The epidemiology of diarrhea: Determination of the burden, etiology and consequences of diarrheal disease in children aged 0-59 months in Manhiça District, Mozambique = La epidemiología de las diarreas: Determinación del peso, etiología y secuelas de la enfermedad diarreica en niños de 0-59 meses de edad en el Distrito de Manhiça, Mozambique

Abstract

The objective of this thesis is to improve our understanding of the epidemiology of diarrhea, particularly to estimate the population-based burden, microbiologic etiology and adverse clinical consequences of moderate-to-severe diarrhea among children 0-59 months of age in a sub-Sahara Africa area to guide public health policy and target appropriate interventions.

This thesis is based on a collection of five articles. The first three articles within this thesis present results from a case-control study about the burden of diseases, risk factors, microbiologic etiology and clinical presentation of MSD among children aged 0-59 months between December 2007 and October 2011 in sub-Saharan Africa (Kenya, Mali, Mozambique, The Gambia) and Southeast Asia (Bangladesh, India, Pakistan). The first article describes results of a multicenter analysis of data collected from the seven sites during the first three years of the study. The estimated incidence of moderate-to-severe diarrhea was highest in India, next highest in Kenya and Mali, and lowest in The Gambia, Pakistan, Bangladesh, and Mozambique. The overall annual incidence of moderate-to-severe diarrhea per 100 child-years was 30.8 (95% CI 24.8–36.8) for infants, 23.1 (95% CI 17.2–29.0) for toddlers, and 7.7 (95% CI 3.9–11.5) for children. Most attributable cases of moderate-to-severe diarrhea were due to four pathogens: rotavirus, Cryptosporidium, ETEC ST (ST only or ST/LT) and Shigella. Odds of dying during follow-up were 8.5-fold higher in patients with moderate-tosevere diarrhea than in controls; most deaths (167 [87.9%]) occurred during the first 2 years of life. Pathogens associated with increased risk of case death were ST-ETEC and typical enteropathogenic E coli and Cryptosporidium.

The second and third articles describe specific results from Manhiça district, (Mozambique site). The incidence of acute diarrhea has dropped by about 80% over the period 2001-2012. Incidence of moderate-to-severe diarrhea per 100 child years at risk for the period 2007-2011 was 9.85, 7.73 and 2.10 for children aged 0-11, 12-23 and 24-59 months respectively. Most cases of moderate-to-severe diarrhea were again due to rotavirus, Cryptosporidium, ETEC ST (ST only or ST/LT), Shigella and Adenovirus 40/41. Having a caretaker who was not the mother and giving stored water were independent risk factors for moderate-to-severe diarrhea. On the other hand, regular washing hands particularly after handling animals or before preparing baby’s food, and having facilities to dispose child’s stool were protective factors for moderate-to-severe diarrhea. Risk of moderate-to-severe diarrhea was not found to be strongly associated with economic indicators of the households and education level of the caretaker.

The fourth paper of this thesis describes the results of two surveys about health services utilization in case of diarrhea performed during the above described case-control study, through interviews conducted with primary caretakers of children aged 0-59 months living in Manhiça district. Of those primary caretakers reporting an episode of diarrhea during the recall period, 65.2% in first survey and 43.8% in second survey reported seeking care at a health facility. The use of health facilities in case of diarrhea was found to be fundamentally associated with the perceived need, lower knowledge of dehydration signs and may have been hampered by the economic status.

The last paper of this thesis describes a retrospective analysis of data recorded through the health facility morbidity surveillance system of all malnutrition cases in children aged less than five years of age seen at Manhiça’s District Hospital during the period 2001 to 2010. During this period, 274,813 children were seen at the outpatient clinic of Manhiça’s District Hospital, almost half of which (47.0%) presenting with some indication of malnutrition, and 6% (17,188/274,813) with severe malnutrition. Of these, only 15% (2,522/17,188) were eventually admitted. Case fatality rate of severe malnutrition was 7% (162/2274). Bacteremia, hypoglycemia, oral candidiasis, edema, pallor, deep breathing and acute diarrhea were independently associated with an increased risk of in-hospital mortality, while malaria parasitaemia and increasing age were independently associated with a lower risk of a poor outcome. Overall Minimum Community-based Incidence rates were 15 cases per 1000 child-years, and children aged 12-23 months of age had the highest incidence.

This thesis presents important results related to diarrheal disease and malnutrition of which may be of great public health utility for policy makers in order to decrease the unacceptable morbidity and mortality still associated with such diseases.

Los cinco artículos de esta tesis surgen de diferentes (pero complementarios) proyectos abarcan desde la investigación social básica de los determinantes del uso de servicios de salud y control de enfermedades en caso de enfermedad diarreica, hasta análisis más específicos de los factores de riesgo y los determinantes microbiológicos de la enfermedad en los niños con edad 0-59 meses en el distrito de Manhiça, Mozambique.

La incidencia de diarrea moderada a grave por cada 100 años-niño a riesgo durante el global del período 2007-2011 fue de 9.85, 7.73 y 2.10 para los niños de 0-11, 12-23 y de 24-59 meses, respectivamente. La mayoría de los casos de diarrea moderada a grave fueron debidos a rotavirus, Cryptosporidium, ETEC ST (ST sólo o ST / LT), Shigella y Adenovirus 40/41. Tener un cuidador diferente de la madre y beber agua almacenada fueran factores de riesgo de episodios de diarrea moderada a grave. Por otro lado, lavarse las manos regularmente y tener facilidades para disponer las heces del niño son factores de protección para la diarrea moderada a grave. Los resultados sobre actitudes de utilización de servicios de salud muestran que una importante proporción de los cuidadores que reportaron un episodio de diarrea (65.2% en la primera encuesta y 43.8 % en el segunda encuesta) informaron que acudieron a un centro de salud. Asimismo, el uso de los servicios de salud en caso de diarrea pudo asociarse a una necesidad percibida y a un bajo conocimiento de los signos de deshidratación; pudiendo haber sido obstaculizado, paradójicamente, por la situación económica. Finalmente, durante la vigilancia de 10 años sobre la desnutrición, se verifico que 6% de los 274,813 niños atendidos en las consultas externas del Hospital Distrital de Manhiça, presentó criterios de malnutrición grave. De éstos, sólo el 15% (2,522 /17,188) fueron finalmente admitidos. Las tasas de incidencia mínima comunitarias fueron 15 casos por cada 1000 niños-año a riesgo, y la tasa de letalidad asociada a la malnutrición grave fue del 7% (162/2,274).

Esta tesis presenta, por tanto, resultados importantes que son de gran utilidad desde el punto de vista de salud pública, y deberían servir a los responsables políticos para tomar medidas basadas en la evidencia y disminuir así la inaceptable morbi-mortalidad todavía asociada con la enfermedad diarreica y la malnutrición.