potential diagnostic candidates due to their accessibility to the host immune system. The large extracellular loops of six TSPs from the secretome (including the soluble excretory/secretory products, tegument and extracellular vesicles) of S. haematobium (Sh-TSP-2, Sh-TSP-4, Sh-TSP-5, Sh-TSP-6, Sh-TSP-18 and Sh-TSP-23) were expressed in a bacterial expression system and polyclonal antibodies were raised to the recombinant proteins to confirm the anatomical sites of expression within the parasite. Sh-TSP-2, and Sh-TSP-18 were identified on the tegument, whereas Sh-TSP-4, Sh-TSP-5, Sh-TSP-6 and Sh-TSP-23 were identified both on the tegument and internal tissues of adult parasites. The mRNAs encoding these TSPs were differentially expressed throughout all schistosome developmental stages tested. The potential diagnostic value of three of these Sh-TSPs was assessed using the urine of individuals (stratified by infection intensity) from an endemic area of Zimbabwe. The three Sh-TSPs were the targets of urine IgG responses in all cohorts, including individuals with very low levels of infection (those positive for circulating anodic antigen but negative for eggs by microscopy). This study provides new antigen candidates to immunologically diagnose S. haematobium infection, and the work presented here provides compelling evidence for the use of a biomarker signature to enhance the diagnostic capability of these tetraspanins

Regulatory and Activated T Cells in Human Schistosoma haematobium Infections

Acquired immunity against helminths is characterised by a complex interplay between the effector Th1 and Th2 immune responses and it slowly manifests with age as a result of cumulative exposure to parasite antigens. Data from experimental models suggest that immunity is also influenced by regulatory T cells (Treg), but as yet studies on Treg in human schistosome infections are limited

Comparing parasitological vs serological determination of Schistosoma haematobium infection prevalence in preschool and primary school-aged children:implications for control programmes

To combat schistosomiasis, the World Health Organization (WHO) recommends that infection levels are determined prior to designing and implementing control programmes, as the treatment regimens depend on the population infection prevalence. However, the sensitivity of the parasitological infection diagnostic method is less reliable when infection levels are low. The aim of this study was to compare levels of Schistosoma haematobium infection obtained by the parasitological method vs serological technique. Infection levels in preschool and primary school-aged children and their implications for control programmes were also investigated. Infection prevalence based on serology was significantly higher compared with that based on parasitology for both age groups. The difference between infection levels obtained using the two methods increased with age. Consequentially, in line with the WHO guidelines, the serological method suggested a more frequent treatment regimen for this population compared with that implied by the parasitological method. These findings highlighted the presence of infection in children aged ⩽5 years, further reiterating the need for their inclusion in control programmes. Furthermore, this study demonstrated the importance of using sensitive diagnostic methods as this has implications on the required intervention controls for the population

Cytokine responses to Schistosoma haematobium in a Zimbabwean population: contrasting profiles for IFN-γ, IL-4, IL-5 and IL-10 with age

<p>Abstract</p> <p>Background</p> <p>The rate of development of parasite-specific immune responses can be studied by following their age profiles in exposed and infected hosts. This study determined the cytokine-age profiles of Zimbabweans resident in a <it>Schistosoma haematobium </it>endemic area and further investigated the relationship between the cytokine responses and infection intensity.</p> <p>Methods</p> <p>Schistosome adult worm antigen-specific IFN-γ, IL-4, IL-5 and IL-10 cytokine responses elicited from whole blood cultures were studied in 190 Zimbabweans exposed to <it>S. haematobium </it>infection (aged 6 to 40 years old). The cytokines were measured using capture ELISAs and the data thus obtained together with <it>S. haematobium </it>egg count data from urine assays were analysed using a combination of parametric and nonparametric statistical approaches.</p> <p>Results</p> <p>Age profiles of schistosome infection in the study population showed that infection rose to peak in childhood (11–12 years) followed by a sharp decline in infection intensity while prevalence fell more gradually. Mean infection intensity was 37 eggs/10 ml urine (SE 6.19 eggs/10 ml urine) while infection prevalence was 54.7%. Measurements of parasite-specific cytokine responses showed that IL-4, IL-5 and IL-10 but not IFN-γ followed distinct age-profiles. Parasite-specific IL-10 production developed early, peaking in the youngest age group and declining thereafter; while IL-4 and IL-5 responses were slower to develop with a later peak. High IL-10 producers were likely to be egg positive with IL-10 production increasing with increasing infection intensity. Furthermore people producing high levels of IL-10 produced little or no IL-5, suggesting that IL-10 may be involved in the regulation of IL-5 levels. IL-4 and IFN-γ did not show a significant relationship with infection status or intensity and were positively associated with each other.</p> <p>Conclusion</p> <p>Taken together, these results show that the IL-10 responses develop early compared to the IL-5 response and may be down-modulating immunopathological responses that occur during the early phase of infection. The results further support current suggestions that the Th1/Th2 dichotomy does not sufficiently explain susceptibility or resistance to schistosome infection.</p