Fighting HIV/AIDS: Reconfiguring the State?

The author wishes to thank the anonymous reviewers of the article and the ESRC for funding part of this research

Awareness regarding eye donation among stakeholders in Srikakulam district in South India

Background There is a huge need for the availability of transplantable donor corneas worldwide to reduce the burden of corneal blindness due to corneal opacity. Voluntary eye donation depends on the awareness levels of various stakeholders in the community. This study aimed to assess the awareness level regarding eye donation among various stakeholders in Srikakulam district in the state of Andhra Pradesh, India. Methods 355 subjects were selected from the district using multi stage random sampling. A pre tested semi structured questionnaire was used to collect information regarding each individual’s awareness, knowledge, and perception regarding eye donation. Each response was scored individually and a total score was calculated. Univariate and multivariate regression analysis was used to determine the factors associated with willingness towards eye donation and increased awareness levels. Results Of the 355 subjects interviewed, 192 (54%) were male and 163 (46%) were female. The mean age of the stakeholders was 35.9 years (SD ±16.1) and all the study subjects were literate. Ninety-three percent of subjects were aware of the concept of eye donation. Knowledge levels were similar among the teaching community and persons engaged in social service, but lower among students (p < 0.05). Among the stakeholders, there was considerable ambiguity regarding whether persons currently wearing spectacles or suffering from a chronic illnesses could donate their eyes. Older age group (p < 0.001), female gender (p < 0.001) and education (p < 0.001) were associated with increased knowledge levels. 82% of the subjects were willing to donate their eyes and this was unaffected by gender or geographical location (rural vs urban). Conclusions Awareness levels and willingness to donate eyes are high among the stakeholders in Srikakulam district in India. The services of stakeholders could be utilized, in conjunction with other community based eye donation counselors, to promote awareness regarding eye donation among the general population

Validity of US norms for the Bayley Scales of Infant Development-III in Malawian children

Most psychometric tests originate from Europe and North America and have not been validated in other populations. We assessed the validity of United States (US)-based norms for the Bayley Scales of Infant and Toddler Development-III (BSID-III), a neurodevelopmental tool developed for and commonly used in the US, in Malawian children

Intrapulmonary Pharmacokinetics of First-line Anti-tuberculosis Drugs in Malawian Patients With Tuberculosis

BACKGROUND: Further work is required to understand the intrapulmonary pharmacokinetics of first-line anti-tuberculosis drugs. This study aimed to describe the plasma and intrapulmonary pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol, and explore relationships with clinical treatment outcomes in patients with pulmonary tuberculosis. METHODS: Malawian adults with a first presentation of microbiologically-confirmed pulmonary tuberculosis received standard 6-month first-line therapy. Plasma and intrapulmonary samples were collected 8 and 16 weeks into treatment and drug concentrations measured in plasma, lung/airway epithelial lining fluid, and alveolar cells. Population pharmacokinetic modelling generated estimates of drug exposure (Cmax and AUC) from individual-level post-hoc Bayesian estimates of plasma and intrapulmonary pharmacokinetics. RESULTS: One-hundred-and-fifty-seven patients (58% HIV co-infected) participated. Despite standard weight-based dosing, peak plasma concentrations of first-line drugs were below therapeutic drug monitoring targets. Rifampicin concentrations were low in all three compartments. Isoniazid, pyrazinamide, and ethambutol achieved higher concentrations in epithelial lining fluid and alveolar cells than plasma. Isoniazid and pyrazinamide concentrations were 14.6 (95% CI: 11.2-18.0) and 49.8-fold (95% CI: 34.2-65.3) higher in lining fluid than plasma respectively. Ethambutol concentrations were highest in alveolar cells (alveolar cells:plasma ratio 15.0, 95% CI 11.4-18.6). Plasma or intrapulmonary pharmacokinetics did not predict clinical treatment response. CONCLUSIONS: We report differential drug concentrations between plasma and the lung. While plasma concentrations were below therapeutic monitoring targets, accumulation of drugs at the site of disease may explain the success of the first-line regimen. The low rifampicin concentrations observed in all compartments lend strong support for ongoing clinical trials of high-dose rifampicin regimens

High intrapulmonary rifampicin and isoniazid concentrations are associated with rapid sputum bacillary clearance in patients with pulmonary tuberculosis

This work was supported by a Wellcome Trust Clinical PhD Fellowship [grant number 105392/B/14/Z to A.D.M. and L69AGB to JM]. ELC was supported by Wellcome [200901/Z/16/Z]. The Malawi-Liverpool-Wellcome Clinical Research Programme is supported by a strategic award from the Wellcome Trust [206545/Z/17/Z]. We also acknowledge infrastructural support for bioanalysis from the Liverpool Biomedical Research Centre funded by Liverpool Health Partners.Background Intrapulmonary pharmacokinetics may better explain response to tuberculosis (TB) treatment than plasma pharmacokinetics. We explored these relationships by modelling bacillary clearance in sputum in adult patients on first-line treatment in Malawi. Methods Bacillary elimination rates (BER) were estimated using linear mixed-effects modelling of serial time-to-positivity in mycobacterial growth indicator tubes for sputum collected during the intensive phase of treatment (weeks 0 to 8) for microbiologically confirmed TB. Population pharmacokinetic models used plasma and intrapulmonary drug levels at 8 and 16 weeks. Pharmacokinetic-pharmacodynamic relationships were investigated using individual-level measures of drug exposure (AUC and Cmax) for rifampicin, isoniazid, pyrazinamide, and ethambutol, in plasma, epithelial lining fluid, and alveolar cells as covariates in the bacillary elimination models. Results Among 157 participants (58% HIV co-infected), drug exposure in plasma or alveolar cells was not associated with sputum bacillary clearance. Higher peak concentrations (Cmax) or exposure (AUC) to rifampicin or isoniazid in epithelial lining fluid was associated with more rapid bacillary elimination and shorter time to sputum negativity. More extensive disease on baseline chest radiograph was associated with slower bacillary elimination. Clinical outcome was captured in 133 participants, with 15 (11%) unfavourable outcomes recorded (recurrent TB, failed treatment, or death). No relationship between BER and late clinical outcome was identified. Conclusions Greater intrapulmonary drug exposure to rifampicin or isoniazid in the epithelial lining fluid was associated with more rapid bacillary clearance. Higher doses of rifampicin and isoniazid may result in sustained high intrapulmonary drug exposure, rapid bacillary clearance, shorter treatment duration and better treatment outcomes.Publisher PDFPeer reviewe

Blindness in Childhood in Developing Countries: Time for a Reassessment?

Paul Courtright and colleagues argue that the changing patterns of global childhood blindness suggest a need to reassess research, training, and programmatic requirements

Evaluating the relationship between ciprofloxacin prescription and non-susceptibility in Salmonella Typhi in Blantyre, Malawi: an observational study

Background: Ciprofloxacin is the first-line drug for treating typhoid fever in many countries in Africa with a high disease burden, but the emergence of non-susceptibility poses a challenge to public health programmes. Through enhanced surveillance as part of vaccine evaluation, we investigated the occurrence and potential determinants of ciprofloxacin non-susceptibility in Blantyre, Malawi. Methods: We conducted systematic surveillance of typhoid fever cases and antibiotic prescription in two health centres in Blantyre, Malawi, between Oct 1, 2016, and Oct 31, 2019, as part of the STRATAA and TyVAC studies. In addition, blood cultures were taken from eligible patients presenting at Queen Elizabeth Central Hospital, Blantyre, as part of routine diagnosis. Inclusion criteria were measured or reported fever, or clinical suspicion of sepsis. Microbiologically, we identified Salmonella enterica serotype Typhi (S Typhi) isolates with a ciprofloxacin non-susceptible phenotype from blood cultures, and used whole-genome sequencing to identify drug-resistance mutations and phylogenetic relationships. We constructed generalised linear regression models to investigate associations between the number of ciprofloxacin prescriptions given per month to study participants and the proportion of S Typhi isolates with quinolone resistance-determining region (QRDR) mutations in the following month. Findings: From 46 989 blood cultures from Queen Elizabeth Central Hospital, 502 S Typhi isolates were obtained, 30 (6%) of which had either decreased ciprofloxacin susceptibility, or ciprofloxacin resistance. From 11 295 blood cultures from STRATAA and TyVAC studies, 241 microbiologically confirmed cases of typhoid fever were identified, and 198 isolates from 195 participants sequenced (mean age 12·8 years [SD 10·2], 53% female, 47% male). Between Oct 1, 2016, and Aug 31, 2019, of 177 typhoid fever cases confirmed by whole-genome sequencing, four (2%) were caused by S Typhi with QRDR mutations, compared with six (33%) of 18 cases between Sept 1 and Oct 31, 2019. This increase was associated with a preceding spike in ciprofloxacin prescriptions. Every additional prescription of ciprofloxacin given to study participants in the preceding month was associated with a 4·2% increase (95% CI 1·8–7·0) in the relative risk of isolating S Typhi with a QRDR mutation (p=0·0008). Phylogenetic analysis showed that S Typhi isolates with QRDR mutations from September and October, 2019, belonged to two distinct subclades encoding two different QRDR mutations, and were closely related (4–10 single-nucleotide polymorphisms) to susceptible S Typhi endemic to Blantyre. Interpretation: We postulate a causal relationship between increased ciprofloxacin prescriptions and an increase in fluoroquinolone non-susceptibility in S Typhi. Decreasing ciprofloxacin use by improving typhoid diagnostics, and reducing typhoid fever cases through the use of an efficacious vaccine, could help to limit the emergence of resistance. Funding: Wellcome Trust, Bill & Melinda Gates Foundation, and National Institute for Health and Care Research (UK)

Review of the Oral Polio Vaccineimmunization Coverage with Regard to Polio Eradication in Zambia: 2000-2009

Objectives: To review the Oral Polio Vaccine (OPV) immunization coverage (routine and supplemental) in Zambia from 2000 to 2009, with the view of identifying opportunities for system strengthening, given that routine immunization is the “bed rock” for polio eradication.Design: A retrospective descriptive analysis design was conducted on secondary routine and supplemental immunization data for Zambia for the period 2000-2009, consisting of all children aged&lt;5years who had received OPV country wide. Immunization performance was evaluated using the WHO-specified 90% targetResults: The target of 90% for Routine Immunization (RI)could not be reached in most provinces. Only Central province attained the target throughout the stated period. In 2004 and 2008, all provinces apart from Copperbelt attained the target. The 90%target for supplemental immunization activities were reached during all rounds of National Immunization Days (NIDs) apart from the first two (2) rounds in1996. The two rounds of Mopping –up immunization in 2002 attained the90% targetConclusion: Routine immunization for the oral polio vaccine has been an integral part of immunization activities in Zambia. The WHO target for OPV immunization was not attained in most districts and provinces in the period under review. This situation needs to be addressed through partner collaboration to raise herd immunity in case of imported polio viruses. While RI alone cannot eradicate the disease, good routine OPV coverage reduces the incidence of polio and makes eradication feasible. It also prevents the re-establishment of poliovirus if it is re-introduced from other countries, through international travelers and migrant populations from conflict area