Real-time parameter estimation of Zika outbreaks using model averaging.

Early prediction of the final size of any epidemic and in particular for Zika disease outbreaks can be useful for health authorities in order to plan the response to the outbreak. The Richards model is often been used to estimate epidemiological parameters for arboviral diseases based on the reported cumulative cases in single- and multi-wave outbreaks. However, other non-linear models can also fit the data as well. Typically, one follows the so called post selection estimation procedure, i.e., selects the best fitting model out of the set of candidate models and ignores the model uncertainty in both estimation and inference since these procedures are based on a single model. In this paper we focus on the estimation of the final size and the turning point of the epidemic and conduct a real-time prediction for the final size of the outbreak using several non-linear models in which these parameters are estimated via model averaging. The proposed method is applied to Zika outbreak data in four cities from Colombia, during the outbreak ocurred in 2015-2016.

Time to initiation of multidrug-resistant tuberculosis treatment and its relation with outcome in a high incidence district in Lima, Peru.

OBJECTIVE: To determine the time from diagnosis to start of multidrug resistant tuberculosis (MDR TB) treatment in Lima, Peru. METHODS: We studied new smear-positive TB adults that were started on MDR TB treatment or that were switched to it between June 2008 and December 2011. RESULTS: Time from the first positive smear to MDR-TB treatment was >30 days in 35% (13/37) of patients. Among the 27% (24/88) of patients that switched to MDR-TB treatment, time from the last dose of a drug-susceptible regimen was >30 days. CONCLUSION: Start of and switching to MDR TB treatment is still delayed.

Manual liquid culture on simple Middlebrook 7H9 or MGIT for the diagnosis of smear-negative pulmonary tuberculosis.

OBJECTIVES: To compare the performance of liquid culture on simple Middlebrook 7H9 to the one of manual mycobacterial growth indicator tube (MGIT) and solid culture on Ogawa for the diagnosis of smear-negative tuberculosis (SN-TB) in a high-burden, resource-constrained setting. METHODS: Sputum samples from patients with clinical suspicion of SN-PTB admitted to two-third-level hospitals in Lima between September 2005 and May 2008 were cultured in parallel on simple Middlebrook 7H9, manual MGIT and Ogawa. A case of SN-TB was defined as one with a positive culture in any medium. RESULTS: Among samples from 542 patients, 151 (28%) cases of SN-TB were identified. The sensitivity of Middlebrook 7H9 (0.76, 95% CI 0.69-0.83) was not substantially different from that of MGIT (0.85, 95% CI 0.79-0.91). Ogawa had the lowest sensitivity (0.63, 95% CI 0.55-0.71). The median turnaround time was similar for both liquid media (18 days), and it was shorter than that of Ogawa (30 days). CONCLUSIONS: Culture on simple Middlebrook 7H9 performs almost as well as MGIT, at a probably more affordable cost. Further studies on the cost-effectiveness of this overlooked technique should be performed.

Isoniazid preventive therapy completion in children under 5 years old who are contacts of tuberculosis cases in Lima, Peru: study protocol for an open-label, cluster-randomized superiority trial.

BACKGROUND: Children < 5 years old in contact with TB cases are at high risk for developing severe and fatal forms of TB. Contact investigation, BCG vaccination, and isoniazid preventive therapy (IPT) are the most effective strategies to prevent TB among children. However, the implementation of IPT faces challenges at several stages of the cascade of care of TB infection among children, particularly those less than 5 years old. In Peru, a large proportion of children do not complete IPT, which highlights the need to design effective interventions that enhance preventive therapy adherence and completion. Although the body of evidence for such interventions has grown, interventions in medium TB incidence settings are lacking. This study aims to test the effectiveness, acceptability, and feasibility of an intervention package to increase information and motivation to complete IPT among children < 5 who have been prescribed IPT. METHODS: An open-label, cluster-randomized superiority trial will be conducted in two districts in South Lima, Peru. Thirty health facilities will be randomized as clusters, 10 to the intervention and 20 to control (standard of care). We aim to recruit 10 children from different households in each cluster. Participants will be caretakers of children aged < 5 years old who initiated IPT. The intervention consists of educational material, and short message services (SMS) reminders and motivators. The primary outcomes will be the proportion of children who picked up > 90% of the 24 weeks of IPT (22 pick-ups) and the proportion of children who picked up the 24 weeks of IPT. The standard of care is a weekly pick-up with monthly check-ups in a health facility. Feasibility and acceptability of the intervention will be assessed through an interview with the caretaker. DISCUSSION: Unfavorable outcomes of TB in young children, high effectiveness of IPT, and low rates of IPT completion highlight the need to enhance adherence and completion of IPT among children < 5 years old. Testing of a context-adapted intervention is needed to improve IPT completion rates and therefore TB prevention in young children. TRIAL REGISTRATION: ClinicalTrials.gov NCT03881228. Registered on March 19, 2019.

Determinants of uptake, short-term and continued use of insecticide-treated curtains and jar covers for dengue control.

OBJECTIVE: To evaluate the acceptance and long-term use of insecticide-treated (IT) materials for dengue vector control. METHODS: In 2007, IT jar covers and/or curtains (PermaNet®) were distributed under routine conditions to 4101 households (10 clusters) in Venezuela and to 2032 households (22 clusters) in Thailand. The use of IT tools was measured at distribution (uptake), at 5/6 months (short-term use) and at 18/22 months (continued use) after distribution. Determinants of use were assessed with logistic regression analysis. RESULTS: The uptake of IT curtains was 76.7% in Venezuela and 92.3% in Thailand. It was associated with being a resident for >5 years (OR Venezuela 3.0 95% CI 2.0-4.4; OR Thailand 3.5 95% CI 1.7-7.3) and with pre-intervention use of ordinary curtains (OR Venezuela 2.2 95% CI 1.4-3.6). The continued use decreased significantly to 38.4% of households in Venezuela and 59.7% in Thailand and was, conditional on short-term use, only determined by the perceived effectiveness of IT curtains (OR Venezuela 13.0 95%CI 8.7-19.5; OR Thailand 4.9 95% CI 3.1-7.8). Disease knowledge and pre-intervention perception of mosquito nuisance were not associated with IT curtains' uptake or use. The uptake of IT jar covers in Venezuela was 21.5% and essentially determined by the presence of uncovered jars in the household (OR 32.5 95% CI 14.5-72.6). Their continued use, conditional on short-time use, was positively associated with the household use of Abate® (OR 7.8 95% CI 2.1-28.9). CONCLUSION: The use of IT curtains rapidly declines over time. Continued use is mainly determined by the perceived effectiveness of the tool. This poses a real challenge if IT curtains are to be introduced in dengue control programmes.

Residual insecticidal activity of long-lasting deltamethrin-treated curtains after 1 year of household use for dengue control.

OBJECTIVE: To evaluate the residual insecticidal activity of the PermaNet(®) curtains on Aedes aegypti after 1 year of use in Thai households and to assess the influence of sun and dust exposure, washing practices and detergent use. METHODS: We sampled UV-protected PermaNet(®) curtains made of a long-lasting deltamethrin-[55 mg/m(2)] treated polyester netting, before (10 curtains) and after 8 (10 curtains) and 12 months (66 curtains) of household use in a field site in Chon Buri, Thailand. We assessed the residual insecticidal activity of the curtains by standard WHO bioassay, using a deltamethrin-susceptible insectarium Aedes aegypti strain. RESULTS: Mosquito mortality was 100% before distribution, 100% at 8 months and 98.2% (95% CI 97.9-98.5) at 12 months of use. Sunlight, hand-washing and detergent use had no effect on the residual insecticidal activity after 12 months. However, the mosquito survival rate increased by a factor of 6.4 (95% CI 3.5-11.8) on machine-washed curtains and by a factor of 2.0 (95% CI 1.4-2.9) on curtains not covered by dust. CONCLUSION: The residual insecticidal activity of PermaNet® curtains remains high after 12 months use under field conditions.

Breteau Index threshold levels indicating risk for dengue transmission in areas with low Aedes infestation.

We used Breteau Indices to - retrospectively - predict dengue transmission. The presence of one house block (on average about 50 houses) with a Breteau Index >or=4 in a neighbourhood (a block plus the surrounding blocks in a radius of 100 m) predicted transmission at the latter level with 81.8% sensitivity and 73.3% specificity during the first month of the Havana 2001 dengue outbreak. This result corroborates the external validity of this threshold, at least in situations with low infestations levels.

Duration of cough, TB suspects' characteristics and service factors determine the yield of smear microscopy.

OBJECTIVE: To determine the efficiency of routine tuberculosis (TB) case detection by examining sputum smear positivity for acid-fast bacilli in relation to duration of cough, characteristics of TB suspects examined and health service factors. METHOD: We combined patient interviews with routine data from laboratory registers in 6 health care facilities in San Juan de Lurigancho district, Lima, Peru. A TB case was defined as a TB suspect with at least one positive sputum smear. We calculated adjusted odds ratios with 95% confidence intervals for the association between smear positivity and health service and patient's characteristics. RESULTS: Smear positivity was 7.3% (321/4376). Of the 4376 adults submitting sputa, 55.3% (2418) reported cough for <14 days. In this group, smear microscopy yielded 3.2% (78/2418) positive results vs. 12.4% (243/1958) in patients coughing for 14 or more days. Having cough for >2 weeks, being referred by health care staff, attending a secondary-level health care facility, male sex and age between 15 and 44 years were independent determinants of smear positivity. CONCLUSIONS: Routine case detection yields a low proportion of smear-positive cases because of the inclusion of a high proportion of patients without cough or coughing for <2 weeks. Adherence to the national TB control programme guidelines on the selection of TB suspects would have a positive impact on the smear positivity rate, reduce laboratory costs and workload and possibly improve the reading quality of smear microscopy.

Intersectoral coordination, community empowerment and dengue prevention: six years of controlled interventions in Playa Municipality, Havana, Cuba.

OBJECTIVE: To document the process, outcome and effectiveness of a community-based intervention for dengue control. METHODS: The primary intervention, focused on strengthening intersectoral coordination, was initiated by researchers in January 2000 in a pilot area in Playa municipality, Havana. In August 2002 health authorities extended the intervention to neighbouring areas, one of which was selected for evaluation. In August 2003 a complementary strategy, focused on community empowerment, was initiated in half of the pilot area. In our control area, routine dengue activities continued throughout the study period. Longitudinal process assessment was carried out using document analysis, interviews and group discussions. Random population surveys in 1999, 2002 and 2005 assessed levels of participation and behavioural changes. Entomological surveillance data from 1999 to 2005 were used to determine effectiveness. RESULTS: Mean scores for participation in the pilot area were 1.6, 3.4 and 4.4 at baseline, and 2 years after initiating intersectoral coordination and intersectoral coordination plus community empowerment interventions, respectively. While in the control area little behavioural change was observed over time, changes were considerable in the pilot and extension areas, with 80% of households involved in the community empowerment intervention showed adequate behavioural patterns. The pilot and extension areas attained comparable entomological effectiveness with significantly lower Breteau indices (BIs) than the control area. The pilot (sub-) area with the community empowerment intervention reached BIs below 0.1 that continued to be significantly lower than the one in the control area until the end of the study. CONCLUSION: The study showed a trend in the levels and quality of participation, behavioural change and effectiveness of Aedes control from the routine activities only over an intervention with intersectoral coordination to one that combined intersectoral coordination and community empowerment approach.

Could clinical audit improve the diagnosis of pulmonary tuberculosis in Cuba, Peru and Bolivia?

OBJECTIVES: To assess the effectiveness of clinical audit in improving the quality of diagnostic care provided to patients suspected of tuberculosis; and to understand the contextual factors which impede or facilitate its success. METHODS: Twenty-six health centres in Cuba, Peru and Bolivia were recruited. Clinical audit was introduced to improve the diagnostic care for patients attending with suspected TB. Standards were based on the WHO and TB programme guidelines relating to the appropriate use of microscopy, culture and radiological investigations. At least two audit cycles were completed over 2 years. Improvement was determined by comparing the performance between two six-month periods pre- and post-intervention. Qualitative methods were used to ascertain facilitating and limiting contextual factors influencing change among healthcare professionals' clinical behaviour after the introduction of clinical audit. RESULTS: We found a significant improvement in 11 of 13 criteria in Cuba, in 2 of 6 criteria in Bolivia and in 2 of 5 criteria in Peru. Twelve out of 24 of the audit criteria in all three countries reached the agreed standards. Barriers to quality improvement included conflicting objectives for clinicians and TB programmes, poor coordination within the health system and patients' attitudes towards illness. CONCLUSIONS: Clinical audit may drive improvements in the quality of clinical care in resource-poor settings. It is likely to be more effective if integrated within and supported by the local TB programmes. We recommend developing and evaluating an integrated model of quality improvement including clinical audit.

A clinical prediction rule for pulmonary tuberculosis in emergency departments.

SETTING: University-affiliated hospital located in an area with a high incidence of pulmonary tuberculosis (PTB). OBJECTIVE: To develop a clinical prediction rule (CPR) based on information obtainable on admission, to permit rapid identification of patients with PTB. DESIGN: Information from patients with respiratory symptoms who attended the emergency department of Cayetano Heredia Hospital, Lima, Peru, was collected prospectively. Clinical symptoms, past medical history, demographic data and results of chest X-rays (CXRs), sputum smear and culture in Löwenstein-Jensen media were obtained. Based on logistic regression, we constructed a scoring system to predict PTB. RESULTS: A total of 345 patients were enrolled in the study, including 109 (31%) culture-proven PTB cases. In logistic regression analysis, we found age, previous history of PTB, weight loss, presence of cavities, upper lobe infiltrate and miliary pattern on CXR as independent predictors of PTB. We designed a scoring system with these variables, taking into account their statistical weight. The score attained 93% sensitivity and 42% specificity. CONCLUSION: The CPR that was developed performed well in our population. It merits further validation in other settings. It should not, however, replace, but should complement sputum microscopy when deciding on isolation, and it does not preclude microbiology in making a definitive diagnosis.

Exploring HIV risk perception and behaviour in the context of antiretroviral treatment: results from a township household survey.

The objective of this cross-sectional household survey was to assess factors influencing HIV risk perception, behaviour and intervention uptake in a community characterised by high HIV prevalence and availability of antiretroviral therapy (ART). The survey was conducted in Khayelitsha, South Africa and involved two-stage sampling with self-weighting clusters and random selection of households within clusters. One man and woman between 14 and 49 years old was interviewed in each household; 696 men and 879 women were interviewed for a response rate of 84% and 92% respectively. Ninety-three percent and 94% were sexually active with median age of sexual debut 15.3 and 16.5 years. Eighty-three percent and 82% reported a partner at the time of interview and 29% and 8% had additional partner(s). Forty-one percent and 33% reported condom use during the last sexual encounter. Thirty-seven percent of men not using condoms did not as they believed their partner to be faithful, whilst 27% of women did not as their partner refused. Twenty-eight percent and 53% had been tested for HIV. Having undergone HIV testing was not associated with condom usage, whilst current relationship status was the strongest association with condom usage for both men and women. In spite of a relatively high uptake of condoms and testing as well as ART availability, the HIV epidemic has continued unabated in Khayelitsha. Even greater coverage of preventive interventions is required, together with a national social and political environment that builds on the availability of both preventive and treatment services.

Improving sputum microscopy services for the diagnosis of tuberculosis in Peru and Bolivia.

SETTING: Sixteen primary care health centres in Peru and Bolivia. OBJECTIVES: To assess the utilisation of microscopy services in Peru and Bolivia and determine if clinical audit, a quality improvement tool, improves the utilisation of these services. DESIGN: We estimated the percentage of patients with suspected tuberculosis (TB) in whom sputum microscopy was effectively utilised in Peru and Bolivia over two 6-month periods before and after a clinical audit intervention that included standards setting, measuring clinical performance and feedback. RESULTS: Before the intervention, only 31% (95%CI 27-35) of TB suspects were assessed with sputum microscopy in Peru. In Bolivia, 30% (95%CI 25-35) underwent at least two sputum microscopy examinations. After clinical audit, the availability of sputum microscopy results improved by respectively 7% (95%CI 1-12, P < 0.05) and 23% (95%CI 15-30, P < 0.05) over 2 years in Peru and Bolivia. CONCLUSIONS: Despite World Health Organization recommendations that all TB suspects should undergo sputum microscopy before treatment, results are available for further assessment for only one third. This is a potentially serious obstacle to TB case detection. Clinical audit can bring some improvement. We recommend regular monitoring of effective utilisation of microscopy services and investigations to ascertain organisational and structural issues in their uptake and use.

Towards active community participation in dengue vector control: results from action research in Santiago de Cuba, Cuba.

Community participation is advocated as essential for attaining effective dengue prevention, but knowledge of how to foster this is limited. In Santiago de Cuba, multiple small task forces were created at the neighbourhood level that included all stakeholders in the control of Aedes aegypti. The task forces assessed the perceived needs and elaborated action plans to promote specific behavioural change and to reduce environmental risks through social communication strategies and intersectoral local government activities. We monitored five dimensions of the participation process and assessed behavioural and environmental results and entomological outcomes. Participation was weak to good. At the household level, uncovered water storage containers decreased from 49.3% to 2.6% between 2000 and 2002, and removing larvicide from them dropped from 45.5% to 1%. There was a reduction of 75% in the absolute number of positive containers and a significant decrease from 1.23% to 0.35% in the house index. Local task forces, in which the interests of householders as well as vector control workers are directly represented, can lead to effective government-community partnerships that resolve problems of mutual concern.

Cost effectiveness of Aedes aegypti control programmes: participatory versus vertical.

We conducted an economic appraisal of two strategies for Aedes aegypti control: a vertical versus a community-based approach. Costs were calculated for the period 2000-2002 in three pilot areas of Santiago de Cuba where a community intervention was implemented and compared with three control areas with routine vertical programme activities. Reduction in A. aegypti foci was chosen as the measure of effectiveness. The pre-intervention number of foci (614 vs. 632) and economical costs for vector control (US$243746 vs. US$263486) were comparable in the intervention and control areas. During the intervention period (2001-2002), a 13% decrease in recurrent costs for the health system was observed. Within the control areas, these recurrent relative costs remained stable. The number of A. aegypti foci in the pilot areas and the control areas fell by 459 and 467, respectively. The community-based approach was more cost effective from a health system perspective (US$964 vs. US$1406 per focus) as well as from society perspective (US$1508 vs. US$1767 per focus).

The economic burden of visceral leishmaniasis for households in Nepal.

Visceral leishmaniasis (VL) affects persons from the lowest socioeconomic strata of the community, but its economic impact is not precisely known. An exploratory survey to document the economic costs of VL to households was conducted in an endemic focus in eastern Nepal. Data were collected from the 20 households in this cluster. Cases of VL over the last 3 years were elicited and information on direct and indirect costs incurred due to the disease as well as income of the households over the last year was estimated. It was reported that 15.0% (16/107) of the residents had suffered from VL and that almost all of the patients had preferred, in the first instance, to visit the private services or local faith healers instead of visiting the local public health facility. Average total costs incurred per episode of VL were above the median annual per capita income, and six of the seven affected households either had to sell part of their livestock or to take a loan to cover the costs. Direct costs consisted of 53% of the total cost, with 75% of this cost incurred before the patients actually received any treatment for VL. This study demonstrates how VL can lead to catastrophic expenditure for affected households.

Private practitioners' contributions to the Revised National Tuberculosis Control Programme in a South Indian district.

SETTING: Tumkur District, South India. OBJECTIVE: To assess the participation of for-profit, formal private practitioners (PPs) under the Revised National Tuberculosis Control Programme's (RNTCP's) public-private mix (PPM) schemes and document their contribution to RNTCP pulmonary tuberculosis (TB) case finding. DESIGN: RNTCP reports at district TB centre were reviewed. PPs were mapped and their referrals of presumptive TB cases to the RNTCP during 2011 were assessed using laboratory registers at designated microscopy centres (DMCs). RESULTS: None of the 424 PPs had signed up for any PPM scheme. However, 22% made at least one referral to a DMC in 2011. PP referrals constituted 15% of the presumptive TB cases examined at the DMCs, and PPs contributed to 23% of the sputum smear-positive TB cases detected. Among PP referrals, the proportion of confirmed smear-positive cases was high (24%). CONCLUSION: Fifteen years after the start of PPM, formal engagement of PPs with RNTCP was non-existent. However, PPs do refer cases to the RNTCP and contribute to a fraction of TB case detection. The high proportion of confirmed sputum smear-positive cases suggests that PPs tend to make selective referrals. More efforts are needed to promote the engagement of PPs in the RNTCP.

Advanced immunodeficiency as a risk factor for heterosexual transmission of HIV.

To define the rate of HIV infection and associated risk factors among heterosexual partners of HIV-infected individuals, 80 partners and 77 index cases were examined for clinical, behavioural and virological variables. The study population included 61 male and 16 female index cases, of whom 40 were European and 37 African. Multiple sexual partners in central Africa was the risk factor for HIV infection in 83%. The overall infection rate among the contact cases was 45%, 53% among female partners and 13% among male partners (P less than 0.001). Variables significantly associated with HIV infection in the partners included advanced clinical stage (AIDS-related complex or AIDS), a low concentration of T4 lymphocytes and African nationality of the index case, young age of the partner, and more than 50 instances of sexual contact with the index cases. In a logistic regression analysis, a low concentration of T4 lymphocytes, clinical stage ARC/AIDS and African nationality of the index case but not number of sexual contacts, remained as independent risk factors for HIV transmission. Our data indicate that there is a significant biological heterogeneity in sexual transmission of HIV and that advanced clinical stage and severe T cell depletion of the index case are major determinants of infectivity.

Operational validation of the direct agglutination test for diagnosis of visceral leishmaniasis.

The validity of the direct agglutination test (DAT) for visceral leishmaniasis (VL) was studied with a standardized field kit on 148 clinically suspected persons and 176 healthy controls recruited between 1993 and 1994 from an endemic area in Gedaref State, Sudan. A sensitivity of 95.9% and a specificity of 99.4% were found at a 1: 8,000 cut-off titer when parasitologically confirmed cases were compared with healthy controls. While corroborating previously reported sensitivity and specificity estimates of this serodiagnostic test, this study examined the bias generated by commonly used test validation procedures. The fundamental methodologic problem in VL test validation is the absence of a reliable gold standard. Moreover, any operational guideline on DAT use has to consider the critical dependency of the predictive values of the test on VL prevalence rates. The DAT diagnostic cut-off titer depends upon many external factors, among which the prevalence of disease in the area and the case mix seem the most important.