They do not have symptoms - why do they need to take medicines? Challenges in tuberculosis preventive treatment among children in Cambodia: a qualitative study.

BACKGROUND: Latent tuberculosis (TB) infection has been known as a seedbed for TB disease later in life. The interruption from latent TB infection to TB disease can be done through TB preventive treatment (TPT). In Cambodia, only 40.0% of children under five years old who were the household contacts to bacteriologically confirmed TB cases were initiated with TPT in 2021. Scientific studies of context-specific operational challenges in TPT provision and uptake among children are scarce, particularly in high TB-burden countries. This study identified challenges in TPT provision and uptake among children in Cambodia from the perspective of healthcare providers and caregivers. METHODS: Between October and December 2020, we conducted in-depth interviews with four operational district TB supervisors, four clinicians and four nurses in charge of TB in referral hospitals, four nurses in charge of TB in health centers, and 28 caregivers with children currently or previously on TB treatment or TPT, and those who refused TPT for their eligible children. Data were audio recorded along with field notetaking. After verbatim transcription, data analyses were performed using a thematic approach. RESULTS: The mean age of healthcare providers and caregivers were 40.19 years (SD 12.0) and 47.9 years (SD 14.6), respectively. Most healthcare providers (93.8%) were male, and 75.0% of caregivers were female. More than one-fourth of caregivers were grandparents, and 25.0% had no formal education. Identified key barriers to TPT implementation among children included TPT side effects, poor adherence to TPT, poor understanding of TPT among caregivers, TPT risk perception among caregivers, TPT's child-unfriendly formula, TPT supply-chain issues, caregivers' concern about the effectiveness of TPT, being non-parental caregivers, and poor community engagement. CONCLUSION: Findings from this study suggest that the national TB program should provide more TPT training to healthcare providers and strengthen supply chain mechanisms to ensure adequate TPT drug supplies. Improving community awareness of TPT among caregivers should also be intensified. These context-specific interventions will play a crucial role in expanding the TPT program to interrupt the development from latent TB infection to active and ultimately lead to ending TB in the country.

Barriers to childhood tuberculosis case detection and management in Cambodia: the perspectives of healthcare providers and caregivers.

BACKGROUND: Diagnosis and treatment of tuberculosis (TB) in children remain challenging, particularly in resource-limited settings. Healthcare providers and caregivers are critical in improving childhood TB screening and treatment. This study aimed to determine the barriers to childhood TB detection and management from the perspectives of healthcare providers and caregivers in Cambodia. METHOD: We conducted this qualitative study between November and December 2020. Data collection included in-depth interviews with 16 healthcare providers purposively selected from four operational districts and 28 caregivers of children with TB and children in close contact with bacteriologically confirmed pulmonary TB residing in the catchment areas of the selected health centers. Data were analyzed using thematic analyses. RESULTS: Mean ages of healthcare providers and caregivers were 40.2 years (standard deviation [SD] 11.9) and 47.9 years (SD 14.6), respectively. Male was predominant among healthcare providers (93.8%). Three-fourths of caregivers were female, and 28.6% were grandparents. Inadequate TB staff, limited knowledge on childhood TB, poor collaboration among healthcare providers in different units on TB screening and management, limited quality of TB diagnostic tools, and interruption of supplies of childhood TB medicines due to maldistribution from higher levels to health facilities were the key barriers to childhood TB case detection and management. Caregivers reported transportation costs to and from health facilities, out-of-pocket expenditure, time-consuming, and no clear explanation from healthcare providers as barriers to childhood TB care-seeking. Aging caregivers with poor physical conditions, lack of collaboration from caregivers, ignorance of healthcare provider's advice, and parent movement were also identified as barriers to childhood TB case detection and management. CONCLUSIONS: The national TB program should further invest in staff development for TB, scale-up appropriate TB diagnostic tools and ensure its functionalities, such as rapid molecular diagnostic systems and X-ray machines, and strengthen childhood TB drug management at all levels. These may include drug forecasting, precise drug distribution and monitoring mechanism, and increasing community awareness about TB to increase community engagement.

Knowledge, attitude, and practices regarding childhood tuberculosis detection and management among health care providers in Cambodia: a cross-sectional study.

BACKGROUND: The World Health Organization (WHO) estimated that 29% of global tuberculosis (TB) and almost 47% of childhood TB cases were not reported to national TB programs in 2019. In Cambodia, most childhood TB cases were reported from health facilities supported by the Global Fund to Fight AIDS, Tuberculosis, and Malaria in 2019. This study aimed to compare the healthcare providers' knowledge, attitude, and practices (KAP) on childhood TB case detection in operational districts (ODs) with high and low childhood TB case detection in Cambodia. METHODS: We conducted a cross-sectional study between November and December 2020 among healthcare providers in 10 purposively selected ODs with high childhood TB case detection and 10 ODs with low childhood TB case detection. A total of 110 healthcare providers from referral hospitals (RHs) and 220 from health centers (HCs) were interviewed. We collected information on socio-demographic characteristics, training, and KAP on childhood TB. Pearson's Chi-square or Fisher's exact and Student's t-tests were performed to explore the differences in KAP of healthcare providers from ODs with low vs. high childhood TB detection. RESULTS: Of the 330 respondents, 193 were from ODs with high childhood TB case detection, and 66.67% were from HCs. A significantly higher proportion (46.11%) of respondents from ODs with high childhood TB case detection received training on childhood TB within the past two years than those from low childhood TB case detection ODs (34.31%) (p = 0.03). Key knowledge on childhood TB was not significantly different among respondents from ODs with high and low childhood TB case detection. A significantly higher proportion of respondents from ODs with high childhood TB case detection had a good attitude (98.96 vs. 97.08%, p = 0.002) and performed good practices (58.55 vs. 45.26%, p = 0.02) on contact investigation in the community than those from low childhood TB case detection ODs. CONCLUSIONS: Healthcare providers from ODs with high childhood TB detection had better attitudes and practices towards childhood TB. The attitudes and practices need to be improved among healthcare providers in ODs with low case detection. Further investment in training and experience sharing on childhood TB case detection among healthcare providers is needed to improve childhood TB case detection.

Development of weight and age-based dosing of daily primaquine for radical cure of vivax malaria.

BACKGROUND: In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax. METHODS: The recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly efficacious against tropical P. vivax and was assumed to produce optimal drug exposure. Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to define weight-for-age relationships. The median age associated with each weight was used to derive an age-based dosing regimen from the weight-based regimen. RESULTS: The proposed weight-based regimen has 5 dosing bands: (i) 5-7 kg, 5 mg, resulting in 0.71-1.0 mg/kg/day; (ii) 8-16 kg, 7.5 mg, 0.47-0.94 mg/kg/day; (iii) 17-40 kg, 15 mg, 0.38-0.88 mg/kg/day; (iv) 41-80 kg, 30 mg, 0.37-0.73 mg/kg/day; and (v) 81-100 kg, 45 mg, 0.45-0.56 mg/kg/day. The corresponding age-based regimen had 4 dosing bands: 6-11 months, 5 mg, 0.43-1.0 mg/kg/day; (ii) 1-5 years, 7.5 mg, 0.35-1.25 mg/kg/day; (iii) 6-14 years, 15 mg, 0.30-1.36 mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35-1.07 mg/kg/day. CONCLUSION: The proposed weight-based regimen showed less variability around the primaquine dose within each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy could be achieved by additional dosing bands for both regimens. The age-based regimen might not be applicable to regions outside the GMS, which must be based on local anthropometric data. Pharmacokinetic data in small children are needed urgently to inform the proposed regimens.

Joint effects of alcohol and stimulant use disorders on self-reported sexually transmitted infections in a prospective study of Cambodian female entertainment and sex workers.

Female entertainment and sex workers (FESW) have high rates of alcohol and amphetamine-type stimulant (ATS) use, increasing risk for HIV/sexually transmitted infections (STI), and other negative outcomes. A prospective cohort of 1,198 FESW in a HIV/ATS use prevention intervention in Cambodia was assessed for alcohol and stimulant use disorders (AUD and SUD) using the Alcohol and Substance Use Involvement (ASSIST) scale. STI history was measured by self-report at baseline and at quarterly follow-up visits. Participants were asked if they had been diagnosed with an STI by a medical provider in the past 3 months. Marginal structural models were used to estimate joint effects of AUD and SUD on recent STI. At baseline, one-in-four screened AUD positive and 7% screened positive for SUD. At 18-months, 26% reported ≥1 recent STI. Accounting for time-varying and other known confounders, the adjusted odds ratio (AOR) for recent STI associated with AUD alone and SUD alone were 2.8 (95% CI:1.5-5.1) and 3.5 (95% CI:1.1-11.3), respectively. The AOR for joint effects of AUD and SUD was 5.7 (95% CI:2.2-15.2). AUD and SUD are independently and jointly associated with greater odds of STI among Cambodian FESW. Further research is critical for understanding how AUD and SUD potentiate biological and behavioural pathways that influence STI acquisition and to inform HIV risk-reduction interventions in FESW.

Proportion and predictors of loss to follow-up in a longitudinal cohort study of female entertainment and sex workers in Cambodia.

We examined the proportion and correlates of loss to follow-up (LTFU) among female entertainment and sex workers (FESWs) in a longitudinal HIV prevention intervention trial in Cambodia. The Cambodia Integrated HIV and Drug Prevention Intervention trial tested a comprehensive package of interventions aimed at reducing amphetamine-type stimulant use and HIV risk among FESWs in ten provinces. The present study estimated the proportion of women LTFU and assessed factors associated with LTFU. Logistic regression analyses were used. Of a total 596 women enrolled, the cumulative proportion of LTFU was 29.5% (n = 176) between zero- and 12-month follow-up. In multivariate analyses, women with no living children (adjusted odds ratio [AOR] 1.6; 95% confidence interval [CI]: 1.1, 2.3) and those who experienced recent food insecurity (AOR 1.7; 95%CI: 1.1, 2.7) were more likely to be LTFU. Women who were members of the SMARTgirl HIV prevention programme for ≥ 6 months compared to non-members were less likely to be LTFU (AOR 0.3; 95%CI: 0.2, 0.6). LTFU was moderately high in this study and similar to other studies, indicating a need for strategies to retain this population in HIV prevention programmes and research. Interventions aimed at stabilizing women's lives, including reducing food insecurity and creating communities of engagement for FESWs, should be considered.

History of malaria treatment as a predictor of subsequent subclinical parasitaemia: a cross-sectional survey and malaria case records from three villages in Pailin, western Cambodia.

BACKGROUND: Treatment of the sub-clinical reservoir of malaria, which may maintain transmission, could be an important component of elimination strategies. The reliable detection of asymptomatic infections with low levels of parasitaemia requires high-volume quantitative polymerase chain reaction (uPCR), which is impractical to conduct on a large scale. It is unknown to what extent sub-clinical parasitaemias originate from recent or older clinical episodes. This study explored the association between clinical history of malaria and subsequent sub-clinical parasitaemia. METHODS: In June 2013 a cross-sectional survey was conducted in three villages in Pailin, western Cambodia. Demographic and epidemiological data and blood samples were collected. Blood was tested for malaria by high-volume qPCR. Positive samples were analysed by nested PCR to determine the Plasmodium species. To identify previous episodes of malaria, case records were collected from village malaria workers and local health facilities and linked to study participants. RESULTS: Among 1343 participants, 40/122 (32.8 %) with a history of clinical malaria were parasitaemic during the cross-sectional survey, compared to 172/1221 (14.1 %) without this history (p < 0.001). Among the 212 parasitaemic participants in the survey, 40 (18.9 %) had a history of clinical malaria, compared to 87 out of 1131 (7.7 %) parasite-negative participants; p < 0.001, adjusted OR 3.3 (95 % CI; 2.1-5.1). A history of Plasmodium vivax was associated with sub-clinical P. vivax parasitaemia in the survey (p < 0.001), but this association was not seen with Plasmodium falciparum (p = 0.253); only three participants had both P. falciparum parasites in the survey and a clinical history of P. falciparum. CONCLUSIONS: A clinical episode of vivax malaria was associated with subsequent sub-clinical parasitaemia. Treatment of P. vivax with artemisinin-based combination therapy without primaquine often resulted in recurrent episodes. Targeting individuals with a history of clinical malaria will be insufficient to eliminate the sub-clinical reservoir as they constitute a minority of parasitaemias.

Survival and quality of life among HIV-positive people on antiretroviral therapy in Cambodia.

In 2004, Cambodia, a low-income country, undertook a rapid scale-up of free antiretroviral therapy (ART) through the public sector in order to respond to the need for treatment for those living with HIV/AIDS. A cohort of patients initiating ART in a provincial national hospital was set up at the beginning of the program to monitor the impact of treatment on patients. Patients provided information on behaviors through face-to-face interviews. Medical data were obtained from clinical files. Health-related quality of life (HRQOL) was assessed using the Medical Outcomes Study 21-Items Short Form (MOS SF-21). Patients were interviewed when initiating ART and followed up at 3 months, 6 months, and each consecutive 6 months thereafter. From March 2005 through January 2008, the cohort included 549 patients followed for a total of 645 person-years. The 4.0% of patients lost to follow-up were considered dead in the analysis. Incidence of mortality was 9.1 per 100 person-years, which is comparable to international standards. HRQOL subscale scores increased dramatically in the first year after initiating ART. The mean of overall HRQOL score rose from 63.0 at baseline to 81.1 at 1 year and 89.9 at 30 months of follow-up (chi(2) for trends p < 0.001). Simultaneously, the proportion of patients with full-time employment increased from 48.8% to 95.7%.We conclude that the rapid scaling-up of ART delivery in a resource poor Asian setting dramatically improved the survival and well-being of its beneficiaries, who in turn resumed productive lives within their communities.

Simultaneous use of multiple condoms among male Cambodian military personnel visiting female sex workers.

OBJECTIVES: To estimate the prevalence of simultaneous use of multiple condoms (SUMC) and identify the characteristics of the multiple condoms users. STUDY DESIGN: Cross-sectional survey among military men from a purposively selected Cambodian military region. Military men were interviewed face to face. RESULTS: From the 1638 respondents, 40% never had sex with female sex workers (FSWs), 55% had used condom(s), and 5% had unprotected sex at their last encounter with a FSW. Among those reporting sex with FSWs, 21% had used multiple condoms simultaneously at their last sex with a FSW. CONCLUSION: Compared with single condom users, multiple condom users were younger, had lower rank, had first sex more recently, had lower knowledge of HIV transmission, had received less HIV peer-education sessions, were more likely to have visited multiple FSWs, and were more likely to have sought their HIV serostatus. As it is unknown if SUMC increases or decreases condom effectiveness, more research is needed to investigate the effect of SUMC on condom failure rates.

HIV, STIs, and sexual behaviors among men who have sex with men in Phnom Penh, Cambodia.

A probability sample of 206 men who have sex with men from 16 sites in Phnom Penh were surveyed about sexual behaviors and tested for HIV and sexually transmitted infections (STIs). HIV and syphilis prevalence was 14.4% and 5.5%, respectively. Out of the total sample, 81% reported anal sex with any male partners in the past 6 months, and 61.2% reported having had vaginal sex. In the past 6 months, 82.8% of the sample reported having male partners who paid them to have sex. Self-reported sexual orientation did not match well with self-reported sexual behavior. Significant risk factors for HIV infection were anal sex with multiple partners, unprotected vaginal sex with commercial female partners in the past month, and any STI. Complex sexual networks indicate that men who have sex with men act as a bridge between higher and lower HIV prevalence populations. Better prevention efforts structured around behaviors rather than sexual identities are needed.