A population‐based study of how children are exposed to saliva in KwaZulu‐Natal Province,South Africa: implications for the spread of saliva‐borne pathogens to children

Objectives In sub‐Saharan Africa, many viral infections, including Epstein–Barr virus, cytomegalovirus, Kaposi’s sarcoma‐associated herpesvirus and hepatitis B are acquired in childhood. While saliva is an important transmission conduit for these viruses, little is known about how saliva is passed to African children. We endeavoured to identify the range and determinants of acts by which African children are exposed to saliva. Methods To identify the range of acts by which African children are exposed to saliva, we conducted focus groups, semi‐structured interviews and participant observations in an urban and a rural community in South Africa. To measure the prevalence and determinants of the identified acts, we administered a questionnaire to a population‐based sample of caregivers. Results We identified 12 caregiving practices that expose a child’s oral–respiratory mucosa, cutaneous surfaces or anal–rectal mucosa to saliva. Several acts were heretofore not described in the contemporary literature (e.g., caregiver inserting finger lubricated with saliva into child’s rectum to relieve constipation). Among 896 participants in the population‐based survey, many of the acts were commonly practised by all respondent types (mothers, fathers, grandmothers and siblings). The most common were premastication of food, sharing sweets and premastication of medicinal plants that are spit onto a child’s body. Conclusions African children are exposed to saliva through a variety of acts, practised by a variety of caregivers, with no single predominant practice. This diversity poses challenges for epidemiologic work seeking to identify specific saliva‐passing practices that transmit viruses. Most acts could be replaced by other actions and are theoretically preventable.     

Monitoring ivermectin distributors involved in integrated health care services through community‐directed interventions – a comparison of Cameroon and Uganda experiences over a period of three years (2004–2006)

Objectives To assess and compare the effectiveness of ivermectin distributors in attaining 90% treatment coverage of the eligible population with each additional health activity they take up. Methods Random sampling was applied every year to select distributors for interviews in community‐directed treatment with ivermectin (CDTI) areas of Cameroon and Uganda. A total of 288 in 2004, 357 in 2005 and 348 in 2006 distributors were interviewed in Cameroon, and 706, 618 and 789 in Uganda, respectively. The questions included treatment coverage, involvement in additional activities, where and for how long these activities were provided, and whether they were supervised. Results At least 70% of the distributors in Cameroon and Uganda during the study period were involved in CDTI and additional health activities. More of the distributors involved in CDTI alone attained 90% treatment coverage than those who had CDTI with additional health activities. The more the additional activities, the less likely the distributors were to attain 90% treatment coverage. In Uganda, distributors were more likely to attain 90% coverage (P < 0.001 if they worked within 1 km of their homesteads were selected by community members, worked among kindred, and were responsible for <20 households. Conclusion Additional activities could potentially undermine the performance of distributors. However, being selected by their community members, working largely among kindred and serving fewer households improved their effectiveness.     

How to improve the validity of sexual behaviour reporting: systematic review of questionnaire delivery modes in developing countries

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 control 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 A total of 28 articles reporting on 26 studies met the inclusion criteria. Heterogeneity of reported trial outcomes between studies made it inappropriate to combine trial outcomes. Eighteen studies compared audio computer‐assisted survey instruments (ACASI) or its derivatives [personal digital assistant (PDA) or computer‐assisted personal interview (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 behaviours 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 conducting sexual health research. Triangulation of self‐reported data using biomarkers is recommended. Standardizing sexual behaviour measures would allow for meta‐analysis.     

The incretins: From the concept to their use in the treatment of type 2 diabetes. Part A: Incretins: Concept and physiological functions

This paper briefly reviews the concept of incretins and describes the biological effects of the two incretins identified so far: the glucose-dependent insulinotropic polypeptide (GIP); and the glucagon-like peptide-1 (GLP-1). GIP is released by the K cells of the duodenum, while GLP-1 is released by the L cells of the distal ileum, in response to nutrient absorption. GIP and GLP-1 stimulate insulin biosynthesis and insulin secretion in a glucose-dependent manner. In addition, they increase beta-cell mass. GIP has a specific effect on adipose tissue to facilitate the efficient disposal of absorbed fat and, thus, may be involved in the development of obesity. GLP-1 has specific effects on pancreatic alpha cells, the hypothalamus, and gastrointestinal and cardiovascular systems. By inhibiting glucagon secretion and delaying gastric-emptying, GLP-1 plays an important role in glucose homoeostasis and, by inhibiting food intake, prevents the increase in body weight. As the metabolic effects of GIP are blunted in type 2 diabetes, this peptide cannot be used as an efficient therapy for diabetes. In contrast, GLP-1 effects are preserved at high concentrations in type 2 diabetes, making this peptide of great interest for the treatment of diabetes, a topic that will be discussed in the second part of this review.     

Suboptimal patterns of provider initiated HIV testing and counselling,antiretroviral therapy eligibility assessment and referral in primary health clinic attendees in Blantyre,Malawi*

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. Results: There were 2398 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 with 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.     

Sharp injuries and their determinants among health care workers at first‐level care facilities in Sindh Province,Pakistan

Objectives To assess the rate and determinants of sharp injuries during the previous 6 months among health care workers at first‐level care facilities in two districts of Pakistan. Methods Cross‐sectional survey at public, general practitioners and non‐licensed private practitioners selected through stratified random sampling. At each facility, we interviewed a prescriber and a dispenser/injection provider about knowledge of bloodborne pathogens transmission and preventive practices, risk perception, and use of precautions and sharp injuries received during the previous 6 months. Multivariable Poisson regression was used to assess the factors associated with the number of sharp injuries. Results Fifty‐four percentage of the 233 workers had at least one injury during the previous 6 months. The overall rate of sharp injuries per person per year was 3.7; among non‐physician prescribers (9%), it was 4.3; among dispensers (69%), it was 3.7, and among physicians (18%), it was 2.1. In the multivariable model, work experience, risk perception and type of health care worker were significantly associated with receiving sharp injuries during the previous 6 months. In the model including dispensers only, a higher knowledge score was associated with fewer sharp injuries, while perceived severity of disease and lack of professional qualification were associated with more. Conclusions Sharp injuries are common in Pakistan. Better knowledge about modes of bloodborne pathogen transmission and professional qualification may reduce their incidence.     

Pharmacokinetics of anti‐tuberculosis drugs in Venezuelan children younger than 16 years of age: supportive evidence for the implementation of revised WHO dosing recommendations

Objectives The World Health Organization (WHO) recently issued revised first‐line antituberculosis (anti‐TB) drug dose recommendations for children, with dose increases proposed for each drug. No pharmacokinetic data are available from South American children. We examined the need for implementation of these revised guidelines in Venezuela. Methods Plasma isoniazid, rifampicin, pyrazinamide and ethambutol concentrations were assessed prior to and at 2, 4 and 8 h after intake of TB drugs by 30 TB patients aged 1–15 years. The effects of dose in mg/kg, age, sex, body weight, malnutrition and acetylator phenotype on maximum plasma drug concentrations (C_max) and exposure (AUC_0‐24) were determined. Results 25 patients (83%) had an isoniazid C_max below 3 mg/l and 23 patients (77%) had a rifampicin C_max below 8 mg/l. One patient (3%) had a pyrazinamide C_max below 20 mg/l. The low number of patients on ethambutol (n = 5) precluded firm conclusions. C_max and AUC_0‐24 of all four drugs were significantly and positively correlated with age and body weight. Patients aged 1–4 years had significantly lower C_max and AUC_0‐24 values for isoniazid and rifampicin and a trend to lower values for pyrazinamide compared to those aged 5–15 years. The geometric mean AUC_0‐24 for isoniazid was much lower in fast acetylators than in slow acetylators (5.2 vs. 12.0, P < 0.01). Conclusion We provide supportive evidence for the implementation of the revised WHO pediatric TB drug dose recommendations in Venezuela. Follow‐up studies are needed to describe the corresponding plasma levels that are achieved by the recommended increased doses of TB drugs.     

Early HIV viral load determination after initiating first‐line antiretroviral therapy for indentifying patients with high risk of developing virological failure: data from a cohort study in a resource‐limited setting

Objectives To evaluate the performance of a single determination of HIV viral load (VL) 6–12 months after starting antiretroviral therapy (ART) for identifying patients who will subsequently develop virological failure. Methods We selected HIV‐infected patients with at least two VL determinations after 6 months of ART from an HIV cohort study in India. Patients were divided in two groups depending on whether the first VL was below (Group 1) or above (Group 2) 1000 copies/ml. Cut‐off for virological failure was defined according to World Health Organization recommendation (>5000 copies/ml). Results The study included 584 patients and 560.1 person‐years of follow‐up. Of all virological failures, 83% were diagnosed at the first VL determination. The cumulative incidence of virological failure after 1 and 2 years since the first VL was 0.9% [95% confidence interval (CI), 0.3–2.7] and 1.7% (95% CI, 0.6–5), respectively, for Group 1, and 58.2% (95% CI, 47–69.7) and 63.1% (95% CI, 49.8–76.4), respectively, for Group 2. Compared with Group 1, patients from Group 2 had a hazard ratio for virological failure of 78.3 (95% CI, 27.8–220.2). Conclusions A single VL determination after 6 months of ART was able to identify patients with high risk of virological failure.     

Determinants of unplanned antiretroviral treatment interruptions among people living with HIV in Yaoundé, Cameroon (EVAL survey,ANRS 12‐116)

Objective To identify correlates of self‐reported antiretroviral therapies (ART) interruptions among people living with HIV and AIDS (PLWHA) in Cameroon. Methods Analyses were based on data collected in the national survey EVAL (ANRS 12‐116) among 533 ART‐treated PLWHA in Yaoundé, the capital city of Cameroon, and its neighbourhood. Logistic regression models were used to identify factors associated with self‐reported ART interruptions longer than two consecutive days during the previous 4 weeks. Results ART interruptions were reported by 68 patients (12.8%). After adjustment for gender, education and household income, characteristics independently associated with interruptions were pharmacy stock shortages [OR (95%CI):3.25 (1.78–5.90)], binge drinking [2.87 (1.39–5.91)] and the number of self‐reported slimming symptoms [1.23 (1.02–1.48)]. Conclusion In poor‐resource settings where access to second and third‐line regimens is still limited, food supply programs and interventions to minimise ART shortage may reduce the risk of ART interruptions.     

Long‐lasting insecticide–treated net usage in eastern Sierra Leone – the success of free distribution

Objective Médecins Sans Frontières (MSF) runs a malaria control project in Bo and Pujehun districts (population 158 000) that includes the mass distribution, routine delivery and demonstration of correct use of free, long‐lasting insecticide–treated nets (LLINs). In 2006/2007, around 65 000 LLINs were distributed. The aim of this follow‐up study was to measure LLIN usage and ownership in the project area. Methods Heads of 900 randomly selected households in 30 clusters were interviewed, using a standardized questionnaire, about household use of LLINs. The condition of any LLIN was physically assessed. Results Of the 900 households reported, 83.4% owning at least one LLIN. Of the 16.6% without an LLIN, 91.9% had not participated in the MSF mass distribution. In 94.1% of the households reporting LLINs, the nets were observed hanging correctly over the beds. Of the 1135 hanging LLINs, 75.2% had no holes or 10 or fewer finger‐size holes. The most common source of LLINs was MSF (75.2%). Of the 4997 household members, 67.2% reported sleeping under an LLIN the night before the study, including 76.8% of children under 5 years and 73.0% of pregnant women. Conclusion Our results show that MSF achieved good usage with freely distributed LLINs. It is one of the few areas where results almost achieve the new targets set in 2005 by Roll Back Malaria to have at least 80% of pregnant women and children under 5 years using LLINs by 2010.     

A new format of the CATT test for the detection of Human African Trypanosomiasis,designed for use in peripheral health facilities

Objectives To test the reproducibility and thermostability of a new format of the Card‐Agglutination Test for Trypanosomiasis (CATT) test for Human African Trypanosomiasis (HAT), designed for use at primary health care facility level in endemic countries. Methods A population of 4217 from highly endemic villages was screened using the existing format of the CATT test (CATT‐R250) on whole blood. All those testing positive (220) and a random sample of negatives (555) were retested in the field with the new format (CATT‐D10). Inter‐format reproducibility was assessed by calculating kappa. All samples testing positive on whole blood with either method were further evaluated in Belgium by CATT titration of serum by two observers, using both old and new format. CATT‐D10 test kits were incubated under four temperature regimens (4, 37, 45 °C and fluctuating) with regular assessments of reactivity over 18 months. Results Inter‐format reproducibility of CATT‐D10 vs. CATT‐R250 on whole blood performed by laboratory technicians in the field was excellent with kappa values of 0.83–0.89. Both inter‐ and intra‐format reproducibility assessed by CATT titration were excellent, with 96.5–100% of all differences observed falling within the limits of ±1 titration step. After 18 months, reactivity of test kits incubated under all four temperature regimens was still well above the minimum threshold considered acceptable. Conclusion The CATT‐D10 is thermostable and can be used interchangeably with the old format of the CATT test. It is highly suitable for use in peripheral health facilities in HAT‐endemic countries.     

Reframing HIV care: putting people at the centre of antiretroviral delivery

The delivery of HIV care in the initial rapid scale‐up of HIV care and treatment was based on existing clinic‐based models, which are common in highly resourced settings and largely undifferentiated for individual needs. A new framework for treatment based on variable intensities of care tailored to the specific needs of different groups of individuals across the cascade of care is proposed here. Service intensity is characterised by four delivery components: (i) types of services delivered, (ii) location of service delivery, (iii) provider of health services and (iv) frequency of health services. How these components are developed into a service delivery framework will vary across countries and populations, with the intention being to improve acceptability and care outcomes. The goal of getting more people on treatment before they become ill will necessitate innovative models of delivering both testing and care. As HIV programmes expand treatment eligibility, many people entering care will not be ‘patients’ but healthy, active and productive members of society 1 . To take the framework to scale, it will be important to: (i) define which individuals can be served by an alternative delivery framework; (ii) strengthen health systems that support decentralisation, integration and task shifting; (iii) make the supply chain more robust; and (iv) invest in data systems for patient tracking and for programme monitoring and evaluation.     

Clinical characteristics and treatment outcome of patients with visceral leishmaniasis and HIV co‐infection in northwest Ethiopia

Objectives To describe the clinical presentation of patients with visceral leishmaniasis (VL) with and without human immunodeficiency virus (HIV) co‐infection and factors associated with poor outcome in northwest Ethiopia. Method Retrospective review of 241 patients with VL (92 with and 149 without HIV co‐infection). Results HIV co‐infection was present in 92 (38%) of the patients. Clinical presentation of VL was indistinguishable between patients with and without HIV co‐infection. Co‐infected patients had a poorer outcome i.e. either death or treatment failure (31.5%vs. 5.6%, P < 0.001). The presence of tuberculosis or sepsis syndrome among patients with VL and HIV co‐infected independently predicted death or treatment failure [odds ratio 4.5 (95% CI 1.47–13.92, P = 0.009) and 9.1 (95% CI 2.16–37.97, P = 0.003), respectively]. Despite having similar clinical presentation at the time of diagnosis, VL and HIV co‐infected patients had a higher mortality and treatment failure than immunocompetent patients. Conclusion The frequency of HIV co‐infection among patients with VL is high in the study area, and this co‐infection was associated with death or treatment failure. The clinical management of VL in HIV co‐infected patients is a major challenge that requires new treatment approaches to improve its outcome.     

Notifying partners of patients with early syphilis in Madagascar: case‐finding effectiveness and public health implications

Objective To evaluate the case‐finding effectiveness of a clinic‐based partner notification effort for early syphilis in Madagascar. Methods We asked index cases who had proven early syphilis to identify and provide contact information of recent sex partners (in the past 3, 6, and 12 months for primary, secondary, and early latent syphilis, respectively). Named sex partners were contacted by index cases (patient notification) or, if approved by the index case, clinic staff members (provider notification); notified of their potential exposure to syphilis; and asked to come to the clinic for evaluation. We assessed case‐finding effectiveness and calculated the ‘brought‐to‐treatment’ index (number of newly‐diagnosed syphilis cases per number of index cases interviewed). Results Of 565 index cases, 534 reported recent sex with at least one sex partner. A total of 3167 sex partners were reported, of whom 276 were contactable (9% of 3167). Providers notified 76% and cases notified 24% of these partners. 270 partners were contacted (98% of 276), and of these, 199 presented to the clinic for evaluation (74% of 270). A total of 99 partners tested positive for syphilis and received treatment (50% of 199). The ‘brought‐to‐treatment’ index was 0.18 (99 diagnoses per 565 index cases). Conclusion Partner notification was possible in this setting, resulting in treatment of syphilis‐infected individuals who otherwise would likely have remained untreated. However, given <10% of the partners reported by index cases were contactable; the results highlight the limitations of partner notification and the need for additional sexually transmitted infection control strategies.     

Long‐term effects of malaria prevention with insecticide‐treated mosquito nets on morbidity and mortality in African children: randomised controlled trial

Objective The objective is to investigate the effect of malaria control with insecticide‐treated mosquito nets (ITNs) regarding possible higher mortality in children protected during early infancy, due to interference with immunity development, and to assess long‐term effects on malaria prevalence and morbidity. Methods Between 2000 and 2002, a birth cohort was enrolled in 41 villages of a malaria holoendemic area in north‐western Burkina Faso. All neonates (n = 3387) were individually randomised to ITN protection from birth (group A) vs. ITN protection from age 6 months (group B). Primary outcome was all‐cause mortality. In 2009, a survey took place in six sentinel villages, and in 2010, a census was conducted in all study villages. Results After a median follow‐up time of 8.3 years, 443/3387 (13.1%) children had migrated out of the area and 484/2944 (16.4%) had died, mostly at home. Long‐term compliance with ITN protection was good. There were no differences in mortality between study groups (248 deaths in group A, 236 deaths in group B; rate ratio 1.05, 95% CI: 0.889–1.237, P = 0.574). The survey conducted briefly after the rainy season in 2009 showed that more than 80% of study children carried asexual malaria parasites and up to 20% had clinical malaria. Conclusion Insecticide‐treated mosquito net protection in early infancy is not a risk factor for mortality. Individual ITN protection does not sufficiently reduce malaria prevalence in high‐transmission areas. Achieving universal ITN coverage remains a major challenge for malaria prevention in Africa.