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1.  Editorial: Towards a global dengue research agenda 
PMCID: PMC4333199  PMID: 17550466
dengue research; dengue burden; dengue vectors; dengue clinical management
2.  [No title available] 
PMCID: PMC4070658  PMID: 24588012
3.  [No title available] 
PMCID: PMC4295018  PMID: 21615631
4.  Progression of leprosy disability after discharge: is multidrug therapy enough? 
To evaluate the risk factors related to worsening of physical disabilities after treatment discharge among patients with leprosy administered 12 consecutive monthly doses of multidrug therapy (MDT/WHO).
Cohort study was carried out at the Leprosy Laboratory in Rio de Janeiro, Brazil. We evaluated patients with multibacillary leprosy treated (MDT/WHO) between 1997 and 2007. The Cox proportional hazards model was used to estimate the relationship between the onset of physical disabilities after release from treatment and epidemiological and clinical characteristics.
The total observation time period for the 368 patients was 1 570 person-years (PY), averaging 4.3 years per patient. The overall incidence rate of worsening of disability was 6.5/100 PY. Among those who began treatment with no disability, the incidence rate of physical disability was 4.5/100 PY. Among those who started treatment with Grade 1 or 2 disabilities, the incidence rate of deterioration was 10.5/100 PY. The survival analysis evidenced that when disability grade was 1, the risk was 1.61 (95% CI: 1.02–2.56), when disability was 2, the risk was 2.37 (95% CI 1.35–4.16), and when the number of skin lesions was 15 or more, an HR = 1.97 (95% CI: 1.07–3.63). Patients with neuritis showed a 65% increased risk of worsening of disability (HR = 1.65 [95% CI: 1.08–2.52]).
Impairment at diagnosis was the main risk factor for neurological worsening after treatment/MDT. Early diagnosis and prompt treatment of reactional episodes remain the main means of preventing physical disabilities.
PMCID: PMC4285222  PMID: 23937704
disability grade; leprosy; risk factors; survival analysis; treatment
5.  Paediatric HIV care in sub-Saharan Africa: clinical presentation and 2-year outcomes stratified by age group 
To examine age differences in mortality and programme attrition amongst paediatric patients treated in four African HIV programmes.
Longitudinal analysis of data from patients enrolled in HIV care. Two-year mortality and programme attrition rates per 1000 person-years stratified by age group (<2, 2–4 and 5–15 years) were calculated. Associations between outcomes and age and other individual-level factors were studied using multiple Cox proportional hazards (mortality) and Poisson (attrition) regression models.
Six thousand two hundred and sixty-one patients contributed 9500 person-years; 27.1% were aged <2 years, 30.1% were 2–4, and 42.8% were 5–14 years old. At programme entry, 45.3% were underweight and 12.6% were in clinical stage 4. The highest mortality and attrition rates (98.85 and 244.00 per 1000 person-years), and relative ratios (adjusted hazard ratio [aHR] = 1.92, 95% CI 1.56–2.37; incidence ratio [aIR] = 2.10, 95% CI 1.86–2.37, respectively, compared with the 5- to 14-year group) were observed amongst the youngest children. Increased mortality and attrition were also associated with advanced clinical stage, underweight and diagnosis of tuberculosis at programme entry.
These results highlight the need to increase access, diagnose and provide early HIV care and to accelerate antiretroviral treatment initiation for those eligible. Adapted education and support for children and their families would also be important.
PMCID: PMC4285230  PMID: 23782065
antiretroviral treatment; children; HIV; outcome assessment; Africa
6.  Malaria in school-age children in Africa: an increasingly important challenge 
School-age children have attracted relatively little attention as a group in need of special measures to protect them against malaria. However, increasing success in lowering the level of malaria transmission in many previously highly endemic areas will result in children acquiring immunity to malaria later in life than has been the case in the past. Thus, it can be anticipated that in the coming years there will be an increase in the incidence of both uncomplicated and severe malaria in school-age children in many previously highly endemic areas. In this review, which focuses primarily on Africa, recent data on the prevalence of malaria parasitaemia and on the incidence of clinical malaria in African school-age children are presented and evidence that malaria adversely effects school performance is reviewed. Long-lasting insecticide treated bednets (LLIN) are an effective method of malaria control but several studies have shown that school-age children use LLINs less frequently than other population groups. Antimalarial drugs are being used in different ways to control malaria in school-age children including screening and treatment and intermittent preventive treatment. Some studies of chemoprevention in school-age children have shown reductions in anaemia and improved school performance but this has not been the case in all trials and more research is needed to identify the situations in which chemoprevention is likely to be most effective and, in these situations, which type of intervention should be used. In the longer term, malaria vaccines may have an important role in protecting this important section of the community from malaria. Regardless of the control approach selected, it is important this is incorporated into the overall programme of measures being undertaken to enhance the health of African school-age children.
PMCID: PMC4285305  PMID: 25145389
malaria; school-age children; Africa
7.  The practice and clinical implications of tablet splitting in international health 
Tablet splitting is frequently performed to facilitate correct dosing, but the practice and implications in low-income settings have rarely been discussed.
We selected eight drugs, with narrow therapeutic indices or critical dosages, frequently divided in the Lao PDR (Laos). These were split, by common techniques used in Laos, by four nurses and four laypersons. The mean percentage deviation from the theoretical expected weight and weight loss of divided tablets/capsules were recorded.
Five of eight study drugs failed, on splitting, to meet European Pharmacopoeia recommendations for tablet weight deviation from the expected weight of tablet/capsule halves with 10% deviating by more than 25%. There was a significant difference in splitting accuracy between nurses and laypersons (P = 0.027). Coated and unscored tablets were less accurately split than uncoated (P = 0.03 and 0.0019 for each half) and scored (0.0001 for both halves) tablets.
These findings have potential clinical implications on treatment outcome and the development of antimicrobial resistance. Investment by drug companies in a wider range of dosage units, particularly for narrow therapeutic index and critical dosage medicines, is strongly recommended.
PMCID: PMC4285309  PMID: 24702766
tablet splitting; therapeutic range; Laos; dose; essential medicines
8.  Inpatient child mortality by travel time to hospital in a rural area of Tanzania 
To investigate the association, if any, between child mortality and distance to the nearest hospital.
The study was based on data from a 1-year study of the cause of illness in febrile paediatric admissions to a district hospital in north-east Tanzania. All villages in the catchment population were geolocated, and travel times were estimated from availability of local transport. Using bands of travel time to hospital, we compared admission rates, inpatient case fatality rates and child mortality rates in the catchment population using inpatient deaths as the numerator.
Three thousand hundred and eleven children under the age of 5 years were included of whom 4.6% died; 2307 were admitted from <3 h away of whom 3.4% died and 804 were admitted from ≥3 h away of whom 8.0% died. The admission rate declined from 125/1000 catchment population at <3 h away to 25/1000 at ≥3 h away, and the corresponding hospital deaths/catchment population were 4.3/1000 and 2.0/1000, respectively. Children admitted from more than 3 h away were more likely to be male, had a longer pre-admission duration of illness and a shorter time between admission and death. Assuming uniform mortality in the catchment population, the predicted number of deaths not benefiting from hospital admission prior to death increased by 21.4% per hour of travel time to hospital. If the same admission and death rates that were found at <3 h from the hospital applied to the whole catchment population and if hospital care conferred a 30% survival benefit compared to home care, then 10.3% of childhood deaths due to febrile illness in the catchment population would have been averted.
The mortality impact of poor access to hospital care in areas of high paediatric mortality is likely to be substantial although uncertainty over the mortality benefit of inpatient care is the largest constraint in making an accurate estimate.
PMCID: PMC4269975  PMID: 24661618
access; hospital; mortality; child; Africa
9.  HIV status, breastfeeding modality at 5 months and postpartum maternal weight changes over 24 months in rural South Africa 
To determine the effect of infant feeding practices on postpartum weight change among HIV-infected and -uninfected women in South Africa.
In a non-randomised intervention cohort study of antiretroviral therapy-naïve women in South Africa, infants were classified as exclusive (EBF), mixed (MF) or non-breastfed (NBF) at each visit. We analysed infant feeding cumulatively from birth to 5 months using 24-hour feeding history (collected weekly for each of the preceding 7 days). Using generalised estimating equation mixed models, allowing for repeated measures, we compared postpartum weight change (kg) from the first maternal postpartum weight within the first 6 weeks (baseline weight) to each subsequent visit through 24 months among 2340 HIV-infected and -uninfected women with live births and at least two postpartum weight measurements.
HIV-infected (−0.2 kg CI: −1.7 to 1.3 kg; P = 0.81) and -uninfected women (−0.5 kg; 95% CI: −2.1 to 1.2 kg; P = 0.58) had marginal non-significant weight loss from baseline to 24 months postpartum. Adjusting for HIV status, socio-demographic, pregnancy-related and infant factors, 5-month feeding modality was not significantly associated with postpartum weight change: weight change by 24 months postpartum, compared to the change in the reference EBF group, was 0.03 kg in NBF (95% CI: −2.5 to +2.5 kg; P = 0.90) and 0.1 kg in MF (95% CI: −3.0 to +3.2 kg; P = 0.78).
HIV-infected and -uninfected women experienced similar weight loss over 24 months. Weight change postpartum was not associated with 5-month breastfeeding modality among HIV-infected and -uninfected women.
PMCID: PMC4251550  PMID: 24720779
HIV infection; body weight change; breastfeeding; postpartum
10.  Prevalence and correlates of treatment failure among Kenyan children hospitalised with severe community-acquired pneumonia: a prospective study of the clinical effectiveness of WHO pneumonia case management guidelines 
To determine the extent and pattern of treatment failure (TF) among children hospitalised with community-acquired pneumonia at a large tertiary hospital in Kenya.
We followed up children aged 2–59 months with WHO-defined severe pneumonia (SP) and very severe pneumonia (VSP) for up to 5 days for TF using two definitions: (i) documentation of pre-defined clinical signs resulting in change of treatment (ii) primary clinician's decision to change treatment with or without documentation of the same pre-defined clinical signs.
We enrolled 385 children. The risk of TF varied between 1.8% (95% CI 0.4–5.1) and 12.4% (95% CI 7.9–18.4) for SP and 21.4% (95% CI 15.9–27) and 39.3% (95% CI 32.5–46.4) for VSP depending on the definition applied. Higher rates were associated with early changes in therapy by clinician in the absence of an obvious clinical rationale. Non-adherence to treatment guidelines was observed for 70/169 (41.4%) and 67/201 (33.3%) of children with SP and VSP, respectively. Among children with SP, adherence to treatment guidelines was associated with the presence of wheeze on initial assessment (P = 0.02), while clinician non-adherence to guideline-recommended treatments for VSP tended to occur in children with altered consciousness (P < 0.001). Using propensity score matching to account for imbalance in the distribution of baseline clinical characteristics among children with VSP revealed no difference in TF between those treated with the guideline-recommended regimen vs. more costly broad-spectrum alternatives [risk difference 0.37 (95% CI −0.84 to 0.51)].
Before revising current pneumonia case management guidelines, standardised definitions of TF and appropriate studies of treatment effectiveness of alternative regimens are required.
Déterminer l'ampleur et les caractéristiques de l’échec du traitement (ET) chez les enfants hospitalisés avec une pneumonie acquise dans la communauté dans un grand hôpital tertiaire du Kenya.
Nous avons suivi des enfants âgés de 2 à 59 mois avec une pneumonie sévère (PS) et une pneumonie très sévère (PTS) telles que définies par l’OMS, sur un maximum de cinq jours pour l’ET, en utilisant deux définitions: (a) documentation des signes cliniques prédéfinis ayant entraîné un changement du traitement, (b) décision primaire du clinicien de changer de traitement avec ou sans documentation des mêmes signes cliniques prédéfinis.
Nous avons recruté 385 enfants. Le risque d’ET variait de 1,8% (IC95%: 0,4 à 5,1) à 12,4% (IC95%: 7,9 à 18,4) pour la PS et de 21,4% (IC95%: 15,9 à 27) à 39,3% (IC95%: 32,5 à 46,4) pour la PTS selon la définition appliquée. Des taux plus élevés étaient associés à des changements précoces du traitement par le clinicien en l'absence d'une justification clinique évidente. Le non-respect des directives de traitement a été observé pour 70/169 (41,4%) et 67/201 (33,3%) enfants avec une PS et une PTS respectivement. Chez les enfants avec une PS, le respect des directives de traitement était associé avec la présence d'une respiration sifflante au cours l’évaluation initiale (P = 0,02) tandis que le non respect par les cliniciens des traitements recommandés pour la PTS tendait à se produire chez les enfants avec une altération de la conscience (P <0,001). L'utilisation du score de propension correspondant pour tenir compte du déséquilibre dans la répartition des caractéristiques cliniques de base chez les enfants avec une PTS n'a révélé aucune différence dans l’ET entre ceux traités avec le régime recommandé par les directives et ceux traités par des alternatives plus coûteuses à large spectre (différence de risque: 0,37 (IC95%: -0,84 à 0,51).
Avant la révision des directives actuelles de prise en charge des cas de pneumonie, des définitions standard d’ET et des études appropriées de l'efficacité des traitements alternatifs sont nécessaires.
Determinar la extensión y el patrón del fallo en el tratamiento (FT) en niños hospitalizados con una neumonía adquirida en la comunidad, ingresados en un gran hospital terciario de Kenia.
Hemos seguido a niños con edades entre los 2-59 meses con una neumonía severa (NS) y neumonía muy severa (NMS) según definición de la OMS de hasta cinco días para FT utilizando dos definiciones: (a) documentación de signos clínicos pre-definidos que resultaron en un cambio de tratamiento (b) decisión del clínico principal de cambiar el tratamiento con o sin documentación de los mismos signos clínicos pre-definidos.
Incluimos a 385 niños. El riesgo de FT varió entre un 1.8% (IC 95% 0.4 a 5.1) y 12.4% (IC 95% 7.9 a 18.4) para NS y 21.4% (IC 95% 15.9 a 27) y 39.3% (IC 95% 32.5 a 46.4) para NMS dependiendo de la definición que se aplicase. Unas mayores tasas estaban asociadas con cambios tempranos en la terapia por el clínico y en ausencia de un razonamiento clínico obvio. Se observaba una no adherencia a las guías de tratamiento en 70/169 (41.4%) y 67/201 (33.3%) de los niños con NS y NMS respectivamente. Entre los niños con SP, la adherencia a las guías de tratamiento estaba asociada con la presencia de sibilancias en la evaluación inicial (P=0.02) mientras que la no adherencia del clínico a los tratamientos recomendados por las guías para NMS tendían a ocurrir en niños con un estado alterado de consciencia (P<0.001). Utilizando el pareamiento por puntaje de propensión para equilibrar los grupos en la distribución de las características clínicas de base de los niños con NMS, se observó que no existían diferencias en FT entre aquellos tratados con el régimen recomendado por las guías versus alternativas más costosas de amplio espectro (diferencias de riesgo 0.37 (IC 95% -0.84 a 0.51).
Antes de revisar las actuales guías de manejo de casos de neumonía, se requieren definiciones estandarizadas de FT y estudios apropiados de la efectividad del tratamiento de regímenes alternativos.
PMCID: PMC4241029  PMID: 25130866
treatment failure; case management; World Health Organization; pneumonia
11.  Early loss to follow-up of recently diagnosed HIV-infected adults from routine pre-ART care in a rural district hospital in Kenya: a cohort study 
To determine the rate and predictors of early loss to follow-up (LTFU) for recently diagnosed HIV-infected, antiretroviral therapy (ART)-ineligible adults in rural Kenya.
Prospective cohort study. Clients registering for HIV care between July 2008 and August 2009 were followed up for 6 months. Baseline data were used to assess predictors of pre-ART LTFU (not returning for care within 2 months of a scheduled appointment), LTFU before the second visit and LTFU after the second visit. Logistic regression was used to determine factors associated with LTFU before the second visit, while Cox regression was used to assess predictors of time to LTFU and LTFU after the second visit.
Of 530 eligible clients, 178 (33.6%) were LTFU from pre-ART care (11.1/100 person-months). Of these, 96 (53.9%) were LTFU before the second visit. Distance (>5 km vs. <1 km: adjusted hazard ratio 2.6 [1.9–3.7], P < 0.01) and marital status (married vs. single: 0.5 [0.3–0.6], P < 0.01) independently predicted pre-ART LTFU. Distance and marital status were independently associated with LTFU before the second visit, while distance, education status and seasonality showed weak evidence of predicting LTFU after the second visit. HIV disease severity did not predict pre-ART LTFU.
A third of recently diagnosed HIV-infected, ART-ineligible clients were LTFU within 6 months of registration. Predictors of LTFU among ART-ineligible clients are different from those among clients on ART. These findings warrant consideration of an enhanced pre-ART care package aimed at improving retention and timely ART initiation.
PMCID: PMC4230408  PMID: 22943164
HIV; lost to follow-up; retention; pre-antiretroviral therapy
12.  Comparing actual and perceived causes of fever among community members in a low malaria transmission setting in northern Tanzania 
To compare actual and perceived causes of fever in northern Tanzania.
In a standardized survey, heads of households in 30 wards in Moshi, Tanzania, were asked to identify the most common cause of fever for children and for adults. Responses were compared to data from a local hospital-based fever etiology study that used standard diagnostic techniques.
Of 810 interviewees, the median (range) age was 48 (16, 102) years and 62.8% were females. Malaria was the most frequently identified cause of fever, cited by 56.7% and 43.6% as the most common cause of fever for adults and children, respectively. In contrast, malaria accounted for 2.0% of adult and 1.3% of pediatric febrile admissions in the fever etiology study. Weather was the second-most frequently cited cause of fever. Participants who identified a non-biomedical explanation such as weather as the most common cause of fever were more likely to prefer a traditional healer for treatment of febrile adults (OR 2.7, p<0.001). Bacterial zoonoses were the most common cause of fever among inpatients, but no interviewees identified infections from animal contact as the most common cause of fever for adults; 0.2% identified these infections as the most common cause of fever for children.
Malaria is perceived to be a much more common cause of fever than hospital studies indicate whereas other important diseases are under-appreciated in northern Tanzania. Belief in non-biomedical explanations of fever is common locally and has important public health consequences.
PMCID: PMC3943636  PMID: 24103083
Africa; fever; malaria; beliefs; Tanzania
13.  Elucidating the temporal and spatial dynamics of Biomphalaria glabrata genetic diversity in three Brazilian villages 
The freshwater snail Biomphalaria glabrata is the principal intermediate host for the parasite Schistosoma mansoni within Brazil. We assessed the potential effects of snail population dynamics on parasite transmission dynamics via population genetics.
We sampled snail populations located within the confines of three schistosome-endemic villages in the state of Minas Gerais, Brazil. Snails were collected from individual microhabitats following seasonal periods of flood and drought over the span of one year. Snail spatio-temporal genetic diversity and population differentiation of 598 snails from 12 sites were assessed at 7 microsatellite loci.
Average genetic diversity was relatively low, ranging from 4.29 to 9.43 alleles per locus and, overall, subpopulations tended to exhibit heterozygote deficits. Genetic diversity was highly spatially partitioned among subpopulations, while virtually no partitioning was observed across temporal sampling. Comparison with previously published parasite genetic diversity data indicated that S. mansoni populations are significantly more variable and less subdivided than those of the B. glabrata intermediate hosts.
Within individual Brazilian villages, observed distributions of snail genetic diversity indicate temporal stability and very restricted gene flow. This is contrary to observations of schistosome genetic diversity over the same spatial scale, corroborating the expectation that parasite gene flow at the level of individual villages is likely driven by vertebrate host movement.
PMCID: PMC3783513  PMID: 23911082
Biomphalaria glabrata; Schistosoma mansoni; population genetics; microsatellite; gene flow; Brazil
14.  Antenatal and Delivery Services in Kinshasa, Democratic Republic of Congo: Care-seeking and Experiences Reported by Women in a Household-based Survey 
Tropical medicine & international health : TM & IH  2013;18(10):10.1111/tmi.12171.
Increasing coverage of quality reproductive health services, including prevention of mother-to-child transmission services, requires understanding where and how these services are provided. To inform scale-up, we conducted a population-based survey in Kinshasa, Democratic Republic of Congo.
Stratified two-stage cluster sampling was used to select women ≥18 years old who had been pregnant within the prior three years. Participants were interviewed about their reproductive healthcare utilization and impressions of services received.
We interviewed 1221 women, 98% of whom sought antenatal care (ANC). 78% of women began ANC after the first trimester and 22% reported <4 visits. Reasons for choosing an ANC facility included reputation (51%), friendly/accessible staff (39%), availability of comprehensive services (29%), medication access (26%), location (26%), and cost (21%). Most women reported satisfactory treatment by staff, but 47% reported that the ANC provider ignored their complaints, 23% had difficulty understanding responses to their questions, 22% wanted more time with the provider, 21% wanted more privacy, and 12% felt uncomfortable asking questions. Only 56% reported someone talked to them about HIV/AIDS. Strongest predictors of seeking inadequate ANC included low participant and partner education and lack of certain assets. Only 32% of women sought postnatal care. Some results varied by health zone.
Scaling-up interventions to improve reproductive health services should include broad-based health systems strengthening and promote equitable access to quality ANC, delivery, and postnatal services. Personal and structural-level barriers to seeking ANC need to be addressed, with consideration given to local contexts.
PMCID: PMC3811924  PMID: 23964667
Antenatal Care; prevention of mother-to-child transmission of HIV; Democratic Republic of Congo; maternal and child health; household survey; implementation research
15.  Incidence of orphanhood before and after implementation of a HIV CARE program in Rakai, Uganda 
Scaling up of HIV care programs in sub-Saharan Africa has resulted in improved survival of HIV-infected adults, but its effect on orphanhood has not been well studied.
To compare the incidence of orphanhood among children <15 years of age before and after implementing HIV care in Rakai, Uganda.
Annual household censuses and surveys were conducted January 2001 to September 2009 in a community cohort, where HIV care including antiretroviral therapy (ART) started in June 2004. Data included parental survival of children aged –14 years, and HIV status from consenting adults aged 15–49 years. The incidence of orphanhood was estimated as the number of new orphans divided by person-years, determined during three time periods: Pre-HIVcare roll-out (January 2001–June 2003) 1–3 years before the advent of HIV care in Rakai program, HIVcare-transition from September2003–May2006, and the Expanded HIVcare period from August2006–September2009. Poisson regression was used to estimate incidence rate ratios (IRR) of orphanhood and 95% confidence intervals, and the Population attributable fraction (PAF) of incident orphanhood due to HIV+ parental status was estimated as pd*(RR-1)/RR.
A total of 20 823, 21 770 and 23 700 children aged 0–14 years were censused at the three periods, respectively. The prevalence of orphanhood significantly declined; 17.2% during Pre-HIVcare roll-out, 16.0% at HIVcare-transition, and 12.6% at Expanded HIVcare period (χ2 for trend, p<0.0001). The incidence of orphanhood also declined significantly with increasing HIV care from 2.10/100py, 1.57/100py and 1.07/100py (χ2 for trend, p<0.0001). The largest declines were observed among children with HIV+ parent(s), 8.2/100pyr, 5.2/100pys and 3.4/100pyr. PAF also declined from 35.3% in the pre-HIVcare to 27.6% in the Expanded HIVcare periods
After the availability of ART there was decline in population attributable fraction of incident orphanhood due to parental HIV+ status, and in the incidence of orphanhood especially among children with HIV-infected parents.
PMCID: PMC4169214  PMID: 22716203
Incidence; orphanhood; HIV care; ART; PAF; Uganda
16.  Socioeconomic determinants of HIV testing and counselling: A comparative study in four African countries 
Research indicates that individuals tested for HIV have higher socioeconomic status than those not tested, but less is known about how socioeconomic status is associated with modes of testing. We compared individuals tested through provider-initiated testing and counselling (PITC), those tested through voluntary counselling and testing (VCT), and those never tested.
Cross-sectional surveys were conducted at health facilities in Burkina Faso, Kenya, Malawi, and Uganda, as part of the MATCH (Multi-country African Testing and Counselling for HIV) study. 3,659 clients were asked about testing status, type of facility of most recent test, and socioeconomic status. Two outcome measures were analyzed: ever tested for HIV, and mode of testing. We compared VCT at standalone facilities and PITC, which includes Integrated facilities where testing is provided with medical care, and PMTCT (prevention of mother-to-child transmission) facilities. The determinants of ever testing and of using a particular mode of testing were analysed using modified Poisson regression and multinomial logistic analyses.
Higher socioeconomic status was associated with the likelihood of testing at VCT rather than other facilities or not testing. There were no significant differences in socioeconomic characteristics between those tested through PITC (integrated and PMTCT facilities) and those not tested.
Provider-initiated modes of testing make testing accessible to individuals from lower socioeconomic groups to a greater extent than traditional VCT. Expanding testing through PMTCT reduces socioeconomic obstacles, especially for women. Continued efforts are needed to encourage testing and counselling among men and the less affluent.
PMCID: PMC3808878  PMID: 23937702
HIV; testing; sub-Saharan Africa; socioeconomic; access; VCT; PITC
17.  Meningococcal carriage in the African meningitis belt 
A meningococcal serogroup A polysaccharide/tetanus toxoid conjugate vaccine (PsA-TT) (MenAfriVac™) is being deployed in countries of the African meningitis belt. Experience with other polysaccharide/protein conjugate vaccines has shown that an important part of their success has been their ability to prevent the acquisition of pharyngeal carriage and hence to stop transmission and induce herd immunity. If PsA-TT is to achieve the goal of preventing epidemics, it must be able to prevent the acquisition of pharyngeal carriage as well as invasive meningococcal disease and whether PsA-TT can prevent pharyngeal carriage needs to be determined. To address this issue, a consortium (The African Meningococcal Carriage Consortium) (MenAfriCar) was established in 2009 to investigate the pattern of meningococcal carriage in countries of the African meningitis belt prior to and after the introduction of PsA-TT. This paper describes how the consortium was established, its objectives and the standardised field and laboratory methods that were used to achieve these objectives. The experience of the MenAfriCar Consortium will help in planning future studies on the epidemiology of meningococcal carriage in countries of the African meningitis belt and elsewhere.
PMCID: PMC3950817  PMID: 23682910
Neisseria meningitidis; meningococcus; meningococcal carriage; meningococcal vaccines; Africa; MenAfriCar
18.  A population-based study of how children are exposed to saliva in KwaZulu-Natal Province, South Africa: implications for the spread of saliva-borne pathogens to children 
In sub-Saharan Africa, many viral infections, including Epstein–Barr virus, cytomegalovirus, Kaposi’s sarcoma-associated herpesvirus and hepatitis B are acquired in childhood. While saliva is an important transmission conduit for these viruses, little is known about how saliva is passed to African children. We endeavoured to identify the range and determinants of acts by which African children are exposed to saliva.
To identify the range of acts by which African children are exposed to saliva, we conducted focus groups, semi-structured interviews and participant observations in an urban and a rural community in South Africa. To measure the prevalence and determinants of the identified acts, we administered a questionnaire to a population-based sample of caregivers.
We identified 12 caregiving practices that expose a child’s oral–respiratory mucosa, cutaneous surfaces or anal–rectal mucosa to saliva. Several acts were heretofore not described in the contemporary literature (e.g., caregiver inserting finger lubricated with saliva into child’s rectum to relieve constipation). Among 896 participants in the population-based survey, many of the acts were commonly practised by all respondent types (mothers, fathers, grandmothers and siblings). The most common were premastication of food, sharing sweets and premastication of medicinal plants that are spit onto a child’s body.
African children are exposed to saliva through a variety of acts, practised by a variety of caregivers, with no single predominant practice. This diversity poses challenges for epidemiologic work seeking to identify specific saliva-passing practices that transmit viruses. Most acts could be replaced by other actions and are theoretically preventable.
PMCID: PMC4104610  PMID: 20149165
Kaposi’s sarcoma-associated herpesvirus; cytomegalovirus; hepatitis B virus; Epstein–Barr Virus; saliva; South Africa
19.  Space-time analysis of hospitalized dengue patients in rural Thailand reveals important temporal intervals in the pattern of dengue virus transmission 
This study uses space-time analysis to determine the temporal intervals at which spatial clustering of dengue hospitalizations occurs.
Analysis of 262 people hospitalized and serologically confirmed with dengue virus infections in Kamphaeng Phet, Thailand was performed. The cases were observed between January 1, 2009 and May 6, 2011. Spatial coordinates of each patient’s home were captured using the Global Positioning System. A novel methodology based on the Knox test was used to determine the temporal intervals between cases at which spatial clustering occured. These intervals are indicative of the length of time between successive illnesses in the chain of dengue virus transmission.
The strongest spatial clustering occurred at the 15–17 day interval. Therewas also significant spatial clustering over short time intervals (2–5 days). The highest excess risk was observed within 200m of a previous hospitalized case and significantly elevated risk persisted within this distance for as long as 32–34 days.
The analyses indicate that 15–17 days is the most likely serial interval between successive dengue illnesses. This novel methodology relies only on passively-detected, hospitalized case data with household locations and provides a useful tool for understanding region-specific and outbreak-specific dengue virus transmission dynamics.
PMCID: PMC4099473  PMID: 22808917
dengue; transmission; serial interval; space-time; clustering; Thailand
20.  Provision of private, piped water and sewerage connections and directly observed handwashing of mothers in a peri-urban community of Lima, Peru 
To estimate the association between improved water and sanitation access and handwashing of mothers living in a peri-urban community of Lima, Peru.
We observed 27 mothers directly, before and after installation of private, piped water and sewerage connections in the street just outside their housing plots, and measured changes in the proportion of faecal-hand contamination and hand-to-mouth transmission events with handwashing.
After provision of water and sewerage connections, mothers were approximately two times more likely to be observed washing their hands within a minute of defecation, compared with when they relied on shared, external water sources and non-piped excreta disposal (RR = 2.14, 95% CI = 0.99–4.62). With piped water and sewerage available at housing plots, handwashing with or without soap occurred within a minute after 48% (10/21) of defecation events and within 15 min prior to 8% (11/136) of handling food events.
Handwashing increased following installation of private, piped water and sewerage connections, but its practice remained infrequent, particularly before food-related events. Infrastructural interventions should be coupled with efforts to promote hygiene and ensure access to water and soap at multiple on-plot locations convenient to mothers.
PMCID: PMC4098569  PMID: 24438038
handwashing; water supply; sanitation; hygiene; Peru
21.  Task-shifting an inpatient triage, assessment, and treatment program improves the quality of care for hospitalized Malawian children 
We aimed to improve pediatric inpatient surveillance at a busy referral hospital in Malawi with 2 new programs: (1) the provision of vital sign equipment and implementation of an inpatient triage program (ITAT) that includes a simplified pediatric severity-of-illness score; (2) task-shifting ITAT to a new cadre of health care workers called “Vital Sign Assistants” (VSAs).
This study, conducted on the pediatric inpatient ward of a large referral hospital in Malawi, was divided into 3 phases, each lasting 4 weeks. In Phase A, we collected baseline data. In Phase B, we provided 3 new automated vital sign poles and implemented ITAT with current hospital staff. In Phase C, VSAs were introduced and performed ITAT. Our primary outcome measures were the number of vital sign assessments performed and clinician notifications to reassess patients with high ITAT scores.
We enrolled 3,994 patients who received 5,155 vital sign assessments. Assessment frequency was equal between Phases A (0.67 assessments/patient) and B (0.61 assessments/patient), but increased 3.6-fold in Phase C (2.44 assessments/patient, p<0.001). Clinician notifications increased from Phases A (84) and B (113) to Phase C (161, p=0.002). Inpatient mortality fell from Phase A (9.3%) to Phases B (5.7) and C (6.9%).
ITAT with VSAs improved vital sign assessments and nearly doubled clinician notifications of patients needing further assessment due to high ITAT scores, while equipment alone made no difference. Task-shifting ITAT to VSAs may improve outcomes in pediatric hospitals in the developing world.
PMCID: PMC3683117  PMID: 23600592
pulse oximetry; pediatric early warning score; task-shift; Malawi; ITAT; vital sign
22.  Development of a severity of illness scoring system (ITAT) for resource-constrained hospitals in developing countries 
To develop a new pediatric illness severity score, called Inpatient Triage, Assessment, and Treatment (ITAT), for resource-limited settings to identify hospitalized patients at highest risk of death and facilitate urgent clinical re-evaluation.
We performed a nested case-control study at a Malawian referral hospital. The ITAT score was derived from 4 equally-weighted variables, yielding a cumulative score between 0 and 8. Variables included oxygen saturation, temperature, and age-adjusted heart and respiratory rates. We compared the ITAT score between cases (deaths) and controls (discharges) in predicting death within 2 days. Our analysis includes predictive statistics, bivariable and multivariable logistic regression, and calculation of data-driven scores.
A total of 54 cases and 161 controls were included in the analysis. The area under the receiver operating characteristic curve was 0.76. At an ITAT cutoff of 4, the sensitivity, specificity, and likelihood ratio were 0.44, 0.86, and 1.70, respectively. A cumulative ITAT score of 4 or higher was associated with increased odds of death (OR: 4.80; 95% CI: 2.39 – 9.64). A score of 2 for all individual vital signs was a statistically significant independent predictor of death.
We developed an inpatient triage tool (ITAT) appropriate for resource-constrained hospitals that identifies high-risk children after hospital admission. Further research is needed to study how best to operationalize ITAT in developing countries.
PMCID: PMC3713504  PMID: 23758198
vital sign; early warning score; PEWS; pediatric; Malawi; ITAT
23.  Evaluation of Enrichment Method for Detection of Vibrio cholerae O1 using a Rapid Dipstick Test in Bangladesh 
Culturing is generally considered to be the gold standard for detecting Vibrio cholerae in stool, though it is not always feasible in resource-limited settings. The Crystal VC dipstick test allows for rapid stool testing for the diagnosis of cholera in the field. However, previous studies have found low specificities (49%–79%) associated with direct testing of stool for cholera using this kit when compared to culturing.
In the present study conducted in Dhaka, Bangladesh in 2013, we compare direct testing using the Crystal VC dipstick test and testing after enrichment for 6-hours in Alkaline Peptone Water (APW) to bacterial culture as the gold standard. Samples positive by dipstick but negative by culture were also tested using PCR.
Stool was collected from 125 patients. The overall specificities of the direct testing and testing after 6-hour enrichment in APW compared to bacterial culture were 91.8% and 98.4% (p=0.125) respectively, and the sensitivities were 65.6% and 75.0% (p=0.07), respectively.
The increase in the sensitivity of the Crystal VC kit with the use of the 6 hour enrichment step in APW compared to direct testing was marginally significant. The Crystal VC dipstick was found to have a much higher specificity than previously reported (91–98%). Therefore this method provides a promising screening tool for cholera outbreak surveillance in resource limited settings where elimination of false positive results is critical.
PMCID: PMC4065385  PMID: 24401137
25.  Direct observation of hygiene in a Peruvian shantytown: not enough handwashing and too little water 
To document frequency of hygiene practices of mothers and children in a shantytown in Lima, Peru.
Continuous monitoring over three 12-h sessions in households without in-house water connections to measure: (i) water and soap use of 32 mothers; (ii) frequency of interrupting faecal-hand contamination by washing; and (iii) the time until faecal-hand contamination became a possible transmission event.
During 1008 h of observation, 55% (65/119) of mothers’ and 69% (37/54) of children's faecal-hand contamination events were not followed within 15 min by handwashing or bathing. Nearly 40% (67/173) of faecal-hand contamination events became possible faecal-oral transmission events. There was no difference in the time-until-transmission between mothers and children (P = 0.43). Potential transmission of faecal material to food or mouth occurred in 64% of cases within 1 h of hand contamination. Mean water usage (6.5 l) was low compared to international disaster relief standards.
We observed low volumes of water usage, inadequate handwashing, and frequent opportunities for faecal contamination and possible transmission in this water-scarce community.
PMCID: PMC4014353  PMID: 19055623
handwashing; water supply; hygiene; Peru

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