Summary

OBJECTIVES

To describe specific causes of the high rates of stillbirth, neonatal death and early child childhood death in Zambia.

METHODS

We conducted a household-based survey in rural Zambia. Socio-demographic and delivery characteristics were recorded, alongside a maternal HIV test. Verbal autopsy questionnaires were administered to elicit mortality-related information and independently reviewed by three experienced paediatricians who assigned a cause and contributing factor to death. For this secondary analysis, deaths were categorized into: stillbirths (foetal death ≥28 weeks of gestation), neonatal deaths (≤28 days) and early childhood deaths (>28 days to <2 years).

RESULTS

Among 1679 households, information was collected on 148 deaths: 34% stillbirths, 26% neonatal and 40% early childhood deaths. Leading identifiable causes of stillbirth were intrauterine infection (26%) and birth asphyxia (18%). Of 32 neonatal deaths, 38 (84%) occurred within the first week of life, primarily because of infections (37%) and prematurity (34%). The majority of early childhood deaths were caused by suspected bacterial infections (82%). HIV prevalence was significantly higher in mothers who reported an early childhood death (44%) than mothers who did not (17%; P < 0.01). Factors significantly associated with mortality were lower socio-economic status (P < 0.01), inadequate water or sanitation facilities (P < 0.01), home delivery (P = 0.04) and absence of a trained delivery attendant (P < 0.01).

CONCLUSION

We provide community-level data about the causes of death among children under 2 years of age. Infectious etiologies for mortality ranked highest. At a public health level, such information may have an important role in guiding prevention and treatment strategies to address perinatal and early childhood mortality.

Summary

Objectives

During mass antibiotic distributions for trachoma, certain individuals are difficult to locate, and go untreated. These untreated individuals may serve as a source of community re-infection. The importance of this difficult-to-locate, untreated population is unclear. We sought to determine whether individuals who are difficult to locate were more likely to be infected with ocular chlamydia than those who were easier to locate.

Methods

We monitored 12 Ethiopian communities 1 year after a third annual mass azithromycin treatment for trachoma. Conjunctival swabbing for chlamydial RNA was performed in a random sample of children from each community. If insufficient numbers of children were enrolled on the first monitoring day, we returned on subsequent days.

Results

Of the 12 communities, 10 required more than 1 monitoring day. On average, 16.1% (95% CI 7.9–30.0) of children were enrolled after the initial day. Evidence of chlamydia was found in 7.1% (95% CI 2.7–17.4) of 0–9 year-old children. No ocular swabs collected after the initial day were positive for chlamydial RNA. Children examined after the initial monitoring day were significantly less likely to have ocular chlamydial infection than children seen on the initial day; Mantel-Haenszel common OR = 0 (95% CI 0 – 0.77).

Conclusions

In a setting of repeated annual mass azithromycin treatments, after approximately 80% of individuals have been located in a community, extra efforts to find absent individuals may not yield significantly more cases of ocular chlamydia.

Summary

Background

Evaluating treatment failure is critical when deciding to modify antiretroviral therapy (ART). Virologic Assessment Forms (VAFs) were implemented in July 2008 as a prerequisite for ordering viral load. The form requires assessment of clinical and immunologic status.

Methods

Using the Electronic Medical Record (EMR), we retrospectively evaluated patients who met 2006 WHO guidelines for immunologic failure (≥15 years old; on ART ≥6 months; CD4 count 50% drop from peak OR CD4 persistently <100 cells) at the Lighthouse Trust clinic from 12/2007–12/2009. We compared virologic screening, VAF implementation and ART modification during the same period using Fisher’s exact tests and unpaired t-tests as appropriate.

Results

Of 7,000 enrolled ART patients ≥ 15 years old with at least two CD4 counts, 10% had immunologic failure with a median follow-up time on ART of 1.4 years (IQR: 0.8–2.3). Forty (6%) viral loads were ordered: 14 (35%) were detectable (>400 HIV RNA copies/mL) and 1 (7%) patient was switched to second-line therapy. Overall, 259 VAFs were completed: 67% for immunologic failure and 33% for WHO Stage 4 condition. Before VAF implementation, 1% of patients had viral loads drawn during routine care, whereas afterwards, 8% did (p<0.0001; 95% CI 0.03–0.08).

Conclusions

Clinicians did not identify a large proportion of immunologic failure patients for screening. Implementation of VAFs produced little improvement in virologic screening during routine care. Better training and monitoring systems are needed.

Summary

We conducted a study to determine whether clinical algorithms would be useful in malaria diagnosis among people living in an area of moderate malaria transmission within Kilifi District in Kenya. A total of 1602 people of all age groups participated. We took smears and recorded clinical signs and symptoms (prompted or spontaneous) of all those presenting to the study clinic with a history of fever. A malaria case was defined as a person presenting to the clinic with a history of fever and concurrent parasitaemia. A set of clinical signs and symptoms (algorithms) with the highest sensitivity and specificity for diagnosing a malaria case was selected for the age groups ≤5 years, 6–14 years and ≥15 years. These age-optimized derived algorithms were able to identify about 66% of the cases among those <15 years of age but only 23% of cases among adults. Were these algorithms to be used as a basis for a decision on treatment among those presenting to the clinic, 16% of children ≤5 years, 44% of those 6–14 years of age and 66% of the adults who had a history of fever and parasitaemia ≥5000 parasites/μl of blood would be sent home without treatment. Clinical algorithms therefore appear to have little utility in malaria diagnosis, performing even worse in the older age groups, where avoiding unnecessary use of antimalarials would make more drugs available to the really needy population of children under 5 years of age.

OBJECTIVE

Both podoconiosis (a geochemical non-filarial disease) and chronic filarial disease result in lower limb elephantiasis. The aims of the present study were to determine whether the elephantiasis in Midakegn district, central Ethiopia is filarial or non-filarial (podoconiosis) using serological, parasitological, and clinical examinations, and to estimate its prevalence.

METHODS

House-to-house visits were made in 330 randomly selected households. All household members that had elephantiasis were interviewed and clinically examined at the nearby health center to confirm presence of elephantiasis, check presence of scrotal swelling, and rule out other causes of lymphoedema. Midnight blood sample was obtained from each participant with elephantiasis for microscopic examination of W. bancrofti microfilaria. Day time blood sample was obtained from half of the participants for serological confirmation using the immuno-chromatographic test card.

RESULTS

Consistent with features of podoconiosis (non-filarial elephantiasis), none of the elephantiasis cases had consistently worn shoes since childhood; 94.3% had bilateral swelling limited below the level of the knees; no individual had thigh or scrotal elephantiasis; parasitological test for microfilariae and serological tests for W. bancrofti antigen turned negative in all samples. The prevalence of the disease was 7.4%. Prevalence peaked in the third decade of life, which also includes the most economically active age groups.

CONCLUSIONS

This study has shown high prevalence of podoconiosis (endemic non-filarial elephantiasis) and absence of filarial elephantiasis in Midakegn district. Prevention, treatment, and control of podoconiosis must be among the top priorities of public health programs in the district.

Summary

Objectives

To assess the uptake of HIV testing among preschool children with HIV positive mothers in a peri-urban population-based study in KwaZulu-Natal (KZN), South Africa, an area of high HIV prevalence.

Methods

All children four to six years old and their primary caregivers from the area were invited to participate. All participants were asked about prior HIV testing and were offered counseling and voluntary HIV testing irrespective of previous testing. 27 HIV-infected mothers were interviewed to identify barriers to testing their children.

Results

1583 children (88% of eligible children) and their caregivers participated. Of the biological mothers, 86% were previously tested for HIV (27% tested positive). Among the surviving 244 children born to an infected mother only 41% had been tested for HIV (23% tested positive). Subsequently, 90% of previously untested children of infected mothers underwent HIV testing (9.3% were positive). Overall seroprevalence among study children was 4.9%. All infected mothers interviewed endorsed the belief that children of HIV-infected women should be tested for HIV. Women who missed opportunities for antenatal HIV testing reported no systematic testing of their children at later ages.

Conclusions

In this community with high HIV prevalence, HIV testing of children is infrequent despite high testing coverage among caregivers. The low proportion of children tested for HIV, particularly those of infected mothers, is of great concern as they are at high risk for morbidity and mortality associated with untreated childhood HIV infection. HIV testing programs should strengthen protocols to include children, especially for those who missed PMTCT opportunities in infancy.

Summary

Objective

To investigate the epidiomology of HPV infection in Malian women, for whom cervical cancer is the most common cancer and the second most common cause of cancer-related mortality.

Methods

Pilot study of 202 women aged 15 to 65 to determine the prevalence rate of high-risk HPV infection among unscreened Malian women. Information on risk factors was collected through a standardized, structured interview and clinical examination. High-risk HPV DNA was detected using signal amplification methods (hybrid capture-II).

Results

High-risk (HR) HPV DNA was detected in 12% of unscreened women, while visual inspection after application of acetic acid and Lugol’s iodine (VIA/VILI) identified suspicious abnormalities in 2.5% of un-screened women. Histopathological evaluation of VIA/VILI positive biopsies revealed no evidence of cervical intraepithelial neoplasia or cervical cancer. The majority of infections occurred among women in the 15-24 year old range. Compared to women who were married or widowed, single women were 3.5 times more likely to be infected with HR HPV.

Conclusions

The prevalence of infection with cancer causing types of HPV in this study was 12%. These prevalence estimates are consistent with what has been reported previously for other west African countries.

Objective

To review methods for the statistical analysis of parasite and other skewed count data.

Methods

Statistical methods for skewed count data are described and compared, with reference to those used over a ten year period of Tropical Medicine and International Health. Two parasitological datasets are used for illustration.

Results

Ninety papers were identified, 89 with descriptive and 60 with inferential analysis. A lack of clarity is noted in identifying measures of location, in particular the Williams and geometric mean. The different measures are compared, emphasizing the legitimacy of the arithmetic mean for skewed data. In the published papers, the t test and related methods were often used on untransformed data, which is likely to be invalid. Several approaches to inferential analysis are described, emphasizing 1) non-parametric methods, while noting that they are not simply comparisons of medians, and 2) generalized linear modelling, in particular with the negative binomial distribution. Additional methods, such as the bootstrap, with potential for greater use are described.

Conclusions

Clarity is recommended when describing transformations and measures of location. It is suggested that non-parametric methods and generalized linear models are likely to be sufficient for most analyses.

Objective

To understand reasons for suboptimal and delayed uptake of antiretroviral therapy (ART) by describing the patterns of HIV testing and counselling (HTC) and outcomes of ART eligibility assessments in primary clinic attendees.

Methods

All clinic attendances and episodes of HTC were recorded at two clinics in Blantyre. A cohort of newly diagnosed HIV-positive adults (>15 years) was recruited and exit interviews undertaken. Logistic regression models were constructed to investigate factors associated with referral to start ART. Qualitative interviews were conducted with providers and patients.

Findings

There were 2,398 episodes of HTC during 18,021 clinic attendances (13.3%) between January and April 2011. The proportion of clinic attendees undergoing HTC was lowest in non-pregnant women (6.3%) and men (8.5%), compared to pregnant women (47.2%). Men had more advanced HIV infection than women (79.7% WHO stage 3 or 4 vs. 56.4%). Problems with WHO staging and access to CD4 counts affected ART eligibility assessments; only 48% completed ART eligibility assessment and 54% of those reporting WHO stage 3/4 illnesses were not referred to start ART promptly. On multivariate analysis, HIV-positive pregnant women were significantly less likely to be referred directly for ART initiation (adjusted OR: 0.29, 95% CI: 0.13-0.63).

Conclusions

These data show that provider initiated testing and counselling (PITC) has not yet been fully implemented at primary care clinics. Suboptimal ART eligibility assessments and referral (reflecting the difficulties of WHO staging in primary care) mean that simplified eligibility assessment tools are required to reduce unnecessary delay and attrition in the pre-ART period. Simplified initiation criteria for pregnant women, as being introduced in Malawi, should improve linkage to ART.

Background and Objective

Visceral leishmaniasis (VL) is a chronic infectious disease that is of major public health importance in the state of Bihar in India. A regional VL Elimination Initiative was launched in 2005 based on the use of the oral drug miltefosine. However, concerns were raised about development of drug resistance. Drug effectiveness cannot be assessed accurately based on the current recording and reporting system of health facilities. In 2009 a random survey was conducted in Muzaffarpur district to document the clinical outcomes of VL patients treated by the public health care system in 2008. We analyze the operational feasibility and cost of such periodic random survey as compared to health facility based routine monitoring.

Methods

A random sample of 150 patients was drawn from registers kept at Primary Health Care centers (PHCs). Patient records were examined and the patients were located at their residence. Both patients and physicians were interviewed with the help of two specifically designed questionnaires by a team of one supervisor, one physician and one field worker. Costs incurred during this survey were properly documented and vehicle log books were maintained for present analysis.

Results

Only 115 (76.7%) of the patients could be located in the first effort and finally 11 patients were not traceable on account of erroneous recording of patients’ characteristics and addresses at the CHCs. Per patient follow-up cost was US$ 15.51 and on average 2.27 patients could be visited per team-day. Human resource involvement constituted 75% of the total cost whereas involvement of physician costs 51% of the total cost.

Interpretation and conclusion

A random survey to document clinical outcomes is costly and labor intensive, but gives probably the most accurate information on drug effectiveness. A health service based retrospective cohort reporting system modeled on the monitoring system developed by tuberculosis programs could be a better alternative. Involvement of community health workers in such monitoring would offer the additional advantage of treatment supervision and support.

SUMMARY

Introduction

Unlike other tapeworms, T. solium infections carry risk for neurocysticercosis. Differential diagnosis of human tapeworm infections relies on morphology of the scolex or proglottids, frequently unavailable. DNA-based assays are poorly available in endemic areas. Ziehl Neelsen staining has been suggested but not tested in controlled designs. We validated whether Ziehl Neelsen staining could differentiate T. solium and T. saginata eggs.

Methods

Tapeworm proglottids (33 specimens, 23 T. solium and 10 T. saginata) and eggs (31 specimens, 13 T. solium and 10 T. saginata) were stained. Four eggs from each sample were measured and average diameters were recorded.

Results

T. saginata eggs stained entirely magenta in seven of 13 cases. T. solium eggs stained entirely blue/purple in 4/18 cases and entirely magenta in one. Eggs of T. saginata were slightly larger and always ovoid, while T. solium eggs were smaller and were mostly spheric.

Conclusions

Ziehl Neelsen staining can occasionally distinguish fully mature T. solium from T. saginata eggs. This distinction is poorly sensitive and not completely specific. Differential staining suggest differences in embryophore components between species, evident along egg maturation. In this small series, egg morphology (shape, maximal diameter) provided appropriate differentiation between T. solium and T. saginata eggs.

Summary

Objective

A recent RCT demonstrated home-based treatment of WHO-defined severe pneumonia with oral amoxicillin was equivalent to hospital-based therapy and parenteral antibiotics. We aimed to determine whether this finding is generalizable across four countries.

Methods

Multi-centre observational study in Bangladesh, Egypt, Ghana and Vietnam between November 2005 and May 2008. Children aged 3 to 59 months with WHO-defined severe pneumonia were enrolled at participating health centers and managed at home with oral amoxicillin (80–90 mg/kg/day) for 5 days. Children were followed-up at home on days 1, 2, 3 and 6 and at a facility on day 14 to look for cumulative treatment failure through day 6 and relapse between days 6–14.

Results

Of 6,582 children screened, 873 were included, of whom 823 had an outcome ascertained. There was substantial variation in presenting characteristics by site. Bangladesh and Ghana had fever (97%) as a more common symptom than Egypt (74%) and Vietnam (66%), while in Vietnam audible wheeze was more common (49%) than at other sites (range 2%–16%). Treatment failure by day 6 was 9.2% (95% CI: 7.3%–11.2%) across all sites, varying from 6.4% (95% CI: 3.1%–9.8%) in Ghana to 13.2% (95% CI: 8.4%–18.0%) in Vietnam. 2.7% (95% CI: 1.5%–3.9%) of the 733 children well on day 6 relapsed by day 14. The most common causes of treatment failure were persistence of LCI at day 6 (3.8%; 95% CI: 2.6%–5.2%), abnormal sleepy or difficult to wake (1.3%; 95% CI: 0.7%–2.3%), and central cyanosis (1.3%; 95% CI: 0.7%–2.3%). All children survived and only one adverse drug reaction occurred. Treatment was more frequent in young infants and those presenting with rapid respiratory rates.

Conclusions

Clinical treatment failure and adverse event rates among children with severe pneumonia treated at home with oral amoxicillin did not substantially differ across geographic areas. Thus home-based therapy of severe pneumonia can be applied to a wide variety of settings.

Summary

OBJECTIVE

To describe the contribution of paediatric HIV and of HIV co-infections to admissions to a hospital in Moshi, Tanzania, using contemporary laboratory methods.

METHODS

During 1 year, we enrolled consecutively admitted patients aged ≥2 months and <13 years with current or recent fever. All patients underwent standardized clinical history taking, a physical examination and HIV antibody testing; standard aerobic blood cultures and malaria film were also done, and hospital outcome was recorded. Early infant HIV diagnosis by HIV-1 RNA PCR was performed on those aged <18 months. HIV-infected patients also received serum cryptococcal antigen testing and had their CD4-positive T-lymphocyte count and percent determined.

RESULTS

A total of 467 patients were enrolled whose median age was 2 years (range 2 months–13 years); Of those patients, 57.2% were female and 12.2% were HIV-infected. Admission clinical diagnosis of HIV disease was made in 10.7% and of malaria in 60.4%. Of blood cultures, 5.8% grew pathogens; of these 25.9% were Salmonella enterica (including 6 Salmonella Typhi) and 22.2% Streptococcus pneumoniae. Plasmodium falciparum was identified on blood film of 1.3%. HIV infection was associated with S. pneumoniae (odds ratio 25.7, 95% CI 2.8, 234.0) bloodstream infection (BSI), but there was no evidence of an association with Escherichia coli or P. falciparum; Salmonella Typhi BSI occurred only among HIV-uninfected participants. The sensitivity and specificity of an admission clinical diagnosis of malaria were 100% and 40.3%; and for an admission diagnosis of bloodstream infection, they were 9.1% and 86.4%, respectively.

CONCLUSION

Streptococcus pneumoniae is a leading cause of bloodstream infection among paediatric admissions in Tanzania and is closely associated with HIV infection. Malaria was over-diagnosed clinically, whereas invasive bacterial disease was underestimated. HIV and HIV co-infections contribute to a substantial proportion of paediatric febrile admissions, underscoring the value of routine HIV testing.

Objectives

To quantify the risk of infection and disease in spouses of tuberculosis patients, and the extent to which intervention could reduce the risk in this highly exposed group.

Methods

We compared HIV prevalence, TB prevalence and incidence and tuberculin (TST) results in spouses of TB patients and community controls. HIV positive spouses were offered isoniazid preventive therapy(IPT), and TST was repeated at 6, 12, and 24 months.

Results

Of 399 smear positive patients ascertained prospectively, 201 reported cohabiting spouses, with 148 recruited. Five (3%) had active TB. We identified 203 spouses of 406 previously diagnosed smear positive patients. 11 had already had TB, and the rate of TB was 2.4 per 100 person years(py) over two years (95% ci 1.15-5.09). 116 were found alive and recruited. HIV prevalence was 37% and 39% in the prospective and retrospective spouse groups and 17% in controls. TST was >=10mm in 80% HIV negative and 57% HIV-positive spouses ascertained retrospectively; 74% HIV negative and 62% HIV positive spouses ascertained prospectively, and 48% HIV-negative and 26 % HIV-positive community controls. 18/54 HIV positive spouses completed 6 months IPT. At two year follow-up, 87% of surviving spouses had TST >=10mm and the rate of TB was 1.1 per 100py (95% ci 0.34-3.29).

Conclusions

Spouses are a high risk group who should be screened for HIV and active TB. TST prevalence was already high by the time the spouses were approached but further infections were seen to occur. Uptake and adherence to IPT was disappointing, lessening the impact of short duration therapy.

Objective

To qualitatively investigate reasons why individuals who reported chronic cough of two weeks or more in a cross-sectional prevalence survey had not accessed community-based outreach or other diagnostic services.

Methods

This study was nested into a cluster randomised trial comparing two methods of providing community-level diagnosis for TB. Twenty individuals (12 males) with previously unreported chronic cough, due to undiagnosed pulmonary TB in 5 cases, were interviewed. An additional twenty individuals who had attended clinical services participated in two focus group discussions. Data were coded and analysed using grounded theory principles.

Results

Participants described cough, and specifically their own symptoms, as having many possible causes other than TB. People avoided care-seeking for cough in order to avoid a possible diagnosis of “TB2” (HIV-related TB). Waiting in the hope of spontaneous resolution was common. Delaying treatment-seeking was also a strategy for deferring costs. Another common theme was negative perceptions of health facilities, as places where people anticipated discourteous treatment and being put at risk of contracting TB and HIV. Expectations that they should be in control of their own health further contributed to delayed health-seeking in men.

Conclusions

Some individuals remain reluctant to be investigated for chronic cough even when provided with community-level services, with fear of the connotations of being diagnosed with TB and an aversion to contact with health providers among the dominant themes. In men, deferred acceptance that a chronic cough should be investigated may be related to concepts of masculinity, especially when symptoms are mild.

Summary

Objectives

To systematically review comparative research from developing countries on the effects of questionnaire delivery mode.

Methods

We searched Medline, EMbase and PsychINFO and ISSTDR conference proceedings. Randomized-controlled trials and quasi-experimental studies were included if they compared two or more questionnaire delivery modes, were conducted in a developing country, reported on sexual behaviours, and occurred after 1980.

Results

28 articles reporting on 26 studies met the inclusion criteria. Heterogeneity of reported trial outcomes between studies made it inappropriate to combine trial outcomes. 18 studies compared audio computer-assisted survey instruments (ACASI) or its derivatives (PDA or CAPI) against another self-administered questionnaires, face-to-face interviews, or random response technique. Despite wide variation in geography and populations sampled, there was strong evidence that computer-assisted interviews lowered item-response rates and raised rates of reporting sensitive behaviours. ACASI also improved data entry quality. A wide range of sexual behaviours were reported including vaginal, oral, anal and/or forced sex, age of sexual debut, condom use at first and/or last sex. Validation of self-reports using biomarkers was rare.

Conclusions

These data reaffirm that questionnaire delivery modes do affect self-reported sexual ehaviours and that use of ACASI can significantly reduce reporting bias. Its acceptability and feasibility in developing country settings should encourage researchers to consider its use when conduct ing sexual health research. Triangulation of self-reported data using biomarkers is recommended. Standardising sexual behaviour measures would allow for meta-analysis.

Summary

Increasingly attention is shifting towards delivering essential packages of care, often based on clinical practice guidelines, as a means to improve maternal, child and newborn survival in low-income settings. Cost effectiveness analysis (CEA), allied to the evaluation of less complex intervention, has become an increasingly important tool for priority setting. Arguably such analyses should be extended to inform decisions around the deployment of more complex interventions. In the discussion, we illustrate some of the challenges facing the extension of CEA to this area. We suggest that there are both practical and methodological challenges to overcome when conducting economic evaluation for packages of care interventions that incorporate clinical guidelines. Some might be overcome by developing specific guidance on approaches, for example clarity in identifying relevant costs. Some require consensus on methods. The greatest challenge, however, lies in how to incorporate, as measures of effectiveness, process measures of service quality. Questions on which measures to use, how multiple measures might be combined, how improvements in one area might be compared with those in another and what value is associated with improvement in health worker practices are yet to be answered.

Summary

This paper presents the results of an investigation into the utility of remote sensing (RS) using meteorological satellites sensors and spatial interpolation (SI) of data from meteorological stations, for the prediction of spatial variation in monthly climate across continental Africa in 1990. Information from the Advanced Very High Resolution Radiometer (AVHRR) of the National Oceanic and Atmospheric Administration’s (NOAA) polar-orbiting meteorological satellites was used to estimate land surface temperature (LST) and atmospheric moisture. Cold cloud duration (CCD) data derived from the High Resolution Radiometer (HRR) on-board the European Meteorological Satellite programme’s (EUMETSAT) Meteosat satellite series were also used as a RS proxy measurement of rainfall. Temperature, atmospheric moisture and rainfall surfaces were independently derived from SI of measurements from the World Meteorological Organization (WMO) member stations of Africa. These meteorological station data were then used to test the accuracy of each methodology, so that the appropriateness of the two techniques for epidemiological research could be compared. SI was a more accurate predictor of temperature, whereas RS provided a better surrogate for rainfall; both were equally accurate at predicting atmospheric moisture. The implications of these results for mapping short and long-term climate change and hence their potential for the study and control of disease vectors are considered. Taking into account logistic and analytical problems, there were no clear conclusions regarding the optimality of either technique, but there was considerable potential for synergy.

Summary

Vector-borne diseases persist in transmission systems that usually comprise heterogeneously distributed vectors and hosts leading to a highly heterogeneous case distribution. In this study, we build on principles of classical mathematical epidemiology to investigate spatial heterogeneity of disease risk for vector-borne diseases. Land cover delineates habitat suitability for vectors, and land use determines the spatial distribution of humans. We focus on the risk of exposure for dengue transmission on the Hawaiian island of Oahu, where the vector Aedes albopictus is well established and areas of dense human population exist. In Hawai'i, dengue virus is generally absent, but occasionally flares up when introduced. It is therefore relevant to investigate risk, but difficult to do based on disease incidence data. Based on publicly available data (land cover, land use, census data, surveillance mosquito trapping), we map the spatial distribution of vectors and human hosts, and finally overlay them to produce a vector-to-host ratio map. The resulting high-resolution maps indicate a high spatial variability in vector-to-host ratio suggesting that risk of exposure is spatially heterogeneous and varies according to land cover and land use.

Introduction

The distribution of vector-borne diseases tends to be highly spatially heterogeneous, varying according to the often-heterogeneous spatial distribution of transmission systems components: vectors, pathogens, and hosts. Vectors and hosts depend on spatially diverse environmental conditions, including land cover. Different land uses modify contact of susceptible humans with infectious vectors (Vanwambeke et al., 2007a), and modify human cases distribution (Vanwambeke et al., 2006, Linard et al., 2007, Norris, 2004). Heterogeneity in the risk of disease transmission results from spatial heterogeneity in both land cover and land use. Understanding sources of spatial heterogeneity can contribute to disease prevention and control. In this context a logical first step is to produce high-resolution maps detailing the spatial heterogeneity of the system. In this study, we combine publicly available data on land cover, land use, and human populations with mosquito surveillance data to produce a spatially disaggregated map representing the vector-to-human host ratio, a quantity originating from process-based epidemiological models of mosquito-borne diseases. The vector-to-host ratio used here allows an evaluation of the level of risk of contact in the absence of the pathogen since it does not rely on sparse epidemiological data. Such evaluations are particularly important in areas that experience occasional epidemic transmission. In such cases, the pathogen may not reach all susceptible population or areas, making epidemiological data an incomplete reflection of areas where conditions are suitable for vector and host presence.

Summary

Objective

To determine the normal haematological and immunological reference intervals for healthy Tanzanian children.

Methods

We analysed data from 655 HIV-seronegative, healthy children from 1 month to 18 years of age from the Kilimanjaro Region of Tanzania for this cross-sectional study. Median and 95% reference ranges were determined for haematological and immunological parameters and analysed by age cohorts, and by gender for adolescents.

Results

Median haemoglobin (Hb) and haematocrit (Hct) for all age groups were higher than established East African reference intervals. Compared to U.S. intervals, reference ranges encompassed lower values for Hb, Hct, mean corpuscular volume, and platelets. Applying the U.S. National Institute of Health Division of AIDS (DAIDS) adverse event grading criteria commonly used in clinical trials to the reference range participants, 128 (21%) of 619 children would be classified as having an adverse event related to Hb level. CD4-positive T-lymphocyte absolute counts declined significantly with increasing age (P < 0.0001). For those aged under five years, CD4-positive T-lymphocyte percentages are lower than established developed country medians.

Conclusions

Country-specific reference ranges are needed for defining normal laboratory parameters among children in Africa. Knowledge of appropriate reference intervals is critical not only for providing optimal clinical care, but also for enrolling children in medical research. Knowledge of normal CD4-positive T-lymphocyte parameters in this population is especially important for guiding the practice of HIV medicine in Tanzania.

Objective

To determine if the inclusion of amoxicillin correlates with better recovery rates in the home-based treatment of severe acute malnutrition with ready-to-use therapeutic food.

Methods

This retrospective cohort study compared data from the treatment of two groups of children in Malawi aged 6–59 months with uncomplicated severe acute malnutrition. The standard protocol group received a 7 day course of amoxicillin at the onset of treatment. The alternate protocol group received no antibiotics. All children were treated with the same ready-to-use therapeutic food. The primary outcome was nutritional recovery, defined as achieving a weight-for-height Z-score > −2 without edema.

Results

498 children were treated according to the standard protocol with amoxicillin and 1955 were treated under the alternate protocol without antibiotics. The group of children treated with amoxicillin was slightly older and more stunted at baseline. The recovery rate for children who received amoxicillin was worse at 4 weeks (40% vs. 71%) but similar after up to 12 weeks of therapy (84% vs. 86%), compared to the children treated without antibiotics. Regression modeling indicated that this difference at 4 weeks was most strongly associated with the receipt of amoxicillin.

Conclusions

This review of two therapeutic feeding programs suggests that children with severe acute malnutrition who were treated without amoxicillin did not have an inferior rate of recovery. Given the limitations of this retrospective analysis, a prospective trial is warranted to determine the effect of antibiotics on recovery from uncomplicated malnutrition with home-based therapy.

Summary

OBJECTIVE

To assess children with retinopathy-positive cerebral malaria (CM) for neurocognitive sequelae.

METHODS

Participants were selected from an ongoing exposure–control study. Eighty-three Malawian children averaging 4.4 years of age and diagnosed with retinopathy-positive CM were compared to 95 controls. Each child was classified as delayed or not using age-based norms for the Malawi Developmental Assessment Tool (MDAT) for developmental delay on the total scale and for the domains of gross motor, fine motor, language and social skills. Groups were also compared on the Achenbach Child Behaviour Checklist (CBCL) (1.5–5 years).

RESULTS

Children with retinopathy-positive CM were delayed, relative to the comparison group, on MDAT total development (P = 0.028; odds ratio or OR = 2.13), with the greatest effects on language development (P = 0.003; OR = 4.93). The two groups did not differ significantly on the Achenbach CBCL internalizing and externalizing symptoms total scores. Stepwise regression demonstrated that coma duration, seizures while in hospital, platelet count and lactate level on admission were predictive of assessment outcomes for the children with retinopathy-positive CM.

CONCLUSIONS

Children who suffer retinopathy-positive CM at preschool age are at greater risk of developmental delay, particularly with respect to language development. This confirms previous retrospective study findings with school-age children evaluated years after acute illness. The MDAT and the Achenbach CBCL proved sensitive to clinical indicators of severity of malarial illness.

Summary

OBJECTIVES

Malaria risk maps have re-emerged as an important tool for appropriately targeting the limited resources available for malaria control. In Sub-Saharan Africa empirically derived maps using standardized criteria are few and this paper considers the development of a model of malaria risk for East Africa.

METHODS

Statistical techniques were applied to high spatial resolution remotely sensed, human settlement and land-use data to predict the intensity of malaria transmission as defined according to the childhood parasite ratio (PR) in East Africa. Discriminant analysis was used to train environmental and human settlement predictor variables to distinguish between four classes of PR risk shown to relate to disease outcomes in the region.

RESULTS

Independent empirical estimates of the PR were identified from Kenya, Tanzania and Uganda (n = 330). Surrogate markers of climate recorded on-board earth orbiting satellites, population settlement, elevation and water bodies all contributed significantly to the predictive models of malaria transmission intensity in the sub-region. The accuracy of the model was increased by stratifying East Africa into two ecological zones. In addition, the inclusion of urbanization as a predictor of malaria prevalence, whilst reducing formal accuracy statistics, nevertheless improved the consistency of the predictive map with expert opinion malaria maps. The overall accuracy achieved with ecological zone and urban stratification was 62% with surrogates of precipitation and temperature being among the most discriminating predictors of the PR.

CONCLUSIONS

It is possible to achieve a high degree of predictive accuracy for Plasmodium falciparum parasite prevalence in East Africa using high-spatial resolution environmental data. However, discrepancies were evident from mapped outputs from the models which were largely due to poor coverage of malaria training data and the comparable spatial resolution of predictor data. These deficiencies will only be addressed by more random, intensive small areas studies of empirical estimates of PR.

Summary

OBJECTIVE

To investigate the prevalence and correlates of missed opportunities for addressing reproductive and mental health needs during patients’ visits to primary healthcare facilities.

METHODS

We selected a random sample of participants from 14 of the 49 clinics in Cape Town’s public health sector using stratified, cluster random sampling (n = 2618). Participants were screened to identify those at risk for unsafe sexual behaviour and a mental disorder (specifically substance use, depression, anxiety, and suicide). Information pertaining to whether or not respondents were asked about these issues during clinic visits during the previous year was elicited. The rates and correlates of missed opportunities for providing reproductive and mental health interventions were calculated.

RESULTS

The criteria of a strict definition of a missed opportunity for reproductive or mental health care information were fulfilled by 25% of the sample, while 46% met criteria for a looser definition. After adjusting for the effects of other variables in the model, men and Coloured respondents were more likely to have satisfied the definition of a missed opportunity for an intervention, while having completed high school and having children increased the likelihood of receiving an intervention.

CONCLUSION

Consultations with primary healthcare providers in which these issues are not discussed may represent missed opportunities. Persons presenting for routine care can be counselled, screened and, if required, treated. Interventions are needed at the patient, provider, and community levels to increase the opportunities to provide reproductive and mental health care to patients during routine visits.

Summary

OBJECTIVES

Human population totals are used for generating burden of disease estimates at global, continental and national scales to help guide priority setting in international health financing. These exercises should be aware of the accuracy of the demographic information used.

METHODS

The analysis presented in this paper tests the accuracy of five large-area, public-domain human population distribution data maps against high spatial resolution population census data enumerated in Kenya in 1999. We illustrate the epidemiological significance, by assessing the impact of using these different human population surfaces in determining populations at risk of various levels of climate suitability for malaria transmission. We also describe how areal weighting, pycnophylactic interpolation and accessibility potential interpolation techniques can be used to generate novel human population distribution surfaces from local census information and evaluate to what accuracy this can be achieved.

RESULTS

We demonstrate which human population distribution surface performed best and which population interpolation techniques generated the most accurate bespoke distributions. Despite various levels of modelling complexity, the accuracy achieved by the different surfaces was primarily determined by the spatial resolution of the input population data. The simplest technique of areal weighting performed best.

CONCLUSIONS

Differences in estimates of populations at risk of malaria in Kenya of over 1 million persons can be generated by the choice of surface, highlighting the importance of these considerations in deriving per capita health metrics in public health. Despite focussing on Kenya the results of these analyses have general application and are discussed in this wider context.