Summary

The purpose of this study was to examine care-seeking during fatal infant illnesses in under-resourced South African settings to inform potential strategies for reducing infant mortality. We interviewed 22 caregivers of deceased infants in a rural community and 28 in an urban township. We also interviewed seven local leaders and 12 health providers to ascertain opinions about factors contributing to infant death.

Despite the availability of free public health services in these settings, many caregivers utilised multiple sources of care including allopathic, indigenous and home treatments. Urban caregivers reported up to eight points of care while rural caregivers reported up to four points of care. The specific pathways taken and combinations of care varied, but many caregivers used other types of care shortly after presenting at public services, indicating dissatisfaction with the care they received. Many infants died despite caregivers’ considerable efforts, pointing to critical deficiencies in the system of care serving these families. Initiatives that aim to improve assessment, management and referral practices by both allopathic and traditional providers (for example, through training and improved collaboration), and caregiver recognition of infant danger signs may reduce the high rate of infant death in these settings.

Summary

In the 1980s, highland malaria returned to the tea estates of western Kenya after an absence of nearly a generation. In order to determine the importance of travel for the spread of malaria in this region, we prospectively collected blood films and travel, demographic and geographic information on well persons and outpatients on tea estates near the western rim of the Rift Valley. Risk factors for malaria asexual parasitaemia included: tribal/ethnic group, home province and home district malaria endemicity. Travel away from the Kericho tea estates within the previous two months showed an odds ratio (OR) for parasitaemia of 1.59 for well persons and 2.38 for outpatients. Sexual stages of malaria parasites (gametocytes) had an OR of 3.14 (well persons) and 2.22 (outpatients) for those who had travelled. Increased risk of malaria parasitaemia with travel was concentrated in children aged <5 years. An increase in population gametocytaemia is possibly due to increased chloroquine resistance and suppressed infections contracted outside of the tea estates.

Summary

Norovirus was detected in 17.4% of 224 diarrhoeal samples from children younger than 24 months of age in Lima, in whom all common pathogens had been excluded (pathogen negative). Norovirus was identified more frequently in children older than 12 months of age than in younger children (34% vs 8%, P<0.001). Among norovirus-positive samples, genogroup II was the predominant group (92%). Compared with rotavirus, norovirus episodes tended to be of shorter duration and less severe. The role of norovirus as a cause of diarrhoea and the ascertainment of its severity in developing countries needs further confirmation by future epidemiological studies.

Summary

Retrospective case series from Thailand have reported the presence of intra-abdominal abscesses in around half of patients with melioidosis, a much higher rate than our clinical experience would suggest. We performed a prospective, observational study of 230 adult patients with culture-confirmed melioidosis in which all patients underwent abdominal ultrasound. One or more abscesses were detected in the liver and/or spleen in 77 (33%) cases. These were often multiple (70%, 31/44 in hepatic abscesses and 88%, 50/57 in splenic abscesses) and clinically silent (27% of cases with abscesses presenting with abdominal pain). The mortality rate at 4 weeks post-discharge was lower in patients who were abscess-positive vs abscess-negative (10%, 8/77 vs 20%, 31/153).

The ImageJ program was applied to the enumeration of Orientia tsutsugamushi organisms in cell culture using indirect immunofluorescence assay (IFA). The highest correlation (r = 0.984) was observed between manual counting methods and the ImageJ program (MaxEntropy threshold algorithm). This software-based methodology is cheaper, more standardised and better reproducible than a manual-based approach.

This study evaluates commercially available rK39 Immunochromatographic (ICT) strips using urine for diagnosis of visceral leishmaniasis (VL). Freshly collected urine and serum samples of 280 parasitologically confirmed VL patients and 66 endemic healthy control (EHC), 48 non-endemic healthy controls (NEHC) and 45 different diseases (DD) were tested with rK39 strips. The sensitivity of rK39 in urine were 96.4% while the specificity was low varying from 66.7% in EHC, 77.08% in NEHC to 62.2% in DD, With serum, sensitivity was 100% whereas the specificity was 100%, 92.4% and 95.55% for respective control group. In its present format, the ICT strips cannot be used for the diagnosis of VL using urine samples.

Melioidosis (Burkholderia pseudomallei infection) has yet to be demonstrated systematically in Bangladesh. A prospective, cross-sectional serological survey was conducted in 2010 at six Bangladeshi hospitals. Age, gender, occupation and residential address were recorded. Of 1244 patients, 359 (28.9%) were positive for B. pseudomallei by indirect haemagglutination assay. Farmers had an increased risk of seropositivity (risk ratio = 1.4, 95% CI 1.0–1.8; p = 0.03). There was no clear geographic clustering of seropositives. Melioidosis should be considered as a possible cause of febrile illness in Bangladesh. Further studies are needed to establish the incidence of clinical disease and distribution of environmental risk.

The diagnostic utility of the Standard Diagnostics Leptospira IgM ELISA for detection of acute leptospirosis was assessed in febrile adults admitted in Vientiane, Laos. Using the cut-off suggested by the manufacturer [optical density (OD) ≥0.75], the assay demonstrated limited diagnostic capacity with a sensitivity of 95% and a specificity of 41% compared with the Leptospira microscopic agglutination test, which is the serological gold standard. However, re-evaluation of the diagnostic cut-off to an OD of 1.7 demonstrated improved diagnostic accuracy overall (sensitivity 70%; specificity 78%).

Summary

In developing countries, micronutrient deficiencies are common and associated with poor pregnancy outcomes, which may in turn have longer-term effects on human health. The peri-conceptional period represents a particularly sensitive window of feto-placental development, during which sub-optimal maternal micronutrition may have far-reaching consequences. The effects of targeted interventions during this period have been little studied in humans.

Malawi faces a critical shortage of nurses. Challenging working conditions and poor remuneration have led many nurses to seek employment overseas. The study uses qualitative biographical methods to describe the experiences of migrant Malawian nurses and compares them with the experiences of nurses who remain in Malawi. Choices made about pursuing a nursing career in Malawi, and decisions to migrate, are complex and heavily entwined with nurses’ personal circumstances. In addition, although nurses in Malawi perceive that conditions in the UK are difficult, many still aspire to migrate themselves.

HIV has become increasingly prevalent in the Northeast region of Brazil where Leishmania infantum chagasi is endemic, and concurrent AIDS and visceral leishmaniasis (VL) has emerged. In this study, persons with HIV/AIDS and VL (n = 17) had a mean age of 37.3 years (range 29–53 years) compared with 12.5 years (1–80 years) for persons with VL alone (n = 2836). Males accounted for 88% of cases versus 65%. The mean CD4 count and antileishmanial antibody titre were lower and recurrence of VL and death were more likely with co-infection. Considering the prevalences of L.i. chagasi and HIV in the region, this may herald the emergence of an important public health problem.

A prospective study in three Egyptian villages (A, B and C) having a high prevalence of hepatitis C virus (HCV) infection examined incidence of community-acquired HCV infection in children; 2852 uninfected infants were prospectively followed from birth for up to 5.5 years. Fifteen seroconverted for either HCV antibodies and/or HCV-RNA (incidence of 0.53%). Ten had both anti-HCV and HCV-RNA; four had only anti-HCV; and one had HCV-RNA in the absence of antibody. The incidence rate at all ages was 2.7/1000 person-years (PY). It was 3.8/1000 PY during infancy and 2.0/1000 PY for the 1–5-years age group. Hospitalization and low birth weight increased the risk of infection; while living in village B, the family having a higher socioeconomic status, and advanced maternal education were protective. Six of eight HCV-infected infants reported iatrogenic exposures (e.g. hospitalization, therapeutic injections, ear piercing) prior to infection whereas only 2/7 children older than 1 year reported these exposures. Having an HCV-positive mother was the only other reported risk in two of these older children. The virus cleared in six (40%) children by the end of follow-up. Health education targeting iatrogenic exposures and focusing on risk factors could reduce HCV infection in children in high-risk populations.

The changing epidemiology of clinical malaria since 1965 among hospitalized patients was studied at a group of tea estates in the western highlands of Kenya. These data indicate recent dramatic increases in the numbers of malaria admissions (6·5 to 32·5% of all admissions), case fatality (1·3 to 6%) and patients originating from low-risk, highland areas (34 to 59%). Climate change, environmental management, population migration, and breakdown in health service provision seem unlikely explanations for this changing disease pattern. The coincident arrival of chloroquine resistance during the late 1980s in the sub-region suggests that drug resistance is a key factor in the current pattern and burden of malaria among this highland population.

Summary

India accounts for over one-third of the world’s burden of lymphatic filariasis (LF). Although most coastal districts of Orissa state (eastern India) are LF-endemic, the western districts of Orissa are considered non-endemic. During a large-scale insecticide-treated bed net/microfinance trial, we tested one randomly selected adult (age 15–60 years) for LF from a random sample of microfinance-member households in five districts of western Orissa, using immunochromatographic card testing (ICT). Overall, 354 (adjusted prevalence 21%, 95%CI 17–25%) of 1563 persons were ICT positive, with district-wide prevalence rates ranging from 15–32%. This finding was not explained by immigration, as only 3% of subjects had ever lived in previously known LF-endemic districts. These results therefore suggest ongoing autochthonous transmission in districts where LF control programs are not operational. Our results highlight the importance of broad, systematic surveillance for LF in India and call for the implementation of LF control programs in our study districts.

Healthcare-associated pneumonia (HCAP) is a common complication in patients with severe tetanus. Nursing tetanus patients in a semi-recumbent body position could reduce the incidence of HCAP. In a randomised controlled trial we compared the occurrence of HCAP in patients with severe tetanus nursed in a semi-recumbent (30°) or supine position. A total of 229 adults and children (aged ≥1 year) with severe tetanus admitted to hospital in Vietnam, were randomly assigned to a supine (n = 112) or semi-recumbent (n = 117) position. For patients maintaining their assigned positions and in hospital for > 48 h there was no significant difference between the two groups in the frequency of clinically suspected pneumonia [22/106 (20.8%) vs 26/104 (25.0%); p = 0.464], pneumonia rate/1000 intensive care unit days (13.9 vs 14.6; p = 0.48) and pneumonia rate/1000 ventilated days (39.2 vs 38.1; p = 0.72). Mortality in the supine patients was 11/112 (9.8%) compared with 17/117 (14.5%) in the semi-recumbent patients (p = 0.277). The overall complication rate [57/112 (50.9%) vs 76/117 (65.0%); p = 0.03] and need for tracheostomy [51/112 (45.5%) vs 69/117 (58.9%); p = 0.04) was greater in semi-recumbent patients. Semi-recumbent body positioning did not prevent the occurrence of HCAP in severe tetanus patients. [Clinical Trials.gov Identifier: NCT01331252]

Leishmaniasis is a vector-borne disease with up to 350 million people at risk of infection worldwide. Among its different clinical manifestations, visceral is the most severe form. Since clinical features of visceral leishmaniasis (VL) mimic several other common diseases, accurate diagnosis of VL is crucial as the treatment is associated with significant toxicity. Invasive and risky techniques involving demonstration of the parasites in stained preparations from splenic and bone marrow aspirate is still the gold standard for VL diagnosis. Serological tests using rk39 in ELISA or rapid immunochromatographic format, Direct Agglutination Test (DAT), immunoblotting have issues related to a significant proportion of asymptomatic individuals being positive with these tests and their inability to diagnose relapses as these remain positive for several months to years after cure. PCR is the most common molecular technique successfully used for diagnosis and differentiation of species. Through this review we focus extensively on the comparative utilities of the various diagnostic tools currently available for VL, describing in depth their advantages and disadvantages, addressing the recent advances attained in the field. A simple, rapid, non invasive, accurate and cost effective marker of active VL, which can be used in field conditions, is necessary to improve diagnosis of VL.

There is an urgent need for a non-toxic and low-cost treatment for cutaneous leishmaniasis. We synthesised and tested in vivo an amphotericin B-poly(methacrylic acid) drug (AmB-PMA) that had previously shown in-vitro activity against Leishmania major and L. donovani parasites. Efficacy was determined using L. major footpad infection in 30 non-healing BALB/c mice. Three subcutaneous injections of AmB-PMA at days 7, 14 and 21 post-infection resulted in a reduction of ~80% in lesion size by day 35 post-infection in 18 treated mice compared with six untreated controls and complete healing of lesions by day 50 with no lesion relapse seen at day 80 post-infection in six treated mice. Healing was associated with decreased IL-10 (P = 0.002) and increased IFN-γ (P = 0.005) in the footpad.

This paper presents the results of an extensive search of the formal and informal literature on annual Plasmodium falciparum entomological inoculation rates (EIR) across Africa from 1980 onwards. It first describes how the annual EIR data were collated, summarized, neo-referenced and staged for public access on the internet. Problems of data standardization, reporting accuracy and the subsequent publishing of information on the internet follow. The review was conducted primarily to investigate the spatial heterogeneity of malaria exposure in Africa and supports the idea of highly heterogeneous risk at the continental, regional and country levels. The implications for malaria control of the significant spatial (and seasonal) variation in exposure to infected mosquito bites are discussed.

A more robust assessment of malaria control through mosquito larval habitat destruction will come from a better understanding of the distribution, productivity and connectivity of breeding sites. The present study examines the significance of vector dispersal ability, larval habitat stability and productivity on the persistence and extinction of a mosquito population inhabiting a dynamic network of breeding sites. We use this novel method of vector modelling to show that when dispersal is limited or vector distribution is patchy, the spread and growth of a mosquito population at the onset of a rainy season is delayed and extinction through larval habitat destruction is more readily achieved. We also determine the impact of two alternative dry-season survival strategies on mosquito dynamics. Simulations suggest that if adult vectors remain dormant throughout the dry season, the stage structure of the population will be synchronized at the onset of the wet season and its growth will be delayed. In contrast, a population that continues to breed throughout the dry season grows more rapidly and is more difficult to control. Our findings have important implications on the development of integrative malaria vector management strategies and on the understanding of dry-season survival mechanisms of African malaria vectors.

Summary

Burkholderia pseudomallei was examined after being maintained in distilled water at 25 °C for 16 years. The Gram stain was atypical (pale pink cocci or coccobacilli). The estimated number of live and dead B. pseudomallei was 3.8 × 107 cells/ml and 1.4 × 105 cells/ml, respectively. A colony count on agar of 1.0 × 106 cfu/ml suggested that a proportion of cells were in a viable but non-culturable state. Colony morphology was different from the parental isolate for 84% of colonies. Pulsed-field gel electrophoresis analysis of AvrII DNA restriction fragments revealed six different but related banding patterns, which may represent genomic rearrangement.

Summary

Point-prevalence recording of the distribution of tropical parasitic diseases at village level is usually sufficient for general monitoring and surveillance. Whilst within-village spatial patterning of diseases exists, and can be important, mapping infected cases in a household-by-household setting is arduous and time consuming. With the development of low-cost GPS-data loggers (< £40) and available GoogleEarthTM satellite imagery, we present a field-applicable method based on crowdsourcing for rapid identification of infected cases (intestinal schistosomiasis, malaria and hookworm) by household. A total of 126 mothers with their 247 preschool children from Bukoba village (Mayuge District, Uganda) were examined with half of these mothers given a GPS-data logger to walk home with, returning the unit the same day for data off-loading, after which, households were assigned GPS coordinates. A satellite image of Bukoba was annotated with households denoting the infection status of each mother and child. General prevalence of intestinal schistosomiasis, malaria and hookworm in mothers and children was: 27.2 vs 7.7%, 28.6 vs 87.0% and 60.0 vs 22.3%, respectively. Different spatial patterns of disease could be identified likely representing the intrinsic differences in parasite biology and interplay with human behaviour(s) across this local landscape providing a better insight into reasons for disease micro-patterning.

Disseminated leishmaniasis (DL) is an emerging form of Leishmania braziliensis infection characterised by multiple cutaneous lesions on different parts of the body and a high rate of mucosal involvement. Systemic production of TNFα and IFNγ in DL patients is lower than in cutaneous leishmaniasis (CL) caused by L. braziliensis, which may account for parasite dissemination due to the decreased ability to control parasite growth. In this study, the systemic and in situ immune response of DL and CL patients was characterised through evaluation of chemokine and cytokine production. In situ evaluation showed similar production of IFNγ, TNFα, IL-10, transforming growth factor-beta (TGFβ), chemokine (C-C motif) ligand 2 (CCL2), CCL3, CCL11 and chemokine (C-X-C motif) ligand 10 (CXCL10) in papular and ulcerative lesions from DL as well as in ulcerated lesions from CL. Serum levels of CXCL9, a chemokine that attracts T-cells, was higher in serum from DL than from CL. These data indicate that a decrease in the type 1 immune response in peripheral blood of DL patients is due to attraction of Leishmania antigen-activated T-cells to the multiple cutaneous lesions. This may account for the absence of or few parasites in the lesions and for the development of ulcers similar to those observed in CL.

Summary

Microsporidia were initially recognized as pathogens of insects and fish but have recently emerged as an important group of human pathogens, especially in immune-compromised individuals, such as those with HIV infection. In this study, we used a PCR-RFLP assay confirmed by quantitative real-time PCR and trichrome staining to determine the prevalence of microsporidian infections among hospital patients and school children in Vhembe region. Enterocytozoon bieneusi was the only microsporidian species detected in these stool samples. It was found in 33 (12.9%) of 255 samples from the hospitals and in 3 (4.5%) of 67 samples from primary school children and was significantly associated (P = 0.039) with diarrhea in HIV-positive patients (21.6%) compared to HIV-negative individuals (9%). However, microsporidian infections were not associated with intestinal inflammation as indicated by the lactoferrin test. These results suggest that microsporidia might be a cause of secretory diarrhea in HIV-positive patients. To our knowledge, this is the first report of E. bieneusi in the Vhembe region of South Africa. Further investigations are needed in order to clarify the pathogenesis of E. bieneusi in HIV-positive patients.

Summary

We assessed the insecticidal effects of fipronil spot-on applied to experimental dogs on the blood-feeding success and other vital parameters of the Trypanosoma cruzi vector Triatoma infestans. In the first trial, the cumulative mortality of 30 third or fourth instar nymphs exposed to eight fipronil-treated dogs differed significantly from those exposed to untreated dogs at 1 week post-treatment, but not at baseline or at 2–6 weeks post-treatment. In the second trial, the effects of multiple exposures to fipronil-treated dogs on bug population dynamics were assessed. A population of 80–84 bugs of various life stages were allowed to colonize eight closed experimental huts, and then exposed twice weekly to control or treated dogs over a period of 110 days and censused at monthly intervals. Throughout the trial, multiple exposure to fipronil did not significantly affect bug population size, fecundity, hatching, molting, survival, blood-feeding success and degree of engorgement. Only when engorgement was taken to include only fully fed bugs, did fipronil significantly reduce their degree of engorgement relative to bugs exposed to control dogs. We conclude that at tested dosages fipronil spot-on would have little effect in controlling (peri)domestic Tri. infestans or protecting dogs from contact with the bugs.

An enzyme-linked immunosorbent assay (elisa) for the detection of antigen secreted by viable Taenia solium metacestodes (Ag-elisa) was applied to 43 pre-treatment and 47 follow-up cerebrospinal fluid (CSF) samples from Peruvian patients with neurocysticercosis demonstrated by computed tomography and enzyme-linked immunoelectrotransfer blot assay. The sensitivity of the assay was 86%. Negative pre-treatment results in the Ag-elisa test were restricted to patients with only a single live cyst or only enhancing lesions. Patients with hydrocephalus had higher levels of circulating antigen. There was no difference between antigen levels in CSF taken before and immediately after treatment (day 14). Levels of parasite antigen were significantly positively correlated with the number of live cysts detected by tomography and were also proportional to the number and intensity of antibody reactions recognized by the immunoblot diagnostic test. In contrast, there was a negative correlation with the number of enhancing lesions revealed by tomography, supporting the hypothesis that enhancing lesions correspond to a terminal, moribund stage of the parasite. The use of antigen-detection tests specific for viable metacestodes has immediate utility in the clinical context, not only providing important information on the viability of the parasites but also leading to an improved understanding of the pathogenesis of neurocysticercosis before and after drug treatment.