Impact of artemisinin-based combination therapy and insecticide-treated nets on malaria burden in Zanzibar

Background

The Roll Back Malaria strategy recommends a combination of interventions for malaria control. Zanzibar implemented artemisinin-based combination therapy (ACT) for uncomplicated malaria in late 2003 and long-lasting insecticidal nets (LLINs) from early 2006. ACT is provided free of charge to all malaria patients, while LLINs are distributed free to children under age 5 y (“under five”) and pregnant women. We investigated temporal trends in Plasmodium falciparum prevalence and malaria-related health parameters following the implementation of these two malaria control interventions in Zanzibar.

Methods and Findings

Cross-sectional clinical and parasitological surveys in children under the age of 14 y were conducted in North A District in May 2003, 2005, and 2006. Survey data were analyzed in a logistic regression model and adjusted for complex sampling design and potential confounders. Records from all 13 public health facilities in North A District were analyzed for malaria-related outpatient visits and admissions. Mortality and demographic data were obtained from District Commissioner''s Office. P. falciparum prevalence decreased in children under five between 2003 and 2006; using 2003 as the reference year, odds ratios (ORs) and 95% confidence intervals (CIs) were, for 2005, 0.55 (0.28–1.08), and for 2006, 0.03 (0.00–0.27); p for trend < 0.001. Between 2002 and 2005 crude under-five, infant (under age 1 y), and child (aged 1–4 y) mortality decreased by 52%, 33%, and 71%, respectively. Similarly, malaria-related admissions, blood transfusions, and malaria-attributed mortality decreased significantly by 77%, 67% and 75%, respectively, between 2002 and 2005 in children under five. Climatic conditions favorable for malaria transmission persisted throughout the observational period.

Conclusions

Following deployment of ACT in Zanzibar 2003, malaria-associated morbidity and mortality decreased dramatically within two years. Additional distribution of LLINs in early 2006 resulted in a 10-fold reduction of malaria parasite prevalence. The results indicate that the Millennium Development Goals of reducing mortality in children under five and alleviating the burden of malaria are achievable in tropical Africa with high coverage of combined malaria control interventions.     

Malaria rapid testing by community health workers is effective and safe for targeting malaria treatment: randomised cross-over trial in Tanzania

Background

Early diagnosis and prompt, effective treatment of uncomplicated malaria is critical to prevent severe disease, death and malaria transmission. We assessed the impact of rapid malaria diagnostic tests (RDTs) by community health workers (CHWs) on provision of artemisinin-based combination therapy (ACT) and health outcome in fever patients.

Methodology/Principal Findings

Twenty-two CHWs from five villages in Kibaha District, a high-malaria transmission area in Coast Region, Tanzania, were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis (CD) only. Each CHW was randomly assigned to use either RDT or CD the first week and thereafter alternating weekly. Primary outcome was provision of ACT and main secondary outcomes were referral rates and health status by days 3 and 7. The CHWs enrolled 2930 fever patients during five months of whom 1988 (67.8%) presented within 24 hours of fever onset. ACT was provided to 775 of 1457 (53.2%) patients during RDT weeks and to 1422 of 1473 (96.5%) patients during CD weeks (Odds Ratio (OR) 0.039, 95% CI 0.029–0.053). The CHWs adhered to the RDT results in 1411 of 1457 (96.8%, 95% CI 95.8–97.6) patients. More patients were referred on inclusion day during RDT weeks (10.0%) compared to CD weeks (1.6%). Referral during days 1–7 and perceived non-recovery on days 3 and 7 were also more common after RDT aided diagnosis. However, no fatal or severe malaria occurred among 682 patients in the RDT group who were not treated with ACT, supporting the safety of withholding ACT to RDT negative patients.

Conclusions/Significance

RDTs in the hands of CHWs may safely improve early and well-targeted ACT treatment in malaria patients at community level in Africa.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00301015","term_id":"NCT00301015"}}NCT00301015     

The global impact of income inequality on health by age: an observational study

Objectives To explore whether the apparent impact of income inequality on health, which has been shown for wealthier nations, is replicated worldwide, and whether the impact varies by age.Design Observational study. Setting 126 countries of the world for which complete data on income inequality and mortality by age and sex were available around the year 2002 (including 94.4% of world human population).Data sources Data on mortality were from the World Health Organization and income data were taken from the annual reports of the United Nations Development Programme.Main outcome measures Mortality in 5-year age bands for each sex by income inequality and income level.Results At ages 15-29 and 25-39 variations in income inequality seem more closely correlated with mortality worldwide than do variations in material wealth. This relation is especially strong among the poorest countries in Africa. Mortality is higher for a given level of overall income in more unequal nations.Conclusions Income inequality seems to have an influence worldwide, especially for younger adults. Social inequality seems to have a universal negative impact on health.     

Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study

Objective To study the diagnosis and outcomes in people admitted to hospital with a diagnosis of severe malaria in areas with differing intensities of malaria transmission.Design Prospective observational study of children and adults over the course a year.Setting 10 hospitals in north east Tanzania.Participants 17 313 patients were admitted to hospital; of these 4474 (2851 children aged under 5 years) fulfilled criteria for severe disease.Main outcome measure Details of the treatment given and outcome. Altitudes of residence (a proxy for transmission intensity) measured with a global positioning system.Results Blood film microscopy showed that 2062 (46.1%) of people treated for malaria had Plasmodium falciparum (slide positive). The proportion of slide positive cases fell with increasing age and increasing altitude of residence. Among 1086 patients aged ≥ 5 years who lived above 600 metres, only 338 (31.1%) were slide positive, while in children < 5 years living in areas of intense transmission (< 600 metres) most (958/1392, 68.8%) were slide positive. Among 2375 people who were slide negative, 1571 (66.1%) were not treated with antibiotics and of those, 120 (7.6%) died. The case fatality in slide negative patients was higher (292/2412, 12.1%) than for slide positive patients (142/2062, 6.9%) (P < 0.001). Respiratory distress and altered consciousness were the strongest predictors of mortality in slide positive and slide negative patients and in adults as well as children.Conclusions In Tanzania, malaria is commonly overdiagnosed in people presenting with severe febrile illness, especially in those living in areas with low to moderate transmission and in adults. This is associated with a failure to treat alternative causes of severe infection. Diagnosis needs to be improved and syndromic treatment considered. Routine hospital data may overestimate mortality from malaria by over twofold.     

Therapy of uncomplicated falciparum malaria in Europe: MALTHER - a prospective observational multicentre study

ABSTRACT: BACKGROUND: Malaria continues to be amongst the most frequent infectious diseases imported to Europe. Whilst European treatment guidelines are based on data from studies carried out in endemic areas, there is a paucity of original prospective treatment data. The objective was to summarize data on treatments to harmonize and optimize treatment for uncomplicated malaria in Europe. METHODS: A prospective observational multicentre study was conducted, assessing tolerance and efficacy of treatment regimens for imported uncomplicated falciparum malaria in adults amongst European centres of tropical and travel medicine. RESULTS: Between December 2003 and 2009, 504 patients were included in 16 centres from five European countries. Eighteen treatment regimens were reported,, the top three being atovaquone-proguanil, mefloquine, and artemether-lumefantrine. Treatments significantly differed with respect to the occurrence of treatment changes (p=0.005) and adverse events (p=0.001), parasite and fever clearance times (p<0.001), and hospitalization rates (p=0.0066) and durations (p=0.001). Four recrudescences and two progressions to severe disease were observed. Compared to other regimens, quinine alone was associated with more frequent switches to second line treatment, more adverse events and longer inpatient stays. Parasite and fever clearance times were shortest with artemether-mefloquine combination treatment. Vomiting was the most frequent cause of treatment change, occurring in 5.5% of all patients but 9% of the atovaquone-proguanil group. CONCLUSIONS: This study highlights the heterogeneity of standards of care within Europe. A consensus discussion at European level is desirable to foster a standardized management of imported falciparum malaria.     

Effect of malaria in pregnancy on foetal cortical brain development: a longitudinal observational study

ABSTRACT: BACKGROUND: Malaria in pregnancy has a negative impact on foetal growth, but it is not known whether this also affects the foetal nervous system. The aim of this study was to examine the effects of malaria on foetal cortex development by three-dimensional ultrasound. METHODS: Brain images were acquired using a portable ultrasound machine and a 3D ultrasound transducer. All recordings were analysed, blinded to clinical data, using the 4D view software package. The foetal supra-tentorial brain volume was determined and cortical development was qualitatively followed by scoring the appearance and development of six sulci. Multilevel analysis was used to study brain volume and cortical development in individual foetuses, RESULTS: Cortical grading was possible in 161 out of 223 (72%) serial foetal brain images in pregnant women living in a malaria endemic area. There was no difference between foetal cortical development or brain volumes at any time in pregnancy between women with immediately treated malaria infections and non-infected pregnancies. CONCLUSION: The percentage of images that could be graded was similar to other neuro-sonographic studies. Maternal malaria does not have a gross effect on foetal brain development, at least in this population, which had access to early detection and effective treatment of malaria.     

Spatial prediction of malaria prevalence in an endemic area of Bangladesh

Background

Malaria is a major public health burden in Southeastern Bangladesh, particularly in the Chittagong Hill Tracts region. Malaria is endemic in 13 districts of Bangladesh and the highest prevalence occurs in Khagrachari (15.47%).

Methods

A risk map was developed and geographic risk factors identified using a Bayesian approach. The Bayesian geostatistical model was developed from previously identified individual and environmental covariates (p < 0.2; age, different forest types, elevation and economic status) for malaria prevalence using WinBUGS 1.4. Spatial correlation was estimated within a Bayesian framework based on a geostatistical model. The infection status (positives and negatives) was modeled using a Bernoulli distribution. Maps of the posterior distributions of predicted prevalence were developed in geographic information system (GIS).

Results

Predicted high prevalence areas were located along the north-eastern areas, and central part of the study area. Low to moderate prevalence areas were predicted in the southwestern, southeastern and central regions. Individual age and nearness to fragmented forest were associated with malaria prevalence after adjusting the spatial auto-correlation.

Conclusion

A Bayesian analytical approach using multiple enabling technologies (geographic information systems, global positioning systems, and remote sensing) provide a strategy to characterize spatial heterogeneity in malaria risk at a fine scale. Even in the most hyper endemic region of Bangladesh there is substantial spatial heterogeneity in risk. Areas that are predicted to be at high risk, based on the environment but that have not been reached by surveys are identified.

     

Using community-owned resource persons to provide early diagnosis and treatment and estimate malaria burden at community level in north-eastern Tanzania

ABSTRACT: BACKGROUND: Although early diagnosis and prompt treatment is an important strategy for control of malaria, using fever to initiate presumptive treatment with expensive artemisinin combination therapy is a major challenge; particularly in areas with declining burden of malaria. This study was conducted using community-owned resource persons (CORPs) to provide early diagnosis and treatment of malaria, and collect data for estimation of malaria burden in four villages of Korogwe district, north-eastern Tanzania. METHODS: In 2006, individuals with history of fever within 24 hours or fever (axillary temperature [greater than or equal to]37.5degreesC) at presentation were presumptively treated using sulphadoxine/pyrimethamine. Between 2007 and 2010, individuals aged five years and above, with positive rapid diagnostic tests (RDTs) were treated with artemether/lumefantrine (AL) while under-fives were treated irrespective of RDT results. Reduction in anti-malarial consumption was determined by comparing the number of cases that would have been presumptively treated and those that were actually treated based on RDTs results. Trends of malaria incidence and slide positivity rates were compared between lowlands and highlands. RESULTS: Of 15,729 cases attended, slide positivity rate was 20.4% and declined by >72.0% from 2008, reaching <10.0% from 2009 onwards; and the slide positivity rates were similar in lowlands and highlands from 2009 onwards. Cases with fever at presentation declined slightly, but remained at >40.0% in under-fives and >20.0% among individuals aged five years and above. With use of RDTs, cases treated with AL decreased from <58.0% in 2007 to <11.0% in 2010 and the numbers of adult courses saved were 3,284 and 1,591 in lowlands and highlands respectively. Malaria incidence declined consistently from 2008 onwards; and the highest incidence of malaria shifted from children aged <10 years to individuals aged 10-19 years from 2009. CONCLUSIONS: With basic training, supervision and RDTs, CORPs successfully provided early diagnosis and treatment and reduced consumption of anti-malarials. Progressively declining malaria incidence and slide positivity rates suggest that all fever cases should be tested with RDTs before treatment. Data collected by CORPs was used to plan phase 1b MSP3 malaria vaccine trial and will be used for monitoring and evaluation of different health interventions. The current situation indicates that there is a remarkable changing pattern of malaria and these areas might be moving from control to pre-elimination levels.     

A head-to-head comparison of four artemisinin-based combinations for treating uncomplicated malaria in African children: a randomized trial

Background

Artemisinin-based combination therapies (ACTs) are the mainstay for the management of uncomplicated malaria cases. However, up-to-date data able to assist sub-Saharan African countries formulating appropriate antimalarial drug policies are scarce.

Methods and Findings

Between 9 July 2007 and 19 June 2009, a randomized, non-inferiority (10% difference threshold in efficacy at day 28) clinical trial was carried out at 12 sites in seven sub-Saharan African countries. Each site compared three of four ACTs, namely amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL), or chlorproguanil-dapsone-artesunate (CD+A). Overall, 4,116 children 6–59 mo old with uncomplicated Plasmodium falciparum malaria were treated (1,226 with AL, 1,002 with ASAQ, 413 with CD+A, and 1,475 with DHAPQ), actively followed up until day 28, and then passively followed up for the next 6 mo. At day 28, for the PCR-adjusted efficacy, non-inferiority was established for three pair-wise comparisons: DHAPQ (97.3%) versus AL (95.5%) (odds ratio [OR]: 0.59, 95% CI: 0.37–0.94); DHAPQ (97.6%) versus ASAQ (96.8%) (OR: 0.74, 95% CI: 0.41–1.34), and ASAQ (97.1%) versus AL (94.4%) (OR: 0.50, 95% CI: 0.28–0.92). For the PCR-unadjusted efficacy, AL was significantly less efficacious than DHAPQ (72.7% versus 89.5%) (OR: 0.27, 95% CI: 0.21–0.34) and ASAQ (66.2% versus 80.4%) (OR: 0.40, 95% CI: 0.30–0.53), while DHAPQ (92.2%) had higher efficacy than ASAQ (80.8%) but non-inferiority could not be excluded (OR: 0.35, 95% CI: 0.26–0.48). CD+A was significantly less efficacious than the other three treatments. Day 63 results were similar to those observed at day 28.

Conclusions

This large head-to-head comparison of most currently available ACTs in sub-Saharan Africa showed that AL, ASAQ, and DHAPQ had excellent efficacy, up to day 63 post-treatment. The risk of recurrent infections was significantly lower for DHAPQ, followed by ASAQ and then AL, supporting the recent recommendation of considering DHAPQ as a valid option for the treatment of uncomplicated P. falciparum malaria.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00393679","term_id":"NCT00393679"}}NCT00393679; Pan African Clinical Trials Registry PACTR2009010000911750 Please see later in the article for the Editors'' Summary     

Influenza virus in human exhaled breath: an observational study

Background

Recent studies suggest that humans exhale fine particles during tidal breathing but little is known of their composition, particularly during infection.

Methodology/Principal Findings

We conducted a study of influenza infected patients to characterize influenza virus and particle concentrations in their exhaled breath. Patients presenting with influenza-like-illness, confirmed influenza A or B virus by rapid test, and onset within 3 days were recruited at three clinics in Hong Kong, China. We collected exhaled breath from each subject onto Teflon filters and measured exhaled particle concentrations using an optical particle counter. Filters were analyzed for influenza A and B viruses by quantitative polymerase chain reaction (qPCR). Twelve out of thirteen rapid test positive patients provided exhaled breath filter samples (7 subjects infected with influenza B virus and 5 subjects infected with influenza A virus). We detected influenza virus RNA in the exhaled breath of 4 (33%) subjects–three (60%) of the five patients infected with influenza A virus and one (14%) of the seven infected with influenza B virus. Exhaled influenza virus RNA generation rates ranged from <3.2 to 20 influenza virus RNA particles per minute. Over 87% of particles exhaled were under 1 µm in diameter.

Conclusions

These findings regarding influenza virus RNA suggest that influenza virus may be contained in fine particles generated during tidal breathing, and add to the body of literature suggesting that fine particle aerosols may play a role in influenza transmission.     

Widespread distribution of insecticide-impregnated curtains reduces child mortality, prevalence and intensity of malaria infection, and malaria transmission in rural Burkina Faso

The results of the first two years of implementation of a large scale trial of insecticide-treated curtains in Burkina Faso are summarised in this presentation. The trial was conducted in a highly malarious area and involved a population of slightly less than 100,000, distributed in 158 villages over an area of almost 1000 km2. A remarkable impact on entomological parameters (Anopheles density, sporozoite rate, entomological inoculation rate) was accompanied by a relatively modest reduction of parasitological indices (prevalence and density of Plasmodium falciparum). All-cause mortality in children 0.5 to 5 year old showed over two years a 15% decline. The authors believe that the wide surface of the protected zone and the almost total coverage achieved in the intervention villages were the major determinants of the observed reduction of transmission. A conclusive interpretation of the mortality results requires a further follow-up of the study population.     

Neurocognitive outcomes in Malawian children exposed to malaria during pregnancy: An observational birth cohort study

BackgroundAnnually 125 million pregnancies are at risk of malaria infection. However, the impact of exposure to malaria in pregnancy on neurodevelopment in children is not well understood. We hypothesized that malaria in pregnancy and associated maternal immune activation result in neurodevelopmental delay in exposed offspring.Methods and findingsBetween April 2014 and April 2015, we followed 421 Malawian mother–baby dyads (median [IQR] maternal age: 21 [19, 28] years) who were previously enrolled (median [IQR] gestational age at enrollment: 19.7 [17.9, 22.1] weeks) in a randomized controlled malaria prevention trial with 5 or 6 scheduled assessments of antenatal malaria infection by PCR. Children were evaluated at 12, 18, and/or 24 months of age with cognitive tests previously validated in Malawi: the Malawi Developmental Assessment Tool (MDAT) and the MacArthur–Bates Communicative Development Inventories (MCAB-CDI). We assessed the impact of antenatal malaria (n [%] positive: 240 [57.3]), placental malaria (n [%] positive: 112 [29.6]), and maternal immune activation on neurocognitive development in children. Linear mixed-effects analysis showed that children exposed to antenatal malaria between 33 and 37 weeks gestation had delayed language development across the 2-year follow-up, as measured by MCAB-CDI (adjusted beta estimate [95% CI], −7.53 [−13.04, −2.02], p = 0.008). Maternal immune activation, characterized by increased maternal sTNFRII concentration, between 33 and 37 weeks was associated with lower MCAB-CDI language score (adjusted beta estimate [95% CI], −8.57 [−13.09, −4.06], p < 0.001). Main limitations of this study include a relatively short length of follow-up and a potential for residual confounding that is characteristic of observational studies.ConclusionsThis mother–baby cohort presents evidence of a relationship between malaria in pregnancy and neurodevelopmental delay in offspring. Malaria in pregnancy may be a modifiable risk factor for neurodevelopmental injury independent of birth weight or prematurity. Successful interventions to prevent malaria during pregnancy may reduce the risk of neurocognitive delay in children.

Andrea Weckman and co-workers study associations between children’s neurodevelopmental outcomes and malaria in pregnancy.     

Low efficacy rate of moxifloxacin-containing Helicobacter pylori eradication treatment: in an observational study in a Turkish population

BACKGROUND: Standard triple therapy for Helicobacter pylori has an eradication rate of about 50% in Turkey. It may be due to an increased resistance of H. pylori to antibiotics. Therefore, we aimed to investigate the effectiveness of a new second-generation fluoroquinolone, moxifloxacin-containing triple therapy in H. pylori eradication. MATERIAL AND METHODS: This is an open-label, prospective, single-center, pilot study. We studied 71 dyspeptic patients infected with H. pylori diagnosed by both histology and rapid urease test. Out of 71 dyspeptic patients, 64 had non-ulcer dyspepsia and seven had peptic ulcer. Patients received pantoprazole (40 mg b.i.d.) plus moxifloxacin (400 mg/day) and amoxicillin (1000 mg b.i.d.) for 14 days. Eradication was assessed 4 weeks after completing the therapy by histology and rapid urease test. Per-protocol and intention-to-treat eradication rates were determined. RESULTS: The eradication rate was 42.2% for the intention-to-treat analysis and 47.6% for the per-protocol analysis. Of all patients included in the study, 29.5% had side-effects and only 2.8% of the patients discontinued the treatment because of side-effects. Most of the complications were mild and self-limiting. CONCLUSION: Triple therapy with pantoprazole, moxifloxacin, and amoxicillin for 14 days yielded unacceptably low eradication rates. However, using tests of susceptibility to antibiotics, further studies with larger sample sizes are needed to judge these eradication rates of moxifloxacin containing eradication treatment.     

Increased use of malaria rapid diagnostic tests improves targeting of anti-malarial treatment in rural Tanzania: implications for nationwide rollout of malaria rapid diagnostic tests

ABSTRACT: BACKGROUND: The World Health Organization recommends parasitological confirmation of all malaria cases. Tanzania is implementing a phased rollout of malaria rapid diagnostic tests (RDTs) for routine use in all levels of care as one strategy to increase parasitological confirmation of malaria diagnosis. This study was carried out to evaluated artemisinin combination therapy (ACT) prescribing patterns in febrile patients with and without uncomplicated malaria in one pre-RDT implementation and one post-RDT implementation area. METHODS: A cross-sectional health facility surveys was conducted during high and low malaria transmission seasons in 2010 in both areas. Clinical information and a reference blood film on all patients presenting for an initial illness consultation were collected. Malaria was defined as a history of fever in the past 48 hours and microscopically confirmed parasitaemia. Routine diagnostic testing was defined as RDT or microscopy ordered by the health worker and performed at the health facility as part of the health worker-patient consultation. Correct diagnostic testing was defined as febrile patient tested with RDT or microscopy. Over-testing was defined as a febrile patient tested with RDT or microscopy. Correct treatment was defined as patient with malaria prescribed ACT. Over-treatment was defined as patient without malaria prescribed ACT. RESULTS: A total of 1,247 febrile patients (627 from pre-implementation area and 620 from post-implementation area) were included in the analysis. In the post-RDT implementation area, 80.9% (95% CI, 68.2-89.3) of patients with malaria received recommended treatment with ACT compared to 70.3% (95% CI, 54.7-82.2) of patients in the pre-RDT implementation area. Correct treatment was significantly higher in the post-implementation area during high transmission season (85.9% (95%CI, 72.0-93.6) compared to 58.3% (95%CI, 39.4-75.1) in pre-implementation area (p=0.01). Over-treatment with ACT of patients without malaria was less common in the post-RDT implementation area (20.9%; 95% CI, 14.7-28.8) compared to the pre-RDT implementation area (45.8%; 95% CI, 37.2-54.6) (p<0.01) in high transmission. The odds of overtreatment was significantly lower in post- RDT area (adjusted Odds Ratio (OR: 95%CI) 0.57(0.36-0.89); and much higher with clinical diagnosis adjusted OR (95%CI) 2.24(1.37-3.67) CONCLUSION: Implementation of RDTs increased use of RDTs for parasitological confirmation and reduced over-treatment with ACT during high malaria transmission season in one area in Tanzania. Continued monitoring of the national RDT rollout will be needed to assess whether these changes in case management practices will be replicated in other areas and sustained over time. Additional measures (such as refresher trainings, closer supervisions, etc) may be needed to improve ACT targeting during low transmission seasons.     

Routine Kato-Katz technique underestimates the prevalence of Schistosoma japonicum: a case study in an endemic area of the People's Republic of China

There is an evidence that the Kato-Katz technique lacks sensitivity and may hence be an unsuitable method for the assessment of the 'real infection status' in community with low-intensity infections. In this study, six Kato-Katz thick smears (examination of two stool samples with three thick smears each) were used as the diagnostic 'gold' standard for estimating the prevalence of Schistosoma japonicum infection and the results were compared with results based on fewer Kato-Katz thick smear readings. A total of 1055 individuals in 2005 and 725 in 2006 from an endemic village were recruited for the study. The observed prevalence increased gradually with the number of Kato-Katz thick smears examined, and hence the rate of underestimation decreased accordingly. The prevalence based on single Kato-Katz thick smear readings was significantly lower than that obtained using five or six thick smears. The rate of underestimation based on using two and three Kato-Katz thick smears, a typical diagnostic effort in the national schistosomiasis control programme, was about 36.0% (28.4-48.9%) and 25.0% (15.9-40.7%). The number of Kato-Katz thick smears required to secure detection of a S. japonicum infection varies with the infection intensity level. Indeed, examination of a single thick smear was sufficient when the geometric mean of the fecal content of eggs per gram (EPG) was 250 or higher in infected individuals, while six Kato-Katz thick smears were required when the EPG score was lower than 10. In conclusion, our results confirm that the prevalence of S. japonicum infection in a community is generally considerably "underestimated". Moreover, our findings provide a benchmark for the proper application of the Kato-Katz technique and the rational evaluation of the epidemic situation, as well as a scientific basis for constructing a mathematic diagnostic model.     

Spatially explicit burden estimates of malaria in Tanzania: bayesian geostatistical modeling of the malaria indicator survey data

A national HIV/AIDS and malaria parasitological survey was carried out in Tanzania in 2007-2008. In this study the parasitological data were analyzed: i) to identify climatic/environmental, socio-economic and interventions factors associated with child malaria risk and ii) to produce a contemporary, high spatial resolution parasitaemia risk map of the country. Bayesian geostatistical models were fitted to assess the association between parasitaemia risk and its determinants. bayesian kriging was employed to predict malaria risk at unsampled locations across Tanzania and to obtain the uncertainty associated with the predictions. Markov chain Monte Carlo (MCMC) simulation methods were employed for model fit and prediction. Parasitaemia risk estimates were linked to population data and the number of infected children at province level was calculated. Model validation indicated a high predictive ability of the geostatistical model, with 60.00% of the test locations within the 95% credible interval. The results indicate that older children are significantly more likely to test positive for malaria compared with younger children and living in urban areas and better-off households reduces the risk of infection. However, none of the environmental and climatic proxies or the intervention measures were significantly associated with the risk of parasitaemia. Low levels of malaria prevalence were estimated for Zanzibar island. The population-adjusted prevalence ranges from 0.29% in Kaskazini province (Zanzibar island) to 18.65% in Mtwara region. The pattern of predicted malaria risk is similar with the previous maps based on historical data, although the estimates are lower. The predicted maps could be used by decision-makers to allocate resources and target interventions in the regions with highest burden of malaria in order to reduce the disease transmission in the country.