Northan Hurtado

Lessons and Challenges for Measles Control from Unexpected Large Outbreak, Malawi

Supplementary immunization activities are crucial to reduce the number of susceptible children.

Reaching Hard-to-Reach Individuals: Nonselective Versus Targeted Outbreak Response Vaccination for Measles

Current mass vaccination campaigns in measles outbreak response are nonselective with respect to the immune status of individuals. However, the heterogeneity in immunity, due to previous vaccination coverage or infection, may lead to potential bias of such campaigns toward those with previous high access to vaccination and may result in a lower-than-expected effective impact. During the 2010 measles outbreak in Malawi, only 3 of the 8 districts where vaccination occurred achieved a measureable effective campaign impact (i.e., a reduction in measles cases in the targeted age groups greater than that observed in nonvaccinated districts). Simulation models suggest that selective campaigns targeting hard-to-reach individuals are of greater benefit, particularly in highly vaccinated populations, even for low target coverage and with late implementation. However, the choice between targeted and nonselective campaigns should be context specific, achieving a reasonable balance of feasibility, cost, and expected impact. In addition, it is critical to develop operational strategies to identify and target hard-to-reach individuals.

Measles seroprevalence in Chiradzulu district, Malawi: Implications for evaluating vaccine coverage

INTRODUCTION Self-reported measles vaccination coverage is frequently used to inform vaccination strategies in resource-poor settings. However, little is known to what extent this is a reliable indicator of underlying seroprotection, information that could provide guidance ensuring the success of measles control and elimination strategies. METHODS As part of a study exploring HIV infection and measles susceptibility, we conveniently sampled consenting HIV-uninfected patients presenting at the HIV voluntary counselling and testing centre, and HIV-infected patients presenting for regular care, in Chiradzulu district hospital, Malawi, between January and September 2012. RESULTS A total of 2106 participants were recruited between January and September 2012, three quarters of whom were HIV positive. Vaccination cards were available for just 7 participants (0.36%). 91.9% of participants were measles seropositive. Older age (OR=1.11 per year increase in age; 95%CI: 1.09-1.14) and being female (OR=1.90; 95%CI: 1.26-2.87) were both associated with significantly increased odds for seroprotection. Prior vaccination history was associated with lower odds (Odds Ratio (OR)=0.44; 95% confidence interval (CI): 0.22-0.85) for confirmed seropositivity. Previous measles infection was not significantly associated with seroprotection (OR=1.31; 95%CI: 0.49-3.51). Protection by history and serological status were concordant for 64.3% of participants <35 years old. However, analysis by age group reveals important differences in concordance between the ages, with a greater degree of discordance among younger ages. Vaccination and/or infection history as a predictor of seropositivity was 75.8% sensitive, but just 10.3% specific. CONCLUSION Reported vaccination and previous infection were poor predictors of seropositivity, suggesting these may be unreliable indicators of seroprotection status. Such serosurveys may be indicated in similar settings in which overestimation of the proportion of seroprotected individuals could have important ramifications if used to guide vaccination strategies.

Exploring HIV infection and susceptibility to measles among older children and adults in Malawi: a facility-based study

BACKGROUND HIV infection increases measles susceptibility in infants, but little is known about this relationship among older children and adults. We conducted a facility-based study to explore whether HIV status and/or CD4 count were associated with either measles seroprotection and/or measles antibody concentration. METHODS A convenience sample was recruited comprising HIV-infected patients presenting for follow-up care, and HIV-uninfected individuals presenting for HIV testing at Chiradzulu District Hospital, Malawi, from January to September 2012. We recorded age, sex, and reported measles vaccination and infection history. Blood samples were taken to determine the CD4 count and measles antibody concentration. RESULTS One thousand nine hundred and thirty-five participants were recruited (1434 HIV-infected and 501 HIV-uninfected). The majority of adults and approximately half the children were seroprotected against measles, with lower odds among HIV-infected children (adjusted odds ratio 0.27, 95% confidence interval 0.10-0.69; p=0.006), but not adults. Among HIV-infected participants, neither CD4 count (p=0.16) nor time on antiretroviral therapy (p=0.25) were associated with measles antibody concentration, while older age (p<0.001) and female sex (p<0.001) were independently associated with this measure. CONCLUSIONS We found no evidence that HIV infection contributes to the risk of measles infection among adults, but HIV-infected children (including at ages older than previously reported), were less likely to be seroprotected in this sample.

Nontuberculous Mycobacteria Infections at a Provincial Reference Hospital, Cambodia

Prevalence of nontuberculous mycobacteria (NTM) disease is poorly documented in countries with high prevalence of tuberculosis (TB). We describe prevalence, risk factors, and TB program implications for NTM isolates and disease in Cambodia. A prospective cohort of 1,183 patients with presumptive TB underwent epidemiologic, clinical, radiologic, and microbiologic evaluation, including >12-months of follow-up for patients with NTM isolates. Prevalence of NTM isolates was 10.8% and of disease was 0.9%; 217 (18.3%) patients had TB. Of 197 smear-positive patients, 171 (86.8%) had TB confirmed (167 by culture and 4 by Xpert MTB/RIF assay only) and 11 (5.6%) had NTM isolates. HIV infection and past TB were independently associated with having NTM isolates. Improved detection of NTM isolates in Cambodia might require more systematic use of mycobacterial culture and the use of Xpert MTB/RIF to confirm smear-positive TB cases, especially in patients with HIV infection or a history of TB.

Drug-resistant tuberculosis in HIV-infected patients in a national referral hospital, Phnom Penh, Cambodia

Background and objective There are no recent data on the prevalence of drug-resistant tuberculosis (DR TB) in Cambodia. We aim to describe TB drug resistance amongst adults with pulmonary and extra-pulmonary TB and human immunodeficiency virus (HIV) co-infection in a national referral hospital in Phnom Penh, Cambodia. Design Between 22 November 2007 and 30 November 2009, clinical specimens from HIV-infected patients suspected of having TB underwent routine microscopy, Mycobacterium tuberculosis culture, and drug susceptibility testing. Laboratory and clinical data were collected for patients with positive M. tuberculosis cultures. Results M. tuberculosis was cultured from 236 HIV-infected patients. Resistance to any first-line TB drug occurred in 34.7% of patients; 8.1% had multidrug resistant tuberculosis (MDR TB). The proportion of MDR TB amongst new patients and previously treated patients was 3.7 and 28.9%, respectively (p<0.001). The diagnosis of MDR TB was made after death in 15.8% of patients; in total 26.3% of patients with MDR TB died. The diagnosis of TB was established by culture of extra-pulmonary specimens in 23.6% of cases. Conclusions There is significant resistance to first-line TB drugs amongst new and previously treated TB–HIV co-infected patients in Phnom Penh. These data suggest that the prevalence of DR TB in Cambodia may be higher than previously recognised, particularly amongst HIV-infected patients. Additional prevalence studies are needed. This study also illustrates the feasibility and utility of analysis of non-respiratory specimens in the diagnosis of TB, even in low-resource settings, and suggests that extra-pulmonary specimens should be included in TB diagnostic algorithms.Background and objective There are no recent data on the prevalence of drug-resistant tuberculosis (DR TB) in Cambodia. We aim to describe TB drug resistance amongst adults with pulmonary and extra-pulmonary TB and human immunodeficiency virus (HIV) co-infection in a national referral hospital in Phnom Penh, Cambodia. Design Between 22 November 2007 and 30 November 2009, clinical specimens from HIV-infected patients suspected of having TB underwent routine microscopy, Mycobacterium tuberculosis culture, and drug susceptibility testing. Laboratory and clinical data were collected for patients with positive M. tuberculosis cultures. Results M. tuberculosis was cultured from 236 HIV-infected patients. Resistance to any first-line TB drug occurred in 34.7% of patients; 8.1% had multidrug resistant tuberculosis (MDR TB). The proportion of MDR TB amongst new patients and previously treated patients was 3.7 and 28.9%, respectively (p<0.001). The diagnosis of MDR TB was made after death in 15.8% of patients; in total 26.3% of patients with MDR TB died. The diagnosis of TB was established by culture of extra-pulmonary specimens in 23.6% of cases. Conclusions There is significant resistance to first-line TB drugs amongst new and previously treated TB-HIV co-infected patients in Phnom Penh. These data suggest that the prevalence of DR TB in Cambodia may be higher than previously recognised, particularly amongst HIV-infected patients. Additional prevalence studies are needed. This study also illustrates the feasibility and utility of analysis of non-respiratory specimens in the diagnosis of TB, even in low-resource settings, and suggests that extra-pulmonary specimens should be included in TB diagnostic algorithms.

Local discrepancies in measles vaccination opportunities: results of population-based surveys in Sub-Saharan Africa

BackgroundThe World Health Organization recommends African children receive two doses of measles containing vaccine (MCV) through routine programs or supplemental immunization activities (SIA). Moreover, children have an additional opportunity to receive MCV through outbreak response immunization (ORI) mass campaigns in certain contexts. Here, we present the results of MCV coverage by dose estimated through surveys conducted after outbreak response in diverse settings in Sub-Saharan Africa.MethodsWe included 24 household-based surveys conducted in six countries after a non-selective mass vaccination campaign. In the majority (22/24), the survey sample was selected using probability proportional to size cluster-based sampling. Others used Lot Quality Assurance Sampling.ResultsIn total, data were collected on 60,895 children from 2005 to 2011. Routine coverage varied between countries (>95% in Malawi and Kirundo province (Burundi) while <35% in N’Djamena (Chad) in 2005), within a country and over time. SIA coverage was <75% in most settings. ORI coverage ranged from >95% in Malawi to 71.4% [95% CI: 68.9-73.8] in N’Djamena (Chad) in 2005.In five sites, >5% of children remained unvaccinated after several opportunities. Conversely, in Malawi and DRC, over half of the children eligible for the last SIA received a third dose of MCV.ConclusionsControl pre-elimination targets were still not reached, contributing to the occurrence of repeated measles outbreak in the Sub-Saharan African countries reported here. Although children receiving a dose of MCV through outbreak response benefit from the intervention, ensuring that programs effectively target hard to reach children remains the cornerstone of measles control.

Sub-national variation in measles vaccine coverage and outbreak risk: a case study from a 2010 outbreak in Malawi

BackgroundDespite progress towards increasing global vaccination coverage, measles continues to be one of the leading, preventable causes of death among children worldwide. Whether and how to target sub-national areas for vaccination campaigns continues to remain a question. We analyzed three metrics for prioritizing target areas: vaccination coverage, susceptible birth cohort, and the effective reproductive ratio (RE) in the context of the 2010 measles epidemic in Malawi.MethodsUsing case-based surveillance data from the 2010 measles outbreak in Malawi, we estimated vaccination coverage from the proportion of cases reporting with a history of prior vaccination at the district and health facility catchment scale. Health facility catchments were defined as the set of locations closer to a given health facility than to any other. We combined these estimates with regional birth rates to estimate the size of the annual susceptible birth cohort. We also estimated the effective reproductive ratio, RE, at the health facility polygon scale based on the observed rate of exponential increase of the epidemic. We combined these estimates to identify spatial regions that would be of high priority for supplemental vaccination activities.ResultsThe estimated vaccination coverage across all districts was 84%, but ranged from 61 to 99%. We found that 8 districts and 354 health facility catchments had estimated vaccination coverage below 80%. Areas that had highest birth cohort size were frequently large urban centers that had high vaccination coverage. The estimated RE ranged between 1 and 2.56. The ranking of districts and health facility catchments as priority areas varied depending on the measure used.ConclusionsEach metric for prioritization may result in discrete target areas for vaccination campaigns; thus, there are tradeoffs to choosing one metric over another. However, in some cases, certain areas may be prioritized by all three metrics. These areas should be treated with particular concern. Furthermore, the spatial scale at which each metric is calculated impacts the resulting prioritization and should also be considered when prioritizing areas for vaccination campaigns. These methods may be used to allocate effort for prophylactic campaigns or to prioritize response for outbreak response vaccination.

Four years of case-based surveillance of meningitis following the introduction of MenAfriVac in Moissala, Chad: lessons learned

Case‐based surveillance of bacterial meningitis in sentinel districts has been recommended after the introduction of the conjugated vaccine against Neisseria meningitidis serogroup A (NmA), MenAfriVac, in the African meningitis belt. Here we report data and lessons learnt from four years of surveillance in the district of Moissala, Chad.

Improved Neonatal Mortality at a District Hospital in Aweil, South Sudan

Abstract Neonatal deaths comprise a growing proportion of global under-five mortality. However, data from the highest-burden areas is sparse. This descriptive retrospective study analyses the outcomes of all infants exiting the Médecins sans Frontières-managed neonatal unit in Aweil Hospital, rural South Sudan from 2011 to 2014. A total of 4268 patients were treated over 4 years, with annual admissions increasing from 687 to 1494. Overall mortality was 13.5% (n = 576), declining from 18.7% to 11.1% (p for trend <0.001). Newborns weighing <2500 g were at significantly increased mortality risk compared with babies ≥2500 g (odds ratio = 2.27, 95% confidence interval = 1.9–2.71, p < 0.001). Leading causes of death included sepsis (49.7%), tetanus (15.8%), respiratory distress (12.8%) and asphyxia (9.2%). Tetanus had the highest case fatality rate (49.7%), followed by perinatal asphyxia (26.5%), respiratory distress (20.4%) and neonatal sepsis (10.5%). Despite increasing admissions, overall mortality declined, indicating that survival of these especially vulnerable infants can be improved even in a basic-level district hospital programme.