Minimum Incidence of Adult Invasive Pneumococcal Disease in Blantyre, Malawi an Urban African Setting: A Hospital Based Prospective Cohort Study

Invasive pneumococcal disease causes substantial morbidity and mortality in Africa. Evaluating population level indirect impact on adult disease of pneumococcal conjugate vaccine (PCV) programmes in infants requires baseline population incidence rates but these are often lacking in areas with limited disease surveillance. We used hospital based blood culture and cerebrospinal fluid surveillance to calculate minimal incidence of invasive pneumococcal disease in the adult (≥15 years old) population of Blantyre, a rapidly growing urban centre in southern Malawi, in the period preceding vaccine introduction. Invasive pneumococcal disease incidence in Blantyre district was high, mean 58.1 (95% confidence interval (CI): 53.7, 62.7) per 100,000 person years and peaking among 35 to 40 year olds at 108.8 (95%CI: 89.0, 131.7) mirroring the population age prevalence of HIV infection. For pneumococcal bacteraemia in urban Blantyre, mean incidence was 60.6 (95% CI: 55.2, 66.5) per 100,000 person years, peaking among 35 to 40 year olds at 114.8 (95%CI: 90.3, 143.9). We suspected that our surveillance may under-ascertain the true burden of disease, so we used location data from bacteraemic subjects and projected population estimates to calculate local sub-district incidence, then examined the impact of community level socio-demographic covariates as possible predictors of local sub-district incidence of pneumococcal and non-pneumococcal pathogenic bacteraemia. Geographic heterogeneity in incidence was marked with localised hotspots but ward level covariates apart from prison were not associated with pneumococcal bacteraemia incidence. Modelling suggests that the current sentinel surveillance system under-ascertains the true burden of disease. We outline a number of challenges to surveillance for pneumococcal disease in our low-resource setting. Subsequent surveillance in the vaccine era will have to account for geographic heterogeneity when evaluating population level indirect impact of PCV13 introduction to the childhood immunisation program

Guardians and research staff experiences and views about the consent process in hospital-based paediatric research studies in urban Malawi: A qualitative study

Background: Obtaining consent has become a standard way of respecting the patient’s rights and autonomy in clinical research. Ethical guidelines recommend that the child’s parent/s or authorised legal guardian provides informed consent for their child’s participation. However, obtaining informed consent in paediatric research is challenging. Parents become vulnerable because of stress related to their child’s illness. Understanding the views held by guardians and researchers about the consent process in Malawi, where there are limitations in health care access and research literacy will assist in developing appropriate consent guidelines. Methods: We conducted 20 in-depth interviews with guardians of children and research staff who had participated in paediatric clinical trial and observational studies in acute and non-acute settings in the Southern Region of Malawi. Interviews were audio-recorded, transcribed verbatim, and thematically analysed. Interviews were compared across studies and settings to identify differences and similarities in participants’ views about informed consent processes. Data analysis was facilitated by NVIVO 11 software. Results: All participants across study types and settings reported that they associated participating in research with therapeutic benefits. Substantial differences were noted in the decision-making process across study settings. Guardians from acute studies felt that the role of their spouses was neglected during consenting, while staff reported that they had problems obtaining consent from guardians when their partners were not present. Across all study types and settings, research staff reported that they emphasised the benefits more than the risks of the study to participants, due to pressure to recruit. Participants from non-acute settings were more likely to recall information shared during the consent process than participants in the acute setting. Conclusion: The health care context, culture and research process influenced participants’ understanding of study information across study types and settings. We advise research managers or principal investigators to define minimum requirements that would not compromise the consent process and conduct study specific training for staff. The use of one size fits all consent process may not be ideal. More guidance is needed on how these differences can be incorporated during the consent process to improve understanding and delivery of consent

Blood culture collection technique and pneumococcal surveillance in Malawi during the four year period 2003–2006: an observational study

BACKGROUND: Blood culture surveillance will be used for assessing the public health effectiveness of pneumococcal conjugate vaccines in Africa. Between 2003 and 2006 we assessed blood culture outcome and performance in adult patients in the central public hospital in Blantyre, Malawi, before and after the introduction of a dedicated nurse led blood culture team. METHODS: A prospective observational study. RESULTS: Following the introduction of a specialised blood culture team in 2005, the proportion of contaminated cultures decreased (19.6% in 2003 to 5.0% in 2006), blood volume cultured increased and pneumococcal recovery increased significantly from 2.8% of all blood cultures to 6.1%. With each extra 1 ml of blood cultured the odds of recovering a pneumococcus increased by 18%. CONCLUSION: Standardisation and assessment of blood culture performance (blood volume and contamination rate) should be incorporated into pneumococcal disease surveillance activities where routine blood culture practice is constrained by limited resources

Prevalence of Covariates Among Adults With and Without Pneumococcal Bacteraemia, Queen Elizabeth Central Hospital, Blantyre Malawi, 1 January 2005 to 31 December 2006.

<p>SD = standard deviation; ART = antiretroviral therapy; TB = tuberculosis</p><p>*Comparing pneumococcal bacteraemic cohort with culture negative cohort. All by X²-test, except antifungal therapy by Fisher's exact test with rounding up of cells.</p><p>† at presentation</p><p>Prevalence of Covariates Among Adults With and Without Pneumococcal Bacteraemia, Queen Elizabeth Central Hospital, Blantyre Malawi, 1 January 2005 to 31 December 2006.</p

Population Incidence of Invasive Pneumococcal Disease in Blantyre, Malawi, among Adults ≥15 years, 1 January 2005 to 31 December 2006.

<p>Includes isolated pneumococcal bacteraemia, isolated pneumococcal meningitis and bacteraemic meningitis in Blantyre District (City and Rural).</p

Ward Level Predictors of Pneumococcal Bacteraemia Incidence.

<p>* All but last covariate are from 2008 Census of Population and Housing [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128738#pone.0128738.ref015" target="_blank">15</a>]</p><p>† Shortest walking distance by mapped road from centre of ward to QECH</p><p>^a Non-grass roofing: tin/iron, tiles, asbestos, cement</p><p>^b Sealed floor: parquet, polished wood, vinyl, asphalt, ceramic tiles, cement, bricks</p><p>^c Crowding index: mean number or occupants divided by mean number of sleeping rooms</p><p>^d Unprotected water source: spring, river/stream, pond/lake, dam, rain water, unprotected well</p><p>Ward Level Predictors of Pneumococcal Bacteraemia Incidence.</p

“At first, I was very afraid”—a qualitative description of participants’ views and experiences in the first Human Infection Study in Malawi [version 2; peer review: 2 approved]

Background: Human infection studies (HIS) involve deliberately infecting healthy volunteers with a pathogen in a controlled environment to understand infection and support the development of effective vaccines or treatments. HIS research is expanding to many low and middle-income settings to accelerate vaccine development. Given the implementation of the first HIS research to establish the experimental human pneumococcal carriage model’s feasibility, we sought to understand the participant’s opinions and experiences. Methods: We used a qualitative, descriptive approach to understand participants perceptions and experiences on HIS participation. Sixteen healthy adult participants were invited to participate in in-depth exit interviews to discuss their experiences, motivations and concerns. Results: Our findings showed that the likelihood of participation in HIS research rests on three essential conditions: motivation to participate, compensation and advocacy. The motivation and decision to participate was based on reasons including altruism, patriotism, monetary and material incentives, and while compensation was deemed appropriate, concerns about unanticipated research-related risks were raised. Participant advocate groups were recommended for increasing awareness and educating others in the broader community about HIS research. Conclusions: Participants’ experiences of HIS in Malawi provide the basis of what can be acceptable in HIS research in lower-income countries and areas where study procedures could be adjusted

<i>Helicobacter pylori</i>, HIV and Gastric Hypochlorhydria in the Malawian Population

<div><p>Background</p><p>HIV and <i>Helicobacter pylori</i> are common chronic infections in sub-Saharan Africa. Both conditions can predispose to gastric hypochlorhydria that may be a risk factor for enteric infections and reduced drug absorption. We have investigated to what extent HIV and <i>H</i>. <i>pylori</i> infections are associated with hypochlorhydria in a Malawian cohort of patients undergoing endoscopy.</p><p>Methods</p><p>104 sequential symptomatic adults referred for gastroscopy at Queen Elizabeth Central Hospital, Blantyre, Malawi, had blood taken for rapid HIV testing and fasting serum gastrin analysis. Gastric fluid was aspirated for pH testing, and gastric biopsies were taken.</p><p>Results</p><p>After 9/104 HIV-infected patients who were already established on anti-retroviral therapy were excluded, 17/95 (25.0%) were seropositive for untreated HIV, and 68/95 (71.6%) patients were <i>H</i>. <i>pylori</i> positive by histology. Hypochlorhydria (fasting gastric pH>4.0) was present in 55.8% (53/95) of patients. <i>H</i>. <i>pylori</i> infection was significantly associated with hypochlorhydria (OR 2.91, [1.02-7.75], p=0.046). While single infection with HIV was not significantly independently associated with hypochlorhydria. <i>H</i>. <i>pylori</i> and HIV co-infection was more strongly associated with hypochlorhydria (OR 6.25, [1.33-29.43], p=0.020) than either infection alone, suggesting an additive effect of co-infection. HIV infection was associated with higher serum gastrin levels (91.3pM vs. 53.1pM, p=0.040), while <i>H</i>. <i>pylori</i> infection was not (63.1pM vs. 55.1pM, p=0.610). Irrespective of <i>H</i>. <i>pylori</i> and HIV status, most patients (>90%) exhibited pangastritis. Only three patients had histological evidence of gastric atrophy, of which only one was HIV-infected.</p><p>Conclusion</p><p><i>H</i>. <i>pylori</i> infection was associated with fasting hypochlorhydria, while HIV was not independently associated. HIV and <i>H</i>. <i>pylori</i> co-infection, however, was more strongly associated with hypochlorhydria than <i>H</i>. <i>pylori</i> infection alone. The mechanism of this apparent additive effect between HIV and <i>H</i>. <i>pylori</i> remains unclear, but appears to be related to chronic pangastritis rather than gastric atrophy, and associated with hypergastrinaemia in HIV-infected individuals.</p></div

The scatterplot displays the serum gastrin (pM) levels for the four groups in relation to <i>H</i>.<i>pylori</i> and HIV infection status.

<p>The scatterplot displays the serum gastrin (pM) levels for the four groups in relation to <i>H</i>.<i>pylori</i> and HIV infection status.</p