To determine the diagnostic accuracy of World Health Organization (WHO) 2010 and 2006 as well as United States Department of Health and Human Services (DHHS) 2008 definitions of immunological failure for identifying virological failure in children on antiretroviral therapy (ART).
Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/percent and HIV-RNA monitoring are performed 6-monthly. Incomplete virological suppression (IVS) was defined as failure to achieve ≥1 HIV-RNA ≤400 copies/mL between 6 and 15 months on ART and viral rebound (VR) as confirmed HIV-RNA ≥5000 copies/mL in a child on ART for ≥18 months who had achieved suppression during the first year on treatment.
Among 3115 children (median (IQR) age 48 (20-84) months at ART initiation) on treatment for ≥1 year, sensitivity of immunological criteria for IVS was 10%, 6% and 26% for WHO 2006
2010 and DHHS 2008 criteria respectively. The corresponding positive predictive values (PPV) were 31% 20% and 20%. Diagnostic accuracy for VR was determined in 2513 children with ≥18 months of follow-up and virological suppression during the first year on ART with sensitivity of 5% (WHO 2006/2010) and 27% (DHHS 2008). PPV results were 42% (WHO 2010), 43% (WHO 2006) and 20% (DHHS 2008).
Current immunological criteria are unable to correctly identify children failing ART virologically. Improved access to viral load testing is needed to reliably identify virological failure in children.
children; antiretroviral therapy; immunological criteria; sensitivity, specificity; virological failure
To evaluate optic nerve sheath (ONS) ultrasound as a non-invasive method of detecting raised intracranial pressure (ICP) and to establish normal ONS diameter data for African children. method Children with acute neurological disease admitted to the Paediatric Department of Queen Elizabeth Central Hospital, Malawi had ultrasound measurements of ONS diameter. Controls were children admitted to the same department with non-neurological disease. The mean of three measurements of the ONS diameter was used for analysis. Children were assessed for clinical signs of raised ICP. Patients had CT brain scans if required for their normal clinical care.
In 14 children with neurological disease and clinical signs suggestive of raised ICP, the mean ONS diameter was 5.4 mm (range 4.3–6.2 mm). Radiological signs on CT scans substantiated the presence of raised ICP in eight (all those scanned). In seven children with neurological disease but no specific signs of raised ICP the mean ONS diameter was 3.6 mm (range 2.8–4.4 mm). None of four of these patients examined by CT scan had signs of elevated ICP. The mean ONS diameter in 30 controls without neurological disease was 3.5 mm (range 2.5–4.1 mm). If 4.2 mm is taken as the upper limit of normal the sensitivity and specificity of this test for elevated ICP is 100% and 86%, respectively.
ONS ultrasound is an accurate method for detecting raised ICP that can be applied in a broad range of settings. It has the advantages of being a non-invasive, bedside test, which can be repeated multiple times for re-evaluation.
intracranial hypertension; optic nerve; ultrasound; Africa; papilloedema
To determine rates of, and factors associated with, disengagement from care in a decentralised antiretroviral programme.
Adults (≥16 years) who initiated antiretroviral therapy (ART) in the Hlabisa HIV Treatment and Care Programme August 2004–March 2011 were included. Disengagement from care was defined as no clinic visit for 180 days, after adjustment for mortality. Cumulative incidence functions for disengagement from care, stratified by year of ART initiation, were obtained; competing-risks regression was used to explore factors associated with disengagement from care.
A total of 4,674 individuals (median age 34 years, 29% male) contributed 13 610 person-years of follow-up. After adjustment for mortality, incidence of disengagement from care was 3.4 per 100 person-years (95% confidence interval (CI) 3.1–3.8). Estimated retention at 5 years was 61%. The risk of disengagement from care increased with each calendar year of ART initiation (P for trend <0.001). There was a strong association between disengagement from care and higher baseline CD4+ cell count (subhazard ratio (SHR) 1.94 (P < 0.001) and 2.35 (P < 0.001) for CD4+ cell count 150–200 cells/μl and >200 cells/μl respectively, compared with CD4 count <50 cells/μl). Of those disengaged from care with known outcomes, the majority (206/303, 68.0%) remained resident within the local community.
Increasing disengagement from care threatens to limit the population impact of expanded antiretroviral coverage. The influence of both individual and programmatic factors suggests that alternative service delivery strategies will be required to achieve high rates of long-term retention.
HIV-1; antiretroviral agents; primary health care; delivery of health care; lost to follow-up; disengagement from care
To describe initial registration characteristics of adult and pediatric TB patients at a large, public, integrated TB and HIV clinic in Lilongwe, Malawi, between January 2008 – December 2010.
Routine data on TB patient category and TB type, stratified by HIV and ART status, were used to explore differences in proportions among TB-only, TB/HIV co-infected patients not on ART, and TB/HIV co-infected patients on ART using Chi-square tests.. Trends over time illustrate strengths and weaknesses of integrated service provision.
Among 10,143 adults, HIV ascertainment and ART uptake were high and increased over time. The proportion of relapse was highest among those on ART (5%). The proportion of smear-positive pulmonary TB (PTB) was highest among HIV-negative TB patients (34.9%); extra-pulmonary TB (EPTB) was lowest among TB-only (16.2%). Among 338 children <15 years, EPTB and smear-positive PTB were more common among TB-only patients. Time trends showed significant increases in the proportion of adults with smear-positive PTB and the proportion of adults already on ART before starting TB treatment. However, some co-infected patients still delay ART initiation.
HIV ascertainment and ART uptake among co-infected patients is successful and improving over time. However, delays in ART initiation indicate some weakness linking TB/HIV patients into ART during TB follow-up care. Improved TB diagnostics and screening efforts, especially for pediatric patients, may help improve quality care for co-infected patients. These results may aid efforts to prioritize TB and HIV prevention, education, and treatment campaigns for specific populations.
TB/ART service integration; Malawi; TB; ART; HIV; smear-positive PTB
A substantial dropout from the first dose of diphtheria-tetanus-pertussis (DTP1) to the 3rd dose of DTP (DTP3) immunization has been recorded in Pakistan. We conducted a randomized controlled trial to assess the effects of providing substantially redesigned immunization card, center-based education, or both interventions together on DTP3 completion at six rural Expanded Programme on Immunization (EPI) centers in Pakistan.
Mother-child units were enrolled at DTP1 and randomized to four study groups: redesigned card, center-based education, combined intervention, and standard care. Each child was followed-up for 90 days to record the dates of DTP2 and DTP3 visits. The study outcome was DTP3 completion by the end of follow-up period in each study group.
We enrolled 378 mother-child units in redesigned card group, 376 in center-based education group, 374 in combined intervention group, and 378 in standard care group. By the end of follow-up, 39% of children in standard care group completed DTP3. Compared to this, a significantly higher proportion of children completed DTP3 in redesigned card group (66%) (crude Risk Ratio [RR] = 1.7; 95% CI = 1.5, 2.0), center-based education group (61%) (RR = 1.5; 95% CI = 1.3, 1.8), and combined intervention group (67%) (RR = 1.7; 95% CI = 1.4, 2.0).
Improved immunization card alone, education to mothers alone, or both together were all effective in increasing follow-up immunization visits. The study underscores the potential of study interventions’ public health impact and necessitates their evaluation for complete EPI schedule at a large scale in the EPI system.
To understand the health status of HIV orphans in a well-structured institutional facility in India.
Prospective longitudinal analysis of growth and anaemia prevalence among these children, between June 2008 and May 2011.
A total of 85 HIV-infected orphan children residing at Sneha Care Home, Bangalore, for at least 1 year, were included in the analysis. Prevalence of anaemia at entry into the home was 40%, with the cumulative incidence of anaemia during the study period being 85%. At baseline, 79% were underweight and 72% were stunted. All children, irrespective of their antiretroviral therapy (ART) status, showed an improvement in nutritional status over time as demonstrated by a significant increase in weight (median weight-for-age Z-score: −2.75 to −1.74, P < 0.001) and height Z-scores (median height-for-age Z-score: −2.69 to −1.63, P < 0.001).
These findings suggest that good nutrition even in the absence of ART can bring about improvement in growth. The Sneha Care Home model indicates that the holistic approach used in the Home may have been helpful in combating HIV and poor nutritional status in severely malnourished orphaned children.
HIV; orphans; institutional facility; growth; nutrition; antiretroviral therapy
To describe temporal trends in baseline clinical characteristics, initial treatment regimens and monitoring of patients starting antiretroviral therapy (ART) in resource-limited settings.
We analysed data from 17 ART programmes in 12 countries in sub-Saharan Africa, South America and Asia. Patients aged 16 years or older with documented date of start of highly active ART (HAART) were included. Data were analysed by calculating medians, interquartile ranges (IQR) and percentages by regions and time periods. Not all centres provided data for 2006 and 2005 and 2006 were therefore combined.
A total of 36 715 patients who started ART 1996–2006 were included in the analysis. Patient numbers increased substantially in sub-Saharan Africa and Asia, and the number of initial regimens declined, to four and five, respectively, in 2005–2006. In South America 20 regimes were used in 2005–2006. A combination of 3TC/D4T/NVP was used for 56% of African patients and 42% of Asian patients; AZT/3TC/ EFV was used in 33% of patients in South America. The median baseline CD4 count increased in recent years, to 122 cells/μl (IQR 53–194) in 2005–2006 in Africa, 134 cells/μl (IQR 72–191) in Asia, and 197 cells/μl (IQR 61–277) in South America, but 77%, 78% and 51%, respectively, started with <200 cells/μl in 2005–2006. In all regions baseline CD4 cell counts were higher in women than men: differences were 22 cells/μl in Africa, 65 cells/μl in Asia and 10 cells/μl in South America. In 2005–2006 a viral load at 6 months was available in 21% of patients Africa, 8% of Asian patients and 73% of patients in South America. Corresponding figures for 6-month CD4 cell counts were 74%, 77% and 81%.
The public health approach to providing ART proposed by the World Health Organization has been implemented in sub-Saharan Africa and Asia. Although CD4 cell counts at the start of ART have increased in recent years, most patients continue to start with counts well below the recommended threshold. Particular attention should be paid to more timely initiation of ART in HIV infected men.
HIV/AIDS; antiretroviral therapy; highly active; gender identity; sub-Saharan Africa; Asia; Latin America
To examine the accuracy of the World Health Organization immunological criteria for virological failure of antiretroviral treatment.
Analysis of 10 treatment programmes in Africa and South America that monitor both CD4 cell counts and HIV-1 viral load. Adult patients with at least two CD4 counts and viral load measurements between month 6 and 18 after starting a non-nucleoside reverse transcriptase inhibitor-based regimen were included. WHO immunological criteria include CD4 counts persistently <100 cells/μl, a fall below the baseline CD4 count, or a fall of >50% from the peak value. Virological failure was defined as two measurements ≥10 0000 copies/ml (higher threshold) or ≥500 copies/ml (lower threshold). Measures of accuracy with exact binomial 95% confidence intervals (CI) were calculated.
A total of 2009 patients were included. During 1856 person-years of follow up 63 patients met the immunological criteria and 35 patients (higher threshold) and 95 patients (lower threshold) met the virological criteria. Sensitivity [95% confidence interval (CI)] was 17.1% (6.6–33.6%) for the higher and 12.6% (6.7–21.0%) for the lower threshold. Corresponding results for specificity were 97.1% (96.3–97.8%) and 97.3% (96.5–98.0%), for positive predictive value 9.5% (3.6–19.6%) and 19.0% (10.2–30.9%) and for negative predictive value 98.5% (97.9–99.0%) and 95.7% (94.7–96.6%).
The positive predictive value of the WHO immunological criteria for virological failure of antiretroviral treatment in resource-limited settings is poor, but the negative predictive value is high. Immunological criteria are more appropriate for ruling out than for ruling in virological failure in resource-limited settings.
highly active antiretroviral therapy; treatment failure; CD4 lymphocyte count; viral load; diagnostic techniques and procedures; Africa
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.
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.
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.
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.
Podoconiosis; Non-filarial elephantiasis; Prevalence; Wuchereria bancrofti; Serology; Ethiopia
Bacterial vaginosis (BV) and Trichomonas vaginalis infection (TV) have been associated with adverse birth outcomes and increased risk for HIV. We compare the performance of simple inexpensive point-of-care (POC) tests to laboratory diagnosis and syndromic management of BV and TV in poor settings.
Between November 2005 and March 2006, 898 sexually active women attending two reproductive health clinics in Mysore, India were recruited into a cohort study investigating the relationship between vaginal flora and HSV-2 infection. Participants were interviewed and screened for reproductive tract infections. Laboratory tests included serology for HSV-2; cultures for TV, Candida sp., and Neisseria gonorrhoeae; Gram stains; and two POC tests: vaginal pH; and Whiff test.
Of the 898 participants, 411 [45.7%, 95% confidence interval (95% CI): 42.4–49.0%] had any laboratory diagnosed vaginal infection. BV was detected in 165 women (19.1%, 95%CI: 16.5–21.9%) using Nugent score. TV was detected in 76 women (8.5%, 95%CI: 6.7–10.4%) using culture. Among the entire study population, POC correctly detected 82% of laboratory diagnosed BV cases, and 83% of laboratory diagnosed TV infections. Among women with complaints of vulval itching, burning, abnormal vaginal discharge, and/or sores (445/898), POC correctly detected 83% (60 of 72 cases) of laboratory diagnosed BV cases vs. 40% (29 of 72 cases) correctly managed using the syndromic approach (P < 0.001). Similarly, POC would have detected 82% (37 of 45 cases) of TV cases vs. 51% (23 of 45 cases) correctly managed using the syndromic approach (P = 0.001).
In the absence of laboratory diagnostics, POC is not only inexpensive and practical, but also significantly more sensitive than the syndromic management approach, resulting in less overtreatment.
bacterial vaginosis; India; point-of-care; vaginal discharge; Trichomonas vaginalis; resource constrained settings
To describe specific causes of the high rates of stillbirth, neonatal death and early child childhood death in Zambia.
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).
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).
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.
autopsy; stillbirth; infant; Zambia; Africa; cause of death
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.
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.
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).
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.
sampling bias; chlamydia; RNA; neglected diseases
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.
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.
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).
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.
antiretroviral therapy; treatment failure; second-line therapy; immunologic and virologic screening; capacity building
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.
malaria diagnosis; clinical algorithms; IMCI guidelines; Kenya
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.
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.
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.
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.
HIV testing; pre-school children; mothers; caregivers; South Africa
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.
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).
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.
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.
cervical cancer; human papillomavirus; Africa; epidemiology
To review methods for the statistical analysis of parasite and other skewed count data.
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.
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.
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.
Statistical Data Analysis; Parasitology; Statistics, Nonparametric; Regression Analysis
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.
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.
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).
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.
HIV; provider initiated testing and counselling; WHO clinical staging; antiretroviral therapy; programmatic evaluation; primary health care; qualitative
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.
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.
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.
Visceral Leishmaniasis; Drug monitoring; Drug effectiveness; Public Health System; Recording and reporting; Supervised treatment; patient follow-up; ASHA Network
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.
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.
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.
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.
Taenia; Taenia solium; Taenia saginata; Ziehl Neelsen; cestodes; Perú
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.
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.
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.
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.
pneumonia; developing countries; integrated management of childhood illness; amoxicillin; effectiveness
To describe the contribution of paediatric HIV and of HIV co-infections to admissions to a hospital in Moshi, Tanzania, using contemporary laboratory 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.
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.
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.
Africa; bacteremia; HIV; paediatrics; Salmonella enterica; Streptococcus pneumoniae
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.
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.
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).
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.
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.
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.
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.
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.
HIV; TB; stigma; interventions; care-seeking; Zimbabwe