Speed kills? Quantifying the association between police traffic stops, types of stops, and motor vehicle collisions.

BACKGROUND: Motor vehicle crashes (MVCs) are a leading cause of traumatic death and injury. Police traffic stops (PTS) are a common approach to enforcing motor vehicle laws intended to prevent MVCs. However, it is unclear which types of PTS are most effective. This study examined the relationship of PTS subtypes among municipal police patrols on non-interstate roads and MVCs and MVC-related deaths. METHODS: PTS subtype data were characterized from six North Carolina cities: Charlotte, Durham, Fayetteville, Greensboro, Raleigh, and Winston-Salem. The primary outcomes of this study were yearly non-interstate MVC and MVC-related death rates per 100 population. The data were analyzed as balanced time-series cross-sectional data. The statistical analysis accounted for time-dependent and city-dependent confounding. We used a two-way fixed effects model to analyze the relationship between PTS and MVC or MVC-related deaths. We also utilized the difference in difference (DID) analysis to analyze if the reduction of PTS following a 2012 policing administrative change in Fayetteville had an association with MVC or MVC-related deaths. RESULTS: We found no significant overall association between non-interstate PTS and MVCs (Coeff: -0.00006; p = 0.43) or MVC-related deaths (Coeff: -0.00011; p = 0.15). Panel regression suggested no significant relationship between MVCs and MVC-related deaths and PTS related to driving while impaired (p = 0.36), safe movement violation (p = 0.43), or seatbelt violations (p = 0.17). However, speed limit violations (Coeff: -0.00025; p = 0.032) and stop-light/sign violations (Coeff: -0.00147; p = 0.017) related to PTS significantly reduced MVC-related deaths. The DID regression showed no significant impact on MVCs (p = 0.924) or MVC-related deaths (0.706) before and after the police reform period. CONCLUSIONS: The evidence regarding the absence of an overall association and any association with most PTS subtypes suggest that PTS are not effective for MVC death prevention. Policymakers may proceed with exploring modifications to policing efforts without detriments to public safety as defined by MVC and MVC-related deaths. LEVEL OF EVIDENCE: Retrospective epidemiological study, level IV.

Improving Surveillance and Epidemic Response in Ohio Childcare Settings.

At the start of the Coronavirus Disease of 2019 (COVID-19) pandemic, the risk of cases in childcare programs was unknown. Thus, a rapid-response research approach was launched in Ohio childcare settings. Passive surveillance data from a state-operated incident reporting system were evaluated to estimate the number of COVID-19 cases from 15 August 2020 to 1 January 2021. Additionally, active surveillance with self-administered reverse transcriptase-polymerase chain reaction (RT-PCR) tests were conducted among staff at 46 childcare programs. Finally, six zoom-based focus groups with program administrators were used to gain feedback. Staff and children in childcare settings contributed 0.38% and 0.15% of the COVID-19 cases in Ohio during this timeframe, respectively. RT-PCR testing identified 3 unrecognized cases (0.88% of tests), and all occurred when the statewide positivity rate was >5%. Focus groups revealed that access to affordable cleaning supplies, masks, and reliable staffing were critical. Perhaps most importantly, we conclude that expanding the incident reporting system to include a childcare census would allow for the tracking of future health problems with highly valuable incidence rate estimations.

Mass drug administration of ivermectin, diethylcarbamazine, plus albendazole compared with diethylcarbamazine plus albendazole for reduction of lymphatic filariasis endemicity in Papua New Guinea: a cluster-randomised trial.

BACKGROUND: A single co-administered dose of a triple-drug regimen (ivermectin, diethylcarbamazine, and albendazole) has been shown to be safe and more efficacious for clearing Wuchereria bancrofti microfilariae than the standard two-drug regimen of diethylcarbamazine plus albendazole in clinical trials. However, the effectiveness of mass drug administration with the triple-drug regimen compared with the two-drug regimen is unknown. We compared the effectiveness of mass drug administration with the triple-drug and two-drug regimens for reducing microfilariae prevalence to less than 1% and circulating filarial antigen prevalence to less than 2%, levels that are unlikely to sustain transmission of lymphatic filariasis, in Papua New Guinea. METHODS: This open-label, cluster-randomised study was done in 24 villages in a district endemic for lymphatic filariasis in Papua New Guinea. Villages paired by population size were randomly assigned to receive mass drug administration with a single dose of the triple-drug oral regimen of ivermectin (200 µg per kg of bodyweight) plus diethylcarbamazine (6 mg per kg of bodyweight) plus albendazole (400 mg) or a single dose of the two-drug oral regimen of diethylcarbamazine (6 mg per kg of bodyweight) plus albendazole (400 mg). This is a follow-on study of a previously reported safety study (ClinicalTrials.govNCT02899936). All residents aged 5 years or older and non-pregnant women were asked to participate. After cross-sectional night blood microfilariae and circulating filarial antigen surveys, mass drug administration was provided at baseline and repeated 12 months later. The primary outcomes were mean prevalence of microfilariae and circulating filarial antigen at 12 months and 24 months, assessed in all residents willing to participate at each timepoint. This study is registered with ClinicalTrials.gov, NCT03352206. FINDINGS: Between Nov 18, 2016, and May 26, 2017, 4563 individuals were enrolled in 24 clusters; 12 clusters (2382 participants) were assigned to the triple-drug regimen and 12 clusters (2181 participants) to the two-drug regimen. Mean drug ingestion rates (of residents aged ≥5 years) were 66·1% at baseline and 63·2% at 12 months in communities assigned to the triple-drug regimen and 65·9% at baseline and 54·9% at 12 months in communities assigned to the two-drug regimen. Microfilariae prevalence in the triple-drug regimen group decreased from 105 (4·4%) of 2382 participants (95% CI 3·6-5·3) at baseline to nine (0·4%) of 2319 (0·1-0·7) at 12 months and four (0·2%) of 2086 (0·1-0·5) at 24 months. In the two-drug regimen group, microfilariae prevalence decreased from 93 (4·3%) of 2181 participants (95% CI 3·5-5·2) at baseline to 29 (1·5%) of 1963 (1·0-2·1) at 12 months and eight (0·4%) of 1844 (0·2-0·9) at 24 months (adjusted estimated risk ratio 4·5, 95% CI 1·4-13·8, p=0·0087, at 12 months; 2·9, 95% CI 1·0-8·8, p=0·058, at 24 months). The prevalence of circulating filarial antigen decreased from 523 (22·0%) of 2382 participants (95% CI 20·3-23·6) at baseline to 378 (16·3%) of 2319 (14·9-17·9) at 12 months and 156 (7·5%) of 2086 (6·4-8·7) at 24 months in the triple-drug regimen group and from 489 (22·6%) of 2168 participants (20·7-24·2) at baseline to 358 (18·2%) of 1963 (16·7-20·1) at 12 months and 184 (10·0%) of 1840 (8·7-11·5) at 24 months in the two-drug regimen group; after adjustment, differences between groups were not significant. INTERPRETATION: Mass administration of the triple-drug regimen was more effective than the two-drug regimen in reducing microfilariae prevalence in communities to less than the target level of 1%, but did not reduce circulating filarial antigen prevalence to less than 2%. These results support the use of mass drug administration with the triple-drug regimen to accelerate elimination of lymphatic filariasis. FUNDING: Bill & Melinda Gates Foundation.

Safety and efficacy of mass drug administration with a single-dose triple-drug regimen of albendazole + diethylcarbamazine + ivermectin for lymphatic filariasis in Papua New Guinea: An open-label, cluster-randomised trial.

BACKGROUND: Papua New Guinea (PNG) has a high burden of lymphatic filariasis (LF) caused by Wuchereria bancrofti, with an estimated 4.2 million people at risk of infection. A single co-administered dose of ivermectin, diethylcarbamazine and albendazole (IDA) has been shown to have superior efficacy in sustained clearance of microfilariae compared to diethylcarbamazine and albendazole (DA) in small clinical trials. A community-based cluster-randomised trial of DA versus IDA was conducted to compare the safety and efficacy of IDA and DA for LF in a moderately endemic, treatment-naive area in PNG. METHODOLOGY: All consenting, eligible residents of 24 villages in Bogia district, Madang Province, PNG were enrolled, screened for W. bancrofti antigenemia and microfilaria (Mf) and randomised to receive IDA (N = 2382) or DA (N = 2181) according to their village of residence. Adverse events (AE) were assessed by active follow-up for 2 days and passive follow-up for an additional 5 days. Antigen-positive participants were re-tested one year after MDA to assess treatment efficacy. PRINCIPAL FINDINGS: Of the 4,563 participants enrolled, 96% were assessed for AEs within 2 days after treatment. The overall frequency of AEs were similar after either DA (18%) or IDA (20%) treatment. For those individuals with AEs, 87% were mild (Grade 1), 13% were moderate (Grade 2) and there were no Grade 3, Grade 4, or serious AEs (SAEs). The frequency of AEs was greater in Mf-positive than Mf-negative individuals receiving IDA (39% vs 20% p<0.001) and in Mf-positive participants treated with IDA (39%), compared to those treated with DA (24%, p = 0.023). One year after treatment, 64% (645/1013) of participants who were antigen-positive at baseline were re-screened and 74% of these participants (475/645) remained antigen positive. Clearance of Mf was achieved in 96% (52/54) of infected individuals in the IDA arm versus 84% (56/67) of infected individuals in the DA arm (relative risk (RR) 1.15; 95% CI, 1.02 to 1.30; p = 0.019). Participants receiving DA treatment had a 4-fold higher likelihood of failing to clear Mf (RR 4.67 (95% CI: 1.05 to 20.67; p = 0.043). In the DA arm, a significant predictor of failure to clear was baseline Mf density (RR 1.54; 95% CI, 1.09 to 2.88; p = 0.007). CONCLUSION: IDA was well tolerated and more effective than DA for clearing Mf. Widespread use of this regimen could accelerate LF elimination in PNG. TRIAL REGISTRATION: Registration number NCT02899936; https://clinicaltrials.gov/ct2/show/NCT02899936.

Molecular epidemiology of residual Plasmodium vivax transmission in a paediatric cohort in Solomon Islands.

BACKGROUND: Following the scale-up of intervention efforts, malaria burden has decreased dramatically in Solomon Islands (SI). Submicroscopic and asymptomatic Plasmodium vivax infections are now the major challenge for malaria elimination in this country. Since children have higher risk of contracting malaria, this study investigated the dynamics of Plasmodium spp. infections among children including the associated risk factors of residual P. vivax burden. METHODS: An observational cohort study was conducted among 860 children aged 0.5-12 years in Ngella (Central Islands Province, SI). Children were monitored by active and passive surveillances for Plasmodium spp. infections and illness. Parasites were detected by quantitative real-time PCR (qPCR) and genotyped. Comprehensive statistical analyses of P. vivax infection prevalence, molecular force of blood stage infection (molFOB) and infection density were conducted. RESULTS: Plasmodium vivax infections were common (overall prevalence: 11.9%), whereas Plasmodium falciparum infections were rare (0.3%) but persistent. Although children acquire an average of 1.1 genetically distinct P. vivax blood-stage infections per year, there was significant geographic heterogeneity in the risks of P. vivax infections across Ngella (prevalence: 1.2-47.4%, p < 0.01; molFOB: 0.05-4.6/year, p < 0.01). Malaria incidence was low (IR: 0.05 episodes/year-at-risk). Age and measures of high exposure were the key risk factors for P. vivax infections and disease. Malaria incidence and infection density decreased with age, indicating significant acquisition of immunity. G6PD deficient children (10.8%) that did not receive primaquine treatment had a significantly higher prevalence (aOR: 1.77, p = 0.01) and increased risk of acquiring new bloodstage infections (molFOB aIRR: 1.51, p = 0.03), underscoring the importance of anti-relapse treatment. CONCLUSION: Residual malaria transmission in Ngella exhibits strong heterogeneity and is characterized by a high proportion of submicroscopic and asymptomatic P. vivax infections, alongside sporadic P. falciparum infections. Implementing an appropriate primaquine treatment policy to prevent P. vivax relapses and specific targeting of control interventions to high risk areas will be required to accelerate ongoing control and elimination activities.

Risk Factors for Malaria Infection in Central Madagascar: Insights from a Cross-Sectional Population Survey.

Community prevalence of infection is a widely used, standardized metric for evaluating malaria endemicity. Conventional methods for measuring prevalence include light microscopy and rapid diagnostic tests (RDTs), but their detection thresholds are inadequate for diagnosing low-density infections. The significance of submicroscopic malaria infections is poorly understood in Madagascar, a country of heterogeneous malaria epidemiology. A cross-sectional community survey in the western foothills of Madagascar during the March 2014 transmission season found malaria infection to be predominantly submicroscopic and asymptomatic. Prevalence of Plasmodium infection diagnosed by microscopy, RDT, and molecular diagnosis was 2.4%, 4.1%, and 13.8%, respectively. This diagnostic discordance was greatest for Plasmodium vivax infection, which was 98.5% submicroscopic. Village location, insecticide-treated bednet ownership, and fever were significantly associated with infection outcomes, as was presence of another infected individual in the household. Duffy-negative individuals were diagnosed with P. vivax, but with reduced odds relative to Duffy-positive hosts. The observation of high proportions of submicroscopic infections calls for a wider assessment of the parasite reservoir in other regions of the island, particularly given the country's current focus on malaria elimination and the poorly documented distribution of the non-P. falciparum parasite species.

Pilot testing of dipsticks as point-of-care assays for rapid diagnosis of poor-quality artemisinin drugs in endemic settings.

BACKGROUND: Good-quality artemisinin drugs are essential for malaria treatment, but increasing prevalence of poor-quality artemisinin drugs in many endemic countries hinders effective management of malaria cases. METHODS: To develop a point-of-care assay for rapid identification of counterfeit and substandard artemisinin drugs for resource-limited areas, we used specific monoclonal antibodies against artesunate and artemether, and developed prototypes of lateral flow dipstick assays. In this pilot test, we evaluated the feasibility of these dipsticks under different endemic settings and their performance in the hands of untrained personnel. RESULTS: The results showed that the dipstick tests can be successfully performed by different investigators with the included instruction sheet. None of the artemether and artesunate drugs collected from public pharmacies in different endemic countries failed the test. CONCLUSION: It is possible that the simple dipstick assays, with future optimization of test conditions and sensitivity, can be used as a qualitative and semi-quantitative assay for rapid screening of counterfeit artemisinin drugs in endemic settings.

Population genomics of the filarial nematode parasite Wuchereria bancrofti from mosquitoes.

Wuchereria bancrofti is a parasitic nematode and the primary cause of lymphatic filariasis--a disease specific to humans. W. bancrofti currently infects over 90 million people throughout the tropics and has been acknowledged by the world health organization as a vulnerable parasite. Current research has focused primarily on the clinical manifestations of disease and little is known about the evolutionary history of W. bancrofti. To improve upon knowledge of the evolutionary history of W. bancrofti, we whole genome sequenced 13 W. bancrofti larvae. We circumvent many of the difficulties of multiple infections by sampling larvae directly from mosquitoes that were experimentally inoculated with infected blood. To begin, we used whole genome data to reconstruct the historical population size. Our results support a history of fluctuating population sizes that can be correlated with human migration and fluctuating mosquito abundances. Next, we reconstructed the putative pedigree of W. bancrofti worms within an infection using the kinship coefficient. We deduced that there are full-sib and half-sib relationships residing within the same larval cohort. Through combined analysis of the mitochondrial and nuclear genomes we concluded that this is likely a results of polyandrous mating, the first time reported for W. bancrofti. Lastly, we scanned the genomes for signatures of natural selection. Annotation of putative selected regions identified proteins that may have aided in a parasitic life style or may have evolved to protect against current drug treatments. We discuss our results in the greater context of understanding the biology of an animal with a unique life history and ecology.

A Framework for Global Collaborative Data Management for Malaria Research.

Data generated during the course of research activities carried out by the International Centers of Excellence for Malaria Research (ICEMR) is heterogeneous, large, and multi-scaled. The complexity of federated and global data operations and the diverse uses planned for the data pose tremendous challenges and opportunities for collaborative research. In this article, we present the foundational principles for data management across the ICEMR Program, the logistics associated with multiple aspects of the data life cycle, and describe a pilot centralized web information system created in PlasmoDB to query a subset of this data. The paradigm proposed as a solution for the data operations in the ICEMR Program is widely applicable to large, multifaceted research projects, and could be reproduced in other contexts that require sophisticated data management.

Evaluating public housing residents for knowledge, attitudes, and practices following dengue prevention outreach in Key West, Florida.

BACKGROUND: In 2009-2010, 93 cases of dengue were identified in Key West, Florida. This was the first outbreak of autochthonous transmission of dengue in Florida since 1934. In response to this outbreak, a multifaceted public education outreach campaign was launched. The aim of this study is to compare dengue prevention knowledge, attitudes, perceptions, and prevention practices among residents of subsidized public housing to the general population in Key West and to assess whether there were barriers preventing effective outreach from reaching specific vulnerable populations. METHODS: A randomized population-based evaluation of knowledge, attitudes, and behaviors toward dengue prevention consisting of 521 separate household interviews was undertaken in July of 2011. A subset analysis was performed on interviews collected from 28 public housing units within four subsidized public housing complexes. Analysis was performed to determine whether knowledge, attitudes, and behaviors exhibited by public housing residents differed from the non-public housing study population. RESULTS: Public housing residents recalled fewer outreach materials (p=0.01) and were 3.4 times (95% confidence interval [CI] 1.4-8.3) more likely not to recall any outreach materials. Public housing residents were less likely to correctly identify how dengue transmission occurs (61% vs. 89%), where mosquitoes lay their eggs (54% vs. 85%), or to identify any signs or symptoms related to dengue (36% vs. 64%). Public housing residents were less likely to perform dengue prevention practices such as removing standing water or always using air conditioning. CONCLUSIONS: Examination of public housing residents identified an at-risk population that recalled less exposure to outreach materials and had less knowledge about dengue infection and prevention than the randomized study population. This provides public health systems the opportunity to target or modify future health messages and interventions to this group. Differences identified in the demographics of this population suggest that alternative methods or non-English materials may be required to reach desired outcomes.

Molecular epidemiology, phylogeny and evolution of the filarial nematode Wuchereria bancrofti.

Wuchereria bancrofti (Wb) is the most widely distributed of the three nematodes known to cause lymphatic filariasis (LF), the other two being Brugia malayi and Brugia timori. Current tools available to monitor LF are limited to diagnostic tests targeting DNA repeats, filarial antigens, and anti-filarial antibodies. While these tools are useful for detection and surveillance, elimination programs have yet to take full advantage of molecular typing for inferring infection history, strain fingerprinting, and evolution. To date, molecular typing approaches have included whole mitochondrial genomes, genotyping, targeted sequencing, and random amplified polymorphic DNA (RAPDs). These studies have revealed much about Wb biology. For example, in one study in Papua New Guinea researchers identified 5 major strains that were widespread and many minor strains some of which exhibit geographic stratification. Genome data, while rare, has been utilized to reconstruct evolutionary relationships among taxa of the Onchocercidae (the clade of filarial nematodes) and identify gene synteny. Their phylogeny reveals that speciation from the common ancestor of both B. malayi and Wb occurred around 5-6 millions years ago with shared ancestry to other filarial nematodes as recent as 15 million years ago. These discoveries hold promise for gene discovery and identifying drug targets in species that are more amenable to in vivo experiments. Continued technological developments in whole genome sequencing and data analysis will likely replace many other forms of molecular typing, multiplying the amount of data available on population structure, genetic diversity, and phylogenetics. Once widely available, the addition of population genetic data from genomic studies should hasten the elimination of LF parasites like Wb. Infectious disease control programs have benefited greatly from population genetics data and recently from population genomics data. However, while there is currently a surplus of data for diseases like malaria and HIV, there is a scarcity of this data for filarial nematodes. With the falling cost of genome sequencing, research on filarial nematodes could benefit from the addition of population genetics statistics and phylogenetics especially in dealing with elimination programs. A comprehensive review focusing on population genetics of filarial nematode does not yet exist. Here our goal is to provide a current overview of the molecular epidemiology of W. bancrofti (Wb) the primary causative agent of LF. We begin by reviewing studies utilizing molecular typing techniques with specific focus on genomic and population datasets. Next, we used whole mitochondrial genome data to construct a phylogeny and examine the evolutionary history of the Onchocercidae. Then, we provide a perspective to aid in understanding how population genetic techniques translate to modern epidemiology. Finally, we introduce the concept of genomic epidemiology and provide some examples that will aid in future studies of Wb.

Wasting among Uganda men with pulmonary tuberculosis is associated with linear regain in lean tissue mass during and after treatment in contrast to women with wasting who regain fat tissue mass: prospective cohort study.

BACKGROUND: Nutritional changes during and after tuberculosis treatment have not been well described. We therefore determined the effect of wasting on rate of mean change in lean tissue and fat mass as measured by bioelectrical impedance analysis (BIA), and mean change in body mass index (BMI) during and after tuberculosis treatment. METHODS: In a prospective cohort study of 717 adult patients, BMI and height-normalized indices of lean tissue (LMI) and fat mass (FMI) as measured by BIA were assessed at baseline, 3, 12, and 24 months. RESULTS: Men with wasting at baseline regained LMI at a greater rate than FMI (4.55 kg/m2 (95% confidence interval (CI): 1.26, 7.83 versus 3.16 (95% CI: 0.80, 5.52)) per month, respectively during initial tuberculosis therapy. In contrast, women with wasting regained FMI at greater rate than LMI (3.55 kg/m2 (95% CI: 0.40, 6.70) versus 2.07 (95% CI: -0.74, 4.88)), respectively. Men with wasting regained BMI at a rate of 6.45 kg/m2 (95% CI: 3.02, 9.87) in the first three months whereas women, had a rate of 3.30 kg/m2 (95% CI: -0.11, 6.72). There were minimal changes in body composition after month 3 and during months 12 to 24. CONCLUSION: Wasted tuberculosis patients regain weight with treatment but the type of gain differs by gender and patients may remain underweight after the initial phase of treatment.

The impact of platelet additive solution apheresis platelets on allergic transfusion reactions and corrected count increment (CME).

BACKGROUND: Allergic transfusion reaction (ATR) incidence ranges from 1% to 3% of all transfusions. We evaluated the impact of InterSol platelet additive solution (PAS) apheresis platelets (APs) on the incidence of ATRs and the posttransfusion platelet (PLT) increment. STUDY DESIGN AND METHODS: This retrospective study evaluated all ATRs among patients at a university hospital that maintained a mixed inventory of PAS APs and non-PAS APs (standard plasma-suspended PLTs). Corrected count increments (CCIs) were calculated for AP transfusions of individuals who received both a PAS and a non-PAS AP transfusion within a 7-day period. Hypothesis testing was performed with chi-square test for dichotomous variables and t tests for continuous variables. RESULTS: The incidence of ATRs among the non-PAS APs was 1.85% (72 ATRs/3884 transfusions) and 1.01% (12 ATRs/1194 transfusions) for PAS APs (risk ratio [RR], 0.54; 95% confidence interval [CI]=0.30-0.99; p=0.04). However, there was no difference in the incidence of febrile nonhemolytic transfusion reactions between non-PAS APs (incidence, 0.70%; 27/3884) compared to PAS APs (incidence, 0.59%; 7/1194; p=0.69). Among 223 individuals with paired non-PAS and PAS AP transfusions, the mean CCI at 1 to 4 hours after transfusion was 4932 (95% CI, 4452-5412) for non-PAS APs and was lower for PAS APs (CCI, 3766; 95% CI, 3375-4158; p ≤ 0.001). However, there was no significant difference in mean CCI at 12 to 24 hours between non-PAS (CCI, 2135; 95% CI, 1696-2573) and PAS APs (CCI, 1745; 95% CI, 1272-2217; p=0.14). CONCLUSIONS: PAS APs substantially reduce the number of ATRs. CCIs for PAS APs were lower immediately after transfusion, but not significantly different at 12 to 24 hours.

Insecticidal bed nets and filariasis transmission in Papua New Guinea.

BACKGROUND: Global efforts to eliminate lymphatic filariasis are based on the annual mass administration of antifilarial drugs to reduce the microfilaria reservoir available to the mosquito vector. Insecticide-treated bed nets are being widely used in areas in which filariasis and malaria are coendemic. METHODS: We studied five villages in which five annual mass administrations of antifilarial drugs, which were completed in 1998, reduced the transmission of Wuchereria bancrofti, one of the nematodes that cause lymphatic filariasis. A total of 21,899 anopheles mosquitoes were collected for 26 months before and 11 to 36 months after bed nets treated with long-lasting insecticide were distributed in 2009. We evaluated the status of filarial infection and the presence of W. bancrofti DNA in anopheline mosquitoes before and after the introduction of insecticide-treated bed nets. We then used a model of population dynamics to estimate the probabilities of transmission cessation. RESULTS: Village-specific rates of bites from anopheline mosquitoes ranged from 6.4 to 61.3 bites per person per day before the bed-net distribution and from 1.1 to 9.4 bites for 11 months after distribution (P<0.001). During the same period, the rate of detection of W. bancrofti in anopheline mosquitoes decreased from 1.8% to 0.4% (P=0.005), and the rate of detection of filarial DNA decreased from 19.4% to 14.9% (P=0.13). The annual transmission potential was 5 to 325 infective larvae inoculated per person per year before the bed-net distribution and 0 after the distribution. Among all five villages with a prevalence of microfilariae of 2 to 38%, the probability of transmission cessation increased from less than 1.0% before the bed-net distribution to a range of 4.9 to 95% in the 11 months after distribution. CONCLUSIONS: Vector control with insecticide-treated bed nets is a valuable tool for W. bancrofti elimination in areas in which anopheline mosquitoes transmit the parasite. (Funded by the U.S. Public Health Service and the National Institutes of Health.).

Sequential modelling of the effects of mass drug treatments on anopheline-mediated lymphatic filariasis infection in Papua New Guinea.

BACKGROUND: Lymphatic filariasis (LF) has been targeted by the WHO for global eradication leading to the implementation of large scale intervention programs based on annual mass drug administrations (MDA) worldwide. Recent work has indicated that locality-specific bio-ecological complexities affecting parasite transmission may complicate the prediction of LF extinction endpoints, casting uncertainty on the achievement of this initiative. One source of difficulty is the limited quantity and quality of data used to parameterize models of parasite transmission, implying the important need to update initially-derived parameter values. Sequential analysis of longitudinal data following annual MDAs will also be important to gaining new understanding of the persistence dynamics of LF. Here, we apply a Bayesian statistical-dynamical modelling framework that enables assimilation of information in human infection data recorded from communities in Papua New Guinea that underwent annual MDAs, into our previously developed model of parasite transmission, in order to examine these questions in LF ecology and control. RESULTS: Biological parameters underlying transmission obtained by fitting the model to longitudinal data remained stable throughout the study period. This enabled us to reliably reconstruct the observed baseline data in each community. Endpoint estimates also showed little variation. However, the updating procedure showed a shift towards higher and less variable values for worm kill but not for any other drug-related parameters. An intriguing finding is that the stability in key biological parameters could be disrupted by a significant reduction in the vector biting rate prevailing in a locality. CONCLUSIONS: Temporal invariance of biological parameters in the face of intervention perturbations indicates a robust adaptation of LF transmission to local ecological conditions. The results imply that understanding the mechanisms that underlie locally adapted transmission dynamics will be integral to identifying points of system fragility, and thus countermeasures to reliably facilitate LF extinction both locally and globally.

Population genetics of the filarial worm wuchereria bancrofti in a post-treatment region of Papua New Guinea: insights into diversity and life history.

BACKGROUND: Wuchereria bancrofti (Wb) is the primary causative agent of lymphatic filariasis (LF). Our studies of LF in Papua New Guinea (PNG) have shown that it is possible to reduce the prevalence of Wb in humans and mosquitoes through mass drug administration (MDA; diethylcarbamazine with/without ivermectin). While MDAs in the Dreikikir region through 1998 significantly reduced prevalence of Wb infection, parasites continue to be transmitted in the area. METHODS: We sequenced the Wb mitochondrial Cytochrome Oxidase 1 (CO1) gene from 16 people infected with Wb. Patients were selected from 7 villages encompassing both high and moderate annual transmission potentials (ATP). We collected genetic data with the objectives to (i) document contemporary levels of genetic diversity and (ii) distinguish between populations of parasites and hosts across the study area. PRINCIPLE FINDINGS: We discovered 109 unique haplotypes currently segregating in the Wb parasite population, with one common haplotype present in 15 out of 16 infections. We found that parasite diversity was similar among people residing within the same village and clustered within transmission zones. For example, in the high transmission area, diversity tended to be more similar between neighboring villages, while in the moderate transmission area, diversity tended to be less similar. CONCLUSIONS: In the Dreikikir region of PNG there are currently high levels of genetic diversity in populations of Wb. High levels of genetic diversity may complicate future MDAs in this region and the presence of dominant haplotypes will require adjustments to current elimination strategies.

Humoral and cellular immunity to Plasmodium falciparum merozoite surface protein 1 and protection from infection with blood-stage parasites.

BACKGROUND: Acquired immunity to malaria develops with increasing age and repeated infections. Understanding immune correlates of protection from malaria would facilitate vaccine development and identification of biomarkers that reflect changes in susceptibility resulting from ongoing malaria control efforts. METHODS: The relationship between immunoglobulin G (IgG) antibody and both interferon γ (IFN-γ) and interleukin 10 (IL-10) responses to the 42-kD C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 (MSP142) and the risk of (re)infection were examined following drug-mediated clearance of parasitemia in 94 adults and 95 children in an area of holoendemicity of western Kenya. RESULTS: Positive IFN-γ enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot assay (ELISPOT) responses to MSP142 3D7 were associated with delayed time to (re)infection, whereas high-titer IgG antibodies to MSP142 3D7 or FVO alleles were not independently predictive of the risk of (re)infection. When IFN-γ and IL-10 responses were both present, the protective effect of IFN-γ was abrogated. A Cox proportional hazard model including IFN-γ, IL-10, MSP142 3D7 IgG antibody responses, hemoglobin S genotype, age, and infection status at baseline showed that the time to blood-stage infection correlated positively with IFN-γ responses and negatively with IL-10 responses, younger age, and asymptomatic parasitemia. CONCLUSIONS: Evaluating combined allele-specific cellular and humoral immunity elicited by malaria provides a more informative measure of protection relative to evaluation of either measure alone.

Low nutrient intake among adult women and patients with severe tuberculosis disease in Uganda: a cross-sectional study.

BACKGROUND: Information regarding dietary nutrient intake during tuberculosis disease is lacking. We established the relationship between disease severity or wasting during pulmonary tuberculosis and nutrient intake. METHODS: In a cross-sectional study of 131 adults with or without pulmonary tuberculosis were screened for human immune-deficiency virus (HIV), wasting, disease severity using 13 item validated clinical TBscore, and 24-hour dietary intake recall. RESULTS: Of the 131 participants, 61 were males and 70 females. Overall men and women had similar age. In average 24-hour nutrient intake, the following nutrients: energy, protein, total fat, carbohydrate, calcium, vitamin A, and folate were low among patients with severe tuberculosis disease. Patients with moderate-to-severe clinical TBscore had lower average energy intake than patients with mild TBscores (6.11 vs. 9.27 MJ, respectively) (p<0.05). The average 24-hour nutrient intakes between wasted and non-wasted tuberculosis patients were comparable. Nutrient intake among men was higher when compared to women regardless of wasting and severity of tuberculosis. Among those with wasting, men had higher average energy intake than women (8.87 vs. 5.81 MJ, respectively) (p<0.05). Among patients with mild disease, men had higher average energy intake than women with mild disease (12.83 vs. 7.49 kcal, respectively) (p<0.001). CONCLUSIONS: Findings suggest that severity of pulmonary tuberculosis and female gender had reduced nutrient intake. Early tuberculosis diagnosis and nutritional support may be important in management of tuberculosis patients.

Broadly reactive antibodies specific for Plasmodium falciparum MSP-1(19) are associated with the protection of naturally exposed children against infection.

BACKGROUND: The 19 kDa C-terminal region of Plasmodium falciparum Merozoite Surface Protein-1 is a known target of naturally acquired humoral immunity and a malaria vaccine candidate. MSP-119 has four predominant haplotypes resulting in amino acid changes labelled EKNG, QKNG, QTSR and ETSR. IgG antibodies directed against all four variants have been detected, but it is not known if these variant specific antibodies are associated with haplotype-specific protection from infection. METHODS: Blood samples from 201 healthy Kenyan adults and children who participated in a 12-week treatment time-to-infection study were evaluated. Venous blood drawn at baseline (week 0) was examined for functional and serologic antibodies to MSP-119 and MSP-142 variants. MSP-119 haplotypes were detected by a multiplex PCR assay at baseline and weekly throughout the study. Generalized linear models controlling for age, baseline MSP-119 haplotype and parasite density were used to determine the relationship between infecting P. falciparum MSP-119 haplotype and variant-specific antibodies. RESULTS: A total of 964 infections resulting in 1,533 MSP-119 haplotypes detected were examined. The most common haplotypes were EKNG and QKNG, followed by ETSR and QTSR. Children had higher parasite densities, greater complexity of infection (>1 haplotype), and more frequent changes in haplotypes over time compared to adults. Infecting MSP-119 haplotype at baseline (week 0) had no influence on haplotypes detected over the subsequent 11 weeks among children or adults. Children but not adults with MSP-119 and some MSP-142 variant antibodies detected by serology at baseline had delayed time-to-infection. There was no significant association of variant-specific serology or functional antibodies at baseline with infecting haplotype at baseline or during 11 weeks of follow up among children or adults. CONCLUSIONS: Variant transcending IgG antibodies to MSP-119 are associated with protection from infection in children, but not adults. These data suggest that inclusion of more than one MSP-119 variant may not be required in a malaria blood stage vaccine.

Lean tissue mass wasting is associated with increased risk of mortality among women with pulmonary tuberculosis in urban Uganda.

OBJECTIVES: We assessed the impact of wasting on survival in patients with tuberculosis by using a precise height-normalized lean tissue mass index (LMI) estimated by bioelectrical impedance analysis and body mass index (BMI). METHODS: In a retrospective cohort study, 747 adult pulmonary patients with tuberculosis who were screened for HIV and nutritional status were followed for survival. RESULTS: Of 747 patients, 310 had baseline wasting by BMI (kg/m(2)) and 103 by LMI (kg/m(2)). Total deaths were 105. Among men with reduced BMI, risk of death was 70% greater (hazard ratio [HR] 1.7, 95% confidence interval [95% CI] 1.03-2.81) than in men with normal BMI. Survival did not differ by LMI among men (HR 1.1; 95% CI 0.5-2.9). In women, both the BMI and LMI were associated with survival. Among women with reduced BMI, risk of death was 80% greater (HR 1.8; 95% CI 0.9-3.5) than in women with normal BMI; risk of death was 5-fold greater (HR 5.0; 95% CI 1.6-15.9) for women with low LMI compared with women with normal LMI. CONCLUSIONS: Wasting assessed by reduced BMI is associated with an increased risk for death among both men and women whereas reduced LMI is among women with tuberculosis.