The American Journal of Tropical Medicine and Hygiene - Volume 90, Issue 1, January 2014

As global efforts to eliminate malaria intensify, accurate information on vector populations and transmission dynamics is critical for directing control efforts, developing new control tools, and predicting the effects of these interventions under various conditions. Currently available sampling tools for mosquito population monitoring suffer from well-recognized limitations. As reported in this workshop summary, a recent gathering of medical entomologists, modelers, and malaria experts reviewed these issues and agreed that efforts are needed to improve methods to monitor key transmission parameters. Identified needs include standardized methods for sampling of both mosquito adults and larvae, improved tools for mosquito species identification and age-grading, and a better means for determining the entomological inoculation rate.

Non-adherence as a major contributor to poor treatment outcomes. This study aimed to explore the effectiveness of existing interventions promoting adherence to antimalarial drugs by systematic review. The following databases were used to identify potential articles: MEDLINE, EMBASE, the Cochrane CENTRAL, and CINAHL (through March 2013). From 1,813 potential papers identified, 16 studies met the selection criteria comprising 9,247 patients. Interventions were classified as packaging aids, visual media, combined visual media and verbal information, community education, medication supervision, and convenient regimen. These interventions were shown to increase adherence to antimalarial drugs (median relative risk = 1.4, interquartile range 1.2–2.0). Although a most effective intervention did not emerge, community education and visual media/verbal information combinations may well have most potential to improve adherence to antimalarial medication. These interventions should be implemented in combination to optimize their beneficial effects. The current understanding on improved adherence would facilitate to contain outbreaks of malaria cost effectively.

There is little evidence on the impact of malaria control on the health system, particularly at the facility level. Using retrospective, longitudinal facility-level and patient record data from two hospitals in Zambia, we report a pre-post comparison of hospital admissions and outpatient visits for malaria and estimated costs incurred for malaria admissions before and after malaria control scale-up. The results show a substantial reduction in inpatient admissions and outpatient visits for malaria at both hospitals after the scale-up, and malaria cases accounted for a smaller proportion of total hospital visits over time. Hospital spending on malaria admissions also decreased. In one hospital, malaria accounted for 11% of total hospital spending before large-scale malaria control compared with < 1% after malaria control. The findings demonstrate that facility-level resources are freed up as malaria is controlled, potentially making these resources available for other diseases and conditions.

Between 2000 and 2010, Médecins Sans Frontières diagnosed and treated 4,831 patients with visceral leishmaniasis (VL) in the Pokot region straddling the border between Uganda and Kenya. A retrospective analysis of routinely collected clinical data showed no marked seasonal or annual fluctuations. Males between 5 and 14 years of age were the most affected group. Marked splenomegaly and anemia were striking features. An rK39 antigen-based rapid diagnostic test was evaluated and found sufficiently accurate to replace the direct agglutination test and spleen aspiration as the first-line diagnostic procedure. The case-fatality rate with sodium stibogluconate as first-line treatment was low. The VL relapses were rare and often diagnosed more than 6 months post-treatment. Post-kala-azar dermal leishmaniasis was rare but likely to be underdiagnosed. The epidemiological and clinical features of VL in the Pokot area differed markedly from VL in Sudan, the main endemic focus in Africa.

We report the first case of visceral leishmaniasis caused by Leishmania siamensis in a seronegative child. She was treated with amphotericin B at 1 mg/kg/day for 3 weeks; however, recurrences occurred twice. The patient was cured after the administration of amphotericin B for 5 weeks and monthly prophylaxis for 6 months.

The Giardia and Cryptosporidium species are widespread and frequent diarrhea-related parasites affecting humans and other mammalian species. The prevalence of these parasites in Mongolia is currently unknown. Therefore, we performed molecular analyses of G. duodenalis and C. parvum in stool samples from 138 patients hospitalized with diarrhea in Mongolia using nested polymerase chain reaction (PCR). A total of 5 (3.62%) and 7 (5.07%) fecal samples were positive for G. duodenalis and C. parvum, respectively. Giardia duodenalis and C. parvum infections were prevalent in children < 9 years of age. The assemblage-specific fragment patterns for the β-giardin gene of G. duodenalis revealed that all five samples testing positive belonged to Assemblage A by the PCR-restriction fragment polymorphism method. For sequencing and phylogenetic analysis of the 18S rDNA and HSP70 genes of all seven patients testing positive the genes were further identified to be of the C. parvum bovine genotype. This study is the first to report the prevalence of G. duodenalis and C. parvum and its molecular characterization of fecal samples from individuals with diarrhea in Mongolia.

We investigated the serum and urine chemokine levels of patients with schistosomal mansoni glomerulonephritis. This cross-sectional study was conducted in the Southeast of Brazil. Overall, 160 subjects were enrolled and divided into five groups: 1) hepatosplenic schistosomiasis with renal disease (N = 12); 2) hepatosplenic schistosomiasis without renal disease (N = 68); 3) hepatointestinal schistosomiasis (N = 27); 4) glomerulopathy caused by other diseases (N = 22); and 5) healthy controls (N = 31). The patients with microalbuminuria > 30 mg in 24 hours were considered to have renal disease. The sera and urine chemokines CCL2, CCL3, CCL5, CCL11, and CXCL8 were measured using an enzyme-linked immunosorbent assay test. A similar profile was observed between the patients with schistosomal glomerulopathy and the patients with glomerulopathy caused by other diseases, with the exception of serum CCL2 ≤ 634.3 pg/mL. In cases with sera CCL2 > 634.3 pg/mL, the diagnosis of schistosomal glomerulopathy should be considered.

In March 2013, the National Institute of Allergy and Infectious Diseases and the Bill and Melinda Gates Foundation co-sponsored a meeting entitled “Schistosomiasis Elimination Strategy and Potential Role of a Vaccine in Achieving Global Health Goals” to discuss the potential role of schistosomiasis vaccines and other tools in the context of schistosomiasis control and elimination strategies. It was concluded that although schistosomiasis elimination in some focal areas may be achievable through current mass drug administration programs, global control and elimination will face several significant scientific and operational challenges, and will require an integrated approach with other, additional interventions. These challenges include vector (snail) control; environmental modification; water, sanitation, and hygiene; and other future innovative tools such as vaccines. Defining a clear product development plan that reflects a vaccine strategy as complementary to the existing control programs to combat different forms of schistosomiasis will be important to develop a vaccine effectively.

Dracunculiasis was rediscovered in Chad in 2010 after an apparent absence of 10 years. In April 2012 active village-based surveillance was initiated to determine where, when, and how transmission of the disease was occurring, and to implement interventions to interrupt it. The current epidemiologic pattern of the disease in Chad is unlike that seen previously in Chad or other endemic countries, i.e., no clustering of cases by village or association with a common water source, the average number of worms per person was small, and a large number of dogs were found to be infected. Molecular sequencing suggests these infections were all caused by Dracunculus medinensis. It appears that the infection in dogs is serving as the major driving force sustaining transmission in Chad, that an aberrant life cycle involving a paratenic host common to people and dogs is occurring, and that the cases in humans are sporadic and incidental.

A panel of 80 compounds was screened for anthelmintic activity against a laboratory strain of Ancylostoma ceylanicum and field isolates of hookworm obtained from school children in the Kintampo North District of the Brong Ahafo Region of Ghana. Although the laboratory strain of A. ceylanicum was more susceptible to the compounds tested than the field isolates of hookworm, a twofold increase in compound concentration resulted in comparable egg hatch percent inhibition for select compounds. These data provide evidence that the efficacy of anthelmintic compounds may be species-dependent and that field and laboratory strains of hookworm differ in their sensitivities to the anthelmintics tested. These data also suggest that both compound concentration and hookworm species must be considered when screening to identify novel anthelmintic compounds.

The diagnosis of hepatic cystic echinococcosis is based on ultrasonography and confirmed by serology. However, no biological marker of cyst viability is currently available implying years-long patient follow-up, which is not always feasible in endemic areas. We characterized the performance of an immunoblotting test based on human hydatid cyst fluid with particular regard to its ability to distinguish between cyst stages. Sera from patients with cysts in different stages showed distinctive band pattern recognition. Most importantly, the test discriminated in 80% of cases CE3a from CE3b transitional cysts, known to have different viability profiles. Interestingly, we observed a rapid change in band pattern recognition of sera from one patient at time points when his cyst passed from active to transitional to inactive stages. Further identification of different antigens expressed by different cyst stages will support the development of diagnostic tools that could early define cyst viability, to guide clinical decision making, and shorten patient follow-up.

We conducted a longitudinal analysis of 117 lymphedema patients in a filariasis-endemic area of Haiti during 1995–2008. No difference in lymphedema progression between those who received or did not receive mass drug administration (MDA) was found on measures of foot (P = 0.24), ankle (P = 0.87), or leg (P = 0.46) circumference; leg volume displacement (P = 0.09), lymphedema stage (P = 0.93), or frequency of adenolymphangitis (ADL) episodes (P = 0.57). Rates of ADL per year were greater after initiation of MDA among both groups (P < 0.01). Nevertheless, patients who received MDA reported improvement in four areas of lymphedema-related quality of life (P ≤ 0.01). Decreases in foot and ankle circumference and ADL episodes were observed during the 1995-1998 lymphedema management study (P ≤ 0.01). This study represents the first longitudinal, quantitative, leg-specific analysis examining the clinical effect of diethylcarbamazine on lymphedema progression and ADL episodes.

Tremendous progress has been made towards the goal of global elimination of lymphatic filariasis (LF) transmission by 2020. The number of endemic countries reducing LF transmission through mass drug administration continues to increase, and therefore, the need for effective post-intervention surveillance also continues to increase. Togo is the first sub-Saharan African country to implement LF surveillance, and it has 6 years of experience with this passive surveillance system. We herein report the results of a recent evaluation of the Togolese LF surveillance system, including an evaluation of blood donors as a surveillance population, and provide updated results of ongoing surveillance, including expansion in remote areas. Since implementation of LF surveillance in 2006, only three cases of positive Wuchereria bancrofti filaremia have been detected, suggesting that interruption of transmission has been sustained. Given the impracticality of validating the surveillance system in the absence of ongoing transmission, we confirmed the lack of transmission through a nationwide reassessment survey.

To determine the influence of onchocercal eye disease on the intraocular pressure of the Yanomami Tribe Aratha-ú of Roraima State, Brazil, considered endemic for onchocerciasis, a total of 86 patients were submitted to an ophthalmologic exam that included external examination, slit lamp examination, intraocular pressure measurement, and a fundus ophthalmoscope examination. A high prevalence of onchocerciasis-related eye lesions was encountered in 68.6% of the patients. Punctate keratitis and microfilariae in the anterior chamber were found in ∼28%. The mean of intraocular eye pressure found was 10.47 mm of Hg.

We determined the prevalence of rifampin-monoresistant tuberculosis (RMR-TB) in Iran. Because development of RMR-TB is not common, we also identified the major risk factors associated with RMR-TB reported from different provinces of Iran. Data for 3,020 TB patients who remained or became smear positive after two, four, six, and nine months of standard first-line chemotherapy were retrospectively analyzed. Of 3,020 patients, 1,242 patients (41.1%) were culture and DNA positive for Mycobacterium tuberculosis. Of these patients, 73 (7.4%) patients had monoresistant isolates to rifampin, which was significantly higher than that for multidrug-resistant TB (5.8%). The average rate of RMR-TB in the studied population ranged from 5% to 10%. Classical investigation showed that 33.6% of patients had either a previous or family history of TB. Molecular epidemiology methods (i.e., spoligotyping and Mycobacterium intespersed repetitive unit–variable number tandem repeat), defined transmission link in three clusters (13%). These results outline the urgent need for a comprehensive plan for detection and treatment of RMR-TB cases.

Epidemiologic studies of co-infection with tuberculosis (TB) and intestinal parasites in humans have not been extensively investigated in China. A cross-section study was conducted in a rural county of Henan Province, China. Pulmonary TB (PTB) case-patients receiving treatment for infection with Mycobacterium tuberculosis and healthy controls matched for geographic area, age, and sex were surveyed by using questionnaires. Fecal and blood specimens were collected for detection of intestinal parasites, routine blood examination, and infection with human immunodeficiency virus. The chi-square test was used for univariate analysis and multivariate logistic regression models were used to adjust for potential confounding factors. A total of 369 persons with PTB and 366 healthy controls were included; all participants were negative for human immunodeficiency virus. The overall prevalence of intestinal parasites in persons with PTB was 14.9%, including intestinal protozoa (7.9%) and helminthes (7.6%). The infection spectrum of intestinal parasites was Entamoeba spp. (1.4%), Blastocystis hominis (6.2%), Trichomonas hominis (0.3%), Clonorchis sinensis (0.3%), Ascaris lumbricoides (0.5%), Trichuris trichiura (2.2%), and hookworm (4.6%). The prevalence of intestinal parasites showed no significant difference between persons with PTB and healthy controls after adjusting for potential confounding factors. There was no factor that affected infection rates for intestinal parasites between the two groups. Infection with intestinal parasites of persons with PTB was associated with female sex (adjusted odds ratio [AOR] = 2.05, 95% confidence interval [CI] = 1.01–4.17), body mass index ≤ 19 (AOR = 3.02, 95% CI = 1.47–6.20), and anemia (AOR = 2.43, 95% CI = 1.17–5.03). Infection of healthy controls was only associated with an annual labor time in farmlands > 2 months (AOR = 4.50, 95% CI = 2.03–10.00). In addition, there was no significant trend between rates of infection with intestinal parasites and duration of receiving treatment for infection with M. tuberculosis in persons with PTB. The prevalence of intestinal parasites was not higher in persons with PTB, and there was no evidence that PTB increased susceptibility to intestinal parasites in this study. However, for patients with PTB, women and patients with comorbidities were more likely to be infected with intestinal parasites.

Rapid diagnostic tests are needed for typhoid fever (TF) diagnosis in febrile children in endemic areas. Five hundred children admitted to the hospital in Cambodia between 2009 and 2010 with documented fever (≥ 38°C) were investigated using blood cultures (BCs), Salmonella Typhi/Paratyphi A real-time polymerase chain reactions (PCRs), and a Typhoid immunoglobulin M flow assay (IgMFA). Test performance was determined by conventional methods and Bayesian latent class modeling. There were 32 cases of TF (10 BC- and PCR-positive cases, 14 BC-positive and PCR-negative cases, and 8 BC-negative and PCR-positive cases). IgMFA sensitivity was 59.4% (95% confidence interval = 41–76), and specificity was 97.8% (95% confidence interval = 96–99). The model estimate sensitivity for BC was 81.0% (95% credible interval = 54–99). The model estimate sensitivity for PCR was 37.8% (95% credible interval = 26–55), with a specificity of 98.2% (95% credible interval = 97–99). The model estimate sensitivity for IgMFA (≥ 2+) was 77.9% (95% credible interval = 58–90), with a specificity of 97.5% (95% credible interval = 95–100). The model estimates of IgMFA sensitivity and specificity were comparable with BCs and better than estimates using conventional analysis.