Michelle C. Stanton

Soil Dust Aerosols and Wind as Predictors of Seasonal Meningitis Incidence in Niger

Background: Epidemics of meningococcal meningitis are concentrated in sub-Saharan Africa during the dry season, a period when the region is affected by the Harmattan, a dry and dusty northeasterly trade wind blowing from the Sahara into the Gulf of Guinea. Objectives: We examined the potential of climate-based statistical forecasting models to predict seasonal incidence of meningitis in Niger at both the national and district levels. Data and methods: We used time series of meningitis incidence from 1986 through 2006 for 38 districts in Niger. We tested models based on data that would be readily available in an operational framework, such as climate and dust, population, and the incidence of early cases before the onset of the meningitis season in January–May. Incidence was used as a proxy for immunological state, susceptibility, and carriage in the population. We compared a range of negative binomial generalized linear models fitted to the meningitis data. Results: At the national level, a model using early incidence in December and averaged November–December zonal wind provided the best fit (pseudo-R2 = 0.57), with zonal wind having the greatest impact. A model with surface dust concentration as a predictive variable performed indistinguishably well. At the district level, the best spatiotemporal model included zonal wind, dust concentration, early incidence in December, and population density (pseudo-R2 = 0.41). Conclusions: We showed that wind and dust information and incidence in the early dry season predict part of the year-to-year variability of the seasonal incidence of meningitis at both national and district levels in Niger. Models of this form could provide an early-season alert that wind, dust, and other conditions are potentially conducive to an epidemic. Citation: Pérez García-Pando C, Stanton MC, Diggle PJ, Trzaska S, Miller RL, Perlwitz JP, Baldasano JM, Cuevas E, Ceccato P, Yaka P, Thomson MC. 2014. Soil dust aerosols and wind as predictors of seasonal meningitis incidence in Niger. Environ Health Perspect 122:679–686; http://dx.doi.org/10.1289/ehp.1306640

Diagnostics for schistosomiasis in Africa and Arabia: a review of present options in control and future needs for elimination.

Within the World Health Organization 2012-2020 roadmap for control and elimination of schistosomiasis, the scale-up of mass drug administration with praziquantel is set to change the epidemiological landscape across Africa and Arabia. Central in measuring progress is renewed emphasis upon diagnostics which operate at individual, community and environmental levels by assessing reductions in disease, infections and parasite transmission. However, a fundamental tension is revealed between levels for present diagnostic tools, and methods applied in control settings are not necessarily adequate for application in elimination scenarios. Indeed navigating the transition from control to elimination needs careful consideration and planning. In the present context of control, we review current options for diagnosis of schistosomiasis at different levels, highlighting several strengths and weaknesses therein. Future challenges in elimination are raised and we propose that more cost-effective diagnostics and clinical staging algorithms are needed. Using the Kingdom of Saudi Arabia as a contemporary example, embedding new diagnostic methods within the primary care health system is discussed with reference to both urogenital and intestinal schistosomiasis.

Soil transmitted helminths and scabies in Zanzibar, Tanzania following mass drug administration for lymphatic filariasis--a rapid assessment methodology to assess impact

BackgroundIvermectin and albendazole are used in annual mass drug administration (MDA) for the lymphatic filariasis elimination programmes in African countries co-endemic for onchocerciasis, but have additional impact on soil transmitted helminths and the ectoparasitic mite which causes scabies. Assessing these collateral impacts at scale is difficult due to the insensitivity of available parasite detection techniques.MethodsThe numbers of cases diagnosed with intestinal helminths and scabies and who received prescriptions for treatment were evaluated in 50 health centres in Zanzibar. Records were examined from 2000, prior to the initiation of MDA to 2005, after six rounds of MDA for lymphatic filariasis had taken place.ResultsHealth centre records showed a consistent decline in the number of cases of intestinal helminths and scabies diagnosed by community health workers in Zanzibar and the number of prescriptions issued across five age groups. A 90-98% decline in soil transmitted helminths and 68-98% decline in scabies infections were recorded. Poisson regression models aggregated to both the island-level and district-level indicated that the decline was statistically significant.ConclusionsThe described method of examining health centre records has the potential for use on a large scale, despite limitations, as a rapid method to evaluate the impacts resulting from both lymphatic filariasis and onchocerciasis MDA. This would result in a reduction in the need for parasitological evaluations to determine prevalence and intensity.

Population Pharmacokinetics and Pharmacodynamics of Praziquantel in Ugandan Children with Intestinal Schistosomiasis: Higher Dosages Are Required for Maximal Efficacy

ABSTRACT Each year, millions of African children receive praziquantel (PZQ) by mass drug administration (MDA) to treat schistosomiasis at a standard single dose of 40 mg/kg of body weight, a direct extrapolation from studies of adults. A higher dose of 60 mg/kg is also acceptable for refractory cases. We conducted the first PZQ pharmacokinetic (PK) and pharmacodynamic (PD) study in young children comparing dosing. Sixty Ugandan children aged 3 to 8 years old with egg patent Schistosoma mansoni received PZQ at either 40 mg/kg or 60 mg/kg. PK parameters of PZQ racemate and enantiomers (R and S) were quantified. PD outcomes were assessed by standard fecal egg counts and novel schistosome-specific serum (circulating anodic antigen [CAA]) and urine (circulating cathodic antigen [CCA]) antigen assays. Population PK and PD analyses were performed to estimate drug exposure in individual children, and the relationship between drug exposure and parasitological cure was estimated using logistic regression. Monte Carlo simulations were performed to identify better, future dosing regimens. There was marked PK variability between children, but the area under the concentration-time curve (AUC) of PZQ was strongly predictive of the parasitological cure rate (CR). Although no child achieved antigenic cure, which is suggestive of an important residual adult worm burden, higher AUC was associated with greater CAA antigenic decline at 24 days. To optimize the performance of PZQ, analysis of our simulations suggest that higher doses (>60 mg/kg) are needed, particularly in smaller children. IMPORTANCE Schistosomiasis is a neglected tropical disease, typically associated with chronic morbidity, and its control is a global health priority. Praziquantel (PZQ) is the only available antiparasitic drug and is often given out, as a single oral dose (40 mg/kg), to school-aged children by mass drug administration (MDA) schemes operating within preventive chemotherapy campaigns as endorsed by the World Health Organization (WHO). This current strategy has several limitations. (i) It excludes preschool children who can be patently infected. (ii) It delivers PZQ at a dose directly extrapolated from adult pharmacological studies. To address these problems, we conducted the first pharmacokinetic and pharmacodynamic study of young children within an area of Uganda where Schistosoma mansoni is hyperendemic. Our results demonstrate that a higher dose (>60 mg/kg) is required, especially in smaller children, and draw attention to the need for further optimization of PZQ treatment based on schistosome antigenic assays, which are more sensitive to pharmacodynamic markers. Schistosomiasis is a neglected tropical disease, typically associated with chronic morbidity, and its control is a global health priority. Praziquantel (PZQ) is the only available antiparasitic drug and is often given out, as a single oral dose (40 mg/kg), to school-aged children by mass drug administration (MDA) schemes operating within preventive chemotherapy campaigns as endorsed by the World Health Organization (WHO). This current strategy has several limitations. (i) It excludes preschool children who can be patently infected. (ii) It delivers PZQ at a dose directly extrapolated from adult pharmacological studies. To address these problems, we conducted the first pharmacokinetic and pharmacodynamic study of young children within an area of Uganda where Schistosoma mansoni is hyperendemic. Our results demonstrate that a higher dose (>60 mg/kg) is required, especially in smaller children, and draw attention to the need for further optimization of PZQ treatment based on schistosome antigenic assays, which are more sensitive to pharmacodynamic markers.

Schistosomiasis in pre-school-age children and their mothers in Chikhwawa district, Malawi with notes on characterization of schistosomes and snails

BackgroundTo complement ongoing schistosomiasis control within national control programmes (NCPs) that administer praziquantel to school-age children, assessing the risk and extent of schistosomiasis in pre-school-age children (PSAC) is important.MethodsIn June 2012, schistosomiasis in Chikhwawa district, Malawi was assessed across 12 villages examining pre-school-age children (PSAC) and their mothers by serological and parasitological diagnosis, as supplemented with urine-antigen and questionnaire-interview methods. Urinary tract morbidity was inferred by haematuria and albuminuria assays.ResultsIn total, 49.5% (CI95 42.6-56.4) of 208 PSAC and 94.5% (CI95 90.9-98.1) of 165 mothers were seropositive for schistosomiasis, in 2 villages seroprevalence exceeded 75% in PSAC. Egg-patent urogenital and intestinal schistosomiasis was observed; 17.7% (CI95 12.4-23.2) of PSAC and 45.1% (CI95 37.4-52.8) of mothers having active schistosomiasis by parasitological and urine-antigen testing combined. PSAC often had extensive daily water contact and many (~25%) had haematuria and albuminuria. As eggs with an atypical morphology of Schistosoma haematobium were observed, a general selection of schistosome eggs was characterized by DNA barcoding, finding Group I S. haematobium and Group IV and V S. mansoni. Malacological surveys encountered several populations of Bulinus globosus but failed to find Biomphalaria.ConclusionsBoth PSAC and their mothers appear to be at significant risk of schistosomiasis and should be considered for treatment within the NCP of Malawi.

Innovative tools for assessing risks for severe adverse events in areas of overlapping Loa loa and other filarial distributions: the application of micro-stratification mapping

BackgroundThe wide distribution of Loa loa infection (loiasis) throughout the Democratic Republic of Congo (DRC) is a major obstacle to the plans to eliminate onchocerciasis and lymphatic filariasis (LF) because the standard drug regime is dependent on ivermectin, which cannot be used in co-endemic areas due to the risk of severe adverse events (SAEs). A better understanding of the micro-epidemiology, overlapping low and high risk areas, and how they relate to SAEs is critical to ensure safe and effective treatment.FindingsBased on published data from the Bas Congo Province in DRC, this study used geographical information systems (GIS) to re-map and analyse onchocerciasis and loiasis prevalence (<20%, 20 to 40%, >40%) at 144 sites in relation to health district areas reporting SAEs. The new maps highlighted the contrasting patterns of the high prevalence sites, and significant geographical overlap between low onchocerciasis and high loiasis sites. Statistical analyses found that sites with medium to high loiasis prevalence were 10 to 16 times more likely to be in a SAE area than those with low prevalence of loiasis. Sites where both onchocerciasis and loiasis prevalence was >20% were also associated with SAE areas.ConclusionsCollaborative efforts between the national onchocerciasis and LF programmes are critical as plans to scale interventions are moving forward and thus, alternative strategies needed in loiasis co-endemic areas which may include the new L. loa test and treat strategy using the Cellscope, or interventions such as integrated vector management, or anti Wolbachia therapy using doxycycline.

Towards interruption of schistosomiasis transmission in sub-Saharan Africa: developing an appropriate environmental surveillance framework to guide and to support 'end game' interventions.

Schistosomiasis is a waterborne parasitic disease in sub-Saharan Africa, particularly common in rural populations living in impoverished conditions. With the scale-up of preventive chemotherapy, national campaigns will transition from morbidity- to transmission-focused interventions thus formal investigation of actual or expected declines in environmental transmission is needed as ‘end game’ scenarios arise. Surprisingly, there are no international or national guidelines to do so in sub-Saharan Africa. Our article therefore provides an introduction to key practicalities and pitfalls in the development of an appropriate environmental surveillance framework. In this context, we discuss how strategies need to be adapted and tailored to the local level to better guide and support future interventions through this transition. As detection of egg-patent infection in people becomes rare, careful sampling of schistosome larvae in freshwater and in aquatic snails with robust species-specific DNA assays will be required. Appropriate metrics, derived from observed prevalence(s) as compared with predetermined thresholds, could each provide a clearer insight into contamination- and exposure-related dynamics. Application could be twofold, first to certify areas currently free from schistosomiasis transmission or second to red-flag recalcitrant locations where extra effort or alternative interventions are needed.

Estimating Individual-Level Risk in Spatial Epidemiology Using Spatially Aggregated Information on the Population at Risk

We propose a novel alternative to case-control sampling for the estimation of individual-level risk in spatial epidemiology. Our approach uses weighted estimating equations to estimate regression parameters in the intensity function of an inhomogeneous spatial point process, when information on risk-factors is available at the individual level for cases, but only at a spatially aggregated level for the population at risk. We develop data-driven methods to select the weights used in the estimating equations and show through simulation that the choice of weights can have a major impact on efficiency of estimation. We develop a formal test to detect non-Poisson behavior in the underlying point process and assess the performance of the test using simulations of Poisson and Poisson cluster point processes. We apply our methods to data on the spatial distribution of childhood meningococcal disease cases in Merseyside, U.K. between 1981 and 2007.

A Country on the Verge of Malaria Elimination – The Kingdom of Saudi Arabia

Significant headway has been made in the global fight against malaria in the past decade and as more countries enter the elimination phase, attention is now focused on identifying effective strategies to shrink the malaria map. Saudi Arabia experienced an outbreak of malaria in 1998, but is now on the brink of malaria elimination, with just 82 autochthonous cases reported in 2012. A review of published and grey literature was performed to identify the control strategies that have contributed to this achievement. The number of autochthonous malaria cases in Saudi Arabia decreased by 99.8% between 1998 and 2012. The initial steep decline in malaria cases coincided with a rapid scaling up of vector control measures. Incidence continued to be reported at low levels (between 0.01 and 0.1 per 1,000 of the population) until the adoption of artesunate plus sulfadoxine-pyrimethamine as first line treatment and the establishment of a regional partnership for a malaria-free Arabian Peninsula, both of which occurred in 2007. Since 2007, incidence has decreased by nearly an order of magnitude. Malaria incidence is now very low, but a high proportion of imported cases, continued potential for autochthonous transmission, and an increased proportion of cases attributable to Plasmodium vivax all present challenges to Saudi Arabia as they work toward elimination by 2015.

Mapping of Schistosomiasis and Soil-Transmitted Helminths in Namibia: The First Large-Scale Protocol to Formally Include Rapid Diagnostic Tests

Background Namibia is now ready to begin mass drug administration of praziquantel and albendazole against schistosomiasis and soil-transmitted helminths, respectively. Although historical data identifies areas of transmission of these neglected tropical diseases (NTDs), there is a need to update epidemiological data. For this reason, Namibia adopted a new protocol for mapping of schistosomiasis and geohelminths, formally integrating rapid diagnostic tests (RDTs) for infections and morbidity. In this article, we explain the protocol in detail, and introduce the concept of ‘mapping resolution’, as well as present results and treatment recommendations for northern Namibia. Methods/Findings/Interpretation This new protocol allowed a large sample to be surveyed (N = 17 896 children from 299 schools) at relatively low cost (7 USD per person mapped) and very quickly (28 working days). All children were analysed by RDTs, but only a sub-sample was also diagnosed by light microscopy. Overall prevalence of schistosomiasis in the surveyed areas was 9.0%, highly associated with poorer access to potable water (OR = 1.5, P<0.001) and defective (OR = 1.2, P<0.001) or absent sanitation infrastructure (OR = 2.0, P<0.001). Overall prevalence of geohelminths, more particularly hookworm infection, was 12.2%, highly associated with presence of faecal occult blood (OR = 1.9, P<0.001). Prevalence maps were produced and hot spots identified to better guide the national programme in drug administration, as well as targeted improvements in water, sanitation and hygiene. The RDTs employed (circulating cathodic antigen and microhaematuria for Schistosoma mansoni and S. haematobium, respectively) performed well, with sensitivities above 80% and specificities above 95%. Conclusion/Significance This protocol is cost-effective and sensitive to budget limitations and the potential economic and logistical strains placed on the national Ministries of Health. Here we present a high resolution map of disease prevalence levels, and treatment regimens are recommended.